1.Study on the pharmacological effects and mechanism of Gegen-Zhimu herb pair in preventing and treating Alzheimer's disease by UHPLC-Q/TOF-MS metabolomics strategy
Liang CHAO ; Hui WANG ; Shuqi SHEN ; Piaoxue YOU ; Kaihong JI ; Zhanying HONG
Journal of Pharmaceutical Practice and Service 2025;43(1):30-40
Objective To evaluate the efficacy of Puerariae lobatae radix (PLR) and Anemarrhenae Rhizoma (AR) in preventing and treating Alzheimer’s disease (AD) and explore its potential mechanism of action by LC-MS serum metabolomics strategy. Methods The AD rat model was established by administering aluminum chloride (AlCl3) and D-galactose (D-gal) for 20 weeks. The traditional Chinese medicine intervention group was given the PLR, AR, and PLR-AR extracts for 8 weeks by gavage. The model effect and efficacy were evaluated by Morris water maze test and biochemical indicators including SOD, NO, and MDA; Metabolomics research based on the UHPLC-Q/TOF-MS method was conducted, and relevant metabolic pathways were analyzed through the MetaboAnalyst online website. Results The learning and memory abilities of AD model rats were significantly decreased compared with the control group, and the levels of oxidative stress and lipid peroxides were significantly increased (P<0.05), while the SOD content was decreased considerably (P<0.01). The learning and memory abilities of AD model rats were improved, oxidative stress and lipid peroxidation levels were reversed, and serum SOD content was increased significantly after the intervention of PLR-AR, with better effects than single drugs. Through metabolomics, 70 differential metabolites were identified between the AD model group and the control group, mainly involving 10 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and unsaturated fatty acid biosynthesis, et.al. The intervention of PLR-AR could adjust 47 metabolites, with 20 metabolites showing significant differences (P<0.05). The significantly adjusted metabolites involve 6 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, et al. Conclusion The combination of PLR and AR could significantly improve the learning and memory abilities of AD rat models. The mechanism may be related to the improvement of oxidative stress and lipid peroxidation levels, the increase of serum SOD content, and the regulation of phenylalanine, tyrosine, and tryptophan biosynthesis pathways.
2.Naringenin ameliorates insulin resistance in HepG2 cells by regulating high miR-29b expression
Yuan WANG ; Kaihong ZENG ; Xuemei YU ; Bo DENG
Acta Universitatis Medicinalis Anhui 2024;59(8):1423-1428
Objective To investigate the impact of naringenin(Nar)on insulin resistance(IR)in HepG2 cells and evaluate the role of mircoRNA-29b(miR-29b)expression in mediating this effect,thereby providing a foundation for further exploration into the mechanisms underlying naringenin's potential as a preventative and therapeutic agent for diabetes.Methods Insulin resistant HepG2(IR-HepG2)was established by stimulating HepG2 cells with 100 nmol/L insulin.Nar was treated with different concentrations(0,25,50,100 μg/ml)in IR-HepG2 cells.The effect of Nar on glucose consumption in IR-HepG2 cells was determined with glucose kit.miR-29b mimic and inhib-itor were transfected into IR-HepG2 cells of the 50 μg/ml Nar intervention group,and the expressions of insulin re-ceptor substrate-1(IRS-1),protein kinase B(Akt)/phosphorylated Akt(p-Akt),glucose transporter-4(GLUT4)genes and proteins in the insulin signaling pathway were detected by Real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR)and Western blot,respectively.Results Compared with IR-HepG2 model group,glucose consumption was increased in Nar intervention group with different concentrations(P<0.01),among which 50 μg/ml Nar intervention group was the most significant(P<0.001),and mRNA ex-pressions of IRS-1 and Akt were increased in Nar intervention group with different concentrations(P<0.05),the mRNA expression of IRS-1 and Akt in 50 μg/ml Nar intervention group was the most significantly increased(P<0.001),and GLUT4 mRNA expression in 50 μg/ml Nar intervention group was increased(P<0.05).The pro-tein expressions of IRS-1 and p-Akt were increased in different Nar concentration groups(P<0.001).Compared with IR-HepG2 model group,mRNA expression of IRS-1,Akt and GLUT4 and protein expression of IRS-1 and p-Akt were decreased in miR-29b mimic transfected cells(P<0.001),mRNA expression of IRS-1,Akt and GLUT4 and protein expression of IRS-1 and p-Akt were not different in miR-29b inhibitor transfection group,Nar interven-tion model group and Nar intervention transfected miR-29b mimic group increased the mRNA expression of IRS-1,Akt and GLUT4(P<0.001),and the protein expression of IRS-1 and p-Akt increased(P<0.05).Compared with Nar intervention model group,Nar transfected miR-29b mimic with Nar intervention did not change the mRNA expressions of IRS-1,Akt and GLUT4,while the protein expressions of IRS-1 and p-Akt were increased(P<0.05),Nar interfered with mRNA expression of IRS-1,Akt and GLUT4 and protein expression of IRS-1 and p-Akt in miR-29b inhibitor group(P<0.001).Conclusion Nar can increase glucose consumption in IR-HepG2 cells,increase the expression of IRS-1,Akt and GLUT4 genes,and increase the expression of IRS-1 and p-Akt proteins in IR-HepG2 cells.Nar increases the expression of IRS-1 and p-Akt in IR-HepG2 cells by inhibiting the overexpres-sion of miR-29b,and improves insulin resistance in HepG2 cells.Nar,as a plant compound,is expected to be a potential drug for the prevention and treatment of diabetes.
3.Curative efficacy of tandem autologous hematopoietic stem cell transplantation for high risk multiple myeloma
Yuanyao FU ; Guifang OUYANG ; Lixia SHENG ; Kaihong XU ; Shanhao TANG ; Zhen WANG
Chinese Journal of Organ Transplantation 2024;45(6):399-407
Objective:To explore the curative efficacy of tandem autologous stem cell transplantation (ASCT) for high-risk multiple myeloma (HRMM).Methods:From January 2017 to December 2021, retrospective analysis was conducted for 240 initially diagnosed HRMM patients. According to different treatment protocols after induction chemotherapy, they were further assigned into three groups of tandem ASCT (n= 20) ,single ASCT (n=80) and non-transplantation (n= 140). Rates of deep response (very good partial response and above) before and after transplantation and differences in 2-year progression-free survival (PFS) and overall survival (OS) were compared among three groups. The prognostic factors of HRMM were examined by univariate and multivariate analyses.Results:In single ASCT group, the rates of deep responses were 67.50% (54/80) after induction chemotherapy and 80.00 % (64/80) post-ASCT ( P=0.072). There were no significant statistical differences. In tandem ASCT group, the rates of deep response were 65.00% (13/20) after induction chemotherapy and 95.00 % (19/20) post-ASCT ( P=0.018). There were significant statistical differences. The 2-year PFS of tandem ASCT, single ASCT and non-transplantation groups were (75.00±2.90) %, (71.25±3.00) % and (61.43±3.10) % respectively. No statistically significant difference existed in 2-year PFS rates between single ASCT and non-transplantation groups, as well as between tandem ASCT and single ASCT groups ( P=0.365 and P=0.052). Significant difference existed in 2-year PFS between tandem ASCT and non-transplantation groups ( P<0.032). Two-year OS rates of tandem ASCT, single ASCT and non-transplantation groups were (90.00±3.50) %, (78.75±2.70) % and (62.86±2.50) % respectively. No statistically significant difference existed in 2-year OS rate between single ASCT and non-transplantation groups, as well as between tandem ASCT and single ASCT groups ( P=0.071 and P=0.057). Significant difference existed in 2-year OS between tandem ASCT and non-transplantation groups ( P=0.003). Univariate and multivariate analyses indicated that the independent prognostic factors affecting PFS were multi-hit, stages RISS-Ⅲ and failure to achieve very good partial response (VGPR) after four cycles of induction therapy and non-tandem ASCT. The independent prognostic factors affecting OS were multi-hit, stages RISS-Ⅲ and non-tandem ASCT. Conclusion:Tandem ASCT not only significantly improves the depth of remission but also further enhances 2-year PFS/OS of HRMM patients. It is a recommended treatment for HRMM.
4.Efficacy of modified anterior robot-assisted laparoscopic radical prostatectomy with preservation of Retzius space in 10 cases
Hui LI ; Chao YANG ; Kaihong WANG ; Yida ZHANG ; Ju GUO ; Bin FU ; Runfu CAO
Journal of Modern Urology 2023;28(3):201-205
【Objective】 To investigate the safety, feasibility and clinical efficacy of modified anterior robot-assisted laparoscopic radical prostatectomy (RALRP) with preservation of Retzius space. 【Methods】 The clinical data of 10 patients who underwent RALRP using the modified anterior approach to preserve the Retzius space in our hospital during June 2021 and March 2022 were retrospectively analyzed, including the preoperative, intraoperative, postoperative and follow-up data. 【Results】 All operations were successful without conversion to open surgery. The average operation time (robotic arm operation time) was (98.6±47.7) min, blood loss (105.0±57.3) mL, postoperative drainage tube indwelling time (5.3±1.3) d, postoperative urinary catheter indwelling time (7.2±0.8) d, and postoperative hospital stay (9.2±2.2) d. Urinary continence was achieved immediately after removal of the urinary catheter in 6 patients, 2 patients recovered 2 weeks after extubation, and 2 patients recovered 3 months after extubation. Postoperative pathology showed pT2a stage in 1 case, pT2b stage in 2 cases, and pT2c stage in 7 cases; Gleason score was 6-7 points; all postoperative resection margins were negative. During the follow-up of 3-12 months, no tumor recurrence was observed, and no patient was readmitted due to surgical complications. 【Conclusion】 RALRP with modified anterior approach to preserve the Retzius space is safe and feasible, with no serious complications during and after surgery, and the early postoperative urinary continence effect is comparable to that of the posterior approach.
5.Association between body mass index and mortality among older Chinese: evidence from CHARLS
Junping WANG ; Zhaojun LU ; Shuo KOU ; Weijun ZHENG ; Kaihong XIE ; Weihao WANG ; Chao RONG
Journal of Preventive Medicine 2022;34(4):346-349
Objective:
To investigate the association between body mass index ( BMI ) and mortality risk among older Chinese based on the China Health and Retirement Longitudinal Study ( CHARLS ).
Methods:
The demographic features, BMI, prevalence of chronic diseases and mortality among the elderly at ages of 60 years and greater were captured from the CHARLS database from 2011 to 2018. A multivariable Cox proportional hazards regression model was used to examine the association between BMI and the risk of death.
Results:
Totally 6 023 subjects were enrolled, including 3 006 men ( 50.09% ) and 3 017 women ( 49.91% ), and 68.69% of the participants ( 4 137 subjects ) were at ages of 60 to 69 years. There were 637 subjects ( 10.58% ) with underweight, 1 544 ( 25.63% ) with overweight, and 557 ( 9.25% ) with obesity. During the follow-up period ( 35 091 person-years ), 1 035 subjects died. Multivariable Cox proportional hazards regression analysis revealed an increased risk of mortality among the underweight elderly ( HR=1.496, 95%CI: 1.261-1.775 ) and a reduced risk of mortality among the obese elderly ( HR=0.671, 95%CI: 0.511-0.881 ) relative to the elderly with normal weight, after adjustment for age, gender, smoking, household registration, administration of anti-diabetic drugs, administration of anti-dyslipidemia drugs, and administration of anti-hypertensive drugs.
Conclusion
It is found that the risk of mortality among the Chinese elderly correlatives with BMI through the analysis of CHARLS data.
6.Deficiency in glutathione synthesis and reduction contributes to the pathogenesis of colitis-related liver injury.
Liangliang WANG ; Ruyue HAN ; Kaihong ZANG ; Pei YUAN ; Hongyan QIN
Journal of Central South University(Medical Sciences) 2022;47(3):271-279
OBJECTIVES:
Liver disease is the most common extra-intestinal manifestation of ulcerative colitis (UC), but the underlying pathogenesis is still not clarified. It is well accepted that the occurrence of UC-related liver disease has close correlation with immune activation, intestinal bacterial liver translocation, inflammatory cytokine storm, and the disturbance of bile acid circulation. The occurrence of UC-related liver disease makes the therapy difficult, therefor study on the pathogenesis of UC-related liver injury is of great significance for its prevention and treatment. Glutathione (GSH) shows multiple physiological activities, such as free radical scavenging, detoxification metabolism and immune defense. The synthesis and the oxidation-reduction all contribute to GSH antioxidant function. It is reported that the deficiency in hepatic GSH antioxidant function participates in multiple liver diseases, but whether it participates in the pathogenesis of UC-related liver injury is still not clear. This study aims to investigate the feature and underlying mechanism of GSH synthesis and oxidation-reduction function during the development of UC, which will provide useful information for the pathogenesis study on UC-related liver injury.
METHODS:
UC model was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS)-ethanol solution (5 mg/0.8 mL per rat, 50% ethanol) via intra-colonic administration in rats, and the samples of serum, liver, and colon tissue of rats were collected at the 3rd, 5th, and 7th days post TNBS. The severity degree of colitis was evaluated by measuring the disease activity index, colonic myeloperoxidase activity, and histopathological score, and the degree of liver injury was evaluated by histopathological score and the serum content of alanine aminotransferase. Spearman correlation analysis was also conducted between the degree of colonic lesions and index of hepatic histopathological score as well as serum aspartate aminotransferase level to clarify the correlation between liver injury and colitis. To evaluate the hepatic antioxidant function of GSH in UC rats, hepatic GSH content, enzyme activity of GSH peroxidase (GSH-Px), and GSH reductase (GR) were determined in rats at the 3rd, 5th, and 7th days post TNBS, and the protein expressions of glutamine cysteine ligase (GCL), GSH synthase, GSH-Px, and GR in the liver of UC rats were also examined by Western blotting.
RESULTS:
Compared with the control, the disease activity index, colonic myeloperoxidase activity, and histopathological score were all significantly increased at the 3rd, 5th, and 7th days post TNBS (all P<0.01), the serum aspartate aminotransferase level and hepatic histopathologic score were also obviously elevated at the 7th day post TNBS (all P<0.05). There was a significant positive correlation between the degree of liver injury and the severity of colonic lesions (P=0.000 1). Moreover, compared with the control, hepatic GSH content and the activity of GSH-Px and GR were all significantly decreased at the 3rd and 5th days post TNBS (P<0.05 or P<0.01), and the protein expressions of GCL, GSH-Px, and GR were all obviously down-regulated at the 3rd, 5th, and 7th days post TNBS (P<0.05 or P<0.01).
CONCLUSIONS
There is a significant positive correlation between the degree of liver injury and the severity of colonic lesions, and the occurrence of reduced hepatic GSH synthesis and decreased GSH reduction function is obviously earlier than that of the liver injury in UC rats. The reduced hepatic expression of enzymes that responsible for GSH synthesis and reduction may contribute to the deficiency of GSH synthesis and oxidation-reduction function, indicating that the deficiency in GSH antioxidant function may participate in the pathogenesis of UC related liver injury.
Animals
;
Antioxidants
;
Aspartate Aminotransferases
;
Colitis/chemically induced*
;
Colitis, Ulcerative/metabolism*
;
Colon/pathology*
;
Glutathione/biosynthesis*
;
Liver/metabolism*
;
Peroxidase/metabolism*
;
Rats
;
Trinitrobenzenesulfonic Acid
7. Feasibility study of the multi-slice dual-source CT double turbo flash mode for one-step coronary and carotid-cerebrovascular CT angiography in patients with heart rate variability
Yunfeng BAO ; Xiaoying HUANG ; Zhifei LI ; Fangkai GUO ; Mingjuan ZHAO ; Kaihong WANG ; Shenjie CAO ; Yingmin CHEN
Chinese Journal of Radiology 2020;54(2):95-100
Objective:
To investigate the feasibility of one-step coronary and carotid-cerebrovascular computed tomography angiography (CTA) using high-pitch Double Turbo Flash mode and to analyze the image quality and radiation dose in patients with heart rate variability using multi-slice detector dual-source CT.
Methods:
A total of 79 patients with heart rate variability higher than 3 beat/min (bpm) were retrospectively analyzed. They were grouped by the scanning methods. Group A (
8.Preparation of immobilized Lactobacillus plantarum agent for silage.
Yunhao SONG ; Null ; Ruigang WANG ; Yongqing WAN ; Jinnan GAO ; Ruihua TIAN ; Kaihong DUAN
Chinese Journal of Biotechnology 2018;34(9):1518-1527
Lactic acid bacteria and cellulose degrading bacteria play an important role in fermentation process of silage, because they can prevent the rancidity and increase the nutritive value of silage. But the propagation of lactic acid bacteria will inhibit the activity of cellulose degrading bacteria in the silage fermentation system. This problem can be solved by releasing lactic acid bacteria and cellulose degrading bacteria in different time. Therefore, we immobilized lactic acid bacteria as a microbial agent for sustained release. Firstly, the optimal balling concentration of the composite immobilized carrier and composite immobilized carrier were obtained by immobilization of blank balls and corncob adsorbed Lactobacillus plantarum S1 respectively. The best immobilization condition of L. plantarum S1 was obtained by comparing the immobilized rate and balling effect of two kinds of balls, which were embedded by sodium alginate (SA), CMC-Na and embedded-crosslinked by SA, CMC-Na, polyvinyl alcohol (PVA). The results showed that the best balling concentration was achieved by using 6% PVA+0.4% SA+0.3% CMC-Na for embedding-crosslinking and 1.2% SA+0.5% CMC-Na for direct embedding respectively. In addition, comparing with the mechanical strength and embedding rate of five kinds of immobilization process, the best immobilized process was obtained by adding of the mixture of immobilized carriers (1.2%SA+ 0.5%CMC-Na) and corncob adsorbed L. plantarum S1 slowly into 4% CaCl₂ for 24 hours. The corncob adsorption and SA embedding methodology can effectively increase the embedding efficiency of Lactobacillus plantarum S1.
9.Percutaneous punctured transcatheter device closure of ventricular septal defect
Xuming MO ; Jirong QI ; Wei PENG ; Kaihong WU ; Zhulun ZHUANG ; Zhiqi WANG ; Yuzhong YANG ; Yu FENG ; Di YU ; Weisong ZUO
Chinese Journal of Thoracic and Cardiovascular Surgery 2017;33(10):577-579
Objective To explore the feasibility of percutaneous puncture for ventricular septal defect(VSD).Methods From March 2015,we did percutaneous punctured transcatheter device closure of VSD for 22 patients.The patients included 15 males and 7 females with age from 2 years 6 months to 11 years 7 months, weight from 13.5 kg to 44.0 kg.Among 22 pa-tients,6 were diagnosed with residual shunt after VSD repair, with size of residual shunt from 4.8 mm to 7.0 mm.Residual shunts are perimembranous, conoventricular and intracristal.The other 16 patients were diagnosed with isolated VSD,with de-fect size from 3.5 to 5.1 mm.For all patients,we punctured directly through the right ventricular surface into the right ventri-cle in the 3th or 4th intercostal space of the left sternal border.Next, we succeeded to extract the guide wire after inserting a conveyor tube for 21 patients.Subsequently,7-10 mm VSD closure device were delivered via the conveyor tube.Only one patient was changed to perform occlusion of VSD through chest small incision due to improper selection of punctured position. Results A total of 21 closure devices were placed for 21 patients.18 of them are equilateral device,and 3 are decentered de-vice,with size from 5 mm to 10 mm.There were small amount of pericardial effusion in 4 patients using TEE examination,and no future treat was performed after observation.For one-year follow-up, all patients have recovered very well.Conclusion Percutaneous punctured transcatheter device closure fits for treatment for children with residual shunt after VSD repair and isola-ted VSD.It has a good recent result.


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