Alopecia areata （AA） is a common hair loss disorder， and the core pathogenesis is the internal gene-ration of turbid toxin caused by qi movement disorder in the liver， spleen， and kidney. Turbid toxin serves as both a pivotal etiological trigger and a pathological driver of disease exacerbation. Clinically， AA can be classified into four principal patterns， including liver constraint with spleen deficiency， internal accumulation of damp-heat， liver-kidney depletion， and qi-blood depletion. Therapeutic strategies prioritize clearing and resolving turbid toxin while regulating the qi movement of the liver， spleen， and kidney. Accordingly， different formulas were applied. Self-formulated Shugan Jianpi Huazhuo Formula （疏肝健脾化浊方） is suggested to drain dampness， resolve turbidity， and unblock qi movement. Self-formulated Sanjiao Fenxiao Jiedu Formula （三焦分消解毒方） can be used to clear heat， drain dampness and resolve toxin. Self-formulated Zishen Yanggan Toudu Decoction （滋肾养肝透毒汤） can clear and vent latent toxins， while Self-formulated Guiqi Shengfa Didu Formula （归芪生发涤毒方） is employed to tonify qi and blood， purge toxins， and regenerate vitality. By differentiating and treating AA based on the functional patterns of the liver， spleen， and kidney， this approach expands the application scope of the turbid toxin theory and provides valuable insights for treatment of AA.

Objective:To establish a predictive model for the risk of cognitive impairment in patients with hypertension.Methods:Data were obtained from the China Health and Retirement Longitudinal Study(CHARLS),and 17 indicators were analyzed,including demographic features,behavioral factors,and health status.The study cohort was randomly divided into a training set(n=2 918)and an internal validation set(n=1 249)at a ratio of 7∶3,and 1 457 patients with hypertension who were treated in Chongqing Traditional Chinese Medicine Hospital from January to December 2024 were included as an external validation set.The least absolute shrinkage and selection operator regression analysis was used to identify predictive variables,and 10-fold cross-validation was used to determine the optimal model.A logistic regression model was used to investigate the risk factors for cognitive impairment in patients with hypertension,and then a nomogram prediction model was established.The calibration curve was used to assess the accuracy of the model,and the area under the ROC curve(AUC)and the decision curve analysis were used to assess the predictive performance of the model.Results:A total of 4167 hypertensive patients aged≥45 years were included from the CHARLS database,among whom 668 had cognitive impairment.The multivariate logistic regression analysis showed that age(odds ratio[OR]=1.408,95%CI=1.040-1.056),sex(OR=0.570,95%CI=0.492-0.660),body mass index(OR=0.931,95%CI=0.914-0.948),educational level(OR=0.235,95%CI=0.200-0.277),place of residence(OR=1.674,95%CI=1.447-1.936),physi-cal activity(OR=0.459,95%CI=0.373-0.562),depression(OR=1.386,95%CI=1.198-1.604),and total cholesterol level(OR=0.997,95%CI=0.995-0.999)were predictive variables.The ROC curve analysis showed that the nomogram model had good performance,with an AUC of 0.814(95%CI=0.802-0.826)in the training set,0.817(95%CI=0.788-0.846)in the internal validation set,and 0.725(95%CI=0.699-0.752)in the external validation set.Conclusion:The nomogram model developed in this study can effectively predict the risk of cognitive impairment in Chinese patients with hyperten-sion and has a good application value.

Objective To observe the clinical efficacy of Lingnan fire needle therapy combined with conventional western medicine in the treatment of mild to moderate uterine prolapse.Methods A total of 96 patients diagnosed with mild to moderate uterine prolapse in the outpatient and inpatient departments of Dongguan Humen Traditional Chinese Medicine Hospital from January 2023 to January 2024 were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 48 cases in each group.Both groups received health education,and the control group received conventional western medicine treatment.The observation group received Lingnan fire needle therapy in addition to the control group's treatment.The treatment course consisted of 12 sessions,with one course completed.After treatment,the clinical efficacy of the two groups was evaluated.Changes in TCM syndrome scores,pelvic floor muscle strength,and ultrasound imaging characteristics were observed before and after treatment.The serum levels of osteopontin(OPN),connective tissue growth factor(CTGF),and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1(MMP-9/TIMP-1)were compared before and after treatment.The safety and incidence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate in the observation group was 97.92%(47/48),while it was 77.08%(37/48)in the control group.The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the TCM syndrome scores and total scores in both groups significantly improved(P＜0.05),and the observation group showed significantly better improvement in these scores compared to the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the pelvic floor muscle strength and ultrasound imaging characteristics in both groups significantly improved(P＜0.05),and the observation group showed significantly better improvement in these aspects compared to the control group,with a statistically significant difference(P＜0.05).(4)After treatment,the serum levels of OPN,CTGF,and MMP-9/TIMP-1 in both groups significantly improved(P＜0.05),and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P＜0.05).(5)There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Lingnan fire needle therapy combined with conventional western medicine can significantly improve symptoms and pelvic floor muscle strength in patients with mild to moderate uterine prolapse,with notable efficacy and high safety.The mechanism may be related to the regulation of OPN,CTGF,and MMP-9/TIMP-1 levels.

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

Autophagy is mediated by multiple molecules and pathways. In cardiovascular diseases， autophagy can play a role through key signaling pathways such as phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， adenosine monophosphate-activated protein kinase （AMPK）/mTOR， mitogen-activated protein kinases （MAPK）， p53， Wnt/β-catenin， etc. Traditional Chinese medicine （TCM） monomers for promoting blood circulation and removing blood stasis such as hydroxysafflor yellow A， ginsenoside Rb1， salidroside， ligustrin， curcumin， etc.， and TCM prescription and preparations such as Huangqi baoxin decoction， Taohong siwu decoction， Tongxinluo capsule， Shuangshen ningxin capsule， Suxiao jiuxin pills， etc. can regulate autophagy through the above-mentioned key signaling pathways， thereby alleviating the progression of cardiovascular diseases.

Microneedles can penetrate the skin barrier to deliver drugs without touching the nociceptive nerves， to effectively increase the efficiency of transdermal drug delivery and improve patient compliance. Exosomes have multiple physiological functions and good biocompatibility， and are natural nanoscale drug carriers. This paper reviews the pathways and advantages of exosomes combined with microneedles for the treatment of diseases， and describes the current research status of exosome microneedle drug delivery system in various diseases. Exosome microneedles can be divided into two categories： （1） exosomes as therapeutic agents， their unique physiological origin can effectively avoid the toxicity and immunogenicity of conventional drugs and other problems； combined with microneedles directly in the specific medication site can greatly improve the metabolic consumption of oral drug delivery and patient compliance of injection drug delivery. （2） Exosomes as drug carriers， their natural vesicle structure and endogenous characteristics can protect the metabolism of foreign drugs in the body and enhance the targeting； combined with microneedles can effectively solve the problem of transdermal delivery of drugs with high efficacy but poor stability. Exosome microneedle drug delivery system is still in the laboratory stage， but it has shown great development prospects in repairing spinal cord injury， promoting diabetic ulcer wound healing， germinating， intervening myocardial infraction， relieving chronic pain and other diseases.

Exosome is a kind of vesicle secreted by a variety of cells with lipid bilayer membrane structure， which has good biocompatibility， high targeting and high stability， and is a natural nanoscale drug carrier with great development potential in drug delivery system. In this paper， exosomes and their properties， exosome drug delivery pathways and methods， the design strategy of engineered exosome drug delivery systems for targeted disease therapy， and the application of exosome drug delivery systems in the treatment of a variety of diseases were reviewed. Exosome drug delivery pathways could be divided into two categories： exogenous and endogenous. Common exosome drug delivery methods included electroporation， co-incubation， and ultrasound. Engineered exosome drug delivery system can further improve drug loading and enhance drug targeting. The main way of engineering is to modify exosome surface through genetic engineering technology， physical modification， chemical modification， etc. Exosome drug delivery system provides a new idea for targeted therapy of arthritis， tumor， brain and other diseases.

Objective:To establish a HPLC method for determinating 9 components simultaneously in Swertia chirayita. Methods:By useing water Sunfire C18 column (4.6 mm× 250 mm,5 μm); Gradient elution was carried out with methanol-0.05% phosphoric acid solution as mobile phase. Setting the column temperature at 30 ℃, the flow rate at 1.0 ml/min, and the detection wavelength at 254 nm.Results:9 components showed good linear relationship within the injection quality range. The recovery rates of wertiamarin, Gentiopicroside, Angelica glycosides,Mangiferin, Isolysine, Gentianoside, Diol glycoside, 8-hydroxy-1,3,5 trimethoxyketone, and Daisy leaf gentinone were 95.38%, 92.41%, 95.14%, 91.87%, 92.24%, 92.51%, 95.08%, 91.72%, 95.74% ( n=6). Conclusion:The method is simple, efficient, sensitive, accurate, economical and practical, with repeatability and stability. It could provide reference for the quality control and comprehensive utilization of Swertia chirayita.

Objective:Evaluation of ultrasound-guided radiofrequency of hyperthermia combined with recombinant human adenovirus H101 for the treatment of hepatocellular carcinoma (HCC).Methods:In vitro cell therapy experiments, luciferase/red fluorescent protein/lentivirus mediated McA-RH7777 cells were conducted and divided into 4 groups. Each group was repeatedly treated for 6 times: (1) recombinant human adenovirus type 5 H101 [(multiplicity of infection, MOI)=0.2]+ RFH group, heated at 42℃ for 30 min; (2) recombinant human adenovirus type 5 H101 alone (MOI=0.2); (3) RFH alone, heated at 42℃ for 30 min; (4) control group: physiological saline group. Twenty-four nude rats weighing 180-220 g were selected to establish a nude rat model of orthotopic HCC. They were divided into 4 groups with 6 rats in each group: (1) H101+ RFH combined treatment group: RFH electrode needles were punctured to the center of the tumor in the liver of nude rats under ultrasound guidance, and H101 was directly injected through the electrode injection end. RFH was delivered to the tumor at a temperature of 42℃ for 30 min; (2) H101 treatment group: MOI=0.2; (3) RFH treatment group; (4) sham surgery group. Fluorescence microscopy imaging was used to evaluate the viability of cells in vitro experiments. For in vivo validation, ultrasound imaging was used to follow up the tumor size. Tumor gross specimens and pathological changes were also evaluated.Results:Twenty-four hours after treatment, the survival rate of cells in the H101+ RFH group was the lowest under fluorescence microscopy. The results of MTS quantitative analysis showed that the relative absorbance of mezzanine in the H101+ RFH group cells was lower than that in the H101 group alone [(25.00±2.27)% vs. (69.50±4.53)%], the RFH group alone [(25.00±2.27)% vs. (92.83±1.66)%], and the control group [(25.00±2.27)% vs. 100%], with statistical significance (all P<0.001). The number of apoptotic cells in the H101+ RFH group was higher than that in the H101 group alone [(54.5±3.1)% vs. (25.2±1.4)%], the RFH group alone [(54.5±3.1)% vs. (5.7±0.6)%], and the control group [(54.5±3.1)% vs. (3.9±0.5)%], all of which showed statistically significant differences (all P<0.001). The relative tumor volume of nude rats in the H101+ RFH combination treatment group was smaller than that in the H101 treatment group (0.776±0.127 vs. 1.312±0.188), RFH treatment group (0.776±0.127 vs. 1.893±0.571), and sham surgery group (0.776±0.127 vs. 1.977±0.590), all of which had statistical significance (all P<0.001). The number of apoptotic cells in nude rats in the H101+ RFH combination treatment group was higher than that in the H101 treatment group [(49.85±4.00%)% vs. (22.70±0.65)%], the RFH treatment group [(49.85±4.00% vs. (5.36±0.84)%], and the sham surgery group [(49.85±4.00)% vs. (5.96±0.78)%], all of which showed statistically significant differences (all P<0.001). Conclusion:Ultrasound guided RFH combined with recombinant human adenovirus H101 has a promoting effect on the treatment of HCC.

Objective    To investigate the surgical methods and efficacy of myocardial infarction combined with ventricular septal perforation. Methods    The clinical data of 60 patients with myocardial infarction combined with ventricular septal perforation admitted to the Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, from 2009 to 2018 were retrospectively analyzed. There were 39 males and 21 females, aged 63.3±8.3 years. Results    Among the 60 patients, 43 (71.7%) patients were perforated in the apex, 11 (18.3%) in the posterior septum and 6 (10.0%) in the anterior septum. There were 24 (40.0%) patients of single coronary artery disease. Fourteen (23.3%) patients received intra-aortic balloon counterpulsation before surgery. The waiting time from ventricular septal perforation to surgery was 48.3 (3-217) d. All patients underwent ventricular septal perforation repair, among whom 53 (88.3%) patients received ventricular aneurysm closure or resection, and 49 (81.7%) patients received coronary artery bypass graft with an average of 2 distal anastomoses during the same period. Perioperative complications in the hospital included 8 (13.3%) deaths, 8 (13.3%) heart failure, 5 (8.3%) ventricular fibrillation, 3 (5.0%) pericardial tamponade, and 11 (18.3%) secondary thoracotomy and 11 (18.3%) residual shunt. Except for 8 patients who died in the hospital, the other 52 cured and discharged patients were followed up. The median follow-up time was 4.9 years. The 2-year and 5-year survival rate of the patients was 95.8%, and the 8-year survival rate was 89.0%. Major adverse cardiovascular events incidence was 19.2%, including 3 (5.8%) deaths, 5 (9.6%) heart failure, 2 (3.8%) myocardial infarction, and 4 (7.7%) cerebrovascular events. Conclusion    For patients with ventricular septal perforation after myocardial infarction, surgery is an effective treatment method. Although the perioperative mortality rate is high, satisfactory long-term results can be achieved by carefully choosing the operation timing and methods.