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Whether the definition of hypertension according to 2017 AHA/ACC guidelines and blood pressure (BP) changes was related to the increased risk of chronic kidney disease (CKD) remained debated. This prospective cohort study aimed to investigate the association of BP and long‐term BP change with CKD risk with different glucose metabolism according to the new hypertension guidelines. This study examined 12 951 participants and 11 183 participants derived from the older people cohort study, respectively. Participants were divided into three groups based on blood glucose and the risks were assessmented by the logistic regression model. During a 10 years of follow‐up period, 2727 individuals developed CKD (21.1%). Compared with those with BP

Introduction Maintenance hemodialysis (MHD) patients are highly threatened in the novel coronavirus disease 2019 (COVID‐19) pandemic, but evidence of risk factors for mortality in this population is still lacking. Methods We followed outcomes of the overall MHD population of Wuhan, including 7154 MHD patients from 65 hemodialysis centers, from January 1 to May 4, 2020. Among them, 130 were diagnosed with COVID‐19. The demographic and clinical data of them were collected and compared between survivors and nonsurvivors. Results Compared to the corresponding period of last year, the all‐cause mortality rate of the Wuhan MHD population significantly rose in February, and dropped down in March 2020. Of the 130 COVID‐19 cases, 51 (39.2%) were deceased. Advanced age, decreased oxygen saturation, low diastolic blood pressure (DBP) on admission, and complications including acute cardiac injury (HR 5.03 [95% CI 2.21–11.14], p

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; p = 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; p < 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.

Studies on the association between healthy lifestyle and cancer risk are limited among the old Chinese population. 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. 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. The current study suggests that healthy lifestyle could reduce cancer risk in the retired Chinese population, especially in males.Key messagesHealthy 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. 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.

Background Reports indicate that those most vulnerable to developing severe coronavirus disease 2019 (COVID-19) are older adults and those with underlying illnesses, such as diabetes mellitus, hypertension, or cardiovascular disease, which are common comorbidities among patients undergoing maintenance hemodialysis. However, there is limited information about the clinical characteristics of hemodialysis patients with COVID-19 or about interventions to control COVID-19 in hemodialysis centers. Methods We collected data retrospectively through an online registration system that includes all patients receiving maintenance hemodialysis at 65 centers in Wuhan, China. We reviewed epidemiologic and clinical data of patients with laboratory-confirmed COVID-19 between January 1, 2020 and March 10, 2020. Results Of 7154 patients undergoing hemodialysis, 154 had laboratory-confirmed COVID-19. The mean age of the 131 patients in our analysis was 63.2 years; 57.3% were men. Many had underlying comorbidities, with cardiovascular disease (including hypertension) being the most common (68.7%). Only 51.9% of patients manifested fever; 21.4% of infected patients were asymptomatic. The most common finding on chest computed tomography (CT) was ground-grass or patchy opacity (82.1%). After initiating comprehensive interventions-including entrance screening of body temperature and symptoms, universal chest CT and blood tests, and other measures-new patients presenting with COVID-19 peaked at 10 per day on January 30, decreasing to 4 per day on February 11. No new cases occurred between February 26 and March 10, 2020. Conclusions We found that patients receiving maintenance hemodialysis were susceptible to COVID-19 and that hemodialysis centers were high-risk settings during the epidemic. Increasing prevention efforts, instituting universal screening, and isolating patients with COVID-19 and directing them to designated hemodialysis centers were effective in preventing the spread of COVID-19 in hemodialysis centers.

ObjectivePancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Thus far, most drugs have failed to significantly improve patient survival. N6-methyladenosine (m6A) plays an important role in the progression of PDAC, but its aberrant regulation driven by germline variants in human diseases remains unclear.DesignWe 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 PIK3CB underlying the PDAC progression. Moreover, the PIK3CB-selective inhibitor KIN-193 was used to block PDAC tumour growth.ResultsWe identified a missense variant rs142933486 in PIK3CB that is significantly associated with the overall survival of PDAC by reducing the PIK3CB m6A level, which facilitated its mRNA and protein expression levels mediated by the m6A ‘writer’ complex (METTL13/METTL14/WTAP) and the m6A ‘reader’ YTHDF2. The upregulation of PIK3CB 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 PIK3CB 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.ConclusionsThese findings demonstrate aberrant m6A homoeostasis as an oncogenic mechanism in PDAC and highlight the potential of PIK3CB as a therapeutic target for this disease.

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.

Background: 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.Methods: 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.Results: 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.Conclusion: 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.

FOXA1 is a pioneer transcription factor which has been established as a carcinogenic factor and can regulate the expression of downstream target genes in breast cancer. We hypothesized that genetic variants modulating FOXA1 expression might play a role in the risk of breast cancer. Physical interaction predicted by PreSTIGE analysis and CHIA-PET data integration with cis-expression quantitative trait loci (cis-eQTL) based SNP-FOXA1 analysis were used to identify potentially regulatory variants modulating the expression of FOXA1. Then, we utilized a case–control study consisting of 855 new diagnosed breast cancer cases and 920 controls in the Chinese population to identify breast cancer associated variants. Biological assays were conducted in breast cancer cell lines to illustrate the effects of associated variants on breast cancer risk. We identified that rs7160774 G > A variant was associated with lower risk of breast cancer (OR = 0.77, 95% confidence interval = 0.62–0.96, P = 0.022). Biological experiments indicated that rs7160774[A] allele down-regulated the expression of FOXA1 compared to the G allele by influencing transcription factor binding affinity, thus playing an important role in the development of breast cancer. Our study suggested that the regulatory variant rs7160774 was associated with risk of breast cancer by long-range modulating FOXA1 expression and provided critical insights into pinpoint causal genetic variants.

Pancreatic cancer is one of the deadliest malignancies with few early detection tests or effective therapies. PI3K‐AKT signaling is recognized to modulate cancer progression. We previously identified that a genetic variant in PKN1 increased pancreatic cancer risk through the PKN1/FAK/PI3K/AKT pathway. In order to investigate the associations between genetic variations in that pathway and pancreatic cancer prognosis, we conducted a two‐stage survival analysis in a total of 547 Chinese pancreatic cancer patients. Consequently, a variant, rs13167294 A>C in PIK3R1, was significantly associated with poor survival in both stages and with hazard ratio being 1.32 (95% CI = 1.13‐1.56, P = 0.0007) in the combined analysis. Function annotation and prediction suggested that genetic variants in this locus might affect overall survival of pancreatic cancer patients by regulating PIK3R1 expression.

To determine the potential risk factors and construct the predictive model of diabetic risk among a relatively low risk middle-aged and elderly Chinese population. Information of participants was collected in the Dongfeng-Tongji cohort study, a perspective cohort study of Chinese occupational population. The main outcome was incident type 2 diabetes (T2DM). Based on the conventional risk factors of diabetes, we defined low risk participants without underlying diseases such as coronary heart disease, stroke, cancer, dyslipidemia, hypertension, metabolic syndrome, obesity and family history of diabetes. Totally, 4833 participants from the Dongfeng-Tongji cohort study were enrolled, and of them, 171 had an incident diagnosis of T2DM during 4.6 years of follow-up period. A Cox proportional hazards model was used to estimate effects of risk factors. The restricted cubic spline regression and the Youden index were used to explore the optimal cutoffs of risk factors, and the C index was used to assess the discrimination power of prediction models. There were significant linear relationships between BMI/TG level/fasting glucose level and incident diabetic risk among low risk participants. In the restricted cubic spline regression, when fasting glucose level was above 5.4 mmol/L, TG above 1.06 mmol/L and BMI above 22 kg/m2, the HRs (95% CIs) of diabetes were above 1.0. The detailed HRs (95% CI) were 1.29 (1.01, 1.64), 2.57 (1.00, 6.58), and 1.49 (1.00, 2.22), respectively. The optimal cutoff determined by the Yonden index was 1.1 mmol/L for TG, 24 kg/m2 for BMI and 5.89 mmol/L for fasting plasma glucose, respectively. The C index was 0.75 (95% CI: 0.7–0.81) when age, sex, smoke status, physical activity, BMI (

Observational studies indicated that resting heart rate (RHR) was associated with diabetes mellitus (DM) risk; however, it remains unclear whether the association between RHR and DM is causal. We aimed to examine whether there was causal association of RHR with DM risk. A prospective study including 16,201 middle-aged and older Chinese (7031 males and 9170 females) derived from the Dongfeng-Tongji cohort was performed. Cox proportional hazard regression models were conducted to estimate the associations between RHR and incident DM risk. In 7481 participants, 65 single nucleotide polymorphisms related to RHR were genotyped. A genetic risk score (GRS) of RHR was calculated based on the RHR-associated variants. The causal associations of RHR with DM risk were investigated by Mendelian randomization analysis. During a mean (SD) follow-up of 4.5 (0.5) years, 1110 diabetes were identified. Compared with the referential RHR group (≤ 60 beats per minute [bpm]), individuals with RHR > 80 bpm have a higher incident diabetes risk, with a hazard ratio of 1.40 (95% confidence interval [CI], 1.05–1.88). With per SD increase in the weighted genetic risk score, the resting heart rate increased by 0.71 bpm (95% CI 0.49–0.93). By using the GRS to estimate the unconfounded effect, we found that higher resting heart rate did not have a causal effect on diabetes risk (OR 1.00 [95% CI 0.95–1.05]). The present study supported a positive but not a causal association of RHR with incident diabetes risk. More studies are needed to verify our findings.

Introduction and aim It is indicated that high levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are associated with increased incident type 2 diabetes risk. However, whether serum ALT levels could improve the discrimination of type 2 diabetes remains unclear. Methods The data was derived from the Dongfeng-Tongji cohort study, which was established in 2008 and followed until October 2013. A total of 17,173 participants free of type 2 diabetes at baseline were included and 1159 participants developed diabetes after 4.51 (0.61) years of follow-up. Cox proportional hazard regression model was used to calculate the hazard ratios (HRs) for the association between ALT and AST levels with incident diabetes risk. Receiver-operating characteristic (ROC) curves analysis was used to evaluate the predictive accuracy of models incorporating traditional risk factors with and without ALT. Results Compared with the lowest quartile of ALT and AST levels, the highest quartile had a significantly higher risk of developing type 2 diabetes (HR: 2.17 [95% CI: 1.78–2.65] and 1.29 [1.08–1.54], respectively) after adjustment for potential confounders. The addition of ALT levels into the traditional risk factors did not improve the predictive ability of type 2 diabetes, with AUC increase from 0.772 to 0.774; P = 0.86. Conclusions Although elevated ALT or AST levels increased incident type 2diabetes risk, addition of ALT levels into the prediction model did not improve the discrimination of type 2 diabetes.

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-prostaglandinF2α (8-isoPGF2α), 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-isoPGF2α were significantly positively associated with BPA (P

Objective: This study was intended to investigate the relationship between COVID-19 disease and ovarian function in reproductive-aged women.Methods: 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.Results: 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 (P = 0.55), menstrual volumes (P = 0.066), phase of menstrual cycle (P = 0.58), and dysmenorrhea history (P = 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, P = 0.003/0.027; AMH ≤ 1.1 ng/ml: 75/70.4 vs. 49.7%, P = 0.009/0.004), higher serum T (0.38/0.39 vs. 0.22 ng/ml, P < 0.001/0.001) and PRL (25.43/24.10 vs. 12.12 ng/ml, P < 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; P = 0.001), T (β = 0.411; 95% CI: 11.154–22.709; P < 0.001), and PRL (β = 0.497; 95% CI: 10.787–20.266; P < 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.Conclusion: 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.Clinical Trial Number: ChiCTR2000030015.

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.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.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 (PThe 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.

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, Nonmenopausal females with COVID-19 had milder severity, better outcome, and shorter hospital stays than menopausal patients. E2 might be a potential protective factor against COVID-19, partly through its regulation of cytokines, which significantly correlated with severity of infection.

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.

Summary The efficient transmission of severe acute respiratory syndrome-2 coronavirus (SARS-CoV-2) from patients to health care workers or family members has been a worrisome and prominent feature of the ongoing outbreak. On the basis of clinical practice and in-vitro studies, we postulated that post-exposure prophylaxis (PEP) using Arbidol is associated with decreased infection among individuals exposed to confirmed cases of COVID-19 infection. We conducted a retrospective cohort study on family members and health care workers who were exposed to patients confirmed to have SARS-CoV-2 infection by real-time RT-PCR and chest computed tomography (CT) from January 1 to January 16, 2020. The last follow-up date was Feb. 26, 2020. The emergence of fever and/or respiratory symptoms after exposure to the primary case was collected. The correlations between post-exposure prophylaxis and infection in household contacts and health care workers were respectively analyzed. A total of 66 members in 27 families and 124 health care workers had evidence of close exposure to patients with confirmed COVID-19. The Cox regression based on the data of the family members and health care workers with Arbidol or not showed that Arbidol PEP was a protective factor against the development of COVID-19 (HR 0.025, 95% CI 0.003–0.209, P=0.0006 for family members and HR 0.056, 95% CI 0.005–0.662, P=0.0221 for health care workers). Our findings suggest Arbidol could reduce the infection risk of the novel coronavirus in hospital and family settings. This treatment should be promoted for PEP use and should be the subject of further investigation.

During the recent ongoing coronavirus disease‐2019 (COVID‐19) outbreak, healthcare workers around the world are fighting at the front lines of this epidemic, as well as the dermatologists. Our previous research revealed that long‐term wearing of N95 masks could lead to various facial skin lesions, which might affect their routine work and mental health. More importantly, severe skin lesions (e.g. ulcers) might put them in danger of being infected. Generally, hydrogels have been used to treat patients with pressure ulcers.

Rationale & Objective Patients receiving maintenance hemodialysis (MHD) are highly vulnerable to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current study was designed to evaluate the prevalence of SARS-CoV-2 infection based on both nucleic acid testing (NAT) and antibody testing in Chinese patients receiving MHD. Study Design Cross-sectional study. Setting & Participants From December 1, 2019, to March 31, 2020, a total of 1,027 MHD patients in 5 large hemodialysis centers in Wuhan, China, were enrolled. Patients were screened for SARS-CoV-2 infection by symptoms and initial computed tomography (CT) of the chest. If patients developed symptoms after the initial screening was negative, repeat CT was performed. Patients suspected of being infected with SARS-CoV-2 were tested with 2 consecutive throat swabs for viral RNA. In mid-March 2020, antibody testing for SARS-CoV-2 was obtained for all MHD patients. Exposure NAT and antibody testing results for SARS-CoV-2. Outcomes Morbidity, clinical features, and laboratory and radiologic findings. Analytical Approach Differences between groups were examined using t test or Mann-Whitney U test, comparing those not infected with those infected and comparing those with infection detected using NAT with those with infection detected by positive serology test results. Results Among 1,027 patients receiving MHD, 99 were identified as having SARS-CoV-2 infection, for a prevalence of 9.6%. Among the 99 cases, 52 (53%) were initially diagnosed with SARS-CoV-2 infection by positive NAT; 47 (47%) were identified later by positive immunoglobulin G (IgG) or IgM antibodies against SARS-CoV-2. There was a spectrum of antibody profiles in these 47 patients: IgM antibodies in 5 (11%), IgG antibodies in 35 (74%), and both IgM and IgG antibodies in 7 (15%). Of the 99 cases, 51% were asymptomatic during the epidemic; 61% had ground-glass or patchy opacities on CT of the chest compared with 11.6% among uninfected patients (P, Graphical abstract

BACKGROUND: In December 2019, an outbreak of the 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 personnels is still lacking. METHODS: 54 cases of SARS-Cov-2 infected medical staff from Tongji Hospital between January 7th to February 11th of 2020 were analyzed in this retrospective study. Clinical and epidemiological characteristics were compared between different groups by statistical method. RESULTS: From January 7 to February 11, 2020, 54 medical staff of Tongji Hospital were hospitalized due to 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 COVID-19 patients, the distribution of age had a significant difference between non-severe type and severe/critical cases (median age: 47 years vs. 38 years, p=0.0015). 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=0.028) and right lung (61% vs. 18.2%, P=0.012). CONCLUSIONS: 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. This article is protected by copyright. All rights reserved.

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.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.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]; p0·0001). 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.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.China National Natural Science Foundation.

ImportanceHow to explain the better prognosis of female coronavirus disease 2019 (COVID-19) patients than that of males?ObjectiveTo determine the correlation between menstruation status/sex hormones and prognosis of COVID-19, and to identify potential protective factors for female patients.Design, Setting, and ParticipantsA cross-sectional study of COVID-19 patients who were hospitalized at Tongji and Mobile Cabin Hospitals from Jan 28, 2020 to March 8, 2020.ExposuresConfirmed SARS-CoV-2 infection.Main Outcomes and MeasuresSex differences in severity and composite endpoints (admission to intensive care unit (ICU), use of mechanical ventilation, or death) of COVID-19 patients were compared. The correlation analysis and cox/logistic regression modeling of menstruation status/sex hormones and prognosis were conducted. Correlation between cytokines related to immunity and inflammation and disease severity or estradiol (E2) was revealed.ResultsChi square test indicated significant differences in distribution of composite endpoints (pp=0.029). E2 showed protective effect against disease severity (HR= 0.335, 95%CI = (0.105-1.070), p= 0.046). In the Mann-Whitney U test, the higher levels of IL6 and IL8 were found in severe group (p= 0.040, 0.033). The higher levels of IL2R, IL6, IL8 and IL10 were also observed in patients with composite end points (p). E2 levels were negatively correlated with IL2R, IL6, IL8 and TNFα in luteal phase (Pearson Correlation=−0.592, −0.558, −0.545, −0.623; p=0.033, 0.048, 0.054, 0.023) and with C3 in follicular phase (Pearson Correlation=-0.651; p=0.030).Conclusions and RelevanceMenopause is an independent risk factor for COVID-19. E2 and AMH are negatively correlated with COVID-19’s severity probably due to their regulation of cytokines related to immunity and inflammation.Key PointsQuestionAny differences in the outcomes between hospitalized female and male COVID-19 patients? If so, why?FindingsFemale patients display better prognosis than male patients. Non-menopausal women have shorter length of hospital stays, and AMH and E2 are negatively correlated with COVID-19’s severity. There is a negative correlation between E2 and the levels of IL6, IL8, IL2R and TNF-α, which are significantly correlated with disease severity or composite endpoint.MeaningNon-menopause and female sex hormones, especially E2 and AMH, are potential protective factors for females COVID-19 patients. E2 supplements could be potentially used for COVID-19 patients.

SummaryBackgroundAs of March 2, 2020, SARS-CoV-2 has infected more than 80174 people and caused 2915 deaths in China. This virus rapidly spreads to 56 countries worldwide. Thus, in order to effectively block its transmission, it is urgent to uncover all the possible transmission routes of SARS-CoV-2.MethodsFrom January 28 to February 18, 2020, 35 female patients diagnosed with COVID-19 in Tongji Hospital were included in this descriptive study. The gynecologic history, clinical characteristics, laboratory findings and chest computed tomography (CT) of all patients were recorded in detail. To examine whether there is sexual transmission through vaginal from female to her partner, we employed real-time polymerase chain reaction testing (RT-PCR) to detect SARS-CoV-2 in vaginal environment (including vaginal discharge, cervical or vaginal residual exfoliated cells) and anal swab samples, and inquired recent sexual behaviors from the patients.FindingsThe age range of the 35 patients with COVID-19 was 37-88 years. Over 50% patients infected with SARS-CoV-2 had chronic diseases. We tested the vaginal environment and anal swabs from the 35 female patients with COVID-19 and found that only an anal swab sample from one patient was positive for SARS-CoV-2. All the samples from vaginal environment were negative for SARS-CoV-2. The infection rate of the patients’ sexual partner was 42·9%. Additionally, two female patients admitted having sex with their partners during a possible infection incubation period, while one patient’s partner was uninfected and the other patient’s partner was diagnosed with COVID-19 (after the diagnosis of the female patient).ConclusionNo positive RT-PCR result was found in the vaginal environment perhaps due to the lack of ACE2 expression, which is the receptor of SARS-CoV-2, in the vagina and cervix tissues (human protein atlas). The results from this study show no evidence of transmission of SARS-CoV-2 through vaginal sex from female to her partner. However, the risk of infection of non vaginal sex and other intimate contacts during vaginal sex should not be ignored.FundingThis work was financially supported by the Clinical Research Pilot Project of Tongji hospital, Huazhong University of Science and Technology (No. 2019CR205).

Background: Since the outbreak of COVID-19 in Wuhan, a large number of people have been infected However the majority of existing medical institutions could no

Background: Since the outbreak of 2019 novel coronavirus (2019-nCoV) pneumonia, thousands of patients with fever, cough or fatigue were flocked to department of fever outpatients of designated hospitals in Wuhan, China, everyday. To date, no data have been provided to reflect the prevalence of Corona Virus Disease 2019 (COVID-19) among these outpatients. Besides, little is known on the distinguishable clinical features between COVID-19 and nucleic acid negative patients in fever clinics. Methods: From January 30 to February 4, 2020, a retrospective study was conducted on 936 patients from the fever clinic of Tongji Hospital, the biggest third-level grade-A hospital in Wuhan, which is located in the worst affected area by 2019-nCoV. The infectious status of 2019-nCoV was estimated among the outpatients in the fever clinics. The epidemiological and clinical characteristics were compared between COVID-19 and nucleic acid negative patients. Findings: From January 30 to February 4 of 2020, 628 (67·1%) of 936 fever outpatients in Tongji Hospital were diagnosed as COVID-19. The average age of 628 COVID-19 patients (53 years ±14·8 years) was obviously older than that of nucleic acid negative patients (49 years ±13·0 years) (P < 0·01). Of the 628 patients diagnosed with COVID-19, 553 cases were mild (88·1%) while 75 cases including severe and critical patients were severe (11·5%). Fever (78·2%) was the predominant initial symptom in COVID-19 patients, followed by cough (15·6%). The highest nucleic acid detection rate for 2019-nCoV infection was observed in patients with muscle ache (80·0%, 95% CI: 45·9-95·0), followed by dyspnea (75·0%, 95% CI: 37·7-93·7). Among 936 patients, Chest CT scans were performed on 780 patients, 511 of whom were diagnosed with COVID-19. Of the 511 COVID-19 patients, 492 (96·3%) cases reported positive chest CT, which was significantly higher than those with nucleic acid negative patients (88·5%, 238/269, P

Background: In colorectal cancer (CRC) 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 CRC screening. Methods: A randomized controlled trial was conducted in 6 centers in China since May, 2018. 19,546 eligible participants aged 50-74 years were recruited and randomly allocated into one of the 3 screening groups in a 1:2:2 ratio: 1) one-time colonoscopy (n=3916); 2) annual FIT (n=7854); 3) annual risk-adapted screening (n=7776). 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. Findings: For baselines screening, the participation rates of the colonoscopy, FIT, and risk-adapted screening groups were 42·5% (1665/3916), 94·0% (7386/7854), and 85·2% (6628/7776), respectively. For the intention-to-screen analysis, the detection rates for advanced neoplasm were 2·40% (94/3916), 1·13% (89/7854) and 1·66% (129/7776), with ORs (95% CIs) of 2·16 (1·61-2·90; P

Background: Since the outbreak of 2019 novel coronavirus (2019-nCoV) pneumonia, thousands of patients with fever, cough or fatigue were flocked to department of fever outpatients of designated hospitals in Wuhan, China, everyday. To date, no data have been provided to reflect the prevalence of Corona Virus Disease 2019 (COVID-19) among these outpatients. Besides, little is known on the distinguishable clinical features between COVID-19 and nucleic acid negative patients in fever clinics. Methods: From January 30 to February 4, 2020, a retrospective study was conducted on 936 patients from the fever clinic of Tongji Hospital, the biggest third-level grade-A hospital in Wuhan, which is located in the worst affected area by 2019-nCoV. The infectious status of 2019-nCoV was estimated among the outpatients in the fever clinics. The epidemiological and clinical characteristics were compared between COVID-19 and nucleic acid negative patients. Findings: From January 30 to February 4 of 2020, 628 (67·1%) of 936 fever outpatients in Tongji Hospital were diagnosed as COVID-19. The average age of 628 COVID-19 patients (53 years ±14·8 years) was obviously older than that of nucleic acid negative patients (49 years ±13·0 years) (P < 0·01). Of the 628 patients diagnosed with COVID-19, 553 cases were mild (88·1%) while 75 cases including severe and critical patients were severe (11·5%). Fever (78·2%) was the predominant initial symptom in COVID-19 patients, followed by cough (15·6%). The highest nucleic acid detection rate for 2019-nCoV infection was observed in patients with muscle ache (80·0%, 95% CI: 45·9-95·0), followed by dyspnea (75·0%, 95% CI: 37·7-93·7). Among 936 patients, Chest CT scans were performed on 780 patients, 511 of whom were diagnosed with COVID-19. Of the 511 COVID-19 patients, 492 (96·3%) cases reported positive chest CT, which was significantly higher than those with nucleic acid negative patients (88·5%, 238/269, P

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Epigenetic mechanisms, such as altered DNA methylation, may participate in the relationship between prenatal phthalate exposure and adverse birth outcomes.To explore the mediation effect of DNA methylation in the associations of phthalate exposure before delivery with birth outcomes in a Chinese cohort.Eight phthalate metabolites in maternal urine before delivery and DNA methylation of Alu and long interspersed nucleotide elements (LINE-1) in cord blood were determined among 106 mother-infant pairs. General additive models were used to assess the associations of maternal urinary phthalate metabolites with birth outcomes and DNA methylation; the mediating role of DNA methylation in cord blood was evaluated by mediation analysis.We found sex-specific associations between prenatal phthalate exposure and birth outcomes and DNA methylation of cord blood. For example, the molar sum of di-2-(ethylhexyl) phthalate (∑DEHPm) metabolites in maternal urine was positively associated with gestational age among male newborns only (P 0.05); maternal urinary monobenzyl phthalate (MBzP) was negatively associated with Alu methylation among female newborns only (P 0.05). Mediation analysis did not find that methylation of Alu and LINE-1 to be a direct mediator in the relationships between maternal urinary phthalate metabolites before delivery and birth outcomes.Prenatal exposure to certain phthalates was associated with altered birth outcomes and decreased repetitive element methylation of newborns. However, the altered birth outcomes exerted by prenatal phthalate exposure does not seem to be directly mediated through repetitive element methylation in cord blood.

Background: Telomere dysfunction triggers cellular senescence and constitutes a driving force for cancer initiation. Genetic variants in genes involved in telomere maintenance may contribute to colorectal cancer susceptibility. Methods: In this study, we firstly captured germline mutations in 192 patients with colorectal cancer by sequencing the coding regions of 13 core components implicated in telomere biology. Five potential functional variants were then genotyped and assessed in a case–control set with 3,761 colorectal cancer cases and 3,839 healthy controls. The promising association was replicated in additional 6,765 cases and 6,906 controls. Functional experiments were used to further clarify the potential function of the significant variant and uncover the underlying mechanism in colorectal cancer development. Results: The two-stage association studies showed that a rare missense variant rs149418249 (c.C1520T and p.P507L) in the 11th exon of TPP1 (also known as ACD, gene ID 65057) was significantly associated with colorectal cancer risk with the ORs being 2.90 [95% confidence interval (CI), 1.04–8.07; P = 0.041], 2.50 (95% CI, 1.04–6.04; P = 0.042), and 2.66 (95% CI, 1.36–5.18; P = 0.004) in discovery, replication, and the combined samples, respectively. Further functional annotation indicated that the TPP1 P507L substitution interrupted TPP1–TIN2 interaction, impaired telomerase processivity, and shortened telomere length, which subsequently facilitated cell proliferation and promoted colorectal cancer development. Conclusions: A rare variant P507L in TPP1 confers increased risk of colorectal cancer through interrupting TPP1–TIN2 interaction, impairing telomerase processivity, and shrinking telomere length. Impact: These findings emphasize the important role of telomere dysfunction in colorectal cancer development, and provide new insights about the prevention of this type of cancer. Cancer Epidemiol Biomarkers Prev; 27(9); 1029–35. ©2018 AACR.

Background MYC is a well-established cancer driver gene regulating the expression of numerous genes, indicating that polymorphisms in MYC response elements could affect tumorigenesis through altering MYC regulation. We performed integrative multistage study to evaluate the effects of variants in MYC response elements and colorectal cancer (CRC) risk. Patients and methods We systematically integrated ChIP-Seq, DNase-Seq and transcription factor motif data to screen variants with potential ability to affect the MYC binding affinity. Then, we conducted a two-stage case–control study, totally consisting of 4830 CRC cases and 4759 controls in Chinese population to identify risk polymorphisms and interactions. The effects of risk variants were confirmed by functional assays in CRC LoVo, SW480 and HCT15 cells. Results We identified a novel polymorphism rs11777210 in KBTBD11 significantly associated with CRC susceptibility (P = 2.43 × 10−12). Notably, we observed a significant interaction between rs11777210 and MYC nearby rs6983267 (P-multi = 0.003, P-add = 0.005), subjects carrying rs6983267 GG and rs11777210 CC genotypes showing higher susceptibility to CRC (2.83-fold) than those carrying rs6983267 TT and rs11777210 TT genotypes. We further demonstrated that rs6983267 T > G increased MYC expression, and MYC bound to and negatively regulated KBTBD11 expression when the rs11777210 C risk allele was present. KBTBD11 was downregulated in tumor tissues, and KBTBD11 knockdown promoted cell proliferation and inhibited cell apoptosis. Conclusion The rs11777210 is a potential predictive biomarker of CRC susceptibility, and KBTBD11 functions as a putative tumor suppressor in tumorigenesis. Our study highlighted the high CRC risk of people carrying rs6983267 G and rs11777210 C alleles, and provided possible biological mechanism of the interaction.

Background: Chronic kidney disease (CKD) is an increasing health problem worldwide. Recent studies have suggested the potential associations between exposure to metals and CKD events, particularly in participants with hypertension. However, relevant studies are limited. Objectives: We aimed to explore the associations of metal exposure with renal function in participants with essential hypertension. Methods: Nine hundred and thirty-four participants with essential hypertension were recruited at the Department of Cardiology, Union Hospital, Wuhan, China. We measured the levels of chromium, cadmium, thallium and uranium in urine and calculated the estimated glomerular filtration rate (eGFR) for renal function. Multivariable linear regression models adjusted for potential confounders were applied. Results: After adjusting for potential confounders and other metals, doubling of urinary chromium or uranium levels decreased eGFR by 2.90 (95% confidence interval, 2.04 to 3.76) and 1.87 (0.58 to 3.15) mL/min per 1.73m2, respectively. Co-exposure to chromium and uranium was found to greatly decrease eGFR, particularly in women. Compared with those in the low exposure group, women with high exposure to chromium and uranium had a 11.36 (3.66 to 19.07) mL/min per 1.73m2 adjusted decline in eGFR. Higher urinary thallium levels were positively related to elevated eGFR in men. The adjusted increase in eGFR with doubling of thallium levels was 3.12 (1.14 to 5.10) mL/min per 1.73m2. Sex-difference in the associations of exposure to heavy metals with eGFR was also suggested. Conclusions: Our findings suggest that environmental exposure to chromium and uranium might contribute to a decline in eGFR in individuals with hypertension. The associations of exposure to heavy metals with eGFR might be sex-different. Further studies are warranted to confirm our findings and clarify the underlying mechanisms. Keywords: Chromium, Cadmium, Thallium, Uranium, Renal function, Hypertension

Plasma homocysteine concentrations have been reported to be associated with type 2 diabetes mellitus (T2DM) with controversial findings. The aim of the present study was to investigate the association between plasma homocysteine concentrations and T2DM.A cross-sectional study including 19,085 eligible participants derived from the Dongfeng-Tongji cohort was conducted. Plasma homocysteine concentrations were measured by Abbott Architect i2000 Automatic analyzer and T2DM was defined according to American Diabetes Association criteria. Logistic regression model was used to explore the association between plasma homocysteine concentrations and T2DM. The prevalence of T2DM was 19.0% in the whole population (mean age 62.9 years), 21.8% in males, and 17.1% in females. In the multivariable logistic regression analyses, compared with those in the lowest quintile, the OR (95% CI) of T2DM was 1.05 (0.92-1.21), 0.99 (0.86-1.14), 0.90 (0.78-1.05), and 0.77 (0.66-0.90) for quintile 2 to quintile 5 of homocysteine concentrations after adjustment for potential confounders (P for trend 0.0001). Homocysteine concentrations were associated with decreased T2DM prevalence risk (OR = 0.88 per SD increase of homocysteine concentration; 95% CI: 0.84-0.93). A significant interaction between homocysteine concentrations and drinking status on T2DM prevalence risk was observed (P for interaction = 0.03). The inverse association of plasma homocysteine concentrations with T2DM prevalence risk was observed in non-drinkers but not in current drinkers.Plasma homocysteine concentrations were inversely correlated with T2DM among a middle-aged and elderly Chinese population.

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 (Pinteraction ≤ 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.

Studies have documented that exposure to organochlorine pesticides (OCPs) is linked with breast cancer, but the underlying biological mechanisms are still unknown. This study included 313 women diagnosed with breast cancer and 313 controls in Wuhan, China, and measured 18 OCPs in serum and 3 oxidative stress biomarkers in urine. Multivariable adjusted regression models were used to evaluate the associations among OCPs, oxidative stress biomarkers, and breast cancer. The mediating effect of oxidative stress was assessed by mediation analysis. We observed that most OCPs were positively associated with risk of breast cancer (all FDR-P values 0.05 or 0.10). Moreover, we found that p,p'-DDT, p,p'-DDD, dieldrin, heptachlor, and heptachlor epoxide were positively associated with 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-iso-prostaglandin F

// Ke Wang 1 , Yansen Bai 2 , Shi Chen 1 , Jiao Huang 1 , Jing Yuan 2 , Weihong Chen 2 , Ping Yao 3 , Xiaoping Miao 1 , Youjie Wang 4 , Yuan Liang 5 , Xiaomin Zhang 2 , Meian He 2 , Handong Yang 6 , Qingyi Wei 7 , Huan Guo 2 and Sheng Wei 1 1 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, Hubei, China 2 Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 3 Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 4 Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 5 Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 6 Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China 7 Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA Correspondence to: Sheng Wei, email: ws2008cn@gmail.com Keywords: tumor biomarker, single nucleotide polymorphisms, genetic correction, digestive cancer, prediction efficiency Received: July 03, 2017 Accepted: September 24, 2017 Published: December 13, 2017 ABSTRACT Although serum tumor biomarkers alpha-fetoprotein (AFP), carbohydrate antigen 19–9 (CA19–9) and carcinoembryonic antigen (CEA) have been used in digestive cancer risk prediction, the prediction efficiency remains unsatisfactory. The aim of this study was to evaluate whether genetic correction could improve the efficiency of these biomarkers for prediction of digestive cancer risk. We conducted a prospective analysis in 9,808 healthy individuals based on a cohort study in the elderly Chinese population. The genotypes of reported single nucleotide polymorphisms (SNPs) associated with serum AFP, CA19–9 and CEA were used to estimate the genetic corrected levels of these markers. Unconditional logistic regression analysis was performed to evaluate the risk of digestive cancer. The Harrell’s C-statistic was used to evaluate the discriminative ability of the raw levels and genetic corrected levels of biomarkers on digestive cancer risk. Up to October 2013, a total of 172 individuals were newly diagnosed with digestive cancer. With the genetic correction, higher odds ratios (ORs) for digestive cancer risk were found for the genetic corrected levels of tumor biomarkers compared with their raw serum levels (1.57 vs. 1.65 for AFP; 1.19 vs. 1.21 for CA19–9; 1.09 vs. 1.10 for CEA, respectively). The same results were observed in the Harrell’s C-statistic analyses. Genetic correction improved the prediction efficiency of tumor biomarkers on the digestive cancer risk in an elderly Chinese population. Our findings provide evidence for further studies of genetic effects on tumor biomarker to improve the predictive efficiency on cancer risk.

Background: Fecal immunochemical tests (FIT) detect colorectal adenoma inefficiently. Alterations in the gut microbiota were associated with the colorectal cancer (CRC) development. We aimed to explore fecal microbial signatures for advanced colorectal adenomas and evaluate their individual diagnostic value and complementary capacity to FIT. Methods: We recruited 1,546 subjects from a CRC screening program, including 268 advanced adenomas, 490 non-advanced adenomas, and 788 healthy subjects. We used a 16S rRNA sequencing based microbiome approach to profile the global microbial composition in fecal samples. Three approaches were applied to feature selections. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic values of microbial signatures and their auxiliary role to FIT and risk-stratified Asia-Pacific Colorectal Screening (APCS) score. We applied ·632+ bootstrapping to adjust the potential overfitting of the prediction models. Findings: We identified 13 microbial signatures showing their joint diagnostic value for advanced adenoma, with genus Tyzzerella 4 demonstrating the highest adjusted area under the curve (AUC) of 0 · 545 (95% CI, 0·520-0·610). A 13-marker classifier was constructed and increased the adjusted AUC to 0·607 (95% CI, 0·548-0·660). Compared with FIT solely, the combination of 13-bacteria panel and FIT reached a promising adjusted AUC of 0·641 (95% CI, 0·579-0·691). At cut-off 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 . APCS score further boosted the adjusted AUC to 0·706 (95% CI, 0·648-0·750). Interpretation: The identified fecal microbial signature could complement the diagnostic capacity of FIT for detecting advanced adenomas. Funding Statement: This work was supported by the CAMS Innovation Fund for Medical Sciences (2017-I2M-1-006, 2019-I2M-2-002), the National Natural Science Foundation of China (81703309). Beijing Nova Program of Science and Technology (Z191100001119065), and Natural Science Foundation of Beijing Municipality (7202169). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College (18-013/1615).

The aim of this study was to develop a new risk score system to predict 5-year incident diabetes risk among middle-aged and older Chinese population. This prospective study included 17,690 individuals derived from the Dongfeng–Tongji cohort. Participants were recruited in 2008 and were followed until October 2013. Incident diabetes was defined as self-reported clinician diagnosed diabetes, fasting glucose ≥7.0 mmol/l, or the use of insulin or oral hypoglycemic agent. A total of 1390 incident diabetic cases were diagnosed during the follow-up period. β-Coefficients were derived from Cox proportional hazard regression model and were used to calculate the risk score. The diabetes risk score includes BMI, fasting glucose, hypertension, hyperlipidemia, current smoking status, and family history of diabetes. The β-coefficients of these variables ranged from 0.139 to 1.914, and the optimal cutoff value was 1.5. The diabetes risk score was calculated by multiplying the β-coefficients of the significant variables by 10 and rounding to the nearest integer. The score ranges from 0 to 36. The area under the receiver operating curve of the score was 0.751. At the optimal cutoff value of 15, the sensitivity and specificity were 65.6 and 72.9%, respectively. Based upon these risk factors, this model had the highest discrimination compared with several commonly used diabetes prediction models. The newly established diabetes risk score with six parameters appears to be a reliable screening tool to predict 5-year risk of incident diabetes in a middle-aged and older Chinese population.

// Jiaoyuan Li 1 , Hui Liu 2 , Li Zou 3 , Juntao Ke 1 , Yi Zhang 1 , Ying Zhu 1 , Yang Yang 1 , Yajie Gong 1 , Jianbo Tian 1 , Danyi Zou 1 , Xiating Peng 1 , Jing Gong 1 , Rong Zhong 1 , Kun Huang 4 , Jiang Chang 5, * and Xiaoping Miao 1, * 1 Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2 National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, China 3 Department of Health Care, Bao’an Maternal and Child Health Hospital, Shenzhen, China 4 Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China 5 Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China * These authors have contributed equally to this work Correspondence to: Xiaoping Miao, email: miaoxp@mail.hust.edu.cn Jiang Chang, email: changjiang815@hust.edu.cn Keywords: TGF-β, GREM1, untranslated region, microRNA, colorectal cancer Received: February 25, 2017 Accepted: April 26, 2017 Published: May 23, 2017 ABSTRACT The transforming growth factor beta (TGF-β) pathway has been implicated in carcinogenesis of intestinal canal. Except for common variants indentified by genome-wide association studies, variants with lower frequency can also explain a part of the disease heritability, especially those in gene regulatory regions. In this study, we searched for colorectal cancer (CRC) related functional low-frequency variants (minor allele frequency 1-5%) in untranslated regions (UTR) involved in the TGF-β signaling using a next-generation sequencing based approach. A case-control study including 1,841 CRC cases and 1,837 controls was performed to identify CRC associated variants and biological experiments were applied to further explore the potential functions of the significant variants. Three low-frequency UTR variants were selected as our candidates and subsequent association analyses showed that a low-frequency variant rs12915554 in the 3’ UTR of GREM1 was significantly associated with CRC risk (Additive model: OR=1.43, 95%CI: 1.04-1.95, P =0.026). Functional annotations suggested that rs12915554 variation increased the expression of GREM1 by perturbing a hsa-miR-185-3p binding site. Moreover, higher expression level of GREM1 was investigated in colon tumor tissues compared with adjacent normal tissues using TCGA data. In conclusion, low-frequency UTR variant rs12915554 in the gene GREM1 was in relation to CRC susceptibility in a Chinese population and this variation might promote CRC development through enhancing GREM1 expression in a miRNA-mediated posttranscriptional manner.

// Ying Zhu 1, * , Kan Zhai 2, * , Juntao Ke 1 , Jiaoyuan Li 1 , Yajie Gong 1 , Yang Yang 1 , Jianbo Tian 1 , Yi Zhang 1 , Danyi Zou 1 , Xiating Peng 1 , Jing Gong 1 , Rong Zhong 1 , Kun Huang 3 , Jiang Chang 1 , Xiaoping Miao 1 1 Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2 Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China 3 Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China * These authors contribute equally to this work Correspondence to: Jiang Chang, email: changjiang815@hust.edu.cn Xiaoping Miao, email: Miaoxp@hust.edu.cn Keywords: prognosis, pancreatic cancer, BRCA, SNP Received: February 09, 2017 Accepted: March 15, 2017 Published: March 21, 2017 ABSTRACT Pancreatic cancer is a highly lethal disease with limited prognostic marker. BRAC1 and BRCA2 are two classic tumor suppressor genes which play an important role in DNA repair. Somatic mutations and germline genetic variants on BRCA1/2 have been found associated with the tumorigenesis of pancreatic cancer. However, the correlations between BRCA1/2 polymorphism and pancreatic cancer prognosis remained unknown. In this study, we genotyped three tag missense variants on BRCA1/2 in 603 sporadic pancreatic cancer patients in a Chinese population. We found rs1799966 on BRCA1 was associated with poor prognosis of pancreatic cancer patients with hazard ratio being 1.23 (95% CI: 1.09–1.40, P = 0.0010). Further stratification analyses showed that significant correlation was particularly in locally advanced stage patients with hazard ratio being 1.36 (95% CI: 1.13–1.64, P = 0.0014), but not in patients in local stage ( P = 0.1139) or metastatic stage ( P = 0.5185). Two missense variants (rs766173 and rs144848) on BRAC2 showed no significant correlation with pancreatic cancer patients’ overall survival. In conclusion, we identified a germline missense variant on BRAC1 significantly associated with poor prognosis of pancreatic cancer patients with locally advanced stage. These results may contribute to the precision medicine of this disease.

Elevated serum bilirubin levels are associated with decreased coronary heart disease (CHD) risk in cross-sectional studies among diabetic patients, but prospective evidence is limited. We investigated the relationship of serum bilirubin levels with incident CHD risk among type 2 diabetes patients. In a prospective study of 2918 type 2 diabetes embedded in the Dongfeng–Tongji cohort, serum total bilirubin (TBil), direct bilirubin (DBil), and indirect bilirubin (IBil) were measured at baseline. Cox proportional hazards models were used to examine the association between serum bilirubin levels and CHD risk. A total of 440 CHD cases were identified during 12,017 person-years of follow-up. Compared with extreme quartiles, the adjusted hazard ratio and 95% confidence interval of incident CHD were 0.74 (0.56–0.99) with P trend = 0.08 in IBil, while in TBil and DBil, the bilirubin–CHD associations were not significant. Moreover, serum TBil and IBil levels were interacted with drinking status on the risk of incident CHD (P interaction = 0.021 and 0.037, respectively), and the associations were evident in ever drinkers. In drinkers, when serum TBil or IBil concentrations increased 1 μmol/L, the CHD risk both decreased 6% (95% CIs 0.89–0.99 and 0.87–1.00, respectively). Serum IBil levels were marginally related to decreased incident CHD risk among type 2 diabetes. Drinking could potentially enhance the associations of serum TBil and DBil levels with incident CHD risk.

// Yi Zhang 1, 2 , Yan Li 2 , Shaojie Jiang 3 , Wei Chen 1, 4 , Jiao Lou 1 , Juntao Ke 1 , Jiaoyuan Li 1 , Ying Zhu 1 , Yajie Gong 1 , Yang Yang 1 , Jianbo Tian 1 , Xiating Peng 1 , Danyi Zou 1 , Jing Gong 1 , Jiang Chang 1 , Xiaoping Miao 1 , Rong Zhong 1 1 Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), Ministry of Education Key Laboratory of Environment & Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China 2 Department of Preventive Medicine, School of Public Health, Zunyi Medical University, Zunyi, Guizhou, China 3 Department of Gastroenterology, Jing Zhou Central Hospital, Jingzhou, China 4 Zhuhai Center for Chronic Disease Control, Zhuhai, China Correspondence to: Rong Zhong, email: rongzhong91@gmail.com Xiaoping Miao, email: miaoxp@mail.hust.edu.cn Keywords: breast cancer, FOXA1, genetic variants, susceptibility, case-control study Received: August 20, 2016 Accepted: October 19, 2016 Published: November 07, 2016 ABSTRACT The DNA-binding protein FOXA1 has been shown to regulate nearly all estrogen receptor-chromatin interactions, thereby influencing target gene expression levels in breast cancer (BC) cells. Recently, the rs4442975 T-allele, which disrupts the recruitment of FOXA1 and interacts with the IGFBP5 promoter, was associated to BC susceptibility in a European population. We conducted a hospital-based case-control study that included 1227 cases and 1285 controls to explore the potential association between rs4442975 and BC risk in Chinese Han population, and the effect of this SNP on BC progression was also observed in cases. No significant associations between rs4442975 and BC risk were observed under any genetic models, with an odds ratio of 0.96 (95% confidence interval = 0.81-1.15) under the additive model. When stratified based on estrogen or progesterone receptor expression, smoking or drinking habits, or menopausal status, similar negative associations were observed for all subgroups. No significant associations were observed between rs4442975 and traditional progression factors such as tumor size, nodal status, distant metastasis, or TNM staging. These results reveal that rs4442975 may not confer a risk of BC occurrence or progression in the Chinese Han population, which indicates a distinct association related to genetic heterogeneity across ethnic populations.

Background Evidence shows that exposure to poor conditions in early life is associated with an increased risk of chronic diseases in adults. Objective We investigated whether exposure to the Chinese famine (1959-1961) in the fetal stage or in childhood (0-9 y) was associated with type 2 diabetes (T2D) and hyperglycemia in adulthood. Methods We included 7801 subjects aged 56.4 ± 3.3 y from the Dongfeng-Tongji cohort. Subjects were classified into late-, middle-, and early-childhood-exposed, fetal-exposed, and unexposed groups. Excess mortality rate was used to evaluate the severity of famine. Logistic regression models were used to analyze the famine-dysglycemia associations. Generalized linear models were used to assess the famine effects on dysglycemia risk during the 5-y follow-up period among 3100 subjects. Results In descriptive analyses, the risk of T2D was significantly greater in the middle-childhood-exposed group (OR: 1.44; 95% CI: 1.10, 1.87; P = 0.007), and the risk of hyperglycemia was higher in the middle- and late-childhood-exposed groups than in the unexposed group (OR: 1.54; 95% CI: 1.26, 1.88 and OR: 1.51; 95% CI: 1.23, 1.85, respectively). In sex-specific analyses, women exposed in middle childhood (OR: 1.55; 95% CI: 1.16, 2.06) and late childhood (OR: 1.40; 95% CI: 1.05, 1.87) had a higher risk of T2D than unexposed women. This association was not found in men. Similar associations were found for hyperglycemia risk. Moreover, subjects who experienced severe famine in childhood had a 38% higher T2D risk (95% CI: 1.05, 1.81) than those exposed to less severe famine. In retrospective cohort analyses, participants who experienced famine in middle childhood had a higher hyperglycemia risk relative to the unexposed group (RR: 2.06; 95% CI: 1.08, 3.90). Conclusion Exposure to the Chinese famine in childhood was related to an increased risk of adulthood T2D and hyperglycemia, particularly in women.