OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

Developmental dysplasia of hip(DDH)usually occurs in children,and delayed diagnosis of DDH might lead to serious complications and influence long-term prognosis.The application of artificial intelligence(AI)in medical images helps to quantitatively individualize image data,reduce bias generated by manual analysis and achieve early and accurate diagnosis of children DDH.The research progresses of AI in imaging diagnosis of children DDH were reviewed in this article.

Objective:To explore the characteristics of the brain functional networks in children with spastic cerebral palsy (SCP) while at rest and to correlate them with motor functioning.Methods:Thirty-six children with SCP were enrolled as the SCP group, while thirty-four age-matched healthy children were recruited as the control group (the HC group). Functional near-infrared spectroscopy was used to detect changes in the concentration of oxygenated hemoglobin in the children′s cerebral cortex while at rest. The left prefrontal cortex (LPFC), right prefrontal cortex (RPFC), left motor cortex (LMC), and right motor cortex (RMC) were selected as regions of interest. Phase locking values (PLVs) were used to evaluate the strength of functional connectivity (FC) among these brain regions, and graph theory methods were applied to analyze the topological properties of the brain networks. Motor functioning was assessed using the gross motor function measure (GMFM).Results:The analyses of FC strength revealed that the SCP group had significantly weaker FC among all of the regions of interest while at rest compared to the HC group. Their PLVs for LPFC-RPFC, LPFC-RMC, RPFC-RMC and LMC-RMC connectivity were all significantly smaller. Graph theory analysis showed that the SCP group had significantly lower global efficiency (GE) and smaller clustering coefficients (CCs) and network density (D), while their characteristic path lengths were significantly longer. According to the correlation analysis, the PLVs for LMC-RMC connections in the SCP group were positively correlated with their scores on dimensions D and E of the GMFM ( r=0.496 and r=0.579 respectively). GE ( r=0.587 and r=0.642) and CC ( r=0.318 and r=0.759) showed similar significant positive correlations with GMFM dimensions D and E. Conclusions:At rest, the functional networks in the brains of children with SCP exhibit abnormalities closely associated with their motor dysfunction.

Objective:To investigate the clinical and pathological characteristics, prognostic factors, and treatment outcomes of bladder adenocarcinoma.Methods:The data of 177 bladder adenocarcinoma patients treated at Renji Hospital, Shanghai Jiaotong University School of Medicine from January 2003 to December 2023, and 2 687 bladder adenocarcinoma patients from the SEER database (2000—2021) were reviewed retrospectively. The clinicopathological and prognostic characteristics were compared between the two cohorts. Patients with urachal adenocarcinoma or primary bladder adenocarcinoma were included, while metastatic bladder adenocarcinoma from other sites and urothelial carcinoma with glandular components were excluded. The Chi-square test was used for comparison of categorical data, and propensity score matching (1∶1) was applied to match baseline data between the Renji and SEER cohorts. Kaplan-Meier survival curves were generated, and log-rank tests were used for comparisons. Univariate and multivariate Cox regression analyses were performed using the survival R package, with P-values calculated via Wald tests. Results:The proportion of localized bladder adenocarcinoma was significantly higher in the Renji cohort than in the SEER cohort [61.0% (108/177) vs. 19.4% (521/2 687), P<0.001], and mucinous adenocarcinoma was more common in Renji cohort [33.3% (59/177) vs. 22.6% (607/2 687), P<0.001]. After matching for baseline factors, including SEER stage and pathological grade, survival analysis revealed that the Renji cohort patients had slightly better survival compared to the SEER cohort [median survival: 55.4 (24.1, 196.2) months vs. 39.2 (13.6, 137.4)months, P=0.033]. Multivariate Cox analysis identified SEER stage [Renji cohort: HR=3.83 (95% CI 1.62-9.07), P=0.002; SEER cohort: HR=3.67 (95% CI 3.13-4.31), P<0.001] and pathological grade [Renji cohort: HR = 2.76 (95% CI 1.54-4.95), P=0.001; SEER cohort: HR=1.46 (95% CI 1.29-1.65), P<0.001] as independent prognostic factors. In the Renji cohort, no significant differences were observed in the median progression-free survival [40.1 (19.5, 91.6) months vs. 40.9 (12.8, not reached)months, P=0.976] and overall survival [79.3 (37.1, 195.8) months vs. 53.9 (16.4, 129.5)months, P=0.374] between patients receiving adjuvant chemotherapy and those not receiving it. However, among patients with lymph node-positive bladder adenocarcinoma, adjuvant chemotherapy significantly improved both progression-free survival [40.1 (38.2, 75.4) months vs. 12.2 (3.1, 12.2)months, P=0.004] and overall survival [68.2 (46.2, 84.5)months vs. 28.1 (4.3, 28.3)months, P=0.006]. Conclusions:Bladder adenocarcinoma is rare and associated with poor prognosis. Compared to the SEER cohort, Renji cohort patients had more localized disease, with no significant differences in other features. SEER stage and pathological grade were independent prognostic factors in both cohorts. Lymph node-positive bladder adenocarcinoma patients in the Renji cohort benefited significantly from adjuvant chemotherapy.

Objective To develop a virtual reality rehabilitation support system and evaluate its effects on improving discharge readiness in caregivers of laryngectomy patients.Methods The system is equipped with a virtual reality-based home nursing skills guidance module for post-laryngectomy patients and an evidence-based artificial intelligence Q&A module.A convenience sampling method was adopted to select 64 caregivers of patients who underwent laryngectomy for the first time in the otorhinolaryngology head and neck surgery department of a tertiary A hospital in Beijing from July 2024 to January 2025 for a systematic study on application effects.To avoid cross-contamination between an experimental group and a control group,ward-based grouping was applied.A coin toss was used to assign Ward 1 to an experimental group and Ward 2 to a control group,with 32 cases in each group.The experimental group received discharge guidance based on the virtual reality technology,while the control group was provided with conventional verbal and written discharge instructions.The readiness for hospital discharge and the quality of discharge teaching scores of caregivers were compared between the 2 groups after the intervention.Results No sample detachment.After the intervention,the patient caregivers in the experimental group scored significantly higher than those in the control group in terms of discharge readiness and quality of discharge guidance,with a statistically significant difference(P＜0.001).Conclusion This study developed the virtual reality rehabilitation system for laryngeal cancer patients demonstrated good feasibility and effectiveness.The application of this system for discharge education significantly improved discharge readiness of caregivers and quality of discharge guidance for post-laryngectomy patients.It also helped with the optimization of health education models,enhancement of nursing resource utilization efficiency,and improvement of transitional care.

Objective To analyze the causes of infection and hemorrhage in patients with malignant obstructive jaundice(MOJ)after ultrasound-guided percutaneous transhepatic biliary drainage(PTBD).Methods A total of 420 patients with MOJ after PTBD in The Third Affiliated Hospital of Naval Medical University from Jun.2023 to Sep.2024 were enrolled,and their condition after PTBD,medical histories,preoperative examinations,and other clinical data were retrospectively analyzed.Univariate and multivariate logistic regression analyses were performed to explore the risk factors for postoperative infection and hemorrhage,and receiver operating characteristic(ROC)curves were plotted.Results Univariate logistic regression analysis showed that ascites,diuretics use,repeated punctures,hepatitis B virus(HBV)DNA and preoperative hemoglobin(Hb)levels,and neutrophil count(NE)were associated with infection after PTBD(all P＜0.05).Multivariate logistic regression analysis showed that ascites,diuretic use,repeated punctures,HBV DNA and preoperative Hb levels,and NE were the independent risk factors for infection after PTBD(all P＜0.05).Six factors including ascites,diuretics use,repeated punctures,HBV DNA and preoperative Hb levels,and NE were used to establish a prediction model.The area under the ROC curve of the model for predicting infection after PTBD was 83.1％(95％confidence interval[CI]75.5％-90.7％,P＜0.001).Univariate logistic regression analysis showed that liver tissue inflammation,ascites,preoperative peritoneal drainage,diuretics use,preoperative Hb and prealbumin(PA)levels were related to bleeding after PTBD(all P＜0.05).Multivariate logistic regression analysis showed that preoperative Hb and PA levels were independent risk factors for bleeding after PTBD.Preoperative Hb and PA levels were included to establish the prediction model.The area under the curve value for predicting bleeding after PTBD was 86.3％(95％CI 80.8％-91.9％,P＜0.001).Conclusion The prediction model for infection and hemorrhage after PTBD can facilitate early preventivon and intervention measures,thereby improving surgical safety.

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.