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 To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

ObjectiveTo evaluate the effect of action observation therapy (AOT) combined with low-frequency repetitive transcranial magnetic stimulation (rTMS) on post-stroke unilateral spatial neglect. MethodsA total of 108 patients with post-stroke unilateral spatial neglect admitted to Suqian Integrated Traditional Chinese and Western Medicine Hospital from January, 2023 to March, 2024 were enrolled. The patients were randomly allocated to AOT group, rTMS group and combined group with 36 patients in each group. All the groups received conventional treatment. The AOT group additionally received AOT, the rTMS group additionally received rTMS, and the combined group received both AOT and rTMS, for four weeks. Before and after treatment, the patients were assessed using the Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment (FMA), modified Barthel Index (MBI), Chinese Behavioural Inattention Test-conventional test (CBIT-C) and CBIT-behavioural test (CBIT-B). The latency and amplitude of the N20 potential on the affected side were also measured. ResultsThree patients dropped out from each group. After intervention, significant main effects of time (F > 77.096, P < 0.001) and group (F > 5.119, P < 0.01) and significant time-by-group interaction effects (F > 3.320, P < 0.05)were observed in the MoCA, FMA, MBI, and CBIT-C scores. For the CBIT-B score, the main effects of time (F = 367.430, P < 0.001) and group (F = 4.995, P = 0.008) were significant. After intervention, MoCA, FMA, MBI, CBIT-C and CBIT-B scores, and N20 amplitude and latency were better in the combined group than in the AOT and rTMS groups (P < 0.05). ConclusionThe combination of AOT and rTMS may further ameliorate cognitive function, motor function, activities of daily living, and the degree of spatial neglect in post-stroke patients with unilateral spatial neglect, potentially attributable to improved nerve conduction function.

Tangye Jingfa Tu is an important content in the ancient book Fuxingjue from Dunhuang， implying the fundamental principles of formula compatibility in traditional Chinese medicine （TCM）. Our research group has delved into nearly 200 formulas （both classical and contemporary formulas） recorded in the Fangjixue under the theoretical framework of the deficiency or excess syndrome of five Zang-organs together with the reinforcing and reducing effects of Chinese medicinal materials of five flavors. We have initially elucidated the essential principles of the correspondence between formulas and syndromes， revealing the deep-level logic of medicinal material selection and compatibility， thus enriching the understanding about the core characteristics and essence of the diseases and syndromes targeted by formulas. The lunar year of 2024 is Jia Chen year. The formula recorded in Sanyin Jiyi Bingzheng Fanglun for treating the epidemic diseases characterized by excessive earth， prevalent dampness and wetness， and invasion of pathogenic factors into the kidney water in Jia Chen year is Fuzi Shanzhuyutang. Therefore， elucidating the compatibility principle of Fuzi Shanzhuyutang is of great significance for clinical prescription and medication modification in Jia Chen year. According to the Tangye Jingfa Tu theory on the deficiency or excess of syndrome of five Zang-organs and the reinforcing and reducing effects of Chinese medicinal materials of five flavors， this article dissects Fuzi Shanzhuyutang regarding the etiology and pathogenesis of the main indications， as well as the five-element properties and efficacy characteristics of Chinese medicinal materials constituting this formula. It explains the compatibility principles of Fuzi Shanzhuyutang and puts forward suggestions for modifying the formula to address different indications， providing a reference for guiding clinical syndrome differentiation and treatment.

Tangye Jingfa Tu is an important content in the ancient book Fuxingjue from Dunhuang， implying the fundamental principles of formula compatibility in traditional Chinese medicine （TCM）. Our research group has delved into nearly 200 formulas （both classical and contemporary formulas） recorded in the Fangjixue under the theoretical framework of the deficiency or excess syndrome of five Zang-organs together with the reinforcing and reducing effects of Chinese medicinal materials of five flavors. We have initially elucidated the essential principles of the correspondence between formulas and syndromes， revealing the deep-level logic of medicinal material selection and compatibility， thus enriching the understanding about the core characteristics and essence of the diseases and syndromes targeted by formulas. The lunar year of 2024 is Jia Chen year. The formula recorded in Sanyin Jiyi Bingzheng Fanglun for treating the epidemic diseases characterized by excessive earth， prevalent dampness and wetness， and invasion of pathogenic factors into the kidney water in Jia Chen year is Fuzi Shanzhuyutang. Therefore， elucidating the compatibility principle of Fuzi Shanzhuyutang is of great significance for clinical prescription and medication modification in Jia Chen year. According to the Tangye Jingfa Tu theory on the deficiency or excess of syndrome of five Zang-organs and the reinforcing and reducing effects of Chinese medicinal materials of five flavors， this article dissects Fuzi Shanzhuyutang regarding the etiology and pathogenesis of the main indications， as well as the five-element properties and efficacy characteristics of Chinese medicinal materials constituting this formula. It explains the compatibility principles of Fuzi Shanzhuyutang and puts forward suggestions for modifying the formula to address different indications， providing a reference for guiding clinical syndrome differentiation and treatment.

Knee osteoarthritis (KOA) is a prevalent degenerative joint disease characterized by synovial inflammation, cartilage loss. Often manifesting as joint pain and limited mobility, it severely affects the quality of life of patients. Traditional treatment methods such as pharmacological injections and surgical interventions primarily aim to alleviate symptoms but have limited effects on cartilage repair. Human umbilical cord mesenchymal stem cells (hUC-MSCs), due to their anti-inflammatory and chondrogenic capabilities, is considered a new hope for the treatment of KOA. This article synthesizes the latest research findings from both domestic and international sources to discuss the theoretical basis for the clinical application of hUC-MSCs in treating KOA, clinical study design, and efficacy evaluation. It also addresses the challenges in the clinical application of hUC-MSCs and explores future directions, in the hope of providing feasible theoretical support for the treatment of KOA with hUC-MSCs.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Objective:To investigate the effects of the Epley and Semont procedures with varying lateral angles of the head on posterior semicircular canal benign paroxysmal positional vertigo （PC-BPPV）. Methods:A total of 115 patients with unilateral PC-BPPV were randomly divided into five groups: Epley group, Semont group, Semont+10° group, Semont+20° group, and Semont+30° group, with 23 patients in each group. Corresponding reduction treatments were performed. Results:The total effective rates for the Epley group, Semont group, Semont+10° group, Semont+20° group, and Semont+30° group were 95.7% （22/23）, 4.3% （1/23）, 30.4% （7/23）, 52.2% （12/23）, and 87.0% （20/23） respectively. The inefficiencies were 4.3% （1/23）, 95.7% （22/23）, 69.6% （16/23）, 47.8% （11/23）, and 13.0% （3/23）. Statistically significant differences were observed in the total effective rates among the five groups （χ²=54.11, P<0.01）. The total effective rates in the Semont group, Semont+10° group, and Semont+20° group were significantly different from that of the Epley group （P<0.01）, while no statistically significant difference was found between the Semont+30° group and the Epley group （P= 0.608>0.012 5）. Conclusion:Among the four Semont methods with different lateral lying angles, the total effective rate of reduction treatment increased with the elevation of the lateral lying angle on the affected side. The efficacy of the Semont+30° group in treating PC-BPPV was not significantly different from the Epley group's reduction effect, which was markedly superior to that of the other four Semont methods at different angles. Therefore, the Semont+30° reduction technique is recommended for the treatment of PC-BPPV.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Benign Paroxysmal Positional Vertigo/therapy* ; Head ; Posture ; Semicircular Canals/physiopathology* ; Treatment Outcome

This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.

Objective: To investigate the expression and functional role of FK506 binding protein 10 (FKBP10) in oral squamous cell carcinoma (OSCC), and to provide a research basis for the estimated prognosis and targeted therapy of OSCC. Methods: A total of 284 OSCC samples and 19 normal samples were selected from the Cancer Genome Atlas (TCGA) database, and diagnostic analysis was performed to determine mRNA expression. Survival analysis for FKBP10 and OSCC was conducted on a gene expression profile interaction analysis website. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression of FKBP10 in four OSCC cell lines and SAS and SCC9 cells transfected with siRNA. The cell proliferation ability of FKBP10-silenced cells was detected using the CCK8 method, and the cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration and invasion ability were detected through wound healing and invasion experiments. The expression changes of total protein and phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT) after FKBP10 silencing were analyzed by proteomics and Western Blot. Results: According to the analysis of gene expression levels, the mRNA expression level of FKBP10 in OSCC was significantly higher than that in normal tissues (P < 0.001). In terms of diagnosis, the expression level of FKBP10 has unique diagnostic value for OSCC (P < 0.05). The survival analysis of FKBP10 and OSCC showed that a high expression of FKBP10 led to a decrease in patient survival and poor prognosis (P < 0.05). The expression of FKBP10 mRNA and protein in OSCC cell lines was higher than that in normal oral keratinocytes (P < 0.001). Silencing FKBP10 can reduce the proliferation, invasion, and migration ability of SAS and SCC9 (P < 0.001), and also block their cell cycle in the G0/G1 phase (P < 0.001), with a significant increase in apoptosis (P < 0.05). Protein mass spectrometry and Western blot analysis revealed that FKBP10 silencing significantly downregulated the expression of multiple proteins in the RAP1 signaling pathway, mainly RAP guanine nucleotide exchange factor 1 (RAPGEF1) (P < 0.05) and the phosphorylation of PI3K-AKT proteins (P < 0.05). Conclusion FKBP10 is highly expressed in OSCC, leading to poor prognosis for patients. Downregulated FKBP10 expression can inhibit the proliferation, migration, and invasion ability of OSCC cells, hinder cell cycle progression, and promote apoptosis via the RAP1-PI3K-AKT axis. FKBP10 is a potential therapeutic target and prognostic biomarker for OSCC.