Synergistic Effects of Matrix Biophysical Properties on Gastric Cancer Cell Behavior via Integrin-Mediated Cell-ECM Interactions.

The biophysical properties of the extracellular matrix (ECM) play a pivotal role in modulating cancer progression via cell-ECM interactions. However, the biophysical properties specific to gastric cancer (GC) remain largely unexplored. Pertinently, GC ECM shows significantly heterogeneous metamorphoses, such as matrix stiffening and intricate restructuring. By combining collagen I and alginate, this study designs an in vitro biomimetic hydrogel platform to independently modulate matrix stiffness and structure across a physiological stiffness spectrum while preserving consistent collagen concentration and fiber topography. With this platform, this study assesses the impacts of matrix biophysical properties on cell proliferation, migration, invasion, and other pivotal dynamics of AGS. The findings spotlight a compelling interplay between matrix stiffness and structure, influencing both cellular responses and ECM remodeling. Furthermore, this investigation into the integrin/actin-collagen interplay reinforces the central role of integrins in mediating cell-ECM interactions, reciprocally sculpting cell conduct, and ECM adaptation. Collectively, this study reveals a previously unidentified role of ECM biophysical properties in GC malignant potential and provides insight into the bidirectional mechanical cell-ECM interactions, which may facilitate the development of novel therapeutic horizons.

Metagenomic analysis of the gut virome in patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder, is recognized for its association with alterations in the gut microbiome and metabolome. This study delves into the largely unexplored domain of the gut virome in IBS patients. We conducted a comprehensive analysis of the fecal metagenomic data set from 277 IBS patients and 84 healthy controls to characterize the gut viral community. Our findings revealed a distinct gut virome in IBS patients compared to healthy individuals, marked by significant variances in between-sample diversity and altered abundances of 127 viral operational taxonomic units (vOTUs). Specifically, 111 vOTUs, predominantly belonging to crAss-like, Siphoviridae, Myoviridae, and Quimbyviridae families, were more abundant in IBS patients, whereas the healthy control group exhibited enrichment of 16 vOTUs from multiple families. We also investigated the interplay between the gut virome and bacteriome, identifying a correlation between IBS-enriched bacteria like Klebsiella pneumoniae, Fusobacterium varium, and Ruminococcus gnavus, and the IBS-associated vOTUs. Furthermore, we assessed the potential of gut viral signatures in predicting IBS, achieving a notable area under the receiver operator characteristic curve (AUC) of 0.834. These findings highlight significant shifts in the viral diversity, taxonomic distribution, and functional composition of the gut virome in IBS patients, suggesting the potential role of the gut virome in IBS pathogenesis and opening new avenues for diagnostic and therapeutic strategies targeting the gut virome in IBS management.

Metagenomic analysis reveals altered gut virome and diagnostic potential in pancreatic cancer.

Pancreatic cancer (PC) is a highly aggressive malignancy with a poor prognosis, making early diagnosis crucial for improving patient outcomes. While the gut microbiome, including bacteria and viruses, is believed to be essential in cancer pathogenicity, the potential contribution of the gut virome to PC remains largely unexplored. In this study, we conducted a comparative analysis of the gut viral compositional and functional profiles between PC patients and healthy controls, based on fecal metagenomes from two publicly available data sets comprising a total of 101 patients and 82 healthy controls. Our results revealed a decreasing trend in the gut virome diversity of PC patients with disease severity. We identified significant alterations in the overall viral structure of PC patients, with a meta-analysis revealing 219 viral operational taxonomic units (vOTUs) showing significant differences in relative abundance between patients and healthy controls. Among these, 65 vOTUs were enriched in PC patients, and 154 were reduced. Host prediction revealed that PC-enriched vOTUs preferentially infected bacterial members of Veillonellaceae, Enterobacteriaceae, Fusobacteriaceae, and Streptococcaceae, while PC-reduced vOTUs were more likely to infect Ruminococcaceae, Lachnospiraceae, Clostridiaceae, Oscillospiraceae, and Peptostreptococcaceae. Furthermore, we constructed random forest models based on the PC-associated vOTUs, achieving an optimal average area under the curve (AUC) of up to 0.879 for distinguishing patients from controls. Through additional 10 public cohorts, we demonstrated the reproducibility and high specificity of these viral signatures. Our study suggests that the gut virome may play a role in PC development and could serve as a promising target for PC diagnosis and therapeutic intervention. Future studies should further explore the underlying mechanisms of gut virus-bacteria interactions and validate the diagnostic models in larger and more diverse populations.

The staining results of early gastric cancer by indigo carmine chromoendoscopy associated with histological structure: a retrospective study.

BACKGROUND: At present, conventional endoscopy and chromoendoscopy using indigo carmine (IC) is a very useful method to determine the demarcation line (DL) of early gastric cancer lesions, but it is not suitable for all lesions. AIMS: This study aimed to determine the applicable conditions for IC chromoendoscopy. METHODS: We retrospectively evaluated 187 lesions in 181 patients who had an endoscopic diagnosis of EGC and were treated with endoscopic submucosal dissection (ESD). According to the existence of the DL between the lesion mucosa and normal mucosa with IC chromoendoscopy, the lesions were divided into two groups: clear group and unclear group. Clinicopathological characteristics were evaluated in each group. From January 2022 to March 2023, the postoperative pathological sections of 19 lesions (81 slices) in the clear group and 19 lesions (80 slices) in unclear group were scanned with high definition, and the crypt structure between the two groups was evaluated. RESULTS: There was no significant difference in clinical factors between the clear group and unclear group. There were significant differences in crypt area, crypt length, and crypt opening diameter between the two groups. In the clear group, there were significant differences in crypt area, crypt length, and crypt opening diameter between the normal area and cancer area, but there was no significant difference in the unclear group. CONCLUSIONS: The margins of lesions with fused or absent crypt structures, a small crypt area, a short crypt length, and a short crypt opening diameter can be easily determined with IC chromoendoscopy.

Nitric oxide and ion channels mediate L-cysteine-induced inhibition of colonic smooth muscle contraction.

Previous studies have suggested that L-cysteine regulates gut motility through hydrogen sulfide. However, the mechanisms involved in the L-cysteine-induced response have not been extensively studied. This study aimed to investigate the underlying mechanisms of action of L-cysteine on spontaneous contraction of rat colon. Longitudinal and circular muscle strips from rat middle colon were prepared to measure the spontaneous contractile activities of colon in an organ bath system. Whole-cell voltage-clamp techniques were applied to record the currents of L-type voltage-dependent Ca2+ channels (VDCCs) and voltage-gated K+ channels (Kv) in isolated smooth muscle cells (SMCs) from colon. L-cysteine inhibited the spontaneous contraction of longitudinal and circular muscle strips from the rat colon in a concentration-dependent manner. The inhibition induced by L-cysteine was significantly decreased by inhibitors of H2S synthesis (p < 0.05). Furthermore, the suppression induced by L-cysteine was partially attenuated by tetrodotoxin, L-NNA and glibenclamide (p < 0.05). Whole-cell voltage-clamp recordings showed that L-cysteine caused a remarkable reduction in the peak currents of VDCCs and significantly increased the membrane currents of Kv channels in isolated SMCs (p < 0.05). We concluded that L-cysteine inhibits the contractile activities of smooth muscle strips from the rat colon. The relaxation in response to L-cysteine may be in part mediated by a nitrergic pathway and by inhibiting the VDCCs in combination with a direct activation of the KV channels and KATP channels.

Lactate combined with SOFA score for improving the predictive efficacy of SOFA score in patients with severe heatstroke.

BACKGROUND: The relationship between lactate levels and multiple organ dysfunction in patients with severe heatstroke remains unclear. In this study, we aimed to elucidate the clinical significance of lactate in severe heatstroke prognosis and assess whether incorporating lactate in the SOFA score improves its predictive efficacy. METHODS: This study was a multicenter retrospective cohort investigation included 275 patients. Logistic regression analysis was performed to examine the relationship between lactate levels and patient outcomes and complications, including acute kidney injury (AKI), disseminated intravascular coagulation (DIC), and myocardial injury. Further, receiver operating characteristic (ROC) curves and clinical decision curve analysis (DCA) were used to evaluate the predictive power of lactate and SOFA scores in severe heatstroke-associated death. Lastly, the Kaplan-Meier survival curve was employed to differentiate the survival rates among the various patient groups. RESULTS: After adjusting for confounding factors, lactate was demonstrated as an independent risk factor for death (OR = 1.353, 95% CI [1.170, 1.569]), AKI (OR = 1.158, 95% CI [1.007, 1.332]), DIC (OR = 1.426, 95% CI [1.225, 1.659]), and myocardial injury (OR = 2.039, 95% CI [1.553, 2.679]). The area under the curve (AUC) of lactate for predicting death from severe heatstroke was 0.7540, with a cutoff of 3.35. The Kaplan-Meier survival curve analysis showed that patients with elevated lactate levels had higher mortality rates. Additionally, the ROC curves demonstrated that combining lactate with the SOFA score provided better predictive efficacy than the SOFA score alone in patients with severe heatstroke (AUC: 0.9025 vs. 0.8773, DeLong test, P < 0.001). Finally, the DCA curve revealed a higher net clinical benefit rate for lactate combined with the SOFA score. CONCLUSIONS: Lactate is an independent risk factor for severe heatstroke-related death as well as a risk factor for AKI, DIC, and myocardial injury associated with severe heatstroke. Thus, combining lactate with the SOFA score can significantly improve its predictive efficacy in patients with severe heatstroke.

An Integrated LSTM-Rule-Based Fusion Method for the Localization of Intelligent Vehicles in a Complex Environment.

To improve the accuracy and robustness of autonomous vehicle localization in a complex environment, this paper proposes a multi-source fusion localization method that integrates GPS, laser SLAM, and an odometer model. Firstly, fuzzy rules are constructed to accurately analyze the in-vehicle localization deviation and confidence factor to improve the initial fusion localization accuracy. Then, an odometer model for obtaining the projected localization trajectory is constructed. Considering the high accuracy of the odometer's projected trajectory within a short distance, we used the shape of the projected localization trajectory to inhibit the initial fusion localization noise and used trajectory matching to obtain an accurate localization. Finally, the Dual-LSTM network is constructed to predict the localization and build an electronic fence to guarantee the safety of the vehicle while also guaranteeing the updating of short-distance localization information of the vehicle when the above-mentioned fusion localization is unreliable. Under the limited arithmetic condition of the vehicle platform, accurate and reliable localization is realized in a complex environment. The proposed method was verified by long-time operation on the real vehicle platform, and compared with the EKF fusion localization method, the average root mean square error of localization was reduced by 66%, reaching centimeter-level localization accuracy.

Impact of the COVID-19 pandemic on liver disease-related mortality rates in the United States.

BACKGROUND & AIMS: The pandemic has resulted in an increase of deaths not directly related to COVID-19 infection. We aimed to use a national death dataset to determine the impact of the pandemic on people with liver disease in the USA, focusing on alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). METHODS: Using data from the National Vital Statistic System from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform and ICD-10 codes, we identified deaths associated with liver disease. We evaluated observed vs. predicted mortality for 2020-2021 based on trends from 2010-2019 with joinpoint and prediction modelling analysis. RESULTS: Among 626,090 chronic liver disease-related deaths between 2010 and 2021, Age-standardised mortality rates (ASMRs) for ALD dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 3.5% to 17.6%, p <0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (15.67 vs. 13.04) and 2021 (17.42 vs. 13.41). ASMR for NAFLD also increased during the pandemic (APC: 14.5%), whereas the rates for hepatitis B and C decreased. Notably, the ASMR rise for ALD was most pronounced in non-Hispanic Whites, Blacks, and Alaska Indians/Native Americans (APC: 11.7%, 10.8%, 18.0%, all p <0.05), with similar but less critical findings for NAFLD, whereas rates were steady for non-Hispanic Asians throughout 2010-2021 (APC: 4.9%). The ASMR rise for ALD was particularly severe for the 25-44 age group (APC: 34.6%, vs. 13.7% and 12.6% for 45-64 and ≥65, all p <0.01), which were also all higher than pre-COVID-19 rates (all p <0.01). CONCLUSIONS: ASMRs for ALD and NAFLD increased at an alarming rate during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. IMPACT AND IMPLICATIONS: The pandemic has led to an increase of deaths directly and indirectly related to SARS-CoV-2 infection. As shown in this study, age-standardised mortality rates for alcohol-associated liver disease and non-alcoholic fatty liver disease substantially increased during the COVID-19 pandemic in the USA and far exceeded expected levels predicted from past trends, especially among the young, non-Hispanic White, and Alaska Indian/Native American populations. However, much of this increase was not directly related to COVID-19. Therefore, for the ongoing pandemic as well as its recovery phase, adherence to regular monitoring and care for people with chronic liver disease should be prioritised and awareness should be raised among patients, care providers, healthcare systems, and public health policy makers.

Intestinal Autotransplantation for Locally Advanced or Locally Recurrent Colon Cancer Invading SMA.

OBJECTIVE: To examine the outcomes of intestinal autotransplantation (IATx) in patients with locally advanced or recurrent colon cancer (LACC or LRCC) invading the superior mesenteric artery (SMA). BACKGROUND: SMA Involvement in LACC or LRCC is deemed unresectable and is associated with a poor prognosis. Combined extended resections of multiple organs together with SMA, followed by IATx may offer favorable clinical outcomes. However, data on its safety and efficacy are scarce. DESIGN: This retrospective cohort study included patients undergoing IATx between May 2018 and December 2022 in intestinal transplant programs at two university-affiliated hospitals in China. Patients with LACC or LRCC concomitantly with SMA contact of more than 180° were included. Patients with a locoregional peritoneal, pelvic, or distal metastasis were excluded. RESULTS: Ten patients underwent either IATx combined with pancreaticoduodenectomy (n=8) or IATx alone (n=2). Eight patients (80%) were male, and the median age was 55 years (range, 32 - 71 y). The Kaplan-Meier estimates for recurrence-free survival and overall survival at 3 years after IATx were 68% and 80%, respectively. No perioperative deaths occurred. All ten patients experienced postoperative complications including Clavien-Dindo grade I (n=1), grade II (n=4), grade IIIa (n=1), grade IIIb (n=3) and grade IVa (n=1), which comprised acute venous thromboses, upper gastrointestinal hemorrhage, anastomotic leak, gastropareses and significant pleural effusions. With an average follow-up of 23.9 months, eight patients (80%) were currently alive without evidence of disease. CONCLUSION: Extended resection for LACC or LRCC invading SMA can be performed safely and is associated with prolonged survival.

Role of Hydrogen Sulfide in the Development of Colonic Hypomotility in a Diabetic Mouse Model Induced by Streptozocin.

Hydrogen sulfide (H2S), a novel gasotransmitter, is involved in the regulation of gut motility. Alterations in the balance of H2S play an important role in the pathogenesis of diabetes. This study was conducted to investigate the role of H2S in the colonic hypomotility of mice with streptozotocin (STZ)-induced diabetes. A single intraperitoneal injection of STZ was used to induce the type 1 diabetes model. Male C57BL/6 mice were randomized into a control group and an STZ-treated group. Immunohistochemistry, Western blotting, H2S generation, organ bath studies and whole-cell patch clamp techniques were carried out in single smooth muscle cells (SMCs) of the colon. We found that STZ-induced diabetic mice showed decreased stool output, impaired colonic contractility, and increased endogenous generation of H2S (p < 0.05). H2S-producing enzymes were upregulated in the colon tissues of diabetic mice (p < 0.05). The exogenous H2S donor sodium hydrosulfide (NaHS) elicited a biphasic action on colonic muscle contraction with excitation at lower concentrations and inhibition at higher concentrations. NaHS (0.1 mM) increased the currents of voltage-dependent calcium channels (VDCCs), while NaHS at 0.5 mM and 1.5 mM induced inhibition. Furthermore, NaHS reduced the currents of both voltage-dependent potassium (KV) channels and large conductance calcium-activated potassium (BK) channels in a dose-dependent manner. These results show that spontaneous contraction of colonic muscle strips from diabetic mice induced by STZ was significantly decreased, which may underlie the constipation associated with diabetes mellitus (DM). H2S overproduction with subsequent suppression of muscle contraction via VDCCs on SMCs may contribute in part to the pathogenesis of colonic hypomotility in DM. SIGNIFICANCE STATEMENT: Hydrogen sulfide may exhibit a biphasic effect on colonic motility in mice by regulating the activities of voltage-dependent calcium channels and voltage-dependent and large conductance calcium activated potassium channels. H2S overproduction with subsequent suppression of muscle contraction via VDCCs may contribute to the pathogenesis of colonic hypomotility in diabetes mellitus.

CRISPR/Cas9-mediated knock-in of masu salmon (Oncorhyncus masou) elongase gene in the melanocortin-4 (mc4r) coding region of channel catfish (Ictalurus punctatus) genome.

Channel catfish, Ictalurus punctatus, have limited ability to synthesize Ω-3 fatty acids. The ccßA-msElovl2 transgene containing masu salmon, Oncorhynchus masou, elongase gene driven by the common carp, Cyprinus carpio, ß-actin promoter was inserted into the channel catfish melanocortin-4 receptor (mc4r) gene site using the two-hit two-oligo with plasmid (2H2OP) method. The best performing sgRNA resulted in a knockout mutation rate of 92%, a knock-in rate of 54% and a simultaneous knockout/knock-in rate of 49%. Fish containing both the ccßA-msElovl2 transgene knock-in and mc4r knockout (Elovl2) were 41.8% larger than controls at 6 months post-hatch (p = 0.005). Mean eicosapentaenoic acid (EPA, C20:5n-3) levels in Elov2 mutants and mc4r knockout mutants (MC4R) were 121.6% and 94.1% higher than in controls, respectively (p = 0.045; p = 0.025). Observed mean docosahexaenoic acid (DHA, C22:6n-3) and total EPA + DHA content was 32.8% and 45.1% higher, respectively, in Elovl2 transgenic channel catfish than controls (p = 0.368; p = 0.025). To our knowledge this is the first example of genome engineering to simultaneously target transgenesis and knock-out a gene in a commercially important aquaculture species for multiple improved performance traits. With a high transgene integration rate, improved growth, and higher omega-3 fatty acid content, the use of Elovl2 transgenic channel catfish appears beneficial for application on commercial farms.

Effects and underlying mechanisms of L-arginine on spontaneous muscle contraction of rat colon.

Arginine (Arg), as a basic amino acid, has been reported to be involved in regulation of gut motility. However, the evidence is limited and the underlying mechanism is not fully understood. Our study was conducted to investigate the effects of L-Arg on spontaneous contraction of the longitudinal muscle strip (LMS) of the rat colon and the relevant mechanisms. An organ bath system was used to detect the contractile force of the LMS. Whole-cell voltage-clamp techniques were applied to observe alterations in the currents of large conductance Ca2+-activated K+ (KCa) channels, voltage-dependent potassium (KV) channels, and L-type Ca2+ channels (LTCCs) in smooth muscle cells (SMCs) of the colon. We found that L-Arg within the physiological concentration had no effect on contraction of LMS, while 1 mM L-Arg significantly increased both the amplitude and frequency of LMS contractility. And the increase in force was mucosa-dependent, whereas changes in frequency as well as in amplitude were inhibited by atropine. In addition, L-Arg (1 mM) activated the LTTCs and inhibited both KCa channels and KV channels on SMCs. Thus, L-Arg above the physiological concentration exerted an excitatory effect on colonic LM contraction, and stimulation by L-Arg was mediated by ACh. In addition, LTCCs, KCa channels, and KV channels on SMCs were involved in the action of L-Arg.

Exercise is inversely associated with functional dyspepsia among a sample of Chinese male armed police recruits.

BACKGROUND: There is no study evaluating the association between exercise and functional dyspepsia (FD) based on the Rome IV criteria. We aimed to investigate the prevalence of FD and evaluate the association between exercise and FD based on Rome IV criteria among a sample of Chinese armed police recruits. METHODS: An on-site questionnaire survey on FD among a sample of Chinese armed police recruits was conducted based on the Rome IV criteria in 2021. Potential confounders included age, body mass index (BMI), race, marriage, education, smoking, and drinking variables were adjusted. RESULTS: A total of 2594 recruits were enrolled, including 46 FD participants and 2548 non-FD participants. In the model adjusted for all demographic variables among participants excluding irritable bowel syndrome (IBS) and functional constipation (FC), compared with no exercise participants, 1 h < each exercise time ≤ 2 h (OR = 0.15, 95% CI: 0.03-0.77, P = 0.0230) was inversely associated with FD and compared with no exercise participants, mild exercise (OR = 0.09, 95% CI: 0.01-0.71, P = 0.0220) was significantly inversely associated with FD. CONCLUSIONS: The incidence rate of FD in this sample Chinese armed police recruits was 1.77%, and 1 h < each exercise time ≤ 2 h and mild intensity exercise were independently inversely associated with FD. However, the causal relationship needs to be verified by further randomized controlled trials.

Knockdown of PHLDA1 alleviates sepsis-induced acute lung injury by downregulating NLRP3 inflammasome activation.

OBJECTIVE: To investigate the regulatory mechanism of pleckstrin homology-like domain, family A, member 1 (PHLDA1) in sepsis-induced acute lung injury (ALI). METHOD: Mice model of sepsis were established by cecal ligation and puncture (CLP). The expression of PHLDA1 was reduced by injecting short hairpin RNA (shRNA)-PHLDA1 into the tail vein. The levels of PHLDA1, pro-inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1ß, IL-18, super-oxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH), molecular mechanism related to pyroptosis, such as caspase 1, adaptor apoptosis-associated speck-like protein containing a CARD (ASC), and gasdermin D (GSDMD)-N, and nucleotide oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) were tested by Western blot analysis, quantitative real-time polymerase chain reaction, and enzyme-linked-immunosorbent serologic assay. Pathological changes in lung tissues were examined by hematoxylin and eosin staining. Wet-dry weight ratio of lung tissues was observed. RESULTS: The expression of PHLDA1 was up-regulated in lung tissues from CLP-induced septic mice. Knockdown of PHLDA1 could reduce lung injury and wet-dry weight ratio in mice with sepsis-induced ALI. Moreover, silencing of PHLDA1 decreased the expressions of IL-1ß, TNF-α, IL-18, IL-6, and MDA but increased SOD and GSH expressions in CLP-induced septic mice. The expressions of NLRP3, GSDMD-N, ASC, and caspase 1 were decreased by PHLDA1 silencing. CONCLUSION: Knockdown of PHLDA1 inhibited lung inflammation and pyroptosis in mice with sepsis-induced ALI by down-regulating NLRP3.

An Adaptive Parameterized Domain Mapping Method and Its Application in Wheel-Rail Coupled Fault Diagnosis for Rail Vehicles.

The rapid development of cities in recent years has increased the operational pressure of rail vehicles, and due to the characteristics of rail vehicles, including harsh operating environment, frequent starting and braking, resulting in rails and wheels being prone to rail corrugation, polygons, flat scars and other faults. These faults are coupled in actual operation, leading to the deterioration of the wheel-rail contact relationship and causing harm to driving safety. Hence, the accurate detection of wheel-rail coupled faults will improve the safety of rail vehicles' operation. The dynamic modeling of rail vehicles is carried out to establish the character models of wheel-rail faults including rail corrugation, polygonization and flat scars to explore the coupling relationship and characteristics under variable speed conditions and to obtain the vertical acceleration of the axle box. An APDM time-frequency analysis method is proposed in this paper based on the PDMF adopting Rényi entropy as the evaluation index and employing a WOA to optimize the parameter set. The number of iterations of the WOA adopted in this paper is decreased by 26% and 23%, respectively, compared with PSO and SSA, which means that the WOA performs at faster convergence speed and with a more accurate Rényi entropy value. Additionally, TFR obtained using APDM realizes the localization and extraction of the coupled fault characteristics under rail vehicles' variable speed working conditions with higher energy concentration and stronger noise resistance corresponding to prominent ability of fault diagnosis. Finally, the effectiveness of the proposed method is verified using simulation and experimental results that prove the engineering application value of the proposed method.

[Prevalence Survey of Functional Dyspepsia and Irritable Bowel Syndrome in Chinese College Students Based on Rome â £ Diagnostic Criteria].

Objective: To investigate the prevalence and risk factors of functional dyspepsia (FD) and irritable bowel syndrome (IBS) among college students in China. Methods: An online questionnaire survey of college students aged 17-35 from across China was conducted. The online questionnaire survey was supplemented by an offline survey. A total of 2025 valid samples were included for statistical analysis. χ 2 test and logistic regression were performed for statistical analysis. Results: The prevalence of FD among college students who met the Rome Ⅳ diagnostic criteria was 5.5% (112/2025), with most of them, or 66.1% (74/112), suffering from postprandial discomfort syndrome (PDS). Smoking (odds ratio [ OR]=2.334, 95% confidence interval [ CI]: 1.187-4.589, P=0.014), depression ( OR=2.447, 95% CI: 1.421-4.214, P=0.001), and insomnia ( OR=1.947, 95% CI: 1.291-2.937, P=0.001) were positively correlated with the prevalence of FD. The prevalence of IBS was 1.9% (38/2025), with IBS-diarrhea dominant (IBS-D) being the most important subtype that accounted for 44.7%. Anxiety ( OR=3.63, 95% CI: 1.34-9.88, P=0.012) and insomnia ( OR=2.35, 95% CI: 1.18-4.68, P=0.015) were positively correlated with the prevalence of IBS. Conclusion: Based on Rome Ⅳ criteria, IBS and FD are not uncommon among Chinese university students. Psychological disorders and some related lifestyle factors may be related to the development of the disease. In the future, more series of studies based on different diagnostic criteria, different regions, and multiple factors should be conducted in China.

Vitamin D receptor inhibits EMT via regulation of the epithelial mitochondrial function in intestinal fibrosis.

We previously showed that the vitamin D receptor (VDR) plays a crucial role in acute inflammatory bowel disease and that intestinal fibrosis is a common complication of Crohn's disease (CD). Epithelial-mesenchymal transition (EMT) is an important hallmark of fibrogenesis through which epithelial cells lose their epithelial phenotype and transform into mesenchymal cells. It is known that the VDR plays an essential role in epithelial integrity and mitochondrial function, but its role in intestinal fibrosis remains unknown. Here, we investigated whether the VDR is involved in epithelial mitochondrial dysfunction that results in EMT in intestinal fibrosis. Using human CD samples, intestine-specific VDR-KO mice, and fibroblast cellular models, we showed that the expression of the VDR was significantly lower in intestinal stenotic areas than in nonstenotic areas in patients with chronic CD. Genetic deletion of the VDR in the intestinal epithelium exacerbated intestinal fibrosis in mice administered with dextran sulfate sodium or 2,4,6-trinitrobenzene sulfonic acid, two experimental colitis inducers. In addition, we found that vitamin D dietary intervention regulated intestinal fibrosis by modulating the intestinal expression of the VDR. Mechanistically, knocking down the VDR in both CCD-18Co cells and human primary colonic fibroblasts promoted fibroblast activation, whereas VDR overexpression or VDR agonist administration inhibited fibroblast activation. Further analysis illustrated that the VDR inhibited EMT in the HT29 cell model and that mitochondrial dysfunction mediated epithelial integrity and barrier function in VDR-deficient epithelial cells. Together, our data for the first time demonstrate that VDR activation alleviates intestinal fibrosis by inhibiting fibroblast activation and epithelial mitochondria-mediated EMT.

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Response of cecropin transgenesis to challenge with Edwardsiella ictaluri in channel catfish Ictalurus punctatus.

Constructs bearing the cecropin B gene from the moth Hyalophora cecropia, driven by the cytomegalovirus (CMV) promoter, or the common carp beta-actin (ß-actin) promoter were transferred to channel catfish, Ictalurus punctatus via electroporation. One F3 channel catfish family transgenic for cecropin transgene driven by the CMV promoter, and one F1 channel catfish family transgenic for cecropin transgene driven by the common carp ß-actin promoter were produced. F3 and F1 individuals exhibited enhanced disease resistance when challenged in tanks with Edwardsiella ictaluri, the causative agent of enteric septicemia of catfish (ESC). Inheritance of the transgene by the F1 and F3 generation was 15% and 60%, respectively. Growth rates of the cecropin transgenic and non-transgenic full siblings (controls) channel catfish were not different (P > 0.05). All transgenic fish showed significant resistance to infection by ESC at day 3 and day 4 post exposure (P = 0.005). No correlation was detected between body weight and time to death for all genetic groups (P = 0.34). Results of our study confirmed that genetic enhancement of E. ictaluri resistance can be achieved by cecropin transgenesis in channel catfish. In addition to survival rate, improving survival time is essential because the extension of survival time gives a better chance to apply treatments to stop the bacterial infection.

Association of serum creatinine with hepatic steatosis and fibrosis: a cross-sectional study.

BACKGROUND: Recent studies have shown that chronic kidney disease (CKD) prevalence is significantly higher in patients with hepatic steatosis (HS); however, it remains unclear whether HS is associated with serum creatinine (SCr). We aimed to explore the association between SCr levels and HS in a Chinese population. METHODS: We performed a cross-sectional study among 56,569 Chinese individuals. SCr level, other clinical and laboratory parameters, abdominal ultrasound and noninvasive fibrosis scores were extracted, and the fibrosis 4 score (FIB-4) was calculated. RESULTS: A total of 27.1% of the subjects had HS. After 1:1 propensity score matching (PSM) according to sex and age, we included 13,301 subjects with HS and 13,301 subjects without HS. SCr levels were significantly higher in the HS group than in the non-HS group [73.19 ± 15.14(µmoI/L) vs. 71.75 ± 17.49(µmoI/L), p < 0.001]. Univariate and multivariate regression analyses showed a positive association between SCr and the prevalence of HS. Stepwise regression analysis showed that the association between SCr and HS was independent of other metabolic syndrome components. The prevalence of HS increased significantly with increasing SCr levels. Metabolism-related indicators and liver enzymes were significantly higher in the HS group than in the non-HS group; furthermore, these parameters increased with increasing SCr levels. FIB-4 was significantly higher in the HS group than in the non-HS group but did not show an increasing trend with increasing SCr levels. CONCLUSIONS: Our results showed an independent association between SCr level and HS risk in a Chinese population.