1.Mechanism of circRNA_0076631 mediated diabetic retinopathy by regulating pyroptosis
Yanyan ZHANG ; Yanyan WANG ; Xueli SHAO ; Quanyong YI ; Yahui XI
International Eye Science 2025;25(3):351-358
AIM: To investigate the role of pyroptosis in the development of diabetic retinopathy(DR)and to explore the regulatory mechanism by which circular RNA(circRNA)and its targeted microRNA(miRNA)mediate pyroptosis in DR, providing new therapeutic targets and strategies for the prevention and treatment of DR.METHODS: A streptozotocin(STZ)-induced model of type 1 diabetes in SD rats was established. The expression of circRNA_0076631, miR-214, and pyroptosis-related factors were measured in retinal tissues. CCK-8 and tube formation assays were used to detect the effect of different concentration of glucose on cell proliferation and angiogenic abilities of human retinal microvascular endothelial cells(HRMECs). The expression levels of circRNA_0076631, miR-214, and pyroptosis-related markers were evaluated through qRT-PCR and Western blot analysis, with additional experiments conducted following circRNA_0076631 knockdown to assess its effect on pyroptosis markers. Previous bioinformatics analysis and luciferase reporter assays identified a shared binding site among circRNA_0076631, miR-214, and caspase-1. To clarify the interaction between these molecules, co-transfection experiments using circRNA_0076631 inhibitors(ASO-circRNA_0076631), miR-214 overexpression transfection reagent, and miR-214 inhibitors(AMO-miR-214)were conducted to elucidate the regulatory pathway involved in DR.RESULTS: Both the diabetic rat model and D-glucose-treated HRMECs showed significantly elevated expression of circRNA_0076631 and pyroptosis-related factors(NLRP3, caspase-1, and IL-1β), while miR-214 expression was reduced(all P<0.05). The mRNA expression of pyroptosis-related factors caspase-1 was reduced after the overexpression of miR-214, and it was upregulated after the inhibition of miR-214(all P<0.05). Knockdown of circRNA_0076631 reduced the mRNA expression of pyroptosis markers caspase-1(P<0.05). Co-transfection experiments revealed that the inhibition circRNA_0076631 suppressed pyroptosis(all P<0.05), but this suppression was reversed upon co-transfection with miR-214 inhibitors, leading to increased mRNA expression of the pyroptosis marker caspase-1(all P<0.05).CONCLUSION: The circRNA_0076631 and pyroptosis play critical roles in the pathogenesis of DR, and circRNA_0076631 may regulate pyroptosis by modulating miR-214, which in turn influences the expression of caspase-1 in the pyroptosis signaling pathway, thereby contributing to DR progression. The circRNA_0076631 may serve as a novel therapeutic target, providing new insights for the prevention and treatment of DR.
2.Mechanism of circRNA_0076631 mediated diabetic retinopathy by regulating pyroptosis
Yanyan ZHANG ; Yanyan WANG ; Xueli SHAO ; Quanyong YI ; Yahui XI
International Eye Science 2025;25(3):351-358
AIM: To investigate the role of pyroptosis in the development of diabetic retinopathy(DR)and to explore the regulatory mechanism by which circular RNA(circRNA)and its targeted microRNA(miRNA)mediate pyroptosis in DR, providing new therapeutic targets and strategies for the prevention and treatment of DR.METHODS: A streptozotocin(STZ)-induced model of type 1 diabetes in SD rats was established. The expression of circRNA_0076631, miR-214, and pyroptosis-related factors were measured in retinal tissues. CCK-8 and tube formation assays were used to detect the effect of different concentration of glucose on cell proliferation and angiogenic abilities of human retinal microvascular endothelial cells(HRMECs). The expression levels of circRNA_0076631, miR-214, and pyroptosis-related markers were evaluated through qRT-PCR and Western blot analysis, with additional experiments conducted following circRNA_0076631 knockdown to assess its effect on pyroptosis markers. Previous bioinformatics analysis and luciferase reporter assays identified a shared binding site among circRNA_0076631, miR-214, and caspase-1. To clarify the interaction between these molecules, co-transfection experiments using circRNA_0076631 inhibitors(ASO-circRNA_0076631), miR-214 overexpression transfection reagent, and miR-214 inhibitors(AMO-miR-214)were conducted to elucidate the regulatory pathway involved in DR.RESULTS: Both the diabetic rat model and D-glucose-treated HRMECs showed significantly elevated expression of circRNA_0076631 and pyroptosis-related factors(NLRP3, caspase-1, and IL-1β), while miR-214 expression was reduced(all P<0.05). The mRNA expression of pyroptosis-related factors caspase-1 was reduced after the overexpression of miR-214, and it was upregulated after the inhibition of miR-214(all P<0.05). Knockdown of circRNA_0076631 reduced the mRNA expression of pyroptosis markers caspase-1(P<0.05). Co-transfection experiments revealed that the inhibition circRNA_0076631 suppressed pyroptosis(all P<0.05), but this suppression was reversed upon co-transfection with miR-214 inhibitors, leading to increased mRNA expression of the pyroptosis marker caspase-1(all P<0.05).CONCLUSION: The circRNA_0076631 and pyroptosis play critical roles in the pathogenesis of DR, and circRNA_0076631 may regulate pyroptosis by modulating miR-214, which in turn influences the expression of caspase-1 in the pyroptosis signaling pathway, thereby contributing to DR progression. The circRNA_0076631 may serve as a novel therapeutic target, providing new insights for the prevention and treatment of DR.
3.Evidence Evaluation and Rationality Analysis for Off-label Use of Tacrolimus in the Kidney Diseases in Adults
LI Xiaomin ; TAN Xinyi ; ZHANG Aobo ; ZHANG Xueli ; SHAO Hua
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1830-1835
OBJECTIVE
To evaluate the levels of evidence and analyze the rationality for off-label use of tacrolimus in the kidney diseases in adults.
METHODS
By systematically reviewing the drug instructions, clinical guidelines and medical literature of tacrolimus in the kidney diseases in adults, screening the highest level of evidence, and an evaluation table based on evidence-based medical for off-label use of tacrolimus in the kidney diseases in adults was established. Based on the evaluation table, collect adult patients from the Department of Nephrology in Zhongda Hospital Southeast University who had a medication history of off-label use of tacrolimus from January 1, 2021 to December 31, 2022, and evaluated the rationality of application for tacrolimus.
RESULTS
A total of 19 indications for off-label use of tacrolimus in the kidney diseases in adults were listed, and their recommended levels were determined based on evidence. Among them, the recommended levels for common types of kidney diseases were higher. In addition, 194 adult patients with off-label use of tacrolimus were selected from the Department of Nephrology in Zhongda Hospital Southeast University, and their application recommended levels with "strongly recommended""moderately strongly recommended""weakly recommended" and "not recommended", were 67.0%, 12.9%, 15.0% and 5.1%, respectively.
CONCLUSION
Tacrolimus has a wide range of indications for off-label use in the kidney diseases in adults, but the evidence for most common types of kidney diseases are relatively sufficient and their use are reasonable.
4.Efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit
Jun NI ; Huisheng CHEN ; Guofang CHEN ; Yong JI ; Fei YI ; Zhuobo ZHANG ; Yi YANG ; Jin WU ; Xueli CAI ; Bei SHAO ; Jianfeng WANG ; Yafang LIU ; Deqin GENG ; Xinhui QU ; Xiaohong LI ; Yan WEI ; Jianping DING ; Hua LYU ; Yining HUANG ; Yonghua HUANG ; Bo XIAO ; Tao GONG ; Liying CUI
Chinese Journal of Neurology 2022;55(5):474-480
Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.
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.Analysis of phenotype and MYH7 gene variant in a family of patients with hypertrophic cardiomyopathy.
Xueli ZHAO ; Bo WANG ; Xiaoli ZHU ; Qianli YANG ; Ying LIU ; Hong SHAO ; Lei ZUO ; Yun LUO ; Yue WANG ; Liwen LIU
Chinese Journal of Medical Genetics 2022;39(8):873-876
OBJECTIVE:
To analyze the clinical phenotype and MYH7 gene variant in a Chinese pedigree affected with hypertrophic cardiomyopathy (HCM).
METHODS:
The proband was screened for variant of 96 cardiomyopathy-associated genes by exonic amplification and high-throughput sequencing. Candidate variant was verified by Sanger sequencing among 300 healthy controls as well as family members of the proband. Co-segregation analysis of genotypes and clinical phenotypes was carried out for the pedigree. Clustal X software was used to analyze the sequence conservation of the variant among various species, and its pathogenicity was predicted by using bioinformatics software.
RESULTS:
6 out of 12 members from this pedigree were found to harbor heterozygous c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene, among whom five were diagnosed with HCM. The remaining one had failed to meet the diagnostic criteria for HCM, but had abnormal ECG. The same variant was not found in the 300 healthy controls. Amino acid sequence analysis showed that the variant is located in a highly conserved region, and bioinformatics analysis predicted that this variant may affect protein function and has a deleterious effect. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM2+ PP1_Moderate+PP3+PP5).
CONCLUSION
The c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene probably underlay the pathogenesis in this pedigree. Above finding has important value for the early diagnosis of patients with HCM.
Cardiac Myosins/genetics*
;
Cardiomyopathy, Hypertrophic/genetics*
;
Genotype
;
Humans
;
Mutation
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Myosin Heavy Chains/genetics*
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Pedigree
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Phenotype
7.Effects of cinepazide maleate injection on blood pressure in patients with acute ischemic stroke and hypertension
Huisheng CHEN ; Yi YANG ; Jun NI ; Guofang CHEN ; Yong JI ; Fei YI ; Zhuobo ZHANG ; Jin WU ; Xueli CAI ; Bei SHAO ; Jianfeng WANG ; Yafang LIU ; Deqin GENG ; Xinhui QU ; Xiaohong LI ; Yan WEI ; Shugen HAN ; Runxiu ZHU ; Jianping DING ; Hua LYU ; Yining HUANG ; Yonghua HUANG ; Bo XIAO ; Tao GONG ; Xiaofei YU ; Liying CUI
Chinese Journal of Internal Medicine 2022;61(8):916-920
Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.
8.Clinical value of radiomics based on CT examination in preoperative differential diagnosis of pancreatic serous cystadenoma and mucinous cystadenoma
Wenjie LIANG ; Wuwei TIAN ; Yubizhuo WANG ; Jingwen XIA ; Shijian RUAN ; Jiayuan SHAO ; Zhihao FU ; Na LU ; Yong DING ; Wenbo XIAO ; Xueli BAI
Chinese Journal of Digestive Surgery 2021;20(5):555-563
Objective:To investigate the clinical value of radiomics based on computed tomography (CT) examination in preoperative differential diagnosis of pancreatic serous cystadenoma (SCA) and mucinous cystadenoma (MCA).Methods:The retrospective case-control study was conducted. The clinicopathological and imaging data of 154 patients with pancreatic cystic neoplasms who were admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2012 to December 2019 were collected. There were 24 males and 130 females, aged (50±13)years. Of the 154 patients, 99 cases were diagnosed as SCA and 55 cases were diagnosed as MCA. All the 154 patients underwent plain and enhanced CT scan of pancreas before operation. The clinical characteristics, radiology features and radiomics features of all patients were collected to construct the clinical characteristics model, radiology model, radiomics model and fused model. The receiver operating characteristic (ROC) curve of each model was drawn, and those constructed models were evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Based on the optimal model, the nomogram was constructed. Observation indicators: (1) establishment and validation of clinical characteristics model; (2) establishment and validation of radiology model; (3) establishment and validation of radiomics model; (4) establishment and validation of fused model; (5) nomogram of fused model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Results:(1) Establishment and validation of clinical characteristics model: 3 clinical characteristics, including age, symptoms and preoperative serum CA19-9, were selected using multinomial logistic linear regression analysis to construct the clinical characteristics model. Result of the multinomial logistic linear regression analysis was expressed by formula ①: clinical characteristics model score=0.635-0.007×age+0.054×clinical symptoms+0.108×preoperative serum CA19-9. The ROC curve for the test dataset of clinical characteristics model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of clinical characteristics model were 0.611(95% confidence interval as 0.488?0.734, P<0.05), 56.6%, 66.7%, 56.3%, 41.5%, 78.4% for the training dataset and 0.771(95% confidence interval as 0.624?0.919, P<0.05), 77.8%, 63.1%, 88.5%, 80.1%, 76.7% for the test dataset, respectively. (2) Establishment and validation of radiology model: 5 radiology characteristics, including tumor location, the number of tumors, tumor diameter of cross section, lobulated tumor and polycystic tumor (more than 6), were selected using multinomial logistic linear regression analysis to construct the radiology model. Result of the multinomial logistic linear regression analysis was expressed by formula ②: radiology model score=?0.034+0.300×tumor location+0.202×the number of tumors+0.014×tumor diameter of cross section?0.251×lobulated tumor?0.170×polycystic tumor (more than 6). The ROC curve for the test dataset of radiology model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of radiology model were 0.862(95% confidence interval as 0.791?0.932, P<0.05), 78.8%, 81.8%, 77.5%, 62.8%, 90.2% for the training dataset and 0.853(95% confidence interval as 0.713?0.994), P<0.05), 88.9%, 89.4%, 88.5%, 85.0%, 92.0% for the test dataset, respectively. (3) Establishment and validation of radiomics model: 4 categories of a total 1 067 radiomics features were extracted from 154 patients with pancreatic cystic neoplasms, including 7 first-order histogram features, 53 texture features, 848 wavelet features and 159 local binary pattern features. A total of 896 stable radiomics features were retained to construct the model, based on the condition of intraclass correlation coefficient >0.9. After selected by variance threshold and correlation coefficient threshold, 350 radiomics features were retained. Fifty synthetic radiomics features were constructed based on the original features in order to obtain potential radiomics features, and the total number of radiomics features was 400. After analyzed by the five-fold recursive feature elimination, 22 radiomics features were screened out, including 13 wavelet features, 7 synthetic radiomics features and 2 local binary pattern features. The support vector machine algorithm was used to construct the radiomics model. The penalty coefficient 'C' and parameter 'γ' of the radiomics model were 35.938 and 0.077, respectively. The kernel function of the radiomics model was 'radial basis function kernel'. The ROC curve of radiomics model using 5-fold cross validation was drawn. The average AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the radiomics model were 0.870 ( P<0.05), 83.1%, 81.8%, 83.8%, 73.8% and 89.2%, respectively. (4) Establishment and validation of fused model: the fused model was constructed after selecting the tumor location and lobulated tumor of radiology characteristics and radiomics score. Result of the multinomial logistic linear regression analysis was expressed by formula ③: fused model socre=?0.154+0.218×tumor location?0.223×lobulated tumor+0.621×radiomics score. The ROC curve for the test dataset of fused model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of fused model were 0.893(95% confidence interval as 0.828?0.958, P<0.05), 83.7%, 81.8%, 84.5%, 71.1%, 90.9% for the training dataset and 0.966(95% confidence interval as 0.921?0.999, P<0.05), 91.1%, 84.2%, 96.2%, 94.1%, 89.3% for the test dataset, respectively. (5) Nomogram of fused model: the nomogram of fused model was illustrated with the Youden index of 0.416. Conclusion:The prediction model based on the radiomics signature and radiological features extracted from preoperative CT examination can make the differential diagnosis of pancreatic SCA from MCA.
9.Cinepazide maleate injection reduced the disability rate for acute ischemic stroke patients: a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase Ⅳ clinical trial
Jun NI ; Huisheng CHEN ; Guofang CHEN ; Yong JI ; Fei YI ; Zhuobo ZHANG ; Yi YANG ; Jin WU ; Xueli CAI ; Bei SHAO ; Jianfeng WANG ; Yafang LIU ; Deqin GENG ; Xinhui QU ; Xiaohong LI ; Yan WEI ; Jianping DING ; Hua LYU ; Yining HUANG ; Yonghua HUANG ; Bo XIAO ; Tao GONG ; Liying CUI
Chinese Journal of Neurology 2020;53(10):790-797
Objective:To assess the efficacy and safety of cinepazide maleate injection in the treatment of patients with acute ischemic stroke.Methods:A multicenter, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial, led by Peking Union Medical College Hospital, was conducted in 65 Hospitals in China. The efficacy of cinepazide maleate injection in patients with acute anterior circulation cerebral infarction with onset time of ≤48 hours, 7≤National Institute of Health stroke scale (NIHSS) score ≤25 was assessed from August 2016 to February 2019, using the proportion of modified Rankin scale (mRS) score≤1 and Barthel index (BI) score≤95 on day 14 as efficacy endpoint. The patients were divided into treatment group who were treated with cinepazide maleate injection and control group who were treated with placebo.Results:A total 937 patients were involved in the final efficacy analysis (466 in treatment group and 471 in control group). The proportion of subjects with mRS score≤1 on day 14 after treatment were higher in the treatment group than that in the control group (102/466(21.89%) vs76/471(16.14%)). Logistic regression analysis showed that patients treated with cinepazide maleate were significantly more likely to have a favorable outcome (mRS score≤1) than patients treated with placebo on day 14 ( OR=0.677, 95% CI 0.484-0.948 , P=0.023), and patients treated with cinepazide maleate were more likely to reach independence in activities of daily living (Barthel Index ≥95) than those treated with placebo on day 14 (125/466(26.82%) vs 91/471(19.32%); OR=0.632, 95% CI0.459-0.869, P=0.005). The rate of adverse events was similar between the treatment and control groups. Conclusion:The 14-day treatment with cinepazide maleate injection could reduce the degree of disability whereas did not increase the risk of adverse events.
10.Discussion on stability of mixed standard application solution by volatilization organic compounds in workplace air
Peng SHAO ; Shanshan LIU ; Xueli SHAO ; Zhen ZHEN ; Jianping YANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(8):625-627
Objective:To discuss the stability of mixed standard application solution by volatilization organic matter (benzene, toluene, xylene, ethylbenzene, acetone, butanone, Ethyl acetate, butyl ester, trichloroethylene) in workplace air.Methods:A total of 11 kinds volatilization organic compounds were separated by capillary chromatographic column, and detected with flame ionization detector. The stability of mixed standard application solution was judged by studying three paratemers during the placement period, such as the linear correlation coefficient of the standard curve, the relative response values of the highest and lowest concentration levels and the accuracy of the measured values of the quality control samples.Results:Within 187 days, the linear correlation coefficient of each compound was ≥0.999. The changes of relative response values at the highest and lowest concentration levels were both <10%; The measured values of toluene were all in the reference range.Conclusion:The mixed standard application solution is stable and reliable within 187 days of storage.


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