OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance （IR） in type 2 diabetes mellitus （T2DM） rats. METHODS T2DM rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet. The rats were randomly divided into normal control group， model group， Qingxue xiaozhi jiangtang formula low-dose and high-dose groups （6.525， 13.05 g/kg， calculated by raw material） and metformin group （positive control， 0.18 g/kg）， with 8 rats in each group. Administration groups were given relevant medicine intragastrically； normal control group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 6 weeks. Body mass and fasting blood glucose （FBG） were determined， and oral glucose tolerance test was conducted. Serum fasting insulin （FINS） level was measured to calculate the insulin resistance index （HOMA-IR） and insulin sensitivity index （ISI）. Additionally， the level of serum lipids， liver function， oxidative stress indicators and inflammatory factors were assessed. The phosphorylation levels of kinase R-like endoplasmic reticulum kinase （PERK） and forkhead box O1 （FOXO1） protein in liver tissue of rats were determined. RESULTS Compared with model group， the body weight， ISI， the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue xiaozhi jiangtang formula high-dose group and metformin group （P＜0.05）； FBG， blood glucose level at 120 minutes of glucose loading， area under the curve of glucose， FINS， HOMA-IR， low-density lipoprotein cholesterol， total cholesterol， triglyceride， alanine transaminase， aspartate transaminase， alkaline phosphatase， malondialdehyde， interleukin-6， tumor necrosis factor-α， and C-reactive protein levels were significantly reduced （P＜ Δ0.05）； the pathological damage of liver tissue had significantlyimproved， and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased （P＜0.05）. CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism， inflammation factor and oxidative stress levels， and alleviate insulin resistance in T2DM rats. Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.

Objective:To explore the effective components and potential mechanisms of Xiefei Lishui Prescription in the treatment of heart failure.Methods:Ultra high-performance liquid chromatography tandem four stage rod time of flight mass spectrometry (UPLC-Q-TOF-MS) technology was used to analyze and identify the active components of Xiefei Lishui Prescription. Drug targets were predicted through the Swiss Target Prediction database, and disease targets were collected from Gene Cards, Dis GENET, and TTD databases. The intersection of drug targets and disease targets was screened using a STRING database for protein interaction to identify core targets. The core targets were included in the DAVID database for GO enrichment and KEGG analysis. Finally, molecular docking validation was performed between the drug components and the corresponding core targets.Results:The results identified 10 active components of Xiefei Lishui Prescription, and 8 potential active components were screened using network pharmacology for the treatment of heart failure with Xiefei Lishui Prescription, corresponding to 160 related action targets. A total of 1 305 disease-related targets were collected, and a total of 51 targets ad 17 core targets were included in the string database for protein interaction analysis. GO functional enrichment and KEGG analysis indicated that the mechanism of Xiefei Lishui Prescription in treating heart failure may be related to pathways such as protein binding, ATP binding, and negative regulation of the VEGF signaling pathway and T cell receptor pathway during apoptosis. The molecular docking results showed that baicalin exhibited good binding activity with ESR1, sorghum isoflavones with ESR1, and quercetin with AKT1, EGFR, IL2, and ABCB1.Conclusion:Xiefei Lishui Prescription may exert therapeutic effects on heart failure through multiple pathways by targeting ESR1, AKT1, EGFR, and other targets.

Diabetic nephropathy is one of the most common and harmful microvascular complications of diabetes. In recent years, it has become a leading cause of end-stage renal disease due to its high incidence rate, challenging control, and poor prognosis. Studies have revealed that patients with diabetic nephropathy often exhibit imbalanced levels of sex hormones such as testosterone, dehydroepiandrosterone, estradiol, sex hormone binding globulin, and gonadotropin. Conversely, the imbalance of sex hormones can also influence the progression of diabetic nephropathy. Therefore, clarifying the potential relationship and interaction between sex hormones and diabetic nephropathy is essential for effective prevention and treatment of diabetic nephropathy. This warrants further research and consideration.

Myocardial infarction is the most common cause of heart failure,and myocardial remodeling can occur after infarction,thus contributing to the progression of heart failure.The occurrence of post-infarction ventricular remode-ling is closely related to m6A methylation.m6A methylation is a reversible and highly dynamic process.This process is mainly mediated by m6A methylation positive and negative regulatory enzymes and is involved in the occurrence of post-in-farction myocardial remodeling through mechanisms such as cellular autophagy.This article mainly reviews relevant litera-ture in recent years.Firstly,a brief introduction is given to m6A methylation,followed by an introduction to the role of m6A methylase in regulating myocardial remodeling.Finally,a summary analysis is conducted on the mechanism of m6A methylation in regulating myocardial remodeling from the perspectives of autophagy,inflammation,cell apoptosis,calcium ion homeostasis,extracellular matrix remodeling,and ferroptosis.The feasibility of using m6A methylation serological de-tection as a diagnostic tool for myocardial remodeling after myocardial infarction is discussed,in order to provide reference for related research.

Objective To investigate the effects and mechanism of Zhachong Shisanwei Pills on rats with cerebral ischemia.Methods Totally 75 rats were randomly divided into sham-operation group,model group,positive drug group(Ginaton,21.6 mg/kg),and Zhachong Shisanwei Pills low-,medium-,and high-dosage groups(81,162,324 mg/kg).Each treatment group was given the corresponding drug by gavage for 5 days.On the 6th day,a cerebral ischemia rat model was prepared by suture method.After 24 hours of modeling,the drugs were given in the same manner for 2 days.Neurological function scoring,horizontal beam walking scoring,and grip strength testing were performed on rats.TTC staining was used to detect the cerebral infarction rate,HE staining and Nissl staining were used to observe the morphology of brain tissue.TUNEL staining was used to detect the apoptosis rate of brain tissue cells.Differential genes in the treatment of cerebral ischemia using Zhachong Shisanwei Pills were screened by transcriptomics,and RT-qPCR,immunohistochemistry and Western blot were used to detect differential gene mRNA and protein expression.Results Compared with the sham-operation group,the model group rats showed a decrease in neurological function scores,horizontal beam walking scores,grip strength,an increase in cerebral infarction rate,neuronal nucleus condensation,vacuolar changes,widened intercellular spaces,the number of Nissl bodies reduced,and the apoptosis rate increased(P<0.01,P<0.001);compared with the model group,the Zhachong Shisanwei Pills medium-dosage group showed an increase in neurological function score,horizontal beam walking score,and grip strength in rats,a decrease in cerebral infarction rate,a lower degree of neuronal damage,an increase in the number of Nissl bodies,and a decrease in cell apoptosis rate(P<0.05,P<0.01).Transcriptome and bioinformatics analysis screened the Hippo signaling pathway related to the anti-cerebral ischemia effect of Zhachong Shisanwei Pills.The key genes of this pathway,mammalian sterile line 20 like kinase(MST1)1,Yes related protein(YAP)1,large tumor suppressor kinase(LATS)1,and TEA domain family member(TEAD)1 were detected.The results showed that the expression of MST1 mRNA and protein in brain tissue of model rats significantly increased,while the expressions of YAP1,LATS1,TEAD1 mRNA and protein significantly decreased;Zhachong Shisanwei Pills could down-regulate the expression of MST1 in brain tissue of model rats,and up-regulate the expressions of YAP1,LATS1 and TEAD1.Conclusion Zhachong Shisanwei Pills may exert anti-cerebral ischemia effects through the Hippo signaling pathway.

Objective:To predict the possible targets and signaling pathways of Jiangtang Xiaoke Granules in the treatment of diabetes mellitus (DM) using computer network pharmacology and molecular docking technology.Methods:The active components and targets of Jiangtang Xiaoke Granules were collected by ETCM; the targets of DM were searched from the databases of DisGeNET and GeneCards, and the intersections of the two were taken to draw a Venny diagram; String database was used for gene transformation and network interaction analysis; the network diagram was constructed with Cytoscape3.6.0; the predicted results were supported by molecular docking technology; GO and KEGG analysis was performed through Metascape database.Results:A total of 128 active components of Jiangtang Xiaoke Granules were screened, with 607 corresponding targets, 1 240 DM related targets, and 53 core targets. Molecular docking showed that the active components had good binding energy with the core targets. GO analysis yielded 46 functional items and KEGG analysis yielded 15 pathways.Conclusion:Jiangtang Xiaoke Granules regulate glucose homeostasis by participating in a variety of biological processes through multiple components, and multiple targets, including affecting lipids and atherosclerosis, Alzheimer disease, AMPK signaling pathway, Apelin signaling pathway, and glucagon signaling pathway.

Humans ; HIV-1/genetics* ; Anti-Retroviral Agents/therapeutic use* ; Mutation/genetics* ; Treatment Failure ; HIV Infections/genetics* ; Drug Resistance, Viral/genetics* ; Anti-HIV Agents/therapeutic use* ; Genotype

ObjectiveTo investigate the current situation of rehabilitation therapists' work, and analyze the factors related to their career development and transformation. MethodsFrom September, 2022 to January, 2023, 153 rehabilitation therapists in Weifang were investigated with a cross-sectional questionnaire, using general questionnaire, Job Satisfaction Scale for Grassroots Health Technicians, Social Responsibility Scale, Job Role and Identity Inventory, and Employee Turnover Scale. ResultsThe majority of rehabilitation therapists interviewed were male (52.28%), under 35 years old (88.24%), with a bachelor's degree (77.78%), income less than 5 000 yuan a month (46.40%), and less than five years of service (48.36%). The work time was (7.78±0.84) hours a day, (5.39±0.51) days a week. The favorable rate of the physical environment of work was 67.32%, and the favorable rate of the interpersonal relationship environment of work was 80.39%. The score of professional identity was (3.61±0.84), the score of job satisfaction was (3.62±0.97), the score of social responsibility was (3.53±0.79), and the score of turnover was (2.39±1.10). Education level, job satisfaction, and social responsibility were the main factors related to the employee turnover (P < 0.05). ConclusionThe overall educational level of rehabilitation therapists is relatively low, and the human resource structure needs to be optimized. There is a significant difference between academic education and continuing education, and career development needs to be improved. The main factors related to career development and transformation are education level, job satisfaction, and social responsibility.

OBJECTIVE To design paclitaxel prodrug nanoparticles with dual reactive oxygen species/glutathione response (ProPTX-SS-NPs), providing new ideas and methods for the application of paclitaxel. METHODS The optimal preparation method and process of prodrug nanoparticles was investigated by using particle size and PDI as indicators; the morphology of prodrug nanoparticles was observed through electron microscopy and their particle size, potential, encapsulation efficiency, drug loading capacity, etc were investigated; the in vitro release characteristics of nanoparticles in reactive oxygen species and glutathione environments were investigated; the in vitro cytotoxicity and cellular uptake of prodrug nanoparticles were investigated through cell experiments. RESULTS The nano particle size prepared by the optimal process was (130.20±2.18)nm, with the PDI of 0.12±0.01, the Zeta potential of (-8.45±0.01)mV, the drug load of (10.27±1.36)%, and the encapsulation rate of (93.22±2.20)%. The prodrug nanoparticles showed reactive oxygen species and glutathione dual responsive release ability, and could significantly inhibit the proliferation of MCF-7, HepG2, and MDA-MB-231. Its inhibitory effect on MDA-MB-231 cells was the most significant. The IC50 of prodrug nanoparticles on MDA-MB-231 cells was (0.71±0.11)μmol·L, while the IC50of PTX was (22.38±3.27)μmol·L. CONCLUSION ProPTX-SS-NPs have excellent tumor microenvironment response performance and significant anti-tumor activity, which is a highly potential and promising anti-tumor nanosystem.

Objective:To analyze the preoperative and postoperative color Doppler ultrasonographic features of Abernethy malformation in children, and to investigate the value of ultrasound diagnosis of Abernethy malformation and postoperative complications.Methods:A retrospective analysis was performed on the clinical and ultrasound data of twelve cases of Abernethy malformation confirmed by surgical treatment in the General Surgery Department of the Children′s Hospital Affiliated to Capital Institute of Pediatrics from February 2017 to November 2021. A comparison was made between preoperative ultrasound and intraoperative portal vein angiography after shunt ligation to explore the accuracy of preoperative ultrasound in diagnosing Abernethy malformation; The common location of thrombosis after shunt ligation was summarized by comparing postoperative ultrasound with CT angiography.Results:Preoperative ultrasonography showed no main portal vein or cable shape in 9 cases, and they were diagnosed as probable Abernethy type Ⅰ; The main portal vein was narrow in 3 cases, and they were diagnosed as Abernethy type Ⅱ. The main portal veins of 11 case were developing and they were confirmed as Abernethy malformation type Ⅱ by portal vein angiography after blocking of portosystemic shunt; the main portal vein of 1 case was not developing which was confirmed as Abernethy type Ⅰ. The classification accuracy of preoperative ultrasound diagnosis of Abernethy malformation was 33.3%. Preoperative ultrasound diagnosis of shunt vessel location: the coarse inferior mesenteric veins of 7 cases flowed into the iliac vein, the coarse inferior mesenteric vein of 1 case flowed into the inferior vena cava, splenic vein and superior mesenteric vein converged and flowed into inferior vena cava in 2 cases, splenic vein and left renal vein communicated in 2 cases. The location of shunt vessels diagnosed by portal vein X-ray angiography was basically consistent with preoperative ultrasonography. At the same time, inferior mesenteric vein shunt combined with tortuous and dilated vein network on colorectal surface was observed. After ligation of shunt vessels, all of shunt vessels were occluded or thrombolized in varying degrees.Splenic vein retropancreatic segment of three cases occured secondary thrombosis, and one case of blocked portal vein occured secondary cavernous change. All the thrombi were confirmed by CT angiography.Conclusions:①The main portal vein of Abernethy malformation type Ⅱ is tenuous, and is easily misdiagnosed Abernethy malformation type Ⅰ by preoperative ultrasound examination; ②Preoperative ultrasound can determine the location of Abernethy malformed shunt vessels; ③The shunt between the inferior mesenteric vein-iliac vein/inferior vena cava should be emphatically explored in children with recurrent hematochezia; ④Postoperative ultrasound can detect portal vein thrombosis early and provide help for clinical anticoagulant therapy.