Publications by authors named "Xiaoping Miao"

242 Publications

Associations of polycyclic aromatic hydrocarbons exposure and its interaction with XRCC1 genetic polymorphism with lung cancer: A case-control study.

Environ Pollut 2021 Sep 1;290:118077. Epub 2021 Sep 1.

State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, China. Electronic address:

Humans are extensively exposed to polycyclic aromatic hydrocarbons (PAHs) daily via multiple pathways. Epidemiological studies have demonstrated that occupational exposure to PAHs increases the risk of lung cancer, but related studies in the general population are limited. Hence, we conducted a case-control study among the Chinese general population to investigate the associations between PAHs exposure and lung cancer risk and analyze the modifications of genetic polymorphisms in DNA repair genes. In this study, we enrolled 122 lung cancer cases and 244 healthy controls in Wuhan, China. Urinary PAHs metabolites were determined by gas chromatography-mass spectrometry, and rs25487 in X-ray repair cross-complementation 1 (XRCC1) gene was genotyped by the Agena Bioscience MassARRAY System. Then, multivariable logistic regression models were performed to estimate the potential associations. We found that urinary hydroxynaphthalene (OH-Nap), hydroxyphenanthrene (OH-Phe) and the sum of hydroxy PAHs (∑OH-PAHs) levels were significantly higher in lung cancer cases than those in controls. After adjusting for gender, age, BMI, smoking status, smoking pack-years, drinking status and family history, urinary ∑OH-Nap and ∑OH-Phe levels were positively associated with lung cancer risk, with dose-response relationships. Compared with those in the lowest tertiles, individuals in the highest tertiles of ∑OH-Nap and ∑OH-Phe had a 2.13-fold (95% CI: 1.10, 4.09) and 2.45-fold (95% CI: 1.23, 4.87) increased risk of lung cancer, respectively. Effects of gender, age, smoking status and smoking pack-years on the associations of PAHs exposure with lung cancer risk were shown in the subgroup analysis. Furthermore, associations of urinary ∑OH-Nap and ∑OH-PAHs levels with lung cancer risk were modified by XRCC1 rs25487 (P ≤ 0.025), and were more pronounced in wild-types of rs25487. These findings suggest that environmental exposure to naphthalene and phenanthrene is associated with increased lung cancer risk, and polymorphism of XRCC1 rs25487 might modify the naphthalene exposure-related lung cancer effect.
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http://dx.doi.org/10.1016/j.envpol.2021.118077DOI Listing
September 2021

Urinary bisphenol A and its interaction with CYP17A1 rs743572 are associated with breast cancer risk.

Chemosphere 2021 Aug 12;286(Pt 3):131880. Epub 2021 Aug 12.

Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Objective: Bisphenol A (BPA), a common endocrine disrupter, can be activated by cytochrome P450 (CYP) metabolizing enzymes and might influence the development of breast cancer (BC). We hypothesized that BPA could interact with CYP genes, synergistically contributing to the BC risk.

Methods: Urinary BPA was measured in a total of 302 newly diagnosed BC patients and 302 healthy controls by ultra-high performance liquid chromatography-high resolution mass spectrometry. A set of seven CYP gene polymorphisms was genotyped by using the Sequenom MassARRAY system. A multivariate logistic regression model was used to assess the associations of BPA and BPA-SNP interaction with BC risk.

Results: BC patients had a higher urinary BPA concentration than healthy individuals (P < 0.001). Each 1-unit increase in log-transformed urinary BPA was associated with a 54 % increased BC risk [95 % confidence interval (CI), 1.34-1.77, P < 0.001]. Individuals with the CYP19A1 rs1902580 GA + AA genotype showed a significantly higher BC risk than those with the GG genotype (OR = 1.45, 95 % CI, 1.01-2.09, P < 0.05). A significant BPA-CYP17A1 rs743572 interaction was found to be associated with a higher risk of BC (P = 0.020). Compared with low-BPA individuals carrying CYP17A1 rs743572 GG genotypes, high-BPA individuals with the GA + AA genotype had a higher BC risk, with an odds ratio of 2.49 (95 % CI, 1.52-4.13, P < 0.05).

Conclusions: The positive association of BPA exposure with BC risk might be modified by CYP17A1 rs743572, providing evidence for the interaction effect of environment-genes on the etiology of BC.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131880DOI Listing
August 2021

Leveraging Fecal Microbial Markers to Improve the Diagnostic Accuracy of the Fecal Immunochemical Test for Advanced Colorectal Adenoma.

Clin Transl Gastroenterol 2021 Aug 19;12(8):e00389. Epub 2021 Aug 19.

Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Introduction: Fecal immunochemical tests (FITs) detect colorectal adenoma inefficiently. The gut microbiota participates in colorectal cancer development. We aimed to explore fecal microbial signatures for advanced adenomas and evaluate their diagnostic value and complementary capacity to FIT.

Methods: Using 16S rRNA sequencing, we studied gut microbiota in feces from 1,546 subjects in a screening setting, including 268 patients with advanced adenomas, 490 patients with nonadvanced adenomas, and 788 healthy subjects. Feature selections were performed using linear discriminant analysis effect size, multivariate association with linear models, and least absolute shrinkage and selection operator. The diagnostic performance of microbial signatures and their auxiliary role to FITs and the added value of the Asia-Pacific Colorectal Screening score were evaluated. We applied 0.632+ bootstrapping to adjust the potential overfitting.

Results: We identified 13 microbial signatures to show the joint diagnostic value for advanced adenoma, with genus Tyzzerella 4 demonstrating the highest adjusted area under the curve (AUC) of 0.545 (95% confidence interval [CI], 0.520-0.610). The 13-bacteria increased the adjusted AUC to 0.607 (95% CI, 0.548-0.660). Compared with individual FIT (adjusted AUC = 0.527; 95% CI, 0.519-0.571), 13-bacteria and FITs collectively reached an adjusted AUC of 0.641 (95% CI, 0.579-0.691). At cutoff values yielding specificities of 90% and 80%, the adjusted sensitivities were 28.4% (95% CI, 19.3-36.8) and 41.1% (95% CI, 29.9-49.4), respectively. The Asia-Pacific Colorectal Screening score further boosted the adjusted AUC to 0.706 (95% CI, 0.648-0.750).

Discussion: In this study using fecal samples from a screening setting, the identified microbial signatures could complement FITs for detecting advanced adenomas. Gut microbiota can act as a promising tool to optimize the current colorectal cancer screening modalities.
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http://dx.doi.org/10.14309/ctg.0000000000000389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373536PMC
August 2021

Implications of Lifestyle Factors and Polygenic Risk Score for Absolute Risk Prediction of Colorectal Neoplasm and Risk-Adapted Screening.

Front Mol Biosci 2021 16;8:685410. Epub 2021 Jul 16.

Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Estimation of absolute risk of developing colorectal neoplasm is essential for personalized colorectal cancer (CRC) screening. We developed models to determine relative and absolute risks of colorectal neoplasm based on lifestyle and genetic variants and to validate their application in risk-adapted screening. We prospectively collected data from 203 advanced neoplasms, 464 non-advanced adenomas, and 1,213 healthy controls from a CRC screening trial in China in 2018-2019. The risk prediction model based on four lifestyle factors and a polygenic risk score (PRS) consisted of 19 CRC-associated single-nucleotide polymorphisms. We assessed the relative and 10-year absolute risks of developing colorectal neoplasm and the yield of a risk-adapted screening approach incorporating risk models, fecal immunochemical test, and colonoscopy. Compared to the participants with favorable lifestyle and lower PRS, those with unfavorable lifestyle and higher PRS had 2.87- and 3.79-fold higher risk of colorectal neoplasm in males and females, respectively. For a 50-year-old man or a 50-year-old woman with the highest risk profile, the estimated 10-year absolute risk of developing colorectal neoplasm was 6.59% (95% CI: 6.53-6.65%) and 4.19% (95% CI: 4.11-4.28%), respectively, compared to 2.80% (95% CI: 2.78-2.81%) for men and 2.24% (95% CI: 2.21-2.27%) for women with the lowest risk profile. The positive predictive value for advanced neoplasm was 31.7%, and the number of colonoscopies needed to detect one advanced neoplasm was 3.2. The risk models, absolute risk estimates, and risk-adapted screening presented in our study would contribute to developing effective personalized CRC prevention and screening strategies.
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http://dx.doi.org/10.3389/fmolb.2021.685410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324207PMC
July 2021

Colorectal cancer risk variant rs7017386 modulates two oncogenic lncRNAs expression via ATF1-mediated long-range chromatin loop.

Cancer Lett 2021 Oct 15;518:140-151. Epub 2021 Jul 15.

Department of Epidemiology and Biostatistics, And the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

The activating transcription factor 1 (ATF1) has been identified as a vital pathogenic factor in the progression of colorectal cancer (CRC), whiles, the precise regulatory mechanisms remain elusive. Here, we comprehensively characterized the ATF1 cistrome by RNA-seq and ChIP-seq assays in CRC cell lines. As the results, we identified 358 genes differentially regulated and 15,029 ATF1 binding sites and demonstrated that ATF1 was widely involved in major signaling pathways in CRC, such as Wnt, TNF, Jak-STAT. Subsequently, by the expression quantitative trait loci (eQTL) analyses, we found that rs7017386 was associated with the expression of CCAT1 and PVT1 in the Wnt pathway. By a two-stage population study with 6,131 CRC cases and 10,022 healthy controls, we identified the variant was associated with CRC risk. Mechanistically, we found rs7017386 allele-specifically enhanced the binding affinity of ATF1 and promoted the expressions of PVT1 and CCAT1, via forming a long-range chromatin loop. Moreover, those two lncRNAs could synergistically facilitate c-Myc expression to activate the Wnt pathway in CRC progression. Our findings not only demonstrated the transcriptomic profiling of ATF1 in CRC, but also provided important clues for the etiology of CRC.
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http://dx.doi.org/10.1016/j.canlet.2021.07.021DOI Listing
October 2021

Aberrant MCM10 SUMOylation induces genomic instability mediated by a genetic variant associated with survival of esophageal squamous cell carcinoma.

Clin Transl Med 2021 06;11(6):e485

Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the common gastrointestinal malignancy with an inferior prognosis outcome. DNA replication licensing aberration induced by dysregulation of minichromosome maintenance proteins (MCMs) causes genomic instability and cancer metastasis. SUMOylation modification plays a pivotal role in regulation of genomic integrity, while its dysregulation fueled by preexisting germline variants in cancers remains poorly understood.

Methods: Firstly, we conducted two-stage survival analysis consisting of an exome-wide association study in 904 ESCC samples and another independent 503 ESCC samples. Then, multipronged functional experiments were performed to illuminate the potential biological mechanisms underlying the promising variants, and MCM10 influences the ESCC progression. Finally, we tested the effects of MCM10 inhibitors on ESCC cells.

Results: A germline variant rs2274110 located at the exon 15 of MCM10 was identified to be significantly associated with the prognosis of ESCC patients. Individuals carrying rs2274110-AA genotypes confer a poor survival (hazard ratio = 1.61, 95% confidence interval = 1.35-1.93, p = 1.35 × 10 ), compared with subjects carrying rs2274110-AG/GG genotypes. Furthermore, we interestingly found that the variant can increase SUMOylation levels at K669 site (Lys[K]699Arg[R]) of MCM10 protein mediated by SUMO2/3 enzymes, which resulted in an aberrant overexpression of MCM10. Mechanistically, aberrant overexpression of MCM10 facilitated the proliferation and metastasis abilities of ESCC cells in vitro and in vivo by inducing DNA over-replication and genomic instability, providing functional evidence to support our population finding that high expression of MCM10 is extensively presented in tumor tissues of ESCC and correlated with inferior survival outcomes of multiple cancer types, including ESCC. Finally, MCM10 inhibitors Suramin and its analogues were revealed to effectively block the metastasis of ESCC cells.

Conclusions: These findings not only demonstrate a potential biological mechanism between aberrant SUMOylation, genomic instability and cancer metastasis, but also provide a promising biomarker aiding in stratifying ESCC individuals with different prognosis, as well as a potential therapeutic target MCM10.
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http://dx.doi.org/10.1002/ctm2.485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236122PMC
June 2021

Bisphenol A exposure, interaction with genetic variants and colorectal cancer via mediating oxidative stress biomarkers.

Environ Pollut 2021 Oct 23;287:117630. Epub 2021 Jun 23.

Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Bisphenol A (BPA) may induce oxidative stress as well as the toxicity of colon cancer cells. We hypothesized that BPA exposure and interactions with genetic variants might be associated with colorectal cancer (CRC) risk, and the association might be partly mediated by oxidative stress. We measured urinary BPA and three oxidative stress markers [8-iso-prostaglandinF (8-isoPGF), 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in 275 new CRC cases and 538 healthy controls. A set of 25 genetic variations in 12 candidate DNA repair genes and 5 metabolic enzyme genes were genotyped by Sequenom MassARRAY approach. In multivariable logistic regression, significant positive associations of CRC risk with BPA, 8-OHdG and HNE-MA were observed. Additionally, 8-OHdG, HNE-MA and 8-isoPGF were significantly positively associated with BPA (P < 0.05). The mediation analysis showed BPA-associated HNE-MA significantly mediated 11.81% of the effect of BPA on CRC risk. Moreover, BPA was found to interact with ERCC5 rs17655 and rs2296147 (both P < 0.05) to increase CRC risk. In brief, our results suggested BPA was associated with CRC risk and the positive association of BPA with CRC risk might be partly mediated by the oxidative stress HNE-MA. BPA might interact with ERCC5 rs17655 and rs2296147 to increase CRC risk.
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http://dx.doi.org/10.1016/j.envpol.2021.117630DOI Listing
October 2021

Genetic variants associated with expression of contribute to the risk of head and neck cancer in Chinese population.

J Med Genet 2021 Mar 5. Epub 2021 Mar 5.

Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China

Background: Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common cancers worldwide and includes cancers arising from the oral cavity, pharynx and larynx. Genome-wide association studies have found several genetic variants related to the risk of SCCHN; however, they could only explain a small fraction of the heritability. Thus, more susceptibility loci associated with SCCHN need to be identified.

Methods: An association study was conducted by genotyping 555 patients with SCCHN and 1367 controls in a Chinese population. Single-variant association analysis was conducted on 63 373 SNPs, and the promising variants were then confirmed by a two-stage validation with 1875 SCCHN cases and 4637 controls. Bioinformatics analysis and functional assays were applied to uncover the potential pathogenic mechanism of the promising variants and genes associated with SCCHN.

Results: We first identified three novel genetic variants significantly associated with the risk of SCCHN (p=7.45×10 for rs2517611 at 6p22.1, p=1.76×10 for rs2524182 at 6p21.33 and p=2.17×10 for rs3131018 at 6p21.33). Further analysis and biochemical assays showed that rs3094187, which was in a region in high linkage disequilibrium with rs3131018, could modify expression by regulating the binding affinity of the transcription factor to the promoter of . In addition, experiments revealed that the inhibition of may affect several important pathways involved in tumourigenesis and attenuate the cell proliferation and migration of SCCHN.

Conclusion: These findings offer important evidence that functional genetic variants could contribute to development of SCCHN and that may function as a putative susceptibility gene for SCCHN.
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http://dx.doi.org/10.1136/jmedgenet-2020-107410DOI Listing
March 2021

Temporal Profiles of Antibody Responses, Cytokines, and Survival of COVID-19 Patients: A Retrospective Cohort in Wuhan, China.

Engineering (Beijing) 2021 May 18. Epub 2021 May 18.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the correlations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing (LOWESS) method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization. The seropositive rates of IgG and IgM were 29.6% and 48.1%, respectively, in the first week, and plateaued within five weeks. For the patients discharged from the hospital, the IgM decreased slowly, while high levels of IgG were maintained at around 188 AU·mL for the 12 weeks since illness onset. In contrast, in the patients who subsequently died, IgM declined rapidly and IgG dropped to 87 AU·mL at the twelfth week. Elevated interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1β (IL-1β), interleukin-2R (IL-2R), and tumor necrosis factor-α (TNF-α) levels were observed in the deceased patients in comparison with the discharged patients, and 12.5% of the association between low IgG level and mortality risk was mediated by these cytokines. Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival, which may help to guide prognosis estimation.
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http://dx.doi.org/10.1016/j.eng.2021.04.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129785PMC
May 2021

A genetic variant conferred high expression of CAV2 promotes pancreatic cancer progression and associates with poor prognosis.

Eur J Cancer 2021 Jul 8;151:94-105. Epub 2021 May 8.

Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China. Electronic address:

Aim: This study aimed to identify the functional genes and genetic variants associated with the prognosis of pancreatic ductal adenocarcinoma (PDAC) and reveal the mechanism underlying their prognostic roles.

Methods: First, we implement a two-stage exome-wide association study in a total of 1070 patients to identify the genetic variant correlated with PDAC prognosis. Then we performed fine mapping through bioinformatics analysis and dual-luciferase reporter assays to reveal the causal functional variant and prognostic gene. Next, we established the gene knockdown, knockout, and overexpression cell lines with small interfering RNA, CRISPR/Cas9, and lentivirus, respectively, and investigated the gene function on cell proliferation and migration in vivo and in vitro. Finally, we performed the RNA-seq to elucidate downstream genes and mechanisms altering PDAC prognosis.

Results: We identified the CAV1-CAV2 locus tagged by rs8940 was significantly associated with PDAC prognosis, and rs10249656 in the 3'untranslated region of CAV2 was the real functional variant, which upregulated CAV2 expression through abolishing miR-548s binding. We observed upregulated CAV2 in PDAC and the higher expression correlated with worse prognosis. Transient knockdown of CAV2 inhibited PDAC migration without affecting proliferation rate. Knockout of CAV2 suppressed PDAC progression and metastasis, whereas stable overexpression of CAV2 promoted. Overexpressed CAV2 promoted the PDAC progression and metastasis via perturbing genes in the focal adhesion (CCND1, IGTA1, and ZYX) and extracellular matrix organisation (PLOD2, CAST, and ITGA1) pathways mechanically.

Conclusion: These findings shed light on an important role of CAV2 on PDAC progression and the prognostic impact of its genetic variation.
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http://dx.doi.org/10.1016/j.ejca.2021.04.008DOI Listing
July 2021

Analysis of Ovarian Injury Associated With COVID-19 Disease in Reproductive-Aged Women in Wuhan, China: An Observational Study.

Front Med (Lausanne) 2021 19;8:635255. Epub 2021 Mar 19.

Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

This study was intended to investigate the relationship between COVID-19 disease and ovarian function in reproductive-aged women. Female COVID-19 patients of reproductive age were recruited between January 28 and March 8, 2020 from Tongji Hospital in Wuhan. Their baseline and clinical characteristics, as well as menstrual conditions, were recorded. Differentials in ovarian reserve markers and sex hormones (including anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], the ratio of FSH to luteinizing hormone [LH], estradiol [E2], progesterone [P], testosterone [T], and prolactin [PRL] were compared to those of healthy women who were randomly selected and individually matched for age, region, and menstrual status. Uni- and multi-variable hierarchical linear regression analyses were performed to identify risk factors associated with ovarian function in COVID-19 women. Seventy eight patients agreed to be tested for serum hormone, of whom 17 (21.79%) were diagnosed as the severe group and 39 (50%) were in the basal level group. Menstrual status ( = 0.55), menstrual volumes ( = 0.066), phase of menstrual cycle ( = 0.58), and dysmenorrhea history ( = 0.12) were similar without significant differences between non-severe and severe COVID-19 women. Significant lower serum AMH level/proportion (0.19/0.28 vs. 1.12 ng/ml, = 0.003/0.027; AMH ≤ 1.1 ng/ml: 75/70.4 vs. 49.7%, = 0.009/0.004), higher serum T (0.38/0.39 vs. 0.22 ng/ml, < 0.001/0.001) and PRL (25.43/24.10 vs. 12.12 ng/ml, < 0.001/0.001) levels were observed in basal level and the all-COVID-19 group compared with healthy age-matched control. When adjusted for age, menstrual status and parity variations in multivariate hierarchical linear regression analysis, COVID-19 disease was significantly associated with serum AMH (β = -0.191; 95% CI: -1.177-0.327; = 0.001), T (β = 0.411; 95% CI: 11.154-22.709; < 0.001), and PRL (β = 0.497; 95% CI: 10.787-20.266; < 0.001), suggesting an independent risk factor for ovarian function, which accounted for 3.2% of the decline in AMH, 14.3% of the increase in T, and 20.7% of the increase in PRL. Ovarian injury, including declined ovarian reserve and reproductive endocrine disorder, can be observed in women with COVID-19. More attention should be paid to their ovarian function under this pandemic, especially regarding reproductive-aged women. ChiCTR2000030015.
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http://dx.doi.org/10.3389/fmed.2021.635255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017139PMC
March 2021

Identification of genetic variants in mA modification genes associated with pancreatic cancer risk in the Chinese population.

Arch Toxicol 2021 03 21;95(3):1117-1128. Epub 2021 Jan 21.

Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

N6-Methyladenosine (mA) is the most prevalent modification of RNA in eukaryotes, and is associated with many cellular processes and even the development of cancers. We hypothesized that single-nucleotide polymorphisms (SNPs) in mA modification genes, including its "writers", "erasers" and "readers", might affect the mA functions and associate with the susceptibility to pancreatic ductal adenocarcinoma (PDAC). We first conducted a two-stage case-control study in Chinese population to interrogate all SNPs in 22 mA modification genes. In the discovery stage, a total of 2735 SNPs were genotyped in 980 patients and 1991 controls. Then, the promising SNP was replicated in another independent population consisting of 858 cases and 2084 controls. As a result, we found the rs7495 in 3'UTR of hnRNPC was significantly associated with increased risk of PDAC in both stages (combined odds ratio = 1.22, 95% confidence interval = 1.12-1.32, P = 2.39 × 10). To further reveal the biological function of rs7495 and hnRNPC, we performed a series of biochemical experiments. Luciferase reporter assays indicated that rs7495G allele promoted hnRNPC expression through disrupting a putative binding site for has-miR-183-3p. Cell viability assay demonstrated that knockdown of hnRNPC suppressed the proliferation of PDAC cells. RNA-seq analysis suggested that as an mA "reader", hnRNPC played an important role in RNA biological processes. In conclusion, our findings elucidated that rs7495G could confer higher risk of PDAC via promoting the expression of hnRNPC through a miRNA-mediated manner. These results provided a novel insight into the critical role of mA modification in tumorigenesis.
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http://dx.doi.org/10.1007/s00204-021-02978-5DOI Listing
March 2021

Safety of biologics for psoriasis patients during the COVID-19 pandemic: the experience from Wuhan, China.

Eur J Dermatol 2020 Dec;30(6):738-740

Department of Dermatology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Hubei Engineering Research Center for Skin Repair and Theranostics, Wuhan, China.

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http://dx.doi.org/10.1684/ejd.2020.3908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880659PMC
December 2020

The function of Wls in ovarian development.

Mol Cell Endocrinol 2021 02 7;522:111142. Epub 2021 Jan 7.

Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, 310036, People's Republic of China. Electronic address:

WNT ligand transporter Wls is essential for the WNT dependent developmental and pathogenic processes. The spatiotemporal expression pattern of Wls was investigated in this study. Immature female mice (21-22 days old) were treated with 5 IU, pregnant mare's serum gonadotrophin (PMSG) to stimulate follicular development, followed 48 h later by injection with 5 IU, human chorionic gonadotrophin (hCG) to induce ovulation. The expression of Wls was stimulated in granulosa cells and the forming corpus luteum after hCG administration. To study the function of Wls, the Amhr2 strain was used to target deletion of Wls in granulosa cells. The deletion of Wls caused a significant decrease in the fertility of Wls female mice. In female Wls mice, decreased ovarian size and number of antral follicles were found. The number of corpus luteum in immature PMSG/hCG primed Wls mice was much less than that in the control group. Compared with control animals, Wls mice have lower serum progesterone levels. RNA sequencing was used to identify genes regulated by Wls after hCG treatment. Several genes known to be critical for follicle development and steroidogenesis were significantly down-regulated, such as Fshr, Lhcgr, Sfrp4, Inhba, Cyp17a1, Hsd3b1, and Hsd17b7. The expression of WNT signaling downstream target genes, Bmp2 and Cyp19a1, also decreased significantly in Wls ovary. In summary, the findings of this study suggest that Wls is critical for female fertility and luteinization.
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http://dx.doi.org/10.1016/j.mce.2020.111142DOI Listing
February 2021

Repurposed Tocilizumab in Patients with Severe COVID-19.

J Immunol 2021 02 9;206(3):599-606. Epub 2020 Dec 9.

Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;

The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. In this multicentered retrospective and observational cohort study, 65 patients with COVID-19 receiving tocilizumab and 130 not receiving tocilizumab were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities from January 20, 2020 to March 18, 2020 in Wuhan, China. After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus nontocilizumab group (hazard ratio = 0.47; 95% confidence interval = 0.25-0.90; = 0.023). Moreover, use of tocilizumab was associated with a lower risk of acute respiratory distress syndrome (odds ratio = 0.23; 95% confidence interval = 0.11-0.45; < 0.0001). Furthermore, patients had heightened inflammation and more dysregulated immune cells before treatment, which might aggravate disease progression. After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19-induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available.
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http://dx.doi.org/10.4049/jimmunol.2000981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812057PMC
February 2021

CancerImmunityQTL: a database to systematically evaluate the impact of genetic variants on immune infiltration in human cancer.

Nucleic Acids Res 2021 01;49(D1):D1065-D1073

Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Tumor-infiltrating immune cells as integral component of the tumor microenvironment are associated with tumor progress, prognosis and responses to immunotherapy. Genetic variants have been demonstrated to impact tumor-infiltrating, underscoring the heritable character of immune landscape. Therefore, identification of immunity quantitative trait loci (immunQTLs), which evaluate the effect of genetic variants on immune cells infiltration, might present a critical step toward fully understanding the contribution of genetic variants in tumor development. Although emerging studies have demonstrated the determinants of germline variants on immune infiltration, no database has yet been developed to systematically analyze immunQTLs across multiple cancer types. Using genotype data from TCGA database and immune cell fractions estimated by CIBERSORT, we developed a computational pipeline to identify immunQTLs in 33 cancer types. A total of 913 immunQTLs across different cancer types were identified. Among them, 5 immunQTLs are associated with patient overall survival. Furthermore, by integrating immunQTLs with GWAS data, we identified 527 immunQTLs overlapping with known GWAS linkage disequilibrium regions. Finally, we constructed a user-friendly database, CancerImmunityQTL (http://www.cancerimmunityqtl-hust.com/) for users to browse, search and download data of interest. This database provides an informative resource to understand the germline determinants of immune infiltration in human cancer and benefit from personalized cancer immunotherapy.
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http://dx.doi.org/10.1093/nar/gkaa805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778991PMC
January 2021

Challenges and recommendations for cancer care in the COVID-19 pandemic.

Cancer Biol Med 2020 08;17(3):515-518

Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan 430030, China.

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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476082PMC
August 2020

Corrigendum to "Circulating essential metals and lung cancer: Risk assessment and potential molecular effects" [Environ. Int. 127 (2019) 685-693].

Environ Int 2020 Oct 1;143:106072. Epub 2020 Sep 1.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.envint.2020.106072DOI Listing
October 2020

Potential Influence of Menstrual Status and Sex Hormones on Female Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Cross-sectional Multicenter Study in Wuhan, China.

Clin Infect Dis 2021 05;72(9):e240-e248

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Recent studies have indicated that females with coronavirus disease 2019 (COVID-19) have a lower morbidity, severe case rate, and mortality and better outcome than those of male individuals. However, the reasons remained to be addressed.

Methods: To find the factors that potentially protect females from COVID-19, we recruited all confirmed patients hospitalized at 3 branches of Tongji Hospital (N = 1902), and analyzed the correlation between menstrual status (n = 509, including 68 from Mobile Cabin Hospital), female hormones (n = 78), and cytokines related to immunity and inflammation (n = 263), and the severity/clinical outcomes in female patients <60 years of age.

Results: Nonmenopausal female patients had milder severity and better outcome compared with age-matched men (P < .01 for both). Menopausal patients had longer hospitalization times than nonmenopausal patients (hazard ratio [HR], 1.91 [95% confidence interval {CI}, 1.06-3.46]; P = .033). Both anti-Müllerian hormone (AMH) and estradiol (E2) showed a negative correlation with severity of infection (adjusted HR, 0.146 [95% CI, .026-.824], P = .029 and 0.304 [95% CI, .092-1.001], P = .05, respectively). E2 levels were negatively correlated with interleukin (IL) 2R, IL-6, IL-8, and tumor necrosis factor alpha in the luteal phase (P = .033, P = .048, P = .054, and P = .023) and C3 in the follicular phase (P = .030).

Conclusions: Menopause is an independent risk factor for female COVID-19 patients. AMH and E2 are potential protective factors, negatively correlated with COVID-19 severity, among which E2 is attributed to its regulation of cytokines related to immunity and inflammation.
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http://dx.doi.org/10.1093/cid/ciaa1022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454316PMC
May 2021

Healthy lifestyle and cancer risk among Chinese population in the Dongfeng-Tongji cohort.

Ann Med 2020 11 30;52(7):393-402. Epub 2020 Jul 30.

Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health,Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Studies on the association between healthy lifestyle and cancer risk are limited among the old Chinese population.

Methods: The healthy lifestyle score was derived from smoking, drinking, diet, body mass index and physical activity among 23734 retired employees from the Dongfeng-Tongji Cohort. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). The rate advancement periods (RAPs) and the population attributable risk percentage (PAR%) were estimated to indicate the benefits of removing risk lifestyle factors.

Results: During a median follow-up of 8.16 years, 2023 cancer cases were identified. Compared with 0-2 points of the healthy lifestyle score, the HRs were 0.87 (95% CI: 0.76, 0.99), 0.83 (95% CI: 0.73, 0.94), and 0.74 (95% CI: 0.64, 0.86) for 3, 4, and 5 points, respectively, with the corresponding RAPs of -4.40 (95% CI: -8.39, -0.41), -5.84 (95% CI: -9.77, -1.90), and -9.14 (95% CI: -14.03, -4.25), respectively. Approximately 15% of incident cancer cases among total population and 22% among men would be prevented by following all 5 healthy lifestyle factors.

Conclusions: The current study suggests that healthy lifestyle could reduce cancer risk in the retired Chinese population, especially in males. Key messages Healthy lifestyle derived by smoking, drinking, diet, body mass index and physical activity presented a strong protective effect on cancer risk among the retired Chinese population, especially in males. We employed the rate advancement periods and the population attributable risk percentage to indicate the benefits of adopting healthy lifestyle and we found that following all 5 healthy lifestyle factors could delay the risk of developing cancer by 9.14 years and prevent 15% of incident cancer cases.
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http://dx.doi.org/10.1080/07853890.2020.1798017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877923PMC
November 2020

Challenges and countermeasures in the prevention of nosocomial infections of SARS-CoV-2 before resumption of work: Implications for the dermatology department.

J Am Acad Dermatol 2020 09 1;83(3):961-963. Epub 2020 Jun 1.

Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Engineering Research Center for Skin Repair and Theranostics, Wuhan, China.

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http://dx.doi.org/10.1016/j.jaad.2020.05.131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262519PMC
September 2020

Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study.

Lancet Oncol 2020 07 29;21(7):893-903. Epub 2020 May 29.

Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: COVID-19 has spread globally. Epidemiological susceptibility to COVID-19 has been reported in patients with cancer. We aimed to systematically characterise clinical features and determine risk factors of COVID-19 disease severity for patients with cancer and COVID-19.

Methods: In this multicentre, retrospective, cohort study, we included all adult patients (aged ≥18 years) with any type of malignant solid tumours and haematological malignancy who were admitted to nine hospitals in Wuhan, China, with laboratory-confirmed COVID-19 between Jan 13 and March 18, 2020. Enrolled patients were statistically matched (2:1) with patients admitted with COVID-19 who did not have cancer with propensity score on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, illness severity, and clinical interventions were compared between patients with COVID-19 with or without cancer as well as between patients with cancer with non-severe or severe COVID-19. COVID-19 disease severity was defined on admission on the basis of the WHO guidelines. Univariable and multivariable logistic regression, adjusted for age, sex, comorbidities, cancer type, tumour stage, and antitumour treatments, were used to explore risk factors associated with COVID-19 disease severity. This study was registered in the Chinese Clinical Trial Register, ChiCTR2000030807.

Findings: Between Jan 13 and March 18, 2020, 13 077 patients with COVID-19 were admitted to the nine hospitals in Wuhan and 232 patients with cancer and 519 statistically matched patients without cancer were enrolled. Median follow-up was 29 days (IQR 22-38) in patients with cancer and 27 days (20-35) in patients without cancer. Patients with cancer were more likely to have severe COVID-19 than patients without cancer (148 [64%] of 232 vs 166 [32%] of 519; odds ratio [OR] 3·61 [95% CI 2·59-5·04]; p<0·0001). Risk factors previously reported in patients without cancer, such as older age; elevated interleukin 6, procalcitonin, and D-dimer; and reduced lymphocytes were validated in patients with cancer. We also identified advanced tumour stage (OR 2·60, 95% CI 1·05-6·43; p=0·039), elevated tumour necrosis factor α (1·22, 1·01-1·47; p=0·037), elevated N-terminal pro-B-type natriuretic peptide (1·65, 1·03-2·78; p=0·032), reduced CD4+ T cells (0·84, 0·71-0·98; p=0·031), and reduced albumin-globulin ratio (0·12, 0·02-0·77; p=0·024) as risk factors of COVID-19 severity in patients with cancer.

Interpretation: Patients with cancer and COVID-19 were more likely to deteriorate into severe illness than those without cancer. The risk factors identified here could be helpful for early clinical surveillance of disease progression in patients with cancer who present with COVID-19.

Funding: China National Natural Science Foundation.
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http://dx.doi.org/10.1016/S1470-2045(20)30309-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259911PMC
July 2020

Functional characterization of a low-frequency V1937I variant in FASN associated with susceptibility to esophageal squamous cell carcinoma.

Arch Toxicol 2020 06 9;94(6):2039-2046. Epub 2020 May 9.

Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Metabolic reprogramming has been regarded as one of the core hallmarks of cancer and increased de novo fatty acid synthesis has been documented in multiple tumors including esophageal squamous cell carcinoma (ESCC). Our previous exome-wide analyses found a Val1937Ile variant (rs17848945) in the 34th exon of fatty acid synthase (FASN) that showed a strong association with the risk of ESCC. In this study, we performed a series of functional assays to investigate the biological functions underlying this variant in the development of ESCC. We demonstrated that FASN was upregulated in ESCC and both knockdown and knockout of FASN significantly inhibited ESCC cell proliferation, suggesting a tumor promoter role for this gene in ESCC. Furthermore, the results showed that overexpression of FASN[I] in the ESCC cells substantially enhanced cell proliferation, compared with overexpression of FASN[V], or the control vector. Intriguingly, we found that the FASN[I] variant can enhance the enzyme activity of FASN, and, thus, increase the amount of the FASN end-product, palmitate in the ESCC cells. We also observed elevated palmitate levels in the plasma of the FASN[I] genotype carriers among a total of 632 healthy Chinese adults. In conclusion, our results suggested that the FASN V1937I variant influenced ESCC cell proliferation and susceptibility by altering the catabolic activity of FASN on palmitate. These findings may highlight an important role of palmitate metabolism in the development of ESCC and may contribute to the personalized medicine of this disease.
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http://dx.doi.org/10.1007/s00204-020-02738-xDOI Listing
June 2020

Severe acute respiratory syndrome coronavirus 2 detection in the female lower genital tract.

Am J Obstet Gynecol 2020 07 4;223(1):131-134. Epub 2020 May 4.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Ave., Hankou, Wuhan 430030, China. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2020.04.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196539PMC
July 2020

N-methyladenosine mRNA methylation of regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression.

Gut 2020 12 20;69(12):2180-2192. Epub 2020 Apr 20.

Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan 430030, China, Huazhong University of Science and Technology Tongji Medical College, Wuhan, China

Objective: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Thus far, most drugs have failed to significantly improve patient survival. N-methyladenosine (mA) plays an important role in the progression of PDAC, but its aberrant regulation driven by germline variants in human diseases remains unclear.

Design: We first performed an exome-wide association analysis in 518 PDAC patients with overall survival and replicated in an independent population containing 552 PDAC patients. Then, a series of biochemical experiments in vitro and in vivo were conducted to investigate potential mechanisms of the candidate variant and its target gene underlying the PDAC progression. Moreover, the PIK3CB-selective inhibitor KIN-193 was used to block PDAC tumour growth.

Results: We identified a missense variant rs142933486 in that is significantly associated with the overall survival of PDAC by reducing the mA level, which facilitated its mRNA and protein expression levels mediated by the mA 'writer' complex (METTL13/METTL14/WTAP) and the mA 'reader' YTHDF2. The upregulation of is widely found in PDAC tumour tissues and significantly correlated with the poor prognosis of PDAC, especially in PTEN-deficient patients. We further demonstrated that overexpression substantially enhanced the proliferation and migration abilities of PTEN-deficient PDAC cells and activated AKT signalling pathway. Remarkably, KIN-193, a PIK3CB-selective inhibitor, is shown to serve as an effective anticancer agent for blocking PTEN-deficient PDAC.

Conclusions: These findings demonstrate aberrant mA homoeostasis as an oncogenic mechanism in PDAC and highlight the potential of as a therapeutic target for this disease.
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http://dx.doi.org/10.1136/gutjnl-2019-320179DOI Listing
December 2020

Comparative Evaluation of Participation and Diagnostic Yield of Colonoscopy vs Fecal Immunochemical Test vs Risk-Adapted Screening in Colorectal Cancer Screening: Interim Analysis of a Multicenter Randomized Controlled Trial (TARGET-C).

Am J Gastroenterol 2020 08;115(8):1264-1274

Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Introduction: In colorectal cancer screening, implementing risk-adapted screening might be more effective than traditional screening strategies. We aimed to compare the effectiveness of a risk-adapted screening strategy with colonoscopy and fecal immunochemical test (FIT) in colorectal cancer screening.

Methods: A randomized controlled trial was conducted in 6 centers in China since May 2018. Nineteen thousand five hundred forty-six eligible participants aged 50-74 years were recruited and randomly allocated into 1 of the 3 screening groups in a 1:2:2 ratio: (i) one-time colonoscopy (n = 3,916), (ii) annual FIT (n = 7,854), and (iii) annual risk-adapted screening (n = 7,776). Based on the risk-stratification score, high-risk subjects were referred for colonoscopy and low-risk ones were referred for FIT. All subjects with positive FIT were referred for diagnostic colonoscopy. The detection rate of advanced neoplasm was the primary outcome. The study is registered with the China Clinical Trial Registry (www.chictr.org.cn Identifier: ChiCTR1800015506).

Results: For baseline screening, the participation rates of the colonoscopy, FIT, and risk-adapted screening groups were 42.5% (1,665/3,916), 94.0% (7,386/7,854), and 85.2% (6,628/7,776), respectively. For the intention-to-screen analysis, the detection rates of advanced neoplasm were 2.40% (94/3,916), 1.13% (89/7,854), and 1.66% (129/7,776), with odds ratios (95% confidence intervals) of 2.16 (1.61-2.90; P < 0.001) for colonoscopy vs FIT, 1.45 (1.10-1.90; P < 0.001) for colonoscopy vs risk-adapted screening, and 1.49 (1.13-1.97; P < 0.001) for risk-adapted screening vs FIT, respectively. The numbers of subjects who required a colonoscopic examination to detect 1 advanced neoplasm were 18 in the colonoscopy group, 10 in the FIT group, and 11 in the risk-adapted screening group.

Discussion: For baseline screening, the risk-adapted screening approach showed a high participation rate, and its diagnostic yield was superior to that of FIT at a similarly low load of colonoscopy.
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http://dx.doi.org/10.14309/ajg.0000000000000624DOI Listing
August 2020

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China.

JAMA Neurol 2020 06;77(6):683-690

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Importance: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations.

Objective: To study the neurologic manifestations of patients with COVID-19.

Design, Setting, And Participants: This is a retrospective, observational case series. Data were collected from January 16, 2020, to February 19, 2020, at 3 designated special care centers for COVID-19 (Main District, West Branch, and Tumor Center) of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. The study included 214 consecutive hospitalized patients with laboratory-confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection.

Main Outcomes And Measures: Clinical data were extracted from electronic medical records, and data of all neurologic symptoms were checked by 2 trained neurologists. Neurologic manifestations fell into 3 categories: central nervous system manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and skeletal muscular injury manifestations.

Results: Of 214 patients (mean [SD] age, 52.7 [15.5] years; 87 men [40.7%]) with COVID-19, 126 patients (58.9%) had nonsevere infection and 88 patients (41.1%) had severe infection according to their respiratory status. Overall, 78 patients (36.4%) had neurologic manifestations. Compared with patients with nonsevere infection, patients with severe infection were older, had more underlying disorders, especially hypertension, and showed fewer typical symptoms of COVID-19, such as fever and cough. Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]), and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]).

Conclusions And Relevance: Patients with COVID-19 commonly have neurologic manifestations. During the epidemic period of COVID-19, when seeing patients with neurologic manifestations, clinicians should suspect severe acute respiratory syndrome coronavirus 2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.
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http://dx.doi.org/10.1001/jamaneurol.2020.1127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149362PMC
June 2020

Clinical characteristics of 54 medical staff with COVID-19: A retrospective study in a single center in Wuhan, China.

J Med Virol 2020 07 6;92(7):807-813. Epub 2020 Apr 6.

Department of Respiratory and Critical Care Medicine, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China.

In December 2019, an outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection occurred in Wuhan, and rapidly spread to worldwide, which has attracted many people's concerns about the patients. However, studies on the infection status of medical personnel is still lacking. A total of 54 cases of SARS-Cov-2 infected medical staff from Tongji Hospital between 7 January and 11 February 2020 were analyzed in this retrospective study. Clinical and epidemiological characteristics were compared between different groups by statistical method. From 7 January to 11 February 2020, 54 medical staff of Tongji Hospital were hospitalized due to coronavirus disease 2019 (COVID-19). Most of them were from other clinical departments (72.2%) rather than emergency department (3.7%) or medical technology departments (18.5%). Among the 54 patients with COVID-19, the distribution of age had a significant difference between non-severe type and severe/critical cases (median age: 47 years vs 38 years; P = .0015). However, there was no statistical difference in terms of gender distribution and the first symptoms between theses two groups. Furthermore, we observed that the lesion regions in SARS-Cov-2 infected lungs with severe-/critical-type of medical staff were more likely to exhibit lesions in the right upper lobe (31.7% vs 0%; P = .028) and right lung (61% vs 18.2%; P = .012). Based on our findings with medical staff infection data, we suggest training for all hospital staff to prevent infection and preparation of sufficient protection and disinfection materials.
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http://dx.doi.org/10.1002/jmv.25793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228263PMC
July 2020

Skin damage among health care workers managing coronavirus disease-2019.

J Am Acad Dermatol 2020 05 18;82(5):1215-1216. Epub 2020 Mar 18.

Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Engineering Research Center for Skin Repair and Theranostics, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194538PMC
May 2020

Risk SNP-Mediated Enhancer-Promoter Interaction Drives Colorectal Cancer through Both and .

Cancer Res 2020 05 3;80(9):1804-1818. Epub 2020 Mar 3.

Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.

Although genome-wide association studies (GWAS) have identified more than 100 colorectal cancer risk loci, most of the biological mechanisms associated with these loci remain unclear. Here we first performed a comprehensive expression quantitative trait loci analysis in colorectal cancer tissues adjusted for multiple confounders to test the determinants of germline variants in established GWAS susceptibility loci on mRNA and long noncoding RNA (lncRNA) expression. Combining integrative functional genomic/epigenomic analyses and a large-scale population study consisting of 6,024 cases and 10,022 controls, we then prioritized rs174575 with a C>G change as a potential causal candidate for colorectal cancer at 11q12.2, as its G allele was associated with an increased risk of colorectal cancer (OR = 1.26; 95% confidence interval = 1.17-1.36; = 2.57 × 10). rs174575 acted as an allele-specific enhancer to distally facilitate expression of both FADS2 and lncRNA AP002754.2 via long-range enhancer-promoter interaction loops, which were mediated by E2F1. AP002754.2 further activated a transcriptional activator that upregulated FADS2 expression. FADS2, in turn, was overexpressed in colorectal cancer tumor tissues and functioned as a potential oncogene that facilitated colorectal cancer cell proliferation and xenograft growth and by increasing the metabolism of PGE2, an oncogenic molecule involved in colorectal cancer tumorigenesis. Our findings represent a novel mechanism by which a noncoding variant can facilitate long-range genome interactions to modulate the expression of multiple genes including not only mRNA, but also lncRNA, which provides new insights into the understanding of colorectal cancer etiology. SIGNIFICANCE: This study provides an oncogenic regulatory circuit among several oncogenes including , and underlying the association of rs174575 with colorectal cancer risk, which is driven by long-range enhancer-promoter interaction loops. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/9/1804/F1.large.jpg.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-2389DOI Listing
May 2020
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