Efficacy of Qingpeng ointment (a Tibetan medicine) for acute gouty arthritis: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION: ISRCTN34355813. Registered on 25/01/2021.

Protocol for rheumatoid arthritis complicated with cardiovascular damage treated with Guanxining tablet with a randomized controlled trial.

Background: Cardiovascular disease (CVD) is the main cause of death in patients with rheumatoid arthritis (RA). Apart from traditional cardiovascular risk factors, immune dysfunction and chronic inflammation of RA are also risk factors for complex cardiovascular damage. Although methotrexate (MTX) is beneficial to CVD in RA patients by inhibiting inflammation, its adverse effects limit its clinical application. Therefore, it is essential to seek safer and more effective drugs. Objective: We aimed to assess the efficacy of Guanxining Tablet (GXNT) for rheumatoid arthritis complicated with cardiovascular damage. Methods: We will conduct a prospective single-center randomized trial. We will randomly divide 56 eligible patients into two groups. The treatment group will take GXNT and MTX treatment, and the control group will receive MTX and the placebo. The primary outcome measure will be aortic distensibility (AD). Secondary outcome measures will be Cardiac function which will contain right ventricular outflow tract diameter (RVOTD), aortic diameter (AOD), left atrium diameter (LAD), right ventricular end diastolic diameter (RVDD), left ventricular end diastolic diameter (LVDD), ejection fraction (EF%), fractional shortening (FS%), stroke volume (SV). Adverse events will be closely monitored during the entire trial period. Discussion: This trial is intended to determine whether the addition of GXNT will improve the prognosis of patients with rheumatoid arthritis and cardiovascular damage without severe adverse reactions. Completing this clinical trial might provide these patients with a novel and effective drug while avoiding adverse reactions similar to methotrexate. Trial registration: ChiCTR2000030247.

Integrated Analysis Identifies Upregulated SAMD9L as a Potential Biomarker Correlating with the Severity of Primary Sjögren's Syndrome.

Background: Primary Sjögren's syndrome (pSS) is an autoimmune disease with lymphocytic infiltration of the salivary and lachrymal glands, whose present disease-specific objective indicators are few and have shortcomings that should be addressed. An integrated analysis of sequencing data from different cohorts has the potential to unveil novel biomarkers in pSS. Methods: We identified 3 GEO datasets, including gene expression data from minor salivary gland (MSG) biopsy samples of 49 patients with pSS and 31 non-pSS and whole blood cells of 30 pSS patients and 30 healthy controls (HCs). Differentially expressed genes (DEGs) involved in pSS were identified from these datasets. Function Enrichment Analyses of common upregulated DEGs and PPI (protein-protein interaction) networks were performed. Furthermore, we have carried out further analysis of these DEGs to explore their potential clinical significance and diagnostic efficacy as a biomarker for pSS. Sterile Alpha Motif Domain Containing 9 Like (SAMD9L), one of the DEGs, has been identified as a promising candidate biomarker that correlates with the severity of pSS. This has been validated by analyzing local clinical samples from 30 pSS and non-pSS patients' MSG biopsies, as well as serum samples of 18 pSS and HC individuals. Finally, we performed correlation analysis to understand the relationship between SAMD9L and infiltrated immune cells. Results: We identified 10 common highly expressed DEGs in pSS of different tissues. These genes were mainly involved in virus infection-related pathways and inferno-related pathways. GEO data and our clinical data showed that SAMD9L increases with disease severity. Public and local cohorts showed that SAMD9L has high diagnostic performance (AUC=0.845-0.867) as a biomarker, and its AUC was comparable to the Focus score when combined with RF or SSA. Conclusion: Up-regulated SAMD9L may serve as a promising novel pSS diagnostic biomarker and have potential value for evaluating the severity of pSS.

Traditional Chinese medicine use is associated with lower risk of pneumonia in patients with systemic lupus erythematosus: a population-based retrospective cohort study.

Objectives: To investigate the association between traditional Chinese medicine (TCM) therapy and the risk of pneumonia in patients with systemic lupus erythematosus (SLE). Methods: This population-based control study analyzed the data retrieved from the National Health Insurance Research database in Taiwan. From a cohort of 2 million records of the 2000-2018 period, 9,714 newly diagnosed patients with SLE were initially included. 532 patients with pneumonia and 532 patients without pneumonia were matched 1:1 based on age, sex, and year of SLE diagnosis using propensity score matching. The use of TCM therapy was considered from the SLE diagnosis date to the index date and the cumulative days of TCM therapy were used to calculate the dose effect. Conditional logistic regression was used to investigate the risk of pneumonia infection. Furthermore, to explore the severity of pneumonia in SLE, sensitivity analyses were performed after stratification using the parameters of emergency room visit, admission time, and antibiotic use. Results: TCM therapy for >60 days could significantly reduce the risk of pneumonia in patients with SLE (95% CI = 0.46-0.91; p = 0.012). Stratified analysis showed that TCM use also reduced the risk of pneumonia in younger and female patients with SLE by 34% and 35%, respectively. TCM for >60 days significantly reduced the risk of pneumonia in the follow-up periods of >2, >3, >7, and >8 years. In addition, the exposure of TCM for >60 days reduced the risk of pneumonia in patients with SLE who were treated with antibiotics for moderate or severe pneumonia. Finally, the study found that using formulae to tonify the kidney for more than 90 days and formulae to activate blood circulation for less than 30 days could significantly reduce the risk of pneumonia infection in patients with SLE. Conclusion: TCM use is associated with a lower risk of pneumonia among patients with SLE.

Whole-genome bisulfite sequencing identified the key role of the Src family tyrosine kinases and related genes in systemic lupus erythematosus.

BACKGROUND: As a multisystemic autoimmune illness, the basic mechanisms behind the pathophysiology of systemic lupus erythematosus (SLE) remain poorly understood. OBJECTIVE: We aimed to investigate the possible significance of SLE's DNA methylation and gain further insight into potential SLE-related biomarkers and therapeutic targets. METHODS: We used whole genome bisulfite sequencing (WGBS) method to analyze DNA methylation in 4 SLE patients and 4 healthy people. RESULTS: 702 differentially methylated regions (DMRs) were identified, and 480 DMR-associated genes were annotated. We found the majority of the DMR-associated elements were enriched in repeat and gene bodies. The top 10 hub genes identified were LCK, FYB, PTK2B, LYN, CTNNB1, MAPK1, GNAQ, PRKCA, ABL1, and CD247. Compared to the control group, LCK and PTK2B had considerably decreased levels of mRNA expression in the SLE group. Receiver operating characteristic (ROC) curve suggested that LCK and PTK2B may be potential candidate biomarkers to predict SLE. CONCLUSIONS: Our study improved comprehension of the DNA methylation patterns of SLE and identified potential biomarkers and therapeutic targets for SLE.

Assessment of bidirectional relationships between systemic lupus erythematosus and anxiety disorder: A two-sample Mendelian randomization study.

BACKGROUND: Observational studies have demonstrated that there was a significant correlation between systemic lupus erythematosus (SLE) and anxiety disorder, but the causal relationship between them is not so clearly established. This study aims to reveal the potential causal link between SLE and anxiety disorder. METHODS: Summary statistical data of SLE and anxiety disorder were from two large-scale genome-wide association studies (GWAS) of European ancestry, followed by a bidirectional two-sample Mendelian randomization (MR) analysis. The inverse variance-weighted (IVW) method was used as the main method to evaluate causal effects, while MR-Egger, weighted median, simple mode, and weighted mode were supplementary methods. Outliers were excluded by MR-pleiotropy residual sum and outlier (MR-PRESSO). Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were used to evaluate the stability of the results. RESULTS: According to the results of IVW, we did not observe that there was a statistically significant causal association between genetically predicted SLE and the risk of anxiety disorder (OR = 1.000, 95%CI = 0.992 to 1.008, p =.997). Conversely, there were no causal effects between anxiety disorder and SLE risk (OR = 1.000, 95%CI = 0.992 to 1.008, p = .997). A similar result was obtained by supplementing the MR method. In addition, sensitivity analysis indicated high stability of the result. CONCLUSION: Bidirectional two-sample MR study does not support the causal relationship between SLE and anxiety disorder.

Assessment of bidirectional relationships between depression and rheumatoid arthritis among adults: a two-sample Mendelian randomization study.

OBJECTIVE: Increasing evidence shows that depression is associated with rheumatoid arthritis (RA). However, the causality and direction of this association remain unclear, because links between the two diseases might be caused by shared environmental confounding factors. Our study aims to understand a putative causal link between the two diseases. METHODS: We retrieved summary statistics from meta-analyses of non-overlapping genome-wide association studies (GWASes) for depression (n = 807,553, 246,363 cases and 561,190 controls) and RA (n = 58,284, 14,361 cases and 42,923 controls). We combined Mendelian randomization (MR) estimates from each genetic instrument using inverse-variance weighted (IVW) meta-analysis, with alternate methods (e.g., simple median approach, weighted median approach, and MR-Egger regression) and conducted sensitivity analyses to assess the robustness of MR analyses. RESULTS: We found no evidence of causal relationships between depression and RA across all MR methods (IVW OR, 1.028 for RA; 95% CI, 0.821-1.287; P = 0.810) or vice versa (IVW OR, 0.999 for depression; 95% CI, 0.984-1.014; P = 0.932), indicating the links between the two diseases might be due to confounders. CONCLUSION: Despite the results, to optimize treatment outcomes of RA patients, we still emphasize depression should be managed as part of routine clinical care to optimize treatment outcomes of RA.

Molecular mechanism of QH-BJ drug pair in the treatment of systemic lupus erythematosus based on network pharmacology and molecular docking.

To analyze the molecular mechanism of Qinghao-Biejia (QH-BJ) drug pair in the treatment of systemic lupus erythematosus (SLE) based on the method of network pharmacology and molecular docking technology. The components and related targets of QH-BJ drug pair, as well as SLE-related targets, were obtained. Intersection targets of QH-BJ drug pair and SLE were screened to construct the protein-protein interaction network, conduct gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and establish the component-target-pathway network. The core active components and core targets of QH-BJ drug pair for the treatment of SLE were selected, and molecular docking was carried out between the ligand components and the receptor target proteins. The core active components of QH-BJ drug pair for the treatment of SLE are luteolin, quercetin, and kaempferol; the core targets are PTGS2, HSP90AA1, RELA, MAPK1, MAPK14, AKT1, JUN, TNF, TP53. The ligand components can spontaneously bind to the receptor target proteins. Besides, QH-BJ drug pair is likely to act on PI3K/Akt signal pathway, interleukin-17 signal pathway, and TNF signal pathway in the treatment of SLE. The study indicates that QH-BJ drug pair might play a role in the treatment of SLE through multi-components, multi-targets, and multi-pathways.

Design, Synthesis, and Antitumor Evaluation of Novel Mono-Carbonyl Curcumin Analogs in Hepatocellular Carcinoma Cell.

Curcumin is a polyphenolic natural product that has promising anticancer properties. However, its clinical utility is limited by its chemical instability and poor metabolic properties. In this paper, a series of new curcumin analogs were synthesized and found to be potent antiproliferative agents against the HepG2 cell line by MTT assay. In general, Group B with single ketone and group C with chalcone were markedly more cytotoxic than group A with diketone. Compound B5 was found as the most potent analog (IC50 = 11.33 µM) compared to curcumin (IC50 = 32.83 µM) and the mechanism of its cytotoxicity was investigated. The result of the wound healing assay indicated B5 strong potential to suppress HepG2 cell migration in a dose- and time-dependent manner. Subsequent assays (including JC-1 staining, Bcl-2, and caspase 3 protein levels by Western blotting) confirmed that B5 exposure induced apoptosis in HepG2 cells. Curcumin-induced comprehensive transcriptomes profile, Western blotting, molecular docking, and molecular dynamics analysis showed that the mechanism may relate to the regulation of cellular metabolic process and the expression of AKT protein. Taken together, we could conclude that curcumin and its analogs induced HepG2 cell proliferation, migration, and apoptosis via AKT signaling pathway and the mitochondrial death pathway. This study could lay the foundation for optimizing curcumin and provide valuable information for finding novel anti-HCC drugs.

Safety of COVID-19 vaccines in patients with non-communicable diseases: a protocol for systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: The COVID-19 global pandemic has posed enormous threats to public health around the world. Vaccines are considered the best therapeutic strategy against the COVID-19 pandemic. However, the adverse reactions of vaccines significantly affect the rates of vaccination and may be more serious in patients with non-communicable diseases (NCDs). This protocol aims to conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) which analysed the safety of vaccines in patients with NCDs. METHODS AND ANALYSIS: This study will be according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. A comprehensive search will be carried out to identify registered RCTs in PubMed, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library between 1 January 2020 and 31 May 2022. Selection of trials, data extraction, risk of bias assessment and quality of evidence assessment will be done by two researchers, and disagreements will be resolved by the corresponding author. The primary outcomes are local and systemic adverse events of vaccines in patients with NCDs. Additional outcomes are related events caused by vaccine adverse events, including but not limited to cases of adverse events leading to discontinuation from a dose or withdrawal from participation in the trial. Heterogeneity will be assessed with I2 statistics and data analysis will be conducted with RevMan V.5.4.1. ETHICS AND DISSEMINATION: This is a protocol and ethical approval is not necessary. The results of this protocol will be disseminated to peer-reviewed publications or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42021254914.

Lianhua Qingwen Capsules Reduced the Rate of Severity in Patients with COVID-19: A System Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The rate of severity is a critical factor affecting the prognosis and mortality in coronavirus disease 2019 (COVID-19). Lianhua Qingwen capsules or granules (LQ) have been a promising Chinese patent medicine in treating infectious diseases and recommended for treating COVID-19. This meta-analysis aims to demonstrate the association between LQ treatment and the rate of severity in patients with mild or moderate COVID-19. METHODS: 7 electronic databases were systematically searched from the inception dates to March 27, 2021, using the search terms to identify randomized controlled trials (RCTs). Two reviewers independently identified studies, extracted the data, and assessed study quality. All analyses were conducted on RevMan 5.3 software. RESULTS: A total of 5 RCTs involving 830 patients with mild or moderate COVID-19 were identified according to the inclusion and exclusion criteria. The quality of included studies is moderate. Compared with conventional therapy, there was a significant association of LQ treatment with a higher clinical efficacy (RR = 1.24, 95% CI (1.13, 1.36), P < 0.00001), rate of CT improvement (RR = 1.22, 95% CI (1.10, 1.34), P=0.0001), and a lower rate of conversion to severe cases (RR = 0.47, 95%CI (0.31, 0.71), P=0.0003). CONCLUSION: LQ combined with conventional therapy had great effects in reducing the rate of severity, and these findings supported the routine treatment of LQ in patients with mild or moderate COVID-19.

Aflatoxin B1: metabolism, toxicology, and its involvement in oxidative stress and cancer development.

Aflatoxins are a class of carcinogenic mycotoxins produced by Aspergillus fungi, which are widely distributed in nature. Aflatoxin B1 (AFB1) is the most toxic of these compounds and its metabolites have a variety of biological activities, including acute toxicity, teratogenicity, mutagenicity and carcinogenicity, which has been well-characterized to lead to the development of hepatocellular carcinoma (HCC) in humans and animals. This review focuses on the metabolism of AFB1, including epoxidation and DNA adduction, as it concerns the initiation of cancer and the underlying mechanisms. In addition to DNA adduction, inflammation and oxidative stress caused by AFB1 can also participate in the occurrence of cancer. Therefore, the main carcinogenic mechanism of AFB1 related ROS is summarized. This review also describes recent reports of AFB1 exposures in occupational settings. It is hoped that people will pay more attention to occupational health, in order to reduce the incidence of cancer caused by occupational exposure.

Association of BCL2 polymorphisms and the IL19 single nucleotide polymorphism rs2243188 with systemic lupus erythematosus.

OBJECTIVE: Abnormal B cell lymphoma-2 (Bcl-2) and interleukin-19 (IL-19) expression is closely related to systemic lupus erythematosus (SLE) pathogenesis. We aimed to determine whether BCL2 polymorphisms and a single nucleotide polymorphism (SNP) of IL19 are significantly associated with SLE susceptibility and if this is affected by synergism between IL19 and BCL2 genotypes. METHODS: This observational cohort study randomly enrolled 150 patients with SLE and 150 healthy controls. Major BCL2 and IL19 allele and genotype distributions were examined in the two groups. The IL19 SNP rs2243188 was determined using the TaqMan-MGB probe method. The synergistic effect between BCL2 and IL19 and clinical symptoms of SLE was also analyzed. RESULTS: The distribution of major BCL2 genotypes and common BCL2 alleles, especially for genotypes 191, 193, and 197, differed significantly between patients and controls. A significant difference in the dominant genetic model was also observed between groups, but not in the recessive model. The risk of disease in individuals who carried both 195-bp BCL2 and 138-bp IL19 susceptibility alleles was higher than in those carrying either allele alone. CONCLUSIONS: This preliminary study suggested that BCL2 polymorphisms and the IL19 SNP rs2243188 are closely related to the pathogenesis of SLE.

The combined therapy of fecal microbiota transplantation and laxatives for functional constipation in adults: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Functional constipation is a prevalent, burdensome gastrointestinal disorder whose treatment remains challenging. Combined therapy uniting multiple treatments may be promising. Fecal microbiota transplantation (FMT) which tends to be an etiological treatment has been increasingly investigated in its management. Meanwhile, laxatives are widely used to relieve constipation temporarily, but their overall efficacy is poor. Therefore, we performed meta-analyses of randomized controlled trials to evaluate the joint efficacy of FMT and laxatives in functional constipation. METHODS: We performed a systematic literature search of 6 electronic databases as of August 11, 2020. Randomized controlled trial of FMT together with laxatives vs laxatives alone in functional constipation in adults were included. Two reviewers independently performed the screening, data extraction, and bias assessment. Dichotomous outcome data were synthesized by risk ratio, and measurement data by weighted mean difference (WMD). RESULTS: A total of 1400 records were identified, of which 5 were eligible (409 patients). Overall, compared to laxatives alone, combined therapy of FMT and laxatives more significantly improved total effective rate (risk ratio: 1.35; 95% confidence interval [CI]: 1.14, 1.60; I2 = 13%), Bristol stool form scale score (WMD: 1.04; 95% CI: 0.57, 1.51; I2 = 76%), reduce Wexner score (WMD: -3.25; 95% CI: -5.58, -0.92; I2 = 92%), Knowles-Eccersley-Scott-Symptom (KESS) score (WMD: -5.65; 95% CI: -7.62, -3.69; I2 = 0%) and patient assessment of constipation quality of life score (WMD: -18.56; 95%; CI: -26.43, -10.68; I2 = 78%). No serious adverse events were reported. The majority of included studies had poor methodological quality. CONCLUSION: Combined therapy of FMT and laxatives may be a reasonably effective and safe treatment for people with functional constipation. However, caution is needed with the interpretation of these data due to the small sample size, high heterogeneity, and low quality of the studies. Besides, we expect that more studies will be performed exploring the efficacy and safety of combined therapy for functional constipation.

An overview of autophagy: Mechanism, regulation and research progress.

Autophagy refers to the formation of autophagosomes by membrane wrapping part of the cytoplasm and the organelles and proteins that need to be degraded in the cells. Autophagosomes are fused with lysosomes to form autophagolysosome, which degrade the contents of the inclusions, to achieve cell homeostasis and organelle renewal. The regulatory mechanism of autophagy is complex, and its upstream signaling pathway mainly involves mTOR dependent pathway and mTOR independent pathway (AMPK, PI3K, Ras-MAPK, p53, PTEN, endoplasmic reticulum stress). Autophagy is a phenomenon of "self-eating" in cells. Apoptosis is a phenomenon of "self-killing". Both of them share the same stimulating factors and regulatory proteins, but the threshold of induction is different. How to transform and coordinate is not clear at present. This paper summarizes the history of autophagy discovery, the structure and function of related molecules, the biological function of autophagy, the regulatory mechanism and the research results of the relationship between autophagy and apoptosis.

The influence mechanism of nano-alumina content in semi-solid ceramic precursor fluid on the forming performance via a light-cured 3D printing method.

The use of three-dimensional (3D) printing technology to form ceramic materials can greatly reduce the technical difficulty and cost of preparing special-shaped ceramic parts. In this work, the formation of the 3D structure of ceramic products was achieved through light-curing 3D printing technology. The semi-solid ceramic precursor fluid prepared from nano alumina particles (Al2O3), photocurable polyurethane acrylate (PUA) and isobornyl methacrylate (IBOMA) resin was used to realize ceramic fluid with self-made light-curing 3D printing equipment. The solidification and forming of the ceramic material was achieved through secondary high temperature sintering. In order to reveal the influence mechanism of nano-alumina content in a ceramic slurry on the forming process and performance of light-curing 3D printing, the composition, micro morphology and mechanical properties of 3D printing ceramic samples under different preparation conditions were investigated. The research results show that the relationship of the ratio of alumina to the forming performance was not a monotonic function in the mathematical sense. When the mass ratio of the resin system and alumina was 1 : 2.50, the performance of the formed sample was the best. At this time, the Vickers strength of the sintered ceramic part was 79 GPa, the bending strength was 340 MPa, and the fracture toughness was 2.90 MPa m-2. This work laid a theoretical and practical foundation for the realization of high-quality, low-cost, and rapid ceramic manufacturing technology in the future.