Evaluate the interventional effect of Lycium barbarum leaves extract on cataract rats and its effects on plasma and liver tissue metabolites. The ultimate goal is to explore the scientific connotation of Lycium barbarum leaves extract on vision improvement. All experiments were approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (202306A067). D-Galactose (D-gal) induced cataract model in rats was established. The lens opacity, lens and liver tissue pathology, level of oxidative stress and polyol metabolism regulation in the lens, level of oxidative stress in serum and liver tissue, and the content of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and liver tissue were analysed to evaluate the effect of Lycium barbarum leaves extract on cataract. The metabolite profiles of plasma and liver tissue of rats were analyzed by UPLC-QTOF-MS/MS. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to compare and analyze the metabolic data in control group and cataract group, and screen potential biomarkers. The related metabolic pathways were further constructed by KEGG database analysis. The results showed that lens and liver pathology of cataract rats were improved after being intervened by the leaves extract of Lycium barbarum. The contents of AR and Ca²⁺ were significantly decreased in lens, and the contents of SDH and GSH and the ability of CAT were significantly increased; the content of GSH and the ability of SOD were significantly improved in serum and liver tissue, the content of MDA, the abilities of ALT and AST and the level of inflammatory factors were significantly reduced. The metabolomics results showed that there were 15 different metabolites in plasma and liver tissue of cataract rats, and 9 different biomarkers including retinyl ester, stearic acid, and palmitic acid, were returned by Lycium barbarum leaves extract. As revealed by pathway enrichment in plasma and liver tissue, it was found that the retinol metabolic pathway was mainly regulated by Lycium barbarum leaves extract. In summary, Lycium barbarum leaves can effectively alleviate the pathological changes of cataract, inhibit inflammation and improve antioxidant capacity, which may relate to the retinol metabolic pathway. It provides scientific basis and support for revealing the scientific connotation of the effect of Lycium barbarum leaves on vision improvement.

The purpose of this study was to investigate the intervention effect and mechanism of Lycium barbarum leaves on letrozole-induced polycystic ovary syndrome (PCOS) mice. The PCOS model was prepared by letrozole combined with high-fat diet. After successful modeling, 40 mice were randomly divided into PCOS group, positive drug metformin group, low-dose Lycium barbarum leaves group, and high-dose Lycium barbarum leaves group. The corresponding drugs were given by gavage for 29 days. At the end of the experiment, the eyeballs were removed for blood collection and ovarian tissue was collected. The ovarian mass, fasting blood glucose (FBG), fasting insulin (FINS), testosterone (T), anti-Mullerian hormone (AMH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E₂) levels were measured in each group. The morphology of ovarian tissue was observed by hematoxylin-eosin staining, and the oocytes, cystic follicles and corpus luteum were counted. Cecal contents of mice were collected for analysis of intestinal flora composition and differential flora. The animal experiment process was approved by the Animal Ethics Committee of Nanjing University of Traditional Chinese Medicine. The results showed that the estrous cycle of PCOS mice was disordered. Compared with the PCOS group, the Lycium barbarum leaves group can significantly reduce the ovarian damage of mice, reduce the number of cystic dilated follicles, and normalize the estrous cycle. After the intervention of Lycium barbarum leaves, the levels of FBG, FINS, T, AMH, LH, FSH and LH/FSH were significantly decreased (P < 0.05), while the level of E₂ was significantly increased (P < 0.001). In addition, Lycium barbarum leaves can regulate the disorder of intestinal flora diversity in PCOS mice, increase the abundance of Bacteroidetes, and reduce the abundance of Firmicutes, Ileibacterium, Romboutsia and Faecalibaculum. In summary, Lycium barbarum leaves can play a therapeutic role in PCOS mice by improving insulin resistance, regulating reproductive hormone disorders and gut microbiota imbalance. It provides scientific basis and useful reference for the rational utilization and development of Lycium barbarum leaves.

ObjectiveTo observe the effects of electroacupuncture at Zhongwan （CV12） on gastric nociceptive response induced by gastric acid stimulation and explore the underlying mechanisms associated with nuclei of the medullary viscerosensory and visceral motor neurons. MethodsTwenty SD rats were given intragastric administration of 0.5 mol/L diluted hydrochloric acid （0.5 ml/100 g） to induce gastric nociceptive response induction. Eight rats were randomly selected to record the gastric slow wave （GSW） area under the curve， and extracellular discharge frequency of neurons in the nucleus of the solitary tract （NTS） and dorsal motor nucleus of the vagus nerve （DMV） before intragastric administration and at 1， 5， 10， 15， 20， 25， 30， 35， 40， 45， 50， 55， and 60 minutes after intragastric administration. The remaining 12 rats received electroacupuncture intervention at Zhongwan within 5 to 25 minutes after intragastric administration of diluted hydrochloric acid， with a duration of one minute. The GSW area under the curve and extracellular discharge frequency of NTS and DMV neurons were compared between the 1-minute intervals before and after electroacupuncture intervention. ResultsCompared to the baseline before intragastric administration， the area under the curve of GSW significantly increased at 1， 5， 10， 15， 20， and 25 minutes after intragastric administration， and the extracellular discharge frequency of excitatory neurons in the NTS （accounting for 90%， 57/63） significantly increased at 1， 5， 10， 15， 20， 25， 30， 35， and 40 minutes， both reaching peak values at 1 minute after intragastric administration （P＜0.01 or P＜0.05）. The extracellular discharge frequency of inhibitory neurons in the DMV （accounting for 91%， 20/22） showed a non-significant increase at 1 minute after intragastric administration （P＞0.05）， but significantly decreased at other timepoints （P＜0.05）. Compared to the baseline before electroacupuncture intervention， the GSW area under the curve and the extracellular discharge frequency of excitatory neurons in the NTS significantly decreased （P＜0.05）， while the extracellular discharge frequency of inhibitory neurons in the DMV showed no significant difference （P＞0.05）. ConclusionElectroacupuncture at Zhongwan can improve gastric nociceptive response induced by gastric acid stimulation， possibly by reducing the transmission of visceral sensation and decreasing the excitability of NTS neurons in the medulla.

Objective To explore the clinical value of vaginoscopy in the diagnosis and treatment of uterine cavity diseases in virgins.Methods We retrospectively reviewed the data of 450 patients who underwent vaginoscopy and traditional hysteroscopy in Obstetrics and Gynecology Hospital,Fudan University from Jan 2020 to Dec 2023,including vaginoscopy group(n=232)and traditional hysteroscopy group(n=218).The average ages of the two groups were 24.9±4.7 years and 25.5±5.4 years,and there was no significant difference between the two groups(P>0.05).The operation time,estimated blood loss,fluid deficit,false passage,surgical failure,incidence of complications and postoperative pain score were compared between vaginoscopy group and traditional hysteroscopy group.Results Compared with the traditional hysteroscopy group,the average operation time in the vaginoscopy group was shorter,the fluid deficit was less,and the VAS pain score was lower,but the rate of surgical failure was higher(7.8%vs.0),all the differences were statistically significant(P<0.05).In terms of complications,the incidence of false passage in the vaginoscopy group was less(0 vs.3.2%)and the rate of hymen injury was lower(0 vs.85.3%),the differences were statistically significant(P<0.05).There was no significant difference in the estimated blood loss between the two groups,and the incidence of postoperative infection was similar in both groups.There were no complications such as uterine perforation and air embolism in both groups.Conclusion Vaginoscopy is safe and effective,more minimally invasive than traditional hysteroscopy,does not damage the hymen,and is suitable for virgins.This technology is worthy of clinical application.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.

Objective To investigate the effects of Chaihuang Yishen Granules on renal fibrosis in unilateral ureteral obstruction(UUO)mice and its underlying mechanisms.Methods Twenty-four 8-week-old male C57BL/6 mice were randomly divided into control group,model group,and low and high dose groups of Chaihuang Yishen Granules(6 in each group).In control group,only right kidney ureter was exposed and dissected.In model group,the UUO animal model was established by UUO.In low and high dose groups,mice were administered intragastrically at doses of 3.8 and 7.6 g/kg of Chaihuang Yishen Granules respectively,following the model group's method to establish the UUO model.After 7 days,the mice were euthanized and renal samples were collected.HE and Masson staining were used to observe pathological changes and fibrosis degree of the kidneys in each group,Sirius red staining was used to observe collagen deposition.The expression levels of α-smooth muscle actin(α-SMA),fibronectin(FN),type Ⅰ collagen(Col-Ⅰ),glycogen synthase kinase 3β(GSK-3β),and β-catenin related proteins were detected using Western blotting.Changes in A33 and GSK-3β,β-catenin mRNA levels were measured by RT-PCR.Additionally,a normal transformed C3H mouse kidney-1(TCMK1)was used as control(normal group);an in vitro fibrosis model was established using TCMK1 stimulated with Transforming Growth Factor-β(TGF-β);and an in vitro drug model was established using TCMK1 treated with serum containing Chaihuang Yishen Granules.A33 was overexpressed in TCMK1 cells using a transfection with an A33 overexpression plasmid,and changes in fibrosis-related indicators and the expression of A33 and GSK-3β,β-catenin mRNA were observed.Results RT-PCR results showed that,compared with control group,A33 level was significantly increased in model group,while it was significantly reduced in both low and high dose groups of Chaihuang Yishen Granules(P＜0.05).Western blotting showed that the expression levels of fibrosis-related factors such as α-SMA,FN,Col-Ⅰ in model group were significantly higher than those in control group(P＜0.05);while compared with model group,the expression levels of α-SMA,FN,Col-Ⅰ in low and high dose groups of Chaihuang Yishen Granules were significantly lower(P＜0.05).HE,Masson,immunohistochemical staining results showed that model group had severe kidney structural damage,significant increase in collagen deposition,and significantly higher expression levels of GSK-3β and β-catenin proteins compared with those in control group(P＜0.01).In contrast,low and high dose groups of Chaihuang Yishen Granules had good kidney structure,significant improvement in kidney damage and fibrosis,and significantly lower expression levels of GSK-3β and β-catenin proteins compared with those in model group(P＜0.05).In vitro experiment results confirmed that,compared with normal group,A33 overexpression promoted the upregulation of fibrosis-related factors in TCMK1 cells,significantly increase the expression of downstream target genes GSK-3β and β-catenin mRNA in the Wnt/β-catenin signaling pathway(P＜0.05),and A33 overexpression reversed the cellular fibrosis changes downregulated by the serum containing Chaihuang Yishen Granules(P＜0.01).Conclusion Chaihuang Yishen Granules significantly improve renal fibrosis in UUO mice by downregulating the A33/Wnt/β-catenin signaling pathway,suggesting that A33 may be a potential therapeutic target for renal fibrosis.

Objective:To investigate the effect of safflower yellow pigment injection combined with alprostadil on patients after coronary artery bypass grafting(CABG).Methods:A total of 92 patients with coronary heart disease who received CABG in Department of Cardiovascular Surgery,Handan Central Hospital between September 2018 and September 2020 were selected.According to order of admission,they were divided into control group(n=46,from September 2018 to Sep-tember 2019,routine therapy+alprostadil after CABG)and study group(n=46,from October 2019 to September 2020,safflower yellow pigment injection based on control group),both groups were treated for 28d.On 3d after drug withdraw-al,therapeutic effect,cardiac function indexes,four myocardial enzyme spectrum and perioperative indexes were compared between two groups.Results:On 3d after drug withdrawal,compared with control group,patients in study group had sig-nificant higher total effective rate(73.9％vs.91.3％),left ventricular ejection fraction(LVEF)[(55.77±4.48)％vs.(62.18±4.21)％](P=0.028,＜0.001),and significant lower left atrial diameter(LAD)[(36.83±3.45)mm vs.(32.09±3.23)mm],left ventricular end-diastolic diameter(LVEDd)[(49.04±4.65)mm vs.(43.83±5.24)mm],levels of creatine kinase(CK)[(125.13±14.21)U/L vs.(62.56±8.42)U/L],lactate dehydrogenase(LDH)[(203.58±31.63)U/L vs.(156.07±22.26)U/L],aspartate aminotransferase(AST)[(44.25±12.98)U/L vs.(35.41±12.37)U/L]and creatine kinase isoenzyme MB(CK-MB)[(28.11±9.84)U/L vs.(17.59±7.41)U/L](P＜0.001 all).Conclusion:The combination of safflower yellow pigment injection and alprostadil can improve the thera-peutic effect and heart function,and reduce myocardial injury in patients after CABG.

Objective To investigate the changes of serum metabolites in patients with occupational chronic lead poisoning using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 14 patients with occupational chronic lead poisoning were selected as the poisoning group, and 14 healthy people without occupational hazard exposure history were selected as the control group using the judgment sampling method. Serum of the individuals from the two groups was collected. Non-targeted metabolomics technology based on ultra high performance liquid chromatography-tandem mass spectrometry was used to detect serum metabolite levels in the two groups. Differential metabolites (DMs) were screened by the principal component analysis, partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis, and related metabolic pathways were explored. Results The blood lead level in the poisoning group was higher than that in the control group (median: 359.59 vs 5.04 μg/L, P<0.01). There were significant differences in serum metabolites between the poisoning group and control group. After the combination of results from the positive and negative ion patterns, a total of 89 DMs were screened in serum of patients in the poisoning group, including 50 upregulated and 39 downregulated metabolites compared with the control group. The serum DMs of poisoning group were mainly enriched in arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism in malignant tumor, glycerophospholipid metabolism and ether lipid metabolism compared with the control group (all P<0.05). Conclusion Abnormal changes of serum metabolic profile occurred in patients with occupational chronic lead poisoning. The metabolic pathways such as arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism, glycerophospholipid metabolism and ether lipid metabolism may be involved in the occurrence and development of lead poisoning.

Objective To construct the demand model of four types of medical resources including beds in hospi-tal,beds in intensive care unit(ICU),ventilators and medical human resources during the major infectious disease epidemic events,simulate and analyze the treatment of infectious diseases when different medical resources are in short supply.Methods Based on the susceptible-exposed-infectious-recovered(SEIR)model,considering the infec-tivity of infected persons,the susceptibility of the population and the immunity of convalescents,the characteristics of asymptomatic COVID-19 patients and different clinical types,the"COVID-19 infection-hospitalization model"was constructed.By collecting and setting the parameters of disease transmission,clinical course and medical re-source shortage scenarios,an analysis model of allocation and supply of urban medical resources during infectious di-sease epidemic events was initially formed based on Anylogic platform,the supply and demand of medical resources during infectious disease events in different scenarios were analyzed.Results In the non-intervention scenario,the peak time of bed demand was on the 107th day,and the peak value was 160.92 beds per thousand people;the peak time of ventilator demand was on the 122nd day,and the peak value was 5.61 units per thousand people;the peak time of ICU bed demand was on the 117th day,and the peak value was 12.78 beds per thousand people;the peak time of the demand for medical human resources was on the 109th day,and the peak value was 151.12 persons per thousand persons.The simulation results suggested that there were some differences in the impact of different medi-cal resources on the outcome of medical treatment.Conclusion This study constructs an analytical tool for the allo-cation and supply of urban medical resources under the epidemic events of infectious diseases,and the results of mul-tiple simulation experiments suggest that bed resources and medical human resources play more important roles in the outcome of medical treatment.