1.Analysis of in Vitro Activity and Mechanism of Dunhuang Yifang Daxiefei Decoction on Pneumonia Based on Chemical Bioinformatics
Jia LIN ; Xiaojie JIN ; Chenghao LI ; Ruifeng WANG ; Yehu HOU ; Yixi ZHANG ; Hao LIU ; Min ZHANG ; Juan YAO ; Jintian LI ; Yongqi LIU
Chinese Journal of Modern Applied Pharmacy 2024;41(7):871-886
OBJECTIVE
To explore the effectiveness, potential mechanism and compatibility characteristics of efficacy groups of Dunhuang medical prescription Daxiefei decoction in preventing and treating pneumonia based on chemical bioinformatics method.
METHODS
To study the effect of Daxiefei decoction freeze-dried powder solution on the proliferation activity of lung epithelial cells through cell experiments. Daxiefei decoction was divided into three groups: clearing away heat group, resolving phlegm group, and nourishing Yin group according to its efficacy characteristics. The chemical components of Daxiefei decoction were obtained by TCMSP database and literature search, and the targets were predicted in Swiss Target Prediction database. Pneumonia disease targets were obtained by DrugBank, TTD, Genecards and DisGeNET databases. STRING database and Cytoscape were used to construct the intersection target interaction network and "drug-component-target- pathway" network and DAVID database was used for KEGG pathway enrichment analysis. The network was used to analyze the scientific connotation of the compatibility of efficacy groups. Furthermore, molecular docking was used to evaluate the target-compound affinity and molecular dynamics was used to explore the dynamic molecular mechanism.
RESULTS
Cell experiments showed that Daxiefei decoction can maintain the proliferation of lung epithelial cells, reverse the decrease of mitochondrial activity induced by LPS and reduce apoptosis. Complex network analysis showed that the pathways enriched by the three functional groups contained in Daxiefei decoction were mainly distributed in two modules: inflammation regulation and reducing airway mucus hypersecretion. Each module was connected by a common target gene and had its own focus. The results of molecular docking showed that the components quercetin, baicalein, isorhamnetin etc. might be the effective multi-target components of Daxiefei decoction. SRC, EGFR, PPARA etc. had good affinity with each potential active component, which might be a potential target of Daxiefei decoction for preventing and treating pneumonia. Molecular dynamics simulation showed that the potential active component quercetin formed stable intermolecular interactions with SRC.
CONCLUSION
This study initially reveal the material basis and molecular mechanism of Daxiefei decoction in the prevention and treatment of pneumonia. It also explores the scientific connotation of Daxiefei decoction in the prevention and treatment of pneumonia with different efficacy groups, and its modern development and clinical application provide chemical bioinformatics basis.
2.Study on the Material Basis of Guiqi Baizhu Prescription Inhibiting the Proliferation of Uveal Melanoma Cells Based on Traditional Chinese Medicine Chemical Bioinformatics
WANG Ruifeng ; JIN Xiaojie ; LIU Hao ; LI Chenghao ; ZHANG Min ; Li Mi ; LI Haotian ; ZHANG Yu ; MA Huanhuan ; ZHANG Yuemei
Chinese Journal of Modern Applied Pharmacy 2024;41(14):1900-1912
ABATRACT
OBJECTIVE To utilize the pharmacophore model-molecular docking combined with the virtual screening strategy of free energy calculation and the chemical bioinformatics method of traditional Chinese medicine in cell biology experiments to investigate the components of Guiqi Baizhu prescription that target phosphatidylinositol 3-kinase(PI3K) and inhibit the proliferation of uveal melanoma(UM) cells.
METHODS The pharmacophore model of PI3K inhibitor was constructed, and the compounds of Guiqi Baizhu prescription were virtual screened. The components that fit the pharmacophore model were calculated by molecular docking and binding free energy, and the potential inhibitory components were selected for biological experimental evaluation. The effects of potential inhibitory components on UM cell proliferation were detected by CCK-8 and clonal formation assay. Flow cytometry was used to detect the cell cycle and apoptosis of UM cells. The mitochondrial membrane potential of UM cells was detected using JC-10 staining. The expressions of PI3K and downstream pathway proteins were detected by Western blotting.RESULTS The pharmacophore model included 2 hydrogen bond receptors, 2 aromatic ring centers, and exclusion volumes. The results of the CCK-8 experiment showed that quercetin, tangerine, and nobiletin at concentrations of 10, 20, 40, 80 μmol·L−1, and cyrtin at concentrations of 20, 40, 80 μmol·L−1, were able to inhibit the proliferation of UM cells. The clonal formation experiment showed that quercetin, tangerine, nobiletin, and morusin, at different concentrations, could significantly inhibit the clonal proliferation of UM cells. Flow cytometry showed that UM cells were arrested in the G0/G1 phase by tangeretin and quercetin, while UM cells were arrested in the G2/M phase by nobiletin and morusin. The results of JC-10 staining showed that quercetin, nobiletin, tangeretin, and morusin could reduce the mitochondrial membrane potential of UM cells. Western blotting results showed that 4 compounds could target PI3K, but their downstream pathways were different.CONCLUSION Based on the method of chemical bioinformatics in traditional Chinese medicine, this study explores the material basis for the inhibition of UM cell proliferation by the Guiqi Baizhu prescription. It also provides insights for the modern development of traditional Chinese medicine prescription.
3.Effect of silencing Ras homolog family member C on proliferation,invasion,and migration of salivary adenoid cystic carcinoma
Wenyuan YU ; Peng ZHAO ; Yu SHAO ; Yong XU ; Jin XU ; Lei XIE ; Chenghao YU ; Qiuping HE ; Zhenggang CHEN
West China Journal of Stomatology 2024;42(6):723-734
Objective This study aimed to investigate the effects of silencing Ras homolog family member C(RhoC)on the proliferation,apoptosis,invasion,migration,and epithelial-mesenchymal transition(EMT)of salivary adenoid cystic carcinoma(SACC)and its molecular mechanisms.Methods A total of 27 SACC lesions and normal salivary gland tissues that were surgically resected at Qingdao Municipal Hospital from January 1,2019 to March 1,2024 were selected,and the expression levels of RhoC were detected by Western blot and immunohistochemistry.Three small interfering RNA(siRNAs)were designed to target the RhoC gene sequence,transfected into SACC-LM and SACC-83 cell lines,and evaluated for transfection efficiency.The protein expression levels of RhoC,Rho-asso-ciated protein kinase-1(ROCK1),p38 mitogen-activated protein kinase(p38MAPK),phosphorylated-p38MAPK(p-p38MAPK),twist family bHLH transcription factor 1(TWIST1),E-cadherin,N-cadherin,and Vimentin were com-pared using Western blot.CCK-8 assay,flow cytometry,transwell invasion assay,and wound healing assay were conducted to assess the differences in cell proliferation,apoptosis,invasion,and migration abilities among the groups.Bioinformatics methods were also used to predict possible upstream micro RNAs(miRNAs)of RhoC and their expression levels in SACC.Moreover,dual-luciferase reporter gene experiments were performed to verify the binding sites of miR-138-5p and RhoC.Results RhoC was highly expressed in SACC(P<0.05).After silencing RhoC,the test group showed a significant decrease in the expression level of ROCK1,p-p38MAPK,TWIST1,N-cadherin,and Vimentin,as well as a significant increase in the expression level of E-cadherin(P<0.05).No signifi-cant difference in the expression level of p38MAPK was observed(P>0.05).The cell proliferation,invasion,and mi-gration ability decreased in the test group,whereas the apoptosis rates significantly increased(P<0.05).miR-138-5p was lowly expressed in SACC,and miR-138-5p mimic can significantly downregulated the luciferase activity of 293T cells after transfection with a RhoC wild-type plasmid(P<0.05).Conclusion RhoC is highly expressed in SACC,and RhoC silencing may target the downstream ROCK1/p38MAPK/TWISTl signaling pathway,thereby in-hibiting the proliferation,invasion,migration,and EMT of SACC while promoting its apoptosis.On the contrary,miR-138-5p is lowly expressed in SACC and is a potential upstream gene of RhoC,and there may be binding sites between the two genes.
4.Analysis of high risk factors affecting delayed recovery of patients undergoing radical mastectomy under general anesthesia
Chenghao JIN ; Qiang LIU ; Meiyi ZHAO ; Yijun SHI
Chinese Journal of Endocrine Surgery 2023;17(5):540-544
Objective:To investigate the risk factors affecting the delay of recovery in patients under general anesthesia.Methods:Patients who underwent radical mastectomy for breast cancer in our hospital from Jul. 2020 to Aug. 2022 were selected as the research objects, and the effective data of 80 patients were obtained after screening. The patients were divided into the non-delayed recovery group (54 cases) and the delayed recovery group (26 cases). The general conditions and perioperative data of the two groups were compared, and the high-risk factors affecting delayed recovery from anesthesia were analyzed using the Logistic hazard proportional regression model. Results:In general, there were no significant differences in body mass index, hypertension, diabetes, tumor size, tumor subtype, tumor location, or tumor stage between the non-delayed awakening group and the delayed awakening group (all P>0.05). The average age of patients in the wake-up delay group was (53.28±11.01), the proportion of anemia was 42.30% (11/26), and the proportion of ASA Ⅱ patients was 76.92% (20/26) compared with the average age of the non-wake-up delay group (46.89±6.91) ( t=3.17, P=0.002), the proportion of anemia was 20.37% (11/54) ( χ2=3.17, P=0.040), the proportion of ASA Ⅱ patients was 27.78% (15/54) ( χ2=17.22, P<0.001), which was significantly increased. In the perioperative data, there was no statistical significance in the intraoperative combined epidural anesthesia between the non-delayed recovery group and the delayed recovery group (all P>0.05). The data of the patients in the delayed recovery group, including average intraoperative blood loss (234.14±32.28), operation time (229.47±29.84), anesthesia time (246.14±35.64) and intraoperative compound sevoflurane inhalation accounted for 69.23% (18/26) ,which were significantly increased compared with the data of non-delayed recovery group following, including the average intraoperative blood loss (215.48±29.54) ( t=2.57, P=0.012), operation time (206.35±27.41) ( t=3.43, P=0.001), anesthesia time (215.61±28.54) ( t=4.13, P<0.001), intraoperative compound sevoflurane inhalation (44.44%, 24/54). Through Logistic hazard ratio regression analysis, it was found that age ( OR=1.15, 95% CI: 1.05-1.30, P=0.008), ASA Ⅱ grade ( OR=9.49, 95% CI: 2.05-60.94, P=0.008), intraoperative bleeding volume ( OR=1.04, 95% CI: 1.01-1.08, P=0.012), operation time ( OR=1.05, 95% CI: 1.01-1.08, P=0.009), and anesthesia time ( OR=1.04, 95% CI: 1.02-1.07, P=0.004) were high-risk factors affecting the delayed recovery from anesthesia. Conclusion:Increasing age, high grade of ASA, heavy intraoperative blood loss, long operation time and anesthesia time are independent risk factors affecting delayed recovery from anesthesia.
5.Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases
Xuheng SUN ; Yijun WANG ; Wei ZHANG ; Yajun GENG ; Yongsheng LI ; Tai REN ; Maolan LI ; Xu'an WANG ; Xiangsong WU ; Wenguang WU ; Wei CHEN ; Tao CHEN ; Min HE ; Hui WANG ; Linhua YANG ; Lu ZOU ; Peng PU ; Mingjie YANG ; Zhaonan LIU ; Wenqi TAO ; Jiayi FENG ; Ziheng JIA ; Zhiyuan ZHENG ; Lijing ZHONG ; Yuanying QIAN ; Ping DONG ; Xuefeng WANG ; Jun GU ; Lianxin LIU ; Yeben QIAN ; Jianfeng GU ; Yong LIU ; Yunfu CUI ; Bei SUN ; Bing LI ; Chenghao SHAO ; Xiaoqing JIANG ; Qiang MA ; Jinfang ZHENG ; Changjun LIU ; Hong CAO ; Xiaoliang CHEN ; Qiyun LI ; Lin WANG ; Kunhua WANG ; Lei ZHANG ; Linhui ZHENG ; Chunfu ZHU ; Hongyu CAI ; Jingyu CAO ; Haihong ZHU ; Jun LIU ; Xueyi DANG ; Jiansheng LIU ; Xueli ZHANG ; Junming XU ; Zhewei FEI ; Xiaoping YANG ; Jiahua YANG ; Zaiyang ZHANG ; Xulin WANG ; Yi WANG ; Jihui HAO ; Qiyu ZHANG ; Huihan JIN ; Chang LIU ; Wei HAN ; Jun YAN ; Buqiang WU ; Chaoliu DAI ; Wencai LYU ; Zhiwei QUAN ; Shuyou PENG ; Wei GONG ; Yingbin LIU
Chinese Journal of Digestive Surgery 2022;21(1):114-128
Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.
6.Clinical characteristics and long-term survival quality in single-center children with low and intermediate-risk neuroblastoma
Shihan ZHANG ; Chenghao CHEN ; Hong QIN ; Chiyi JIANG ; Qianqian LUO ; Yan SU ; Mei JIN ; Dawei ZHANG ; Huanmin WANG ; Qi ZENG ; Xiaoli MA
Chinese Journal of Applied Clinical Pediatrics 2021;36(21):1623-1627
Objective:To summarize the clinical characteristics of single-center children with low and intermediate-risk neuroblastoma (NB), report the long-term follow-up results of the growth and survival quality, and provide a basis for further clinical research.Methods:Clinical characteristics, including the sex, age, stage, risk of disease, and metastatic site of 370 newly treated children with low and intermediate-risk NB admitted to Hematology Oncology Center, Beijing Children′s Hospital from March 2007 to June 2019 were retrospectively analyzed.Kaplan-Meier method was used for survival analysis.WHO Anthro Plus was used for calculating Z score.Results:A total of 370 eligible children with low and intermediate-risk NB were included, with the mean age at onset of 16.8 months (1-191 months). Among them, 148 cases (40%) were younger than 12 months old.Mediastinal region was the most common primary site of NB (47.8%, 177 cases), followed by retroperitoneum/adrenal gland (41.4%, 153 cases). The median follow-up time of 370 patients was 31 months (0.3-157.0 months), the 5-years event free survival (EFS) and 5-year overall survival (OS) were 86.2% and 96.9%, respectively.Thirty-seven cases had growth and deve-lopment problems, of which 22 cases had stunted growth, 6 cases had low body mass, 9 cases had wasting, and 7.3%(27/370 cases) had scoliosis.5.5% of them had heart damage and 5.0%(18/357 cases) had kidney damage, involving 12 cases related to the primary tumor and 6 cases were surgically related.30.2%(95/315 cases) of them had hair changed after chemotherapy, and curly hair was the most common change.Compared with before treatment, 14.9% of the children had a personality change, with an impatient being the most common.Conclusions:The 5-year overall survival rate of the single-center large sample of low and intermediate-risk NB was high, mediastinal was the most common primary site of tumor, and the long-term quality of life is good, but there were still treatment-related side effects, and further clinical monitoring and long-term follow-up were needed.
7.High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors.
Yao ZHAO ; Xiaoyu DU ; Yinkai DUAN ; Xiaoyan PAN ; Yifang SUN ; Tian YOU ; Lin HAN ; Zhenming JIN ; Weijuan SHANG ; Jing YU ; Hangtian GUO ; Qianying LIU ; Yan WU ; Chao PENG ; Jun WANG ; Chenghao ZHU ; Xiuna YANG ; Kailin YANG ; Ying LEI ; Luke W GUDDAT ; Wenqing XU ; Gengfu XIAO ; Lei SUN ; Leike ZHANG ; Zihe RAO ; Haitao YANG
Protein & Cell 2021;12(11):877-888
A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use*
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Binding Sites
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COVID-19/virology*
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Coronavirus Papain-Like Proteases/metabolism*
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Crystallography, X-Ray
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Drug Evaluation, Preclinical
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Drug Repositioning
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High-Throughput Screening Assays/methods*
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Humans
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Imidazoles/therapeutic use*
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Inhibitory Concentration 50
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Molecular Dynamics Simulation
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Mutagenesis, Site-Directed
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Naphthoquinones/therapeutic use*
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Protease Inhibitors/therapeutic use*
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Protein Structure, Tertiary
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Recombinant Proteins/isolation & purification*
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SARS-CoV-2/isolation & purification*
8.Clinical characteristics and prognostic analysis of 458 children with high-risk neuroblastoma in a single center
Yan SU ; Xiaoli MA ; Huanmin WANG ; Hong QIN ; Maoquan QIN ; Fuquan ZHANG ; Mei JIN ; Dawei ZHANG ; Chenghao CHEN ; Qi ZENG ; Lejian HE ; Xin NI
Chinese Journal of Pediatrics 2020;58(10):796-801
Objective:To summarize the clinical characteristics of high-risk neuroblastoma (HR-NB) in a single center, analyze the prognostic factors of HR-NB.Methods:The clinical data of children with HR-NB who were treated and followed up at the hematology-oncology center of Beijing Children′s Hospital from February 1, 2007 to June 30, 2018 were analyzed retrospectively. The clinical features were summarized. Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. The last follow-up time was June 30, 2019.Results:A total of 458 children with HR-NB were enrolled in this study, including 265 males (57.9%) and 193 females (42.1%), the age at diagnosis was 40.0 months (4.5-148.0 months), the follow-up time was 22.0 months (0.2-138.0 months) and the time of tumor progression or recurrence was 15 months (1-72 months). The 5-year event-free survival (EFS) rate was (31.2±2.6)% and the 5-year overall survival (OS) rate was (43.9±3.2)%. The 5-year EFS rate and 5-year OS rate in 142 hematopoietic stem cell transplantation (HSCT) patients with bone marrow metastases were better than that in 196 non-transplantation cases with bone marrow metastases ((26.5±4.5)% vs. (25.1±3.6)%, χ2=13.773, P=0.001; (38.1±5.5)% vs. (35.7±4.7)%, χ2=9.235, P=0.002); 128 transplantation patients with bone metastases had higher 5-year EFS rate and 5-year OS rate than 188 non-transplantation cases with bone metastases ((28.5±5.0)% vs. (26.7±3.8)%, χ2=10.222, P=0.001; (37.1±6.0)% vs. (36.2±4.8)%, χ2=7.843, P=0.005). The 5-year EFS rate was higher in 37 HSCT patients with MYCN amplification than in 49 non-transplantation cases with MYCN amplification ((26.8±8.0) % vs. (20.5±6.4) %, χ2=5.732, P=0.017). No significant difference was found in 5-years OS rate between transplantation group with MYCN amplification and non-transplantation group with MYCN amplification ((31.4±8.6) % vs. (26.2±7.4) %, χ2=3.230, P=0.072). Univariate survival analysis showed that lactate dehydrogenase (LDH)≥1 500 U/L was associated with poor prognosis of patients with MYCN amplification (χ2=6.960, P=0.008). Multivariate Cox analysis showed bone marrow metastasis and LDH≥1 500 U/L were independent risk factors for poor prognosis of patients with non-MYCN amplification ( HR=2.427, 1.618;95 %CI:1.427-4.126, 1.275-2.054, P<0.05) for both comparisons. Conclusions:LDH≥1 500 U/L was the poor prognostic factor for patients with MYCN amplification. The bone marrow metastasis and LDH≥1 500 U/L were the poor prognostic factors for HR-NB patients with non-MYCN amplification. HSCT can improve the prognosis of patients with bone or bone marrow metastasis. It can also retard the time of progression or recurrence for patients with MYCN amplification.
9.Selection strategy of neoadjuvant therapy for pancreatic cancer
Chunyou WANG ; Gang JIN ; Menghua DAI ; Chenghao SHAO ; Xiaohan SHI ; Suizhi GAO ; Qiang XU ; Xing LIANG
Chinese Journal of Digestive Surgery 2019;18(7):648-656
Pancreatic cancer is a common malignancy with the worst prognosis.Radical surgery has been the only curative treatment for pancreatic cancer.With the advancement of surgical techniques and the implementation of the concept of comprehensive treatment for cancer in recent years,neoadjuvant therapy for pancreatic cancer has received more attention.There are continuing controversies in the hotspots and difficulties,with opportunities and challenges coexisting.Four famous experts and their teams in pancreatic surgery discussed selection strategy of neoadjuvant therapy for pancreatic cancer based on clinical experiences.Professor Wang Chunyou proposed that surgery was prior for patients with a higher likelihood of achieving R0 resection for pancreatic cancer to avoid the possibility of tumor progression and loss the opportanity of radical resection during neoadjuvant therapy.For patients with less chance of radical resection for pancreatic cancer and unresectable pancreatic cancer,neoadjuvant therapy is worthy of a positive attempt.Professor Jin Gang and his team believed that neoadjuvant therapy played an important role in improving the survival time of patients with pancreatic head cancer,especially with borderline resectable pancreatic head cancer.After neoadjuvant therapy,pancreatic surgeons should pay attention to improvement of surgery safety and R0 resection rate.Professor Dai Menghua and his team suggested that patients with resectable pancreatic cancer and borderline resectable pancreatic cancer could benefit from neoadjuvant therapy,which required proof from clinical trials.Surgeons should choose the appropriate treatment strategy based on guidelines and individual conditions for patients with pancreatic cancer.Professor Shao Cheghao and his team suggested that surgical treatment after neoadjuvant therapy or translational therapy for locally advanced pancreatic head cancer is safe,effective and feasible,especially for pancreaticoduodenectomy with combined revascularization.For the treatment of patients with pancreatic head cancer after neoadjuvant chemotherapy,the choice of next treatment options,evaluation indicators,timing of surgery and surgical methods need to be further studied.
10.Antiproliferative and apoptosis effect of atorvastatin on K562 cells
Chunfang KONG ; Jianglong ZHOU ; Weirong DING ; Jianghua DING ; Guoan CHEN ; Hongbo CHENG ; Chenghao JIN
Chongqing Medicine 2018;47(3):299-301,305
Objective To explore the effect of atorvastatin on the proliferation and apoptosis of K562 cells andto investigate its mechanisms.Methods The cells were treated by different concentrations of atorvastatin.The CCK-8 assay was employed to detect the cell proliferation.The cell apoptosis was detected by AnnexinV-FITC/PI dual staining;the flow cytometry was used to detect the cellular cycle;the activities of caspase-3,-8,-9 were detected by the colorimetric method;qRT-PCR was employed to measure the mRNA expression levels of Bcl-2 and PDCD5 in K562 cells.Results Atorvastatin could inhibit the proliferation of K562 cells in a time-and dose-dependent manner(P<0.05);and induced the apoptosis of K562 cells,the percentage of G0/G1 phase cells was increased after atorvastatin treating k562 cells(P<0.01),while the percentage of S phase cells was decreased(P<0.01),moreover which showing the concentration dependence(P<0.01);atorvastatin activated the caspase-3,-8,-9 (P<0.01);down-regulated Bcl-2 mRNA expression and up-regulated PDCD5 mRNA expressionin a concentration dependence(P<0.01).Conclusion Atorvastatin can inhibit the proliferation and induce apoptosis in K562 cells.


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