ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

Objective:To investigate the ameliorative effects of N-acetyl-D-mannosamine(ManNAc) on glucose and lipid metabolic disorders in obese mice.Methods:In vivo experiments were conducted using 21 four-week-old C57BL/6JGpt mice, randomly divided into three groups( n=7 per group): a normal control group, a high-fat diet(HFD) control grooup, and a ManNAc treatment group(400 mg·kg -1·d -1). The intervention lasted for 20 weeks. Body weight, food intake, and fasting blood glucose levels were monitored weekly. Glucose tolerance tests(GTT), insulin sensitivity tests(ITT), and respiratory metabolism monitoring were performed in the 17th, 18th, and 19th weeks, respectively. At the end of the experiment, whole-body fat distribution was assessed, and serum lipid profiles were measured. Liver and adipose tissue weights were recorded, and histological analyses including HE staining of liver, adipose and pancreatic tissues were performed. Liver transcriptome sequencing and quantitative real-time PCR(qPCR) were conducted to evaluate hepatic gene expression. In vitro, a hepatic steatosis model was established by inducing HepG2 cell with 0.4 mmol/L oleic acid, followed by treatment with 500 μg/mL ManNAc. Lipid accumulation was assessed using BODIPY staining, and the expression of lipid metabolism-related genes was quantified by qPCR. Results:ManNAc administration attenuated HFD-induced weight gain, reduced total body fat volume, and decreased liver and adipose tissue weights as well as intracellular lipid accumulation. Pancreatic islet numbers increased, while fasting blood glucose levels, glucose tolerance, and insulin sensitivity significantly improved. Serum levels of triglycerides, total cholesterol, and low-density lipoprotein levels were decreased, accompanied by enhanced energy expenditure. Additionally, hepatic expression of Cd36, Fabp3, and Scd1 was downregulated. In vitro, ManNAc significantly reduced lipid accumulation in HepG2 cells and downregulated the expression of Cd36, Fabp3, and Scd1 genes.Conclusion:ManNAc may improve glucose and lipid metabolism by modulating the PPARs-mediated fatty acid metabolic pathway, reducing lipogenesis, promoting fatty acid oxidation and energy expenditure, and enhancing insulin sensitivity, ultimately ameliorating disorders in obese mice.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To analyze the effect of different doses of estrogen on endometrial blood flow after tran-scervical resection of adhesion(TCRA)surgery in patients with intrauterine adhesion(IUA).Methods:A total of 70 moderate and severe IUA patients who underwent TCRA in the General Hospital of Ningxia Medical University from 2021 to 2023 were divided into group A(4 mg/day)and group B(6 mg/day)according to the dosage of es-trogen after operation.Reexamination of hysteroscopy was performed 2 months later,menstrual volume was fol-lowed up,uterine parameters in secretory phase were detected by B-ultrasound,and factors related to prolifera-tion,fibrosis and blood flow were detected by immunofluorescence after 3 months.Results:① In the severe IUA group,there was no difference in the rate of intrauterine re adhesion between group A2 and group B2.The satis-faction rate of endometrial epithelialization and endometrial glandular duct density in group B2 was higher than that in group A2,and the difference was statistically significant(P＜0.05).There was no significant difference in the three indicators within the moderate IUA group(P＞0.05).②Three months after operation,in the severe IUA group,there were statistically significant differences(P＜0.05)in menstrual flow,endometrial thickness ET,endo-metrial volume EV,endometrial blood flow values(VI,FI,VFI),and uterine artery blood flow values(PI,RI)be-tween the two groups;The above indicators showed no statistically significant differences within the moderate IUA group(P＞0.05).③Detection of endometrial markers:the expression of proliferation marker(Ki-67)and angio-genesis marker(CD31,CD34,CD146,b-FGF,VEGF)in group B2 was higher than that in group A2,while the ex-pression of fibrosis marker(α-SMA,TGF-β1)was lower,with statistical significance(P＜0.05).There was no sig-nificant difference in the expression of above indexes between group A,and group B,in moderate IUA group(P＞0.05).Conclusions:Short-term application of relatively high dose estrogen(6 mg/day)after TCRA can pro-mote better endometrial repair by improving endometrial blood flow in patients with severe IUA,while in patients with moderate IUA there is no significant difference in the effect on endometrial repair.

Objective:To understand the workflow and key tasks of the transformation of scientific and technological achievements in public hospitals,and propose optimization strategies from the perspective of managers.Methods:Based on the research method of Grounded Theory,semi-structured interviews were conducted among 23 managers of scientific and technological achievements transformation in public hospitals,and relevant concepts and categories were summarized by three stages coding with NVivo 12.Results:Through the three stages of coding,64 initial concepts,19 categories and 4 main categories were sorted out,and a framework diagram of the process of transforming scientific and technological achievements in public hospitals covering four stages was constructed.Conclusion:The scientific and technological achievements of public hospitals can be divided into four phases:project initiation and demand docking,research and development process and achievements incubation,achievements transformation and market docking,product promotion and industrial development,which can be used to achieve high-quality development of scientific and technological achievements through standardized management of the whole process,excavation of high-quality results,enhancement of humanistic construction,accumulation of scientific research experience,and standardization of qualification of technological managers.

Objective:To explore the application value of problem-based learning (PBL) combined with mini-clinical evaluation exercise (Mini-CEX) in the development of post competency for interns in the Department of Neurology.Methods:A total of 56 interns rotating at the Department of Neurology of The First Affiliated Hospital of Chongqing Medical University from June 2023 to January 2024 were enrolled as the study subjects. They were randomly divided into a control group and an experiment group using the random number table method, with 28 interns in each group. The control group received traditional methods including small lectures and teaching rounds, while the experimental group received the PBL teaching method combined with Mini-CEX. The teaching effectiveness was evaluated through theoretical assessments, practical skill evaluations, teacher and student satisfaction surveys, and Mini-CEX scale assessments conducted at the beginning, middle, and end of the rotation for the experimental group. The data were analyzed using SPSS 23.0 software. For continuous data, the independent-samples t test or Mann-Whitney U test was used for comparison between groups. The chi-square test was used for categorical data and the Kruskal-Wallis H test for repeated-measurement data. Results:The theoretical scores [(45.36±2.67) vs. (42.00±4.29), P<0.01] and practical skill scores [(45.11±2.53) vs. (42.39±4.53), P<0.01] were significantly higher in the experimental group compared to the control group. The Mini-CEX score of the experimental group at the end of the rotation was notably higher than that at the beginning of rotation ( P<0.05), and their abilities improved continuously. The satisfaction rates of teachers and students in the experimental group were 71.43% (20/28) and 67.86% (19/28), respectively, which were significantly higher than those in the control group [39.29% (11/28) and 35.71% (10/28), P<0.05]. Conclusions:The teaching model integrating PBL and Mini-CEX can effectively enhance the post competency of interns in the Department of Neurology, thus offering a new perspective for clinical undergraduate teaching.

Objective:To explore the application value of the integrated situational simulation teaching model based on the "Internet+"in obstetrics and gynecology clinical clerkship.Methods:Fifty-eight undergraduate students enrolled in 2019 who participated in the clinical clerkship at the Chengdu Fifth People's Hospital from June to September 2023 were selected and divided into a research group ( n=29) and a control group ( n=29) using the random number table method. The research group received the integrated situational simulation teaching model based on "Internet+", while the control group received traditional teaching methods. After clinical clerkship, theoretical tests, teacher evaluation, and questionnaire surveys were conducted to evaluate and compare the teaching effectiveness of the two groups of students. SPSS 23.0 was used for t test and chi-square test. Results:After receiving the integrated situational simulation teaching model based on "Internet+" for clinical clerkship, the research group achieved significantly higher theoretical test scores than the control group [(83.62±4.95) vs. (72.93±4.70), t=8.43, P<0.001]. The scores of all items in the mini-clinical evaluation exercise of the research group were higher than those of the control group ( P<0.01). According to the teaching feedback questionnaire, all students were satisfied with this new teaching model and reported that this model increased their interest in learning. Moreover, 86.21% (25/29) and 96.55% (28/29) of the students believed that the new model not only improved learning efficiency but also facilitated the integration of theory and practice. Conclusions:The integrated situational simulation teaching model based on "Internet+" is feasible in obstetrics and gynecology clinical clerkship and contributes to enhancing the quality of clinical clerkship teaching. This model is worthy of further research and promotion.

Objective To establish the reference interval of urine Alzheimer-associated neuronal thread protein(AD7c-NTP)for healthy adults in Mianyang area using the indirect method.Methods The detection results of urine AD7c-NTP from 5 093 healthy in-dividuals were collected from the information management database of Medical Laboratory Department of Sichuan Science City Hospital from March 2017 to March 2022.Skewness-kurtosis and Kolmogorov-Smirnov tests were used to determine whether the data followed a normal distribution.After removing outliers using the Box Plots method,the enrolled subjects were grouped by gender and age.The Mann-Whitney U or Kruska-Wallis H tests were used to analyze the between-group differences of urine AD7c-NTP in healthy individu-als with different genders and ages.The adjacent age groups without statistically significant difference(P＞0.05)were combined,and the indirect method(non-parametric test method)was used to calculate the reference intervals for different gender and age groups.Results Skewness-kurtosis and Kolmogorov-Smirnov tests showed that the data followed a non-normal distribution.After removing 293 outliers using the Box Plots method,a total of 4 800 subjects,including 3 199 males and 1 601 females,were enrolled.The enrolled subjects were grouped by gender and age,and the non-parametric test method were used to establish the reference intervals of urine AD7c-NTP in healthy populations with different genders.The Mann-Whitney U test confirmed that urine AD7c-NTP levels existed gen-der differences(Z=14.09,P＜0.01),and the reference intervals for males and females were≤1.10 ng/mL and≤1.40 ng/mL,re-spectively.There were also statistical differences in urine AD7c-NTP levels among different age groups of the same gender.After combi-ning adjacent age groups without statistically significant difference(P＞0.05),the reference intervals of urine AD7c-NTP in healthy populations with different genders and ages were established by the non-parametric test method,which were≤1.00 ng/mL for male 20-39 years old group,≤1.10 ng/mL for male 40-79 years old group,≤1.60 ng/mL for male≥80 years old group,≤1.30 ng/mL for female 20-69 years old group,and≤1.60 ng/mL for female≥70 years old group,respectively.The established reference intervals of urine AD7c-NTP were further verified by healthy individuals,and the results met the standards.Conclusion The reference intervals of urine AD7c-NTP in healthy populations with different genders and ages in Mianyang area are established successfully using the indi-rect method,which may help to predict the risk of Alzheimer's disease in clinical practice and provide support for the diagnosis and treatment of the disease.

BACKGROUND:The abnormal aggregation of proteins and the loss of neurons are typical pathological changes observed in neurodegenerative diseases.Changes in the levels of O-linked N-acetylglucosamine glycosylation are closely related to relevant pathological changes and are promising potential therapeutic targets.OBJECTIVE:To review the role of O-linked N-acetylglucosamine glycosylation in neurodegenerative diseases and the current advancements in its clinical applications,aiming to provide new insights for the treatment of neurodegenerative disorders.METHODS:The first author conducted a literature search in the CNKI,VIP,WanFang Database,ChiCTR,Web of Science,PubMed,Cochrane Library,Clinical Trials and Alzforum,using the search terms"O-GIcNAcylation,Neurodegenerative diseases,Alzheimer's disease,Parkinson's disease,Amyotrophic lateral sclerosis,Huntington's disease,OGA inhibitors,Clinical trial"in Chinese and English.A total of 66 relevant articles were included for review.RESULTS AND CONCLUSION:O-linked N-acetylglucosamine glycosylation is involved in the development and functional regulation of neurons,and its levels gradually decrease as neuronal development matures.In neurodegenerative diseases,the pathological proteins involved are regulated by O-linked N-acetylglucosamine glycosylation.Most evidence suggests that using O-GIcNAcase inhibitors to enhance O-linked N-acetylglucosamine glycosylation levels can significantly alleviate related pathological changes,making it a potential therapeutic strategy for neurodegenerative diseases.Some O-GIcNAcase inhibitors have completed Phase I clinical trials,demonstrating good safety and tolerability.