1.CDA C435T gene polymorphism significantly extends the long-term efficacy of gemcitabine in advanced non-small cell lung cancer
Mengjiao WANG ; Chao GAO ; Tao WANG ; Qian ZHANG ; Juan WEN ; Dongmei LV ; Lili HU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(12):1337-1343
AIM:To research the effects of cyti-dine deaminase(CDA)C435T polymorphism on the long-term effectiveness of gemcitabine in non-small cell lung cancer(NSCLC).METHODS:Enrolled 145 NSCLC patients received gemcitabine-platinum regiments at the Affiliated Hospital of Xuzhou Med-ical University from August 2016 to February 2019,characteristics recorded such as:age,gender,path-ological type,clinical stage(Ⅰ-ⅢA/ⅢB-Ⅳ)and so on.Followed-up and evaluated according to RECIST1.1,the disease-free survival(DFS),progression-free survival(PFS)and overall survival(OS)was study endpoint.Cases were categorized into wild-type CC and mutant CT/TT group.Kaplan-Meier method and log-rank test were utilized to analyze the rela-tionship between CDA C435T and DFS/PFS/OS.A cox model was implemented to analyze the prog-nostic factors.RESULTS:In stage Ⅰ-ⅢA,median DFS of CT/TT compared with CC was not obvious(16.8 vs.35.7 months,P=0.294),same in median OS(54.3 vs.81.9 months,P=0.256).In stage ⅢB-Ⅳ,the median PFS in CT/TT was longer than CC(10.4 vs.5.0 months,P=0.009),the median OS was undiffer-entiated(16.2 vs.24.3 months,P=0.087).No differ-ence of overall median OS in CC and CT/TT geno-types was seen(21.5 months vs.25.3 months,P=0.077).Cox regression model showed CDA C435T polymorphism was an independent factor of PFS in stage ⅢB-Ⅳ(P=0.019).CONCLUSION:CDA C435T polymorphism shows a function as a prediction in-fluencing PFS of gemcitabine in ⅢB-Ⅳ NSCLC,CT/TT genotype is significantly prolonged.
2.CDA C435T gene polymorphism significantly extends the long-term efficacy of gemcitabine in advanced non-small cell lung cancer
Mengjiao WANG ; Chao GAO ; Tao WANG ; Qian ZHANG ; Juan WEN ; Dongmei LV ; Lili HU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(12):1337-1343
AIM:To research the effects of cyti-dine deaminase(CDA)C435T polymorphism on the long-term effectiveness of gemcitabine in non-small cell lung cancer(NSCLC).METHODS:Enrolled 145 NSCLC patients received gemcitabine-platinum regiments at the Affiliated Hospital of Xuzhou Med-ical University from August 2016 to February 2019,characteristics recorded such as:age,gender,path-ological type,clinical stage(Ⅰ-ⅢA/ⅢB-Ⅳ)and so on.Followed-up and evaluated according to RECIST1.1,the disease-free survival(DFS),progression-free survival(PFS)and overall survival(OS)was study endpoint.Cases were categorized into wild-type CC and mutant CT/TT group.Kaplan-Meier method and log-rank test were utilized to analyze the rela-tionship between CDA C435T and DFS/PFS/OS.A cox model was implemented to analyze the prog-nostic factors.RESULTS:In stage Ⅰ-ⅢA,median DFS of CT/TT compared with CC was not obvious(16.8 vs.35.7 months,P=0.294),same in median OS(54.3 vs.81.9 months,P=0.256).In stage ⅢB-Ⅳ,the median PFS in CT/TT was longer than CC(10.4 vs.5.0 months,P=0.009),the median OS was undiffer-entiated(16.2 vs.24.3 months,P=0.087).No differ-ence of overall median OS in CC and CT/TT geno-types was seen(21.5 months vs.25.3 months,P=0.077).Cox regression model showed CDA C435T polymorphism was an independent factor of PFS in stage ⅢB-Ⅳ(P=0.019).CONCLUSION:CDA C435T polymorphism shows a function as a prediction in-fluencing PFS of gemcitabine in ⅢB-Ⅳ NSCLC,CT/TT genotype is significantly prolonged.
3.CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer.
Yu-Zhao WANG ; Yu-Chen QIAN ; Wen-Jie YANG ; Lei-Hong YE ; Guo-Dong GUO ; Wei LV ; Meng-Xi HUAN ; Xiao-Yu FENG ; Ke WANG ; Zhao YANG ; Yang GAO ; Lei LI ; Yu-Le CHEN
Asian Journal of Andrology 2023;25(2):152-157
Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
Male
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Humans
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Von Hippel-Lindau Tumor Suppressor Protein/metabolism*
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DNA-Binding Proteins/metabolism*
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Prolyl Hydroxylases/metabolism*
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Hypoxia
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Prostatic Neoplasms/pathology*
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Glycolysis
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Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
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Cell Line, Tumor
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DNA Helicases/metabolism*
4. Biological Implication of Chimeric RNAs in Cancer
Wen-Qian LV ; Yue TANG ; Fu-Jun QIN ; Wen-Qian LV ; Yue TANG ; Fu-Jun QIN ; Fu-Jun QIN ; Fu-Jun QIN
Chinese Journal of Biochemistry and Molecular Biology 2023;39(8):1087-1097
Chimeric RNA is a fusion transcript composed of exons from two or more different genes and generated by chromosome rearrangement or RNA splicing. Chimeric RNAs have the potential to encode novel proteins or function as non-coding RNAs. Chimeric RNAs were ubiquitously expressed across different cancers and normal tissues. To date, mechanistic and functional studies of chimeric RNAs still remain unclear. Precise definition and terminology in the research field of chimeric RNA will be discussed in this review. The formation, classification and clinical significance of chimeric RNAs in cancer progression will be summarized. Previous studies showed that products of chimeric RNAs may play important roles in regulating cell proliferation, motility, invasion and apoptosis through encoded fusion proteins or long non-coding chimeric RNAs. In cancer, chimeric RNA and its encoded specific protein or non-coding RNA can regulate tumorigenesis by changing cell phenotypes or directly affecting gene expression or regulatory pathways, which have the potential to be important diagnostic biomarkers and therapeutic targets. In recent years, more and more cancer-specific chimeric RNAs have been discovered from multiple types of cancers and used as therapeutic targets due to their vital roles in disease prognosis. Therefore, this review will focus on the functions and applications of chimeric RNAs in different tumors, which can shed a light on cancer diagnosis and therapeutics from the new perspective.
5.Development of an eco-friendly and fast HPLC method for quantitative analysis of four nucleosides in Cordyceps and related products.
Zheng-Ming QIAN ; Zi WU ; Qi HUANG ; Chuan-Xi WANG ; Guo-Yin TAN ; Wen-Jia LI ; Wan-Yang SUN ; Gen-Pin LV ; Hao GAO
Chinese Journal of Natural Medicines (English Ed.) 2021;19(12):954-960
An eco-friendly and fast HPLC method was developed for the determination of adenosine, inosine, guanosine and uridine in Cordyceps and related products (fermented mycelia of Hirsutella sinensis andPaecilomyces hepiali). The sample was ultrasonically extracted using 0.5% phosphoric acid solutions for 2.5 min. Sample separation was performed on a Poroshell SB-Aq column (50 mm × 4.6 mm, 2.7 μm) using eco-friendly mobile phase consisting of formic acid and ammonium formate aqueous solution at a flow rate of 1.0 mL·min
Adenosine
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Chromatography, High Pressure Liquid
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Cordyceps
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Nucleosides
6.Application for a Bridge Therapy of Percutaneous Balloon Aortic Valvuloplasty in the Era of Transcatheter Aortic Valve Replacement: A Single Center Experience
Mo-Yang WANG ; Guang-Yuan SONG ; Han-Jun PEI ; Yuan WANG ; Qian ZHANG ; Guan-Nan NIU ; Zheng ZHOU ; Hao ZHANG ; Wen-Jia ZHANG ; Jian-De WANG ; Bin LV ; Yong-Jian WU ; Shu-Bin QIAO ; Yue-Jin YANG ; Run-Lin GAO
Chinese Circulation Journal 2018;33(4):336-340
Objectives: To explore the clinical experience for a bridge therapy of percutaneous balloon aortic valvuloplasty (PBAV) in treating the patients with severe aortic stenosis (AS). Methods: A total of 37 patients with severe AS who were not suitable for surgical valvular replacement received PBAV in our hospital from 2011-03 to 2017-03 were retrospectively studied. The patient's mean age was (74±12) years, their clinical and anatomical features, efficacy and safety of operation were observed and the outcomes were evaluated by follow-up study. Results: Patients presented the high surgical risk and worse cardiac function, 50% of them had bicuspid leaflet morphology with severe calcification [HU850=(856.0±658.2) mm3]. Balloon size was chosen by the intra-operative supra-annular diameters; at 7 days after operation, aortic valve orifice area (AVOA) was increased from (0.37±0.10) cm2to (0.87±1.10) cm2, the mean trans-aortic valve gradient pressure decreased form (55.1±22.9) mmHg to (44.8±17.8) mmHg, P<0.001 and LVEF elevated form(35.8±14.3)% to(41.0±12.2)%,P<0.001.There were 4 patients died in hospital,1 received permanent pacemaker and 1 developed severe aortic valve regurgitation. The patients were followed-up for (16.5±11.1)months after operation, 13/37 (35.1%) patients were in transition to surgical or transcatheter aortic valve replacement (TAVR). Conclusions: PBAV may have good early clinical efficacy in severe AS patients who were not suitable for surgical valvular replacement and TAVR; PBAV could be expected to become a bridge therapy, smaller supra-annular diameter was safe and effective for patients having bicuspid leaflet with severe calcification.
7.Biliverdin protects against cisplatin-induced apoptosis of renal tubular epithelial cells.
Qian LV ; Ying YAO ; Wei WANG ; Wei XIONG ; Wen-hui LIAO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(1):48-52
Biliverdin (BV) has long been thought to be a cytotoxic metabolic waste product. It has also been demonstrated to have important cytoprotective functions during oxidative stress. The present study aimed to examine the cytoprotective effect of BV on NRK-52E cells, a proximal tubular cell line derived from rat kidney. Cells were treated with 50 µmol/L cisplatin for 24 h (cisplatin group) or pre-treated with BV for 30 min, then with 50 µmol/L cisplatin for 24 h (cisplatin+BV group). Those given no treatment served as a control. Cell apoptosis was evaluated by flow cytometry and cell viability by Cell Counting Kit-8 (CCK-8). The protein expressions of cleaved caspase3, Bax and Bcl-2 were assessed by Western blotting. Reactive oxygen species (ROS) levels were measured using carboxydichlorodihydrofluorescein diacetate (H2DCF). The results showed that cisplatin induced the apoptosis of NRK-52E cells, decreased cell viability, and increased the formation of ROS by upregulating the expression of cleaved caspase3 and Bax and decreasing Bcl-2 protein expression. These effects could be significantly reversed by pretreatment with BV. It was concluded that BV can protect against cisplatin-induced cell apoptosis through the anti-oxidative effects.
Animals
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Antioxidants
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pharmacology
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Apoptosis
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Biliverdine
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pharmacology
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Cell Line
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Cisplatin
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toxicity
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Epithelial Cells
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drug effects
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metabolism
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Kidney Tubules
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cytology
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Rats
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Reactive Oxygen Species
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metabolism
8.Improving the researchers' compliance and the quality of clinical study on acupuncture and moxibustion:thoughts on the role conflict between doctors and researchers.
Qian WEN ; Jianqin LV ; Yang YANG ; Mengyue LIU ; Chengwei WANG ; Ning LI
Chinese Acupuncture & Moxibustion 2016;36(6):561-563
The coordination and collaboration of many links are required to achieve the successful development of a high-quality clinical randomized controlled trial, in which, the compliance of the researchers affects the ultimate results and quality of the study since it is responsible for the safety and benefits of subjects in the trials and study quality. Focusing on the researchers' compliance, it is believed that the improvements in the researchers' compliance are very significant in the implementation of study scheme. At present, commonly, the researchers are of the low compliance, manifest as failure to obey the study scheme (such as inclusive criteria, enrollment sequence), failure to obey the rules of operation and data collection, failure to store the original documents but to modify the data, failure to report timely adverse events, etc. In view of clinical research monitors, the reasons on the low compliance are analyzed and the solutions are proposed.
9.Electroacupuncture for severe acute pancreatitis accompanied with paralytic ileus:a randomized controlled trial.
Jia LI ; Yu ZHAO ; Qian WEN ; Qiming XUE ; Jianqin LV ; Ning LI
Chinese Acupuncture & Moxibustion 2016;36(11):1126-1130
OBJECTIVETo observe the clinical efficacy differences between electroacupuncture (EA) and regular treatment for severe acute pancreatitis accompanied with paralytic ileus.
METHODSThis was a prospective pragmatic randomized controlled trial. A total of 140 cases of severe acute pancreatitis accompanied with paralytic ileus were randomly assigned into an EA group and a regular treatment group, 70 cases in each one. The patients in the regular treatment group were treated with regular treatment, including intensive care, gastrointestinal decompression, fasting, blood capacity supplement, acid suppression treatment, internal environment maintenance, infection prevention, inhibition of pancreatic exocrine secretion, etc. Based on the regular treatment, patients in the EA group were treated with EA at Zusanli (ST 36) and Zhigou (TE 6), 30 min for each treatment, once a day for totally 5 days. The VAS-based abdominal distension severity scale and abdominal pain severity scale were compared before and during treatment in the two groups, moreover, the number of patients who transferred to surgery or ICU was compared.
RESULTS(1) After the 1st EA, the abdominal pain and distension severity scales were both improved in the EA group, which were superior to those of the regular treatment group (all<0.05); afterwards, the abdominal distension and pain severity scales of each day in the EA group were all significantly superior to those of the regular treatment group (all<0.05). (2) The number of patients who transferred to surgery or ICU was not significantly different between the two groups (>0.05).
CONCLUSIONSEA at Zusanli (ST 36) and Zhigou (TE 6) can significantly reduce the abdominal distension and pain severity scales in patients of severe acute pancreatitis accompanied with paralytic ileus, indicating positive clinical significance; in addition, EA is safe and can be recommended to the treatment of severe acute pancreatitis in combination with treatment plan of integrated Chinese and western medicine.
10.A time series analysis on under 5 mortality rate in Zhejiang Province
Na LV ; Dong-Mei JIN ; Shao-Shuai QI ; Qian-Qian LIANG ; Ling-Zi DAI ; Tian WU ; Wen-Jie FAN ; Yu-Ying XU ; Wei-Fang ZHANG ; Xiu-Yang LI ; Huai-Zhuang YE
Journal of Preventive Medicine 2016;(1):13-16
Objective To study the temporal distribution regular pattern of under 5 mortality rate(U5MR)from 1 998 to 201 4 in Zhejiang Province,and to predict the under 5 mortality rate in 201 5.Methods A time series ARIMA (p,d,q) forecasting model for U5MR was conducted using IBM SPSS Statistics 20.0 statistical analysis software.Results The UMAR showed downward trend.The ARIMA(2,1 ,2)model of U5MR from 1 998 to 201 4 in Zhejiang Province is yt =-0.696 +0.636yt -1 +0.024yt -2 +0.340yt -3 +αt -0.003αt -1 +0.997αt -2 ,and the model fitting was good.Each of the actual mortality was consistent with the trend of model prediction,and was within the 95% confidence interval.The predicted value of U5MR was 4.08‰ (95% CI:1 .52‰ -6.64‰)in 201 5.Conclusion Time series analysis is an effective way to analyze the temporal distribution regular pattern of U5MR,which could be used for short -term prediction.

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