The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals ; Antidepressive Agents/chemistry* ; Mice ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/immunology* ; Oils, Volatile/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Glycation End Products, Advanced/immunology* ; Humans

Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P＜0.01),splenic coefficient and hepatic coefficient were significantly decreased(P＜0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P＜0.01),the serum GAS content was significantly increased(P＜0.01),and the MTL,GC contents were significantly reduced(P＜0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P＜0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P＜0.01),and the protein expression level of VEGFA was reduced(P＜0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P＜0.05 or P＜0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of Resina Draconis, in our laboratory. In this study, we investigated the effects of C13 on the proliferation and apoptosis of human gastric cancer HGC-27 and AGS cells and its potential mechanism of action. Firstly, through methyl thiazolyl tetrazolium (MTT), colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, we found that C13 inhibited the proliferation ability of human gastric cancer HGC-27 and AGS cells. Using flow cytometry and Western blot, it was found that C13 induced apoptosis in human gastric cancer HGC-27 and AGS cells, and up-regulated the protein level of cleaved poly ADP-ribose polymerase (cleaved-PARP). The results of RNA sequencing analysis showed that the Erb-b2 receptor tyrosine kinase 4/phosphoinositide 3-kinases/AKT (ErbB4/PI3K/AKT) signaling pathway may be involved in anti-gastric cancer activity of C13. Finally, the results of immunoblotting assay showed that C13 treatment down-regulated the protein levels of ErbB4 and phospho-ErbB4, as well as down-regulated the phosphorylation levels of PI3K and AKT in human gastric cancer HGC-27 and AGS cells, which verified the results from RNA-seq analysis. In conclusion, C13 inhibited the proliferation and induced apoptosis of human gastric cancer cells, which may be related to the down-regulation of ErbB4/PI3K/AKT signaling pathway. This study may provide a candidate drug for the treatment of gastric cancer.

Objective To explore the influential factors and predictive value of early femoral head collapse progression following allogeneic fibula grafting(AFG)surgery.Methods Clinical and radiological data of 68 patients(75 hips)with osteonecrosis of the femoral head(ONFH)who underwent AFG between January 2008 and December 2022 at the Orthopedics and Traumatology Department,Affiliated Hospital of Nanjing University of Chinese Medicine were retrospectively analyzed.Seventy-five hips were divided into stable(n=40)and progressive(n=35)groups based on the presence or absence of postoperative collapse progression.Age,gender,etiology,location of the lesion,Association Research Circulation Osseous(ARCO)stage,Japanese Committee of Osteonecrosis Investigation(JIC)classification,China-Japan Friendship Hospital(CJFH)classification,and Hounsfield units(HU)value of anterolateral sclerosis rim(ⅠSHU)were collected.Univariate and multivariate logistic regression analyses were used to identify the factors influencing early collapse progression after AFG.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of the identified factors influencing postoperative early collapse progression.Results Of the 75 hips,35(46.7%)had postoperative collapse progression.Univariate logistic regression analysis showed that age,ARCO stage,JIC classification,and ⅠSHU were in fluencing factors for early femoral head collapse progression after AFG(P<0.05).Multivariate logistic regression analysis showed that ARCO stage ⅢA and JIC classification C2 were independent risk factors for early femoral head collapse progression after AFG,while ⅠSHU was identified as an independent protective factor(P<0.05).The ROC curve analysis showed that the sensitivities of ARCO stage,JIC classification,ⅠSHU,and the combined predictive model were 0.850,0.725,0.800,and 0.775,the specificities were 0.486,0.657,0.743,and 0.914,and the area under the ROC curve(AUC)were 0.668,0.725,0.811,and 0.896,respectively.Conclusions ⅠSHU is associated with early collapse progression after AFG in patients with ONFH.ARCO stage ⅢA,JIC classification C2,and ⅠSHU are independent factors influencing postoperative early collapse progression and have a certain predictive value.

AIM To investigate the clinical effects of Yiqi Shengjin Prescription on patients with primary Sj?gren's syndrome due to Dual Deficiency of Qi and Yin.METHODS Ninety-two patients were randomly assigned into control group(46 cases)for 8-week intervention of conventional treatment,and observation group(46 cases)for 8-week intervention of both Yiqi Shengjin Prescription and conventional treatment.The changes in clinical effects,TCM syndrome scores,ESSDAI score,ESSPRI score,salivary flow rate,immunoinflammatory indices(ESR,hs-CRP,IgG,C3,C4),SAS score,SDS score,T lymphocytes(CD4+,CD8+,Treg,Th17)and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the observation group exhibited decreased TCM syndrome scores(P＜0.05),which was lower than those in the control group(P＜0.05);the two groups displayed decreased ESSDAI score,ESSPRI score,ESR,hs-CRP,IgG,SAS score,SDS score,CD8+,Th17(P＜0.05),and increased salivary flow rate,C3,C4,Treg(P＜0.05),especially for the observation group(except for CD4+)(P＜0.05).No obvious adverse reactions were observable in the two groups.CONCLUSION For the patients with primary Sjogren's syndrome due to Deficiency of Qi and Yin,Yiqi Shengjin Prescription can safely and effectively improve dry mouth and eye symptoms,and reduce inflammatory indices,whose mechanism may contribute to the regulation of T lymphocyte balance in vivo.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Plant polysaccharides are effective components that widely present in traditional Chinese medicine(TCM), exhibiting rich biological activities. However, as most plant polysaccharides cannot be directly absorbed and utilized by the human digestive system, it is now believed that their mode of action mainly involves interaction with intestinal microbiota, leading to the production of functional small molecules. The efficacy of Astragalus polysaccharide(APS) is extensive, including weight loss, improvement of fatty liver, reduction of blood lipids, and enhancement of insulin sensitivity, which may also be related to the regulation of intestinal microbiota. Adipose tissue senescence is an important characteristic of the physiological aging process in the body, often occurring prior to the aging of other important organs. Its main features include the accumulation of senescent cells and exacerbation of inflammation within the tissue. Therefore, to explore the potential protective effects of APS on aging, the improvement of adipose tissue aging phenotype in naturally aging mice was observed using APS, and combined with metagenomic metabolomics, corresponding microbial metabolic functional molecules were identified. Furthermore, functional tests in cell aging models were conducted. The results showed that APS significantly improved the adipocyte aging characteristics of naturally aging mice: specifically reducing aging-induced adipocyte hypertrophy; decreasing the protein expression of aging markers cyclin-dependent kinase inhibitor p21(P21) and multiple tumor suppressor 1(P16); lowering the tissue inflammation reaction. Metagenomic metabolomic analysis of serum from mice in each group revealed that APS significantly increased the content of indole-3-lactic acid(ILA) in naturally aging mice. Further in vitro studies showed that ILA could improve the aging of 3T3-L1 mouse embryonic fibroblasts induced by bleomycin, reduce the protein expression of the aging marker P21, alleviate inflammation, and enhance the ability of preadipocytes to mature. Therefore, APS had the efficacy of protecting naturally aging mice, and its action may be related to the increase in the intestinal microbiota metabolite ILA. This study suggested that TCM may serve as an important entry point for explaining the mechanism of action of TCM by regulating intestinal microbiota and their functional metabolites.
Animals ; Mice ; Aging/drug effects* ; Adipose Tissue/metabolism* ; Polysaccharides/pharmacology* ; Indoles/pharmacology* ; Male ; Astragalus Plant/chemistry* ; 3T3-L1 Cells ; Humans ; Adipocytes/cytology* ; Mice, Inbred C57BL ; Cellular Senescence/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Gastrointestinal Microbiome/drug effects*

Objective:To compare the clinical efficacy between bone transport technique combined with bone grafting plus internal fixation and simple bone transport technique in the treatment of large segmental bone defects at lower limbs after trauma.Methods:A retrospective study was conducted to analyze the clinical data of 42 patients with large segmental bone defects at lower limbs after trauma who had been treated at Department of Trauma Orthopaedics, Honghui Hospital Affiliated to Medicine College, Xi'an Jiaotong University from September 2015 to September 2019. The patients were divided into 2 groups according to the different methods of repairing bone defects. In group A of 18 patients subjected to bone transport combined with bone grafting plus internal fixation, there were 11 males and 7 females with an age of (35.2±10.3) years, and 12 tibial defects and 6 femoral defects; in group B of 24 patients subjected to simple bone transport, there were 15 males and 9 females with an age of (37.3±9.4) years, and 17 tibial defects and 7 femoral defects. The external fixation time (EFT), external fixation index (EFI), total cure time and complications were recorded and compared between the 2 groups. At the last follow-up, the Ennecking score for limb functional recovery (score/total score 30) and Self-rating Anxiety Scale (SAS) were used to evaluate respectively the functional recovery of the limbs and postoperative anxiety.Results:The 2 groups were comparable because there was no significant difference between them in preoperative general data or follow-up time ( P>0.05). There was no statistically significant difference in the number of surgeries between the 2 groups ( P>0.05). The EFT [(5.9±1.5) months], EFI [(0.45±0.09) months/cm], total treatment time [(16.2±2.4) months], Ennecking score for limb functional recovery (87.0%±8.6%), SAS score [(43.2±9.0) points], and complications per capita [(0.4±0.2) times/case] in group A were significantly better than those in group B [(15.3±4.2) months, (1.19±0.28) months/cm, (19.7±3.5) months, (77.3%±9.2%), (58.2±9.3) points, and (1.2±0.5) times/case] (all P<0.05). Conclusion:In the treatment of large segmental bone defects at lower limbs, compared with simple bone transport technique, bone transport technique combined with bone grafting plus internal fixation has advantages of shorter external fixation time and overall cure time, a lower rate of complications, and better functional recovery of the limbs.

Objective:To observe the effect of percutaneous auricular vagus nerve stimulation on myocardial structural remodeling, electrical remodeling and apoptosis in rats of heart failure with preserved ejection fraction, and to explore the relationship between this effect and oxidative stress.Methods:The arteriovenous fistula was closed by ligation two weeks after establishment in SD rat.By increasing cardiac volume load in the short term, a rat model of heart failure with preserved ejection fraction was constructed.Forty rats were randomly divided into four groups, with 10 rats in each group: sham operation group(S), abdominal aorta-inferior vena cava fistula + closure group(AVF+ L), abdominal aorta-inferior vena cava fistula + closure+ percutaneous auricular vagus nerve stimulation group(AVF+ L+ tVNS)and abdominal aorta-inferior vena cava fistula + closure+ percutaneous auricular vagus nerve stimulation + acetylcholine M 2 receptor antagonist group(AVF+ L+ tVNS+ M -). Rats in the AVF+ L+ tVNS group received percutaneous vagal nerve stimulation on the basis of those in the AVF+ L group.Rats in the AVF+ L+ tVNS+ M - group received daily injection of acetylcholine M 2 receptor antagonist mesotramine(0.5mg/Kg)into tail vein on the basis of those in the AVF+ L+ tVNS group.The parameters of cardiac structural remodeling and electrical remodeling in each group were obtained by cardiac ultrasound and cardiac electrophysiological stimulator.Enzyme-linked immunosorbent assay(ELISA)was used to detect the values of B-type natriuretic peptide precursor(NT-proBNP)and oxidative stress-related indicators in each group.hematoxylin-eosin(HE)staining was used to observe the damage of myocardial structure, disorder of cell arrangement and infiltration of inflammatory cells.Cardiomyocyte apoptosis was observed by TdT-mediated dUTP nick end labeling(TUNEL)staining and apoptosis index was calculated.reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting were used to detect the mRNA and protein expression of B cell lymphoma / leukemia-2(BCL-2)and apoptosis promoting gene(BAX)in BCL-2 gene family. Results:The rats in the AVF + L group developed heart failure characterized by ventricular wall hypertrophy and diastolic dysfunction, and the left ventricular ejection fraction(LVEF)was >50 %.The rat heart failure model with preserved ejection fraction was successfully established.HE staining showed that the myocardial tissue structure damage, cell arrangement disorder and inflammatory cell infiltration were obvious in AVF+ L group, while the pathological changes of myocardial tissue in AVF+ L+ tVNs were significantly less than those in AVF+ L group.Compared with AVF+ L group, in the AVF+ L+ tVNs, the value of NT-proBNP decreased[(301.25 ± 16.07)ng/L vs.(79.33±5.63)ng/L, P<0.05], the value of E/A increased(1.28 ± 0.06 vs.1.66 ±0.05, P<0.05), the expression of BCL-2 mRNA[0.08(0.07, 0.08) vs.0.70(0.64, 0.76), P<0.05]and BCL-2 protein(0.19±0.03 vs.0.46±0.04, P<0.05)both increased, the expression of BAX mRNA(5.00±0.32 vs.2.14±0.36, P<0.05)and BAX protein(0.76±0.04 vs.0.43±0.05, P<0.05)both decreased, while the apoptotic index was also decreased(16.26±0.32 vs.7.04±0.24, P<0.05). Compared with AVF + L group, the indexes of myocardial structural remodeling, electrical remodeling and oxidative stress were decreased in AVF + L + tVNs group(P<0.05). Compared with AVF + L group, there was no significant difference in the above indexes in AVF + L + tVNS + M - group( P>0.05). Conclusions:tVNS can alleviate myocardial structural remodeling, electrical remodeling and apoptosis in HFpEF rats, which may be related to the reduction of oxidative stress response activity.