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.

Melicope pteleifolia is a plant belonging to the Melicope genus of the Rutaceae family. Known for a bitter taste and cold nature, its stems and tender branches with leaves possess properties of clearing heat, detoxifying, dispelling wind, and removing dampness and can be used to treat sore throat, malaria, jaundice hepatitis, rheumatic bone pain, eczema, dermatitis, and sores and ulcers. In this study, 19 compounds were isolated from the chloroform and n-butanol extracts of M. pteleifolia leaves by using liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR)-guided separation techniques. The compounds were identified as isoleptonol(1), leptaones B-E(2-5), friedelin(6), evodionol(7), ethyl p-hydroxybenzoate(8), litseachromolaevane A(9), quercetin-7,3',4'-trimethyl ether(10), kokusaginin(11), 8-(1-hydroxyethyl)-5,6,7-trimethoxy-2,2-dimethyl-2H-1-benzopyran(12), ethyl p-hydroxycinnamate(13), 3-hydroxy-9-methyl-6H-benzo\[c\]chromen-6-one(14), agrimonolide(15), 7-hydroxycoumarin(16), scopoletin(17), isoscutellarein(18), and agrimonolide 6-O-glucoside(19). Among these, the new compounds included one chromene and four meroterpenoid(1-5). The anti-inflammatory activities of the newly identified compounds 1-5 were screened in vitro, showing that the five compounds(1-5) exhibited inhibitory effects on nitric oxide(NO) production in BV2 cells induced by lipopolysaccharide(LPS)/interferon(IFN)-γ, with IC_(50) values ranging from 12.25 to 36.48 μmol·L~(-1).
Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Rutaceae/chemistry* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; Nitric Oxide/immunology*

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

On the basis of that the fluorescence wavelength of copper nanoclusters(CuNCs)could cover the entire visible region,multicolor fluorescent CuNCs/starch composites were prepared and applied in fingermark development.With L-glutathione as the reducing agent and protective ligand,blue emissive and orange emissive CuNCs solutions were obtained in alkaline solutions at 90℃and 25℃,respectively.With the aggregation-induced emission effect induced by ethanol as a poor solvent,the fluorescence of orange emissive CuNCs with a higher intensity was achieved in an ethanol-water solution.With ascorbic acid as the reducing agent and 3-mercaptopropionic acid as the protective agent,green emissive CuNCs solution was prepared in an acid solution.Particle morphologies,chemical compositions and optical properties of these three CuNCs above were investigated using physical characterization and spectroscopic analysis,indicating that well-dispersed CuNCs had excellent photoluminescent properties.These CuNCs solutions were combined with starch to form composite powders by simply drying.The influences of the type of CuNCs and the ratio of CuNCs to starch on the emission wavelength and fluorescence intensity of the products were studied.The obtained CuNCs/starch composites could emit blue,green and orange fluorescence under 365 nm ultraviolet light,respectively,which were suitable for fingermark development.Minutiae and partial level-3 features of latent fingermarks could be effectively developed.High-quality fluorescence fingermark images would be captured using appropriate optical filters to eliminate background interference of various substrates.

Objective To explore the risk factors of early femoral head necrosis in patients with femoral neck fracture after operation,and to establish a nomogram prediction model.Methods A total of 167 patients with femoral neck fracture from Jan-uary 2020 to April 2022 were selected and divided into necrosis group and non-necrosis group according to whether femoral head necrosis occurred in the early postoperative period.There were 21 males and 17 females in the necrosis group,aged from 33 to 72 years old,with an average of(53.49±10.96)years old,and the time from injury to operation ranged from 40 to 67 hours,with average time of(53.46±7.23)hours.There were 72 males and 57 females in the non-necrosis group,aged from 18 to 83 years,with an average of(52.78±12.55)years old,and the time from injury to operation was 18 to 65 hours,with an aver-age time of(39.88±7.79)hours.The potential influencing factors,including patient gender,diabetes mellitus,hypertension,chronic liver disease,posterior inclination angle of the femoral head,operation mode,fracture displacement,fracture line loca-tion,preoperative braking traction,screw arrangement mode,reduction quality,age,body mass index(BMI),and injury to operation time were subjected to single factor analysis.Logistic multivariate regression analysis was conducted for factors with a significance level of P＜0.05.Results The incidence of femoral head necrosis in 167 patients with femoral neck fracture was 22.76％.The following factors were identified as independent risk factors for early postoperative femoral head necrosis in pa-tients with femoral neck fractures:coexisting diabetes[OR=5.139,95％CI(1.405,18.793),P=0.013],displaced fracture[OR=3.723,95％CI(1.105,12.541),P=0.034],preoperative immobilization[OR=3.444,95％CI(1.038,11.427),P=0.043],quality of reduction[OR=3.524,95％CI(1.676,7.411),P=0.001],and time from injury to surgery[OR=1.270,95％CI(1.154,1.399),P=0.000].The Hosmer-Lemeshow goodness-of-fit test(x2=3.951,P=0.862),the area under the receiver operator characteristic(ROC)curve was 0.944[P＜0.001,95％CI(0.903,0.987)],with a sensitivity of 89.50％,the specificity was 88.40％,the maxi-mum Youden index was 0.779,and the overall trend of the model correction curve was close to the ideal curve.Model regres-sion equation was Z=1.637 × diabetes+1.314× fracture displacement+1.237 × preoperative braking traction+1.260 × reduc-tion quality+0.239 ×injury to operation time-18.310.Conclusion The occurrence of early femoral head necrosis in patients with femoral neck fracture postoperatively is affected by multiple factors.The risk early warning model established according to the factors has good predictive efficacy.

Objective To observe the clinical efficacy of meridian massage in the treatment of lumbar disc herniation(LDH).Methods Between July 2020 and April 2023,82 patients with lumbar disc herniation were selected,including 58 males and 24 females,aged from 23 to 55 years old with an average of(43.76±6.64)years old.According to the different treatment methods,they were divided into observation group and control group with 41 cases in each group.The control group was treated with routine treatment,and the observation group was treated with meridian massage on the basis of routine treatment.In the control group,there were 30 males and 11 females;aged from 22 to 52 years old with an average of(42.27±9.34)years old;the Body mass index(BMI)ranged from 19 to 28 kg·m-2 with an average of(23.82±1.08)kg·m-2;the course of disease ranged from 0.5 to 3.0 years(2.40±0.48)years.There were 28 cases in L4,5 segment and 13 cases in L5S1 segment.In the observation group,there were 28 males and 13 females;the age ranged from 19 to 54 years old(42.19±9.26)years old;the BMI ranged from 18 to 29 kg·m-2 with an average of(23.73±1.15)kg·m-2;the course of disease ranged from 0.6 to 2.8 with an average of(2.56±0.45)years;there were 26 cases in L4,5 segment and 15 cases in L5S1 segment.Visual analogue scale(VAS),Oswestry disability index(ODI),M-JOA score and TCM syndrome score were measured before and after 3 courses of treatment,and the clinical efficacy was evaluated by the standard of curative effect evaluation.Results After treatment,VAS[(3.24±1.45)vs(4.46±0.64)],ODI[(11.45±1.98)％vs(17.21±2.74)％]and TCM symptom score[(2.03±0.27)vs(3.99±0.54)]of the observation group were lower than those of the control group.The score of M-JOA[(23.43±2.61)vs(19.37±1.62)]increased(P＜0.05).The scores of VAS,ODI andTCM symptoms in the observation group were lower than those in the control group,while the scores of M-JOA were higher than those in the control group(P＜0.05).Conclusion Meridian massage is effective in the treatment of LDH,which can effectivelyrelieve low back pain,improve clinical symptoms and increaselumbar function,which is worthy of clinical promotion.

Objective To investigate the clinical effect of lengthened proximal femoral nail anti-rotation(PFNA)in the treatment of Seinsheimer type Ⅴ subtrochanteric fracture of femur.Methods The clinical data of 21 patients with Seinsheimer type Ⅴ subtrochanteric fracture of femur treated by closed reduction or limited incision wire binding combined with lengthened PFNA in our hospital from January 2020 to August 2022 were retrospectively analyzed.The fracture healing status,treatment effect,postoperative complications and Harris score of hip joint function at the last postoperative follow-up of patients were recorded and evaluated.Results All patients were followed up for 6 to 12 months,and the fractures healed well.There were no cases of internal fixation breakage or cutting,no cases of vascular injury,and 1 case of ectopic ossification.At the last follow-up,the hip joint function was excellent in 15 cases,good in 4 cases and fair in 2 cases,with an excellent and good rate of 90.48％.Conclusion Lengthened PFNA can effectively treat Seinsheimer type Ⅴ subtrochanteric fracture of femur,and minimally invasive steel wire cerclage is performed when the closed reduction is not ideal,which has the advantages of less trauma,fast fracture healing,fewer postoperative complications and good recovery of hip joint function,and is worthy of clinical promotion and application.

To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

Objective:This study was aimed to provide ideas for identifying the antibodies to high-frequency antigens by analyzing a female case of high-frequency antigen antibody(anti-Ku)using serological and sequencing method.Methods:The methods for identification of blood group,erythrocyte antigen,screening and identification of antibody were used to detect the blood type and antibody in the proband.The proband's serum and reagent screening cells treated with Sulfhydryl reagent were applied to judge the type and characteristics of this antibodies when reacted with the regaent screening cells or proband's serum respectively.Gene sequencing was used to determine the genotype of the proband's blood group.Results:The proband's red blood cells were determined as O type RhD positive,whose serum showed strong positive reaction to antibody-screening cells and antibody identification cells with the same intensity in saline and IAT medium,however,the self-cells showed negative effect.The Direct Antihuman Globulin of proband's red blood cells also showed weak positive reaction,and the other blood types were CcEe,Jk(a+b-),P1-,Le(a-b-),Lu(a-b+),K-,k-,Kp(a-b-).Serum of the proband treated with 2-ME still react with three groups of screening cells in IAT medium.The reaction intensity of proband's serum was also unchanged with the cells modified with papain and bromelain,but showed negative effect when the cells were treated with sulfhydryl agents including DTT and 2-ME.Gene sequencing revealed that the KEL genotype of the patient was KEL*02N.24.This patient had a rare K0 phenotype.Conclusion:The rare Kell-null blood group(also known as K0)were identified by serological and molecular tests in the proband who produced both IgG and IgM type of antibody to high-frequency antigen(anti-Ku).These two methods are of great significance in the identification of this rare blood group as well as the antibody to high frequency antigen.