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Abstract Aims The endoscopic treatment of esophagogastric varices is challenging, and the nationwide application of endoscopic therapies for various types of esophagogastric varices and different clinical scenarios remains unclear. This study investigated the use of endoscopic therapy for portal hypertension in China. Methods This study used a questionnaire survey initiated by the Liver Health Consortium in China to investigate the use of endoscopic therapies for portal hypertension. Questionnaires were released online from January 30, 2023 to February 28, 2023 and filled out by chief physicians or senior instructors responsible for endoscopic therapies in participating hospitals across 31 provinces (autonomous regions and municipalities) in China. Comparisons of guideline adherence between primary and referral medical centers were performed using the chi‐square test or Fisher's exact test. Results In total, 836 hospitals participated in the survey. For primary and secondary prophylaxis of esophagogastric variceal bleeding (EGVB), adherence to the national guidelines was 72.5% (606/836) and 39.2% (328/836), respectively. Significant differences were observed in the rate of adherence between the primary and referral centers for primary (79.9% [111/139] vs. 71.0% [495/697], p = 0.033) and secondary prophylaxis (27.3% [38/139] vs. 41.6% [290/697], p = 0.002). Of the hospitals, 78.2% (654/836) preferred endoscopic therapies for acute EGVB, and the timing of endoscopy was usually within 12 h (48.5%, 317/654) and 12–24 h (36.9%, 241/654) after bleeding. Endoscopic therapy was more likely to be the first choice of treatment for acute EGVB in referral centers than in primary centers (82.6% [576/697] vs. 56.1% [78/139], p

Background: Acute variceal bleeding (AVB), a life-threatening complication of liver cirrhosis, can be effectively treated by endoscopy, but there is a risk of early rebleeding after endoscopic variceal treatment (EVT). Thrombocytopenia is the most common hemostatic abnormality in liver cirrhosis. However, it is still unclear about whether thrombocytopenia increases the failure of EVT in cirrhotic patients with AVB. Objectives: We investigated the association between thrombocytopenia and the failure of EVT in cirrhotic patients with AVB. Design: International multicenter, retrospective study. Methods: Overall, 2467 cirrhotic patients with acute gastrointestinal bleeding who were enrolled into an international multicenter study between September 30, 2020 and June 30, 2023 were retrospectively screened. Thrombocytopenia was defined as platelet count below 150 × 10 9 /L and further classified as mild (100 × 10 9 /L–150 × 10 9 /L), moderate (50 × 10 9 /L–100 × 10 9 /L), and severe (

BackgroundLegumes, in the initial event of symbiosis, secrete flavonoids into the rhizosphere to attract rhizobia. This study was conducted to investigate the relationship between crop root exudates and soybean nodule development under intercropping patterns.MethodA two years field experiments was carried out and combined with pot experiments to quantify the effects of planting mode, i.e., relay intercropping and monocropping, and genotypes, i.e., supernodulating NTS1007(NTS), Nandou-12(ND) and Guixia-3(GX) on root exudates, rhizobium community structure, nodule development and nitrogen fixation ability.ResultThe result demonstrated that, maize–soybean relay strip intercropping not only promoted daidzein and genistein exudates of soybean root to soil but also reshaped the community structure and diversity of nodule endophytic rhizobia. Compared with monocropping, the nodule number significantly decreased in relay strip intercropping soybean, and NTS achieved 97% at soybean five trifoliolate stage. At soybean full bloom stage, despite the nodulation capacity of relay strip intercropping soybean was unrestored, the nodule number, nodule dry weight, nodule diameter and root dry weight were the highest in ND under relay strip intercropping. Compared with monocropping, the nodule average diameters of ND and GX in relay strip intercropping significantly increased 26.30% and 21.11%, respectively, the single nodule nitrogenase activity and nifH gene was increased up to the higher level of 3.16-fold and 1.96-fold, 70.8% and 107.6%, respectively. Combined with pot experiments, the nodule number of ND and NTS in maize root maize root exudates (RE) treatment increased with growth period, the GX reached its maximum at full bloom stage. And the nodule diameter of ND under RE treatment showed the best response. At R2 stage, compared with distilled water (DW) treatment, the nodule average diameter of ND and GX in RE treatment was significantly higher, and the GmEXPB2 gene was significantly up-regulated 3.99-fold and 1.02-fold, respectively.ConclusionIn brief, the maize–soybean relay strip intercropping enhanced the soybean root exudates nodulation signaling molecules, meanwhile, maize root exudates caused increased nodule diameter, and enhanced nodule nitrogen fixation, but had little effect on supernodulation varieties.

Dioxin is a typical class of persistent organic pollutants (POPs) that could cause cancer. In China, the contribution of dietary dioxins to the cancer burden remains underexplored. This study evaluates the cancer risk and burden due to dietary dioxins and dioxin-like compounds among Chinese residents from 2000 to 2020. Based on adjustments in China’s dioxin policies, the study period was divided into three stages with split years of 2007 and 2014 to estimate the toxic equivalent (TEQ) of dioxins. Participants in dietary surveys conducted in 31 provinces were included. Dietary exposure to dioxins was estimated in a probability model and compared with the provisional tolerable monthly intake (PTMI). The risk was assessed using carcinogenic slope factors and expressed as the incremental lifetime cancer risk (ILCR). A two-stage model evaluated the burden of cancer attributable to dietary dioxins and dioxin-like compounds. Among all food categories, the highest concentration of dioxins and dioxin-like compounds was observed in aquatic foods at 0.15 pg TEQ/kg. Median dietary exposure to dioxins among Chinese residents decreased from 12.39 pg TEQ/kg/month to 8.72 pg TEQ/kg/month between 2000 and 2020. Consequently, the ILCR due to dietary dioxins declined from 6.44 × 10-5 to 4.53 × 10-5. The health risks were higher in younger groups and among residents of coastal areas (P

ABSTRACTDiet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited effective interventions available. A novel approach to address this issue is through gut microbiota-based therapy. In our study, we utilized multi-omics analysis to identify Phocaeicola vulgatus (P. vulgatus) as a potential probiotic for the treatment of MASLD. Our findings from murine models clearly illustrate that the supplementation of P. vulgatus mitigates the development of MASLD. This beneficial effect is partly attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by P. vulgatus, which reduces the acetylation levels of H3K27 and downregulates the transcription of Squalene Epoxidase (SQLE), a rate-limiting enzyme in steroid biosynthesis that promotes lipid accumulation in liver cells. This study underscores the significant role of P. vulgatus in the development of MASLD and the critical importance of its metabolite 3-HPAA in regulating lipid homeostasis. These findings offer a promising avenue for early intervention therapy in the context of MASLD.

Continuous technological and economic development has led to the extensive use of bisphenol A analogues (BPs) in products, leading to their release to aquatic environments and posing threats to aquatic plants. However, few papers have systemically reviewed the interactions between BPs and aquatic plants. This review comprehensively summarizes the properties, occurrence, fate, and hazardous influences of BPs on aquatic plants. BPs have been widely detected in the global aquatic environment, with concentrations generally ranging from a lower range of ng/L or ng/g to an upper range of μg/L or μg/g in surface water, groundwater, seawater, and sediments. Aquatic plants effectively uptake and translocate BPs, and metabolize them into new compounds. Meanwhile, BPs exposures have diverse toxic effects on the growth, photosynthesis, antioxidant, phytohormones, and structural integrity of aquatic plants. High-throughput omics assays provide significant evidence showing how BPs disturb gene transcription, proteins, and metabolism in plants. This review highlights the need for increased attention on the effects of emerging BPA alternatives, joint treatment, long-term exposure with environmental relevant doses, and potential hazards posed by ingesting polluted plants.

Background: Endoscopy is important for the diagnosis and treatment of acute upper gastrointestinal bleeding (AUGIB), especially acute variceal bleeding (AVB), in liver cirrhosis. However, the optimal timing of endoscopy remains controversial, primarily because the currently available evidence is of poor quality, and the definition of early endoscopy is also very heterogeneous among studies. Herein, a multicenter randomized controlled trial (RCT) is performed to explore the impact of the timing of endoscopy on the outcomes of cirrhotic patients with AVB. Methods: A total of 368 cirrhotic patients presenting with AUGIB who are highly suspected to be from AVB will be enrolled. They will be stratified according to the severity of liver function and clinical presentation at admission and then randomly assigned at a 1:1 ratio into early (within 12 h after admission) and delayed (within 12–24 h after admission) endoscopy groups within each stratum. The primary outcomes include the rates of 5-day failure to control bleeding after admission and 6-week rebleeding. The secondary outcomes include 6-week mortality and incidence of adverse events. Conclusion: Considering existing evidence originates from non-randomized studies, this RCT will provide high-quality evidence to uncover whether cirrhotic patients with AVB should undergo early endoscopy to control bleeding and improve survival. Trial registration: ClinicalTrials.gov identifier: NCT06031402.

Abstract Background Tumor-associated macrophages (TAMs) constitute a substantial part of human hepatocellular carcinoma (HCC). The present study was devised to explore TAM diversity and their roles in HCC progression. Methods Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines. Results We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism. Conclusions These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.

Introduction Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%–6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy.Methods and analysis This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable.Ethics and dissemination The study protocol has been approved by the ethics committees of the Sixth People’s Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences.Trial registration number ChiCTR2300073864.

Abstract In this work, a new method to solve the Reynolds equation including mass-conserving cavitation by using the physics informed neural networks (PINNs) is proposed. The complementarity relationship between the pressure and the void fraction is used. There are several difficulties in problem solving, and the solutions are provided. Firstly, the difficulty for considering the pressure inequality constraint by PINNs is solved by transferring it into one equality constraint without introducing error. While the void fraction inequality constraint is considered by using the hard constraint with the max-min function. Secondly, to avoid the fluctuation of the boundary value problems, the hard constraint method is also utilized to apply the boundary pressure values and the corresponding functions are provided. Lastly, for avoiding the trivial solution the limitation for the mean value of the void fraction is applied. The results are validated against existing data, and both the incompressible and compressible lubricant are considered. Good agreement can be found for both the domain and domain boundaries.

Abstract Background Toxoplasma gondii (T. gondii) is increasingly considered a risk factor for neurodegenerative diseases. However, there is only limited information on the development of drugs for T. gondii infection. Lentinan from Lentinula edodes is a bioactive ingredient with the potential to enhance anti-infective immunity. The present study aimed to investigate the neuroprotective effect of lentinan on T. gondii-associated cognitive deficits in mice. Methods A chronic T. gondii infection mouse model was established by administering 10 cysts of T. gondii by gavage. Lentinan was intraperitoneally administered 2 weeks before infection. Behavioral tests, RNA sequencing, immunofluorescence, transmission electron microscopy and Golgi-Cox staining were performed to assess the effect of lentinan on cognitive deficits and neuropathology in vivo. In vitro, the direct and indirect effects of lentinan on the proliferation of T. gondii tachyzoites were evaluated in the absence and presence of BV-2 cells, respectively. Results Lentinan prevented T. gondii-induced cognitive deficits and altered the transcriptome profile of genes related to neuroinflammation, microglial activation, synaptic function, neural development and cognitive behavior in the hippocampus of infected mice. Moreover, lentinan reduced the infection-induced accumulation of microglia and downregulated the mRNA expression of proinflammatory cytokines. In addition, the neurite and synaptic ultrastructural damage in the hippocampal CA1 region due to infection was ameliorated by lentinan administration. Lentinan decreased the cyst burden in the brains of infected mice, which was correlated with behavioral performance. In line with this finding, lentinan could significantly inhibit the proliferation of T. gondii tachyzoites in the microglial cell line BV2, although lentinan had no direct inhibitory effect on parasite growth. Conclusions Lentinan prevents cognitive deficits via the improvement of neurite impairment and synaptic loss induced by T. gondii infection, which may be associated with decreased cyst burden in the brain. Overall, our findings indicate that lentinan can ameliorate T. gondii-related neurodegenerative diseases. Graphical Abstract

Abstract Interlayer coupling strength dichotomizes two-dimensional (2D) materials into layered and non-layered types. Traditionally, they can be regarded as atomic layers intrinsically linked via van der Waals (vdW) forces or covalent bonds, oriented orthogonally to their growth plane. In our work, we report a material system that differentiates from layered and non-layered materials, termed quasi-layered domino-structured (QLDS) materials, effectively bridging the gap between these two typical categories. Considering the skewed structure, the force orthogonal to the 2D QLDS-GaTe growth plane constitutes a synergistic blend of vdW forces and covalent bonds, with neither of them being perpendicular to the 2D growth plane. This unique amalgamation results in a force that surpasses that in layered materials, yet is weaker than that in non-layered materials. Therefore, the lattice constant contraction along this unique orientation can be as much as 7.7%, tantalizingly close to the theoretical prediction of 10.8%. Meanwhile, this feature endows remarkable anisotropy, second harmonic generation enhancement with a staggering susceptibility of 394.3 pm V−1. These findings endow further applications arranged in nonlinear optics, sensors, and catalysis.

Objectives: This study analyzed the synergistic development of the Traditional Chinese Medicine (TCM) service trade within the Greater Bay Area (GBA) in China, aiming to provide suggestions and references for the development of TCM service trade around the world. Methods: Taking the typical and representative Guangdong, Hong Kong and Macao Greater Bay Area as the research object, this paper focused on four modes of “cross-border supply, offshore consumption, commercial presence, and movement of natural persons”, and explored the current situation of TCM service trade from four macroscopic aspects: political, economic, social, and technological, through case studies. The challenges in the development of TCM service trade were analyzed. Results: Our study found that the degree of synergistic openness of Guangdong, Hong Kong and Macao needs to be improved. The integration of trade in TCM services is the integration of TCM services with tourism. However, there is a relative lack of human resources in TCM in Hong Kong and Macao, with weak competitiveness of service bases. The resources of TCM services are still under-utilized, and the GBA market of TCM services lacks momentum. Conclusions: We have come to the conclusion that the GBA need to promptly improve the unified standard system of TCM service trade. Actively building cultivating a “Bay Area GBA brand” for TCM service trade, steadily building a social climate in support of TCM service trade and vigorously promote the development of TCM service trade through digital technology, thus promoting the synergistic development of TCM service trade within the GBA.

Chatbot services have become an essential communication tool for interacting with consumers in e-commerce. To understand consumer behavior in the context of chatbot services, we apply the Theory of Planned Behavior (TPB) to analyze continuance intention to use and additional predictors to explain behavioral intention. An analysis of data collected from 300 digital shopping users who had experienced chatbot services revealed that an extended TPB model holds for the continuous use of chatbot services, driven by both interaction and information quality. Accordingly, these findings provide a better understanding of consumer behavior toward chatbot services and valuable insights into digital customer relationship management.

Abstract Intercropping can obtain yield advantages, but the mechanism of yield advantages of maize-legume intercropping is still unclear. Then, we explored the effects of cropping systems and N input on yield advantages in a two-year experiment. Cropping systems included monoculture maize (Zea mays L.) (MM), monoculture soybean (Glycine max L. Merr.) (MS), monoculture peanut (Arachis hypogaea L.) (MP), maize-soybean substitutive relay intercropping (IMS), and maize-peanut substitutive strip intercropping (IMP). N input included without N (N0) and N addition (N1). Results showed that maize’s leaf area index was 31.0% and 34.6% higher in IMS and IMP than in MM. The specific leaf weight and chlorophyll a (chl a) of maize were notably higher by 8.0% and 18.8% in IMS, 3.1%, and 18.6% in IMP compared with MM. Finally, N addition resulted in a higher thousand kernels weight of maize in IMS and IMP than that in MM. More dry matter accumulated and partitioned to the grain, maize's averaged partial land equivalent ratio and the net effect were 0.76 and 2.75 t ha−1 in IMS, 0.78 and 2.83 t ha−1 in IMP. The leaf area index and specific leaf weight of intercropped soybean were 16.8% and 26% higher than MS. Although soybean suffers from shade during coexistence, recovered growth strengthens leaf functional traits and increases dry matter accumulation. The averaged partial land equivalent ratio and the net effect of intercropped soybean were 0.76 and 0.47 t ha−1. The leaf area index and specific leaf weight of peanuts in IMP were 69.1% and 14.4% lower than in the MP. The chlorophyll a and chlorophyll b of peanut in MP were 17.0% and 24.4% higher than in IMP. A less dry matter was partitioned to the grain for intercropped peanut. The averaged pLER and NE of intercropped peanuts were 0.26 and -0.55 t ha−1. In conclusion, the strengthened leaf functional traits promote dry matter accumulation, maize-soybean relay intercropping obtained a win–win yield advantage, and maize-peanut strip intercropping achieved a trade-off yield advantage.

Abstract Background In the early stages of the coronavirus disease 2019 (COVID-19) outbreak, the most widely recognised symptoms of the disease were fever, cough, shortness of breath, myalgia, and fatigue. However, in addition to these symptoms, COVID-19 can cause systemic symptoms outside the lungs. Older patients with severe COVID-19 often require admission to the intensive care unit (ICU). Acute rectal ulcer bleeding, characterised by painless, profuse haematochezia, caused by solitary or multiple rectal ulcers, is one of the main causes of severe haematochezia in patients with COVID-19 in the ICU. However, recurrent duodenal ulcer bleeding followed by rectal ulcer bleeding has not previously been reported in older patients during ICU treatment for severe COVID-19. Cases presentation Herein, we report the case of an 81-year-old woman admitted to the emergency department due to severe COVID-19 and transferred to the ICU 2 days later for treatment. During treatment in the ICU, the patient developed recurrent duodenal ulcer bleeding and underwent endoscopic electrocoagulation haemostasis and gastroduodenal artery embolisation. However, the night after the final haemostatic operation, due to rectal ulcer bleeding, the patient discharged bloody stools intermittently, which was effectively controlled using endoscopic electrocoagulation, topical medication, blood transfusion, and haemostatic drugs. Conclusions To the best of our knowledge, this is the first report of duodenal ulcer bleeding followed by rectal ulcer bleeding in an older patient with severe COVID-19 infection. This report creates awareness for clinicians about the multiple and complex gastrointestinal symptoms that may occur during COVID-19 treatment.

Abstract Background Deoxynivalenol (DON), one of the most prevalent mycotoxins, has been found to cause fetal growth retardation in animals. However, limited evidence exists regarding its effects on pregnant women. Methods Maternal urinary concentration of total DON (tDON) and free DON (fDON) in the second trimester was measured using liquid chromatography with tandem mass spectrometry. Provisional daily intake (PDI) of DON was calculated based on tDON concentration. Linear and logistic regression models were used to evaluate the association between DON exposure levels and birth weight, birth length, and the risk of small for gestational age (SGA). Results Among 1538 subjects, the median concentrations of tDON and fDON were 12.1 ng/mL and 5.1 ng/mL, respectively. The PDI values revealed that the median DON intake was 0.7 µg/kg bw, and 35.9% of the total population exceeded the provisional maximum tolerable daily intake (PMTDI) of 1 µg/kg bw. Compared with the lowest tertile, birth weight decreased by 81.11 g (95% CI: -127.00, -35.23) for tDON (P-trend

Abstract Background While some lung adenocarcinoma (LUAD) patients benefit long-term from treatment with immune checkpoint inhibitors, the sad reality is that a considerable proportion of patients do not. The classification of the LUAD tumor microenvironment (TME) can be used to conceptually comprehend primary resistance mechanisms. In addition, the most recent research demonstrates that the release of damage-associated molecular pattern (DAMP) in TME by immunogenic cell death (ICD) may contribute to the adaptive immune response. Currently, however, there is no such comprehensive research on this topic in LUAD patients. Therefore, we set out to investigate how to reverse the poor infiltration characteristics of immune cells and boost antitumor immunity by identifying DAMP model. Methods In this study, ICD-related DAMP genes were selected to investigate their effects on the prognosis of LUAD. To create a risk signature using the TCGA-LUAD cohort, the univariate COX regression and the least absolute shrinkage and selection operator regression were carried out, and the results were verified in a GEO dataset. Subsequently, the multivariate COX regression was applied to establish a prognostic nomogram. And the ESTIMATE and ssGSEA algorithms were utilized to analyze immune activity and the TIDE algorithm was for responsiveness to immunotherapy. Moreover, clinical tissue samples were used to verify the differential expression of 9 DAMP genes in the signature. Results We identified two distinct DAMP molecular subtypes, and there are remarkable differences in survival probability between the two subtypes, and patients with higher levels of DAMP-related genes are “hot tumors” with increased immune activity. In addition, 9 DAMP genes were selected as prognostic signature genes, and clinical outcomes and immunotherapy response were better for participants in the low-risk group. Importantly, according to the area under the curve (AUC) value in evaluating the efficacy of immunotherapy, this signature is superior to existing predictors, such as PD-L1 and TIDE. Conclusions Our study suggests ICD plays an important part in modeling the TME of LUAD patients. And this signature could be utilized as a reliable predictor to estimate clinical outcomes and predict immunotherapy efficacy among LUAD patients.

We extracted the spatial characteristics of the health-related behaviors of 1223 older adults of Tujia, Yao, Miao and Dong ethnicity living in 20 villages in western Hunan, considering three dimensions: spontaneously healthy, health-necessary, and mentally healthy behavior. We constructed separate prediction models using logistic regression, support vector machine, categorical boosting, random decision forest, light gradient boosting machine, and extreme gradient boosting. We then combined these models with Shapley additive explanations to complete a global explanatory analysis to explore the correlation between location and the health behaviors of older adults of different ethnicities living in villages. The support vector model and gradient boosting tree models produced the most accurate simulations of the health behaviors of older adults. We found significant differences in the health behaviors of the older adults in the different villages, noting the preferences of the older adults of specific ethnicities. This study provides a reference for the excavation of the health behavior of older adults and the aging design of village spaces.

Background & Aims: Association studies have greatly refined the important role of the major histocompatibility complex (MHC) region in autoimmune hepatitis (AIH). However, the effects of human leucocyte antigen (HLA) polymorphisms on AIH are not well established. The aim of this study is to systematically characterise the association of MHC variants with AIH in our well-defined cohort of patients. Methods: We performed an imputation-based analysis on the extensive association observed within the MHC region using the Han-MHC reference panel, and tested the comprehensive associations of HLA polymorphisms with AIH in 1622 Chinese AIH type 1 patients and 10,466 population controls. Results: A total of 588 HLA variants were significantly associated with AIH, with HLA-B∗35:01 (p = 8.17 × 10−304; odds ratio [OR] = 7.32) contributing the strongest signal. Stepwise conditional analysis revealed additional independent signals at HLA-B∗08:01 (p = 1.35 × 10−33; OR = 4.26) and rs7765379 (p = 5.08 × 10−18; OR = 1.66). A strong link between the lead HLA variant and clinical phenotypes of AIH was observed: patients with HLA-B∗35:01 were less frequently positive for ANA and tended to have higher serum AST and ALT levels at diagnosis, but lower serum IgG levels. Conclusions: Our study reveals three novel and independent variants at HLA-B∗35:01, HLA-B∗08:01, and rs7765379 associated with AIH across the whole MHC region in the Han Chinese population. The findings illustrate the value of the MHC region in AIH and provide a new perspective for the immunogenetics of AIH. Impact and implications: This study revealed three novel and independent variants associated with autoimmune hepatitis across the whole major histocompatibility complex region in the Han Chinese population. These findings are significant in identifying autoantigens, providing insights into the activation of the autoimmune processes, and further advancing our understanding of the immunogenetic basis underlying autoimmune hepatitis.

Over the past decade, high-throughput sequencing and high-resolution single-cell transcriptome sequencing technologies have undergone rapid development, leading to significant breakthroughs. Traditional molecular biology methods are limited in their ability to unravel cellular-level heterogeneity within woody plant tissues. Consequently, techniques such as single-cell transcriptomics, single-cell epigenetics, and spatial transcriptomics are rapidly gaining popularity in the study of woody plants. In this review, we provide a comprehensive overview of the development of these technologies, with a focus on their applications and the challenges they present in single-cell transcriptome research in woody plants. In particular, we delve into the similarities and differences among the results of current studies and analyze the reasons behind these differences. Furthermore, we put forth potential solutions to overcome the challenges encountered in single-cell transcriptome applications in woody plants. Finally, we discuss the application directions of these techniques to address key challenges in woody plant research in the future.

Background & Aims Acute kidney injury (AKI) is conventionally evaluated by a dynamic change of serum creatinine (Scr). Cystatin C (CysC) seems to be a more accurate biomarker for assessing kidney function. This retrospective multicenter study aims to evaluate whether AKI re-defined by CysC can predict the in-hospital outcomes of patients with liver cirrhosis and acute gastrointestinal bleeding.Methods Overall, 677 cirrhotic patients with acute gastrointestinal bleeding, in whom both Scr and CysC levels were detected at admissions, were screened. eGFRScr, eGFRCysC, and eGFRScr-CysC were calculated. MELD-Na score and AKI were re-evaluated by CysC instead of Scr. Odds ratios (ORs) were calculated in the logistic regression analyses. The receiver operating characteristic (ROC) curve analyses were performed.Results Univariate logistic regression analyses demonstrated that baseline Scr and CysC levels, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, MELD-Na score re-defined by CysC, and AKI re-defined by CysC, but not conventional AKI defined by Scr, were significantly associated with in-hospital death. ROC analyses showed that baseline CysC level, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, and MELD-Na score re-defined by CysC, but not baseline Scr level, could significantly predict the risk of in-hospital death.Conclusions AKI re-defined by CysC may be superior for predicting the in-hospital mortality of cirrhotic patients with acute gastrointestinal bleeding.

Abstract Precision medicine is the ultimate goal for current disease therapies, including tumor and infection. The lack of specific targeted drugs for liver cancer and the lack of specific anti-infective drugs in the treatment of diabetic foot ulcer with infection (DFI) are the representative obstacles in those 2 major diseases currently plaguing human beings. Inventing natural biocompatible polymers derived from natural materials is one of the main development directions of current bio-medical materials. Though previous studies have demonstrated the potential application values of human black hair-derived nanoparticles (HNP) in cancer, methicillin-resistant Staphylococcus aureus (MRSA) infection, and thrombosis scenarios treatments, it still has not solved the problem of low local therapeutic concentration and general targeting ability. Here, we firstly modified the HNP with membrane encapsulations, which endowed these dual-pure natural bio-fabricated materials with better targeting ability at the disease sites with no reduction in photothermal therapy (PTT) effect. HNP coated by red blood cell membrane loaded with DSPE-PEG-cRGD peptide for the therapeutic application of liver cancer greatly prolonged in vivo circulation time and enhanced local targeting efficacy as well as low toxicity; HNP coated by the murine macrophage cell membrane (RAWM) for the DFIs treatment greatly promoted the adhesive ability of HNP on the bacteria and thereby improved the killing effect. Briefly, the appropriate cell membranes camouflaged HNP nanomedicine has the characteristics of excellent photothermal effect, an all-natural source with excellent biocompatibility and easy access, which is expected to have huge potential in both benign and malignant diseases.

Objectives: We aimed to analyze the secular trends in mesothelioma burden, the effect of age, period, and birth cohort, and project the global burden over time. Material and methods: Based on the mesothelioma incidence, mortality, and Disability-Adjusted Life Years (DALYs) data from 1990 to 2019 in Global Burden of Diseases (GBD) database, the annual percentage change (APC) and average annual percent change (AAPC), calculated from joinpoint regression model, was used to describe the burden trends. An age-period-cohort model was utilized to disentangle age, period, and birth cohort effects on mesothelioma incidence and mortality trends. The mesothelioma burden was projected by the Bayesian age-period-cohort (BAPC) model. Results: Globally, there were the significant declines in age-standardized incidence rate (ASIR) (AAPC = −0.4, 95%CI: −0.6,−0.3, P

A pan-cancer analysis demonstrates that pyroptosis is involved in tumor development, prognosis and immunotherapy through the promotion of tumor immunity.

Abstract Background Salicaceae species have diverse sex determination systems and frequent sex chromosome turnovers. However, compared with poplars, the diversity of sex determination in willows is poorly understood, and little is known about the evolutionary forces driving their turnover. Here, we characterized the sex determination in two Salix species, S. chaenomeloides and S. arbutifolia, which have an XY system on chromosome 7 and 15, respectively. Results Based on the assemblies of their sex determination regions, we found that the sex determination mechanism of willows may have underlying similarities with poplars, both involving intact and/or partial homologs of a type A cytokinin response regulator (RR) gene. Comparative analyses suggested that at least two sex turnover events have occurred in Salix, one preserving the ancestral pattern of male heterogamety, and the other changing heterogametic sex from XY to ZW, which could be partly explained by the “deleterious mutation load” and “sexually antagonistic selection” theoretical models. We hypothesize that these repeated turnovers keep sex chromosomes of willow species in a perpetually young state, leading to limited degeneration. Conclusions Our findings further improve the evolutionary trajectory of sex chromosomes in Salicaceae species, explore the evolutionary forces driving the repeated turnovers of their sex chromosomes, and provide a valuable reference for the study of sex chromosomes in other species.

Primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and ulcerative colitis (UC) are immune diseases of the digestive system. Some patients develop overlap syndrome, the presentation of two or more of the clinical, biochemical, immunological, and histological features of these conditions simultaneously or sequentially. The incidence of UC in PSC-AIH overlap syndrome is as high as 50%. In contrast, PSC-AIH overlap syndrome is rare in UC patients. However, because it has a low prevalence and has been studied in less detail, PSC is often misdiagnosed as primary biliary cholangitis (PBC) in its early stage. Herein, we reported a case of a 38-year-old male patient who presented to a clinician in 2014 with irregular bowel habits. A colonoscopy suggested UC. In 2016, the patient was found to have abnormal liver function and was diagnosed with PBC by pathology. He was treated with ursodeoxycholic acid (UDCA) but this had no effect on his liver function. Additional liver biopsies in 2018 indicated PBC-AIH overlap syndrome. The patient refused hormone therapy for personal reasons. Following UDCA monotherapy, his liver function remained abnormal. The patient was reexamined after repeated abnormal liver function tests and bowel symptoms. Systematic laboratory testing, imaging diagnosis, colonoscopy, liver biopsy, and various pathological examinations conducted in 2021 were used to diagnose the patient with PSC-AIH-UC overlap syndrome. He was treated with various drugs, including UDCA, methylprednisolone, mycophenolate mofetil, and mesalazine. His liver function improved significantly after treatment and follow-up is ongoing. Our case report highlights the need to raise awareness about rare and difficult-to-diagnose clinical disorders.

ObjectivesThis study aimed to investigate the effect of vascular risk factors on the outcomes of endolymphatic sac decompression (ESD) surgery in patients with Meniere’s disease.MethodsThe study included 56 patients with Meniere’s disease, who had undergone unilateral ESD surgery. The patients’ vascular risk factors were assessed based on the preoperative 10-year atherosclerotic cardiovascular diseases risk classification. Those with no or low risk were defined as the low-risk group, while those with medium, high, or very high risk were defined as the high-risk group. The correlation between the vascular risk factors and ESD efficacy was evaluated by the comparison of vertigo control grade between the two groups. The functional disability score was also assessed to investigate whether ESD improved the quality of life in Meniere’s disease patients with vascular risk factors.ResultsAfter ESD, 78.95 and 81.08% of patients from the low-risk and high-risk groups, respectively, demonstrated at least grade B vertigo control; no statistically significant difference was observed (p = 0.96). The postoperative functional disability scores in both groups were significantly lower compared with those before surgery (p

Background The prevalence of Helicobacter pylori (H. pylori) keeps rising while the eradication rate continues to decline due to the increasing antibiotic resistance. Regional variations of antimicrobial resistance to H. pylori have been recommended by guidelines in recent years. This study aims to investigate the antibiotic resistance rate of H. pylori and its association with infected subjects’ characteristics in Liaoning Province, an area in north China. Methods Gastric tissues from 178 H. pylori positive participants without previous antibiotic use within four weeks were collected for H. pylori culture. Antibiotic susceptibility to furazolidone (AOZ), tetracycline (TC), levofloxacin (LFX), metronidazole (MET), clarithromycin (CLA), and amoxicillin (AMX) were examined with the agar dilution method. Associations between H. pylori resistance and patient characteristics were further analysed. Results No resistance was observed in AOZ or TC. For LFX, MET, CLA, and AMX, the overall resistance rates were 41.10%, 79.14%, 71.78%, and 22.09% respectively. There were significant differences between resistance to CLA and MALToma (P = 0.021), and between resistance to MET and age (P

Leaf spot is a common disease of Zanthoxylum schinifolium (Z. schinifolium), which can seriously harm the plant’s ability to grow, flower, and fruit. Therefore, it is important to identify the mechanism of leaf spot caused by Pestalotiopsis kenyana (P. kenyana) for thorough comprehension and disease control. In this study, to verify whether the mycotoxins produced by P. kenyana cause leaf spot disease, the best medium for P. kenyana, namely PDB, was used. The mycotoxins were determined by ammonium sulfate precipitation as non-protein substances. The crude mycotoxin of P. kenyana was prepared, and the optimal eluent was eluted with petroleum either/ethyle acetate (3:1, v/v) and purified by silica gel column chromatography and preparative high-performance liquid chromatography to obtain the pure mycotoxins PK-1, PK-2, and PK-3. The PK-3 had the highest toxicity to Z. schinifolium, which may be the primary mycotoxin, according to the biological activity test using the spray method. The physiological and biochemical indexes of Z. schinifolium plants treated with PK-3 mycotoxin were determined. Within 35 days after mycotoxin treatment, the results showed that the protein content and malondialdehyde content of leaves increased over time. The soluble sugar and chlorophyll content decreased over time. The superoxide dismutase activity and catalase activity of the leaves increased first and then decreased, and the above changes were the same as those of Z. schinifolium inoculated with the spore suspension of the pathogen. Therefore, it is believed that the mycotoxin pestalopyrone could be a virulence factor that helps P. kenyana induce the infection of Z. schinifolium. In this study, the pathogenic mechanism of Z. schinifolium leaf spot was discussed, offering a theoretical foundation for improved disease prevention and control.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most fatal cancers. Due to limited strategies for effective treatments, patients with advanced HCC have a very poor prognosis. This study aims to identify new insights in HCC to develop novel strategies for HCC management. Methods The role of WIP1 (wild type p53 induced protein phosphatase1) in HCC was analyzed in HCC cells, xenograft model, DEN (Diethylnitrosamine) induced mice liver cancer model with WIP1 knockout mice, and TCGA database. DNA damage was evaluated by Gene Set Enrichment Analysis, western blotting, comet assay, and Immunofluorescence. Results High expression of WIP1 is associated with the poor prognosis of patients with HCC. Genetically and chemically suppression of WIP1 drastically reduced HCC cell proliferation. Besides, WIP1 knockout retarded DEN induced mice hepato-carcinogenesis. Mechanically, WIP1 inhibition induced DNA damage by increasing H2AX phosphorylation (γH2AX). Therefore, suppression of WIP1 and PARP induced synthetic lethality in HCC in vitro and in vivo by augmenting DNA damage. Conclusion WIP1 plays an oncogenic effect in HCC development, and targeting WIP1-dependent DNA damage repair alone or in combination with PARP inhibition might be a reasonable strategy for HCC management. Video abstract

Methylmercury (MeHg) is a neurodevelopmental toxicant that is widespread in the environment and food. Considering the presence of multiple sources of MeHg exposure in the environment, the burden attributable to different exposure sources needs to be determined. This study aimed to estimate the burden of mild intellectual disability (MID) caused by in-utero exposure to MeHg and identify the attributable burden related to MeHg exposure from different sources in China. We applied the hair mercury concentrations from studies to evaluate the burden of MID associated with maternal MeHg exposure and quantify it by disability-adjusted life years (DALYs). The DALYs attributable to MeHg exposure sources were calculated by combining the total DALYs and the contribution rates of various sources of MeHg exposure. The maternal MeHg exposure resulted in 6504 MID cases and a loss of 63,354 DALYs in China in 2017. The contribution rates of aquatic products and rice were 52.2% and 27.1%, respectively, leading to health losses of 28,115 and 18,011 DALYs. The burden of MeHg-induced MID associated with aquatic products was high in coastal areas. Several sites such as Zhejiang, Hunan, and Guangxi had high DALYs caused by rice MeHg exposure. Regions with high DALYs of MID related to MeHg exposure require more attention. Local governments should establish targeted measures to reduce MeHg exposure, thus preventing health loss.

Abstract Cell membrane encapsulation is a growing concept in nanomedicine, for it achieves the purpose of camouflage nanoparticles, realizing the convenience for drug delivery, bio‐imaging, and detoxification. Cell membranes are constructed by bilayer lipid phospholipid layers, which have unique properties in cellular uptake mechanism, targeting ability, immunomodulation, and regeneration. Current medical applications of cell membranes include cancers, inflammations, regenerations, and so on. In this article, a general bibliometric overview is conducted of cell membrane‐coated nanoparticles covering 11 years of evolution in order to provide researchers in the field with a comprehensive view of the relevant achievements and trends. The authors analyze the data from Web of Science Core Collection database, and extract the annual publications and citations, most productive countries/regions, most influential scholars, the collaborations of journals and institutions. The authors also divided cell membranes into several subgroups to further understand the application of different cell membranes in medical scenarios. This study summarizes the current research overview in cell membrane‐coated nanoparticles and intuitively provides a direction for future research.

Current treatments for advanced hepatocellular carcinoma (HCC) have limited success in improving patients’ quality of life and prolonging life expectancy. The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies. Recently, there has been increased interest in oncolytic viruses (OVs) as a therapeutic modality for HCC. OVs undergo selective replication in cancerous tissues and kill tumor cells. Strikingly, pexastimogene devacirepvec (Pexa-Vec) was granted an orphan drug status in HCC by the U.S. Food and Drug Administration (FDA) in 2013. Meanwhile, dozens of OVs are being tested in HCC-directed clinical and preclinical trials. In this review, the pathogenesis and current therapies of HCC are outlined. Next, we summarize multiple OVs as single therapeutic agents for the treatment of HCC, which have demonstrated certain efficacy and low toxicity. Emerging carrier cell-, bioengineered cell mimetic- or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described. In addition, we highlight the combination treatments between oncolytic virotherapy and other modalities. Finally, the clinical challenges and prospects of OV-based biotherapy are discussed, with the aim of continuing to develop a fascinating approach in HCC patients.

Gastroesophageal cancers (GECs) comprise malignancies in the stomach, esophagus, and gastroesophageal junction. Despite ongoing improvements in chemoradiotherapy, the clinical outcomes of GEC have not significantly improved over the years, and treatment remains challenging. Immune checkpoint inhibitors (ICIs) have been the subject of clinical trials worldwide for several years. Encouraging results have been reported in different countries, but further research is required to apply ICIs in the clinical care of patients with GEC. This review summarizes completed and ongoing clinical trials with programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway blockers in GEC and current biomarkers used for predicting PD-1/PD-L1 blockade efficacy. This review captures the main findings of PD-1/PD-L1 antibodies combined with chemotherapy as an effective first-line treatment and a monotherapy in second-line or more treatment and in maintenance therapy. This review aims to provide insight that will help guide future research and clinical trials, thereby improving the outcomes of patients with GEC.

PurposeLymph node (LN) involvement is a key factor in ovarian clear cell carcinoma (OCCC) although, there several indicators can be used to define prognosis. This study examines the prognostic performances of each indicator for OCCC patients by comparing the number of lymph nodes examined (TNLE), the number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of metastatic lymph nodes (LODDS).Methods1,300 OCCC patients who underwent lymphadenectomy between 2004 and 2015 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Primary outcomes were Overall Survival (OS) and the cumulative incidence of Cancer-Specific Survival (CSS). Kaplan–Meier’s and Fine-Gray’s tests were implemented to assess OS and CSS rates. After conducting multivariate analysis, nomograms using OS and CSS were constructed based upon an improved LN system. Each nomograms’ performance was assessed using Receiver Operating Characteristics (ROC) curves, calibration curves, and the C-index which were compared to traditional cancer staging systems.ResultsMultivariate Cox’s regression analysis was used to assess prognostic factors for OS, including age, T stage, M stage, SEER stage, and LODDS. To account for the CSS endpoint, a proportional subdistribution hazard model was implemented which suggested that the T stage, M stage, SEER stage, and LNR are all significant. This enabled us to develop a LODDS-based nomogram for OS and a LNR-based nomogram for CSS. C-indexes for both the OS and CSS nomograms were higher than the traditional American Joint Committee on Cancer (AJCC), 8th edition, staging system. Area Under the Curve (AUC) values for predicting 3- and 5-year OS and CSS between nomograms also highlighted an improvement upon the AJCC staging system. Calibration curves also performed with consistency, which was verified using a validation cohort.ConclusionsLODDS and LNR may be better predictors than N stage, TNLE, and PLNs. For OCCC patients, both the LODDS-based and LNR-based nomograms performed better than the AJCC staging system at predicting OS and CSS. However, further large sample, real-world studies are necessary to validate the assertion.

Ankylosing spondylitis (AS) is a type of chronic rheumatic immune disease, and the crucial point of AS treatment is identifying the correct stage of the disease. However, there is a lack of effective diagnostic methods for AS staging. The primary objective of this study was to perform an untargeted metabolomic approach in AS patients in an effort to reveal metabolic differences between patients in remission and acute stages. Serum samples from 40 controls and 57 AS patients were analyzed via gas chromatography–mass spectrometry (GC–MS). Twenty-four kinds of differential metabolites were identified between the healthy controls and AS patients, mainly involving valine/leucine/isoleucine biosynthesis and degradation, phenylalanine/tyrosine/tryptophan biosynthesis, glutathione metabolism, etc. Furthermore, the levels of fatty acids (linoleate, dodecanoate, hexadecanoate, and octadecanoate), amino acids (serine and pyroglutamate), 2-hydroxybutanoate, glucose, etc., were lower in patients in the acute stage than those in the remission stage, which may be associated with the aggravated inflammatory response and elevated oxidative stress in the acute stage. Multiple stage-specific metabolites were significantly correlated with inflammatory indicators (CRP and ESR). In addition, the combination of serum 2-hydroxybutanoate and hexadecanoate plays a significant role in the diagnosis of AS stages. These metabolomics-based findings provide new perspectives for AS staging, treatment, and pathogenesis studies.

Abstract p62/SQSTM1 is frequently up-regulated in many cancers including hepatocellular carcinoma. Highly expressed p62 promotes hepato-carcinogenesis by activating many signaling pathways including Nrf2, mTORC1, and NFκB signaling. However, the underlying mechanism for p62 up-regulation in hepatocellular carcinoma remains largely unclear. Herein, we confirmed that p62 was up-regulated in hepatocellular carcinoma and its higher expression was associated with shorter overall survival in patients. The knockdown of p62 in hepatocellular carcinoma cells decreased cell growth in vitro and in vivo. Intriguingly, p62 protein stability could be reduced by its acetylation at lysine 295, which was regulated by deacetylase Sirt1 and acetyltransferase GCN5. Acetylated p62 increased its association with the E3 ligase Keap1, which facilitated its poly-ubiquitination-dependent proteasomal degradation. Moreover, Sirt1 was up-regulated to deacetylate and stabilize p62 in hepatocellular carcinoma. Additionally, Hepatocyte Sirt1 conditional knockout mice developed much fewer liver tumors after Diethynitrosamine treatment, which could be reversed by the re-introduction of exogenous p62. Taken together, Sirt1 deacetylates p62 at lysine 295 to disturb Keap1-mediated p62 poly-ubiquitination, thus up-regulating p62 expression to promote hepato-carcinogenesis. Therefore, targeting Sirt1 or p62 is a reasonable strategy for the treatment of hepatocellular carcinoma.

Pancreatic neuroendocrine neoplasms (PNEN) are tumors that originate from neuroendocrine cells. Only about 1% patients are related to mutation of tuberous sclerosis complex gene. Here, we reported a rare case with involvement of multiple organs and space-occupying lesions. Initially, the patient was thought to have metastasis of a pancreatic tumor. However, the patient was diagnosed as pancreatic neuroendocrine tumors, liver perivascular epithelioid tumors, splenic hamartoma, and renal angiomyolipoma by pathological examination after surgery. We performed genetic mutation detection to identify that tuberous sclerosis complex 2 gene presented with a heterozygous variant. Tuberous sclerosis often presents with widespread tumors, but it is less common to present with pancreatic neuroendocrine tumors and liver perivascular tumors as highlighted in the case. So we analyzed the relationship between TSC gene mutations and related tumors. And we also reviewed the current molecular mechanisms and treatments for tuberous sclerosis complex.

Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide due to the sedentary and overeating lifestyle. Yet, the pathophysiology of MAFLD is still unclear and no drug has been approved for MAFLD treatment. Extracellular vesicles (EVs) are heterogenous membrane-bound particles released from almost all types of cells. These nano-sized particles mediate intercellular communication through their bioactive cargos including nucleic acids, proteins, and lipids. The EVs modulate metabolic homeostasis via communication between adipose tissue and liver. The dysregulation of lipid metabolism leads to inflammation in liver and the number and compounds of EVs are changed during MAFLD. The injured hepatocytes secrete EVs to induce the migration of bone marrow-derived monocytes and the activation of macrophages in liver. The EVs secreted by different cells regulate the alteration of hepatic stellate cell (HSC) phenotypes and HSC activation gives rise to liver fibrosis. Based on the participation of EVs in MAFLD progression, we discuss the prospects of EVs as a therapeutic target and their application in drug delivery.

Immune checkpoint inhibitors (ICIs) have opened up a new way for tumor therapy but simultaneously led to the occurrence of immune-related adverse events. We report a case of successful treatment of PD-1 inhibitor-associated colitis with fecal microbiota transplantation (FMT). The patient was a palatal malignant melanoma who developed diarrhea and hematochezia accompanied by fever, gastrointestinal bleeding, and infection after the third treatment with PD-1 (Toripalimab). The patient received general treatment unsuccessful, corticosteroid therapy after initial success but rapid loss of response, and finally successful treatment after fecal microbiota transplantation.

Background: Acrylamide is widely found in food as a side-product of high-temperature heating of starch-rich food. It has attracted much attention because of its neurotoxicity and carcinogenicity. However, the cancer risk and disease burden of dietary acrylamide exposure have not been quantified in China. Objective: To estimate the cancer risk and the disease burden attributable to dietary acrylamide exposure and quantify its health hazards. Method: We first performed an exposure assessment of acrylamide in food, based on which the incremental excess lifetime cancer risk (ELCR) was calculated for cancer risk assessment. The DisMod Ⅱ software and the DALY calculator in R were used to calculate the disease burden due to dietary acrylamide exposure. Results: Average dietary acrylamide exposure in males was 0.1531 μg·kg−1·d−1 and that in females was 0.1554 μg·kg−1·d−1, resulting in an ELCR of 7.81 × 10−5 for males and 7.92 × 10−5 for females in China. The dietary acrylamide exposure resulted in about 23,688.09 DALYs of cancers among the Chinese population in 2016, including 1331.93 DALYs of breast cancer, 243.32 DALYs of endometrial cancer, 248.91 DALYs of ovarian cancer, and 176.28 DALYs of kidney cancer, respectively. Conclusion: The health hazards of dietary acrylamide exposure deserve attention. The burden of disease assessment could quantify the health hazards of food contaminants for prioritizing policies.

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.

Purpose – Service innovation is a key source of competence for service enterprises. Along with the emergence of crowdsourcing platforms, consumers are frequently involved in the process of service innovation. In this paper, the authors describe the crowdsourcing ideation website—MyStarbucksIdea.com—and find the motivations of customer-involved service innovation. Design/methodology/approach – Using a rich data set obtained from the website MyStarbucksIdea.com, a dynamic structural model is proposed to illuminate the learning process of consumers. Findings – The results indicate that initially individuals tend to underestimate the costs of the firm for implementing their ideas but overestimate the value of their ideas. By observing peer votes and feedbacks, individuals gradually learn about the true value of ideas, as well as the cost structure of the firm. Overall, the authors find that the cumulative feedback rate and the average potential of ideas will first increase and then decline. Originality/value – First, the previous researches concerning the crowdsourcing show that the creative implementation rate is low and the number of creative ideas decreases, and few scholars have studied the causes behind the problems. Second, the data used in this paper are true and valid, and it is difficult to obtain now. These data can provide strong empirical support for the model proposed in this paper. Third, it is relatively novel to combine the customer learning mechanism and heterogeneity theory to explain the phenomenon of reduced creativity and low implementation rate in crowdsourcing platform, and the research results can provide a reasonable reference for the construction of this industry.

BackgroundTransforming growth factor-beta (TGF-β) signaling is essential in initialization and progression of hepatocellular carcinoma (HCC). Therefore, a treatment targeting TGF-β pathway may be a promising option for HCC control.MethodsFirst, publicly available RNA-seq datasets and clinical characteristics of 374 HCC patients in The Cancer Genome Atlas (TCGA) database were downloaded. Then, Cox regression analysis and LASSO analysis were used to construct a prognostic model for TGF-β family genes. The area under the curve (AUC) of the risk signature was calculated to evaluate the predictive power of the model. Cox regression analysis was applied to predict whether TGF-β1 can be an independent prognosis factor for HCC. Next, hazard ratio and survival analyses were performed to investigate the correlation between TGF-β1 expression and survival time. Furthermore, differential expression level of TGF-β1 in HCC tissues and cells was determined. In addition, Gene Set Enrichment Analysis (GSEA) identified the top significantly activated and inhibited signal pathways related to high expression of TGF-β1. Finally, the CIBERSORT tool was adopted to correlate the tumor-infiltrating immune cells (TICs) with TGF-β1 expression in HCC cohorts.ResultsCox regression analysis and LASSO analysis revealed that seven TGF-β family members (including TGF-β1) could be used as prognostic factors for HCC. Interestingly, TGF-β1 was demonstrated to be an independent prognostic factor of HCC. RT-qPCR and immunofluorescence staining confirmed the high expression of TGF-β1 in HCC cell lines and tissues, which is significantly related to pathological classifications, poor prognosis, and short survival time. Finally, GSEA and CIBERSORT analyses suggested that TGF-β1 may interact with various immune cells and influence the prognosis of HCC patients through Tregs and γδ T cells.ConclusionWe established a novel prognostic prediction method to predict the risk scores of TGF-β genes in HCC prognosis. TGF-β1 is highly expressed in HCC cell lines and tissues, correlates to poor prognosis, and thus can be used as a potential biomarker to predict HCC prognosis. We showed that TGF-β1 may play its roles in HCC prognosis by modulating the immune microenvironment of tumor cells. Our data may shed more light on better understanding the role of TGF-β1 in HCC prognosis.

Background and Objectives: Inorganic arsenic (iAs) can cause a wide range of health problems, including coronary heart disease (CHD) and lung, bladder, and skin cancer. Although dietary iAs intake is the primary source of iAs, the burden of CHD and cancers from dietary iAs exposure in Chinese adults has not been well known. Methods: To estimate the iAs exposure level in Chinese adults’ diet, we systematically collected food-specific iAs concentrations in China from Chinese and English literature databases during 2000-2020. Food consumption was extracted from two nationwide food and nutrition surveys in China. The population attributable fraction was calculated based on the dose-response relationship between iAs and CHD risk. Combining the 2016 Chinese tumor registry data, we calculated the annual incidence of cancer from dietary iAs exposure to measure the disability-adjusted life year (DALY) in 2016. Findings: The total amount of daily foodborne iAs intake was 0.55 μg/kg bw/day among Chinese adults. The DALY of foodborne iAs-associated CHD was 3,017,510, which accounted for 10.18% of total CHD DALY in Chinese adults in 2016. Moreover, the carcinogenic DALY for lung cancer, bladder cancer, and skin cancer of Chinese residents in 2016 related to dietary iAs was 314.24, 9.89, and 167.32 thousand, accounting for 2.05%, 1.70%, and 35.5% of the total cancer burden, respectively. Conclusions: Our findings suggested that dietary iAs exposure causes a substantial disease burden in Chinese adults. More efforts for foodborne iAs control are critical to reducing the disease burden of CHD and cancer in China and other countries with similar dietary patterns.

ObjectiveTo investigate the incidence and risk factors of gallbladder stones and polyps in individuals undergoing physical examinations in Liaoning province, China.MethodsThis is a retrospective study of adults who underwent routine health examinations at Xikang Medical Center in Liaoning Province (Shenyang, Dandong, and Dalian) from 01/2016 to 12/2020. The routine health examination included anthropometry, blood tests, and liver ultrasound. Based on liver ultrasound results, patients were grouped into those with gallbladder stones, those with gallbladder polyps, those with both stones and polyps, and those with neither.ResultsOf the 284,129 included subjects, 6,537 (2.30%) were diagnosed with gallbladder stones, and 18,873 (6.64%) were diagnosed with gallbladder polyps. The overall prevalence in Liaoning province increased each year, peaking in 2020. The prevalence of gallbladder stones was higher among females than males (2.39% vs. 2.23%, respectively), while the prevalence of gallbladder polyps was higher among males. The gallbladder polyp group had higher BMI, FBG, SBP, DBP, TG, TC, LDL-C, HDL-C, AST, ALP, GGT, BUN, Scr, SUA. Except for HDL-C, all factors were also higher in the gallbladder stone group. Patients with fatty liver had a higher prevalence of gallbladder stones and polyps than participants without fatty liver.ConclusionThe prevalence of gallbladder stones and polyps in Liaoning varies by sex, economic status of the city of residence, BMI, and metabolic indicators.

Research on the biological role of exosomes is rapidly developing, and recent evidence suggests that exosomal effects involve ferroptosis. Exosomes derived from different tissues inhibit ferroptosis, which increases tumour cell chemoresistance. Therefore, exosome-mediated regulation of ferroptosis may be leveraged to design anticancer drugs. This review discusses three pathways of exosome-mediated inhibition of ferroptosis: (1) the Fenton reaction; (2) the ferroptosis defence system, including the Xc-GSH-GPX4 axis and the FSP1/CoQ10/NAD(P)H axis; and (3) lipid peroxidation. We also summarize three recent approaches for combining exosomes and ferroptosis in oncology therapy: (1) promoting exosome-inhibited ferroptosis to enhance chemotherapy; (2) encapsulating exosomes with ferroptosis inducers to inhibit cancers; and (3) developing therapies that combine exosomal inhibitors and ferroptosis inducers. This review will contribute toward establishing effective cancer therapies.