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.

OBJECTIVE: miR-34c-3p is down-regulated in nasopharyngeal carcinoma (NPC). The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study. METHODS: Flow cytometry and immunohistochemical staining were employed to detect cluster of differentiation 86 (CD86) and cluster of differentiation 206 (CD206) expression; quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were employed to examine mRNA expression and protein levels; cell counting kit-8 (CCK8) and transwell assays were employed to assess cell proliferation, migration, and invasion; and hematoxylin-eosin (HE) staining was employed to assess pathological changes in tumor tissues. RESULTS: Our results revealed that the miR-34c-3p mimic markedly inhibited M2 polarization of macrophages by targeting SLC7A11, and M2 macrophages transfected with the miR-34c-3p mimic inhibited the proliferation, migration, and invasion of NPC cells. The in vivo experiments further confirmed that miR-34c-3p mimics blocked tumor growth and reduced inflammatory infiltration in tumor tissues. CONCLUSION This study provides novel insights into the pathogenesis of NPC and a new treatment strategy.
MicroRNAs/metabolism* ; Nasopharyngeal Carcinoma/genetics* ; Humans ; Animals ; Nasopharyngeal Neoplasms/genetics* ; Macrophages/physiology* ; Cell Line, Tumor ; Mice ; Cell Proliferation ; Mice, Inbred BALB C ; Cell Movement ; Male ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Female

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To investigate the levels of C reactive protein(CRP)and interleukin(IL)-6 in patients with myocardial infarction(MI)and their association with cardiac function.Methods:We enrolled 140 MI patients ad-mitted to Sanya Harbin Medical University Hongsen Hospital Co.,Ltd between January 2020 and December 2022,as MI group.According to coronary stenotic severity,they were divided into mild group(n=62),moderate group(n=41)and severe group(n=37),and 75 healthy individuals who underwent physical examination simultaneously were selected as control group.Serum CRP,IL-6,cardiac troponin Ⅰ(cTnⅠ)and creatine kinase isoenzyme MB(CK-MB)levels were measured by automatic biochemical analyzer,and left ventricular ejection fraction(LVEF)was assessed by echocardiography.Above-mentioned indexes were compared between MI group and control group,and among groups of different coronary disease severity.Pearson/Spearman correlation was used to analyze the asso-ciation of serum CRP and IL-6 levels with Gensini score,cTnⅠ,CK-MB levels,and LVEF in MI patients.Diag-nostic value of serum CRP and IL-6 levels for MI was analyzed by receiver operating characteristic(ROC)curve.Results:Compared with participants in control group,those in MI group had significant higher serum CRP,IL-6,cTnⅠ and CK-MB,and significant lower LVEF(P＜0.001 all).Serum CRP,IL-6,cTnⅠ and CK-MB levels sig-nificantly increased,and LVEF significant decreased in the order of mild group,moderate group and severe group(P＜0.01 all).Pearson/Spearman correlation analysis showed that serum CRP and IL-6 levels were positively cor-related with Gensini score,cTnⅠ,and CK-MB levels(r=0.496～0.646,P＜0.001all),and negatively correlated with LVEF(r=-0.530,-0.572,P＜0.001 all)in MI patients.ROC curve showed that the area under the curve(AUC)of CRP combined IL-6 diagnosing MI was 0.856(95％CI 0.802～0.900),which was significantly higher than those of CRP(AUC=0.770,95％CI 0.708～0.824)and IL-6(AUC=0.793,95％CI 0.733～0.845)alone(Z=3.295,2.877,P＜0.01 all).Conclusion:Serum CRP and IL-6 levels rise in MI patients,and they are closely associated with increased severity of coronary artery disease and reduced cardiac function.

Attention refers to the body's capacity to maintain alert awareness of internal and external stimuli.Attention deficit can impair an individual's learning capacity and working proficiency,resulting in a heavy burden to the family and society.Vagus nerve stimulation(VNS)is an emerging neuro regulatory technique that can achieve reciprocal interaction between the central and peripheral nervous systems,which has demonstrated great potential for the treatment of neurological and psychiatric diseases;however,it has not been used clinically to treat attention-deficient developmental disorders in children or neurodegenerative diseases in the aged population.We briefly review the anatomical and physiological bases of VNS,and its application status and potential use in treating attention deficit diseases.A potential mechanism by which VNS participates in attention-related nervous regulation is proposed,to lay a theoretical foundation for the application of VNS in the field of attention nervous regulation.

Ergonomic Principle for the Prevention of Work-Related Musculoskeletal Disorders Part 1: General Principles (T/WSJD 14.1-2020) is the first guideline standard for the prevention of work-related musculoskeletal disorders provided to employers and occupational health technical service institutions in China, which covers ergonomic risk factors and their hazard definition, ergonomic prevention principles, risk assessment process, risk control process and risk evaluation principles. The standard specifically clarify the specific types of adverse ergonomic risk factors and control strategies and the standard process of systematic ergonomic risk assessment, providing implementation paths and practical guidance for eliminating/reducing adverse ergonomic risks and enhance workplace environments to prevent work-related musculoskeletal disorders. This paper interprets and analyzes the background of standard establishment, formulation process, fundamental basis, and main content, etc., to provide scientific and accurate technical support for enterprise managers, labours and technical personnel of occupational health institutions to optimize the use of this standard.

Objective:To explore the structural relationship between WMSDs in the upper limbs and various risk factors in the occupational population in China, based on a large sample epidemiological survey and structural equation analysis, and to establish a structural equation model, so as to lay a foundation for the prevention and control of such diseases.Methods:The Chinese version of the Musculoskeletal Disorders Electronic Questionnaire was used to conduct a nationwide survey on the prevalence of WMSDs in the upper extremity. Six factors related to WMSDs in the upper extremity were extracted by the classification standard of adverse ergonomic factors and their source and confirmatory factor analysis, including work organization, work type, upper extremity work posture, individual factors, upper extremity fatigue and upper extremity WMSDs. The structural equation analysis was carried out and the structural equation model was established.Results:The incidence of WMSDs and fatigue in the upper limbs was 24.44% and 43.76%, respectively. The adjusted structural equation model fitting indicators were generally up to the standard (GFI=1.000, AGFI=1.000, RMSEA=0.043, NFI=0.808, TLI=0.784) . The four exogenous latent variables of work organization, work type, upper limb work posture and individual factors were correlated. There was a strong positive correlation between job type and upper limb work posture ( r=0.865) , a moderate positive correlation between work organization and job type and upper limb work posture ( r=0.570, 0.490) , and a weak negative correlation between individual factors and the other three exogenous latent variables. Upper limb work posture and individual factors had direct effects on upper limb WMSDs, and the effect coefficients were 0.10 and 0.06, respectively. Upper limb fatigue played a mediating role between work organization, work type, upper limb work posture and upper limb WMSDs. The effect coefficient was 0.46, and the composition ratios of indirect effects were 100.0%, 100.0%, and 38.3%, respectively. The direct path effect of upper limb work posture, individual factors and upper limb WMSDs was weaker than the mediating path through upper limb fatigue. Conclusion:When carrying out the prevention and control of upper limbWMSDs, it is necessary to comprehensively consider the pathogenesis path of upper limb muscle fatigue and upper limb WMSDs caused by work organization, work type, and upper limb work posture, so as to provide theoretical reference for improving the prevention and control level of such diseases.

Objective:To investigate the risk factors,clinical characteristics,and bacterial resistance of bloodstream infections caused by Streptococcus mitis in children with hematological disease,so as to provide a reference for infection control.Methods:The clinical information and laboratory findings of pediatric patients complicated with blood cultures positive for Streptococcus mitis from January 2018 to December 2020 in the Institute of Hematology & Blood Diseases Hospital were searched and collected.The clinical characteristics,susceptibility factors,and antibiotic resistance of the children were retrospectively analyzed.Results:Data analysis from 2018 to 2020 showed that the proportion of Streptococcus mitis isolated from bloodstream infections in children(≤14 years old)with hematological diseases was the highest(19.91％)and significantly higher than other bacteria,accounting for 38.64％of Gram-positive cocci,and presented as an increasing trend year by year.A total of 427 children tested positive blood cultures,including 85 children with bloodstream infections caused by Streptococcus mitis who tested after fever.Most children experienced a recurrent high fever in the early and middle stages(≤6 d)of neutropenia and persistent fever for more than 3 days.After adjusting the antibiotics according to the preliminary drug susceptibility results,the body temperature of most children(63.5％)returned to normal within 4 days.The 85 children were mainly diagnosed with acute myeloid leukemia(AML),accounting for 84.7％.The proportion of children in the neutropenia stage was 97.7％.The incidence of oral mucosal damage,lung infection,and gastrointestinal injury symptoms was 40％,31.8％,and 27.1％,respectively.The ratio of elevated C-reactive protein(CRP)and procalcitonin was 65.9％and 9.4％,respectively.All isolated strains of Streptococcus mitis were not resistant to vancomycin and linezolid,and the resistance rate to penicillin,cefotaxime,levofloxacin,and quinupristin-dalfopristin was 10.6％,8.2％,9.4％,and 14.1％,respectively.None of children died due to bloodstream infection caused by Streptococcus mitis.Conclusion:The infection rate of Streptococcus mitis is increasing year by year in children with hematological diseases,especially in children with AML.Among them,neutropenia and oral mucosal damage after chemotherapy are high-risk infection factors.The common clinical symptoms include persistent high fever,oral mucosal damage,and elevated CRP.Penicillin and cephalosporins have good sensitivity.Linezolid,as a highly sensitive antibiotic,can effectively control infection and shorten the course of disease.

Objective:To explore the effects of hydroxychloroquine(HCQ)on immune mediators dysregulation in severe infection after chemotherapy in acute myeloid leukemia(AML)and its molecular mechanism.Methods:Bone marrow or peripheral blood samples of 36 AML patients with severe infection(AML-SI)and 29 AML patients without infection(AML-NI)after chemotherapy were collected from the First Affiliated Hospital of Gannan Medical University from August 2022 to June 2023.In addition,the peripheral blood of 21 healthy subjects from the same period in our hospital was selected as the control group.The mRNA expressions of CXCL12,CXCR4 and CXCR7 were detected by RT-qPCR technology,and the levels of IL-6,IL-8 and TNF-α were detected by ELISA.Leukemia-derived THP-1 cells were selected and constructed as AML disease model.At the same time,bone marrow mesenchymal stem cells(BM-MSCs)from AML-SI patients were co-cultured with THP-1 cells and divided into Mono group and Co-culture group.THP-1 cells were treated with different concentration gradients of HCQ.The cell proliferation activity was subsequently detected by CCK-8 method and apoptosis was detected by Annexin V/PI double staining flow cytometry.ELISA was used to detect the changes of IL-6,IL-8 and TNF-α levels in the supernatant of the cell co-culture system,RT-qPCR was used to detect the mRNA expression changes of the core members of the CXCL12-CXCR4/7 regulatory axis,and Western blot was used to detect the expressions of apoptosis regulatory molecules and related signaling pathway proteins.Results:CXCL12,CXCR4,CXCR7,as well as IL-6,IL-8,and TNF-α were all abnormally increased in AML patients,and the increases were more significant in AML-SI patients(P＜0.01).Furthermore,there were statistically significant differences between AML-NI patients and AML-SI patients(all P＜0.05).HCQ could inhibit the proliferation and induce the apoptosis of THP-1 cells,but the low concentration of HCQ had no significant effect on the killing of THP-1 cells.When THP-1 cells were co-cultured with BM-MSCs of AML patients,the levels of IL-6,IL-8 and TNF-α in the supernatance of Co-culture group were significantly higher than those of Mono group(all P＜0.01).After HCQ intervention,the levels of IL-6,IL-8 and TNF-α in cell culture supernatant of Mono group were significantly decreased compared with those before intervention(all P＜0.01).Similarly,those of Co-culture group were also significantly decreased(all P＜0.001).However,the expression of the core members of the CXCL12-CXCR4/7 regulatory axis was weakly affected by HCQ.HCQ could up-regulate the expression of pro-apoptotic protein Bax,down-regulate the expression of anti-apoptotic protein Bcl-2,as well as simultaneously promote the hydrolytic activation of Caspase-3 when inhibiting the activation level of TLR4/NF-κ B pathway,then induce the programmed death of THP-1 cells after intervention.Conclusion:The core members of CXCL12-CXCR4/7 axis and related cytokines may be important mediators of severe infectious immune disorders in AML patients.HCQ can inhibit cytokine levels to reverse immune mediators dysregulation and suppress malignant biological characteristics of leukemia cells.The mechanisms may be related to regulating the expression of Bcl-2 family proteins,hydrolytically activating Caspase-3 and inhibiting the activation of TLR4/NF-κ B signaling pathway.

Aim To explore the mechanism of Gano-derma lucidum polysaccharides(GLPS)promoting my-elin repair and regeneration in mice with chronic demy-elination induced by cuprizone(CPZ).Methods A total of 40 C57BL/6 mice were randomly divided into four groups:Normal+NS,Normal+GLPS,CPZ+NS and CPZ+GLPS.A chronic demyelination model was established using 0.2％CPZ.Open field and elevated plus maze tests were performed to observe the behavior-al changes in the mice.Immunofluorescence staining and Western blot were used to detect changes in myelin basic protein expression in the corpus callosum.ELISA was performed to measure the levels of TNF-α,IL-6,IL-1β and IL-10 in brain homogenates.Immunofluo-rescence staining was also used to observe the expres-sion of ionized calcium binding adapter molecule 1(Iba1)and neural-glial antigen 2(NG2).RT-qPCR and Western blot were conducted to assess the mRNA and protein expression levels of MBP,iNOS,COX-2,JAK2 and STAT3.Results Mice in the CPZ+NS group showed a significant decrease in body weight,cognitive behavior abnormalities,and impaired myelin regeneration.The expression of pro-inflammatory fac-tors increased,while anti-inflammatory factors de-creased.Additionally,Iba1 and NG2 expression in-creased,and the JAK2/STAT3 signaling pathway was activated.After GLPS intervention,the mouse body weight increased,myelin regeneration occurred,cogni-tive behavior was improved,the expression of inflamma-tory factors decreased,anti-inflammatory factors in-creased,NG2 expression was further elevated,and the proliferation of microglia as well as the activation of the JAK2/STAT3 signaling pathway was inhibited.Conclu-sions GLPS can improve cognitive behavior abnormali-ties and inflammatory responses in chronic demyelinated mice by inhibiting the JAK2/STAT3 signaling pathway,thereby promoting myelin repair and regeneration.