1.c-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2.
Min-Xia SU ; Yu-Lian XU ; Xiao-Ming JIANG ; Mu-Yang HUANG ; Le-Le ZHANG ; Luo-Wei YUAN ; Xiao-Huang XU ; Qi ZHU ; Jian-Li GAO ; Jia-Hong LU ; Xiuping CHEN ; Ming-Qing HUANG ; Yitao WANG ; Jin-Jian LU
Acta Pharmaceutica Sinica B 2022;12(3):1240-1253
The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.
2.Compound oleum lithospermi in improving clinical symptoms of mild to moderate diaper dermatitis: a multicenter, open-labeled, randomized controlled clinical study
Jing TIAN ; Fenglei WEI ; Ping CHEN ; Hong SHU ; Yanping GUO ; Aihua JI ; Qiufang QIAN ; Yonghong LU ; Jinping CHEN ; Yunling LI ; Ting YANG ; Liuhui WANG ; Ji CHEN ; Li SONG ; Su YANG ; Xiangdong WANG ; Hua QIAN ; Xiuping HAN ; Ping LI ; Lin MA
Chinese Journal of Dermatology 2022;55(10):864-868
Objective:To evaluate clinical efficacy and safety of topical compound oleum lithospermi in the treatment of mild to moderate diaper dermatitis.Methods:A multicenter, randomized, positive-drug parallel-controlled clinical trial was conducted in 19 hospitals from July 2019 to August 2020. Children aged 0 - 12 months with mild to moderate diaper dermatitis were enrolled and randomly divided into 2 groups using a random number table: test group topically treated with compound oleum lithospermi, and control group topically treated with zinc oxide cream. The treatment was carried out 6 - 8 times a day for 7 days. Visits were scheduled on days 0 and 7, and total response rate and clinical healing time were evaluated. Changes in the dermatitis family impact (DFI) score were compared between the test group and control group, and adverse events were recorded. Statistical analysis was carried out by using independent-sample t test for normally distributed continuous data, Wilcoxon rank sum test for non-normally distributed continuous data, and chi-square test or Fisher′s exact test for unordered categorical data; survival curves were drawn, and log-rank test was used for comparisons between two groups. Results:A total of 343 children with diaper dermatitis were enrolled in this study. Among them, 31 children violated the protocol, so 312 were included in the per protocol set, including 157 in the test group and 155 in the control group, and all completed the visits on days 0 and 7. The total response rate was significantly higher in the test group (87.26%, 137/157) than in the control group (78.71%, 122/155; χ2 = 4.04, P = 0.044) . The clinical healing time was significantly shorter in the test group (5.33 days) than in the control group (6.13 days; χ2 = 4.67, P = 0.025) . After 7-day treatment, the DFI score significantly decreased in both the 2 groups compared with that before the treatment, but there was no significant difference in the DFI score between the 2 groups (test group: 4.02 ± 6.96, control group: 3.58 ± 5.90, Z = -0.39, P = 0.686) . The incidence of adverse events was 2.92% (5/171) and 5.45% (9/165) in the test group and control group respectively, and there was no significant difference between the 2 groups ( χ2 = 0.03, P = 0.865) . Conclusion:Compound oleum lithospermi can markedly reduce the clinical severity of diaper dermatitis, improve the total response rate, shorten the clinical treatment period, and improve the quality of life of children′s families with a favorable safety profile.
3. Expression of type 1 and type 2 cytokines from serum of coal miners and the evaluation in surveillance of coal workers' pneumoconiosis at earlier stage
Sanqiao YAO ; Ningwei YANG ; Feifei GUO ; Tianbang QIN ; Xiuping ZHU ; Zhigang DONG ; Zhichun LI ; Bijie JIANG ; Jingshun GAO ; Yongcheng YAO ; Guofu ZHANG ; Yang LIU ; Yao LU ; Haibin LI ; Jianfei SHUAI ; Yuping BAI ; Yulan JIN
Chinese Journal of Preventive Medicine 2018;52(11):1158-1163
Objectives:
To explore the expression regulation of type 1 and type 2 (Th1 and Th2) cytokines from serum of coal miners and the evaluation in surveillance of coal workers' pneumoconiosis, 630 coal miners were studied.
Methods:
A total of 90 male patients diagnosed as coal workers' pneumoconiosis (CWP) in a institute for occupational health and 19 male workers newly diagnosed as CWP patients was chosen as CWP group with simple random sampling method from a coal mine group from January 2013 to December in 2015. 180 male coal miners with abnormal but not diagnosed as CWP were selected as CWP suspected group with simple random sampling methods, meanwhile 180 male coal miners with normal chest X-ray photograph was as dust-exposed group by 1∶1 matched as age. And 161 healthy males accepted pre-employed examination were selected as control group, CWP suspected group, dust-exposed group and control group called as non-CWP group. According to screening test and diagnosis test, the basic information and occupational history of all subjects were collected, and cytokines including IL-1β, IL-8, IFN-γ, IL-6 and IL-10 of serum were detected. Receiver operator characteristic (ROC) curve was used to determine the optimal cutoff value of each cytokine. Area under curve (AUC), the validity and reliability were calculated and judged.
Results:
The average age of control group, dust-exposed group, CWP suspected group and CWP group were (27.4±5.0) , (43.4±10.7) , (48.2±6.2) , (64.7±7.0) years old, respectively. The median level of IL-1β, IL-8, IFN-γ and IL-6 in cases group (1 638.30, 2 099.49, 815.18,140.32 pg/ml) were higher than that of non-cases group (1 445.57, 1 402.26, 736.38, 95.73 pg/ml) (
4.Preliminary study on therapeutic effect of Baimai Ointment on stroke and blood circulation mechanism
Weiwu CHEN ; Jing LIU ; Jie LU ; Xiuping SHEN
Drug Evaluation Research 2017;40(2):196-200
Objective To observe the preventive and therapeutic effect of Baimai Ointment on stoke,and explore the principle of promoting blood circulation and removing blood stasis.Method By dermal administration,the crude drug contents of Baimai Ointment given to rats were 0.075,0.150,and 0.300 g/kg respectively.Focal cerebral ischemic model was induced by the middle cerebral artery occlusion (MCAO),and the preventive and therapeutic effect of Baimai Ointment was evaluated.The degree of hematoma absorption in rats was measured to observe the effect on promoting blood circulation and removing blood stasis of Baimai Ointmnent.The acute blood stasis model and carotid thrombosis model were established in rats to study the effects on blood viscosity and thrombosis time.Results Baimai Ointment had no significant prevent effect on stroke in rats.It effectively improved behavior coordination in stroke model rats.It also significantly decreased the area of hematoma on rats,speeded up the repairment of local demage.After administration of Baimai Ointment,blood viscosity of blood stasis model rats was obviously decreased,while thrombosis time was effectively prolonged on carotid thrombosis model.Conclusion Baimai Ointment can significantly improve the behavior coordination in stroke model rats,plays a significant role in treatment,but no significant preventive effect,a preliminary study shows that the possible therapeutic principles may be promoting blood circulation and removing blood stasis.
5.Comparison of Applicability Test of Sterile Examination Method for Artemether Injection
Qin LIU ; Hongyu ZHANG ; Lu WANG ; Xiuping LUO
China Pharmacist 2017;20(10):1874-1876
Objective:To develop a more suitable sterile examination method for artemether injection in order to control its quality better. Methods:The direct inoculation and the membrane filtration was respectively used for the sterile examination of artemether in-jection. Results:In the direct inoculation method, Staphylococcus aureus, Bacillus subtilis and Clostridium perfringens grew well in the test tubes containing artemether injection in 24 h, and Escherichia coli, Aspergillus niger and Candida albicans grew well in 48 h. In the membrane filtration method, Staphylococcus aureus grew well in 24 h in the test group containing artemether injection, and the other 5 strains grew well in 48 h. Conclusion:The positive strains can grow well in the applicability test of both methods. However, due to the simpler operation and higher accuracy of membrane filtration method, it is recommended to be used for the sterile test of artemether injection.
6.Comparison of Applicability Test of Sterile Examination Method for Artemether Injection
Qin LIU ; Hongyu ZHANG ; Lu WANG ; Xiuping LUO
China Pharmacist 2017;20(10):1874-1876
Objective:To develop a more suitable sterile examination method for artemether injection in order to control its quality better. Methods:The direct inoculation and the membrane filtration was respectively used for the sterile examination of artemether in-jection. Results:In the direct inoculation method, Staphylococcus aureus, Bacillus subtilis and Clostridium perfringens grew well in the test tubes containing artemether injection in 24 h, and Escherichia coli, Aspergillus niger and Candida albicans grew well in 48 h. In the membrane filtration method, Staphylococcus aureus grew well in 24 h in the test group containing artemether injection, and the other 5 strains grew well in 48 h. Conclusion:The positive strains can grow well in the applicability test of both methods. However, due to the simpler operation and higher accuracy of membrane filtration method, it is recommended to be used for the sterile test of artemether injection.
7.Effects of apelin-13 on myocardium metabolism in diabetic rats
Mengze DU ; Jinghui FENG ; Hang ZHAO ; Ying LU ; Xiuping WU
Chinese Journal of Geriatrics 2017;36(4):454-458
Objectives To investigate the effects of Apelin 13 on myocardial metabolism in diabetic rats.Methods A total of 40 male Wister rats were randomly divided into normal control group (NC,n=8) and experimental group (n =32).Diabetic rats model were induced by high-sugar and high-fat diet combined with low-dose intraperitoneal injection of streptozotocin (STZ).The wellestablished 28 diabetic model rats were randomly divided into diabetic model group (DM,n=14) and apelin-13 treated group (n=14).In the Apelin-13 group,diabetic rats were administered Apelin-13 [0.1 μmol/(kg · d)]by intraperitoneal injection for 10 weeks,while the control group and diabetic model group were given an equal volume of 0.9% NaCl.At the end of the 10th week,all rats were sacrificed after fasting glucose measurement.Levels of serum free fatty acids (FFA) and myocardial FFA were measured by ELISA.Expression of myocardial glucose transporter member 4 (GLUT4) were detected by immunohistochemistry.The mRNA expressions of myocardial PPARα,CD36 and CPT-1 were detected by real-time fluorescence quantitative PCR.Results Fasting blood glucose,serum FFA and myocardial FFA were significantly higher in DM group than in NC group (all P< 0.05).The level of plasma glucose and myocardial FFA were significant lower(P>0.05) in Apelin-13 treated group than in DM group;but serum FFA was not significantly lower(P<0.05).The mRNA expressions of PPARα,CD36,CPT-1 in cardiac myocyte were higher in DM group and Apelin-13 treated group than in control(P<0.05),and lower in Apelin-13 treated group than in DM group(P< 0.05).The expression of myocardial GLUT4 was significantly lower in DM group(1.138±0.316)and in Apelin-13-treated group (4.631 ± 1.832) than in NC group(9.132 ± 2.156),(F=65.507,P< 0.05),and higher in Apelin-13-treated group than in DM group(P<0.05).Conclusions Apelin-13 increases myocardial expression of GLUT4,improves utilization of FFA,and it can effectively reduce the expression of PPARα,CD36 and CPT-1.Therefore,it may play a vital role in the improvement of myocardial metabolism in diabetic rats.
8.Efficiency analysis of medical equipment deployment in Liaoning province based on data envelopment analysis
Yuhua ZHU ; Xiuping JIA ; Ming LU ; Shuang LI ; Li LIU ; Lei FENG ; Hui SU
Chinese Journal of Hospital Administration 2017;33(5):381-383
Objective To learn the present efficiency of medical equipments at public hospitals in Liaoning province, and provide scientific basis for rational distribution of such resources, and for control of medical expenses.Methods Data envelop analysis (DEA) was used to appraise the deployment efficiency of 2 784 such equipments worth over 100 000 yuan per unit, with equipments randomly sampled from 31 public hospitals in the province.Results The equipment deployment at public hospitals in Liaoning was found at a low level.9.7% of the hospitals were found as relatively efficient, 3.2% of them as in relatively weak efficiency, while 87.1% of them relatively inefficient.Gaps were found between urban hospitals and tertiary hospitals, and rural hospitals and secondary hospitals in their deployment efficiency, as evidenced in overinvestment of equipments and insufficiency of competent operators.Conclusions Hospitals should strengthen their scientific management of the equipments, and emphasize human resource investment, thus elevating the efficiency of equipment deployment.
9.Construction and application of nursing quality information feedback system based on QUACERS model
Wei WANG ; Wenhong ZHOU ; Dong KONG ; Xiuping FENG ; Hongmei YANG ; Qian GAO ; Fengjuan LU ; Zhenxiang LI
Chinese Journal of Practical Nursing 2016;32(22):1691-1696
Objective To construct and implement the nursing quality information feedback system based on QUACERS model and control theory, and discuss its application effect and the problems that should be paid attention to and to provide operational cases and practical basis for nursing quality management. Methods Through literature review and expert consultation, the framework and content of nursing quality information feedback system were set up and implemented. The changes of the nursing quality and the repeated occurrence of nursing problems were evaluated before (2013) and after (2015) the implementation of this project. And in December 2015, a self-made questionnaire was conducted among the nurses in the hospital to evaluate the importance of the feedback and it′s effect of improving the nursing quality. And evaluate the timeliness and effectiveness of different feedback forms. Results 1 120 and 1 136 nurses were followed-up in 2013 and 2015 respectively. The scores of human resource management, clinical nursing service and nursing safety management were higher than before, and the repeated occurrence of nursing problems was lower than before. A total of 450 questionnaires were distributed, 438 copies were collected, the effective recovery rate was 97.33%. Ratings for the importance of each item was from 3.37 to 4.57. Ratings for the effect of improving the quality of care was 3.79 to 4.39. The percentage of quality information received by nurses was more than 95%, and the average score of feedback timeliness was 4.29 to 4.53. Conclusions Quality information feedback system based on QUACERS model can cover multiple dimensions of quality management, and it was conducive to obtaining comprehensive information;Combined with multiple feedback forms can improve the effect of information feedback.
10.Effect of apelin-13 on myocardium apoptosis in diabetic rats
Hang ZHAO ; Jinghui FENG ; Ying LU ; Xiuping WU
Chinese Journal of Geriatrics 2016;35(1):85-90
Objective To investigate the effect of exogenous apelin-13 on oxidative stress, myocardial inflammatory cytokines and apoptosis in diabetic model rats.Methods A total of 40 male Wistar rats were randomly divided into 2 groups: normal control group (NC, n=8) and experimental group (EX, n=32).Diabetes was induced by feeding with high-sugary and high-fat diet for 8 weeks and a single intraperitoneal injection of streptozotocin (STZ) (30 mg/kg).The wellestablished 28 diabetic model rats were then randomly divided into 2 subgroups: model group (DM, n =14) and apelin-13 administration group (AP, n =14).The rats in AP group were given intraperitoneal administration of apelin-13 at a single dose of 0.1 μtmol · kg-1 · d-1 for 10 weeks, while NC group and DM group were given 0.9% NaCl in the same way.All rats were sacrificed at the end of the week 10.Blood hydrogen peroxide (H2O2), nitric oxide (NO) and malonaldehyde (MDA) were measured by colorimetry, and superoxide dismutase (SOD) was measured by enzyme-linked immunosorbent assay (ELISA).The expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in rat myocardium were detected by immunohistochemistry.Masson staining was used to observe the myocardial fibrosis in rats of different groups.Cardiomyocyte apoptosis was determined by TUNEL.Results (1) Compared with NC groups, DM group showed that MDA, H2O2 and NO were significantly increased, while SOD was significantly decreased (F=22.400, 6.230, 4.267 and 8.901, all P<0.0167).There was a statistically significant difference in the levels of MDA, H2O2,SOD between DM group and AP group.(2) The expression of TNF-α and IL-6 was significantly higher inDMgroup than inNCgroup (0.0599±0.0208 vs.0.0076±0.0031, F=35.139;0.0503±0.0243 vs.0.0071± 0.0024, F=15.946, both P<0.0167).After 10 weeks of apelin-13 administration, the levels of inflammatory cytokines were significantly decreased in AP group than in DM group.(3) The myocardial apoptosis and fibrosis were significantly increased in DM group than in NCgroup [0.0293±0.0061 vs.0.0030-t-0.0013 and 0.0708±0.0420 vs.0.0013±0.0003, F=84.930 and 19.420, both P<0.0167].The myocardial apoptosis and fibrosis were significantly decreased in AP group than in DM group (both P<0.0167).Conclusions To some extent, apelin13 reduces the levels of oxidative stress and myocardial inflammation reaction in type 2 diabetes.Moreover, it may play a vital role in the improvement of myocardial apoptosis and fibrosis.

Result Analysis
Print
Save
E-mail