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.

Hepatocellular carcinoma （HCC） is a highly prevalent malignant tumor in China， and minimally invasive local intervention has become the core curative treatment for early- and intermediate-stage HCC. Leveraging its advantages of noninvasiveness， real-time operation， and bedside accessibility， ultrasound plays a pivotal role throughout the entire clinical pathway of screening for high-risk populations， qualitative diagnosis of focal lesions， ablation guidance， and efficacy monitoring throughout the entire post-treatment course. In this theme issue of Journal of Clinical Hepatology titled “Ultrasound diagnosis and treatment of hepatocellular carcinoma： Current status， challenges， and future prospects”， six leading experts in the field of ultrasound from China have been invited to contribute to a series of expert forums， systematically addressing the research hotspots， current bottlenecks， and translational pathways in this field from six key dimensions of integrated diagnosis and treatment in primary care， early differential diagnosis， intelligent imaging technologies， precision interventional ablation， standardized assessment of ablation efficacy， and bibliometric analysis and emerging techniques of contrast-enhanced ultrasound. With reference to the core viewpoints of the six reviews， this article provides a stratified commentary on the main trajectories of precise and intelligent development in HCC ultrasound， identifies key breakthroughs and unresolved challenges across various directions， and envisions a new landscape of multi-technological integration and collaborative clinical translation.

BACKGROUND:Intertrochanteric fracture of femur has various fracture types and fixation methods,and the mechanical stability of each fixation system is quite different.It is of scientific clinical significance to use finite element analysis method to carry out biomechanical research on various fixation systems. OBJECTIVE:To compare and analyze the mechanical stability of various internal fixations applied to femoral intertrochanteric fracture A031-A2.1 by finite element method. METHODS:Based on the validated finite element model of femur(Intact),the model was cut and made into A031-A2.1 intertrochanteric fracture of femur.Different internal fixation systems were implanted by simulating clinical operation methods,and fixation models of proximal femoral nail antirotation,dynamic hip screw,percutaneous compression plate and proximal femoral locking plate were established respectively.All nodes under the distal femur of the four groups of models were constrained,and compression loads of 700,1 400 and 2 100 N were applied to the femoral head.Von Mises stress distribution and compression stiffness of each group of models were observed through calculation and analysis,and mechanical stability of each group was compared. RESULTS AND CONCLUSION:(1)Through calculation and analysis,after calculating the compression stiffness by comparing the deformation of each model,the compression stiffness of each model under various loads showed the trend:physiological group>proximal femoral nail antirotation group>proximal femoral locking plate group>percutaneous compression plate group>dynamic hip screw group.The compressive stiffness of the complete physiological group model was significantly higher than that of all surgical group models.(2)The stress index was observed.Due to the stress shielding effect,the stress peak value of each fixed group was higher than that of physiological group,and the maximum peak value was concentrated on each internal fixation.Proximal femoral nail antirotation group had the smallest stress peak,while dynamic hip screw group had the highest stress.The stress distribution trend showed physiological group

Sophorae Flavescentis Radix is one of the commonly used traditional Chinese medicine in China, and a large amount of pharmaceutical residue generated during its processing and production is discarded as waste, which not only wastes resources but also pollutes the environment. Therefore, elucidating the chemical composition of the residue of Sophorae Flavescentis Radix and the differences between the residue and Sophorae Flavescentis Radix itself is of great significance for the comprehensive utilization of the residue. This study, based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) technology combined with multivariate statistical methods, provides a thorough characterization, identification, and differential analysis of the overall components of Sophorae Flavescentis Radix and its residue. Firstly, 61 compounds in Sophorae Flavescentis Radix were rapidly identified based on their precise molecular weight, fragment ions, and compound abundance, using a self-constructed compound database. Among them, 41 compounds were found in the residue, mainly alkaloids and flavonoids. Secondly, through principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA), 15 key compounds differentiating Sophorae Flavescentis Radix from its residue were identified. These included highly polar alkaloids, such as oxymatrine and oxysophocarpine, which showed significantly reduced content in the residue, and less polar flavonoids, such as kurarinone and kuraridin, which were more abundant in the residue. In summary, this paper clarifies the overall composition, structure, and content differences between Sophorae Flavescentis Radix and its residue, suggesting that the residue of Sophorae Flavescentis Radix can be used as a raw material for the extraction of its high-activity components, with promising potential for development and application in cosmetics and daily care. This research provides a scientific basis for the future comprehensive utilization of Sophorae Flavescentis Radix and its residue.
Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Mass Spectrometry/methods* ; Sophora/chemistry* ; Flavonoids/chemistry* ; Alkaloids/chemistry*

Objective To report the genetic analysis of a family with a fetus suspected of Ellis-van Creveld(EVC)syndrome based on ultrasound findings such as ventricular septal defect(VSD),short long bones in the limbs and polydactyly,and to conduct a literature review to clarify the pathogenic cause.Methods A 27-year-old pregnant woman,who was pregnant for the first time and had no prior deliveries,was admitted to the prenatal diagnosis center of Shijiazhuang Obstetrics and Gynecology Hospital in October 2021.At 17 weeks of gestation,ultrasound detected multiple fetal malformations.The genomic DNA of the fetal proband's amniotic fluid cells and the parents'peripheral blood samples were sequentially subjected to chromosomal karyotype analysis,chromosomal microarray analysis(CMA),and whole exome sequencing(WES).Suspected pathogenic mutations were verified by Sanger sequencing in the proband and its parents.Subsequently,a Minigene in vitro experiment was used to analyze one splicing mutation.Meanwhile,databases such as PubMed were searched,and literature reports were combined for genetic analysis.Results Chromosomal karyotype analysis of the fetus showed no abnormalities,and CMA did not detect any copy number variation(CNV)with clinical significance.WES results revealed two mutations in the EVC gene(NM_153717.2)of the fetus:a nonsense mutation c.1405G>T(p.E469X)in exon 10 and a splicing mutation c.1886+5G>A in intron 13.Family verification using Sanger sequencing showed that the father was a carrier of the c.1405G>T(p.E469X)mutation in exon 10,and the mother was a carrier of the c.1886+5G>A mutation in intron 13.The compound heterozygous mutation of the fetus was inherited from the parents.According to the guidelines of the American College of Medical Genetics and Genomics(ACMG)for classifying genetic variations,c.1405G>T(p.E469X)was classified as likely pathogenic mutation(PVS1+PM2),and c.1886+5G>A was classified as likely pathogenic mutation(PM2+PM3_Strong).The Minigene experiment results showed that the c.1886+5G>A mutation caused a 115-bp segment retention in intron 13,further supporting its pathogenicity.Review of the literature showed that the typical clinical manifestations of EVC syndrome include short limbs,short ribs,postaxial polydactyly,nail and tooth dysplasia,and congenital heart defects.Gene mutations in EVC/EVC2 were found to be the main pathogenic cause through whole exome sequencing,with mutation types including missense mutations,large-scale duplications/deletions,in-frame microdeletions,nonsense mutations,frameshift mutations,and splicing mutations.Conclusions The compound heterozygous mutations in the EVC gene are the pathogenic cause of the fetus.The detection of these mutations expands the genetic variation spectrum of Ellis-van Creveld syndrome.

Objective To analyze the clinical characteristics,treatment,and prognosis of immune checkpoint inhibitor-related diabetes mellitus(ICI-DM).Methods The clinical characteristics,laboratory examinations,treatment regimens,and follow-up outcomes of 10 ICI-DM patients who were diagnosed and treated in the First Medical Center of Chinese PLA General Hospital between July 2019 and December 2024 were retrospectively analyzed.Relevant literatures were retrieved from domestic and foreign databases such as PubMed,CNKI,and VIP.The clinical characteristics of ICI-DM were summarized based on the literature results.Results All 10 patients were PD-1 inhibitor users,including 5 males and 5 females,with a median age of 54.5(51.3,64.0)years and a body mass index(BMI)of(22.0±2.15)kg/m2.Among them,9 cases(90.0%)were fulminant type 1 diabetes mellitus(FT1DM);9 cases(90.0%)had a severity of adverse events reaching grade 3-4 according to the Common Terminology Criteria for adverse events(CTCAE).The median time from PD-1 inhibitor treatment to the occurrence of the classic diabetes symptoms referred to as"three more and one less"(polyuria,polydipsia,polyphagia,and weight loss)in all patients was 145.5(110.5,204.8)days,and the medication duration was 6.0(4.3,7.8)cycles.The average blood glucose level of the 10 patients at the time of consultation was 25.3(10.0-41.4)mmol/L,and the glycated hemoglobin(HbA1c)level was 8.0%(6.6%-10.9%).Eight patients had fasting and 2-hour C-peptide levels<0.1 ng/ml(fasting C-peptide from<0.010 to 0.067 ng/ml,2-hour C-peptide from<0.010 to 0.077 ng/ml).Nine of the 10 patients were negative for diabetes autoantibodies,while 1 was not tested.All 10 patients were successfully treated with insulin and other therapies.During the follow-up after discharge,all patients still relied on insulin treatment,and no significant recovery of pancreatic islet β cell function was observed compared with that at discharge.Literature review revealed that ICI-DM was more common in PD-1 inhibitor users,with clinical mainly manifested as diabetic ketoacidosis(DKA)(65.4%)and diabetic ketosis(13.1%).Patients had severely impaired pancreatic islet function and required long-term insulin treatment,and some cases were complicated by thyroid or pituitary dysfunction.Conclusions ICI-DM typically presents as FT1DM,often manifesting with DKA or diabetic ketosis at onset.It is characterized by severe and irreversible loss of pancreatic islet function,necessitating lifelong insulin therapy.To enable early detection and prompt treatment,close monitoring of blood glucose is essential during ICI treatment.

Objective To discuss the causes and the therapeutic strategy of acute cardiac tamponade(ACT)occurring as a complication of transcatheter aortic valve replacement(TAVR)so as to improve the success rate of the surgery and to make a further understanding of this complication.Methods The general clinical data,surgical procedures,and postoperative follow-up results of five patients,who received TAVR at the Affiliated Northern Jiangsu People's Hospital of Yangzhou University of China and developed ACT from March 2018 to September 2024,were retrospectively analyzed.Results After developing ACT,all the 5 patients received pericardiocentesis together with other adjuvant therapies including blood volume expansion with infusion,vasopressors,heparin neutralization,and blood transfusion.However,due to no obvious reduction in drainage volume and unstable hemodynamics all the 5 patients had eventually to receive open-chest surgery to identify the source of bleeding and to make hemostasis.Surgical exploration revealed that the perforation or rupture of cardiac structures caused by the temporary pacemaker lead or a super-stiff guide wire during the procedure was the main cause of ACT.Finally,after active treatment four patients recovered and discharged,and one patient died.The discharged patients were followed up for 3-12 months,and no procedure-related complications such as acute coronary artery occlusion,severe arrhythmia,exacerbation of heart failure symptoms,valve displacement,or stroke occurred.Conclusion As a severe complication occurring during the TAVR procedure,ACT requires to get a rapid diagnosis and management.Improvement of surgical techniques and operative methods,comprehensive preoperative assessment,and close intraoperative monitoring are crucial points for the prevention of ACT.

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature