Chengping Wen

Central sensitization is a critical pathophysiological mechanism underlying chronic pain in rheumatoid arthritis (RA). CD4 ⁺ T cells not only promote chronic inflammation in RA but may also migrate into the central nervous system to stimulate central sensitization. However, the regulatory mechanism by which CD4 ⁺ T cells contribute to central sensitization in RA remains unclear. In this study, we report that CD4 ⁺ T cells were significantly accumulated in the spinal dorsal horn (SDH) of collagen‐induced arthritis (CIA) mice and promoted their central sensitization‐like behaviors. Mechanistically, PKM2‐dependent lactate facilitated H3K9 lactylation (H3K9la) in CD4 ⁺ T cells. H3K9la was highly enriched at the promoters of XBP1, which facilitated the transcription of KIF4 and MYO1B and the accumulation of CD4 ⁺ T cells in SDH. Furthermore, XBP1 may facilitate the transcription of PKM2, establishing a positive feedback loop between PKM2‐induced H3K9la and XBP1 signaling in CIA mice. Crucially, the clinical relevance of this pathway was validated in patients with RA, where the expression of PKM2/H3K9la/XBP1 was significantly increased and positively correlated with central sensitization scores. Overall, our study indicates a positive feedback loop of PKM2/H3K9la/XBP1 in facilitating CD4 ⁺ T cell spinal recruitment, which may provide a promising therapeutic strategy for mitigating central sensitization in RA.

Background: Rheumatoid arthritis (RA) is influenced by environmental exposures. High humidity has been clinically associated with worsened joint symptoms, but the microbial and metabolic mechanisms remain unclear. We investigated whether a gut microbiota–metabolism axis contributes to humidity-associated aggravation of collagen-induced arthritis (CIA). Methods: CIA mice were maintained under normal or high relative humidity. We integrated 16S rRNA and metagenomic sequencing, liquid chromatography–tandem mass spectrometry metabolomics, and intestinal barrier assessments. Fecal microbiota transplantation (FMT) was performed to evaluate microbiota dependency. Based on multi-omics findings, we quantified chondroitin sulfate (CS) and conducted functional experiments involving Prevotella stercorea (P. stercorea) supplementation, CS administration, and in vitro degradation assays. Results: High humidity aggravated arthritis severity and systemic inflammation, including increased interleukin-6, interleukin-17A, and granulocyte colony-stimulating factor, and was accompanied by impaired intestinal barrier integrity. FMT supported a microbiota-dependent contribution. Metagenomic analysis identified enrichment of P. stercorea and glycosaminoglycan degradation pathways under high humidity. CS abundance was reduced in articular cartilage, P. stercorea degraded CS in vitro and was associated with cartilage CS loss in vivo, and CS supplementation attenuated arthritis under high humidity and reduced the arthritis-promoting effects associated with P. stercorea. Conclusions: High humidity is associated with microbiota-dependent functional remodeling, enhanced CS degradation, and aggravated arthritis in CIA mice. These findings suggest that humidity-associated alterations in microbial CS metabolism may link environmental exposure to cartilage disruption and joint inflammation.

This systematic review evaluated the performance and risk of bias in Systemic Lupus Erythematosus (SLE) disease manifestations and case fatality prediction models, based on a search of PubMed, Embase, and Cochrane Library up to October 17, 2025. Risk of bias was assessed using the Prediction model Risk Of Bias Assessment Tool (PROBAST). A random-effects meta-analysis pooled the Area Under the Curve (AUC) values with 95% Confidence Intervals (CIs), with sensitivity and subgroup analyses. The study included 35 studies comprising 89 prediction models, primarily from China (92.3%). Designs were mainly cross-sectional (46.2%) or retrospective cohort (42.3%). Common predictor categories included immunologic/autoantibody profile s (n = 148) and biochemical parameters (n = 126). During development, pulmonary (AUC = 0.92, 95% CI: 0.78–0.87), perinatal (0.92, 0.83–1.03), and case fatality models (0.91, 0.89–0.95) performed highly, while cardiovascular models scored lower (0.78, 0.74–0.81). Upon validation, pulmonary models remained superior (0.86, 0.81–0.91); perinatal (0.82, 0.77–0.87) and cardiovascular models (0.80, 0.76–0.83) remained robust, whereas case fatality models declined markedly. Machine learning models showed greater potential for pulmonary outcomes (0.83, 0.78–0.89). Predictor number improved renal model performance but reduced accuracy for case fatality. All 89 models were rated high risk of bias and mostly low applicability per PROBAST.

The SARS-CoV-2 pandemic had unprecedented impacts on public health and the economy. Many studies have focused on the mechanisms of SARS-CoV-2 entry into host cells, particularly the spike (S) protein mediated receptor engagement and subsequent virus-host membrane fusion dynamics. However, the mechanistic contribution of cholesterol within spike-incorporated viral envelopes to infectivity has not been well characterized. Herein, we show that targeted cholesterol depletion from the viral envelopes of SARS-CoV-2, SARS-CoV, and MERS-CoV directly impaired viral infectivity in a dose-dependent manner. Although modulation of host cell membrane cholesterol exerted relatively minor effects on viral entry, host cellular cholesterol homeostasis critically governs progeny virion infectivity by determining cholesterol content within nascent viral envelopes. Virions derived from cells with reduced plasma membrane cholesterol demonstrate significantly attenuated infectivity in SARS-CoV-2 and related coronaviruses. In addition, we detected that exogenous cholesterol replenishment restored SARS-CoV-2 entry efficiency by augmenting virus attachment. Collectively, our data demonstrate that biophysical properties of human coronavirus envelopes, particularly cholesterol stoichiometry, function as a key molecular determinant regulating host cell susceptibility. These findings position viral lipidome remodeling as a viable therapeutic target for developing host-directed broad-spectrum antivirals.

Background: Methotrexate (MTX), a folate antagonist, is widely used in the treatment of tumors and autoimmune diseases such as rheumatoid arthritis (RA), due to its antiproliferative, antimetabolic, and potent anti-inflammatory properties. However, high-dose or long-term use of MTX can result in toxicity to the gastrointestinal, hemopoietic, and reproductive tissues. Yunpi Jiedu Tongluo Qushi Decoction (YJT), an effective Chinese herbal formula, is utilized in RA treatment to mitigate the toxic and side effect of MTX. Despite its clinical application, the precise effects and the underlying mechanisms through which it mitigates reproductive damage have yet to be elucidated.Purpose: This study was conducted to investigate the protective effects and mechanisms of YJT against MTX-induced reproductive toxicity.Methods: Here we used an integrated approach combining Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS), in vitro and vivo experiments, and molecular docking technology to systematically elucidate the protective effects and mechanism of YJT.Results: We identified nine active ingredients in YJT that contributed to its efficacy. YJT alleviated testicular damage in MTX-exposed rats, resolved abnormalities of sperm morphology, structure, and quality, decreased the number of TUNEL-positive cells in testicular tissue, and reduced oxidative stress (OS). YJT affected GC2spd cell apoptosis by regulating OS response. Both in vitro and vivo experiments showed that YJT can activate the Nrf2/HO-1 signaling pathway against OS response. Molecular docking results further confirmed the strong binding activity between the core components of YJT and Nrf2, HO-1.Conclusion: Collectively, our findings indicate that YJT protects against MTX-induced apoptosis in spermatogenic cells by inhibiting OS and Nrf2/HO-1 signaling pathway. This study provides a theoretical foundation and experimental basis for the use of YJT to alleviate MTX-induced reproductive toxicity.

Background: The relationship between lung function and depression in middle-aged and older adults remains poorly understood. To address this knowledge gap, we conducted cross-sectional and longitudinal analyses using data from the nationally representative China Health and Retirement Longitudinal Study (CHARLS) to examine the association between peak expiratory flow (PEF) status and depression among middle-aged and older Chinese adults.Methods: A total of 15,137 participants aged 45 years and older were included from the 2015 China Health and Retirement Longitudinal Study (CHARLS). Participants were categorized into three PEF status groups based on their percentage of predicted PEF: severe impairment (n = 1,044) in the cross-sectional sample, with higher rates observed in participants with poorer lung function (9.53, 7.11, and 5.03% for good, moderately good, and poorer lung function, respectively). During a 3.6-year follow-up, 6.73% (n = 130) of participants developed depression. Fully adjusted logistic regression analysis demonstrated a significant inverse linear association between PEF percentage and depression risk (OR: 0.898, 95% CI: 0.862–0.935, per 1 SD increase). These findings were corroborated by restricted cubic spline (RCS) regression analysis, which revealed a linear relationship without evidence of nonlinearity (P for nonlinearity = 0.631).Conclusion: Our study revealed a noteworthy correlation between PEF percentage and depression among the middle-aged and older population. The PEF percentage emerges as a valuable tool that may enhance the primary prevention and treatment of depression.