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.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

OBJECTIVE To investigate the effects of osthole （OST） on skin wound healing and angiogenesis in rats by regulating the sonic hedgehog （SHH） signaling pathway. METHODS Full-layer skin defect wound model rats were established and then randomly separated into Model group， OST low-dose， medium-dose and high-dose groups （OST-L group， OST-M group， OST-H group， 20， 30， 40 mg/kg OST）， high-dose OST+SHH inhibitor cyclopamide group （OST-H+cyclopamide group， 40 mg/kg OST+10 mg/kg cyclopamide）， with 12 rats in each group. Another 12 rats were selected as the control group. The wound healing of rats on 1， 7 and 14 days of administration was observed， and the wound healing rate of rats in each group was measured. The pathological changes and collagen deposition in rat wound tissue were observed； the levels of angiopoietin-1 （Ang-1） and basic fibroblast growth factor （bFGF） in wound tissue of rats were detected； the relative expressions of vascular endothelial growth factor A （VEGFA） and vascular endothelial growth factor receptor-2 （VEGFR-2） mRNA were also detected in wound tissue of rats； the protein expressions of VEGFA， VEGFR-2， SHH and glioma-associated oncogene homolog-1 （GLI1） were determined in wound tissue of rats. RESULTS Compared with Model group， the healing rate of skin wound， relative expression of collagen protein， the levels of Ang-1 and bFGF， the mRNA and protein expressions of VEGFA and VEGFR-2， and the protein expressions of SHH and GLI1 were all significantly increased in OST-M and OST-H groups （P＜0.05）. The wound tissue underwent significant re- epithelialization， with reduced inflammatory cell infiltration and granulation tissue edema， and an increase in the number of new blood vessels. SHH inhibitor cycloparamide weakened the promoting effects of OST on skin wound healing and angiogenesis in rats. CONCLUSIONS OST may promote skin wound healing and angiogenesis in rats by activating the SHH signaling pathway.

Social robots play an important role in the field of medical companionship， providing services such as companion communication， drug monitoring， and rehabilitation guidance for the elderly and other subjects. However， social robots also pose the risk of deceiving medical users. Although certain forms of social robots’ deception can be used for therapeutic purposes， unethical deception can have adverse consequences for patients， doctors， and even society. These risks include causing patients to develop attachment disorders， violating their privacy， endangering their health， and even undermining the credibility of the healthcare system. Faced with the deception problem of social robots， starting from relational theory， medical artificial intelligence developers can conduct ethical regulation from the following two paths. First， social robots should be ethically programmed， including embedding programs for limiting benevolent lies， implementing informed consent principles， and ensuring information accuracy. Second， the deceptive behaviors of social robots should be controlled， requiring developers to take full-process supervision responsibility， design medical social robots that can supervise each other， and participate in formulating quality standards and evidence mechanisms for deception issues.

[Abstract] [Objective] To assess the effect of a centrifugal haemocyte separator on platelet counts in patients with neurological immune-mediated disorders during/after therapeutic plasma exchange (TPE). [Methods] This study included 189 patients (108 females and 81 males) who were treated in the department of neurology at Huashan Hospital, Fudan University, from March 2021 to March 2022. A total of 820 TPE treatments were carried out. Each patient received 2 to 5 TPEs, with each TPE amounting to the patient's plasma volume. The peripheral blood cell counts of the patients were evaluated before TPE and after 2 to 5 TPEs. [Results] The duration of a single TPE in this study was 94(84,107) minutes, and the actual volume of a single TPE replacement was 2 456(2 142, 2 785) mL. The number of patients who underwent TPE for 2, 3, 4, and 5 sessions was 17, 28, 18, and 126, respectively. The platelet (PLT) counts of the patients before and after the TPE were 195×10⁹/L (range:150 to 245) and 220×10⁹/L (range:170 to 270), respectively (P<0.05). Consequently, the overall PLT counts exhibited a significant decrease from baseline following TPE, yet the PLT counts remained within the normal range after TPE. Spearman's correlation analysis indicated that platelet loss did not correlate with the duration of TPE (ρ=0.037), the age of the patient (ρ=0.015), or the volume of the single replacement fluid (ρ=0.034), P>0.05, weakly correlated with the number of TPE sessions (ρ=0.017), and moderately correlated with the PLT counts before TPEs (ρ=0.446). [Conclusion] The TPE procedure exhibited a measurable impact on the patients' platelet levels, but the platelet counts remained within the normal range, therefore did not interfere with the patients' subsequent treatment protocols. The decrease in platelet level was correlated with the baseline platelet level before treatment and the number of TPE sessions.

Objective Nowadays, radioactive xenon isotopes, including ^131mXe, ^133mXe, ¹³³Xe, and ¹³⁵Xe, are primarily released into the atmosphere through various reactor operation and major accidents of reactors. To improve the online monitoring capability of xenon in nuclear facilities and their gaseous effluents, a highly sensitive online xenon monitoring system was developed to monitor, warn, and alarm the activity concentration of radioactive xenon. Methods The online monitoring system for radioactive xenon gas in nuclear facilities was established using xenon membrane separation and concentration, xenon high-efficiency selective adsorption, and low-background gamma-ray spectrometry analysis methods. Results Under the operation mode of one-hour sampling and one-hour measuring, the minimum detectable activity concentration of the radioactive xenon online monitoring system for ¹³³Xe was approximately (1.43 ± 0.03) Bq/m³. Conclusion This system can be effectively used for online monitoring of xenon activity concentration in nuclear facilities such as nuclear power plants and isotope production reactors, as well as in gaseous effluents. It helps improve the safety level of personnel, the environment, and nuclear facilities.

Objective To evaluate the clinical efficacy of Ningxin decoction in treating patients with permanent atrial fibrillation(AF)of deficiency of both qi and yin type infected by coronavirus disease 2019(COVID-19).Methods From February to August 2023,120 patients with permanent AF of deficiency of both qi and yin type infected by COVID-19 were collected from the outpatient clinic of Guang'anmen Hospital South Campus,China Academy of Chinese Medical Sciences.Patients were randomly divided into a control group and a treatment group using a random number table method,there were 60 cases in each group,and 1 case fell off in each group,leaving 59 cases in each group.The treatment group was given Ningxin decoction(drug composition:Cassia branch 15 g,Cornus officinalis 15 g,Rehmannia 15 g,Rhodiola rosea 15 g,Ginseng 6 g,Mulberry parasitica 10 g,Coptis coptis 3 g,Salvia miltiorrhiza 12 g,Ligusticum chuanxiong 10 g,Ophiopogon 12 g,and schisandra Vinegar 6 g)using formula granules to rinse with water,twice a day.The control group was given 10 mg of coenzyme Q10 twice a day,and both groups were treated continuously for 4 weeks.The improvements in traditional Chinese medicine(TCM)symptoms,including chest pain,dizziness,fatigue,lethargy,palpitations,chest tightness and shortness of breath,insomnia,and excessive dreams before and after treatment in two groups,as well as changes in heart rate variability(HRV)and heart rate deceleration indicators were observed.Results The treatment group showed significant therapeutic effects in improving chest pain,fatigue,palpitations,chest tightness and shortness of breath,there were also improvements in lethargy,insomnia,and excessive dreaming,there was no significant therapeutic effect in improving dizziness.The control group showed significant therapeutic effects in improving palpitations,there were also improvements in chest pain,chest tightness and shortness of breath,while there was no significant therapeutic effect in other aspects.The treatment group showed significantly higher effective rates in improving chest pain,fatigue,lethargy,chest tightness and shortness of breath,insomnia,and excessive dreaming compared to the control group[chest pain:95.45%(42/44)vs.78.57%(33/42),fatigue:83.67%(41/49)vs.31.25%(15/48),lethargy:73.91%(34/46)vs.12.77%(6/47),chest tightness and shortness of breath:88.89%(48/54)vs.63.64%(35/55),insomnia:78.43%(40/51)vs.12.24%(6/49),excessive dreaming:76.09%(35/46)vs.43.75%(21/48),all P<0.05].The standard deviation of all normal to normal RR intervals(SDNN),root mean square of the difference between adjacent NN intervals(RMSSD),standard deviation of all 5-minute RR intervals(SDANN),and percent of NN50 in the total number of NN intervals(PNN50)in both groups after treatment were significantly increased compared to before treatment,and the RMSSD,SDANN,and PNN50 in the treatment group were significantly higher than those in the control group after treatment[RMSSD(ms):28.96±3.59 vs.24.34±2.66,SDANN(ms):108.55±11.80 vs.100.44±13.58,PNN50:7%(6%,7%)vs.5%(5%,6%),all P<0.05].There was no statistically significant difference in heart rate deceleration between the two groups before and after treatment.Conclusion Ningxin decoction has a good effect on the improvement of TCM syndromes and heart rate variability in patients with permanent atrial fibrillation of deficiency of both qi and yin type after being infected by COVID-19.

Objective:To investigate the epidemiology features, intervention effects and influencing factors of thrombosis in arteriovenous graft (AVG), and to provide reference for optimizing vascular access scheme in hemodialysis patients.Methods:It was a retrospective study. The clinical and follow-up data of patients with AVG constructed in the Blood Purification Center, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were analyzed. According to whether AVG thrombosis occurred during the follow-up period, they were divided into thrombosis group and non-thrombosis group, and the epidemiology status, influencing factors and patency rates of AVG thrombosis were analyzed. AVG was followed up until June 30, 2023 or abandonment or death of patient or loss of follow-up. Kaplan-Meier method was used to analyze the patency rates of AVG. Log-rank test was used to compare the differences of patency rates between groups. Logistic regression model was used to analyze the influencing factors of AVG thrombosis.Results:The study included 475 AVG from 464 patients, with age of (55.50 ± 11.85) years old, 193 males (40.6%), 185 diabetes patients (38.9%) and dialysis age of 24 (1, 68) months. One hundred and fifty-four AVG (32.4%) had a total of 307 AVG thrombotic events during the follow-up of 602 (380, 920) days, with a standardized incidence of 0.34 times per patient-year. Among them, 60 cases (19.5%, 60/307) had frequent thrombosis. Kaplan-Meier survival analysis showed that AVG secondary patency rates at 2-years and 3-years in the thrombosis group and frequent thrombosis subgroup were inferior to those in the non-thrombosis group (84.0% vs. 92.5%, P=0.017; 66.5% vs. 85.7%, P<0.001; 78.9% vs. 92.5%, P=0.030; 54.6% vs. 85.7%, P<0.001). Two hundred and sixty-nine AVG thrombotic events were analyzed to evaluate the treatment effects. Endovascular interventional surgery was used for thrombectomy in 215 cases (79.9%), and hybrid surgery (endovascular interventional surgery combined with surgical incision) was used in 54 cases (20.1%), with a technical success rate of 98.9% (266/269) and a clinical success rate of 98.1% (264/269). Kaplan-Meier survival analysis showed that there were no statistically significant differences in the primary post-intervention patency rates at 90 days and 365 days, respectively (all P>0.05), and there was statistically significant difference in the primary post-intervention patency rate at 180 days (45.1% vs. 26.5%, Z=2.563, P=0.015). Multivariate logistic regression analysis showed that graft-applied type (intering as the reference, propaten OR=1.953, 95% CI 1.139-3.350, P=0.015; acuseal OR=2.628, 95% CI 1.438-4.800, P=0.002), body mass index < 18.5 kg/m 2 (18.5-24.0 kg/m 2 as the reference, OR=0.291,95% CI 0.090-0.943, P=0.040), serum albumin < 40 g/L ( OR=1.579, 95% CI 1.019-2.445, P=0.041), serum ferritin < 200 μg/L ( OR=1.818, 95% CI 1.162-2.845, P=0.009) and mean arterial pressure < 70 mmHg ( OR=7.180, 95% CI 1.339-38.501, P=0.021) were the independent influencing factors of AVG thrombosis. Conclusions:The incidence of AVG thrombotic events is 0.34 times per patient-year, mainly concentrated in a small number of patients. Thrombosis reduces the secondary patency rate of AVG. AVG thrombosis treatment with endovascular interventional surgery or hybrid surgery has a high technical success rate and a clinical success rate. The thrombosis is related to graft-applied types, nutritional status of patients and mean arterial pressure level.

Objective: Observational studies often report disturbed sleep patterns in individuals with diabetic nephropathy (DN). The possible causal relationship behind these connections remains unknown. This research assessed the possible cause-and-effect relationship between eleven sleep-related characteristics and the risk of developing DN using a two-sample Mendelian randomization (MR) study. Methods: This study employed a two-sample bidirectional MR analytical approach. Genetic data for eleven sleep-related characteristics were acquired from the genome-wide association studies (GWAS) database of individuals of European ancestry which involve scanning complete sets of DNA, or genomes. GWAS summary data for DN included 4,111 DN cases and 308,539 controls. Instrumental variables were single nucleotide polymorphisms strongly linked to sleep-related characteristics. The main analysis used the random-effects inverse variance weighted (IVW) approach, with validation through sensitivity testing. Results: MR analysis revealed that a higher genetic predisposition for sleep efficiency reduced the chance of developing DN (odds ratio [OR]: 0.384; 95% confidence interval [CI] 0.205–0.717; p=0.003). Genetic susceptibility to DN was associated with a higher likelihood of experiencing more sleep episodes (OR: 1.015; 95% CI 1.003–1.028; p=0.016). Sensitivity analysis confirmed the robustness of these correlations. No significant connections were found between other genetically predicted sleep characteristics and the likelihood of developing DN. Conclusion Our research indicates that a genetic predisposition for better sleep efficiency is linked to a lower risk of developing DN. There is also evidence suggesting that genetic predisposition to DN may directly impact sleep episodes. Further research is needed to explore the molecular mechanisms underlying these findings.