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 protective effect of Xielitang on dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group， a model group， a sulfasalazine group （0.6 g·kg^-1）， and low-， medium-， and high-dose Xielitang groups （1.67， 3.34， 6.68 g·kg^-1）. After treatment for 42 d， the colon length was recorded， and the disease activity index （DAI） score was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10）. Hematoxylin-eosin （HE） staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor （FXR）， small heterodimer partner （SHP）， liver receptor homolog-1 （LRH-1）， cholesterol 7α-hydroxylase （CYP7A1）， and fibroblast growth factor receptor 4 （FGFR4） in liver and FXR， sodium-dependent bile acid transporter （ASBT）， and fibroblast growth factor 15 （FGF15） in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover， ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group， the model group showed significantly decreased colon length， IL-10 content， α-diversity index， abundance of Firmicutes and Lactobacillus， and content of deoxycholic acid （DCA） and lithocholic acid （LCA） （P<0.01）， significantly increased DAI score， IL-6 and TNF-α content， abundance of Bacteroidetes， and the content of cholic acid （CA）， chenodeoxycholic acid （CDCA）， and taurocholic acid （TCA） （P<0.05， P<0.01）， significantly down-regulated protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. In addition， the structure of colonic mucosa was destroyed， and inflammatory cells infiltrated in the model group. Compared with the model group， Xielitang could significantly increase the colon length， IL-10 content， α-diversity index， the abundance of Firmicutes and Lactobacillus， and DCA and LCA content （P<0.05， P<0.01）， decrease DAI score， abundance of Bacteroidetes， and the content of IL-6， TNF-α， CA， CDCA， and TCA （P<0.01）， up-regulate the protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and down-regulate the protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis， regulating intestinal flora imbalance， and maintaining bile acid homeostasis.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

Objective: To explore the effects of Cldn14 gene knockout on renal metabolism and stone formation in rats，so as to provide reference for research in the field of urinary calium metabolism and stone formation. Methods: Cldn14 gene knockout homozygous rats and wild-type rats of the same age were randomly divided into 4 groups：wild-type control (WC) group，wild-type ethylene glycol (WE) group，gene knockout control (KC) group and gene knockout ethylene glycol (KE) group，with 10 rats in each group.The WE and KE groups were induced with ethylene glycol + ammonium chloride to form kidney stones，while the WC and KC groups received normal saline gavage.After 4 weeks of standard maintenance feeding，the urine samples were collected to detect the venous blood.The kidneys were collected for HE，Pizzolatto's staining and transmission electron microscopy.The protein in renal tissues was extracted to detect the expressions of Claudin16 and Claudin19. Results: Crystal deposition was observed in the renal tubular lumen of the WE and the KE groups，and more crystals were detected in the KE group.The WE group had a large number of intracytoplasmic black crystalline inclusions observed in renal tubular epithelial cells under transmission electron microscope，followed by the KE and KC groups.Compared with WC and WE groups，KC and KE groups had significantly decreased serum calcium and magnesium levels but significantly increased urinary calcium level.In addition，the urinary calcium level was higher in the WE group than in the WC group and higher in the KE group than in the KC group.The KE group had lower level of Claudin16，but there was no significant difference in the level of Claudin19 among the 4 groups(P>0.05). Conclusion: Knockout of Cldn14 gene alone cannot effectively reduce urinary calcium excretion or reduce the risk of stone formation in rats，which may be related to the decrease of Claudin16 level.

Objective To explore the application value of ultrasound combined with elastography in grading inflammation in patients with chronic liver disease at S2 stage of liver fibrosis.Methods Totally 51 patients who were hospitalized at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from Jan.2022 to Mar.2024 and underwent liver biopsy with pathological results indicating a stage of S2 liver fibrosis in chronic liver disease were enrolled.All patients underwent ultrasound-guided liver biopsy to obtain the stage of pathological liver fibrosis(S1 to S4)and the grade of liver inflammation(G0 to G4).In addition,all the patients were examined by ultrasound combined with elastography;and shear wave velocity(Vs),acoustic attenuation coefficient(ATT),liver fibrosis index(LFI),fibrosis-related index(F index),and inflammatory activity index(A index)were obtained.The correlation between ultrasound combined with elastography parameters and pathological inflammation grading was analyzed.Results According to the pathological inflammation grading,there were 15 cases in group G1,28 cases in group G2,and 8 cases in group G3.There were significant differences in F index,A index,Vs and ATT among the 3 groups(all P＜0.05).Among them,F index,A index and Vs in group G1 were significantly lower than those in group G3(P=0.007,0.006,0.040),while ATT was significantly higher than that in group G3(P=0.005);and there was no significant difference in LFI among the 3 groups(P=0.373).Vs,ATT,F index and A index were correlated with pathological inflammation grade(r=0.404,-0.417,0.379,0.383;P=0.003,0.002,0.006,0.006).The mean plot showed that with the increase of pathological inflammation grade,the age of patients showed a linear upward trend,ATT showed a linear downward trend,and A index showed a linear upward trend.Vs was positively correlated with alanine transaminase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),γ-glutamyltransferase(GGT),total bilirubin,and direct bilirubin(DBil)(all P＜0.05).ATT was negatively correlated with ALT,AST,GGT,and DBil(all P＜0.05);and both F index and A index were positively correlated with ALT,AST,ALP,GGT,and DBil(all P＜0.05).Conclusion Ultrasound combined with elastography can be used to evaluate the degree of inflammation in patients with chronic liver disease at S2 stage of liver fibrosis.

Objective:To analyze the effect of rapid division of left Glisson pedicle and Arantius tube plane in laparoscopic anatomical left hemihepatectomy (LALH).Methods:Clinical data of 25 patients (15 with intrahepatic bile duct calculus and 10 with liver tumor) undergoing LALH in the Department of Hepatobiliary and Pancreatic Surgery, Jiangyin Hospital Affiliated to Nantong University from June 2020 to November 2024 were retrospectively analyzed, including 14 males and 11 females, aged (66.6±11.9) years. Among the patients, 15 received LALH with rapid division of left Glisson pedicle and Arantius tube plane in " one-clamp" fashion, and the others received LALH after traditional dissection of left Glisson pedicle. Age, sex, body mass index, time of left Glisson pedicle dissection, whether the MHV exposure, the time of liver transection, whether MHV and its important branches or bile duct injury occurred, intraoperative blood loss, the incidence of postoperative biliary leakage, the time of abdominal drainage remove, the hospital stay, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, albumin 3 days after postoperative were compared between the groups.Results:The times of left Glisson pedicle dissection in the new-fasion and traditional group were (6.1±1.6) min and (13.8±3.0) min, and the time of liver transection was (24.9±3.5) min and (33.4±3.3) min, respectively ( t=-8.34, 6.08, P<0.001 for both). After division of left Glisson pedicle, the MHV was well exposed in 14 cases of new-fashion group and none of traditional group ( P<0.001). All the patients successfully completed the operation without conversion to laparotomy. Intraoperative blood loss, incidence of postoperative bile leakage, time of peritoneal drainage tube removal, postoperative hospital stay, AST, ALT, total bilirubin and albumin 3 days after surgery between the two groups were no significant differences (all P>0.05). Conclusion:LALH using the rapid division of left Glisson pedicle and Arantius tube plane in " one-clamp" fashion could be safe and feasible, the time of left Glisson pedicle and liver transection was short.

Aim To analyze the incidence of major adverse cardiovascular and cerebrovascular events(MACCE)in patients with different types of acute coronary syndrome(ACS)undergoing coronary artery rotational atherec-tomy(RA)within two years.Methods 268 patients with ACS who underwent RA in the Department of Cardiology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School of Nanjing University,between November 2011 and December 2022 were retrospectively included.According to whether ST-segment elevation myocardial infarction(STEMI)occurred,they were divided into 25 cases in the ST-segment elevation myocardial infarction(STEMI)group and 243 cases in the non-ST-segment elevation acute coronary syndrome(NSTE-ACS)group.The NSTE-ACS group included unstable angina pectoris(UAP)and non-STEMI(NSTEMI).The basic information and intraoperative data related to percutaneous coronary intervention(PCI)in the two groups were collected,and the occurrence of MACCE(including car-diovascular death,non fatal myocardial infarction,worsening heart failure,ischemic stroke and target vessel revasculariza-tion)within two years after RA was followed up and analyzed.Results Compared with the NSTE-ACS group,the STEMI group had a higher incidence of MACCE and cardiovascular mortality during the two-year follow-up period(10.3％and 0.4％vs.28.0％and 8.0％;P＜0.05).There was no statistical difference between the incidence of target vessel revascularization,nonfatal infarction,ischemic stroke and worsening heart failure between the two groups(P＞0.05).According to subgroup analysis based on enrollment periods,the results showed that over time(2011-2017 compared to 2018-2022),the incidence of MACCE in all patients within two years after RA showed a decreasing trend(18.97％vs.6.58％).Combined with previous studies,gender,hypertension,diabetes,renal insufficiency,smoking and left ven-tricular ejection fraction(LVEF)were included in the Cox regression model.It was found that the use of intravascular ul-trasound(IVUS)was an independent factor to reduce the incidence of MACCE in ACS patients within two years after RA(HR=0.333,95％CI:0.153～0.723,P＜0.01).Kaplan-Meier analysis showed that among ACS patients undergoing RA,the cumulative incidence of MACCE events was higher in the STEMI group than that in the NSTE-ACS group(P＜0.05).Conclusion STEMI patients have a higher incidence of MACCE and cardiovascular mortality within two years after RA compared to NSTE-ACS patients,and the use of IVUS during RA surgery can reduce the incidence of MACCE in ACS patients after RA.

AIM:To explore the relationship be-tween the level of myeloid-derived suppressor cell(MDSC)infiltration in tumor tissues and the clinical efficacy and prognosis of combined PD-1 inhibitor and chemotherapy in the treatment of advanced non-small cell lung cancer(NSCLC).METHODS:A retrospective analysis was conducted on 92 NSCLC patients who received PD-1 inhibitor combined with chemotherapy at the First Affiliated Hospital of Anhui Medical University from June 2019 to June 2024.Tumor tissue samples were examined using immunohistochemistry to detect the level of MDSC infiltration,dividing the patients into high-in-filtration group(MDSC≥2)and low-infiltration group(MDSC＜2).The objective response rate(iORR),disease control rate(iDCR),progression-free survival(PFS),and overall survival(OS)were compared between the two groups.Kaplan-Meier survival analysis and Log-rank test were used to plot PFS and OS survival curves,and Cox regression analysis was applied to identify factors influencing prognosis.RESULTS:Among the 92 patients,53 were in the low MDSC infiltration group,and 39 were in the high MDSC infiltration group.The low MDSC infiltration group showed significantly better treatment responses compared to the high MDSC infiltration group.The objective response rate(iORR)was 77.3％in the low MDSC infiltration group,higher than the 56.4％in the high MDSC in-filtration group(P=0.033).The disease control rate(iDCR)was 94.3％,also significantly higher than the 66.7％in the high MDSC infiltration group(P=0.001).Moreover,the median progression-free sur-vival(PFS)and overall survival(OS)in the low MD-SC infiltration group were 16.9 months and 27.6 months,respectively,which were significantly lon-ger than those in the high MDSC infiltration group(PFS 12.6 months,OS 22.3 months).Kaplan-Meier analysis revealed that both PFS and OS in the low MDSC infiltration group were significantly longer than those in the high MDSC infiltration group.Cox univariate analysis showed that smoking,PD-L1 ex-pression levels,tumor stage,and MDSC infiltration level were closely associated with PFS and OS.Mul-tivariate Cox regression analysis further indicated that high MDSC infiltration was an independent risk factor for both PFS(HR=2.678,P=0.013)and OS(HR=2.254,P=0.022).CONCLUSION:The level of MDSC infiltration in tumor tissues is closely related to the efficacy and prognosis of PD-1 inhibitor com-bined with chemotherapy in NSCLC patients.High MDSC infiltration suggests reduced treatment sen-sitivity and poor prognosis.MDSC infiltration level may serve as a predictive biomarker for the effica-cy and prognosis of PD-1 inhibitor combined with chemotherapy in advanced NSCLC.

Objective: To explore the relationship between stigma and mental resilience in adolescent epilepsy patients and associated factors, so as to provide reference for future psychological intervention in adolescent patients with epilepsy. Methods: A total of 295 adolescent patients with epilepsy from Wuhan Mental Health Center were enrolled as participants from February 2021 to October 2024. The stigma was evaluated by Kilifi Stigma Scale for Epilepsy (KSSE), and psychological resilience was evaluated by Connor-Davidson Resilience Scale (CD-RISC). Associated factors of stigma and psychological resilience in adolescent patients with epilepsy were analyzed by multivariate Logistic regression analysis. Results: In the adolescent patients with epilepsy, KSSE score was (10.90±4.13) points, with 138 cases (46.78%) at low level, 154 cases (52.20%) at moderate level and 3 cases (1.02%) at high level. CD-RISC score was (50.19±5.97) points, there were 170 cases (57.63%) at low level and 125 cases (42.37%) at high level. Multivariate Logistic regression analysis showed that disease course >3 years ( OR =2.22), family history of epilepsy ( OR = 4.18) , monthly family income ≤5 000 yuan ( OR =2.05), single parent family ( OR =2.46) and middle and high stigma level ( OR = 1.72) had a higher risk on low level of mental resilience ( P <0.05). The course of disease >3 years ( OR =2.20), family history of epilepsy ( OR =3.54), general seizure ( OR =2.12), monthly family income ≤5 000 yuan ( OR =2.70), low level of mental resilience ( OR =2.03) of adolescent epilepsy patients showed a high risk on moderate high level of stigma ( P <0.05). Conclusions The stigma level is higher, while psychological resilience is lower in adolescent patients with epilepsy. Clinically, targeted intervention should be implemented based on related factors such as stigma in addescent patients with epilepsy.