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Background The association of early-life undernutrition and dyslipidemia found in previous studies may be confounded by the uncontrolled age difference between exposed and unexposed participants. The study aimed to investigate the association of early-life undernutrition and the risk of dyslipidemia in adulthood with good control of the age variable. Methods We took the Great Chinese Famine (1959–1961) as a natural experiment of severe undernutrition. This study was based on the baseline investigation of a population-based cohort in rural China. Undernutrition in early life was defined as being exposed to famine at younger than 3 years of age. Three approaches including Adjustment, Restriction, and Matching were applied to control the confounding effect of age. Logistic regression models were applied to evaluate the association between early-life famine and the presence of dyslipidemia. Stratified analysis by gender was also performed, and potential effect modification was tested by adding the interaction term of the famine exposure variable and gender into the model. Results Undernutrition in early life was associated with increased risk of borderline high and above (BHA) levels of total cholesterol (TC, ORAdjustment = 1.61; ORRestriction = 1.56; ORMatching = 1.87), triglycerides (TG, ORAdjustment = 1.33; ORRestriction = 1.30; ORMatching = 1.34), low-density lipoprotein cholesterol (LDL-C, ORAdjustment = 1.75; ORRestriction = 1.53; ORMatching = 1.77) and dyslipidemia (ORAdjustment = 1.52; ORRestriction = 1.45; ORMatching = 1.60), as well as high levels of TC, TG, LDL-C and dyslipidemia. An inverse association of undernutrition and risk of low high-density lipoprotein cholesterol (HDL-C) was found. Female participants with undernutrition experience had an increased risk of BHA TG and LDL-C (TG: ORAdjustment, female = 1.45; ORRestriction, female = 1.39; ORMatching, female = 1.51; LDL-C: ORAdjustment, female = 2.11; ORRestriction, female = 1.80; ORMatching, female = 2.15), but this association was not found in males. Conclusion Early-life undernutrition increased the risk of TC, TG, LDL-C, and dyslipidemia. Gender would significantly modify this effect for TG and LDL-C. These results emphasize the importance of nutritional conditions in the early stages of life to long-term health consequences.

OBJECTIVE: We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk. METHODS: We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China. The oral microbiome was evaluated with 16S ribosomal RNA (rRNA) gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above (SDA) and 168 matched healthy controls. DESeq analysis was performed to identify taxa of differential abundance. Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models. RESULTS: A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls (all P0.84. CONCLUSIONS: The oral microbiome may play an etiological and predictive role in esophageal cancer, and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.

Background: To assess potential roles for tumor-associated autoantibodies (TAAs) in esophageal squamous cell carcinoma (ESCC) screening: detecting early-stage malignancy, and predicting future cancer risk. Methods: Thirteen candidate autoantibodies identified in previous literatures were measured using multiplex serological assays in sera from cases and matched controls nested in two population-level screening cohorts in China. To evaluate the role of TAAs in detecting prevalent esophageal malignant lesions, an identification set (150 cases vs. 560 controls) and an external validation set (34 cases vs. 121 controls) were established with pre-screening sera collected ≤ 12 months prior to screening-related diagnosis. To explore the role of TAAs in predicting future ESCC risk, an exploration set (105 cases vs. 416 controls) with pre-diagnostic sera collected > 12 months before clinical diagnosis was established. Two models, the questionnaire-based model and full model additionally incorporating TAA markers, were constructed. Area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI) were calculated to compare the performance of the two models. Findings: In the identification set, NY-ESO-1 (OR=2·12, 95% CI=1·02-4·40) and STIP1 (OR=1·83, 95% CI=1·10-3·05) were positively associated with higher risk of esophageal malignancy. Elevated MMP-7 was associated with higher risk of malignancy in females (ORfemale=5·07, 95% CI=1·30-19·71). The estimates in validation set were consistent with these results, but were close to null in exploration set. Integration of selected TAAs improved the performance of questionnaire-based models in detecting prevalent esophageal malignancy (female: AUCfull model=0·745, 95% CI=0·675-0·814, AUCquestionnaire-based model=0·658, 95% CI=0·585-0·732, NRI=0·604, P

Hepatitis B virus (HBV) can induce chronic inflammation, cirrhosis, and eventually hepatocellular carcinoma (HCC). Despite evidence suggesting a link between adaptive immunity and HBV-related diseases in humans, the immunopathogenic mechanisms involved are seldom described. Here we show that expression of TIGIT, a promising immune checkpoint in tumor immunotherapy, increases with age on hepatic CD8+ T cells in HBsAg-transgenic (HBs-tg) mice whose adaptive immune system is tolerant to HBsAg. TIGIT blockade or deficiency leads to chronic hepatitis and fibrosis, along with the emergence of functional HBsAg-specific cytotoxic T lymphocytes (CTLs), suggesting adaptive immune tolerance could be broken by TIGIT blockade or deficiency. Importantly, HBsAg vaccination further induces nonresolving inflammation and HCC in a CD8+ T cell-dependent manner in TIGIT-blocked or -deficient HBs-tg mice. Therefore, CD8+ T cells play an important role in adaptive immunity-mediated tumor progression and TIGIT is critical in maintenance of liver tolerance by keeping CTLs in homeostatic balance., Chronic hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC) and is associated with immune tolerance to HBV. Here the authors show, in a transgenic mouse model, that rescuing T cells function via inhibition of co-inhibitory receptor TIGIT results in HCC development via supporting inflammation.

Objective To evaluate the accuracy of identifying cancer patients by use of medical claims data in a health insurance system in China, and provide the basis for establishing the claims-based cancer surveillance system in China. Methods We chose Hua County, Henan Province as the study site, and randomly selected 300 and 1,200 qualified inpatient electronic medical records (EMRs) as well as the New Rural Cooperative Medical Scheme (NCMS) claims records for cancer patients in Hua County People's Hospital (HCPH) and Anyang Cancer Hospital (ACH) in 2017. Diagnostic information for NCMS claims was evaluated on an individual level, and sensitivity and positive predictive value (PPV) were calculated taking the EMRs as the gold standard. Results The sensitivity of NCMS was 95.2% (93.8%-96.3%) and 92.0% (88.3%-94.8%) in ACH and HCPH, respectively. The PPV of the NCMS was 97.8% (96.7%-98.5%) in ACH and 89.0% (84.9%-92.3%) in HCPH. Overall, the weighted and combined sensitivity and PPV of NCMS in Hua County was 93.1% and 92.1%, respectively. Significantly higher sensitivity and PPV in identifying patients with common cancers than non-common cancers were detected in HCPH and ACH separately (P Conclusions Identification of cancer patients by use of the NCMS is accurate on individual level, and it is therefore feasible to conduct claims-based cancer surveillance in areas not covered by cancer registries in China.

Background: The protocol for surveillance for Esophageal Squamous Cell Carcinoma (ESCC) in China following screening lacks evidence from large-scale population-based studies. We aim to establish an evidence-based surveillance target and respective intervals for ESCC surveillance. Methods: This study enrolled 14980 subjects from a large-scale randomized controlled trial in China. Poisson regression models were applied to estimate adjusted incidence rate ratios (IRR) for subjects with Lugol-unstained lesions (LUL) of differing size and baseline pathologic diagnosis. We clustered subgroups of subjects with LULs of varying size and pathologic status into three categories (low, moderate and high risk) according to their risk of progression to ESCC. Cumulative incidence of ESCC was calculated year by year for these three categories to determine appropriate surveillance intervals. Findings: LUL size is a principal predictor of post-screening risk of ESCC besides the pathologic diagnosis (adjusted IRR 6-10 mm VS none = 8·54, 95%CI: 2·78-26·24; adjusted IRR >10 mm VS none = 30·91, 95%CI: 10·69-89·39). Subjects with LULs >10mm (irrespective of the pathologic diagnosis) had the highest risk of progression, and the risk grew rapidly after the 2 nd year following the index endoscopy. Subjects with LULs of 6-10mm (irrespective of the pathologic diagnosis) or dysplastic LULs of 1-5mm had moderate risk, and the risk started to rise after the year three. Interpretation: We propose a novel surveillance strategy for ESCC that combines Lugol’s chromoendoscopy findings and the pathologic diagnosis. Use of this strategy would improve the effectiveness of ESCC screening programs in China. Funding: This study was supported by the National Key R&D Program of China (2016YFC0901404) and the National Natural Science Foundation of China (81773501). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Research protocols were approved by the Institutional Review Board of Peking University School of Oncology.

Background. Delayed-onset muscle soreness (DOMS), also known as tenderness of touch, refers to the pain caused by muscle mechanical stimulation, such as contraction and stretching. Chinese massage has been widely used in the treatment of sports fatigue and sports injury, but there is controversy in the efficacy. In this experiment, we established DOMS model in rats to observe the prevention and treatment effect of massage, to find the best time for intervention, and to provide scientific basis for the prevention and treatment of exercise fatigue.Methods. 130 male SD(sprague-dawley, SD) healthy rats were randomly divided into blank group, control group and massage group. Except for blank group, the other rats received DOMS model. Professionals applied kneading and twisting methods on both lower limbs of rats. The expression of IL-2, IL-6 and IL-8 in skeletal muscle of rats were determined by western blot, PCR and ELISA, and the content of serum creatine kinase was determined by ELISA. In addition, we measured the concentration of Ca2+, Ca2+-ATPase in mitochondria of skeletal muscle. The changes of skeletal muscle structure were observed by scanning electron microscopy.Result. After massage, the expression of IL-2, IL-6, IL-8 and CK decreased compared with control group (P < 0.01), the expression of IL-2, IL-6 and IL-8 in post massage group was lower than that in front massage group (P < 0.01), and the content of CK in front massage group was lower than that in post massage group(P < 0.01). The content of Ca2+ in front massage 24, 48 and 72h group was lower than that in post massage (P < 0.01), the concentration of Ca2+-ATPase in front massage 24h and 72h group was lower than that in post massage group (P < 0.05).Conclusion. Massage can prevent the injury of muscle and reduce the inflammatory reaction of muscle after exercise. It can also improve the activity of Ca2+-ATPase, enhance the transport of Ca2+ by mitochondria and protect the skeletal muscle.

Background and Aims At present, the surveillance strategy for premalignant esophageal lesions in China is based solely on the pathologic diagnosis in Lugol’s chromoendoscopy (LCE). In this study, we sought to determine the degree to which various unstained features under LCE may lead to improved ability to predict the risk of progression in esophageal lesions. Methods We re-examined and followed up on 1058 subjects who had Lugol-unstained lesions (LULs) together with a pathologic diagnosis that was lower than severe dysplasia at baseline screening based on a population-based randomized controlled trial over a median time of 5.8 years. We established a logistic regression model and calculated the adjusted cumulative incidence of severe dysplasia or malignancy. Results LUL size was predictive of progression to malignant lesions in individuals with a nondysplastic diagnosis (adjusted odd ratio6-10 mm vs ≤5 mm, 6.7; 95% confidence interval, 1.7-25.7; adjusted odds ratio>10 mm vs ≤5 mm, 27.9; 95% confidence interval, 7.3-105.7), and the corresponding adjusted cumulative incidence of malignant lesions was 3.6 and 13.2 per 100 persons. This is higher than that of small (≤5 mm) lesions, which showed mild dysplasia (2.7 per 100 persons), a condition for which surveillance every 3 years is recommended. Under the current approach, 65.3% of interval cancers missed at surveillance would be detected if individuals with medium (6-10 mm) and large (>10 mm) nondysplastic LULs were additionally monitored. Conclusions We propose a modified surveillance strategy that combines findings under LCE examination and the pathologic analysis, where follow-up endoscopy is recommended for individuals with relatively large nondysplastic lesions.

Background Heterogeneity should be carefully addressed to facilitate establishment of effective population-level blood lipid management. The primary aim of the study was to investigate gender heterogeneity in prevalence of dyslipidemia, including trends with age and associated factors in middle age rural Chinese. Methods This is a cross-sectional study based on a baseline investigation of a population-based randomized controlled trial in rural China, involving 26,378 permanent residents of age 45–69. The age-specific prevalence of dyslipidemia was estimated for men and women, and the trends of prevalence with age were compared. Logistic regression was used to explore the factors associated with prevalent risk of dyslipidemia. Results The overall prevalence of dyslipidemia was significantly higher in females than in males for borderline high and above (BHA) total cholesterol (TC ≥ 200 mg/dL), BHA triglycerides (TG ≥ 150 mg/dL) and BHA low-density lipoprotein cholesterol (LDL-C ≥ 130 mg/dL), but was lower for low high-density lipoprotein cholesterol (HDL-C Conclusion Heterogeneity was found in comparing the prevalence of dyslipidemia in men and women, and gender heterogeneity was found in its trend with age and associated factors in middle aged rural Chinese. The effectiveness of population-level blood lipid management and CVD primary prevention programs in China is expected to be improved if gender heterogeneity is considered.

Objective To investigate the risk factors for osteonecrosis of the femoral head (ONFH) after the treatment of femoral neck fracture in patients under 60 years old. Methods A total of 250 cases of femoral neck fracture treated at 3 hospitals in Xuzhou from January 2002 to January 2016 were studied. The patients were followed up for 1~15 years, and the clinical data on femoral head necrosis after the femoral neck operation were analysed retrospectively. Risk factors were recorded, including age, gender, preoperative traction, time from injury to operation, reduction method, type of reduction, BMI, ASA classification, and quality of reduction. Logistic regression analysis was used to evaluate the independent risk factors for ONFH after treatment of femoral neck fracture. Results The duration of follow-up was 1~15 years, with an average of 7.5 years. None of the 250 patients had fracture non-union, but 40 (16%) had necrosis of the femoral head. The time to necrosis of the femoral head was 1~7 years after the operation, with an average of 3.8 years. Univariate analysis showed that the type of fracture, the quality of reduction, the removal of internal fixation, BMI and ASA classification were risk factors affecting necrosis of the femoral head in patients with femoral neck fracture, and the difference was statistically significant (P < 0.05). Multivariate analysis showed that internal fixation, fracture type (displacement), reduction quality (dissatisfaction), BMI (> 25), and ASA grade (III + IV) were independent risk factors affecting femoral head necrosis in patients with femoral neck fracture. Conclusion A variety of high-risk factors for femoral head necrosis are present after surgery with hollow compression screws for femoral neck fracture in adults. Removal of internal fixation, type of fracture, quality of reduction, BMI, and ASA classification were the most important risk factors influencing the development of femoral head necrosis. During treatment, there should be some targeted measures to reduce the incidence of necrosis of the femoral head.

ObjectiveDescription of the design and preliminary results of baseline recruitment and screening in the endoscopic screening for esophageal cancer in China (ESECC), the first randomised controlled trial (RCT) assessing efficacy and cost-effectiveness of endoscopic screening for esophageal squamous cell carcinoma (ESCC).DesignESECC trial is a cluster RCT, and 668 villages in rural Hua County, Henan Province, a high-incidence area of ESCC in China, were randomised into two arms at a ratio of 1:1. Screening arm participants were screened by Lugol chromoendoscopy; no screening was performed in the control arm. ESCC-specific and all-cause mortality, incidence of advanced ESCC and cost-effectiveness of screening will be evaluated in the next 10-year follow-up. Here, we report the performance of baseline recruitment and randomisation, prevalence of upper GI lesions and risk factors for ESCC.ResultsA total of 17 151 and 16 797 participants were enrolled in screening and control arms from January 2012 to September 2016. The truncated prevalence (aged 45–69 years) of oesophageal and overall upper GI high-grade lesions was 744.0/100 000 and 902.0/100 000. 69.9% of the 113 patients with high-grade oesophageal lesions were of early stage. Risk factors for severe oesophageal dysplasia and more severe lesions in this population included higher age, family history of ESCC, lower body mass index, eating rapidly and frequent ingestion of leftovers.ConclusionThis ESECC trial met the predesigned recruitment and randomisation requirements. Age, family history, undernutrition and unhealthy dietary habits increased the risk for high-grade oesophageal lesions in this high-risk population.Trail registration numberNCT01688908; Pre-results.

The microbiota control regional immunity using mechanisms such as inducing IL-17A-producing γδ T (γδT-17) cells in various tissues. However, little is known regarding hepatic γδT cells that are constantly stimulated by gut commensal microbes. Here we show hepatic γδT cells are liver-resident cells and predominant producers of IL-17A. The microbiota sustain hepatic γδT-17 cell homeostasis, including activation, survival and proliferation. The global commensal quantity affects the number of liver-resident γδT-17 cells; indeed, E. coli alone can generate γδT-17 cells in a dose-dependent manner. Liver-resident γδT-17 cell homeostasis depends on hepatocyte-expressed CD1d, that present lipid antigen, but not Toll-like receptors or IL-1/IL-23 receptor signalling. Supplementing mice in vivo or loading hepatocytes in vitro with exogenous commensal lipid antigens augments the hepatic γδT-17 cell number. Moreover, the microbiota accelerate nonalcoholic fatty liver disease through hepatic γδT-17 cells. Thus, our work describes a unique liver-resident γδT-17 cell subset maintained by gut commensal microbes through CD1d/lipid antigens.

Surface electromyogram(sEMG) signals have been widely used in the control of upper limb rehabilitation robot for their easy collection and acquisition. However, the medical sEMG devices are expensive and the signal processing is complicated. Unlike previous research, our goal is to identify as many motions as possible with as few channels as possible. This paper designed a four-channel hand motion recognition system that could accurately identify eleven common hand movements. The cores of the sEMG acquisition system are CC2530 and ADS1299. The signal processing includes three parts:signal acquisition, feature extraction, and classification. The dimension-reduced Fast Fourier Transformation(FFT) is selected as the feature extraction method to extract the frequency domain information from sEMG signal. In addition, the linear discriminant analysis (LDA) is selected as the classifier. The whole system is easy to promote and the algorithms proposed by this paper take less time, even the accuracy rate can reach 93%. It has the potential of cooperating with robot-aided rehabilitation and being the robot-human interface.

The ability of the host to clear hepatitis B virus (HBV) is closely correlated to the establishment of commensal microbiota. However, how microbiota affects anti-HBV immunity is still unclear. Using a well-known hydrodynamical HBV transfection mouse model and treatment with antibiotics (Atb), we explored the change in adaptive immunity (CD4+ cells, germinal center B cells and anti-HBs Ab). In our setting, normal mice exhibited complete clearance of HBV within 6 weeks post-hydrodynamic injection (HDI) of HBV-containing plasmid, whereas Atb-treated mice lost this capacity, showing high serum level of hepatitis B surface antigen (HBsAg) without hepatitis B surface antibodies (anti-HBs), similar as what happened in Rag1 -/- mice or CD4 -/- mice, suggesting that microbiota may influence the function of CD4+ T cells. Furthermore, the numbers of splenic and hepatic effector CD4+ T cells (CD44hiCD62L-CD4+ T cells) both decreased with impaired function (IFN-γ synthesis), resulting in lower frequency of germinal center B cells and CD4+ follicular helper T cells, and impaired anti-HBs production. We further tried to find the bacterial species responsible for maintaining anti-HBV immunity, and found that each antibiotic alone could not significantly influence HBV clearance compared to antibiotic combination, suggesting that global commensal microbial load is critical for promoting HBV clearance. We also confirmed that TLRs (e.g., TLR2, 4, 9) are not major players in immune clearance of HBV using their agonists and knock-out mice. These results suggest that commensal microbiota play an important role in maintaining CD4+ T cell immunity against HBV infection.

Population-level endoscopic screening for esophageal cancer has been conducted in China for years. In this study, we aim to provide an updated and precise cost estimation for esophageal cancer screening based on a randomized controlled trial in a high-risk area in China. We estimated the cost of esophageal cancer screening with chromoendoscopy using a micro-costing approach based on primary data of the ESECC (Endoscopic Screening for Esophageal Cancer in China) randomized controlled trial (NCT01688908) from a health sector perspective. Unit costs and quantities of resources were collected to obtain annual screening costs. The screening project was then theoretically expanded to a 10-year period to explore long-term trends of costs. Costs were adjusted to US dollars for the year 2018. In the ESECC trial, screening cost per endoscopy with a valid pathologic diagnosis was $196, accounting for 3.82% of the gross domestic product per capita in Hua County, and the costs for detecting one esophageal cancer and one early-stage esophageal cancer were $26,347 and $37,687, respectively. In conventional screening in which protocol-driven costs were excluded, costs as above were $134, $18,074, and $25,853. The cost for detecting one gastric cardia cancer or stomach cancer was nine times higher than detecting one esophageal cancer owing to low prevalences of the two cancers. In a simulated 10-year screening project, annual cost decreased notably over time. Despite the relatively low absolute cost, population-level endoscopic screening will still be a heavy burden on local government considering the socioeconomic conditions. Long-lasting programs would be less costly and population-level screening would make little sense in non-high-risk regions.

Cytochrome P450 2C8 (CYP2C8) is one of the enzymes that primarily participate in producing metabolisms of medications and P‐glycoprotein (P‐gp) has been regarded as one of the important molecules in chemotherapeutically induced multidrug resistance (MDR). In addition, the pregnane X receptor (PXR) is involved in regulating both CYP2C8 and P‐gp. We aim to research the effect of PXR on Taxol‐resistant non–small‐cell lung cancer (NSCLC cells) via regulating CYP2C8 and P‐gp. NSCLC cells were treated with SR12813, LY335979, or PXR siRNA. Cell counting kit (CCK‐8) assay was used to detect cell vitality. Colony formation assay was used to observe cell proliferation. Western blotting, real‐time polymerase chain reaction (RT‐PCR), and immunofluorescence staining were conducted to analyze the expressions of PXR, CYP2C8, and P‐gp. Taxol and its metabolic products were detected by high‐performance liquid chromatography (HPLC). The expression of PXR in A549 cell line was higher than that in other cell lines. The accumulation of PXR was observed in the nucleus after cells were treated with SR12813. Besides, SR12813 induced higher expressions of CYP2C8 and P‐gp proteins. We also discovered that pretreatment with SR12813 reversed the inhibition of cell viability and proliferation after the Taxol treatment in comparison to the SR12813 untreated group. Furthermore, the hydroxylation products of Taxol analyzed by HPLC were increased in comparison to the SR12813 untreated group, indicating that high expressions of CYP2C8 and P‐gp enhanced the resistance of A549 cells to Taxol. For cells treated with PXR siRNA, cell viability, cell proliferation, and Taxol metabolites were significantly reduced after the Taxol treatment in comparison to the siRNA‐negative group. The cell viability, cell proliferation, and Taxol metabolites were regulated by the expressions of PXR, P‐gp, and CYP2C8. That is, PXR expression has an important effect on the resistance of NSCLC cells to Taxol via upregulating P‐gp and CYP2C8.

Background & Aims Chromoendoscopy with iodine staining is used to identify esophageal squamous dysplasia and esophageal squamous cell carcinomas (ESCCs)—absence of staining indicates suspicious regions of dysplasia. However, screening detects precancerous lesions (mild and moderate dysplasia) that do not require immediate treatment; it is a challenge to which lesions are at risk for progression. We investigated the association between absence of iodine staining at chromoendoscopy screening and lesion progression using 6 years of follow-up data from a population-based randomized controlled trial in China. We then constructed and validated a model to calculate risk of progression to severe dysplasia, carcinoma in situ, or ESCC. Methods We collected data from 1468 participants (45–69 years old) who were either negative for iodine staining at a baseline chromoendoscopy or found to have mild or moderate dysplasia in histologic analysis of biopsies in the Endoscopic Screening for Esophageal Cancer study in China, from January 2012 through September 2016; 788 of these participants were re-examined by endoscopy after a median interval of 4.2 years (development cohort). We investigated the association between absence of iodine staining and progression of esophageal lesions using Cox prediction models, considering corresponding baseline pathology findings and patient answers to a comprehensive questionnaire. Patients who did not receive a follow-up examination (n = 680) was used as the validation cohort; outcome events in these patients were identified by annual door to door active interviews or linkage with local electronic registry data. The primary outcome was incident esophageal severe dysplasia, carcinoma in situ, or ESCC. Results In the development cohort, 11 lesions that did not stain with iodine but were classified as not dysplastic in the histology analysis were found to be severe dysplasia, carcinoma in situ, or ESCC at the follow-up evaluation. These lesions accounted for 39.3% of all progressed lesions (n = 28). In the validation cohort, 6 patients with lesions did not stain with iodine but were classified as not dysplastic by histology had a later diagnosis of ESCC, determined from medical records; these patients accounted for 50.0% of all patients with lesion progression (n = 12) until the closing date of this study. We developed a model based on patient age, body mass index, pathology findings, and baseline iodine staining to calculate risk for severe dysplasia, carcinoma in situ, or ESCC. It identified patients for severe dysplasia, carcinoma in situ, or ESCC in the development set with an area under the curve of 0.868 (95% CI, 0.817–0.920) and in the validation set with an area under the curve of 0.850 (95% CI, 0.748–0.952). Almost no cases would be missed if subjects determined to be high or intermediate–high risk subjects by the model were included in surveillance. Conclusions Absence of iodine staining at baseline chromoendoscopy identifies esophageal lesions at risk of progression with a high level of sensitivity. A model that combines results of iodine chromoendoscopy with other patient features identifies patients at risk of lesion progression with greater accuracy than histologic analysis of baseline biopsies.

Background and Aims Prediction models for esophageal squamous cell carcinoma are not common, and no model targeting a clinical population has previously been developed and validated. We aimed to develop a prediction model for estimating the risk of high-grade esophageal lesions for application in clinical settings and to validate the performance of this model in an external population. Methods The model was developed based on the results of endoscopic evaluation of 5624 outpatients in one hospital in a high-risk region in northern China and was validated using 5765 outpatients who had undergone endoscopy in another hospital in a non-high-risk region in southern China. Predictors were selected with unconditional logistic regression analysis. The Akaike information criterion was used to determine the final structure of the model. Discrimination was estimated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed using a calibration plot with an intercept and slope. Results The final prediction model contained 5 variables, including age, smoking, body mass index, dysphagia, and retrosternal pain. This model generated an AUC of 0.871 (95% confidence interval, 0.842-0.946) in the development set, with an AUC of 0.862 after bootstrapping. The 5-variable model was superior to a single age model. In the validation population, the AUC was 0.843 (95% confidence interval, 0.793-0.894). This model successfully stratified the clinical population into 3 risk groups and showed high ability for identifying concentrated groups of cases. Conclusions Our model for esophageal high-grade lesions has a high predictive value. It has the potential for application in clinical opportunistic screening to aid decision making for both health care professionals and individuals.

The objective of this study was to establish an optimal population-level follow-up strategy for identifying incident cancers using health insurance reimbursement data in rural China.We compared active follow-up and passive linkage with claims data for identification of incident cancer cases. Claims data were derived from the New Rural Cooperative Medical Scheme (NCMS). Follow-up data from subject enrollment to December 31, 2016, regarding 33,948 subjects in a large-scale randomized controlled trial were used in this study.The overall sensitivity of passive linkage with NCMS claims data was significantly higher than that of active follow-up (95.6% vs. 54.9%, P 0.001). Of 12 cases missed by the NCMS data set, seven were treated on an outpatient basis and there were therefore no records in the NCMS system, and five were diagnosed at primary (township-level) health facilities and excluded from the quality control process. Of the 123 cases missed by active follow-up, 54 were reported as negative, 69 were reported as positive but had inaccurate information regarding the site of cancer, or exceeded the 6-month limitation from the date of diagnosis.Passive linkage with NCMS claims data is an efficient approach for identifying incident cancers in areas without cancer registries in rural China.

Jinfang Ma,1 Jinping Zheng,1 Nanshan Zhong,1 Chunxue Bai,2 Haoyan Wang,3 Juan Du,4 Fenglei Li,5 Yanwei Chen,6 Zhe Shi,7 Xin Li,8 Pingyan Chen9 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Respiratory Medicine, Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Respiratory Medicine, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of China; 4Department of Respiratory Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 5Department of Respiratory Medicine, The Liwan Hospital of the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 6Department of Respiratory Medicine, Nanshan People’s Hospital, Shenzhen, People’s Republic of China; 7Department of Respiratory Medicine, The First People’s Hospital, Huizhou, People’s Republic of China; 8Department of Respiratory Medicine, China Resource and Wisco General Hospital, Wuhan, People’s Republic of China; 9Department of Biostatistics, Southern Medical University, Guangzhou, People’s Republic of China Purpose: Recurrence of acute exacerbations has a major impact on patients with COPD. Therefore, effective prevention and treatment of exacerbation is crucial in the management of COPD, especially for patients with moderate to severe disease. This study evaluated the effectiveness of YuPingFeng granule administration in preventing exacerbation and improving symptom score, as well as its long-term (1 year) safety profile, in patients with COPD. Patients and methods: This was a randomized, double-blind, parallel, placebo-controlled study of 240 patients from eight centers in China. Participants were eligible if they had mild to severe COPD as defined by Global Initiative for Chronic Obstructive Lung Disease, had a history of at least two COPD exacerbations or one hospitalization within the previous year, and had remained clinically stable for over 4weeks before the study. They were randomly assigned to receive 5g of YuPingFeng or placebo, three times per day, for 1year. The primary end point was the exacerbation rate over 1year, and the analysis was by intention to treat. Secondary end points included symptom score, which was assessed by COPD assessment test (CAT) score and safety profiles. This trial was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn; registration number: ChiCTR-IPR-15007023). Results: The YuPingFeng group had a significantly lower exacerbation rate than the placebo group (1.15 vs 1.55; risk ratio=0.677 [95% CI 0.531–0.863]; P=0.002) and a significantly reduced risk of second exacerbation (95% CI 0.326–0.772; P=0.002). After treatment, the mean change in the CAT score in the YuPingFeng group (-4.41±7.01) differed significantly from that in the placebo group (-2.49±5.31; P=0.001). YuPingFeng was well tolerated. Conclusion: YuPingFeng granules can be considered as a treatment option for COPD; this treatment prevents acute exacerbations of COPD and has a good safety profile. Keywords: COPD, exacerbation, treatment, YuPingFeng

Evidence is required to evaluate the effectiveness of population-level endoscopic screening for esophageal cancer (EC). In this study, 5,632 permanent residents aged 25-65 years from 6 villages in Hua County, Henan Province, China, were defined as the screening cohort and were offered intensive endoscopic screening. Residents of all 914 remaining villages in Hua County were included as the control cohort, and age-sex standardization was used to calculate the expected numbers of EC and upper gastrointestinal (GI) tract cancer cases and deaths in the screening cohort. The effectiveness of screening was assessed by comparing observed numbers of cases and deaths with expected numbers after 9-year follow-up of these screened subjects (2007-2016). In the screening cohort, 23 upper GI cancers (including 16 ECs) and 10 upper GI cancer deaths (including 5 EC deaths) were identified, and 47% (standardized incidence ratio = 0.53, 95% confidence interval (CI): 0.33, 0.87) and 66% (standardized mortality ratio = 0.34, 95% CI: 0.14, 0.81) reductions in cumulative EC incidence and mortality were found. For upper GI cancers, incidence and mortality were lowered by 43% (standardized incidence ratio = 0.57, 95% CI: 0.38, 0.86) and 53% (standardized mortality ratio = 0.47, 95% CI: 0.25, 0.88), respectively. This study showed that upper GI tract endoscopy is an effective population-level screening test for EC in high-risk regions.

Objective There have been few population-based studies evaluating health related quality of life (HRQOL) in rural populations in China, and this study aimed to assess the current status of and risk factors for HRQOL in a general rural population in high risk region of esophageal cancer in China. Methods From November 2015 to September 2016, 12,085 permanent residents aged 45-69 years from 257 villages in the Endoscopic Screening for Esophageal Cancer in China (ESECC) trial (ClinicalTrials.gov: NCT01688908) randomly selected from Hua County, Henan Province, China were interviewed. The EQ-5D-3L, a generic measure of HRQOL, and a questionnaire were used to assess their HRQOL and potential risk factors. Results Among all the participants, 30.62% of the participants reported problems in at least one EQ-5D dimension. Pain/discomfort (25.52%) was the most frequently reported problem followed by anxiety/depression (7.97%), mobility (5.82%), usual activities (2.61%) and self-care (1%). These rural residents had a mean EQ-5D index score of 0.948, and lower EQ-5D index scores were associated with older age, female gender, lower levels of household annual per capita income, living alone, using shallow wells as main source of drinking water, exposure to family members smoking, testiness, unhealthy dietary habits, overweight or obesity, upper gastrointestinal cancer related symptoms and chronic diseases. Conclusions Rural residents in China have a relatively low quality of life. Health promotion programs in this population should focus on the elderly, especially elderly women and the elderly living alone. Improving basic living circumstances and primary medical care services should be priorities. Results of this study will also serve as the basis for the cost-utility evaluation in our ESECC screening trial.

BackgroundPatients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. MethodsIn a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 μg) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV1) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV1 after bronchodilator use and the between-group difference in...

Background & Aims Chromoendoscopy with Lugol dye is used to screen for early-stage esophageal squamous dysplasia (ESD) and esophageal cancer. However, the sensitivity with which Lugol chromoendoscopy detects ESD or esophageal cancer has not been fully assessed in large populations in China. Methods From 2012 to 2016, a total of 15,264 residents in rural Hua County, Henan Province, which is a high-incidence area of esophageal cancer in China, were screened by Lugol chromoendoscopy. Biopsies were collected from endoscopically visualized lesions, identified before and after Lugol chromoendoscopy, and analyzed histologically. Biopsies were also collected from standard sites in the esophagus (28 and 33 cm distal to the incisors) if no abnormalities were found. We calculated the sensitivity with which Lugol chromoendoscopy detects esophageal dysplasia and carcinoma, using findings from biopsy analysis as the reference standard. Results A total 586 participants were found by biopsy analysis to have ESD or more severe lesions. After endoscopy images were reviewed twice, Lugol chromoendoscopy sensitivity values for the detection of mild, moderate, and severe dysplasia, and esophageal cancer, were 45.9%, 55.3%, 87.0%, and 97.7%, respectively. ESDs were most frequently missed by Lugol chromoendoscopy in younger patients and men with moderate levels of dysplasia. Conclusion In a screening analysis of a general population in China, we found Lugol chromoendoscopy to identify individuals with ESD with lower levels of sensitivity (46%–87%) than previously believed, although it identified patients with esophageal cancer with almost 98% sensitivity. Prospective studies are needed to evaluate the clinical significance of esophageal lesions that are not detected by endoscopy.

We studied the functions of natural killer (NK) cells and the role of the NK cell inhibitory receptor (NKG2A) during hepatitis B virus (HBV) infection in patients and mice.We analyzed levels of NKG2A on peripheral blood NK cells from 42 patients with active chronic hepatitis B (CHB), 31 patients with inactive CHB, and 35 healthy volunteers (controls). Five patients with CHB treated with antiviral therapy were also included to evaluate changes in NK cells after HBV titers decreased. We examined the effects of blocking antibodies against NKG2A or its ligand Qa-1 (equivalent to HLA-E in humans) in immunocompetent mice that express HBV from a plasmid and are positive for serum hepatitis B surface antigen (a mouse model of HBV infection).A higher percentage of NK cells from patients with active CHB were positive for NKG2A (38.47%) than from patients with inactive CHB (19.33%; P.01) or controls (27.96%; P.05). The percentage of NKG2A(+) cells correlated with serum viral load (r = 0.5457; P.001). The percentage of NKG2A(+) cells decreased along with HBV load in patients that received antiviral therapy (P.05). Blocking NKG2A interaction with HLA-E in peripheral NK cells from patients with active CHB increased their cytotoxicity in vitro. NK cells of HBV carrier mice also had higher percentages of NK cells that expressed NKG2A compared with control mice; NKG2A was likely to be up-regulated by production of interleukin-10 by hepatic regulatory CD4(+)CD25(+) T cells. Blocking Qa-1 in these mice promoted viral clearance in an NK cell-dependent manner.Infection with HBV increases levels of the inhibitory receptor NKG2A on NK cells in mice and humans, and reduces their ability to clear HBV. Reagents designed to block the interaction between NKG2A and HLA-E might be developed to treat CHB infection.

Background: Occupational noise exposure in the workplace is a significant health problem and hypertension is a widespread chronic disease. This study aimed to investigate whether occupational noise exposure is associated with hypertension in a Chinese population. Methods: A total of 286 hypertensive workers and 630 normotensive workers were enrolled and analyzed in a case-control study. Results: We revealed that workers exposed to noise can increase the risk of hypertension (adjusted OR 1.52, 95% CI: 1.11–2.08). This effect was more pronounced in ever smoking group (adjusted OR 2.54, 95% CI: 1.16–5.53). When noise exposure combined with never drinking status, it can reduce the risk of hypertension (adjusted OR 1.48, less than 1.52). Conclusions: Our results provide a clue that occupational noise exposure may increase the risk of hypertension in a Chinese population.

The neurofibromatosis type 1 (NF1) gene encodes the GTPase-activating protein (GAP) neurofibromin, which negatively regulates Ras activity. The yeast Saccharomyces cerevisiae has two neurofibromin homologs, Ira1 and Ira2. To understand how these proteins are regulated, we utilized an unbiased proteomics approach to identify Ira2 and neurofibromin binding partners. We demonstrate that the Gpb1/Krh2 protein binds and negatively regulates Ira2 by promoting its ubiquitin-dependent proteolysis. We extended our findings to show that in mammalian cells, the ETEA/UBXD8 protein directly interacts with and negatively regulates neurofibromin. ETEA contains both UBA and UBX domains. Overexpression of ETEA downregulates neurofibromin in human cells. Purified ETEA, but not a mutant of ETEA that lacks the UBX domain, ubiquitinates the neurofibromin GAP-related domain in vitro. Silencing of ETEA expression increases neurofibromin levels and downregulates Ras activity. These findings provide evidence for conserved ubiquitination pathways regulating the RasGAP proteins Ira2 (in yeast) and neurofibromin (in humans).

The microbiota control regional immunity using mechanisms such as inducing IL-17A-producing γδ T (γδT-17) cells in various tissues. However, little is known regarding hepatic γδT cells that are constantly stimulated by gut commensal microbes. Here we show hepatic γδT cells are liver-resident cells and predominant producers of IL-17A. The microbiota sustain hepatic γδT-17 cell homeostasis, including activation, survival and proliferation. The global commensal quantity affects the number of liver-resident γδT-17 cells; indeed, E. coli alone can generate γδT-17 cells in a dose-dependent manner. Liver-resident γδT-17 cell homeostasis depends on hepatocyte-expressed CD1d, that present lipid antigen, but not Toll-like receptors or IL-1/IL-23 receptor signalling. Supplementing mice in vivo or loading hepatocytes in vitro with exogenous commensal lipid antigens augments the hepatic γδT-17 cell number. Moreover, the microbiota accelerate nonalcoholic fatty liver disease through hepatic γδT-17 cells. Thus, our work describes a unique liver-resident γδT-17 cell subset maintained by gut commensal microbes through CD1d/lipid antigens., γδ T cells are major producers of IL-17A in response to microbial infection. Here the authors show that a high load of commensal microbes can maintain homeostasis of IL-17A+ γδ T cells in the liver via CD1d antigen presentation, with implications for liver diseases.

Both male and female rats were exposed to SO2 while their controls were exposed to filtered air. Levels of interlukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor- β1 (TGF- β1) in rat lung and serum were measured by the enzyme-linked immunosorbent assay (ELISA) after chronic exposure to SO2. A statistically significant increase in the levels of IL-6 and TNF-α was observed in the lung tissues of both male and female rats. No effects on tested cytokines were observed in rat serum, except for a significant increase in TNF-α level in male rats. There is no significant change in TGF- β1 level in rat lung and serum.