However, the number patients undergoing planned revascularisation by either stent or surgery was significantly lower with an FFR-guided strategy . Conclusion: In patients with obstructive CAD, an FFR-guided management strategy did not impact on all-cause mortality, MI and unplanned revascularisation, when compared to an angiography-guided management strategy, but led to up to a quarter less patients needing revascularisation.Background and Aims: Randomised controlled trials (RCTs) comparing outcomes after fractional flow reserve (FFR)-guided versus angiography-guided management for obstructive coronary artery disease (CAD) have produced conflicting results. We investigated the efficacy and safety of an FFR-guided versus angiography-guided management strategy among patients with obstructive CAD. Methods: A systematic electronic search of the major databases was performed from inception to September 2022. We included studies of patients presenting with angina or myocardial infarction (MI), managed with medications, percutaneous coronary intervention, or bypass graft surgery. A meta-analysis was performed by pooling the risk ratio (RR) using a random-effects model. The endpoints of interest were all-cause mortality, MI and unplanned revascularisation. Results: Eight RCTs, with outcome data from 5077 patients, were included. The weighted mean follow up was 22 months. When FFR-guided management was compared to angiography-guided management, there was no difference in all-cause mortality [3.5% vs. 3.7%, RR: 0.99  0.62–1.60),  Current guidelines recommend fractional flow reserve (FFR) to guide revascularisation for intermediate stenoses with no prior evidence of myocardial ischaemia on non-invasive testing and in the setting of multivessel coronary disease . These rSubsequent randomised controlled trials (RCTs), performed in a variety of clinical settings, comparing outcomes after FFR-guided versus angiography-guided revascularisation have produced conflicting results, but have, in general, failed to demonstrate the expected additional benefit from using FFR in addition to angiography to guide diagnosis, management and revascularization ,5,6,7,8.Given the discrepant outcome data, the aim of this study was to perform a contemporary meta-analysis of RCTs  or coronary artery bypass grafts surgery (CABG), to compare clinical outcomes after an FFR-guided versus an angiography-guided management strategy in patients with obstructive CAD. This study was performed following the PRISMA  guidelines . The proA systematic search of the online databases Medline and Embase via Ovid was performed, from inception to September 2022. Peer-reviewed RCTs were selected using combinations of the following keywords: ‘fractional flow reserve’; ‘pressure wire’; ‘FFR’; ‘coronary angiogram’; and ‘coronary angiography’. The electronic database search was supplemented by using the clinical trial registry ‘ClinicalTrials.gov’, to identify other relevant studies. The reference lists of included trials were also reviewed, for other appropriate trials. For completeness, we searched conference abstracts from recent major cardiology meetings, specifically the European Society of Cardiology, EuroPCR, Transcatheter Cardiovascular Therapeutics, the American College of Cardiology and the American Heart Association. Two investigators (C.J.M and A.M) independently screened abstracts against eligibility criteria. In case of discrepancies among the two independent investigators, a third independent investigator (H.B) was available to review the data, to resolve discrepancies by consensus among the investigators.We included all RCTs comparing an FFR-guided versus an angiography-guided management strategy in patients with obstructive CAD, and reporting outcomes on death, MI and unplanned revascularisation. For studies with multiple publications, we used data from the longest reported follow-up. We included RCTs in which patients presented with either stable coronary artery disease, or acute coronary syndrome (ACS), including RCTs assessing non-infarct related artery stenoses following revascularisation of the culprit vessel in STEMI. RCTs of patients undergoing revascularisation with either coronary artery bypass graft surgery or percutaneous coronary intervention were included. Non-randomised trials, publications not in English, and those not reporting clinical outcomes of interest were excluded. We also excluded studies that used an FFR cut-off other than ≤0.8 to define significant ischaemia, because 0.8 is the FFR threshold accepted by international clinical guidelines for defining haemodynamically significant lesions .Baseline demographic and clinical outcome data were extracted from the main study reports. Supplementary material was also reviewed. Clinical outcome data were extracted on an intension-to-treat basis. For RCTs including an all-comer population undergoing angiography, we only included outcomes on the subsets with obstructive CAD.We assessed the risk of bias and the quality of included studies, according to the Cochrane risk of bias assessment tool  Figure .The main endpoints of interest were all-cause mortality, MI and unplanned revascularisation. We also investigated the number of stents implanted and number of patients proceeding to revascularisation in each group. We originally planned to stratify the results according to patients presenting with stable CAD or ACS, but outcome data for these individual endpoints were not available from the trial-level data. However, we were able to provide the pooled, trial-defined major composite endpoint analysis, stratified by stable CAD or ACS if available, from the selected RCTs.2, with a threshold of >50% suggestive of significant heterogeneity , The number patients undergoing planned revascularisation by either stent or surgery was significantly lower in the FFR-guided group , The pooled average number of stents was significantly lower in the FFR-guided group compared to the angiography-guided group [mean difference −0.45 (95%CI −0.70 to −0.20), In this contemporary meta-analysis of RCTs comparing FFR-guided (using a cut-off of ≤0.80) to angiography-guided management strategy for obstructive CAD, we found no difference in mortality, MI, or unplanned revascularisation, between the 2 strategies. However, an FFR-guided approach was associated with a lower number of patients who underwent revascularisation by up to a quarter (upper limit of the 95% CI). The latter finding is of considerable importance, highlighting the benefit to patients and the local health resource of such an approach. In fact, our findings could be summarised as follows: despite reducing the number of patients requiring revascularisation by up to 25%, an FFR-guided management strategy has no penalty in terms of the rate of adverse clinical events.Two previous meta-analyses included 5094 patients from 7 RCTs , and an The role of FFR in acute MI setting has been a subject of debate. FFR is usually performed in the non-infarct related artery in the setting of STEMI rather that the infarct related artery. Therefore, the impact of acute infarct and edema is minimal. However, STEMI patients may have caffeine or caffeine-containing product on board, and therefore FFR done during the index procedure would have a high false-negative rate. In NSTEMI, FFR can be done both in the infarct-related artery and the non-infarct related artery as shown in FAMOUS-NSTEMI but was not powered for clinical outcomes. One would expect that if a NSTEMI patient with a large infarct size or area of edema, FFR could be falsely negative in view of the inability of that infarct related territory to reach maximum hyperemia. We did attempt to stratify the trial-defined MACE by clinical presentation and in view of the inherent limitation of doing FFR in acute MI setting, although there was no difference in MACE between the 2 groups, the heterogeneity was high at 61%. Further studies are required to confirm the role of FFR in acute MI setting. It is well known that discrepancy exists between angiographic visual estimates of stenosis severity, and physiologically significant flow limitation that causes downstream myocardial ischaemia . The preThere are a number of limitations to our study. Firstly, it is an aggregate of trial-level data, rather than individual patient-level data. Therefore, we could not perform in-depth sub-group analyses, stratified by diabetes status, clinical presentation, or treatment with CABG. We cannot exclude the possibility that heterogeneity of the populations, for example the prevalence of diabetes, may have influenced the conclusions. Nonetheless, evidence suggests that robustly performed trial-level meta-analyses often produce similar conclusions to patient-level meta-analyses . We did In conclusion, this contemporary meta-analysis shows that an FFR-guided management strategy did not impact on all-cause mortality, MI and unplanned revascularisation, when compared to an angiography-guided management strategy, after a weighted mean follow-up of 22 months. However, an FFR-guided approach led to up to 1 in 4 less patients needing revascularisation, which has important benefits to patients and the local provision of health resources.


BackgroundStents utilized for pyloric, duodenal, or anastomotic malignant strictures are generally uncovered and are not retrievable. Taewoong Medical created a through-the-scope stent that is fully covered, retrievable, and can be placed beyond the esophagus for benign gastroduodenal strictures as an alternative to surgical approaches. The aim of this paper is to examine the safety and efficacy of short-term, fully covered, self-expanding metal stents (FC-SEMS) in refractory benign strictures of the pylorus, duodenum, and gastrojejunal anastomosis.MethodologyThis multicenter case series was conducted at four hospitals from January 2018 through December 2020. Patients presenting with benign strictures of the pylorus, duodenum, or gastrojejunal anastomosis were entered into the study. A therapeutic channel scope was utilized to place FC-SEMS to open strictures. The stents were removed a few weeks later. A four-point gastric outlet obstruction scoring system (GOOSS) was used to record improvement.ResultsStatistically significant improvement in GOOSS was found between the pre-procedure and the four-week follow-up.ConclusionsFully covered, retrievable metal stents appear safe and effective in the management of refractory benign pyloric, duodenal, and anastomotic strictures. This may provide a less invasive option in the management of these strictures compared to surgery. Strictures of the upper gastrointestinal (GI) tract can be classified as either benign or malignant. The most common etiologies of benign upper GI strictures include peptic ulcer disease, chronic pancreatitis, extrinsic compression due to acute pancreatitis, post-surgical anastomotic strictures, or ischemic strictures. Common sites of benign upper GI strictures include the esophagus, the pylorus, the duodenum, and surgical anastomoses -3. PalliEthics approval was obtained from the Oak Lawn Ethics Committee of Illinois Endoscopy Society to conduct the study. Consent was obtained for each patient included in the study. Patients with significant luminal narrowing exhibiting symptoms of upper GI obstruction such as nausea, vomiting, upper abdominal pain and/or discomfort, and bloating were included in the study. Luminal narrowing was confirmed via upper GI series and/or esophagogastroduodenoscopy (EGD). This multicenter study was conducted at four different hospitals . All procedures were performed by a single, advanced endoscopist. The inclusion criteria included the presence of symptomatic upper GI tract strictures beyond the esophagus that were refractory to balloon dilation. The exclusion criteria included any contraindication to upper endoscopy or stent placement or inability to obtain consent. FC-SEMS with the scope deployment capability produced by Taewoong Corporation were used in all patients for treatment of stated symptoms. The stents were placed under endoscopic and fluoroscopic guidance. The FC-SEMS were inserted through the therapeutic channel of the endoscope and were deployed across the site of stricture. The size of the stents used was either 18 mm or 20 mm in diameter  pre-procedure Table .The patients were re-evaluated at week one and week four post-procedure and were similarly scored based on GOOSS. A minimum of one-point improvement in GOOSS was considered significant. To remove the stents follow-up EGD was performed two to three weeks after FC-SEMS placement in pyloric and duodenal strictures and after four to six weeks in gastric bypass and Whipple jejunostomy anastomosis. FC-SEMS were removed using biopsy forceps or Rat Tooth Forceps during the follow-up EGD. The sutures were cut using Enzisor Endoscopic Scissors or loop cutters. Long-term follow-up was performed in all patients with a minimum follow-up duration of four months to a maximum of 24 months. Repeat EGD with FC-SEMS placement was performed in case of recurrent obstructive symptoms and restenosis on long-term follow-up. A chi-square test of independence was used to determine the significance of clinical improvement based on GOOSS pre- and post-procedure.The study involved 28 symptomatic patients with benign upper GI strictures. These patients had significant luminal narrowing combined with symptoms of upper gastric outlet obstructions which included nausea, vomiting, upper abdominal pain and/or discomfort, and bloating. In total, 13 patients had strictures in the duodenum, six in the pylorus, six in the gastric bypass anastomosis, and three with Whipple gastrojejunostomy and efferent limb obstruction. Luminal narrowing was confirmed via upper GI series and/or EGD. Eight patients had their duodenal stents receive one suture for fixation. The remaining patients received two or three sutures for the fixation of their respective stents. Suturing was performed using the Apollo Overstitch Device .Statistical results2 = 13.89; p < 0.001; 1 df). A significant change was also found between the pre-procedure and the four-week follow-up from GOOSS 1 to GOOSS 2 . When looking for overall improvement in GOOSS score, significance was only found between pre-procedure and one-week follow-up .Statistical analysis was performed on pre-procedure and post-procedure data on the GOOSS score. Pre-procedure, one-week post-procedure, and four-weeks post-procedure GOOSS scores were documented Table . Chi-squThe data suggests that the stent procedures are significantly effective in cases with GOOSS scores greater than zero. Patients with a GOOSS score of 1 were seen to improve to a GOOSS score of 2 at both the one-week and four-week follow-up. Improvement in higher score patients was not evident in the pre-procedure to one-week post-procedure GOOSS scores, but it was significant from pre-procedure to four-week follow-up scoring.ComplicationsFC-SEMS migration occurred in eight patients. Three patients had distal migration while five had proximal migration into the stomach. Among patients who experienced distal migration, two had a spontaneous passage of FC-SEMS from the alimentary tract and one had the stent removed by double-balloon enteroscopy. Five patients had proximal migration of stents into the stomach, and all patients had the sutures intact and the stents seemed to have retracted into the stomach. These stents were removed after cutting the sutures using Enzisor Endoscopic Scissors or loop cutters. Subsequently, biopsy forceps or Rat Tooth forceps were used to pull the proximal end of the stent into the distal attachment. Migrations were observed in patients who received one suture for fixation of the duodenal stent. No distal migration of the duodenal stents was observed in patients who received two or three stitches for fixation. Two patients had a recurrence of obstructive symptoms; one patient was noted to have antro-pyloric stenosis (six months post-procedure) while the other one had gastric bypass anastomosis (12 months post-procedure). Both patients were treated with a repeat EGD with FC-SEMS replacement. Post-procedure pain was noted in eight patients and this required narcotic analgesics for approximately four days. Other complications, including perforation, tissue ingrowth/overgrowth, and hemorrhage, did not occur in any patient.Stents have been used to maintain luminal patency and widen a stenosed lumen. Originally, stents were composed of hard plastic and were typically utilized for obstructive esophageal malignancies. The stents utilized today are composed of metal and are either made with stainless steel or nitinol. Nitinol mesh consists of a nickel-titanium alloy allowing it to be soft and flexible. The wire ends are smoother resulting in a reduced risk of tissue overgrowth. These metal stents can be uncovered, partially covered, or fully covered. Only FC-SEMS were utilized in the study. This prospective study demonstrates a significant improvement in gastric outlet obstructive symptoms up to four weeks post-FC-SEMS placement in all patients. The only immediate complication noted in this study was the migration of the stents in eight patients. Long-term follow-ups did document the recurrence of obstructive symptoms in two patients; however, they were treated by repeat EGD with FC-SEMS replacement without complications. Thus, FC-SEMS placement for benign, refractory upper GI strictures appears to be a safe and effective treatment.A therapeutic option, endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ), involves the identification of the jejunum directly from inside of the stomach with subsequent placement of a lumen-apposing metal stent. Target identification, as well as proper stent placement, are challenging steps for the EUS-GJ technique, and this technique is only available at a few centers. Furthermore, patients with pyloric obstruction associated with chronic pancreatitis are especially resistant to endoscopic balloon dilation .Another treatment modality is surgical gastrojejunostomy which can typically be performed in patients with pyloric or duodenal obstruction but not in patients with gastric bypass anastomotic strictures or post-Whipple strictures. Traditionally, gastroduodenal obstruction has been treated by various surgical gastrojejunostomy techniques. Although it has been an effective treatment, these procedures result in operative morbidity requiring hospitalization ,15. In oThe limitations of our study include a relatively small sample size and a lack of a comparison with surgical gastrojejunostomy or EUS-GJ counterparts. Future studies utilizing a larger sample size and randomized comparison to surgical gastrojejunostomy and/or EUS-GJ will be required to further validate this technique.In patients with refractory, benign strictures of the pylorus, duodenum, gastric bypass, and Whipple gastrojejunostomy anastomosis, the placement of FC-SEMS with two to three sutures appears to be a safe and effective modality as it resolved obstructive symptoms and treated benign strictures with minimal risk of complications. Additionally, applying two to three sutures to secure the stents appears to reduce the risk of migration when compared to using one suture.


Background: The incidence and mortality rates of hepatocellular carcinoma (HCC) are increasing worldwide. Therefore, there is an urgent need to elucidate the molecular drivers of HCC for potential early diagnosis and individualized treatment. Whether c-Myc expression plays a role in the clinicopathology and prognosis of patients with HCC remains controversial. This meta-analysis aimed to survey the prognostic role of c-Myc in HCC.Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, and Google Scholar databases for studies published through March 2020 that examined the association between c-Myc expression and clinicopathology or prognosis in HCC patients. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to investigate the prognostic significance of c-Myc expression. Odds ratios were calculated to evaluate the association between c-Myc expression and clinicopathologic features. We also tested for publication bias.Results: Our meta-analysis included nine studies with 981 patients with HCC published between 1999 and 2016. A meta-analysis of these studies demonstrated that high c-Myc expression indicated a poor overall survival (OS)  and disease-free survival (DFS)  in patients with HCC. However, high c-Myc expression was not associated with HBsAg, pathological type, TNM stage, or cirrhosis. We did not find any significant publication bias among the included studies, indicating that our estimates were robust and reliable.Conclusion: c-Myc overexpression could predict poor OS and DFS in HCC patients. c-Myc could be a useful prognostic biomarker and therapeutic target for HCC. Primary liver cancer (PLC) is a high-risk malignant tumor worldwide, with approximately one million new patients every year . Hepatocc-Myc, a predominant member of the MYC family, is the most frequently activated oncogene. c-Myc is a transcription factor that binds to the enhancer box sequence CACGTG  and direWe comprehensively searched PubMed, Cochrane Library, Embase, Web of Science, and Google Scholar databases for studies published through March 2020. The following keywords were variably combined and used as the search criteria: hepatocellular cancer, HCC, liver cancer, c-Myc, and prognosis. Additional relevant references cited in the retrieved articles were also included in the evaluation.in situ hybridization, genome quantitative polymerase chain reaction, immunohistochemistry, or other techniques; and 4) the clinical characteristics of c-Myc dysregulation were compared with detailed survival information, including overall survival (OS) and disease-free survival (DFS).The following criteria were used to identify articles eligible for inclusion in this systematic review: 1) published in English with the full text available; 2) all patients were diagnosed with HCC based on pathology; 3) c-Myc expression levels were detected in tumor tissues by fluorescence p-values, and 95% confidence intervals (CIs)]. Multivariate analysis results were selected when both univariate and multivariate analysis results were available in the same article.The available data were independently extracted by two reviewers (Zhao M and Zhang XL). Any dispute between the two reviewers was resolved by consensus or by a third reviewer (Chen HZ). The following details of each publication were extracted: the name of the first author; year of publication; country; ethnicity of the patients; number of patients; assessment method of c-Myc; cutoff value; follow-up time; clinicopathologic parameters, including sex, age, tumor size, tumor number, HBsAg, pathological type, cirrhosis, and TNM stage; OS or DFS; and outcomes of univariate and/or multivariate analyses [including hazard ratios (HRs), Two investigators independently conducted quality assessments for all included studies (Zhao WY and Yu HY). The Newcastle–Ottawa Quality Assessment Scale, recommended by the Cochrane Collaboration as a risk-of-bias assessment tool for observational studies, was applied to assess the quality of the included studies . Three pp-values to assess the heterogeneity among the eligible studies. A chi-squared p value < 0.1 or an I2 value > 50% was defined as statistically significant heterogeneity  . High c-Myc expression was also associated with poorer DFS in the random model . However, high heterogeneity among the studies was observed (p < 0.001 and I2 = 95.30%)  . No stat 95.30%) .p = 0.361), pathological type , TNM stage , or cirrhosis .We next calculated the association between elevated c-Myc expression and clinical parameters . Overexpp = 0.635 for OS and p = 0.706 for DFS). The results of the sensitivity analysis demonstrated that our assessment was accurate and reliable. Due to the limited number of articles included, sensitivity analyses of the association between c-Myc expression and clinical features were not performed.We used Begg’s funnel plot and Egger’s test to examine potential publication bias. Sensitivity analysis was executed by sequentially omitting each trial one at a time. As shown in This meta-analysis analyzed the association between c-Myc expression and prognosis among patients with HCC. We showed that high c-Myc expression was significantly associated with prognosis.via the upregulation of downstream proteins involved in protein translation, cell cycle regulation, apoptosis, and metabolism (Cell survival and growth are promoted by c-Myc tabolism . Cancer tabolism , breast tabolism , and coltabolism . c-Myc atabolism .c-Myc is considered an important therapeutic target because of its dysregulation in approximately 50% of human cancers . AbnormaIn this meta-analysis, we included nine articles including 981 patients with HCC to accurately assess this issue. Our results indicated that overexpression of c-Myc significantly predicted poor OS and DFS in patients with HCC. This implies that c-Myc may be a biological marker of poor prognosis, and its expression can be used as a risk assessment tool for HCC patients. However, c-Myc expression was not associated with any clinicopathologic parameters we assessed, including HBsAg, pathological type, TNM stage, and cirrhosis. This may be because there were not enough patients included in our analysis. Additionally, a high degree of heterogeneity complicated the analysis. Our systematic review of a large number of researched studies shows that MYC has a known effect on the prognosis of liver cancer, although the Human Protein Atlas indicates that MYC is not prognostic in liver cancer. The reason may be that most of these studies included Asians, because of ethnic differences. Our research results indicated that c-Myc overexpression could predict poor OS and DFS in HCC. It is necessary to study the relationship between c-Myc expression and clinicopathologic characteristics in the future.Although significant efforts have been made to conduct a comprehensive analysis, this meta-analysis has some limitations. First, all the studies in this meta-analysis were written in English. This might have caused publication bias to some extent, although we did not identify any publication bias. In the process of searching for references, we ruled out one animal study that was published in a language other than English. Therefore, there were also other reasons for exclusion. Second, our results might not apply to patients of other ethnicities because most of the patients in this study were from Asia. Third, there were not enough patients to conduct a good pooled analysis. Because of the lack of relevant data, we did not analyze all clinicopathologic features in this meta-analysis. Although our meta-analysis suggests that c-Myc is associated with HCC prognosis because of these limitations, detailed clinical studies are warranted to establish the prognostic prediction value of c-Myc in HCC in the future.This meta-analysis revealed that c-Myc overexpression predicts poor OS and DFS in patients with HCC. Our results suggest that c-Myc is a useful prognostic biomarker and therapeutic target for HCC.


One of the effective ways to control hypertension is long-term self-management, which is difficult to maintain. Therefore, understanding how people engage in the process of self-management behaviour change is necessary. In this study, we aimed to examine the dynamic relationship between self-perceived disease control and self-management behaviours in Chinese middle-aged and older hypertensive patients, namely, medication use, self-monitoring, physical activity, tobacco and alcohol avoidance, and to explore the mediating role of subjective life expectancy (SLE) on this relationship.Data were obtained from a nationally representative sample of 508 middle-aged and older hypertensive patients (aged 45+) from the 2013, 2015, and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey. A cross-lagged panel model combined with mediation analysis was used to determine the dynamic relationship between self-perceived disease control and self-management behaviours and to clarify the mediating effect of SLE on this ascertained relationship.Good self-perceived disease control subsequently predicted good medication use, self-monitoring and physical activity, and vice versa. Subjective life expectancy (SLE) partially mediated the prospective reciprocal relationships between self-perceived disease control and these self-management behaviours, which accounted for 37.11, 25.88, and 19.39% of the total effect of self-perceived disease control on medication use, self-monitoring and physical activity, respectively. These self-management behaviours had a significant and positive feedback effect on self-perceived disease control. However, neither the direct and indirect effects (via SLE) of self-perceived disease control on tobacco and alcohol avoidance were revealed.Positive feedback loops of present self-perceived disease control, future SLE and self-management behaviours  help middle-aged and older hypertensive patients adhere to these behaviours but are useless for the avoidance of addictive behaviours. Interventions aimed at enhancing the effect perception of general self-management behaviours  on the present disease control perspective, and future lifespan perspective would be beneficial for the consistent self-management behaviours of middle-aged and older hypertensive patients. The utility of present disease control perception to these self-management behaviours was much higher than the utility of future expectations. Alternative stress relief strategies may be conducive to long-term changes in addictive behaviours.The online version contains supplementary material available at 10.1186/s12889-022-12990-8. Hypertension has become a serious national disease in China , affectiThe concept of self-management originated from responsible stewardship of one’s health , which eBecause behavioural decisions guide subsequent behaviours later than individuals’ social-cognition factors do, researchers regularly apply social cognition theories to explore the mechanism of hypertension self-management adherence , 22. HowHowever, several systematic reviews have found that the relationship between the dimensions of disease-related perceptions and individuals’ self-management persistence behaviour is weak , 26. OthIt is worth noting that the relationship between SLE and health-related behaviours is fuzzy. The vast majority of studies believed that adults who had low survival expectations were reluctant to engage in health-related behaviour and were even more likely to participate in a range of risky behaviours , 34, 40.Although some previous studies are valuable for identifying insight into the pathway among SLE, self-perceived disease control and self-management behaviours, the conclusions are difficult to evaluate the complex interactions among specific variables in the dynamics of self-management processes based on the cross sectional-based research design , 22. At This study used secondary data analysis to test robust causal relationships. The data in our study came from the China Health and Retirement Longitudinal Survey (CHARLS), a dynamic cohort study with first-wave data collected in 2011 and three follow-up surveys in 2013, 2015, and 2018. The survey is one of the international health and pension survey series and is sponsored by the National Development Research Institute of Peking University, the Chinese Social Sciences Survey Center of Peking University, and the League Committee of Peking University. It recruits a representative sample of middle-aged and older adults over the age of 45 from 150 counties and 450 communities (villages) of 28 provinces, accounting for 85% of the total population in China. Ethical approval for all the CHARLS waves was granted from the Institutional Review Board at Peking University. In this study, all participants knew the purpose of the study and signed informed consent forms. The Institutional Review Board (IRB) approval number for the main household survey, including anthropometrics, is IRB00001052–11015; the IRB approval number for biomarker collection is IRB00001052–11014 –46.Meanwhile, hypertension management has been behaviourally demanding and complex , and theThe current study used CHARLS’s last three waves of the data in 2013, 2015 and 2018 . The inclusion criteria were middle-aged and older hypertensive patients who participated in all three-wave investigations (2801 hypertensive patients). The exclusion criteria were (i) persons who lived with mental retardation and physical disabilities (429 hypertensive patients) and (ii) participants with missing data on the main variables (outcome variable and independent variable) (1864 hypertensive patients). Therefore, the final sample for analyses consisted of 508 respondents.Self-management behaviours were the interaction of health behaviours, and patients and families engaging in the caring for a chronic condition was a related process . Based oA single question, “Are you now taking any of the following medications to treat or control your hypertension?” was administered to assess participants’ medication use status. Each option of taking Chinese traditional medicine or modern Western was scored 1 when the answer was yes and 0 for none of the above, so higher scores indicated better medication use.The question “During last year (last 12 months), how many times have you had a blood pressure examination?” was asked to inform the patients about their self-monitoring behaviour. The examination time was scored as 0, 1 for ?”. Therefore, the response options for this item were 1 = almost impossible, 2 = not very likely, 3 = maybe, 4 = very likely, 5 = almost certain, which correspond to the SPS of 0, 25, 50, 75 and 100%, respectively.We included several covariates that were known to be associated with self-perceived disease control, and self-management behaviours were controlled in our statistical analyses to minimize the disturbing possibility of other variables and to maximize the parsimony of our analytic model , 52, 53.SPSS v26 (IBM Corp 2019) was used to test the demographic differences among self-management behaviours (independent-sample t test and one-way ANOVA) and the correlation among self-perceived disease control, SLE, and self-management behaviours .χ2/df). Model fit is good when RMSEA< 0.06, SRMR< 0.08, χ2/df < 3.Two types of separate autoregressive cross-lagged models in Mplus v7.4 (Muthen & Muthen 1998–2015) were used to estimate the main hypotheses . The firFurthermore, because the data distribution of variables was skewed, we used the bootstrapping method, which is an approach for implementing statistical tests and construct confidence intervals without the use of the traditional statistical assumption of normality used to test the statistical significance of the paths and to compute an estimation of the indirect effect with a 95% CI. The indirect effect was significant when the confidence interval did not include zero.The distribution of the study variables measured in 2013, 2015, and 2018 are presented in Table p < .001) and self-monitoring status  decreased from 2013 to 2018, while individuals’ medication use  and physical activity  increased.Among the 508 respondents, the results of repeated-measures analysis of variance indicated that individuals’ self-perceived disease control  , self-monitoring , physical activity ; and medication use , self-monitoring , physical activity  on subsequent self-perceived disease control were significant. No evidence for bidirectional causality was observed in the association between self-perceived disease control and tobacco/alcohol avoidance.Longitudinal cross-lagged models Models 1–5) between self-perceived disease control and self-management behaviours  after controlling for covariates, with the autoregressive and concurrent estimates as well as cross-lagged paths, are illustrated in Figs. –5 betwee2/df = 1.88 ~ 2.73) , self-monitoring , and physical activity  through SLE over time. The reverse cross-lagged direct effect but not the indirect effect from self-management behaviours  to self-perceived disease control was shown over time. Meanwhile, these mediation models demonstrated that partial effects accounted for 37.11, 25.88, and 19.39% of the total effect of self-perceived disease control on medication use, self-monitoring and physical activity, respectively. Moreover, this mediation path was not observed between self-perceived disease control and tobacco/alcohol avoidance.As Figs. This study examined the reciprocal association between self-perceived disease control and self-management behaviours in middle-aged and older hypertensive patients and the underlying mechanism of SLE by explaining the process. The current longitudinal study documented the differentiated causal relationships among self-perceived disease control, SLE and various self-management behaviours through three waves over a 5-year period. These relationships are more complex than previously thought from cross-sectional research and have implications for adherence to middle-aged and older patients’ self-management behaviours , 62.This study found a positive bidirectional association between self-perceived disease control and medication use, self-monitoring, and physical activity. It demonstrates that people will continue to implement self-management behaviours if they believe that these behaviours will help to prevent disease . By valiMoreover, the positive regulatory role of SLE among self-perceived disease control and medication use, self-monitoring, and physical activity was separately identified in our study. This result indicates that when individuals perceive their disease control better, they tend to anticipate more positive and less negative outcomes over time — in turn, they tend to invest more self-regulatory effort  and report high-level self-management behaviours. According to socioemotional selectivity theory , 75, indWe also found that our results do not show reverse mediating effects, but that these behaviours feed back into self-perceived disease control, forming a potential feedback loop or spiral. This feedback loop may affect an individual’s adherence to medication use, self-monitoring and physical activity trajectory. Even though SLE has been shown to be associated with health behaviours, smoking status, alcohol status and physical activity through several studies , 35, thiFurthermore, we discover that in contrast to medication use, self-monitoring, and physical activity, the current study found no consistent patterns in self-perceived disease control and the avoidance of addictive behaviours . Self-perceived disease control can significantly influence SLE, but it does not affect tobacco and alcohol avoidance directly or indirectly through SLE. Additionally, addictive behaviours  have been regarded as the main risk factors for hypertension, but avoiding addictive behaviours  does not lead to better self-perceived disease control or SLE. High levels of social isolation and feelings of personal uselessness are more common among middle-aged and older individuals, leading to the further exacerbations of hypertension. Folkman and Lazarus (1986) defined “coping” as the cognitive and behavioural efforts to deal with  the internal and external demands of an interaction with the environment that a person determines may be burdensome to him or her, even beyond the resources available to him or her . In addiThis longitudinal study attempted to shed light on the underlying mechanisms linking self-perceived disease control and self-management behaviours among middle-aged and older hypertensive patients by using three waves of CHARLS data in 2013, 2015, and 2018, and the results were of great interest, as they had implications for the development of future intervention strategies for self-management behaviours. The present study indicates a bidirectional causality between self-perceived disease control and medication use, self-monitoring and physical activity, and the individual perception of “how long he or she will live” partially mediated the predtion of self-perceived disease control on these self-management behaviours  by forming a potential feedback loop or spiral. Individual adherence to medication use, self-monitoring and physical activity may be affected by these factors. However, this predictive relationship was not confirmed in tobacco and alcohol avoidance behaviours. Based on these findings, in establishing their health trajectories, the middle-aged and older hypertensive patients’ present self-perceived disease control and future lifespan expectations played important roles, which could uncover pathways to shape their self-management behaviours. It might be helpful to stress the notion of plasticity . In particular, it might also encourage those with a limited time perspective to try to think about the short-term effect of self-management behaviours for disease control and the long-term effect on lifespan. However, because addictive behaviours  are difficult to affect by changing one’s self-perception of disease control and one’s future time perspective, patients might benefit from promoting the use of adaptive coping strategies  to actively cope with stress.There are also some limitations to this study. First, autoregressive cross-lagged path analyses cannot separate the between-person effects from the within-person effects. Future studies should use the random intercept cross-lagged panel model focusing on within-person longitudinal associations to further test our results. Second, the study sample only comprised middle-aged and older hypertensive patients in China. It is unknown whether our findings will generalize to other cultural contexts and any other hypertensive patients. The results should be replicated in diverse social environments and patient populations. Third, there is a lack of analysis of other self-management behaviours  due to the limitation of data. Other constructs of the illness belief domains or other mediators that have been well documented in empirical studies should also be examined further. Fourth, the complex associations between self-perceived disease control and self-management behaviours could be moderated by other factors . Future studies should elucidate the protective factors to strengthen self-perceived disease control or SLE to adherent self-management behaviours.Additional file 1: Table 2. Pearson correlation test for self-perceived disease control, subjective life expectancy and self-management behaviors.Additional file 2: Supplementary Table 1. Fit index for longitudinal cross-lagged models (Model 1–5) between self-perceived disease control and self-management behaviors.Additional file 3: Supplementary Table 2. Tested the longitudinal mediation cross-lagged models (Model 6–10) adding SLE as the mediator.


Anemia is common in heart failure (HF) patients with chronic kidney disease (CKD) and is associated with worse outcomes. Iron supplementation improves symptoms and is associated with reduced risk of hospitalization for HF in iron-deficiency HF patients. However, iron deficiency is present in <30% of anemic HF patients. Erythropoiesis stimulating agents (ESAs) improve symptoms but are associated with increased risk of thromboembolic events in anemic HF patients with CKD. Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are a new class of agents for the treatment of anemia. These agents work by stabilizing the HIF complex, thereby stimulating endogenous erythropoietin production. We hypothesized that HIF-PH inhibitors may be associated with reduced risk of cardiovascular outcomes compared with ESAs in anemic HF patients with CKD. Accordingly, we aim to perform the meta-analysis of studies on the efficacy and safety of HIF-PH inhibitors compared with ESAs in anemic HF patients with CKD.This meta-analysis will include prospective cohort studies and randomized controlled trials on the effect of HIF-PH inhibitors compared with ESAs in anemic HF patients with CKD. Information of studies will be collected from PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov. The primary outcome will be cardiovascular death. The secondary outcomes will be all-cause death, hospitalization for HF, HF symptoms, exercise capacity, health-related quality of life, and hemoglobin levels.This meta-analysis will evaluate the effect of HIF-PH inhibitors in anemic HF patients with CKD, providing evidence regarding the use of HIF-PH inhibitors in these patients.INPLASY202230103. Heart failure (HF) is a major clinical and public health problem. Despite the significant progress in the treatment of HF, the mortality of HF remains high and, in most recent years, ≈50% at 5 years .Chronic kidney disease (CKD) is a common comorbidity in HF patients and HF patients with CKD frequently have anemia . In anemThe effect of erythropoiesis stimulating agents (ESAs) in anemic HF patients with CKD has been examined in multiple randomized controlled trials (RCTs) –11. SeveHypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitors are a new class of agents for the treatment of anemia , 14. Thehttps://www.doi.org;DOI: 10.37766/inplasy2022.3.0103). This protocol for meta-analysis will be performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) statement [This study has been registered on International Platform of Registered Systematic Review and Meta-analysis Protocols with registration number of INPLASY202230103 (tatement .hypoxia-inducible factor prolyl hydroxylase inhibitor(s), roxadustat, daprodustat, vadadustat, molidustat, desidustat, enarodustat, and heart failure. Only articles published in the English language will be included.The electronic databases for literature search will include PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov. For search of the eligible studies, the following keywords and Medical Subject Heading will be used: Prospective cohort studies and RCTs will be included. Retrospective cohort and case–control studies will be excluded.Inclusion criteria for this meta-analysis included: (1) included HF patients with anemia and CKD; (2) prospective cohort studies or RCTs; (3) administration of HIF-PH inhibitors; (4) compared with ESAs; and (5) assessed cardiovascular death, all-cause death, hospitalization for HF, HF symptoms, exercise capacity, health-related quality of life, or hemoglobin levels.The primary outcome will be cardiovascular death. The secondary outcomes will be all-cause death, hospitalization for HF, HF symptoms, exercise capacity , health-related quality of life, and hemoglobin levels.Information on the study and patient characteristics, methodological quality, intervention strategies, and clinical outcomes will be systematically extracted separately by 2 reviewers. Disagreements will be resolved by consensus. We will contact the corresponding author of eligible studies when insufficient information is available to perform our meta-analysis.http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp). The quality of evidence for the outcomes will be evaluated by use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system [The Cochrane Risk of Bias tool will be used to assess quality of RCTs included . The qua) system . The quaWe will determine the required meta-analysis sample size as previously reported . BrieflyIf the required meta-analysis sample size is not available, a systematic narrative synthesis will be provided with information presented in the text and tables to summarize and explain the characteristics and findings of the included studies. The narrative synthesis will explore the relationship and findings both within and between the included studies, in compliance with the guidance from the Centre for Reviews and Dissemination .I2 statistic; for the Cochran’s Q and I2 statistic, a p value of <0.1 and I2>50%, will be considered significant, respectively. When there is significant heterogeneity, the data will be pooled using a random-effects model, otherwise a fixed-effects model will be used. Publication bias will be assessed graphically using a funnel plot and mathematically using Egger test. For these analyses, Comprehensive Meta Analysis Software version 2  and STATA 16 software  will be used.For morbidity and mortality, hazard ratios will be pooled. For continuous outcomes, the effect size for the intervention will be calculated by the difference between the means of the intervention and control groups at the end of the intervention. If the outcome is measured on the same scale, the weighted mean difference and 95% confidence interval (CI) will be calculated. Otherwise, the standardized mean difference and 95% CI will be calculated. For each outcome, heterogeneity will be assessed using the Cochran’s Q and Subgroup analysis stratified by study design (RCT or prospective cohort study) will be performed. Meta-regression will be used to determine whether the effect of HIF-PH inhibitors will be confounded by baseline clinical characteristics such as age, sex, New York Heart Association functional class, CKD stage, and hemoglobin levels.This meta-analysis is a literature study. Ethical approval is not required because this meta-analysis will not involve any subject directly.In the recent guidelines, HIF-PH inhibitors are recommended as alternatives to ESAs in correcting and maintaining hemoglobin level for renal anemia in CKD patients . HoweverSeveral experimental studies have reported that HIF-PH inhibitors have advantages over ESAs. Specifically, it is suggested that exogenous erythropoietin generated by ESAs can largely increase C-terminal fibroblast growth factor 23 (FGF23) levels . FurtherTo the best of our knowledge, this is the first meta-analysis protocol on the effect of HIF-PH inhibitors in anemic HF patients with CKD. The results will evaluate whether HIF-PH inhibitors are beneficial for anemic HF patients with CKD, providing evidence regarding the use of HIF-PH inhibitors in these patients.


Non-islet-cell-tumor-induced hypoglycemia (NICTH) is caused on rare occasions by secretion of insulin from tumor cells that are reported to have a single tissue origin.  A 67-year-old male patient had cardia adenocarcinoma and concomitant lung adenocarcinoma with extensive metastases and repeated episodes of intractable hypoglycemia. Immunohistochemical staining for insulin showed that lung adenocarcinoma stained positive and gastric cardia adenocarcinoma stained weakly positive. These results indicate that tumor cells of different tissue origins co-secreted insulin.  This is the first report on intractable hypoglycemia due to co-secretion of insulin from two kinds of primary tumor cells in a single patient. Non-islet-cell-tumor-induced hypoglycemia (NICTH) is a rare paraneoplastic syndrome characterized by repeated episodes of hypoglycemia. NICTH is commonly associated with excessive secretion of immature insulin-like growth factor (IGF)-2 precursor or IGF-1, by mesenchymal or epithelial tumor cells. Several studies have also reported that NICTH is related to excessive secretion of insulin from some tumors originating from a single tissue. Here, we report the first case of intractable hypoglycemia due to co-secretion of insulin from gastric cardia adenocarcinoma (GCA) and lung adenocarcinoma (LA), as confirmed by immunohistochemical staining for insulin. We obtained approval from our institution’s ethics committee to report this case and the patient’s family consented to the publication.A cardia mass was found in a 67-year-old male patient in May 2012, and surgical resection was performed. Postoperative pathological examination showed moderately to poorly differentiated ulcerative gastroesophageal junction (GEJ) adenocarcinoma. In March 2015, the patient complained of frequent dizziness in the mornings, which improved after eating. On the morning of May 4, 2015, he presented limb convulsion unconsciously and could not be awakened. The patient’s blood glucose level was 0.9 mmol/L. Five minutes after 50% glucose treatment, he recovered consciousness. Positron emission tomography-computed tomography (PET-CT) showed pulmonary, adrenal, intracranial, intrahepatic, retroperitoneal and thoracic vertebral lesions.On May 11, the patient underwent CT-guided biopsy of a lesion in the left lung . PatholoImmunohistochemical staining for insulin showed that LA samples were stained positive  and GCA In NICTH, there are mainly three mechanisms leading to hypoglycemia: tumor cells secrete excessive high-molecular-weight IGF-2 precursor, IGF-1, and insulin.When hypoglycemia occurred in our patient, both serum C-peptide and insulin levels increased. The patient had hypoglycemia due to endogenous hyperinsulinism. Drug-induced hypoglycemia and insulin autoimmune syndrome were ruled out. Our patient had GCA and concomitant LA, thus suggesting the possibility of ectopic secretion of insulin from non-islet-cell tumors. Immunohistochemical staining for insulin showed that LA stained positive and GCA stained weakly positive, thus indicating that high levels of endogenous insulin were secreted from both GCA and LA. The control tumor tissue was stained negative for insulin . AdditioDiazoxide can inhibit secretion of insulin and ease the condition of hypoglycemia. In 1979, Fajans used diazoxide for the first time to treat insulinoma.We reviewed the literature in MEDLINE and EMBASE using the English keywords “Hyperinsulinism”, “Hypoglycemia”, “Cardia neoplasms” and “Lung neoplasms” . No otheIn summary, this is the first reported case of hypoglycemia associated with co-secretion of insulin by LA and GCA. Regardless of the type of tumor tissues, NICTH should be taken into consideration for some nonspecific symptoms of hypoglycemia in tumor patients, such as dizziness, convulsions, hallucinations and coma. Early diagnosis and timely treatment are recommended for these patients, to improve their quality of life.


The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at   Across all kingdoms of life, organisms produce specialised metabolites: molecules that are produced by bacteria, fungi and plants to gain an advantage over their competitors in challenging environments. Specialised metabolites, also referred to as secondary metabolites or natural products, exhibit a wide variety of biological activities, including many that are useful for pharmaceutical and agricultural applications, e.g. antibiotics, anti-cancer drugs, pesticides and herbicides. The production of specialised metabolites is typically encoded by biosynthetic gene clusters (BGCs): groups of co-localised and co-regulated genes that jointly encode a biosynthetic pathway. Therefore, microbial and plant genomes can be mined for novel specialised metabolite production by detecting BGCs and predicting their encoded products and functions. Similar to how the relationship between DNA, mRNA and protein describes the flow of information in cells, we can define a ‘central dogma’ of specialised metabolism: a BGC sequence encodes a set of enzymes, which together assemble a compound structure , which in turn dictates specialised metabolite function. Understanding how information is translated from sequence to structure to function is key to natural product discovery. To address the first stage, sequence information, various tools have been developed that automatically detect BGCs from DNA sequence, including antiSMASH and its siblings fungiSMASH and plantiSMASH ,2, GECCOTo facilitate dereplication and comparative analysis of predicted BGCs with known BGCs, and to characterise the interplay between sequence, structure and function, standardised data annotation and storage are essential. To this purpose, we developed the Minimum Information about a Biosynthetic Gene cluster (MIBiG) standard and built a database which contains standardised entries for experimentally validated BGCs of known function ,8. Each Here, we present MIBiG 3.0: an update designed to increase the number of non-minimal entries in our database and adding new data entries through a large-scale community annotation effort. We focused on three features: the characterisation and cross-linking of 1188 chemical structures, the annotation of 1002 bioactivities of BGC products, and the validation and annotation of 2020 protein domain substrates of nonribosomal peptide synthetases (NRPSs). In addition, we added 661 novel BGCs to the MIBiG database which were published since the last database update and removed 69 duplicate and low-quality entries  add structures for compounds in SMILES format , includiTo improve MIBiG as a resource for machine learning models predicting sequence-structure-function relationships, we added bioactivity data for 1002 compounds and chemical target data for 95 compounds. 708 of these annotations were transferred from the dataset assembled by Walker and Clardy, who designed a machine learning model to predict BGC function from sequence . To accol-aspartic acid); the substrate as recognised by the A-domain (e.g. (3R)-3-hydroxy-l-aspartic acid); or the post-tailored integrated monomer that ends up in the final NRP scaffold (e.g. (3R)-3-hydroxy-d-aspartic acid). We chose to annotate the substrates as recognised by the A-domain, as this best reflects the biological relationship between A-domain and incorporated monomer. In addition to substrate identity, we also recorded evidence for substrate selectivity in the form of an evidence code and literature references. To this purpose, we added 13 evidence codes to the JSON schema which is used to standardise MIBiG entries , we annotated and validated the substrate selectivities of 2775 NRPS adenylation (A) domains. A-domains dictate which monomers (predominantly amino acids) are incorporated into (hybrid) NRP scaffolds. Substrate annotation can be performed at different levels: we can define the pre-tailored substrate precursor , bioactivities (1002) and NRPS substrates (2020). In total, we added 661 novel BGCs and 4871 separate data entries to our database, increasing our number of non-minimal entries from 486 to 928  domains for PKS and A-domains for NRPS), these consistent architectures make it possible to predict the structure of chemical scaffolds with reasonable accuracy. Most AT domains in PKS systems recognise one of two substrates, malonyl-CoA or methylmalonyl-CoA, and excellent bioinformatics tools exist to distinguish between the two . HoweverSince version 2.0, we have added structural identifiers of 1188 compounds to our database in SMILES format , increasBy centering MIBiG 3.0 around the annotation of substrate building blocks, compound structures, and bioactivities, we aspired to streamline future research into all aspects of sequence-structure-function relationships that lie at the heart of natural product research. All data can be easily downloaded and parsed in bulk from our database in JSON and GenBank format or accessed on an entry-by-entry basis through our searchable online repository. As such, we hope that MIBiG 3.0 will prove an important resource for future machine learning endeavours that aim to decode the central dogma of specialised metabolism.https://mibig.secondarymetabolites.org/. There is no access restriction for academic or commercial use of the repository and its data. The source code components, JSON-formatted data standard, and SQL schema for the MIBiG Repository are available on GitHub (https://github.com/mibig-secmet) under an OSI-approved Open Source licence.The MIBiG Repository is available at gkac1049_Supplemental_FilesClick here for additional data file.


Potential deleterious injuries resulting from reperfusion therapies remain a clinical challenge for physicians. This study aimed to explore the metabolomic alterations during ischemia-reperfusion injury by employing metabolomic analysis coupled with gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultraperformance liquid chromatography quadrupole (UPLC/Q)-TOF-MS. Metabolomic data from mice subjected to middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) were compared to those of the sham and MCAO groups. A total of 82 simultaneously differentially expressed metabolites were identified among each group. The top three major classifications of these differentially expressed metabolites were organic acids, lipids, and organooxygen compounds. Metabolomics pathway analysis was conducted to identify the underlying pathways implicated in MCAO/R. Based on impactor scores, the most significant pathways involved in the response to the reperfusion after cerebral ischemia were glycerophospholipid metabolism, linoleic acid metabolism, pyrimidine metabolism, and galactose metabolism. 17 of those 82 metabolites were greatly elevated in the MCAO/Reperfusion group, when compared to those in the sham and MCAO groups. Among those metabolites, glucose-6-phosphate 1, fructose-6-phosphate, cellobiose 2, o-phosphonothreonine 1, and salicin were the top five elevated metabolites in MCAO/R group, compared with the MCAO group. Glycolysis, the pentose phosphate pathway, starch and sucrose metabolism, and fructose and mannose degradation were the top four ranked pathways according to metabolite set enrichment analysis (MSEA). The present study not only advances our understanding of metabolomic changes among animals in the sham and cerebral ischemia groups with or without reperfusion  Cerebral ischemia, resulting from compromised blood flow, is one of the leading causes of death worldwide with limited therapeutic options . Acute rThe brain requires 20%–25% of the energy provided by basal metabolism, which is a massive demand for energy considering its relatively small size and weight . Energy Advances in omics have allowed for comprehensive and systemic profiling of small molecular substances alterations, which provided scientists with comprehensive insight into mechanisms underlying the pathogenesis of diseases. Metabolomic analysis can be used to identify potential pathways and understand pathological mechanisms . In thisAdult male C57BL/6 mice  were obtained from the Animal Center of the Army Medical University . Colonies were maintained in a specific pathogen-free grade environment with a 12 h light/12 h dark cycle. The use of mice was performed in accordance with the Guide of Care and Use of Experimental Animals of the Animal Ethics Committee of the Army Medical University.As shown in the flow chart in Infarct volume measurements and neuroscore assessments were performed according to a previously developed method . Brain tNeuroscore assessment was performed by an experimenter blinded to the experimental groups .For LC with tandem mass spectrometry (LC-MS/MS) detection, metabolite extraction was performed according to a previously developed method . Fifty mFor GC/TOF-MS analysis, metabolite extraction was performed according to a previously developed method . A 50 ± LC-MS/MS analyses were performed using an UHPLC system  with a UPLC HSS T3 column  coupled to a Q Exactive mass spectrometer  according to a previously developed method . Mobile GC-TOF-MS analysis was performed using an Agilent 7,890 gas chromatograph coupled with a TOF mass spectrometer according to a previously developed method . The sysRaw data from the LC-MS/MS analysis were converted to the mzXML format using ProteoWizard and processed using an in-house program, which was developed using R and based on XCMS, for peak detection, extraction, alignment, and integration according to a previously described method . An in-hRaw data from the GC-TOF-MS analysis, including peak extraction, baseline adjustment, deconvolution, alignment and integration, were completed using the Chroma TOF  software. The LECO-Fiehn Rtx5 database was used for metabolite identification by matching the mass spectrum and retention index according to a previously described study . Finallyp-value of <0.05 was considered statistically significant.Differences among multiple groups were determined using one-way ANOVA, followed by Bonferroni’s multiple comparisons test. Statistical analyses were performed using the GraphPad software . Data are presented as the mean ± SD. A pTo examine and compare the ischemic brain damage induced by MCAO with or without reperfusion, TTC  staining was applied to analyze the infarct size in the sham, MCAO, and MCAO/R groups. Transient MCAO for 90 min followed by 24 h-reperfusion induced a significant increase in the infarct volume and neurological deficit compared with those in the sham and MCAO groups (< 0.05) . Notably< 0.05) .Multivariate statistical analysis methods, including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), were employed to investigate the separation of the gas-liquid chromatography data of the sham, MCAO, and MCAO/R groups. As shown in Differential metabolomic profiling analysis was performed to identify the correlated metabolites involved in the reperfusion-induced alterations. A total of 188 differentially expressed metabolites were identified in the sham versus MCAO group, while 190 metabolites were significantly altered in the MCAO/R versus sham group. A total of 82 metabolites were simultaneously differentially expressed in these three groups, according to the Venn diagram . The catp) value (y-axis)  or -ln (y-axis) . In addi(y-axis) . Relativ(y-axis) .We focused on the reperfusion-induced alterations in the levels of metabolites and found that concentrations of the 17 identified metabolites  was used to perform metabolite set enrichment analysis (MSEA) to identify pathways and biological functions significantly enriched in these 17 differential metabolites. MSEA results are presented graphically; the horizontal bar summarizes the most significant metabolites sets identified during this analysis. The bars are colored based on their p-values and the bar length is based on the fold enrichment. The top four ranked pathways of MSEA were glycolysis, the pentose phosphate pathway, starch and sucrose metabolism, and fructose and mannose degradation   .In the current study, TTC staining showed that reperfusion caused an increased brain infarct volume, when compared with that in the sham group and permanent occlusion . TherefoThe primary goal of the current study was to investigate reperfusion-induced metabolic alterations. Therefore, we compared the metabolic changes in the MCAO/R group with those in the MCAO group. The results indicated that only the metabolites in the green and red boxes in via a hexokinase 2-dependent mechanism, which might account for the reperfusion injury , a rate-limiting enzyme in this pathway, can alleviate the reactive oxygen species-induced damage through the elevation of NADPH . Consistotein 27 . Furtherotein 27 . Moreoveotein 27 .Salicin and cellobiose two are another two major differentially expressed metabolites identified in this study. Although their metabolisms in the brain is still under investigation, a recent study revealed the neuroprotective potential of salicin against cerebral ischemia-reperfusion through the activation of the PI3K/AKT pathway and its antioxidant efficacy . Moreovep component, which was neurocytotoxic and present in cerebrovascular diseases (In addition to organooxygen metabolites, amino acids, including N-acetylhistidine and N-methyl-dl-alanine, were also significantly upregulated among the metabolites in the MCAO/R group when compared with those in the sham group. Our findings are consistent with a previous metabolomic analysis of the cerebrospinal fluid of patients with Alzheimer’s disease . Interesdiseases . In addiBesides glucose metabolism and the pentose phosphate pathway, we also found that other important metabolic pathways, such as starch and sucrose metabolism, fructose and mannose degradation, and linoleic acid metabolism are also implicated in cerebral ischemia-reperfusion injury. A GO enrichment analysis suggested the involvement of starch and sucrose metabolism in an estrogen neuroprotection study of cerebral ischemia . IschemiAlthough reperfusion could a reason for the differentially expressed metabolites in the current study, a study limitation is that, despite the importance of penumbral tissue, metabolic differences between the infarct core and penumbra were not analyzed. Targeting the ischemic penumbra, the potentially salvageable tissue, is the cornerstone for the development of novel therapeutic strategies for ischemic stroke . Follow-via metabolomic profiling, but also provides the basis for exploring potential molecular mechanisms associated with the pathogenesis of reperfusion injury. Therefore, these findings contributed to the exploration of novel therapeutic strategies against injury induced by the re-establishment of blood flow.In summary, the current study demonstrated that significant changes in metabolites and pathways are involved in cerebral ischemia-reperfusion. This work not only advances our understanding of metabolomic changes in response to cerebral ischemia-reperfusion


Epstein Barr virus (EBV) can affect 90% of the human population. It can invade B lymphocytes, T lymphocytes and natural killer cells of the host and remain in the host for life. The long latency and reactivation of EBV can cause malignant transformation, leading to various lymphoproliferative diseases (LPDs), including EBV-related B-cell lymphoproliferative diseases (EBV-B-LPDs) , classic Hodgkin’s lymphoma (cHL), and posttransplantation and HIV-related lymphoproliferative diseases) and EBV-related T-cell lymphoproliferative diseases (EBV-T/NK-LPDs) , aggressive NK cell leukaemia (ANKL), and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). EBV-LPDs are heterogeneous with different clinical features and prognoses. The treatment of EBV-LPDs is usually similar to that of EBV-negative lymphoma with the same histology and can include chemotherapy, radiotherapy, and hematopoietic stem cell transplant (HSCT). However, problems such as serious toxicity and drug resistance worsen the survival prognosis of patients. EBV expresses a variety of viral and lytic proteins that regulate cell cycle and death processes and promote the survival of tumour cells. Based on these characteristics, a series of treatment strategies for EBV in related malignant tumours have been developed, such as monoclonal antibodies, immune checkpoint inhibitors, cytotoxic T lymphocytes (CTLs) and epigenetic therapy. These new individualized therapies can produce highly specific killing effects on tumour cells, and nontumour cells can be protected from toxicity. This paper will focus on the latest progress in the treatment of EBV-LPDs based on pathological mechanisms. Epstein Barr virus (EBV) is classified as a gamma-1 herpesvirus, and people are generally susceptible to this virus. Patients with EBV infection are usually asymptomatic, and the development of symptomatic disease is associated with delayed primary infection, leading to infectious mononucleosis in young people. In addition, EBV infection is associated with various EBV-related malignancies, such as nasopharyngeal carcinoma (NPC), gastric cancer subtypes, and several lymphoproliferative diseases (LPDs), especially B-cell and T-cell lymphomas . It causThere is increasing evidence that virus latent and lytic proteins can maintain the proliferation and survival of EBV-positive cancer cells by influencing cellular mechanisms regulating the cell cycle, apoptosis and immune recognition of host cells. Research to identify therapeutics for EBV has produced many surprising results. The specific killing effect not only improves the curative effect but also greatly reduces toxicity and side effects. Therefore, in addition to chemotherapy, regulatory immunosuppressive therapy and allogeneic hematopoietic stem cell transplant , different EBV-based treatment strategies, such as immunotherapy, gene therapy and epigenetic therapy, are research hotspots. This paper will summarize EBV-LPD treatment methods and discuss research advances regarding these new schemes.EBV was initially detected by Epstein MA et al. in isolated and cultured cells from a BL child in Uganda . BL is aEBV is detected in 25–50% of Hodgkin’s lymphoma (HL) cases in the United States and Europe , 40. In in situ hybridization showed that this disease was related to EBV  was first described as a unique entity in elderly patients, and d to EBV . In 2008d to EBV –50, and d to EBV . Therefod to EBV . Sarah Pesponses . CD20 isesponses . CD30 isesponses . Clinicaesponses Table 3.Reactivation of EBV after bone marrow transplantation usually leads to a LPD that does not respond well to standard treatment and is usually fatal. As early as 1969, the incidence rate of LPDs in solid organ and bone marrow transplant recipients was very high, between 0.5% and 17% , 80. EBVProgrammed death ligand 1 (PD-L1) is an immunomodulatory molecule expressed by antigen-presenting cells that selectively binds to the PD-1 receptor on T cells to inhibit T cell immune function. Both RS cells of cHL and malignant B cells of PTLD express PD-L1, and this expression is promoted by EBV. Therefore, these diseases share this immune escape mechanism , 36, 84 in vitro and then injected into the recipient, where they can restore cellular immunity after EBV infection and eradicate EBV-infected cells. The most common adverse reaction is graft-versus-host disease (GVHD). Compared with adoptive therapy with monoclonal antibodies, CTLs can actively migrate through the microvascular wall to reach isolated tumour cells and undergo self-expansion. CTLs can kill tumour cells through cytotoxic effectors and have advantages in biological distribution and antitumour activity -matched donors or autologous lymphocytes can be activated and expanded activity . In someactivity , 91. In activity . Subsequout GVHD . The teaout GVHD . In addiout GVHD   can cause B-cell lymphoma and is also found in some T or NK cell lymphoid tumours, such as extranodal NK/T-cell lymphoma (ENKTCL), invasive NK cell leukaemia (ANKL) and chronic active Epstein Barr virus infection (CAEBV). The WHO classification of haematopoietic and lymphoid tumours was revised in 2017 (WHO 2017), and CAEBV is defined as an T cell or NK cell tumour . The infThe prototype of EBV-driven lymphoma is extranodal NK/T cell lymphoma of the nasal type. Due to the high expression level of P-glycoprotein in NK lymphoma cells, chemotherapy, such as CHOP- and doxorubicin-based regimens, is largely ineffective. However, the lack of asparagine synthase makes ENKTCL sensitive to L-asparaginase. DDGP  was recommended as the first-line chemotherapy for NK/T-cell lymphoma in the National Comprehensive Cancer Network (NCCN) guidelines in 2020. Other schemes based on L-asparaginase, such as SMILE , also showed good efficacy; however, this regimen is highly toxic and can even lead to death . DDGP, PEBV+ PTCL-NOS is a highly heterogeneous mature post-thymic T cell tumour. CHOP is the most commonly used first-line treatment for systemic PTCL, but this disease is usually incurable. When EBV-related LPD is pathological grade 3 and the patient has severe systemic symptoms, chemotherapy can be considered to control the disease condition but cannot improve patient prognosis .Numerous studies at home and abroad have proven that allo-HSCT can cure EBV-T/NK-LPD. In 2000, K Kawa et al. first reported the cure of a patient with CAEBV by allogeneic bone marrow transplantation, which also eradicated EBV-infected peripheral T cells and natural killer cells . A serieTo date, several monoclonal antibodies against human CD38 have been successfully developed, such as daratumumab, isatuximab (SAR650984) and MOR202 . Wang L in vitro results /T cell NHL, nasal type, are related to latent type II EBV. Tumour cells can express the weakly immunogenic EBV antigens LMP1, LMP2 and EBNA1. The stimulation of cytotoxic T lymphocytes (CTLs) targeting LMP1 and LMP2 showed efficacy in EBV+ NKTCL. In a clinical trial of LMP-CTLs in 52 EBV-associated lymphomas in the United States, 5 of 11 NKTCL patients received CTLs as consolidation treatment after primary radiotherapy or autologous stem cell transplantation. CR was achieved for 2–6 years, 8 patients survived for at least 2 years, and the longest period of CR was 6 years. In half of the patients, EBV levels could not be detected in plasma during CR . One patReactivation of the EBV lytic cycle can enable cytotoxic antiviral drugs to achieve a specific killing effect on EBV-positive cells. These types of therapy include chemical lytic inducers and nucleoside analogue antiviral prodrugs. Studies have shown that HDAC inhibitors can reactivate the lytic cycle and lead to enhanced apoptosis of NPC and gastric cancer cells –114. HDA125I]2’-fluoro-2’-deoxy-β-D-5-iodouracil-arabinofuranoside, selectively inhibiting the growth of BL xenografts in severe combined immunodeficiency (SCID) mice (in vivo (Proteasome inhibitors have been shown to inhibit cell growth and promote cell death in a variety of cancers. Bortezomib is the first proteasome inhibitor approved by the FDA in 2003 for the treatment of multiple myeloma (MM) and mantle cell lymphoma . The manID) mice . GranatoID) mice . In addiID) mice , 124. BoID) mice . It has  , growth regulators , and oncogenic proteins . In healthy cells, this process is strictly regulated to maintain an appropriate balance between cell growth and apoptosis . StudiesExosomes are small membrane-bound vesicles secreted by cells. These extracellular vesicles (EVs) carry a wide range of molecules and affect intercellular communication, which contributes to the pathogenesis of various diseases and infections , 135. Thin vitro and in vivo using xenotransplantation models. The effects of rituximab, nivolumab, pembrolizumab, daratumumab, bortezomib and CTLs have been confirmed in clinical trials. However, we must appreciate that most of the research results are limited to specific groups. For heterogeneous populations of EBV-LPDs, immunotherapy targets, checkpoint inhibitors, CTLs, small molecule targets and even gene therapy are still elusive. We hope that as the data and science related to these methods mature, they will provide alternative treatments as both monotherapy and combination therapy.In general, there has been great progress in our understanding and treatment of EBV-LPDs in recent years from traditional chemotherapy, changes in immunosuppressants and HSCT to immunotherapy, gene therapy and epigenetic therapy stemming from discoveries of signaling pathways and virus latency and lysis cycles; together, this improved understanding will lead to the development of better treatment options with fewer side effects. Among such potential treatments, proteasome inhibitors, HDAC inhibitors and JAK inhibitors have been tested KL and TY design, analysis and draft the manuscript. MY, ZC: supervision, funding acquisition, writing–review and editing. YZ: methodology, and writing–review and editing. FL: design, supervision, funding acquisition, methodology, project administration, writing–review and editing. All authors contributed to the article and approved the submitted version.This work was financially supported by grants from the National Natural Science Foundation of China , Natural Science Foundation of Jiangxi Province (20192ACB20030), Science and Technology Innovation Base Construction Project of Jiangxi Province .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.


Signature-related lncRNAs may be involved in immune activities in the tumorigenesis and progression of GBM. In summary, the novel IRLncSig shows a promising clinical value in predicting the prognosis and immune landscape of GBM.Emerging evidence shows immune-related long noncoding RNAs (ir-lncRNAs) perform critical roles in tumor progression and prognosis assessment. However, the identification of ir-lncRNAs and their clinical significance in human glioblastoma multiforme (GBM) remain largely unexplored. Here, a designed computational frame based on immune score was used to identify differentially expressed ir-lncRNAs (DEir-lncRNAs) from The Cancer Genome Atlas (TCGA) GBM program. The immune-related lncRNA signature (IRLncSig) composed of prognosis-related DEir-lncRNAs selected by Cox regression analysis and its clinical predictive values were verified, which was further validated by another dataset from the Gene Expression Omnibus database (GEO). Subsequently, the association between IRLncSig and immune cell infiltration, immune checkpoint inhibitor (ICI) biomarkers, O6-methylguanine-DNA methyltransferase (MGMT) gene expression, and biological function were also analyzed. After calculation, five prognosis-related ir-lncRNAs were included in the establishment of IRLncSig. The risk assessment based on IRLncSig indicated that the high-IRLncSig-score group was significantly associated with poor prognosis ( Glioblastoma multiforme (GBM) is one of the most aggressive and deadly malignant solid tumors. It has been reported that the 5-year survival rate of 12,120 newly diagnosed glioblastoma patients in the United States is only 5% , has been widely recognized as an effective treatment strategy for tumors. An emerging study demonstrated that innate immune cells change the TME and gradually weaken human immune surveillance with cytokines during tumor development . With anThe human genome is widely transcribed, but only approximately 2% of expressed transcripts can encode proteins, and the remaining transcripts longer than 200 t are defined as long noncoding RNAs (lncRNAs). Further studies of lncRNAs demonstrated the pathological process of some incurable diseases, especially the occurrence of cancer. Emerging studies have shown that lncRNAs are closely related to tumor immune activities. The lncRNA small nucleolar RNA host gene 1 (SNHG1) can affect the immune escape of breast cancer by regulating the differentiation of Treg cells . By stabIn this study, the GBM patients were defined as immune-score-high (IH) and immune-score-low (IL) groups based on the immune score in The Cancer Genome Atlas (TCGA) GBM cohort. Based on the expression data, the differentially expressed ir-lncRNAs (DEir-lncRNAs) were screened to construct IRLncSig. The prognostic predictive value of the IRLncSig was then estimated among patients with GBM. The correlations between IRLncSig and immune cell infiltration, ICI biomarkers, and O6-methylguanine-DNA methyltransferase (MGMT) gene expression were also analyzed.https://tcga-data.nci.nih.gov/tcga/). After checking the sample processing information, most samples that met the requirements were enrolled in the research. All included transcriptome profiles were annotated by gene transfer format (GTF) files (downloaded from Ensembl (http://asia.ensembl.org)) to distinguish messenger RNAs (mRNAs) and lncRNAs. Immune-related gene (ir-gene) profiles were obtained from the ImmPort database (http://www.immport.org). Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) profiles were downloaded from the ESTIMATE database (https://bioinformatics.mdanderson.org/estimate/). The independent GBM validation set GSE53733  of GBM was obtained from TCGA . The median immune score from ESTIMATE profiles was used to divide all samples into IL and IH groups. The R package DESeq2 was used to identify the DEir-lncRNAs between the two groups. A log fold change (logFC) > 1.0 and false discovery rate (FDR) <0.05 were regarded as the cutoff values.Coexpression analyses were used between ir-genes and transcriptome data to identify ir-lncRNAs . The survival outcome, IRLncSig score, and lncRNA expression patterns were also visualized by R tools (Version: 4.0.3). Univariate and multivariate Cox regression analyses between the IRLncSig score and clinical feature characteristics were then performed to evaluate whether IRLncSig can be used as an independent clinical prognostic predictor. A time-dependent receiver operating characteristic (ROC) curve was used to verify the clinical performance of IRLncSig. All R packages used in this process included survival, survivalROC, pheatmap, and survminer.p values were <0.05. All these procedures were performed by the R ggplot2 package. Next, the differences in immune cell scores between the low-IRLncSig-score and high-IRLncSig-score groups were calculated by Wilcoxon signed-rank analysis. The gpubr R package was used to perform this part.Marker-gene-based approaches (M)  and IRLncSig, the Wilcoxon signed-rank test was used to evaluate the gene expression differences between the high-IRLncSig-score and low-IRLncSig-score groups. The same method was also used to explore the correlation between MGMT gene expression and IRLncSig. The ggstatsplot package was used to visualize the results.The hclust function was used to identify outlier samples by sample clustering for all samples. The soft threshold of the gene expression matrix of the remaining samples was extracted by weighted correlation network analysis (WGCNA) . A scalep < 0.001) , IRLncSig score , multivariate Cox regression analysis: age , IRLncSig score ). The area under the curve (AUC) of the time-dependent ROC curve analysis of the IRLncSig score was 0.696 (1 year), 0.766 (2 years), and 0.705 (3 years) , which could be a potential therapeutic target (Tumor-associated macrophages (TAMs) account for 30%–40% of GBM immune infiltrating cells , 35 and ICIs show good performance in the treatment of several tumors –43. In tTemozolomide (TMZ) is the most widely used alkylating agent in glioblastoma and is cytotoxic to cells by inducing DNA damage . SeveralIn this article, the IRLncSig constructed by five ir-lncRNAs showed a good performance in stratifying GBM patients, which may contribute to the personalized treatment of GBM patients in the future. At the same time, emerging articles have shown the potential of lncRNAs in the diagnosis and treatment of some kinds of cancers, including lung cancer, gastric cancer, colon cancer, and so on –66, thusWith the improvement of technologies based on the CRISPR-Cas system, complex genetic manipulations in human cells have been made possible to treat incurable diseases . MeanwhiRegarding the biological functions of the five lncRNAs included in IRLncSig, the IRLncSig score was used as an independent phenotype to perform correlation analysis with gene modules obtained by scale-free clustering and DynamicTreeCut algorithms to obtain the most associated gene module. The enrichment analysis of the selected gene module showed that the main biological functions were immune receptor activity, MHC class II receptor activity, MHC class II protein complex binding, and IgG binding, which verified that the five included lncRNAs are related to tumor immunity.In this article, the IRLncSig constructed by five prognosis-related ir-lncRNAs was carefully evaluated and verified for its correlation with prognostic outcomes to ensure its clinical predictive value. At the same time, the association between IRLncSig and immune cell infiltration, ICI biomarkers, and MGMT gene expression was also analyzed. Thus, we assumed that the novel IRLncSig shows a promising clinical value in predicting the prognosis and immune landscape of GBM.The study also has some limits. The current literature has limited reports on the ir-lncRNAs involved in constructing the IRLncSig in the research. Because the methodology applied in this study is mainly mathematical means and not molecular biological experiments, the detailed biological functions of these involved ir-lncRNAs are still not well known, so it is necessary to carry out further experimental research on this prognosis-related ir-lncRNAs in the future.The IRLncSig established by ir-lncRNA has a significant relationship with immune cell infiltration, ICI biomarkers, and MGMT gene expression, which shows a promising clinical value in predicting the prognosis and immune landscape of GBM.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Data extraction and data analysis: DS, WZ, DL, SH, YY, HY, YX, and HX. Original draft: DS, WZ, YZ, LA, and HY. Article review and editing: DS, WZ, XS, JZ, and HX. All authors contributed to the article and approved the submitted version.The research was funded by Chongqing Natural Science Foundation (Application number: 2022NSCQ-MSX0963).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.


Assumptions linking poverty with sex, associating poverty with agency, as well as connecting agency with suicide, are widespread. Women are often seen as being affected more by poverty than men. Men are frequently considered to possess more agency than women, and men are also more prone to suicide than women.The research aims to assess if poverty, agency and suicide differences occur across sexual lines. The study will attempt to establish if a poverty-agency-suicide relationship is supported by data, and how the poverty-agency and the agency-suicide relationships are in turn influenced by sex.A cross-sectional survey design was used and interviews were conducted with 3 531 respondents. Chi-squared tests were used to calculate whether differences on poverty, agency and suicide ideation exist across sexual lines. Correlation analysis was implemented to test for the poverty-agency-suicide relationship, and regression analyses were used to test the moderating effects of sex on the poverty-agency and the agency-suicide relationships.Men and women did not differ significantly on levels of poverty, agency, nor suicide ideation. Poverty did relate to agency (a negligible effect), but agency did not have an effect on suicide ideation. Sex did not moderate the poverty-agency nor the agency-suicide relationship.The data do not support established stereotypes nor empirical findings regarding sex differences across the poverty, agency and suicide ideation spectrums. The data also do not support the poverty-agency-suicide relationship and sex does not influence this relationship. Healthcare professionals should be aware that (well-founded) stereotypes do not necessarily materialize in all populations.No significant relationships.