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Background: Colorectal cancer (CRC) is a highly prevalent cancer, and the global healthcare system bears a significant burden due to its incidence. Modulating the gut microbiota is a promising approach to enhance the efficacy of CRC treatment and reduce its adverse effects. The causal relationship between specific microorganisms' presence and CRC development has been widely validated. However, few studies have investigated this relationship using bibliometric methods. Therefore, this study analyzed the research hotspots and trends in human gut microbiology and CRC over the last two decades from a bibliometric perspective. The study aims to provide novel insights into basic and clinical research in this field. Methods: The articles and reviews on gut microbiota in CRC were obtained from the Web of Science Core Collection (WOSCC) on November 2, 2022. CiteSpace and VOSviewer were used to conduct the bibliometric and knowledge-map analysis. Results: A total of 2,707 publications were obtained, with a rapid increase in the number of publications since 2015. The United States and China are the main contributors in this field and have established a network of partnerships in several countries. 414 academic journals have published articles on this topic. The author with the highest number of publications is Jun Yu from the Chinese University of Hong Kong. In addition to "intestinal flora" and "colorectal cancer," high frequency terms in the keyword co-occurrence network analysis included inflammatory bowel disease, Fusobacterium nucleatum, inflammation, long-chain fatty acids, ulcerative colitis, bile acids, and resistant starch. Analysis of keyword trends using burst testing revealed that biomarkers, abnormal crypt foci, bifidobacteria, β-glucuronidase, short-chain fatty acids, bile acids, and DNA methylation are at the forefront of research in this area. Conclusion: The findings of this study provide a bibliometric analysis and visualization of the key research areas in gut microbiota and CRC over the past 20 years. The results suggest that the role of gut microbiota in CRC and its underlying mechanisms should be closely monitored, particularly in the areas of biomarkers, metabolic pathways, and DNA methylation, which may emerge as hot topics in this field. [ABSTRACT FROM AUTHOR]

About ten years ago, Wenhui Li's research group in China identified the sodium taurocholate co-transporting polypeptide (NTCP), a bile acid transporter predominantly expressed in the liver, as a functional receptor for hepatitis B virus (HBV) and its satellite hepatitis delta virus (HDV) through biochemical and genetic studies. This finding unraveled a longtime mystery in the HBV field and led to the establishment of efficient and easy-to-use HBV infection models, which paved the way for the in-depth study of the HBV entry mechanism and facilitated the development of therapeutics against HBV and HDV. The whole picture of the complex HBV entry process became clear upon the follow-up studies over the years, including the recent resolution found for the NTCP structure. As one of the first authors of the 2012 eLife paper on NTCP identification, here, I (H. Y.) share our experience on the bumpy and exciting journey of receptor hunting, particularly on the photo-cross-linking study and some detailed descriptions of the "fishing" process and summarize the key factors for our successful receptor identification. This review may also provide helpful insights for identifying a protein target by peptide or protein baits through cross-linking and immunoprecipitation. [ABSTRACT FROM AUTHOR]

Objective. Intrahepatic cholestasis of pregnancy (ICP) significantly impacts the maternal and fetal safety. Research on the role of clinical pharmacists in guiding drug therapy for this condition remains limited. This study aimed to evaluate the effectiveness of graded pharmaceutical care for women with intrahepatic cholestasis of pregnancy and to provide a theoretical foundation for clinical pharmacist services. Study Design. This study comprises a pre‐and‐post analysis of women with intrahepatic cholestasis of pregnancy (ICP) treated between December 2019 and June 2023 at a tertiary hospital in Jiangsu province. Each group consisted of 102 participants. The control group received standard treatment, while the guardianship group received graded pharmacological care provided by a clinical pharmacist. The effectiveness of pharmacological monitoring by clinical pharmacists was assessed by comparing and analyzing clinical outcome indicators, quality management indicators, safety indicators, and economic factors. Results. The guardianship group exhibited a noteworthy 12.8% reduction in combined adverse pregnancy outcome and more effective management of total prenatal bile acids compared to the control group (16.05 µmol/L vs. 22.85 µmol/L, P < 0.05). The guardianship group displayed superior rationalization of therapeutic drugs and medication duration (P < 0.05). The cost‐benefit analysis revealed a favorable economic impact concerning medication costs but did not indicate economic significance regarding total inpatient costs. Conclusion. The implementation of a graded pharmaceutical care model by a clinical pharmacist holds the potential to enhance outcomes for women experiencing intrahepatic cholestasis during pregnancy, mitigate adverse pregnancy results, optimize the rational utilization of therapeutic medications, and yield positive economic results. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice. [ABSTRACT FROM AUTHOR]

Characterization of metabolic perturbation prior to hepatocellular carcinoma (HCC) may deepen the understanding of causal pathways and identify novel biomarkers for early prevention. We conducted two 1:1 matched nested case‐control studies (108 and 55 pairs) to examine the association of plasma metabolome (profiled using LC‐MS) with the risk of HCC based on two prospective cohorts in China. Differential metabolites were identified by paired t tests and orthogonal partial least‐squares discriminant analysis (OPLS‐DA). Weighted gene coexpression network analysis (WGCNA) was performed to classify metabolites into modules for identifying biological pathways involved in hepatocarcinogenesis. We assessed the risk predictivity of metabolites using multivariable logistic regression models. Among 612 named metabolites, 44 differential metabolites were identified between cases and controls, including 12 androgenic/progestin steroid hormones, 8 bile acids, 10 amino acids, 6 phospholipids, and 8 others. These metabolites were associated with HCC in the multivariable logistic regression analyses, with odds ratios ranging from 0.19 (95% confidence interval [CI]: 0.11‐0.35) to 5.09 (95% CI: 2.73‐9.50). WGCNA including 612 metabolites showed 8 significant modules related to HCC risk, including those representing metabolic pathways of androgen and progestin, primary and secondary bile acids, and amino acids. A combination of 18 metabolites of independent effects showed the potential to predict HCC risk, with an AUC of 0.87 (95% CI: 0.82‐0.92) and 0.86 (95% CI: 0.80‐0.93) in the training and validation sets, respectively. In conclusion, we identified a panel of plasma metabolites that could be implicated in hepatocellular carcinogenesis and have the potential to predict HCC risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Père David's deer (Elaphurus davidianus) are classified as extinct in the wild from the International Union for Conservation of Nature Red List. In 2021, there were more than 6000 individuals in Dafeng Reserve, China. With the increasing of population size for Père David's deer in Dafeng Reserve, it is urgently needed to conduct disease research in order to protect this animal better. Diarrhea is one of the most common diseases affecting the health of Père David's deer. However, little is known about how the intestinal ecology changes in these diarrheic animals. The aim of this study is to reveal the changes of intestinal microbiome and metabolic pathways in diarrheic Père David's deer based on gut microbiome and metabolic pathways. Using 16S rRNA gene sequencing and ultra-high performance liquid chromatography combined with tandem mass spectrometry, the gut microbiota and fecal metabolites were analyzed in five diarrheic Père David's deer. Results demonstrated the distinct changes in the diversity and composition of gut microbiota, as well as great changes in numerous fecal metabolic profiles in diarrheic Père David's deer. The integrated pathway analysis revealed serious disturbances in several metabolic pathways, such as lipid, bile acid, cofactor and vitamin metabolism. These data provided important gut ecology information for diarrheic Père David's deer, which may facilitate improved diagnostic and treatment strategies for sick animals in the future. Diarrhea is one of the most common diseases affecting the health of Père David's deer (Elaphurus davidianus). It is believed that an imbalanced intestinal ecology contributes to the etiology of the condition. However, little is known about how the intestinal ecology changes in these diarrheic animals. In this study, 16S rRNA gene sequencing and ultra-high performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS) were used to investigate the gut microbiota and fecal metabolites in five Père David's deer with diarrhea. The results showed that when compared with healthy individuals, considerable changes in the gut microbiome were observed in diarrheic animals, including a significant reduction in microbial diversity and gut microbiota composition alterations. Furthermore, the profiles of numerous fecal metabolites were altered in diarrheic individuals, showing large-scale metabolite dysregulation. Among metabolites, acylcarnitines, lysophosphatidylcholine, bile acids, and oxidized lipids were elevated significantly. Constantly, several metabolic pathways were significantly altered. Interestingly, predicted metabolic pathways based on 16S rRNA gene sequence and differential metabolite analysis showed that lipid metabolism, cofactor, and vitamin metabolism were altered in sick animals, indicating microbiota-host crosstalk in these deer. When combined, the results provide the first comprehensive description of an intestinal microbiome and metabolic imbalance in diarrheic Père David's deer, which advances our understanding and potential future treatment of diarrheic animals. [ABSTRACT FROM AUTHOR]

Cholestasis is caused by intrahepatic retention of excessive toxic bile acids and ultimately results in hepatic failure. Da-Chai-Hu-Tang (DCHT) has been used in China to treat liver and gallbladder diseases for over 1800 years. Here, we demonstrated that DCHT treatment prevented acute intrahepatic cholestasis with liver injury in response to α-naphthylisothiocyanate (ANIT) not to bile duct ligation (BDL) induced-extrahepatic cholestasis. ANIT (80 mg/kg) increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBiL), total bilirubin (TBiL), and total bile acids (TBA) which was attenuated by DCHT treatment in a dose-dependent manner. DCHT treatment at high dose of 1.875 g/kg restored bile acid homeostasis, as evidenced by the recovery of the transcription of genes implicated in bile acid biosynthesis, uptake and efflux. DCHT treatment (1.875 g/kg) reversed ANIT-evoked disordered glutathione homeostasis (as determined by GSH/GSSG ratio) and increased in the mRNA levels for Il6 , Il1b and Tnfa associated with liver inflammation. Using network pharmacology-based approaches, we identified 22 putative targets involved in DCHT treatment for intrahepatic cholestasis not extrahepatic cholestasis. In addition, as evidenced by dual-luciferase reporter assays, compounds from DCHT with high affinity of PPARα increased luciferase levels from a PPARα-driven reporter. PPARα agonist fenofibrate was able to mimic the cytoprotective effect of DCHT on intrahepatic cholestasis, which was abolished by the PPARα antagonist GW6471. KEGG enrichment and western blot analyses showed that signaling axes of JNK/IL-6/NF-κB/STAT3 related to PPARα might be the principal pathway DCHT affects intrahepatic cholestasis. Taken together, the present study provides compelling evidence that DCHT is a promising formula against acute intrahepatic cholestasis with hepatotoxicity which works via PPARα activation. [ABSTRACT FROM AUTHOR]

Background: At present, ursodeoxycholic acid (UDCA) is internationally recognized as a therapeutic drug in clinic. However, about 40% Primary Biliary Cholangitis (PBC) patients are poor responders to UDCA. It has been demonstrated that Transcutaneous Neuromodulation (TN) can be involved in gut motility, metabolism of bile acids, immune inflammation, and autonomic nerve. Therefore, this study aimed to explore the effect of TN combined with UDCA on PBC and related mechanisms. Methods: According to inclusion and exclusion criteria, 10 healthy volunteers and 15 PBC patients were recruited to control group and TN group, respectively. PBC patients were alternately but blindly assigned to group A (TN combined with UDCA) and group B (sham-TN combined with UDCA), and a crossover design was used. The TN treatment was performed via the posterior tibial nerve and acupoint ST36 (Zusanli) 1 h twice/day for 2 weeks. T test and nonparametric test were used to analyze the data. Results: 1. TN combined with UDCA improved the liver function of PBC patients shown by a significant decrease of alkaline phosphatase and gamma-glutamyltransferase (γ-GT) (P < 0.05). 2. The treatment also decreased serum IL-6 levels (P < 0.05), but not the level of Tumor Necrosis Factor-α, IL-1β or IL-10. 3. TN combined with UDCA regulated autonomic function, enhanced vagal activity, and decreased the sympathovagal ratio assessed by the spectral analysis of heart rate variability (P < 0.05). 4. There was no change in 13 bile acids in serum or stool after TN or sham-TN. Conclusions: TN cssombined with UDCA can significantly improve the liver function of PBC patients. It is possibly via the cholinergic anti-inflammatory pathway. TN might be a new non-drug therapy for PBC. Further studies are required. Trial registration: The study protocol was registered in Chinese Clinical Trial Registry (number ChiCTR1800014633) on 25 January 2018. [ABSTRACT FROM AUTHOR]

Oleanolic acid (OA), a natural triterpenoid, which has the development prospects in anti-tumor therapy is a widely used hepatoprotective drug in China. It has been reported that OA can cause liver toxicity after higher doses or longer-term use. Therefore, the study aims to explore the possible hepatotoxicity mechanism based on liver metabolic profiles. Liver metabolic profiles were obtained from untargeted ultrahigh performance liquid chromatography (UHPLC)-Q Exactive Orbitrap mass spectrometry (MS) technique. It was found that altered bile acid, amino acid, and energy metabolism might be at least partly responsible for OA-induced hepatotoxicity. Bile acid metabolism, as the most important pathway, was verified by using UHPLC-TSQ-MS, indicating that conjugated bile acids were the main contributors to OA-induced liver toxicity. Our findings confirmed that increased bile acids were the key element of OA hepatotoxicity, which may open new insights for OA hepatotoxicity in-depth investigations, as well as provide a reference basis for more hepatotoxic drug mechanism research. [ABSTRACT FROM AUTHOR]

Streptococcus thermophilus plays important roles in the dairy industry and is widely used as a dairy starter in the production of fermented dairy products. The genomes of S. thermophilus strains CS5, CS9, CS18, and CS20 from fermented milk in China were sequenced and used for biodiversity analysis. In the present study, the phylogenetic analysis of all 34 S. thermophilus genomes publicly available including these four strains reveals that the phylogenetic reconstruction does not match geographic distribution as strains isolated from the same continent are not even clustered on the nearby branches. The core and variable genes were also identified, which vary among strains from 0 to 202. CS9 strain contained 127 unique genes from a variety of distantly related species. It was speculated that CS9 had undergone horizontal gene transfer (HGT) during the long evolutionary process. The safety evaluation of these four strains indicated that none of them contains antibiotic resistance genes and that they are all sensitive to multiple antibiotics. In addition, the strains do not contain any pathogenic virulence factors or plasmids and thus can be considered safe. Furthermore, these strains were investigated in terms of their technological properties including milk acidification, exopolysaccharide (EPS) and γ-aminobutyric acid (GABA) production, and in vitro survival capacity in the gastrointestinal tract. CS9 possesses a special eps gene cluster containing significant traces of HGT, while the eps gene clusters of CS5, CS18, and CS20 are almost the same. The monosaccharide compositional analysis indicated that crude EPS-CS5, EPS-CS9, EPS-CS18, and EPS-CS20 contain similar monosaccharide compositions with different ratios. Furthermore, CS9 was one of a few GABA-producing strains that could ferment glutamate to produce GABA, which is beneficial for improving the acid tolerance of the strain. CS18 has the most potential for the production of fermented food among these four strains because of its fast growth rate, rapid acidifying capacity, and stronger acid and bile salt resistance capacity. This study focused on the genome analysis of the four new S. thermophilus strains to investigate the diversity of strains and provides a reference for selecting excellent strains by use of the genome data. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is currently the major cause of chronic liver disease globally. Bile acids (BAs) have emerged as relevant signaling molecules that are associated with NAFLD development. This study was aimed to examine the association of serum total bile acids (TBAs) with NAFLD in a large population of Chinese subjects. Methods: This cross sectional study recruited 152,336 participants from the Second Xiangya Hospital, China. NAFLD was diagnosed based on the presence of hepatic steatosis on ultrasonography, without significant alcohol consumption and other known causes for chronic liver disease. A multivariate logistic regression model was used to test for the association of serum TBAs with NAFLD, adjusting for conventional risk factors of NAFLD. Results: A total of 27.4% of the participants had NAFLD. Patients with NAFLD had slightly higher TBA levels than those without, 3.4 vs. 3.0 μmol/L (p < 0.001). However, TBA levels were not associated with NAFLD in the multivariate logistic regression model, which adjusted for age, gender and other acknowledged risk factors for NAFLD (OR = 1.00. 95% CI: 1.00–1.00, p = 0.797). Conclusions: We found that the serum TBA levels were not associated with NAFLD. Future studies in a large population, focusing on serum BA composition may improve the understating of the role of BAs in NAFLD. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the probiotic properties of Enterococcus strains isolated from traditional naturally fermented cream in China. Four E nterococcus isolates showed high cholesterol removal ability in media were identified as E nterococcus durans ( KLDS 6.0930 and 6.0933) and E nterococcus faecalis ( KLDS 6.0934 and 6.0935) by 16S rRNA and pheS gene sequences, respectively, and selected for further evaluation. In order to assess the probiotic potential and safety of these strains, the property of four E nterococcus strains were examined, including acid and bile tolerance, adherence to Caco-2 cells and antibiotics susceptibility. All four strains showed potential cholesterol assimilation, de-conjugation of bile salts and/or cholesterol degradation to remove cholesterol in vitro. In addition, the potential effect of E. durans KLDS 6.0930 on serum cholesterol levels was evaluated in Sprague- Dawley rats. After 4 weeks administration, compared with rats fed a high-cholesterol diet without lactic acid bacteria supplementation, there was a significant ( P < 0.05) decrease in the total cholesterol and low-density lipoprotein cholesterol levels in the serum of rats treated with KLDS 6.0930. Furthermore, total bile acid level in the feces was significantly ( P < 0.05) increased after KLDS 6.0930 administration. These observations suggested that the strain E. durans KLDS 6.0930 may be used in the future as a good candidate for lowering human serum cholesterol levels. [ABSTRACT FROM AUTHOR]