In recent years, more and more reports are focused on the application of traditional Chinese medicine injection (TCMJ) for the treatment of viral pneumonia. There are about 200 million cases of viral pneumonia worldwide every year, half of which are children. At present, many kinds of TCMJ are created for the treatment of viral pneumonia in children, with good therapeutic effects. However, there are many kinds of TCMJ, and the treatment advantages are different, thus bringing difficulties to the selection of clinical drugs. In order to provide evidence-based evidence support for the clinical selection of TCMJ for the treatment of viral pneumonia in children, this study selected the commonly used TCMJ for clinical treatment of viral pneumonia for meta-analysis to evaluate its efficacy.The Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data, Viper information databases, Cochran library Web of Science, PubMed, MEDLINE and EMBASE will be searched. The literature will be searched, with language restriction in English and Chinese. The related reference will be retrieved as well. Two reviewers will independently extract data and perform quality assessment of included studies. Review Manager 5.3 will be applied to conduct this meta-analysis.The results of this systematic review and meta-analysis will be published in a peer-reviewed journal once we finish this study.This study provides reliable evidence-based evidence for the efficacy of TCMJ in the treatment of viral pneumonia in children.We will not be allowed to publish private information from individuals. This kind of systematic review should not harm the rights of participants. No ethical approval was required. The results can be published in peer-reviewed journals or at relevant conferences.DOI 10.17605/OSF.IO/795MB. If it is not controlled in time, it can cause serious damage to the body. The disease has two characteristics, namely rapid onset and rapid progression. Most of the clinical manifestations include fever, cough, expectoration, wheezing and other symptoms.,6 In severe cases, it can cause respiratory failure, and then endanger children's live. At present, the incidence of the disease is gradually increasing. It cannot be a targeted treatment, because there are many kinds of pathogenic viruses, frequent variation and easily produced drug resistance.Viral pneumonia in children is one of the common diseases in pediatrics, and it is commonly caused by respiratory syncytial virus, influenza virus, adenovirus and so on. However, due to the large variety of viruses and frequent variation, it is not difficult to produce drug resistance, poor efficacy, and other problems.,11Western medicine is mainly treated with antiviral drugs, including ribavirin, acyclovir, interferon and adenosine arabinoside, but a unified treatment plan has not yet been formed. Although the pathogens are different, there are similarities in the mechanism, clinical manifestation and treatment of the disease that is caused by the virus.TCM treatment should clear heat and detoxify, release the lung and dissipate phlegm.,15 Studies have revealed that traditional Chinese medicine injection (TCMJ) such as Xiyanping, Tanreqing and Reduning, has obvious advantages and characteristics in terms of the prevention and treatment of infantile viral pneumonia.,16 However, the homogenization of these TCMJ is serious, and the efficacy and indications are similar, but the difference in curative effect is not clear, so doctors and patients are at a loss when choosing drugs. The purpose of this study is to systematically evaluate the efficacy of TCMJ in the treatment of viral pneumonia in children by adopting the principles and methods of evidence-based medicine. At the same time, it also provides some reference materials for the treatment plan of coronavirus disease 2019 for children.Viral pneumonia belongs to the category of “wind-warming and lung-heat disease” in traditional Chinese medicine (TCM).22.1 Moreover, it has been registered on Open Science Framework (Registration number: DOI 10.17605/OSF.IO/795MB).The protocol followed the guideline of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols.2.2No patients involved.2.3The Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data, Viper information databases, Cochran library Web of Science, PubMed, MEDLINE and EMBASE databases will be searched from inception time to date. Studies concerning the effects of TCMJ in the treatment of viral pneumonia in children will be included in this meta-analysis, and randomized controlled trials (RCTs). The related reference will be retrieved as well. The literature will be searched, with language restriction in English and Chinese. The detailed information of PubMed search strategy is presented in Table 2.4RCTs will be included in this meta-analysis.2.51) Incomplete data or misrepresentation of data reports; 2) repeated publication of documents; 3) case reports, reviews, etc.; 4) inability to obtain original documents.2.6Children enrolled should be diagnosed as virus pneumonia.2.7The experimental group was treated with both control group treatment and TCMJ, and the type of TCMJ was not limited. The control group was standard treatment .2.8Main outcomes: Effective rate.Additional outcomes: 1) Time for body temperature to return to normal; 2) Cough disappearance time; 3) Rale disappearance time; 4) Hospitalization time; 5)Body temperature began to drop time; 6) Antiasthmatic time; 7) X-ray inflammation absorption time; 8) Adverse reactions.2.92.9.1Two reviewers independently select studies, and any disagreement between the two reviewers should be consulted by a third reviewer for a consensus. We will remove repetitive articles at first and exclude irrelevant studies based on the title, abstract and the full text. The study selection process is displayed in a Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols flow diagram Figure .2.9.2A standardized form will be used by two reviewers to extract data independently, and disagreements between them should be solved with the help of a third reviewer. The detailed extraction information is as follows: the first author, publication date, country, sample size, age, type of TCMJ, content and duration, intervention time, intervention details, etc.2.10The Cochrane Systematic Review Manual recommended bias risk assessment method for risk assessment for inclusion in RCT. The main items are as follows: 1) Randomization plan; 2) Group concealment; 3) Blind method; 4) Incomplete data reporting; 5) Selective outcome report; 6) Other sources of bias. Each item is evaluated as “high”, “low” or “unclear”.2.112.11.1Review Manager 5.3 ) will be used to conduct this meta-analysis. The standardized mean difference with 95% confidence intervals (95% CIs) is applied to calculate continuous variables. The relative risk ratio with 95% CIs is used to calculate binary variables.2.11.2Statistical heterogeneity among included studies will be assessed by carrying out the χ2 test and I2 test. We will adopt a fixed-effect model for data analysis at first. If I2 > 0.5 or p < 0.1, it is considered that there is a significant heterogeneity among the studies, and random-effect model will be accepted without examining the probable cause for the high heterogeneity.2.11.3Subgroup analyses will be performed on the type of TCMJ and the efficacy of TCMJ.2.11.4Sensitivity analysis is conducted by excluding studies one by one, so we can determine the source of heterogeneity.2.11.5Egger's test and Begg's test will be conducted to quantitatively assess the publication bias.2.12Due to the nature of this meta-analysis, ethical approval is not required, which is based on published papers. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal once we finish this study.3 At present, the treatment of viral pneumonia in children is not unified. Western medicine is often applied to treat this disease with antiviral drugs such as ribavirin, but it is obvious that the therapeutic effects of these drugs are not satisfactory, and there are many adverse reactions.Viral pneumonia is a disease characterized by pulmonary dysfunction, and it is caused by the downward spread of the virus and the inflammation of the lung parenchyma. In recent years, the incidence of viral pneumonia has gradually increased, especially in infants under 2 years old. In China, the effectiveness of TCM in the control of infectious diseases has been proved. Therefore, the Chinese government encourages the application of TCM to fight viral pneumonia. Xiyanping injection, Xuebijing injection, Reduning injection and Tanreqing injection can improve the total clinical effective rate, shorten the duration of main clinical symptoms, and sign in the treatment of viral pneumonia.–27 However, in many countries in the world, TCMJ for the treatment of viral pneumonia in children is still challenging.TCM treatment is generally based on clearing lung and detoxification, and relieving cough and asthma. TCMJ has been widely used in clinical practices in China, and it is widely used by patients suffering from respiratory diseases.At present, the clinical trial data on the efficacy and safety of TCMJ for the treatment of viral pneumonia in children are limited, and there is insufficient comprehensive review and summary. Therefore, the purpose of this paper is to explore the efficacy of drug injection in the treatment of viral pneumonia in children, and to provide decision-making basis for clinical diagnosis and treatment of viral pneumonia in children. As far as we know, this is the first systematic review and meta-analysis of the efficacy of TCMJ for the treatment of viral pneumonia in children.This work is supported by the Scientific Research Project of Shanghai Health Bureau(20174341).Conceptualization: siqiong jiang.Data collection: Li Fang and Jiaoru Pei.Data curation: Li Fang, Jiaoru Pei.Formal analysis: Li Fang.Funding acquisition: siqiong jiang.Funding support: Siqiong Jiang.Literature retrieval: Song Mao.Project administration: siqiong jiang.Resources: Jiaoru Pei.Software operating: Liangxia Wu.Software: Jiaoru Pei, Song Mao.Supervision: Siqiong Jiang, Song Mao.Validation: Song Mao, Liangxia Wu.Visualization: Liangxia Wu.Writing – original draft: Li Fang, Jiaoru Pei, and Siqiong Jiang.Writing – review & editing: Li Fang, Jiaoru Pei, and Siqiong Jiang.


Background and Aims: Acute liver injury (ALI) is a clinical syndrome characterized by rapid loss of liver function, which may progress to life-threatening liver failure. We conducted this meta-analysis to examine the evidence on the effects of probiotics or prebiotics on ALI.Methods and Results: Several databases, including PubMed, EMBASE, and Cochrane Library, were scrutinized from the inception through February 2021 by combining key search terms, yielding 26 eligible studies, which concluded that modulation of gut microbiota significantly decreased aspartate transaminase , alanine aminotransferase , and bilirubin . In addition, administration of probiotics or prebiotics also promoted proliferation of Bifidobacterium  and inhibited Enterococcus , contributing to lower levels of endotoxin . Tight junction protein ZO-1  was upregulated after intervention, thereby reducing bacterial translocation to the liver  and mesenteric lymph node , with decreased tumor necrosis factor-α  and interleukin-6 . Oxidative stress was also relieved by reducing malondialdehyde  while elevating superoxide dismutase  and glutathione .Conclusion: Our findings suggest that probiotics and prebiotics could be a promising therapeutic strategy in ALI and possess a potential for clinical applications.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=255888, CRD42021255888. Acute liver injury (ALI) is defined as a rapid degeneration of liver biochemistry within 6 months in patients with no prior liver disease . With thvia toll-like receptors (TLRs) and nod-like receptors, resulting in the production of inflammatory mediators and chemokines, with the activation of stellate cells involved in fibrosis progression .This meta-analysis was registered on PROSPERO  principle was followed during the literature screening. Studies that met the following inclusion criteria were considered for selection: Participants (P): patients or animal models of ALI regardless of the cause. It should be noted that no clinical studies were available at the end of the selection process, and all the literature involved was on animal research; therefore, the objectives were finally limited to animal models; Intervention (I): the intervention group received microbial agents, such as prebiotics or probiotics regardless of dosage, route, and duration; Comparison (C): control group without receiving microbial agents; Outcome (O): the studies should at least measure one of the following indicators: alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin, TNF-α, interleukin-6 (IL-6), IL-10, cholesterol, triglyceride, BT, endotoxin, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), or ZO-1; Study design (S): randomized controlled studies. Studies with the occurrence of acute liver failure during the trial or unavailable data were excluded.Since all clinical studies were removed during the screening process, with only preclinical studies included according to the selection criteria, the methodological quality was evaluated based on the rules detailed in systematic review centre for laboratory animal experimentation's (SYRCLE) risk of bias tool . The folQ-test and I2 statistics . A random-effects model will be performed due to the exploratory nature of the animal studies. A value of p < 0.05 was considered statistically significant. Subgroup analysis was also performed for indicators with more than 10 included studies according to the type of microbial agents, bacterial strain, animal model, and modeling method to explore the source of heterogeneity. We also used the meta-regression to detect where the potential factor for heterogeneity originated. Sensitivity analysis was conducted to identify the studies that significantly affected the findings by excluding studies from the analysis one by one to gauge the robustness of our results. Publication bias was estimated quantitatively using Egger's test. A contour-enhanced funnel plot with the “trim and fill” method was obtained as an aid to differentiate asymmetry caused by publication bias or other factors such as heterogeneity  were applied to determine differences in outcomes of continuous variables, with results of the dichotomous variables reported as odds ratio (OR) and 95% CI. Heterogeneity was assessed by using the Cochran ogeneity . If the As shown in the PRISMA flow diagram, a total of 3,802 studies were initially retrieved by searching the databases, which reduced to 3,649 after the deletion of duplicates. Preliminary screening of the titles and abstracts reduced the number to 67 articles after the exclusion of 3,582 studies. A further 41 articles were rejected based on a detailed full-text evaluation, with 26 studies ultimately being eligible for the data extraction and analysis. All the literature involved was on animal studies, as there were no clinical studies that met the selection criteria  8–33)..33).Lactobacillus and Bifidobacterium, were more commonly used in the intervention group compared to prebiotics (including lactulose and inulin), which were employed by only six studies. Oral gavage was the most commonly used route of drug delivery, while transrectal administration through a rectal tube was used by only two studies. Saline was used as the control in most of the studies, while a standard diet was used by Nardone, G.Two reviewers independently evaluated the methodological quality by employing SYRCLE's risk of bias tool. Each item was judged as “low risk,” “unclear,” or “high risk.” Blinding was the major contributor to bias; the blinding and allocation bias were unclear in most studies, as specific details of relevant information were often not provided. All studies were scored as having a low risk of bias in reporting bias. Overall, the assessment result was similar across the studies used in this meta-analysis with high quality and low risk of bias . DiscrepI2 = 82%, and p < 0.01) and ALT  and prebiotics , but reduced in the subgroup animal model of AST (p < 0.01). Although there is an obvious asymmetry in the contour-enhanced funnel plot : −1.51, 95% CI: −2.03 to −1.00, l of AST , indicatl of AST . Subgroul of AST , 3A. Pubnel plot , it was nel plot . ResultsI2 = 0%, p = 0.85 and I2 = 0%, p = 0.97, respectively). Notably, although the horizontal lines of most of the selected studies intersect with the invalid line, which may be caused by the small sample size, the combined results showed significance. After the use of prebiotics or probiotics, the abundance of detrimental Enterococcus in the ileocecal region was less than that of the control group  with good homogeneity , while most studies believed that the colonization of Bifidobacterium, a beneficial bacterium, increased in this area   and mesenteric lymph node  , indicatI2 = 93%, p < 0.01 and I2 = 95%, p < 0.01, respectively). However, except for significant heterogeneity , an interesting trend was noted for the pooled result of IL-10, which showed higher levels in the microbial intervention group than in the placebo-treated group  and decreased in the serum , showing the opposite trend. Subgroup analysis and meta-regression of TNF-α suggested that the animal model and modeling methods were the sources of heterogeneity (p < 0.01). The contour-enhanced funnel plot with the trim-and-fill method , along with the enhancement of antioxidant capacity, which was reflected in the increased level of SOD  and GSH , with obvious heterogeneity  transactivate the epidermal growth factor receptor  and NF-κB that initiates the production of inflammatory cytokine TNF-α, IL-6, and IL-1β . In the The study presents several limitations. First, unavoidable heterogeneity emerged when we combined certain indicators due to the exploratory nature of animal studies, even if the random-effects model and subgroup analysis were performed. However, meta-regression indicated the source of heterogeneity, and sensitivity analysis confirmed that our results were robust. In addition, asymmetry appeared in the funnel plot, and Egger's test indicated the existence of publication bias. However, the contour-enhanced funnel plot with trim-and-fill methods ultimately demonstrated that heterogeneity was the main cause of the asymmetry, and the number of unpublished nonsignificant literature was estimated to be very small. In this context, our conclusions based on 26 articles are still of reference significance. Furthermore, we did not include symbiotics and postbiotics because the quality of the literature did not meet our expectations. Finally, we did not explore a dose–response relationship between microecological therapy and ALI efficacy because of the limited data provided by the literature.Our study demonstrated that probiotics and prebiotics have a significant ameliorative effect on ALI through the gut–liver axis by upregulating tight junction protein ZO-1, correcting the abundance of the ileum flora, reducing BT and endotoxin invasion, and suppressing oxidative stress and proinflammatory mediators, thus, in turn, improving liver biochemical indicators. Our findings also provide a novel insight into the microbial therapies for ALI in clinical practice and imply a promising prospect of applying the gut–liver axis in the management of liver diseases. More clinical studies are required to facilitate the transformation of these preclinical research results into practical applications.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.CX and FW conceived the study idea, guided the work, checked the data, and revised the manuscript. SX designed the retrieval strategy, analyzed the data, drew the pictures, and drafted the manuscript. MZ and QW screened the studies, assessed the methodology quality, extracted study information, and made the flow charts. ZXu and BP analyzed and checked the data. YX and ZD designed retrieval strategy and beautified the pictures. SW beautified the pictures and made the tables. ZXue guided the work and revised the manuscript. All co-authors had full access to and approved the final version of the manuscript.This work was supported by grants from the Zhejiang Provincial Natural Science Foundation of China (LY20H180010) and Wenzhou Science and Technology Bureau (Y20180142).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.


A total of 103 patients with AD and 146 healthy controls were recruited. A total of 46 single-nucleotide polymorphisms (SNPs) spanning the three genes were genotyped, of which only 19 SNPs were included in the final analyses after excluding non-polymorphic and Hardy–Weinberg equilibrium-violating SNPs. Apart from our previously reported APOE ε4, four other SNPs in APOE , one in EGFR (rs6970262), and one in ACTB (rs852423) showed a significant association with AD (p < 0.05). Our results validate the reliability of genomic convergence and network analysis approach in identifying the AD-associated candidate genes.Previously, we demonstrated an integrated genomic convergence and network analysis approach to identify the candidate genes associated with the complex neurodegenerative disorder, Alzheimer’s disease (AD). Here, we performed a pilot study to validate the  Alzheimer’s disease (AD), the most common cause of dementia, is becoming a major health burden worldwide among the elderly due to the aging population, absence of early diagnostic markers, and the lack of disease-modifying treatment . GloballAPP) and the presenilins (PSEN1 and PSEN2), while sporadic AD involves the contribution of both genetic and environmental factors  from 2010 to 2012 were enrolled in this cross-sectional study. Family members gave written informed consent, and the study was approved by the Institutional Ethics Committee. The other details related to diagnosis, assessment, investigations, and recruitment of the patients with AD (PwAD) and healthy controls are provided in APOE, EGFR, and ACTB genes were screened from the literature, and then the functional significance of the SNPs was determined by screening databases including HaploReg, RegulomeDb, rVarBase, and Braineac (in build in vitro and in vivo evidence). Please refer to Genomic DNA was isolated from the peripheral blood leukocytes using a modification of a salting out procedure . The funhttps://zzz.bwh.harvard.edu/plink/gplink.shtml). The imputation, quality control (QC), and association analysis procedure are described in The SNP association analysis was conducted in PLINK version 1.09  and gPLILogistic regression analysis was conducted to assess the differences of genotype frequencies between AD and non-demented control groups. The additive model, the dominant model and the recessive model were used in the logistic regression analysis for SNP association with disease phenotype adjusting for age, gender, and education status as covariates. In the additive model, homozygotes for the major allele, and heterozygotes and homozygotes for the minor allele were coded to a quantitative numeric variable for genotypes , implying the additive effects of allele dosage. The dominant and recessive models assume the full dominance [genotype coding ] or recessive [genotype coding ] for the minor allele . The linp < 0.05)  fulfilling the selection criteria along with 159 healthy controls (51.6% men) of similar ethnicity were enrolled . A signi < 0.05) , requiriAPOE, 24 from EGFR, and 12 from ACTB were selected for the case–control association analysis. Out of the total 267 individuals, 12 were excluded either due to the lack of phenotypic data or insufficient DNA and 6 due to the failure of genotyping, resulting in data from 249 total individuals (103 PwAD and 146 controls). Of the 46 SNPs, 12 were found to be non-polymorphic in individuals from the two groups, while 15 failed the Hardy–Weinberg equilibrium (HWE) test in the controls , ε3 , and ε4  haplotypes. We previously reported ε3 to be the most common in both cases and controls, while the presence of the ε4 allele increased the risk of having AD   . None ofadditive = 0.003, OR = 0.51, 95% CI = 0.33–0.79 and Pdom = 0.003, and OR = 0.39, 95% CI = 0.21–0.73), rs7259620 , rs769449 , and rs7256173  from APOE. In EGFR, rs6970262 showed significant association only in the additive model , and in case of ACTB, rs852423 showed significant association only in the recessive model  with AD risk after adjustment for age, gender, and education status. The data for significant associations are provided in APOE was found to be in a strong degree of LD with rs429358 (R2 = 0.96) and rs7259620 was in LD with rs405509 (R2 = 0.88). Despite this, we did not observe the formation of any haplotype block in the study.Logistic regression analysis performed for genotypic association analysis after adjustment for age, gender, and education status showed a significant association of rs405509  aggregates, and hyperphosphorylated tau-mediated neurodegeneration . Due to the highly conserved sequence and ubiquitous expression of ACTB, the gene is used as a reference for the normalization of target gene expression in mRNA and protein studies. However, in silico analysis involving four different gene expression datasets also found ACTB to be a central gene in AD pathophysiology (ACTB variant rs852423 with increased susceptibility to AD. The association of this SNP with AD also appears in the signaling network presented in the database NeuroMMSig (Our study also involved important SNPs from the gene ysiology . Our stuuroMMSig .in vitro experiment that generated insulin-secreting beta cells from human pluripotent stem cells has shown the fundamental role of actin in pancreatic progenitor gene expression and endocrine function (APOE ε4 genotype. The subjects carrying an APOE ε4 allele without dementia have shown a reduction in the cerebral metabolic rate of glucose (The current knowledge is limited, but a connection from this gene and glucose metabolism in AD pathophysiology is worth to be explored in the future studies. In fact, function . The panfunction . Moreovefunction , especia glucose .in silico approach (in silico findings, future studies with larger sample sizes using an expanded gene list need to be performed.The present study has some inherent limitations such as the low sample size. However, our study was a pilot investigation to validate the findings of our approach , and theapproach . In addiEGFR genetic variant rs6970262. Our previous in silico analysis (APOE, EGFR, and ACTB, highlighting the importance of integration of experimental and computational approaches to reveal the clinical significance of genetic variants in a disease phenotype. However, as multiple SNPs are implicated in complex disorders such as AD, a combination of genetics with biochemical serum markers would be crucial to uncover the pathophysiological cascade (In summary, this study provides the first evidence of the association of the analysis  and its  cascade . Our res


Health-related quality of life (HrQoL) and workability are related parameters to measure success of therapy. Both have been insufficiently explored in patients after liver transplantation (LT). Particularly little is known about patients’ attitude to return to work, employment status before LT, and how frequently there is any employment at any time after LT.This is a single-center retrospective cohort study including 150 adult outpatients after LT. Liver transplantations had been performed between 1993 and 2018. The study was carried out from February to July 2018. The exclusion criteria were combined transplantations, positive screening for current alcohol abuse, and anxiety or depression. To evaluate HrQoL and fitness to work, the patients were tested using the Short Form 36, the Chronic Liver Disease Questionnaire, and the Work Ability Index.The return rate of sufficiently filled-in questionnaires was 46.8% (66 patients). The mean age of patients was 59.9 years (SD=10.8), ranging from 25 to 78 years old. HrQoL was partly comparable to the normal population. Workability sum scores with a mean value of 31.61 (SD 9.79) suggested moderate workability at present. While only 28.8% of respondents were ever employed after LT, 45.5% currently wished to work or would have wished to work.HRQL seems to be partly similar to population data, and subjective workability seems to be moderate in patients after LT. Despite a positive attitude to return to work in almost half of respondents, a lower rate of actual return to work was found in this study. Liver transplantation (LT) is the treatment of choice for patients with terminal liver disease . It has Two systematic reviews have confirmed improvement of HrQoL after LT compared to preoperative status , 4. ThisSubjective workability and return to work have been scarcely studied in patients after LT, although both might impact on HrQoL. To help liver transplant recipients in this respect, the aim was to further explore the interrelations between HrQoL, workability, and employment after LT. Therefore, the primary objective of this study was to quantify generic and specific HrQoL after LT and to explore workability and employment status before and after LT. As a second objective, the study investigated the correlation of age, gender, highest level of education, employment status, attitude to RTW, indication for LT, and time since transplantation with HrQoL and workability.This is a single-center retrospective cohort study, conducted at the General, Visceral and Transplant Surgery, Dept. of Surgery, Medical University of Graz. The ethics committee of the Medical University of Graz has approved the study (ethics committee number 29-622 ex 16/17).n=150). Liver transplantation in these patients had been performed between 1993 and 2018. The study was carried out from February to July 2018. The following exclusion criteria were applied in screening these patients for participation in this questionnaire study: combined transplantations (n=4), patients with current positive screening for alcohol abuse (AUDIT) (n=2), and current anxiety or depression (HADS-D) (n=3). Current alcohol abuse and current anxiety or depression were chosen as exclusion criteria to test for workability only in those patients after LT who were not additionally challenged by these prevalent mental health problems. The return rate of sufficiently filled-in questionnaires was 46.8% (66 patients) .The HADS-D is a standardized questionnaire that is commonly used to screen for depression and anxiety in patients with physical illnesses and complaints . It consThe AUDIT, developed by the WHO, is a screening tool for the identification of people with pathological alcohol consumption , 22. TheThe 36-Item Short Form Health Survey (SF-36) is a disease non-specific multidimensional questionnaire assessing various aspects of health-related quality of life . It examThe CLDQ-D is a disease-specific questionnaire to evaluate the health-related quality of life in people with chronic liver disease . The queFrom an occupational health perspective, workability as measured by the WAI is determined by the demands of the job, on the one hand, and the individual’s health status, skills, and education, on the other . This teComparative values of a healthy population are available in the SF-36 manual. It contains data from 1453 healthy persons  . The ageU tests for gender and by Kruskal-Wallis tests for all variables with three or four factor levels . Statistical significance was assumed at a p-value of <0.05.Statistical analysis was done using Microsoft Excel 2016 and IBM SPSS Statistics Versions 22 and 26. Due to the unknown distribution of the healthy control group’s data in the SF-36, comparisons of medians between patients after LT and healthy controls were calculated by Wilcoxon signed-rank tests. Shapiro-Wilk tests for normality showed that most continuous variables were not normally distributed within our sample. In these cases, differences between patient subgroups in quality of life and workability were detected by Mann-Whitney Sixty-six patients after LT 52 male, 14 female) were included in the analysis. The mean age of patients at present was 59.9 years old (SD=10.8), ranging from 25 to 78 years old. Details on demographic and clinical characteristics are displayed in Table 4 female n=25), HCC , HCV , and other indications including primary and secondary sclerosing cholangitis, primary biliary cholangitis, hepatitis B virus-associated liver cirrhosis, hemochromatosis, autoimmune-hepatitis, alpha-1-antitrypsin deficiency, and acute liver failure (n=24)  at present was 50.17 IQR 9.31) and 50.19 (IQR 13.13) for “mental health” (MCS)  and “physical health (PCS)”  scales.When comparing male and female patients in terms of the SF-36, female patients after LT reported lower quality of life in the “role emotional” ; retired patients formed the second group ; and the third group consisted of patients who were unable to work due to early retirement, sick leave, or unemployment . Group comparisons between these three employment groups showed that two dimensions of HrQoL, in particular, were associated with employment status . Concerning social functioning, there was a statistical tendency that patients in early retirement, sick leave, or unemployment had lower HrQoL than employed patients or retired patients , which demonstrates a limitation of HrQoL of 18.96% Table .U=206.5, p=0.043). With regard to all other dimensions of their disease-specific HrQoL, no differences between genders could be found . Patients in the three different age groups did not differ in their disease-specific quality of life as measured by the CLDQ-D . Age does not appear to have any influence on the overall index or individual categories .The total workability score, with a mean value of 31.61 (SD 9.79), is within the range of subjectively perceived moderate ability to work (28–36). The results of all seven dimensions of the WAI are shown in Table H=2.214, p=0.330). When considering the individual dimensions of workability, significant differences  could be found for dimension 5 (sick leave during the past 12 months): the older the patient, the fewer days absent. The other individual dimensions showed no significant age-specific differences , (ii) those who wanted to work but could not for several reasons , and finally (iii) the group who did not want to work after LT and also did not work . Workability among the first two groups was similar , whereas the mean score of group 3 was several points lower . Although these differences did not achieve statistical significance , a score of 28.6 according to the WAI classification would correspond to the bottom of the category of moderate workability , whereas scores of 35 and 36 belong to the upper end of moderate workability .As a next step, we wanted to compare subjective workability and quality of life at present among three groups of patients: (i) patients who wanted to work after LT and succeeded in working .Concerning quality of life as measured by the sum scores of SF-36 and CLDQ-D, these three groups did not differ from each other employment, patients may lose their jobs before this status is granted, e.g., during long periods of sick leave, and it may become particularly difficult to get hired again.H=7.21, p=0.027) and, in a statistical tendency, better social functioning .On average, study participants reported moderate workability according to WAI measurement, which seems sufficient to consider RTW accordingly. It should be mentioned that WAI is typically applied in occupational medicine to test for difficulties in working life, with the aim of providing preventive interventions to ensure that working life can be maintained . FurtherThese findings may suggest a discrepancy between the reported interest to RTW along with a sufficient self-perceived workability, on the one hand, and the possibility to RTW, on the other. This may deserve further attention as RTW can be assumed to be beneficial for long-term outcome, particularly with regard to HrQoL. Both individual and system-related reasons for such a discrepancy should be explored. It has been recently suggested that fatigue and weakness may hinder patient social reintegration after liver transplantation . AlthougIn accordance with previous research in patients after LT, the findings of this study suggest a similar mental health component as compared to population data and a partly reduced physical health component of HRQL in this patient group. On average, subjective workability seems to be moderate in patients after LT. Despite a positive attitude to return to work in almost half of respondents, a lower rate of actual return to work was found in this study. To better understand this finding, the impact of individual and systemic factors which can influence attitudes to returning to work and actual RTW need to be considered. This may be crucial to better support patients after LT with regard to potentially unmet needs on this matter of interest in RTW and actual (re)employment. Therefore, a prospective multicenter study should be conducted to further analyze the interrelations between HrQoL, workability, attitude to RTW, and employment status prior to and after LT, which also allows social, cultural, and economic factors to be taken into account.


Sahtak bi Sahnak on dietary knowledge and adherence to dietary guidelines in Lebanese adolescents.To evaluate the effectiveness of A cluster randomised controlled trial was conducted in public and private secondary schools located in urban and rural regions in Lebanon.n = 739) or control group (n = 833).Sixteen secondary schools including 1,572 adolescents were randomly assigned to the intervention .Multivariate multilevel regression models were used to examine intervention effects on outcomes, controlled for background characteristics  and intake of healthy items , compared to the control group. Intake of unhealthy items decreased significantly , compared to the control group. These results were adjusted for age, gender, type of school, location, BMI z-score, study group, and score at baseline.The intervention group showed significant improvements in total dietary knowledge (Sahtak bi Sahnak is an effective and culturally appropriate school-based intervention for targeting diet among a variety of Lebanese adolescents. According to the World Health Organization , paediatHealth experts have elaborated several comprehensive recommendations and strategic objectives to plan and implement effective interventions addressing paediatric obesity. This includes specifying the intervention setting and determinants to be changed. Researchers confirm that obesity prevention efforts should target children and that such interventions should be based on appropriate theoretical frameworks , 8. In aSahtak bi Sahnak , the first educational school-based nutrition intervention targeting Lebanese adolescents aged 15–18 years, living in urban and rural regions, to prevent obesity   provides obesity . This isn = 4), agreed to participate. In parallel, private schools from the rural region were randomly selected and approached until four of them accepted to participate. Similarly in the urban region , public schools were randomly selected and approached. The recruitment of public schools in Beirut was stopped when the required sample size of six schools was met. As for the urban private schools, two private schools accepted to participate.The current cluster randomised controlled trial was conducted between October 2017 and March 2018 and targeted 15- to 18-year-old Lebanese adolescents attending public and private high schools in Beirut (urban region), Baalbeck and Rayak  in Lebanon. Beirut represents the urban region as it is the capital and largest city of Lebanon. Baalbeck and Rayak represent the rural region, located in the Bekaa region, which is considered Lebanon’s most important agricultural region. Schools, representing the cluster unit, were randomly selected from the 96 high schools located in the selected regions with standard day-time schedules (classes finishing by 15:00 in the afternoon at the latest). During the recruitment phase, the schools were divided according to the indicated study location  and type of school (public vs. private). All the public secondary schools located in the rural region  was calculated based on an expected mean change in nutrition knowledge (one of the main outcomes) based on previous literature of 18.2% with a standard deviation of 0.54 , from both common types of schools in Lebanon (private and public) and from both selected grades (grades 10 and 11) in both study groups, we recruited more participants and ended up with a total of 1,572 adolescents from 16 schools  that accepted the invitation to participate were randomly divided into two groups (intervention and control), with the restriction of balancing public and private high schools as the number of public schools was higher compared to private ones see . During To avoid bias, participants were not pre-informed about any data collection moment. During the first meeting with adolescents, the PI explained the research goals and the procedure related to data collection. Students’ consent was also orally confirmed by the PI before administering the questionnaire. The questionnaire further clearly stated that once it was filled in and handed in, this meant that the adolescent accepted and assented to participate in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Lebanese MEHE  and the Institutional Review Board of the Lebanese International University (LIUIRB-171212-LS1).Several measures were considered to decrease the risk of exposing the control group to the intervention and subsequent bias. Randomisation into the intervention and control group was conducted by the PI (first author) at the school level, so that participants from the same school would be exposed to the same information , followiThe socio-demographic information was assessed at baseline and included the following: date of birth to calculate the age in years; gender (boys/girls); school class (grade 10/grade 11); school’s name to determine type of school (public or private); and school address to determine region .z-scores were calculated using the WHO AnthroPlus software . Height was measured without shoes and recorded to the nearest 0.1 cm, using a portable stadiometer (Numed). Weight and height were measured using standardised protocols and procedures  and calisoftware . The BMIsoftware , 32. Howsoftware , and due0) and post-intervention (T1). The DKQ includes 23 questions divided to five parts  was administrated to adolescents at baseline (Tve parts : (1) knove parts , as Cron0) and post-intervention (T1), to assess their level of adherence to the dietary recommendations from the American Heart Association   was admiociation  and the ociation , as Lebaociation . ExampleThe school-based data collection was performed by a dietitian (PI) and a trained research assistant. The questionnaires, administered in Arabic (native language of the participants), were specifically designed to suit the Lebanese adolescent population, having been pre-tested and validated using qualitative  and quantitative methods among Lebanese adolescents . In addiSahtak bi Sahnak intervention (صحتك بصحنك) was a school-based intervention targeting Lebanese adolescents. Sahtak bi Sahnak was developed using the IM framework .Once the school was enrolled in the programme, each school principal designated one or two sessions per week, depending on the school’s courses, exam schedule, and holidays. The total length of the intervention was around seven educational sessions, until all the 11 lessons were covered, spread over an average of 2 months. Each education session lasted 20–40 min. Each lesson tackled a different topic about nutrition. An interactive discussion followed the lesson explanation to answer any additional questions and to recapitulate what was learnt. The current intervention targeted several types of knowledge, such as declarative knowledge  and procedural knowledge  . In addierweight  and woulz-score; (7) study group (intervention/control); and (8) score at baseline. Chi-square tests were applied to analyse the variation in frequency of the categorical background characteristics  between the intervention and control group. Independent t-tests were used to compare differences between groups (intervention vs. control) at baseline for continuous variables . The intervention effect was analysed using a multilevel analysis with random intercepts, adjusting for significant covariates found in the baseline analysis as well as baseline scores for the outcome variables, with total dietary knowledge and healthy items scores as dependent variables. As these analyses were adjusted for baseline scores, the reported regression coefficients reflect difference between intervention and control group in the change between baseline and follow-up. Three levels were included: (i) level 1: adolescents; (ii) level 2: schools; and (iii) level 3: location . Where the random intercept was non-significant in the multilevel analysis, a multivariate regression model was performed to test the intervention effect, adjusting for the same significant covariates. In addition, a multilevel analysis was performed to evaluate the interaction between background variables and the intervention variable associated with the dependent variables . Separate multivariate regression analyses were conducted to evaluate the intervention effect in different subgroups , for which continuous variables were recoded into categories as follows: BMI z-score was classified into: <−3 indicating severe malnutrition; −2 to −2.9 indicating moderate malnutrition; −1 to −1.99 indicating mild malnutrition  the relationship between the independent and dependant variables was linear; (2) there was no multicollinearity in the data; (3) the values of the residuals were independent; (4) the variance of the residuals was constant; (5) the values of the residuals were normally distributed; and (6) there were no influential cases biassing the model. p-Values below 0.05 were considered statistically significant.Data were entered and analysed using the Statistical Package for Social Sciences . Descriptive statistics were used to analyse the participants’ characteristics and outcomes. There were three dependent variables: (1) healthy items score, post-intervention; (2) unhealthy items score, post-intervention; and (3) total knowledge score, post-intervention. The independent variables included the following: (1) age; (2) gender; (3) grade (grade 10/11); (4) type of school (public/private); (5) location ; (6) BMI utrition ; −0.99 tutrition . KnowledThe school recruitment phase lasted from January till September 2017, while the date collection started in October 2017 and ended in March 2018. The background characteristics of the 1,572 participating adolescents are shown in p < 0.001), location (p < 0.001), type of school (p < 0.001), and grade (p < 0.001). There was a significant difference in the average BMI z-score between the intervention  and the control group ; t = −2.72, p = 0.007. Additionally, there was a significant difference in the baseline total knowledge score between the intervention  and the control  groups; t = 3.60, p < 0.001. There was also a significant difference in the baseline healthy items score between the intervention  and the control group ; t = −4.42, p < 0.001. Furthermore, the average unhealthy items score at baseline of the intervention group  was significantly higher compared to the control group ; t = 3.72; p < 0.001  and in the healthy adherence score specifically  compared to the control group  in the intervention group compared to the control group. The unhealthy adherence score decreased by 27.7% in the intervention group. Changes in separate DAQ items are shown in Based on the adjusted multilevel models, the intervention group showed significant improvements in total dietary knowledge (ol group . The totp = 0.019), knowledge score at baseline (p < 0.001), and weight status (p = 0.045). Subgroup analyses based on significant interaction between the intervention and background variables (see p = 0.011). The intervention showed larger improvements among adolescents from rural regions, compared to urban regions. There was no significant differential intervention effect among public and private schools. In addition, when analysing the total dietary knowledge score, significant interactions were found between the intervention and the following background variables: grade  , 25. AnoSahtak bi Sahnak was more effective in impacting the dietary knowledge of participants with a lower baseline score. This is a positive outcome because during the intervention design, specific attention was paid to simplify the nutrition information and key terms as much as possible to make it suitable for participants of all dietary knowledge levels. The intervention appears to have succeeded in this, having significant effects on adolescents with low as well as with acceptable knowledge level. Nonetheless, adolescents with an acceptable baseline knowledge level were also able to significantly benefit from the intervention. Furthermore, and surprisingly, the intervention seems to present a larger improvement among underweight adolescents compared to overweight/obese ones, even though it was initially intended to prevent paediatric obesity. This could be related to the baseline knowledge scores, as a higher BMI z-score was significantly positively correlated with higher knowledge score  and improving the delivery of the intervention. In addition, ge score . The higge score .In addition to improving knowledge, the current intervention succeeded in significantly improving self-reported dietary adherence by increasing the healthy items score and decreasing the unhealthy items score. This is partially in line with an intervention for Tunisian adolescents , which sSahtak bi Sahnak was demonstrated using advanced and rigorous statistical tests to evaluate its effectiveness, adjusting for relevant background characteristics and the multilevel structure of the data. Fifth, the applied randomisation guarantees the internal validity for statistical tests of significance that are used to compare the intervention effects . These differences were, however, adjusted for in the statistical analyses. The analyses were not, however, adjust for class size, although class size is related to grade in Lebanon, and the analyses were adjusted for grade. Third, the dietary knowledge and adherence variables were based on self-reports rather than on objective assessment, potentially resulting in social desirability bias. However, direct objective measurements are not feasible in studies with large populations . In addiSahtak bi Sahnak was administered and evaluated in 16 public and private secondary schools located in urban and rural regions in Lebanon, including a diverse sample. However, future studies should focus on including participants from all Lebanese regions to be able to generalise the obtained results on the whole population.Sahtak bi Sahnak showed substantial positive effects on the dietary behaviours and knowledge of diverse Lebanese adolescents, an understudied population. Given the great potential of the intervention, further dissemination in Lebanon and the region is recommended. The intervention can be easily integrated into the Lebanese school curriculum, and can be directly applied in schools within the context of an adolescent’s natural environment  and school policy changes are needed to improve eating patterns and physical activity levels at the same time.The current study presents the effect evaluation of a school-based intervention designed according to the IM framework, targeting Lebanese adolescents from different geographical regions. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Lebanese Ministry of Education and Higher Education  and the Institutional Review Board of the Lebanese International University (LIUIRB-171212-LS1). 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.LS: conceptualisation, data collection, conducting intervention, formal analysis, investigation, and writing—original draft preparation. LS, JG, and SK: methodology, writing—review and editing, interpretation of the data, and approval of the final version. JG and SK: validation and supervision. All authors have read and agreed to the published version of the manuscript.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.


Listronotus setosipennis, in a Pakistani context. We tested several native and crop or ornamental species that have cultural importance in Pakistan. Our results suggest that the risk of releasing this weevil into Pakistan for the control of parthenium is extremely low and the benefits are likely to be great.Parthenium is an extremely damaging weed in Pakistan and there are not many sustainable and effective management options for its control. Biological control may offer a solution, provided that effective and safe agents are released. In this study we explore the host range and potential risk of a weevil, Parthenium hysterophorus, has extended its range in Pakistan throughout Punjab and into Khyber Pakhtunkhwa, the Federally Administrated Tribal Areas, Azad Jammu and Kashmir, and Sindh Provinces. Without control measures against parthenium, the negative impacts of this weed will go unchecked having deleterious effects on native biodiversity, human and animal health, as well as crop productivity. The weevil Listronotus setosipennis was obtained and imported from the Plant Health and Protection of the Agricultural Research Council (ARC-PHP), in Cedara, South Africa, in April 2019. A total of 22 plant species or cultivars in the Asteraceae family were assessed during no-choice oviposition tests in Pakistan. During these tests, the only plant species accepted for oviposition were the 10 cultivars of Helianthus annuus that are grown in Pakistan. All cultivars were thus tested for development of L. setosipennis from egg to adult. Only three cultivars were able to support some larval development, but at such low levels that it is unlikely to be the basis of a viable population. To support this, a risk assessment was conducted to ascertain the probability of L. setosipennis being able to sustain viable populations in the field, the results of which concur with native (Argentina) and introduced  field host-range information where L. setosipennis has never been recorded as a pest of sunflowers. The results of laboratory-based host-range trials, together with host records from its native and introduced range, indicate that L. setosipennis is sufficiently specific to parthenium and is thus suitable for release in Pakistan.Parthenium, or  Parthenium hysterophorus L. (“parthenium”) is a highly invasive ruderal annual weed which is spreading rapidly through vast areas of the tropics and sub-tropics, with highly deleterious effects on native biodiversity, human and animal health, and productivity of both crops and grasslands [asslands . Parthenasslands ,3. It waasslands . In Pakiasslands . For theasslands . Parthenasslands ,12,13,14Despite the extent of parthenium and its deleterious effect on the livelihoods of millions of people globally, control programmes have not been given much attention. Successful management of parthenium is possible through a combination of control methods including biological and chemical control, containment strategies, the utilisation of competitive plant species and other cultural control methods ,16,17. SCactoblastis cactorum against Opuntia species [It is widely acknowledged that integrated control is the most effective strategy in managing pests. In the case of plants, it involves the use of herbicides, manual or mechanical control, and biological control agents in an integrated way. The main benefits of classical biological control are that the agents establish self-perpetuating populations and often establish throughout the range of the target weed, including areas which are not accessible for chemical or physical control; control of the weed is permanent; the cost is low relative to other approaches and usually requires a once-off investment; and benefits can be reaped by many stakeholders regardless of their financial status and whether they contributed to the initial research . Pakista species .Zygogramma bicolorata Pallister, known as the Mexican or parthenium leaf beetle, which was deliberately introduced from Mexico to India in 1983, was reported in Pakistan in 2006 and now has a widespread distribution in the country [Z. bicolorata has offered Pakistan an opportunity to benefit from the biological control of parthenium with limited investment into host range testing and applications for permissions for release. Although future research into the biology, ecology and impact of this species in Pakistan is warranted, studies have shown that this species alone is unlikely to achieve full control of parthenium [In most cases, weed biological control relies on a classical biological control approach, in which natural enemies from the native range have been intentionally released as biological control agents in the introduced range after host range testing. In some cases, however, the agent has been found to be already present following an unknown or accidental introduction. In Pakistan, biological control options against parthenium are limited and there have so far been no deliberate introductions of agents to control parthenium. Nevertheless,  country . The inarthenium .Puccinia abrupta Diet. & Holw. var. partheniicola (Jackson) Parmelee, has also been recorded from Pakistan and is now widely distributed throughout the range of parthenium in Pakistan [The winter rust, Pakistan ,29. AlthPakistan . Whilst Listronotus setosipennis (Hustache), another potential biological control agent for parthenium, is native to Brazil and Argentina. This weevil has had previous testing in Australia, South Africa and Ethiopia, which indicated that it is host specific and a safe biological control agent and has been released in these three countries as well as Uganda. With a view of evaluating L. setosipennis as a biological control agent for parthenium in Pakistan, CABI applied for the importation of this weevil to perform host range testing in its post entry quarantine facility in Rawalpindi [L. setosipennis were imported from the rearing facility at the Plant Protection Research Institute of the Agricultural Research Council (ARC-PHP), in Cedara, South Africa, in April 2019 [L. setosipennis was issued by the Ministry of National Food Security and Research, Department of Plant Protection, Plant Quarantine Division under permit number IPKA-3787-016/18-2019. The aim of this study was to determine the host specificity of L. setosipennis in a Pakistani context.Therefore, strategically, the resources available for biological control should focus on the evaluation of additional agents for release into Pakistan in order to obtain long-term sustainable control of parthenium . The stewalpindi . The natril 2019 . The impParthenium hysterophorus belongs is only represented by 27 species in Pakistan. Comprehensive testing of the host range of L. setosipennis has already been done on a total of 151 species from 27 families, in Australia (73 species and/or cultivars), South Africa (52 species and/or cultivars) and Ethiopia tested (36 species and/or cultivars)  . In addiltivars) . During ltivars) . In thisL. setosipennis culture was built up and maintained in quarantine at a day/night cycle of 14 L:10 D, mean temperature of 25 ± 5 °C, and mean relative humidity of 65 ± 5%. A culture of about 1000 adult weevils was maintained at all times. The nocturnal adult weevils feed mainly on parthenium leaves and flowers. The females oviposit in holes chewed in flowers, leaf bases or stem surfaces and axillary buds and seal the hole with black frass [Following importation from South Africa, the ck frass . In the ck frass . Oviposick frass . Larvae ck frass . Adults ck frass . The lifck frass .In all tests, potted plants (not excised leaves or stems) were used to ensure that test conditions were as optimal as possible. Depending on the size of the plant, the appropriate pot size was used, ranging from 1–4 L pots, filled with a standard commercial potting soil. Standardized potting soil was prepared by mixing 18 kg of all-purpose potting soil (Miracle-Gro) with 185 g Osmocote fertilizer with N:P:K of 19-6-12 and 125 g Dolomite lime. The plants were watered ad libitum. Each test plant was ensured to be in the correct phenological stage for oviposition, which was flowering with still-developing florets.L. setosipennis were conducted by comparing oviposition on parthenium to that on the 22 non-target plant species (including the 10 sunflower cultivars). This was achieved through an initial series of no-choice oviposition tests for all 22 selected non-target species , followed by an assessment of larval survival on non-target plants that proved suitable for oviposition in no-choice tests, and finally, the development of a risk assessment for non-target species that received eggs in no-choice tests.Host-range trials for No-choice tests were conducted as the initial step to determine whether any non-target species would be accepted for oviposition in the absence of parthenium. While no-choice tests determine the plant species on which the insect is physiologically capable of feeding and egg laying, i.e., the ‘physiological’ host range , choice Adults used in no-choice oviposition tests were between two and four weeks old, to ensure that females were of egg-laying age following the period of pre-oviposition while ovarioles develop. For each test series of no-choice oviposition tests, about 100 adults from the culture maintained in quarantine were placed in several Petri dishes containing filter paper moistened with a dilute (2%) sodium hypochlorite solution. Adults were held for up to 24 h, depending on the duration required to collect sufficient mating pairs. Copulating weevils were collected to ensure that they were male and female as it was difficult to differentiate the sexes morphologically.2 (SE-1836) of dimensions 45 × 45 × 90 cm3 for five days, with a day/night cycle of 14 L:10 D, mean temperature of 25 ± 5 °C, and mean relative humidity of 65 ± 5%. For each series of tests, there was at least a single parthenium control plant. All plants were washed with water to remove any pests before the start of the trial, and watered daily during the trial. As eggs are difficult to accurately count without destructive sampling, egg counts were conducted only at the end of each experiment. After five days, all adults were removed from plants and returned to the culture but were not re-used in tests. All above-ground parts of each test and control plant were carefully examined for eggs, using a microscope, and plants were dissected. Between four and five replicates were conducted for each plant species tested and 25 control plants were used in total. As data were not normally distributed, even if log-transformed, non-parametric independent samples Kruskal–Wallis test was conducted by comparing the number of eggs laid on test plant replicates against that on parthenium control plants. Data were analysed using IBM SPSS Statistics v25.Five pairs of adults were exposed to a single test or parthenium control plant at the correct phenological stage, in this case flowering, in separate gauze cages with mesh diameter of 1 mmPlants that received eggs in no-choice tests were further tested in larval development tests; in this case only the sunflower varieties were tested, because they were the only ones accepted for oviposition. In order to obtain eggs for the trial, adult weevils from the culture were exposed to severed parthenium flowers on moistened filter paper in Petri dishes, for a period of 24 h. Petri dishes with eggs in flowers were then held for one to two days. The rim of the Petri dish was sealed using a layer of Parafilm to avoid desiccation.3 for 11 weeks. Four replicates were conducted for each test plant cultivar as well as eight replicates for parthenium. After three weeks, plants were checked several times per week for adult emergence, and the newly emerged adults were recorded. New flowers and dead leaves were removed from plants periodically so that adult weevils were easier to find. After about 11 weeks all plants were dissected and the number of larvae and pupae were recorded. Pupae were transferred to moistened soil on filter paper within Petri dishes. Non-parametric independent samples Kruskal–Wallis test was conducted to compare the number of adults that developed on each sunflower cultivar with those on the parthenium control plants. Data were analysed using IBM SPSS Statistics v25 .In South Africa, several attempts using eggs removed from flowers and placing newly hatched larvae in varying numbers on plants, failed to achieve adequate larval survival on parthenium . TherefoL. setosipennis. The performance of L. setosipennis at various stages (oviposition and development) of the host selection process on sunflower cultivars was compared as a proportion of that on parthenium.A risk assessment, as performed by Wan and Harris , was conThe performance criteria used included relative oviposition preference (R1) and relative performance from egg to adult (R2). For each criterion, R represented the weevil’s performance on the test plant proportional to that on parthenium in the same test. Oviposition preference was determined by the mean number of eggs laid per plant for each test plant species during no-choice tests. Relative performance was determined by the number of individuals that completed development from egg to adult on test plant species during larval development tests relative to that on parthenium. The reproductive risk  was calculated as the product of oviposition preference and survival from egg to adult (R1 × R2). Zero values were designated as 0.001 to facilitate calculations, as used by others ,39,40.H. annuus) cultivars that were assessed received eggs by L. setosipennis females, while all other test plants were completely avoided and no eggs were recorded (p < 0.001).In the no-choice tests, adult feeding was sporadic and difficult to quantify (or even find in some cases) and thus was deemed negligible and not recorded. In the no-choice oviposition tests, all 10 sunflower (recorded . Averagep < 0.0001)  , and a total of only 6 adults emerged from an initial total of 360 eggs placed on these 3 sunflower cultivars . This translates to 0.8 % survival from egg to adult on ParSun-3, 1.6 % survival from egg to adult on Hysun-33 and 2.5 % survival from egg to adult on S-278, while, on parthenium there was 42.9% survival from egg to adult. This is significantly fewer adults in comparison, to the successful development recorded on the parthenium plants setup with a total of 103 adults from 240 eggs  .L. setosipennis. Although during larval development tests, no larvae completed development on seven of the ten sunflower cultivars  on which one, two and three individuals respectively completed development in larval development trials, was also extremely low, as indicated by their final risk assessment scores  which were more than three orders of magnitude less than that of parthenium  have been implemented for several decades, there has been a measurable reduction in the losses caused by the weed ,34. BiolZinnia and Helianthus annuus cultivars in no choice tests conducted in South Africa [H. annuus under quarantine choice cage conditions [L. setosipennis being able to sustain a population on sunflowers. Guided by these results, L. setosipennis was shown to be safe for release in all three countries and first released in 1982 in Australia, 2013 in South Africa and 2016 in Ethiopia. To complement the existing knowledge of the host range of L. setosipennis established from tests conducted in Brazil, Australia, South Africa and Ethiopia, additional host-range testing was conducted in a Pakistani context.During host-specificity testing for the Australian research programme, 68 plant species from 26 families were tested; for the South African research programme, 39 plant species from 2 families were tested; and for the Ethiopian research programme, 31 plant species from 7 families were investigated . Limitedh Africa , Brazil h Africa , while Eh Africa . In quarh Africa . In Soutnditions . This isL. setosipennis, indicating a narrow physiological host range. These results are in line with other host range tests already conducted in Australia [L. setosipennis, albeit receiving an extremely limited number of eggs. Typically, these would then be tested under multiple choice conditions to obtain an understanding of the realized host range; however, due to space limitations in the quarantine facility in Pakistan this was not possible and thus the data presented in this study are conservative and likely over-inflate the risk. Despite this, complete development of L. setosipennis, even though extremely limited, could be achieved on three sunflower cultivars  under laboratory conditions. However, quantified analyses, combining the relative oviposition performance under no-choice conditions and relative performance from egg to adult, indicated that the likelihood of L. setosipennis being able to sustain viable populations or have an impact on these three cultivars in the field was extremely low  and negligible relative to parthenium. Although it is not possible to completely exclude the risk of potential spillover of adults onto sunflowers if parthenium is growing in close proximity, our analysis suggests that this is unlikely and even more unlikely to cause any considerable damage to sunflowers.Of the 13 plant species in the Asteraceae family that were assessed during no-choice oviposition tests in Pakistan, 12 were not accepted for oviposition by ustralia , South Australia  and Ethiustralia . Of all L. setosipennis oviposited on some sunflower cultivars under no-choice and paired-choice conditions, and complete development occurred in some instances [L. setosipennis adults confined to sunflowers in the laboratory was less than 1% of that on parthenium, and less than 2% of those eggs survived to adulthood [L. setosipennis. It had not been recorded as a pest of any crop or pasture species in South America and was not known to entomologists of the National Institute of Agricultural Technology in Argentina [L. setosipennis had never been recorded attacking the crop [Ambrosia and Xanthium species but never found L. setosipennis larvae in these plants [Similar to the current study, in both Australia and South Africa, nstances ,37. It wdulthood . Prior tdulthood , there wrgentina . Sunflowthe crop . Additioe plants .L. setosipennis has never been recorded feeding on sunflowers, nor is it a recorded pest of sunflowers in its native range of Argentina where sunflowers are also widely cultivated [Listronotus setosipennis was widespread and seasonally abundant throughout the parthenium infestations of North and Central Queensland but there were never any reports of damage to sunflowers  [These results are corroborated by the fact that almost four decades after its establishment in Australia, ltivated . During cited in ). In concited in ). Similactively) .L. setosipennis in its native range of Argentina is parthenium [L. setosipennis was tested on 38 native and economically important non-target Asteraceae species [L. setosipennis is host specific and a safe biological control agent for use against parthenium, leading to approval for release by all regulatory authorities after a thorough review of submitted risk assessments. The quarantine laboratory assessments of the host range of L. setosipennis conducted in Pakistan are in line with these findings and in combination with evidence of the weevil’s native field host range in South America and introduced field host range in Australia, South Africa and Ethiopia indicate that it is highly unlikely that L. setosipennis will cause any damage to any plant, native or cultivated, other than parthenium, in Pakistan.The only known host of rthenium . The Ausrthenium . In Sout species ,37, whil species . All cou


Oral squamous cell carcinoma (OSCC) represents 90% of oral malignant neoplasms. The search for specific biomarkers for OSCC is a very active field of research contributing to establishing early diagnostic methods and unraveling underlying pathogenic mechanisms. In this work we investigated the salivary metabolites and the metabolic pathways of OSCC aiming find possible biomarkers. Salivary metabolites samples from 27 OSCC patients and 41 control individuals were compared through a gas chromatography coupled to a mass spectrometer (GC-MS) technique. Our results allowed identification of pathways of the malate-aspartate shuttle, the beta-alanine metabolism, and the Warburg effect. The possible salivary biomarkers were identified using the area under receiver-operating curve (AUC) criterion. Twenty-four metabolites were identified with AUC > 0.8. Using the threshold of AUC = 0.9 we find malic acid, maltose, protocatechuic acid, lactose, 2-ketoadipic, and catechol metabolites expressed. We notice that this is the first report of salivary metabolome in South American oral cancer patients, to the best of our knowledge. Our findings regarding these metabolic changes are important in discovering salivary biomarkers of OSCC patients. However, additional work needs to be performed considering larger populations to validate our results. Oral cancer refers to the set of malignant neoplasms that affect the lips and other intraoral regions . It reprThe predominant etiological factors for oral cancer are well established in the literature and include the use of tobacco and alcohol which act as carcinogenic substances responsible for constituting the so-called “field cancer” . The carThe search for biomarkers for chronic diseases and malignant neoplasms is a very active field of research worldwide . MetabolBiofluids—urine, blood, and saliva—are often used as clinical specimens of patients for metabolomic analysis . Saliva Previous studies have identified metabolomic biomarkers for OSCC ,41,42,43However, despite existing limitations, previous studies have shown consistent changes between OSCC and healthy patients , mainly In the present work we investigated the salivary metabolites profile from a sample of OSCC patients from a South American population. The objectives were to identify possible salivary metabolomic biomarkers and also altered metabolic pathways.p < 0.05).The main clinical data of patients are summarized in A total of 108 metabolites were identified as relevant for OSCC and control discrimination. All metabolites found in both groups studied were allocated on a Venn diagram to assess their distribution between groups . The anaThe dispersion score plot PC2 against PC1  shows a The heatmap showing the clustering of classes against metabolites is shown in The precedent analysis enables us to investigate the altered metabolic pathways in OSCC patients and find the role of each metabolite in these pathways.We analyzed 25 metabolites which were found exclusively in the OSCC group. Cystamine was absent from the databases of the chosen metabolomic compound and was excluded from further analysis. Thus, the role of 2-ketoglutaric acid, 2-hydroxyglutaric acid, 3-hydroxypropionic acid, 4-hydroxyphenylatic acid, galacturonic acid, gluconic acid, hippuric acid, indol-3-acetic acid, isocitric acid, malic acid, pantothenic acid, protocatechuic acid, ureidosuccinic acid, spermidine, dihydroxyacetone phosphate, inosine, lactitol, lyxose, maltose, methionine, O-phospho-serine, ribose 5-phosphate, sorbose, thymidine, and uracil in metabolic pathways was investigated. The pathway enrichment analysis is shown in p = 0.0229), beta-alanine metabolism (p = 0.0467), and the Warburg effect (p = 0.048) signaling pathways.A total of 41 metabolic pathways were identified as present in OSCC salivary samples. However, only 25 presented statistical relevance. From these we can mention the malate-aspart (A receiver operating characteristic (ROC) curve was used to establish promising biomarkers for OSCC. The area under the ROC curve value (AUC) measures the performance of the biomarkers. Thus, an excellent biomarker has an AUC value of 1.0. Good biomarkers have AUC > 0.80. Using this criterion, we list in The relevance of the investigation of the salivary metabolome of OSCC relies on the identification of predominantly altered metabolic pathways which may lead to the discovery of possible biomarkers. This could improve the capacity of early diagnosis and, consequently, the quality of life of patients.Reports of the salivary metabolome of patients with oral cancer described in the literature are presented in OSCC is mostly diagnosed at late stages, as also evidenced by our study, in which only 15% of patients were diagnosed with early-stage cancer (stage I), revealing that early diagnosis remains a challenge . It is nATP consumption is higher for cancer cells compared to healthy ones. Thus, high glycolytic rates and mitochondrial oxidative phosphorylation are observed in tumor cells to deliver a greater amount of ATP in a short period of time . GlycolyThe tricarboxylic acid cycle (Krebs cycle) and oxidative phosphorylation occur within the mitochondria. The malate-aspartate shuttle is responsible for transporting NADH from the cytoplasm to the mitochondrial matrix in the ATP production process ,58. In oCancer metabolism has been studied for decades, mainly because cells exhibit rapid growth, proliferation, and survival . These cAlthough the Warburg effect is established as the way tumor cells acquire energy, some studies have shown that several types of cancer can obtain energy through oxidative phosphorylation in conjunction with glycolysis. A study on breast cancer metabolism reported that 20% of energy production comes from the glycolytic pathway and 80% from oxidative phosphorylation . FurtherXu and Guppy conducted a study with different types of cancers  to measure the rate of ATP production through glycolytic and oxidative processes. Among the types of cancer studied, the average contribution of the glycolytic pathway to the production of ATP was 17%. The authors concluded that the vast majority of tumor cells can generate ATP via oxidative phosphorylation, but also through glycolysis, in addition to the fact that some tumors are glycolytic as a result of the hypoxic environment . This coBeta-alanine is a non-essential amino acid responsible for reducing fatigue and increasing muscle strength ,68. Its We have found that some metabolites such as malic acid, maltose, methionine, and inosine were over-expressed in the saliva of patients with OSCC. Malic acid was reported above to be present in the malate-aspartate pathway. It has been reported that maltose is a possible natural substance with carcinogenic potential .Ishikawa et al. identified the following metabolites over-expressed in the saliva of OSCC patients: hypoxanthine, guanine, guanosine, trimethylamine N-oxide, spermidine, pipecolate, methionine . Of thesHelicobacter pylori infection, which produces urease, reducing the availability of urea [Ohshima et al., also found urea in lower concentrations in OSCC patients and in higher concentrations in control patients, indicating that the urea cycle might be altered in oral cancer. This was the first study to describe urea as a possible biomarker for oral cancer. It was carried out using capillary electrophoresis-mass spectrometry (CE-MS) to evaluate saliva from Japanese patients with OSCC . Liang e of urea .Another metabolite present in salivary metabolome studies found in our study is leucine. Leucine was present in a study with 24 salivary metabolites that are candidate biomarkers in OSCC . Wei et In summary, we conclude that the whole nature of cellular energy production was altered in the OSCC group. This is the first salivary metabolomic study of a South American population with OSCC. Therefore, carrying out new studies covering larger populations may bring similar results and new insights so that these metabolites can be used as a non-invasive tool in oral cancer screening. Thus, salivary metabolic screening in populations exposed to risk factors, such as smoking and alcohol consumption, can reveal possible salivary biomarkers of oral cancer and improve the early diagnosis of carcinoma.This study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Research Ethics Committee of the Institute of Science and Technology of São José dos Campos (ICT-UNESP), as part of the study entitled “Genetic study of the main risk factors in the prognosis of patients with oral squamous cell carcinoma”, protocol number 1.033.312/2015 PH/CEP. Patients were informed about the objectives, propositions, and conditions of this project, and those who agreed to participate signed the Free and Informed Consent Term (FICT). After acceptance, all patients underwent an extra and intraoral physical examination. Patients were divided into OSCC and control groups.The OSCC group consisted of 27 patients diagnosed with OSCC. Inclusion criteria were patients over 18 years of age concomitant with the diagnosis of OSCC. The exclusion criterion considered patients diagnosed with cancer anywhere on the body that had already undergone some type of treatment, that is, surgery, radiotherapy, and chemotherapy. Cancer staging followed tumor-node-metastasis (TNM) classification according to the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual . The conPatients were instructed not to ingest pasty or hardened foods for 1 h before collection, as well as not to consume alcoholic beverages for at least 12 h before saliva collection. They could only swallow water and had to brush their teeth at least 2 h before the collection. Patients were instructed to expectorate 3 mL of saliva in the plastic tubes, which were then hermetically closed, immersed in ice, and transported within 1 h to the storage location. Salivary samples were stored in a freezer at −80 °C at the Laboratory of Microbiology and Immunology of the ICT-UNESP.g for 2 min. The supernatant was analyzed via GC-MS. The data obtained were processed using GCMS solution and the metabolites identified using Smart metabolite database version 4.2. GC-MS analysis conditions:MRM analysis methodrunning time: 67 mininjection temperature: 280 °Cinterface temperature: 280 °Cionization source temperature: 200 °Cheating rate: from 100 °C to 320 °C in a linear ramp of 4 °C/min, remaining at this temperature for 8 min.The methodology for analyzing the salivary metabolome was adapted from a previous study . First, p < 0.05). Descriptive statistical analysis of clinical data was performed using GraphPad Prism 5.03 software . For the salivary metabolomic analysis, principal component analysis (PCA) was performed, which allows the amount of information collected to be reduced. Its results select a subset of n variables capable of describing variability of data. The heatmap cluster was also used as a way to visualize the metabolites and hierarchical grouping of the compounds in each group. To demonstrate the significance of the metabolic data, we used the Wilcoxon-Mann-Whitney test. The p values to assess differences in metabolite concentrations between oral cancer and controls were corrected using the false discover rate (FDR) analysis of Benjamin-Hockberg [q < 0.05.Clinical data were analyzed from the description of categorical variables with counts and proportions and quantitative variables with normal and asymmetric distribution and described as mean and deviation. For the consideration of normality, visual inspection of histograms or application of a normality test was used when appropriate. For all analyses, we considered the significance level of 5%  was used to analyze the metabolomic data.The volcano plot was used to visibly identify and illustrate the metabolites that are significant and most expressed in each study group. The volcano plot presents a diagram showing the set of metabolites in the salivary samples that would be down- and up-regulated. That is, it can indicate whether the compound is present with significance in the control group or in the OSCC group. The volcano plot combines the measure of statistical significance, in this case the q-value (FDR) with the measure of magnitude variation FC (fold change). In order to identify possible salivary biomarkers for OSCC, a ROC (receiver operating characteristic) curve was drawn for each metabolite. For this, the ROC curve uses the parameters of sensitivity and specificity. The area under the ROC curve, also called AUC, allows identification of whether a condition is present or not. That is, an AUC of 0.5 has no discriminating capacity, while an AUC of 1.0 shows an ideal discrimination . For ourhttp://www.interactivenn.net/ accessed on 18 December 2020) was used for the analysis of the Venn diagram. The relative quantification of the metabolites for each group was performed from specific peak areas for each metabolite using the MRM analysis method. For the search for metabolites to be effective in the main databases, the Kyoto Encyclopedia of Genes and Genomes (KEGG pathway) and Small Molecule Pathway Database (SMPDB), the initial standardization of compound names was carried out on the MetaboAnalyst platform.All metabolites found were allocated on a Venn diagram to assess their distribution between groups. InteractiVenn (In summary, in our study, three important altered metabolic pathways were identified in OSCC for South American patients: the malate-aspartate shuttle, the beta-alanine metabolism pathway and the Warburg effect. These pathways are related to the cellular energy production in carcinogenesis, promoting a favorable environment for high energy consumption and cell survival. It was possible to statistically distinguish the salivary metabolites of control patients compared to patients with oral cancer. These metabolic changes may help in the discovery of salivary biomarkers of oral cancer and stimulate interest for new studies with larger populations to validate our results.


Aims: The present study aimed to investigate the prognostic role of derived neutrophil-to-lymphocyte ratio (dNLR) in patients with coronary heart disease (CHD) after PCI.Methods: A total of 3,561 post-PCI patients with CHD were retrospectively enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The patients  were divided into three groups according to dNLR tertiles: the first tertile , second tertile , and third tertile. The mean follow-up time was 37.59 ± 22.24 months. The primary endpoint was defined as mortality , and the secondary endpoint was major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs).Results: There were 2,644 patients with acute coronary syndrome (ACS) and 838 patients with chronic coronary syndrome (CCS) in the present study. In the total population, the all-cause mortality (ACM) and cardiac mortality (CM) incidence was significantly higher in the third tertile than in the first tertile . Multivariate Cox regression analyses suggested that compared with the patients in the first tertile than those in the third tertile, the risk of ACM was increased 1.763 times , and the risk of CM was increased 1.763 times  in the higher dNLR group during the long-term follow-up. In both ACS patients and CCS patients, there were significant differences among the three groups in the incidence of ACM in univariate analysis. We also found that the incidence of CM was significantly different among the three groups in CCS patients in both univariate analysis  and multivariate analysis .Conclusion: The present study suggested that dNLR is an independent and novel predictor of mortality in CHD patients who underwent PCI. Previous studies suggested that systemic inflammation is a predictive marker of clinical outcome of coronary heart disease (CHD) –5. Some n = 2,644) and CCS (n = 838) were involved in this study. The diagnostic criteria of ACS were described previously. ACS includes unstable angina, ST segment elevation myocardial infarction, and non-ST segment elevation myocardial infarction. All the patients were administered with standard-dose double antiplatelet, statins, and β receptor blockers before PCI if there are no contraindications.In the present study, we enrolled 3,561 CHD patients who underwent PCI from January 2013 to December 2017 in the First Affiliated Hospital of Zhengzhou University. All the participants were CHD patients who underwent coronary angiograph and at least one stent being implanted. Both ACS  or acute infections. Finally, there were 3,462 patients who were enrolled to the present study. A flowchart of inclusion and exclusion of patients is shown in The basal blood collection was performed before PCI. Routine blood testing performed in accordance with standard methods was as described previously. Briefly, 2 ml of venous blood samples were collected in standardized dipotassium EDTA tubes. The blood routine test was measured using an automated blood counter within 2 h of collection to minimize variations due to sample aging. We calculated the dNLR according to the formula as follows: neutrophil count/(leukocyte count—neutrophil count) as described previously –15.In the present study, we defined a primary endpoint and several secondary endpoints. The primary endpoint was the long-term mortality, including all-cause death and cardiac death. The secondary endpoints include major adverse cardiac events (MACE) and the major adverse cardiac and cerebrovascular events (MACCEs) as described previously –21.We carried out the follow-up at least 18 months for each patient. The longest follow-up time is 80 months. All the patients were followed either by office visits or by telephone contacts as necessary.t-test was utilized to analyze the differences between normally distributed numeric variables, while the Mann–Whitney U-test was used to analyze the difference between non-normally distributed variables. The categorical data were presented as frequencies and percentages. Chi-square (χ2) test was employed for the comparison of categorical variables. The patients were divided into three groups according to the dNLR tertiles: the first tertile , second tertile , and third tertile dNLR ≥ 1.96; n = 1,157). We utilized the Kaplan–Meier analysis to analyze the cumulative incidence of long-term outcomes among three groups. The log-rank test was used to compare the difference between each group. To adjust the confounders, we used the multivariable Cox regression analysis to evaluate the predictive value of dNLR and to calculate the hazard ratios (HRs) and its 95% confidence intervals (CIs). Two-side p < 0.05 was considered significant.The SPSS 22.0 for windows statistical software  was used to analyze the data. The continuous data were presented as mean ± standard deviation (mean ± SD). The n = 1,139), second tertile , and third tertile . The baseline data are shown in p < 0.05). We did not find a significant difference among these three groups in age, hypertension, diabetes mellitus, and alcohol drinking. We also showed the baseline data characteristics of ACS and CCS patients in The study included 3,462 patients who were divided into three groups according to the dNLR tertiles: the first tertile . We did not find a significant difference between the three groups in the incidence of CM, MACEs, and MACCEs. In ACS patients, the incidence of ACM was higher in the third tertile group than that in the first tertile group . In the CCS patients, both ACM  and CM  had significant frequency in the third tertile group than that in the first tertile group.As shown in the p = 0.006 and HR = 2.1 (95% CI: 1.23–3.8), p = 0.009, respectively]. Multivariate Cox regression analyses suggested that compared with the patients in the first tertile, the risk of ACM was increased 1.763 times , and the risk of CM was increased 1.961 times  in the third tertile dNLR group during the long-term follow-up. All individual dNLR values for survival or not survival are shown in p = 0.027) and multivariate Cox regression analysis .As shown in This study suggested that increased dNLR was independently associated with the prognosis of CHD patients who underwent PCI. This is the first study to investigate the relation between dNLR and prognosis in CHD patients.n = 1,139), the second tertile , and the third tertile . We found that the patients in the third tertile have higher mortality. After multivariable Cox regression analysis to adjust the confounders, the dNLR remains an independent predictor of mortality of CHD patients who underwent PCI. In addition, we also found that kidney function is the worst in the third tertile group, which may be an important impact factor of outcomes. A previous study , and C-reactive protein (CRP) play an important role in the progress of atherosclerosis –5. Thereus study  showed tin vivo, the number of neutral granulocytes will be improved, and the number of lymphocytes will be reduced accordingly, thereby increasing the level of NLR. In addition, lymphopenia is related to age. Also, approximately 70% of lymphocytes in the peripheral blood are produced in the thymus. Therefore, thymus functional degradation may affect the production of lymphocytes. In our study, we utilized multivariable Cox regression analysis to adjust age and other confounders, and dNLR remains a significant predictive value of outcomes.Recently, Agarwal et al.  reviewedSeveral mechanistic pathways may connect NLR to adverse prognosis in CHD patients. First, previous studies , 31suggeThere were several strengths in our study. First, the long-term follow-up is the main strength of our study. Second, the larger sample size is another strength of our study. Finally, we performed the statistical analysis that used multivariable analysis, which improved the credibility of the study. In addition, there were also some limitations, which are as follows: First, we only collected the baseline data of dNLR; therefore, the influence of dynamic changes of dNLR on the mortality was unclear. Second, there were several patients who were excluded from this study for data not available. Third, our study is a single-center retrospective cohort design; therefore, a multicenter cohort design is needed in the future. Fourth, all the patients were not continuously included in this study, which will be of the selection bias. Finally, we did not collect the revascularization characteristics in this study. Therefore, we cannot analyze the impact of revascularization on outcomes in the present study.In conclusion, our results suggest that baseline dNLR is a novel independent predictor of mortality in CHD patients who underwent PCI. This founding will help the interventional physician to make clinical decisions on daily practice.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by The ethics committee of the First Affiliated Hospital of Zhengzhou University. The patients/participants provided their written informed consent to participate in this study.G-QL and W-JZ made substantial contributions to study conception and design and to the drafting and critical revision of the manuscript for important intellectual content. J-HS, X-DZ, WW, Q-QG, J-CZ, and KW made substantial contributions to the study conception and design and critical revision of the manuscript for important intellectual content. Z-YL, F-HS, and LF made substantial contributions to study conception and design. Y-YZ and J-YZ made substantial contributions to study conception and design, drafting and critical revision of the manuscript for important intellectual content, including study supervision. All authors read and approved the final manuscript.This research was funded by the National Natural Science Foundation of China .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.