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Intestinal disease is a group of complex digestive system diseases imposing a significant burden globally. Identifying the risk factors and potential complications of intestinal disease is important for its prevention and treatment. However, traditional observational clinical studies are limited by confounding factors and reverse causation, making causal inference challenging. Mendelian randomisation (MR) method has been developed to effectively mitigate these constraints and assess the causal relationships. This review briefly introduces the MR method, summarises MR research on intestinal disease and delineates the prospective avenues for future research. Conventional risk factors, such as lifestyle behaviours (eg, physical activity, smoking and alcohol consumption), nutrients (eg, selenium), obesity markers (eg, body mass index and waist-to-hip ratio) and inflammatory biomarkers, have been validated in MR studies. Multiomics MR studies are becoming novel hotspots, which provide a theoretical foundation for the exploration of pathogenesis and the investigation of new drug targets. However, most of the recent studies are based on European individuals, and thus it is necessary to replicate the results in other ancestries. Moreover, triangulation integrating MR and other epidemiology methods is suggested as a validated paradigm for causal inference in future MR studies.

Summary: Background: The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization analysis to examine these associations. Methods: Genetic instruments associated with leisure screen time (LST, an indicator of a sedentary lifestyle) and moderate-to-vigorous intensity physical activity (MVPA) at the genome-wide significance (P

Summary: Skeletal muscle may mutually interact with gastrointestinal disease through metabolic homeostasis and nutritional status and therefore may be a marker for early risk detection. We conducted a prospective cohort analysis including 393,606 participants (mean age 56.0 years, 53.9% female) from the UK Biobank. The exposures were grip strength and skeletal muscle mass (SMM). The primary outcomes were 24 incident gastrointestinal diseases. During a mean follow-up of 12.1 years, we found that one sex-specific SD increase in grip strength and SMM were associated with reduced risk of 16 and 19 gastrointestinal diseases, respectively. For grip strength, the HRs ranged from 0.94 (for ulcerative colitis) to 0.80 (for liver cancers). For SMM, the HRs ranged from 0.92 (for colorectal cancer) to 0.51 (for non-alcoholic fatty liver disease). Our finding suggested that grip strength and SMM might be significant indicators for gastrointestinal diseases risk screen.

Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder with complex pathophysiological mechanism. It is reported that even a modest weight loss of 5–10% substantially may improve the reproductive and metabolic profile. This study aims to assess the efficacy of the low dose of liraglutide (0.6 mg QD) combined with metformin (0.85 mg BID) in weight loss in Chinese Han women with PCOS.Methods We included clinical data of 102 obese/overweight (≥18 years, body mass index ≥28 kg/m2 or ≥24 kg/m2) women who were diagnosed with PCOS from October 2016 to March 2018 in Wuhan Union Hospital initially. They were treated with dinae-35, low dose of liraglutide (0.6 mg QD) and metformin (0.85 mg BID) for 12 weeks. The demographic and clinical data were retrieved retrospectively, and weight loss was the main outcome measure. Student’s paired t-test and Wilcoxon rank sum test were used to compare the differences before and after therapy, p

Abstract Background and Aims Distinguishing pancreatic cancer from nonneoplastic masses is critical and remains a clinical challenge. The study aims to construct a deep learning‐based artificial intelligence system to facilitate pancreatic mass diagnosis, and to guide EUS‐guided fine‐needle aspiration (EUS‐FNA) in real time. Methods This is a prospective study. The CH‐EUS MASTER system is composed of Model 1 (real‐time capture and segmentation) and Model 2 (benign and malignant identification). It was developed using deep convolutional neural networks and Random Forest algorithm. Patients with pancreatic masses undergoing CH‐EUS examinations followed by EUS‐FNA were recruited. All patients underwent CH‐EUS and were diagnosed both by endoscopists and CH‐EUS MASTER. After diagnosis, they were randomly assigned to undergo EUS‐FNA with or without CH‐EUS MASTER guidance. Results Compared with manual labeling by experts, the average overlap rate of Model 1 was 0.708. In the independent CH‐EUS video testing set, Model 2 generated an accuracy of 88.9% in identifying malignant tumors. In clinical trial, the accuracy, sensitivity, and specificity for diagnosing pancreatic masses by CH‐EUS MASTER were significantly better than that of endoscopists. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were respectively 93.8%, 90.9%, 100%, 100%, and 83.3% by CH‐EUS MASTER guided EUS‐FNA, and were not significantly different compared to the control group. CH‐EUS MASTER‐guided EUS‐FNA significantly improved the first‐pass diagnostic yield. Conclusion CH‐EUS MASTER is a promising artificial intelligence system diagnosing malignant and benign pancreatic masses and may guide FNA in real time. Trial registration number: NCT04607720.

Background: Beverage consumption was found to be associated with cardiovascular disease and mortality in the general population. However, it is unclear whether this association still exists in individuals with inflammatory bowel disease (IBD). Objectives: To investigate the associations of sugar-sweetened beverages, artificially sweetened beverages, and natural juices with cardiovascular disease and all-cause mortality among individuals with IBD. Design: Prospective cohort study. Methods: We included 1981 participants with IBD in the UK Biobank. Consumption of beverages was measured using a validated 24-h diet recall. Outcomes of interest were overall cardiovascular disease and all-cause mortality. Cox proportional hazard models were used to estimate the hazard ratios and 95% confidence intervals (CIs). Results: During a mean (SD) follow-up of 10.1 (1.7) years, we documented 205 cardiovascular events and 133 deaths. Compared to non-consumers, those consuming sugar-sweetened beverages more than 1 unit/day (reported in glasses/cans/250 ml/cartons) were associated with 64% (95% CI: 5–155, p = 0.030) and 97% (95% CI: 16–233, p = 0.012) increased risk of cardiovascular disease and all-cause mortality, respectively. We also observed a 78% (95% CI: 3–205, p = 0.038) increased risk of cardiovascular disease in participants who consumed artificially sweetened beverages more than 1 unit/day when compared with non-consumers. We did not observe significant associations between natural juice consumption and the two outcomes in IBD. Conclusion: Higher sugar- and artificially sweetened beverage consumption were associated with adverse cardiovascular and mortality outcomes in IBD. These exploratory results were consistent with the evidence in the general population and highlighted the importance of diet management in individuals with IBD.

A new transmission model of Zika virus with three transmission routes including human transmission by mosquito bites, sexual transmission between males and females and vertical transmission is established. The basic reproduction number $ R_{0} $ is derived. When $ R_{0} < 1 $, it is proved that the disease-free equilibrium is globally stable. Furthermore, the optimal control and mitigation methods for transmission of Zika virus are deduced and explored. The MCMC method is used to estimate the parameters and the reasons for the deviation between the actual infection cases and the simulated data are discussed. In addition, different strategies for controlling the spread of Zika virus are simulated and studied. The combination of mosquito control strategies and internal human control strategies is the most effective way in reducing the risk of Zika virus infection.

Highly pathogenic influenza A(H5N8) viruses have caused several worldwide outbreaks in birds and are able cross the species barrier to infect humans, posing a substantial threat to public health. After the first detection of H5N8 viruses in deceased swans in Inner Mongolia, we performed early warning and active monitoring along swan migration routes in central China. We isolated and sequenced 42 avian influenza viruses, including 40 H5N8 viruses, 1 H5N2 virus, and 1 H9N2 virus, in central China. Our H5N8 viruses isolated in swan stopover sites and wintering grounds showed high nucleotide homologies in the whole genome, revealing a common evolutionary source. Phylogenetic analysis revealed that the H5 viruses of clade 2.3.4.4b prevalent in 2020 have further diverged into two sub-clades: b1 and b2. The phylogeographic analysis also showed that the viruses of sub-clade b2 most likely originated from poultry in Russia. Notably, whooper swans were found to be responsible for the introduction of sub-clade b2 viruses in central China; whooper and tundra swans play a role in viral spread in the Yellow River Basin and the Yangtze River Basin, respectively. Our findings highlight swans as an indicator species for transborder spreading and monitoring of the H5N8 virus.

ABSTRACTEnterohemorrhagic Escherichia coli (EHEC) O157:H7 is a common food-borne pathogen that can cause acute diseases. Lysine acetylation is a post-translational modification (PTM) that occurs in various prokaryotes and is regulated by CobB, the only deacetylase found in bacteria. Here, we demonstrated that CobB plays an important role in the virulence of EHEC O157:H7 and that deletion of cobB significantly decreased the intestinal colonization ability of bacteria. Using acetylation proteomic studies, we systematically identified several proteins that could be regulated by CobB in EHEC O157:H7. Among these CobB substrates, we found that acetylation at the K44 site of CesA, a chaperone for the type-III secretion system (T3SS) translocator protein EspA, weakens its binding to EspA, thereby reducing the stability of this virulence factor; this PTM ultimately attenuating the virulence of EHEC O157:H7. Furthermore, we showed that deacetylation of the K44 site, which is deacetylated by CobB, promotes the interaction between CesA and EspA, thereby increasing bacterial virulence in vitro and in animal experiments. In summary, we showed that acetylation influences the virulence of EHEC O157:H7, and uncovered the mechanism by which CobB contributes to bacterial virulence based on the regulation of CesA deacetylation.

Purpose: Vonoprazan (VPZ) produces a strong acid-inhibitory effect, which can potentially eradicate Helicobacter Pylori (H. pylori). We aimed to assess whether a 14-day VPZ-containing triple therapy was safe and effective in the Chinese population and the potential mechanism.Methods: Enrolled patients confirmed to be infected with H. pylori were randomly divided into four groups: VPZ + doxycycline + furazolidone, VPZ + doxycycline + amoxicillin, esomeprazole (EPZ) + bismuth + doxycycline + furazolidone, and EPZ + colloidal bismuth + doxycycline + amoxicillin for 14 days. The eradication rate, medication adherence, and incidence of adverse events (AEs) were evaluated. Inhibition of H. pylori by VPZ and EPZ in vitro was assessed. H. pylori treated with appropriate concentrations of VPZ and EPZ were sequenced by transcriptome analysis to explore the antibacterial mechanism.Results: A higher eradication rate were observed in VPZ-containing triple therapy. No obvious differences were observed in medication adherence or the incidence of AEs. VPZ had no direct inhibitory effect on H. pylori, whereas EPZ directly inhibited H. pylori may through downregulated genes related to the ribosome.Conclusion: In the Chinese population, 14-day VPZ-containing triple therapy was safe and more effective and can be used clinically as first-line H. pylori treatment.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT05097846

Freshwater lakes represent a potential source of methane (CH4) emission into the atmosphere. However, the CH4 emission contribution to the total emission in the littoral zones of lakes, especially emergent macrophytes (e.g., lotus), is poorly known. Lotus has been cultivated in almost all provinces in China; it is not only an aquatic plant, but also a kind of vegetable. In this study, two sampling zones (lotus plant and open water) were established in the lake of the middle reaches of the Yangtze River. The CH4 emission was measured using a floating opaque chamber and gas chromatography between April and December in the years 2021 and 2022. The results indicated that the flux of CH4 emissions ranged from 0.10 to 59.75 mg m−2 h−1, with an average value of 5.61 mg m−2 h−1, in the open water, while ranging from 0.19 to 57.32 mg m−2 h−1, with an average value of 17.14 mg m−2 h−1, in the lotus plant zone. The maximal CH4 emissions occurred in July and August for the open water, which was highly related to the air and water temperature, whereas it happened in September for the lotus plant zone, possibly due to the high vegetation biomass, indirectly enhancing the high soil organic carbon content, plant-mediated CH4 emission, as well as the lower dissolved oxygen concentration, thus strengthening the production and emissions of CH4. Considering the carbon emissions (both CH4 and CO2) and plant productivity, although greater CH4 emission occurred in the lotus plant zone, it could still represent a potential carbon sink (213 g m−2 yr−1) compared to the open water.

During October 2020, we identified 13 highly pathogenic avian influenza A(H5N8) clade 2.3.4.4b viruses from wild ducks in Ningxia, China. These viruses were genetically related to H5N8 viruses circulating mainly in poultry in Europe during early 2020. We also determined movements of H5N8 virus‒infected wild ducks and evidence for spreading of viruses.

Reconstruction of defects around the knee region requires thin and pliable skin. The superior lateral genicular artery (SLGA) flap provides an excellent alternative to muscle-based flaps. The anatomy and the surgical techniques of the SLGA flap were reviewed and the results of cases using the SLGA flap for coverage of knee and proximal leg defects were analyzed. SLGA flaps were performed in two cases and followed up for at least 6 months. Twelve articles on the use of the SLGA flap were also identified. A review of 39 cases showed that the mean diameter of the perforator supplying the skin of the flap was 1.04 mm, while the mean diameter of the SLGA at its origin was 1.78 mm. The mean length of the pedicle measured from the origin of the popliteal artery was 7.44 cm. The average dimensions of the flap were 14.8×6.6 cm with primary closure of the donor site in 61.5% of cases. Of these cases, 38.5% were due to trauma, 23.1% were post-burn complications, 12.8% were defects after resection of tumors, and 10.3% were for ulcers post-bursectomy. The most common complication was flap tip necrosis. All studies reported favorable outcomes with complete wound healing.

Inflammatory bowel disease (IBD) is an incurable digestive disease. Since patients have to live with it, improving patients’ quality of life is important. Caregiver’s positive feelings and closeness may have a positive effect on patients’ quality of life. We hypothesized that caregiver’s positive feeling affected patient’s quality of life through caregiver’s caring ability, and closeness might be the upstream of this chain. In this study, we conducted a single-center cross-sectional survey by questionnaire in China to tested the hypothesis. A total of 181 patient-caregiver pairs were included. The short version of the IBD questionnaire (SIBDQ), the twelve-item short-form health survey (SF-12), the positive aspects of caregiving (PAC) and Capacity Scale of caregivers were used to collect data. All the data were collected in one interview. Spearman correlation and Bootstrap method were used to analyze the data. Mediation analysis results indicated that caregiver’s caring ability mediated the association between caregiver’s positive feelings and patients’ quality of life (p < 0.01), which explained 34.1% of the total variation of patients’ quality of life. Mediation analysis results also revealed that patient-evaluated or caregiver-evaluated closeness had a positive effect on patients’ quality of life through caregiver’s positive feeling and caregiver’s caring ability (p < 0.05), which explained 2.1 and 2.3% of the variation of patients’ quality of life. Caregiver’s positive feelings were related to caregivers’ quality of life (p < 0.01), but there was no significant association between caregivers’ ability and caregivers’ quality of life. In summary, our model revealed that caregiver’s positive feeling affected patients’ quality of life through caregiver’s caring ability.

Background: Social well-being of patients with inflammatory bowel disease (IBD) is garnering increased attention; however, the impact of social isolation remained poorly understood. Objectives: We investigated the joint association of social isolation and IBD with premature deaths to articulate the profound impact of social isolation in IBD prognosis. Design: Longitudinal cohort study. Methods: We leveraged data of 486,014 participants from UK Biobank (including 5791 with IBD), the mean follow-up was 11.84 years. Diagnoses of IBD and its subtypes of Crohn’s disease (CD) and ulcerative colitis were confirmed with the combination of self-reporting, primary care, and hospital admission data. Social isolation was measured by the frequency of meeting family/friends, leisure and social activity, and communal/solitary living. Mortality was ascertained through data linkage with national death registries. Multivariable Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI). Results: Comparing non-isolated non-IBD population, the HRs of mortality in patients with IBD who were socially isolated or not were 2.06 (95% CI: 1.69, 2.51) and 1.33 (95% CI: 1.21, 1.45), respectively. The excess risk of death was observed in socially isolated patients with IBD (HR = 1.69, 95% CI: 1.36, 2.11), particularly among patients with CD (HR = 2.06, 95% CI: 1.48, 2.87) than their non-isolated counterparts. Data from subgroup and sensitivity analyses were consistent with those from the primary analysis. Conclusion: Socially isolated patients with IBD especially CD increases the risk of premature death. Preventing social isolation might be a promising approach to improve IBD prognosis. Plain language summary Social isolation as a risk factor to excess mortality in patients with IBD: findings from a longitudinal cohort study Social isolation is prevalent in individuals with inflammatory bowel disease (IBD); however, its potential health impact on IBD prognosis has not been quantitatively well examined. In this study, we explored the association between social isolation and subsequent death, with the focus on patients with IBD. We leveraged data of 486,014 participants (including 5791 with IBD) from UK Biobank. We measured social isolation by the frequency of meeting family/friends, leisure and social activity, and communal/solitary living. We ascertained patients with IBD and mortality by self-report data and data linkage with primary care, hospital, and national death registry. Participants were followed up for a mean of 11.84 years. Comparing non-isolated non-IBD population, we found that patients with IBD who were deemed as socially isolated or not were associated with a 2.06-fold (1.69–2.51) and 1.33-fold (1.21–1.45) risk of death, respectively. Furthermore, we revealed that socially isolated patients with IBD and subtype Crohn’s disease (CD) had 69% (36–111%) and 106% (48–187%) increased risk of premature death compared with their non-isolated counterparts, respectively. Social isolation merits attention in IBD care and management. Patients with IBD, especially CD, are more likely to be affected when socially isolated. Targeted social support strategies ought to be devised to improve IBD prognosis.

The human ether-á-go-go-related gene (hERG) encodes the pore-forming subunit (Kv11.1), conducting a rapidly delayed rectifier K+ current (IKr). Reduction of IKr in pathological cardiac hypertrophy (pCH) contributes to increased susceptibility to arrhythmias. However, practical approaches to prevent IKr deficiency are lacking. Our study investigated the involvement of ubiquitin ligase Nedd4-2-dependent ubiquitination in IKr reduction and sought an intervening approach in pCH. Angiotensin II (Ang II) induced a pCH phenotype in guinea pig, accompanied by increased incidences of sudden death and higher susceptibility to arrhythmias. Patch-clamp recordings revealed a significant IKr reduction in pCH cardiomyocytes. Kv11.1 protein expression was decreased whereas its mRNA level did not change. In addition, Nedd4-2 protein expression was increased in pCH, accompanied by an enhanced Nedd4-2 and Kv11.1 binding detected by immunoprecipitation analysis. Cardiac-specific overexpression of inactive form of Nedd4-2 shortened the prolonged QT interval, reversed IKr reduction, and decreased susceptibility to arrhythmias. A synthesized peptide containing the PY motif in Kv11.1 C-terminus binding to Nedd4-2 and a cell-penetrating sequence antagonized Nedd4-2-dependent degradation of the channel and increased the surface abundance and function of hERG channel in HEK cells. In addition, in vivo administration of the PY peptide shortened QT interval and action potential duration, and enhanced IKr in pCH. We conclude that Nedd4-2-dependent ubiquitination is critically involved in IKr deficiency in pCH. Pharmacological suppression of Nedd4-2 represents a novel approach for antiarrhythmic therapy in pCH.

Objective: A process was developed for the purification of bran polyphenols from HPD 600 macroporous resin. The purity and antioxidant activity of the extracts were analyzed before and after purification, and the polyphenol fractions in the purified products were characterized. Methods: The bound polyphenols in wheat bran were extracted by alkali hydrolysis, and the dynamic adsorption-desorption conditions of the macroporous resin were optimized by single-factor test to determine the optimal purification process. The antioxidant activity fraction was determined by ABTS and DPPH radical scavenging rate. The characterization of the polyphenol fraction in the purified product was completed by UPLC-MS/MS. Results: Under optimal process conditions, the purity of the polyphenols and the antioxidant activity of the purified product were significantly increased. The purified products contained mainly nine polyphenolic compounds, in order of retention time: p-hydroxybenzoic acid, caffeic acid, vanillin, p-coumaric acid, trans-ferulic acid and salicylic acid. Conclusion: The macroporous resin purification process is effective in enriching bran polyphenols and the resulting purified product has a significantly higher antioxidant capacity, while maintaining the richness of the polyphenolic species.

Summary: Background: Whether meat consumption is related to risk of mortality in patients with inflammatory bowel disease (IBD) remains poorly understood. Methods: In the UK Biobank, 5763 patients with IBD were recruited from 2007 to 2010 and finished a brief food frequency questionnaire at baseline. We followed them until March 13, 2021 to document all-cause death events. Cox proportional hazard models were used to estimate hazard ratios (HRs) for all-cause mortality associated with consumptions of fish, unprocessed poultry, unprocessed red meat, and processed meat among the patients. Findings: During 67,095 person-years (mean follow-up 11·7 years, mean age 57·3, 52·5% female), we documented 590 death events. Higher consumption of processed meat was associated with an increased risk of all-cause mortality in patients with IBD (HR comparing >4·0 with 0–0·9 time/week=1·52, 95% confidence interval (CI) 1·05–2·19), but the P-trend for each 25 g increment was 0·075. This association remained significant in patients with Crohn's disease (HR 1·77, 95% CI 1·01–3·10) but not in patients with ulcerative colitis (HR 1·34, 95% CI 0·82–2·20). Consumptions of fish (HR 1·27, 95% CI 0·84–1·91), unprocessed poultry (HR 0·59, 95% CI 0·28–1·21), or unprocessed red meat (HR 0·87, 95% CI 0·60–1·26) were not significantly associated with the mortality of patients with IBD. Interpretation: More frequent consumption of processed meat was associated with an increased risk of mortality in patients with IBD, while no associations were observed for consumption of other types of meat. Our exploratory and speculative findings should be cautiously interpreted and need further replication in other cohorts. Funding: The National Natural Science Foundation of China (81,970,494); Key Project of Research and Development Plan of Hunan Province (2019SK2041).

In October 2020, highly pathogenic avian influenza A(H5N8) viruses were detected in 2 dead swans in Inner Mongolia, China. Genetic analysis showed that the H5N8 isolates belong to clade 2.3.4.4b and that the isolates cluster with the H5N8 viruses isolated in Eurasia in the fall of 2020.

Lung cancer is the most common malignant tumor in the world with the highest incidence of deaths. In recent years, the treatment of lung cancer has made a significant breakthrough. However, as the tumor progresses, lung cancer cells inevitably acquire resistance and the efficacy of the treatment are greatly reduced. P21 protein plays a dual role in tumors, which not only regulates the cell cycle, induces apoptosis, inhibits cell proliferation, but also protects cells against apoptosis and promotes tumor cell resistance. This article reviews the research on P21 and lung cancer resistance, to provide new ideas for individualized treatment of lung cancer and overcoming lung cancer resistance.

Abstract Background Tumor necrosis factor (TNF) has been investigated to be correlated with the occurrence and progression of lung cancer. This investigation was to assess the efficacy and safety of recombinant mutant human tumor necrosis factor (rmhTNF) for controlling malignant pleural effusion (MPE) through thoracic perfusion. Methods Through searching from MEDLINE, Web of Science, EMBASE, Cochrance Library, OVID and China National Knowledge Infrastructure (CNKI), a total of 12 studies with 694 patients were included in this study. A series of meta-analysis methods were used to analyze the extracted data. Results Thoracic perfusion of rmhTNF combined with cisplatin promoted the objective response rate (ORR) (P

Japanese Ardisia is widely used as a hepatoprotective and anti-inflammatory agent in China. However, the active ingredients in Japanese Ardisia and their potential mechanisms of action in the treatment of autoimmune hepatitis (AIH) are unknown. The pharmacodynamic substance and mechanism of action of Japanese Ardisia in the treatment of AIH were investigated using network pharmacology and molecular docking technology in this study. Following that, the effects of Japanese Ardisia were evaluated using the concanavalin A (Con A)-induced acute liver injury rat model. The active ingredients and targets of Japanese Ardisia were searched using the Traditional Chinese Medicine Systems Pharmacology database, and hepatitis-related therapeutic targets were identified through GeneCards and Online Mendelian Inheritance in Man databases. A compound–target network was then constructed using Cytoscape software, and enrichment analysis was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Molecular docking technology was used to simulate the docking of key targets, and the AIH rat model was used to validate the expression of key targets. Nineteen active chemical components and 143 key target genes were identified. GO enrichment analysis revealed that the treatment of AIH with Japanese Ardisia mainly involved DNA–binding transcription factor binding, RNA polymerase II-specific DNA transcription factor binding, cytokine receptor binding, receptor-ligand activity, ubiquitin-like protein ligase binding, and cytokine activity. In the KEGG enrichment analysis, 165 pathways were identified, including the lipid and atherosclerotic pathway, IL-17 signaling pathway, TNF signaling pathway, hepatitis B pathway, and the AGE–RAGE signaling pathway in diabetic complications. These pathways may be the key to effective AIH treatment with Japanese Ardisia. Molecular docking showed that quercetin and kaempferol have good binding to AKT1, IL6, VEGFA, and CASP3. Animal experiments demonstrated that Japanese Ardisia could increase the expression of AKT1 and decrease the expression of CASP3 protein, as well as IL-6, in rat liver tissues. This study identified multiple molecular targets and pathways for Japanese Ardisia in the treatment of AIH. At the same time, the effectiveness of Japanese Ardisia in treating AIH was verified by animal experiments.

The mechanism of action of Ardisia japonica in the treatment of immune liver injury was systematically analyzed from the perspective of the biological metabolic network by using non-targeted metabolomics combined with biological network analysis tools. A rat model of acute immune hepatic injury was established by Concanavalin A (Con A) and the efficacy of the treatment of acute immune liver injury was judged by gavage of A. japonica. Liquid chromatography-mass spectrometry (LC-MS)-based plasma metabolomics was used to identify the key metabolites and metabolic pathways for the hepatoprotective effects of A. japonica. The results demonstrated that A. japonica reduced the levels of inflammatory parameters, decreased hepatic malondialdehyde levels, and enhanced hepatic antioxidant enzyme activity in animal experiments. The clustering of metabolomic samples showed significant separation in principal component analysis plots and the three groups in PLS-DA and OPLS-DA models could be clearly distinguished in multivariate statistical analysis. Among the 937 total metabolites, 445 metabolites were significantly different between the control and model groups, while 144 metabolites were identified as metabolites with differences between the model and administration groups, and a total of 39 differential metabolites were identified to affect the metabolic levels of the three groups. The differential metabolites were principally involved in the citric acid cycle, glutathione metabolism, vitamin B6 metabolism, and steroid hormone biosynthesis. This study found that A. japonica can significantly inhibit acute liver injury in rats, and exert a hepatoprotective effect through anti-inflammatory effect, inhibition of lipid peroxidation, improvement of the antioxidant defense system, and regulation of metabolites and related metabolic pathways. This study will provide a theoretical basis for the application of A. japonica in the treatment of the liver injury.

Background: The cardioprotective diet was reported to be associated with several chronic cardiometabolic diseases through an anti-inflammation effect. However, the association between the cardioprotective diet and the risk of inflammatory bowel disease (IBD) was unclear and deserved to be further explored. Methods: We calculated the cardioprotective diet score based on the consumptions of seven common food groups using the validated food frequency questionnaire data in the UK Biobank. Incident IBD was ascertained from primary care data, inpatient data, and the death registry. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between the cardioprotective diet score and the risk of IBD. Results: During a mean follow-up of 12.1 years, we documented 2717 incident IBD cases, including 851 cases of Crohn’s disease and 1866 cases of ulcerative colitis. Compared to participants with a cardioprotective diet score of 0–1, we observed a decreased risk of IBD among participants with cardioprotective diet scores of 3 (HR 0.85, 95% CI 0.73–0.99), 4 (HR 0.84, 95% CI 0.72–0.98), and 5–7 (HR 0.77, 95% CI 0.66–0.89) (p-trend < 0.001). Conclusions: A greater adherence to the cardioprotective diet was associated with a lower risk of IBD. Our finding highlighted the importance of focusing on the cardioprotective diet to prevent IBD.

Background: In China, we have seen dramatic increases in public concern over depression and mental health after the suicide of some famous persons. The objective of this study is to investigate the changes of search-engine query patterns to monitor this phenomenon based on the tragic suicide of a young Chinese pop star, Kimi Qiao.Methods: The daily search volume for depression was retrieved from both the Baidu Index (BDI) and the Sina MicroBlog Index (SMI). Besides, the daily BDI for suicide, schizophrenia, obsessive-compulsive disorder, common cold, stomach cancer, and liver cancer were collected for comparison. According to the time of Qiao's suicide, all data were divided into two periods (i.e., Period One from 1 September 2015 to 31 August 2016 while Period Two ranged from 1 October 2016 to 30 September 2017). The paired t-test was used to compare the differences in search volumes between two periods. The Pearson correlation analysis was used to estimate correlations between the BDI and SMI for depression.Results: The average BDI for depression, BDI for suicide, and SMI for depression in Period Two were significantly higher than in Period One (p < 0.05). There was a strong positive correlation between the BDI and SMI for depression (r = 0.97, p < 0.001). And no significant difference in BDI for other diseases between the two periods was found.Conclusions: The changes of search-engine query patterns indicated that the celebrity's suicide might be able to improve the netizens' concern about depression in China. The study suggests publishing more practical knowledge and advice on depression through the Internet and social media, to improve the public's mental health literacy and help people to cope with their depressive symptoms appropriately.

For efficient biodiesel production, an acid-activated clay (AC) modified by calcium hydroxide and sodium hydroxide (CaNa/AC) was prepared as a catalyst. CaNa/AC and Na/AC were characterized by Hammett indicators, CO2-TPD, FT-IR, XRD, and N2 adsorption techniques. The influence of catalyst dose, reaction temperature, methanol/oil molar ratio, and reaction time on the transesterification of Jatropha oil was studied. Due to the introduction of calcium, CaNa/AC displayed a higher activity and stability, thereby achieving an oil conversion of 97% under the optimal reaction conditions and maintaining over 80% activity after five successive reuses. The reaction was accelerated as the temperature rose, and the apparent activation energy of CaNa/AC was 75.6 kJ·mol−1. The enhanced biodiesel production by CaNa/AC was ascribed to the increase in active sites and higher basic strength. This study presents a facile and practical method for producing biodiesel on large-scale operation.

In December 2017, an influenza A(H9N2) virus (B51) was isolated from migratory waterfowl in Hubei Province, China. Phylogenetic analysis demonstrated that B51 is a novel reassortant influenza virus containing segments from human H7N4 virus and North American wild bird influenza viruses. This suggest that B51 has undergone multiple reassortment events.

Abstract Background Interleukin-2 (IL-2) is an important immunotherapy cytokine for various diseases including cancer. Some studies reported the efficacy and safety on cisplatin combined with IL-2 versus cisplatin alone for treating malignant pleural effusion (MPE) through thoracic injection. Methods We searched these studies from medical electronic database. A total of 18 studies that met the inclusion criteria were recruited in this meta-analysis. Pooled odds ratios (OR) with 95% confidence intervals (CI) were determined by the fixed effects model of meta-analysis. Results The objective response rate (ORR) and disease control rate (DCR) of cisplatin plus IL-2 for controlling MPE was significantly higher than that of cisplatin alone (p 0.05). Conclusions The low-dose IL-2 improved the ORR, DCR and QOL of patients in the treatment of MPE. Although it may cause fever in patients, it did not increase other AEs.

Abstract Background Previous studies show that overexpression of EMMPRIN involved in the malignant biological behavior of tumors. This investigation was to disclose the expression status of EMMPRIN in non-small cell lung cancer (NSCLC) and its clinical value for the diagnosis of NSCLC. Methods The expression of EMMPRIN was examined using immunohistochemistry and enzyme-linked immunosorbent assay. The clinical value of EMMPRIN was evaluated by drawing a receiver operating characteristic (ROC) curve. Results NSCLC tissues and serum exhibited higher expression levels of EMMPRIN than the normal control (p

Today it is accepted that the development of gifted and talented children is important to enable a nation to compete successfully. In China, though the estimated number of gifted children reaches 20 million (Chu, 2012), gifted education has seldom received sufficient support. The objections to gifted education always suppress suggestions that support programs for gifted students when educational policy is drafted. Starting with a historical review of the gifted education programs and policies in China since 1978, this paper discusses the main reasons for lack of support for gifted education in China from social and cultural perspectives. I conclude that the long-lasting ideology of egalitarianism, the overwhelming pursuit of educational equity and the dominant ideology of socialism have significantly hindered the development of gifted education. Driven by such beliefs and ideologies, the concept of giftedness and gifted education, the relationship between egalitarianism and elitism, and between equity and equality, are often severely misunderstood, which not only harms existing gifted education programs, but suppresses the potential for open discussion about the implementation of gifted education. Finally, I propose how gifted education should be framed in the future educational reform scheme in China and other countries with similar cultural and social environments.

The main adverse effect of tyrosine kinase inhibitors, such as sunitinib, is cardiac contractile dysfunction; however, the molecular mechanisms of this effect remain largely obscure. MicroRNAs (miRNAs) are key regulatory factors in both cardiovascular diseases and the tyrosine kinase pathway. Therefore, we analyzed the differential expression of miRNAs in the myocardium in mice after exposure to sunitinib using miRNA microarray. A significant downregulation of miR-146a was observed in the myocardium of sunitinib-treated mice, along with a 20% decrease in left ventricle ejection fraction (LVEF). The downregulation of miR-146a was further validated by RT-qPCR. Among the potential targets of miR-146a, we focused on Pln and Ank2, which are closely related to cardiac contractile dysfunction. Results of luciferase reporter assay confirmed that miR-146a directly targeted the 3′ untranslated region of Pln and Ank2. Significant upregulation of PLN and ANK2 at the mRNA and protein levels was observed in the myocardium of sunitinib-treated mice. Cardiac-specific overexpression of miR-146a prevented the deteriorate effect of SNT on calcium transients, thereby alleviating the decreased contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). SiRNA knockdown of PLN or ANK2 prevented sunitinib-induced suppression of contractility in hiPSC-CMs. Therefore, our in vivo and in vitro results showed that sunitinib downregulated miR-146a, which contributes to cardiac contractile dysfunction by regulating the downstream targets PLN and ANK2, and that upregulation of miR-146a alleviated the inhibitory effect of SNT on cardiac contractility. Thus, miR-146a could be a useful protective agent against sunitinib-induced cardiac dysfunction.

Heavy oil reservoirs are widely scattered across China with proved reserves over 10 billion tons, most of which are unconsolidated sandstone reservoirs. As a consequence, some problems are encountered as to the choice of production stimulation and stabilization process. This paper attempts to provide a summary of the geological characteristics of heavy oil unconsolidated sandstone reservoirs and the difficulties of production stimulation reconstruction process, in order to preferably choose the system for cleaning, viscosity reducing, acidizing and unplugging, optimize the construction process of viscosity reducing and acidizing, guarantee that service fluids can enter reservoirs uniformly, and improve the deliverable of chemical production stimulation, which would be taken as a good reference for chemical production stimulation construction of heavy oil unconsolidated sandstone reservoirs.

The bilayered structure of hard thin film on soft substrate can lose stability and form specific patterns, such as wrinkles or creases, on the surface, induced by external stimuli. For bilayer hydrogels, the surface morphology caused by the instability is usually controlled by the solvent-induced swelling/shrinking and mechanical force. Here, two important issues on the instability of bilayer hydrogels, which were not considered in the previous studies, are focused on in this study. First, the upper layer of a hydrogel is not necessarily too thin. Thus we investigated how the thickness of the upper layer can affect the surface morphology of bilayer hydrogels under compression through both finite element (FE) simulation and theoretical analysis. Second, a hydrogel can absorb water molecules before the mechanical compression. The effect of the pre-absorption of water before the mechanical compression was studied through FE simulations and theoretical analysis. Our results show that when the thickness of the upper layer is very large, surface wrinkles can exist without transforming into period doublings. The pre-absorption of the water can result in folds or unexpected hierarchical wrinkles, which can be realized in experiments through further efforts.

BACKGROUND:The scarcity of grafts available necessitates a system that considers expected posttransplant survival, in addition to pretransplant mortality as estimated by the MELD. So far, however, conventional linear techniques have failed to achieve sufficient accuracy in posttransplant outcome prediction. In this study, we aim to develop a pretransplant predictive model for liver recipients' survival with benign end-stage liver diseases (BESLD) by a nonlinear method based on pretransplant characteristics, and compare its performance with a BESLD-specific prognostic model (MELD) and a general-illness severity model (the sequential organ failure assessment score, or SOFA score). METHODOLOGY/PRINCIPAL FINDINGS:With retrospectively collected data on 360 recipients receiving deceased-donor transplantation for BESLD between February 1999 and August 2009 in the west China hospital of Sichuan university, we developed a multi-layer perceptron (MLP) network to predict one-year and two-year survival probability after transplantation. The performances of the MLP, SOFA, and MELD were assessed by measuring both calibration ability and discriminative power, with Hosmer-Lemeshow test and receiver operating characteristic analysis, respectively. By the forward stepwise selection, donor age and BMI; serum concentration of HB, Crea, ALB, TB, ALT, INR, Na(+); presence of pretransplant diabetes; dialysis prior to transplantation, and microbiologically proven sepsis were identified to be the optimal input features. The MLP, employing 18 input neurons and 12 hidden neurons, yielded high predictive accuracy, with c-statistic of 0.91 (P