Association between iron deficiency and prevalence of thyroid autoimmunity in pregnant and non-pregnant women of childbearing age: a cross-sectional study Background: Thyroid autoimmunity (TAI) is prevalent among women of reproductive age and associated with adverse pregnancy outcomes. This study aimed to investigate the association between iron nutritional status and the prevalence of TAI in women during the first trimester of pregnancy and in non-pregnant women of childbearing age. Methods: Cross-sectional analysis of 7463 pregnant women during the first trimester of pregnancy and 2185 non-pregnant women of childbearing age nested within the sub-clinical hypothyroid in early pregnancy study, a prospective collection of pregnant and non-pregnant women's data, was conducted in Liaoning province of China between 2012 and 2015. Serum thyrotropin, free thyroxine, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), serum ferritin, and urinary iodine were measured. Iron deficiency (ID) was defined as serum ferritin <15 μg/L and iron overload (IO) was defined as ferritin >150 μg/L. TPOAb-positive was defined as >34 U/mL and TgAb-positive was defined as >115 U/mL. Multilevel logistic regression was conducted to examine the association between TAI and different iron nutritional status after adjusting for potential confounders. Results: The prevalence of isolated TPOAb-positive was markedly higher in women with ID than those without ID, in both pregnant and non-pregnant women (6.28% vs. 3.23%, χ2 = 10.264, P = 0.002; 6.25% vs. 3.70%, χ2 = 3,791, P = 0.044; respectively). After adjusting for confounders and the cluster effect of hospitals, ID remained associated with TPOAb-positive in pregnant and non-pregnant women (odds ratio [OR]: 2.111, 95% confidence interval [CI]: 1.241–3.591, P = 0.006; and OR: 1.822, 95% CI: 1.011–3.282, P = 0.046, respectively). Conclusion: ID was associated with a higher prevalence of isolated TPOAbs-positive, but not with isolated TgAb-positive, in both pregnant women during the first trimester of pregnancy and non-pregnant women of childbearing age, while IO was not associated with either isolated TPOAb-positive or isolated TgAb-positive. Clinical trial registration: ChiCTR-TRC-13003805, http://www.chictr.org.cn/index.aspx.

Peripheral leukocyte count and risk of bleeding in patients with non-valvular atrial fibrillation taking dabigatran: a real-world study Background: The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran. Methods: A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed. Results: During 6-month follow-up, 87 participants occurred bleeding events. For every 1 × 109/L increase in leukocyte count, the risk of bleeding increased by 11% (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99–1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75 × 109/L. For leukocyte counts < 6.75 × 109/L, the HR (95% CI) was 0.88 (0.69–1.13), and for leukocyte counts ≥ 6.75 × 109/L, the HR (95% CI) was 1.28 (1.09–1.51). Conclusion: This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran. Clinical trial registration: NCT02414035, https://clinicaltrials.gov.

Design, methodology, and preliminary results of the follow-up of a population-based cohort study in rural area of northern China: Handan Eye Study Background: Handan Eye Study (HES), a large population-based cohort study in rural area of northern China, was one of the few studies focusing on the major eye diseases of rural Chinese population. The aim of this study was to introduce the design, methodology and to assess the data quality of the follow-up phase of HES. Methods: All participants were recruited in Yongnian county of Handan city between 2012 and 2013. Main outcomes were measured by visual quality scales and ocular examinations. We performed the Chi-square test to make comparison of categorical data among groups, One-way analysis of variance and Kruskal-Wallis test was applied to make comparison of continuous data among groups, a post-hoc test was done to make further pairwise comparison. Inter-class correlation coefficients (ICCs) and Kappa coefficients were used to evaluate the consistency between different operators. Logistic regression was used to explore the influence factors of death, odds ratio (OR) and 95% confidence interval (CI) were used to estimate the effect size of each influence factor. Results: The follow-up rate was 85.3%. Subjects were classified into three groups: the follow-up group (n = 5394), the loss to follow-up group (n = 929), and the dead group (n = 507), comparison of their baseline information was done. Compared with the other two groups, age of the dead group (66.52 ± 10.31 years) was the oldest (Z = 651.293, P < 0.001), male proportion was the highest (59.0%) (χ2 = 42.351, P < 0.001), only 65.9% of the dead finished middle school education (Z = 205.354, P < 0.001). The marriage percentage, body mass index (BMI), best-corrected visual acuity (BCVA), and intra-ocular pressure of the dead group was the lowest either. Spherical equivalent error (SER) of the dead group was the highest. Besides, history of smoking, hypertension, diabetes, and heart disease were more common in the dead group. Multivariate analysis showed that age (OR = 1.901, 95% CI: 1.074–1.108), gender (OR = 0.317, 95% CI: 0.224–0.448), and BCVA (OR = 0.282, 95% CI: 0.158–0.503) were associated with death. While between the follow-up group and the loss to follow-up group, there was only difference on age, gender, BMI, systolic blood pressure and SER. The Cronbach coefficients of all scales used in the follow-up were ≥0.63 and the cumulative variances were ≥0.61, indicating good reliability and validity. The ICCs and Kappa coefficients between different operators were ≥0.69. Conclusions: HES has a high follow-up rate and a low risk of loss to follow-up bias. Age, gender, and BCVA are influence factors of death. Specifically, male subjects are at a higher risk of death than female, age is a risk factor of death while BCVA is a protective factor for death.

Value of intra-operative Doppler sonographic measurements in predicting post-operative anastomotic leakage in rectal cancer: a prospective pilot study Background: Anastomotic leakage is a serious surgical complication in rectal cancer; however, effective evaluation methods for predicting anastomotic leakage individual risk in patients are not currently available. This study aimed to develop a method to evaluate the risk of leakage during surgery. Methods: The 163 patients with rectal cancer, who had undergone anterior resection and low-ligation procedures for Doppler sonographic hemodynamic measurement from April 2011 to January 2015 in Peking University Cancer Hospital, were prospectively recruited. A predictive model was constructed based on the associations between anastomotic leakage and alterations in the anastomotic blood supply in the patients, using both univariate and multivariate statistical analyses, as well as diagnostic methodology evaluation, including Chi-square test, logistic regression model, and receiver operating characteristic curve. Results: The overall anastomotic leakage incidence was 9.2% (15/163). Doppler hemodynamic parameters whose reduction was significantly associated with anastomotic leakage were peak systolic velocity, pulsatility index, and resistance index. The areas under the receiver operating characteristic curve of residual rates of peak systolic velocity, pulsatility index, and resistance index in predicting anastomotic leakage were 0.703 (95% confidence interval [CI]: 0.552–0.854), 0.729 (95% CI: 0.579–0.879), and 0.689 (95% CI: 0.522–0.856), respectively. The predictive model revealed that the patients with severely reduced blood-flow signal exhibited a significantly higher incidence rate of anastomotic leakage than those with sufficient blood supply (19.6% vs. 3.7%, P = 0.003), particularly the patients with low rectal cancer (25.9% vs. 3.9%, P  = 0.007) and those receiving neoadjuvant chemoradiotherapy (32.1% vs. 3.7%, P = 0.001), independent of prophylactic ileostoma. Multivariate analysis revealed that insufficient blood supply of the anastomotic bowel was an independent risk factor for anastomotic leakage (odds ratio: 10.37, 95% CI: 2.703–42.735, P = 0.001). Conclusion: Based on this explorative study, Doppler sonographic hemodynamic measurement of the anastomotic bowel presented potential value in predicting anastomotic leakage.

Acute exacerbation of idiopathic pulmonary fibrosis: usual interstitial pneumonitis: vs.: possible usual interstitial pneumonitis pattern Background: The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is very poor with a high mortality. The aim of this study was to describe the clinical features and survival of patients with AE-IPF with usual pulmonary fibrosis (UIP) and possible UIP (P-UIP) pattern on chest high resolution computed tomography (HRCT). Methods: This retrospective study included 107 patients with AE-IPF admitted to Nanjing Drum Tower Hospital from January 2010 to December 2016. The subjects were divided into UIP (n = 86) and P-UIP group (n = 21) based on chest HRCT. Continuous variables were analyzed using Student's t test or Mann-Whitney U test. Categorical variables were analyzed using χ2 test. Log-rank test was used for the survival analysis. Cox proportional models evaluated the risk factors for AE occurrence and survival. Results: The male, older patients, previous N-acetylcysteine use, elevated white blood cell (WBC) counts, and microbiology infection were more common in the UIP group than the P-UIP group (χ2 = 13.567, P < 0.001; z = −2.936, P = 0.003; χ2 = 5.901, P = 0.015; t = 2.048, P = 0.043; χ2 = 10.297, P = 0.036, respectively). The percentage of AE with UIP pattern in idiopathic interstitial pneumonia (IIP) was significantly higher than P-UIP pattern (χ2 = 40.011, P < 0.001). Smoking was the risk factor for AE within 6 months after IPF diagnosis in the UIP group. The cumulative proportion survival of 30-days was significantly higher in the UIP group compared with the P-UIP group (χ2 = 5.489, P = 0.019) despite of the similar overall survival in the two groups. Multivariate Cox regression analysis indicated WBC count, partial pressure of oxygen in artery (PaO2)/fractional concentration of inspired oxygen (FiO2), and computed tomography (CT) score were the independent predictors for survival in the UIP group (hazard ratio [HR]: 1.070, 95% confidential interval [CI]: 1.027–1.114, P = 0.001; HR: 0.992, 95% CI: 0.986–0.997, P = 0.002; and HR: 1.649, 95% CI: 1.253–2.171, P < 0.001, respectively). Conclusions: AE occurrence of UIP patients in IIP was significantly more than P-UIP cases. The short-term survival was better in the UIP group despite of the similar overall survival in the two groups. WBC count, PaO2/FiO2, and CT score were the independent predictors for survival in UIP subjects.

A feasibility study of jaw thrust as an indicator assessing adequate depth of anesthesia for insertion of supraglottic airway device in morbidly obese patients Background: Jaw thrust has been proven as a useful test determining adequate depth of anesthesia for successful insertion of supraglottic airway device (SAD) in normal adults and children receiving intra-venous or inhalational anesthesia induction. This prospective observational study aimed to determine the feasibility and validity of this test when using as an indicator assessing adequate depth of anesthesia for successful insertion of SAD in spontaneously breathing morbidly obese patients receiving sevoflurane inhalational induction. Methods: Thirty morbidly obese patients with a body mass index 40 to 73 kg/m2 undergoing bariatric surgery in Beijing Friendship Hospital from October 2018 to January 2019 were included in this study. After adequate pre-oxygenation, 5% sevoflurane was inhaled and inhalational concentration of sevoflurane was increased by 1% every 2 min. After motor responses to jaw thrust disappeared, a SAD was inserted and insertion conditions were graded. The anatomic position of SAD was assessed using a fiberoptic bronchoscope. Results: The SAD was successfully inserted at the first attempt in all patients. Insertion conditions of SAD were excellent in nine patients (30%) and good in 21 patients (70%), respectively. The fiberoptic views of SAD position were adequate in 28 patients (93%). Conclusions: Jaw thrust test is a reliable indicator determining adequate anesthesia depth of sevoflurane inhalational induction for successful insertion of SAD in spontaneously breathing morbidly obese patients. Clinical trial registration: ChiCTR1800016868; http://www.chictr.org.cn/showproj.aspx?proj=28646.

Venovenous extra-corporeal membrane oxygenation for severe acute respiratory distress syndrome: a matched cohort study Background: Although the use of extra-corporeal membrane oxygenation (ECMO) has been rapidly increasing, the benefit of ECMO in patients with acute respiratory distress syndrome (ARDS) remains unclear. Our objective was to investigate the effect of venovenous ECMO (VV-ECMO) on adult patients with severe ARDS. Methods: We conducted a multi-center, retrospective, cohort study in the intensive care units (ICUs) of six teaching hospitals between January 2013 and December 2018. Patients with severe ARDS who received VV-ECMO support were included. The detailed demographic data and physiologic data were used to match ARDS patients without ECMO. The primary endpoint was the 28-day mortality. Results: Ninety-nine patients with severe ARDS supported by VV-ECMO and 72 patients without ECMO were included in this study. The acute physiology and chronic health evaluation II score was 23.1 ± 6.3 in the ECMO group and 24.8 ± 8.5 in the control group (P = 0.1195). The sequential organ failure assessment score was 12.8 ± 3.4 in the ECMO group and 13.7 ± 3.5 in the control group (P = 0.0848). The 28-day mortality of patients with ECMO support was 39.4%, and that of the control group was 55.6%. The survival analysis curve showed that the 28-day mortality in the ECMO group was significantly lower than that in the control group (P = 0.0097). Multivariate Cox regression analysis showed that the independent predictors of the 28-day mortality were the requirement of vasopressors before ECMO (hazard ratio [HR]: 1.006; 95% confidence interval [CI]: 1.001–1.013; P = 0.030) and duration of mechanical ventilation before ECMO (HR: 3.299; 95% CI: 1.264–8.609; P = 0.034). Conclusions: This study showed that ECMO improved the survival of patients with severe ARDS. The duration of mechanical ventilation and the requirement of vasopressors before ECMO might be associated with an increased risk of death.

Brain function differences in drug-naïve first-episode auditory verbal hallucination-schizophrenia patients with versus without insight Background: Few studies have reported brain function differences in drug-naïve first-episode schizophrenia patients who had auditory verbal hallucinations (AVH) with insight vs. those without insight. This study aimed to investigate brain function differences between drug-naïve first-episode AVH-schizophrenia patients with and without insight. Methods: Forty first-episode drug-naïve AVH-schizophrenia patients with or without insight and 40 healthy controls between December 2016 and December 2018 were recruited in this study. The auditory hallucinations rating scale (AHRS) was used to assess AVH severity, while the insight and treatment attitudes questionnaire was used to distinguish insight. The global functional connectivity density (gFCD) between different groups was compared using a voxel-wise one-way analysis of covariance. The relationship between gFCD and AHRS total scores were analyzed using voxel-wise multiple regression. Results: Finally, 13 first-episode drug-naïve AVH-schizophrenia patients with insight, 15 AVH-schizophrenia patients without insight, and 20 healthy controls were included for analysis. Except for global assessment of functioning scores, there were no significant differences in sociodemographic information between the AVH-schizophrenia and healthy groups (P > 0.05). Compared to the healthy controls, AVH-schizophrenia patients with insight demonstrated a decreased gFCD in the supra-marginal gyrus within the primary auditory cortex, while those without insight demonstrated an increased gFCD in the inferior frontal gyrus and superior temporal gyrus and decreased gFCD in the supplemental motor area. Compared to the AVH-schizophrenia patients with insight, those without insight demonstrated an increased gFCD in the supra-marginal gyrus and posterior superior temporal lobule and a decreased gFCD in the frontal lobe. No significant correlation between gFCD and AVH severity (AHRS total score: r = 0.23, P = 0.590; and frequency: r = 0.42, P = 0.820) was found in both AVH-schizophrenia groups. Conclusions: The gFCD-aberrant brain regions in the AVH-schizophrenia patients without insight were wider compared to those with insight, although the AHRS scores were not significantly different. The AVH-schizophrenia patients without insight had wide functional impairment in the frontal lobule, which may underlie the lack of insight and the abnormal hyperactivity in the inferior frontal gurus and temporal lobe related to the AVH symptoms.

Persistent depression is a predictor of quality of life in stroke survivors: results from a 5-year follow-up study of a Chinese cohort Background: Whether the time course of post-stroke depression (PSD) can be used to predict the quality of life (QoL) of patients with late-stage stroke remains unclear, this study investigated whether persistent depression at 1 year after stroke predicts QoL at 5 years following stroke. Methods: We analyzed the demographic and clinical data of patients with stroke in 56 hospitals across China that participated in the Prospective Cohort Study on the Incidence and Outcome of Patients with PSD in China Study. Follow-up assessments were performed at the following time points after stroke: in person, 2 weeks, 3 months, 6 months, and 1 year; by telephone, 5 years. National Institutes of Health Stroke Scale (NIHSS) score on admission, recurrence, disability, depression, QoL, and chronic complications were recorded. Depression was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders. QoL was measured using short form-12 (SF-12). Multivariable ordinal logistic regression analysis was used to identify factors that independently affected the physical component summary (PCS) and mental component summary (MCS) scores of the SF-12. Results: Of the 801 patients evaluated in this study, 80 had persistent depression. The multivariable regression analysis of data obtained at 5 years showed that persistent depression at 1 year (odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.29–0.81) and disability at 5 years (OR: 0.34; 95% CI: 0.23–0.49) were associated with poor MCS scores at 5 years. Old age, a high NIHSS score on admission, disability at 5 years, and stroke recurrence within 5 years were associated with poor PCS scores at the 5-year follow-up. Conclusions: Persistent depression at the 1-year follow-up could predict poor MCS scores at the 5-year follow-up. The development of interventional strategies targeting post-stroke patients with persistent depression is warranted.

Identification of microRNAs as novel biomarkers for esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas (TCGA) and bioinformatics Background: MicroRNAs (miRNAs) have played important roles in the regulation of gene expression in many cancers, but their roles in esophageal squamous cell carcinoma (ESCC) are still unclear. The aim of this study was to determine the potential ESCC-specific key miRNAs from a large sample dataset in The Cancer Genome Atlas (TCGA). Methods: Integrative bioinformatics analysis was used to identify key ESCC-specific miRNAs related to the ESCC patients’ tumor histological grade and lymphatic metastasis from TCGA. Next, these key miRNA potential gene regulatory functions and relationships with ESCC patients’ clinical characteristics and overall survival were analyzed. Finally, three key miRNAs were selected randomly and quantificational real-time polymerase chain reaction (qRT-PCR) was used to validate in 51 newly diagnosed ESCC patients’ tissues samples (collected from Nov. 2017 to Feb. 2019, in Wuwei, China) whether the bioinformatics analyses results were reliable and valid. Two-tailed Student's t test, Pearson Chi-squared test and Kaplan-Meier survival analysis were used in this study. Results: Thirty-five ESCC-specific miRNAs from TCGA database were investigated (fold-change > 2.0, P < 0.05), and 28 participated in the miRNAs-mRNAs co-expression network construction, while 17 were related with ESCC patients’ tumor histological grade, TNM stage, and lymphatic metastasis (P < 0.05). Meanwhile, six miRNAs (including miR-200b-3p, miR-31-5p, miR-15b-5p, miR-141-3p, miR-135b-5p, and miR-195-5p) were correlated with overall survival of ESCC patients (log-rank, P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p were selected for verification of the expression levels in 51 ESCC patients’ tissue samples by using qRT-PCR. We found that the fold-changes between qRT-PCR and TCGA were completely consistent. The results also suggested that miR-135b-5p, miR-15b-5p, and miR-195-5p were significantly correlated with tumor differentiation degrees (P < 0.05), miR-195-5p was significantly correlated with tumor TNM stage (P < 0.05), and miR-135b-5p was significantly correlated with lymph-node metastasis (P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p expression levels, ESCC patient clinical features association analysis results and the aforementioned TCGA bioinformatics analyses were similar. Conclusion: This study identified key ESCC-related miRNAs. The key miRNAs are worthy of further investigation as potential novel biomarkers for diagnosis, classification, and prognosis of ESCC.