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.

This study aims to evaluate the efficacy of Chinese medicine injections in treating transient ischemic attack(TIA) based on network Meta-analysis. Randomized controlled trial(RCT) about Chinese medicine injections in treating TIA were retrieved from PubMed, Web of Science, Cochrane Library, EMbase, CNKI, VIP, Wanfang, and SinoMed with the time interval from inception to March 1, 2024. The methodological quality of the included articles was assessed by ROB 2.0, and the GRADE system was employed to evaluate the quality of evidence. The gemtc package of R 4.1.2 was used to perform the network Meta-analysis. Finally, 63 RCTs with a total sample size of 5 750 cases were included, involving 11 Chinese medicine injections(Shuxuetong Injection, Danhong Injection, Shuxuening Injection, Ginkgo Damo Injection, Shenxiong Glucose Injection, Ligustrazine Injection, Salviae Miltiorrhizae and Ligustrazine Hydrochloride Injection, Salvianolic Acids for Injection, Dengzhan Xixin Injection, Guhong Injection, and Xueshuantong Injection). All patients received conventional western medicine treatment, and the experimental group was additionally treated with Chinese medicine injection. Network Meta-analysis yielded the following results.(1) In terms of improving the clinical total response rate, 11 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Dengzhan Xixin Injection + conventional western medicine had the best effect.(2) In terms of reducing plasma viscosity, 7 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Shenxiong Glucose Injection + conventional western medicine had the best effect.(3) In terms of reducing whole blood high shear viscosity, 6 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Guhong Injection + conventional western medicine had the best effect.(4) In terms of reducing whole blood low shear viscosity, 6 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Shuxuening Injection + conventional western medicine had the best effect.(5) In terms of reducing fibrinogen, 9 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Ginkgo Damo Injection + conventional western medicine had the best effect.(6) In terms of increasing the average blood flow velocity, 3 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Shuxuening Injection + conventional western medicine had the best effect. In summary, compared with conventional western medicine alone, Chinese medicine injections combined with conventional western medicine were effective in improving the clinical total response rate and the average blood flow velocity, as well as reducing plasma viscosity, whole blood high shear viscosity, whole blood low shear viscosity, and fibrinogen. However, due to the limited quality and quantity of the included articles, the above conclusions need to be verified by more high-quality, multi-center, and large-sample RCT.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Injections ; Ischemic Attack, Transient/drug therapy* ; Randomized Controlled Trials as Topic ; Treatment Outcome

The molecular mechanisms underlying the develop-ment and metastasis of prostate cancer remain elusive.This comprehensive review delves into the intricate role of cofilin,an actin-binding protein,in the pathogenesis and progression of prostate cancer.Cofilin is a significant protein in cytoskeletal dynamics,and any dysregulation may result in the morphological changes in normal cells and the invasion and metastasis of tumor cells.Research has revealed that the activity of cofilin is regula-ted by various mechanisms,including phosphorylation/dephos-phorylation and interactions with other molecules.Moreover,this review discusses promising therapeutic interventions,such as co-filin inhibitors and gene therapy,which have demonstrated effica-cy in preclinical models.The challenge of clinically preventing the transition to castration-resistant prostate cancer and tumor metastasis is widely recognized,necessitating the development of precise drug treatments and biomarker identification.As a key regulatory protein,cofilin provides a more comprehensive refer-ence for the prevention and treatment of prostate diseases.

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.

This study systematically reviewed the randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment of post-stroke depression(PSD) and analyzed the clinical study characteristics and outcome indicators, aiming to optimize the design and establish the core outcome set in the future clinical trials of the TCM treatment of PSD. PubMed, Web of Science, Cochrane Library, EMbase, CNKI, VIP, Wanfang, and SinoMed were searched for the relevant RCT published in recent 3 years. The basic characteristics, intervention measures, and outcome indicators of the included RCT were extracted, and the descriptive analysis was carried out. A total of 76 RCTs were eventually included, with the sample size concentrated in 80-100 cases. The most frequent TCM syndromes were liver depression and Qi stagnation(15 times, 31.91%) and phlegm combined with stasis(5 times, 10.63%). The frequency of intervention methods followed a descending trend of TCM decoction(35 times, 46.05%) and TCM decoction + acupuncture(4 times, 5.26%), Chinese patent medicine(3 times, 3.94%), and the intervention mainly lasted for 1 to 3 months(43 times, 60.56%). The adverse reactions of patients were mainly digestive system reaction(150 patients, 39.37%) and nervous system reaction(112 patients, 29.39%). Most of the included studies had unclear risk of bias, involving 84 outcome indicators, which belonged to 8 indicator domains. The RCTs of TCM treatment of PSD showed a variety of problems, such as non-standard TCM syndrome differentiation, inconsistent names of TCM syndrome scores and measurement tools, low quality, unclear risk of bias, neglect of endpoint indicators, unreasonable selection of substitute indicators, lack of differentiation between primary and secondary outcome indicators, non-standard reporting of safety indicators, insufficient attention to economic indicators, and lack of long-term prognosis evaluation. It is suggested that the future research should improve the quality of methodology and build a standardized core outcome set to promote the development of high-quality clinical research in this field.
Humans ; Randomized Controlled Trials as Topic ; Drugs, Chinese Herbal/administration & dosage* ; Stroke/psychology* ; Depression/etiology* ; Treatment Outcome ; Medicine, Chinese Traditional

The molecular mechanisms underlying the develop-ment and metastasis of prostate cancer remain elusive.This comprehensive review delves into the intricate role of cofilin,an actin-binding protein,in the pathogenesis and progression of prostate cancer.Cofilin is a significant protein in cytoskeletal dynamics,and any dysregulation may result in the morphological changes in normal cells and the invasion and metastasis of tumor cells.Research has revealed that the activity of cofilin is regula-ted by various mechanisms,including phosphorylation/dephos-phorylation and interactions with other molecules.Moreover,this review discusses promising therapeutic interventions,such as co-filin inhibitors and gene therapy,which have demonstrated effica-cy in preclinical models.The challenge of clinically preventing the transition to castration-resistant prostate cancer and tumor metastasis is widely recognized,necessitating the development of precise drug treatments and biomarker identification.As a key regulatory protein,cofilin provides a more comprehensive refer-ence for the prevention and treatment of prostate diseases.

Objective:The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer(HSPC).Methods:Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chi-nese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups.The patients in the control group were treated with androgen deprivation therapy(ADT).And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group.The baseline data of the two groups were analyzed.After 36 months of treat-ment,the differences between the two groups were compared in terms of overall survival(OS),prostate-specific antigen(PSA)level,PSA response rate,Functional Assessment Scale for Prostate Cancer Therapy(FACT-P),Chinese medicine evidence scores,testoster-one level and safety.Results:A total of 80 study subjects were included in this study,including 42 cases in the treatment group and 38 cases in the control group.There was no statistical difference in the baseline data between the two groups before treatment(P＞0.05).At the end of the observation period,a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months(P＜0.05).There was no statistically signif-icant difference in PSA levels in the treatment group at 3 months(P＞0.05).And the differences in the proportion of PSA50(98.1％vs 91.4％),PSA90(92.9％ vs 84.6％)and the proportion of decrease in PSA(56.7％vs 33.8％)in the treatment group were found compared to those in the control group after 6 months of tre atment.After 12 months of treatment,the scores of FACT-4 and re-nal-yang deficiency in the treatment group were(95.28±7.93)and(15.73±5.70)respectively,compared to the scores in the con-trol group([85.46±10.12]and[18.20±4.27](P＜0.05).However,there was no significant difference in serum testosterone([0.60±0.24]nmol/L vs[1.09±2.10]nmol/L)between the two groups(P＞0.05).After 24 months of treatment,there were significant differences in in the FACT-4 total score([97.95±7.54]vs[80.33±8.58]),renal-yang deficiency syndrome score([14.64±5.15]vs[24.94±8.75])between the treatment group and the control group(P＜0.05).However,there was no signifi-cant difference in serum testosterone([0.73±1.01]nmol/L vs[0.59±0.25]nmol/L)between the two groups(P＞0.05).Bet-ter therapeutic results were showed in the treatment group in terms of total FACT-P score,physical situation score,social and family situation score,emotional state score,functional state score,additional score and renal-yang deficiency symptom score(P＜0.05).After treatment,there was no serious adverse reaction in the course of treatment,and no obvious abnormality was found in the liver and kidney function of the patients from two groups.Conclusion:Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients,and the earlier the intervention,the longer the overall survival of the pa-tients.In addition,this treatment regimen can increase the PSA response rate,improve patients'quality of life,and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To observe the sedative and analgesic effects of bupivacaine hydrochloride injection combined with neostigmine methylsulfate injection in critically ill patients after general anesthesia operation.Methods Acute and critical patients who were to undergo general anesthesia were randomly divided into control group and treatment group.Two groups received general anesthesia combined with epidural block anesthesia.After operation,the control group was continuously pumped 0.75％bupivacaine hydrochloride injection 45 mL through the epidural catheter,the treatment group was given 2 μg·kg-1 neostigmine methylsulfate injection on the basis of continuous pumping of bupivacaine injection through epidural catheter in the control group.Comparing the pain numerical rating scale(NRS)for 12 h,24 h,48 h,and 72 h of postoperative analgesia and the Ramsay sedation scores(Ramsay),hemodynamic index and safety in the two groups.Results Treatment group were enrolled 32 cases,2 cases dropped out,and 30 cases were finally included in the statistical analysis.Control group were enrolled 32 cases,2 cases dropped out,and 30 cases were finally included in the statistical analysis.The 12-hour Ramsay in the control group and the treatment group were(2.62±0.46)and(2.58±0.51)points;the 24-hour Ramsay were(2.32±0.45)and(2.27±0.39)points;the 48-hour Ramsay were(2.12±0.36)and(2.04±0.32)points;and the 72-hour Ramsay were(1.68±0.34)and(1.57±0.29)points,respectively;the 12-hour NRS were(1.64±0.26)and(1.53±0.28)points;the 24-hour NRS were(2.14±0.37)and(2.23±0.34)points;the 48-hour NRS were(2.57±0.39)and(2.44±0.42)points;the 72-hour NRS were(2.89±0.46)and(2.61±0.51)points,respectively.The NRS score at 72 h after operation in the treatment group was significantly lower than that in the control group(P＜0.05).The 12 h heart rate(HR)in the control group and treatment group were(75.90±6.45)and(75.42±6.24)time·min-1;24 h HR were(76.37±6.28)and(76.43±5.34)times·min-1,48 h HR(78.57±5.14)and(76.95±5.27)time·min-1;72 h HR were(76.49±4.41)and(78.17±4.64)time·min-1,respectively.The 12 h mean arterial pressure(MAP)in the control group and treatment group were(94.34±7.86)and(95.24±7.45)mmHg;24 h MAP were(95.71±7.55)and(96.56±7.29)mmHg;48 h MAP were(96.58±7.36)and(97.64±7.69)mmHg;72 h MAP were(97.63±8.15)and(96.77±8.53)mmHg,respectively the differences of the above indexes between the control group and the treatment group were not statistically significant(all P＞0.05).The extubation time of control group and treatment group were(63.42±16.34)and(59.56±17.27)h,respectively,with no statistical significance(P＞0.05).The adverse drug reactions of two groups were nausea and vomiting,use of rescue analgesics 12 h after surgery,and wound infection.The incidences of postoperative adverse drug reactions in the control group and the treatment group were 26.67％and 23.33％,respectively,with no statistical significance(P＞0.05).Conclusion Bupivacaine hydrochloride injection combined with neostigmine methylsulforte injection can significantly enhance the epidural analgesia effect in acute and critical patients undergoing general anesthesia,and the safety is better.

AIM To analyze the constituents absorbed into blood and brain from Zhishe Tongluo Capsules.METHODS Sixteen rats were randomly assigned into four groups and given intragastric administration(3.1 g/kg),after which the cerebral ischemia-reperfusion injury(MACO)model was established,the blood and brain tissues were collected,and UHPLC-Q Exactive Focus MS/MS was adopted in the identification of prototype constituents.RESULTS Total 70 constituents were identified,20 of which were found in the blood,mainly including flavonoids,tanshinones and Ligusticum chuanxiong phthalides,and 7 of them could enter the brain through blood-brain barrier.Compared with the normal administration group,the MACO administration group demonstrated added constituents absorbed into blood containing 3-hydroxybenzoic acid,calycosin-7-glucoside,curcumenol,senkyunolide B,dihydrotanshinone I and cryptotanshinone;removed constituents absorbed into brain containing puerarin,elemicin,sedanolide,and added those containing salvianolic acid A,senkyunolide I,dihydrotanshinone I in the left brain tissues(infarcted side).CONCLUSION The constituents absorbed into blood and brain from Zhishe Tongluo Capsules,along with the enhanced absorptions of phthalides,quinones and phenols in MACO rats in vivo may be the active substances for treating cerebral infarction.