2.Clinicopathological and molecular features of metaplastic thymoma.
X WANG ; R S ZHANG ; R LI ; S B YE ; Q LI ; H CHEN ; Q Y XIA ; N WU ; Q RAO
Chinese Journal of Pathology 2023;52(12):1237-1243
Objective: To investigate the clinicopathological features, and molecular genetic alterations of metaplastic thymoma (MT). Methods: A total of ten MT cases, diagnosed from 2011 to 2021, were selected from the Department of Pathology of Jinling Hospital, Nanjing University Medical School, Nanjing, China for clinicopathological and immunohistochemical (IHC) examination and clinical follow-up. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and YAP1 C-terminus (YAP1-CT) IHC were performed to detect YAP1::MAML2 fusions. Results: There were four males and six females, ranging in age from 29 to 60 years (mean 50 years, median 54 years). Microscopically, all tumors showed a typical biphasic morphology consisting of epithelial components and gradually or abruptly transitioning spindle cell components. The two components were present in varying proportions in different cases. Immunophenotypically, the epithelial cells were diffusely positive for CKpan, CK5/6 and p63. The spindle cells were diffusely positive for vimentin and focally positive for EMA. TdT was negative in the background lymphocytes. Ki-67 proliferation index was less than 5%. YAP1 and MAML2 break-apart FISH analyses showed that all ten cases had narrow split signals with a distance of nearly 2 signal diameters and may be considered false-negative. Using YAP1::MAML2 fusion FISH assays, abnormal fusion signals were observed in all the ten cases. NGS demonstrated YAP1::MAML2 fusions in all eight cases with adequate nucleic acids; in two cases the fusions were detected by DNA sequencing and in eight cases by RNA sequencing. All ten cases of MT demonstrated loss of YAP1 C-terminal expression in epithelioid cells. Conclusions: MT is a rare and low-grade thymic tumor characterized by a biphasic pattern and YAP1::MAML2 fusions. Break-apart FISH assays may sometimes show false-negative results due to the proximity of YAP1 and MAML2, while YAP1 C-terminal IHC is a highly sensitive and specific marker for MT. Loss of YAP1 C-terminal expression can also be used to screen YAP1::MAML2 fusions for possible MT cases.
Male
;
Female
;
Humans
;
Adult
;
Middle Aged
;
Thymoma/genetics*
;
In Situ Hybridization, Fluorescence
;
Transcription Factors/genetics*
;
Mutation
;
Thymus Neoplasms/genetics*
4.Sex Hormone-binding Globulin, Cardiometabolic Biomarkers, and Gestational Diabetes: A Longitudinal Study and Meta-analysis
Meng-Ying LI ; Shristi RAWAL ; Hinkle Stefanie N. ; Ye-Yi ZHU ; Fasil TEKOLA-AYELE ; Tsai Michael Y. ; Si-Min LIU ; Cui-Lin ZHANG
Maternal-Fetal Medicine 2020;02(1):2-9
Objective::This study investigated the prospective associations of circulating levels of sex hormone-binding globulin (SHBG) levels with cardiometabolic biomarkers and risk of gestational diabetes (GDM) during pregnancy. It also examines the longitudinal trajectory of SHBG in women with and without GDM.Methods::We conducted a nested case-control study of 107 incident GDM cases and 214 matched controls within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort. The cohort enrolled non-obese and obese women aged 18-40 years with a singleton pregnancy between 8 and 13 weeks of gestation from 2009 to 2013. GDM was ascertained via medical records review. Blood samples were drawn four times at gestational weeks 10-14, 15-26, 23-31, and 33-39. The prospective associations between SHBG levels and cardiometabolic biomarkers were examined using the Spearman partial correlation among the controls. The longitudinal trajectories of SHBG levels were examined among the cases and the controls. Meta-analysis of prospective studies were performed to examine the association between SHBG levels and GDM risk.Results::SHBG levels at gestational weeks 10-14 were significantly inversely associated with fasting insulin ( r= -0.17, P= 0.01) and insulin resistance as measured by HOMA-IR ( r= -0.17, P= 0.01) at gestational week 15-26. SHBG at gestational weeks 10-14 and 15-26 was lower in cases than controls (mean ± standard deviation: (204.0±97.6) vs. (220.9±102.5) nmol/L, P= 0.16 and (305.6±124.3) vs. (322.7±105.1) nmol/L, P= 0.14, respectively), yet the differences were not significant. In the meta-analysis, SHBG was 41.5 nmol/L (95% confidence interval: 23.9, 59.1, P < 0.01) significantly lower among women with GDM than without, and each 50 nmol/L increase in SHBG was significantly associated with an odds ratio of 0.85 (95% confidence interval: 0.76-0.95, P= 0.01) for GDM. Conclusion::Lower SHBG levels in early pregnancy were prospectively associated with higher high insulin levels and insulin resistance in mid-pregnancy and subsequent risk of GDM, independent of adiposity. SHBG may serve as a marker for the identification of high-risk pregnancies during early pregnancy.
5.Sex Hormone-binding Globulin, Cardiometabolic Biomarkers, and Gestational Diabetes: A Longitudinal Study and Meta-analysis
Meng-Ying LI ; Shristi RAWAL ; Hinkle Stefanie N. ; Ye-Yi ZHU ; Fasil TEKOLA-AYELE ; Tsai Michael Y. ; Si-Min LIU ; Cui-Lin ZHANG
Maternal-Fetal Medicine 2020;02(1):2-9
Objective::This study investigated the prospective associations of circulating levels of sex hormone-binding globulin (SHBG) levels with cardiometabolic biomarkers and risk of gestational diabetes (GDM) during pregnancy. It also examines the longitudinal trajectory of SHBG in women with and without GDM.Methods::We conducted a nested case-control study of 107 incident GDM cases and 214 matched controls within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort. The cohort enrolled non-obese and obese women aged 18-40 years with a singleton pregnancy between 8 and 13 weeks of gestation from 2009 to 2013. GDM was ascertained via medical records review. Blood samples were drawn four times at gestational weeks 10-14, 15-26, 23-31, and 33-39. The prospective associations between SHBG levels and cardiometabolic biomarkers were examined using the Spearman partial correlation among the controls. The longitudinal trajectories of SHBG levels were examined among the cases and the controls. Meta-analysis of prospective studies were performed to examine the association between SHBG levels and GDM risk.Results::SHBG levels at gestational weeks 10-14 were significantly inversely associated with fasting insulin ( r= -0.17, P= 0.01) and insulin resistance as measured by HOMA-IR ( r= -0.17, P= 0.01) at gestational week 15-26. SHBG at gestational weeks 10-14 and 15-26 was lower in cases than controls (mean ± standard deviation: (204.0±97.6) vs. (220.9±102.5) nmol/L, P= 0.16 and (305.6±124.3) vs. (322.7±105.1) nmol/L, P= 0.14, respectively), yet the differences were not significant. In the meta-analysis, SHBG was 41.5 nmol/L (95% confidence interval: 23.9, 59.1, P < 0.01) significantly lower among women with GDM than without, and each 50 nmol/L increase in SHBG was significantly associated with an odds ratio of 0.85 (95% confidence interval: 0.76-0.95, P= 0.01) for GDM. Conclusion::Lower SHBG levels in early pregnancy were prospectively associated with higher high insulin levels and insulin resistance in mid-pregnancy and subsequent risk of GDM, independent of adiposity. SHBG may serve as a marker for the identification of high-risk pregnancies during early pregnancy.
6.Sentinel surveillance for viral hepatitis C in China, 2016-2017.
G W DING ; S D YE ; F X HEI ; Q L LIAN ; X D PEI ; J Y BAI ; D ZHOU ; Q YANG ; S HUI ; W WANG ; A X TU ; L PANG
Chinese Journal of Epidemiology 2019;40(1):41-45
Objective: To understand the prevalence of hepatitis C virus (HCV) infection in 5 populations in China during 2016-2017 and provide evidence for the estimation of prevalence trend of hepatitis C and evaluation on the prevention and control effect. Methods: A total of 87 national sentinel surveillance sites for hepatitis C were set up in 31 provinces (autonomous regions and municipalities) of China to obtain the information about HCV infection prevalence in 5 populations, including volunteer blood donors, people receiving physical examination, patients receiving invasive diagnosis and treatment, patients receiving hemodialysis, and clients visiting family planning outpatient clinics. From April to June, 2016 and 2017, cross-sectional surveys were repeatedly conducted in the 5 populations and blood samples were collected from them for HCV antibody detection. Results: In 2016, 86 sentinel sites completed the surveillance (one sentinel site was not investigated), and 115 841 persons were surveyed. The overall HCV positive rate was 0.38% (442/115 841, 95%CI: 0.23%-0.53%). In 2017, all the 87 sentinel sites completed the surveillance, and 120 486 persons were surveyed. The overall HCV positive rate was 0.37% (449/120 486, 95%CI: 0.23%-0.52%). In 2016 and 2017, the anti-HCV positive rates were 4.46% (223/5 005, 95%CI: 2.18%-6.73%) and 4.39% (216/4 919, 95%CI: 2.29%-6.50%) respectively in hemodialysis patients, 0.85% (44/5 200, 95%CI: 0.27%-1.42%) and 0.70% (36/5 150, 95%CI: 0.15%-1.24%) respectively in patients receiving invasive diagnosis and treatment and remained to be ≤0.25% in volunteer blood donors, people receiving physical examination and clients visiting family planning outpatient clinics. Results for the comparison of the anti-HCV positive rates in the 5 populations indicated that the differences were significant (F=23.091, P<0.001 in 2016 and F=20.181, P<0.001 in 2017). Conclusions: Data from the sentinel surveillance of HCV infection on prevalence in China showed that the anti-HCV positive rates varied in the 5 populations during 2016-2017. The anti-HCV positive rate appeared the highest in the hemodialysis patients, followed by that in the patients receiving invasive diagnosis and treatment, and the prevalence of HCV infection in other 3 populations were at low levels.
China/epidemiology*
;
Cross-Sectional Studies
;
Hepacivirus
;
Hepatitis C/epidemiology*
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Hepatitis C Antibodies
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Humans
;
Prevalence
;
Sentinel Surveillance
7.Disease burden of animal injury in China, 1990-2016.
P P YE ; Y JIN ; C R JI ; Y L ER ; L L DUAN ; Z X LI
Chinese Journal of Epidemiology 2019;40(1):52-58
Objective: To analyze the disease burden of animal injury in China between 1990 and 2016. Methods: Data obtained from the Global Burden of Disease 2016 were used to analyze the age and gender specific disease burden of animal injury in China, using the incidence and disability adjusted of life years (DALYs) rate. Relative and annual changes were evaluated. Results: In 2016, the age-standardized incidence and DALYs rate of animal injury in China showed as 245.05 per 100 000 people and 12.73 per 100 000. The age-standardized incidence of non-venomous animal injury was significantly higher than that of venomous animal injury, but the differences in age-standardized incidence and DALYs rate between venomous animal injury and non-venomous animal injury were not significant. Between 1990 and 2016, there was a significantly decreasing trend in the age-standardized incidence and DALYs rate of animal injury, and obvious decline could be seen in the incidence of non-venomous animal injury, compared with venomous animal injury. The incidence and DALYs rate of animal injury declined in both males and females and in different age groups. The obvious decline of incidence and DALYs rate could be found in children aged 5-14 years and aged <5 years. Conclusions: Between 1990 and 2016, there was a significant alleviation of the disease burden of animal injury in China. Young children were most prone to animal injury, resulting in serious disability and death, indicating more attention should be paid to this population at high risk and in animal injury prevention and control programs.
Adolescent
;
Child
;
Child, Preschool
;
China/epidemiology*
;
Cost of Illness
;
Disabled Persons/statistics & numerical data*
;
Female
;
Global Burden of Disease
;
Humans
;
Incidence
;
Male
;
Quality-Adjusted Life Years
;
Wounds and Injuries/epidemiology*
8.Molecular transmission clusters on HCV genotypes among newly reported HIV/HCV co-infection in Dehong Dai and Jingpo autonomous prefecture of Yunnan province, 2016.
Y K WANG ; X C CHEN ; J B WANG ; X DUAN ; S J ZHOU ; J YANG ; T YANG ; R H YE ; Y C YANG ; S T YAO ; S DUAN ; N HE
Chinese Journal of Epidemiology 2019;40(2):191-195
Objective: To understand the characteristics on major strain subtypes of hepatitis C virus among HIV/HCV co-infected patients, so as to explore the molecular transmission clusters and related risk factors of HCV strains. Methods: A total of 336 newly reported HIV-infected patients were diagnosed as HIV/HCV co-infection in Dehong Dai and Jingpo autonomous prefecture (Dehong) in 2016. We used Nested PCR to amplify CE1 and NS5B genes among 318 samples with plasma levels above 200 μl, before using the combining phylogenetic tree and constructing molecular propagation network method to analyze the related data. Results: A total of 267 HIV/HCV co-infection patients who had met the HCV genotyping requirements were screened the gene subtypes were diversified. Among these genotypes, proportions of 3b, 6n, 6u, 1a, 3a and other subtypes appeared as 32.6% (87/267), 18.4% (49/267), 15.7%(42/267), 13.1%(35/267), 11.2%(30/267) and 9.0%(24/267) respectively. Molecular transmission network of five major HCV genotypes was constructed with a clustering rate of 39.1% (95/243). The clustering rate of subtype 1a was the highest, as 71.4% (25/35). Results from the multivariate logistic regression showed that ethnic minorities other than the Yi and Jingpo (vs. the Han, OR=0.17, 95%CI: 0.04-0.71), the married spouses (vs. the unmarried, OR=0.42, 95%CI: 0.18-0.94), the 6n and 3a subtype (vs. the 3b subtype, OR=0.34, 95%CI: 0.12-0.95; OR=0.22, 95%CI: 0.05-0.93) were more difficult to form transmission clusters. However, the 6u and 1a subtype (vs. the 3b subtype, OR=3.10, 95%CI: 1.21-7.94; OR=4.00, 95%CI: 1.32-12.11) seemed more likely to form the transmission clusters. Conclusion: Ethnicity, marital status and genetic subtypes were factors significantly associated with the formation of transmission clusters related to the major HCV gene subtypes among newly reported HIV/HCV co-infection in Dehong.
AIDS-Related Opportunistic Infections/virology*
;
Asian People
;
China/epidemiology*
;
Coinfection
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Genotype
;
HIV Infections/virology*
;
Hepacivirus/isolation & purification*
;
Hepatitis C/virology*
;
Humans
;
Phylogeny
;
Polymerase Chain Reaction
9. Progranulin promotes tamoxifen-resistance of breast cancer cells by enhancing proliferation and anti-apoptosis
Tumor 2018;38(12):1097-1105
Objective: To investigate the mechanism of progranulin (PGRN) in the development of tamoxifen resistance of human breast cancer cells. Methods: The breast cancer MCF-7 and T47D cells as well as tamoxifen-resistant MCF-7R and T47DR cells were treated by 4-hydroxytamoxifen (OHT). The 50% inhibitory concentration (IC50) of OHT was detected by CCK-8. The expressions of C-myc, Cyclin D1 and Bcl-2 were determined by Western blotting. The cell proliferation was detected by CCK-8, the apoptosis was detected by FCM. The expression levels of PGRN mRNA and protein were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The expression of PGRN in MCF-7R and T47DR cells was interfered by transfection of PGRN-siRNA. Then the changes of PGRN, C-myc, Cyclin D1 and Bcl-2 expressions were detected by Western blotting. Furthermore, the PGRN-interfered MCF-7R and T47DR cells were stimulated by OHT, then the apoptosis was tested by FCM again. Results: The IC50 of OHT in tamoxifen-induced MCF-7R or T47DR cells was higher than that of MCF-7 or T47D cells (both P < 0.001). As compared with MCF-7 or T47D cells, the proliferation of MCF-7R or T47DR cells was enhanced (both P < 0.01), the apoptotic rate was decreased (both P < 0.01), the expressions of proliferation-related proteins C-myc and Cyclin D1 as well as apoptosis-related protein Bcl-2 were significantly increased (all P < 0.01), and the mRNA and protein levels of PGRN were significantly increased in MCF-7R and T47DR cells (both P < 0.05). After the transfection of PGRN-siRNA into MCF-7R and T47DR cells, the protein levels of PGRN, C-myc, Cyclin D1 and Bcl-2 were significantly decreased (all P < 0.01). After stimulation with OHT, the apoptosis rate of PGRN-downregulated MCF-7R and T47DR cells was increased (both P < 0.01). Conclusion: PGRN is overexpressed in human breast cancer MCF-7R and T47DR cells with tamoxifen-resistance. Interference of PGRN gene expression can enhance the sensibility of breast cancer cells to tamoxifen.
10.Associations of obesity and physical activity with cognition in people aged 50 and above in Shanghai.
Z Z HUANG ; Y C ZHANG ; Y ZHENG ; Y F GUO ; Y RUAN ; S Y SUN ; Y SHI ; S N GAO ; J H YE ; Y J YAN ; K WU ; R F XU ; F WU
Chinese Journal of Epidemiology 2018;39(3):273-279
Objective: To investigate the associations of obesity and physical activity with cognition in the elderly. Methods: A cross-sectional survey was conducted from October 2009 to June 2010 among people aged ≥50 years selected through multistage random cluster sampling in Shanghai. The subjects' body weight, body height, waist circumference and hip circumference were measured to calculate body mass index (BMI) and waist-hip ratio (WHR), and the data on self-reported physical activity level were collected through questionnaire survey. A comprehensive battery of cognitive tests was conducted to assess subjects' cognitive functions, including verbal recall, forward digit span (FDS), backward digit span (BDS), and verbal fluency (VF). General linear model was used to examine the associations of BMI, WHR and physical activity with cognition. Results: A total of 7 913 participants were included, with a median age of 60 years. Age, sex, education level, income level, BMI, WHR and physical activity level were significantly associated with cognitive scores in univariate analysis. After adjusted for age, sex, education level and income level, BMI was no longer significantly associated with cognitive scores in all cognitive functions (all P>0.01). WHR was significantly associated with VF score (P<0.01). Abdominally obese participants had lower VF score than non-abdominally obese participants (P<0.01). Physical activity level was significantly associated with all cognitive functions (P<0.01). Compared with participants with moderate physical activity level, participants with low physical activity level had lower scores in all cognitive functions (P<0.01). Conclusion: Abdominal obesity and low physical activity level were negatively associated with cognition level in the elderly, suggesting that waist circumference control and physical activity might help maintain cognition in the elderly.
Aged
;
Body Height
;
Body Mass Index
;
Body Weight
;
China
;
Cognition/physiology*
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Cross-Sectional Studies
;
Exercise
;
Humans
;
Middle Aged
;
Obesity
;
Surveys and Questionnaires
;
Waist Circumference
;
Waist-Hip Ratio

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