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*

OBJECTIVE: To explore clinical effects of bone setting manipulation combined with pry reduction and Kirschner needle internal fixation in treating SandersⅡ-Ⅲ calcaneal fracture. METHODS: Clinical data of 52 patients with types Sanders Ⅱand Ⅲ calcaneal fracture (foot) treated with bone-setting manipulation combined with pry reduction and Kirscher needle internal fixation from July 2017 to July 2019 were retrospectively analyzed, including 43 males and 9 females, aged from 31 to 72 years old with an average of (50.83±10.48) years old; 15 patients with Sanders typeⅡ and 37 patients with Sanders type Ⅲ. The changes of Bühler angle, Gissane angle, calcaneus width and calcaneus height before operation and 24 months after operation were compared, and Maryland foot function score was performed to evaluate clinical effects. RESULTS: All patients were followed up from 24 to 60 months with an average of (41.50±9.86)months. The fracture healed normally and the healing time was (11.00±0.95) weeks. Bühler angle, Gissane angle, calcaneal bone width and calcaneal bone height were increased from (16.37±8.36)°, (96.27±9.62)°, (46.82±4.67) mm, (38.41±3.58) mm before operation to (31.48±8.24)°, (111.62±8.69)°, (42.06±4.83) mm, (44.21±3.82) mm at 24 months after operation, and the difference were statistically significant (P<0.01). Postoperative Maryland score at 24 months was (93.04±8.83), 40 patients got excellent result, 7 good and 5 fair. CONCLUSION Orthopedic manipulation combined with percutaneous reduction and Kirschner wire internal fixation could significantly improve Bühler angle, Gissane angle, width, and height of Sanders typeⅡ and Ⅲ calcaneal fractures, and the curative effect is satisfactory.
Humans ; Male ; Female ; Calcaneus/surgery* ; Middle Aged ; Fracture Fixation, Internal/methods* ; Adult ; Aged ; Fractures, Bone/therapy* ; Retrospective Studies ; Bone Wires ; Manipulation, Orthopedic/methods*

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

Objective To investigate the role of membrane-associated tyrosine/threonine-protein ki-nase 1(PKMYT1)in glucocorticoid(GC)-induced osteoblast(OB)apoptosis,providing a theoretical basis and potential therapeutic targets for early-stage steroid-induced avascular necrosis of the femoral head(SANFH).Methods(1)Mouse calvarial osteoblastic cells(MC3T3-E1)were selected for the study.The control group was cultured in standard medium,while the experimental group was subject-ed to osteogenic induction culture,with osteogenic capacity verified by alkaline phosphatase(ALP)and Alizarin Red S(ARS)staining.Then,mouse osteoblasts(mOB)were treated with different con-centrations of GC.After that,apoptosis was detected by using Annexin V-FITC/PI double staining as-say,while cell proliferation was assessed by using Cell Counting Kit-8(CCK8).Moreover,the expres-sions of anti-apoptotic protein B-cell lymphoma/leukemia-2(BCL-2),pro-apoptotic proteins cleaved caspase-3andcleavedcaspase-9(cleavedcaspase 3/9)weredetectedbyusing Westernblotting(WB).Meanwhile,proteomic analysis was employed to identify molecules potentially regulating GC-in-duced apoptosis in mOBs.What's more,quantitative real-time PCR(qPCR)and WB were used to further analyze PKMYT1 expression.(2)mOBs were treated with PKMYT1 inhibitor GSK-1520489A of different concentrations to screen the optimal one,and all subjects were then further divided into a control,a GC,a GSK-1520489A,and a GC+GSK-1520489A group.Later,the expression of PK-MYT1 and apoptosis-related proteins BCL-2 and cleaved caspase 3/9 of all groups were detected us-ing WB,and cell viability and cytotoxicity were evaluated by CCK8 assay,with cell proliferation by using 5-ethynyl-2'-deoxyuridine(EDU)assay and apoptosis by cell live/dead staining and Annexin V-FITC/PI double staining.(3)mOBs were infected with PKMYT1 overexpression lentiviral vectors,and its efficiency was verified by using immunofluorescence,qPCR,and WB.After successful overexpres-sion of PKMYT1,all cells were divided into the control,GC,PKMYT1 overexpression(OE),and OE+GC groups,whose cell proliferation was detected by EDU assay,and apoptosis was assessed by Annexin V-FITC/PI double staining and cell live/dead staining.(4)To verify the changes in PKMYT1 expression in human osteoblasts(hOB),hOBs extracted from human femoral heads of healthy individu-als were chosen into the control group,while those from patients with hormone-induced avascular ne-crosis of the femoral head(hSANFH)were selected into the hSANFH group.Then,PKMYT1 expres-sion in both groups was detected by using qPCR and WB.Results(1)After inducing the differentia-tion of mouse calvarial osteoblastic cells(MC3T3-E1)into mature osteoblasts,under the action of GC,compared with the control group,with the increase of GC concentration,the experimental group showed increased mOB apoptosis(P<0.01)and expression of cleaved caspase 3/9(P<0.01),but de-creased cell viability(P<0.01)and expressionof apoptosis-relatedprotein BCL-2(P<0.01).More-over,according to the proteomic sequencing,significant decrease was observed in the PKMYT1 expres-sion in mature mOBs treated with GC.(2)As to treatment of mOBs with different concentrations of PKMYT1 inhibitor GSK-1520489A,with the increase of concentration,cell viability decreased and cy-totoxicity increased(P<0.001).Moreover,compared with the control group,mOBs proliferation de-creased(P<0.001)and apoptosis increased(P<0.001)in the GSK-1520489A group.Meanwhile,com-pared with the GC group,mOB proliferation decreased(P<0.05)and apoptosis increased significantly(P<0.01)in the GC+GSK-1520489A group.(3)After overexpression of PKMYT1,in comparison with the control group,mOB proliferation increased(P<0.001)but apoptosis did not increase significantly(P>0.05)in the OE group.Moreover,compared with the GC group,mOB proliferation increased(P<0.001)but apoptosis decreased(P<0.001)significantly in the OE+GC group.(4)In hOBs extracted from human femoral head tissues,qPCR and WB results showed that PKMYT1 expression of the hSANFH group was significantly lower than the control group(P<0.001).Conclusion Down regulation of PKMYT1 expression promotes GC-induced apoptosis of mOBs.Conversely,over expression of PK-MYT1 inhibits GC-induced apoptosis of mOBs.Therefore,PKMYT1 may serve as a potential target for the early treatment of SANFH.

Objective:To explore the efficacy of combined therapy with composite skin grafting, photoelectric technology, and functional rehabilitation in repairing pediatric scar contracture deformities.Methods:A total of 15 children with scar contractures (9 males and 6 females, aged 1-7 years) admitted to the First Affiliated Hospital of the Air Force Medical University from January to June 2024 were included. The scars were distributed on the extremities (12 cases) and trunk (3 cases), all formed 1 month to 1 year after burns/scalds, with areas ranging from 2 cm×7 cm to 6 cm×20 cm. The surgery was divided into two stages: Stage Ⅰ involved complete release and resection of scar tissue (wound area: 3 cm×8 cm to 9 cm×22 cm); Stage Ⅱ involved composite skin grafting combined with autologous thick split-thickness scalp skin coverage. Skin graft survival and complications were evaluated 10 days postoperatively. Anti-scar medications, pressure therapy, laser therapy, and functional training were initiated 2 weeks postoperatively, with dynamic efficacy evaluation throughout the process. During the 6-12 month follow-up, scar characteristics of the repaired area [Vancouver Scar Scale (VSS)] and joint range of motion were assessed.Results:All skin grafts survived in the children. Subcutaneous hematomas occurred in 2 cases (1 cm×2 cm and 0.5 cm×1 cm), which healed after aspiration and compression. The skin of the repaired area was soft with color close to normal skin; VSS scores were significantly lower than those before scar treatment ( P<0.05); joint range of motion was significantly improved before treatment ( P<0.05). The edges of the skin grafts showed linear scars without functional impact. Thirteen families were very satisfied with the efficacy, and 2 families were satisfied. No scar recurrence or other adverse reactions occurred after scar treatment in all cases. Conclusions:The combined therapy of composite skin grafting, photoelectric technology, and functional rehabilitation can effectively repair pediatric scar contracture deformities, with advantages such as good recovery of appearance and function, and minimal damage to the donor site.

Objective : To analyze the current status of anti-PD-1 combined with chemotherapy in advanced gastric cancer. Methods: The clinical data of 120 patients with advanced gastric cancer treated with chemotherapy or anti-PD-1 plus chemotherapy were retrospectively analyzed. The efficacy [measures include objective response rate(ORR), disease control rate(DCR), and progression-free survival(PFS)]and the occurrence of adverse reactions in patients was monitored. Univariate and multivariate Cox were used to analyze the relationship between clinicopathologic data [including age, gender, body mass index(BMI), differentiation degree, and related hematological indexes], specific treatment conditions and PFS, and to analyze the influence of treatment plan and line number on the curative effect. Results : The PFS of chemotherapy plus immunotherapy was significantly better than that of chemotherapy alone(P<0.05), and the median PFS of the two was 7.17 months(95%CI5.85-8.49) and 5.33 months(95%CI3.96-5.70), respectively. In the combination group, the overall ORR was 27.5% and DCR was 94.8%. In the chemotherapy group alone, the overall ORR was 9.7% and DCR was 69.4%.In the chemotherapy plus anti-PD-1 group, a high prognostic nutritional index(PNI) level also provided superior PFS in patients with a 47% reduction in the risk of progression versus a low PNI level [HR0.53(95%CI0.30-0.96);P<0.05]. The median PFS was 7.47 months(95%CI5.83-9.11) with a high PNI level versus 6.00 months(95%CI4.45-7.55) with a low PNI level. The overall incidence of adverse reactions of chemotherapy combined with anti-PD-1 was slightly higher than that of chemotherapy alone, and the incidence of adverse reactions of grade 3-4 was similar, within a controllable range, and could be improved after clinical treatment. Conclusion The efficacy of anti-PD-1 combined with chemotherapy in patients with advanced gastric cancer is better than that of chemotherapy, and the adverse reactions are controllable. In the chemotherapy plus anti-PD-1 group, patients with high PNI levels achieved a higher PFS.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.