1.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.
2.Effect of neuroelectrophysiological changes on the clinical manifestations and surgical outcomes of lumbar degenerative diseases.
Dao-Dong CHEN ; Da-Kai ZHOU ; Hui-Ning LI ; Ya-Lin WANG ; Zhen-Jun ZHU
China Journal of Orthopaedics and Traumatology 2023;36(7):686-691
OBJECTIVE:
To evaluate the effects of electromyography on the clinical manifestations and prognosis after posterior lumbar interbody fusion(PLIF) of degenerative lumbar diseases.
METHODS:
A retrospective analysis was performed on 68 patients with degenerative lumbar diseases, including 29 males and 39 females, aged 21 to 84 years old, who underwent electromyogram (EMG) from January 2018 to October 2019. The patients were divided into negative and positive groups according to whether theresults of EMG was normal or abnormal, PLIF surgery was performed in both groups. The preoperative duration of illness, postoperative recovery time, operative time, intraoperative blood loss, postoperative ambulation time and length of postoperative hospital stay were recorded. The clinical efficacy was evaluated by visual analogue scale(VAS) of low back and lower limb, the Japanese Orthopedic Association(JOA) score before and after operation.
RESULTS:
All patients were follow-up from 26 to 39 months. The subjective symptoms, clinical signs, daily activities and JOA total scores after operation in two groups were significantly higher than those before preoperation(P<0.05);the clinical signs score and total JOA score in the negative group at 3 months after operation were higher than those in the positive group(P<0.05). The VAS score of leg pain in the negative group after 1 and 3 months was less than that in the positive group(P<0.05). Patients 's illness time, postoperative recovery time, hospitalization time and implantation time in the negative group were shorter than those in the positive group(P<0.05). At other time points, there was no significant difference in low pain VAS, leg pain VAS, JOA scores in the two groups(P>0.05). There was no significant difference in the operation time and intraoperative bleeding volume between the two groups(P>0.05).
CONCLUSION
Patients with normal electromyography had shorter disease duration than ones with abnormal electromyography in lumbar degenerative disease;after PLIF, patients with normal electromyography recovered faster than ones with abnormal electromyography, but the results of electromyography had no effect on the final prognosis of PLIF surgery.
Male
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Female
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Humans
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Young Adult
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Adult
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Middle Aged
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Aged
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Aged, 80 and over
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Retrospective Studies
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Spinal Fusion/methods*
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Lumbar Vertebrae/surgery*
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Treatment Outcome
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Pain
3.Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research.
Wei XU ; Shu Hua YI ; Ru FENG ; Xin WANG ; Jie JIN ; Jian Qing MI ; Kai Yang DING ; Wei YANG ; Ting NIU ; Shao Yuan WANG ; Ke Shu ZHOU ; Hong Ling PENG ; Liang HUANG ; Li Hong LIU ; Jun MA ; Jun LUO ; Li Ping SU ; Ou BAI ; Lin LIU ; Fei LI ; Peng Cheng HE ; Yun ZENG ; Da GAO ; Ming JIANG ; Ji Shi WANG ; Hong Xia YAO ; Lu Gui QIU ; Jian Yong LI
Chinese Journal of Hematology 2023;44(5):380-387
Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female
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Humans
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Male
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Aged
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Middle Aged
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Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy*
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Prognosis
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Lymphoma, B-Cell
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Immunohistochemistry
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Immunoglobulin Heavy Chains/therapeutic use*
4.A monocentric ambispective cohort study of new-onset postoperative atrial fibrillation after lobectomy
Da GONG ; Xiao LI ; Jian ZHOU ; Kai ZHANG ; Bingbing LIN ; Fan YANG ; Jun WANG ; Yun LI
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(9):565-571
Objective:To analyze the incidence and risk factors of postoperative new-onset atrial fibrillation(POAF) after lobectomy.Methods:A monocentric ambispective cohort study was conducted. The retrospective cohort included 1 902 patients who underwent lobectomy in our hospital between January 2017 and December 2019. The prospective cohort included 692 patients who underwent lobectomy in our hospital between August 2020 and July 2021. A total of 2 594 patients were enrolled in this study. The median age of enrolled patients was 61 years(interquartile range, 54-67 years), and the cohort consisted of 1 384(51.97%) females and 1 246(48.03%) males. Baseline and perioperative clinical data of enrolled patients were collected. Univariate and multivariate logistic regression analyses were performed to identify the risk factors related to POAF. Results:There was no patient died in hospital after surgery. A total of 111 cases of POAF were followed up during the postoperative hospital period, and the incidence of POAF was 4.28%. Multivariate regression analysis found that the elderly patients(aged 60 and above)( OR=1.58, 95% CI: 1.01-2.47, P=0.044), history of percutaneous coronary intervention( OR=2.50, 95% CI: 1.04-6.03, P=0.041), history of arrhythmia excluding atrial fibrillation/flutter( OR=3.96, 95% CI: 1.95-8.00, P<0.001), left upper lobectomy( OR=1.73, 95% CI: 1.11-2.68, P=0.015), low preoperative albumin level( OR=1.07, 95% CI: 1.00-1.14, P=0.048) and large cell neuroendocrine carcinoma( OR=4.70, 95% CI: 1.38-15.98, P=0.013) were independent risk factors for POAF after lobectomy. Conclusion:The incidence of POAF after lobectomy is 4.28% in this study. Elderly patients(aged 60 and above), history of percutaneous coronary intervention, history of arrhythmia excluding atrial fibrillation/flutter, left upper lobectomy, low preoperative albumin level, and large cell neuroendocrine carcinoma are the independent risk factors related to POAF after lobectomy.
5.Review and Prospects of Pathogen Detection Related to Autopsy of Coronavirus Infectious Diseases.
Yun Yi WANG ; Nan ZHOU ; Jia Cheng YUE ; Kai ZHANG ; Qian Hao ZHAO ; Da ZHENG ; Bing Jie HU ; Jian Ding CHENG
Journal of Forensic Medicine 2021;37(1):69-76
In the past, coronavirus caused two serious human-to-human pandemics in the world, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In late 2019, coronavirus disease 2019 (COVID-19) caused another major global public health event. Due to the strong infectivity of novel coronavirus, it is difficult to carry out the autopsy of related death cases widely. This paper reviews the previous status of the pathogen detection related to the autopsy of coronavirus infection diseases, and introduces the ongoing detection methods of novel coronavirus in clinical practice, in order to provide reference for the pathogen detection and study related to autopsy of COVID-19.
Autopsy
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COVID-19
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Communicable Diseases
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Coronavirus Infections/diagnosis*
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Humans
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Middle East Respiratory Syndrome Coronavirus
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SARS-CoV-2
6.Correlation between Abdominal Wall Subcutaneous Fat Thickness and Heart Weight in Southern Chinese Population.
Jia Cheng YUE ; Qiu Ping WU ; Nan ZHOU ; Kai ZHANG ; Da ZHENG ; Guo Li LÜ ; Jian Ding CHENG
Journal of Forensic Medicine 2021;37(3):351-357
Objective To study the correlation between the abdominal wall subcutaneous fat thickness and heart weight, so as to provide reference for prediction methods of normal range of heart weight that is suitable for autopsy in China. Methods The forensic pathology autopsy cases accepted by Center for Medicolegal Expertise of Sun Yat-sen University from 1998 to 2017 were collected. Then the exclusion criteria were determined, and according to them the total case group was selected, and the 6 disease groups and the normal group were further selected from the total case group. The rank sum test was used to compare the heart weight of the normal group and the disease groups to determine the influence of diseases on heart weight. Then the Spearman rank correlation analysis of abdominal wall subcutaneous fat thickness and heart weight in different genders and different ages in the total case group and the normal group was conducted to get the correlation coefficient (rs). Results In the total case group, correlation between abdominal wall subcutaneous fat thickness and heart weight was shown in males of all ages (P<0.05); while in females, the correlation had no statistical significance (P>0.05) in 15-<20 age and 50-<60 age, but was statistically significant (P<0.05) in other age groups. For the males in the normal group, rs was respectively 0.411, 0.541 and 0.683 in the 15-<40 age, the 40-<60 age, and the ≥60 age. For the females, rs was respectively 0.249 and 0.317 in the 15-<40 age and the 40-<60 age. The correlation in the ≥60 age had no statistical significance(P>0.05). Conclusion In the general population and the normal population, abdominal wall subcutaneous fat thickness is correlated with the heart weight of males. It is of significance to include the abdominal wall subcutaneous fat thickness in the prediction of normal range of heart weight for males in China.
Abdominal Wall/diagnostic imaging*
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China
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Female
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Heart/diagnostic imaging*
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Humans
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Male
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Middle Aged
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Reference Values
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Subcutaneous Fat/diagnostic imaging*
7.Chromosome polymorphisms and their influence on semen quality and sperm DNA integrity in males undergoing IVF/ICSI.
Xian-Bao MAO ; Lin-Tao XUE ; Wei-Ying MO ; Yao-Xi MO ; Jun-Ping CHENG ; Shi-Kai WANG ; Yue-Yue HUANG ; Zheng-da LI ; Xiao-Hui ZHANG ; Ting-Ting ZHOU ; Ping-Pin WEI ; Wei-Hong TAN
National Journal of Andrology 2019;25(3):223-230
Objective:
To investigate the incidence of chromosome polymorphisms and their influence on semen quality and sperm DNA integrity in male patients receiving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).
METHODS:
We retrospectively analyzed the chromosomal karyotypes and the types and incidence rate of chromosome polymorphisms in 2 370 male patients undergoing IVF/ICSI between June 2016 and June 2018. We classified the patients into groups A (with variation in the secondary constriction region in the autosomal long arm), B (with variation in the short arm of the D/G group chromosomes), C (with interbrachial inversion of chromosome 9) and D (with Y chromosome polymorphisms), and compared the semen parameters and sperm DNA fragmentation indexes (DFI) between the patients with chromosome polymorphisms and those with normal chromosomes.
RESULTS:
Totally, 154 (6.50%) of the patients undergoing IVF/ICSI were found with chromosome polymorphisms, including 34 cases of secondary constriction variation in the long arm of the autosome (1.43% [34/2 370], 22.08% [34/154]), 82 cases of short arm polymorphisms of the D/G group chromosomes (3.46% [82/2 370], 53.25% [82/154]), 26 cases of interbrachial inversion of chromosome 9 (1.10% [26/2 370], 16.88% [26/154]), 10 cases of Y chromosome polymorphisms (0.42% [10/2 370], 6.50% [10/154]), and 2 cases of mixed chromosome polymorphisms (0.08% [2/2 370], 1.42% [2/154]). The total sperm count was lower in group D than in the other polymorphism groups and the normal chromosome group, but with no statistically significant difference among the five groups (P > 0.05). The sperm progressive motility was also lower in group D than in the other five groups, with statistically significant difference from group B (27.5 ± 13.5 vs. 41.5 ± 21.1, P = 0.027), but not from the other groups (P > 0.05). No statistically significant difference was observed in the sperm DFI between the polymorphism groups and the normal chromosome group (P > 0.05), or among the polymorphism groups (P > 0.05). The proportion of normal semen was lower in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05). The incidence rate of asthenospermia was higher in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05), and so was that of oligoasthenospermia, with statistically significant difference from the normal chromosome group (30.0% vs 8.0%, P = 0.041), but not from the other polymorphism groups (P > 0.05).
CONCLUSIONS
Short arm polymorphisms of the D/G group chromosomes are the most common type of chromosome polymorphisms in male patients undergoing IVF/ICSI. Polymorphisms of the Y chromosome have a negative effect on semen quality, while those of the other chromosomes do not significantly affect semen quality and sperm DNA integrity.
8.Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized-Controlled Trial.
Yong-An YE ; Xiao-Ke LI ; Da-Qiao ZHOU ; Xiao-Ling CHI ; Qin LI ; Li WANG ; Bing-Jiu LU ; De-Wen MAO ; Qi-Kai WU ; Xian-Bo WANG ; Ming-Xiang ZHANG ; Jing-Dong XUE ; Yong LI ; Wei LU ; Jian-Chun GUO ; Feng JIANG ; Xin-Wei ZHANG ; Hong-Bo DU ; Xian-Zhao YANG ; Hui GUO ; Da-Nan GAN ; Zhi-Guo LI
Chinese journal of integrative medicine 2018;24(9):653-660
BACKGROUNDThe domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate.
METHODSThe study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment.
DISCUSSIONThe study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).
9.Effect of histone acetylation/deacetylation imbalances on key gene of planar cell polarity pathway.
Hong-Yu DUAN ; Yi ZHANG ; Kai-Yu ZHOU ; Chuan WANG ; DA-Jian QIU ; Yi-Min HUA
Chinese Journal of Contemporary Pediatrics 2017;19(4):475-483
OBJECTIVETo investigate the effect of histone acetylation/deacetylation imbalances on embryonic hearts of mice and its effect on key genes of planar cell polarity (PCP) pathway-Vangl2, Scrib and Rac1 in H9C2 cells.
METHODSForty pregnant C57/B6 mice were randomly assigned into three groups: blank group (n=10), vehicle group (n=10), and valproic acid (VPA)-treated group (n=20). In the VPA-treated group, VPA, a histone deacetylase (HDAC) inhibitor, was administered to each individual dam intraperitoneally at a single dose of 700 mg/kg on embryonic day 10.5 (E10.5). The vehicle and blank groups received equivalent saline or no interventions, respectively. Dams were sacrificed on E15.5, and death rates of embryos were evaluated. Subsequently, embryonic hearts of survival fetus were removed to observe cardiac abnormalities by hematoxylin-eosin (HE) staining. H9C2 cells were cultured and allotted to the blank, vehicle, and VPA-treated groups: the VPA treated group received VPA exposure at concentrations of 2.0, 4.0 and 8.0 mmol/L; the vehicle and blank groups received equivalent saline or no interventions, respectively. HDAC1-3 as well as Vangl2, Scrib and Rac1 mRNA and protein expression levels were determined by quantitative real-time PCR and Western blot, respectively. The total HDAC activity was analyzed by colorimetric assay.
RESULTSThe fetus mortality rate after VPA treatment was 31.7%, with a significantly higher rate of cardiac abnormalities in comparison with the controls (P<0.05). In comparison with the blank and vehicle groups, HDAC1 mRNA was significantly increased at various concentrations of VPA treatment at all time points of exposure (P<0.05), together with a reduction of protein level after 48 and 72 hours of exposure (P<0.05). The inhibition of HDAC2 mRNA after various concentrations of VPA incubation was pronounced at 24 hours of exposure (P<0.05), while the protein levels were reduced at all time points (P<0.05). HDAC3 mRNA was prominently induced by VPA (4.0 and 8.0 mmol/L) at all time points of treatment (P<0.05). In contrast, the protein level was inhibited after VPA treatment (P<0.05). In comparison with the blank and vehicle groups, Vangl2 mRNA as well as Scrib mRNA/protein expression levels were markedly reduced after 48 and 72 hours of VPA treatment (P<0.05), together with a reduction of protein level in Vangl2 at 72 hours (P<0.05). Compared with the blank and vehicle groups, a significant repression in the total HDAC activity was observed in the VPA-treated group at concentrations of 4.0 and 8.0 mmol/L after 24 hours of treatment (P<0.05), and the effect persisted up to 48 and 72 hours, exhibiting pronounced inhibition at all concentrations (P<0.05).
CONCLUSIONSVPA might result in acetylation/deacetylation imbalances by inhibiting HDAC1-3 protein expression and total HDAC activity, leading to the down-regulation of mRNA and protein expression of Vangl2 and Scrib. This could be one of the mechanisms contributing to congenital heart disease.
Acetylation ; Animals ; Cell Polarity ; Cells, Cultured ; Fetal Heart ; drug effects ; metabolism ; Heart Defects, Congenital ; etiology ; Histone Deacetylase 1 ; genetics ; Histone Deacetylase 2 ; genetics ; Histones ; metabolism ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; genetics ; RNA, Messenger ; analysis ; Valproic Acid ; pharmacology
10.Relief Effect of Bevacizumab on Severe Edema Induced by Re-irradiation in Brain Tumor Patients.
Ge SHEN ; Ying-Jie WANG ; Yan-Jun GUAN ; Da-Peng DONG ; Gang YANG ; Dan LI ; Rui-Min HAO ; Hui-Ru SUN ; Ming ZHOU ; Kun-Peng WANG ; Shi-Xiang ZHOU ; Qin-Wen WANG ; Shi-Kai WU ; Yan-Jun ZENG
Chinese Medical Journal 2015;128(15):2126-2129
Adult
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Aged
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Bevacizumab
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therapeutic use
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Brain Neoplasms
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drug therapy
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therapy
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Edema
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drug therapy
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etiology
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Female
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Humans
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Male
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Middle Aged
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Re-Irradiation
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adverse effects

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