摘要：
Background and Aims: Rifampicin (RFP) and isoniazid (INH) are widely used as anti-tuberculosis agents. However, the mechanisms underlying the involvement of reactive oxygen species and mitochondria in RFP- and INH-related hepatotoxicity have not been established yet. This study aimed to observe the intracellular mechanisms leading to mitochondrial dysfunction and morphological changes in RFP- and INH-induced hepatocyte injury. Methods: Cell injury, changes in mitochondrial function, and expression and activation of dynamin related protein 1 (Drp1), known as the main protein for mitochondrial fission, were analyzed in cultured QSG7701 cells exposed to RFP and INH. Results: INH and RFP treatment induced pronounced hepatocyte injury and increased cell death. In the similar context of aspartate aminotransferase elevation and adenosine triphosphate synthesis decrease, changes in mitochondrial membrane permeability and reactive oxygen species in hepatocytes induced by RFP were significantly different from those induced by INH (p < 0.05). Particularly, we observed the overactivation and mitochondrial translocation of Drp1 in RFP-induced cell injury, which was not occurred with exposure to INH. Conclusions: RFP-induced hepatotoxicity may be closely related to mitochondrial dysfunction and Drp1-mediated mitochondrial fission.
期刊：
Digestive and Liver Disease,2019年51(3):425-433 ISSN：1590-8658
通讯作者：
Wang, Xianbo;Sun, Kewei;Li, Hai
作者机构：
[Gao, Fangyuan; Liu, Yao; Wang, Xianbo] Capital Med Univ, Beijing Ditan Hosp, Ctr Integrat Med, Beijing 100015, Peoples R China.;[Sun, Kewei; Zhang, Qianqian] Hunan Univ Chinese Med, Hosp 1, Dept Hepatol, Changsha 410007, Hunan, Peoples R China.;[Gong, Guozhong] Ctr South Univ, Xiangya Hosp 2, Dept Infect Dis, Changsha, Hunan, Peoples R China.;[Mao, Dewen] Guangxi Univ Chinese Med, Affiliated Hosp 1, Dept Hepatol, Nanning, Peoples R China.;[Gong, Zuojiong] Wuhan Univ, Renmin Hosp, Dept Infect Dis, Wuhan, Hubei, Peoples R China.
通讯机构：
[Wang, Xianbo] C;[Sun, Kewei] H;[Li, Hai] S;Capital Med Univ, Beijing Ditan Hosp, Ctr Integrat Med, Beijing 100015, Peoples R China.;Hunan Univ Chinese Med, Hosp 1, Dept Hepatol, Changsha 410007, Hunan, Peoples R China.
关键词：
Acute-on-chronic liver failure;Hepatitis B virus;Nomogram;Prognosis
摘要：
BACKGROUND: The current definitions and etiologies of acute-on-chronic liver failure (ACLF) are clearly very different between East and West. AIMS: This study aimed to develop an effective prognostic nomogram for acute-on-chronic hepatitis B liver failure (ACHBLF) as defined by the Asia Pacific Association for the Study of the Liver (APASL). METHODS: The nomogram was based on a retrospective study of 573 patients with ACHBLF, defined according to the APASL, at the Beijing Ditan Hospital. The results were validated using a bootstrapped approach to correct for bias in two external cohorts, including an APASL ACHBLF cohort (10 hospitals, N=329) and an EASL-CLIF ACHBLF cohort (Renji Hospital, N=300). RESULTS: Multivariate analysis of the derivation cohort for survival analysis helped identify the independent factors as age, total bilirubin, albumin, international normalized ratio, and hepatic encephalopathy, which were included in the nomogram. The predictive value of nomogram was the strongest compared with CLIF-C ACLF, MELD and MELD-Na and similar to COSSH-ACLF in both the derivation and prospective validation cohorts with APASL ACHBLF, but the CLIF-C ACLF was better in the EASL-CLIF ACHBLF cohort. CONCLUSIONS: The proposed nomogram could accurately estimate individualized risk for the short-term mortality of patients with ACHBLF as defined by APASL.
期刊：
International Journal of Endocrinology,2019年2019:5151678 ISSN：1687-8337
通讯作者：
Li, Yuehua
作者机构：
[Zhang, Yulong; Ren, Fengying; Bao, Tingting] Beijing Univ Chinese Med, Beijing 100029, Peoples R China.;[Zhang, Yulong; Ren, Fengying; Gao, Ziren; Li, Yuehua; Bao, Tingting] China Acad Chinese Med Sci, Xiyuan Hosp, Beijing, Peoples R China.;[Zeng, Liuting; Yang, Kailin] Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Li, Yuehua] C;China Acad Chinese Med Sci, Xiyuan Hosp, Beijing, Peoples R China.
摘要：
Objective: To assess the effectiveness and safety of melatonin for perimenopausal and postmenopausal women with osteopenia. Methods: In this meta-analysis, data from randomized controlled trials were obtained to assess the effects of melatonin versus placebo or western medicine in perimenopausal and postmenopausal women with osteopenia. The study's registration number is CRD42018086238. The primary outcomes included bone mineral density (BMD) and T-score. Result: From 551 articles retrieved, three trials involving 121 patients were included. Due to the high-to-substantial heterogeneity (BMD: I(2)=96.9%, P=0.000; T-score: I(2)=74.9%, and P=0.019), the statistical analysis of BMD and T-score was abandoned. A systematic review was undergone for the two outcomes. Compared with the control group, melatonin may increase osteocalcin (WMD 4.97; 95% CI 3.14, 6.79; P < 0.00001). Conclusion: Based on current evidence, melatonin might be used as a safe nutritional supplement to improve bone density in perimenopausal and postmenopausal women, but its efficacy needs to be further affirmed.
摘要：
Objective：To observe the effect of Xintongtai on the expression of TLR4,p38 MAPK,MPO,RhoAand eNOS,and to explore possible mechanisms of Xintongtai on atherosclerosis. Methods：Rabbit models ofatherosclerosis were established by feeding with high-fat diet combined with immune injury. After administrationand tissue extraction,the expression levels of TLR4,p38 MAPK,MPO,RhoA,eNOS protein and mRNA were detected by Western blot and RT-PCR. Results：Compared with the control group,the mRNA expressions of TLR4,p38 MAPK,MPO and RhoA protein in the model group were increased significantly,and the mRNA expression ofeNOS protein was decreased significantly （P〈 0.01）. Compared with the model group,the mRNA expressions ofMPO,RhoA protein and p38MAPK were decreased significantly,and the mRNA expression eNOS protein was in鄄creased significantly in the low-dose group of Xintongtai （P〈 0.05）. Compared with the model group,the mRNAexpressions of p38 MAPK,MPO,RhoA protein and TLR4 were decreased significantly,and the mRNA expressionof eNOS protein was increased significantly in the middle-dose group of Xintongtai（P〈 0.05）. Compared with themodel group,the mRNA expressions of TLR4,p38 MAPK,MPO and RhoA decreased significantly,and the mRNAexpression of eNOS increased significantly in the high-dose group of Xintongtai （P〈 0.01）. The difference abovehad statistical significance. There was no significant change between the positive drug group and the high-dose group of Xintongtai in the mRNA expressions of TLR4,p38 MAPK,MPO,RhoA and eNOS （P 跃0.05）. Conclu-sion：Xintongtai can inhibit inflammation in blood vessels,and protect the vascular endothelium of aorta by de-creasing mRNA expression of TLR4,p38 MAPK,MPO and RhoA protein and up-regulating mRNA expression of eNOS,so as to achieve the aim of treating atherosclerosis.
作者：
Zheng, H.;Liu, Z. -S.;Zhang, W.;Chen, M.;Zhong, F.;...
期刊：
NEUROGASTROENTEROLOGY AND MOTILITY,2018年30(7):e13307- ISSN：1350-1925
通讯作者：
Li, Y.;Zhu, B.
作者机构：
[Li, Y.; Zheng, H.] Chengdu Univ Tradit Chinese Med, Chengdu, Sichuan, Peoples R China.;[Li, Y.; Zhu, W. -Z.; Liu, Z. -S.] China Acad Chinese Med Sci, Guanganmen Hosp, Beijing, Peoples R China.;[Zhong, F.; Zhang, W.] Hunan Univ Tradit Chinese Med, Affiliated Hosp 1, Changsha, Hunan, Peoples R China.;[Chen, M.] Chengdu Univ Tradit Chinese Med, Teaching Hosp, Chengdu, Sichuan, Peoples R China.;[Rong, P. -J.; Zhu, B.; Jing, X. -H.] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing, Peoples R China.
通讯机构：
[Li, Y.; Zhu, B.] C;Chengdu Univ Tradit Chinese Med, Chengdu, Sichuan, Peoples R China.;China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing, Peoples R China.
摘要：
OBJECTIVE: To evaluate the pharmacokinetics and relative bioavailability of two allopurinol tablets in healthy Chinese volunteers. METHODS: A single-center, randomized, cross-over, two-period study design was conducted in healthy male subjects who were identified as not carrying the HLA-B*58:01 allele. Under fasting conditions, a single oral dose of 300 mg test or reference tablets was given with a 1-week washout period. The blood samples were collected for up to 12 hours after the administration and the plasma concentrations of allopurinol were determined by high performance liquid chromatography. Subject interviews and physical examinations were done over regular intervals to monitor the adverse events. RESULTS: 18 subjects were enrolled in the study, and none dropped out. The main pharmacokinetic parameters of allopurinol test and reference preparations were as follows: AUC<sub>0-tlast</sub> was 6,725.1 +/- 1,390.0 ngxhxmL<sup>-1</sup> and 6,425.6 +/- 1,257.6 ngxhxmL<sup>-1</sup>; AUC<sub>0-infinity</sub> was 7,069.1 +/- 1,503.2 ngxhxmL<sup>-1</sup> and 6,750.6 +/- 1,347.7 ngxhxmL<sup>-1</sup>; t<sub>max</sub> was 1.3 +/- 0.8 hours and 1.3 +/- 0.8 hours; C<sub>max</sub> was 2,203.7 +/- 557.4 ngxmL<sup>-1</sup> and 2,310.8 +/- 662.8 ngxmL<sup>-1</sup>; and T<sub>1/2</sub> was 2.0 +/- 1.6 hours and 1.7 +/- 0.7 hours. The relative bioavailability was 105.1 +/- 12.6%. The 90% confidence intervals for the geometric mean ratios (test/reference) of C<sub>max</sub>, AUC<sub>0-tlast</sub>, and AUC<sub>0-infinity</sub> of both preparations fell within the bioequivalence acceptance criteria (80 - 125%). No adverse events were found or reported during the study. CONCLUSION: The test allopurinol preparations and the reference preparations are bioequivalent and both are well tolerated..
作者机构：
[Zeng, Fang; Lan, Lei; Liang, Fanrong; Li, Zhengjie; Guo, Taipin; Wu, Feng; Li, Ying; Yin, Tao; Gao, Yujie; Yang, Jie; Dong, Mingkai] Chengdu Univ Tradit Chinese Med, Teaching Hosp 3, Chengdu, Sichuan, Peoples R China.;[Jorgenson, Kristen; Kong, Jian; Makris, Nikos] Harvard Med Sch, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.;[Jorgenson, Kristen; Kong, Jian; Makris, Nikos] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.;[Liu, Mailan] Hunan Univ Chinese Med, Acupuncture & Tuina Sch, Changsha, Hunan, Peoples R China.;[Gong, Qiyong] Sichuan Univ, West China Hosp, Huaxi MR Res Ctr, Chengdu, Sichuan, Peoples R China.
通讯机构：
[Liang, Fanrong] C;[Kong, Jian] H;[Kong, Jian] M;Chengdu Univ Tradit Chinese Med, Teaching Hosp 3, Chengdu, Sichuan, Peoples R China.;Harvard Med Sch, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
关键词：
Migraine;Amplitude of low-frequency fluctuations;Brainsterm;Trigeminocervical complex;Acupuncture;Resting state fMRI
摘要：
Migraine is a common neurological disease with a high prevalence and unsatisfactory treatment options. The specific pathophysiological mechanisms of migraine remain unclear, which restricts the development of effective treatments for this prevalent disorder. The aims of this study were to 1) compare the spontaneous brain activity differences between Migraine without Aura (MwoA) patients and healthy controls (HCs), using amplitude of low-frequency fluctuations (ALFF) calculation method, and 2) explore how an effective treatment (verum acupuncture) could modulate the ALFF of MwoA patients. One hundred MwoA patients and forty-six matched HCs were recruited. Patients were randomized to four weeks' verum acupuncture, sham acupuncture, and waiting list groups. Patients had resting state BOLD-fMRI scan before and after treatment, while HCs only had resting state BOLD-fMRI scan at baseline. Headache intensity, headache frequency, self-rating anxiety and self-rating depression were used for clinical efficacy evaluation. Compared with HCs, MwoA patients showed increased ALFF in posterior insula and putamen/caudate, and reduced ALFF in rostral ventromedial medulla (RVM)/trigeminocervical complex (TCC). After longitudinal verum acupuncture treatment, the decreased ALFF of the RVM/TCC was normalized in migraine patients. Verum acupuncture and sham acupuncture have different modulation effects on ALFF of RVM/TCC in migraine patients. Our results suggest that impairment of the homeostasis of the trigeminovascular nociceptive pathway is involved in the neural pathophysiology of migraines. Effective treatments, such as verum acupuncture, could help to restore this imbalance.
