Quality assessment of heatstroke videos on TikTok.

Background: The prevalence of heatstroke is rising due to global warming, making it a serious but preventable condition, highlighting the urgent need for effective dissemination of relevant health education to the general public. Advances in technology have made accessing health information more convenient and rapid. In recent years, short videos have become a primary medium for delivering health education, with TikTok gaining considerable popularity among the general public. However, the quality of heatstroke-related health education content on TikTok deserves closer scrutiny. Objective: This study aimed to evaluate the quality and content of heatstroke-related videos available on TikTok. Methods: The present study analyzed the top 100 heatstroke-related short videos on TikTok, focusing on their characteristics, quality, and the content they conveyed. The quality of these videos was assessed using the DISCERN instrument. In addition, the completeness of the videos was assessed by examining six key aspects: disease definition, clinical manifestations, risk factors, assessment, management, and outcomes. Results: The study included a total of 90 videos. The results showed that news organizations and healthcare professionals were the primary contributors to these videos, with those from news organizations receiving the most attention. In contrast, those from healthcare professionals received comparatively less engagement. Overall, the quality of the information was found to be moderately low, with the highest quality videos posted by non-profit organizations, followed by those posted by healthcare professionals. The majority of videos uploaded described the disease definition, clinical presentation, risk factors, assessment, management, and outcomes of heatstroke. Conclusion: The quality of information provided in heatstroke-related short videos on TikTok is generally inadequate and requires significant improvement. In addition, such content should be subject to government review to ensure its accuracy and reliability.

Accuracy of ChatGPT3.5 in answering clinical questions on guidelines for severe acute pancreatitis.

BACKGROUND: Guidelines must be interpreted comprehensively and correctly to standardize the clinical process. However, this process is challenging and requires interpreters to have a medical background and qualifications. In this study, the accuracy of ChatGPT3.5 in answering clinical questions related to the 2019 guidelines for severe acute pancreatitis was evaluated. METHODS AND RESULTS: An observational study was conducted using the 2019 guidelines for severe acute pancreatitis. The study compared the accuracy of ChatGPT3.5 in English versus Chinese and found that it was more accurate in English (71%) than in Chinese (59%) (P value: 0.203). Additionally, the study assessed the accuracy of ChatGPT3.5 in answering short-answer questions versus true/false questions and found that it was more accurate in answering short-answer questions (76%) than in answering true/false questions (60%) (P value: 0.405). CONCLUSIONS: For clinicians managing severe acute pancreatitis, ChatGPT3.5 may have potential value. However, it should not be relied upon excessively for clinical decision making.

Exploring the diagnostic potential of immunoglobulin A-microbiota interplay in liver cirrhosis and spontaneous bacterial peritonitis.

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes.

Short-chain fatty acid-producing bacterial strains attenuate experimental ulcerative colitis by promoting M2 macrophage polarization via JAK/STAT3/FOXO3 axis inactivation.

BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms. METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays. RESULTS: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro. CONCLUSIONS: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.

Pretreatment with an antibiotics cocktail enhances the protective effect of probiotics by regulating SCFA metabolism and Th1/Th2/Th17 cell immune responses.

BACKGROUND: Probiotics are a potentially effective therapy for inflammatory bowel disease (IBD); IBD is linked to impaired gut microbiota and intestinal immunity. However, the utilization of an antibiotic cocktail (Abx) prior to the probiotic intervention remains controversial. This study aims to identify the effect of Abx pretreatment from dextran sulfate sodium (DSS)-induced colitis and to evaluate whether Abx pretreatment has an enhanced effect on the protection of Clostridium butyricum Miyairi588 (CBM) from colitis. RESULTS: The inflammation, dysbiosis, and dysfunction of gut microbiota as well as T cell response were both enhanced by Abx pretreatment. Additionally, CBM significantly alleviated the DSS-induced colitis and impaired gut epithelial barrier, and Abx pretreatment could enhance these protective effects. Furthermore, CBM increased the benefit bacteria abundance and short-chain fatty acids (SCFAs) level with Abx pretreatment. CBM intervention after Abx pretreatment regulated the imbalance of cytokines and transcription factors, which corresponded to lower infiltration of Th1 and Th17 cells, and increased Th2 cells. CONCLUSIONS: Abx pretreatment reinforced the function of CBM in ameliorating inflammation and barrier damage by increasing beneficial taxa, eliminating pathogens, and inducing a protective Th2 cell response. This study reveals a link between Abx pretreatment, microbiota, and immune response changes in colitis, which provides a reference for the further application of Abx pretreatment before microbiota-based intervention.

Rapamycin extenuates experimental colitis by modulating the gut microbiota.

BACKGROUND AND AIM: Autophagy and gut microbiota correlates closely with the inflammatory bowel disease. Herein, we aimed to study the roles of rapamycin on the gut microbiota in inflammatory bowel disease. METHODS: Acute colitis was induced with dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzenesulfonic acid solution in mice. Mice were administered with rapamycin or hydroxychloroquine. Weight loss, disease activity index scores, histopathological score, serum inflammatory cytokines, intestinal permeability, and colonic autophagy-related proteins were detected. Cecal content was also preserved in liquid nitrogen and subsequently analyzed following the 16S DNA sequencing. The antibiotic cocktail-induced microbiome depletion was performed to further investigate the relationship between autophagy activation and gut microbiota. RESULTS: Compared with the control group, the colonic autophagy-related proteins of P62, mTOR, and p-mTOR increased significantly, while the levels of LC3B and ATG16L1 decreased (all P < 0.05) in the model group. After rapamycin intervention, the colonic pathology of mice improved, while the disease activity index score decreased substantially; the colon length increased, and the expression of IL-6 and TNF-α decreased. Following hydroxychloroquine treatment, some indicators suggested aggravation of colitis. Principal coordinates analysis showed that the DSS group was located on a separate branch from the rapamycin group but was closer to the hydroxychloroquine group. Compared with the DSS group, the rapamycin group was associated with higher abundances of f_Lactobacillaceae (P = 0.0151), f_Deferribacteraceae (P = 0.0290), g_Lactobacillus (P = 0.0151), g_Mucispirillum (P = 0.0137), s_Lactobacillus_reuteri (P = 0.0028), and s_Clostridium_sp_Culture_Jar-13 (P = 0.0082) and a lower abundance of s_Bacteroides_sartorii (P = 0.0180). Linear discriminant analysis effect size showed that rapamycin increased the abundances of Lactobacillus-reuteri, Prevotellaceae, Paraprevotella, Christensenella and Streptococcus and decreased those of Peptostreptococcaceae and Romboutsia Bacteroides-sartorii. Besides, the improvement effect of autophagy activation on colitis disappears following gut microbiome depletion. CONCLUSION: The therapeutic effects of rapamycin on extenuating experimental colitis may be related to the gut microbiota.

Infiltration of a Unique CD8+CD274+ Cell Subgroup in Hepatocellular Carcinoma is Associated with Poor Clinical Outcomes.

Introduction: Immune checkpoint (IC) inhibitor-related immunotherapies have attracted considerable attention in hepatocellular carcinoma (HCC). High IC expression and high tumor infiltrating lymphocyte levels are the current indicators of sensitivity to IC inhibitors. Thus, it is imperative to apply precision medicine strategies for patient selection. Methods: Six independent HCC cohorts were used for analysis at the single-cell and tissue levels. Multiplex immunofluorescence and immunochemistry staining assays were used to validate our results. A series of methodologies were used for immune-related evaluations. Results: Herein, we uncovered a unique CD8+CD274+ cell subpopulation that is associated with tumor progression and poor survival in HCC at the single-cell level. We assessed this subset at the tissue level and found that the prognostic significance of CD274 is dependent on CD8A expression in HCC. Subsequently, we identified a unique high-risk subpopulation that showed high CD8A expression coupled with intense CD274 expression in multiple HCC cohorts. CD8AHighCD274High* subgroup was correlated with malignant indexes and remained an independent prognostic factor when considering the influence of these indexes. Molecular characteristic analyses showed that the CD8AHighCD274High* subgroup harbored more mutations, had higher immune response activity and presented enrichment of cancer-related biological processes. Moreover, this high-risk subpopulation in HCC was characterized by high immune cell infiltration, low tumor purity, and enrichment of cancer-related signatures. Finally, cases with this phenotype demonstrated higher immunomodulator and IC levels and greater sensitivity to IC inhibitors. Conclusion: Our findings illustrate that some HCC patients may have a poor prognosis despite high CD8+ T-cell infiltration. These patients would probably benefit from IC inhibitor-based combination treatment.

Pattern recognition receptors in the development of nonalcoholic fatty liver disease and progression to hepatocellular carcinoma: An emerging therapeutic strategy.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and has become the leading chronic liver disease worldwide. NAFLD is viewed as the hepatic manifestation of metabolic syndrome, ranging from simple steatosis and nonalcoholic steatohepatitis (NASH) to advanced fibrosis, eventually leading to cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of NAFLD progression is still not clear. Pattern recognition receptor (PRR)-mediated innate immune responses play a critical role in the initiation of NAFLD and the progression of NAFLD-related HCC. Toll-like receptors (TLRs) and the cyclic GMP-AMP (cGAMP) synthase (cGAS) are the two major PRRs in hepatocytes and resident innate immune cells in the liver. Increasing evidence indicates that the overactivation of TLRs and the cGAS signaling pathways may contribute to the development of liver disorders, including NAFLD progression. However, induction of PRRs is critical for the release of type I interferons (IFN-I) and the maturation of dendritic cells (DCs), which prime systemic antitumor immunity in HCC therapy. In this review, we will summarize the emerging evidence regarding the molecular mechanisms of TLRs and cGAS in the development of NAFLD and HCC. The dysfunction of PRR-mediated innate immune response is a critical determinant of NAFLD pathology; targeting and selectively inhibiting TLRs and cGAS signaling provides therapeutic potential for treating NALF-associated diseases in humans.

Nucleolar protein treacle ribosome biogenesis factor 1 maintains gastric cancer cell proliferation by regulating R-loop associated DNA replication stress.

BACKGROUND AND AIM: Gastric cancer (GC) is a common malignant neoplasm in the gastrointestinal tract, accounting for high mortality globally. Treacle ribosome biogenesis factor 1 (TCOF1) is a nucleolar protein, which has been reported to be implicated in the pathogenesis of Treacher Collins syndrome and the development of several types of human cancer. However, the role of TCOF1 in GC is not known. METHODS: Immunohistochemistry was carried out to determine TCOF1 expression in GC tissues. Immunofluorescence, co-IP, and DNA fiber assays were conducted to investigate the function of TCOF1 in GC-derived BGC-823 and SGC-7901 cell lines. RESULTS: TCOF1 expression was aberrantly increased in GC tissues compared with adjacent normal tissues. In addition, we found that TCOF1 left the nucleolus and localized to R-loops (DNA/RNA hybrids) during S phase in GC cells. Furthermore, TCOF1 interacted with DDX5 and suppressed R-loop levels. Knockdown of TCOF1 led to increased nucleoplasmic R-loops specifically during S phase, which restrained DNA replication and cell proliferation. Overexpression of R-loop eraser RNaseH1 rescued the DNA synthesis defects and decreased DNA damage caused by TCOF1 depletion. CONCLUSION: These findings demonstrate a novel role of TCOF1 in maintaining GC cell proliferation by alleviating R-loop associated DNA replication stress.

Worldwide research on extraction and recovery of cobalt through bibliometric analysis: a review.

Cobalt is a strategic and critical mineral whose demand is expected to grow rapidly. This study aims to provide a comprehensive summary of cobalt extraction and recovery research from 2012 to 2021 in the form of bibliometric analysis. The work was based on the Science Citation Index Expanded (Web of Science) and carried out using the InCites of Clarivate for bibliometric data analysis and the software VOSviewer for science mapping. By analyzing a dataset of 4967 publications, the most influential journals, countries, authors, institutions, and publications were identified, and the keyword co-occurrence networks were mapped. The China mainland produced the most publications, while the USA had the highest average number of citations per publication and the UK was the most collaborative with other countries. The keyword analysis shows that the research hotspots gradually shifted over time from early means and methods for determination of cobalt in solution to recovery of cobalt from spent lithium batteries, smelting slag, copper-cobalt ore, etc. The research will be focused on further improvement and optimization of the separation, extraction, and recovery processes of cobalt from spent batteries in recent and future years, and three approaches were promoted to facilitate economization and industrialization of the processes in this field.

Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection.

Neuroepithelial crosstalk is critical for gut physiology. However, the mechanisms by which sensory neurons communicate with epithelial cells to mediate gut barrier protection at homeostasis and during inflammation are not well understood. Here, we find that Nav1.8+CGRP+ nociceptor neurons are juxtaposed with and signal to intestinal goblet cells to drive mucus secretion and gut protection. Nociceptor ablation led to decreased mucus thickness and dysbiosis, while chemogenetic nociceptor activation or capsaicin treatment induced mucus growth. Mouse and human goblet cells expressed Ramp1, receptor for the neuropeptide CGRP. Nociceptors signal via the CGRP-Ramp1 pathway to induce rapid goblet cell emptying and mucus secretion. Notably, commensal microbes activated nociceptors to control homeostatic CGRP release. In the absence of nociceptors or epithelial Ramp1, mice showed increased epithelial stress and susceptibility to colitis. Conversely, CGRP administration protected nociceptor-ablated mice against colitis. Our findings demonstrate a neuron-goblet cell axis that orchestrates gut mucosal barrier protection.

Altered Pattern of Immunoglobulin A-Targeted Microbiota in Inflammatory Bowel Disease After Fecal Transplantation.

Adaptive immune response to the gut microbiota is one of the main drivers of inflammatory bowel disease (IBD). Under inflammatory conditions, immunoglobulin (Ig)-targeted bacteria are altered. However, changes in Ig-targeted bacteria in Asian patients with IBD with ulcerative colitis (UC) remain unclear. Furthermore, changes in IgA-targeted bacteria in patients with UC treated with fecal microbiota transplantation (FMT) are unclear. Here, we analyzed fecal samples of patients with IBD and patients with UC before and after FMT by flow cytometry. We found that the percentage of IgA/G-coated bacteria can be used to assess the severity of IBD. Besides oral pharyngeal bacteria such as Streptococcus, we hypothesized that Megamonas, Acinetobacter, and, especially, Staphylococcus might play an important role in IBD pathogenesis. Moreover, we evaluated the influence of FMT on IgA-coated bacteria in patients with UC. We found that IgA-bacterial interactions were re-established in human FMT recipients and resembled those in the healthy fecal donors. Additionally, the IgA targeting was not influenced by delivery methods: gastroscopy spraying and colonic transendoscopic enteral tubing (TET). Then, we established an acute dextran sulfate sodium (DSS)-induced mouse model to explore whether FMT intervention would impact IgA/G memory B cell in the intestine. We found that after FMT, both IgA/G memory B cell and the percentage of IgA/G-targeted bacteria were restored to normal levels in DSS mice.

Characterization of short-chain fatty acids in patients with ulcerative colitis: a meta-analysis.

BACKGROUND: Studies investigating the changes in short-chain fatty acids (SCFAs) in patients with ulcerative colitis (UC) have yielded inconsistent results. We performed a meta-analysis of studies that investigated the alterations in different SCFAs among UC patients to assess their role in the development of UC. METHODS: Three databases were searched for relevant studies published as of April 2021. Results are presented as standardized mean difference (SMD) with 95% confidence interval (95% CI). RESULTS: Eleven studies were included in the meta-analysis. Compared to healthy subjects, UC patients had significantly lower concentrations of total SCFAs (SMD = - 0.88, 95%CI - 1.44, - 0.33; P < 0.001), acetate (SMD = - 0.54, 95% CI - 0.91, - 0.17; P = 0.004), propionate, (SMD = - 0.37, 95% CI - 0.66, - 0.07; P = 0.016), and valerate (SMD = - 0.91, 95% CI - 1.45, - 0.38; P < 0.001). On subgroup analysis based on disease status, patients with active UC had reduced concentrations of acetate (SMD = - 1.83, 95% CI - 3.32, - 0.35; P = 0.015), propionate (SMD = - 2.51, 95% CI - 4.41, - 0.61; P = 0.009), and valerate (SMD = - 0.91, 95% CI - 1.45, - 0.38; P < 0.001), while UC patients in remission had similar concentrations with healthy subjects. Patients with active UC had lower butyrate level (SMD = - 2.09, 95% CI - 3.56, - 0.62; P = 0.005) while UC patients in remission had higher butyrate level (SMD = 0.71, 95% CI 0.33, 1.10; P < 0.001) compared with healthy subjects. CONCLUSION: UC patients had significantly decreased concentrations of total SCFAs, acetate, propionate, and valerate compared with healthy subjects. In addition, inconsistent changes of certain special SCFAs were observed in UC patients with different disease status.

Effectiveness and Safety of Tofacitinib for Ulcerative Colitis: Systematic Review and Meta-analysis.

BACKGROUND: The objective of our systematic review and meta-analysis was to evaluate the effectiveness and safety of tofacitinib in the treatment of moderate-severe ulcerative colitis (UC). METHODS: We searched Medline, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on tofacitinib use in UC. Primary outcome assessed was remission. Secondary outcomes included clinical response, steroid free remission, and adverse events (AEs). RESULTS: A total of 26 studies were included. The rates of remission were 29.81% [95% confidence interval (CI): 22.37%-37.25%, I2 : 90%] at week 8, 32.27% (95% CI: 27.67%-36.88%, I2 : 42%) at 6 months and 38.03% (95% CI: 33.59%-42.48%, I2 : 0%) at 1-year. Clinical response rates were 59.41% (95% CI: 55.03%-63.94%, I2 : 61%) at week 8, 48.99% (95% CI: 36.92%-61.06%, I2 : 91%) at 6 months and 50.87% (95% CI: 42.16%-59.58%, I2 : 67%) at 1-year. Odds ratio of clinical response at week 8 in biologic naive versus biologic experienced patients was 1.59 (95% CI: 0.54-4.63). Pooled incidence rate for serious infections, major adverse cardiovascular events, and nonmelanotic squamous cell malignancies across all doses was 4.41 per 100-patient years (PYs) (95% CI: 2.32-8.38 per 100-PY, I2 : 78%), 0.91 per 100-PY (95% CI: 0.43-1.93 per 100-PY, I2 : 37%) and 0.91 per 100-PY (95% CI: 0.61-1.34 per 100-PY, I2 : 0%), respectively. Higher dose was associated with an increased frequency of AEs. CONCLUSIONS: While the overall efficacy and safety of tofacitinib in moderate-severe UC is consistent with clinical trial data, the dose dependent increase in AEs highlights the significance of early dose de-escalation. Rate of clinical response after tofacitinb induction was similar in biologic naive and biologic experienced patients.

Guideline Adherence of ß-blocker Initiating Dose and its Consequence in Hospitalized Patients With Heart Failure With Reduced Ejection Fraction.

Background: We aim to investigate the guideline adherence of ß-blocker (BB) initiating dose in Chinese hospitalized patients with heart failure with reduced ejection fraction (HFrEF) and whether the adherence affected the in-hospital outcomes. Methods: This was a retrospective study of patients hospitalized with HFrEF who had initiated BBs during their hospitalization. We defined adherence to clinical practice guidelines as initiating BB with standard dose and non-adherence to guidelines if otherwise, and examined the association between adherence to guidelines and in-hospital BB-related adverse events. Subgroup analyses based on sex, age, coronary heart disease, and hypertension were performed. Results: Among 1,104 patients with HFrEF initiating BBs during hospitalization (median length of hospitalization, 12 days), 304 (27.5%) patients received BB with non-adherent initiating dose. This non-adherence was related to a higher risk (hazard ratio [95% confidence interval]) of BB dose reduction or withdrawal (1.78 [1.42 to 2.22], P < 0.001), but not significantly associated with risks of profound bradycardia, hypotension, cardiogenic shock requiring intravenous inotropes, and severe bronchospasm requiring intravenous steroid during hospitalization. Conclusion: This study identified that over a fourth of patients had received BBs with an initiating dose that was not adherent to guidelines in Chinese hospitalized patients with HFrEF, and this non-adherence was associated with BB dose reduction or withdrawal during hospitalization.

Genome insights of Enterococcus raffinosus CX012922, isolated from the feces of a Crohn's disease patient.

BACKGROUND: Enterococcus raffinosus is one of the Enterococcus species that often cause nosocomial infections. To date, only one E. raffinosus genome has been completely assembled, and the genomic features have not been characterized. Here, we report the complete genome sequence of the strain CX012922, isolated from the feces of a Crohn's disease patient, and perform a comparative genome analysis to the relevant Enterococcus spp. strains in silico. RESULTS: De novo assembly of the sequencing reads of the strain CX012922 generated a circular genome of 2.83 Mb and a circular megaplasmid of 0.98 Mb. Phylogenomic analysis revealed that the strain CX012922 belonged to the E. raffinosus species. By comparative genome analysis, we found that some strains previously identified as E. raffinosus or E. gilvus should be reclassified as novel species. Genome islands (GIs), virulence factors, and antibiotic genes were found in both the genome and the megaplasmid, although pathogenic genes were mainly encoded in the genome. A large proportion of the genes encoded in the megaplasmid were involved in substrate utilization, such as raffinose metabolism. Giant megaplasmids (~1 Mb) equipped with toxin-antitoxin (TA) systems generally formed symbiosis relationships with the genome of E. raffinosus strains. CONCLUSIONS: Enterococcus spp. have a higher species-level diversity than is currently appreciated. The pathogenicity of E. raffinosus is mainly determined by the genome-encoded virulence factors, while the megaplasmid broadens the gene function pool. The symbiosis between the genome and the megaplasmids endows E. raffinosus with large genomic sizes as well as versatile gene functions, especially for their colonization, adaptation, virulence, and pathogenesis in the human gut.

Selection strategy of dextran sulfate sodium-induced acute or chronic colitis mouse models based on gut microbial profile.

BACKGROUND: Dextran sulfate sodium (DSS) replicates ulcerative colitis (UC)-like colitis in murine models. However, the microbial characteristics of DSS-triggered colitis require further clarification. To analyze the changes in gut microbiota associated with DSS-induced acute and chronic colitis. METHODS: Acute colitis was induced in mice by administering 3% DSS for 1 week in the drinking water, and chronic colitis was induced by supplementing drinking water with 2.5% DSS every other week for 5 weeks. Control groups received the same drinking water without DSS supplementation. The histopathological score and length of the colons, and disease activity index (DAI) were evaluated to confirm the presence of experimental colitis. Intestinal microbiota was profiled by 16S rDNA sequencing of cecal content. RESULTS: Mice with both acute and chronic DSS-triggered colitis had significantly higher DAI and colon histopathological scores in contrast to the control groups (P < 0.0001, P < 0.0001), and the colon was remarkably shortened (P < 0.0001, P < 0.0001). The gut microbiota α-diversity was partly downregulated in both acute and chronic colitis groups in contrast to their respective control groups (Pielou index P = 0.0022, P = 0.0649; Shannon index P = 0.0022, P = 0.0931). The reduction in the Pielou and Shannon indices were more obvious in mice with acute colitis (P = 0.0022, P = 0.0043). The relative abundance of Bacteroides and Turicibacter was increased (all P < 0.05), while that of Lachnospiraceae, Ruminococcaceae, Ruminiclostridium, Rikenella, Alistipes, Alloprevotella, and Butyricicoccus was significantly decreased after acute DSS induction (all P < 0.05). The relative abundance of Bacteroides, Akkermansia, Helicobacter, Parabacteroides, Erysipelatoclostridium, Turicibacter and Romboutsia was also markedly increased (all P < 0.05), and that of Lachnospiraceae_NK4A136_group, Alistipes, Enterorhabdus, Prevotellaceae_UCG-001, Butyricicoccus, Ruminiclostridium_6, Muribaculum, Ruminococcaceae_NK4A214_group, Family_XIII_UCG-001 and Flavonifractor was significantly decreased after chronic DSS induction (all P < 0.05). CONCLUSION: DSS-induced acute and chronic colitis demonstrated similar symptoms and histopathological changes. The changes in the gut microbiota of the acute colitis model were closer to that observed in UC. The acute colitis model had greater abundance of SCFAs-producing bacteria and lower α-diversity compared to the chronic colitis model.

Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation.

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography-mass spectrometry (LC-MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.

Deficiencies in Planning Interventional Trial Registration of COVID-19 in China.

Background: The coronavirus disease 2019 (COVID-19) pandemic has affected the world since late 2019. The efforts to control the spread of the virus need to be supported by credible evidence. Therefore, we analyzed the rationality of the timeline and geographic distribution of COVID-19 trial registration in mainland China. Methods: We searched the Chinese Clinical Trial Registry (ChiCTR, http://www.chictr.org.cn/) and International Clinical Trials Registry Platform (ICTRP, https://www.who.int/ictrp/en/) using keywords including novel coronavirus, coronavirus pneumonia, 2019-nCoV, COVID-19, and SARS-COV-2 from 1 December 2019 to 27 April 2020 and included interventional randomized and non-randomized trials including patients with confirmed cases of COVID-19 in mainland China. The registered trials were reviewed, and data were independently extracted by two reviewers based on the inclusion criteria. Results: A total of 263 registered interventional trials were included in the study. We defined the sample size index (SI) as the total number of patients needed by the trials divided by the total number of patients diagnosed with COVID-19. A total of 84,341 patients had been diagnosed with COVID-19 in China as of 26 April 2020, and the included trials had a combined sample size of 31,156 patients (SI: 0.37). After control of the COVID-19 epidemic was achieved in China (February 18, 2020), the SI was 1.54, suggesting that the number of patients needed by the trials was greater than the number of newly diagnosed patients. The SIs in 8 out of 26 provinces in mainland China were >1. Conclusions: Our results suggested a clear over registration of COVID-19 trials in China, especially after control of the pandemic was achieved, preventing the generation of high-quality evidence.

Population diversity of cardiovascular outcome trials and real-world patients with diabetes in a Chinese tertiary hospital.

BACKGROUND: Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials. METHODS: This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation. RESULTS: We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the real-world inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population. CONCLUSIONS: The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.