Triclosan exposure induced disturbance of gut microbiota and exaggerated experimental colitis in mice.

BACKGROUND: Triclosan, an antimicrobial agent in personal care products, could be absorbed into the human body through the digestive tract. This animal experiment aimed to clarify the effects of triclosan exposure on the microbiome and intestinal immune functions in healthy and ulcerative colitis models. METHODS: Balb/c mice were maintained on an AIN-93G diet containing 80ppm triclosan dissolved in polyethylene as vehicle or vehicle alone for 1 week or 4 weeks. In the end, the mice were sacrificed, blood samples and colon tissues were collected for analysis of inflammation, and fecal samples were collected for 16 S rRNA sequencing of gut microbiota. To establish ulcerative colitis mice model, at the beginning of the 4th week, mice maintained on the diet with or without triclosan were treated with 2% Dextran sulfate sodium(DSS) in drinking water for 1 week. Then mice were sacrificed for analysis of colitis and gut microbiota. RESULTS: Triclosan exposure to common mice enhanced the levels of p-NF-κb and Toll-like receptor 4 (TLR4), and decreased the Occludin in the colon. Triclosan exposure to DSS-induced mice increased the level of inflammatory cytokines, reduced the levels of Occludin, and exacerbated the degree of damage to intestinal mucosa and crypt, infiltration of inflammatory cells and atypia of glandular cells. Low-grade intraepithelial neoplasia appeared. Both in common and DSS-induced mice, triclosan exposure changed the diversity and composition of gut microbiota. Fecal samples showed higher enrichment of sulfate-reducing bacteria and Bacteroides, and less butyrate-producing bacteria. CONCLUSION: Triclosan exposure induced disturbance of gut microbiota and exaggerated experimental colitis in mice. And changes in the composition of gut microbiota were characterized by the increase of harmful bacteria, including sulfate-reducing bacteria and Bacteroides, and the reduction of protective probiotics, butyrate-producing bacteria.

Efficacy and safety of different doses of baricitinib for rheumatoid arthritis: A Bayesian network meta-analysis.

BACKGROUND: To evaluate the comparative efficacy and safety of baricitinib with different dosages in patients with rheumatoid arthritis (RA). METHODS: PubMed, Embase, and the Cochrane Library were retrieved by computer to gather randomized controlled trials (RCTs) of baricitinib for RA from their beginning to September 2021. After 2 researchers independently screened the literature and extracted the data, the risk of bias of included RCTs was assessed, and Bayesian network meta-analysis was performed by GeMTC0.14.3 and Stata15.1 software. RESULTS: Ten publications reporting 9 RCTs were included, with 4129 patients randomized to receive 1 of the 7 interventions. Seven interventions were baricitinib 1 mg + conventional disease-modifying antirheumatic drugs (cDMARD), baricitinib 2 mg + cDMARD, baricitinib 4 mg + cDMARD, baricitinib 8 mg + cDMARD, baricitinib 4 mg, placebo + cDMARD, and cDMARD. In the efficacy outcomes at 12 weeks, nearly all doses of baricitinib with or without cDMARD were superior to placebo plus cDMARD and baricitinib 8 mg combined with cDMARD might have the best curative effect in most outcomes. In the efficacy outcomes at 24 weeks, all doses of baricitinib with or without cDMARD were superior to placebo plus cDMARD and baricitinib 4 mg monotherapy might have the best curative effect in most outcomes. The intervention with the highest incidence of adverse events (AEs) might be baricitinib 8 mg combined with cDMARD, and the intervention with the highest incidence of infections might be baricitinib 4 mg combined with cDMARD. CONCLUSIONS: Baricitinib 8 mg combined with cDMARDs was suitable for short-term control of RA symptoms, and baricitinib 4 mg was more effective for treating RA over a longer period of time. But attention should be paid for the risk of baricitinib at 4 to 8 mg in clinical application due to the high incidence of AEs and infections.

An mRNA vaccine candidate for the SARS-CoV-2 Omicron variant

The newly emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains more than 30 mutations on the spike protein, 15 of which are located within the receptor binding domain (RBD). Consequently, Omicron is able to extensively escape existing neutralizing antibodies and may therefore compromise the efficacy of current vaccines based on the original strain, highlighting the importance and urgency of developing effective vaccines against Omicron. Here we report the rapid generation and evaluation of an mRNA vaccine candidate specific to Omicron. This mRNA vaccine encodes the RBD of Omicron (designated RBD-O) and is formulated with lipid nanoparticle. Two doses of the RBD-O mRNA vaccine efficiently induce neutralizing antibodies in mice; however, the antisera are effective only on the Omicron variant but not on the wildtype and Delta strains, indicating a narrow neutralization spectrum. It is noted that the neutralization profile of the RBD-O mRNA vaccine is opposite to that observed for the mRNA vaccine expressing the wildtype RBD (RBD-WT). Our work demonstrates the feasibility and potency of an RBD-based mRNA vaccine specific to Omicron, providing important information for further development of bivalent or multivalent SARS-CoV-2 vaccines with broad-spectrum efficacy.

JAK Inhibitors Therapy for Rheumatoid Arthritis ：An Overview of Systematic Reviews / 中国药房

OBJECTIVE：To overview t he s ystematic revi ews on JAK inhibitors in the treatment of rheumatoid arthritis （RA）， and to provide evidence-based basis for the treatment of RA with these drugs. METHODS ：The Cochrane Library ，PubMed， Embase，CNKI，Wanfang database and VIP were electronically searched to collect systematic reviews of JAK inhibitors in the treatment of RA from inception to Dec. 2020. After data extraction of included systematic review ，PRISMA statement ，AMSTAR2 scale and GRADE were used to evaluate the report quality ，methodological quality and the level of evidence for outcome indicators. RESULTS ：A total of 12 systematic reviews involving 103 outcomes were included. PRISMA score of systematic reviews was between 17.5 and 22.5，and the reported quality defects were mainly reflected in scheme ，registration and other aspects. AMSTAR 2 evaluation results showed that there were 6 studies of low quality and 6 studies of very low quality ，without high-quality study and medium-quality study. GRADE assessment results for outcome indicators showed low to medium quality of evidence. The summary of evidence showed that compared to placebo ，JAK inhibitor could alleviate various indicators of RA ； compared to adalimumab ，the advantage was not obvious. JAK inhibitors did not increase the incidence of serious adverse events ， but the systematic reviews were inconsistent in their effects on the incidence of total adverse events and liver injury. CONCLUSIONS：The efficacy of JAK inhibitors in the treatment of RA has certain advantages over placebo ，but more studies are needed to demonstrate the efficacy of JAK inhibitors in the treatment of RA compared to other drugs ；the advantage of safety is uncertain.

Pathological classification and clinical symptoms of heterotopic gastric mucosa in upper esophagus / 中华消化杂志

Objective:To explore the pathological type and clinical symptoms of heterotopic gastric mucosa in upper esophagus (HGM).Methods:From December 2018 to August 2019, at the First Affiliated Hospital of Xinjiang Medical University, the patients with HGM, reflux esophagitis (RE), Barrett esophagus (BE) and chronic non-atrophic gastritis (CNAG), who underwent gastroscopy were selected. The pathological type of HGM including acid secretion, mucinous and mixed type. The differences in the symptoms among HGM, RE, BE, and CNAG, as well as the differences in the clinical symptoms of different pathological types of HGM were analyzed. Chi-square test and analysis of variance were used for statistical analysis.Results:There were 82, 104, 76, and 178 cases of HGM, RE, BE, and CNAG, respectively. The acid secretion, mucinous and mixed types of HGM were 22, 20 and 40 cases, respectively. The incidence rates of pharyngeal reflux symptoms foreign body sensation in the throat, swallowing discomfort, hoarseness, and cough of HGM patients were higher than those of RE patients (63.4%, 52/82 vs. 14.4%, 15/104; 58.5%, 48/82 vs. 14.4%, 15/104; 50.0%, 41/82 vs. 6.7%, 7/104; 43.9%, 36/82 vs. 12.5%, 13/104), while the incidence rates of gastroesophageal reflux symptoms acid reflux, heartburn and belching were lower than those of RE patients (34.1%, 28/82 vs. 61.5%, 64/104; 14.6%, 12/82 vs. 72.1%, 75/104; 34.1%, 28/82 vs. 67.3%, 70/104), and the differences were statistically significant ( χ2= 47.80, 39.80, 44.80, 23.30, 13.80, 60.90 and 20.20, all P<0.01). The incidence rates of pharyngeal reflux symptoms foreign body sensation in the throat, swallowing discomfort, hoarseness, and cough of HGM patients were higher than those of BE patients (63.4%, 52/82 vs. 22.4%, 17/76; 58.5%, 48/82 vs. 19.7%, 15/76; 50.0%, 41/82 vs. 9.2%, 7/76; 43.9%, 36/82 vs. 6.6%, 5/76), and the incidence rates of reflux symptoms acid reflux, heartburn, belching, and post-sternal burning sensation were lower than those of BE patients (34.1%, 28/82 vs. 61.8%, 47/76; 14.6%, 12/82 vs. 55.3%, 42/76; 34.1%, 28/82 vs. 65.8%, 50/76; 20.7%, 17/82 vs. 42.1%, 32/76), and the differences were statistically significant ( χ2=27.00, 24.80, 31.00, 28.60, 12.10, 28.90, 15.80 and 8.40, all P<0.01). The incidence rates of pharyngeal reflux symptoms foreign body sensation in the throat, swallowing discomfort, hoarseness and cough, gastroesophageal reflux symptoms acid reflux, heartburn, belching and post-sternal burning, and non-reflux symptoms digestion, bloating and abdominal pain of HGM patients were higher than those of CNAG patients (63.4%, 52/82 vs. 5.1%, 9/178; 58.5%, 48/82 vs. 3.9%, 7/178; 50.0%, 41/82 vs. 3.9%, 7/178; 43.9%, 36/82 vs. 4.5%, 8/178; 34.1%, 28/82 vs. 12.4%, 22/178; 14.6%, 12/82 vs. 2.8%, 5/178; 34.1%, 28/82 vs. 3.9%, 7/178; 20.7%, 17/82 vs. 11.2%, 20/178; 30.5%, 25/82 vs. 15.2%, 27/178; 32.9%, 27/82 vs. 14.6%, 26/178; 15.9%, 13/82 vs. 9.6%, 17/178), and the differences were statistically significant ( χ2=106.50, 100.40, 79.10, 62.00, 17.20, 4.10, 74.00, 12.80, 8.20, 11.60 and 2.20, all P<0.01). The incidence rates of pharyngeal reflux symptoms foreign body sensation, swallowing discomfort, and hoarseness of patients with acid secretion type of HGM were higher than those of mucinous type (72.7%, 16/22 vs. 35.0%, 7/20; 72.7%, 16/22 vs. 15.0%, 3/20; 50.0%, 11/22 vs. 20.0%, 4/20), and the differences were statistically significant ( χ2=6.00, 14.10 and 4.10, all P<0.01). The incidence rates of pharyngeal reflux symptoms foreign body sensation in the throat, swallowing discomfort, hoarseness, and cough of mixed type were higher than those of mucinous type (72.5%, 29/40 vs. 35.0%, 7/20; 72.5%, 29/40 vs. 15.0%, 3/20; 65.0%, 26/40 vs. 20.0%, 4/20; 62.5%, 25/40 vs. 15.0%, 3/20), and the differences were statistically significant ( χ2=7.80, 17.70, 10.80 and 12.10, all P<0.01). Conclusions:The pathological classification of HGM patients with clinical symptoms of pharyngeal reflux may be acid secretion type or mixed type, which can be treated with acid suppression drugs or argon plasma coagulation under gastroendoscopy.

Association of intestinal epithelial tight junctions, E.coli, intestinal mucosa Toll-like receptor-4 and tumor necrosis factor-alpha in rabbit with non-alcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the variation and association of intestinal epithelial tight junctions, E.coli, and expression of Toll-like receptor-4 (TLR-4) and tumor necrosis factor-alpha (TNFα) in a rabbit model of non-alcoholic fatty liver disease (NAFLD).</p><p><b>METHODS</b>Fourteen male New Zealand rabbits were randomly divided into two groups. The control group was given a normal diet, while the NAFLD group was given a high-fat diet. After 12 weeks, the two groups were sacrificed. Both length and width of the tight junctions of ileum epithelial cells were measured by electron microscopy. Enzyme-linked immunosorbent assay was used to detect the concentration of TNFα in venous blood serum. Location and expression of TLR-4 were observed by immunohistochemical staining. Copies of E.coli genes were measured by RT-PCR. The relationship between TNFα and tight junctions, TLR-4, and E.coli were respectively analyzed by stepwise multiple linear regression.</p><p><b>RESULTS</b>Compared with the control group, the NAFLD group has significantly shortened ileum epithelial fight junctions (t=5.031, P<0.01), increased copies of E. coli genes (t=-3.492, P<0.01), and increased ileal expression of TLR-4 (t=-44.089, P<0.01). A significant increase of TNFα was also observed in the NAFLD group (t=-17.768, P<0.01). Regression analysis showed that E.coli and intestinal epithelial tight junctions were correlated (standardized beta=-0.385), and showed a positive correlation between E. coli and TLR-4 (standardized beta=0.332 and 0.427).</p><p><b>CONCLUSION</b>Damage to the intestine as a physical barrier, biological barrier and immune barrier is closely related to TNFα expression, and the relation between the immune barrier and TNFα is more significant.</p>

Prevention of postoperative complications after single-stage hypospadias repair / 中国医师进修杂志

Objective To summarize experience to prevent the main postoperative complications after hypospadias repairs. Method The clinical data of 189 cases of hypospadias repairs was from May 2005 to August 2010,retrospectively analyzed. Results One hundred and seventy-four cases were surgically cured by single-stage operation. All cases had been followed up for 4-36 (18.5 ± 5.5) months, the cases who had become adults were normal penile development and erectile function. Postoperative complications occurred in 15 cases,9 cases of them were urethral fistulas,6 cases were urethral strictures,all were cured or improved after symptomatic treatments. Conclusions Some methods are necessary to raise single-stage urethroplasty success rate and decrease the incidence of fistulas and strictures, such as preoperative antibiotic prophylaxis,appropriate procedure,intraoperative suprapublic urinary diversion,the good blood supply of the flap, modified enswathement, postoperative manage and nursing.

Toll-like Receptors Signaling and Regulation of Immune Response / 生物化学与生物物理进展

Toll-like receptors (TLRs), a large family consisting of at least 10 members, are evolutionarily conserved to recognize pathogen-associated molecular patterns (PAMPs). TLRs activation not only initiates innate immunity, but also regulates enhance antigen-specific acquired immunity, and thus associates innate and adaptive immunity. In recent years, studies on the TLRs signaling, especially their negative regulation, rapidly progressed. TLRs signaling pathway and their roles in regulating immune responses against invading pathogens were reviewed.