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Cholangiocarcinoma (CCA) is a bile duct malignancy with a dismal prognosis. This study systematically investigated the role of the ribosomal protein S6 (RPS6) gene, which is dependent in CCA. We found that RPS6 upregulation in CCA tissues was correlated with a poor prognosis. Functional investigations have shown that alterations in RPS6 expression, both gain- and loss-of function could affect the proliferation of CCA cells. In xenograft tumor models, RPS6 overexpression enhances tumorigenicity, whereas RPS6 silencing reduces it. Integration analysis using RNA-seq and proteomics elucidated downstream signaling pathways of RPS6 depletion by affecting the cell cycle, especially DNA replication. Immunoprecipitation followed by mass spectrometry has identified numerous spliceosome complex proteins associated with RPS6. Transcriptomic profiling revealed that RPS6 affects numerous alternative splicing (AS) events, and combined with RNA immunoprecipitation sequencing, revealed that minichromosome maintenance complex component 7 (MCM7) binds to RPS6, which regulates its AS and increases oncogenic activity in CCA. Targeting RPS6 with vivo phosphorodiamidate morpholino oligomer (V-PMO) significantly inhibited the growth of CCA cells, patient-derived organoids, and subcutaneous xenograft tumor. Taken together, the data demonstrate that RPS6 is an oncogenic regulator in CCA and that RPS6-V-PMO could be repositioned as a promising strategy for treating CCA.

Abstract. Background:. Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. Methods:. This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results:. The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P

Abstract Background Type 2 diabetes is associated with a variety of complications, including micro- and macrovascular complications, neurological manifestations and poor wound healing. Adhering to a Mediterranean Diet (MED) is generally considered an effective intervention in individuals at risk for type 2 diabetes mellitus (T2DM). However, little is known about its effect with respect to the different specific manifestations of T2DM. This prompted us to explore the effect of MED on the three most significant microvascular complications of T2DM: diabetic retinopathy (DR), diabetic kidney disease (DKD), and vascular diabetic neuropathies (DN). Methods We examined the association between the MED and the incidence of these microvascular complications in a prospective cohort of 33,441 participants with hyperglycemia free of microvascular complications at baseline, identified in the UK Biobank. For each individual, we calculated the Alternate Mediterranean Diet (AMED) score, which yields a semi-continuous measure of the extent to which an individual’s diet can be considered as MED. We used Cox proportional hazard models to analyze hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographics, lifestyle factors, medical histories and cardiovascular risk factors. Results Over a median of 12.3 years of follow-up, 3,392 cases of microvascular complications occurred, including 1,084 cases of diabetic retinopathy (DR), 2,184 cases of diabetic kidney disease (DKD), and 632 cases of diabetic neuropathies (DN), with some patients having 2 or 3 microvascular complications simultaneously. After adjusting for confounders, we observed that higher AMED scores offer protection against DKD among participants with hyperglycemia (comparing the highest AMED scores to the lowest yielded an HR of 0.79 [95% CIs: 0.67, 0.94]). Additionally, the protective effect of AMED against DKD was more evident in the hyperglycemic participants with T2DM (HR, 0.64; 95% CI: 0.50, 0.83). No such effect, however, was seen for DR or DN. Conclusions In this prospective cohort study, we have demonstrated that higher adherence to a MED is associated with a reduced risk of DKD among individuals with hyperglycemia. Our study emphasizes the necessity for continued research focusing on the benefits of the MED. Such efforts including the ongoing clinical trial will offer further insights into the role of MED in the clinical management of DKD.

BackgroundLimited epidemiological evidence exists concerning the impact of healthy dietary patterns on reducing the risk of cholelithiasis. We aimed to examine the association of seven established dietary patterns with subsequent cholelithiasis risk and whether this association was modified by genetic risk.MethodsWe conducted a prospective cohort study from the UK Biobank, including 155,323 participants initially free of cholelithiasis and cholecystectomy. Dietary patterns were assessed using a validated food frequency questionnaire (Oxford WebQ), covering Mediterranean Diet Score (MED), alternate Mediterranean Diet Score(aMED), overall Plant-based Diet Index (PDI), healthy Plant-based Diet Index (hPDI), unhealthy Plant-based Diet Index (uPDI), Healthy Eating Index 2015 (HEI-2015) and EAT-lancet Score. Genetic risk was quantified and stratified by a polygenic risk score (PRS) incorporating 13 known cholelithiasis-associated loci. Cox proportional hazards regression was employed to estimate the association between dietary patterns, PRS, and cholelithiasis incidence, adjusting for potential confounders.ResultsDuring a median follow-up of 13.3 years, 5,056 cases of cholelithiasis were identified. After adjusting for potential confounders, adherence to aMED and HEI-2015 dietary patterns reduced cholelithiasis risk by 10% (HR: 0.90; 95%CI: 0.83–0.98) and 11% (HR: 0.89; 95%CI: 0.82–0.96), respectively. A significant decrease in cholelithiasis risk was observed across PRS quintiles, low PRS was associated with a 16% reduced risk (HR: 0.84; 95%CI: 0.77–0.92). Participants with both high dietary scores and low genetic risk had the lowest cholelithiasis risk, with an HR of 0.76 (95%CI: 0.64–0.91) for aMED and 0.73 (95%CI: 0.61–0.88) for HEI-2015.ConclusionHigher adherence to aMED and HEI-2015 might significantly decrease the risk of cholelithiasis, irrespective of genetic risk. Our results highlighted the potential of diet intervention for cholelithiasis prevention in the general population.

Abstract Proton pump inhibitors (PPIs) are commonly used for gastric acid-related disorders, but their safety profile and risk stratification for high-burden diseases need further investigation. Analyzing over 2 million participants from five prospective cohorts from the US, the UK, and China, we found that PPI use correlated with increased risk of 15 leading global diseases, such as ischemic heart disease, diabetes, respiratory infections, and chronic kidney disease. These associations showed dose-response relationships and consistency across different PPI types. PPI-related absolute risks increased with baseline risks, with approximately 82% of cases occurring in those at the upper 40% of the baseline predicted risk, and only 11.5% of cases occurring in individuals at the lower 50% of the baseline risk. While statistical association does not necessarily imply causation, its potential safety concerns suggest that personalized use of PPIs through risk stratification might guide appropriate decision-making for patients, clinicians, and the public.

Background Early diagnosis of acute gallstone pancreatitis severity (GSP) is challenging in clinical practice. We aimed to investigate the efficacy of CT features and radiomics for the early prediction of acute GSP severity.Methods We retrospectively recruited GSP patients who underwent CT imaging within 48 h of admission from tertiary referral centre. Radiomics and CT features were extracted from CT scans. The clinical and CT features were selected by the random forest algorithm to develop the ML GSP model for the identification of severity of GSP (mild or severe), and its predictive efficacy was compared with radiomics model. The predictive performance was assessed by the area under operating characteristic curve. Calibration curve and decision curve analysis were performed to demonstrate the classification performance and clinical efficacy. Furthermore, we built a web-based open access GSP severity calculator. The study was registered with ClinicalTrials.gov (NCT05498961).Results A total of 301 patients were enrolled. They were randomly assigned into the training (n = 210) and validation (n = 91) cohorts at a ratio of 7:3. The random forest algorithm identified the level of calcium ions, WBC count, urea level, combined cholecystitis, gallbladder wall thickening, gallstones, and hydrothorax as the seven predictive factors for severity of GSP. In the validation cohort, the areas under the curve for the radiomics model and ML GSP model were 0.841 (0.757–0.926) and 0.914 (0.851–0.978), respectively. The calibration plot shows that the ML GSP model has good consistency between the prediction probability and the observation probability. Decision curve analysis showed that the ML GSP model had high clinical utility.Conclusions We built the ML GSP model based on clinical and CT image features and distributed it as a free web-based calculator. Our results indicated that the ML GSP model is useful for predicting the severity of GSP.

Abstract Background Paracetamol induces hepatotoxicity and subsequent liver injury, which may increase the risk of liver cancer, but epidemiological evidence remains unclear. We conducted this study to evaluate the association between paracetamol use and the risk of liver cancer. Methods This prospective study included 464,244 participants free of cancer diagnosis from the UK Biobank. Incident liver cancer was identified through linkage to cancer and death registries and the National Health Service Central Register using the International Classification of Diseases (ICD)-10 codes (C22). An overlap-weighted Cox proportional hazards model was utilized to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of liver cancer associated with paracetamol use. The number needed to harm (NNH) was calculated at 10 years of follow-up. Results During a median of 12.6 years of follow-up, 627 cases of liver cancer were identified. Paracetamol users had a 28% higher risk of liver cancer than nonusers (HR 1.28, 95% CI 1.06–1.54). This association was robust in several sensitivity analyses and subgroup analyses, and the quantitative bias analysis indicated that the result remains sturdy to unmeasured confounding factors (E-value 1.88, lower 95% CI 1.31). The NNH was 1106.4 at the 10 years of follow-up. Conclusion The regular use of paracetamol was associated with a higher risk of liver cancer. Physicians should be cautious when prescribing paracetamol, and it is recommended to assess the potential risk of liver cancer to personalize the use of paracetamol.

Abstract Objective The association between Metabolic Syndrome (MetS), its components, and the risk of osteoarthritis (OA) has been a topic of conflicting evidence in different studies. The aim of this present study is to investigate the association between MetS, its components, and the risk of OA using data from the UK Biobank. Methods A prospective cohort study was conducted in the UK Biobank to assess the risk of osteoarthritis (OA) related to MetS. MetS was defined according to the criteria set by the International Diabetes Federation (IDF). Additionally, lifestyle factors, medications, and the inflammatory marker C-reactive protein (CRP) were included in the model. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). The cumulative risk of OA was analyzed using Kaplan–Meier curves and log-rank tests. To explore potential nonlinear associations between MetS components and OA risk, a restricted cubic splines (RCS) model was employed. In addition, the polygenic risk score (PRS) of OA was calculated to characterize individual genetic risk. Results A total of 45,581 cases of OA were identified among 370,311 participants, with a median follow-up time of 12.48 years. The study found that individuals with MetS had a 15% higher risk of developing OA (HR = 1.15, 95%CI:1.12–1.19). Additionally, central obesity was associated with a 58% increased risk of OA (HR = 1.58, 95%CI:1.5–1.66), while hyperglycemia was linked to a 13% higher risk (HR = 1.13, 95%CI:1.1–1.15). Dyslipidemia, specifically in triglycerides (HR = 1.07, 95%CI:1.05–1.09) and high-density lipoprotein (HR = 1.05, 95%CI:1.02–1.07), was also found to be slightly associated with OA risk. When stratified by PRS, those in the high PRS group had a significantly higher risk of OA compared to those with a low PRS, whereas no interaction was found between MetS and PRS on OA risks. Furthermore, the presence of MetS significantly increased the risk of OA by up to 35% in individuals with elevated CRP levels (HR = 1.35, 95% CI:1.3–1.4). Conclusion MetS and its components have been found to be associated with an increased risk of OA, particularly in individuals with elevated levels of CRP. These findings highlight the significance of managing MetS as a preventive and intervention measure for OA.

Abstract Background Genetic and lifestyle factors both contribute to the pathogenesis of bladder cancer, but the extent to which the increased genetic risk can be mitigated by adhering to a healthy lifestyle remains unclear. We aimed to investigate the association of combined lifestyle factors with bladder cancer risk within genetic risk groups. Methods We conducted a prospective study of 375 998 unrelated participants of European ancestry with genotype and lifestyle data and free of cancer from the UK biobank. We generated a polygenic risk score (PRS) using 16 single nucleotide polymorphisms and a healthy lifestyle score based on body weight, smoking status, physical activity, and diet. Cox models were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of genetic and lifestyle factors on bladder cancer. Results During a median follow-up of 11.8 years, 880 participants developed bladder cancer. Compared with those with low PRS, participants with intermediate and high PRS had a higher risk of bladder cancer (HR 1.29, 95% CI 1.07–1.56; HR 1.63, 95% CI 1.32–2.02, respectively). An optimal lifestyle was associated with an approximately 50% lower risk of bladder cancer than a poor lifestyle across all genetic strata. Participants with a high genetic risk and a poor lifestyle had 3.6-fold elevated risk of bladder cancer compared with those with a low genetic risk and an optimal lifestyle (HR 3.63, 95% CI 2.23 –5.91). Conclusions Adhering to a healthy lifestyle could substantially reduce the bladder cancer risk across all genetic strata, even for high-genetic risk individuals. For all populations, adopting an intermediate lifestyle is more beneficial than a poor one, and adhering to an optimal lifestyle is the ideal effective strategy for bladder cancer prevention.

Abstract Background Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor, and its diagnosis is still a challenge. This study aimed to identify a novel bile marker for CCA diagnosis based on proteomics and establish a diagnostic model with deep learning. Methods A total of 644 subjects (236 CCA and 408 non-CCA) from two independent centers were divided into discovery, cross-validation, and external validation sets for the study. Candidate bile markers were identified by three proteomics data and validated on 635 clinical humoral specimens and 121 tissue specimens. A diagnostic multi-analyte model containing bile and serum biomarkers was established in cross-validation set by deep learning and validated in an independent external cohort. Results The results of proteomics analysis and clinical specimen verification showed that bile clusterin (CLU) was significantly higher in CCA body fluids. Based on 376 subjects in the cross-validation set, ROC analysis indicated that bile CLU had a satisfactory diagnostic power (AUC: 0.852, sensitivity: 73.6%, specificity: 90.1%). Building on bile CLU and 63 serum markers, deep learning established a diagnostic model incorporating seven factors (CLU, CA19-9, IBIL, GGT, LDL-C, TG, and TBA), which showed a high diagnostic utility (AUC: 0.947, sensitivity: 90.3%, specificity: 84.9%). External validation in an independent cohort (n = 259) resulted in a similar accuracy for the detection of CCA. Finally, for the convenience of operation, a user-friendly prediction platform was built online for CCA. Conclusions This is the largest and most comprehensive study combining bile and serum biomarkers to differentiate CCA. This diagnostic model may potentially be used to detect CCA.

Background: Recent studies have shown that bile acids are essential in irritable bowel syndrome (IBS) pathology, and cholecystectomy has direct effects on bile acid metabolism. However, whether cholecystectomy increases the risk of IBS remains unclear. We aimed to investigate the association between cholecystectomy and IBS risk in the UK Biobank (UKB).Methods: This study is a prospective analysis of 413,472 participants who were free of IBS, inflammatory bowel disease, cancer, or common benign digestive tract diseases. We identified incidents of IBS through self-reporting or links to primary healthcare and hospitalization data. We evaluated hazard ratios (HRs) adjusted for sociodemographic characteristics, health behaviours, comorbidities, and medications.Results: During a median follow-up period of 12.7 years, we observed 15,503 new cases of IBS. Participants with a history of cholecystectomy had a 46% higher risk of IBS than those without (HR = 1.46, 95% CI: 1.32–1.60), and further subtype analysis showed that the risk of IBS with diarrhoea was significantly higher than the risk of IBS without diarrhoea (HR = 1.71, 95% CI: 1.30–2.25 vs. HR = 1.42, 95% CI: 1.28–1.58). The overall covariate-adjusted HRs for IBS were similar between the group with both cholecystectomy and gallstones (HR = 1.45, 95% CI: 1.32–1.58) and the group with cholecystectomy without gallstones (HR = 1.50, 95% CI: 1.36–1.67) when the group without both cholecystectomy and gallstones was used as a reference. The overall covariate-adjusted HR was not significantly different in the group without cholecystectomy with gallstones (HR = 1.18, 95% CI: 0.95–1.47). The positive association of cholecystectomy with IBS risk did not change when stratifying the data based on age, sex, BMI, smoking, alcohol consumption, healthy diet, quality sleep, physical activity, type 2 diabetes, hypertension, hyperlipidaemia, mental illness, NSAID intake, or acid inhibitor intake. Sensitivity analyses, including propensity score matching analysis and lagging the exposure for two or four years, indicated that the effects were robust.Conclusion: Cholecystectomy was associated with a higher risk of IBS, especially IBS with diarrhoea. Additional prospective randomized controlled and experimental studies are warranted to further validate the association and to explore the relevant biological mechanisms.

BackgroundGut microbiome dysbiosis has been implicated in various gastrointestinal and extra-gastrointestinal diseases, but evidence on the efficacy and safety of fecal microbiota transplantation (FMT) for therapeutic indications remains unclear.MethodsThe gutMDisorder database was used to summarize the associations between gut microbiome dysbiosis and diseases. We performed an umbrella review of published meta-analyses to determine the evidence synthesis on the efficacy and safety of FMT in treating various diseases. Our study was registered in PROSPERO (CRD42022301226).ResultsGut microbiome dysbiosis was associated with 117 gastrointestinal and extra-gastrointestinal. Colorectal cancer was associated with 92 dysbiosis. Dysbiosis involving Firmicutes (phylum) was associated with 34 diseases. We identified 62 published meta-analyses of FMT. FMT was found to be effective for 13 diseases, with a 95.56% cure rate (95% CI: 93.88–97.05%) for recurrent Chloridoids difficile infection (rCDI). Evidence was high quality for rCDI and moderate to high quality for ulcerative colitis and Crohn’s disease but low to very low quality for other diseases.ConclusionGut microbiome dysbiosis may be implicated in numerous diseases. Substantial evidence suggests FMT improves clinical outcomes for certain indications, but evidence quality varies greatly depending on the specific indication, route of administration, frequency of instillation, fecal preparation, and donor type. This variability should inform clinical, policy, and implementation decisions regarding FMT.

Summary: Background: Metformin shows beneficial effects on cardiometabolic health in diabetic individuals. However, the beneficial effects in the general population, especially in non-diabetic individuals are unclear. We aim to estimate the effects of perturbation of seven metformin targets on cardiometabolic health using Mendelian randomization (MR). Methods: Genetic variants close to metformin-targeted genes associated with expression of the corresponding genes and glycated haemoglobin (HbA1c) level were used to proxy therapeutic effects of seven metformin-related drug targets. Eight cardiometabolic phenotypes under metformin trials were selected as outcomes (average N = 466,947). MR estimates representing the weighted average effects of the seven effects of metformin targets on the eight outcomes were generated. One-sample MR was applied to estimate the averaged and target-specific effects in 338,425 non-diabetic individuals in UK Biobank. Findings: Genetically proxied averaged effects of five metformin targets, equivalent to a 0.62% reduction of HbA1c level, was associated with 37.8% lower risk of coronary artery disease (CAD) (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.46–0.84), lower levels of body mass index (BMI) (β = −0.22, 95% CI = −0.35 to −0.09), systolic blood pressure (SBP) (β = −0.19, 95% CI = −0.28 to −0.09) and diastolic blood pressure (DBP) levels (β = −0.29, 95% CI = −0.39 to −0.19). One-sample MR suggested that the seven metformin targets showed averaged and target-specific beneficial effects on BMI, SBP and DBP in non-diabetic individuals. Interpretation: This study showed that perturbation of seven metformin targets has beneficial effects on BMI and blood pressure in non-diabetic individuals. Clinical trials are needed to investigate whether similar effects can be achieved with metformin medications. Funding: Funding information is provided in the Acknowledgements.

IntroductionNon-communicable diseases (NCDs) represent the leading cause of mortality and disability worldwide. Robust evidence has demonstrated that modifiable lifestyle factors such as unhealthy diet, smoking, alcohol consumption and physical inactivity are the primary causes of NCDs. Although a series of guidelines for the management of NCDs have been published in China, these guidelines mainly focus on clinical practice targeting clinicians rather than the general population, and the evidence for NCD prevention based on modifiable lifestyle factors has been disorganized. Therefore, comprehensive and evidence-based guidance for the risk management of major NCDs for the general Chinese population is urgently needed. To achieve this overarching aim, we plan to develop a series of expert consensuses covering 15 major NCDs on health risk management for the general Chinese population. The objectives of these consensuses are (1) to identify and recommend suitable risk assessment methods for the Chinese population; and (2) to make recommendations for the prevention of major NCDs by integrating the current best evidence and experts’ opinions.Methods and analysisFor each expert consensus, we will establish a consensus working group comprising 40–50 members. Consensus questions will be formulated by integrating literature reviews, expert opinions, and an online survey. Systematic reviews will be considered as the primary evidence sources. We will conduct new systematic reviews if there are no eligible systematic reviews, the methodological quality is low, or the existing systematic reviews have been published for more than 3 years. We will evaluate the quality of evidence and make recommendations according to the GRADE approach. The consensuses will be reported according to the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has induced a significant global concern on mental health. However few studies have measured the ability of individuals to “withstand setbacks, adapt positively, and bounce back from adversity” on a global scale. We aimed to examine the level of resilience, its determinants, and its association with maladaptive coping behaviours during the pandemic. Methods The Association of Pacific Rim Universities (APRU) conducted a global survey involving 26 countries by online, self-administered questionnaire (October 2020-December 2021). It was piloted-tested and validated by an expert panel of epidemiologists and primary care professionals. We collected data on socio-demographics, socioeconomic status, clinical information, lifestyle habits, and resilience levels measured by the Brief Resilience Scale (BRS) among adults aged ≥ 18 years. We examined factors associated with low resilience level, and evaluated whether low resilience was correlated with engagement of maladaptive coping behaviours. Results From 1,762 surveys, the prevalence of low resilience level (BRS score 1.00–2.99) was 36.4% (America/Europe) and 24.1% (Asia Pacific). Young age (18–29 years; adjusted odds ratio [aOR] = 0.31–0.58 in older age groups), female gender (aOR = 1.72, 95% C.I. = 1.34–2.20), poorer financial situation in the past 6 months (aOR = 2.32, 95% C.I. = 1.62–3.34), the presence of one (aOR = 1.56, 95% C.I. = 1.19–2.04) and more than two (aOR = 2.32, 95% C.I. = 1.59–3.39) medical conditions were associated with low resilience level. Individuals with low resilience were significantly more likely to consume substantially more alcohol than usual (aOR = 3.84, 95% C.I. = 1.62–9.08), take considerably more drugs (aOR = 12.1, 95% C.I. = 2.72–54.3), buy supplements believed to be good for treating COVID-19 (aOR = 3.34, 95% C.I. = 1.56–7.16), exercise less than before the pandemic (aOR = 1.76, 95% C.I. = 1.09–2.85), consume more unhealthy food than before the pandemic (aOR = 2.84, 95% C.I. = 1.72–4.67), self-isolate to stay away from others to avoid infection (aOR = 1.83, 95% C.I. = 1.09–3.08), have an excessive urge to disinfect hands for avoidance of disease (aOR = 3.08, 95% C.I. = 1.90–4.99) and transmission (aOR = 2.54, 95% C.I. = 1.57–4.10). Conclusions We found an association between low resilience and maladaptive coping behaviours in the COVID-19 pandemic. The risk factors identified for low resilience in this study were also conditions known to be related to globalization-related economic and social inequalities. Our findings could inform design of population-based, resilience-enhancing intervention programmes.

Fouling is a continuous challenge for the effective application of membranes in oily wastewater treatment. Here, the authors present a hydrophobic chain engineering strategy to regulate the surface of graphene oxide-based membranes at a molecular scale for increased antifouling even at high permeance.

Proton pump inhibitors (PPIs) are the most used acid-inhibitory drugs, with a wide range of applications in the treatment of various digestive diseases. However, recently, there has been a growing number of digestive complications linked to PPIs, and several studies have indicated that the intestinal flora play an important role in these complications. Therefore, developing a greater understanding of the role of the gut microbiota in PPI-related digestive diseases is essential. Here, we summarize the current research on the correlation between PPI-related digestive disorders and intestinal flora and establish the altered strains and possible pathogenic mechanisms of the different diseases. We aimed to provide a theoretical basis and reference for the future treatment and prevention of PPI-related digestive complications based on the regulation of the intestinal microbiota.

BackgroundMetabolic syndrome has been linked to an increased risk of colorectal cancer (CRC) incidence and mortality, but whether adopting a healthy lifestyle could attenuate the risk of CRC conferred by metabolic syndrome remains unclear. The aim of the study is to investigate the individual and joint effects of modifiable healthy lifestyle and metabolic health status on CRC incidence and mortality in the UK population.MethodsThis prospective study included 328,236 individuals from the UK Biobank. An overall metabolic health status was assessed at baseline and categorized based on the presence or absence of metabolic syndrome. We estimated the association of the healthy lifestyle score (derived from 4 modifiable behaviors: smoking, alcohol consumption, diet, physical activity and categorized into “favorable,” “intermediate”, and “unfavorable”) with CRC incidence and mortality, stratified by metabolic health status.ResultsDuring a median follow-up of 12.5 years, 3,852 CRC incidences and 1,076 deaths from CRC were newly identified. The risk of incident CRC and its mortality increased with the number of abnormal metabolic factors and decreased with healthy lifestyle score (P trend = 0.000). MetS was associated with greater CRC incidence (HR = 1.24, 95% CI: 1.16 – 1.33) and mortality (HR = 1.24, 95% CI: 1.08 – 1.41) when compared with those without MetS. An unfavorable lifestyle was associated with an increased risk (HR = 1.25, 95% CI: 1.15 – 1.36) and mortality (HR = 1.36, 95% CI: 1.16 – 1.59) of CRC across all metabolic health status. Participants adopting an unfavorable lifestyle with MetS had a higher risk (HR = 1.56, 95% CI: 1.38 – 1.76) and mortality (HR = 1.75, 95% CI: 1.40 – 2.20) than those adopting a favorable healthy lifestyle without MetS.ConclusionThis study indicated that adherence to a healthy lifestyle could substantially reduce the burden of CRC regardless of the metabolic status. Behavioral lifestyle changes should be encouraged for CRC prevention even in participants with MetS.

BackgroundObesity is a common and highly convincing risk factor for many cancers, including liver cancer. Sex disparities in the body composition and regulatory mechanisms involved in energy homeostasis may contribute to the difference in the incidence of cancer. However, evidence on the gender-specific association between body composition and liver cancer incidence is limited. We performed this study to investigate the linear and non-linear associations of body composition with liver cancer risk by gender.Materials and methodsThis prospective analysis included 4,75,659 participants free of cancer, based on the UK Biobank. We used Cox proportional hazard models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for potential confounders. Restricted cubic spline was performed to investigate the potential non-linear associations.ResultsDuring a median follow-up, 275 cases (174 male patients and 101 female patients) of liver cancer were identified. Male patients in the highest body fat percentage group are more likely to develop liver cancer (HR = 1.89, 95% CI: 1.17–3.03) compared with those in the lowest group. The one-unit increase of whole-body fat mass, arm fat mass, and trunk fat mass was associated with 1.03-, 1.14-, and 1.05-fold increased risk of liver cancer in male subjects, respectively. U-shaped associations of body composition with liver cancer risk were observed in the female subjects. Both high and low levels of whole-body fat-free mass, particularly in the arm and trunk, were associated with an increased risk of liver cancer.ConclusionThis study found a gender-specific association between body composition and liver cancer risk and provided evidence for individualized weight management for the prevention of liver cancer.

Summary: Background: Mechanical lithotripsy produces stone fragments that are not easily detected by cholangiography and is a potential cause of recurrence of common bile duct stones (CBDS). This study aims to clarify whether 100 ml saline irrigation after mechanical lithotripsy reduces the recurrent rate of CBDS. Methods: In this randomized controlled trial performed at the Surgical Endoscopy Center, the First Hospital of Lanzhou University between May 10, 2019, and Dec 31, 2020, patients undergoing endoscopic mechanical lithotripsy were randomly assigned to receive saline irrigation (study group) or no irrigation (control group). The saline irrigation was given 100 ml saline pulse irrigation after cholangiography showed no residual stones. Patients were followed up for at least 24 months after endoscopic stone removal to assess the recurrence of CBDS. This study was registered with ClinicalTrials.gov (NCT03937037). Findings: During the median follow-up period of 35.6 months (interquartile range, 26.0–40.7), 43 of the 180 patients had stone recurrence (24%). The frequency of recurrence of CBD stones was 12.22% in the saline irrigation group and 35.56% in the control group, with a difference of 23.33% between the two groups (95% confidence interval [CI], 11.35%–35.32%, p

Covalent organic frameworks (COF) hold great promise in filtration and separation but combining facile processing, high crystallinity and high separation performance remains challenging. Here, the authors demonstrate that heterocrystalline COF membranes in which high-crystalline regions are tightly linked by low-crystalline regions can improve molecular sieving properties at high solvent flux.

Abstract Background Improving health-related quality of life (HRQOL) is becoming a major focus of old age care and social policy. Researchers have been increasingly examining subjective social status (SSS), one’s self-perceived social position, as a predictor of various health conditions. SSS encompasses not only concrete socio-economic (SES) factors but also intangible aspects of status. This study’s main objective was to examine the association between SSS and long-term change in HRQOL in older Chinese adults. Methods A longitudinal Hong Kong study recruited 2934 community-dwelling adults (age > 65 years). Participants completed SF-12 physical health (PCS) and mental health (MCS) HRQOL scales. This study analyzed baseline SSS-Society (self-perceived social status within Hong Kong) and SSS-Community (self-perceived status within one’s own social network) as predictors of long-term HRQOL decline. After stratifying for sex, multiple-linear-regression was performed on 4-year follow-up SF-12 PCS and MCS scores after adjusting for baseline SF-12 scores, traditional SES indicators, demographic variables, clinical conditions, and lifestyle variables. Results In the multivariable analyses, lower SSS-Society was associated with declines in MCS in males (βstandardized = 0.08, p = 0.001) and declines in PCS (βstandardized = 0.07, p = 0.006) and MCS (βstandardized = 0.12, p

Abstract Background For patients taking esophagogastroduodenoscopy (EGD), sedation should ideally be used individually based on patients’ comfort and tolerance level. However, currently there is no valid predictive tool. We undertook this study to develop and temporally validate a self-assessment tool for predicting discomfort and tolerance in Chinese patients undergoing EGD. Methods We recruited 1522 patients undergoing routine diagnostic EGD without sedation. We collected candidate predictor variables before endoscopy and evaluated discomfort and tolerance with a 5-point visual analogue scale after the procedure. We developed logistic regression predictive models based on the first 2/3 of participants, and evaluated the calibration and discrimination of the models in the later 1/3 of patients. Results 30.2% and 23.0% participants reported severe discomfort or poor tolerance to EGD respectively. The predictive factors in the model for discomfort included sex, education, expected level of discomfort, and anxiety before endoscopy. The model for tolerance included income, expected level of discomfort, and anxiety before endoscopy. In the validation population, the established models showed a moderate discriminative ability with a c-index of 0.74 for discomfort and 0.78 for tolerance. Hosmer–Lemeshow test suggested the models had fine calibration ability (discomfort: P = 0.37, tolerance: P = 0.41). Conclusions Equations for predicting discomfort and tolerance in Chinese patients undergoing EGD demonstrated moderate discrimination and variable calibration. Further studies are still required to validate these tools in other population. Trial registration Chinese Clinical Trial Registry (ChiCTR1800020236).

Covalent organic framework (COF) membranes are important in low energy and cost-effective molecular separations but most COF membranes are assembled via a one-step procedure by concurrent polymerization and crystallization which compromises the ordered structure. Here, the authors propose a two-step phase switching strategy for assembling compact and highly crystalline COF membranes decoupling the polymerization and the crystallization process.

Introduction: In addition to lipid-lowering effects, statins might modulate the gut microbiome and alleviate systematic inflammation, which in turn, may have a protective effect against irritable bowel syndrome (IBS). The aim of our study was to evaluate the gender-specific association between statin exposure and the risk of IBS.Method: We undertook a prospective analysis based on the United Kingdom Biobank, a large ongoing cohort including 477,293 participants aged 37–73 years. We included participants based on information on their personal statin use and also those free of IBS and cancer at the baseline. We evaluated the gender-specific hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demographic factors, lifestyle factors, comorbidities, and statin indications.Result: A total of 438,805 participants (206,499 males and 232,306 females) were included in the analysis. Among male participants, the regular use of statins was associated with a decreased risk of IBS (HR: 0.77; 95% CI: 0.61–0.97). This association persists across multiple sensitivity and subgroup analyses and did not show clear evidence of variance among the major types of statins. We did not find sufficient evidence of the association between the statin use and IBS risk in females (HR: 0.98; 95% CI: 0.82–1.16).Conclusion: Our study found that the regular use of statins was associated with a decreased risk of IBS in male participants. Further studies are required to confirm the beneficial effect of statins.

Background Men who have sex with men (MSM), a population bearing the greatest HIV burden in many countries, may also be vulnerable to COVID-19. COVID-19 vaccines are essential to containing the pandemic. However, vaccine hesitancy may compromise vaccine coverage. We aimed to understand the uptake of COVID-19 vaccine and factors associated with COVID-19 vaccine hesitancy among HIV-infected MSM in mainland China. Methods A cross-sectional online survey among HIV-infected MSM was conducted between 13 and 21 February 2021 in mainland China. Variables including demographics, mental health status, HIV characteristics, and knowledge of and attitudes toward COVID-19 pandemic and COVID-19 vaccine were collected. Chi-square tests and multivariable logistic regression were used to analyze factors associated with COVID-19 vaccine hesitancy. Results A total of 1295 participants were included. The median age was 29.3 years (interquartile range [IQR] 25.2–34.0 years). The uptake of COVID-19 vaccine was 8.7%. Two main reasons for receiving vaccines were “regarded vaccination as self-health protection” (67.3%) and “trust in domestic medical technology” (67.3%). Among participants who did not initiate vaccination, concern about side effects (46.4%) and disclosure of HIV infection (38.6%) were top two reasons, and 47.2% had higher vaccine hesitancy. Men who had with high antiretroviral therapy (ART) adherence (adjusted odds ratio [aOR] 0.53, 95% confidence interval [CI] 0.35–0.80), often (0.26, 0.17–0.40) or sometimes (0.46, 0.31–0.67) paid attention to information about the COVID-19 vaccine, preferred domestic vaccines (0.37, 0.24–0.59), thought the pandemic had moderate (0.58, 0.38–0.90) and moderately severe or severe impact (0.54, 0.38–0.78) on immunity, who were waiting for vaccination programs organized at workplace (0.60, 0.44–0.81) and who were unaware of where to get COVID-19 vaccine (0.61, 0.45–0.82) had lower degree of COVID-19 vaccine hesitancy. Men who were concerned about the efficacy (1.72, 1.16–2.54) and side effects (2.44, 1.78–3.35) had higher degree of COVID-19 vaccine hesitancy. Conclusion COVID-19 vaccine uptake among HIV-infected MSM is still suboptimal. Understanding influencing factors of vaccine hesitancy among this group and making tailored measures to alleviate hesitancy would help improve the coverage of COVID-19 vaccination in this population.

Abstract Background Although randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified population groups at high net risk. Methods This is a prospective analysis of 492,479 participants free of stroke from the UK biobank. Incident stroke was identified through linkage to hospital admission and death registries using the International Classification of Diseases (ICD)-10 codes (I60, I61, I63, and I64). We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, prevalent comorbidities, concomitant use of medications, and indications of PPIs. We assessed the risk differences (RDs) according to the baseline Framingham Stroke Risk Score. In the meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (from 1988 to 1 June 2020) for randomized trials comparing PPIs with other interventions, placebo, or no treatment on stroke risk. Results were combined using a fix-effect meta-analysis (Mantel-Haenszel method). Results We documented 5182 incident strokes over 3,935,030 person-years of follow-up. Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27). The estimated effect was similar to our meta-analysis of nine RCTs (case/participants 371/26,642; RR 1.22, 95% CI 1.00 to 1.50; quality of evidence: moderate). The absolute effect of PPI use on stroke increased with the baseline Framingham Stroke Risk Score, with an RD of 1.34‰, 3.32‰, 4.83‰, and 6.28‰ over 5 years for the lowest, quartile 2, quartile 3, and the highest quartile, respectively. Conclusions Regular use of PPIs was associated with an increased risk of stroke, with a higher absolute risk observed in individuals with high baseline stroke risk. Physicians should therefore exercise caution when prescribing PPIs. An assessment of the underlying stoke risk is recommended for individualized use of PPIs.

Abstract Background & Aims Little is known on the gender-specific effect and potential role of non-linear associations between metabolic syndrome (MetS) components and liver cancer risk. We evaluated these associations based on the UK Biobank cohort. Methods We included 474,929 individuals without previous cancer based on the UK Biobank cohort. Gender-specific hazard ratios (HRs) and 95% confidence interval (CIs) were calculated by Cox proportional hazards regression, adjusting for potential confounders. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method. Results Over a median follow-up of 6.6 years, we observed 276 cases of liver cancer (175 men, 101 women). MetS [HR 1.48, 95% CI 1.27–1.72] and central obesity [HR 1.65, 95% CI 1.18–2.31] were associated with higher risk of liver cancer in men but not in women. Participants with hyperglycaemia has higher risk of liver cancer. High waist circumference and blood glucose were dose-dependently associated with increased liver cancer risk in both genders. For high density lipoprotein (HDL) cholesterol (both genders) and blood pressure (women), U-shaped associations were observed. Low HDL cholesterol ( 1.52 mmol/L) were associated with increased liver cancer risk. Conclusions MetS components showed gender-specific linear or U- shaped associations with the risk of liver cancer. Our study might provide evidence for individualized management of MetS for preventing liver cancer.

Abstract Background Oxaliplatin is one of the most commonly used chemotherapeutic agent for the treatment of various cancers, including gastric cancer. It has, however, a narrow therapeutic index due to its toxicity and the occurrence of drug resistance. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect and reduce the toxicity of oxaliplatin. In our previous study, we demonstrated that ethaselen (BBSKE), an inhibitor of thioredoxin reductase, effectively inhibited the growth of gastric cancer cells and promoted apoptosis in vitro. In the present study, we investigated whether BBSKE can potentiate the anti-tumor effect of oxaliplatin in gastric cancer in vivo and vitro. Methods Cellular apoptosis and ROS levels were analyzed by flow cytometry. Thioredoxin reductase 1 (TrxR1) activity in gastric cancer cells, organoid and tumor tissues was determined by using the endpoint insulin reduction assay. Western blot was used to analyze the expressions of the indicated proteins. Nude mice xenograft models were used to test the effects of BBSKE and oxaliplatin combinations on gastric cancer cell growth in vivo. In addition, we also used the combined treatment of BBSKE and oxaliplatin in three cases of gastric cancer Patient-Derived organoid (GC-PDO) to detect the anti-tumor effect. Results We found that BBSKE significantly enhanced oxaliplatin-induced growth inhibition in gastric cancer cells by inhibiting TrxR1 activity. Because of the inhibition of TrxR1 activity, BBSKE synergized with oxaliplatin to enhance the production of ROS and activate p38 and JNK signaling pathways which eventually induced apoptosis of gastric cancer cells. In vivo, we also found that BBSKE synergized with oxaliplatin to suppress the gastric cancer tumor growth in xenograft nude mice model, accompanied by the reduced TrxR1 activity. Remarkably, we found that BBSKE attenuated body weight loss evoked by oxaliplatin treatment. We also used three cases of GC-PDO and found that the combined treatment of BBSKE and oxaliplatin dramatically inhibited the growth and viability of GC-PDO with increased ROS level, decreased TrxR1 activity and enhanced apoptosis. Conclusions This study elucidates the underlying mechanisms of synergistic effect of BBSKE and oxaliplatin, and suggests that the combined treatment has potential value in gastric cancer therapy.

BackgroundMetabolic syndrome (MetS) and its components have been shown as risk factors for several solid cancers. However, current epidemiological evidence about the relevance of MetS and bladder cancer risk was limited.MethodsWe conducted a prospective cohort study of 476,986 participants with undiagnosed bladder cancer based on the UK Biobank. MetS was defined as the presence of at least three of the five selected indicators: hypertension, central obesity, raised triglyceride, reduced HDL-cholesterol, and raised fasting plasma glucose. Bladder cancer has been identified through contact with the British Cancer Registry (median follow-up time: 6.6 years). We assessed hazard ratio (HR) and 95% confidence interval (CI) through Cox proportional hazard regression after adjusting for demographic and lifestyle factors. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method.ResultsDuring a follow-up of 3,112,566 person-years, 487 cases of bladder cancer were ascertained. MetS (HR = 1.32, 95% CI = 1.08–1.61), central obesity (HR = 1.39, 95% CI = 1.15–1.68), dyslipidemia for HDL cholesterol (HR = 1.31, 95% CI = 1.04–1.66), and hyperglycemia (HR = 1.44, 95% CI = 1.16–1.79) were associated with elevated risk of bladder cancer. Bladder cancer risk increased with the number of MetS components. In stratified analyses, MetS showed similar effects in bladder cancer independently with sex, age, cigarette and alcohol use, physical activity, and dietary factors. Higher waist circumference, BMI, fasting blood glucose, and glycosylated hemoglobin were independently associated with increased risk of bladder cancer, with no evidence against non-linearity.ConclusionMetS might be an independent risk factor for bladder cancer. Our findings highlighted the importance of individualized management of MetS components for preventing bladder cancer.

Abstract Background There are limited evidences clarifying the impact of metabolic syndrome (MS) and its components on head and neck cancer (HNC) incidence risk. We explored the correlation between MS, MS components, and the combined effects of MS and C-reactive protein (CRP) and HNC risk. Methods This is a prospective analysis of 474,929 participants from the UK Biobank cohort. Cox proportional hazard regression was utilized to assess the hazard ratio (HR) and 95% confidence interval (CI) and to explore the non-linear correlation between an individual MS component and HNC risk. Results Individuals with MS (HR, 1.05; 95%CI, 0.90–1.22) had no higher HNC risk than those without MS. More MS components showed no higher HNC risk. Nevertheless, hyperglycemia (HR, 1.22; 95%CI, 1.02–1.45) was independently correlated with elevated HNC risk. In a non-linear manner, waist circumference and high-density lipoprotein cholesterol (HDL-C) showed a U-shaped association with HNC risk. Further, piecewise linear model analysis indicated that higher male waist circumference, female waist circumference (≥93.16 cm), blood glucose (≥4.70 mmol/L) and male HDL-C (≥1.26mmo/L), and lower male HDL-C (

Summary: Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an established treatment for common bile duct (CBD) stones. Post- ERCP cholecystitis (PEC) is a known complication of such procedure and there are no effective models and clinical applicable tools for PEC prediction. Methods: A random forest (RF) machine learning model was developed to predict PEC. Eligible patients at The First Hospital of Lanzhou University in China with common bile duct (CBD) stones and gallbladders in-situ were enrolled from 2010 to 2019. Logistic regression analysis was used to compare the predictive discrimination and accuracy values based on receiver operation characteristics (ROC) curve and decision and clinical impact curve. The RF model was further validated by another 117 patients. This study was registered with ClinicalTrials.gov, NCT04234126. Findings: A total of 1117 patients were enrolled (90 PEC, 8.06%) to build the predictive model for PEC. The RF method identified white blood cell (WBC) count, endoscopic papillary balloon dilatation (EPBD), increase in WBC, residual CBD stones after ERCP, serum amylase levels, and mechanical lithotripsy as the top six predictive factors and has a sensitivity of 0.822, specificity of 0.853 and accuracy of 0.855, with the area under curve (AUC) value of 0.890. A separate logistic regression prediction model was built with sensitivity, specificity, and AUC of 0.811, 0.791, and 0.864, respectively. An additional 117 patients (11 PEC, 9.40%) were used to validate the RF model, with an AUC of 0.889 compared to an AUC of 0.884 with the logistic regression model. Interpretation: The results suggest that the proposed RF model based on the top six PEC risk factors could be a promising tool to predict the occurrence of PEC. Funding: This work was supported by National Natural Science Foundation of China (8187103130; 32160255); Gansu Competitive Foundation Projects for Technology Development and Innovation (1602FKDA001); Gansu Province Science and Technology Planning Project (20YF8WA085); Science and Technology Planning Project of Chengguan District in Lanzhou (2020JSCX0043). The Foundation of The First Hospital of Lanzhou University (ldyyyn-2018-16).

Background: Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis–related complications has been recognized during recent years. This article aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis–related complications. Methods: Hepatobiliary Study Group of the Chinese Society of Gastroenterology of the Chinese Medical Association and Hepatology Committee of the Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts’ clinical experiences. Results: Overall, 10 major guidance statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. Conclusion: The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis–related complications.

Background This study aimed to evaluate the updated burden and temporal trends of cancer incidence and mortality in Asian countries. Methodology The data used in this study were retrieved from the Global Cancer Observatory, Cancer Incidence in Five Continents volumes I-XI, and the World Health Organization mortality database. These data were used to calculate the Average Annual Percentage Change (AAPC), with a 95% confidence interval (CI) by joinpoint regression analysis to determine the epidemiological trend in the past decade. Results In 2020, the cancer incidence in Asia was 169.1 per 1 00 000, accounting for 49.3% of the global cancer incidence. The most common cancers included lung (13.8%), breast (10.8%) and colorectal (10.6%) cancers. Its mortality was 101.6 per 1 00 000 (58.3% of the global cancer death) with lung (19.2%), liver (10.5%) and stomach (9.9%) cancers being the most common causes of cancer death. The cancer incidence had been increasing in female population, with Korea (AAPC = 5.73, 95% CI [5.30, 6.17], P < .001), Japan (AAPC = 2.67, 95% CI [2.12, 3.23], P < .001) and Kuwait (AAPC = 2.08, 95% CI [.49, 3.69], P = .016) showing the most significant increases in the past decade. The incidence increase was also observed among population aged

Coronavirus Disease 2019 (COVID-19) vaccination together with good compliance with personal preventive measures may help eradicate the ongoing pandemic. This observational prospective cohort study investigated the changes in compliance with personal preventive measures, depressive symptoms, and sleep quality among factory workers within a 3-month follow-up period. A total of 663 workers were recruited by a stratified multi-stage cluster sampling in March 2020, and all of them completed a follow-up survey three months later. Multilevel logistic and linear regression models (level 1: factories; level 2: individual participants) were fitted. A significant decline was observed in consistent facemask wearing in workplace (from 98.0 to 90.3%, P < 0.001) and in other public spaces (from 97.1 to 94.4%, P = 0.02), sanitizing hands (from 70.9 to 48.0%, P < 0.001), household disinfection (from 47.7 to 37.9%, P < 0.001) and probable depression (from 14.9 to 1.5%, P < 0.001) over the follow-up period. A significant improvement in avoiding crowded places (from 69.8 to 77.4%, P = 0.002) and sleep quality (proportion of participants reporting poor sleep quality dropped from 3.9 to 1.2%, P = 0.002) was also observed. Efforts are needed to maintain compliance with personal preventive measures during the pandemic. Mental health problems were uncommon and likely to be one-off among Chinese factory workers.

Background: Gastric acid suppressants have a major impact on gut microbiome which in turn, may increase the risk of cholelithiasis, but epidemiological evidence remains unclear. We undertook this research to evaluate the association between regular use of proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) with risk of cholelithiasis.Methods: Prospective cohort study included 477,293 UK residents aged 37–73 years from the UK Biobank. We included the participants reported PPI or H2RA use, and were free of cholelithiasis or cancer. We evaluated hazard ratios (HRs) of regular use of PPIs or H2RAs and risk of cholelithiasis adjusting for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications, and clinical indications.Results: We identified 12,870 cases of cholelithiasis over a median follow-up of 8.1 years. Regular use of PPIs (HR 1.22 95% CI 1.16–1.29) or H2RAs (HR 1.16, 95% CI 1.05–1.28) was associated with an increased risk of cholelithiasis after confounding adjustment. There were no major differences among individual PPIs/H2RAs. The absolute risk of PPI-associated cholelithiasis was increased with the baseline predicted risk evaluated by known environmental and genetic risk factors (Risk differences in the lowest vs. the highest quartile: 1.37 vs. 4.29 per 1,000 person-years).Conclusion: Regular use of PPIs and H2RAs was associated with increased risk of cholelithiasis. Future prospective studies are required to confirm whether the observed associations are casual.

Ultrathin membranes have demonstrated great promise for water purification technologies owing to their high permeance. Here the authors fabricate sub-10 nm, defect-free, robust membranes for dye remediation from water through the coordination-driven assembly of metal-organophosphates.

Summary: Interfacial polymerization (IP) is a platform technology for ultrathin membranes. However, most efforts in regulating the IP process have been focused on short-range H-bond interaction, often leading to low-permselective membranes. Herein, we report an electrostatic-modulated interfacial polymerization (eIP) via supercharged phosphate-rich substrates toward ultra-permselective polyamide membranes. Phytate, a natural strongly charged organophosphate, confers high-density long-range electrostatic attraction to aqueous monomers and affords tunable charge density by flexible metal-organophosphate coordination. The electrostatic attraction spatially enriches amine monomers and temporally decelerates their diffusion into organic phase to be polymerized with acyl chloride monomers, triggering membrane sealing and inhibiting membrane growth, thus generating polyamide membranes with reduced thickness and enhanced cross-linking. The optimized nearly 10-nm-thick and highly cross-linked polyamide membrane displays superior water permeance and ionic selectivity. This eIP approach is applicable to the majority of conventional IP processes and can be extended to fabricate a variety of advanced membranes from polymers, supermolecules, and organic framework materials.

Objectives: Maternal smoking causes fetal underdevelopment and results in births which are small for gestation age due to intrauterine undernutrition, leading to various metabolic disorders in adulthood. Furthermore, postnatal high fat diet (HFD) consumption is also a potent obesogenic factor, which can interact with maternal smoking. In this study, we aimed to determine whether maternal HFD consumption during pregnancy can reverse the adverse impact of maternal smoking and change the response to postnatal HFD consumption.Methods: Female mice were exposed to cigarette smoke (SE, 2 cigarettes/day) or sham exposed for 5 weeks before mating, with half of the SE dams fed HFD (43% fat, SE+HFD). The same treatment continued throughout gestation and lactation. Male offspring from each maternal group were fed the same HFD or chow after weaning and sacrificed at 13 weeks.Results: Maternal SE alone increased body weight and fat mass in HFD-fed offspring, while SE+HFD offspring showed the highest energy intake and glucose metabolic disorder in adulthood. In addition, postnatal HFD increased the body weight and aggravated the metabolic disorder caused by maternal SE and SE+HFD.Conclusions: Maternal HFD consumption could not ameliorate the adverse effect of maternal SE but exaggerate metabolic disorders in adult offspring. Smoking cessation and a healthy diet are needed during pregnancy to optimize the health outcome in the offspring.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-021-02052-z.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background. Phacoemulsification under local anesthesia is regarded as the major surgery for cataract treatment. Recent research has compared the pain perception between the first eye and the second eye during phacoemulsification. However, these studies have also yielded controversial findings. Consequently, we performed a systematic review and a meta-analysis to investigate the difference in the pain perception between the first and second eyes during phacoemulsification. Method. We searched the PubMed, EMBASE, and Cochrane CENTRAL databases for the studies published up to October 5, 2018. Prospective observational studies were included. The meta-analysis was conducted by means of random-effects model and fixed-effects model according to the heterogeneity. Evaluation of the methodological quality of studies was based on Newcastle-Ottawa Scale (NOS). Results. Overall, eight studies were included in the meta-analysis. The analysis of pooled data showed that the pain scores of the first eye shortly after surgery under local anesthesia were significantly lower as compared to the second eye (WMD: 0.69; 95% CI: 0.40, 0.98; P

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In vitro and in vivo experimental studies have shown garlic has protective effects on the aging process; however, there is no evidence that garlic consumption is associated with all-cause mortality among oldest-old individuals (≥80 years). From 1998 to 2011, 27,437 oldest-old participants (mean age: 92.9 years) were recruited from 23 provinces in China. The frequencies of garlic consumption at baseline and at age 60 were collected. Cox proportional hazards models adjusted for potential covariates were constructed to estimate hazard ratios (HRs) relating garlic consumption to all-cause mortality. Among 92,505 person-years of follow-up from baseline to September 1, 2014, 22,321 participants died. Participants who often (≥5 times/week) or occasionally (1−4 times/week) consumed garlic survived longer than those who rarely (less than once/week) consumed it (p < 0.001). Participants who consumed garlic occasionally or often had a lower risk for mortality than those who rarely consumed garlic at baseline; the adjusted HRs for mortality were 0.92(0.89−0.94) and 0.89(0.85−0.92), respectively. The inverse associations between garlic consumption and all-cause mortality were robust in sensitivity analyses and subgroup analyses. In this study, habitual consumption of garlic was associated with a lower all-cause mortality risk; this advocates further investigation into garlic consumption for promoting longevity.

Multidrug-resistant tuberculosis (MDR-TB) represents a major obstacle towards successful TB control. Directly observed therapy (DOT) was recommended by WHO to improve adherence and treatment outcomes of MDR-TB patients, however, the effectiveness of DOT on treatment outcomes of MDR-TB patients was mixed in previous studies. We conducted this systematic review and meta-analysis to assess the association between DOT and treatment outcomes and to examine the impact of different DOT providers and DOT locations on successful treatment outcomes in MDR-TB patients.We searched studies published in English between January 1970 and December 2015 in major electronic databases. Two reviewers independently screened articles and extracted information of DOT, treatment success rate and other characteristics of studies. Random effects model was used to calculate the pooled treatment success rate and 95% confidence interval (CI). Sub-group analyses were conducted to access factors associated with successful treatment outcomes.A total of 31 articles 7,466 participants were included. Studies reporting full DOT (67.4%, 95% CI: 61.4-72.8%) had significantly higher pooled treatment success rates than those reporting self-administration therapy (46.9%, 95% CI: 41.4-52.4%). No statistically difference was found among DOT provided by healthcare providers (65.8%, 95% CI: 55.7-74.7%), family members (72.0%, 95% CI: 31.5-93.5%) and private DOT providers (69.5%, 95% CI: 57.0-79.7%); and neither did we find significantly difference on pooled treatment success rates between patients having health facility based DOT (70.5%, 95% CI: 61.5-78.1%) and home-based DOT (68.4%, 95% CI: 51.5-81.5%).Providing DOT for a full course of treatment associated with a higher treatment success rate in MDR-TB patients.

Alpha-fetoprotein not only serves as a diagnostic marker for liver cancer, but also posses a variety of biological functions. However, the role of Alpha-fetoprotein on tumor angiogenesis and cell invasion remains incompletely understood. In this study, we aimed to evaluate if Alpha-fetoprotein can regulate the major angiogenic factors and matrix metalloproteinases in human liver cancer cells. Alpha-fetoprotein silencing was achieved by Stealth RNAi. Expression of Alpha-fetoprotein was examined by a full-automatic electrochemistry luminescence immunity analyzer. Expression of VEGF, VEGFR-2, MMP-9, and MMP-2 was examined by Western blot and immunocytochemistry. Apoptosis was detected by TUNEL assay. Angiogenesis was detected by in vitro angiogenesis assay kit. Silencing of Alpha-fetoprotein led to an increased apoptosis, which was associated with a decreased expression of vascular endothelial growth factor, vascular endothelial growth factor receptor 2, matrix metalloproteinases-2/9. These results suggest that Alpha-fetoprotein may play a regulatory role on angiogenesis and cell invasion during liver cancer development.

BACKGROUND: Individual patient data meta-analyses (IPDMAs) prevail as the gold standard in clinical evaluations. We investigated the distribution and epidemiological characteristics of published IPDMA articles. METHODOLOGY/PRINCIPAL FINDINGS: IPDMA articles were identified through comprehensive literature searches from PubMed, Embase, and Cochrane library. Two investigators independently conducted article identification, data classification and extraction. Data related to the article characteristics were collected and analyzed descriptively. A total of 829 IPDMA articles indexed until 9 August 2012 were identified. An average of 3.7 IPDMA articles was published per year. Malignant neoplasms (267 [32.2%]) and circulatory diseases (179 [21.6%]) were the most frequently occurring topics. On average, each IPDMA article included a median of 8 studies (Interquartile range, IQR 5 to 15) involving 2,563 patients (IQR 927 to 8,349). Among 829 IPDMA articles, 229 (27.6%) did not perform a systematic search to identify related studies. In total, 207 (25.0%) sought and included individual patient data (IPD) from the "grey literature". Only 496 (59.8%) successfully obtained IPD from all identified studies. CONCLUSIONS/SIGNIFICANCE: The number of IPDMA articles exhibited an increasing trend over the past few years and mainly focused on cancer and circulatory diseases. Our data indicated that literature searches, including grey literature and data availability were inconsistent among different IPDMA articles. Possible biases may arise. Thus, decision makers should not uncritically accept all IPDMAs.