Background: Chronic kidney disease (CKD) is a serious public health issue worldwide, but the disease burden of CKD caused by different etiologies and changing trends has not been fully examined. Methods: We collected data from Global Burden of Disease Study 2019 (GBD 2019), including incident cases, age-standardized incidence rate (ASIR), disability-adjusted life years (DALYs), and age-standardized DALY rate between 1990 and 2019 by region, etiology, age, and sex, and calculated the estimated annual percentage change (EAPC) of the rate to evaluate the epidemiological trends. Results: Globally, incident cases of CKD increased from 7.80 million in 1990 to 18.99 million in 2019, and DALYs increased from 21.50 million to 41.54 million. ASIR increased with an EAPC of 0.69 (95% uncertainty interval [UI] 0.49–0.89) and reached 233.65 per 100,000 in 2019, while the age-standardized DALY rate increased with an EAPC of 0.30 (95% UI 0.17–0.43) and reached 514.86 per 100,000. North Africa and the Middle East, central Latin America, and North America had the highest ASIR in 2019. Central Latin America had the highest age-standardized DALY rate, meanwhile. Almost all countries experienced an increase in ASIR, and over 50% of countries had an increasing trend in age-standardized DALY rate from 1990 to 2019. CKD due to diabetes mellitus type 2 and hypertension accounted for the largest disease burden with 85% incident cases and 66% DALYs in 2019 of known causes, with the highest growth in age-standardized DALY rate and a similar geographic pattern to that of total CKD. Besides, the highest incidence rate of total and four specific CKDs were identified in people aged 70 plus years, who also had the highest DALY rate with a stable trend after 2010. Females had a higher ASIR, while males had a higher age-standardized DALY rate, the gap of which was most distinctive in CKD due to hypertension. Conclusion: The disease burden of CKD remains substantial and continues to grow globally. From 1990 to 2019, global incident cases of CKD have more than doubled and DALYs have almost doubled, and surpassed 40 million years. CKD due to diabetes mellitus type 2 and hypertension contributed nearly 2/3 of DALYs in 2019 of known causes, and had witnessed the highest growth in age-standardized DALY rate. Etiology-specific prevention strategies should be placed as a high priority on the goal of precise control of CKD.

A comprehensive evaluation of the burden of inflammation bowel disease (IBD) is important for identifying potential strategies to control the disease. We present results from the Global Burden of Diseases (GBD) 2017 of IBD at the national level, the trends in disease burden and its epidemiological features in China. Using the methods and results from GBD 2017, we describe the IBD burden based on the prevalence, incidence, mortality, years of lost (YLLs), the years of life lived with disability (YLDs) and disability-adjusted life years (DALYs) in China estimated using DisMod-MR 2·1. We additionally evaluated the rate of DALYs at national locations in 2017. From 1990 to 2017, the cases, deaths, YLLs, YLDs and DALYs for IBD in China were from 1,047,991 to 2,665,081, from 5701 to 5198, from 188,814 to 107,373, from 157,581 to 394,887, from 346,396 to 502,260, respectively. Increasing trends were observed in prevalence (APC: 2·9%), incidence (APC: 1·1%), DALYs (APC: 0·8%) and YLDs (APC:2·9%). There were decreasing trends in mortality (APC: -1·0%) and YLLs (APC: -2·7%). As to the age-standardized rates of DALYs, it observed a decreasing trend (APC: -0·78%). Similar trends were observed in men and women. The age-standardized APCs in incidence, mortality and rate of YLLs among women were higher than those among men. The age-standardized rate of DALYs was 27·51 per 100,000 in 2017. Between 1990 and 2017, China experienced a decrease in the age-standardized DALYs, mortality rates and YLLs due to IBD, despite an increase in the age-standardized rate of prevalence, incidence and YLDs. China is still one of the low endemic areas. This work had no supporting funding.

Motivation: Despite the prevalence of copy number variation (CNV) in the human genome, only a handful of confirmed associations have been reported between common CNVs and complex disease. This may be partially attributed to the difficulty in accurately genotyping CNVs in large cohorts using array-based technologies. Exome sequencing is now widely being applied to case–control cohorts and presents an exciting opportunity to look for common CNVs associated with disease. Results: We developed ExoCNVTest: an exome sequencing analysis pipeline to identify disease-associated CNVs and to generate absolute copy number genotypes at putatively associated loci. Our method re-discovered the LCE3B_LCE3C CNV association with psoriasis (P-value = 5 × 10e−6) while controlling inflation of test statistics (λ < 1). ExoCNVTest-derived absolute CNV genotypes were 97.4% concordant with PCR-derived genotypes at this locus. Availability and implementation: ExoCNVTest has been implemented in Java and R and is freely available from www1.imperial.ac.uk/medicine/people/l.coin/. Contact:wangj@genomics.org.cn or Lachlan.J.M.Coin@genomics.org.cn

Metastatic hepatocellular carcinoma (HCC) seriously threatens patients' prognosis. It was previously suggested that the insulin growth factor binding protein (IGFBP) family could serve as cancer suppressors in the development and metastasis of HCC. However, the role of IGFBP4 and its underlying molecular mechanism in HCC metastasis is elusive. In the present study, it was found that IGFBP4 is significantly downregulated in HCC, whose expression is positively correlated with the prognosis of patients with HCC. Overexpression of IGFBP4 restrained migration abilities and cancer metastasis of HCC cells both in vitro and in vivo. Furthermore, it was found that IGFBP4 represses HCC metastasis by inhibiting epithelial‑mesenchymal transition. Molecular mechanism studies showed that overexpression of IGFBP4 obviously suppresses NOTCH1 signaling in HCC. As for the upstream regulatory mechanism, it was revealed that downregulation of IGFBP4 in HCC was caused by CpG islands' hyper‑methylation‑dependent degradation mediated by MYBBP1A. Inhibition of MYBBP1A limited HCC metastatic ability and silence of IGFBP4 at the same time restored HCC metastatic potentials. Clinical data demonstrated that low expression of IGFBP4 was found in patients with HCC, especially with lymphatic metastasis. High MYBBP1A expression and low IGFBP4 expression in HCC were correlated with poor survival of patients with HCC. Summarily, in the present study, it was revealed that MYBBP1A/IGFBP4/NOTCH1 pathway could play a crucial role in the progression and metastasis of HCC, which stimulates novel therapeutic and diagnostic strategies against metastatic HCC.

The long-term persistence of hepatitis B surface antibody (anti-HBs) after hepatitis B vaccination among adults was not known clearly. This study aimed to assess the immunogenicity and persistence of antibodies 8 years after hepatitis B immunization with different vaccination schedules among adults who tested negative for hepatitis B surface antigen (HBsAg), anti-HBs, and hepatitis B core antibody (anti-HBc). A total of 771 participants who received the full vaccination course (three doses) and also had a blood sample taken 1 month after the first vaccination were recruited. Of these, 529 were excluded due to the missing data of anti-HBs 8 years after the first vaccination. Vaccinations were carried out at 0–1–3, 0–1–6 and 0–1–12 month vaccination schedules, and 104, 45, and 93 participants were included, respectively. The positive seroprotection rate was 85.9% 1 month after the third vaccination, and 58.3% 8 years later (χ² = 54.52, P < 0.001), while the geometric mean titer (GMT) of anti-HBs was 158.49 mIU/mL [95% confidence interval (CI): 131.83-190.55)] and 15.14 mIU/mL (95% CI: 10.96–20.42) after 1 month and 8 years, respectively. Compared with the standard 0–1–6 month vaccination schedule, the positive seroprotection rate and the GMT of the 0–1–3 month vaccination schedule had no difference. The long-term immune effect of the 0–1–3 month vaccination schedule was better than that of the 0–1–12 month vaccination schedule. No correlation was found between the GMT of anti-HBs 1 month and 8 years later.

Objective: To determine the prevalence, degree of trust and usefulness of the online health information seeking source and identify associated factors in the adult population from the rural region of China. Design: A cross-sectional population-based study. Setting: A self-designed questionnaire study was conducted between May and June 2015 in four districts of Zhejiang Province. Participants: 652 adults aged ≥18 years (response rate: 82.8%). Primary outcome measures: The prevalence, degree of trust and usefulness of online health information was the primary outcome. The associated factors were investigated by χ ² test. Results: Only 34.8% of participants had faith in online health information; they still tended to select and trust a doctor which is the first choice for sources of health information. 36.7% of participants, being called ‘Internet users’, indicated that they had ever used the internet during the last 1 year. Among 239 internet users, 40.6% of them reported having sought health information via the internet. And 103 internet users responded that online health information was useful. Inferential analysis demonstrated that younger adults, individuals with higher education, people with a service-based tertiary industry career and excellent health status used online health information more often and had more faith in it (p<0.001). Conclusions: Using the internet to access health information is uncommon in the rural residential adult population in Zhejiang, China. They still tend to seek and trust health information from a doctor. Internet as a source of health information should be encouraged.