The close association of abdominal obesity rather than general obesity with colorectal cancer (CRC) risk might be mediated by IR and inflammation, which has never been systematically explored in large-scale prospective studies.We prospectively examined the mediation effects of the fasting triglyceride-glucose (TyG) index and C-reactive protein (CRP) on the associations of obesity  with CRC risk among 93,659 participants. We used the Cox proportional hazards regression models and subgroup analyses to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC. The CAUSALMED procedure was used to perform the mediation analyses.During 13.02 years of follow-up, a total of 586 CRC cases were verified. Male participants with general obesity and abdominal obesity had a 1.29-fold and a 1.28-fold increased risk of CRC. However, a significant association was only observed among female individuals with abdominal obesity. Both TyG index and CRP were associated with an elevated risk of CRC, and A significant interaction between the TyG index and CRP was found for the risk of CRC (P for interaction<0.05). CRP and the TyG index significantly mediated the positive association between abdominal obesity and CRC risk.CRP and TyG index increased the risk of CRC independently and synergistically. Mediation effects of CRP and the TyG index were found for the association between abdominal obesity and CRC risk. In addition, abdominal obesity [as assessed by waist circumference ] is closely associated with CRC risk in both sexes. One possible explanation for the disparity is that men and women have distinct body compositions, with fat constituting a more significant percentage of body mass in women (30%) than in men (20%)  is deadly and expensive to treat . Previouen (20%) . Anotheren (20%) , 9.The insulin resistance (IR) and inflammation hypotheses postulate that there is a relationship between abdominal obesity and CRC risk since the buildup of visceral fat is a significant predictor of IR and inflammation , 11. IR The Kailuan study is an ongoing, prospective cohort study that includes biennial follow-ups for each participant. The anthropometric and laboratory parameter measurements offer us a valuable opportunity to investigate 1) the association of the TyG index and CRP with the risk of CRC incidence and 2) the mediation effects of the TyG index and CRP on the associations of obesity  with CRC risk.As previously stated , this stIn this study, individuals were excluded if they 1) were diagnosed with cancer previously(n=377); 2) had missing data on BMI, WC, CRP and the components of the TyG index, including fasting blood glucose  and triglycerides  ; and 3) lacked information about any potential confounders, including age, sex, social economic factors, laboratory tests and lifestyle behaviors . After factoring for the exclusion criteria, 93,659 individuals were enrolled, including 18,988 women and 74,671 men Figure 1Patient’s venous blood was drawn into EDTA tubes after an overnight fast (8–12 h). All blood samples were analyzed in the Central Laboratory of Kailuan General Hospital using an autoanalyzer . The details regarding the assessment of plasma CRP, FBG, HDL-C, TG, and TC can be found elsewhere . The TyGFor the duration of the follow-up, incident CRC cases were identified via: 1) tracking participants’ biennial health check-ups; 2) examining medical records linked with the Tangshan medical insurance system and the Kailuan Social Security Information System once a year, and 3) checking death certificates from the Provincial Vital Statistics Offices (PVSO) to further confirmed the outcome yearly. Clinical professionals assessed medical records and pathology reports to reconfirm the diagnosis of incident CRC, and CRC patients were categorized as C18-21 using the International Classification of Diseases, Tenth Revision (ICD-10).via a standard questionnaire. BMI was calculated as body weight divided by the square of the body height and was grouped into the following three categories: normal (< 24.0 kg/m2), overweight (24.0-27.9 kg/m2), and general obesity (≥ 28.0 kg/m2). Abdominal obesity was defined as WC >90 cm in men and >85 cm in women. Drinking was defined as consuming ≥ 100 mL/day of alcoholic beverages for more than 6 months. Smoking status was defined as consuming ≥ 1 cigarette/day for more than 6 months. Physical activity was defined as having ≥ 3 times weekly with each time lasting ≥ 30 minutes based on the response to the question of frequency of Physical activity. Tea consumption was defined as ≥ 5 times weekly regardless of the tea types. High-fat diets were evaluated in the questionnaire as “Regularly” consumed.Information on age, sex, socioeconomic factors, living habits, and personal and family members’ medical histories was collected The mean ± SD and T-test were used to describe and compare continuous variables in the normal distribution. The median (IQR) and nonparametric tests  were used to describe and compare the skewed distributed variables . Absolute values with percentages and the chi-square test were utilized to represent and compare categorical variables. Person-years were computed from the date of the baseline examination to the date of CRC diagnosis, death, or December 31, 2019, whichever occurred first. The hazard ratios (HRs) and 95% confidence intervals (CIs) for the development of incident CRC were calculated using Cox proportional hazards models. We firstly explored the association of general obesity (assessed by BMI) and central obesity (assessed by WC) with subsequent CRC risk among men and women, due to the distinct body compositions between men and women. Secondly, we investigated the effect of IR (assessed by TyG index) and inflammation (assessed by CRP) on the occurrence of CRC, multiplicative models were used to examine the interactions between CRP, TyG index, and CRC risks. Third, because there was an interaction between TyG index, CRP, and CRC risk, participants were further divided into four groups based on the presence/absence of the elevated TyG index (≥ 8.59) and CRP (>1 mg/L).P values < 0.05 (two-sided) were judged statistically significant. Statistical analyses were carried out using SAS software , version 9.4.The CAUSALMED procedure was used to perform the mediation analyses based on the variance-covariance matrix and the maximum likelihood method. It calculated the total effect , the direct effect (the effect without the mediator’s influence), and the indirect effect (the effect of the independent variable on the mediator multiplied the effect of the mediator on the outcome). All The baseline characteristics of the participants stratified by sex are listed in 85.0 vs. ≤85.0, HR [95%] CI: 1.22, 1.03-1.50).During 13 years of follow-up, a total of 586 incident CRC was developed. P for interaction<0.05). There was a statistically significant trend of increasing relative risks of CRC across different CRP groups . The adjusted HRs (95% CI) for the association of the TyG index and CRP with the risk of CRC are shown in The significant interaction between the TyG index and inflammation affects CRC development. We further divided participants into four groups based on the absence/presence of an elevated TyG index and CRP Table 4.In the mediation effect analysis, both CRP and the TyG index significantly mediated the positive association between abdominal obesity (elevated WC) and CRC risk after adjustments were made for the confounding factors. However, null or weaker mediation effects of the TyG index and CRP were found to associate general obesity with the risk of CRC incidence Figure 3In this large-scale community-based cohort study, we found the following: I) abdominal obesity was associated with an elevated risk of CRC in both sexes, while general obesity was found to only increase the risk of CRC in men; II) TyG and CRP could raise the risk of CRC independently. In addition, IR along with inflammation may function synergistically to accelerate the initiation of CRC; III) CRP and TyG index only mediated the association between obesity assessed by WC and CRC risk, indicating the IR and inflammation hypotheses may help to explain the etiological importance of abdominal fat disposition, rather than overall adiposity.2) increased the risk of CRC among male participants, while abdominal obesity (WC>90 cm in men and >85 cm in women) was associated with an elevated risk of CRC incidence in both sexes. This finding is consistent with most previous epidemiological studies (We found that general obesity BMI> 28 kg/m8 kg/m2 i studies . The clo studies . A case- studies . A syste studies .Little research has been designed to investigate the effect of the TyG index on the occurrence of CRC risk. In a retrospective population-based cohort study of 27,944 individuals, Takuro Okamura et al. found that the TyG index was a useful and accessible tool for predicting incident CRC. Recently, by analyzing 510,471 individuals from six European cohorts, Josef Fritz et al. found that the TyG index was associated with an increased risk of cancers of the digestive system, including colon, rectal, liver, and pancreatic cancer . SimilarEpidemiological studies have found that WC is more significantly associated with CRC risk than BMI , 29, empThe underlying mechanism by which inflammation and IR increase subsequent CRC risk includes two aspects. First, long-term, low-grade inflammation, which causes protein and DNA damage, can increase tumor growth and progression. Critical pathways that maintain normal cellular homeostasis can be altered by genetic and epigenetic variations in response to inflammatory mediators such as cytokines, free radicals, prostaglandins, and growth factors. Point mutations in tumor suppressor genes, DNA methylation, and posttranslational modifications are examples of these alterations, all of which can contribute to the existence and development of cancer . Second,The main strength of the current study is that it provides a unique perspective on the possible mediation effects of inflammation and IR on the association of obesity with future CRC risk based on a population-based cohort study. Additionally, this study fully considered the influence of potential confounders, such as lifestyle habits and a history of cancer-related illnesses. Additionally, the strengths of this study include the prospective study design, large sample size, and long-term follow-up. Sensitivity analysis and subgroup analyses were conducted to infer the robustness of our conclusion.There are certain limitations in this study that should be mentioned. First, colon and rectal cancer could not be analyzed separately due to the scarcity of data. Inflammation and IR may have distinct carcinogenic impacts on the development of colon and rectal cancers. Second, although we controlled for most potential confounders, we could not exclude the possibility of residual cancer-related causal variables, such as the consumption of cereal, vegetable, and high-fiber foods, owing to a lack of information on how these products are consumed. On the other hand, dietary factors are substantially associated with BMI, TC, and TG. Because those factors were adjusted in the multivariate analysis, they may only have had a modest influence on the findings. Third, all participants were from the Kailuan community, with a higher proportion of men than women. As a result, this group could not be considered typical of the Chinese population. The findings could not be immediately extrapolated to other communities with various cultures and socioeconomic backgrounds. Fourth, instead of the gold standard, HOMA-IR, the TyG index was used as an indicator of insulin resistance, which may have resulted in misclassification and underestimation of the potential effect of IR.The results of this prospective cohort study showed that elevated CRP and TyG index increased the risk of CRC independently and synergistically. Mediation effects of CRP and the TyG index were found for the association between abdominal obesity and CRC risk, which may help to elucidate the etiological importance of abdominal fat disposition rather than overall adiposity.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Aerospace Center Hospital and Kailuan General Hospital. The patients/participants provided their written informed consent to participate in this study.All authors have read and approved the manuscript. WQL: Methodology, Software, Writing-Original draft preparation. TL: Writing-Reviewing and Editing. LQ: Writing-Reviewing and Editing. YMW: Supervision, Validation. XMM: Software. LYC: Resources. QSZ: Conceptualization, Supervision. JQ: Conceptualization, Supervision, Validation, Resources. All authors contributed to the article and approved the submitted version.We thank all the staff and participants of the Kailuan study for their important contributions.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Alzheimer's disease (AD) is a neurological disorder of unknown cause, resulting in the death of brain cells. Identifying some of the modifiable risk factors for AD could be crucial for primary prevention and could lead to a reduction in the incidence of AD.This study aimed to perform a meta-meta-analysis of studies in order to assess the effect of blood pressure (BP) on the diagnosis of AD.The search was restricted to meta-analyses assessing high systolic BP (SBP) and diastolic BP (DBP) and AD. We applied the PRISMA guidelines.A total of 214 studies were identified from major databases. Finally, five meta-analyses (52 studies) were analyzed in this review. Results confirm that high SBP is associated with AD. The exploration of parameters  shows that only region significantly moderates the relationship between BP and AD. Asian people are those whose SBP levels >140 mmHg are associated with AD. BP is associated with AD in both people aged ≤65 years and those aged ≥65 years and in cross-sectional and longitudinal studies. In the case of DBP, only women are at a higher risk of AD, particularly when its levels are >90.SBP is associated with both cerebrovascular disease and AD. Therefore, future studies should use other uncontrolled factors, such as cardiovascular diseases, diabetes, and stroke, to explain the relationship between SBP and AD. There are 55 million people affected by dementia worldwide . AlzheimAlzheimer's disease is a neurological disorder of unknown cause, resulting in the death of brain cells . AD is tSome of the first symptoms that occur with AD (neuropsychiatric) are a direct cause of early institutionalization . In AD, The most important non-modifiable risk factor for developing AD is age. Many cardiovascular risk factors increase with age, such as high blood pressure (BP), which, in turn, could affect the mechanisms that lead to impairment in the brain .According to Ballard et al. , the devFindings also established that the association between AD and hypertension was determined by age of onset (early-onset AD ≤ 65 years and late-onset AD ≥ 65 years). In fact, AD has been classified as presenile or early onset (≤ 65 years) and as senile or late onset (≥65 years) that tend to be sporadic and slow moving . HoweverOther studies have studied the relationship between hypertension and gender. Gillis and Sullivan  concludeRelated to regions due to the high incidence of hypertension in developed countries, studies are aimed at prevention strategies , 34. In The literature refers to various degrees of hypertension. This study was based on the cutoff points established by the International Society of Hypertension (ISH) . On the Furthermore, longitudinal , 40 and Based on the results and evidence of other articles and meta-analyses, we aimed to perform a meta-meta-analysis of longitudinal and cross-sectional studies to test the association between BP (high SBP and high DBP) and the risk of AD. We also aimed to pool findings separately from cross-sectional and longitudinal studies and assess the effect of BP on the risk of subsequent diagnosis of AD.The search was restricted to meta-analyses assessing high SBP and DBP and AD. We applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . The litThe procedures applied to carry out this meta-meta-analysis were as follows: (1) search and selection of meta-analyses assessing high SBP and DBP and AD and (2) selection of primary studies contained in the meta-analyses and the deletion of duplicates.Meta-analyses and primary studies that met each of the following criteria were selected: (1) meta-analysis and primary studies that measured the relationship between hypertension (high SBP and DBP) and the risk of AD; (2) meta-analysis and primary studies reported data that allowed the estimation of a pooled effect size; (3) meta-analysis and primary studies that diagnosed AD through clinical examination, using defined diagnostic criteria, DSMV  and NINCk = 1), the authors were contacted to request additional data to be subsequently added to the meta-analysis. Then, duplicate reports were excluded to pool the primary studies. After all meta-analyses and primary studies were selected, a third researcher independently extracted the highlighted data (S.U.). Information on all data collected from the primary studies included in the meta-analysis is presented in the To avoid bias in eligible studies, all abstracts were independently reviewed by two investigators (O.S. and A.P.). After excluding all irrelevant abstracts, the remaining articles were analyzed, and data precision was examined in detail. In meta-analysis where relevant data were lacking  tool , which hInitially, we reported the associations between hypertension and AD for each primary study included in the previous meta-analysis see .Q statistic  ] of AD for both SBP and DBP for each primary study. Second, we identified separate effect sizes for SBP and DBP measurements and their relationships with the risk of AD. Third, study outcomes were grouped according to the definition of BP (SBP or DBP) and the measurement of hypertension established by the ISH: (1) SBP: elevated (130–139 mmHg), grade 1 (140–159 mmHg), and grade 2 (160–179 mmHg), and (2) DBP: elevated (85–89 mmHg), grade 1 (90–99 mmHg), and grade 2 (100–109 mmHg) , 37. Hettatistic . The I2 ogeneity . StatistNJ, USA) . Additiok or number of studies, (b) effect size, (c) 95% confidence interval (95%CI) of the effect, and (d) p (two-tailed significance)  k oficance) . We usedk effect size = 29 vs. cross-sectional k effect size = 46) and the measures of SBP (>140 mmHg k effect size = 52 and >160 mmHg k effect size = 8) and DBP (>85 mmHg k effect size = 2 and >90 mmHg k effect size = 9). Finally, we also considered whether age at exposure assessment (early age of onset ≤ 65 k effect size = 39 vs. late age of onset or ≥65 k effect size = 36) could account for heterogeneity in associations. When possible, we used separate summary measures for early- and late-life measures of BP. Otherwise, BP in early life or late life was defined according to the mean of age. Moreover, we also analyzed the sex  in the different BP measurements. In the same line, we also analyzed the continent where the sample was recruited  in the different BP measurements.Additionally, moderating variables were selected based on substantive considerations and the availability of data across studies included in the meta-analysis. We anticipated interstudy heterogeneity as there was some variation between studies according to the study design  k = 100, in which no information was provided on the relationship between BP and AD.A total of 214 studies were identified from major databases: 61 in ISI Web of Science, 55 in Scopus, 17 in PubMed, 79 in Elsevier Science Direct, and 2 in Google Scholar. In total, 189 articles were excluded from this review for various reasons: (a) k = 14 studies were duplicated data; (b) k = 2 were systematic reviews about other issues; (c) k = 2 aimed to study the effect of antihypertensives on AD; and (d) k = 2 aimed to study genetic factors   factors .t = 1.65, df = 73, indicating no publication bias.k = 52 primary studies. Also, 60 effect sizes provided information about high SBP and risk of AD (80%); k = 11 about high DBP (14.7%); and k = 4 about the combined effect (5.3%)  .p = 0.001, and heterogeneity was high . These findings suggest that heterogeneity of effect may be present in some analyses.For the pooling LnRR analysis, we analyzed primary studies. The total effect size was LnRR = 0.07, Se = 0.02 , Z = 3.27, k = 11 effect sizes; N = 7,666; n = 1,520 participants with AD and high SBP; nHC = 6,146 HC participants), Xu et al. , Meng et al. , and Wang et al.  compared HC and AD subjects with high SBP. Only two of them   see . The hetk = 1 effect size; N = 378; n = 78 with AD and high DBP; n = 300 HC participants), Xu et al. , and Wang et al. . None of the three meta-analyses show significant associations between high DBP and AD.Three meta-analyses showed the relationship between DBP and AD: Lennon et al.   did not find an association between high DBP and the risk of AD   see . The hetk = 4 effect sizes; N = 7,494; n = 211 with AD and high SBP/DBP; n = 7,283 HC participants) found a non-significant association between high SBP and high DBP and AD   see . The hetResults of the subgroup analysis on the primary outcomes are presented in p ≤ 0.50). These results indicate that the risk of AD in participants with hypertension did not change significantly according to sex, age, and study design groups. However, it can be observed that there are significant relationships between different categories of the variables such as sex, age, study design, and AD (Z: p ≤ 0.50). Findings revealed a significant relationship only between being women and a greater risk of AD (p = 0.008). Age was also associated with increased risk of AD in early (p = 0.008) and late (p = 0.047) age of onset, and this association was also significant in cross-sectional (p = 0.021) and longitudinal (p = 0.013) studies. Regions moderated the association between BP and AD. The risk of AD was greater in studies that used samples from Asia and North America than those performed in Europe.The results of pooling studies that reported RRs for a total score of BP showed that sex, age, and design did not moderate the relationship between hypertension and AD risk (Qb: Results did not find significant differences in the risk of AD according to the measures of SBP (>140 and >160 mmHg) and DBP (>85 and >90 mmHg). Similarly, sex, age, design, and region did not moderate the relationship between SBP and DBP and the risk of AD, except sex in the case of DBP. Results found that women showed a stronger risk of developing AD than men. It is also observed that only in longitudinal studies and Asia regions, significant associations were found between SBP and AD.According to measures of SBP (>140 and >160 mmHg), results indicated that SBP had no significant differences in effect sizes on the risk of AD at different sexes, ages, and designs. However, for SBP > 140 mmHg, there was evidence of heterogeneity between regions in RRs of AD. Asian countries showed stronger effect sizes between SBP and risk of AD than European and North American countries. Also, results found that elevated SBP (>160 mmHg) was significantly associated with AD risk in the young elderly (≤ 65), longitudinal studies, and in Europa and Asia.For DBP (>85 and >90 mmHg), there was evidence of heterogeneity between the sexes. Women with elevated DBP (>90 mmHg) showed a greater risk of AD than men. Furthermore, there were no significant differences in AD risk according to age, design, and region.Finally, age and region did not moderate the relationship between the combined effects of BP and the risk of AD.This study analyzes the association between high BP and the risk of AD. This is the first study to evaluate this relationship by identifying previous meta-analyses and analyzing primary studies worldwide. The present study summarized the information on meta-analyses of hypertension (DBP and SBP) and AD and expanded the findings from individual studies. In this study, 52 primary studies and 75 effect sizes were extracted. Furthermore, we included some moderator variables between high DBP and high SBP and AD, such as sex, age, study design, regions, and measures of SBP and DBP.RR = 1.08, 95%CI: 1.032, 1.13, Z = 3.273, p = 0.001). It indicates that the risk of AD increases by 8% for patients with SBP.Overall, results suggest that hypertension is associated with an increased risk of AD . These results indicate that participants with high SBP increase the rate risk of AD by 9% and support findings of previous studies, suggesting that there were consistent demonstrations of a relationship between SBP and the risk of developing AD. In this vein, research demonstrated that high SBP could increase the risk of AD since it could cause neurobiological alterations (deposits of beta-amyloid protein), which lead to lesions in the brain, such as cerebral atrophy, senile plaques, and neurofibrillary tangles, which could be explanatory factors of the development of AD   , 51, 54.nalyses) –110. Fornalyses)  or type nalyses) , 109, coRelated to the combined BP hypertension, only a meta-analysis  with fouRR = 0.99, 95%CI: 0.887, 1.125, Z = −0.109, p = 0.913) and women  (rate risk of AD increases by 85%) in the relationship of high DBP and AD, but not between SBP and AD. Specifically, the data suggest that women with high DBP (>90 mmHg) had an increased risk of AD compared with men , which increase the rate risk of AD by 86%. These results have been shown in previous studies that worked with different samples (women and men), where AD was also associated with high DBP mainly in women  and DBP (>85 and >90 mmHg). Total scores reveal significant differences between men , with the rate risk of AD increases by 10% and 7%. However, the age of onset (early onset ≤ 65 years and late onset ≥65 years) does not moderate the relationship between high SBP/DBP and AD, showing similar effect sizes for both categories. Related to the measure of BP, this study found that elevated SBP > 160 mmHg was associated with the risk of AD in the young elderly (≤ 65 years), but not in those ≥65 years of age. In this vein, several studies have found that hypertension has different impacts on cognitive function at different ages  compared with European  and North America . Therefore, the rate risk of AD in Asia increases by 34%. These results are related to the findings of some studies. During the past four decades, the highest BP measurements worldwide have shifted from high-income countries to low-income countries, such as South Asia and Africa  and Asia  is significant. However, North America  did not find a significant relationship. Despite these results, the strength of the association between SBP (>160 mmHg) and AD risk is similar in the three regions.The only variable that moderates the relationship between BP and AD is the region. We observe a higher risk of AD in Asia with SBP >140 mmHg , so the rate risk of AD increases by 23%, while high DBP (>85 and >90 mmHg) is not related to increased AD risk. In this vein, previous work found differences according to the type of design that may result in part from the use of different definitions of hypertension and non-uniform measures of high or low BP. In this study, we use standardized criteria to define BP (SBP > 140/160 mmHg and DBP > 85/90 mmHg) and AD  which could explain that there are no differences according to the study design. After controlling for this confounding factor, the effect size of longitudinal studies is higher in all the BP and SBP measures, although the differences do not reach significance. Longitudinal studies provide an opportunity to assess the temporal relationship between BP and AD and the length of follow-up remains relevant since hypertension could render individuals more vulnerable to comorbid conditions, such as cerebrovascular disease, that confer greater risk for AD during long periods of follow-up.Finally, results do not find differences in the effect size of the association between high SBP and DBP and the risk of AD according to the type of design . Our results found an association between BP and the risk of AD in both types of studies. However, findings confirm that the relationship between higher SBP and AD is only significant in longitudinal studies and with SBP > 160 mmHg . Likewise, not all the cutoff points established by ISH could be analyzed since the stages of SBP ≥ 130–139 and DBP ≥ 100 could not be defined due to the lack of primary studies. Other confounders may also influence the study's findings. For example, results were not adjusted for other risk variables including cardiovascular disease, stroke, alcohol consumption, smoking, kidney disease, and many others. Also, two studies did not report the mean age of the sample, and they were not included in the moderator analysis. Moreover, the relationship between hypertension and AD could not be thought of as binary but rather as a dynamic one, changing with life stage and disease state. Hence, a single measurement of BP may not accurately reflect the participant's average BP measurements. Additionally, data on the age at the onset of hypertension and years of living with the condition may be important in clarifying temporal relationships between hypertension and AD. Also, we did not examine the potentially modifying impact of antihypertensive therapy on the relationship between hypertension and AD. In addition, another limitation is the absence of studies from South America and Australia. Finally, we did not include educational level as a moderator variable since the external validity of some of the results has been questioned. The primary studies contained in this meta-analysis used very different forms of measurement. For instance, some studies analyzed education using individual  , 88 or cSeveral strengths of our review of a meta-analysis should be emphasized. First, most prior studies were drawn from general community samples or non-AD-specific studies , whereas the current study relied on AD. Second, we add to the current literature by analyzing 52 primary studies extracted from the previous meta-analysis increasing the statistical power of our results. Third, we analyzed the impact of different moderators  to explore the influence of other research parameters in the relationship between high SBP and DBP and AD. Finally, we want to focus on effect sizes since the statistical significance should never be interpreted as evidence that an effect had clinical importance. It is important to note that the effect sizes were “relatively small” and the variation is great within the same meta-analysis. Therefore, the clinical significance and practical importance of these results should be considered in relation to the patient's status, goals, and clinician experience.As a practical implication, this study suggests that high SBP could be a risk factor for AD. There is limited evidence that single cardiovascular risk factors affect AD risk, but the strength of the association is influenced greatly by changing the parameters of the risk factors and in particular by identifying interactions between the factors. Future research should confirm this and determine whether stabilizing BP might be a target to slow or decline the development of AD.This study analyzes the association between SBP/DBP/combined BP and the risk of developing AD. A total of five meta-analyses and 52 primary studies were analyzed in this review of meta-analysis. Our study found that SBP is associated with an increased risk of AD by 11%, although no association was found for DBP. Measures of SBP >140, SBP >160, DBP >85, and DBP >90 do not moderate the relationship between SBP and DBP and AD. Moderator analysis  shows a significant association between high DBP (>90) and AD in women. The age of onset (early-onset AD ≤ 65 years and late-onset AD or senile AD ≥65 years) did not moderate the relationship between SBP and DBP and AD. Finally, regarding the type of study, there were no differences in the association between BP and AD between longitudinal and cross-sectional studies. However, Asian countries showed stronger effect sizes between SBP > 140 and risk of AD than European and North American countries. Future work should use other uncontrolled factors  to explain the relationship between high BP and AD.The original contributions presented in the study are included in the article/OS-V and AP-M conceived and designed the analysis, collected the data, contributed data or analysis tools, performed analysis, and wrote the paper. JP-B wrote the paper. SU-L contributed data or analysis tools, performed analysis, and wrote the paper. All authors take full responsibility for the data, the analyses and interpretation, and the conduct of the research, full access to all of the data and the right to publish any and all data. All authors contributed to the article and approved the submitted version.


Biochemical and morphological evaluation confirmed that most of the water resources reported a high number of coliforms and Gram-negative microorganisms due to sewage-water infiltration. These microorganisms in the water are responsible for the liver infection that ultimately causes jaundice. For safe and potable water, infiltration of municipal wastewater must be prevented at any cost. Scientific disposal of wastewater and purification of uncooked water have to be conducted earlier than consumption or use for different domestic functions, to avoid water crises and fetal ailment outbreaks in the near future.The felicitous tourist destination “Hills Queen” and the capital city of Himachal Pradesh, an enticing state in the Himalayan region, are met with water crisis every year and jaundice outbreaks occasionally. In 2016, there was a severe jaundice outbreak in Shimla city. In a contemporaneous investigation, we attempted to trace out the possible reason for these crises in Shimla. Samples were collected month wise from different water-supply sources and their physicochemical and microbial loads were analyzed. The microbiological examination found a totally excessive microbial load (1.064 × 10 Water is the primary component of every living organism, with fluids derived from numerous sources on Earth. It is necessary for all known forms of life on Earth and covers 71% of the planet’s surface ,3. IndiaE. coli and other coliforms) [According to one of WHO’s reports, by 2030, water shortage in some developing countries may surpass 50%, resulting in 80% of water-borne or water-linked human diseases owing to biological pollution of drinking water [liforms) ,10. Manyliforms) .Enterobacter, Klebsiella, Citrobacter, E.coli, etc. [Authorities halted the supply of drinking water from polluted sources (the city’s primary water sources), exacerbating Shimla’s water crisis. The epidemic was caused by a rise in fecal coliform concentrations in drinking water. Aside from jaundice, other disorders, such as ear infections, dysentery, typhoid fever, viral and bacterial gastroenteritis, and so on, are also associated with the presence of fecal coliforms such as li, etc. . Regular2 [Shimla, a picturesque hill station and popular tourist destination in the Himalayas  faced wa2 ,14. ShimWater samples were collected as per WHO guidelines from different water-supply sources every month of one year in sterile bottles and brought to laboratory for further processing. Various physio-chemical parameters such as temperature, pH, TDS, salt concentration, color and conductivity were recorded. −6-fold dilution of samples. Further, 100 µL of each dilution was spread on different basic as well as selective media  plates and incubated at 37 °C for 24 h [The microbial load was analyzed by standard plate-count technique using a serial dilution agar-plate method up to 10Selected isolates were examined for various morphological as well as biochemical features such as colony morphology, Gram’s staining, methyl red, oxidase test, catalase test, glucose, lactose, maltose, sorbitol fermentation test, Vogues–Proskaure test, hydrolysis of casein, etc., following the standard protocols.Standard protocols were used for analysis of dissolved, biological and chemical oxygen demands ,15.Samples were chronologically collected from source, i.e., raw water, to finale filtration tanks and finally to distribution points, as shown in The physical and chemical parameters of water were analyzed at the time of sampling and data generated are shown in E. coli and Klebsiella sp. were most-commonly present lactose-fermenting Enterobacter, while Pseudomonas sp. and Proteus sp. were non-lactose fermenting isolates commonly present in all samples . BOD value of public-tap water was in range from 0.2 to 1.0 mg/L. BOD were calculated on the basis of the difference between the DO value of the water sample on first ady and the DO value after a specific time interval (5 days).Chemical oxygen demand (COD) is an indicative measure of the amount of oxygen that can be consumed by chemical reactions in the solution under test. It is commonly expressed in mass of oxygen consumed over volume of solution, which in SI units is milligrams per liter (mg/L). Maximum COD was observed with the raw water of Churat Nallah (0.384 ± 0.005 mg/L). Kadam and Agrawal  also anaE. coli, Pseudomonas sp. Klebsiella sp. and Proteus sp. etc. and resulted in higher microbial growth, which supports our findings that a microbiological load higher than that of the permissible range of water potability standards might be a possible reason for jaundice outbreak in Shimla. Further, shortage in the rainfall intensified the issue and increases the concentration of microbes in the water sources, resulting in water shortage and crisis in the hill region. The observed TDS in the present study was varied from 75 to 225 ppm. According to the WHO, the TDS standard for drinking water is <1000 ppm. The collective amount of all dissolved cation and anions in the water is known as TDS and it is mainly associated with conductivity [Different water samples were collected month-wise from different sites of the main water-supply sources of Shimla and almost all physiochemical parameters were found to be suitable for potable water according to WHO standards, except microbial load. Kistemann et al.  also anauctivity . The meauctivity . Conductuctivity . The lowE. coli and Pseudomonas sp. were prominently observed in all the samples throughout the year. Both of these bacteria are opportunistic pathogens for humans. E. coli is an indicator organism of water pollution. Water was highly contaminated with Klebsiella sp. in the months of June, July, August and September. Onyango et al. [E. coli and other coliforms in drinking water during their study. Presence of E. coli or fecal contaminants in water is the main cause for the outbreak of jaundice [BOD and COD of water samples were also analyzed using standard protocol and were found to be higher than the permissible limit. o et al.  also repjaundice ,31. Accojaundice , the DO jaundice , the jauAll the water distribution channels in Shimla were badly contaminated with various opportunistic pathogens, as revealed through our investigation. Fortunately, much less contamination appeared in the distribution line after treatment, but microbial load was still beyond the permitted limit. Results of this research could help the MC/IPH officials to take remediate measures in good time. Authorities should also look for alternative water sources to prevent any water crisis in the future that may also arise due to a shortage of rainfall in the catchment areas. The efforts will also help to establish a cleaning schedule for the MC water-supply sources and create proper wastewater treatment facilities for the villages/towns situated nearby the catchment areas, to prevent the infiltration of domestic and industrial sewage, which will help to provide safe drinking water to the consumers in MC Shimla. Moreover, based upon our findings, the MC/IPH department may install a heavy-duty UV system to control the heavy microbial load. Using these recommended corrective measures, such future disasters could be avoided, and the public of such areas will have potable drinking water free from all types of contaminants and opportunistic pathogens.


Few studies have focused on the incidence and correlation of social frailty (SF) with adverse health events in Southwest China. This study aims to explore the predictive value of SF for adverse health events.A 6-year prospective cohort study was employed, a total of 460 community-dwelling older adults aged 65 years and above were analyzed to provide a baseline in 2014. Participants completed two longitudinal follow-ups at 3  and 6  years later. A modified social frailty screening index was used in this study, and adverse health events such as physical frailty (PF) deterioration, disability, hospitalization, falls, and mortality were evaluated.P = 0.047) and having family members die in the past year  were risk factors of SF, whereas having a mate  and having family members to help with care  were protective factors of SF. The cross-sectional study demonstrated that SF was only significantly associated with disability  at wave 1. Baseline SF significantly explained the incidence of mortality at the 3-year  and 6-year follow-ups .Among these participants in 2014, the median age was 71 years, 41.1% were male, and 71.1% were married or cohabiting, up to 112 (24.3%) of them were classified as SF. It was observed that aging  is urgently needed for the purposes of early prevention and multidimensional intervention in adverse health events, including disability and mortality. Among the worldwide aged population, frailty is an important health issue and is characterized by decreased physiological reserve and function across multiple physiologic systems , 2. It iAs for the screening tools, seven-item SF index was first constructed by Teo et al.  based onChina has the largest older population in the world . China iAll data were obtained from “the Survey on the Disease, Psychology and Social Support of the older Community-dwelling Population in Dujiangyan,” a prospective cohort study for older individuals aged 65 years and older in China supported by Johnson & Johnson global novel project (2013), which has been described in detail in our previous study . The excTaking the practicable and available into consideration, a modified social frailty index   or ADL  item(s).via self-reported hospitalizations or reviewing computerized HIS records from 2014 to 2020.Hospitalization was assessed Falls were defined as any sudden drop from one surface to a lower surface. We assessed falls by asking the participants: “Did you fall in the previous year?” (response categories “yes” and “no”).Mortality data were collected by local government records or family members' self-reports.A personal information questionnaire was used to collect the participants' characteristics. The sociodemographic covariates of participants included age, gender, marital status (with or without life partner), education level , self-rated sleep quality, self-reported memory status , Residency Period , family member has died in 1 year. Social characteristics were assessed through the following dimensions: medical service support , expenditure (in debt), social engagement (whether having family members to help with care), and emotional support (willingness to make friends and with a confidant in one's life). Geriatric syndrome  and physical profile .U, or chi-square tests according to the type of variables. Multivariate logistic regression using forward stepwise regression (P < 0.10 for variable inclusion criteria) were conducted with the aim of examining the association of SF with adverse health events in cross-sectional and predictive value of SF on adverse events in longitudinal scenarios.The Statistical Package for Social Science (SPSS) for Windows version 21.0  was used to calculate descriptive statistics and to obtain the frequency and percentage distributions. The characteristics of participants' at baseline were compared by using Mann–Whitney n = 2), refused to revisit (n = 15), changed the contact information (n = 8), and other , 28.9% (123/426 wave 2), and 60.4% (217/359 wave 3). During the two waves of follow-up, we observed a significant increase in SF deterioration [from 72 (15.7%) to 154 (42.9%)], and only 23 (6.4%) participants had improved in wave 3. A high prevalence of SF was observed among participants who were older, without a mate, had lower levels of education, with family members died in the last year, had family members to take care, who lacked social activity, who lacked contact with neighbors, had financial difficulties, had a disability or cognitive impairment. There were no significant difference between the two groups in terms of who had the worse sleep patterns, physical frailty, number of falls, hospitalizations within the past year and other geriatric syndromes , 2.P = 0.047) and having family members die in the past year , whereas, having a mate  and having family members to help with care  were protective factors of SF.Multivariate logistic regression analysis was used to determine the possible associated factors for SF (wave 1) in The prevalence of adverse health events from wave 1 to wave 3  was descP = 0.001) and age . Poor sleep quality , residency period  and medical insurance  were related to hospitalization. Male participants  and those with poor sleep quality  at baseline had an increased risk of falling. However, baseline PF was not significantly associated with an increased risk of disability, hospitalizations or fall incidents.P = 0.000), whereas SF did not have a significant effect on disability, hospitalizations, falls or PF deterioration. At the third wave of follow-up, the multivariate logistic regression analysis indicated that baseline SF significantly increased the risk of 6-year mortality . However, baseline SF was significantly associated with a decreased risk of hospitalization . No significant correlations with disability, falls or PF deterioration were found  showed that SF significantly predicted the incidence of mortality  and having a family member who died within 1 year  were negative factors of SF, while having a mate  and having family members to help with care  were protective factors for SF in the Chinese culture. In the clinical setting, understanding who is more likely to deteriorate and who may remain stable, or even revert back to the better state, will allow clinicians to focus on those at the highest risk for early interventions  and wave 3 , and medium-term mortality was higher than long-term mortality. Ma et al.  revealed that SF was significantly associated with mortality during wave 2  during the 6-year follow-up. It is speculated that the baseline SF individuals were prone to having lower incomes and did not have equal hospitalizations; therefore, SF individuals in Southwest China predicted a decreased risk of hospitalization longitudinally.Third, some studies found that social factors could be associated with an increased incidence of hospitalizations. Social factors of self-neglect have been linked to poor social support, reduced nutritional intake and physical function , resultiImpaired falls in the older are a major source of injury resulting in disability . AlthougIn addition to SF, the current study also found that those resident <3 years and without a confidant also had an increased risk of developing adverse health events, such as falls and mortality. In the future, these factors should be taken into account as supplementary components of SF screening tools. This modified tool may better detect adverse health events, but it may need further validation.This study also has some limitations. First, the instrument used to evaluate SF was self-reported, so it may be subject to potential recall bias despite all the questionnaires were conducted face-to-face one by one at all waves, and all investigators participated in the study were trained by standard protocol, so that the subjects had no understanding error. Second, due to the vary widely across regions and smaller geographic and cultural units, perhaps we miss an opportunity to take full advantage of this framing to educate the world outside China about those changes. Finally, considering these limitations, further studies will be needed to explore a consecutive comprehensive health management of SF for the purposes of early prevention and multidimensional intervention in adverse health outcomes.This study reported the incidence of SF and its associated factors and highlights the predictive values of SF on adverse health events longitudinally. First, the incidence of SF was higher and its transitions was the majority of participants remained SF status stable or deteriorated at the end of 6 years in community-dwelling older adults in Southwest China. Second, this study found that avoiding living alone (having a partner) and increasing social engagement (having family members to help with care) can contribute to SF. Finally, older adults with SF had a significantly increased incidence of mortality at the longitudinal follow-up. Consecutive comprehensive health management of SF  is urgently needed for the purposes of early prevention and multidimensional intervention in adverse health events. The present study provided new, additional evidence for assessing SF in Chinese community-dwelling older people aiming to prevent or delay adverse events, including disability, hospitalization, and mortality.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Review Committee of Sichuan University. The patients/participants provided their written informed consent to participate in this study.Q-qS wrote the manuscript and participated in all aspects of this research. KT, H-yT, Y-yL, HZ, and XX assisted with study design, data analysis, and interpretation. HQ, MZ, Y-yC, and S-sN helped in collecting data. SW reviewed the final article. All authors: revision of manuscript for important intellectual content and approval of final draft.


Subgingival plaque samples from healthy and periodontitis subjects were used as inocula to grow normobiotic and dysbiotic microbiomes in MBEC assay plates. Saliva supplemented with 1%, 2%, 3.5%, or 5% (v/v) heat-inactivated human serum was used as a growth medium under shaking or non-shaking conditions. The microbiomes were harvested at 4, 7, 10 or 13 days of growth  and analyzed by 16S rRNA gene sequencing. Biomass significantly increased as a function of serum concentration and incubation period. Independent of growth conditions, the health- and periodontitis-derived microbiomes clustered separately with their respective inocula. Species richness/diversity slightly increased with time but was adversely affected by higher serum concentrations especially in the periodontitis-derived microbiomes. Microbial dysbiosis increased with time and serum concentration. Porphyromonas and Alloprevotella were substantially enriched in higher serum concentrations at the expense of Streptococcus, Fusobacterium and Prevotella. An increase in Porphyromonas, Bacteroides and Mogibacterium accompanied by a decrease in Prevotella, Catonella, and Gemella were the most prominent changes over time. Shaking had only minor effects. Overall, the health-derived microbiomes grown for 4 days in 1% serum, and periodontitis-derived microbiomes grown for 7 days in 3.5%–5% serum were the most similar to the respective inocula. In conclusion, normobiotic and dysbiostic subgingival microbiomes can be grown reproducibly in saliva supplemented with serum, but time and serum concentration need to be adjusted differently for the health and periodontitis-derived microbiomes to maximize similarity to in vivo inocula. The optimized model could be used to identify drivers of dysbiosis, and to evaluate interventions such as microbiome modulators.Modeling subgingival microbiome in health and disease is key to identifying the drivers of dysbiosis and to studying microbiome modulation. Here, we optimize growth conditions of our previously described  Treponema spp., Fretibacterium spp., Prophyromonas gingivalis, Tannerella forsythia, and Desulfobulbus spp. at the expense of facultative Gram-positive species belonging to the genera Actinomyces and Streptococcus , generally existing in a harmonious and mutually beneficial relationship with the host. However, this mutualistic relationship can breakdown due to changes in the balance of the microbiome and/or to the integrity of the host defenses (dysbiosis), and this increases the risk of disease . The widtococcus .in vitro microbiome models are important research tools in this respect. Various attempts have been made to model oral microbial communities including continuous flow models, static models or more recent sophisticated models that are based on microfluidics or impedance-based technologies  and from five periodontally healthy subjects . The samples were collected using paper points and placed in 1 ml of reduced transport fluid (RTF) as previously described . The twoHeat inactivated human serum  was added to Sterile pooled human saliva (SPHS) prepared as described above at final concentrations of 1%, 2%, 3.5%, and 5% (v/v) to obtain a total of four different growth media.in vitro microbiomes.Health- and periodontitis-derived microbiomes were grown on hydroxyapatite-coated pegs of MBEC plates  as described before . BrieflyPegs with the grown microbiomes were each snapped off from the lid, placed in 1.5 ml tubes containing 180 μl lysozyme solution  and incubated for 30 min at 37°C. DNA was extracted from the lysate using Purelink Genomic DNA mini Kit  according to the manufacturer’s instructions. DNA was quantified using Qubit 2.0 Fluorimeter and stored at −80°C until subjected to further analysis. Biomass was measured in terms of DNA yield (ng/microbiome).in vitro microbiomes to the respective inocula in terms of species richness, alpha and beta diversity and SMDI values.Degenerate primers 27FYM  and 519RA total of 26,208,640 paired-end reads were obtained , of which 95.24% reads merged successfully. Around 17%  of the sequences passed our stringent quality filtration, resulting in a final sequencing depth of 4,681 to 20,450 reads/sample. Raw sequences were submitted to Sequence Read Archive (SRA) under project no. PRJNA881921.in vitro-grown microbiomes, the comparable profiles were 58–103 species, 20–33 genera, 4–7 phyla in the health-derived microbiomes, and 75–135 species, 32–52 genera and 6–8 phyla in the periodontitis-derived microbiomes. The relative abundances and detection frequencies of identified phyla, genera and species in each of the samples are listed in in vitro microbiomes as a function of serum concentration, incubation period and shaking are presented in A total of 119 and 137 species belonging to 39 and 40 genera and 8 phyla were detected in the two health inocula, respectively; in the two periodontitis inocula, 178 and 172 species, 55 and 65 genera, and 9 phyla were identified, respectively. In the in vitro microbiomes. The same phyla were also the most abundant in periodontitis but in the order of Bacteroidetes, Firmicutes and Fusobacterium by abundance. However, in both health and periodontitis, these three phyla were over-represented in the in vitro microbiomes at the expense of the Saccharibacteria, Proteobacteria, and Actinobacteria , and in the periodontitis-derived-microbiomes after growth in 1% serum for 13 days (Median SMDI of 1.33 in the microbiomes compared to 1.38 in the periodontitis inoculum); those grown in 3.5%–5% for 7 days or 2% for 10 days came next (SMDI ~1.25). Beta diversity analysis for health and periodontitis separately resulted in two main clusters by biological replicate along PC1 and sub-clusters by growth time along PC2  cutoff of 0.1 when applicable. Biofilm biomass significantly increased with time and with increasing serum concentrations for both the health- and periodontitis-derived microbiomes . Speciesin vitro , being clong PC2 ; analysiPorphyromonas and Alloprevotella as a function of serum concentration at the expense of Streptococcus, Fusobacterium and Prevotella, and an increase in Porphyromonas, Bacteriodes, and Mogibacterium accompanied by a decrease in Prevotella, Catonella, and Gemella as a function of time. The relative abundances of phyla and genera that significantly changed as a function of time and serum concentration are shown in Treponema and Pyramidobacter at the expense of Gemella and Granulicatella   . During acterium . Along tngivalis . In our ngivalis , it was in vitro microbiomes were quantified in far greater detail and at a finer resolution than our previous study. The major findings of the study are as follows. First, the study demonstrates the reliability of the model to reproducibly generate normobiotic and dysbiotic subgingival microbiomes in vitro. Second, the health-derived and periodontitis-derived microbiomes have different requirements for optimizing their community structure. Overall, and taking into consideration species richness, alpha and beta diversity and SMDI values, the health-derived microbiomes grown for 4 days at 1% serum were closest to the health inoculum, while for periodontitis, the microbiomes grown for 7 days at 35–5% serum, or for 10 days at 1%–2% serum, were comparable and the most similar to the respective inoculum. The third important finding is that serum and time independently and differently contributed to dysbiosis. For example, while P. gingivalis increased as a function of both factors, Treponema, Fretibacterium, and Pyramidobacter increased primarily as a function of time, while Tannerella and Selenomonas increased with serum concentration. There were taxa that changed in opposite directions. For examples, Veillonella increased with serum concentration but decreased with time.Consequently, in this study we used lower concentrations of serum in saliva, and also varied the length of incubation and evaluated the impact of shaking during biofilm development. Composition of the in vitro microbiomes. While there was an overlap in SMDI values between health-derived microbiome grown at 3.5%–5% serum for 13 days and periodontitis-derived microbiomes grown at 1%–2% for 4 days, it is unlikely that the former would fully assimilate into periodontitis-associated microbiomes if grown for longer periods or higher serum concentrations since some key periodontal pathogens were missing, e.g., P. gingivalis.It is important to note that the increase in SMDI was relative within each microbiome type, i.e., the microbiomes still separated by type regardless of time and serum concentration . In othein vitro microbiomes are consistent with those reported for in vivo biofilms. For instance, during the early stages of oral biofilm development, Firmicutes including Streptococcus and Veillonella are primary colonizers  model  model , but thein vivo biofilms. The study also shows that time and serum are independent drivers of dysbiosis. This model is an easy and effective system to study subgingival biofilm colonization in disease and health, and to evaluate interventions to prevent or reverse dysbiosis.In conclusion, this study demonstrates that saliva supplemented with heat-inactivated serum can be used to reliably and reproducibly grow normobiotic and dysbiotic subgingival microbiomes from clinical samples. However, serum and incubation periods need to be adjusted differently for the health- and periodontitis-derived microbiomes to maximize their similarity to The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: NCBI—PRJNA881921.The studies involving human participants were reviewed and approved by Temple University’s Institutional Review Board under protocol no. 25586. The patients/participants provided their written informed consent to participate in this study.DB contributed to design, the data acquisition, analysis, and interpretation and drafted the manuscript. TC contributed to the data analysis and critically revised the manuscript. JA and SC contributed to the data acquisition and critically revised the manuscript. TD, DD, and PM contributed to the design and data interpretation and critically revised the manuscript. NA conceived the study, contributed to the design, data analysis, and interpretation, and critically revised the manuscript. All authors contributed to the article and approved the submitted version.This study was supported by the National Institute of Dental and Craniofacial Research (grant 1R03DE028379). Publication of this article was funded in part by the Temple University Libraries Open Access Publishing Fund and in part by Cary R. Klimen Oral Health Sciences Research Program Fund.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.https://www.frontiersin.org/articles/10.3389/fmicb.2022.1031029/full#supplementary-materialThe Supplementary material for this article can be found online at: Click here for additional data file.Click here for additional data file.Click here for additional data file.


Background and Objectives: This study aimed to examine the impact of postacute rehabilitation duration on the outcome of the functional recovery and patients’ quality of life after the stroke. Materials and Methods: One hundred patients  who experienced a stroke (50 with ischemic stroke (IS) and 50 with intracranial hemorrhage (ICH)) took part in the study. Patients (treated with postacute rehabilitation measures for six months) were examined after one, three, and six months of postacute rehabilitation. Functional independence was measured using the functional independence measure (FIM) test, while the EQ-5D-3L questionnaire was used to assess the quality of life. Results: Patients with ICH had a slightly lower FIM score  on admission compared to patients with IS , but, after six months of postacute rehabilitation, patients with ICH reached an approximate level of functional independence , as did patients with IS . The motor and cognitive FIM, as well as quality of life, was statistically significantly increased at all four measurement points (p < 0.001). Furthermore, there is a statistically significant connection between functional independence and quality of life at all tested times. Conclusion: Patients achieved the highest degree of functional independence after six months. Furthermore, our findings point out that inpatient rehabilitation as well as outpatient rehabilitation are effective in functionality and quality of life improvement after a stroke; thus, both should be emphasized and regularly implemented. Stroke is a clinically defined syndrome of acute, focal neurological deficit attributed to vascular injury of the central nervous system (CNS) . It can There are two main types of stroke: ischemic stroke (IS) and hemorrhagic stroke (ICH) . IS is tIn the systematic analysis of GBD 2016 Stroke Collaborators, it was stated that the global burden of stroke is likely to remain high despite the sharp decrease in age-standardized mortality rates from 1990–2016 and with more than 80 million stroke survivors in 2016 . More reThe disability rates in post-stroke patients vary across different studies. In the study of Lv et al.,  the threWell-organized rehabilitation, the process which enables individuals to regain physical, intellectual, psychological, sensory, and social functionality is key to acute, short-, and long-term recovery outcomes . In the More innovative treatments, particularly in stroke rehabilitation, are being considered. A randomized controlled trial of mobile game-based virtual reality program was shown to effectively promote the recovery of the upper extremities in patients with stroke . MoreoveThe stroke was shown to incur substantial economic loss to the country, and 34% of total healthcare expenditure worldwide is spent on stroke . In the According to the Serbia Health System Review, it was stated that the total expenditure on health for rehabilitation services in 2017 was 5.40% .Although previous findings indicate that rehabilitation has a positive effect on the outcome of functional recovery and quality of life, further studies are needed in order to evaluate the optimal type, as well as amount, of therapy needed in this group of patients ,23.This study aimed to examine the impact of postacute rehabilitation duration on the outcome of functional recovery and patients’ quality of life after the stroke.The research was conducted as a prospective study at the Special Hospital for Progressive Muscular and Neuromuscular Diseases in Novi Pazar after obtaining the consent of the Ethics Committee . Data were collected by monitoring and examining patients who experienced a stroke, based on a neurological examination, magnetic resonance imaging (MRI), or computed tomography (CT) findings. Patients were examined at admission, after one month, after three months, and after six months of secondary rehabilitation. There were two groups of subjects, one group consisting of patients with IS, and the other group consisting of patients with ICH. All patients had the nature and purpose of the study, as well as the possibility of asking questions regarding participation in the study and withdrawing at any time without any consequences, carefully explained to them. All patients gave written informed consent to participate in the research.A total of 100 patients participated in the study, of which 50 (50%) had IS and 50 (50%) had ICH. Further risk factors were evaluated: high blood pressure, high cholesterol, diabetes mellitus, alcohol, coffee, and cigarette (current and ex-smokers) consumption. Inclusion criteria were being over 18 years old, having first experienced IS or ICH no earlier than one month from the start of the treatment, the patient’s ability to participate in a postacute rehabilitation program, the patient’s ability to communicate, and giving written consent to participate in the research. Exclusion criteria were being below 18 years old, having experienced IS or ICH before, the patient’s inability to speak, the refusal to give written consent, patients with some other neurological diseases that affected functional ability before the occurrence of stroke, the presence of pain worsened by exercising, the appearance of complications that do not allow further rehabilitation, and the occurrence of a second stroke during the monitoring of the patient and patient’s death.The postacute rehabilitation treatment of study participants was conducted five days a week, and it included: motor learning with kinesitherapy, functional electrical stimulation (FES), and, where needed, static or dynamic orthoses, cognitive and speech rehabilitation, psychological and social integration, and patient and family education. It started after stabilization of the patients’ vital parameters and with the permission of a board-certified specialist in neurology, due to changes related to the CNS. Each patient was individually and multidisciplinarily assessed, and, based on that, an individual rehabilitation program was determined, which was adjusted daily to the patient’s condition. Patients were treated in the hospital for 3–4 weeks, and, after discharge from the hospital, they took a break of 3–4 weeks. After that, they were included in the outpatient program, which was in accordance with their needs, as individually and multidisciplinary assessed. Time intervals of 3–4 weeks alternated over 6 months, while the patients were monitored and examined in the meantime.The kinesitherapy program was adapted to each patient, according to their functional abilities and usually lasted between 30 and 40 min per day. Passive or actively assisted exercises were performed in patients whose muscle activity was insufficient to move independently —grade 3 and below), while active or resistance exercises were performed in patients with greater muscle strength (MMT—grade 4 and above). Analgesic medications were applied in the case of occasional pain in the treated segment in some patients. Aids such as walkers, crutches, or canes were used in patients with balance disorders. Practicing walking was performed in the loom in front of a mirror in patients with gait problems. Occupational therapy was carried out using various props and equipment, with the main goal being improving mobility and transfer skills, as well as training hand movements, so that patients could use their hands correctly when eating, dressing, and maintaining personal hygiene as much as possible. In order to properly position or perform movements, static or dynamic orthoses were used in patients with balance disorders and reduced strength. Of the electrotherapeutic procedures, galvanic current , interference current , and FES were applied to strengthen muscles. Psychologists encouraged patients to manage illness-related emotions and to be optimistic and motivated about the rehabilitation. Speech therapists were in charge of solving speech problems and developing speech skills. Patients and their family members were educated about the correct way of living, to prevent complications and comorbidities.The Functional Independence Measure test (FIM) was used to examine the functional ability of the patients. This test has two subscales: motor, which includes the domain of independent care, i.e., sphincter control, transfers, and movement, and cognitive, which involves communication and social cognition. Scores can be between 1 and 7, with the lowest indicating total assistance and the highest indicating complete independence. The total score of the FIM motor subscale can be between 13 and 91, while the score of the cognitive subscale can be between 5 and 35. The total score of the FIM scale can be between 18 and 126 .The European Quality of Life—EuroQol EQ-5D-3L questionnaire, a general standardized quality-of-life indicator, was used to assess the quality of life. In our study, we used the descriptive system of EQ-5D-3L that is composed of five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, at three severity levels  . A desigStatistical analyses were performed using IBM SPSS version 24.0 software . The normality of the obtained values distribution was tested by Kolmogorov’s test, where the values of statistical significance are at the level of 0.05 and 2-tailed. A comparison of certain categories of attributive features frequency was performed using the Chi-square test. To determine the differences in repeated measurements, we analyzed the difference of variance with the ANOVA test (non-parametric Friedman), and then we used the Wilcoxon test of equivalent pairs. The analysis of the association of variables was performed using correlation analysis (Pearson or Spearman correlation). The change of FIM and EQ-5D-3L values after one, three, and six months of postacute rehabilitation in relation to admission is showed as a delta value (Δ). The descriptive statistics are presented as mean ± standard deviation (SD) or number (N) and frequency (%).Patient’s sociodemographic and clinical characteristics are shown in p < 0.001), (one month (p < 0.012), three months (p = 0.034), and six months (p = 0.012)). For EQ-5D-3L, the values significantly differed at admission (p < 0.001), one month (p = 0.001), and six months (p = 0.007).Descriptive statistic data for the FIM scale and the EQ-5D-3L questionnaire are shown in p = 0.230), the use of cigarettes (p = 0.870), alcohol (p = 0.409), and coffee (p = 0.601) did not significantly differ between stroke types (IS vs. ICH).Applying the Chi-square test, it was examined whether there is a relationship between the type of stroke and certain sociodemographic variables, as shown in p < 0.001), one month (p < 0.001), three months (p = 0.001), and six months (p = 0.002)). In addition, the results show that there is a statistically significant correlation between the quality of life and the type of stroke at three measurements (at admission (p < 0.001), one month (p = 0.018), three months (p = 0.028), and six months (p = 0.049)).Results of the Spearman correlation analysis of stroke type and FIM, and stroke type and EQ-5D-3L are shown in p < 0.001). The same applies to those with ICH. The Bonferroni correction was used with a new statistical significance level of 0.025.For patients with IS, the Friedman test demonstrated a statistically significant difference between FIM values  at admission and FIM values  after one, three, and six months post admission, respectively, (p < 0.001), three (p < 0.001), and six (p < 0.001) months post admission of postacute rehabilitation, respectively, for both IS and ICH , three (p < 0.001), and six (p < 0.001) months post admission of postacute rehabilitation, respectively, for both IS and ICH , one months (p < 0.001), three months (p < 0.001), and six months (p < 0.001). The correlation is positive and strong, which means that greater functional independence leads to a better quality of life for patients.The results of the correlation analysis, presented in The results of our study demonstrate that there is a statistically significant correlation of functional independence in all four time points of assessment with regards to the stroke type. Furthermore, our findings point out the presence of a statistically significant increase for the motor FIM and for the cognitive FIM scores between admission and after one, three, and six months post admission of postacute rehabilitation, respectively, for both IS and ICH. Moreover, we have demonstrated a statistically significant increase for EQ-5D-3L questionnaire scores between admission and after one, three, and six months post admission of postacute rehabilitation, respectively, for both IS and ICH. Additionally, a statistically significant relationship between the values of the FIM test and the EQ-5D-3L questionnaire at admission, one, three, and six months, respectively, was noticed in tested stroke patients.From the 100 patients that were admitted to rehabilitation treatment, 53 (53%) of them completed the six-month postacute rehabilitation program and none of the studied participants had negative trends for FIM scores from admission up to 6 months of follow-up on all four testing time points. Unlike research dealing with similar topics, in our sample, there were slightly more women than men ,27. It iWith advancements in the knowledge, there is a better understanding of the mechanisms related to stroke-induced paralysis; thus, the ability to stimulate the neuroplasticity is improving . In the Regarding the impact of postacute rehabilitation on the outcome of functional recovery and quality of life, our findings pointed to the increase in total FIM scores on all tested occasions during postacute rehabilitation  when compared to the score at admission. Changes in the total FIM score at each measurement compared to the total FIM score at admission were statistically significant. In the study of Kamo et al., the authors evaluated the impact of the intensity of rehabilitation on the patients’ functionality level by determining the FIM score and proved that a longer rehabilitation program during the day is associated with higher values of the total FIM score . TherefoConsidering that the EQ-5D-3L questionnaire can be used as a reliable tool for quality-of-life measurement, particularly in stroke survivors , our resSome authors believe exercise is one of the most effective and feasible rehabilitation strategies that significantly improve motor and cognitive abilities after IS, thanks to brain neuroplasticity . In our It has been proven that, in addition to people who experience IS or ICH, family members and caregivers also suffer a certain level of burden, during which their quality of life decreases . That isThere are several limitations to this study. The first limitation is that the included patients were treated in only one rehabilitation center, so future research may include patients from more rehabilitation centers. An additional limitation refers to the number of participants, thus further studies on larger samples are needed. One more limitation of our study was not having data on the stroke localization, as well as using recanalization treatments or other drugs that can alter neuroplasticity or surgical procedures, particularly for ICH. So future research that will be dealing with a similar topic should collect that data as well.Analyzing the collected data and comparing the obtained results, it can be concluded that postacute rehabilitation measures substantially impact patients’ conditions after a stroke. By following up for six months and examining on several occasions , it can be pointed out that including patients into an adequate postacute rehabilitation program increases their degree of functional independence. Furthermore, since there is a significant connection between functional independence and quality of life, it can be stressed that the longer duration of postacute rehabilitation, the greater functionality is achieved and thus a better quality of life for patients after a stroke.


Urban parks can mitigate the urban heat island (UHI) and effectively improve the urban microclimate. In addition, quantifying the park land surface temperature (LST) and its relationship with park characteristics is crucial for guiding park design in practical urban planning. The study’s primary purpose is to investigate the relationship between LST and landscape features in different park categories based on high-resolution data. In this study, we identified the land cover types of 123 parks in Luoyang using WorldView-2 data and selected 26 landscape pattern indicators to quantify the park landscape characteristics. The result shows that the parks can alleviate UHI in most seasons, but some can increase it in winter. While the percentage of bare land, PD, and PAFRAC have a positive impact on LST, AREA_MN has a significant negative impact. However, to deal with the current urban warming trend, a compact, clustered landscape configuration is required. This study provides an understanding of the major factors affecting the mitigation of thermal effects in urban parks (UP) and establishes a practical and feasible urban park renewal method under the idea of climate adaptive design, which provides valuable inspiration for urban park planning and design. The pace of urbanization worldwide is unprecedented, since reform and opening-up, China’s urbanization rate has increased by 45.9%, much higher than the global average in the same period ,2. In adThe LST is an essential parameter for studying the urban thermal environment and is also the main index to regulate the temperature of the urban bottom air and determine the surface radiation ,19. WhatHowever, due to the limited geographic coverage of meteorological stations and the complexity of dynamic heat transfer processes, it frequently provides evidence of the impact of urbanization on climate warming at regional scales ,21. In cThe important influence of landscape structure on UHI has been widely demonstrated. An accurate assessment of land cover types is also essential for exploring the spatial pattern of UP and improving its quality . Along wNumerous studies have used remote sensing data to explore the change mechanism and scale of LST. In terms of urban climate, urban greening is often done to offset the negative impact of impervious surfaces on urban temperatures . It has Nevertheless, due to the complex interaction of various factors and the spatial heterogeneity of cities, the causes of UHI are complex and site-specific, and the relationship between landscape structure and LST is inconsistent. A single measure cannot be effectively applied to all regions ,43 and aTherefore, this study conducted an accurate definition of the landscape pattern based on the high-resolution remote sensing data and a comprehensive comparison of the seasonal variation of the effects of the landscape pattern on park LST by specific park categories to put forward a concrete and implementable urban planning scheme for urban management with the focus on (1) Use high-resolution remote sensing data to obtain UP landscape types and their shape indicators accurately. (2) Retrieve LST from remote sensing satellite infrared data and probe the relationship between LST and park morphological indicators and landscape patterns. (3) Analyze the maximization mode of LST regulation in Luoyang UP and provide targeted recommendations and models for urban planning on mitigating the UHI effects through the rational allocation of the interior landscape of the park.2 [Luoyang, the sub-city center of the Central Plains city group in China (33°21′ N–35°3′ N and 111°48′–112°35′ E) , is loca2 . The urbThe flowchart of the study is as follows . First, The most commonly used surface temperature inversion methods include split-window algorithms, single-channel methods, the mono-window algorithm, and the radiative transfer equation-based method (RTE) ,53. The https://www.usgs.gov/ (accessed on 25 August 2021).), which had a spatial resolution of 30 m and cloud-free, acquired on 8 January 2021, 27 April 2020, 14 July 2019 and 18 September 2020, to represent winter spring, summer, and autumn, respectively. The radiative transfer equation can be express as:λL represents the thermal radiation intensity of the wavelength received by the satellite sensor, ε is the land surface emissivity (LSE), and B(Ts) represents the radiation brightness received by the sensor for a blackbody with temperature (W·m−2·sr−1·µm−1). τ is the atmospheric transmissivity. L↑ and L↓ are the upwelling and downwelling atmospheric radiances. Atmospheric profile parameters  were obtained by NASA (http://atmcorr.gsfc.nasa.gov/(accessed on 28 August 2021)) [Seasonal LST data were derived from the thermal infrared (TIR) band for four Landsat-8 images (Row 36/Path 125) obtained from the United States Geological Survey (USGS) (t 2021)) .First, ENVI 5.3 is used to preprocess the raw images, including radiometric calibration, atmospheric correction, cutting, splicing, etc. The LSE is required when using RET to retrieve surface temperature. Referring to the numerical value in the study of José A. Sobrino , the LSEsoilNDVI, and vegNDVI, correspond to the values of NDVI for bare land (vP = 0) and a surface with a fractional vegetation cover of 100%, respectively [s) can be expressed as:sT is the real land surface temperature (K), then according to the inverse function of Planck’s formula, the real surface temperature sT can be obtained as follows:K1 and K2 indicate the preset constant before the satellite launch, which is presented in the metadata MTL file query, for the Landsat-8 TIRS 10th, K1 = 774.8853 W m−2 sr−1 µm−1, K2 = 1321.0789.In Equation (3), ectively . After pWe use high-spatial-resolution WorldView-2 satellite images based on landscape ecology theory and ENVI 5.3 combined with the human-computer interaction interpretation method of manual correction to divide the land cover types. In this study, supervised classification is applied using maximum likelihood, a parametric classification based on a Gaussian probability density second-order statistic model, based on WorldView-2 imagery at 0.5 m resolution on 23 December 2020. The land cover types of UP in the study area are classified into four types: vegetation , bare land , water bodies , and impervious surfaces  . The tra2, MP), small parks , medium parks , large parks , and super large parks . Water is the most critical landscape type affecting the park’s LST and provides the most excellent cooling effect. Therefore, parks are divided into parks with water (WP) and without water (NWP). The land cover of parks is the major impact of LST; the four land cover types are divided according to the direction of impact. Water and vegetation can have a negative effect on the park’s LST; therefore, the parks where water bodies and vegetation account for more than half of the total area are defined as Vegetation&Water parks (VWP). Bare&Imper parks (BIP) are those that have more than half of the area covered by impervious surfaces and bare land. The remaining parks are classified as “balance parks” (BP) since no category of land cover makes up more than half of the total park area.Based on the statistical yearbook of Luoyang and municipal planning and field surveys, the boundaries of UP in Luoyang were manually extracted based on high-resolution image maps. A total of 123 parks in the study area were extracted and classified using various classification features, with the four main criteria listed below. To begin with, the national industry standard “Standard for classification of urban green space” (CJJ/T85-2002) combined with the “Code for classification of urban land use and planning standards of development land” (GB50137-2011). Some of the street gardens are reclassified into pocket parks (PP) and plaza parks (PLP), which are finally classified into five categories: pocket parks (PP), community parks (CP), plaza parks (PLP), comprehensive parks (COP), and specific parks (SP). According to the nature of the parks, they are classified by area as mini parks  was used to determine whether there was a statistically significant relationship between LST and landscape metrics in different seasons and determine the influence of various landscape metrics on LST. Furthermore, stepwise multiple linear regression was used to model the linkage between LST and landscape metrics. The best-fit model was selected based on regression statistics , and its coefficients are statistically significant. Collinearity between the independent variables was evaluated regarding the variance inflation factor (VIF). The final regression model was obtained after removing the variables with collinearity from the model and re-analyzing them. Several analytic methodologies were integrated to determine the leading factors of LST and analyze the importance ranking of its influencing factors in order to propose better strategies to alleviate UHI.As we all know, urban park LST is affected by many driving factors. What is less known, however, are the dominant factors . VariousThe LST varied significantly in various parks and seasons . The meaThe classification of nature, area, water, and landscape pattern all significantly affected the LST of parks in all seasons except winter . The mea2, with the longest park reaching a perimeter of 9.27 km. In the parks, the land cover type with the largest average percentage was vegetation (54%), followed by impervious surfaces (28%), bare land (10%), and only 8% of water bodies.Same with LST, the distributions of landscape patterns had considerable variations in different categories of parks. The park area is distributed between 0.04 and 587.76 hmThe landscape metrics difference of various parks is shown in With an increased area in parks of various sizes, AREA, Ci, and Cv greatly grew c,i,k. SHAmong parks with different land cover, the SHDI, SIDI, PAFRAC, and SHEI of BP were significantly greater than those of other parks o,p,s,n. The Pi and PD of WP were significantly lower than NWP. Moreover, except for SHAPE_MN, PARA_MN, PAFRAC, IJI, Pb, Pv, SHAPE, and CIRCLE, all indicators of parks with water are significantly larger than those of parks without water.For all the landscape metrics examined in this study, the direction and magnitude of their impact on LST were generally different in different seasons . The PeaThe LST of the PP and CP was positively correlated with Pb and PD and negatively significantly correlated with Cw, AI, and AREA_MN, respectively. The correlations between PLP LST and Pv were negative except for winter, and Pb was positive in summer and autumn. In spring and summer, the LST of COP positively correlated with Pi and AI, and Pv was the most substantial negative performer. Unlike other seasons, LST showed a strong negative correlation with PERIM (−0.99) and AREA (−0.94) in winter. The correlations of LST of SP to SHEI, SHDI, and SIDI were positive (0.71~0.87) and negative to Pv (−0.68~−0.8) and AI (−0.64~−0.79) in spring, summer, and autumn, respectively.Among the parks of different sizes, the LST of the MP in winter was positively correlated with Cb (0.42) and Pb (0.41). Meanwhile, the LST of the SMP in spring was positively correlated with Pb (0.5) and PAFRAC (0.54). Except for winter, LST was positively correlated with Pw, Cw AI, and AREA_MN and negatively correlated with PD for LP, respectively. The landscape coefficients associated with the LST of SLP were higher, with significant positive correlations with SHEI, SHDI, and SIDI, significant negative correlations with Pv and AI, and the strongest negative correlation with Pb (−0.84), respectively.Moreover, VWP LST was negatively correlated with AREA_MN, AI, Pw, and PD, respectively. BP LST was positively correlated with Pb (0.59) and negatively correlated with Pi (−0.57) in winter and AI (−0.58) and Pw (−0.76) in summer, respectively. In contrast, AREA_MN (−0.76) was negatively correlated with VWP in the summer. It was worth noting that the LST of WP significantly but inconsistently correlated with landscape patterns. For example, it was positively correlated with the diversity index in winter, negatively and strongly associated with AI and AREA_MN in other seasons, and negatively correlated with PD in all seasons. In spring, the LST of the NWP was negatively correlated with Pv (−0.48) and positively correlated with LSI (0.31) and Cb (0.33) in winter, respectively.The stepwise regression analysis showed that park LST changes are closely related to landscape patterns, and the specific influencing factors and their degree of influence vary seasonally and by park type, with landscape patterns explaining significantly more of the variation in LST by season than park shape factors . OverallGenerally speaking, the larger the park area was, the better the fit of the regression model was, and the clearer the influencing factors of LST were e–h. Pb aAmong the parks with different landscape percentages, the lower the percentage of water bodies and vegetation was, the lower the explanation of the regression model was i–l. In aOur result indicated that Luoyang’s overall thermoregulation intensity values are in the range of 1–2 °C, with the most robust cooling at 2.75 °C, which confirmed that the UP could mitigate the UHI effect. We also found that the mitigating effect of parks on UHI varies by season in Luoyang, being strongest in the autumn, followed by spring and summer, although the UP had a lifting influence on LST in the winter. In the intensity of the UP to regulate the urban thermal environment, our result is in agreement with previous studies that the UP is an essential urban landscape for thermal environment regulation ,63,64. IThe relationship between UP and UHI depends on local climate conditions, the heterogeneity in ecological conditions of different climate zones contrasts sharply . GeneralIn this study, landscape patterns were used to characterize the composition features of UP. Many studies have shown that the landscape pattern highly correlates with LST’s temporal variation and spatial distribution ,78. By cThe positive effect of Pb on LST has been mentioned in many studies, which is due to heat concentration, low water-holding capabilities, minor thermal inertia, deficient relative humidity, and topsoil aridity in the upper layers of the sandy soil. Additionally, variations in LST in the bare areas may be due to the soil properties  . HoweverIn addition to the landscape composition factor, AREA_MN had the most significant negative effect on LST in spring, summer, and autumn, and PD had the most significant positive impact on LST. PAFRAC had the most important positive effect on LST in the winter. AREA_MN and PD have been important landscape pattern factors in LST-related studies , which cOur work shows the influence of landscape pattern on LST in different parks, the specific correlations, and the potential value of managing urban surface temperatures to reduce heat exposure risk. Landscape patterns can be controlled by design, and urban planners can optimize UP internal landscape patterns to regulate urban LST to explore optimal cooling patterns and enhance urban ecology. The fraction of each type of landscape is the most significant element influencing LST, as determined by the results of our study. Vegetation and water are beneficial in providing a cooling effect ,49,97. TThe impervious surface and bare land produce the highest regional heat. Impervious surfaces are difficult to change extensively due to their nature and role. However, bare land can be reduced by enhancing vegetation planting. Increasing the quantity of vegetation is thus the principal focus of the park’s rehabilitation . ReducinThe landscape pattern in different parks can also provide various degrees of influence on LST. As previous studies mentioned in the suggestions for urban management before, increasing perimeter, area ,100, morThis study selected 22 standard features describing landscape patterns and 4 park morphology indices to provide a more comprehensive description of the landscape patterns of UP in Luoyang City. The chosen variables explained 78.2% of the variation in surface temperature. However, the mechanism of landscape patterns on the LST of parks over various seasons requires additional research. Managing the cooling impact of UP by altering landscape patterns is an important study topic. While most research on the cooling effect of UP is measured using remote sensing images, this paper likewise employs remote sensing images of a single period to describe LST in different seasons, despite the difficulty of obtaining continuous, high-quality meteorological data. The results may deviate from the actual results in a practical sense. This study considered investigating LST during the daytime. Therefore, adding nighttime data, multiple daytime readings, and viewing the winter season could show interesting variations over time. Therefore, future research should focus more on using more accurate field survey data to supplement remote sensing image data and introducing multi-source data into the study, combining multiple quantitative methods to measure LST and its influencing factors accurately. Future research on landscape characteristics should include a wide range of geographically distributed cities. This research should be conducted in as many diverse cities as possible and focus on the investigation’s practical implications and effects.Rapid urbanization has produced a profound heat island effect globally, which has caused great harm to the ecological environment and human health. The main factors affecting LST and the intensity of their products are different in different seasons. Still, their main factors are interrelated, so it is significant to understand the specific patterns of UP to mitigate the urban heat island effect for park green space design and urban planning. To assist planners in tackling climate change, heat waves, and general high urban temperatures, we seek to determine how different urban characteristics are associated with land surface temperatures. The results strongly support initiatives for increasing green infrastructure in cities. We found that the landscape pattern explained to a great extent the variation of LST and its regulation of UHI in the UP (78.2%), and the park had the worst ability to regulate LST in winter and the strongest in summer. Patch density and type determined the spatial variation of LST in the exploration area. Four different ground cover types significantly affected park LST in different seasons. In contrast, diversity factors and patch distribution had little effect on LST variation. The PD, Pb, and Pi had a negative impact on UHI mitigation, which was most prominent in the spring and summer. The unfavorable impact of PD, Pb, and Pi was more evident in the spring and summer. The influence of landscape variety and the form component of the park itself were much more pronounced in winter. With greater LST, the more complicated the park shape and the more diverse the landscape type. For the landscape pattern selection, 22 standard features describing the landscape pattern and 4 indices describing the park morphology were selected for this study, which explained the variation in surface temperature (78.2%). However, the process of changing landscape patterns on the LST of the park over the various seasons requires more research. Meanwhile, this study paid less attention to the internal composition of plants. We mainly focused on the overall percentage and area of vegetation, which can be combined with empirical measurements in future studies to introduce multi-source data to quantify the pattern changes of vegetation and climate in detail. According to the results, urban planning and managers can justify planning the park’s shape, increase the proportion of greenery and water bodies, replace impervious surfaces with bare land, and reduce the degree of landscape fragmentation, which can alleviate the urban heat island effect to a greater extent and provide a comfortable urban ecological living environment for urban residents.