OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*

Objective To explore the bioactive components in Jiawei Xiaoyao Pills(JWXYP)and their mechanisms for alleviating depression-like behaviors.Methods The active compounds,key targets,and pathways of JWXYP were identified using TCMSP and TCMIP databases.Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress(CUMS)-induced depression groups.After modeling,the 5 model groups were treated with daily gavage of normal saline,1.8 mg/kg fluoxetine hydrochloride(positive control drug),or JWXYP at 1.44,2.88,and 4.32 g/kg.The depression-like behaviors of the rats were evaluated using behavioral tests,and pathological changes in the liver and hippocampus were examined with HE staining.The biochemical indicators in the serum and brain tissues were detected using ELISA.Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA,and gut microbiota changes were analyzed using 16S rDNA sequencing.Results Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system.In the rat models subjected to CUMS,treatment with JWXYP significantly improved body weight loss,sucrose preference and open field activities,reduced liver inflammation,alleviated structural changes in the hippocampal neurons,decreased serum levels of TNF-α,IL-1β,IL-6 and LBP,and increased 5-HT and VIP concentrations in the serum and brain tissue,and these effects were the most pronounced in the high-dose group.Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats,involving the pathways for bile acid biosynthesis and amino acid metabolism.16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats.Conclusion JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters,inhibiting inflammation and oxidation,and modulating gut microbiota.

BackgroundIn recent years， the incidence of non-suicidal self-injury （NSSI） behaviors among adolescents has been increasing annually. Self-esteem and alexithymia are strongly associated with NSSI behaviors， and alienation is closely linked to both self-esteem and alexithymia. However， there is limited research on the relationship between alienation and NSSI behaviors among adolescents in China. ObjectiveTo analyze the relationship between alienation and NSSI behaviors among adolescents， and to explore the factors influencing NSSI behaviors in this population， so as to provide insights for the prevention and treatment of NSSI behaviors in adolescents. MethodsAdolescents admitted to the Department of Psychiatry and Psychology at the 923^rd Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from September 1， 2021 to March 1， 2023， who met the diagnostic criteria for NSSI in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were selected as the study group （n=60）. Concurrently， middle school students from Nanning were recruited as the control group （n=60）. Participants were assessed using Adolescent Self Harm Scale （ASHS）， Rosenberg Self-Esteem Scale （RSES）， Toronto Alexithymia Scale （TAS） and Adolescent Students′ Alienation Scale （ASAS）. Pearson correlation analysis was employed to examine the relationships between scale scores in the study group， and Logistic regression analysis was used to identify the influencing factors of NSSI behaviors among adolescents. ResultsThe RSES score of the study group was significantly lower than that of the control group （t=-7.033， P<0.01）. The TAS and ASAS scores of the study group were significantly higher than those of the control group （t=5.591， 8.124， P<0.01）. The ASHS score was negatively correlated with RSES score （r=-0.410， P<0.01） and positively correlated with ASAS score （r=0.555， P<0.01）. The RSES scores of the study group were negatively correlated with TAS and ASAS scores （r=-0.317， -0.590， P<0.05 or 0.01）. Logistic regression analysis showed that being female （OR=0.714， 95% CI： 0.042~0.709） was a protective factor for NSSI behaviors among adolescents， while high alienation （OR=1.028， 95% CI： 1.013~1.043） and residing in rural areas （OR=6.692， 95% CI： 2.038~21.967） were risk factors for NSSI behaviors among adolescents. ConclusionAlienation was positively correlated with NSSI behaviors in adolescents. Female adolescents had a lower risk of NSSI behaviors， while those with higher levels of alienation or residing in rural areas were more prone to NSSI behaviors. ［Funded by Self-financed Scientific Research Project of the Health Commission of Guangxi Zhuang Autonomous Region （number， Z20210656）； Self-financed Scientific Research Project of the Health Commission of Guangxi Zhuang Autonomous Region （number， Z-A20231057）］

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To investigate the relationship between C-reactive protein(C-RP)/albumin ratio(CAR)and peripheral artery disease(PAD)in elderly patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 elderly patients with T2DM hospitalized in the Department of Endocrinology of our hospital were enrolled in this study from December 2022 to December 2023 and divided into PAD group with ankle brachial index(ABI)≤0.9(n=78)and T2DM group with ABI>0.9(n=72).The general data,biochemical indicators and CAR were compared between the two groups.Pearson correlation analysis was used to analyze the correlation between CAR and each biochemical index.Logistic regression analysis was used to explore the influencing factors for PAD in T2DM patients.Receiver operator characteristic(ROC)curve was used to evaluate the predictive value of CAR for PAD.Results Age,DM duration,body mass index,systolic blood pressure,diastolic blood pressure,C-RP,white blood cell count,fasting plasma glucose(FPG),total cholesterol(TC),triglycerides(TG),blood uric acid,low density lipoprotein cholesterol(LDL-C),and blood urea nitrogen(BUN),CAR was higher(P<0.05),while albumin,high density lipoprotein cholesterol(HDL-C),and ABI were lower in the PAD group than in the T2DM group(P<0.05).Pearson correlation analysis showed that CAR was positively correlated with FPG,TG,and BUN(P<0.05),and negatively correlated with HDL-C and ABI(P<0.05).Logistic regression analysis showed that CAR(OR 1.594,95%CI 1.236～2.062),TC(OR 1.070,95%CI 1.017～1.130),TG(OR 1.101,95%CI 1.021～1.184),HDL-C(OR 0.883,95%CI 0.813～0.965),LDL-C(OR 1.090,95%CI 1.012～1.186),FPG(OR 1.065,95%CI 1.020～1.104)were influencing factors for the occurrence of PAD in elderly patients with T2DM.ROC curve analysis showed that the area under the curve of CAR was 0.82 for predicting PAD in elderly patients with T2DM,the cut-off value was 0.35,the sensitivity was 78%,and the specificity was 85%.Conclusions CAR is correlated with ABI in elderly patients with T2DM.Given CAR is an influencing factor for the occurrence of PAD,it may serve as a potential predictor for PAD development in this population.

Objective To investigate the relationship between C-reactive protein(C-RP)/albumin ratio(CAR)and peripheral artery disease(PAD)in elderly patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 elderly patients with T2DM hospitalized in the Department of Endocrinology of our hospital were enrolled in this study from December 2022 to December 2023 and divided into PAD group with ankle brachial index(ABI)≤0.9(n=78)and T2DM group with ABI>0.9(n=72).The general data,biochemical indicators and CAR were compared between the two groups.Pearson correlation analysis was used to analyze the correlation between CAR and each biochemical index.Logistic regression analysis was used to explore the influencing factors for PAD in T2DM patients.Receiver operator characteristic(ROC)curve was used to evaluate the predictive value of CAR for PAD.Results Age,DM duration,body mass index,systolic blood pressure,diastolic blood pressure,C-RP,white blood cell count,fasting plasma glucose(FPG),total cholesterol(TC),triglycerides(TG),blood uric acid,low density lipoprotein cholesterol(LDL-C),and blood urea nitrogen(BUN),CAR was higher(P<0.05),while albumin,high density lipoprotein cholesterol(HDL-C),and ABI were lower in the PAD group than in the T2DM group(P<0.05).Pearson correlation analysis showed that CAR was positively correlated with FPG,TG,and BUN(P<0.05),and negatively correlated with HDL-C and ABI(P<0.05).Logistic regression analysis showed that CAR(OR 1.594,95%CI 1.236～2.062),TC(OR 1.070,95%CI 1.017～1.130),TG(OR 1.101,95%CI 1.021～1.184),HDL-C(OR 0.883,95%CI 0.813～0.965),LDL-C(OR 1.090,95%CI 1.012～1.186),FPG(OR 1.065,95%CI 1.020～1.104)were influencing factors for the occurrence of PAD in elderly patients with T2DM.ROC curve analysis showed that the area under the curve of CAR was 0.82 for predicting PAD in elderly patients with T2DM,the cut-off value was 0.35,the sensitivity was 78%,and the specificity was 85%.Conclusions CAR is correlated with ABI in elderly patients with T2DM.Given CAR is an influencing factor for the occurrence of PAD,it may serve as a potential predictor for PAD development in this population.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To identify easily confused Chinese herbal pieces by micro-macroscopical identification method,and study its application value in quality acceptance of Chinese herbal pieces in medical institutions.Methods Using the method of micro-macroscopical identification,with the help of related instruments,the microscopic characteristics of 10 groups of 31 kinds of Chinese herbal pieces,which were easy to be confused and could not be observed by naked eye and ordinary magnifying glass,were analyzed and summarized according to the classification of different medicinal parts,such as flowers,fruits,seeds,whole grass,roots and rhizomes,stems,and others,and pictures were taken to save them.Results The micro-characters of 10 groups of 31 easily confused Chinese herbal medicines,including Eriocauli flos,Eriocaulon sexangulare,Eriocaulon australe,Aurantii fructus,Citrus changshan-huyou,Chaenomelis fructus,Chaenomeles cathayensis,Perillae fructus,Perillae fructus(Physalis alba),Perillae fructus(Wild),Astragali complanati semen,Astragalus chinensis,Selaginellae herba,Selaginella pulvinata,Selaginella moellendorfii,Selaginella doederleinii,Selaginella uncinata,Lysimachiae herba,Lysimachia hemsleyana,Desmodium styracifolium,Dryopteris crassirhizoma,Woodwardia japonica,Brainea insignis,root of Valvate actinidia,Actinidia arguta,Tripterygium wilfordii,root of Romanet grape,Trogopterus dung,Bat dung,Hare dung and Silkworm sand were observed.The various traditional Chinese medicines possessed unique identification characteristics.Flower-based medicines could be studied for their color,tissue structure,and surface features such as texture and trichomes.Fruit-based medicines could be studied for their fruit peel structure,color,degree of development,and outer characteristics such as cuticle layer and wax.Seed-based medicines could be studied for their morphology,size,color,and texture.Whole plant-based medicines could be studied for leaf length-to-width ratio,widest point,surface characteristics,and splitting situation,as well as stem trichomes and stomata.Root-based medicines,rhizome-based medicines,and stem-based medicines could be studied for their bark,wood structure,and the morphology and arrangement of vascular bundles or ducts.Other kinds of medicines could be studied from their sources,and these unique micro-characteristic identification features could be easily discovered with the help of a microscope.Conclusion Compared with the traditional characteristic identification,micro-macroscopical identification is more capable of improving the accuracy of Chinese herbal pieces identification,which is economical,practical,simple and intuitive,and can be popularized as a commonly used identification method of herbal medicines in medical institutions,and it is a feasible solution to realize the rapid inspection of herbal medicines.

Objective To compare and analyze the operation time,detection rate and detection number of sentinel lymph node(SLN)who was using contrast-enhanced ultrasound(CEUS)body surface localization combined with nano carbon tracking and single dye method for sentinel lymph node biopsy(SLNB)in patients with cN0 invasive breast cancer(IBC).To explore the feasibility of CEUS body surface localization combined with nano carbon tracking for SLNB.Methods The clinicopathological data of 199 patients with cN0 IBC who were diagnosed and treated in Beijing Shunyi District Hospital from January 1st,2018 to April 30th,2023 were collected.We divided all patients into dye method group(100 cases)and combined method group(99 cases)according to SLN missing method.In dye method group,SLNB was performed with nano carbon tracer;In combined method group,SLN was marked and located by CEUS before surgery and SLNB was performed with nano carbon tracer during surgery.Results The detection rate of SLN in this study was 96.48％(192/199).In the dye method group,the detection rate of SLN was 95.00％and the average detection number of SLN was(2.79±1.228).while in the combination method group,the detection rate was 97.98％and the average detection number of SLN was(3.32± 1.469).There was no statistically significant difference in the detection rate of SLN between the two groups(P＞0.05).The average detection number in combination method group was more than that in dye method group(P＜0.05).However,there was no statistically significant difference in the distribution of SLN detection number between the two groups(P＞0.05).The duration of SLNB surgery in the combination method group was significantly shorter than that in the dye method group[(13.83±4.58)minutes vs(19.85±3.20)minutes),P＜0.05].Conclusion Combined method for SLNB can reduce surgical time and increase the detection rate and number of SLN.

Objective To investigate the effects of nuclear respiratory factor 1(NRF1)on mitochondrial and cog-nitive dysfunction in Alzheimer's disease(AD)model mice.Methods The 5 × FAD mice were utilized as a mod-el for Alzheimer's disease,and the sparsely labeled AAV virus overexpressing NRF1(AAV-NRF1)was adminis-tered via stereotaxic injection into the brain.The expression of NRF1 in hippocampus was determined by Western blot,the morphology of mitochondria in hippocampus was observed by transmission electron microscope,the den-dritic spines of sparsely labeled neurons in the CA1 region were visualized and quantified using confocal laser mi-croscopy,cognitive and memory functions of mice were evaluated using the Morris water maze test,while electro-physiological methods were employed to detect long-term potentiation(LTP)of synaptic efficacy.Results The ex-pression of NRF1 in the hippocampus was significantly upregulated following stereotactic injection of AAV-NRF1(P＜0.001).This intervention led to notable improvements in mitochondrial morphology within hippocampal neurons,as well as enhanced cognitive and memory functions in mice(P＜0.01).Moreover,there was a significant in-crease in dendritic spine density among neurons located in the CA1 region of the hippocampus(P＜0.001),ac-companied by long-lasting and stable long-term potentiation(LTP)and a substantial elevation in fEPSP slope(P＜0.01).Conclusion The overexpression of NRF1 in a 5 × FAD mouse model of Alzheimer's disease(AD)initia-ted the restoration of mitochondrial dysfunction and enhanced synaptic plasticity,indicating that these alterations may contribute to the therapeutic efficacy of NRF1 overexpression in ameliorating cognitive dysfunction associated with AD.