Objective To pick up the Chinese materia medica with principal antidepressive effect in Kaixin Jieyu prescription based on uniform distribution. Methods 11 groups of concerted application with different dosages of six simplex Chinese materia medica (X 1-X 6) of Kaixin Jieyu prescription were arranged by the designlist and sustentacular table of U11(1110). Positive and negative control groups were also formed. Mice were randomized into 13 groups according to body weight and fed with medicine 14 d and estimated by tail suspension test, forced swim test and autonomic activities test. Results Relationship of percentage of immovability time (Y 1) in the tail suspension test and X 1-X 6 were analyzed with multivariant non-linear regression analysis and resulted in Y 1=1.133 1-0.842 3×X 1+0.438 2×X 3-0.712 9×X 6. It indicated that both Radix Ginseng and Fructus Aurantii Immaturus had obvious antidepressive function, and Radix Paeoniae Rubra may facilitate depression. Relationship of immovability time (Y 2) in forced swim test and X1-X6 were analyzed with multivariant non-linear regression analysis and resulted in Y 2=167.69-2.99×X 12-2.14×X 1-1.65×X 6. It also indicated that both Radix Ginseng and Fructus Aurantii Immaturus had obvious antidepressive function. Relationship of autonomic activities index (Y 3) in autonomic activities test indicated that X 1-X 6 had no obvious influence on Y 3 and antidepressive function of KaixinJieyu prescription was not concerned with excitability to the central nervous system. Conclusion Radix Ginseng and Fructus Aurantii Immaturus were the Chinese materia medica with principal antidepressive effect in Kaixin Jieyu prescription.

AIM To aim at investigating the function of Kaixin Jieyu Pills (Ginseng Radix et Rhizoma,Bupleuri Radix,Morindae officinalis Radix,etc.) to vascular depression and their mechanism of action.METHODS A vascular depression model of rat was established by chronic unpredictable mild stress and separation after ligation of the bilateral common carotid arteries.The rats were treated with Kaixin Jieyu Pills and fluoxetine hydrochloride (FLU) for 28 days,respectively.The sucrose preference test and open-field test were performed.Cerebral perfusion was investigated with a Perfusion Speckle Imager.The monoamines including serotonin,dopamine and noradrenaline,and brain-derived neurotrophic factor (BDNF) were determined with ELISA and Western bolt,respectively.RESULTS Kaixin Jieyu Pills significantly increased sucrose preference,moving distance and cortical blood flow.Kaixin Jieyu Pills could upregulate,to different extents,the expressions of monoamines,including serotonin,noradrenaline and dopamine,and BDNF.Kaixin Jieyu Pills had a function similar to FLU in behavior,upregulating monoamines and BDNF,but it is superior to FLU in cortical blood flow.CONCLUSION Kaixin Jieyu Pills has the advantage of reducing the depression-like behavior and improving cerebral hypoperfusion,which might be mediated by the upregulation of the serotonin,noradrenaline and BDNF.

The delivery of bioactive macromolecular substances into cells provides an efficient approach to changing cellular conditions, and is thus of enormously potential therapeutic significance. It has also been an extremely difficult approach due the the impediment and protective nature of cell membrance until the protein transduction domain's (PTD's) capability to ferry macromolecule across cell membrance was discovered. PTD's efficient transductive function has rendered an exciting promise to the clinical treatment of diseases, therapeutic proteins drug development, and basic medical and applied research. The technology has been successfully applied to deliver a variety of substances into cells or tissue organs, and its superior application values have been explicitly demonstrated.
Cell Membrane Permeability ; physiology ; Drug Delivery Systems ; methods ; Genetic Therapy ; Humans ; Protein Sorting Signals ; Protein Transport ; physiology

This study was aimed to explore the antidepressant effect of Kai-Xin Jie-Yu (KXJY) prescription on depressive model of rats,and to explore the level of inflammatory cytokines in peripheral blood.According to sucrose preference and weight,male SD rats were randomly divided into the normal group,model group and traditional Chinese medicine (TCM) group.The model of depression was established by chronic unpredictable mild stress and separation for @@6 weeks.Body weight,sucrose preference and forced swimming test were used to evaluate the depressive state.The levels of IL-1β,IL-2,IL-6 and TNF-α in the serum of rats were measured by ELISA.The results showed that compared with the normal group,the weight,sucrose preference and total drinking water of rat model gToup were significantly reduced.The immobility time of forced swimming was significantly prolonged.The level of IL-1β,IL-2,IL-6 and TNF-α expression in serum was significantly increased.There was no significant difference between the body weight of rats in the model group and TCM group.The total amount of drinking water and sucrose preference were significantly increased.The immobility time of forced swimming was reduced.Levels of IL-1 β,IL-2,IL-6 and TNF-α expression were decreased significantly.It was concluded that KXJY prescription can improve depression symptoms in depression model of rats.It may be related to regulate the expression level of serum inflammatory cytokines.

This study was aimed to detect the expression of miR-665 in the hippocampal of depression rat model treated with Kai-Xin Jie-Yu (KXJY) decoction and bioinformatic analysis of target genes of miR-665,in order to investigate the role of miR-665 in the pathogenesis of depression and the antidepressant mechanism of KXJY decoction.The rat model of chronic stress depression was established and then treated with KXJY decoction for 42 days.The total RNA from hippocampus tissues was extracted.And the relative expression of miR-665 in hippocampus of rats in each group was detected by RT-qPCR.TargetScan and microRNAorg databases were used to predict target genes for miR-665.DAVID database was used to classify GO function and to analyze KEGG signaling pathway of target genes.The results showed that compared with the normal group,the expression level of miR-665 in hippocampus of the model group was significantly higher with significant difference (P ＜ 0.01).Compared with the model group,the expression level of miR-665 in hippocampus of Chinese medicine group and western medicine group decreased significantly with significant difference (P ＜ 0.01).The biological functions of miR-665 target genes were mainly concentrated in the response to organic substance.The signal pathway was mainly concentrated in N-Glycan biosynthesis.It was concluded that miR-665 may be involved in the pathological process of depression,by correcting the abnormal expression of miR-665,which may be one of the antidepressant mechanisms of KXJY decoction.Through the analysis and prediction of the target genes,it provided a certain direction and theoretical basis for further study on the specific mechanism of KXJY decoction intervention on miR-665.

Previous studies have indicated that ERp44 inhibits inositol 1,4,5-trisphosphate (IP(3))-induced Ca(2+) release (IICR) via IP(3)R(1), but the mechanism remains largely unexplored. Using extracellular ATP to induce intracellular calcium transient as an IICR model, Ca(2+) image, pull down assay, and Western blotting experiments were carried out in the present study. We found that extracellular ATP induced calcium transient via IP(3)Rs (IICR) and the IICR were markedly decreased in ERp44 overexpressed Hela cells. The inhibitory effect of C160S/C212S but not C29S/T396A/ΔT(331-377) mutants of ERp44 on IICR were significantly decreased compared with ERp44. However, the binding capacity of ERp44 to L3V domain of IP(3)R(1) (1L3V) was enhanced by ERp44 C160S/C212S mutation. Taken together, these results suggest that the mutants of ERp44, C160/C212, can more tightly bind to IP(3)R(1) but exhibit a weak inhibition of IP(3)R(1) channel activity in Hela cells.
Adenosine Triphosphate ; pharmacology ; Amino Acid Substitution ; Biological Transport ; drug effects ; physiology ; Blotting, Western ; Calcium ; metabolism ; Calcium Signaling ; drug effects ; physiology ; HeLa Cells ; Humans ; Immunoprecipitation ; Inositol 1,4,5-Trisphosphate ; metabolism ; Inositol 1,4,5-Trisphosphate Receptors ; physiology ; Membrane Potentials ; drug effects ; physiology ; Membrane Proteins ; genetics ; metabolism ; Microscopy, Confocal ; Molecular Chaperones ; genetics ; metabolism ; Mutation ; Plasmids ; Transfection

Objective To describe the status and influencing factors of psychological distress in older people living with HIV in Shanghai.Methods Convenience sampling was used to select HIV patients with the age of 50 years old and above who attended follow-up visits at the voluntary counselling & testing clinic in Shanghai Public Health Clinical Center from December 2022 to October 2023.Data were collected using a general information questionnaire,HIV disclosure questionnaire,Distress Thermometer and Lubben Social Network Scale-6.Binary logistic regression was employed to analyze the factors influencing psychological distress.Results The prevalence of psychological distress among 332 participants was 105 cases(31.6％).The top 3 items selected by participants in Psychological Distress Problem List were insurance/financial issues,worry and sleep,relationship with children.Factors associated with a higher level of psychological distress included lower monthly income,not HIV disclosure and higher levels of social isolation.Conclusion Psychological distress among older people living with HIV remains to be further reduced,and it is affected by many factors.Health care providers should pay more attention to psychological distress among older HIV patients,and develop targeted intervention according to relevant influencing factors,aiming to reduce their psychological distress.

This article was aimed to investigate the function and mechanism of Kai-Xin Jie-Yu (KXJY) pill on depression.The depression model rats were established by chronic unpredictable mild stress and separation.The sucrose preference test and Morris water maze (MWM) were performed.The regulation effects of neural plasticity-related genes including glycogen synthase kinase-3β (GSK-3β),cAMP-response element binding protein (CREB),5-hydroxytryptamine 2C receptors (HTR2C),and vascular endothelial growth factor (VEGF) were determined.The results showed that among depression model rats,KXJY pill significantly increased the sucrose preference and the escape latency of MWM in a certain extent.The neural plasticity-related genes including GSK-3β and HTR2C mRNA were decreased significantly,whereas CREB and VEGF mRNA were increased significantly with the treatment of KXJY pill.It was concluded that KXJY pill had the function of reducing depression-like behavior,which might be mediated by the regulation of GSK-3β,CREB,HTR2C and VEGF.

Objective:To investigate the effect of dapagliflozin on cognitive function in middle-aged and elderly type 2 diabetes mellitus patients and related factors.Methods:This was a retrospective study. A total of 200 patients who were hospitalized in the Department of Endocrinology, the Second Affiliated Hospital of Anhui Medical University from August 2021 to August 2022 were recruited randomly. They were divided into the dapagliflozin group and control group. Clinical data were collected; plasma levels of β-amyloid protein(Aβ) 40 and Aβ42 were measured. The Montreal cognitive assessment(MoCA) and the mini-mental state examination(MMSE) were employed to assess cognitive function in both groups. Based on MoCA scores, patients in the dapagliflozin group were further categorized into mild cognitive impairment(MCI) and non-MCI subgroups. Differences among groups were analyzed and compared using t-test, χ2 test, and Mann-Whitney U test, and multivariable logistic regression was used to identify relevant factors associated with cognitive impairment in diabetes patients. Results:Compared to the control group, the dapagliflozin group exhibited significant increases in MMSE and MoCA scores, estimated glomerular filtration rate, and plasma concentration Aβ40(all P<0.05); And the incidence of MCI, homeostasis model assessment for insulin resistance(HOMA-IR), total cholesterol, triglycerides, urine albumin creatine ratio, plasma Aβ42, and Aβ42/Aβ40 ratio were significantly decreased(all P<0.05). Compared with the MCI subgroup, duration of dapagliflozin treatment in the non-MCI subgroup were significantly increased( P<0.05); There were statistically significant decreased in the non-MCI subgroup in age, systolic blood pressure, fasting plasma C-peptide, and HOMA-IR(all P<0.05). Multivariable logistic regression analysis showed that duration of dapagliflozin treatment was a protective factor for cognitive dysfunction( OR=0.322, 95% CI 0.150-0.692, P=0.004) and the age and HOMA-IR were risk factors( OR=1.109, 95% CI 1.014-1.212, P=0.023; OR=3.376, 95% CI 1.276-8.931, P=0.014). Conclusion:Dapagliflozin may improve cognitive function and significantly reduce the incidence of MCI in middle-aged and elderly patients with type 2 diabetes mellitus, possibly associated with the improvement of insulin resistance.