1.Ursolic acid in
Yanhong BAO ; Qiang WANG ; Wenlong ZHANG ; Na GE ; Nan LI ; Jun SU ; Kexin LI
Journal of Clinical Hepatology 2023;39(7):1617-1626
Objective To investigate the inhibitory effect of ursolic acid in Hippophae rhamnoides L. on hepatocyte apoptosis in rats with alcoholic liver disease based on the mitochondria-cytochrome c pathway. Methods A total of 50 specific pathogen-free male Wistar rats were divided into normal control group, alcohol model group, and low-, middle-, and high-dose ursolic acid groups using a random number table, with 10 rats in each group. The rats in the normal control group were given normal saline by gavage once a day for 8 weeks; the rats in the alcohol model group were given alcohol at increasing concentrations by gavage for 8 consecutive weeks; the rats in the low-, middle-, and high-dose ursolic acid groups were given ursolic acid at a dose of 50, 100, and 150 mg/kg, respectively, followed by an equal volume of alcohol as the model group 1 hour later. Serum liver function parameters were measured for each group; HE staining was used to observe liver histopathology; an electron microscope was used to observe hepatocyte ultrastructure; the TUNEL method was used to measure hepatocyte apoptosis; Western Blotting was used to measure the protein expression levels of cytochrome c and activated caspase-3 in hepatocyte mitochondria and cytoplasm. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significant reductions in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase (all P < 0.05). The rats in the alcohol model group had disordered arrangement of hepatic cords with marked hepatocyte edema and fatty degeneration, while those in the middle- and high- dose ursolic acid groups had basically normal arrangement of hepatic cords and a significant improvement in hepatocyte fatty degeneration, as well as a significant increase in the number of hepatocyte mitochondria and a significant improvement in morphology. Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significantly lower hepatocyte apoptosis rate and protein expression levels of cytochrome c and caspase-3 in cytoplasm (all P < 0.05). Conclusion Ursolic acid in Hippophae rhamnoides L. can improve the liver function and histomorphology of rats with alcoholic liver disease, possibly by inhibiting the release of cytochrome c in hepatocyte mitochondria, the activation of caspase-3, and the apoptosis of hepatocytes via the mitochondria-cytochrome c pathway.
2.Influencing factors of death in patients with MDR-TB based on Bayesian Cox regression model
Zhiyong WANG ; Yuqi ZHANG ; Wenlong GAO ; Zongyu LI ; Ming LI ; Qiuxia LUO ; Yuanyuan XIANG ; Kai BAO
Journal of Central South University(Medical Sciences) 2023;48(11):1659-1668
Objective:Multidrug-resistant tuberculosis(MDR-TB)has a high mortality and is always one of the major challenges in global TB prevention and control.Analyzing the factors that may impact the adverse outcomes of MDR-TB patients is helpful for improving the systematic management and optimizing the treatment strategies for MDR-TB patients.For follow-up data,the Cox proportional hazards regression model is an important multifactor analysis method.However,the method has significant limitations in its application,such as the fact that it is difficult to deal with the impacts of small sample sizes and other practical issues on the model.Therefore,Bayesian and conventional Cox regression models were both used in this study to analyze the influencing factors of death in MDR-TB patients during the anti-TB therapy,and compare the differences between these 2 methods in their application. Methods:Data were obtained from 388 MDR-TB patients treated at Lanzhou Pulmonary Hospital from November 1,2017 to March 31,2021.Survival analysis was employed to analyze the death of MDR-TB patients during the therapy and its influencing factors.Conventional and Bayesian Cox regression models were established to estimate the hazard ratios(HR)and their 95% confidence interval(95% CI)for the factors affecting the death of MDR-TB patients.The reliability of parameter estimation in these 2 models was assessed by comparing the parameter standard deviation and 95% CI of each variable.The smaller parameter standard deviation and narrower 95% CI range indicated the more reliable parameter estimation. Results:The median survival time(1st quartile,3rd quartile)of the 388 MDR-TB patients included in the study was 10.18(4.26,18.13)months,with the longest survival time of 31.90 months.Among these patients,a total of 12 individuals died of MDR-TB and the mortality was 3.1%.The median survival time(1st quartile,3rd quartile)for the deceased patients was 4.78(2.63,6.93)months.The majority of deceased patients,accounting for 50%,experienced death within the first 5 months of anti-TB therapy,with the last mortality case occurring within the 13th month of therapy.The results of the conventional Cox regression model showed that the risk of death in MDR-TB patients with comorbidities was approximately 6.96 times higher than that of patients without complications(HR=6.96,95% CI 2.00 to 24.24,P=0.002)and patients who received regular follow-up had a decrease in the risk of death by approximately 81% compared to those who did not receive regular follow-up(HR=0.19,95% CI 0.05 to 0.77,P=0.020).In the results of Bayesian Cox regression model,the iterative history plot and Blue/Green/Red(BGR)plot for each parameter showed the good model convergence,and parameter estimation indicated that the risk of death in patients with a positive first sputum culture was lower than that of patients with a negative first sputum culture(HR=0.33,95% CI 0.08 to 0.87).Additionally,compared to patients without complications,those with comorbidities had an approximately 6.80-fold increase in the risk of death(HR=7.80,95% CI 1.90 to 21.91).Patients who received regular follow-up had a 90% reduction in the risk of death compared to those who did not receive regular follow-up(HR=0.10,95% CI 0.01 to 0.30).The comparison between these 2 models showed that the parameter standard deviations and corresponding 95% CI ranges of other variables in the Bayesian Cox model were significantly smaller than those in the conventional model,except for parameter standard deviations of receiving regular follow-up(Bayesian model was 0.77;conventional model was 0.72)and pulmonary cavities(Bayesian model was 0.73;conventional model was 0.73). Conclusion:The first year of anti-TB therapy is a high-risk period for mortality in MDR-TB patients.Complications are the main risk factors of death in MDR-TB patients,while patients who received regular follow-up and had positive first sputum culture presented a lower risk of death.For data with a small sample size and low incidence of outcome,the Bayesian Cox regression model provides more reliable parameter estimation than the conventional Cox model.
3.Hybrid aortic arch replacement for aortic arch disease
Ren WANG ; Guoxing WENG ; Qi XIE ; Zhiqun CHEN ; Jiayin BAO ; Rongdong XIAO ; Huan WANG ; Zhi DOU ; Fuzhen ZHENG ; Wenlong CAI ; Yuanxiang CHEN
Chinese Journal of Thoracic and Cardiovascular Surgery 2017;33(6):347-350
Objective we assessed our institutional outcomes of hybrid treatment for aortic arch disease with supra-aortic debranching and endovascular stent graft repair.Methods From March 2016 to November 2016,6 patients underwent Hybrid total aortic arch repair:1 had aortic arch pseudoaneurysm;1 had type Ⅲ aortic dissection;4 had aortic arch aneurysm because of hypotension,of whom 1 with aneurysm prerupture and 1 with Aortic intramural hematoma.Supra-aortic vessels were involved and high-risk for traditional operations in all patients.Bifurcated artificial vessels were used,main vessel was end-to-side anastomosed with ascending aorta.Branching vessel were end-to-end anastomosed with right innominate artery and left subclavian artery,end-to-side anastomosed with left common carotid artery.Then,stent graft was implanted into ascending aorta and aortic arch.All patients were followed postoperatively,with regularly contrast computed tomography angiogram (CTA) and echocardiography(discharge,three months,six months,and yearly).Results Hybrid procedure with supra-aortic debranching and endovascular stent graft repair were completed in all patients,technical success rate was 100%.There were no perioperative obvious morbidity and mortality,follow-up period were 2-9 months.1 patients had stroke during follow-up period,condition improved after treatment.Supra-aortic vessels were patency and there were no endoleak in all patients.There were no recurrent aortic disease during follow-up period.Conclusion Hybrid aortic arch replacement can be performed with good postoperative and early results in high-risk patients for traditional open repair.
4.The relation between vitamin D deficiency and susceptibility to spinal tuberculosis
Liang TANG ; Yucheng BAO ; Ruixiao GAO ; Chenfu HAN ; Xiaochen SUN ; Wenlong ZHANG ; Shiqing FENG
Tianjin Medical Journal 2016;44(12):1492-1495
Objective To explore the relation between vitamin D deficiency and susceptibility to spinal tuberculosis. Methods A total of 163 hospitalized patients with untreated spinal tuberculosis in Tianjin Haihe hospital were enrolled in this study from June 2013 to May 2016. A total of 170 individuals participated in health examination program at the same period were enrolled as the control group. The serum level of 25-hydroxyvitamin D [25(OH)D] was measured by enzyme linked immunosorbent assay. The 25(OH)D grading included serious deficiency group (<25 nmol/L), deficiency group (≥25 nmol/L and <50 nmol/L), insufficiency group (≥50 nmol/L and <75 nmol/L) and sufficiency group (≥75 nmol/L). Histopathological classification was confirmed by intraoperative findings. Results The serum level of 25(OH)D was significantly lower in patient group [23.99(20.55,29.54)nmol/L] than that of control group [42.94(35.68,51.04) nmol/L] (P<0.01), and which was also significantly lower in four seasons than that of controls (P<0.05). The serum levels of 25(OH)D were significantly higher in summer group than those of winter group in both patient and control groups (P<0.008 3). The proportion of patients with serious deficiency of 25(OH)D was significantly higher in spring and winter groups in patient group, which was significantly lower in summer group (P<0.01). There was no significant difference in patients with serious deficiency of 25(OH)D between four seasons (P<0.01). For control group, there was a higher proportion of cases with deficiency of 25(OH)D in four seasons, and there was no significant difference in the distribution of seasons (P>0.05). In patient group, there were 107 cases of caseous necrosis type, 56 cases of hyperplasia type, and the proportion of caseous necrosis type was significantly higher in the severe deficiency group (79.17%, 76/96) than that of deficiency group (46.27%, 31/67, P<0.01). Conclusion Excluding the effect of season, vitamin D deficiency is associated with susceptibility to spinal tuberculosis and histopathologic classification.
5.Release and distribution of anti-tuberculosis drug delivery materials locally oriented in the rabbit radius
Ruirui MIAO ; Wenlong ZHANG ; Yucheng BAO ; Mei LI
Chinese Journal of Tissue Engineering Research 2016;20(38):5691-5696
BACKGROUND:Polylactic acid-glycolic acid polymer is a sustained-release material with relatively large drug loading and long-term release abilities that can degrade with cel growth in the body. However, its poor hydrophily easily leads to aseptic inflammation that is detrimental to the body’s recovery. OBJECTIVE:To study the release and distribution of anti-tuberculosis drug delivery materials local y oriented within the rabbit radius. METHODS:After modeling, 20 New Zealand white rabbits with distal radius bone defect were randomly divided into a control group and an experimental group, which were respectively given implantation of isoniazid-rifampicin polylactic acid-glycolic acid polymer/β-tricalcium phosphate material and isoniazid-rifampicin polylactic acid-glycolic acid polymer into the defect. Then, X-ray examination of the defect region was conducted at weeks 4, 8, 12 post implantation. Histological observation and detection of peripheral blood or local blood concentration were performed at week 12. RESULTS AND CONCLUSION:After implantation, Lane-Sandhu X-ray scores were significantly higher in the experimental group than the control group (P<0.05). The defect in the experimental group was healed completely with less release residual among newborn bone trabeculae and osteocytes were markedly visible on the material surface, while in the control group, new bone tissues were interconnected with the surrounding bone tissues at the defect site, and less release residual was found. Both peripheral blood and local blood concentrations in the experimental group were significantly higher than those in the control group after implantation (P<0.05). To conclude, the anti-tuberculosis drug delivery material, isoniazid-rifampicin polylactic acid-glycolic acid polymer/β-tricalcium phosphate, has ideal release effect that can stably deliver anti-tuberculosis drugs for a long term at a high bactericidal concentration.
6.Effect of elemene on the expressions of TRAF6 and caspase-8 in H22 liver tumor tissues of mice
Dehou DENG ; Hua SHI ; Yongjun ZHANG ; Wenlong BAO ; Danlin GU
Journal of Chinese Physician 2015;17(2):221-223,227
Objective To investigate the effect of elemene on mRNA expressions of tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) and caspase-8 in tumor tissues of mice bearing hepatoma H22.Methods Forty BALB/c mice models bearing hepatoma H22 were established by subcutaneous inoculating tumor cells.Forty BALB/c mice were randomly divided into 4 groups:model group,low-and high-elemene dosage groups,and cisplatin group.The tumors after executing mice were weighted.The mRNA expressions of TRAF6 and caspase-8 in tumor tissues were detected by quantitative real-time reversetranscription polymerase chain reaction (RT-PCR).Results The dosage of elemene could inhibit tumor growth.The inhibition ratio of cancer in the low-and high-elemene dosage and cisplatin group was 24.2%,27.4%,and 28.2%,respectively.It reduced significantly tumor weights(P <0.01).Compared to the model group,the expression level of TRAF6 mRNA on tumors was decreased significantly,while the expression level of caspase-8 mRNA was increased significantly in the other groups(P < 0.05).Conclusions The present results indicated that molecular mechanism of inhibition of liver cancer growth treated by elemene might be through down-regulating mRNA expressions of TRAF6 and caspase-8,promoting tumor cells apoptosis,and achieving the anti-tumor effect.
7.Practice and exploration of medical equipment's preventive maintenance based on risk analysis.
Miankang CHEN ; Shizhun YU ; Juncheng BAO ; Wenlong ZHANG ; Na ZHOU ; Guanqun XIA
Chinese Journal of Medical Instrumentation 2014;38(2):149-151
This paper analyzes the characteristics of medical equipment's preventive maintenance, and it expounds the objective and methods of introducing risk management to medical equipment's preventive maintenance,what's more,the problem of establishment object and cycle of preventive maintenance was solved scientifically.
Equipment and Supplies, Hospital
;
Maintenance
;
Risk Assessment
8.Practice and Exploration of Medical Equipment's Preventive Maintenance Based on Risk Analysis
Miankang CHEN ; Shizhun YU ; Juncheng BAO ; Wenlong ZHANG ; Na ZHOU ; Guanqun XIA
Chinese Journal of Medical Instrumentation 2014;(2):149-151
This paper analyzes the characteristics of medical equipment's preventive maintenance, and it expounds the objective and methods of introducing risk management to medical equipment's preventive maintenance,what's more,the problem of establishment object and cycle of preventive maintenance was solved scientifical y.
9.Exploration and practice of the medical equipment maintenance management based on HRP.
Miankang CHEN ; Jin ZHANG ; Shizhun YU ; Juncheng BAO ; Wenlong ZHANG ; Zhenghai SHEN
Chinese Journal of Medical Instrumentation 2013;37(1):68-71
Based on HRP (Hospital Resource Planning) system's device management module, A new online information management system is proposed and realized to meet the new challenge of medical devices' repairing and maintenance. the traditional telephone report or online report can all be deal. the repair progress can be visualized in real time PM planning and it's early warning are added.
Equipment and Supplies, Hospital
;
Maintenance and Engineering, Hospital
10.Dual-drug sustained-release carrier:Preparation and performance
Yucheng BAO ; Wenlong ZHANG ; Yong WANG ; Jie ZHANG ; Yongmei WANG
Chinese Journal of Tissue Engineering Research 2013;(29):5345-5350
BACKGROUND: During conventional treatment for bone tuberculosis, there is a low effective concentration of anti-tuberculosis drugs, and the therapeutic effect is poor. OBJECTIVE:To develop a new biomaterial as a slow-release artificial carrier that can be directly implanted into the surrounding tissue of bone tuberculosis, maintain a certain anti-tuberculosis drug concentration for a long time, thereby playing an effective therapeutic action. METHODS:Rifampicin/polylactic acid/glycolic acid microspheres and isoniazid/polylactic acid/glycolic acid microspheres were prepared using the emulsion-solvent evaporation method. Usingα-cyanoacrylate, a biological adhesive, two kinds of microspheres were processed into a long-term slow-release bicomponent drug carrier. Then, in vitro release characteristics of the dual-drug sustained-release carrier were observed. After that, the dual-drug sustained-release carrier was implanted into rabbit intertrochanteric femur bone defects for observing drug release concentrations, histocompatibility and bone defect healing at different time points after drug delivery carrier implantation. RESULTS AND CONCLUSION:For rifampicin/polylactic acid/glycolic acid microspheres, the mean particle size was (240±13)μm, and the drug loading load rate was (26±1.5)%. For isoniazid/polylactic acid/glycolic acid microspheres, the mean particle size was (250±10)μm, and drug loading rate was (28±1.8)%. The in vitro cumulative release rate could reach 80%for rifampicin and 90%for isoniazid at day 90. The in vivo released concentration of rifampicin and isoniazid within 90 days was (0.5±0.4) and (0.6±0.3)μg/g, respectively. There were a smal amount of infiltrated neutrophils between the fascia and muscle fibers after the drug delivery carrier was implanted, and the amount of neutrophils in the muscle were reduced significantly at day 59. X-ray plain film showed that bone defects decreased obviously in size. These findings indicate that this dual-drug sustained-release carrier can maintain a certain anti-tuberculosis drug concentration in the surrounding tissues of bone tuberculosis, which is expected to provide a new type of dual-drug delivery carrier in the surgical treatment of bone tuberculosis.

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