This study aimed to explore the risk factors of urinary tract infection (UTI) in patients with intracranial cerebral hemorrhage (ICH).  This is a retrospective study, and a total of 77 patients with ICH consecutively admitted to the First Affiliated Hospital of USTC  during the period of August 2015 to August 2017 were included. The patients were divided into an UTI group (24 cases) and a non-UTI group (53 cases); patients with UTI were diagnosed according to clinical manifestations, recent urinary routines, and urine culture results. The following information in these two groups was recorded: age, sex, course of disease, side of paralysis, location and type of cerebral hemorrhage, disturbance of consciousness or not, the Brunnstrom stage of paralysed lower limbs, number of basic diseases, whether there were complications , whether rehabilitation interventions were conducted, blood routine, biochemistry index, DIC complete set, urine routine, and urine culture data. Univariate analysis and multivariate logistic regression analysis were used to examine the risk factors of UTI in patients with ICH. P < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022–1.424), P < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022–1.424), P < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022–1.424), P < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022–1.424),  Univariate analysis showed that age, side of paralysis, disturbance of consciousness, the Brunnstrom stage of lower limbs, tracheotomies, retention catheterization, pulmonary infection, leukocyte count, neutrophil proportion, sodium, uric acid, D-dimer, and fibrinogen may be related to UTI in patients with ICH ( Increased age and high D-dimer are independent risk factors for UTI in patients with ICH, while right-sided paralysis is a protective factor for UTI in patients with ICH. Urinary tract infection (UTI) is not only a significant complication but also a potential risk factor for poor prognosis of stroke. It has been reported that the incidence of UTI in stroke patients is 14.2–34.7% , with a Previous studies have reported that increased age is a risk factor for UTI in ICH patients, and patients over 76 years old account for 28.6% of hospital-acquired UTI, while ICH accounts for 34.2% . However  Inclusion criteria were as follows: (1) diagnosed with cerebral hemorrhage (including subarachnoid hemorrhage) by CT in accordance with the fourth national diagnostic criteria for cerebrovascular disease of 1995 in China ; (2) age  Exclusion criteria: (1) clinical data are incomplete; (2) UTI presented before the ICH.A retrospective analysis was conducted for the study. A total of 77 ICH patients who met the above criteria and admitted to the Department of Rehabilitation Medicine of the First Affiliated Hospital of USTC  from August 2015 to August 2017 were included in the study. Among them, 47 males and 30 females, ranging in age from 50 to 87 years, were included.Information recorded included age, sex, course of disease, paralysis side , location and type of bleeding : D type), number of underlying diseases, disturbance of consciousness or not, and the motor function of paralysed lower limbs. Brunnstrom staging was used to make assessments: Brunnstrom Stage 1 was set for paralysis of lower limbs with a disturbance of consciousness, Brunnstrom Stage 2 was set for spasm without involuntary activity, and Brunnstrom Stage 3 was set for spasm and involuntary activity. If the patient had bilateral paralysis, Brunnstrom staging of the serious side was considered for the study. Other information recorded at admission included complications , whether rehabilitation intervention was conducted or not after the onset of ICH, blood routine, biochemistry index, DIC complete set, urine routine, and urine culture clinical data.The patients were divided into a UTI group (24 cases) and a non-UTI group (53 cases). The general data of the two groups are listed in t test was used when the two groups of measurement data were in accordance with normal distribution, and a rank-sum test (Mann–Whitney U test) was used when there was no such accordance. The results are expressed as Mean ± SD. A comparison of the categorical data between the UTI group and the non-UTI group was performed by the chi-square test or Fisher's exact test, and the results are expressed by the number of cases. When analyzing the risk factors of UTI in ICH patients, UTI was used as a dependent variable, and meaningful indicators were used as independent variables after univariate analysis. A multivariate logistic regression analysis was carried out.  P < 0.05 was considered statistically significant.SPSS 21.0 statistical software was used for analysis in this study. An independent sample P < 0.01), as shown in P < 0.05), suggesting that the Brunnstrom stage of lower limbs may also be related to UTI. However, there was no significant difference in pressure sore, venous thrombosis, and rehabilitation intervention between the UTI group and the non-UTI group (P > 0.05), indicating that these factors may not be associated with UTI in patients with ICH.By analyzing data using univariate analysis, it can be found that there were significant differences between the UTI group and the non-UTI group with respect to consciousness disorders, tracheotomies, retention catheterization, and pulmonary infection (P < 0.01). The levels of serum uric acid and sodium in the UTI group were significantly lower than those in the non-UTI group (P < 0.01), while there were no statistically significant differences between the two groups in serum albumin, globulin, blood sugar, creatinine, potassium, calcium, and magnesium (P > 0.05). These results suggest that leukocyte count, neutrophil proportion, D-dimer level, and fibrinogen level may be risk factors for UTI in patients with ICH.Because blood indices play a key role in the reflection of infection, we compared several blood indices in the UTI and non-UTI groups. As can be inferred from the results using univariate analysis in P=0.026), right-sided paralysis (OR (95% CI) = 0.20 (0.001–0.650), P=0.028), and D-dimer (OR (95% CI) = 1.403 (1.003–1.961), P=0.048) were related to ICH concurrent with UTI, as shown in To further find potential independent risk factors for UTI in patients with ICH, 13 significant variables identified by univariate analysis were introduced into the logistic regression equation. The multivariate analysis results showed that age (OR (95% CI) = 1.207 (1.022–1.424), χ2 = 6.873, P=0.032), Among them, the incidence of UTI with right paralysis is significantly lower than left, while the incidence of UTI in female with left and right paralysis was not significantly different .Our results showed that right-sided paralysis is a protective factor of UTI. To address this question, we reanalyzed the data by taking sex into consideration and compared the infection rate of the left and right urethra in a subgroup analysis. As shown in Tables UTI not only led to reduced exercise during rehabilitation, but also prolonged hospitalization time and reduced the effect of rehabilitation, which is a heavy economic and psychological burden to patients, their families, and society. Therefore, understanding the risk factors of UTI in ICH patients may lead to more effective prevention and intervention with respect to ICH patients. Here, we demonstrated that age, right-sided paralysis, and D-dimer are risk factors associated with UTI in ICH patients and that right-sided paralysis is a protective factor.Univariate and multivariate analysis showed that increased age was associated with UTI in this study, which is consistent with previous findings suggesting that age (>75 years) is a factor associated with UTI in stroke patients ,16,17. WOur results indicate that the location and type of bleeding have no influence on the UTI in patients after ICH, but whether there is any difference in the amount of bleeding between UTI and non-UTI groups is unclear at the current stage. Future studies are required for determining whether the size of hemorrhage is related to UTI in patients after ICH. Since the bleeding data for many patients in our hospital are lacking, it is impossible to analyze the relationship between the size of hemorrhage and the UTI in patients after ICH. We hope that neurologists can record more patient information, including the amount of ICH, so as to provide richer information for later clinical research.The association of the side of paralysis with respect to UTI in patients with ICH is not clear. Our results showed that right-sided paralysis was related to UTI after ICH. Compared with left-sided paralysis, right-sided paralysis was a protective factor of UTI, and the risk of right-sided paralysis UTI was only 0.020 times that of left-sided paralysis (OR = 0.020), which might be due to hemiplegia slowing down the ipsilateral ureteral peristalsis. The length of the left and right ureter is different in humans. This study found that the infection rate of right paralysis was lower than left, but we neglected the anatomical differences between the males and females. To solve this problem, we conducted a recalculation and subgroup analysis of the infection rate of left and right paralysis by the sex group. Finally, we found that the infection rate of right paralysis in males was lower than left. However, there was no statistically significant difference in the infection rate of the left and right in females, indicating that the right paralysis may be a protective factor for UTI in males. Future studies are required to address this question by increasing the number of patients. An alternative explanation could relate to the shorter anatomical characteristics of the right ureter (shorter than the left ureter). Pathogens such as bacteria and fungi of retrograde urine are easier to remove when right ureter peristalses occur. The left ureter is relatively long, and the slow peristalsis of the left ureter has a greater impact on it. The pathogen stays in the interior for a long time after the occurrence of retrograde urine, allowing it to more easily adhere and reproduce. Interestingly, by dividing ICH patients according to hemorrhage side, brainstem and ventricle, and subarachnoid hemorrhage groups, there were no significant difference in terms of hemorrhage side or location with respect to UTI, which further indicates that the paralysis side may only come from the paralysis itself but not from the hemorrhage side or the location in the brain.Moreover, our results indicated that D-dimer increased significantly in UTI patients, and D-dimer increased the risk of UTI by 1.403 times (OR = 1.403). D-dimer is a soluble degradation product of fibrin under the action of the fibrinolytic system. The increased concentration of D-dimer indicates that the fibrinolytic activity of fibrin is enhanced in vivo, which could be a factor predicting the occurrence of deep venous thrombosis . HoweverA tracheotomy can improve ventilation and strengthen airway management in ICH patients but can easily cause laryngeal defensive reflex weakening and dysphagia, aspiration of food, and oropharyngeal esophageal secretions, which may result in pulmonary infection . Our stuIn summary, this study demonstrated that age and D-dimer are independent risk factors for UTI in ICH patients, and right-sided paralysis is a protective factor. The results indicate that attention should be paid to the effects of age, paralysis, and D-dimer on UTI for the treatment of patients. Based on the results, to better prevent or treat UTI effectively, we suggest the following: (1) sitting up rather than lying down in bed as much as possible; (2) drinking more water; (3) keeping the ureter open continuously, avoiding urine reflux, and removing the ureter as early as possible; (4) actively reducing D-dimer. These methods may help to prevent UTI. However, our results suggest that consciousness disorders, lower limb motor function, tracheotomies, pulmonary infection, indwelling catheters, leukocyte count, neutrophil proportion, serum sodium, uric acid, and FIB may also be related to UTI in patients after ICH. To provide more clinical evidence for effective prevention and intervention measures, the design of prospective studies with larger sample sizes that further analyze these potential influencing factors of UTI is urgent.


Chronic consumption of alcohol and marijuana, especially when initiated at an early age, has been implicated in cognitive alterations in the domain of executive functioning. Despite the robustness of this finding in Western populations, its generalizability to other cultural contexts is largely unknown. In this study, we examined whether the regular use of alcohol or marijuana use relates to impaired executive functioning in male students of a Nigerian university.n=39), chronic marijuana users (n=35) and drug-abstinent control participants (n=40) recruited through snow-ball sampling technique completed a computerized version of the Wisconsin Card Sorting Test (cWCST). As an established measure of executive functioning, the cWCST allows for the simultaneous assessment of three distinct executive processes: set shifting, rule inference, and set maintenance. Results revealed a selective set-shifting deficit in both alcohol and marijuana users.Chronic alcohol users (Both groups committed significantly more perseverative errors than the control group, and group differences were significantly stronger on this indicator of set shifting than on indicators of rule inference or set maintenance.Our findings support the generalizability of drug-related deficits in executive functioning and contribute to the characterization of executive dysfunction in non-Western populations. Future longitudinal studies are required to clarify whether executive dysfunction is an antecedent or consequence of alcohol and marijuana use in young Nigerians. Alcohol and marijuana are the two most commonly used drugs among adolescents and emerging adults . The chrChronic use of alcohol and marijuana seems to relate to alterations in executive functioning and its neural correlates . For exaIn the present study, we administered the cWCST to simultaneously assess the executive domains of set shifting, rule inference, and set maintenance in chronic alcohol and marijuana users from Nigeria. To our knowledge, this is the first examination of executive functioning in users of these drugs in sub-Saharan Africa. Most previous studies in the field have been conducted in Western and Asian countries and it is unclear whether these results can be generalized to the Nigerian population. The cWCST data collected in this study address this question of generalizability and provide first insights into the profile of executive deficits in Nigerian alcohol and marijuana users.M = 24.89; SD = 2.54) recruited through snow-ball sampling technique from the university town Nsukka in south-east Nigeria. Participants were included in one of three groups. Chronic marijuana users  self-reported to smoke at least five grams of marijuana per week  and they reported not to drink more than four bottles of beer  per week. Chronic alcohol drinkers  self-reported to drink at least five bottles of beer per week  and not to smoke at least five grams of marijuana per week. Controls  self-reported to have abstained from alcohol use at least for the past one year, to have never smokedmarijuana in their lifetime, and to have consumed no more than five bottles of alcoholic beverages in their lifetime. The three groups did not differ significantly with regard to age, F = 2.31, p = .104, and education, F = 1.83, p = .166. All procedures were in accordance with the Declaration of Helsinki and approved by the local ethics committee.Participants for the study consisted of 114 male college students . On each trial of the cWCST, participants were required to match cards according to one of three possible sorting rules. Card sorts were followed by a feedback cue that indicated whether the applied sorting rule should be repeated or switched. Rules changed after runs of two or more repetitions. Participants completed six practice runs and 42 task runs or a maximum of 250 trials, whichever occurred first.Eligible participants were approached and scheduled for computerized assessment at the nearest convenient laboratory or library in the University. Study objectives were explained in a consent form, which participants signed prior to participation. All participants completed the latest version of the cWCST  = 3.05, p = .051, η2 = .052, but the interaction between Group and Error Type did, F = 2.93, p = .027, η2 = .050 (see p = .001) and marijuana users (p < .001) committed significantly more perseverative errors than controls. In contrast, no group differences were observed with regard to the other two error types . Simple effects tests did not show any significant differences between the two drug groups on any error measure . The same analysis strategy was repeated using mean response times as the outcome variable. A Trial Type  × Group ANOVA did not reveal a significant main effect of Group, F = 0.92, p = .402, η2 = .016. The Trial Type × Group interaction was not significant either, F = 1.00, p = .404, η2 = .018.Error rates on the cWCST were subjected to a 3×3 ANOVA involving the within-subject factor Error Type  and the between-subjects factor Group . The main effect of Group did not reach significance, .050 see . BonferrA fine-grained analysis of cWCST error profiles revealed that chronic alcohol and marijuana users committed significantly more perseverative errors than controls. This performance measure was significantly more affected than other error scores, thus pointing to a selective set-shifting deficit in chronic alcohol and marijuana users.The result from our study is consistent with similar studies with western population samples . In contThere are several possible explanations for the differences observed between drug-consuming individuals and control participants. One possibility is that continued exposure of marijuana and alcohol has over time resulted in neural alterations that manifest themselves as set-shifting deficits on the cognitive level. Many of our participants reported to have started using substances at a very early age where the brain might be particularly susceptible to these substances . AlternaThe results of this study should be interpreted in the light of some limitations. First, the cross-sectional design of this study has limited our ability to make conclusions about the direction of the relationship between set-shifting deficits and alcohol and marijuana use. Second, while our groups were reasonably matched with regard to age and education, there could have been other variables not taken into account. For example, participants were asked if they had abstained from alcohol and marijuana use for at least 12 h prior to participation, but due to logistics, no urinalysis was done for confirmation. Additionally, only males were recruited for the study, thus precluding generalization to the female population. Future studies might benefit from addressing these limitations to further elucidate the relationship between executive functioning and drug use.In conclusion, this study revealed specific perseverative tendencies on the cWCST in alcohol and marijuana users that are suggestive of a deficit in cognitive set shifting. By confirming the findings of previous studies from Western countries, our results indicate that alcohol- and marijuana-related executive impairment generalizes to the Nigerian population. As such, our study illustrates the value of studying the cognitive correlates of drug use in non-Western cultures as well as the use of a fine-grained analysis of executive functioning.Supplementary materials


Limited data is available on retinal vessel morphology in the north China. The study aimed to evaluate the prevalence of retinal vascular abnormalities (RVAs) and investigate their associations with the self-reported diagnosis of cardiovascular and cerebrovascsular diseases (CCVds) in a rural adult population of northeast China.A population-based, cross-sectional study was conducted, using the cluster random sampling method. One eye of each participant was photographed with a non-mydriatic fundus camera. RVAs including focal and general arteriolar narrowing (FAN and GAN), arteriovenous nicking (AVN), arteriolar sheathing (AS), and retinopathy were evaluated. Data on self-reported diagnosis of cardiovascular and cerebrovascular diseases and status of smoking and alcohol drinking were obtained from questionnaires.P < 0.01). After adjusting for age, gender, and left/right eyes, hypertension, hyperlipidaemia, diabetes mellitus, habits of past or current smoking and alcohol consumption, AVN was strongly associated with the self-reported diagnosis histories of coronary heart diseases(CHD)  and retinopathy was significantly associated with a self-reported diagnosis of stroke .Among the 6267 participants with an age ≥ 50 years, photographs were obtained of 99.2%, with quality sufficient to perform retinal evaluations in 82.5%. The prevalence of FAN, AVN, AS, retinopathy and GAN were 9.1, 8.9, 5.0, 6.6 and 6.2%, respectively. All the retinal lesions were associated with hypertension (all The overall prevalence of retinal microvascular abnormalities in this population was relatively higher than that reported in other regions of the world. Retinopathy is associated with the self-reported diagnosis of stroke while AVN was associated with the self-reported diagnosis of CHD, but the remaining retinal lesions were not consistently associated with CCVds. Thus, an examination of retinal microvascular characteristics may offer clues to CCVds and could be a potentially novel biomarkers for CCVds risk. Retinal vascular abnormalities , arteriovenous nicking (AVN), arteriolar sheathing (AS), and retinopathy) –4, have In the past decades, the development of ocular fundus photography and image-processing software has enabled accurate and reproducible assessment of retinal microcirculatory alterations , 15–17. Considering the role retinal vascular changes may have in the early detection of CCVds and the lack of research on retinal vessel morphology in the adult Asian population, we conducted the present study to assess the RVAs in northeastern China. This study focused on the prevalence of RVAs and their associations with CCVds among subjects aged 50 years or older.Shuangcheng Fig. , a speciGeographically defined clusters based on village register census data were used as the study sampling frame within each county/district. In this study, a cluster random sampling method, similar to that used in the study by Doumen  was emplThe research protocol was approved by the Medical Ethics Committee of the First Affiliated Hospital of Harbin Medical University (No:201532) and all the subjects provided informed consent, according to the Declaration of Helsinki. Households listings of names of residents ≥50 years of age were obtained from the village registers, followed by door-to-door visits conducted by the enumeration team. Individuals temporarily absent at the time of the household visit were included in the enumeration. Unregistered adults ≥50 years of age were enumerated and included in the study sample if they had been living in the household for at least 6 months. Refusal to provide informed consent was considered as an exclusion criterion.All participants were administered a questionnaire , basic pThe methods for the assessment of hypertension, CCVds, and their risk factors are highlighted here.self-reported diagnosis histories of CCVds and smoking habits and alcohol consumption were obtained from a questionnaire. Sitting brachial blood pressure was measured three times by trained technicians with a random-zero sphygmomanometer after 5 min of rest. Blood samples were collected between 7:00 and 9:00 a.m. after at least an 8 h overnight fasting. Sterile vacuum tubes with and without ethylenediaminetetraacetic acid were used, and centrifugation was performed within 3-h of blood collection. Serum analysis was performed in the laboratory of the First Affiliated Hospital of Harbin Medical University . Hypertension was diagnosed, if the systolic blood pressure was ≥140 mmHg or diastolic blood pressure was ≥90 mmHg, or a self-reported diagnosis history of hypertension and antihypertensive therapy was self-reported. Hyperlipemia was diagnosed, if Triglycerides were ≥ 2.0 mmol/L and high-density lipoprotein was ≤1.0 mmol/L, or a self-reported history of hyperlipemia and lipid-lowering therapy was self-reported. Diabetes mellitus was diagnosed, if the fasting glucose was ≥7.0 mmol/ L (≥126 mg/dl) or the use of insulin or oral hypoglycaemic medication was self-reported .To evaluate RVAs, two 40° non-mydriatic retinal photographs of one eye from each participant were taken using a fundus camera . One photograph was centred on the optic disc and another on the fovea centre . The exclusion criteria of this study population were as follows: subjects whose fundus photographs were not clear and could not be evaluated; and subjects who lacked relevant data.The colour photographs  of each subject were evaluated, according to the evaluation criteria of the ARIC study . The phoFor the evaluation of RVAs, FAN, AVN, AS, retinopathy and GAN were assessed. The grader compared possible abnormalities with standard and example photographs to help determine their presence and severity. The ARIC grid  describ was applFAN  was diagFor retinopathy, the following lesions were evaluated in each of the four quadrants of the retina: microaneurysms, hemorrhages, soft exudates or cotton wool spots, hard exudates, macular oedema, intraretinal microvascular abnormalities, venous beading, new vessels in the disc or elsewhere, and vitreous haemorrhage. Retinopathy was diagnosed if any of these lesions were definite or probable in any of the four quadrants. The severity of retinopathy was summarized according to the ETDRS severity scale .To examine the reproducibility of the assessment of RVAs, 100 pictures were randomly selected and evaluated by two ophthalmologists respectively. Every observer repeated the work 2 weeks later.P-values were determined a 2-sided test and were regarded as significant when they were less than 0.05.The statistical analysis was carried out using SPSS 19.0 . The five primary endpoints in the study were FAN, AVN, AS, retinopathy and GAN. We calculated the prevalence of each retinal outcome, according to gender and age group. The association between RVAs  and CCVds and their risk factors was determined using logistic regressions. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. All the P = 0.38) and gender (P = 0.63) between participants with evaluable photographs (5172) and those with unevaluated photographs (1095)  were eligible for retinal evaluations. There was no difference in age , arteriovenous nicking (AVN), arteriolar sheathing (AS), retinopathy and generalized arteriolar narrowing (GAN), respectively, were 9.1, 8.9, 5.0%,6.6 and 6.2% . However, the above two types of retinal lesions were not significantly associated with a self-reported diagnosis history of stroke  (8.6% vs 14.0 and 8.3% vs 14.8%), hyperlipidaemia (8.0% vs 13.4 and 8.6% vs 10.2%), and past or current smoking and alcohol consumption habits  , with hyperlipidaemia (6.1% vs 8.8%) and with habits of past or current smoking and alcohol consumption habits  Table . After aP > 0.05) and stroke  but were independently associated with hyperlipidaemia (4.6% vs 6.5 and 4.9% vs 11.1%), past or current smoking and alcohol consumption habits. For all types of retinal lesions, no significant associations were found between the subjects with or without the presence of diabetes mellitus (P > 0.05).AS and GAN were not associated with the self-reported diagnosis of CHD  in persons with diabetes was lower than that in Chinese in Beijing  , KoreansAfter stratifying the population by age and gender Table , males aThe focus of the present study was the correlation between RVAs and CCVds, which was discussed respectively. In general, after adjusting for age, gender and left/right eyes, FAN, and AVN were found to be associated with a self-reported diagnosis histories of CHD , and its risk factors , and when we further adjusted for these above risk factors, the FAN association with CHD disappeared, suggesting that FAN was only related to the risk factors of CHD but was not related to CHD itself. And the AVN-CHD association was attenuated but still existed  (Tables The rest, except for retinopathy, of the RVAs were not related to the self-reported diagnosis history of stroke, but were associated with its risk factors; AS, retinopathy and GAN were not related to the self-reported diagnosis history of CHD, but were associated with the risk factors of CHD Table . Althougκ values, for intraobserver and interobserver variation. Third, we used questionnaires to collect the histories of diseases as the basis of the prevalence estimates of CCVds. This may underestimate the associations with systemic diseases. Fourth, for the assessment of GAN, considering the engorged and tortuous of veins may caused by other reasons, such as branch or central retinal vein occlusion, so these eyes were not defined as GAN. This would lead to an underestimation of the prevalence of GAN. Last, due to the use of a cross-sectional study design rather than a cohort study design, the current study could not elucidate the evolution of RVAs and their real-time relationship with systemic diseases.Some factors may have influenced our evaluation of the prevalence of RVAs and their possible correlation with CCVds. First, images were not obtained from some of the participants, and some photos could not be evaluated due to refractive interstitial opacity. A relatively high proportion of these images were obtained from elderly patients, who generally have more RVAs. Second, the evaluation of retinal abnormalities was performed manually, which may lead to the relatively low What is the innovative points and clinical significance of the present study? Previous studies mostly tended to describe the association between RVAs and CCVds in general or to explore the association between retinal vessel diameter and CCVds with image analysis technology , 36–39. This study details retinal microvascular abnormalities in a rural population in a region of northeast China with a low altitude and cold climate. The overall prevalence of retinal microvascular abnormalities in this population was relatively higher than that reported in other regions of the world. However, the prevalence of retinopathy was low. Retinopathy was associated with a self-reported diagnosis of stroke history and AVN was associated with the self-reported diagnosis of CHD; FAN, GAN and AS were not consistently associated with the diagnoses of CHD or previous cerebrovascular events such as stroke. Thus, an examination of retinal microvascular characteristics may offer clues to CCVds and could be potentially be considered as of a novel biomarker of CCVd risk.


Most importantly, the fruit pattern network was inversely associated with the risk of GC for the highest tertile . The identified vegetable and seafood network and the fruit network showed a protective effect against GC development in Koreans.Gaussian graphical models (GGMs) are novel approaches to deriving dietary patterns that assess how foods are consumed in relation to one another. We aimed to apply GGMs to identify dietary patterns and to investigate the associations between dietary patterns and gastric cancer (GC) risk in a Korean population. In this case-control study of 415 GC cases and 830 controls, food intake was assessed using a 106-item semiquantitative food frequency questionnaire that captured 33 food groups. The dietary pattern networks corresponding to the total population contained a main network and four subnetworks. For the vegetable and seafood network, those who were in the highest tertile of the network-specific score showed a significantly reduced risk of GC both in the total population (OR = 0.66, 95% CI = 0.47–0.93,  Gastric cancer (GC) has been identified as the fifth most common cancer type and is one of the main causes of cancer-related death worldwide . The GC Several lifestyle factors, particularly dietary factors, can influence the risk of GC . The neeTo address these challenges, a dietary pattern approach has been suggested as a complementary strategy for investigating diet and disease relationships . This apInnovative methods for deriving dietary patterns, such as Gaussian graphical models (GGMs), have been applied as exploratory approaches by addressing pairwise correlations between two food variables while controlling for the indirect effects of the other food variables . As GGMsIn the present study, we aimed to use GGMs to identify dietary pattern networks associated with GC based on the partial correlations of the food groups. Furthermore, we aimed to investigate the associations between the identified dietary pattern networks and GC risk in a Korean population.p < 0.001). The proportion of nondrinkers was similar in the case group (28.7%) and the control group (28.4%). The case group was more likely to have a family history of GC (p < 0.001). Patients in the case group engaged in less regular exercise (p < 0.001), were less educated (p < 0.001), and exhibited lower employment rates (p < 0.001) and lower monthly incomes (p < 0.001) than those in the control group. The proportion of Helicobacter pylori (H. pylori) seropositivity in the case group (92.1%) was higher than that in the control group (58.6%). Men and women in the control group had higher education levels, had higher monthly incomes, were more likely to be employed, were less likely to be smokers, engaged in more regular exercise, and had a lower proportion of H. pylori infection than those in the case group.Regarding the male population, refined grain intake was significantly higher in the case group than in the control group, whereas intakes of tubers and roots, bread, legumes, meat byproducts, poultry, eggs, milk, fruit, fruit products, green/yellow vegetables, light-colored vegetables, mushrooms, condiments/seasonings and coffee/tea intakes were significantly higher in the control group than in the case group. For females, refined grain intake was significantly higher in the case group than in the control group, whereas the intake of rice cakes, bread, legumes, nuts and seeds, processed meat, eggs, dairy products, fruit, fruit products, and condiments/seasonings were significantly higher in the control group than the case group .Dietary pattern networks were derived for the whole study population and for each sex. Regarding the dietary networks derived for the male population, four patterns were identified . The vegFor the females, five dietary networks were derived: the vegetable and seafood network, snacks and fats network, meat network, dairy network, and fruit network . The vegRegarding the dietary networks derived for the intestinal type of GC, five patterns were identified . The vegp for trend = 0.018) compared to those in the lowest tertile. Most importantly, the fruit pattern network was inversely associated with the risk of GC in the highest vs the lowest tertile .In the vegetable and seafood network, those who were in the highest tertile of the network-specific score showed a significantly reduced risk of GC in model II .p = 0.064) in model II. However, none of the association results were significant in the other dietary pattern networks . However, those who were in the highest tertile of the network-specific score showed a marginally significant decreasing association with GC risk , and there was a borderline significant linear trend (networks .p for trend = 0.021) compared to those in the lowest tertile. Most importantly, the fruit pattern network was inversely associated with the risk of GC in the highest vs the lowest tertile . p for trend = 0.016 in model II and OR = 0.55, 95% CI = 0.33–0.92, p for trend = 0.019 in model III).In this case-control study, GGMs derived a main dietary pattern network, which was the vegetable and seafood network, and four additional four subnetworks. The vegetable and seafood network consisted of green/yellow vegetables, light-colored vegetables, pickled vegetables, tubers and roots, tofu/soy milk, condiments and seasonings, seafood products, seaweeds, and fish. This indicates that the foods in the vegetables and seafood network were conditionally independent of any specific food group of other networks. The vegetable and seafood network and fruit network were associated with a decreased risk of GC for the whole study population. GGMs are a powerful exploratory method for dietary pattern analysis . TheoretWe identified a main dietary pattern network for the whole study population, that was composed mainly of vegetable and seafood food groups. Basically, the vegetable, mushrooms, tofu/soymilk, tubers and roots, condiments and seasonings, and seafood food groups were conditionally dependent on the main dietary pattern network, indicating that dietary behavior among Koreans mainly involves vegetables and seafood items. In addition, four subnetworks were obtained as dietary pattern networks for the whole study population. In the snacks and fats pattern network, cereals and snacks, bread, cakes and sweets and oils/fats were correlated with the other food groups. This dietary pattern network represents snacking behavior in the Korean diet. Most importantly, milk and milk products were correlated in the dairy network, whereas fruit and fruit products were highly correlated in the fruit network.A study conducted using the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort showed that two main dietary networks were derived for males and females separately . Both neIt is important to observe the association between derived dietary pattern networks and health outcomes, and it helps to have a clear understanding of the diet and disease relationship to be compared . In the We observed that those who were in the highest tertile of the fruit pattern network-specific score showed a significantly reduced risk of GC compared to those in the lowest tertile for the whole population and for males. A study carried out in Japan focusing on dietary patterns and stomach cancer among middle-aged male workers concluded that vegetable and fruit consumption patterns were negatively associated with GC . The WorA study conducted in Korea using the Cancer Screening Examination Cohort to identify the major dietary patterns in Korean adults found four major dietary patterns, namely ”rice and kimchi”, “vegetables and fish”, ”fruits and dairy”, and ”meats and sweets” . The stuIt is well known that there are several approaches for deriving dietary patterns and that those approaches have been applied in nutritional epidemiology research . A populH. pylori infection as a group 1 carcinogen in humans  to improve normality. Dietary intake data were converted into a data matrix, and the inverse covariance matrix was obtained. A series of regularization parameter λ values was obtained using the “huge” package [First, the food intake variables were checked for normal distribution using histograms to address the Gaussian assumption. Since most of the dietary intake variables had a skewed distribution, the intake variables were log transformed [log package . The ran package . Then, t package . The anaH. pylori infection status. Association analysis was performed for men and women separately. The test for interaction between dietary pattern networks and sex in relation to GC was conducted using logistic regression models via likelihood ratio tests. All statistical analyses were carried out using SAS version 9.4 software  and the R platform (version 3.5.1) .The strength of each node in the identified network was calculated in terms of its centrality value in the network theory. Then, we combined the strength of each node with the dietary intake data to calculate a network-specific score for each study participant. The network (pattern) scores were used as exposure variables for further association analysis. The network-specific scores were categorized into tertiles according to the distribution of the controls. The lowest tertile of the pattern score was used as the reference group. The odds ratio (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. The median values of the network scores in each category were used as continuous variables to test for trends. OR estimates were calculated for three models: model I was the crude model; model II was adjusted for age, sex, family history of GC, smoking status, regular exercise, education, occupation, income and total energy intake; and model III was additionally adjusted for In conclusion, this study showed that the GGMs identified that the vegetable and seafood network was associated with a reduced risk of GC for the whole population and the male population. Moreover, the fruit pattern network was significantly associated with a reduction in GC risk for the whole study population, indicating that fruit consumption behavior has a remarkable effect on the reduction of GC risk among Koreans. However, additional studies to validate this methodological approach in other populations are needed.


Obsessive-compulsive disorder is common, chronic mental disorder, which is characterized by recurrent, unwanted, or intrusive thoughts and repetitive behaviors or mental action. Acupuncture and moxibustion, as a popular form of complementary and alternative therapy, have the advantages of low side effects, high safety, and low cost. The research showed that acupuncture and moxibustion have a good clinical efficacy on obsessive-compulsive disorder. However, there is no literature to systematically evaluate the efficacy and safety of acupuncture and moxibustion in treating obsessive-compulsive disorder. Thus, this study is aimed to evaluate the efficacy and safety of acupuncture and moxibustion for obsessive-compulsive disorder patients, providing reliable evidence for clinical application.Randomized controlled trials of acupuncture and moxibustion combined with western medicine for the treatment of obsessive-compulsive disorder will be searched in the databases including PubMed, EMBASE, the Cochrane library, Web of science, China National Knowledge Infrastructure(CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database (CBM) from inception to June, 2020. In addition, Baidu, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain the gray literature and relevant data that have not yet been published. Two qualified researchers will extract data and assess the risk of bias from included studies dependently. Statistical analysis is performed in RevMan 5.3 software.The efficacy and safety of acupuncture and moxibustion combined with western medicine for obsessive-compulsive disorder will be assessed based on the total effective rate, Hamilton Anxiety Scale score, Hamilton Rating Scale for Depression score, Clinical Global Impression score, side effects, and so on.The proposed systematic review and meta-analysis of acupuncture and moxibustion combined with western medicine for treating obsessive-compulsive disorder is expected to provide reliable evidence for clinical application.The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.DOI 10.17605/OSF.IO/CDGTW There is no significant sex difference in incidence rate among adults. However, OCD is common among mental workers. Epidemiological studies have shown that OCD can lead to severe damage to quality of life, mainly in terms of social functions. Some researches indicated that OCD was linked to serious impairment in various areas of quality of life including mental quality of life, social relations, family, or work life.–12 Although the pathogenesis of OCD is unclear, it is likely to be the changes of corticostriato-thalamo-cortical circuitry including pivotal gray matter nodes.,14 At present, OCD is mainly treated with western medicine, and the remission rate of drug treatment is only 40% to 60%. However, western medicine treatment has some shortcomings including side effects, long course of treatment, easy to relapse, and high cost. Therefore, it is urgent to explore an effective and safe alternative therapy for OCD.Obsessive-compulsive disorder (OCD) is common, chronic mental disorder, which is characterized by recurrent, unwanted, or intrusive thoughts (obsessions) and repetitive behaviors or mental action (compulsions), affecting about 1% to 2% of the general population. In traditional Chinese medicine, acupuncture and moxibustion are 2 inseparable therapies, the former is to stimulate acupoints with needles, the latter is to burn Artemisia Vulgaristhe and produce heat. Acupuncture and moxibustion can strengthen and tonify the brain. And they have the advantages of low side effects, high safety, and low cost.Acupuncture and moxibustion, as a popular form of complementary and alternative therapy, have a good clinical efficacy all over the world.,19 However, there is no systematic review assessing the efficacy and safety of acupuncture and moxibustion for OCD. Thus, the systematic review and meta-analysis is aimed to evaluate the efficacy and safety of acupuncture and moxibustion for OCD patients, providing reliable evidence for clinical application.The research showed that acupuncture and moxibustion have a good clinical efficacy on OCD, with high safety and slight side effects, which may be related to the improvement of 5-hydroxytryptamine and dopamine (DA) functions in the brain of OCD patients.22.1This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P). Moreover, it has been registered on open science framework (OSF) on June 22, 2020 (Registration number: DOI 10.17605/OSF.IO/CDGTW).2.2Ethical approval is not required because there is no patient recruitment and personal information collection, and the data included in our study are derived from published literature.2.32.3.1Randomized controlled trials (RCTs) involving acupuncture and moxibustion for the treatment of OCD will be included. Blinding and publication status are not limited, but language will be restricted to Chinese and English.2.3.2All participants diagnosed as OCD will be included regardless their country, age, race, and sex.2.3.3In the experimental group, OCD patients will be treated with acupuncture and moxibustion therapy  combined with western medicine. In the control group, OCD patients will be treated with western medicine alone.2.3.4 Partial disappearance of clinical symptoms and the reduction rate of Y-BOCS >25% are effective. If the clinical symptoms do not disappear or worsen, or the reduction rate of Y-BOCS is <25%, the efficacy evaluation is not effective. The total effective rate is the sum of apparent efficiency plus effective rate.The primary outcome is the total effective rate, as measured by Yale-Brown Obsessive Compulsive Scale .The secondary outcomes are Hamilton Anxiety Scale score, Hamilton Rating Scale for Depression score, Clinical Global Impression score, and side effects.2.4If the study is published repeatedly, the one with the most complete data will be included.Studies with missing data, and cannot get the data after contacting the author.Studies with obviously wrong data.① if randomization or allocation concealment is evaluated as high risk of bias, regardless of other risks, it will be evaluated as low-quality study; ② when randomization and allocation concealment are evaluated as low risk of bias, and all other quality evaluation items are evaluated as low or unclear risk of bias, it will be rated as high-quality study; ③ if the study will not meet the standards of high quality and low quality, it is considered as moderate-quality research.Low-quality study will be excluded. According to the following criteria, the included study was evaluated as low-quality, moderate-quality and high-quality:2.5We will perform a comprehensive search in the databases including PubMed, EMBASE, the Cochrane library, Web of science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database (VIP), and China biomedical literature database (CBM) from inception to June, 2020. In addition, we will search in Baidu, Google Scholar, International Clinical Trials Registry Platform (ICTRP), and Chinese Clinical Trials Registry (ChiCTR) to obtain the gray literature and relevant data that have not yet been published. The search terms are as follows: “acupuncture,” “moxibustion,” “auricular,” and “obsessive-compulsive disorder,” and so on. The search strategy (PubMed) is shown in Table 2.6Searches were conducted in the above database according to guidance from The Cochrane Collaborative Network System Evaluator's Manual Version 5.0. Two researchers will select the literature by reading the title and abstract independently. Relevant studies will be initially included and imported into Endnote X7 for removal of duplications. Then, by reading the full text of the article, new screening is carried out by referring to the inclusion criteria and exclusion criteria. Two qualified researchers will extract data from included studies dependently. Any inconsistent views will be solved by a third researcher through discussion. The following information will be extracted: basic information of included studies ; basic characteristics ; interventions ; the entry of risk of bias assessment; the outcomes and relevant measurement data. The literature screening process is shown , risk of bias is classified into the following levels: unclear, low, and high risk of bias. Any divergences will be solved through discussion by a third researcher.2.82.8.1P value and I2 statistics. If P ≥.1, I2 ≤50%, there is no significant heterogeneity; thus, the fixed-effect model is used. When P < .1, I2≥50%, the sources of heterogeneity are analyzed, and subgroup analysis may be performed. If there is statistical heterogeneity between studies but no clinical heterogeneity, the random-effect model is selected to analyze. Otherwise, we exclude the study from meta-analysis.Statistical analysis is performed in RevMan 5.3 software. For dichotomous outcome data, the risk ratio with 95% confidence intervals (CIs) is calculated. For continuous outcome data, if the measurement index unit or measurement tool is the same, the weighted mean difference (WMD) with 95% CIs is adopted; if the measurement index unit or measurement tool is different, the standard mean difference (SMD) with 95% CIs is used. Statistical heterogeneity will be checked by 2.8.2When occurring missing, incomplete, and unclear data, we will contact the primary author to obtain it. If data are not acquired, we will analyze the present data and discuss its possible effect on the conclusion.2.8.3Subgroup analysis will be constructed based on the age of patients, the course of disease, and the intervention type including the type of acupuncture and moxibustion, the type of western medicine, and intervention time.2.8.4Sensitivity analysis will be performed to measure the stability of study results by removing the study of high risk of bias.2.8.5When >10 studies are included, funnel plots and statistic tests are used to detect overall estimated reporting bias. Egger and Begg test are used to quantitatively assess potential publication bias.2.8.6The evidence evaluation of results is summarized by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence is divided into high, moderate, low, and very low. There are 8 factors that affect the quality of evidence. Among them, the factors that may reduce the quality of evidence are: risk of bias, inconsistency, indirectness, imprecision, publication bias; the factors that may improve the quality of evidence are: the large effect value, the confounding factors reducing the clinical efficacy, dose–response relationship. As we include RCTs, the default is a high-quality study. According to the above 8 factors, we will upgrade or downgrade.3 It is a kind of disease caused by the disorder of emotion and will, which leads to the obstruction of Qi, the loss of liver function and the disorder of viscera function, which seriously affects the patients’ mental health and quality of life.OCD belongs to the category of “Yu Zheng” (depression syndrome) in the traditional Chinese medicine. With the increasing pressure of life, the incidence rate has been increasing year by year. The first onset age of OCD is mostly around adolescence or adolescence. Acupuncture and moxibustion treatment of OCD is mainly to invigorate the brain and open the mind. At present, there are mainly ordinary acupuncture, electroacupuncture, ear acupuncture, and so on. The common acupoints of acupuncture and moxibustion for the treatment of OCD are as follows: Baihui (DU20), Yintang (EX-HN3), Taiyang (EX-HN5), Neiguan (PC6), Sanyinjiao (SP6), Jiaji (EX-B2), and so on. It was found that acupuncture at Baihui (DU20) and Yintang (EX-HN3) points could effectively improve the behavior changes of rats with OCD, and its mechanism might be related to the decrease of 5-HT activity and DA content in the brain of rats with OCD. Some studies have shown that acupuncture or electroacupuncture is effective in the treatment of OCD, with faster effect and lower side effects than western medicine alone.In recent years, many clinical explorations of acupuncture and moxibustion in the treatment of OCD have made some progress.However, so far, there is no systematic review and meta-analysis evaluating the efficacy and safety acupuncture and moxibustion for the treatment of OCD. Thus, it is important to evaluate the efficacy and safety of acupuncture and moxibustion for OCD patients, providing reliable evidence for clinical application. However, the study has some limitations. There are certain heterogeneity due to the type of acupuncture and moxibustion and difference of acupoints. And only studies published in English and Chinese are retrieved, so important studies published in other languages may be missed.Data collection: Jingyu Xu and Yang Huang.Funding acquisition: Shenjun Wang and Ruiwen Song.Resources: Wen Wang and Xinju Li.Software: Chunying Tian.Supervision: Shenjun Wang and Ruiwen Song.Writing – original draft: Chunying Tian and Yihua Fan.Writing – review & editing: Chunying Tian, Shenjun Wang,and Ruiwen Song.


The present study aimed to evaluate the effects of physical activities on human health in forests in countryside and rural areas. The test experiment was conducted in a countryside forest, whereas the controlled experiment was conducted in an urban area where the study participants resided. A total of 22 participants (aged 20.9 ± 1.3 years) were evaluated in this study. Heart rate variability and salivary cortisol level were used as indices of physiological conditions, and semantic differential method, profile of mood states (POMS), and state-trait anxiety inventory (STAI) were used to evaluate the participants’ emotional states. The participants were asked to walk around forest and urban areas for 15 min. The results were as follows. As compared to the urban area, in the forest area, (1) the power of the high-frequency (HF) component of the heart rate variability (HRV) was significantly higher; (2) low-frequency (LF)/(LF + HF) was significantly lower; (3) salivary cortisol level was significantly lower; (4) the participants felt more comfortable, natural, relaxed, and less anxious and showed higher levels of positive emotions and lower levels of negative emotions. Consequently, walking in the forest area induces relaxing short-term physiological and psychological effects on young people living in urban areas. In the last several decades, due to compressive industrialization and modernization after the 1960s, Korea has achieved a rapid economic growth . AccordiTo solve this demographic problem, until the 1990s, the Korean government pursued policies for the development of agricultural and mountain villages, focusing on regional infrastructure maintenance (community facilities and housing) . Since tPrevious studies ,7,8 haveChamaecyparis obtusa, Cryptomeria japonica, and Pinus koraiensis. Among these, Chamaecyparis obtusa was reported to emit a relatively larger total amount of phytoncides as compared to other species [Chamaecyparis obtusa were reported to provide physiological relaxing effects [Recently, interest in ecology and health has continued to grow worldwide, and a number of studies have reported that natural and green spaces promote modern human health ,22,23,24 species . In addi effects , immunit effects , and ant effects . Based o effects .Rural tourism is a multi-faceted activity occurring in the countryside and it includes walking, climbing, adventure, and hunting . WalkingShort-term walking in the forest in rural areas will increase parasympathetic nervous activity.Short-term walking in the forest in rural areas will decrease sympathetic nervous activity.Short-term walking in the forest in rural areas will reduce salivary cortisol levels.Short-term walking in the forest in rural areas will reduce negative emotions .Short-term walking in the forest in rural areas will make one feel more comfortable, natural, and relaxed.In order to promote the rural health tourism, it is necessary to clarify the health promotion effects of rural visits. Therefore, the present study aimed to evaluate the effects of walking in forests in rural areas on human health. The hypotheses tested in the present study are as follows: Study participants were college students in their 20s who were urban residents and who volunteered to participate in the study. They were recruited through advertisements posted on campus bulletin board, social network service, and website. Exclusion criteria included smoking or taking any medications. The experiment was performed among a total of 24 healthy college students . All participants were fully informed about the experimental procedures and methods prior to participating in the experiment. The research was conducted according to the guidelines of the Declaration of Helsinki, and all experimental procedures were reviewed and approved by the Research and Bioethics Committee of Chungnam National University.This study was conducted in the forest area of Chukreong Mountain and the Daejeon metropolitan city as an urban area.Chamaecyparis obtusa (Siebold & Zucc.) Endl. and Cryptomeria japonica. This mountain comprises six walking trails  and rural tourism villages, which offer overnight accommodation and recreational activities. The Korean government designated some forests as healing forests, with themes of well-being, wellness, and relaxation, under the motto of “Welfare-to-Forest”.The Chukreong Mountain is located in Seosam-myeon, Jangseong-gun, Jeollanam-do, Republic of Korea . The ChuSome parts of Chukreong Mountain are designated as a healing forest and “national healing forest of Jangseong” and various health-enhancing activities using the fragrant smell of the forest and landscapes are available for visitors.The control site was an urban area in Gung-dong, Yuseong-gu, Daejeon metropolitan city, Republic of Korea . We seleChamaecyparis obtusa. The urban walking course was selected in the residential areas among houses and stores with few trees. All the selected walking courses were almost flat.The forest walking course was selected in the forest zone of HRV is a reliable measure of autonomous nervous system functioning using R–R intervals in heart rate (thereafter referred to as RRI) ,41. In tThe HF component was used as an index of parasympathetic nervous system activity, which is typically more active during relaxation. Higher HF values indicate a greater parasympathetic nervous system activity. The LF/(LF + HF) value was used as an index of sympathetic nervous system activity, which is typically enhanced in hypertension ,42. LF/ system. The Salivette® kit comprises a centrifuge vessel, a suspended insert, and a swab stopper. The swab from the kit was placed in each participant’s mouth, and approximately 2 mL of saliva were collected over 2 min. The kit was then frozen and tested for the quantitative measurement by Samkwangmedical laboratories, Republic of Korea, using enzyme immunoassay (EIA).Cortisol, a typical stress hormone, has been widely used as an index of stress levels , and itsAfter completing the walks, the participants completed three types of psychological questionnaires that asked them about their emotions, mood, and anxiety.The SD method  is widelThe profile of mood state (POMS) was used to evaluate psychological reactions. This study used a shortened version of POMS, which is a method to evaluate respondents’ emotions, such as “tension and anxiety”, “depression”, “anger and hostility”, “vigor”, “fatigue”, “confusion”, and “total mood disturbance (TMD)” using 30 questions ,48. TMD STAI-X  is a selField experiments were conducted in both forest and urban areas. The experiments were designed using the single-group crossover design . The phyEach experiment was conducted during a one-day field trip in sunny weather. All procedures of the experiment were conducted identically. The procedures are described in First, a waiting room was set up for the participants near the starting point of each walking course. In this room, all participants were informed about the experiment while they were waiting. Electrodes were then attached to their skin in this room. All participants walked for 15 min along each course at the same speed. The participants were asked to walk slowly, viewing the landscape of the given area. To obtain electrocardiogram (ECG) data, three disposable electrodes were attached to their chests before walking. ECG data were sequentially recorded by a portable electrocardiogram  while the participants were walking each course. After completing the walk, all participants then rested for approximately 3 min by sitting on chairs and filled in the three questionnaires .®  was placed in the participants’ mouths, and saliva samples were collected for 2 min.Salivary cortisol levels were measured at the end of the experiment to avoid the influence caused by any form of physical activity. To measure the cortisol levels in saliva, absorbent cotton for Salivettet-test with Holm’s correction was used to compare the differences in physiological responses for 1 min during walking in the forest and urban areas. Wilcoxon signed-rank test was used to analyze the differences in psychological responses between forest and urban areas. A one-sided test was used in this study. The significance level was set at p < 0.05.The data were analyzed for a total of 22 participants; 2 participants were excluded from the analysis . All statistical analyses were performed using Statistical Package for Social Sciences software version 21 . A paired 2 in the forest and urban areas, respectively. The HF values of the forest area were by 161.50% higher than that of the urban area  of HRV, which is an index of sympathetic nervous system activity, were 0.49 ± 0.03 and 0.71 ± 0.02 in the forest and urban areas, respectively. The LF/(LF + HF) value of the forest area was 30.99% lower than that of the urban area  value of HRV, which is an index of sympathetic nervous activity. These results are consistent with the previous findings that walking in the forest provides relaxation to the autonomic nervous system ,13,14. TThe results of psychological evaluations showed that forest environment can promote psychological relaxing effects. Walking in the forest in a rural area enhanced the participants’ feelings of comfort, naturalness, and feeling soothed, as well as reduced their negative emotions, such as tension–anxiety, depression, anger–hostility, and confusion. These results are consistent with those reported in previous studies ,22,23,24The findings of the present study strongly support the biophilia hypothesis , psycho-According to the attention restoration theory (ART), a period of prolonged mental effort leads to directed attention fatigue ,56. It cPrevious research suggested that quality is an important criterion of a green space . The quaThe integration of rural tourism with healthcare activities can solve the problem of modern people who suffer from continuous stress, thereby improving their physical, mental, and social health, and can help in overcoming the constraints of mountain villages. Promoting the health-enhancing effects of rural healthcare tourism is the key to help people understand rural healthcare tourism better and encourage their participation. The results of the present study provide scientific evidence in support of this conclusion.The present study has several limitations. First, we could not check the respiration rate of the participants. Respiration rate can affect measurements of HRV from the frequency domain . TherefoThe results of this study clearly revealed the relaxing effects of a short-term walk in the forest in a rural area. However, we do not know how long the effects would last. Therefore, follow-up studies that would estimate the duration of the effects are needed. For the mutual prosperity of mountain villages and urban areas, long-term projects need to be conducted to establish a well-organized database of scientific evidence based on forest resources.The results of this study indicate that, as compared to walking in an urban area, walking in a forest area increases parasympathetic nervous activity, decreases sympathetic nervous activity, and reduces cortisol levels in saliva. Moreover, walking in a forest area was found to make the study participants feel more comfortable, natural, relaxed, and vigorous, as well as to experience less anxious and negative emotions, as compared to walking in an urban area. In conclusion, walking in a forest area induces short-term relaxing physiological and psychological effects on young people living in urban settlements.


Dementia is one of the most common health problems affecting older adults, and the population with dementia is growing. Dementia refers to a comprehensive syndrome rather than a specific disease and is characterized by the loss of cognitive abilities. Many factors are related to dementia, such as aging, genetic profile, systemic vascular disease, unhealthy diet, and physical inactivity. As the causes and types of dementia are diverse, personalized healthcare is required. In this review, we first summarize various diagnostic approaches associated with dementia. Particularly, clinical diagnosis methods, biomarkers, neuroimaging, and digital biomarkers based on advances in data science and wearable devices are comprehensively reviewed. We then discuss three effective approaches to treating dementia, including engineering design, exercise, and diet. In the engineering design section, recent advances in monitoring and drug delivery systems for dementia are introduced. Additionally, we describe the effects of exercise on the treatment of dementia, especially focusing on the effects of aerobic and resistance training on cognitive function, and the effects of diets such as the Mediterranean diet and ketogenic diet on dementia. Dementia is the most common health problem in older adults. Worldwide, 47 million people have dementia, and this is expected to increase to 131 million by 2050 . This isParkinson’s disease dementia (PDD), which usually progresses from Parkinson’s disease (PD), is also a neurodegenerative disease. Similar to LD, Lewy bodies are abnormally deposited in the brain with PDD . FurtherMild cognitive impairment (MCI) is commonly caused by non-neurodegenerative processes. MCI is defined as having the ability to maintain daily function, but with lower-than-normal results in cognitive neuropsychological testing . The treThe diagnosis and distinction between different types of dementia are considered most important because the complexity and inconsistency of symptoms make the early stages of dementia challenging to distinguish. Dementia can be clinically characterized by progressive memory loss and impairment of cognitive functions or pathologically diagnosed by neuropathogenic changes. To date, practical methods of diagnosing dementia have begun with clinical approaches. There are several signs and symptoms, possibly indicating the need for evaluating dementia : (1) cogBased on the symptoms, a diagnostic sequence for dementia was suggested by Santacruz and Swagerty . Based oBiomarkers for dementia can be a promising option for the pathological diagnosis of dementia in early stages because they help objectively evaluate pathological sequences and disease progression in dementia ,23. Manyα-synuclein in the cerebrospinal fluid (CSF) can be used to differentiate LD from AD and healthy subjects. In a previous study, in patients with LD, α-synuclein levels were increased by 81.8% and 90% compared to control and AD groups, respectively . HoweverMiRNAs in biofluids can be used as a biomarker for neurodegenerative disease. They are present in all human biofluids with varying distributions . In a prOther actively investigated biomarkers for AD include nerve growth factor precursor proteins ,30,31, wOne popular source of biomarkers is blood samples. Blood can be easily extracted from patients at a low cost and provides a lot of information on bodily conditions. However, many biomarkers for neurodegenerative diseases do not exist at sufficient levels in the blood. To obtain pathological information regarding the central nervous system (CNS), CSF can be a candidate source for biomarkers of neurodegenerative diseases. The CSF surrounds the brain, and it protects and maintains the brain’s condition both physically and biologically.Biomarkers for dementia are the best indicators for pathological changes in the brain. The Aβ/tau/neurodegeneration (A/T/N) classification system, proposed by the National Institute on Aging and Alzheimer’s Association, provides meaningful information on cognitive decline and the risk of dementia . The Aβ Many studies have applied the A/T/N classification ,43,44,45Neuroimaging techniques that measure glucose metabolism, amyloid deposition, and the hippocampal volume on MRI are other approaches to diagnose AD ,50. NeurNeuroimaging can be structural, which includes computed tomography (CT) and MRI, or functional. AD, the most common type of dementia, can be differentiated by structural imaging based on brain atrophy in the medial temporal lobe (MTL). The MTL is present between multiple regions of the brain; thus, it is the interactive hub. It coordinates both learning and retrieval from the neocortex. Further, the hippocampus in MTL is related to spatial localization and associated with olfaction . Thus, lp = 0.022), which distinguishes between PD and AD, exhibits a significantly better performance in predicting MTL atrophy than the quantitative analysis of plaques (p = 0.375), tangles (p = 0.330), or Lewy bodies (p = 0.086). Additionally, the development of AD from MCI can be predicted by MTL atrophy with 73% sensitivity and 81% specificity -2-fluoro-2-deoxy-D-glucose, which is a glucose analog, is widely used in PET examination for brain disorders . Co. Co73]. Furthermore, many engineering technologies, such as neural interface technologies , electroDrug delivery system (DDS) refers to the technologies that optimize drug treatment by minimizing side effects and maximizing efficacy and effects by delivering the required amount of drug to the target . Ideal DSung et al. reported a flexible microdevice for drug delivery with controlled administration on a curved organ surface  89]. A . A 89]. 2) nanoparticle-mediated DDS using a computational biology approach to transport drugs through the blood–brain barrier (BBB) into the CNS [2. The α-synuclein activity with biocompatible metal nanoparticles was also used to compare the efficacy and inhibition of CeO2 nanoparticles. The fitting of CeO2 nanoparticles was optimized to the active site of α-synuclein with intimate contacts and interactions. The features of CeO2 nanoparticles that inhibit α-synuclein offer the potential for employment as nanodrugs to treat dementia resulting from PD.Kaushik et al. reported a cerium oxide  and increasing the intake of vegetables, legumes, fruits, and whole grains was associated with the improvement and prevention of decline in cognitive function in AD . MoreoveThe Mediterranean diet (MeDi) is one of the most widely described and studied dietary patterns . The MeDThe ketogenic diet (KD) is a very low carbohydrate and high fat diet. The KD converts the system from glucose metabolism to the production of ketone bodies and metabolism of fatty acids . KetosisDementia is a common disease that will affect an increasing percentage of the world’s population over the next 50 years. In this review, we provide several methods to diagnose and distinguish different types of dementia, including clinical approaches, biomarkers, and neuroimaging techniques. Furthermore, we have provided an overview of the treatments for dementia focused on nonpharmacological approaches including engineering design-assisted treatments, exercise, and diet.There remain several hurdles to be overcome before a personalized healthcare system can be applied to patients with dementia. For the diagnosis of each type of disease associated with dementia, biomarkers should be increasingly researched for improved diagnostic accuracy. Moreover, new types of biomarkers, such as digital biomarkers, can be used for constant monitoring of the patient condition. In addition, advances in engineering designs, including advanced materials and data science, are accelerating technologies for the diagnosis and treatment of dementia. However, further studies are required for dementia biomarkers to be valuable research tools. Exercise and diet treatments provide meaningful benefits in the management of dementia. Most previous studies for dementia were performed in animal models. Direct evidence regarding the impact of engineering technologies on dementia should be demonstrated in a clinical setting.


U-tests and logistic regression models were applied in the data analysis. Participants in the video group reported significantly more frequent headache (P = 0.01), fatigue (P = 0.00), memory loss (P = 0.03), inattention (P = 0.00), and higher level of depression (P = 0.05) than those in the control group. Additionally, the prevalence of memory loss  and inattention  were significantly higher in participants with higher level of depression who watched the video. Media warnings about the possible health hazards of MP use promote people to report physical symptoms and psychological problems. Considering this tendency, more moderate and scientific media information is needed to alleviate public worries about MP use.Along with gradually increases in mobile phone (MP) use, the mass media has played a vital role in informing the public regarding the potential health hazards of MP use. These media warnings have prompted public worries about health. The aim of the present study is to investigate the effects of media warnings about the possible health hazards of MP use on self-reported symptoms. Participants were 703 undergraduate students who volunteered to take part in an experimental study between August 2013 and July 2015. After completing baseline questionnaires containing information on demographics, MP usage and possible confounding variables, the participants were randomly clustered assigned to a video treatment group  or a control group. Then, they completed another set of questionnaires containing 6 self-reported physical symptoms and the Beck Depression Inventory (BDI). Chi-squared tests, Mann-Whitney  At the beginning of the twenty-first century, concerns about the safety of mobile phone (MP) use, environmental pollution, food, etc. have led to a generally heightened awareness of the effects of environmental changes on health . PervasiPeople usually get information from daily media, such as internet, TV, newspapers, magazines. People would seldom search for scientific articles or reviews for health information and look into the results and discussion. These would result in the misleading of people from the media and misinterpretation of media contents. Currently, the mass media plays a vital role in informing the public about the possible health effects of exposure to MP. It is very popular to obtain health information through the Internet, with over 50% of Internet users searching for health information . People In the meantime, scientists are increasingly concerned about the potential health effects of MP use. In some epidemiological studies, headache –14, dizzIn the present study, we investigated the effects of media warnings about the possible health hazards of MP use on self-reported physical symptoms. Additionally, we sought to study the moderation of a psychological factor on these effects.A between-group experimental study was performed between August 2013 and July 2015 at Third Military Medical University. This trial is an analyzer- and participant-blinded trial. Participants were recruited from among the freshmen of undergraduate students and written consents were obtained before experiment. After completing the baseline survey, participants were randomly clustered assigned to either the video or control group. Participants in the video group watched a 5-min video about the health effects of MP use and completed questionnaires containing physical symptoms and the Beck Depression Inventory (BDI). Participants in the control group completed the questionnaires for physical symptoms and the BDI without watching the video.The protocol of the current study was approved by the Third Military Medical University Ethical Committee. All participants who participated in the study completed a written consent form before baseline survey. This study and protocol were not pre-registered.A total of 703 participants were recruited from undergraduate students at Third Military Medical University. During recruitment, participants were informed that they would participate in a study on the relationship between mobile phone use and health symptoms. After obtaining written consent, the baseline survey by the questionnaires including the information on demographics, MP usage and possible confounding variables was conducted. Excluding uncompleted questionnaires, 685 (97.44%) participants were randomly clustered assigned to the video or control group. Of the received questionnaires for physical symptoms and the BDI, 674 (95.87%) valid questionnaires were used in the statistical analysis.Baseline survey questionnaire include three parts: The demographic information, MP usage and possible confounding variables. After participants were assigned to the video group and the control group, they were asked to complete another questionnaire including self-reported physical symptoms and BDI.The demographic information requested included name, gender , age, grade, home address, and telephone number.MP usage included ownership of MP, the years of MP usage, daily duration of MP calls and weekly number of MP calls. The ownership of MP was assessed by the following question: “Do you own a MP?” The years of MP usage was assessed by the following question: “How many years have you used MP?” The daily duration of MP calls was assessed by the following question: “How much time do you spend making MP calls daily?” Finally, the question “How many calls do you make weekly?” was used to assess the weekly number of MP calls. For all of the above questions, MP usage included the use of other people's phones.The self-reported physical symptoms included headache, dizziness, fatigue, memory loss, inattention and irritability, which were taken from the Zerssen complaint list , 34. TheDepression status during the previous week was evaluated using the 21-item version of the BDI, which is a self-report inventory created by Beck et al. . This inDaily physical exercise (yes/no), smoking (yes/no), and drinking (yes/no) as well as gender and age were considered to be confounding factors.In the video group, participants watched a 5-min video, which was made by an information technology professional colleague. The title of the video was “Electromagnetic radiation—a concealed killer around us.” This video included description of electromagnetic radiation in daily life, potential health effects of electromagnetic radiation, the present status of MP use, potential cancers related to MP and some results of the studies that have investigated the possible health effects of MP use. Video was narrated in Chinese, and the English translation for the video narrator was provided as supplementary material .Before watching the video, participants provided written consent and completed the baseline questionnaires for demographics, MP usage and possible confounding factors, such as engaging in daily physical exercise, smoking, and drinking. Then, they were randomly assigned to either the video group or control group. In the video group, participants watched a 5-min video on a block of all video group participants divided into three groups in three different classrooms playing the video in the class time. Participants in control group fill in the rest questionnaire without watching the video at the same time. After watching the video, participants completed another set of the questionnaires containing 6 self-report physical symptoms and the BDI items. In the control group, participants complete these questionnaires without watching the video. The procedure was shown in t-test was used to analyze normally distributed variable, such as age. Mann-Whitney U-tests were applied to analyze non-normally distributed variables, including years of MP usage, daily duration of MP calls, weekly number of MP calls and level of depression between the two groups. Logistic regressions were used to test whether increases in the prevalence of physical symptoms would be predicted by the higher level of depression, by watching the video or by the interaction between these two factors. The inclusion of interaction terms in the logistic regression models references the approach described by Witthöft and Rubin ], and categorical variables were generally summarized using the corresponding percentages. Statistical analysis was undertaken using SPSS version 19.0 .Chi-squared tests were used to compare the distribution of sex, daily physical exercise, smoking, drinking, MP ownership, prevalence of physical symptoms and the BDI score between the two groups. Student nd Rubin . StatistAmong the 703 undergraduate students recruited to participate in this study, 685 (97.44%) participants completed the baseline questionnaires and took part in the experimental portion. After the experiment, 674 (95.87%) valid questionnaires were returned and used in the statistical analysis.The participants included 544 males (80.71%) and 130 females (19.29%). The mean age was 22.69 ± 1.76 years. Nearly every participant (98.96%) owned MP at the time of the survey, and the average length of MP usage was 5.68 ± 2.03 years. Participants spent 18.97 ± 17.15 min per day on making MP calls and made 17.49 ± 2.05 phone calls per week, on average. The detailed distribution of demographics for the two groups is shown in P = 0.01), fatigue (P = 0.00), memory loss (P = 0.03), and inattention (P = 0.00) were significantly higher in the video group , followed by inattention (35.2%) and memory loss (30.9%). In the video group, all physical symptoms were more frequently reported than in the control group. Additionally, the prevalence of headache (eo group . Logistieo group .P = 0.05)  .P = 0.03, P = 0.00, To investigate the interaction effect on physical symptoms between depression and watching video, we estimated a logistic regression. The result showed that the prevalence of physical symptoms was higher among participants with higher level of depression who watched the video . AdditioAs MP is integrated into our lives, more news headlines have reported the health hazards of MP use. Thus, people start to worry about whether MP use is likely to endanger their health. We investigate the effects of media warnings about the health hazards of MP use on the self-reported symptoms of young adults for the first time in China. Our results revealed that watching a video about the health effects of MP use elevated the prevalence of self-reported physical symptoms, and this effect was stronger in participants with higher level of depression.In contrast to participants in the control group, participants who watched the video were significantly more likely to feel headache, fatigue, memory loss, inattention, and depression. Several previous studies have shown that people with long-duration MP use reported more physical symptoms –15 or deUnique findings from our study include several significant interactions between watching the video and the level of depression on self-reported physical symptoms. The BDI score in this study was 4.9 ± 6.7 and 5.2 ± 6.6 in control group and in video group, respectively. This BDI score is comparable with average population, such as young male military recruits in Brazil  , non-patThis experimental study is the first study to indicate that students who watched a video about the possible health hazards of MP use felt physical symptoms more frequently and reported higher level of depression in China. It adds evidence about the impact of the scary media effect from a Chinese student population. Based on similar previous research , the samOur results added evidence to the body of research on the effects of media warnings about the health hazards of MP use on physical and psychological health. However, several limitations should be noted. One of the main limits of this study is that most information about mobile phone use is based on self-reported information collected by questionnaire. To collect mobile phone exposure data by self-reported questionnaire is one of effective and convenient methods to collect information in epidemiological study related with mobile phone use and health which had been used before , 49. HowIn this study, based on similar mobile phone use background in two groups, watching a video about mobile phone health hazards resulted in more frequently reported health symptoms and higher level of BDI score. There is evidence that media warnings about the health hazards of MP use promote people to report physical symptoms and psychological problems in the present study. However, since few participants reported heavy and moderate symptoms, and seldom reported relatively high BDI scores, the effects of video are really minor. Greater collaboration between social media and scientific organizations is needed to provide more credible and pertinent health information about MP use.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by Third Military Medical University Ethical Committee. The patients/participants provided their written informed consent to participate in this study.Z-PY and LZ: conceptualization, funding acquisition, and writing—review and editing. PG, F-ZZ, and PD: formal analysis. PG, F-ZZ, M-DH, ML, and LZ: investigation. PG, F-ZZ, and LZ: methodology. PG, M-DH, and ZZ: validation. PG and F-ZZ: writing—original draft.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.