Associations between rheumatoid arthritis and intestinal flora, with special emphasis on RA pathologic mechanisms to treatment strategies.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that primarily affects the joints. Individuals at risk for RA and people with RA develop intestinal dysbiosis. The changes in intestinal flora composition in preclinical and confirmed RA patients suggest that intestinal flora imbalance may play an important role in the induction and persistence of RA. METHODS: Based on the current research on the interaction between RA and intestinal microbiota, intestinal microbiota metabolites and intestinal barrier changes. This paper systematically summarized the changes in intestinal microbiota in RA patients, the metabolites of intestinal flora, and the influence mechanism of intestinal barrier on RA, and further discussed the influence of drugs for RA on intestinal flora and its mechanism of action. RESULTS: Compared with healthy controls, α diversity analysis of intestinal flora showed no significant difference, ß diversity analysis showed significant differences. The intestinal flora produces bioactive metabolites, such as short-chain fatty acids and aromatic amino acids, which have anti-inflammatory effects. Abnormal intestinal flora leads to impaired barrier function and mucosal immune dysfunction, promoting the development of inflammation. Traditional Chinese medicine (TCM) and chemical drugs can also alleviate RA by regulating intestinal flora, intestinal flora metabolites, and intestinal barrier. Intestinal flora is closely related to the pathogenesis of RA and may become potential biomarkers for the diagnosis and treatment of RA. CONCLUSIONS: Intestinal flora and its metabolites play an important role in the pathogenesis of autoimmune diseases such as RA, and are expected to become a new target for clinical diagnosis and treatment, providing a new idea for targeted treatment of RA.

An Analysis of Infection Prevention and Control Practices in Designated Hospitals that Treat COVID-19: A Systematic Review and Meta-Analysis.

Objective: The present investigation aims to conduct a comprehensive examination of the infection prevention and control efforts in hospitals of Xinjiang Production and Construction Corps designated for COVID-19 treatment. Methods: By searching the Cochrane Library, PubMed, Embase, Chinese Academic Journal, Full Text Database, Chinese Biomedical Literature Database (CBM), VIP Chinese Scientific, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (CECDB), and using Review Manager 5.2 software, the quality assessment, data extraction, and meta-analysis were carried out for the included literature. Results: Between both the experimental and the control groups, there was a statistically significant difference in the level of public awareness of COVID-19 prevention and control [OR = 1.61, 95% confidence interval (CI) (1.31, 1.99), P < .00001, I2 = 32%, Z = 4]; public concern about COVID-19 prevention and control [OR = 1.56, 95% CI (1.28, 1.90), P < .0001, I2 = 0%, Z = 4.35]; public anxiety on COVID-19 prevention and control [OR = 1.67, 95% CI (1.37, 2.03), P < .00001, I2 = 32%, Z = 5.13]. Conclusion: Chinese prophylaxis and controlling measures for COVID-19 are mainly to protect vulnerable populations, cut off transmission routes, and control the source of infection. Therefore, we must also do our best to prevent and control novel coronavirus pneumonia to protect our health and reduce the burden on our country.

Effects of a combination of lauric acid monoglyceride and cinnamaldehyde on growth performance, gut morphology, and gut microbiota of yellow-feathered broilers.

A total of 480 one-day-old male yellow-feathered broilers were randomly divided into 4 groups with 6 replicates of 20 chicks per replicate. A basal diet was administered to the control group (CON), whereas CML350, CML500, and CML1000 groups were fed with basal diet supplemented with 350, 500, and 1,000 mg/kg of lauric acid monoglyceride and cinnamaldehyde complex, respectively. However, adding 500 mg/kg of lauric acid monoglyceride and cinnamaldehyde complex improved weight gain (P < 0.01), enhanced intestinal morphology, increased serum total protein and albumin content, and total antioxidant capacity (P < 0.01), and significantly increased the Chao1 and Ace indices (P < 0.01), indicating an increase in the richness of the gut microbiota. At the phylum level, CML500 group reduced the abundance of Fusobacteriota at 21 d and Proteobacteria at 42 d (P < 0.01). At the genus level, CML500 group increased the abundance of Faecalibacterium and Alistipes at 42 d (P < 0.01) and decreased the abundance of Escherichia-Shigella (P < 0.01). At the species level, CML500 group reduced the abundance of Escherichia coli at 42 d (P < 0.01) and increased the abundance of Alistipes_sp_CHKCI003 at 42 d (P < 0.01). According to these results, adding 500 mg/kg of lauric acid monoglyceride and cinnamaldehyde complex in feed can improve the growth performance, intestinal morphology, and gut microbiota of yellow-feathered broilers.

Gandouling inhibits hepatic fibrosis in Wilson's disease through Wnt-1/ß-catenin signaling pathway.

ETHNOPHARMACOLOGIC SIGNIFICANCE: Wilson's disease (WD) hepatic fibrosis is the result of chronic liver injury induced by Cu2+ deposition in the liver. Gandouling (GDL) is a hospital preparation of the First Affiliated Hospital of Anhui University of Chinese Medicine. Previous studies have found that GDL can play an anti-inflammatory, anti-oxidation, and promote Cu2+ excretion, which has a clear anti-WD effect. AIM OF THE STUDY: We found that Wnt-1 was significantly up-regulated in the liver tissue of toxic-milk (TX) mouse in the WD gene mutant model, and the monomer components of GDL could combine well with Wnt-1. Therefore, in this work, we used RT-qPCR, Western blot, immunofluorescence, network pharmacology, molecular docking, and related methods to study the effects of GDL on hepatic stellate cell (HSC) activation and Wnt-1/ß-catenin pathway in TX mice to clarify the effect of GDL on WD hepatic fibrosis. RESULTS: GDL could alleviate hepatic fibrosis, improve liver function, and inhibit the activation of HSC in TX mice. Network pharmacology predicted that the Wnt-1/ß-catenin was the target of GDL, and molecular dynamics further revealed that GDL has a good binding ability with Wnt-1 and inhibits the Wnt/ß-catenin signaling pathway through Wnt-1. Furthermore, we found that GDL blocked the Wnt-1/ß-catenin signaling pathway in the liver of TX mice in vivo. In vitro, serum containing GDL blocked the Cu2+ ion-induced Wnt-1/ß-catenin signaling pathway in LX-2 cells. Therefore, GDL blocked the Wnt-1/ß-catenin signaling pathway, inhibited HSC activation, and improved WD hepatic fibrosis by binding to Wnt-1. CONCLUSION: GDL improves hepatic fibrosis in WD model mice by blocking the Wnt-1/ß-catenin signaling pathway, and Wnt-1 may be a new target for the diagnosis and treatment of WD. This reveals a new mechanism of GDL against WD, and promotes the clinical promotion of GDL.

Huangqin Qingre Qubi Capsule inhibits RA pathology by binding FZD8 and further inhibiting the activity of Wnt/ß-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Qingre Qubi Capsule (HQC) is a Chinese herbal compound for the treatment of rheumatoid arthritis (RA), which is made from dry roots of Scutellaria baicalensis Georgi, dry mature seeds of Gardenia jasminoides J.Ellis, dry and mature seeds of Coix lacryma-jobi var. stenocarpa Oliv., dry mature seeds of Amygdalus persica L. and roots and rhizomes of Clematis chinensis Osbeck in the proportion of 10:9:30:5:10. HQC has a significant effect in clinical treatment of RA, which can inhibit RA inflammation, improve oxidative stress state, and effectively relieve symptoms of RA patients. AIM OF THE STUDY: The anti-arthritis effect of HQC and its mechanism, especially whether it improves RA through FZD8-Wnt/ß-catenin signal axis, were studied using adjuvant arthritis (AA) rats and FLS from RA patients. MATERIALS AND METHODS: Real time qPCR (RT-qPCR), Western blot (WB), confocal microscopy and other molecular biological methods were used to study the anti-RA effect of HQC and its mechanism. RESULTS: The expression of FZD8 was significantly up-regulated in synovium and FLS of AA rats and RA FLS. FZD8 significantly activated the Wnt/ß-catenin signaling pathway, promoted abnormal proliferation of FLS, increased the levels of inflammatory factors IL-1ß, IL-6 and IL-8, and significantly increased the expression of matrix metalloproteinase 3 (MMP3) and fibronectin. HQC has significant therapeutic effect on AA rats. Molecular docking and molecular dynamics showed that HQC had a good binding ability with FZD8. We also confirmed that HQC inhibited Wnt/ß-catenin signaling pathway by binding FZD8, and reduced the levels of the above inflammatory factors and pathological genes of RA. CONCLUSIONS: The expression of FZD8 is significantly increased in AA rats and FLS from RA patients. Clarify that HQC improves RA through the FZD8-Wnt/ß-catenin signal axis, provide a clear therapeutic mechanism for HQC to improve RA, and also provide a basis for clinical promotion of HQC.

Clematichinenoside AR inhibits the pathology of rheumatoid arthritis by blocking the circPTN/miR-145-5p/FZD4 signal axis.

BACKGROUNDS: Traditional Chinese medicine roots and rhizomes of Clematis chinensis Osbeck (CCO) has the effect of improving rheumatoid arthritis (RA), Clematichinenoside AR (CAR) is an effective monomer of CCO and a promising natural product for the treatment of RA. METHODS: In this work, we aim to systematically evaluate whether CAR can improve RA pathology, inhibit the fibroblast-like synoviocytes (FLS) proliferation and inflammatory response, and further investigate the mechanism of CAR inhibiting RA through molecular docking, molecular dynamics and molecular biology methods. RESULTS: Combined with the research results of CIA mice and FLS from RA patients, we found that CAR significantly improved the severity of CIA mice, and inhibited the proliferation and inflammatory response of FLS. Combined with bioinformatics prediction, we confirmed that circPTN promoted frizzled-4 (FZD4) expression through sponging miR-145-5p, then activating the Wnt/ß-catenin pathway. The circPTN/miR-145-5p/FZD4 signal axis was involved in the pathogenesis of RA. Furthermore, CAR blocked the circPTN/miR-145-5p/FZD4 signal axis by combining with FZD4 and improved RA pathology. CONCLUSIONS: The circPTN/miR-145-5p/FZD4 signal axis plays an important role in promoting the pathogenesis of RA, and CAR from CCO may inhibit RA pathology by combining the FZD4 and further blocking this signal axis.

Successful treatment with matched unrelated donor peripheral blood stem cell transplantation for very severe aplastic anemia in presence of active infections: A case report.

RATIONALE: Very severe aplastic anemia (vSAA) with active infections is always fatal. Adequate infection control before hematopoietic stem cell transplantation is recommended. PATIENT CONCERNS: A 38-year-old woman with vSAA suffered from acute perforated appendicitis and invasive pulmonary fungal infection, and she failed to respond to intense antimicrobial therapies. DIAGNOSIS: She was diagnosed with refractory vSAA with stubborn acute perforated appendicitis and invasive pulmonary fungal infection. INTERVENTIONS: We successfully completed an emergent reduced intensity conditioning-matched unrelated donor (MUD)-peripheral blood stem cell transplantation (PBSCT) as a salvage therapy in the presence of active infections. The conditioning regimens consisted of reduced cyclophosphamide 30 mg/kg/day from day-5 to day-3, fludarabine 30 mg/m/day from day-5 to day-3 and porcine-antilymphocyte immunoglobulin 15 mg/kg/day from day-4 to day-2 without total body irradiation. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. Neutrophils and platelets were engrafted on day+15 and day+21. Appendiceal abscess and severe pneumonia developed after neutrophil engraftment, which were successfully managed with intense antimicrobial therapy and surgical intervention. OUTCOMES: Only limited cutaneous chronic GVHD was observed 5 months after transplantation. The patient still lives in a good quality of life 2 years after transplantation. LESSONS: Active infections may be no longer a contraindication to hematopoietic stem cell transplantation for some patients with vSAA.