1.Effect of Quzhi Ruangan decoction on the mRNA and protein expression of organic anion transporting polypeptide 2B1 in the small intestine of rats with nonalcoholic fatty liver disease
Suyan ZHANG ; Enrui XIA ; Qingli ZHOU ; Shunzhen ZHANG
Journal of Clinical Hepatology 2020;36(11):2484-2488
ObjectiveTo investigate the effect of Quzhi Ruangan decoction on the mRNA and protein expression of organic anion transporting polypeptide 2B1 (OATP2B1) in the small intestine of rats with nonalcoholic fatty liver disease (NAFLD). MethodsAfter 1 week of adaptive feeding, 36 male Sprague-Dawley rats were randomly divided into normal group, model group, simvastatin group, and high-, middle-, and low-dose Quzhi Ruangan decoction groups, with 6 rats in each group. Liver tissue was collected and HE staining was used to observe hepatic steatosis; an automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), and cholesterol (CHOL); RT-PCR and Western blot were used to measure the mRNA and protein expression of OATP2B1 in the small intestine of rats. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results There were significant differences in liver index, GLU, and CHOL between groups (F=10.814, 12.298, and 5.024, all P<0.05), and there were also significant differences in the mRNA and protein expression of OATP2B1 in the small intestine (F=13.384 and 73.025, both P<0.05). Compared with the normal group, the model group had significant increases in the mRNA and protein expression of OATP2B1 (both P<0.05); compared with the model group, the simvastatin group and the high- and middle-dose Quzhi Ruangan groups had a significant reduction in the mRNA expression of OATP2B1 (all P<0.05); compared with the simvastatin group, the middle- and low-dose Quzhi Ruangan groups had a significant reduction in the mRNA expression of OATP2B1 (both P<0.05). Compared with the normal group, the model group had a significant increase in the protein expression of OATP2B1 (P<0.05); compared with the model group, all treatment groups had a significant reduction in the protein expression of OATP2B1 (all P<0.001); compared with the simvastatin group, the high-, middle-, and low-dose Quzhi Ruangan groups had a significant reduction in the protein expression of OATP2B1 (all P<0.05). ConclusionQuzhi Ruangan decoction may alleviate the pathological changes of NAFLD by reducing the overexpression of OATP2B1.
2.Methyltransferase-like 3 affects glycolysis and proliferation of esophageal squamous cell carcinoma cells by regulating the GLUT4-mTORC1 axis
ZHOU Xia,b ; ZHONG Xiaowua,b,c ; GAO Chuanlia ; LI Qingrongb ; CHENG Jibingb ; MA Qiangb,c ; GUO Xiaolana,b,c
Chinese Journal of Cancer Biotherapy 2022;29(12):1076-1086
[摘 要] 目的:探讨甲基转移酶样因子3(METTL3)在食管鳞状细胞癌(ESCC)组织和细胞中的表达水平及其对ESCC细胞糖酵解和增殖能力的影响和潜在的分子机制。方法:基于TCGA数据库分析METTL3在ESCC细胞中的表达及可能的富集通路。收集2021年1月至2021年6月间在北川医学院附属医院外科手术切除的34例ESCC组织及相应癌旁组织,采用免疫组化法验证ESCC组织中METTL3的表达。采用CCK-8法和平板克隆形成实验检测干扰METTL3后ESCC细胞增殖能力的变化,利用比色法检测干扰METTL3后ESCC细胞总RNA中m6A的表达水平,采用甲基化RNA免疫沉淀定量PCR(MeRIP-qPCR)检测METTL3对葡萄糖转运蛋白4(GLUT4)基因mRNA的m6A修饰水平的影响,采用WB和qPCR等技术探索METTL3参与ESCC细胞糖酵解的生物学机制。结果:METTL3在ESCC组织以及细胞中均呈高表达(均P<0.001)。干扰METTL3表达后,ESCC细胞的增殖能力明显减弱、细胞内总RNA的m6A修饰水平显著降低(均P<0.001)。此外,干扰METTL3可显著抑制KYSE150和TE-1细胞中GLUT4基因mRNA的m6A修饰水平(均P<0.01),并通过下调GLUT4的表达抑制葡萄糖的摄取以及乳酸的释放(均P<0.01),最终下调mTORC1通路活性并抑制ESCC细胞的增殖;在干扰METTL3的ESCC细胞同时联合运用mTORC1通路抑制剂显示有协同的抗癌作用。结论:METTL3介导的m6A修饰通过调控GLUT4-mTORC1信号轴影响ESCC细胞的糖酵解及增殖。
3.Analysis of driver gene mutations in “Xuanwei” multi-nodular non-small cell lung cancer
WANG Xiaoxionga ; LI Quana ; SHEN Zhenghaib ; CAI Jingjinga ; LI Zhuoyinga ; SHEN Shaoconga ; LI Hongshenga ; LIU Xina ; LIU Xia ; LIU Junxia ; GUO Yinjina ; DU Yaxia ; LAN Yunyia ; MA Luyaoa ; YANG Ruijiaoa ; WU Shunxiana ; ZHOU Yongchuna ; HUANG Yunchaob
Chinese Journal of Cancer Biotherapy 2024;31(4):377-382
[摘 要] 目的:探讨多结节非小细胞肺癌(NSCLC)组织中的驱动基因突变情况与临床病理特征的关系,为多结节NSCLC患者治疗提供分子诊断依据。方法:本研究共纳入2018年1月至2023年10月间云南省肿瘤医院分子诊断中心检测的121例多结节NSCLC患者的253个肺结节肿瘤组织标本,以第二代测序(NGS)技术或扩增阻滞突变系统PCR(ARMS-PCR)技术检测多结节NSCLC 组织中驱动基因突变情况,分析其与患者临床病理特征的关系,比较不同结节间肺癌驱动基因的突变异质性。结果:与非“宣威”NSCLC相比,“宣威”多结节NSCLC患者驱动基因突变具有显著的地域特点,表现在“宣威”患者具有较低(20%)的EGFR敏感突变(L858R、19-del)及较高(27.26%)的EGFR少见突变(主要为G719/S768I、G719);“宣威”多结节NSCLC患者的KRAS突变率(27.27%)亦显著高于非“宣威”患者突变率(12.59%)(P<0.05)。此外,“宣威”多结节NSCLC患者驱动基因突变不一致率高达69.23%,远高于非“宣威”患者驱动基因突变不一致率(55.07%)(P<0.05)。结论:“宣威”多结节NSCLC患者具有较高的EGFR少见突变及KRAS突变率,同一患者不同病灶之间存在更高的驱动基因突变异质性,本研究将为“宣威”多结节NSCLC的诊疗策略提供更多的选择。
4.The Biological Significance of Multi-copy Regions and Their Impact on Variant Discovery
Sun JING ; Zhang YANFANG ; Wang MINHUI ; Guan QIAN ; Yang XIUJIA ; Ou Xia JIN ; Yan MINGCHEN ; Wang CHENGRUI ; Zhang YAN ; Li ZHI-HAO ; Lan CHUNHONG ; Mao CHEN ; Zhou HONG-WEI ; Hao BINGTAO ; Zhang ZHENHAI
Genomics, Proteomics & Bioinformatics 2020;18(5):516-524
Identification of genetic variants via high-throughput sequencing (HTS) technologies has been essential for both fundamental and clinical studies. However, to what extent the genome sequence composition affects variant calling remains unclear. In this study, we identified 63,897 multi-copy sequences (MCSs) with a minimum length of 300 bp, each of which occurs at least twice in the human genome. The 151,749 genomic loci (multi-copy regions, or MCRs) harboring these MCSs account for 1.98%of the genome and are distributed unevenly across chromosomes. MCRs containing the same MCS tend to be located on the same chromosome. Gene Ontology (GO) anal-yses revealed that 3800 genes whose UTRs or exons overlap with MCRs are enriched for Golgi-related cellular component terms and various enzymatic activities in the GO biological function cat-egory. MCRs are also enriched for loci that are sensitive to neocarzinostatin-induced double-strand breaks. Moreover, genetic variants discovered by genome-wide association studies and recorded indbSNP are significantly underrepresented in MCRs. Using simulated HTS datasets, we show that false variant discovery rates are significantly higher in MCRs than in other genomic regions. These results suggest that extra caution must be taken when identifying genetic variants in the MCRs via HTS technologies.
5.DJ-1 over-expression promotes proliferation, migration, invasion and epithelial-mesenchymal transformation of human gastric cancer MGC803 cells through PTEN/Akt pathway
ZHOU Juana ; XIA Honga ; LIU Fanga ; SU Jianb ; SU Boc ; SU Qia
Chinese Journal of Cancer Biotherapy 2023;30(7):577-585
[摘 要] 目的:探讨DJ-1基因过表达对人胃癌MGC803细胞增殖、迁移、侵袭与上皮间质转化(EMT)的影响及其机制。方法:利用基因转染技术构建DJ-1基因过表达MGC803细胞,实验分为MGC803、空载体和DJ-1过表达组。采用MTT、平板克隆形成、细胞划痕和Transwell实验分别检测DJ-1过表达对MGC803细胞增殖、克隆形成、迁移与侵袭的影响;qPCR和WB法检测DJ-1过表达对各组细胞DJ-1、PTEN、Akt、p-Akt、Snail、vimentin、E-cadherin、MMP-9与TIMP-3表达的影响,相差显微镜下观察MGC803细胞形态学的变化。裸鼠荷瘤实验检测DJ-1过表达对MGC803细胞移植瘤体内生长的影响。结果:成功构建DJ-1基因稳定过表达的MGC803细胞。与MGC803组和空载体组比较,DJ-1过表达组细胞的增殖能力与克隆形成数均显著增加(均P<0.05),细胞迁移距离明显增加、划痕距离明显缩短(均P<0.05),迁移与侵袭细胞数显著增多(均P<0.05),DJ-1 mRNA与蛋白表达明显上调、PTEN mRNA与蛋白表达下调(均P<0.05),Akt总蛋白各组比较无明显差异(均P>0.05),p-Akt蛋白表达明显上调(P<0.05),Snail、vimentin与MMP-9表达上调、E-cadherin与TIMP-3表达下调(均P<0.05)。相差显微镜下见长梭形细胞数目增多,圆形与椭圆形细胞减少,异型性更为明显。荷瘤裸鼠体内实验结果表明,与MGC803组相比较,DJ-1过表达组MGC803细胞移植瘤生长速度明显加快、移植瘤质量显著增加(均P<0.05)。结论:DJ-1过表达可通过PTEN/Akt通路在体内外抑制MGC803细胞的增殖、迁移、侵袭与EMT。
6.Study on the distribution of ABO blood group in patients with pancreatic cancer
Xiaoliang YANG ; Xiaoqin ZHOU ; Jing LI ; Xia ZHONG ; Kun WANG ; Xiaoyan TANG ; Xing GU
Chinese Journal of Blood Transfusion 2023;36(2):152-155
【Objective】 To investigate whether there is a correlation between the differences in ABO blood group distribution in patients with pancreatic cancer, and to evaluate the relative risk. 【Methods】 Patients with pathological diagnosis or discharge diagnosis of pancreatic cancer who underwent ABO blood group typing in our hospital from January 2017 to October 2021 were selected, and the blood group distribution of patients and the correlation were analyzed. 【Results】 There was a statistically significant difference between the pancreatic cancer group and the control group (P<0.05). The study showed that type A may be a relative risk factor for pancreatic cancer patients (χ2=42.44, P<0.001), and type B may play a protective role (χ2=16.28, P<0.01). Significant differences were found in distribution between different gender groups (χ2=64.35, P<0.05). The test results showed that type A may be a risk factor for pancreatic cancer in men (χ2=35.2, OR=1.7, 95%CI=0.59-1.02, P<0.001), and type O may play a protective role in pancreatic cancer(χ2=18.22, OR=0.6, 95%CI=0.25-0.32, P<0.01); type A may be a relative risk factor for female pancreatic cancer patients (χ2=7.06, OR=1.4, 95%CI=0.59-1.02, P<0.001), while type B may play a protective role (χ2=20.32, OR=0.5, 95%CI=0.32-0.43, P<0.01). In pancreatic cancer group, the risk factors of blood type A were higher than those of non-A group, and the protective effect of type B was significantly higher than that of non-B group. 【Conclusion】 The distribution of blood group and relative risk factors in pancreatic cancer patients suggest that A type is predominant; in the population with A blood group, more attention should be paid to early prevention and early treatment, so as to reduce the risk of disease.
7.Association between maternal body height and risk of preterm birth.
H LI ; L L SONG ; L J SHEN ; B Q LIU ; X X ZHENG ; L N ZHANG ; Y Y LI ; W XIA ; B ZHANG ; A F ZHOU ; Y J WANG ; S Q XU
Chinese Journal of Epidemiology 2018;39(3):313-316
<b>Objective:b> To investigate the association between maternal body height and risk of preterm birth. <b>Methods:b> A total of 11 311 pregnant women who gave birth of live singletons were recruited from the Healthy Baby Cohort Study in Hubei province, China from September 2012 to October 2014. Finally 11 070 pregnant women were selected as study subjects. Data were collected by using questionnaires, their prenatal care records and medical records. The women were divided into 4 groups according to the quartiles distribution (<158 cm, 158- cm, 160- cm, and >164 cm). Gestational age was estimated according to maternal last menstrual time. Preterm birth was defined as delivering a live singleton infant at 28-37 weeks' gestational age. Logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the association between body height and preterm birth. <b>Results:b> Among the 11 070 pregnant women, the incidence of preterm birth was 5.9%. Logistic regression analysis indicated that women in group with body height <158 cm had 46% (OR=1.46, 95%CI: 1.16-1.83) higher risk of giving preterm birth than those in group with body height >164 cm after adjustment for potential confounders. Every 1- cm increase in body height was associated with 3% lower risk of preterm birth (OR=0.97, 95%CI: 0.95-0.99). <b>Conclusion:b> Shorter body height was a risk factor for preterm birth. It is necessary to strengthen the monitoring in pregnant women with short body height to reduce the risk of preterm birth.
Body Height
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China/epidemiology*
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Cohort Studies
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Female
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Gestational Age
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Humans
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Incidence
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Infant, Newborn
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Odds Ratio
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Pregnancy
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Premature Birth/epidemiology*
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Prenatal Care
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Risk Factors
8.Genotyping and characterization of Toxoplasma gondii strain isolated from pigs in Hubei province, central China
Xia, N.B. ; Lu, Y. ; Zhao, P.F. ; Wang, C.F. ; Li, Y.Y. ; Tan, L. ; Fang, R. ; Zhou, Y.Q. ; Shen, B. ; Zhao, J.L.
Tropical Biomedicine 2020;37(No.2):489-498
Toxoplasma gondii, a ubiquitous pathogen that infects nearly all warm-blooded animals and humans, can cause severe complications to the infected people and animals as well as serious economic losses and social problems. Here, one local strain (TgPIG-WH1) was isolated from an aborted pig fetus, and the genotype of this strain was identified as ToxoDB #3 by the PCR RFLP typing method using 10 molecular markers (SAG1, SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, C22-8, C29-2 and Apico). A comparison of the virulence of this isolate with other strains in both mice and piglets showed that TgPIG-WH1 was less virulent than type 1 strain RH and type 2 strain ME49 in mice, and caused similar symptoms to those of ME49 such as fever in piglets. Additionally, in piglet infection with both strains, the TgPIG-WH1 caused a higher IgG response and more severe pathological damages than ME49. Furthermore, TgPIG-WH1 caused one death in the 5 infected piglets, whereas ME49 did not, suggesting the higher virulence of TgPIG-WH1 than ME49 during piglet infection. Experimental infections indicate that the virulence of TgPIG-WH1 relative to ME49 is weaker in mice, but higher in pigs. This is probably the first report regarding a ToxoDB #3 strain from pigs in Hubei, China. These data will facilitate the understanding of genetic diversity of Toxoplasma strains in China as well as the prevention and control of porcine toxoplasmosis in the local region.
9.Effect of health literacy and exercise-focused interventions on glycemic control in patients with type 2 diabetes in China.
X N LIU ; Q H XIA ; H FANG ; R LI ; Y Y CHEN ; Y J YAN ; P ZHOU ; B D YAO ; Y JIANG ; W G ROTHMAN ; Wanghong XU
Chinese Journal of Epidemiology 2018;39(3):357-362
<b>Objective:b> To evaluate the effect of health literacy and exercise-focused interventions on glycemic control in patients with type 2 diabetes (T2DM) in China. <b>Methods:b> In this cluster randomized controlled trial, a total of 799 T2DM patients with most recent hemoglobin A1c (HbA1c) ≥ 7.5% (or fasting plasma glucose level ≥10 mmol/L) were recruited from 8 communities in Minhang and Changning districts of Shanghai, and randomized into a health literacy intervention group, an exercise intervention group, a comprehensive intervention group and a control group. After baseline survey and examination, a one-year intervention and 3 times (at 3(rd), 6(th), and 12(th) month) follow-up surveys were conducted. <b>Results:b> The follow-up rates for all the subjects were 99.4%, 98.4% and 95.2%, respectively, at 3(rd), 6(th) and 12(th) month. Patients in intervention groups were more likely to achieve a goal HbA1c level (HbA1c <7.0%) than those in control group, with the highest glycemic control rate (25.3%) observed in comprehensive intervention group at 3(rd) month and then in exercise intervention group (25.3% and 34.6%) respectively, at 6(th) month and 12(th) month. The average levels of HbA1c in three intervention groups were lower at each follow-up time point than those at baseline survey. However, the decreases in HbA1c were obvious only at 6(th) month (P<0.001), with ls-mean (95%CI) of -0.48% (-0.71%, -0.25%), -0.33% (-0.55%, -0.11%) and -0.70% (-0.92%, -0.48%), respectively, in comprehensive, health literacy and exercise intervention groups, but it increased slightly by 0.03% (-0.19%, 0.25%) in control group. Compared with control group, the interventions were significantly associated with the decrease of HbA1c level, with the most improvement observed in comprehensive group (β=-0.47, 95% CI: -0.73, -0.20) at 3(rd) month, and in exercise intervention group at 6(th) month (β=-0.73, 95%CI: -0.98, -0.47) and at 12(th) month (β=-0.75, 95%CI: -1.05, -0.45) of follow-up. Stratified analyses showed that patients with lower health literacy level could benefit from any intervention, while those with higher numeracy skill benefited more from exercise intervention. <b>Conclusion:b> Both health literacy and exercise-focused interventions may decrease HbA1c level in patients with T2DM, which would be helpful in reducing the risks of complications and deaths in diabetes patients.
Blood Glucose/analysis*
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China
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Diabetes Mellitus, Type 2/therapy*
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Disease Management
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Exercise
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Follow-Up Studies
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Glycated Hemoglobin/analysis*
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Health Literacy
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Humans
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Patient Education as Topic
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Self Care
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Surveys and Questionnaires
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Treatment Outcome