To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

This article reports a case of an elderly male patient presenting with nephrotic syndrome. Renal biopsy pathology indicated membranous nephropathy, with both renal tissue staining for M-type phospholipase A2 receptor (PLA2R) and serum anti-PLA2R antibodies being negative. Nephrotic syndrome achieved remission following treatment with prednisone combined with tacrolimus; however, the patient relapsed during tacrolimus maintenance therapy. Subsequent laboratory evaluation revealed positive anti-nuclear antibodies and anti-double-stranded DNA antibodies, accompanied by decreased complement levels. Exostosin 1 and Exostosin 2 staining performed on the initial renal biopsy specimen yielded positive results, leading to a diagnosis of lupus nephritis. Due to the patient's history of rituximab-related allergic reactions, pulmonary infection, and acute kidney injury, the subsequent treatment regimen consisted of obinutuzumab sequentially combined with belimumab, in addition to prednisone 10 mg/d. During the two-year follow-up period, the patient's anti-double-stranded DNA antibodies converted to negative, complement levels normalized, proteinuria achieved complete remission, and no adverse events such as severe infection occurred. This article reviews the diagnosis, treatment, and relevant literature for this case, aiming to provide clinical insights for the early diagnosis and selection of therapeutic strategies for similar patients.

Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

ObjectiveTo analyze the epidemiological and etiological characteristics of a cluster of human metapneumovirus (HMPV) infection in a kindergarten in Gongshu District of Hangzhou City in May 2024, and to provide reference for the prevention and control of similar outbreaks. MethodsAn on-site investigation was conducted using an epidemiological case investigation form. Throat swab specimens collected from cases were screened for 13 respiratory pathogens using real-time fluorescent polymerase chain reaction (PCR). For HMPV nucleic acid positive specimens, the F gene of HMPV was used as the target gene for amplification and sequencing. The sequencing results were then compared with sequences in GenBank database to determine the virus subtypes and perform phylogenetic analyses. ResultsThe outbreak occurred in a kindergarter junior class with a total of 28 preschoolers and 3 teachers and childcare workers. A total of 11 cases (10 preschoolers and 1 teacher) were identified, including 8 male cases and 3 female cases. Clinical manifestations included fever in all 11 cases (100.00%), cough in 8 cases (72.72%), catarrhal symptoms in 4 cases (36.36%), and headache in 3 cases (27.27%). All symptoms were mild, and no severe cases were observed. A total of 11 throat swab samples were collected. Real-time fluorescent PCR test results showed that 3 samples were positive for HMPV nucleic acid, 2 samples were positive for both HMPV and Streptococcus pneumoniae, and 1 sample was positive for both HMPV and rhinovirus. The sequences of the 6 HMPV nucleic acid positive specimens were amplified and analyzed using specific primers, and all were determined to be HMPV subtype A2b. The F gene fragment sequence showed the highest similarity to PV081665.1/Brazil/2024 (99.65%), and also exhibited high similarity to PP683455.1/Indonesia/2021 (99.48%), PV016275.1/Beijing/2024 (99.31%), and PV052230.1/USA/2024 (99.13%). ConclusionThis cluster of acute respiratory tract infection was caused by HMPV subtype A2b, with co-infection of rhinovirus and Streptococcus pneumoniae. The F gene fragment sequences of the HMPV in this outbreak were highly homologous to those of the A2b strains isolated from Brazil, Beijing, Indonesia, and the the United States.

This article systematically reviews the role and relationship of heme oxygenase （HO） in the pathogenesis of metabolic associated fatty liver disease （MAFLD） and discusses the biological function of HO， its expression in the liver， its association with lipid metabolism， and its regulatory role in inflammatory reaction and oxidative stress， in order to reveal the potential therapeutic targets and mechanism of HO in MAFLD and provide new perspectives and directions for future treatment strategies.

The deep integration of Party building and professional work is crucial for promoting high-quality development in university-affiliated hospitals.To address the current insufficient integration of Party building and operational development in such hospitals,the Tuina Department of the Second Affiliated Hospital of Anhui University of Chinese Medicine has adopted the"Seven Ones"Party building brand as a carrier.Using Party building as a driving force and traditional Chinese medicine culture as the core,the department has actively implemented a series of innovative Party building initiatives.By deeply integrating Party build-ing with medical services,it explores pathways for the fusion of"Party building+professional work,"leveraging high-quality Party building to facilitate the high-quality development of the hospital and contribute to the realization of the Healthy China strategy.

Aim To study the therapeutic effect of al-licin on senna-induced diarrhea in mice and to explore the underlying mechanism.Methods Forty-eight C57BL/6J mice were randomly divided into six groups:control,model,loperamide positive control group(2 mg·kg-1),allicin low-dose group(6 mg·kg-1),allicin medium-dose group(12 mg·kg-1)and allicin high-dose group(18 mg·kg-1).Except for the con-trol group,the diarrhea model was induced in the other groups by intragastric administration of senna leaf ex-tract.After drug administration,several diarrhea indi-ces were measured:the rate of loose stools,diarrhea index,accumulated frequency of loose stools at differ-ent time points within 5 hours,and small intestine pro-pelling rate.Serum levels of TNF-α and IL-6 were de-tected by ELISA.Serum NO content was determined u-sing the Griess method.The activities of SOD and CAT,as well as MDA content in the ileum and colon,were measured.The pathological changes and the ex-pression of mRNA related to intestinal barrier proteins in the ileum and colon were evaluated using HE stai-ning and RT-qPCR.Results Allicin improved diar-rhea symptoms in mice induced by senna leaf.It re-duced the rate of loose stools,diarrhea index,cumula-tive number of loose stools in five hours,and the intes-tinal propulsion rate.Allicin also protected the intesti-nal mucosa,decreased serum TNF-α and IL-6 levels,and lowered MDA content in the intestines.It in-creased serum NO levels and enhanced SOD and CAT activities in the intestines.Additionally,allicin upreg-ulated the mRNA expression of AQP1,AQP4,and ZO-1 in intestinal tissues.Conclusions Allicin has a significant therapeutic effect on senna-induced diarrhea in mice.The underlying molecular mechanisms may involve anti-inflammatory and antioxidant effects,in-creased NO content,and upregulation of mRNA ex-pression of aquaporins and tight-junction proteins.

Objective To establish a stable liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for detecting gamma-aminobutyric acid(GABA)in plasma,and to evaluate the value of GABA detection in the diagnosis of sleep disorders.Methods GABA was detected using a UPLC Xevo TQs system.The method was pre-validated and its performance was verified to establish a reference range for healthy individuals.The difference in plasma GABA levels between apparently healthy individuals and patients with sleep disorders was compared.Results We employed deuterated compounds as isotopic internal standards and utilized an Amide chromatographic column for separation.The mobile phase was 0.050%formic acid in water and 90%acetonitrile in water containing 0.175%formic acid and 5 mmol/L ammonium acetate with gradient elution in the column temperature of 35℃.The linear range for the detection of GABA by LC-MS/MS was 0.05-10.00 μmol/L,with a lower limit of quantification of 0.02 μmol/L,the inter-day CV<3.00%and intra assay CV<4.00%,respectively,and the recovery rate was 101.06%-109.02%.The reference ranges for plasma GABA were established by analyzing 300 healthy controls stratified by age:18-34 years(0.08-0.15 μmol/L),35-49 years(0.10-0.20 μmol/L),and≥50 years(0.12-0.23 μmol/L).Then plasma GABA was used as a biomarker for auxiliary diagnosis of sleep disorders in analyzing 221 patients and 300 healthy controls,which revealed that AUC values were 0.510(P=0.850),0.686(P=0.002),and 0.890(P<0.001)in the groups of 18-34 years,35-49 years,and≥50 years,respectively,with optimal cut-off values of 0.09,0.10 and 0.11 μmol/L.Conclusion A reliable LC-MS/MS method for detecting GABA has been established,which can detect plasma GABA levels sensitively and accurately and can be used in assisting the clinical diagnosis of sleep disorders.

The traditional teaching model centered on courses has disadvantages such as interdisciplinary barriers, repetitive learning of content, and students being unable to enter clinical practice early. The Human Body Overview I is a core course at the basic stage under the integrated curriculum system centered on "organ-systems" at Chongqing Medical University. The course deeply integrates interdisciplinary resources and reconstructs the contents of systematic anatomy, embryology, and physiology under the traditional teaching model. The "Three in One" curriculum ideology and politics are implemented to assist students in their comprehensive development. By strengthening the cultivation of clinical application abilities and empowering with virtual simulation technology, the teaching effectiveness and quality have been improved. The teaching practice of the Human Body Overview I suggests that the teaching reform of integrated curriculum at the basic stage has broken interdisciplinary barriers, avoided repetitive learning of contents, and promoted the cultivation of students' interdisciplinary integration ability and clinical application ability. It can provide a reference for the teaching reform of integrated curriculum for other colleges.

WDFY1 is a member of the protein family containing the WD repeat and FYVE structural domains,acting as a junction that assists the recruitment of downstream molecules by Toll-like receptor 3/4(TLR3/TLR4)and promotes the body's natural anti-viral and anti-bacterial immune response.In recent years,the role of WDFY1 has been successively reported in various disease models,such as neurological diseases,autophagy and tumors.This paper aims to provide a comprehensive review of the current state of WDFY1 research,encompassing its expression distribution,cell biological function and its role in disease development,and take a prospect on the potential of WDFY1 as a target in rheumatoid arthritis.