In this study, we investigated whether the levels of heavy metal and pesticide residues in herbal decoctions in Korea in 2019 were within normal limits. In total, 30 decoctions composed of multi-ingredient traditional herbs were sampled from traditional Korean medicine (TKM) clinics, TKM hospitals, and external herbal dispensaries in 2019. The decoctions were analyzed for heavy metal content such as lead, arsenic, and cadmium using inductively coupled plasma optical emission spectrometry. For mercury, an automatic mercury analyzer based on the gold amalgamation process was used. For pesticide residues, gas chromatography with electron capture detection and gas chromatography with mass selective detection were used for the analyses. Based on the testing, heavy metals were identified in most of the decoctions . Pesticide residues  were not detected at all. All of these were no more than the limit values in preceding studies. Therefore, this study confirms that the contents of heavy metals and pesticides in herbal decoctions are within safe levels based on a previous study and provides evidence for establishing safety management standards for herbal decoctions in Korea. Currently, the demand for traditional and complementary medicine (T&CM) is increasing . Herbal However, raw plants, which are the main ingredients of herbal medicines, are easily contaminated by various materials since they assimilate the elements in soil quickly through their roots . EspeciaIn the United States, these issues caused the United States Environmental Protection Agency to develop detailed step instructions in order to assess potential health risks . As for In Korea, herbal medicine manufactured by good manufacturing practice (GMP) company used in the Traditional Korea Medicine (TKM) institution, and the amounts of hazardous substances  in medicinal herbs are restricted by the Regulations on Limits and Test Methods for Residues and Contaminants in Herbal Medicines. TKM institutions in Korea must use medicinal herbs manufactured by the herb-GMP (hGMP) facilities that are licensed by the Ministry of Food and Drug Safety (MFDS) for safety . HoweverSeo  reportedSince 2020, the South Korean government has been implementing pilot programs to provide health care coverage to herbal decoctions. Despite decoctions being proved safe in history, there is no system to verify the safety of herbal decoctions, and there is a national demand for verification. Accordingly, the government is taking a leading role in implementing a project to establish the safety management criteria for herbal decoctions. The authors monitored the quality control of herbal decoctions as part of this project. As herbal decoctions are prepared in the three facilities  in Korea, the researchers collected the 10 most commonly used herbal decoctions in TKM institutions from TKM clinics, TKM hospitals, and external herbal dispensaries . In this study, we aimed to monitor the decoctions in Korea for heavy metal and pesticide residue contents and to prepare the evidence for establishing management standards at the government level.Based on the TKM Consumption Statistics Survey 2017, which is the official government statistics data, the researchers tested ten different decoctions, including Galgeuntang, which are prescribed commonly in TKM institutions to examine them for any heavy metal or pesticide residue contents [l-cysteine . HG-MHT and HG-BHT  were used as the additives for the analyses of mercury.For the heavy metal standard, the 1000 mg/kg  product was used. The standards for lead, arsenic, and cadmium were diluted using 0.5 M nitric acid  before use. The standard for mercury was diluted using 0.001% The standards used for testing pesticide residues were α-benzene hexachloride (BHC), β-BHC, γ-BHC, δ-BHC, aldrin, dieldrin, endrin, P.P-dichlorodiphenyldichloroethane (DDD), P.P-dichlorodiphenyldichloroethylene (DDE), O.P-dichlorodiphenyltrichloroethane (DDT), and for P.P-DDT, Dr. Ehrenstorfer  products were used. The solvents used in extraction and refining were acetone and methylene chloride, and n-hexane from Merck was used for pesticide residue analysis, while the Florisil Cartridges  for refining were from Waters (USA).For the testing of heavy metals, the testing solution was prepared in accordance with Korea Pharmacopoeia (KP) General Testing Process 30. Botanical Medicine Testing Method Item B. Heavy Metals Testing Method. As for the pesticide residues, KP General Testing Process 30. Botanical Medicine Testing Method Item C. Pesticide Residues Testing Method was used as the basis for preparing testing solutions .For some heavy metals, namely lead, arsenic, and cadmium, 10.0 mL of the sample was mixed with 20 mL of nitric acid, before standing for 30 min to remove the emitting gas. Subsequently, a wet pyrolysis device was used to conduct pyrolysis before it is cooled down to room temperature. The separated liquid was corrected to 50 mL using distilled water as the test solution. Separately, nitric acid 20 mL was prepared in the same way and was used as the blank test solution. For mercury, which is a heavy metal, 50 µL was measured exactly and added to the vessel for mercury analysis in the order of M reagent → sample (50.0 µL → M reagent → B reagent → M reagent) before conducting the analysis.As for the analysis of pesticide residues, 10.0 mL of sample was added to 15 mL of distilled water and 90 mL of acetone before homogenization and vacuum filtration. This filtered solution was transferred to a 500 mL separating funnel followed by the addition of saturated sodium chloride solution, 50 mL distilled water, 100 mL dichloromethane, and 70 mL and shook rapidly to mix. Then, the solution was left to stand for stratification. The dichloromethane layer was gathered, and 70 mL dichloromethane was added to the water layer and extracted for mixing with the dichloromethane layer. Next, this mixture underwent dewatering filtration with sodium sulfate anhydrous. The filtered solution was vacuum-evaporated at <40 °C and melted in 4 mL of hexane. For refining, the solution was added to an activated Florisil cartridge and extracted using hexane–dichloromethane–acetone mixture (50–48.5–1.5 mL). The extracted solution was added with 5 mL and melted in a 2-mL mixture of hexane and acetone (8:2) to conduct the analysis.For the analysis of lead, arsenic, and cadmium, an inductively coupled plasma optical emission spectrometer  was used. The instrument analysis conditions are presented in The recovery rate was measured as follows. First, a sample from which no analysis material was detected was selected. Then, a standard solution of appropriate concentration was added, and this process was repeated three times. With this, the difference between the concentration of the samples containing standard and the concentration of the control was calculated. The limit of detection (LOD) and the limit of quantitation (LOQ) were calculated using the following formula, on top of the method in which the standard deviation of the reaction and the gradients of the measurement graph were used as the basis and the measurement graph was based on the average of three repetitions of measurement of the standard solution in a stepwise manner. Recovery rate, LOD, and LOQ of analysis equipment are listed in * σ: the mean standard deviation* S: the individual slopThe test items and safety management criteria for heavy metals and pesticide residues were developed in accordance with the findings in literature reviews and consensus between experts. More details on the development process are presented in a previous study . As for In the analysis of 30 samples for their lead, arsenic, cadmium, and mercury contents, heavy metal contents were below the criteria in all the samples . The detRegarding total DDT, total BHC, aldrin, endrin, and dieldrin contents, pesticide residues were less than the detection limit in all of the samples.In the researchers’ previous study , a set oIn this study analyzing the heavy metal content in 30 decoctions, most of them contained heavy metals . As the detection limits identified in the previous study for TKM decoctions safety management criteria were, respectively, lead 5 ppm, arsenic 3 ppm, cadmium 0.3 ppm, and mercury 0.2 ppm, none of the 30 samples exceeded the criteria in any heavy metal items. Here, the detected levels of As, Cd, and Pb were lower than those in the previous study  . In Seo’ s study , no pestPaeonia lactiflora, and there was a regulation on herbal preparation separately, it was of little importance. PIC/S emphasized that regulation should be determined in accordance with the relevant current national or international guidance on quality. As we mentioned before, South Korea is required to follow several practice guidelines, so the regulation in South Korea should follow the international guidance quickly.South Korea is a member state of the Pharmaceutical Inspection Cooperation Scheme (PIC/S), and is required to follow the GMP, good laboratory practice (GLP), and good clinical practice (GCP) guidelines ,33. ThesIn the study of Yu et al. , 155 decRehmanniae radix preparata (熟地黃) and Rehmanniae radix (地黃) had the standards for testing benzopyrene. According to Yoon et al. [Our study had several limitations. First, the number of the samples included in the analyses insufficient to make this study available as the supporting evidence to introduce the standard set in the preceding study as a legal requirement. Thus, gathering and analyzing more samples in the future are necessary in order to verify the safety management criteria. Second, only the heavy metals and pesticide residues were analyzed, and sulfur dioxide, benzopyrene, aflatoxin, and micro-organism limits should also be analyzed. According to KP , Rehmannn et al. , 46.8% oOur study presents the status of herbal decoctions regarding the contamination with heavy metals and pesticides, which are within the safe range in Korea. These data provide the supporting evidence to set the safety management criteria for decoction. The researchers hope that more samples would be gathered and analyzed for their heavy metal and pesticide residue contents in order to establish the safety management criteria and successfully introduced a program on this.


Social determinants of health (SDH) are known to impact hospital and intensive care unit (ICU) outcomes. Little is known about the association between SDH and pediatric rapid response (RR) events and understanding this impact will help guide future interventions aimed to eliminate health disparities in the inpatient setting.The primary objective of this study is to describe the association between SDH and RR utilization . The secondary objective is to determine if SDH can predict hospital length of stay (LOS), ICU transfer, critical deterioration (CD), and mortality.A retrospective cohort study was conducted. We reviewed all RR events from 2016 to 2019 at a large, academic, pediatric hospital system including a level 1 trauma center and two satellite community campuses. All hospitalized patients up to age 25 who had a RR event during their index hospitalization were included. Exposure variables included age, gender, race/ethnicity, language, income, insurance status, chronic disease status, and repeat RR event. The primary outcome variables were hospital LOS, ICU transfer, CD, and mortality. The odds of mortality, CD events and ICU transfer were assessed using unadjusted and multivariable logistic regression. Associations with hospital LOS were assessed with unadjusted and multivariable quantile regression.p = 0.002). Families who are non-English speaking are also less likely to activate the RR system . LOS was longest for patients speaking languages other than Spanish or English and CD was more common in patients with government insurance. In adjusted logistic regression, Hispanic patients had 2.5 times the odds of mortality  compared with non-Hispanic white patients.Four thousand five hundred and sixty-eight RR events occurred from 3,690 unique admissions and 3301 unique patients, and the cohort was reduced to the index admission. The cohort was largely representative of the population served by the hospital system and varied according to race and ethnicity. There was no variation by race/ethnicity in the number of RR events or the shift in which RR events occurred. Attending physicians initiated RR calls more for event for non-Hispanic patients of mixed or other race (31.6% of events), and fellows and residents were more likely to be the callers for Hispanic patients (29.7% of events, Disparities exist in access to and within the inpatient management of pediatric patients. Our results suggest that interventions to address disparities should focus on Hispanic patients and non-English speaking patients to improve inpatient health equity. More research is needed to understand and address the mortality outcomes in Hispanic children compared to other groups. The Institute for Healthcare Improvement's “100,000 Lives Campaign” and other patient safety reports contributed to the development of rapid response (RR) systems as an effort to decrease morbidity and mortality associated with healthcare in the United States –4. In anTo our knowledge, no study has evaluated the correlation between social determinants of health, including race, ethnicity, language, or socioeconomic status with RR utilization or post-RR clinical outcomes. Evaluating these associations is imperative to assess the impact of RR systems for several reasons. First, health disparities remain prevalent among racial and ethnic minorities and those who primarily speak a language other than English, and are well-described in inpatient, emergency department, and outpatient settings. In pediatric intensive care units (PICUs) specifically, Latino children, children from families of lower socioeconomic status, or children with public insurance have higher risk of hospital mortality –13. RelaThis study aims to fill the gap in current RR system research by describing the association between social determinants of health, specifically race, ethnicity, language, and socioeconomic status, and RR utilization. Our secondary aim is to determine if social determinants of health predict critical deterioration events, hospital length of stay, or mortality after RR events.We conducted a retrospective cohort study of hospitalized children who had RR events from 2016 to 2019 at our large, academic, pediatric hospital system in the southwest United States. Our hospital system serves a diverse, multiethnic metropolis with a population of 57% Caucasian, 45% Hispanic or Latino, 22.6% Black or African American, and 7% Asian, Pacific Islander, and American Indian . The hosWe included all hospitalized patients up to age 25 who had RR events, cardiac and/or respiratory arrests from January 2016 to December 2019. All escalation of clinical concerns at our institution, including non-emergent transfers to higher levels of care, occur primarily through the RR process. Patients with RR events during their hospitalization were chosen in order to evaluate the effect of social determinants of health on in-hospital care.Data were collected from three sources: a centralized RR database, the electronic medical record (EMR), and the Pediatric Health Information System (PHIS) database, a national database of clinical data from over 49 children's hospitals. PHIS was created to collect administrative and financial data but has since included clinical, treatment, and outcomes-related data, among others . We exclExposure variables included age, gender, race/ethnicity, language, income, and insurance status. Race and ethnicity were self-identified by parents and were categorized as non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic, and non-Hispanic Mixed/Other. Insurance was categorized as commercial, government, and other/self-pay; income was stratified into quartiles. We also included chronic (complex vs. non-complex) and non-chronic disease status as defined by PHIS. Risk of mortality scores were also collected from PHIS to determine risk of mortality scores upon admission as a surrogate for disease severity. Each level retrospectively appraises the mortality risk  for each patient on the basis of the patient's age, diagnoses and certain procedures. We identified repeat RR events for the same admission and time from admission to RR. For RR-related variables, the shift in which the RR event occurred, and the primary caller for the event were collected.The primary outcome variables were hospital length of stay (LOS), ICU transfer, mortality, and critical deterioration (CD). CD was defined as meeting criteria for initiation of non-invasive positive pressure ventilation, intubation, or vasoactive infusion within 24 h of admission to the intensive care unit. We created a binary yes/no variable for critical deterioration within 24 h of ICU admission. Using the PHIS database, we calculated the total LOS for each admission, and defined mortality as death during the hospitalization in which the RR event occurred.t-test, Wilcoxon rank sum test, ANOVA, Kruskal–Wallis, Chi-square test, or Fisher's exact test. The odds of mortality, CD events, and ICU transfer were assessed using unadjusted logistic regression and multivariable logistic regression. Length of stay was assessed using unadjusted and multivariable quantile regression. Multivariable regression models included SES characteristics, risk of mortality score, chronic disease status, and time from admission to RR event regardless of statistical significance. Chronic disease status, mortality scores, and time from admission to RR event were included regardless of significance because of a known association with CD events and mortality. Other characteristics were included if statistically significant (p < 0.05) in unadjusted regression. Characteristics with more than 5% missing data were not included in the multivariable regression. All analyses are performed using Stata v 15 .Patient and RR characteristics and outcomes were summarized using mean with standard deviation, median with 25th and 75th percentiles, and frequency with percentage. Characteristics and outcomes were compared using There are a total of 4,568 RR events from 3,690 unique admissions with 83% of patients having only 1 RR event during the admission (range of 1–11 RR events in a single admission). There are 3,301 unique patients with 89% having only one admission in the study time frame (range 1–6 admissions). The cohort was reduced to one RR event per patient using the index RR event from the index admission .n = 104) were over 18 years of age. As expected, preferred language varies according to self-identified race and ethnicity with the highest proportion of Spanish speakers identifying as Hispanic (<0.001). Age, income, and metropolitan housing also varied according to self-identified race and ethnicity. The highest proportion of patients in the lowest income quartile are Hispanic (33.4%), and the highest proportion in the highest income quartile are non-Hispanic Asian . The highest proportion of patients with commercial insurance were non-Hispanic white (63.0%) and the highest proportion of government insurance were Hispanic (71%). Patients with complex chronic conditions accounted for 62% of the total number of patients, with the highest proportion among non-Hispanic Asian patients . Upon admission, the risk of mortality categories varied by self-identified race and ethnicity (p = 0.002).Patient characteristics for the index cohort are displayed in p = 0.002). Attending physicians most commonly call for patients who are English speakers . Among RR events activated by families, 88% (n = 66) were English speakers, 8% (n = 6) were Spanish speakers and 4% (n = 3) were other language speakers (p = 0.048).p = 0.005), and CD events were most common in patients with government insurance (37.6%) compared to those with private insurance (34.2%) or who are self-pay . p = 0.006). Hispanic race was associated with more than two-fold odds of mortality , but was not associated with increased odds of ICU transfer  or CD events . This association appears to be independent of language, as patients who prefer Spanish did not have increased odds of mortality. Patients with complex chronic diseases also had a significantly higher odds of mortality compared to patients with non-chronic conditions .Our study evaluated the relationship between social determinants of health and RR utilization at a large pediatric hospital system looking at over 4,500 RR events. As demonstrated in Similar to other published reports, we noted that Hispanics have increased odds of mortality and adverse events while in the hospital , 14, 19.We also noted that attending activation of RR is more common with English speakers. However, it is difficult to draw conclusions from this finding since the decision to call a RR can often reflect a collaborative decision process between the medical and nursing team at the bedside. Although only 17.7% of RRs were activated by attendings, there was no significant difference in the timing of the call (day shift vs. night shift). More studies are needed to evaluate if there is truly more attending communication with English-speakers vs. non-English speakers and to examine the language proficiency of the medical team with non-English speakers.Notably, our study found that among Spanish and other non-English speakers, families are less likely to activate the RR system suggesting that language barriers impede communication of clinical concerns and awareness of the RR system. This finding is like the study by Chandra et al.  which deOur study has several limitations, including the use of retrospective databases of a single hospital center . Unfortunately, our data does not demonstrate the severity of illness at the time of the RRT call, although we evaluated critical deterioration events after RR as a surrogate for illness severity in addition to using the risk of mortality score. However, the risk of mortality score was calculated at admission and not at time of RRT. Additionally, our data entry in our internal RR dataset limits the “caller” to one individual and fails to account for the collaborative process between the patient's family, nursing, and medical teams in the activation of an RR. Furthermore, although our study found an increased mortality in patients who had a primary language other than English or Spanish, there is a large confidence interval associated with this finding given the small number of patients included. Additionally, both language and ethnicity are self-reported in our data set and do not fully encompass the diversity represented in this large category. While our findings showed differences related to race and ethnicity, we acknowledge that these are constructs that may not fully grasp the complexity of social and environmental influence on health.Our study adds to the growing body of literature that demonstrates that health care inequities exist not only in accessing health care, but also within the inpatient utilization of response service and outcomes of pediatric patients. Based on our results, we suggest that patients who have primary languages that are not English be recognized as a high-risk population, with future efforts directed to improving communication and enhancing cultural competency in order to reduce their in-hospital risk.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Baylor College of Medicine. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.NL, DA, JB, AB, and NA: conceptualization. NL, DA, DG, AB, and NA: methodology. NL, DA, JB, DG, and NA: investigation. DG: data curation. NL, DA, AB, PC, and NA: writing. All authors have read and agreed to the published version of this manuscript.Publication costs were generously supported by the Texas Children's Hospital Young Investigators Endowed 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.


Studies with silicon (Si) in sugarcane indicate a greater response in productivity in plants under stress, and the underlying mechanisms of Si in the crop are poorly reported. In this context, the benefits of Si in the crop’s stem production are expected to occur at the C:N:P stoichiometry level in plant tissues, benefiting plants with and without stress. However, the extension of this response may vary in different soils. Thus, this research aimed to evaluate if fertigation with Si modifies the C:N:P stoichiometry and if it can increase sugarcane’s nutritional efficiency and vegetative and productive parameters. Therefore, three experiments were installed using pre-sprouted seedlings to cultivate sugarcane in tropical soils belonging to the Quartzarenic Neosol, Eutrophic Red Latosol, and Dystrophic Red Latosol classes. The treatments comprised a 2 × 2 factorial scheme in each soil. The first factor was composed without water restriction  and with water restriction . The second factor presented Si concentrations (0 mM and 1.8 mM) arranged in randomized blocks with five replications. Fertigation with Si increases the Si and P concentration, the C and N efficiency, the C:N ratio, and the dry mass production. However, it decreases the C and N concentration and the C:P, C:Si, and N:P ratios in sugarcane leaves and stems regardless of the water regime adopted in the three tropical soils. Cluster and principal components analysis indicated that the intensity of the beneficial effects of Si fertigation on sugarcane plants varies depending on the cultivation soil and water conditions. We found that Si can be used in sugarcane with and without water stress. It changes the C:N:P homeostasis enough to improve the nutritional efficiency of C, P, N, and, consequently, the dry mass accumulation on the stems, with variation in the different cultivated soils. On the sorption . SiliconSaccharum officinarum L.)  , 2022, aarum L.) . Howeverarum L.)  and biotarum L.) . There aarum L.) , 2022 anarum L.)  and 80 darum L.) . Howeverarum L.) , which coC)  . TherefooC) , Rhodic oC) ,2021b, aoC) ,b.Currently, researchers aim to reduce the amount of Si in crops using soluble sources via fertigation, favoring ion-root contact, increasing the plant’s Si absorption efficiency , and proIn this context, using soluble sources of Si applied via irrigation systems is a promising technique, and fertigation can improve the decrease in the polymerization rate and crop yield under water deficit conditions. According to In this scenario, it is pertinent to evaluate two hypotheses: first, that Si applied via fertigation is efficient and, after absorbed, is sufficient to modify the stoichiometric homeostasis of C, N, and P; and whether it is sufficient to increase nutritional efficiency and, consequently, if it would alleviate the losses in the dry mass production of leaves and stems of sugarcane cultivated under water deficit, or enhance the dry mass production of leaves and stems in the irrigated crop without water deficit, in different types of soil.If these hypotheses are accepted, it will be proven for the first time that the Si effect via fertigation on the C:N:P elemental stoichiometry is relevant. It favors not only the initial growth but also a more advanced stage in sugarcane. In other words, until stem production achieving agronomic importance. This finding should strengthen the Si agricultural use for the sustainable cultivation of sugarcane in tropical soils, in marginal regions with water restriction, and improve production in irrigated areas (without water restriction), where the cultivation of both sugarcane producing regions is growing in the world. Therefore, this research was carried out to evaluate whether Si fertigation can modify the C:N:P stoichiometry and whether this can increase nutritional efficiency and, consequently, the biomass production of leaves and especially stems of sugarcane cultivated with and without water deficit, depending on the soil.The study comprised three experiments with the sugarcane variety RB 962860 in a greenhouse at the Universidade Estadual Paulista “Júlio Mesquita Filho” (UNESP), Jaboticabal Campus, Brazil. The three experiments were independent and included three soil types: Quartzarenic Neosol (NQ); Eutrophic Red Latosol (Oxisol) (LVe); and Dystrophic Red Latosol (Oxisol) (LVd). The temperature and relative humidity inside the greenhouse were recorded using a thermo-hygrometer, showing a maximum average temperature of 45.6 ± 1.3°C, minimum of 26.8 ± 2.5°C, and relative humidity of 63.1 ± 6.3% .Rhyzobium meliloti in a 20 L polypropylene pot containing 18 L of soil sample during a 150-day cycle. The inoculation of the Rhizobium meliloti strain was used to aid in the biological fixation of N. After transplanting, the seedlings were pruned at 0.3 ± 0.02 m from the soil surface, to avoid water loss.The experimental design used in the three experiments was in randomized blocks, in a 2 × 2 factorial scheme, with two water conditions: without water restriction  and with water restriction ; combined with Si absence (0 mM) and presence (1.8 mM), in five repetitions. The experimental plot comprised a pre-sprouted seedling aged 60 days after the bud emergence and inoculated with The three experiments carried out the collection of soils from the surface layer of a native vegetation area. Then, the soil samples were dried in the open air and sieved with sieves (2 mm). Next, chemical analysis was performed for soil fertility using the method described by 2O5 mg dm–3 was used for Quartzarenic Neosol, Eutrophic Red Latosol, and Dystrophic Red Latosol, respectively. The dose used for nitrogen fertilization was 15 mg N dm–3 and, for K fertilization, 100 mg K2O dm–3. As for the micronutrients, 2 mg B dm–3 and 5 mg Zn dm–3 were used.Soil acidity was corrected 45 days before transplanting, correcting base saturation to 60%. Nutrient supply was performed via fertigation from phosphate fertilization 30 days after liming, nitrogen, potassium, and nitrogen fertilization of micronutrients in transplanting, and the topdressing at 76 days after transplanting N and K. For phosphate fertilization, a dose of 90, 70, and 50 PThe soil water retention capacity was determined for each soil by filling the pots (lysimeters) (20 L) with soil (18 L), with three replications and, later, placing them in a water tank filled with water (2/3 of the height of the pots) for a period of 24 h. Then, the pots were covered with plastic film, drained freely, and their mass was measured at 0, 24, 36, 48, 60, and 72 h after saturation. After draining the excess water, the water replacement capacity was determined through the difference between the wet and dry soil masses. Finally, the treatments’ gravimetric and volumetric moisture, soil density, and gross irrigation depths were calculated .In each experiment, two lysimeters were installed, one for each level of water retention in the soil (35 and 70%). The daily mass variation of the lysimeters was measured using load cells  with a 0.57 mm precision. Data were stored in a data logger  by connecting a differential channel multiplexer data acquisition system . Data logger data were extracted using the PC200W software interface. Every fifteen days, the measurement of the masses of the lysimeters was performed using a digital scale to adjust possible variations.The maintenance of soil moisture retention levels lost by evapotranspiration was performed manually every two days for 16–18 h. At 30 days after transplanting, the water retention level in the soil was maintained at 70% in all treatments. Then, two retention levels (35 and 70%) were installed. The installation of the 35% water retention was gradual, first reducing to 50% and, after seven days, to 35% of the soil’s water retention capacity.–1, 18.9 g K2O L–1, 100 mL sorbitol L–1, and pH 11.8). The pH value of the silicate solution was adjusted to 6.0 ± 0.5 using HCl 1 mM. Finally, potassium balance was performed using KCl fertigation (8.43 mg K L–1) in treatments without Si fertigation.Silicon fertigation was performed every two days using a source of sodium-potassium silicate stabilized with sorbitol at a concentration of 1.8 mM , HCl solution (0.3% v/v), and deionized water, respectively. Then, the samples were dried in an oven with forced air circulation (65 ± 5°C) until reaching constant mass, and, finally, the leaf dry mass (LDM) and stem dry mass (SDM) were determined.2O2 and NaOH) and the reading of the colorimetric reaction with ammonium molybdate using the spectrophotometer  of the LDM and SDM using the elemental analyzer (LECO truspec CHNS), calibrated with the LECO 502-278 standard (C = 45.0%). The P concentration was determined from the nitric-perchloric digestion and the spectrophotometer reading . The Si otometer .Carbon, Nitrogen, Phosphorus, and Silicon concentrations from leaves and stems were used to establish the C:N, C:P, N:P, and C:Si stoichiometric ratios. The C, N, P, and Si content were estimated for the leaves and stems from the product of the nutrient concentration and the dry mass of the studied organ.The C, N, and P use efficiencies in leaves and stems were estimated from the quotient of the square of dry matter and nutrient content (g of accumulated nutrient) .p < 0.05) and, when significant, the comparison test of Tukey mean (p < 0.05). In addition, a hierarchical cluster analysis was performed using the Euclidean distance as the similarity coefficient and the single linkage method as the group connection algorithm. Furthermore, principal components analysis (PCA) was performed using the correlation matrix. Finally, statistical analyzes were performed using the Python programming language .Data were submitted to preposition tests   and, latThe water deficit did not change the Si concentration in the leaves in the three tropical soils in the absence of fertigation with Si. However, there was a decrease in the stems of sugarcane plants cultivated in Quartzarenic Neosol and Eutrophic Red Latosol . RegardiThe C concentration in the leaves increased with the water deficit in sugarcane plants without fertigation with Si in Eutrophic Red Latosol. At the same time, there was a decrease in the C concentration in the stems in Dystrophic Red Latosol under PWD with the absence of fertigation with Si . RegardiThe water deficit decreased the N concentration in the plant’s leaves in the absence of fertigation with Si in Eutrophic Red Latosol. While in Dystrophic Red Latosol, there was an increase in this nutrient’s concentration . RegardiPhosphorus concentration in leaves and stems decreased with the water deficit in sugarcane plants without Si fertigation in Quartzarenic Neosol and Eutrophic Red Latosol. However, there was an increase in the P concentration in Dystrophic Red Latosol . The incThe C:N ratio in leaves increased with the water deficit in sugarcane plants without Si fertigation in Eutrophic Red Latosol. However, there was a decrease in this ratio in plants cultivated in Dystrophic Red Latosol . AdditioThe water deficit increased the C:P ratio in the leaves of plants cultivated in the three tropical soils without Si fertigation . There wThe water deficit did not change the C:Si ratio in the leaves of sugarcane plants without Si fertigation in the three tropical soils . HoweverThere was an increase in the N:P ratio in leaves and stems with the water deficit in plants without Si fertigation in the three tropical soils , except Water deficit decreased Si content in leaves and stems in sugarcane plants without Si fertigation in the three tropical soils, except for plants cultivated in Dystrophic Red Latosol . ConversCarbon content in leaves and stems decreased with the water deficit in the three tropical soils without Si fertigation . AdditioWater deficit also decreased the N content in leaves and stems in sugarcane plants without Si fertigation in the three tropical soils, except for stems in plants cultivated in Eutrophic Red Latosol and leaves in plants cultivated in Dystrophic Red Latosol . On the Phosphorus content in leaves and stems of plants was reduced with the water deficit in sugarcane without Si fertigation . FurtherThe water deficit reduced the C use efficiency in the leaves and stems of plants grown in the three tropical soils without Si fertigation . AdditioThe N use efficiency decreased with the water deficit in sugarcane plants without Si fertigation in the three tropical soils, except for leaves cultivated in Quartzarenic Neosol and Eutrophic Red Latosol . SiliconWater deficit increased P use efficiency in sugarcane plants without Si fertigation in Quartzarenic Neosol. However, there was decreased P use efficiency in stems in Eutrophic Red Latosol and Dystrophic Red Latosol . In PWD,The water deficit also decreased dry mass in leaves and stems in the three tropical soils cultivated without Si fertigation . AdditioThe hierarchical cluster analysis for leaves indicated that under water restriction conditions, without Si fertigation, there was greater dissimilarity from the other conditions evaluated in Quartzarenic Neosol. On the other hand, in Eutrophic Red Latosol, two groups were formed, dividing the two water conditions. In Dystrophic Red Latosol, the greatest dissimilarity was observed in the AWD treatment with Si fertigation .There were similar groups in leaves and stems for response variables, however, with a difference in the groups’ composition for tropical soils. For Quartzarenic Neosol, two groups were formed in leaves and stems: the first group comprised the subgroup of N and C concentrations and the C:Si ratio; and the second group comprised the P use efficiency and the C:P and N:P ratios. The second group also comprised two subgroups: the first subgroup comprising the content of C, N, P, the dry mass production, and the P concentration; and the second subgroup comprising the C:N ratio, the efficiency of C and N use, and the Si concentration and content, except for the P use efficiency, which was grouped in the second group in stems .In Eutrophic Red Latosol, there were two groups for leaves and stems: the first group indicated greater similarity between the C:N, C:P, and N:P ratios, the P use efficiency, and the C concentration; the second group comprised two subgroups, one with the N concentration and the C:Si ratio, and the second with the P and Si concentrations and the C, N, P, and Si contents, due to the C and N use efficiency and the dry mass production. However, there was a change in the C:N stoichiometric ratio and the P use efficiency for the second group in stems . For DysThe hierarchical cluster analysis indicated a greater dry mass production similarity with AWD treatment fertilized with Si in leaves and stems in the three tropical soils. It also found that Si fertigation in PWD showed similar results under AWD conditions in leaves and stems in Quartzarenic Neosol, and stems in Eutrophic Red Latosol . The C aThe stoichiometric ratios C:Si, C:P, and N:P are inversely proportional to the dry mass production, which showed high similarity with AWD treatment fertigated with Si in leaves and stems in tropical soils . The P uPrincipal component analysis (PCA) in leaves and stems explained 99.3 and 92.4, 98.6 and 98.2, and 98.1 and 96.9% of the variable responses of sugarcane cultivated in Quartzarenic Neosol, Eutrophic Red Latosol, and Dystrophic Red Latosol, respectively . In the In sugarcane cultivation in Quartzarenic Neosol, the C concentration is associated with the PWD treatment without Si fertigation and the C:N ratio with the PWD treatment with Si fertigation . The N uFor Eutrophic Red Latosol, there was an association of the C:Si and C:P stoichiometric ratios with the treatments not fertigated with Si in the two water conditions studied, while the Si and P concentration and the Si content are associated with the fertigated treatments in the two water conditions . FurtherFor the sugarcane stem cultivated in Dystrophic Red Latosol, PCA indicated an association of increased N concentration and C:Si, N:P, and C:P stoichiometric ratios with treatments without Si fertigation. However, N use efficiency, P and Si concentration, P and Si content, and the C:N stoichiometric ratio were associated with treatments fertigated with Si in both water conditions . Carbon There is a predominance of studies regarding water deficit in sugarcane crops without Si supply. They have reported losses in crop productivity, which is generally explained by damage to the plant’s physiological aspects . These wSilicon use is a known alternative to alleviate the water deficit in sugarcane crops, but this may depend on the crop’s ability to absorb this element. This fact favors sugarcane because it is classified as a plant that accumulates Si, having specific transporters in the roots and high efficiency in absorbing this beneficial element . AdditioIn order to ensure adequate silicate nutrition for the crop, most studies have evaluated its effects on stem production using Si in solid form with sources of very low solubility in water , implying the use of the element in high doses . HoweverIt is important to highlight that the soil’s water condition also influenced the Si fertigation efficiency. It led to a higher content of the element in the leaves and stems of plants without water deficit. In other words, plants under water restriction presented a loss in Si uptake , 3. The The Si supply in the soil can also positively affect the nutrients uptake, especially P in sugarcane in the stem production phase. However, these effects are almost unknown when the beneficial element is supplied via fertigation in different soil water regimes. The presence of Si in the soil can compete for binding sites in minerals, decreasing P uptake, consequently increasing this nutrient’s availability for plants . PhosphoAn interesting Si effect was observed regarding P absorption in the plant. The nutrient content in the leaves and stems promoted by the Si supply increased in plants cultivated in both water regimes, especially in Dystrophic Red Latosol and Quartzarenic Neosol . This reThe initial underlying benefit of Si on plant life may be involved in modifying the C:N:P stoichiometry, as there was previous evidence in a short-term study in the tillering phase in the sugarcane crop . HoweverThus, we found that the stoichiometric changes seen from the C:P, C:N, C:Si, and N:P ratios promoted by Si fertigation in the two water conditions, except for the C:P ratios in Eutrophic Red Latosol and, in AWD condition, in Quartzarenic Neosol, were sufficient to increase the C, N, and P nutritional efficiency , 5. It iThe Si role in sugarcane production is an important topic verified by many authors . HoweverOur study showed for the first time that fertigation with Si in sugarcane without stress was responsible for gains in leaf biomass, which reflected in stems in sugarcane plants cultivated in Quartzarenic Neosol and Eutrophic Red Latosol, except in Dystrophic Red Latosol . This reAccording to the multivariate analysis, under water deficit, there was something similar indicating a strong relationship between the C use efficiency and the dry mass production in leaves and stems in the three tropical soils studied associated with fertigation with Si. It revealed that Si increases C use efficiency to increase dry mass biosynthesis in plants. This effect is probably due to the plant’s metabolic economy strategy since C needs 10 to 20 times more energy than Si to be incorporated into the organic skeleton. A 1% increase in Si in the biomass composition promotes a C decrease from 1.3 to 5.9% .It should be noted that, for the first time, using soluble sources via fertigation with Si is also proven efficient in mitigating the damage caused by the water deficit regime in different soils , which iOur studies indicated a difference in the response of plants to the Si supply in different soils. Such effects reinforce that using the fertigation strategy with Si in a water deficit regime is more beneficial in tropical soils with low Si availability in the soil solution, such as Quartzarenic Neosol. The cluster analysis also confirmed the soil type effect on sugarcane cultivation, indicating that in Quartzarenic Neosol and Eutrophic Red Latosol, there were similar responses for Si fertigation for the variables evaluated in the stem, as it reduced the biomass losses with water deficit. Meanwhile, plants cultivated in Dystrophic Red Latosol were different. Our results show that dry mass production in the stem under water deficit conditions was associated with an increase in the Si concentration and content and a decrease in the C:Si and C:P stoichiometric ratios, especially in sugarcane plants grown in Quartzarenic Neosol and Eutrophic Red Latosol . It indiConsidering the results, it was clear that the first hypothesis can be accepted since Si, after fertigation application and uptake, is sufficient to modify C, N, and P stoichiometric homeostasis in leaves and stems. However, the second hypothesis tested can be partially accepted. Although Si induced stoichiometric modification, it was sufficient to increase nutritional efficiency and alleviate the losses in dry mass production of leaves and stems of sugarcane cultivated under water deficit. It also increases dry mass production of leaves and stems in the irrigated crop without water deficit, but it did not occur in all soils. In Dystrophic Red Latosol, Si benefits were limited to increasing stem production, especially in crops without water deficit. Therefore, Si use is not indicated in this soil type in properly irrigated sugarcane areas.Our discovery enables adequate Si use, via fertigation, to increase the productivity of the sugarcane crop under water stress and without stress, depending on the cultivated soil, allowing a better understanding of the underlying Si mechanisms involved.The biological losses caused by water deficit in sugarcane plants are related to the homeostatic imbalance of C:N:P, causing reductions in nutrient use efficiencies and directly impacting dry mass biosynthesis. Silicon becomes a viable agronomic alternative in sugarcane crops with water restrictions, reducing the biological losses of water deficit, modifying the homeostatic balance of C:N:P, improving the use efficiency of these nutrients, and improving plant performance. Using Si in sugarcane cultivation without stress also proved to be efficient in improving plant performance, alternating homeostatic nutritional balance, increasing the C, N, and P use efficiencies, and increasing the dry mass production of leaves and stems.The responses of sugarcane plants to Si application are limited depending on the type of cultivation soil, altering the intensity of responses to the benefits of the beneficial element. The strategic use of Si fertigation in a water deficit regime becomes more advantageous in tropical soils with low availability of Si in the soil solution, such as Quartzarenic Neosol. The research perspective is that Si can contribute to the sustainable cultivation of sugarcane in tropical soils in irrigated regions or under a water deficit regime.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.MdS and MC did the conceptualization, performed the data curation and formal analysis, investigated the data, performed the methodology, wrote the original draft of the manuscript and wrote, revised, and edited the manuscript. RdM and LP did the conceptualization, undertook the acquisition of funding, administration of the project, resources, executed the methodology, supervised the data, and wrote, revised, and edited the manuscript. JdS carried out the formal analysis, investigated the data, carried out the methodology, and wrote the original version of the manuscript. MdC carried out the acquisition of resources and financing and wrote the original version of the manuscript. All authors contributed to the article and approved the submitted version.


Parkinson’s disease (PD) is a multifaceted neurodegenerative disease. The optic nerve, as a window into the central nervous system (CNS), is known to be an important part of the CNS and can be detected non-invasively. With the widespread availability of optical coherence tomography (OCT) devices, an increasing number of studies have paid attention to the neuropathological disorders in the retina of PD patients in recent years. However, it is still controversial whether OCT can be used as a complementary tool for PD diagnosis.This review is registered with PROSPERO, number CRD42022301258. The Embase, PUBMED, and The Cochrane Library databases were independently retrieved by 2 investigators to identify relevant papers published from 1 January 2017 to 24 January 2022. These studies used OCT or OCTA to evaluate the difference in the retinal nerve fiber layer (RNFL) thickness, ganglion cell layer(GCL) thickness, macula thickness, Cup and disk area superficial retinal capillary plexus (SCP), and deep retinal capillary plexus(DCP). The standard mean difference (SMD) with the 95% confidence interval (CI) was pooled for continuous outcomes.P < 0.00001), GCL thickness , macula thickness  were significantly thinner in patients with PD. The SCP  was significantly lower in PD patients. The DCP  is lower in PD patients, but the difference was statistically insignificant.In total, 26 studies had been enrolled in this meta-analysis with a total number of 2,790 eyes, including 1,343 eyes from the PD group along with 1,447 eyes from the HC group. The results revealed that the RNFL thickness (SMD: −0.53; 95%CI, −0.71∼−0.35; Retinal nerve fiber layer thickness, GCL thickness, macular thickness, and SVD of PD patients are lower than those of healthy control. OCT and OCTA could detect morphological retinal changes in PD and might be objective and reproducible auxiliary tools to assist clinician diagnosis.https://www.crd.york.ac.uk/prospero/], identifier [CRD42022301258].[ Parkinson’s disease (PD) is often accompanied by severe degeneration of dopaminergic neurons within the substantia nigra pars compacta  and pathThe optic nerve, as part of the CNS , has a sThus, the main purpose of the present systematic review and meta-analysis was to evaluate the difference in the RNFL, macular, GCL, vessel density, and optic disk area between PD patients and health control. The study aimed to provide evidence for the reliability of OCT in the screening and diagnosis of patients with Parkinson’s disease.This review was registered at PROSPERO (CRD42022301258), and conducted with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . EMBASE,Under the guidance of the PICOS statement , two review authors (DY and LZQ) independently determined study eligibility using a standardized inclusion form. Only articles written in English-language were included. Inclusion criteria consisted of: (1) Original article. (2) All patients were clinically diagnosed with Parkinson’s disease and without the medical histories of neither glaucoma, retinal vein obstruction, or other eye diseases. OCT or OCTA was used to observe RNFL thickness as well as other morphological changes. People who matched the subjects for age, and gender were recruited as the healthy control group (HC). (3) Outcome indicators: RNFL thickness, GCL thickness, macular nerve fiber layer thickness, optic disk area. All measurement data are mean ± standard deviation (ME ± SD). (4) The study must be a randomized controlled trial, cross-sectional study, prospective cohort study, or retrospective cohort study. Exclusion criteria were as follows:(1) unclear research question, undefined study object, (2) basic experiments, case series, case reports, meta-analyses, systematic reviews, and commentaries, (3) unable to extract key information from the literature, (4) no control group or incomplete data, (5) did not match the purpose of this article.Based on the inclusion and exclusion criteria, each piece of literature was independently screened by 2 reviewers(DY and LZQ)and cross-checked. When meeting disagreement, it is necessary to discuss with another reviewer(WJW)to decide whether or not to include studies. The specific screening steps comprised three steps. Firstly, the reviewers would evaluate whether the title and abstract meet the inclusion and exclusion criteria. Secondly, the full text of the remaining articles would be further screened to evaluate whether they meet the eligibility criteria. Finally, two reviewers would check the literature included with each other. When meeting inconsistencies, another reviewer would resolve this problem and determine the inventory of the literature finally included. The extracted information from each study, including the first author, year of publication, study design type, sample size, the mean age of the patients, outcome, and so on, would be carefully and independently extracted by two reviewers.1 was used to perform the meta-analysis and draw the risk of bias plots. Instead of mean difference (MD), standardized mean difference (SMD) alone with a 95% confidence interval (95%CI) will be used to assess the continuous outcome, because measurement scales of OCT equipment were consistent between studies. p < 0.05 indicated a significant difference, on the other hand, testing for heterogeneity among the included studies was evaluated by the chi-square-based Q test and the I2 statistics. When P ≥ 0.1 and I2 ≤ 50%, the possibility of heterogeneity was low and the fixed effect model was adopted. When P < 0.1 and I2 > 50%, the possibility of heterogeneity was high, and the random effect model was adopted. Using egger’s test to judge publication bias when P > 0.1 indicated that there was no publication bias. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies for cohort studies.RevMan version 5.3 softwareThe initial search strategy of the four databases retrieved 126 publications in English. A flow diagram of the study selection process is summarized in I2 = 74%). After removing articles one by one, the heterogeneity remained substantial, therefore a random-effects model was used for the analysis. The results indicated that RNFL thickness in the PD group was significantly thinner than in the HC group . Additionally, the result is consistent with that of the most included studies (P = 0.0001);; ;] ] . The EggI2 = 76%). After removing articles one by one, the heterogeneity remained substantial, therefor a random-effects model was used for the analysis. The results indicated that GCL thickness in the PD group was significantly thinner than in the HC group . Additionally, the result is consistent with the 4 included studies , so the random-effects model was used for the analysis. The results indicated that there was no statistically significant difference in a cup and disk area among the PD group and the HC group .In total, 2 studies had been enrolled in this meta-analysis with a total number of 144 eyes, including 69 eyes from the PD group, and 75 eyes from the HC group , 5. FirsI2 = 0%), so the fixed-effects model was used for the analysis. The results indicated that macula thickness in the PD group was significantly reduced compared with the HC group . Nevertheless, there were only two studies consistent with our finds . After removing articles one by one, the heterogeneity remained substantial, therefore the random-effects model was used for the analysis. The results indicated that SCP in the PD group was significantly lower than in the HC group . Furthermore, a meta-analysis of SCP in superior, inferior, nasal, and temporal quadrants showed that SCP in the PD group of all quadrants, especially in nasal quadrants, was significantly lower than in the HC group  (P = 0.09) ] . However = 0.09) . The EggIn the present meta-analysis, we directly assessed OCT parameters such as the RNFL thickness, GCL thickness, macula thickness, etc., to evaluate neuropathological changes in PD patients. PD patients are often accompanied by visual symptoms such as visual illusions and minor hallucinations. A post-mortem study revealed that retinal dopamine content was reduced in PD patients , and theThe present study found that RNFL, GCL, and macula thickness are thinning in PD patients, moreover, OCT can reliably classify the PD patients according to retinal changes. Structural and functional retinal changes, such as thinning in RNFL thickness, have been described in a variety of neurodegenerative diseases like multiple sclerosis and Alzheimer’s disease , suggestAs a promising non-invasive technique that can be used for imaging the microvasculature of the retina, optical coherence tomography angiography (OCTA) enables doctors to get a quantitative and rapid characterization of the retinal capillary in different layers . OCTA caP < 0.05). Inflammation is the key pathogenesis and potential therapeutic target of PD (P < 0.05), while superior and temporal DCP had no significant difference. DVD is greatly affected by projection artifacts and different OCTA devices are probable to have different OCTA algorithms (There is limited literature on retinal microvascular disorders in patients with PD, by OCTA scanning. As far as we know, this paper is the first systematic review of retinal microvascular density in patients with PD by OCTA scanning. The present study found that the SCP in PD patients was lower than that of the HC group. The result is in good agreement with former studies , 34, 36.et of PD ; α-synucet of PD . The decet of PD  reportedet of PD , and theet of PD . OCT in gorithms , this coAccounting for decreased RNFL thickness with advancing age, the average RNFL thickness decreased at a range of 0.4 μm per year . There wHowever, the following limitations still exist in this study. First, retinal thickness is correlated with retinal dopamine concentrations. It is unclear whether dopaminergic medications have any effect on measurements obtained from OCT or OCTA. As an effective treatment for PD patients, dopaminergic medications are the drug of choice to relieve motor and non-motor symptoms of PD patients. Additionally, a majority of the included studies didn’t illustrate whether PD patients take dopaminergic medications, which may lead to bias in the results and consequently affect the accuracy of it. This may be the reason for the differences in the results of different studies. Second, different OCT devices of different manufacturers have different scanning strategies  which leRetinal nerve fiber layer thickness, GCL thickness, macular thickness, and SVD of PD patients are lower than those of healthy control. Serving as supplementary diagnostic tools, OCT and OCTA could detect early morphological retinal changes in PD and might be objective and reproducible auxiliary tools to assist clinician diagnosis. In the future, OCT and OCTA can be used to judge the progression of PD.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.CJ contributed to the conception and design of the study. JW, ZL, XH, and YL retrieved the articles and organized the database. YD performed the statistical analysis and wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.


This study aimed to examine the potential effectiveness of personalized nursing interventions on improving the heart-related quality of life of patients with CVDs versus an usual care. Data Sources. The study researched the article between January 2011 and December 2021 from four electronic databases: PubMed, Embase, Cochrane library, and Web of Science. Review Methods. Randomized controlled trials (RCTs) related to personalized nursing in CVDs population were included. The main variables were analyzed by standardized mean differences with 95% confidence intervals and heterogeneity was used by the I2 test and P value.  A systematic review and meta-analysis. P = 0.000, I2 = 66.1%) which needs to be further subgroup analyzed. The nurse-led intervention was considered the main-related effect to influence the heterogeneity with value of 0.39 ; SMD = 0.21, 95% CI ; SMD = 0.39, 95% CI  and SMD = 0.28, 95% CI ].  Of 734 studies, fourteen articles were eligible for this study. Personalized nursing significantly improved the quality of life  with obvious heterogeneity ( Effectiveness studies of personalized care focus on more relevant outcomes have higher health outcomes, whereas evidence of the effectiveness of personalized nursing approach is still limited. Therefore, more and more high-quality RCT are needed. Cardiovascular diseases (CVDs) is the main reason for mortality with more than 17 million deaths each year  and responsible for one-third of the deaths worldwide. In particular, 80% of CVD-related deaths were recorded and increasing in low- and middle-income countries .Health-related quality of life covers multidimensional domains that are linked to the physical, emotional, psychological, and social functions which has the important role in the prevention of chronic disease relapse like cardiology sequel . QualityFor CVDs, some patients may ignore its continuous treatment throughout life and compliance behavior mainly by motor disturbances and emotional caring following their discharge from a healthcare institution, therefore, in order to improve the health status and treatment outcome related to quality of life, it is necessary to apply nursing theories integrated care interventions in patients after-treatment , 8. The It should be noted that intense care by nurses for CVDs has contributed immensely in the complete success after hospital treatment . As we kThe study was reported following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020). We registered the study on PROSPERO under the registration number (CRD42022354872).The electronic network databases were researched in PubMed, EMBASE, Web of Science, and the Cochrane Library. The retrieval teams were mainly based on a combination of MeSH subject words and related-free words.st, 2011 to December 31st, 2021. The detailed full electronic search strategy of Embase is shown in supplementary file. . With “Nursing” OR “Nursings” OR “Caring” OR “Empathy” OR “Compassion” as the intervention searched terms. The type of study was limited “randomized controlled trial (RCT) OR placebo” in English. The measurement of outcome used for “Quality of life OR Health-Related Quality Of Life” in English and so on. Reference lists of studies and relevant systematic reviews were manually screened to identify further eligible research. The retrieval type or blinding were not limited, and the research time was conducted from January 1ry file. .(1) Studies on patients with related cardiovascular and cerebrovascular diseases who were diagnosed by coronary heart disease, hypertension, heart failure and so on. There were no age or gender limits; (2) the intervention group was treated with personalized care, while the control group was treated with usual care; (3) the primary outcome was health-related quality of life as measured by reliable and validated instruments, with athletic ability and mental health as secondary outcomes (details of the indicators were shown in “Outcome indicators”).(1) Non-RCTs; (2) systematic reviews, meta-analysis, case reports, meeting abstracts, animals tests, and related commentaries; (3) inconsistent, incomplete, or ambiguous baseline data on disease and other associated characteristics of the participants; (4) Lack of original data, only partial abstracts or data provided, no full text, or no response to contacting the author.The intervention group was treated with personalized care, such as education, follow-up, rehabilitation exercise and so on. Meanwhile, the control group received only usual care(1) Primary Outcomes. The retrieved studies contained primary and secondary indicators, with quality of life being the primary outcome measured in reliable and valid scales. The quality of life was measured at the time of baseline and the end of intervention, based on reliable and valid scales that have been used around the world including the following scoring tools: the 36-Item Short Form Health Survey (SF-36), SF-12, and WHOQOL-BREF.SF-36 is a set of generic, coherent, and easily administered QOL measure. Its measures rely on patient self-reporting and are widely utilized for routine monitoring and assessment of care outcomes in adult patients. It comprises 36 questions which cover eight domains of health: physical activities, social activities, usual role activities, bodily pain, general mental health , usual role activities, vitality (energy and fatigue), and general health perceptions. Each scale is directly transformed into a 0–100 scale on the assumption that each question carries equal weight. The lower score means that the more disability.WHOQOL-BREF, World Health Organization Quality of Life project 26-item instrument. The lower score means that the more disability.(2) Secondary Outcomes. The secondary outcome measures with caring-related outcome included QOL-related outcomes like athletic ability, mental health, and the intervention methods like follow-up and education.After the selected studies were extracted and imported into Note Express for electronic and manual duplicate checks,  two reseI2 statistic and P value to evaluate heterogeneity among the studies. If the outcome indicator is a continuous variable, we used the standardized mean difference (SMD) or mean difference (MD) and 95% confidence interval (CI) to analyze the studies. The MD and SMD were used as a summary statistic if all trails collected the same outcome indicator by the same scale. According to the results of quantitative analysis, we considered P < 0.05 and I2 < 50% to be statistically significant that meant good agreement and the fixed effect model was chosen.Extracted data were analyzed by the Stata 16.0 software to perform meta-analysis. We used the chi-square test and the To test the stability of the meta-analysis results of each index, we used the one-by-one elimination method to analyze the sensitivity of the main outcome indicators. To test the stability results of each index, a sensitivity analysis was conducted to investigate the potential source of heterogeneity and determine whether the final conclusion of the research is for a specific method or research design features used. We will further explore the effect of different detailed care approaches and related outcome indicators and other factors. They are analyzed based on the apparent homogeneity of results that can be qualitatively measured. Stata 16.0 software was used for sensitivity analysis, subgroup analysis, and sensitivity analysis and charts were drawn.Funnel chart is used to evaluate whether there is publication bias and Begg's test is used for the evaluation of potential publication bias.n = 24, Web of Science: n = 316, Embase: n = 154, Cochrane: n = 240). The retrieved articles were recorded in Note Express and 128 duplicated papers have been excluded by automatically screening. In addition, inappropriate studies like reviews, meta-analysis, and animal mechanism experiments (n = 156) were removed after reading the titles and abstracts. Furthermore, articles that did not meet the study inclusion standard, including 379 studies with inconsistent content, 36 studies with unreasonable design, and 21 inconsistent outcome indicators, they were eliminated after reading the full text. Finally, 14 documents were included in the quantitative meta-analysis.n = 844 and control group: n = 718) covering the period from 2011 to 2021. The researched subjects were patients who were diagnosed with related cardiovascular disease, and there was no significant difference between groups for these outcomes. The age of patients varied from 18 to 85 years. The duration of intervention ranged from ten weeks to one year. Quality of life was categorized as a primary outcome measurement in all trials. The intervention group received the personalized care while the control group received the usual care or routine care. The included studies were conducted in the all of world, and all of the outcomes of quality of life were scored using reliable and valid ranking scales. The included studies had a total of 1562 patients ; thus, the random effects model was used to analyze the data  and control care . 14 studies involving 1562 patients (844 patients in the intervention group and 718 patients in the control group) showed that, compared to the control group, the meta-analyses indicated that personalized care improved the level of quality of life , and there was obvious heterogeneity , suggesting that nurse-led intervention as a treatment may influence the heterogeneity and improve the QOL among cardiovascular disease patients. The results of the subgroup analysis could be carried out and found in In this meta-analysis, the nurse-led intervention was considered as the main related effect to influence the heterogeneity, and the two subgroups  indicated that they were extremely heterogeneous. There was no heterogeneity within each subgroup as shown by an effective value of 0.39 , thus, fixed effects model was applied for data analysis. The results indicated that the intervention group had higher quality of life than that in the control group by focusing on improving athletic ability, which showed a statistically significant difference  ] .I2 = 26.4%, P=0.237) and the fixed effects model was applied for data analysis. The results indicated that the intervention group had higher level of quality of life by increasing mental health, which showed a statistically significant difference  ] .2 = 26.2%, P=0.229) and a fixed effects model was used. Meanwhile, a positive influence on improving quality of life was noted after the follow-up intervention  ] .I2 = 49.5%, P=0.078); therefore, a fixed effects model was used. The analysis showed a significant improvement effect on QOL in the intervention group compared to the control group by education care intervention  ] .X = 0 vertical line, suggesting that publication bias and small sample effects are less likely.  . In the According to the findings of our study, personalized nursing related the detailed approach of educational management and follow-ups can be effective in improving the quality of life of CVDs patients. For CVDs patients, the medical focus changes from “cure” to “care” which includes providing education support to families who usually provided detailed information and practical skills by using patient-directed goal setting and introducing the experience of role models that facilitated the participants' confidence in improving the health situation . ObviousIn this meta-analysis, we performed a detailed classification and analysis of the intervention group which will enhance reproducibility of the intervention. Meanwhile, this work included the inclusion of only RCTs, two authors assessed study quality ratings, adverse events were analyzed using the Cochrane and Grade, and subgroup analyses were performed to identify potential associations between intervention nursing methods and quality of life.While this systematic review still has some limitations, firstly, due to many different specific established standardized intervention caring regimens and contain a small size of participants identified will increase the uncertainty of generalizability of these studies. In addition, most studies had follow-up care of no more than 1 year with being lacked the long-termfollow-up data, therefore, we did not perform the meta-analysis to assess the long-term effect of the improvement of quality of life for CVD patients. Finally, the QoL is a kind of subjective data, which are influenced by many factors such as the situation of understanding or communication and prone to be biased.Nurse-led disease management program appears to be effective in improving the quality of life for patients with CVDs. Our study reviewed new and valuable insight from patients and nursers on the post-treatment of those CVDs primary care providers. This meta-analysis showed that patients with personalized caring who attended this program revealed higher levels of quality of life, physical activity, and emotional activity compared with the usual caring. However, the promising results should be cautiously interpreted and generalized. Large-scale, prospective, randomized controlled trials are still needed to verify the preliminary findings of the current study.


There is limited evidence regarding the impact of pregnancy loss on the subsequent risk of metabolic disorders. We aimed to investigate whether history of pregnancy loss is associated with the subsequent risk of prediabetes (pre-DM), diabetes (DM), and metabolic syndrome (METs) among couples.In this population-based cohort study, 2765 couples with and without history of pregnancy loss and free of DM, pre-DM, and METs at baseline were included and followed for incidents of DM, pre-DM, and METs by 3-year intervals visits from 1999 to 2018. Detailed data of variables was collected using standard questionnaires, interviews, clinical and laboratory assessments. A modified Poisson regression for binary outcome data with a log link function and robust error variance was used to estimate relative risks (RRs) in couples with and without history of pregnancy loss. Both unadjusted and adjusted models were fitted, and effect measures were calculated.During a median follow-up of 15 years, females with history of pregnancy loss were experienced more pre-DM (50% vs. 45.5%), DM (28.9% vs. 21.3%), and METs (70% vs. 60.1%) than females without such history. Moreover, history of pregnancy loss increased the risk of METs by 8% among females. The incidence of DM in males with history of pregnancy loss in their spouses was higher than in males without it (28.8% vs. 23.5%). Among males, having a spouse with history of pregnancy loss was positively associated with the risk of pre-DM ; furthermore, they were more prone to the risk of METs than females with a history of pregnancy loss .Although pregnancy loss is a female-specific factor, may foreshadow the subsequent METs, our study identified a higher risk of subsequent pre-DM and METs in males with history of pregnancy loss in their spouses. Pregnancy loss could be considered a possible future risk factor for metabolic disorders in couples. Metabolic syndrome (METs), diabetes mellitus (DM), and prediabetes (pre-DM) are the leading health problems around the world –3 and coIt is well established that each pregnancy poses a diabetogenic effect on maternal metabolism . Indeed,The spousal concordance of cardio-metabolic risk factors received more attention in recent literature , 23. A cThe exact mechanisms related to the adverse pregnancy outcomes and disease risk in couples later in life remain incompletely understood. It has been proposed that rather than biological factors related to pregnancy, some non-biological factors contribute to an increased risk of chronic disease in males and females . ConcordPregnancy loss is among the most common complication of pregnancy and might be a stressor event for both parents ; as a reIn the present study, we aimed to investigate the risk of pre-DM, DM, and METs in couples with pregnancy loss history in a population-based cohort study with, on average, 15 years of follow-up.This study has been undertaken using data from an ongoing population-based longitudinal Tehran Lipid and Glucose Study. The protocol of TLGS was developed according to the World Health Organization approach for surveillance of risk factors for non-communicable diseases . The basIn the present study, among a total of 20,145 subjects in TLGS, there were 3,650 matched couples. Regarding the female participants, we chose individuals who met the following criteria: married females aged > 18 at baseline, females whose spouses had complete records of variables, and females without DM, pre-DM, and METs at baseline and before exposure to pregnancy loss. Also, the inclusion criteria for males include married males aged > 18 at baseline, males whose spouses had complete records of variables, and males without DM, pre-DM, and METs at baseline and before exposure to pregnancy loss in their spouses.After exclusion of those with history of pre-DM (n = 4), DM (n = 4), or METs (n = 9), and couples with no pregnancy (n = 79), finally, 3,554 couples remained eligible for the present analysis. Of the remaining participants, 1585 have history of pregnancy loss. In order for the percentage of women with history of pregnancy loss to represent the community (around 25% to 30%), we selected a random sample of these women (n = 796). Eventually, 2765 couples, including 1969 women who had never experienced pregnancy loss and 796 women who had experienced at least one pregnancy loss over the follow-up, remained in this study  , which wContinuous variables were checked for normality using the Shapiro–Wilk test; those with normal distribution were expressed as mean (standard deviation), and non-normal distributed variables were expressed as median (interquartile range). Categorical variables were expressed as percentages. Characteristics of participants were compared between the pregnancy loss categories by applying the independent t-test or Pearson’s Chi-squared test for continuous and categorical data, respectively. The Mann–Whitney U test was applied to compare variables with skewed distribution.For this study, we do a post hoc analysis, which involves looking at the data after a study has been concluded and trying to find patterns that were not the primary objectives of the study. TLGS was initiated in 1999 to investigate non-communicable disease (NCD) and its associated risk factors or determinants among a representative family-based population of Tehran, the capital of Iran; however, in this study, we aimed to discover the impact of pregnancy loss on the subsequent risk of metabolic disorders among couples.A modified Poisson regression for binary outcome data with a log link function and robust error variance was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the associations between pregnancy loss and incidence of pre-DM, DM, and METs in males and females over the follow-up . We consIn the present study, 2765 couples were included. Among those pairs, 1969 (71.2%) had no pregnancy loss, and 796 (28.8%) experienced at least one pregnancy loss. Among couples with history of pregnancy loss, those with only abortion history were 618, only stillbirth history were 42, and those who experienced both types were 136 couples.The total median (IQR) follow-up time was 15 (10–16) years which was 14 (8–16) years, and 15 (11–16) years for males and females, respectively.Tables The incidence of outcome variables pre-DM, DM and METs in females with history of pregnancy loss increases compared to females with no pregnancy loss (50% vs. 45.5% for pre-DM (p = 0.03), 28.9% vs. 21.3% for DM (p < 0.001) and 70% vs. 60.1% for METs (p < 0.001)). Moreover, there was a significantly higher incidence of DM outcome in males with history of pregnancy loss in their spouses compared to males with no history of pregnancy loss in their spouses (28.8% vs. 23.5% (p = 0.004)) ; however, after adjustment for confounders, this association just remained significant for METs. There is limited study in terms of determining the subsequent risk of DM in women with history of pregnancy loss , 21, 46 Moreover, our study showed that males with a history of pregnancy loss or abortion in their spouses were more likely to experience METs and per-DM than females. This may be explained by the impact of the paternal metabolic conditions on pregnancy loss. Kasman et al. reported that in men with increasing components of METs in the preconception period, the risk of pregnancy loss was significantly increased . As a reThe exact underlying pathophysiology of an association between pregnancy loss and DM and METs is unknown. It is established that gut microbiota triggers metabolic inflammation and subsequent metabolic disorders –59. All The findings of this study should be interpreted in the context of weakness and strength. This study was conducted on a longitudinal cohort study with a large number of participants that were followed on average for 15 years. All variables were measured based on a standard protocol with several follow-up visits with 3-years intervals. We adjusted the results based on most potential confounders. Our study has several limitations as well. There is a number of biases concerning study design in terms of indication bias. This is a cohort study which was conducted on an urban population, so the observed effect may be exaggerated, and findings from the research population may not apply to the rural population. The visit intervals were 3-years, and we could not capture shorter variability estimates of metabolic conditions. The length of the time after losing a pregnancy may affect the outcome; since we have no data on the exact date, we assumed the outcomes occurred in the mid-time interval. Diet and nutrition status might influence the metabolic profile, which was not considered in the present study. Moreover, in our study, data related to physical activity were drawn from a questionnaire, which tends to be overestimated by individuals . In this study, we have no data on the genetic background of participants, which may affect the risk of metabolic abnormality. There was no data on lifestyle and psychological situation during and before pregnancy as potential influential factors.Although pregnancy loss is a female-specific factor, may foreshadow the subsequent METs, our study identified a higher risk of subsequent pre-DM and METs in males with a history of pregnancy loss in their spouses. Pregnancy loss could be considered as a future risk factor for metabolic disorders in couples. Despite well-documented impact of some pregnancy complications in developing chronic disease in later life, long-term preventive care for those couples with such history of adverse pregnancy outcomes is lacking . This is