The efficacy and safety of sacubitril/valsartan for patients with heart failure with preserved ejection fraction (HFpEF) are controversial. Hence, the primary objective of the study was to evaluate the efficacy and safety of sacubitril/valsartan treatment for patients with HFpEF.OR): 0.78; 95% CI: 0.70–0.88; p < 0.0001] and the incidence of worsening renal function  among patients with HFpEF in the three trials, but there was no significant reduction in all-cause mortality  or cardiovascular mortality . Moreover, sacubitril/valsartan was associated with an increased risk of symptomatic hypotension  and angioedema ; there was no difference for decreasing the incidence of hyperkalemia .We used the PubMed, Embase, and Web of Science databases to search for randomized controlled trials of sacubitril–valsartan in patients with HFpEF. Three studies, involving a total of 7,663 patients, were eligible for inclusion. Sacubitril–valsartan reduced the risk of hospitalization for heart failure (HF) [odds ratio , sacubitril/valsartan significantly decreased the risk of hospitalization for HF and reduced the incidence of renal dysfunction. Heart failure (HF) is a clinical syndrome caused by structural or functional cardiac abnormalities and manifests as an increase in internal pressure or a decrease in cardiac output. Due to increases in the size of the aging population and the incidence of risk factors, the prevalence of heart failure has been on the rise as well . To dateSacubitril/valsartan is the first new angiotensin receptor neprilysin inhibitor for treating hypertension and heart failure ; such drKuno et al.  demonstrWe registered the protocol for this systematic review with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020207370).We searched for articles in the PubMed, Embase, and Web of Science databases through 13 December 2021 using the following search terms: “heart failure with preserved ejection fraction” or “heart failure with normal ejection fraction” or “diastolic heart failure” or “diastolic dysfunction” or “preserved cardiac function heart failure” or “HFpEF” and “sacubitril valsartan” or “sacubitril/valsartan” or “lcz696” or “sacubitril” or “entresto” In addition, we reviewed the corresponding reference lists of the retrieved articles to avoid missing any relevant studies. The meta-analysis was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines .Eligible studies had to meet the following inclusion criteria: (1) the enrolled participants had HFpEF (LVEF ≥ 45%); (2) the study design was a randomized controlled trial (RCT) of the treatment group  and the control group; and (3) the trial provided primary outcome data .The exclusion criteria were as follows: (1) duplicated trials; (2) studies, such as systematic reviews, comments, case reports, conference abstracts, and editorials; and (3) RCTs that did not involve humans. The details are shown in YW and ZH independently extracted data and assessed the quality of the studies from the electronic database. The relevant data we extracted included the following: the baseline characteristics of the trials, interventions, comparisons, sample size, the medication used, and follow-up duration. The outcomes included death from any cause, death from cardiovascular causes, hospitalization for HF, symptomatic hypotension, renal dysfunction, hyperkalemia, and angioedema. Disagreements were resolved by discussion with a third author (W. Q. H.).The methodological quality of the three included RCTs was assessed by using the Cochrane Collaboration Risk of Bias Tool (Review Manager 5.4.1), which included the following sections: selection, performance, detection, attrition, reporting, and other biases. The results are shown in OR) or risk ratio (RR) and the corresponding 95% confidence interval (CI) were calculated in the comparative analyses. We assessed heterogeneity by using the I2 test and Cochran's χ2 test. The total variation in the studies was described by the I2 statistic, which reflected heterogeneity. When the heterogeneity test result was I2 < 50% and p > 0.10, we used a fixed-effects model for data analysis; I2 > 50% or a corresponding p-value < 0.10 indicated statistical heterogeneity among the studies that needed further analysis. All p-values were two-tailed, with statistical significance indicated at 0.05 and CIs reported at the 95% level. When I2 was >45%, a sensitivity analysis was further performed by sequentially deleting each study and reanalyzing the datasets of all remaining studies.Review Manager Version 5.4.1 was used to analyze the data. The efficacy and safety outcomes were measured as dichotomous outcome variables and compared between the sacubitril–valsartan group and the control group. The pooled odds ratio ; thus, the meta-analysis was carried out using a fixed-effects model. Regarding the outcome of all-cause mortality, the pooled OR based on three studies was 0.99 . The OR of cardiovascular mortality based on three studies was 0.95 . There were no significant differences in all-cause mortality or cardiovascular mortality among the patients with HFpEF between the sacubitril–valsartan group and the control group , and a fixed-effects model was used. Compared with valsartan or individualized medical therapy (IMT), sacubitril–valsartan reduced the composite risk of hospitalization for HF by 22% based on the three studies, and the pooled OR was 0.78 .As shown in p = 0.17, I2 = 44%), as shown in RR of 0.89 . However, there was no obvious difference in the reduction in all-cause mortality or in the rate of death from cardiovascular diseases. Sacubitril/valsartan increased the risk of hypotension and angioedema, but it could reduce the incidence of worsening renal function. At the same time, the occurrence of hyperkalemia was numerically higher, but not statistically significant, in the sacubitril/valsartan group than in the control group.The present meta-analysis, which involved 7,663 patients, is the first to provide composite evidence of the efficacy and safety of sacubitril/valsartan in patients with HFpEF by pooling data from relevant RCTs. All of the studies included in this meta-analysis were randomized, controlled, and double-blind multicenter clinical trials. The results suggest that compared with valsartan or IMT, sacubitril/valsartan showed a significant advantage in reducing the rate of hospitalization for hazard ratio  (The PARAMOUNT study  was a pr 0.0001) . Left at 0.0001) . In addiRR: 0.87, 95% CI: 0.75–1.01, p = 0.06). Notably, the subgroup analysis in this trial showed that sacubitril/valsartan had a beneficial effect on patients with an LVEF between 45 and 57% . This could be because these patients have systolic dysfunction, and sacubitril/valsartan has the same physiologic effects in these patients as it does in those with heart failure with reduced ejection fraction (HFrEF). For the secondary endpoints, sacubitril/valsartan significantly improved the New York Heart Association (NYHA) grade by 45% compared with valsartan . Similarly, compared with the valsartan group, the sacubitril/valsartan group had a higher percentage of patients with a KCCQ clinical summary score of 5 or higher (33.0 vs. 29.6%). In addition, the incidence of the compound renal endpoint in the sacubitril/valsartan group was significantly reduced compared with that in the valsartan group . The reasons for the negative results of the PARAGON trial  compared with enalapril or valsartan. This finding coincides with previous studies , which was consistent with previous studies . However, the occurrence of angioedema is known to be related to the inhibition of bradykinin degradation  ind studies ; and (C) studies , 32. Con studies . Althougradation , and sac6 p = 0.0 comparedradation . The reaHR), 0.91; 95% CI: 0.76–1.0]), with no benefit for all-cause mortality. In addition, the SOLOIST-WHF trial , which was driven by the reduction in HF hospitalizations. Sacubitril/valsartan and empagliflozin, two new drugs in the field of heart failure, have some similarities and differences in the clinical trials associated with them . In terms of safety outcome events, while both drugs resulted in symptomatic hypotension, patients taking empagliflozin were more prone to volume depletion and urinary tract infections  , a numbeHF trial  showed tith them . In the fections , while tClinicalTrials.gov. Fifth, for meaningful conclusions from the meta-analysis of randomized trials, we used secondary outcomes, not primary outcomes. Sixth, there were many mixed factors that may have caused bias. For example, the comparator drug was different among the three trials included in our work. Finally, the majority of the sample in our work was from the PARAGON-HF trial, which may lead to sample imbalance and affect the results of our work. Thus, further studies are needed to assess more potential clinical benefits of sacubitril/valsartan in patients with HFpEF.There were some limitations to our study. First, because only three RCTs were included in our work, the sample size of this systematic review was too small, and we could not produce a funnel plot. Second, HFpEF was defined as LVEF ≥ 50%, but the studies included in our work defined HFpEF as LVEF ≥ 45%. Third, unpublished data or articles published not in English were excluded. Fourth, we used data that were not published but were available on In conclusion, the existing evidence shows that sacubitril/valsartan not only is effective in the treatment of heart failure but also has a protective effect on kidney function. Although there was no significant reduction in all-cause mortality or cardiovascular mortality, patients treated with sacubitril/valsartan could obtain the benefits of a reduction in hospitalizations for HF and prevention of renal functional deterioration. Moreover, compared with valsartan or IMT, sacubitril/valsartan could increase the risk of symptomatic hypotension and angioedema but did not differ in the elevation of serum potassium. Compared with ACEIs or ARBs, sacubitril/valsartan is a better choice, but it is best to monitor blood pressure and renal function during treatment.The original contributions presented in the study are included in the article/Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study.YW and ZH reviewed the articles, performed the meta-analysis and wrote the manuscript. SW, LF, and YS were responsible for the statistical analysis. ZY provided editing assistance. YP and WQ designed and revised the manuscript. All authors have reviewed and agreed on this information before submission.This work was supported by the Provincial Plans-Social Development Areas—Major Projects of Jiangxi Province (No. 20161ACG70012) and the incubation project of the National Natural Science Foundation of the Second Affiliated Hospital of Nanchang University (No. 2021YNFY2021).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.


In this study we analyzed the prognostic value of the HALP Score and the GNRI calculated prior to first-line treatment in patients diagnosed with De novo mNSCLC patients were retrospectively evaluated from January 2016 to December 2019. Patients with Driver’s mutation, severe comorbidities, active infection, or insufficient organ function, and those receiving anti-inflammatory treatment were excluded from the study. Optimal cut-off points for the HALP score and the GNRI were calculated with the receiver operating characteristic (ROC) curve analysis. Predictive factors for overall survival (OS) were assessed with univariate and multivariate Cox proportional hazard analyses, and OS was studied with the Kaplan–Meier analysis.p < 0.001) for HALP, and 53.60  for GNRI. Groups with lower HALP scores and lower GNRI had significantly shorter OS compared to those with higher HALP scores and GNRIs. Univariate analysis showed that male gender, smoking, high ECOG score, low HALP score and low GNRI were associated with worse survival rates. Multivariate analysis showed that low HALP score ; low GNRI score  and smoking history  were independent factors associated with worse OS rates.The study included 401 patients in total. In the ROC curve analysis, the cut-off points were found 23.24 (AUC = 0.928; 95% CI: 0.901–0.955, de novo mNSCLC patients.Our study showed the HALP score and the GNRI to be of prognostic value as simple, cost-effective, and useful markers that predict OS in  Lung cancers are among the top causes of cancer-related deaths in many industrialized countries, in women and men alike, accounting for about one-fifth of all cancer-related deaths . AdenocaThere is an increasing focus on identifying the molecular changes critical to the oncogenic phenotype of NSCLC and the treatments targeting Driver’s mutations. Moreover, the use of immunomodulatory drugs, especially of anti-PD1 drugs in advanced NSCLC patients is increasing. Yet, majority of the patients are still treated with cytotoxic chemotherapy for reasons such as their molecular/pathological characteristics or the unavailability of other treatment options. Availability of prognostic and predictive indexes that allow physicians to make the most suitable treatment decision for these patients are of great importance.Current studies show that the systemic inflammatory response is associated with tumor characteristics such as proliferation, invasion, metastasis, and that inflammation has a significant role in the formation and growth of tumors , 6. BlooIt is known that a combination of these parameters can predict the patient’s prognosis much better than a single index. To that end, the HALP score—an index which is calculated based on hemoglobin, albumin, lymphocyte, and platelet levels—has been recently defined. The HALP score assesses both the immune system and the nutritional status of the patient. The score has been reported to be a good prognostic marker in various types of cancers, including gastrointestinal and genitourinary , 11. TheMalnutrition is often seen in oncology patients. The prevalence of malnutrition and weight loss among cancer patients ranges from 20% to 70% depending on the type and stage of the cancer, and patients with upper gastrointestinal tract, lung and pancreatic cancer are at greater risk. Many patients suffer nutritional deficiency even at the diagnosis stage . The GerAlthough a number of clinicopathological indicators such as the metastasis site, histology, PD-L1 expression, tumor mutation burden, and EGFR, ALK, ROS, KRAS mutation may predict the prognosis of NSCLC, simpler and more precise indexes are also needed. In this study, we aimed to investigate whether pre-treatment HALP score and GNRI could serve as independent and strong risk factors of overall survival (OS) in mNSCLC patients.de novo mNSCLC patients who were treated and followed-up in our medical oncology clinic from January 2016 to December 2019 were included  × albumin (g/L) × lymphocytes (/L)/platelets (/L). GNRI was calculated using serum albumin concentration and body weight as described elsewhere  with theT-test and categorical parameters with the χ2 test. The power of the HALP scores and the GNRI were analyzed using ROC curve analysis. A significant cut-off point was observed, and sensitivity, specificity, and positive and negative predictive values were detected. Survival analyses of prognostic indexes, and clinical and pathological features were calculated using the Kaplan–Meier method (log-rank test). Multivariate analyses were used to identify independent prognostic variables based on a stepwise Cox proportional hazards regression model and variables that potentially affected survival . Parameters that appeared significant in univariate analysis for survival and did not show multicollinearity were included in the Cox multivariate regression analysis. The 95% confidence interval (CI) was used to indicate the relationship between survival time and each independent factor. Statistical significance level was p < 0.05.The Statistical Package for Social Sciences for Windows 20.0  was used for analysis. Overall Survival (OS) was defined as the time from diagnosis to death or the last visit. Descriptive statistics summarized frequencies and percentages for categorical, mean, and standard deviation for continuous variables. Categorical variables were compared with the Independent Samples Clinical characteristics of the 401 patients included in the study were analyzed: their mean age was 63.47 ± 9.75 years ; 211 patients were < 65 years and 190 patients were ≥ 65 years of age; 317 (79.1%) of the patients were male. The most common histopathological type was adenocarcinoma at a rate of 51.1% (205 patients). Mean follow-up time was 18  months. Two-hundred-and-sixty-one patients (65.1%) died by the end of the follow-up period. All patients received platinum-based combination therapy as first-line chemotherapy. The most commonly used regime was the cisplatin-gemcitabine combination , followed by the carboplatin-paclitaxel combination  and the carboplatin-gemcitabine combination . Two-hundred-and-forty-two patients (60.3%) were progressive after their first-line treatment. Basic characteristics of the patients are given in p < 0.001) for the HALP score. For GNRI, the ROC curve showed an optimal cut-off point of 53.60   and a median GNRI of 54.26 . ROC analysis was done to determine the most appropriate cut-off points for the HALP score and the GNRI levels. The ROC curve showed an optimal cut-off point of 23.24  . Patientp < 0.005)  .p < 0.001)  .In all 401 patients, univariate analysis identified male gender, smoking, high ECOG score, low HALP score and low GNRI score to be significantly associated with worse survival rates.p ≤ 0.001); low GNRI score  and smoking history   .The presented study aimed to identify the value of pre-treatment HALP scores and GNRI levels in predicting OS in mNSCLC. Review of the literature showed our study to be the first to demonstrate in multivariate analysis that low HALP score (≤ 23.24) and low GNRI are prognostic markers that independently define worse OS. We assessed simple prognostic markers like complete blood count, serum albumin levels, height, and weight, which are based on basic laboratory and anthropometric measurements as part of the routine evaluation process for each patient.Despite the emergence of new treatments, mNSCLC remains an incurable disease with significant morbidity and high symptom burden. Although some patients show improvement with anticancer therapy, in most patients survival is only a few months. A realistic understanding of its prognosis and the goals of cancer treatment will determine the treatment decision for both patients and physicians. The importance of our study comes forth at this point. The study cohort consisted of mNSCLC patients, excluding those who had Driver’s mutation—because of better prognosis and more treatment options available—or were treated with molecular target agents. After other characteristics that could potentially have confounding effects on prognosis were excluded per the relevant exclusion criteria of the study design, a total of 401 patients who were comparable in terms of clinicopathological characteristics and treatments were analyzed.As consistent with the literature, the majority of the patients in our study were male with adenocarcinoma morphology . Since pThe roles of inflammatory response and nutritional status in predicting prognosis in cancer patients are being investigated with increasing interest –18. SeruLymphocytes are of critical importance in the host’s anti-cancer defense. Lymphocytes, which can release cytokines such as interferon−γ and tumor necrosis factor−alpha (TNF−α), can improve the prognosis by causing apoptosis, suppressing cancer cell proliferation, invasion, and migration , 23. As via TNF−α  patient group.Smoking tobacco is known to be the main risk factor for lung cancer and associated with high morbidity and mortality. However, smoking is associated with better survival in NSCLC patients receiving immune checkpoint inhibitors in different lines of treatment . Our stude novo mNSCLC patients, its retrospective single-center design has been a limiting factor of our study. Nevertheless, the exclusion of patients with Driver’s mutation and those who received targeted therapy has, we believe, helped to eliminate any effects on prognosis, hence, to achieve reliable results. Our low/high HALP score and low/high GNRI groups had similar clinicopathological characteristics. Another limiting factor was the lack of consensus on the cut-off points for the HALP and GNRI scores in NSCLC due to the limited number of studies. A better understanding of the effects of the dynamic changes in HALP and GNRI scores on long-term survival will help to better understand the relationship between these scores and NSCLC. We hope that our study will provide a basis for further prospective multi-center studies that are needed to more clearly assess how these scores should be used in the follow-up and for the survival benefit of patients.Whilst being the first to demonstrate the HALP score and the GNRI score as independent predictive factors for OS in To conclude, the HALP score and the GNRI are reliable, simple, easily accessible, and inexpensive indexes for predicting the prognosis of advanced stage NSCLC patients treated with platinum-based chemotherapeutics. Low HALP score and GNRI level can be considered clinical triggers for nutritional support in patients with advanced NSCLC.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.ZG and AA: study concept, study design, and statistical analysis. ZG and MK: data acquisition. ZG, SÜ, and YY: quality control of data. ZG and UO: data analysis and interpretation. ZG, TS, and AA: manuscript editing. ZG, YK, AA, and MT: manuscript review. All authors contributed to the article and approved the submitted version.


BackgroundThere has been a tremendous increase in self-poisoning behavior worldwide, with different trends depending on cultural and geographic aspects.ObjectivesOur study aims to assess the trends, outcomes, and predictors in patients of suicide attempts by poisoning at King Abdulaziz Medical City (KAMC) ED.Materials and methodsA retrospective cohort study took place at KAMC. Frequencies and percentages were used to display categorical variables. Minimum, maximum, mean, and SD were used to display continuous variables. Chi-squared test and independent t-test were utilized to test for factors associated with suicidal intention.Resultsp < 0.001), gender (p < 0.001), age (p = 0.012), and a history of neuropsychiatric disorders (p < 0.001) were associated factors.A total of 130 cases were identified. The participants were mostly females . Most of the participants were pediatric patients . The most consumed agents were acetaminophen in 59 (45.83%) and non-steroidal anti-inflammatory drugs (NSAIDs) in 22 (16.92%). The ICU admission rate was 8.5% (n = 11). The management for both populations was unspecific, involving observation, supportive measures, and symptomatic treatment. BMI (ConclusionIt is crucial that the trends and risk factors of self-poisoning suicide attempts are identified to provide support to those in need. Several variables of interest were noted since the two most observed agents share several key features, such as accessibility and availability. However, contradicting literature reports warrant further investigation to confirm or negate the evidence. Suicide is the act of intentionally causing one's own death . Many faIntentional self-poisoning, the non-violent method of suicide, occurs most commonly through the utilization of medication, either prescribed  or over-the-counter (paracetamol), chemical agents (pesticides), or illicit drugs . Cases oThere has been a tremendous increase in self-poisoning behavior worldwide, especially among adolescents and young adults. These individuals have a higher risk of repeating such behavior in the future . TherefoStudy design, settings, and inclusion criteriaThis study was a retrospective cohort study conducted at King Abdulaziz Medical City (KAMC) for patients aged more than 14 years and King Abdullah Specialized Children Hospital (KASCH) for the patients aged 14 and less in Riyadh, Saudi Arabia. The inclusion criteria for this study were all patients presenting with acute poisoning that resulted from an intentional suicide attempt from January 1, 2016, to January 1, 2021. A total of 1505 patients presented to the ED with acute poisoning during that period. Among them, 130 cases were due to a suicidal intention. These patients were identified and included if the history of the presenting complaint indicated a suicide attempt.Data collectionThe patients' records were retrospectively tracked, and data were collected from them. Collected data included demographics, medical history, poisoning agents, length of stay, discharge type, either a complete discharge or a premature discharge, which often happens if the hospital is overcrowded or understaffed. We also gathered the presenting complaints, types of intervention provided, and outcomes. The parameters were obtained from the BESTCare system . For example, if a patient had an ICU admission, organ transplantation, and mortality, they were classified as poor outcomes. Any outcomes that differed from the three aforementioned outcomes were labeled as good outcomes.Statistical analysisStatistical analysis was done using the SPSS version 23.0 . Frequencies and percentages were used to display categorical variables. Minimum, maximum, mean, and SD were used to display continuous variables. Chi-squared test and independent t-test were utilized to test for factors associated with suicidal intention. In order for the test of association to be carried on and to determine factors associated with suicidal poisoning, the initially excluded group (patients who presented to the ER as a case of poisoning for a reason other than suicide) were compared to patients.EthicsEthical approval with the number RC20/676/R was obtained from the Institutional Review Board of King Abdullah International Medical Research Center. Patient confidentiality was ensured, and the patient data were collected and used only by the research team. Due to the study's retrospective nature and the use of anonymized patient data, the requirement for informed consent was waived.A total of 1505 poisoning cases were identified in the records. Among them, only 130 were suicide cases and thus were included in the study. The study population was predominantly composed of males  regarding the demographic profile. When it comes to age groups, most of the participants were classified as pediatric patients  aged less than 18. Furthermore, most patients were not smokers . As for the BMI status, most patients had normal weight .The patient population predominantly had no comorbidities . However, the most observed medical conditions were neuropsychiatric disorders in 26 (20%), cardiovascular diseases in six (4.6%), diabetes mellitus in four (3.1%), renal disease in three (2.3%), cancer in two (1.5%), and nine patients (7.2%) had other miscellaneous comorbidities.Table Table Table Table Table The most observed clinical presentations were vomiting in 33.08%, abdominal pain in 27.69%, altered level of consciousness in 17.69%, dizziness in 11.54%, and nausea in 19.23%, while 21% of the patients were asymptomatic. These are all characteristic presentations of poisoning patients and predictors of poisoning-related fatalities [Our study showed that 14% of females presenting to our ED due to poisoning were suicidal. This percentage was significantly higher when compared with males, which were only 4%. This is substantiated by Rajapakse T et al., that conducted a comparison study in Sri Lanka over a 14-month period to describe the gender differences in non-fatal self-poisoning. The findings here highlight that the patterns of non-fatal self-poisoning indicate a greater incidence of both self-poisoning and medicinal overdoses in females when compared with males . An addiWhen looking at the BMI status, those with higher BMI had a higher incidence of suicide in our study. However, this is not well reported in the literature, and the investigations substantiating these findings are scarce. A systematic review by Perera S et al. represents the most up-to-date collation of the literature on this variable and its relationship with suicide behaviors. This review, however, does not support our findings that a higher BMI may result in a higher incidence of suicide, with the current literature suggesting an inverse relationship. In an assessment of 38 observational studies, Perera S et al. highlight that an inverse association between BMI and completed suicide exists. A pooled summary suggests that a significantly low BMI is associated with an increased risk of suicide. While being obese and overweight were significantly associated with a reduced risk of suicide compared to those of a normal BMI .Notably, non-smokers had a higher incidence of suicide attempts when compared to smokers. The demographic profile of the cohort included in our study revealed that 93.1% of the patients presenting with a case of poisoning were non-smokers. However, as with BMI, this variable is not widely discussed as a risk factor to suicide; hence, our observation here may only be a coincidence. This is also suggested in the contradictory findings of the current literature. A meta-analysis by Poorolajal J and Darvishi N concluded that when compared to non-smokers, smokers were at an enhanced risk of suicidal ideation, suicide planning, suicide attempt, and suicide death in a cohort of over eight million participants spanning 63 studies . This neThe majority of our cohort who attempted suicide had no comorbidities , and in those with comorbidities, patients with neuropsychiatric disease represent the highest proportion (20%). These findings warrant further investigation as our results are not conclusive, and the current literature is scarce. The outcomes of the suicide attempts in our study, on the other hand, are in concordance with the previous international published reports except for the use of antibiotics. ICU admission was necessary for 9% of patients assessed, with admission duration being an average of two days. Moreover, the most consumed agents were acetaminophen, NSAIDs, and antibiotics. Antibiotics are rarely reported as a suicide agent; however, the current literature does suggest that exposure to several antibiotics may be associated with suicidal behavior .Despite the data discussed in this study and the current literature, the under-reporting of suicide represents a global challenge. This is emphasized in several studies, including Li F and Yip PS, that discussed the severe under-reporting of the national suicide rates published by the Chinese Ministry of Health . TøllefsThe primary strength of our study is that, to the best of our knowledge, this represents one of the first investigations that discusses the topic of suicide attempts by poisoning in Saudi Arabia, with a relatively large sample size. Moreover, our study was conducted in a single large tertiary care center; hence, more patients were included in this study than other investigations focusing on primary care centers. However, there are several limitations of note. The study design being a retrospective chart review represents the primary limitation. Moreover, being conducted in only a single center. This introduces several types of bias that must be considered. Further studies should adopt a prospective approach and include more than one center to reduce bias within the findings and enhance the overall credibility of the results.The incidence of poisoning as a method of suicide is increasing, with the presentation of this at the ED being characteristic. However, it is crucial that the risk factors to self-poisoning and suicide attempts are identified to support those who require it. Our study noted several variables of interest, including being female, a high BMI, non-smokers, being medically free, and having a neuropsychiatric disease. Although some of our findings are contradicted in the current literature, they warrant further investigation in future studies to confirm or negate the evidence provided in this study.


To investigate and analyze the effect of fast track surgery (FTS) based on nutritional support on the improvement of rehabilitation efficacy and nutritional status of patients after radical lumpectomy for thyroid cancer.Eighty-six patients admitted to our hospital for radical lumpectomy for thyroid cancer between April 2018 and April 2021 were selected, of which 40 patients admitted between April 2018 and April 2019 were included in the control group with conventional perioperative care. Forty-six patients admitted between May 2019 and April 2021 were included in the trial group with FTS care based on nutritional support. The two groups of patients were compared in terms of postoperative feeding time, length of stay, time out of bed, VAS scores, albumin (ALB), total protein (TP) and prealbumin (PA) levels, negative emotions [Mental Health Test Questionnaire (DCL-90)], quality of life [General Quality of Life Inventory (GQOLI-74)] and complication rates.P < 0.05). After the intervention, ALB, TP and PA levels were higher in the trial group than in the control group vs. preoperatively (P < 0.05); VAS scores in the trial group were lower than VAS scores in the control group during the same period (P < 0.05). The postoperative DCL-90 scores of the trial group were lower than those of the control group (P < 0.05); the GQOLI-74 scores and total scores of the trial group were higher than those of the control group at the 3-month postoperative follow-up (P < 0.05). The overall incidence of complications such as hoarseness, choking on water, hand and foot numbness, wound infection, and hypocalemia was lower in the trial group than in the control group (P < 0.05).The patients in the trial group had shorter feeding time, hospitalization time and time out of bed than the control group (The implementation of FTS care based on nutritional support for patients after endoscopic radical thyroidectomyr can effectively improve the postoperative recovery and reduce their pain level, as well as help improve their nutritional status, negative emotions and improve their quality of life, which is worth promoting. Thyroid cancer (TC) is a malignant tumor occurring in the thyroid area, with a low incidence rate, but due to its special location, the disease is more serious after its onset. TC is a common malignant tumor in endocrine, and surveys show that the incidence of TC in our population is increasing year by year, and it is mostly seen in young and middle-aged women , 2. CurrFast track surgery (FTS) refers to an innovative concept that perfectly combines the diagnosis and treatment plans with the latest research evidence during the perioperative period to promote the early recovery of organ function after surgery, including the latest minimally invasive techniques, anesthesia, postoperative analgesia, early postoperative enteral nutrition, early bed mobility, active rehabilitation exercises and psychological care , 9. GradEighty-six patients admitted to our hospital who underwent lumpectomy for radical thyroid cancer between April 2018 and December 2020 were selected and their clinical data were collected.I. Diagnosis of thyroid cancer confirmed by puncture biopsy; II. Those who met the indications for radical thyroid cancer surgery and agreed to take surgical treatment; III. No distant metastasis on preoperative imaging, no combination of other malignant tumors, and no contraindication to relevant surgery; patients with cosmetic intention and no history of neck surgery or radiotherapy; post-hospital nutrition risk screening tool (NRS) 2002 score ≥ 3 points.I. Those with speech impairment and impaired consciousness, unable to communicate basically; II. Combined with other thyroid diseases; III. Contraindications related to surgery and anesthesia; IV. Comorbid with other tumors.Among them, 40 patients admitted from April 2018 to April 2019 with conventional perioperative care were included in the control group. Fort-six patients admitted between May 2019 and April 2021 with rapid rehabilitation surgical care based on nutritional support were included in the experimental group.P > 0.05)  .Patients were perfected with preoperative routine examination and completed preoperative preparation. Combined anesthesia was used, a catheter was left in place before surgery, and patients' vital signs were closely monitored intraoperatively. Postoperatively, they gradually received rehabilitation training, and analgesic drugs were given when pain occurred during exercise. Patients in the control group ordered the regular package from the hospital nutrition cafeteria and were not given standard nutritional support treatment, while the rest were given routine perioperative care.FTS care based on nutritional support was used, and nutritional support was individualized according to the patient's physical condition.Application of parenteral nutrition support or enteral nutrition for more than 5 days was considered to be the use of nutritional support, nutritional support regimen for oral nutrition preparations and tube feeding, parenteral nutrition support regimen includes intravenous infusion of amino acids, glucose and fat emulsion. Patients without gastrointestinal motility disorders were fasted from solid diet 6 h before surgery, fasted from clear liquid 2 h before surgery, and given sugar water for energy supplement 2 h before surgery. Actively educate patients about the rapid recovery program to obtain better cooperation from patients. Before the operation, we perfected the routine examination and entered the operating room after completing the preoperative preparation.After the patient entered the room, we explained the surgical instruments and instructed the patient to cooperate well to ensure the smooth operation. Intraoperatively, a cardiac monitor was connected and all vital signs were closely monitored for 15 min/time. Control the intraoperative infusion volume <1,000 ml, and control the infusion temperature at about 36°C. The non-operative site was kept warm to prevent hypothermia and extremely wasted patients were given intraoperative warming blankets to maintain 37°C. Postoperative ECG was monitored continuously for 12 h, and pulse, blood pressure, temperature and respiratory changes were monitored.Placed oxygen devices, suction devices and tracheotomy kits at the bedside, and reported to the physician as soon as the patient developed symptoms such as vocal cord paralysis, laryngeal edema, respiratory distress and asphyxia, and prepared for tracheotomy. Adequate postoperative pain relief can be achieved by providing patients with early intermittent neck ice, systematic pain education and, if necessary, non-steroidal analgesics, depending on the circumstances. After the patient was awake from anesthesia and the vital signs were stable, a small amount of water could be given, leg flexion and extension and turning activities could be performed in bed, and vocal exercises could be performed. Twelve hours after surgery, patients could eat semi-liquid diet and do some exercises around the bed; 24 h after surgery, they could gradually transition to general diet and walk in the corridor and rest area. On the first postoperative day, the patients were instructed to carry out functional neck exercises in a gradual manner, and the standard was that the patients did not show any discomfort symptoms, and at the same time, psychological guidance was provided to avoid patients being afraid to carry out exercises because they were worried about wound pain.The postoperative feeding time, hospitalization time and the first postoperative bed activity time and the 24 h postoperative pain level were compared between the two groups. The pain level was assessed by visual analog scoring (VAS), which was divided as 0–10, and the higher the score, the more severe the pain symptoms.Before the intervention and on the second postoperative day of the patient, serum albumin (ALB), prealbumin (PA) and total protein (TP) levels were measured in the morning fasting venous blood of two groups of patients using a fully automated biochemical analyzer .Before the intervention and on the second postoperative day, the patient's negative emotion was evaluated using the mental health test questionnaire (DCL-90), which includes 9 dimensions such as somatization, obsessive-compulsive symptoms, interpersonal relationship, sensitivity, depression, hostility, terror, paranoia, and psychoticism, with each dimension scored from 1 to 5.Patients were followed up at 3 months after discharge and their quality of life was evaluated using the General Quality of Life Inventory (GQOLI-74), which consists of four dimensions: physical, social, psychological and role, with a score of 100 out of 100.−1 was defined as hypocalcemia.The occurrence of postoperative complications, including hypocalcemia, choking on water, wound infection, numbness of hands and feet, and hoarseness, was recorded in both groups. Among them, serum calcium <8.7 mg·dLt-tests were performed between groups. The statistical data were expressed as rate (%), and the χ2 test was performed between groups. p < 0.05 was considered as a statistically significant difference.All data in this study were statistically analyzed using SPSS 20.0, and Prism 8.0 software was used to produce statistical graphs. The measures in the data were expressed as mean ± standard deviation , and P > 0.05)  .P < 0.05), suggesting that the FTS model based on nutritional support can promote the postoperative recovery of patients and shorten the hospital stay. In addition, the VAS score of the experimental group was lower than that of the control group at 24 h after surgery (P < 0.05), suggesting that the FTS model based on nutritional support can effectively prevent the occurrence of postoperative pain and reduce the degree of pain in patient . After the intervention, the levels of ALB, TP and PA in the control group were lower than those in the preoperative and concurrent experimental groups (P < 0.05), and the differences between the levels of ALB, TP and PA in the experimental group and the preoperative group were not significant (P > 0.05). It is suggested that the FTS model based on nutritional support can effectively reduce the occurrence of nutritional risks caused by various reasons in the perioperative period and improve the clinical outcomes of patients . After the intervention, the DCL-90 scores in both groups decreased significantly compared with the preoperative scores, and the scores of somatization, obsessive-compulsive symptoms, interpersonal relationship, sensitivity, depression, hostility, terror, paranoia, and psychoticism in the experimental group were lower than those in the control group (P < 0.05). It is suggested that the FTS model based on nutritional support can improve patients' negative emotions and is conducive to improving patients' treatment adherence . It is suggested that the FTS model based on nutritional support has a better effect on the improvement of patients' quality of life . It is suggested that the FTS model based on nutritional support can reduce the incidence of perioperative complications (In the control group, the incidence of hoarseness, choking on water, numbness of hands and feet, wound infection, hypocalcemia, and overall incidence were 5.00%, 7.50%, 10.00%, 5.00%, 2.50%, and 30.00%, respectively. In the trail group, the incidence of hoarseness, choking cough, numbness of hands and feet, traumatic infection, hypocalcemia, and overall incidence were 0.00%, 2.17%, 2.17%, 2.17%, 0.00%, and 6.52%, respectively. The analysis showed that the overall complication rate in the experimental group was lower than that in the control group (ications .Thyroid cancer is a malignant tumor originating from thyroid follicular epithelial cells. It mainly presents as painless neck nodules or masses, it is more common in young adults, and the incidence in women is about 2–4 times that of men. Currently, the disease is mainly treated by surgery, radionuclide therapy and endocrine therapy , 13. In FTS refers to the application of various methods that have been proven effective by evidence-based medicine before, during, and after surgery to reduce surgical stress and complications and accelerate postoperative recovery , 19. FTSImproved nutrition may lead to earlier time to floor in patients undergoing radical lumpectomy for thyroid cancer, while early activity may promote gastrointestinal motility as well as reduce the incidence of perioperative complications. This study confirms that the FTS model based on nutritional support can effectively reduce the incidence of postoperative complications, shorten the number of hospital days, and promote postoperative recovery in patients undergoing lumpectomy for radical thyroid cancer, thereby improving clinical outcomes.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.This study was approved through the Hospital Ethics Committee. The patients/participants provided their written informed consent to participate in this study.FQ and CX are the mainly responsible for the writing of the article. HB is mainly responsible for research design. FQ is mainly responsible for data analysis. LY and HL are responsible for the guidance of the entire research. All authors contributed to the article and approved the submitted version.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.


Severe traumatic brain injury (sTBI) is a public health issue with great disparity among low- and middle-income countries where the implementation of evidence-based guidelines is challenging because resources are often unavailable. A consensus process including experts in the prehospital, emergency department, neurosurgery, and intensive care unit took place in Colombia to develop a set of stratified protocols called BOOTStraP, targeting resource-poor environments, but it has not been systematically implemented and tested.To identify the facilitators of, and barriers to, collecting data about patients with sTBI and to implement a stratified protocol across the treatment phases of prehospital, emergency department, neurosurgery, and intensive care unit in low-resource settings. We also aim to identify a possible association between adherence to these protocols and outcomes for these patients.A prospective, observational, before and after, pilot study will be performed in three phases as follows: before implementation, implementation, and after implementation. The BOOTStraP protocols will be implemented in three Colombian centers.We expect to find numerous barriers during the implementation phase. We also expect moderate adherence to the protocols. However, we expect to find an increase in the survival rate to hospital discharge and an improvement in neurological outcomes at discharge.This pilot study will serve as a first step to identify variables that are critical to successful implementation, to be considered for the design of a future large-scale international study to measure the effectiveness of resource-based protocols and to improve outcomes from sTBI. DCdata collectorEDemergency departmentEMSEmergency Medical ServiceGOS-EGlasgow Outcome Scale ExtendedLMICslow- and-middle income countriesRTAsroad traffic accidentsSCstudy coordinatorsTBIsevere traumatic brain injury.Beyond One Option for the Treatment of Severe Traumatic Brain Injury: BOOTStraP.U1111-1272-0282 version 1.National Institute for Health Research Biomedical Research Centre.University College London Hospitals, Suite A, 1st Floor, Maple House, 149 Tottenhan Court Road, London W1T 7DN, UK.Prof Andres M. Rubiano, MD, PhD(c)Prof Peter J. A. Hutchinson, MBBs, PhD, FRCSDr Angelos Kolias, MD, PhD, FRCSDr Nancy Carney, PhDDylan Griswold, BA, MD(c), PhD(c)Dr Laura Fernandez, MDNicolas M. Ballarini, PhDResearch site 1: Clinica Uros Neiva, Cra. 6 #16-35, Neiva, Huila, Colombia.Research site 2: Clinica La Sagrada Familia, Cr. 15, Cl. 10 Esquina, Armenia, Quindio, Colombia.Research site 3: Clinica Putumayo, Cr. 48 #10-29 862060Puerto Asis, Putumayo, Colombia.1 and where more than 90% of trauma-related deaths occur.2 Road traffic accidents (RTAs) are the most frequent cause of sTBI, especially among the economically productive population, costing at least 3% of their gross domestic product each year.4 LMICs are particularly vulnerable to economic loss, given that 93% of all road traffic deaths occur in LMICs, despite owning less than 60% of the world's vehicles.4Severe traumatic brain injury (sTBI) is a public health crisis that disproportionately affects low- and-middle income countries (LMICs), where suffering an sTBI more than doubles the risk of death6 Of the nearly 7000 deaths due to RTAs that occurred in Colombia in 2019, more than 3600 deaths were motorcycle operators. In countries such as Colombia with a high incidence of sTBI, evidence-based guidelines are essential for decreasing risk of mortality and serious morbidity.Colombia is one of 68 countries where RTA deaths have increased since 2010.Although evidence-based guidelines for the management of sTBI exist, their applicability in low-resource environments is limited because the resources required to follow the guidelines are often unavailable. To address this gap, a consensus process involving clinical experts was conducted in Colombia to develop a series of management protocols to articulate treatment options for TBI specific to different levels of resources and system complexity across the prehospital, emergency department (ED), neurosurgery, and intensive care unit (ICU) phases. The set of protocols is called BOOTStraP (Beyond One Option for Treatment of Traumatic Brain Injury: A Stratified Protocol).The BOOTStraP protocols are divided into 4 main categories, which are based on 13 recommendations from 20 clinical experts as follows: (1) management in a basic vs advanced ambulance , (2) ED care in a low vs medium-high complexity institution with or without access to a CT scan, (3) neurosurgery department, and (4) intermediate or ICU availability. Each of them is subcategorized according to the TBI severity and can be used as a guiding tool by different levels of health professionals The user can select from a menu of treatment options depending on what resources are available  to follow best practice given the prevailing circumstances.To identify the facilitators of, and barriers to, collecting data about patients with sTBI across the treatment phases of prehospital, ED, neurosurgery, and ICU in low-resource settings.To identify the facilitators of, and barriers to, implementing a stratified protocol for treatment of patients with sTBI across the treatment phases of prehospital, ED, neurosurgery, and ICU in low-resource settings.To identify whether there is an association between adherence to the protocols and outcomes for patients with sTBI.The 3 objectives of the study are:This is a prospective, observational, before and after, pilot investigation of treatment process and outcomes for patients with sTBI, who are transported by any means to a medical center for treatment. Data will be collected for each patient through the four treatment phases of prehospital, ED, neurosurgery, and ICU or until the patient is dead. Data will be abstracted from hospital medical records; requirement for consent has been waived by the ethics committee. We will collect data on 48 patients in each of the before and after phases of the study.Patients age ≥15 yearsClinical indications of sTBIGlasgow Coma Scale ≤8 on hospital arrival, or within 48 hours of admission, or Glasgow Coma Scale ≥9 on hospital arrival, but who are either admitted to the ICU or undergo surgery within 48 hours of admission.Patients dead at the scene on EMS arrival  are included).Forty-eight patients in both before and after phase (N = 96).From initiation of the “before” phase, data for each patient will be collected from initial patient encounter to hospital discharge, until sample size is met. The BOOTStraP protocol will be implemented during the month following the end of initial data collection. After implementation (“after” phase), data for each patient will be collected from initial patient encounter to hospital discharge, until sample size is met.Study timeline is described in Figure. Study month 1 was initiated in September 2021.Supplement 1, http://links.lww.com/NEU/D140. Variables to be collected across the four phases are provided in the case report forms (CRFs) in Supplement 2, http://links.lww.com/NEU/D141.The treatment protocols to be implemented in the three centers are provided in Phenomenological variables (narratives)Adherence (derived from objective measures)Patient outcomesSurvival to hospital dischargeGlasgow Outcome Scale Extended (GOS-E) at discharge.Each day during active data collection, the data collector (DC) for each site accesses the ED records and identifies patients admitted during the previous 24 hours who may meet inclusion criteria for the study.The DC ascertains information about the potential included patients from ED records and attending caregivers and identifies those screened and excluded and those screened and included.Data are transcribed from ED records and caregiver notes directly into a web-based database.The DC completes data abstraction for included patients.The DC identifies the location and status of newly included patients and transcribes data about each patient into the database, up to and including the current status.After completing data abstraction for new patients entered within the previous 24 hours, the DC identifies the location and status of patients previously included into the study and transcribes data about each patient into the database, up to and including the current status.Each day during active data collection, the study coordinator (SC) accesses the electronic records and reviews new data entries for errors and missing data.Twice monthly, the SC compares abstracted data with chart records and meets with the site DC to discuss errors and missing data.The SC and DC make any revisions together, directly into the database.During these visits, the SC records narrative information about reasons for errors and missing data, what is working and not working, and the DCs' perspectives on the barriers to and facilitators of conducting the study.The SC transcribes this narrative information into a qualitative data collection/analysis database.This is the first study to develop, implement, and test resource-stratified protocols for neurotrauma in low-resource settings. It is an important first step toward conducting a much larger multicenter, international study. A feasibility study asks whether something can be done, should we proceed with it, and if so, how? By evaluating the barriers and facilitators to implementing the protocols in these three centers in Colombia, we will better understand the feasibility of implementing the protocols in a larger, international trial. Ultimately, this study will generate data that will serve as an important evidence base from which comprehensive guidelines for treatment of sTBI in LMICs can be developed.The current status of the trial is in the preimplementation stage.Risks to the patients are proportional to the level of experience of the providers. These protocols are based on clinical consensus and have not yet been tested for efficacy and associated mortality and morbidity.Patients will be followed to discharge.The data will be recorded in a web database and handled and stored to enable accurate reporting, analysis, and interpretation. The statistician will also periodically review the data entered for completeness and accuracy and raise any queries in the system if necessary. Changes in the data entered will be recorded in an audit trail including initials, dates, and the reason for change. The database will be locked for analysis once all necessary actions have been taken to ensure the data are complete and accurate.Demographic and baseline data will be summarized descriptively for all participants by phase (before and after). Categorical data will be summarized as frequencies and percentages while continuous variables will be summarized using mean, median, minimum, maximum, and 25th and 75th percentiles.We will record narrative information from personnel at each site to investigate the barriers to and facilitators of data collection and intervention implementation. These data will be entered into a qualitative data analysis instrument, and a modified Grounded Theory approach will be used to identify common themes.Adherence will be derived by tracking if each recommended BOOTStraP resource was available (yes/no), and if yes, whether it was used (yes/no). The analysis of adherence will be presented by treatment phase . The percentage of adherence to the BOOTStraP protocol will be used as a summary statistic.Survival status and GOS-E at discharge will be recorded for each patient. The analysis will explore correlations between adherence levels by phase and individual treatments on outcome data. No hypothesis will be tested.The sample size for the study was determined based on feasibility, and no formal calculation of power was performed.Access to data set will be made available on requestFindings of this study will be published in a peer-reviewed journal and will be presented at relevant conferences.DCs will be trained in data management. The research team will perform a constant improvement and feedback system on the protocols at each of the centers during the implementation phase.We expect to discover (a) what level of successful implementation is possible in the context of the prevailing conditions and (b) what changes will be required to enhance that level of success. We further expect that implementation of BOOTStraP will improve survival to hospital discharge and GOS-E at discharge. We expect there will be many barriers to implementation documented, especially in the prehospital stage. We expect adherence to protocols to be modest. The overall aim of this pilot trial is to assess the feasibility of implementing these protocols in a larger multicenter international study.Before implementation data collection: 3 months.Implementation: 2 months.After implementation data collection: 3 months.Principal Investigators: Prof A. M. Rubiano, MD, PhDCoinvestigators: D. P. Griswold, BA; Dr N. Carney, PhD; Dr A. K. Kolias, MD, PhD; and Prof P. J. A. Hutchinson MBBS, PhD, FRCSHead Statistician: N. M. Ballarini, PhDSite and Study Coordinator: L. L. Fernandez, MD7 The BOOTStraP protocol was approved by the Institutional Review Board of both Clinica Uros and Fundacion Meditech.This study will be performed in accordance with the Declaration of Helsinki.


Farmers are the integral members of rural communities. In the present study, we determined the association between occupational physical activity (OPA) of farmers and dyslipidaemia.We included 7649 farmers from The China Multi-Ethnic Cohort (CMEC) Study. The working modes of all farmers were divided into four types according to their self-reported seasonal changes in farming work and/or other job changes . OPA was self-reported, and the OPA levels in the four groups were classified as Q1, Q2–Q3, and Q4 by quantile. Dyslipidaemia was defined as the presence of abnormalities in lipid indicators. Binary logistic regression was used to estimate the association between OPA and dyslipidaemia.Compared with those in the no change group, the participants in other three groups were younger with lower level of education, annual income, and leisure-time physical activity (LTPA). Active OPA could reduce the risk of dyslipidaemia in the no change  and seasonal change  groups. However, in the seasonal and job change group , active OPA increased the risk of dyslipidaemia.Different OPA levels might lead to differences in association with blood lipid levels. Thus, OPA guidelines must be developed for farmers, especially for those who experience seasonal changes in farming work and job changes.The online version contains supplementary material available at 10.1186/s12889-022-13266-x. Cardiovascular disease (CVD) is a major public health problem. According to the China cardiovascular report 2018, CVD was the main cause of death, with the mortality rate being higher in rural areas than in urban areas .Physical activity (PA) is essential for healthy living. It can reduce the risk of many diseases . PreviouTherefore, the present study evaluated the association between OPA of farmers and dyslipidaemia according to different working modes in the 30–79-year-old population of the China Multi-Ethnic Cohort (CMEC) Study.Relevant data were obtained from the CMEC Study. The CMEC Study is a large-scale prospective cohort study. Related detailed information has been reported in the previous literature . BrieflyPA was measured using a self-reported questionnaire. The questions were set according to the China Kadoorie Biobank (CKB) . The queOPA during the past year was considered. Two sets of work-related questions, including nine questions about OPA, were asked to the farmers. However, for non-farmers, only one related question was asked: ‘In the past year, how active were you at work?’ Thus, our analysis was limited to the farmers in Dong, Miao, and Bouyei areas of Guizhou Province, wherein more detailed information about OPA was collected. Notably, the farmers in this study mainly refer to those engaged in agriculture and animal husbandry in the past year.The following working mode-related questions were asked: 1) In the past 12 months, did your farming work change seasonally? 2) Apart from the agriculture work, did you have any other job? Accordingly, we divided the participants into four characteristic groups , 2: changing job group (only other jobs), 3: seasonal change group , and 4: seasonal and job change group .The covariates were collected through face-to-face interview by using the standard questionnaire; these covariates comprised sociodemographic characteristics  and lifestyle behaviours .2).Body mass index (BMI) was obtained from baseline measurements of weight and height by specially trained staff using calibrated instruments. It was calculated by dividing the measured weight (kg) by the height in metres square (mAll the measurements (including data collection through self-reported questionnaire and face-to-face interviews and baseline measurements) were performed simultaneously throughout the day. The survey in our study was conducted from May 2018 to September 2019.The collected blood samples were sent to the JinYu Medical Laboratory Center of Guizhou Province for analysis of plasma high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) levels after more than 8 h of fasting. Blood samples were collected in the morning, and the participants did not perform any exercise before blood collection. All the blood samples were analysed using the automatic biochemical instrument . According to the Guideline for Prevention and Treatment of dyslipidaemia in China (2016 revised) , dyslipi25, P75)] because they did not follow the normal distribution. The continuous variables were compared using the Kruskal–Wallis test. Categorical variables  are expressed in terms of percentage or constituent ratio. The categorical variables were compared using the chi-square test.Continuous variables  are expressed as median and interquartile range [M  by quartile. The results are as follows: no change group, P25 = 10.6 and P75 = 42.3 MET-hr/day; changing job group, P25 = 20.2 and P75 = 59.4 MET-hr/day; seasonal change group, P25 = 10.7 and P75 = 24.6 MET-hr/day; and seasonal and job changes group, P25 = 20.1 and P75 = 45.2 MET-hr/day. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each type of dyslipidaemia associated with OPA of farmers with different working modes were estimated using the binary logistic regression models, after adjusting for the confounding factors, which included age, sex, smoking, drinking, leisure sedentary time, sleeping time, total energy intake, married or cohabitating, beverage intake, BMI, TPA, DPA, LTPA, ethnicity , education , and annual income . We used the directed acyclic graph (DAG) to identify the possible confounding factors .To compare the association between OPA in different working modes of farmers and dyslipidaemia, we divided the OPA under each working mode into three levels  was used for data analysis. Statistical tests were two-sided, and a A total of 7649 participants were included in this study. The mean age of the participants was 52.7 years, and 63.4% participants were women. Overall, 14.0%, 5.5%, 61.1%, and 19.4% of the participants constituted the no change, changing job, seasonal change, and seasonal and job change groups, respectively. Generally, on an average, in the changing job, seasonal change, and seasonal and job change groups, younger men (more likely to be married men) had a lower level of education, LTPA, and annual income and a higher level of total energy intake than those in the no change group. In addition, the men in the three groups tended to smoke and drink more than those in the no change group .Figure Table Table Table In the present large population-based study of Chinese farmers, OPA with different work patterns exhibited differences in the association with varying blood lipid levels. In the no change and seasonal change groups, the level of OPA was low, and active OPA reduced the risk of dyslipidaemia. In the changing job and seasonal and job change groups, the level of OPA was high; however, active OPA increased the risk of dyslipidaemia only in the seasonal and job change group. No association was observed between any level of OPA and any type of dyslipidaemia in the changing job group.In terms of population characteristics and OPA, generally on an average, in the changing job, seasonal change, and seasonal and job change groups, younger men (more likely to be married men) had lower education level and annual income and a higher level of total energy intake. In addition, they tended to smoke and drink. This finding is consistent with the actual situation and those of some previous studies , 19. GenPrevious studies have reported that PA could reduce the risk of dyslipidaemia but had weak association with LDL-C or TC , 26, 27.Additionally, the OPA level was high in people who reported other jobs regardless of seasonal changes in farming work, indicating that engagement in other jobs might increase the OPA level. In the seasonal and job change group, men had higher levels of TG, TC, and LDL-C and lower levels of HDL-C than women, and the Q2–Q3 level of OPA could increase the risk of dyslipidaemia. Holtermann A et al. reported six reasons for the ineffectiveness of OPA in improving cardiovascular health like LTPA . We specAlthough the development of global economy has brought the era of mechanisation into the life of farmers , most arThis study has important implications for public health. Exercise can improve body’s metabolism and promote mental health. The present data suggest the necessity to develop OPA guidelines for farmers. Moderate OPA may help in reducing the risk of dyslipidaemia in a primary care setting or a large cohort. Farmers with seasonal changes in farming work and those involved in other jobs should carefully manage their OPA level. Considering the ongoing dyslipidaemia epidemics affecting contemporary society, understanding the association of OPA in different working modes with dyslipidaemia among farmers is of great importance for public health.This study presents several advantages. First, to the best of our knowledge, this study is the first large-scale epidemiological study conducted by a Chinese group on ethnic minorities in Southwest China by using a suitable electronic questionnaire to investigate the OPA characteristics of farmers and preliminarily explored their relationship with dyslipidaemia, which may be useful for further research. Second, it combined the characteristics of current farmers’ working modes, divided the farmers into four different characteristic groups, and discussed the relationship between OPA and dyslipidaemia under different working modes. To our knowledge, this study is the first in southwest China to link OPA with dyslipidaemia among farmers, which holds reference significance in clinical and public health.This study also has some limitations. First, OPA in our questionnaire was self-reported. Second, because of the cross-sectional study design, causal inference was limited and could only provide clues about aetiology, warranting further follow-up studies. Finally, the influence of genetic factors could not be addressed in the present study.This study suggested that different OPA levels might exhibit different associations with blood lipid levels. According to our results, in the no change and seasonal change groups, the active OPA reduced the risk of dyslipidaemia. In the seasonal and job change groups, active OPA led to the increase in the risk of dyslipidaemia. Therefore, in the no change and seasonal change groups, the working mode of OPA was feasible. In addition, this study showed that the OPA guidelines vary for farmers with different working modes. In particular, our research suggested that farmers in the seasonal and job change groups should try to reduce the level of OPA. We will continue to study the relationship between OPA and blood lipids in this population and explore OPA conducive to maintaining a high blood lipid level.Additional file 1: Figure S1. Directed acyclic graphs adjusting for confounders.Additional file 2: Supplemental Material S1. The China Multi-Ethnic Cohort (CMEC) Study questionnaire on occupational physical activity among non-farmers and farmers. Supplemental Material S2. The measurement methods for weight and height. Supplemental Table S1. Occupational physical activity types, MET values, and intensity categories.


In this review, we present current knowledge of sex hormones in the process of development of malignant diseases. The impact of sex hormones on immune system is presented. A special account is devoted to estrogens and their role in modification of anticancer immune response.Sex hormones are included in many physiological and pathological pathways. Estrogens belong to steroid hormones active in female sex. Estradiol (E2) is the strongest female sex hormone and, with its receptors, contributes to oncogenesis, cancer progression and response to treatment. In recent years, a role of immunosurveillance and suppression of immune response in malignancy has been well defined, forming the basis for cancer immunotherapy. The interplay of sex hormones with cancer immunity, as well as the response to immune checkpoint inhibitors, is of interest. In this review, we investigate the impact of sex hormones on natural immune response with respect to main active elements in anticancer immune surveillance: dendritic cells, macrophages, lymphocytes and checkpoint molecules. We describe the main sex-dependent tumors and the contribution of estrogen in their progression, response to treatment and especially modulation of anticancer immune response. Malignant diseases constitute a growing problem worldwide, with increasing incidence and mortality. The main type of malignant neoplasms are solid tumors with principal representatives: cancers. Cancers are the first or second leading cause of death among people younger than 70 years of age in many countries . Breast The aim of this review is to summarize current knowledge on the role of estrogens in carcinogenesis, as well as their reactivity in anticancer immune responses.Estrogens are steroid hormones that regulate multiple physiological processes in order to maintain homeostasis . CholestAndrogens are precursors of estrogens. The enzyme aromatase (CYP19A1) is responsible for the bioconversion of precursor androgens into estrogens. Aromatase is a member of the cytochrome P450 superfamily. Aromatase is expressed in gonads, endometrium, blood vessels, liver, lung, bone, skin, adipose tissue and brain. Estrogens are synthetized in the ovaries during procreation and, after that, are produced in gynecological and non-gynecological organs. Adipose tissue is a main site of steroid hormones in the body. Primary sites of estrogens include the ovaries, placenta, and breast tissue, although they can also be detected in the skin, bones, brain, liver, lung and adrenal glands [There are endogenous or exogenous sources of estrogens. Synthetic estrogens are taken as contraceptive or substitutive in hormonal replacement therapy (HRT). Other sources of estrogens include food (phytoestrogens) and metabolites from the environment (xenoestrogens) . HormonaESR1 and ERS2, respectively [Estrogens interact with their receptors. There are two nuclear receptors: estrogen receptor α  and estrogen receptor β . ERα and ERβ are nuclear receptors encoded by genes: ectively ,10.Other receptors active in estrogen function include membrane receptor (mER) and G protein-coupled receptor 1 (GPER1) ,5,11,12.Estrogen receptors belong to the family of transcription factors and act by genomic (gene transcription) and nongenomic pathways. ERs are widely distributed in the body, but the distribution and action of the two types of ERs in organs and tissues differ . ERα occ-Direct genomic pathway binding to ERs in cytoplasm;-Indirect genomic signaling;-Non-genomic signaling  ,11.Sex hormones act by the following signaling pathways:ERs are also expressed in immune cells, including macrophages, dendritic cells and lymphocytes, wherein ERα is expressed rather on T cells and ERβ is expressed on B cells. The presence and expression of ERs determine the effect of estrogens on immune response ,13.E2 not only mediates biological reactions and preserves homeostasis in normal conditions but is also responsible for the development and spread of malignant tumors. Estrogens influence the progression of a range of hormonally responsive tumors. These include breast, prostate, gynecologic, lung, colorectal cancer and other tumors .As much as 80% of breast carcinomas have been found to be ER-positive and plausibly influenced by circulating estrogens . The figMost results from prospective observational studies and randomized controlled trials show that the use of HRT increases breast cancer incidence ,27,28. CTriple-negative breast cancer (TNBC) is an exceptionally aggressive type of breast cancer that remains the most challenging subtype to treat ,32. It iOvarian cancer is known as a hormone-dependent malignant tumor. For many years. estrogens were suspected as a main risk factor. Recently, it was show in many studies that hormonal dependence in ovarian cancer is complex . In vitruishable ,39. ERβ uishable . ERβ agouishable . The resuishable . Progestuishable ,41. Takeuishable ,43. In the prostate, androgen receptors (ARs) function as gene regulators that promote cell survival. It is well known that the ERβ is also present in prostate tissue, yet its role concerning the suppression or enhancement of cancer development remains undetermined ,44,45. ISERMs (selective estrogen receptor modulators) are successfully used in the treatment of breast cancer. Considering the presence of ERs and their modulating activity towards prostate cancer (PCa) progression, it has been proposed to use SERMs as therapeutic agents in PCa . Zazzo eERβ plays a crucial role in sustaining proper epithelial architecture in healthy colonic tissue. Moreover, it has an impact on gastrointestinal physiology and can mediate various immune responses ,54. It hAs mentioned above, lung cancer is the best example of a common solid tumor. There are different histological types of lung cancer. The two main types are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC is divided into three major subtypes: adenocarcinoma, squamous cell carcinoma and large cell carcinoma. The morphological characteristics, as well as molecular alterations, of lung cancer are well defined . This caEstrogen can be produced locally in lung tissue, mainly by aromatase, which converts androgen into estrogen . The intAnother important pathway is the relationship between epidermal growth factor receptor (EGFR) activity and estrogens in NSCLC. EGFR is mutated in high frequency in adenocarcinoma and acts in carcinogenesis . EstrogeRegarding the association of HRT use and risk of developing lung cancer, the findings are conflicting; some studies report a reduced risk of lung cancer ,78, wherRecently, it has been concluded that gliomas and, more specifically, astrocytomas are hormone-sensitive tumors that could be influenced by estrogens present in brain . The mosAlthough tumors of hematopoietic and lymphoid tissues are not sex-related diseases, there are some discrepancies in their incidence between genders. It has been reported that peripheral blood mononuclear cells (PBMCs) express both estrogen receptor subtypes in subjects with chronic lymphocytic leukemia (CLL) , whereasSex hormones and their receptors take part in regulation of immune status in health and disease. Clinical data, basic research and experimental studies provide evidence of the important role of estrogens in immunity. Clinical observations show that there is a prevalence of some diseases with immune background in women . The besAn improvement of some diseases during pregnancy is observed . The effect of rituximab is more pronounced in women than in men . HRT is The direct impact of sex hormones on the immune system is known. In general, testosterone is related to an immunosuppressive effect, whereas estrogens correlate with immunoenhancement. Dendritic cells (DCs), macrophages, natural killer T-cells (NKT), T cells and B-cells are sex-hormone-sensitive immune cells. The effects of estrogens include the elevation of phagocytic activity of macrophages; antigen-presenting function of DCs; differentiation in the Th2 direction; higher T-cell and B-cell contributions but lower eosinophils contribution; and cytotoxic CD8 cells, NK and ILC-2 cells ,87. E2 sSome genes on chromosome X are included in the regulation of immunity . Some inESR1 and ESR2 genes for ERα and ERβ, respectively [ESR1 and ESR2 RNA is high in human B cells but lower in T cells and DCs. ESR1 expression changes during differentiation of DCs. Estrogens are involved in the regulation of the genetics of ERs.ERs are involved in the regulation of the immune system by estrogens. It was found that ERs are encoded by ectively . ExpressEpigenetic and environmental factors can modulate this sex-dependent immune phenotype. Sex hormones affect the immune system ; thus, iThe success of immunotherapy with checkpoint inhibitors (ICIs) of solid tumors has introduced a new perception of cancer interplay with the tumor environment (TME). The role of immune response in cancer has been known for years. Many methods of cancer immunotherapy before ICIs were found to be more or less effective but with no established order among recommended therapies in oncology. Finally, ICIs found their place in the first-line of treatment of patients with advanced tumors . HoweverThe term “immunoscoring” illustrates the role of TME in susceptibility to ICIs. Galon et al. described the methods of immunoscoring evaluation in colon cancer . The resThe TME of tumors with a high resection rate, such as melanoma, colon carcinoma and breast cancer, have been well-characterized ,98, wherNSCLC is a good example of the role of the TME in cancer prognosis. In a meta-analysis, Soo et al. presented the significance of specific cells in the TME . The anaThere are numerous mechanisms of resistance to ICIs: lack of immunogenicity, enhanced T-cell exclusion, lack of response to IFNγ, an increased prevalence of immunosuppression in the TME, upregulation of other immunosuppressive receptors on T cells: cytotoxic T cell antigen- 4 (CTLA-4), T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM3); lymphocyte activation gene 3 (LAG-3); and V-domain Ig suppressor of T-cell activation (VISTA), low neoantigen production .There are some important processes other than the strict immune response in the interplay between cancer and the host. These are autophagy and epithelial–mesenchymal transition (EMT). Autophagy serves the preservation of cell homeostasis. It is a biological process of intracellular degradation, recycling and removing cell products. Autophagy may be induced by extrinsic factors, such as stress. In malignancy, the role of autophagy is complex; it may contribute to cancer cell survival and tumor progression or to cell death. Autophagy and apoptosis are associated with what is important in the context of anticancer therapy: autophagy protects cancer cells. The role of EMT in cancer progression is to facilitate the ability to spread and increase the metastatic potential. This is a process in which epithelial features of cancer cells change into mesenchymal-like phenotypes .A natural response in women;Fluctuation of hormonal balance during life;Immunoaging;Direct impact of estrogens on immune cells and their progenitors; Influence of hormones given in HRT;Interplay of cancer immune response and natural hormonal status.In the analysis of the relationship between sex hormones and cancer immunity, some aspects need to be considered to achieve a broad overview:Thanks to numerous studies, recognition of this difficult topic has been achieved. Sex hormones, i.e., estrogens, have an impact on almost all known directions of anticancer immune response. In general, estrogens contribute to immunosuppression, thus helping malignant tumors to escape from immunosurveillance.The TME consists of heterogenous components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), T and B cells, natural killer cells (NK), endothelial cells and the matrix . Thus, cDCs are crucial in antigen presentation and are important players in anticancer responses. The population of DCs is not uniform . ERs, whAn estrogen-rich environment might contribute to an enhanced differentiation of pulmonary macrophages into M2 phenotypes . In studEstrogen receptors were found to influence the process of autophagy in cancer tissue and in the TME . This prThe role of the PD-1/PD-L1 axis in suppression of anticancer response is well-known . UpregulThe majority of malignant tumors develop in the elderly. However, aging is not the only reason for the appearance of cancers. In the breast, ERα cancers occur during menopause, and with age there, is an increased risk of chromosomal alterations that accumulate over time. Similarly, a decrease in physical exercise can lead to overweight and changes in steroid hormone balance. It is important to remember that the development of cancer is multifactorial.Some remarks need to be made in relation to changes of the immune system in older age. It has been reported that immunoaging generally reflects chronic inflammation . Innate An instructive lesson on the subject of the impact of estrogens on cancer immunity can be drawn from studies in breast cancer. In general, breast cancers are silent, with low mutational activity, modest immune infiltration by lymphocytes  and low PD-L1 expression . Other fThe expression of the PD-1 pathway correlates with TILs . WhereinTNBC were shown to be responders to ICIs, thanks to high TMB, rich TILs and high PD-L1 expression . ICIs . Reports show that high aromatase concentration is a poor prognostic factor in NSCLC for both genders . AnotherExosomes are small extracellular vesicles (EVs) originating from cells bearing important molecules capable of reflecting cell signature. Tumor-derived exosomes (TEXs) were found to play an important role in cancer progression. TEXs are able to modify the immune environment of malignant tumors ,147. TheSex hormones are ubiquitous. The balance of female and male hormones is observed in both sexes. The impact of estrogens on the development and spread of different neoplasms seems to be strong. Estrogens are present and locally produced in many cancers. Estrogen receptors are not without importance in oncogenesis. In this review we summarized that the female hormones engage in modification of immune anticancer response by weakening it. To summarize concluding remarks we present here Estrogen activity is not simple and unidirectional; there is a complex interplay between hormones, receptors and enzymes. Many signaling pathways are triggered, and sometimes the actions are opposite. The hormonal balance resamples immune reactions; the nature of the environment is capable of modifying and directing processes. Sex hormones are involved in oncogenesis and progression of many malignant tumors, not only those known to be hormone-dependent, such as lung cancer. Immune anticancer response and TME have an undeniable and well-known meaning in cancer development and remain an important target for therapy. The results of many studies show that sex hormones are involved in a plethora of immune reactions. The direction of estrogen activity in TME is connected with suppression of anticancer response. Recently, the use of immunotherapy with immune checkpoint inhibitors was established; however, the biomarkers are widely investigated. Our results, as well as those of other studies, support the value of TME investigation before therapy. Our knowledge on tumor biology and host status could be improved by evaluating hormone concentration, expression of sex hormone receptors and enzyme activity. The standardization of TEX detection may by valuable. Altogether, research to date indicates a very important and interesting direction for future studies, as well as new methods of combined therapies, which have been shown to be more effective than monotherapy. However, many questions remain.