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 evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

Objective To explore the mediating role of mindful attention and awareness in depressive symptoms and insomnia severity among patients with comorbid depression and insomnia.Methods A cross-sectional study was conducted,enrolling 267 patients with comorbid depression and insomnia who were treated in the outpatient Department of Medical Psychology of Second Affiliated Hospital of Army Medical University,from March to May 2024.Basic demographic and clinical data were collected using a general information questionnaire.Depressive symptom severity was measured via the Patient Health Questionnaire-9(PHQ-9),insomnia severity via the Insomnia Severity Index(ISI),perceived stress via the Perceived Stress Scale-10(PSS-10),and mindful attention and awareness via the Mindful Attention Awareness Scale(MAAS).Pearson correlation analysis was used to examine the correlations between depressive severity,insomnia severity,perceived stress,and mindful attention and awareness.Mediation analysis was performed using Process 4.1.Results The PHQ-9 score was(13.80±5.98)and the ISI score was(17.10±5.56)in the 267 patients.Pearson correlation analysis showed that depressive severity and insomnia severity were positively correlated with perceived stress(r=0.531,0.351,P<0.001)and negatively correlated with mindful attention and awareness(r=-0.373,-0.350,P<0.001).Mediation analysis using Process 4.1 indicated that the combined mediating effect of mindful attention and awareness and insomnia between perceived stress level and depressive level was 0.157,with a 95%confidence interval(CI)of 0.102～0.217,and the total mediating effect was significant(P<0.001).Conclusion Perceived stress directly positively affects depression and indirectly exacerbates depression through insomnia as a mediator,and mindful attention and awareness can weaken the promoting effect of perceived stress on insomnia.

An ion chromatography method was developed for detection of nine kinds of trace organic amines(Methylamine,dimethylamine,trimethylamine,ethylamine,diethylamine,triethylamine,n-propylamine,n-butylamine,and ethanolamine)and six kinds of trace water-soluble inorganic cations(Li+,Na+,NH4+,K+,Ca2+,and Mg2+)in atmospheric fine particulate matter(PM2.5)in this wok.Various chromatographic columns(IonPac CS12,IonPac CS17 and IonPac CS19)were compared in terms of their separation efficiency for target analytes,and IonPac CS19 column was ultimately selected.Through meticulous optimization of the column temperature,a low temperature condition of 20℃was found to achieve the highest separation efficiency(All are above 1),effectively separating all 15 kinds of target analytes.Under the optimal analytical conditions inculding methanesulfonic acid(MSA)as eluent,100 μL of injection volume,column temperature at 20℃and eluent at flow rate of 1 mL/min,the detection limits of this method ranged from 0.05 to 7.15 μg/L,the quantification limits were 0.16-23.82 μg/L,and the spiking recoveries were 84%-105%.The proposed method exhibited high accuracy and excellent reproducibility,and was suitable for concurrent analysis and measurement of organic amines and water-soluble inorganic cations in PM2.5.

The stability of ammonium ion selective electrode is an important indicator to ensure accurate monitoring of ammonia nitrogen concentration in drinking water.However,in long-term monitoring process,interfering ions and water molecules in water samples may penetrate into the interior of the ammonium ion selective electrode to form a water layer,which affects the potential response and stability of the electrode.Perfluorooctanoic acid is a low surface energy material,and doping it in polyaniline can reduce surface energy of the composite and improve surface roughness.In this work,five ammonium ion selective electrodes were prepared by doping polyaniline with different concentrations of perfluorooctanoic acid as a solid contact layer,which made the solid contact layer of electrode had hydrophobic properties,thereby improving stability of the ammonium ion selective electrode.The stability of the ion-selective electrode was evaluated by potential drift experiment,and the optimal doping concentration of perfluorooctanoic acid in the sediment solution was determined to be 5 mmol/L.The experiment results showed that the solid contact layer had a water contact angle of 132o under the doping concentration,the potential drift rate was 41.66 μV/h,and potential drift rate in the aqueous layer test was 1.31 mV/h,which were all better than those of the unmodified electrode.The standard deviation of the electrode potential was 1.42 mV,which was obviously superior to that of the unmodified electrode.The characteristics of high stability of the electrode made it suitable for long-term monitoring of ammonia nitrogen content in water samples.

The electrocatalytic nitrate reduction reaction(NO3RR)presents a sustainable pathway for large-scale ammonia production,yet it faces significant challenges due to proton supply limitations caused by the high energy barrier for water dissociation,which slows ammonia(NH3)generation.Herein,a palladium(Pd)-modified copper-cobalt(CuCo)hollow fiber penetration electrode that enabled H2 injection through its hollow structures,thereby enhancing proton availability for NO3RR was developed.The active Pd component efficiently dissociated H2,facilitating active hydrogen(*H)spillover and speeding up the cascade NO3RR process on Cu and Co sites.As a result,a half-cell energy efficiency of 39.53%and an NH3 Faradaic efficiency(FE)of 97.11%±1.17%at-0.1 V(vs RHE)were achieved,comparable to state-of-the-art systems.Importantly,the H2-assisted approach prevented the oxidation of active Cu and Co phases,demonstrating exceptional stability with less than 5.6%decay in current density(267 mA/cm2)and retention of NH3 FE at 94.8%after over 70 h of electrolysis.These findings offered valuable insights into proton supply pathways and design of NO3RR electrodes.

Objective To explore the technical process and clinical application of laparoscopic combined upper midline incision minimally invasive liver transplantation. Methods A retrospective analysis was conducted on 30 cases of laparoscopic combined upper midline incision minimally invasive liver transplantation. The cases were divided into cirrhosis group (15 cases) and liver failure group (15 cases) based on the primary disease. The surgical and postoperative conditions of the two groups were compared. Results All patients successfully underwent laparoscopic "clockwise" liver resection, with no cases of passive conversion to open surgery or intolerance to pneumoperitoneum. In 6 cases, the right lobe was relatively large, and the right hepatic ligaments could not be completely mobilized. One case required an additional reverse "L" incision during open surgery. All patients successfully completed the liver transplantation, with no major intraoperative bleeding, cardiovascular events, or other occurrences in the 30 patients. The model for end-stage liver disease (MELD) score in the cirrhosis group was lower than that in the liver failure group (P<0.001). There were no statistically significant differences between the two groups in terms of age, surgical time, blood loss, anhepatic phase, or cold ischemia time (all P>0.05). During the perioperative period, there was 1 case of hepatic artery embolism, 1 case of portal vein anastomotic stenosis, no complications of hepatic vein and inferior vena cava, and 3 cases of biliary anastomotic stenosis, all of which occurred in the liver failure group. Conclusions In strictly selected cases, the minimally invasive liver transplantation technique combining laparoscopic hepatectomy with upper midline incision for graft implantation has the advantages of smaller incisions, less bleeding, relatively easier operation, and faster postoperative recovery, which is worthy of clinical promotion and application.

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.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome