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.

ObjectiveTo investigate the therapeutic effects and mechanisms of modified Huangqi Jianzhong decoction （HQJZ） on gastric precancerous conditions （GPC）. MethodsIn the cell experiment， human gastric mucosal epithelial cells underwent malignant transformation induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） for the modeling of GPC （MC cells）. The cells were allocated into four groups： control ， model， low-dose HQJZ （HQJZ-L）， and high-dose HQJZ （HQJZ-H）. The control and model groups were cultured with the complete medium， while HQJZ-L and HQJZ-H groups received additional interventions with HQJZ at low （0.5 g·L^-1） and high （1.0 g·L^-1） doses， respectively. Cell counting kit-8 （CCK-8） assay was used to evaluate cytotoxicity， Transwell assay to assess cell invasion， Annexin V-FITC/PI staining to detect apoptosis， immunofluorescence assay to analyze reactive oxygen species （ROS） expression and mitochondrial autophagy， and Western blot to verify expression of proteins in key pathways. In the animal experiment， the GPC model was established in healthy BALB/c mice through MNNG induction. Twenty-four mice were allocated into four groups： control， model， HQJZ-L， and HQJZ-H. Control and model groups received normal saline （10 mL·kg^-1·d^-1） orally， while HQJZ-L and HQJZ-H groups were administrated with low-dose （6.24 g·kg^-1·d^-1） and high-dose （12.48 g·kg^-1·d^-1） HQJZ， respectively. After treatment， hematoxylin‑eosin （HE） staining and AB-PAS staining were performed to observe histopathological changes in the gastric tissue. Immunofluorescence assay was used to detect reactive oxygen species （ROS） and microtubule-associated protein 1 light chain 3 （LC3） levels in the gastric mucosa， TdT-mediated dUTP nick-end labeling （TUNEL） staining to assess apoptosis rates， and Western blotting and immunohistochemistry （IHC） to analyze the expression levels of Ki67， proliferating cell nuclear antigen （PCNA）， and foxhead box O3 （FoxO3）. ResultsCell viability assays showed that HQJZ dose-dependently reduced MC cell viability compared with the control group （P<0.05， P<0.01）. Transwell assays revealed that the model group exhibited enhanced cell invasion compared with the control group （P<0.05）. Compared with the model group， HQJZ treatment attenuated the cell invasion （P<0.05）. Gastric mucosal pathology in mice demonstrated that compared with the control group， the model group showed elevated HE and AB-PAS pathological scores （P<0.05）， while HQJZ treatment reduced these scores （P<0.05）. Transmission electron microscopy revealed increased mitochondrial number and volume in the model group compared with the control group. HQJZ treatment resulted in abnormal mitochondrial structure and significant alterations in rough endoplasmic reticulum morphology and distribution， presenting as dilated and hollow forms. Mitochondrial and apoptosis assessments indicated that compared with the control group， the model group exhibited enhanced Mito Tracker Green fluorescence （P<0.05）， no significant change in DCFH-DA fluorescence， Mito Tracker Red CMXRos fluorescence， ROS immunofluorescence， or malondialdehyde （MDA） level， increased GSH level （P<0.05）， enhanced LC3 fluorescence （P<0.05）， no significant change in apoptosis rate， and elevated ATP content in cells and mouse serum （P<0.05）. Compared with the model group， HQJZ treatment reduced Mito Tracker Green fluorescence （P<0.05）， increased DCFH-DA fluorescence， Mito Tracker Red fluorescence， MDA level， LC3 fluorescence， and apoptosis rate （P<0.05）， and decreased cellular ATP content （P<0.05）. The HQJZ-L group showed no significant change in ROS immunofluorescence or GSH level， whereas the HQJZ-H group demonstrated enhanced ROS immunofluorescence and glutathione （GSH） level （P<0.05）. Immunohistochemistry and Western blotting revealed that compared with the control group， the model group exhibited increased numbers of PCNA- and Ki67-positive cells （P<0.05） and elevated protein levels of FoxO3， sirtuin 1 （SIRT1）， and B-cell lymphoma 6 （Bcl-6） （P<0.05）. HQJZ treatment reduced the numbers of PCNA- and Ki67-positive cells （P<0.05） and lowered the protein levels of FoxO3， SIRT1， and Bcl-6 （P<0.05）. ConclusionHQJZ alleviates the progression of gastric precancerous lesions by regulating mitochondrial function via the FoxO3/ROS pathway and promoting apoptosis of GPC-malignant cells.

Objective To investigate the molecular mechanism by which HMGA2 participates in the TGF-β/Smad pathway in the regulation of the proliferation, aggression, and metastasis of laryngeal cancer. Methods shRNA transfection was used to construct the HMGA2 knockdown laryngeal cancer TU686 cell model, and subcutaneous transplantation tumor model and tail vein metastasis tumor model were established in nude mice. Western blot was conducted to detect the expression of HMGA2 and TGF-β/Smad pathway-related molecules in cells and tumor tissues. Results The proliferation, invasion, and metastasis of TU686 cells with HMGA2 knockdown decreased. The expression of TGF-β, Smad2, Smad3, and phosphorylated Smad2/3 protein also decreased. TGF-β1 stimulation of the TGF-β/Smad pathway could partially offset the antitumor effect caused by HMGA2 knockdown. Through in vitro experiments, we determined that low expression of HMGA2 significantly inhibited the growth of subcutaneously transplanted tumors, and TGF-β1 stimulation of the TGF-β/Smad pathway reduced the tumor-inhibitory effect resulting from the low expression of HMGA2. In tail vein metastases of nude mice, E-cadherin expression was elevated but N-cadherin expression was reduced in the HMGA2 knockdown group, suggesting that HMGA2 could inhibit the progression of EMT. After TGF-β1 stimulated the TGF-β/Smad pathway, the EMT effect due to HMGA2 knockdown was lessened. Conclusion HMGA2 may promote the proliferation, invasion, and metastasis of laryngeal cancer by upregulating the TGF-β/Smad signaling pathway.

ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

Objective To report a case of tibial synovial sarcoma and review relevant literature to enhance understanding of this disease.Methods The clinical data of a patient with tibial synovial sarcoma treated at Kaifeng Central Hospital were retrospectively analyzed.A literature search was conducted in domestic and international databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,PubMed,Web of Science,and Embase,up to July 2024.Relevant literature was comprehensively reviewed to summarize the imaging and pathological characteristics,treatment,and prognosis of synovial sarcoma.Results A 29-year-old female patient was admitted with left lower extremity pain.X-ray examination revealed a proximal tibia space-occupying lesion suggestive of malignancy,and a mid-tibial space-occupying lesion considered benign.Contrast-enhanced computed tomography(CT)and plain magnetic resonance imaging(MRI)of the proximal tibial lesion also suggested malignancy.Ultrasound-guided biopsy of the proximal tibial tumor revealed a poorly differentiated malignant tumor.Immunohistochemistry results indicated monophasic synovial sarcoma,requiring genetic testing for definitive diagnosis.The patient underwent wide resection of the proximal left tibial malignancy with tumor-type artificial joint replacement,combined with curettage and bone cement filling for the left mid-tibial lesion under anesthesia.Postoperative pathology of space-occupying lesions in the proximal tibia confirmed monophasic synovial sarcoma,and fluorescence in situ hybridization(FISH)demonstrated a rupture of the synovial sarcoma translocation gene(SYT)(i.e.,SS18 positive).There was no recurrence or metastasis found in the patient during the reexamination 6 months after postoperative chemotherapy.As of July 2024,15 cases of genetically confirmed primary intraosseous synovial sarcoma have been reported internationally.Symptoms included pain and swelling,with a medical history of 1-2 years.The X-ray and CT findings showed osteolytic destruction with bone cortical discontinuity.In 13 cases,the intraosseous masses extended to the extraosseous area;in 2 cases,punctate calcifications were detected within the masses.Plain MRI scan showed iso-signal or hypo-signal on T1WI and hyper-signal,iso-signal,and hypo-signal on fat-suppressed T2WI,and enhanced MRI scan demonstrated heterogeneous enhancement.Pathological examination showed spindle-shaped cells under microscopy.Immunohistochemistry results showed positive epithelial membrane antigen(EMA),broad-spectrum cytokeratin(AE1/AE3),Ewing's sarcoma marker(CD99),and transducin-like enhancer of Split 1(TLE1).Twelve patients underwent surgical treatment;6 patients received adjuvant chemotherapy after surgery,of whom 4 developed local recurrence or distant metastasis at initial diagnosis,and 3 died during follow-up.Among the 6 patients who did not receive adjuvant chemotherapy,3 suffered from recurrence or distant metastasis.Conclusions Primary intraosseous synovial sarcoma is a rare malignant tumor with non-specific clinical manifestations.Imaging features typically include osteolytic destruction and intraosseous masses extending extraosseously,suggesting an intraosseous origin.Pathology and immunohistochemistry aid diagnosis,but definitive confirmation relies on further genetic testing.At present,the main treatment regimens for synovial sarcoma involve comprehensive therapies such as surgery and adjuvant chemotherapy,and the prognosis of patients is poor.

Objective To investigate the effects of estrogen signaling on T-cell recruitment and polarization in acutely injured skeletal muscle.Methods One hundred C57BL/6 male mice,one hundred and eighty C57BL/6 female mice were selected.Twenty-five female mice were ovariectomized(OVX)and 10 male mice were taken as the sham-operated(sham).Then,cardiotoxin(CTX)induced tibialis anterior(TA)injury for preparing mice myoinjury model.Subcutaneous injection of 17β-estradiol(E2)or estrogen receptor antagonist 4-hydroxytamoxifen(4-OHT)was performed.A total of 140 mice(70 males and 70 females)were divided into four group including:PBS-male,CTX-male,PBS-female,and CTX-female.Serum estradiol(E2)levels were measured by ELISA,and muscle injury models were validated via HE staining.Subsequently,20 male and 20 female mice were selected for immunofluorescence(IF)and Real-time PCR to assess estrogen receptors(ER)expression in injured muscle tissue.Further,10 male and 40 female mice were allocated into five experimental groups,including CTX,CTX+E2,CTX+4-OHT,CTX+OVX,CTX+sham.HE staining and IF were performed to evaluate inflammatory infiltration in the injured muscle.Additionally,50 female mice were divided into CTX and CTX+OVX groups,and IF combined with flow cytometry were used to analyze T-cell phenotypes and muscle fiber regeneration in the injured muscle.Results In vivo,serum E2 and myofiber ERβ increased post-injury in mice of both sexes,significantly higher in females.Compared to the control group,E2 alleviated inflammation,OVX exacerbated inflammation,increased CD4+T-cell infiltration,elevated T helper 1 cell(Th1)response,decreased regulatory T cells(Tregs),impaired regeneration.In vitro,IFN-γ/LPS significantly upregulated ERβ in myotubes.Conclusion Estrogen signaling critically regulates muscle inflammation.Estrogen deficiency(OVX)delays repair of skeletal muscle by promoting Th1 response and suppressing Tregs function.

Objective To analyze the effects of left bundle branch area pacing(LBBaP)on atrial fibrillation occurrence after dual-chamber pacemaker implantation.Methods The medical records of 87 patients who underwent dual-chamber pacemaker implantation at People's Hospital between May 2021 and September 2022 were retrospectively analyzed.According to different implantation methods,the patients were divided into an observation group(n=45)and a control group(n=42).The control group received traditional right ventricular pacing(RVP),while the observation group received LBBaP.Serum N-terminal pro B-type natriuretic peptide(NT-proBNP),QRS onset-to-end duration(QRSd),echocardiographic parameters,cardiac pacing parameters,complications,atrial high-rate events,and atrial fibrillation incidence were compared between the two groups.Results Twelve months after surgery,serum NT-proBNP levels in the observation group were significantly lower than those in the control group(P＜0.05),and QRS duration(QRSd)was shorter in the observation group than in the control group(P＜0.05).There were no significant differences in left ventricular ejection fraction(LVEF)or left ventricular end-systolic diameter(LVESD)between the two groups at 12 months postoperatively(P＞0.05).Left atrial diameter(LAD)was smaller in the observation group than in the control group at 12 months postoperatively(P＜0.05).No significant differences were observed in sensing levels or the proportion of cardiac pacing between the two groups(P＞0.05).However,the proportion of ventricular pacing was higher in the observation group than in the control group(P＜0.05).Intraoperatively and at 12 months postoperatively,impedance levels were lower in the observation group than in the control group(P＜0.05),while threshold values were higher in the observation group(P＜0.05).Total complication rates did not differ significantly between the two groups(P＞0.05).At 12 months postoperatively,the incidence of atrial fibrillation was similar between the two groups(P＞0.05),but the incidence of atrial high-rate events was lower in the observation group than in the control group(P＜0.05).At 24 months postoperatively,both the incidence of atrial high-rate events and atrial fibrillation were lower in the observation group than in the control group(P＜0.05).Conclusion Compared with traditional RVP implantation,LBBaP implantation can significantly improve left heart function,provide more stable pacing parameters,and reduce the risk of long-term atrial high-rate events and atrial fibrillation.The risk of complications is similar for both groups,but LBBaP implantation increases the pacing threshold.

Objective To analyze the effect of dronedarone and propafenone in preventing postoperative recurrence in patients with atrial fibrillation(AF)and to discuss its influence on inflammatory response and myocardial injury.Methods A total of 113 patients with AF,who were admitted to the Qiandongnan People's Hospital of China from July 2022 to March 2024,were enrolled in this study.By using random number table method,the patients were divided into control group(n=56)and study group(n=57).All patients received circumpulmonary vein electrical isolation.After treatment,the patients of control group were given propafenone orally for three months,while the patients of study group received dronedarone orally for three months.Both the preoperative and postoperative 3-month inflammatory response indicators including hypersensitive C-reactive protein(Hs-CRP),leucolipin,nucleotide-bound oligomeric domain-like receptor protein 3(NLRP3)inflammasome,and tumor necrosis factor α(TNF-α),the echocardiographic indicators including left atrial maximum volume(LAMV),left ventricular end-systolic diameter(LVESD),and left ventricular ejection fraction(LVEF),the myocardial injury markers including creatine kinase(CK),cardiac troponin I(cTn I),the central nervous specific protein β(S100β),the creatine kinase isoenzyme(CK-MB),the adverse reactions,and the recurrence of AF were compared between the two groups.Results At 3 months after treatment,the serum levels of hs-CRP,leucolipin,NLRP3 inflammasome and TNF-α were decreased in both groups(all P＜0.01),which in the study group were obviously lower than those in the control group(all P＜0.001);the levels of LAMV and LVESD were decreased in both groups(both P＜0.01),which in the study group were remarkably lower than those in the control group(both P＜0.001);the level of LVEF was increased in both groups(P＜0.01),which in the study group was significantly higher than that in the control group(P＜0.001);the levels of CK,cTn I,S100β,and CK-MB were decreased in both groups(all P＜0.01),which in the study group were strikingly lower than those in the control group(all P＜0.001).The incidence of adverse drug reactions in control group and in the study group was 5.36％(3/56)and 7.02％(4/57 cases)respectively,and the difference was not statistically significant(P＞0.05).Within 3 months after treatment,the recurrence rate in the study group was 5.26％(3/57),which was lower than 19.64％(11/56)in the control group,and the difference was statistically significant(P＜0.05).Conclusion Compared with propafenone,the use of dronedarone after circumferential pulmonary vein electrical isolation in patients with AF can improve the cardiac functions,reduce myocardial injury and inflammatory responses,and lower the risk of postoperative recurrence of AF.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Objective Understanding the population structure of mosquitoes in the drainage system of Minhang District,Shanghai,and exploring the physical prevention and control technology of mosquito traps with a Vazor mosquito repellent film in the drainage system.Methods A 500 mL water spoon was used to assist in visual inspection to investigate the breeding status of mosquito larvae in the drainage system.A carbon dioxide mosquito trap method was used to monitor adult mosquitoes around the ground drainage system,and the artificial hour method was used to monitor adult mosquitoes around the underground drainage system.Mosquito-repellent film was applied at a rate of 1 mL/m2 to the drainage system where mosquito larvae or pupae are found,and the breeding situation was observed and recorded.Results The positivity rate of mosquitoes breeding in the ground drainage system was 50%.The mosquito larvae in the drainage channels were primarily Aedes albopictus,whereas Ae.albopictus were primarily noted in the sewage wells.The proportions of Ae.albopictus and Culex pipiens pallens in the rainwater wells were similar,and the dominant mosquito species around the surface drainage system was Ae.Albopictus.The positive rate of mosquito breeding in the underground drainage system was 47%,with the dominant mosquito species being Cx.pipiens pallens(58.39%)followed by Ae.albopictus(41.6%).The dominant adult mosquito species around the drainage system were Cx.pipiens pallens(83%)followed by Ae.albopictus(11%).In terms of the effectiveness of mosquito-repellent water film,the mosquito breeding rates of the ground and underground drainage systems using mosquito-repellent water film decreased to 2.78%and 5%after 1 week of use,respectively,and then rebounded after the 3rd week.After a supplementary dose during the 5th week,the breeding rates returned to normal.No statistically significant differences were observed in the effect compared with the standard control group using 1%bisulfite granules;however,a statistically significant difference was noted compared with the blank control group without special treatment.Conclusions In the drainage system of Minhang District,Shanghai,mosquito breeding is severe,and variations exist in the dominant mosquito species in different environmental drainage facilities.The simultaneous use of mosquito-repellent films can effectively control mosquito breeding in drainage systems.