Platelets are small, anucleated cells generated by cytoplasmic fragmentation and shedding from mature megakaryocytes. Upon vascular stimulation or injury, platelets become activated and adhere to exposed vascular endothelial cells, ultimately forming thrombi to promote blood coagulation and wound healing. In recent years, increasing evidence from in-depth studies on platelet function has revealed that autophagy plays a crucial role in platelet production and functional performance. Autophagy is an intracellular process of material recycling and reuse, involving autophagosome formation, cargo degradation, and nutrient recycling, which facilitates the maintenance of homeostasis and defense against pathogen infection. Numerous studies have demonstrated that autophagy participates in the regulation of platelet production, activation, and aggregation, and is closely implicated in the pathogenesis of platelet dysfunction-related diseases such as immune thrombocytopenia. Additionally, platelet-rich plasma therapy, by modulating the autophagic process, has shown great potential in treating osteoarthritis and promoting diabetic foot wound healing. This review thoroughly explores the potential roles of autophagy in regulating platelet production and function, as well as in platelet-related diseases. Future research should focus on the molecular mechanisms of platelet autophagy, investigate its dynamic changes under different disease conditions, and explore how autophagy modulation can improve platelet function and treat related diseases. This will provide a theoretical foundation for developing novel therapeutic strategies and is expected to bring breakthroughs in the treatment of platelet-related diseases.

ObjectiveTo investigate the effects of Tianma Goutengyin on the tumor necrosis factor-α （TNF-α）/signal transducer and activator of transcription 3 （STAT3）/α1-antichymotrypsin C-terminal tail fragment （α1ACT） signaling pathway and A1-type astrocytes in a rat model of vascular dementia. MethodsSeventy-two male Sprague-Dawley rats were randomly divided into six groups （n=12 per group）： Sham-operated group， model group， Tianma Goutengyin high-， medium-， and low-dose groups （5.13， 10.26， and 20.52 g·kg^-1）， and a nimodipine group （8.1 mg·kg^-1）. The vascular dementia model was established by permanent bilateral common carotid artery occlusion， followed by 4 weeks of intervention. Learning and memory ability were evaluated using the novel object recognition test， and behavioral performance was assessed using the forced swimming test. Levels of interleukin-6 （IL-6） and C-C motif chemokine ligand 2 （CCL2） in hippocampal tissue were measured by enzyme-linked immunosorbent assay （ELISA）. Hippocampal neuronal morphology was observed by Nissl staining， and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Immunohistochemistry was used to detect positive expression of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， and myelin basic protein （MBP）. Western blot analysis was performed to measure the protein expression levels of TNF-α， TNF receptor 1 （TNFR1）， phosphorylated STAT3 （p-STAT3）， α1ACT， IL-6， complement component 3 （C3）， BDNF， S100 calcium-binding protein A10 （S100A10）， and GFAP in hippocampal tissue. ResultsCompared with the sham-operated group， the model group showed a significantly reduced relative recognition index in the novel object recognition test （P<0.01）， prolonged immobility time and increased immobility frequency in the forced swimming test （P<0.01）. Hippocampal IL-6 and CCL2 levels were significantly increased （P<0.01）. Nissl staining revealed a marked reduction in neuronal number and loss of Nissl bodies （P<0.01）. MBP-positive expression was significantly decreased （P<0.01）， apoptosis was significantly increased （P<0.01）， BDNF-positive expression was significantly reduced （P<0.05）， and GFAP-positive expression was significantly increased （P<0.01）. In addition， the protein expression levels of TNF-α， TNFR1， p-STAT3， α1ACT， IL-6， and C3 were significantly elevated （P<0.01）， while BDNF and S100A10 expression levels were significantly decreased （P<0.01）. Compared with the model group， all Tianma Gouteng yin dose groups exhibited a significant increase in the relative recognition index （P<0.05）， shortened immobility time and reduced immobility frequency （P<0.05， P<0.01）. IL-6 and CCL2 levels were significantly decreased （P<0.01）， neuronal number was significantly increased （P<0.05， P<0.01）， and MBP-positive expression was significantly enhanced （P<0.01）. Apoptosis was significantly reduced （P<0.01）， BDNF-positive expression was significantly increased （P<0.05）， and GFAP-positive expression was significantly decreased （P<0.01）. Moreover， the protein expression levels of TNF-α， TNFR1， p-STAT3， α1ACT， IL-6， and C3 were significantly decreased （P<0.01）， while BDNF and S100A10 protein expression levels were significantly increased （P<0.01）. ConclusionTianma Goutengyin may inhibit A1-type astrocyte activation in rats with vascular dementia through the TNF-α/STAT3/α1ACT signaling pathway， thereby reducing neuronal apoptosis and improving learning and memory function.

To evaluate the application value of the Peyton four-step teaching method in the standardized training of intestinal ultrasound and compare it with traditional teaching methods, so as to provide an optimized approach for clinical ultrasound training.

The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate ⁺" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.

Objective:To explore the role and molecular mechanisms of S100A6 protein in neonatal meningitis caused by Streptococcus agalactiae. Methods:Human brain microvascular endothelial cells (HBMECs) were used as an in vitro experimental model, and siRNA was employed to construct S100A6 gene knockdown HBMECs strain. The S100A6 gene overexpression cell line was established by lentiviral transfection method. Western blot was used to detect the expression level of S100A6 protein in HBMECs after Streptococcus agalactiae infection, and the change in intracellular inflammatory cytokine protein levels after S100A6 gene knockdown or overexpression. A neonatal bacterial meningitis model was established by injecting Streptococcus agalactiae suspension into the cisterna magna of neonatal Sprague-Dawley (SD) rats. HE staining was used to observe pathological changes in brain tissue; immunohistochemistry was used to detect the expression and distribution of S100A6 protein in brain tissue; Western blot and ELISA were used to measure S100A6 protein levels in cerebrospinal fluid (CSF). Results:Compared with the control group, the intracellular S100A6 protein level in HBMECs increased significantly following Streptococcus cgalactiae infection. After S100A6 gene knockdown, the invasion rate of Streptococcus agalactiae into the HBMECs was significantly reduced ( P<0.01), while intracellular TNF-α and IL-6 protein levels were elevated markedly ( P<0.01). In contrast, overexpression of S100A6 gene increased the invasion rate ( P<0.01) and notably decreased TNF-α and IL-6 protein levels ( P<0.001). In the neonatal SD rat bacterial meningitis model, HE staining revealed substantial neutrophil infiltration in brain tissue after Streptococcus agalactiae infection. Immunohistochemistry showed extensive deposition of S100A6 protein around the meninges, and significant expression of S100A6 protein was also detected in CSF. Conclusions:S100A6 protein is crucial in mediating neonatal meningitis caused by Streptococcus agalactiae infection. S100A6 gene knockdown promotes the production of intracellular inflammatory cytokines and reduces Streptococcus agalactiae invasion into cells, thereby alleviating bacteria-induced cellular damage. Additionally, the increased expression of S100A6 protein in brain tissue and CSF after Streptococcus agalactiae infection suggests its potential as a diagnostic biomarker for bacterial meningitis.

Objective:To investigate the efficacy of naloxone in improving health-related quality of life in patients with chronic arsenic exposure-related pruritus, and to explore the modification effect of gene polymorphisms associated with arsenic metabolism and endorphin receptors.Methods:A randomized, double-blind, placebo-controlled trial was conducted between January and March 2019 in Changde City, Hunan Province, China. Eligible patients with moderate to severe chronic pruritus under arsenic exposure were recruited, and randomly assigned to the naloxone group and the control group to receive sublingual naloxone and placebo (0.4 mg/d) respectively for 7 consecutive days. Outcomes were assessed before treatment and on day 7 after treatment, including the primary outcome (the dermatology life quality index [DLQI]) and secondary outcomes (depression symptoms, anxiety symptoms, and quality of sleep). Genotyping of the arsenic (+3 oxidation state) methyltransferase and 3 opioid receptor genes was performed using ligase detection reaction. Data analysis was performed using t test for normally distributed continuous variables, non-parametric tests for skewed continuous variables, and chi-square test for categorical data. Linear regression analysis was carried out to evaluate the effect of naloxone on outcome measures, while the interactive effect of demographic factors, genotypes and treatment methods on changes in DLQI were assessed by the generalized linear model. Results:A total of 126 patients with chronic arsenic exposure-related pruritus were enrolled, including 73 males and 53 females. They were randomly divided into the control group (64 cases) and the naloxone group (62 cases), with the ages being 60.0 ± 9.1 years and 58.4 ± 8.6 years, respectively. There were no significant differences between the two groups in terms of age, gender, income, education levels, or hair arsenic concentrations (all P > 0.05). After treatment, the decrease in DLQI scores was significantly higher in the naloxone group than in the control group (-8.79 ± 6.84 vs. -5.19 ± 8.10; P = 0.008). However, there were no significant changes in depression symptoms, anxiety symptoms, or quality of sleep between the naloxone group and control group (all P > 0.05). Linear regression analysis showed that naloxone significantly affected DLQI with a crude regression coefficient of -3.60 (95% CI: -6.25, -0.96; P = 0.008). Stratification analysis revealed that patients with the κ-opioid receptor gene rs1051660 (wild-type, CC) responded better to the treatment than those with the mutated genotype (CA), and there was a significant interaction between the rs1051660 genotype and therapeutic drugs in relation to DLQI changes ( P = 0.014) . Conclusion:Naloxone can effectively improve health-related quality of life in patients with chronic arsenic exposure-related pruritus, and its efficacy is modified by the gene polymorphism of the κ-opioid receptors.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective:To evaluate the efficacy of corticosteroids in male children with Duchenne muscular dystrophy (DMD), and provide evidence for the rational clinical use of medication.Methods:This was a multicenter medical record series study which conducted from January 15 th to March 14 th, 2025. A total of 53 male children with DMD admitted to the Department of Rehabilitation of Children′s Hospital, Zhejiang University School of Medicine, Children′s Hospital of Chongqing Medical University and Affiliated Children′s Hospital of Soochow University from 2020 to 2024 were enrolled. Clinical data, corticosteroid usage, and the follow-up data were collected. The North star ambulatory assessment (NSAA) was used as the primary efficacy indicator. Generalized estimating equations (GEE) exchangeable working matrices were used for longitudinal analysis, and the least squares mean were used to compare the change trend of the efficacy evaluation index across different medication durations. Results:The age at the initiation of corticosteroid treatment was (6.3±1.9) years. The follow-up duration was 1.2 (0.9, 2.2) years. After treatment, the raw scores and linear scores of NSAA were both significantly higher than those before treatment ((22±7) vs. (19±5) points, (60±16) vs. (53±8) points; t=3.98, 3.69; both P<0.001). The 10 meter running time and time rising from floor were both shorter than those before treatment (6 (4, 8) vs. 7 (6, 9) s, 5 (3, 6) vs. 6 (5, 9) s; Z=2.62, 3.47; both P<0.01). GEE model analysis revealed all nonlinear correlation between motor function (NSAA linear score, 10-meter running velocity, and rising from floor velocity) and the duration of corticosteroid treatment (all P<0.05). Least squares mean comparison all showed that the medication effect first increased and then decreased with duration, reaching the peak at 1.1-2.0 years after treatment (all P<0.05). Conclusions:Corticosteroids can improve the motor function in male children with DMD, with the maximum treatment effect occurring 1 to 2 years after the initiation of treatment. It is necessary to comprehensively leverage time-varying efficacy of corticosteroids to optimize individualized treatment regimens for maximal motor function benefits in children with DMD.

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.