1.Impact of ERCC1 C8092A gene polymorphism on the efficacy of platinum-based chemotherapy for lung cancer
LI Yixuan ; WANG Yiwei ; FU Yihui ; MENG Chong ; KUANG Shicheng ; LYU Pengfei ; ZHOU jing ; XU Qiongjun ; HUANG Hairong ; XIAO Sha
China Tropical Medicine 2024;24(1):65-
Objective To explore the relationship between the polymorphism of excision repair cross-complementation group 1 (ERCC1) C8092A locus and the efficacy and prognosis of platinum-based chemotherapy for lung cancer (LC), and to provide a theoretical basis for precision treatment of LC. Methods From January 2014 to October 2017, 120 patients from two tertiary hospitals in Haikou City, and with pathologically confirmed lung cancer treated with platinum-based chemotherapy were selected as the research objects. After informed consent was obtained, peripheral blood samples were collected for DNA extraction, and the genotype of ERCC1 C8092A locus was detected by mass spectrometry. WHO's Response Evaluation Criteria in Solid Tumours (RECIST) was used to judge patients' chemotherapy efficacy and patients' survival status was obtained by telephone follow-up and other means. Results Among the 120 LC patients, the genotype frequencies of ERCC1 C8092A locus were 67 cases of CC wildtype (55.8%), 45 cases of CA heterozygous type (37.5%), and 8 cases of AA rare mutation type (6.7%), which conformed to Hardy-Weinberg equilibrium (χ2=0.140, P>0.05). The total effective rate of chemotherapy was 32.5%, with the highest effective rate in patients with the CA genotype (42.2%) at the ERCC1 C8092A locus and the lowest in patients with the CC genotype (25.4%). The overall one-year survival rate was 68.3% and the three-year survival rate was 35.8%. The patients with ERCC1 C8092A AA genotype had the lowest survival rate, with a one-year survival rate of 50.0% and three-year survival rate of only 25.0%. However, there were no statistical differences in the overall survival rate among the three genotypes of carriers of ERCC1 C8092A (χ2=0.328, P=0.849). Conclusions The polymorphism of ERCC1 C8092A locus is associated with the efficacy of platinum-based chemotherapy for LC, and patients with CA genotype have the highest efficacy. The one-year and three-year survival rates of patients with CC genotype are significantly higher than those of CA and AA genotypes.
2.Early prediction of growth patterns after pediatric kidney transplantation based on height-related single-nucleotide polymorphisms
Yi FENG ; Yonghua FENG ; Mingyao HU ; Hongen XU ; Zhigang WANG ; Shicheng XU ; Yongchuang YAN ; Chenghao FENG ; Zhou LI ; Guiwen FENG ; Wenjun SHANG
Chinese Medical Journal 2024;137(10):1199-1206
Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.
3.Clinical study on the influence of source of infection on the pathophysiology and prognosis of sepsis
Mengyu LI ; Xingqin ZHANG ; Shicheng GAO ; Senqing YE ; Weixian XU ; Bin ZHANG
China Modern Doctor 2024;62(33):28-31,95
Objective To investigate the similarities and differences in the pathophysiological responses caused by different infection sites in sepsis patients and to evaluate the clinical significance of the source of infection on the prognosis of patients.Methods A total of 159 patients with a clear source of infection in Foshan Hospital of Traditional Chinese Medicine from January 1,2021 to January 1,2023 were selected and divided into survival group(n=98)and death group(n=61)based on their survival status within 28 days.The independent risk factors affecting the prognosis of sepsis patients were determined by multivariate Logistic regression analysis.The 28-day mortality rates of different infection source groups were compared,and the distribution differences of serum biomarkers in different infection source groups were explored by analysis of variance.Results Among the 159 patients,the frequency of infection source distribution was as follows in descending order:Respiratory tract(62.89%),urinary tract(13.84%),abdomen(13.21%),skin and soft tissue(10.06%).Multivariate Logistic regression analysis showed that age,procalcitonin,sepsis-related organ failure assessment score,and respiratory tract infection source were significant risk factors affecting the 28-day mortality of sepsis patients(P<0.05).Different infection source groups showed different degrees of differences in inflammation,coagulation,and organ dysfunction,with heterogeneity.Conclusion The differences in the source of infection lead to significant differences in the pathophysiological features(inflammatory response,coagulation activation,and organ dysfunction)and short-term prognosis(28-day mortality)of sepsis.
4.Study on the characteristics of lymphocyte-specfic protein-tyrosine kinase methylation in the peripheral blood circulation of patients with rheumatoid arthritis
Lingxia XU ; Cen CHANG ; Ping JIANG ; Kai WEI ; Jia′nan ZHAO ; Yixin ZHENG ; Yu SHAN ; Yiming SHI ; Hua Ye JIN ; Yi SHEN ; Shicheng GUO ; Dongyi HE ; Jia LIU
Chinese Journal of Rheumatology 2024;28(3):155-161
Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.
5.Application of autoregressive integrated moving average model to predict and analyze the incidence trend of mumps in Jiangxi Province
Yuqin ZHAO ; Jinghong SHI ; Fei XU ; Shicheng GUO
Chinese Journal of Epidemiology 2023;44(12):1911-1915
Objective:To predict and analyze the incidence trend of mumps using the Autoregressive integrated moving average model (ARIMA) in Jiangxi Province.Methods:The ARIMA was used to model the number of mumps cases per month from 2015 to 2019 in Jiangxi Province. The number of mumps cases in 12 months was predicted and was compared with the actual reported cases in 2020, 2021, and 2022, respectively.Results:The optimal model was ARIMA (0,2,1)(1,2,0) 12. The predicted number of cases was significantly higher than that reported in 2020, 2021 and 2022. The number of reported cases of mumps in 2020, 2021, and 2022 decreased by 54.02%, 63.40%, and 66.09% compared with the forecast. Conclusions:From 2020 to 2022, the reported incidence of mumps in Jiangxi Province was significantly lower than the predicted incidence. Considering that it was related to non-drug intervention measures and changes in immunization strategies, it was suggested to strengthen mumps surveillance further to better cope with the epidemic situation of mumps.
6.Multi-locus sequence typing of human Brucella isolated in Sichuan Province from 2014 to 2020
Wenbo LI ; Shicheng ZHAO ; Dan GAO ; Chunhua LUO ; Linzi ZENG ; Hongyu LIAO ; Teng QI ; Lixin XU
Chinese Journal of Endemiology 2023;42(1):24-29
Objective:To learn about the genotyping of human Brucella isolated from Sichuan Province. Methods:BCSP31-PCR and AMOS-PCR were used to identify the genus and biotype of the 66 strains isolated from confirmed human brucellosis cases in Sichuan Province from 2014 to 2020, respectively. The isolated strains were genotyped by multi-locus sequence typing (MLST)-9. The sequence type (ST) was compared trough the online MLST database. A minimum spanning tree (MST) was constructed to cluster the newly discovered and known ST using the BioNumerics software version 7.6.Results:The 66 strains isolated from human cases of brucellosis in Sichuan Province from 2014 to 2020 were Brucella, and 65 of them were Brucella melitensis while one strain was Brucella abortus. The MLST method identified three known STs (ST-8, ST-39 and ST-2) and one newly type (ST-101). Among them, ST-8 was the main ST in Sichuan Province (90.91%, 60/66), another 4 strains of Brucella melitensis were ST-39, and 1 strain of Brucella abortus was ST-2. The newly type ST-101 was isolated from Leshan City in 2019, belonging to the Brucella melitensis and closely related to the evolution of ST-8. Conclusion:Brucella melitensis is the main epidemic Brucella strain in Sichuan Province, ST-8 is predominant genotype, with a small amount of ST-39, ST-101 and ST-2.
7.Expert consensus on recombinant B subunit/inactivated whole-cell cholera vaccine in preventing infectious diarrhea of enterotoxigenic Escherichia coli
Chai JI ; Yu HU ; Mingyan LI ; Yan LIU ; Yuyang XU ; Hua YU ; Jianyong SHEN ; Jingan LOU ; Wei ZHOU ; Jie HU ; Zhiying YIN ; Jingjiao WEI ; Junfen LIN ; Zhenyu SHEN ; Ziping MIAO ; Baodong LI ; Jiabing WU ; Xiaoyuan LI ; Hongmei XU ; Jianming OU ; Qi LI ; Jun XIANG ; Chen DONG ; Haihua YI ; Changjun BAO ; Shicheng GUO ; Shaohong YAN ; Lili LIU ; Zengqiang KOU ; Shaoying CHANG ; Shaobai ZHANG ; Xiang GUO ; Xiaoping ZHU ; Ying ZHANG ; Bangmao WANG ; Shuguang CAO ; Peisheng WANG ; Zhixian ZHAO ; Da WANG ; Enfu CHEN
Chinese Journal of Clinical Infectious Diseases 2023;16(6):420-426
Enterotoxigenic Escherichia coli(ETEC)infection can induce watery diarrhea,leading to dehydration,electrolyte disturbance,and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera(rBS/WC)vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC,as well as the effectiveness,safety,and health economics of rBS/WC vaccine,National Clinical Research Center for Child Health(The Children’s Hospital,Zhejiang University School of Medicine)and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.
8.Non-small molecule PROTACs (NSM-PROTACs): Protein degradation kaleidoscope.
Sinan MA ; Jianai JI ; Yuanyuan TONG ; Yuxuan ZHU ; Junwei DOU ; Xian ZHANG ; Shicheng XU ; Tianbao ZHU ; Xiaoli XU ; Qidong YOU ; Zhengyu JIANG
Acta Pharmaceutica Sinica B 2022;12(7):2990-3005
The proteolysis targeting chimeras (PROTACs) technology has been rapidly developed since its birth in 2001, attracting rapidly growing attention of scientific institutes and pharmaceutical companies. At present, a variety of small molecule PROTACs have entered the clinical trial. However, as small molecule PROTACs flourish, non-small molecule PROTACs (NSM-PROTACs) such as peptide PROTACs, nucleic acid PROTACs and antibody PROTACs have also advanced considerably over recent years, exhibiting the unique characters beyond the small molecule PROTACs. Here, we briefly introduce the types of NSM-PROTACs, describe the advantages of NSM-PROTACs, and summarize the development of NSM-PROTACs so far in detail. We hope this article could not only provide useful insights into NSM-PROTACs, but also expand the research interest of NSM-PROTACs.
9.Cucumber downy mildew and the mechanisms of host resistance: a review.
Shicheng XU ; Hebing WANG ; Junjie FENG ; Huafeng XIANG ; Mengdan WU ; Zhimin WANG ; Dayong WEI ; Hongcheng ZHANG ; Qinglin TANG
Chinese Journal of Biotechnology 2022;38(5):1724-1737
The cultivation and production of cucumber are seriously affected by downy mildew caused by Pseudoperonospora cubensis. Downy mildew damages leaves, stems and inflorescences, and then reduces the yield and quality of cucumber. This review summarized the research advances in cucumber downy mildew, including pathogen detection and defense pathways, regulatory factors, mining of pathogens-resistant candidate genes, proteomic and genomic analysis, and development of QTL remarks. This review may facilitate clarifying the resistance mechanisms of cucumber to downy mildew.
Cucumis sativus/genetics*
;
Oomycetes/genetics*
;
Peronospora
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Plant Diseases/genetics*
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Proteomics
10.Comparison of cross-sectional area measurement and width measurement by high frequency ultrasound in the diagnosis of congenital adrenal hyperplasia in infants
Zesheng YANG ; Shicheng WANG ; Guanghua PEI ; Weijun XU ; Xiaoying XIE ; Shuo DONG ; Haijuan ZHANG
Chinese Journal of Ultrasonography 2020;29(5):411-415
Objective:To investigate and compare the value of cross-sectional area measurement and width measurement by high frequency ultrasound in the diagnosis of congenital adrenal hyperplasia (CAH) in infants.Methods:The abdominal ultrasound images of 20 infants who were diagnosed as CAH in Tianjin Children′s Hospital and clinical diagnosised from November 2013 to August 2018 were analyzed retrospectively. The maximum cross-sectional area of adrenal gland and the maximum width of single limb were measured respectively to assess the size of adrenal gland. Fifty normal full-term infants were selected as control group at the same period. The differences of maximum cross-sectional area of adrenal gland, the maximum width of single limb between CAH group and control group were compared. ROC curve was plotted to compare the diagnostic values of cross-sectional area measurement and width measurement.Results:①There was significant difference in maximum cross-sectional area of adrenal gland between infants with CAH and normal infants[(129.47±37.39)mm 2 vs (54.42±20.85)mm 2; t=10.004, P<0.001]. There was significant difference in maximum width of adrenal gland between infants with CAH and normal infants [(4.56±1.20)mm vs (3.25±0.66)mm; t=5.445, P<0.001]. ②The area under ROC curve(AUC) of cross-sectional area measurement was 0.966, the best cutoff value was 87.5 mm 2, the sensitivity was 95.0%, and the specificity was 92.5%. AUC of width measurement was 0.817, the best cutoff value was 5.25 mm, the sensitivity was 90.0%, and the specificity was 62.5%. The difference of AUC between cross-sectional area measurement and width measurement was 0.149, which was statistically significant ( Z=2.309, P=0.021). Conclusions:Both cross-sectional area measurement and width measurement by high frequency ultrasound have diagnostic values for CAH in infants, with the former more valuable than the latter.

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