Objective To optimize the process conditions and analyze the components of alkaloids from Zanthoxylum bungeanum Maxim（Z. bungeanum）using macroporous resin. Methods Combining single factor tests and orthogonal tests, the content of hydroxy-α-sanshool（HAS）and hydroxy-β-sanshool（HBS）were considered as indexes to determine the best process parameters. Ultra-performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E）was used to identify the structures of alkaloids. Results The optimal conditions were Mitsubishi HP-20 macroporous resin, the loading solution concentration was 0.2 g crude drug/ml, the ratio of crude drug to resin volume was 1 g∶2.5 ml, the diameter/height ratio of resin column was 1∶7, the dynamic adsorption flow rate was 4 times of bed volume（BV）per hour, and the adsorption time was 1 h. Impurities were removed by using 2 BV of 20% ethanol, 5 BV of 80% ethanol was used to elution, and the content of HAS and HBS was 4.71% and 1.02%, respectively. A total of 20 alkaloids were identified from Z. bungeanum. Conclusion This method was stable and feasible, obtaining high purity and various kinds of alkaloids, which could be used for the enrichment and purification of alkaloids from Z. bungeanum.

BACKGROUND:Acute exercise tends to cause skeletal muscle tissue damage and lipid metabolism disorders in vivo,but the mechanism by which acute exercise combined with electroacupuncture modulates metabolic and autophagic pathways in vivo is unclear. OBJECTIVE:To observe the changes in metabolic enzymes and autophagy levels in skeletal muscle of rats subjected to acute exercise by electroacupuncture at the acupoints of"Zusanli"and"Huantiao." METHODS:Fifty male Sprague-Dawley rats were randomly divided into three groups:quiet control group(n=10),model group(n=20),and reverse electroacupuncture group(n=20).The latter two groups were set up with two time points,i.e.immediate and 3 hours after exercise groups(n=10 per time point).The model group and the reverse electroacupuncture group underwent acute exercise training after adaptive treadmill training.The rats in the reverse electroacupuncture group underwent electroacupuncture treatment(parameters:electroacupuncture on both sides of the rats at the acupoints of"Zusanli"and"Huantiao,"continuous wave,frequency of 2 Hz,intensity of 2 mA,leaving the needle in the body for 30 minutes,once a day for 7 consecutive days)before treadmill training.Bilateral gastrocnemius muscle tissues were taken under anesthesia immediately after exercise and 3 hours after exercise,and hematoxylin-eosin staining was used to observe the histopathological changes of rat skeletal muscle.ELISA kit was used to detect the activities of hepatic lipase,fatty acid synthase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 in rat skeletal muscle tissues.Immunohistochemistry and western blot were used to detect the changes in the expression of autophagy genes. RESULTS AND CONCLUSION:After hematoxylin-eosin staining,the arrangement of gastrocnemius muscle fibers in the model group was disturbed,swollen and ruptured immediately after exercise and 3 hours after exercise.In the reverse electroacupuncture group,gastrocnemius muscle fibers were tightly arranged and the number of swollen and ruptured cells was greatly reduced immediately after exercise and 3 hours after exercise,and there was no significant difference when compared with the quiet control group.Compared with the quiet control group,the activities of hepatic lipase and fatty acid synthase were lower while the activities of lipoprotein lipase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 were higher in the model group and the reverse electroacupuncture group 3 hours after exercise(P＜0.05 or P＜0.01).Compared with the model group,the activities of lipoprotein lipase and carnitine palmitoyltransferase 1 were higher in the reverse electroacupuncture group immediately after exercise(P＜0.05),while the activity of lipoprotein lipase was higher and the activity of hormone-sensitive lipase was lower in the reverse electroacupuncture group 3 hours after exercise(P＜0.01).Immunohistochemical results showed that compared with the quiet control group,the expression of P62,autophagy-related gene 5 and autophagy-related gene 7 was higher in the model group immediately and 3 hours after exercise,as well as in the reverse electroacupuncture group immediately after exercise(P＜0.05 or P＜0.01);compared with the model group,the expression of P62 and autophagy-related gene 7 was lower in the reverse electroacupuncture group immediately and 3 hours after exercise(P＜0.05).Western blot results showed that the protein expression of P62 and autophagy-related gene 7 in the reverse electroacupuncture group was lower than that in the model group immediately after exercise(P＜0.05);the protein expression of Parkin in the model group was higher than that in the quiet control group immediately and 3 hours after exercise(P＜0.05);and the protein expression of Parkin in the reverse electroacupuncture group was lower than that in the model group immediately and 3 hours after exercise(P＜0.05).To conclude,acute exercise induces disorders,swelling and rupture of gastrocnemius muscle fibers in rats and electroacupuncture on both sides of the acupoints of"Zusanli"and"Huantiao"can improve the level of lipid metabolism and regulate autophagy cells in rat skeletal muscle,preventing the disorders of lipid metabolism and damage of gastrocnemius muscle tissues caused by acute exercise.The mechanism may be closely related to the regulation of autophagy-related factor P62,autophagy-related gene 5,autophagy-related gene 7,and Parkin protein expression to promote the occurrence of autophagy or regulate the autophagy pathway in rat skeletal muscle cells.

ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.

ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.

ObjectiveFunctional near-infrared spectroscopy (fNIRS), a novel non-invasive technique for monitoring cerebral activity, can be integrated with upper limb rehabilitation robots to facilitate the real-time assessment of neurological rehabilitation outcomes. The rehabilitation robot is designed with 3 training modes: passive, active, and resistance. Among these, the resistance mode has been demonstrated to yield superior rehabilitative outcomes for patients with a certain level of muscle strength. The control modes in the resistance mode can be categorized into dynamic and static control. However, the effects of different control modes in the resistance mode on the motor function of patients with upper limb hemiplegia in stroke remain unclear. Furthermore, the effects of force, an important parameter of different control modes, on the activation of brain regions have rarely been reported. This study investigates the effects of dynamic and static resistance modes under varying resistance levels on cerebral functional alterations during motor rehabilitation in post-stroke patients. MethodsA cohort of 20 stroke patients with upper limb dysfunction was enrolled in the study, completing preparatory adaptive training followed by 3 intensity-level tasks across 2 motor paradigms. The bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM) were examined in both the resting and motor training states. The lateralization index (LI), phase locking value (PLV), network metrics were employed to examine cortical activation patterns and topological properties of brain connectivity. ResultsThe data indicated that both dynamic and static modes resulted in significantly greater activation of the contralateral M1 area and the ipsilateral PM area when compared to the resting state. The static patterns demonstrated a more pronounced activation in the contralateral M1 in comparison to the dynamic patterns. The results of brain network analysis revealed significant differences between the dynamic and resting states in the contralateral PFC area and contralateral M1 area (F=4.709, P=0.038), as well as in the contralateral PM area and ipsilateral M1 area (F=4.218, P=0.049). Moreover, the findings indicated a positive correlation between the activation of the M1 region and the increase in force in the dynamic mode, which was reversed in the static mode. ConclusionBoth dynamic and static resistance training modes have been demonstrated to activate the corresponding brain functional regions. Dynamic resistance modes elicit greater oxygen changes and connectivity to the region of interest (ROI) than static resistance modes. Furthermore, the effects of increasing force differ between the two modes. In patients who have suffered a stroke, dynamic modes may have a more pronounced effect on the activation of exercise-related functional brain regions.

Objective: To examine the casual association between age at first sexual intercourse and gynecologic malignant tumors using Mendelian randomization (MR) approach. Methods: The single nucleotide polymorphisms (SNPs) associated with age at first sexual intercourse were obtained from a meta-analysis of genome-wide association study (GWAS), and the SNPs related to gynecologic malignant tumors (ovarian cancer, endometrial cancer, cervical cancer), and their subtypes were sourced from the IEU OpenGWAS database. Using age at first sexual intercourse as the exposure and gynecologic malignant tumors as the outcome, a MR analysis was performed with the inverse-variance weighted (IVW) method. Heterogeneity was assessed using Cochran's Q test, horizontal pleiotropy was evaluated using MR-Egger regression and MR-PRESSO test, and bias was examined using funnel plots. Results: The Mendelian randomization analysis demonstrated that younger age at first sexual intercourse was significantly associated with an increased risk of low-grade serous ovarian carcinoma (OR=0.553, 95%CI: 0.335-0.911), cervical cancer (OR=0.674, 95%CI: 0.466-0.974), endometrial cancer (OR=0.854, 95%CI: 0.730-0.999), and endometrioid carcinoma (OR=0.830, 95%CI: 0.690-0.998). No statistical association was found between the age at first sexual intercourse and ovarian cancer, high-grade serous ovarian cancer, mucinous ovarian cancer, endometrioid ovarian cancer, or non-endometrioid ovarian cancer (all P>0.05). Sensitivity analysis showed no evidence of undetected instrumental variable heterogeneity or horizontal pleiotropy (all P>0.05), and the funnel plot indicated no presence of bias. Conclusion Younger age at first sexual intercourse may be associated with an increased risk of certain gynecologic malignant tumors, highlighting the need to strengthen adolescent sex education.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective To investigate the effect of sakubatrotril and valsartan in the treatment of heart failure after percutaneous coronary intervention(PCI)for acute myocardial infarction(AMI).Methods AMI patients who received PCI were randomly divided into treatment group and control group.Both groups were given routine basic treatment such as anti-platelet aggregation,lipidregulation,β-blocker and diuretic tolasemide,while the control group was given enalapril maleate tablet(5 mg,bid).The treatment group was given sacubactril valsartan sodium tablets(5 mg,bid)in addition to basic treatment.The clinical efficacy,myocardial injury markers,cardiac function,ventricular remodeling indexes,vascular endothelial function and cardiovascular adverse events(MACEs)were compared between the two groups.Results The treatment group and the control group were enrolled in 40 patients.After 3 months of treatment,the total effective rate of the treatment group was 95.00％and that of the control group was 80.00％.The difference between the total effective rate of the treatment group and the control group was statistically significant(P＜0.05).After 3 months of treatment,the levels of creatine kinase isoenzyme(CK-MB)in treatment group and control group were(30.23±5.28)and(36.58±7.05)U·L-1,respectively;cardiac troponin Ⅰ(cTnⅠ)were(1.04±0.18)and(1.25±0.31)ng·mL-1,respectively;left ventricular ejection fraction(LVEF)were(40.29±6.32)％and(34.39±5.62)％,and endothelium-dependent diastolic function(FMD)were(15.72±2.83)％and(9.55±2.05)％,respectively;nitric oxide(NO)levels were(47.41±5.85)and(41.28±3.37)μmol·L-1;endothelin-1(ET-1)was(70.53±8.29)and(83.62±10.11)ng·L-1,respectively.Compared with the control group,the above indexes in treatment groups were statistically significant(all P＜0.05).The incidence of MACEs was 10.00％in treatment group and 25.00％in control group,with no statistical significance(P＞0.05).After 3 months of treatment,the incidence of adverse drug reactions in AMI patients in treatment group was 12.50％,and that in control group was 17.50％.There was no statistical significance in the incidence of adverse drug reactions in treatment group compared with control group(P＞0.05).Conclusion Sacubactril valsartan can effectively prevent ventricular remodeling and improve vascular endothelial function in patients with heart failure after PCI.

Objective To investigate the protective effect of silymarin extract(SME)and its complex preparation on ethanol liver injury.Methods An ethanol liver injury model was established by gavage of 12 mL·kg-1 50％ethanol.Male mice were divided into blank group(distilled water),model group(ethanol liver injury model),SME-L,-H groups(6,20 mg·mL-1 SME),SME+Ganoderma lucidum extract(GLE)-L,-H groups(10,30 mg·mL-1 SME+GLE,SME∶GLE=1∶1),Jian An Shi Silymarin Pueraria Mirifica and Tansy tablets(JAS)-L,-H groups(68,204 mg·mL-1 JAS),there were 12 mice in each group.The serum levels of glutamic-oxaloacetic transaminase(GOT)in mice were measured by fully automated biochemical analyzer assay;the serum levels of interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in mice were measured by enzyme-linked immunosorbent assay(ELASA);the hepatic tissue of oxidative stress indexes[catalase(CAT)and total superoxide dismutase(T-SOD)]were measured by ultraviolet spectrophotometer.Results The T-SOD activity in the blank group,model group,SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L and JAS-H groups were(192.54±49.00),(141.65±34.72),(205.83±32.77),(191.68±25.83),(192.31±28.79),(177.82±32.61),(218.58±74.80)and(210.24±31.65)U·mg·prot-1;CAT activity were(37.78±5.73),(28.92±8.44),(44.12±11.52),(41.41±9.15),(47.01±10.48),(41.63±8.95),(47.14±8.91)and(48.29±10.06)U·mg-1;GPT levels were(47.61±13.00),(97.84±26.00),(62.33±18.92),(51.84±17.91),(70.77±28.00),(58.00±21.27),(52.28±18.78)and(45.55±9.27)U·L-1;IL-6 levels were(21.03±1.52),(28.43±5.75),(21.90±3.24),(21.23±1.55),(22.26±2.58),(21.24±2.91),(22.17±4.14)and(21.14±3.02)pg·mL-1.Comparing the above indexes in the model group with the blank group,and comparing the above indexes in the SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L,JAS-H groups with the model group,the differences were statistically significant(all P＜0.01).The TNF-α levels in blank,model,SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L and JAS-H groups were were(28.07±7.72),(69.02±16.34),(40.29±8.94),(48.84±10.17),(41.91±14.96),(40.07±12.75),(50.72±11.44)and(45.05±11.34)pg·mL-1.Comparing the model group with the blank group,the SME,SME+GLE-L,-M and JAS,-M groups with the model group,the differences were statistically significant(all P＜0.01).Conclusion Silybum marianum extract and its compound preparation can increase the antioxidant level and reduce the inflammation of mouse liver,and have a certain improvement effect on liver injury caused by acute ethanol poisoning.

【Objective】 To explore the feasibility of using autologous platelet-rich plasma (PRP) in the treatment of deep second-degree burns complicated with wound infection. 【Methods】 A retrospective analysis was conducted on the treatment process of a patient with deep second-degree burns and bacterial infection on the wound using autologous PRP. Clinical treatment highlights and outpatient follow-up were combined to discuss the feasibility and clinical effects of using autologous PRP in the treatment of burn wounds complicated with infection. 【Results】 The patient had a deep second-degree burn with a coagulase-negative Staphylococcus infection on the left lower limb. After one week of conventional wound dressing and antibiotic treatment, the patient's body temperature returned to normal. However, wound healing was slow and yellow secretion persisted. Subsequently, the burn wound was treated combined with topical autologous PRP. The wound pain score gradually decreased from 8 to 1. After 2 weeks, the bacterial culture of the wound secretion was negative, and the wound healed completely after 18 days. The wound scar score decreased from 5 to 2 at 1, 3 and 6 months after PRP treatment, and no obvious scar formation was observed. In the course of PRP treatment, there were no adverse reactions such as increased wound inflammation, abnormal blood routine and liver and kidney function test results. 【Conclusion】 For deep second-degree burn patients with localized wound bacterial infections who either refuse surgery or are not suitable for surgery, autologous PRP is a safer alternative that can effectively promote tissue regeneration and wound healing. The patient in this case achieved a curative effect in a short period of time.