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 compare the clinical efficacy of neuroendoscope-assisted evacuation and navigation-assisted puncture drainage in treating thalamic hemorrhage breaking into the ventricle. Methods A retrospective analysis was conducted on the clinical data of 93 patients with thalamic hemorrhage breaking into the ventricle at Taihe Hospital of Wannan Medical College between January 2022 and February 2024. The patients received neuroendoscope-assisted removal of thalamic hematoma combined with contralateral extraventricular drainage (n＝44, neuroendoscope group) and navigation-assisted thalamic hematoma puncture drainage combined with contralateral extraventricular drainage (n＝49, navigation group), respectively. The treatment efficacy, surgical situation, and prognosis between the two groups were compared. Results The neuroendoscope group had longer operation duration, more intraoperative blood loss, higher hospitalization costs than the navigation group (P＜0.05). The neuroendoscope group had higher hematoma clearance rate 3rd after surgery and shorter length of stay than the navigation group (P＜0.05). There was no significant difference in the incidence of intracranial infection after surgery between the two groups. The neuroendoscope group had higher Glasgow coma scale (GCS) score at 1 week after surgery and Glasgow outcome scale (GOS) score at 3 months after surgery (P＜0.01). Conclusions Compared with navigation-assisted puncture, neuroendoscope-assisted evacuation can improve the thalamic hemorrhage clearance rate, shorten the length of stay, and improve the prognosis of patients.

BackgroundIn recent years， the incidence of depression among adolescents has been increasing steadily， posing a serious threat to their physical and mental health and even leading to severe consequences such as self-harm and suicide. At the same time， the detection rate of subclinical depression symptoms among adolescents is even higher. Although these symptoms do not meet the clinical diagnostic criteria， they have significantly affected their quality of life， and their persistence over time may further develop into depression. Therefore， in-depth exploration of adolescent depression symptoms and the predictive factors holds significant practical significance and research value. However， up to now， no large-scale investigation and research on depression symptoms among children and adolescents has been conducted in Inner Mongolia Autonomous Region. ObjectiveTo understand the prevalence of depressive symptoms among children and adolescents in Inner Mongolia Autonomous Region， in order to provide references for formulating scientific and effective prevention strategies and intervention measures. MethodsBy using the cluster stratified random sampling method， 6 281 students from the third grade of primary school to the second grade of high school in 12 leagues and cities of Inner Mongolia Autonomous Region were selected in March 2024. A self-designed questionnaire and the Self-rating Depression Scale （SDS） were used for on-site investigation. ResultsA total of 6 058 （96.45%） children and adolescents completed the valid questionnaire survey， and 2 728 cases （45.03%） were found to have depressive symptoms. There were statistically significant differences in the detection rates of depressive symptoms among children and adolescents of different genders， ages， whether they were only children， different family types， family monthly income， parents' educational levels， and whether the mother was employed （χ²=33.769， 40.618， 48.593， 29.972， 142.648， 195.999， 168.190， 5.445， P<0.05 or 0.01）.The results of the Logistic regression analysis showed that for children and adolescents， being female， aged between 12 and 16， over 16 years old， not being an only child， living in a reconstituted family， having a monthly family income of less than 5 000 yuan， and having parents with an education level of primary school or below were predictors of depressive symptoms （OR=1.241， 1.427， 1.273， 1.177， 1.549， 1.278， 1.462， 1.417， 1.514， 1.929， 1.660， 1.528， P<0.05 or 0.01）. ConclusionThe detection rate of depressive symptoms among children and adolescents in Inner Mongolia Autonomous Region is relatively high. Factors that may predict depressive symptoms in children and adolescents include female gender， ages between 12 and 16， ages over 16 years old， non-only children， families with a restructured structure， monthly family income of less than 5 000 yuan， and parents with an education level of primary school or below. ［Funded by Science and Technology Planning Project of the Inner Mongolia Autonomous Region （number， 2022YFSH0119）］

Esophageal cancer is a prevalent malignant tumor of the digestive tract in China, and radical surgery remains the cornerstone of its comprehensive treatment. However, multifactorial challenges such as postoperative gastrointestinal tract reconstruction, traumatic stress, and tumor-related metabolic disturbances render esophageal cancer patients highly susceptible to malnutrition. Perioperative nutritional support therapy plays a crucial role in enhancing surgical safety, improving clinical outcomes, and elevating patients' quality of life by regulating metabolic homeostasis, preserving organ function, and optimizing the immune microenvironment. This article reviews the mechanisms underlying malnutrition in esophageal cancer, methods for nutritional status assessment, and precision intervention pathways based on multi-omics evaluations. The aim is to strengthen clinicians' awareness of standardized perioperative nutritional management for esophageal cancer patients and promote its clinical implementation, thereby facilitating postoperative recovery and improving long-term quality of life.

Objective To investigate the 30-day mortality risk factors in elderly patients with heart failure with reduced ejection fraction (HFrEF) after isolated coronary artery bypass grafting (CABG) and to construct a nomogram for predicting mortality risk. Methods A retrospective analysis of elderly (≥70 years) HFrEF patients undergoing isolated CABG at Tianjin Chest Hospital from 2010 to 2024 was performed. Simple random sampling in R software was used to divide the dataset into training and validation sets in a 7 : 3 ratio. The training set was further divided into survivors and non-survivors. Univariate logistic regression was performed to identify differences between groups, followed by multivariate logistic regression to select independent risk factors for death and to establish a death-risk nomogram, which underwent internal validation. The predictive value of the nomogram was assessed by plotting receiver operating characteristic (ROC) curves, calibration curves, and decision-curve analyses for both the training and validation sets. Results A total of 656 patients were included. The training set consisted of 458 patients (survivors 418, deaths 40); the validation set consisted of 198 patients (survivors 180, deaths 18). In the training set, univariate analysis showed significant differences between survivors and deaths for creatinine (Cr) level, brain natriuretic peptide (BNP), maximum Cr, intra-aortic balloon pump (IABP) use, assisted ventilation, reintubation, hyperlactatemia, low cardiac output syndrome, and renal failure (P<0.05). After multivariable logistic regression, five independent risk factors were identified: IABP use (OR=3.391, 95%CI 1.065-11.044, P=0.038), reintubation (OR=15.991, 95%CI 4.269-67.394, P<0.001), hyperlactatemia (OR=8.171, 95%CI 2.057-46.089, P=0.007), Cr (OR=4.330, 95%CI 0.997-6.022, P=0.024), and BNP (OR=1.603, 95%CI 1.000-2.000, P=0.010). Accordingly, a nomogram predicting mortality risk was constructed. The ROC and calibration analyses indicated good predictive value: area under the curve (AUC) in the training set was 0.898 (95%CI 0.831-0.966) and in the validation set was 0.912 (95%CI 0.805-1.000). Calibration and decision-curve analyses showed good agreement and clinical utility. Conclusion The nomogram incorporating IABP use, reintubation, hyperlactatemia, creatinine, and BNP provides good predictive value for 30-day mortality after CABG in elderly patients with HFrEF and demonstrates potential clinical utility.

Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

[摘 要] 目的：探讨嗜酸性粒细胞（Eos）和其他循环血细胞和炎症指标在预测小细胞肺癌（SCLC）免疫治疗疗效和免疫相关不良反应（irAE）中的价值。方法:回顾分析2013年8月至2023年7月期间海军军医大学第一附属医院呼吸科收治的410例SCLC患者临床信息；在化疗或免疫治疗前，以及治疗后的3个周期，分别检测患者全血细胞计数和细胞因子等指标；记录irAE的发生时间、类型、分级，以及随访情况。结果: 接受化疗联合免疫检查点抑制剂（ICI）治疗（简称联合治疗）的患者116例，其中一线联合治疗患者91例、后线联合治疗25例。联合组患者的总有效率（ORR）为44.8%，疾病控制率（DCR）为90.5%，单用化疗（单化）组患者的ORR为38.4%，DCR为85.0%。联合组中位PFS为8.9（7.2～10.5）个月，中位OS为17.7（13.9～21.5）个月。将联合组与单化组行倾向得分匹配（PSM）法配对，对比二组治疗后3周期的绝对嗜酸性粒细胞计数（AEC）水平、相对嗜酸性粒细胞计数（REC）水平；计算历次复查Eos水平与基线Eos水平的比值（AECT1/0、AECT2/0、AECT3/0、RECT1/0、RECT2/0、RECT3/0），联合组的AECT3/0和RECT3/0显著高于单化组。单因素分析表明，基线AEC和REC的升高与较好的治疗至失败时间（TTF）和OS显著相关（P < 0.05）；治疗后Eos水平与基线水平的比例（AECT3/0、RECT3/0）与较好的PFS和TTF显著相关（P < 0.05）；RECT3/0升高同样与OS改善显著相关（P < 0.05）。多因素分析提示，AECT3/0 > 0.41与较好的PFS和TTF显著相关（P < 0.05）；当RECT3/0 > 0.32时，与较好的PFS、TTF、OS均显著相关（P < 0.05）；RECT3/0 > 0.27仅与较好的TTF、OS显著相关（P < 0.05）。亚组分析发现，缓解组的RECT3/0显著高于非缓解组（P < 0.05）。一线应用ICI与二线/后线应用ICI患者的PFS、TTF、OS无统计学差异，但一线应用ICI时ORR（50% vs 25%，P < 0.05）和DCR（93.48% vs 79.17%，P < 0.05）显著优于二线/后线。116例联合治疗患者发生43例irAE（35.34%）, 最常见的为免疫相关性皮炎8.62%；Ⅲ级以上的irAE共17例（14.66%）；因irAE停药10例（8.62%），死亡2例;发生irAE的患者PFS较未发生irAE的患者显著延长（P < 0.05），而TTF和OS无统计学差异。发生irAE患者的RECT3较未发生irAE患者显著升高（P < 0.05），AECT3/0 > 0.29的患者irAE发生率显著增高（P < 0.05）。结论: Eos是SCLC接受ICI治疗的保护性因素，通过监测AECT3/0、RECT3/0，并结合患者的临床病理生理特征、细胞因子和炎症标志物水平进行综合评估，可有效预测SCLC患者的免疫治疗疗效和irAE的发生。

BACKGROUND:Dental mesenchymal stem cells are considered a promising source for bone tissue repair due to their high proliferation potential,osteogenic differentiation capacity,and immunomodulatory properties.However,some allogeneic applications of stem cells still have potential carcinogenic effects and immune rejection risks.Recently,studies have highlighted the paracrine effects mediated by secretions from dental mesenchymal stem cells in bone tissue repair.These secretions include the soluble factors and extracellular vesicles.OBJECTIVE:To review the research progress of dental mesenchymal stem cells in repairing bone defects through paracrine effects.METHODS:Using search terms"dental mesenchymal stem cell,paracrine,osteogenesis,conditioned medium,extracellular vesicle"in Chinese and English,relevant literature published between 2019 and 2024 was retrieved from databases including CNKI,PubMed,and Elsevier ScienceDirect.A total of 104 studies were ultimately selected for this review.RESULTS AND CONCLUSION:(1)Dental mesenchymal stem cells-conditioned medium contains multiple bioactive factors beneficial for bone repair.These factors directly promote bone formation through regulatory agents such as osteocalcin,osteopontin,bone morphogenetic protein,and dentin sialophosphoprotein.They also play an indirect promoting role in bone tissue repair through neurotrophic factors,vascular endothelial growth factor,and immunomodulatory and anti-inflammatory agents.(2)Dental derived mesenchymal stem cell-derived extracellular vesicles not only contain some cytokines from dental conditioned medium,but also various miRNAs,which promote bone repair by directly promoting osteogenesis,angiogenesis,regulating immune cells,and inflammation control.These extracellular vesicles can be engineered within different scaffold materials to achieve controlled or sustained release,enhancing therapeutic efficacy.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:The exact pathogenesis of temporomandibular joint osteoarthritis is currently unclear.Traditional clinical treatment strategies for temporomandibular joint osteoarthritis are symptomatic treatments such as pain relief and reduction of inflammation,which can stop the progression of the disease to a certain degree but cannot reverse the destruction of the cartilage.Cartilage degeneration,as one of the most prominent pathologic features in the development of temporomandibular joint osteoarthritis,has been the subject of an increasing number of studies that focus on its pathogenesis.Consequently,we hope to provide an ideal radical solution for the regeneration of the temporomandibular joint.OBJECTIVE:To review the progress of research on cartilage degeneration in temporomandibular joint osteoarthritis.METHODS:The search terms were"temporomandibular joint osteoarthritis,degradation of cartilage matrix,synovitis,oxidative stress,chondrocyte hypertrophy,chondrocyte apoptosis,ferroptosis,autophagy,angiogenesis,extracellular vesicles"in Chinese and English.Literature search was conducted in PubMed database and CNKI,and the time limit for the search was from January 2004 to October 2024.Screening was performed by analyzing and reading the literature,and according to the inclusion and exclusion criteria,81 papers were finally included for review.RESULTS AND CONCLUSION:(1)Increased secretion of cartilage matrix degrading enzymes causes degradation of the cartilage matrix,leading to cartilage degeneration.(2)Synovitis promotes cartilage degeneration through macrophage M1-type polarization and production of inflammatory mediators.(3)Oxidative stress promotes cartilage degeneration by exacerbating the inflammatory response through overproduction of reactive oxygen species.(4)Chondrocyte phenotypic changes and death lead to the decrease of cartilage matrix synthesis,resulting in cartilage degeneration.(5)Blood vessels of subchondral bone penetrate the calcified cartilage layer to reach the superficial cartilage layer,which destroys the cartilage structure and leads to cartilage degeneration.(6)Bioactive substances carried by serum-derived extracellular vesicles in inflammatory states also promote cartilage degeneration in temporomandibular joint osteoarthritis.