1.Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract improves radiation-induced pulmonary fibrosis in rats by regulating NLRP3/caspase-1/GSDMD pyroptosis pathway
Chun-Zhen REN ; Jian-Fang YUAN ; Chun-Ling WANG ; Xiao-Dong ZHI ; Qi-Li ZHANG ; Qi-Lin CHEN ; Xin-Fang LYU ; Xiang GAO ; Xue WU ; Xin-Ke ZHAO ; Ying-Dong LI
Chinese Pharmacological Bulletin 2024;40(11):2124-2131
Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P<0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P<0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P<0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P<0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.
2.Effects of graft recipient weight ratio on early prognosis of split liver transplantation in children
Linxiao LI ; Chong DONG ; Chao SUN ; Kai WANG ; Yang YANG ; Zhen WANG ; Xinzhe WEI ; Ganlin CUI ; Weihan LI ; Wei GAO
Chinese Journal of Organ Transplantation 2024;45(5):315-322
Objective:To explore the effects of graft recipient weight ratio (GRWR) on the early prognosis (within 1 year after operation) of recipients of different ages after split liver transplantation (SLT) in children.Methods:From April 2015 to December 2022, the relevant clinical data were retrospectively reviewed for 188 children aged under 12 years undergoing initial SLT. Based upon operative age, they were assigned into groups of L (age≤18 months, 123 cases) and H (18 months< age≤12 years, 65 cases). Draw receiver operating characteristic (ROC) curves for predicting survival rates in H and L groups using GRWR and determine the cut-off value, and subgroup dassification was based the value. Compare the general condition, intraoperative condition, postoperative condition, and major complications of recipients. Follow-ups were conducted until 12 months post-SLT, death or retransplantation within 12months post-SLT. Kaplan-Meier survival rate analysis was utilized for comparing early postoperative survival rate of recipient/graft. The incidence of major early postoperative complications was examined by χ2 test or Fisher exact probability method. Results:The survival rate of recipients at Month 12 post-SLT was 92.6% (174/188), and graft survival rate was 91.0% (171/188). The survival rate of recipients in group L at Month 12 post-SLT was 94.3% (116/123), and graft survival rate was 92.7% (114/123). The GRWR value determined of 3.1 %. According to the level of GRWR, group L was divided into groups of L-L (GRWR≤3.1%, 36 cases) and L-H (GRWR>3.1%, 87 cases) while group H groups of H-L (GRWR≤3.1%, 55 cases) and H-H (GRWR>3.1%, 10 cases). The survival rates of recipients in groups L-L/L-H were 88.9% (32/36) and 96.6% (84/87) at Month 12 post-SLT. Inter-group difference was not statistically significant ( P=0.077). Graft survival rates were 83.3% (30/36) and 96.6% (84/87 ). Inter-group difference was statistically significant ( P=0.007). The intraoperative cold ischemia time were 479.0 (194.0, 593.0) min and 204.0 (122.0, 495.0) min in groups L-L/L-H. Inter-group difference was statistically significant ( P=0.002 ). The incidence of hepatic artery thrombosis were 13.9 % (5/36) and 2.3 % (2/87) in groups L-L/L-H. Inter-group difference was statistically significant ( P=0.036). The survival rate of recipients in group H at Month 12 post-SLT was 89.2% (58/65), and graft survival rate was 87.7% (57/65). No significant inter-group difference existed during surgery ( P>0.05 ). The survival rates of recipients in group H-L/H-H at Month 12 post-SLT were 92.7 % (51 /55) and 70.0 % (7/10 ). Inter-group difference was statistically significant ( P=0.019). Graft survival rates were 90.9% (50/55) and 70.0% (7/10). Inter-group difference was statistically significant ( P=0.036). No significant inter-group difference existed in the incidence of complications ( P>0.05) . Conclusion:During pediatric SLT, recipients of different ages have different requirements for GRWR. GRWR≤3.1 % implies poor early prognosis of recipients aged ≤18 months and GRWR>3.1% is associated with poor early prognosis of recipients aged between 18 months and 12 years.
3.Risk factors and treatments of portal vein thrombosis after pediatric living donor liver transplantation
Ganlin CUI ; Chong DONG ; Chao SUN ; Kai WANG ; Weiping ZHENG ; Yang YANG ; Zhen WANG ; Xinzhe WEI ; Linxiao LI ; Weihan LI ; Wei GAO
Chinese Journal of Organ Transplantation 2024;45(11):788-795
Objective:To explore the risk factors and treatments of portal vein thrombosis (PVT) in children after pediatric living donor liver transplantation (pLDLT) .Method:From January 2014 to December 2021, the relevant clinical data were retrospectively reviewed for 975 LDLT children at Department of Pediatric Organ Transplantation of Tianjin First Central Hospital. Based upon the postoperative occurrence of PVT, they were assigned into two groups of PVT (19 cases) and non-PVT (956 cases). Univariate and multivariate analyses were performed for screening the risk factors of PVT post-LDLT and discussing the managements and prognoses of PVT.Result:Among them, overall incidence of PVT post-LDLT was 1.9% (19/975), and median time for an initial occurrence of PVT 8 (1-495) day. Single-factor analysis indicated that donor height ( P=0.014), operative duration ( P=0.002) and vascular interposition ( P=0.001) were correlated with the occurrence of postoperative PVT post-pLDLT. Multifactorial analysis revealed that operative duration ( P=0.008) and vascular interposition ( P<0.01) were independent risk factors for PVT post-pLDLT. For 19 cases of postoperative PVT, the measures included surgical thrombectomy (8 cases), urokinase thrombolysis plus warfarin anticoagulation (3 cases), interventional treatment (3 cases), warfarin anticoagulation (4 cases) and retransplantation (1 cases). After treatment, the outcomes were a disappearance of PVT (15 cases), symptomatic improvement (2 cases) and unrelated mortality (2 cases) . Conclusion:During pLDLT, intraoperative placement of blood vessels and operative duration are independent risk factors for the occurrence of PVT. Timely standardized treatment may achieve satisfactory therapeutic outcomes.
4.Treatment of uncontrolled motion faults of TiRobot surgery robot:Four case reports
Ran GAO ; Da-Wei GUO ; Zhen-Wei WANG ; Wei GUO ; Dong-Yan LIU
Chinese Medical Equipment Journal 2024;45(11):117-120
The composition and working principle of TiRobot surgery robot were introduced.Four cases of uncontrolled motion faults of the robot in image alignment of the main control trolley,precision of the navigation and positioning instruments,positional offset of the robotic arm and initialization of the optical tracking system were explored in terms of phenomenon,cause and treatment.References were provided for medical engineers to treat similar faults.[Chinese Medical Equipment Journal,2024,45(11):117-120]
5.In vitro expression and functional analyses of the mutants p.R243Q,p.R241C and p.Y356X of the human phenylalanine hydroxylase
Yong-Hong PANG ; Xiang-Yu GAO ; Zhen-Ya YUAN ; Hui HUANG ; Zeng-Qin WANG ; Lei PENG ; Yi-Qun LI ; Jie LIU ; Dong LIU ; Gui-Rong CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):188-193
Objective To study the in vitro expression of three phenylalanine hydroxylase(PAH)mutants(p.R243Q,p.R241C,and p.Y356X)and determine their pathogenicity.Methods Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein.Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells.Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants,and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay.Results Bioinformatics analysis predicted that all three mutants were pathogenic.The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control(P>0.05),while the mRNA expression level of the p.Y356X mutant significantly decreased(P<0.05).The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control(P<0.05).The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control(P<0.05),while there was no significant difference between the p.R243Q mutant and the wild type control(P>0.05).Conclusions p.R243Q,p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells,with p.R241C and p.Y356X mutants also affecting the function of PAH protein.These three PAH mutants are to be pathogenic.[Chinese Journal of Contemporary Pediatrics,2024,26(2):188-193]
6.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
7.Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China
Feng Yu FAN ; Xin Dong LIU ; Wang Yi CHEN ; Chao Xi OU ; Zhi Qi MAO ; Ting Ting YANG ; Jiang Xi WANG ; Cong Wen HE ; Bing ZHAO ; Jiang Zhen LIU ; Maiweilanjiang ABULIMITI ; Maimaitiaili AIHEMUTI ; Qian GAO ; Lin Yan ZHAO
Biomedical and Environmental Sciences 2024;37(2):157-169
Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.
8.Cohort study on the incidence,mortality and risk factors of malignant tumors in the middle-aged and elderly population in Chengguan district of Lanzhou
Xing-Wen SHI ; Hong-Tao YIN ; Jin-Jin LIU ; Yan MA ; Ting SUN ; Gao-Peng TIAN ; Jing-Jing XIE ; Dong-Hu ZHEN
Medical Journal of Chinese People's Liberation Army 2024;49(7):761-769
Objective To analyze the incidence and mortality of malignant tumors among the middle-aged and elderly population in Chengguan district of Lanzhou from 2011 to 2021,and to discuss the related risk factors.Methods Using the research data of REACTION in Lanzhou,an epidemiological survey was conducted through cluster sampling in three communities in Chengguan district of Lanzhou since April 2011.The target population was middle-aged and elderly residents over 40 years old.Two follow-up surveys were carried out in 2014-2016 and 2021 successively,and 6543 people with complete follow-up data were finally included.The incidence and mortality rates of malignant tumors were calculated,as well as their age standardized rates with reference to the age composition of Segi's world standard population.Multivariate Cox regression analysis was used to screen the risk factors affecting the incidence and mortality of malignant tumors.Results After an average follow-up of 10.6 years,314 new cases of malignant tumors were found in middle-aged and elderly residents in Chengguan district of Lanzhou,with an incidence rate and age standardized incidence rate of 454.30/100 000 and 128.93/100 000,respectively.A total of 158 deaths were attributed to malignant tumors,with a mortality rate and age standardized rate of 228.41/100 000 and 607.9/100 000,respectively;The age standardized incidence rate and mortality rate of malignant tumors males were both higher than those females(P<0.05).During the follow-up period,the age standardized incidence rate of malignant tumors in the general population showed an significant upward trend(P<0.05),whereas the age standardized mortality rate gradually decreased after a brief increase(P<0.05).Lung cancer,colorectal cancer,gastric cancer,and liver cancer were the main types of malignant tumors ranking in the top five in terms of incidence and mortality by gender.Multivariate Cox regression results indicate that male,age≥60 years old,college education level or above,smoking history,drinking history,having been hit by major stressful events,central obesity,hypertension,and coronary heart disease are risk factors for the onset or death of malignant tumors(HR>1).Married,with family size≥4,frequent consumption of fresh fruit,frequent consumption of fresh vegetables,frequent consumption of grains and tubers are protective factors for the onset or death of malignant tumors(HR<1).Conclusion The incidence of malignant tumors among middle-aged and elderly people in Chengguan district of Lanzhou from 2011 to 2021 showed an increasing trend,while the overall mortality was decreasing.Our study indicates early cancer screening in elderly populations,maintaining a healthy lifestyle and strengthening the management of chronic diseases are crucial for the prevention and treatment of malignant tumors.
9.Effect of Interval Between Neoadjuvant Chemotherapy and Surgery on Oncological Outcomes in Poor Responders With Locally Advanced Breast Cancer
Man LONG ; Chunxia LI ; Keyu MAO ; Zhenhui LI ; Zhen LI ; Guili DONG ; Xia ZHENG ; Songliang GAO ; Zhuolin LI ; Guangjun YANG ; Yu XIE
Journal of Breast Cancer 2024;27(4):270-280
Purpose:
The interval between neoadjuvant chemotherapy (NAC) and surgery for locally advanced breast cancer (LABC) remains controversial. At the same time, the prognostic effect of delayed surgery in patients with poor responses is currently unclear.
Methods:
Data was collected from patients who had poor responses to NAC and underwent modified radical surgery from January 2013 to December 2018. The interval from completion of NAC to surgery was divided into two groups: a longer (greater than four weeks) or shorter (four weeks or less) interval. The associations of these interval groups with overall survival (OS) and recurrence-free survival (RFS) were evaluated by multivariable Cox models adjusting for the existing prognostic factors. Propensity score matching (PSM) was used to minimize election bias.
Results:
A total of 1,229 patients (mean age, 47.2 ± 8.9 years; median follow-up duration, 32.67 [6.57–52.63] months) were included. The 5-year OS rates were 73.2% and 60.8% in the shorter (n = 171) and longer interval group (n = 1,058), respectively, while the 3-year RFS rates were 80.8% and 71.7%, respectively. In multivariate Cox analysis, the longer interval was associated with an increased risk of mortality (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.01–2.02; p = 0.046) and recurrence (HR, 1.50; 95% CI, 1.12–1.99; p = 0.006).There was an interaction between the molecular subtype and the surgery interval for OS (pinteraction = 0.014) and RFS (pinteraction = 0.027). After PSM, no significant difference in OS (p = 0.180) and RFS (p = 0.069) was observed between the two groups.
Conclusion
Among LABC patients with a poor response, those with a longer interval between NAC and surgery had worse OS and RFS. The results indicate that these patients should receive modified radical surgery timely, which may in turn improve their prognosis.
10.Study on the effects and mechanism of total glucosides of paeony on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside in the treatment of eczema
Minghao ZHANG ; Zhen WANG ; Yiying GAO ; Pengkun XUE ; Weiyang MA ; Wenxia DONG ; Liya MA ; Dawei ZHANG
China Pharmacy 2023;34(4):444-449
OBJECTIVE To investigate the effects of total glucosides of paeony (TGP) on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside (TWP) in the treatment of eczema. METHODS Totally 50 SD male rats were collected to establish eczema model by sensitizing with 2,4-dinitrofluorobenzene-acetone olive oil solution (volume ratio was 4∶1) on the abdominal area and provoking on the back and ear. Model rats were randomly divided into model group, loratadine group (0.9 mg/kg), TWP group (9.45 mg/kg), TGP group (162 mg/kg) and compatibility group (TWP 9.45 mg/kg+TGP 162 mg/kg), with 10 rats in each group. Other 10 rats were collected to set as normal group. Three days after the first sensitization, administration groups were given relevant medicine intragastrically, and normal group and model group were given constant volume of 0.1% CMC-Na solution intragastrically, once a day, for consecutive 21 d. Twenty-four hours later after the final administration, the general condition of rats in each group was observed, and the eczema area and severity index (EASI) were scored; ear swelling degree of rats was measured, and the skinhistomorphology observation and pathological score were performed; protein expressions of p38 mitogen-activated 13938427612@126.com protein kinase (p38 MAPK), phosphorylated p38 MAPK (p- MAPK) and phosphorylation level of p38 MAPK in rat skin tissue were detected; the levels of inflammatory indexes (interleukin-4, interferon- γ), liver and kidney function indexes [glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), serum creatinine (SCr) and blood urea nitrogen (BUN)] and oxidant stress indexes [total superoxide dismutase (T-SOD) and malondialdehyde (MDA)] were measured. RESULTS Compared with normal group, EASI score, ear swelling degree, pathological score, protein expressions of p38 MAPK and p-p38 MAPK, phosphorylation level of p38 MAPK, the levels of inflammatory indexes and BUN were all increased significantly in model group (P<0.05). Compared with model group, EASI scores, ear swelling degree, pathological scores, protein expressions of p38 MAPK and p-p38 MAPK, phosphorylation levels of p38 MAPK and levels of inflammatory indexes were all improved significantly in administration groups (P<0.05). The levels of GPT, GOT, SCr and BUN were increased significantly in TWP group, while the serum levels of GOT and SCr in TGP group and serum level of SCr in loratadine group were all decreased significantly (P<0.05). The levels of T-SOD in liver and kidney tissue were all decreased significantly in TWP group and compatibility group, while the levels of MDA were increased significantly (P<0.05). The compatibility group showed more obvious effect in improving the ear swelling degree, pathological score, p38 MAPK expression and its phosphorylation level and levels of inflammatory indexes, and could reverse the abnormality of liver and kidney indexes caused by TWP (P<0.05). CONCLUSIONS The combination of TGP and TWP has the effects of anti-inflammatory, synergistic and hepatorenal detoxification in eczema model rats. Its mechanism may be associated with down-regulating the expression of serum proinflammatory indexes and inhibiting the activation of p38 MAPK pathway.

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