Clinical significance of RNA methylation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a primary liver malignancy with high mortality rates and poor prognosis. Recent advances in high-throughput sequencing and bioinformatic technologies have greatly enhanced the understanding of the genetic and epigenetic changes in liver cancer. Among these changes, RNA methylation, the most prevalent internal RNA modification, has emerged as a significant contributor of the development and progression of HCC. Growing evidence has reported significantly abnormal levels of RNA methylation and dysregulation of RNA-methylation-related enzymes in HCC tissues and cell lines. These alterations in RNA methylation play a crucial role in the regulation of various genes and signaling pathways involved in HCC, thereby promoting tumor progression. Understanding the pathogenesis of RNA methylation in HCC would help in developing prognostic biomarkers and targeted therapies for HCC. Targeting RNA-methylation-related molecules has shown promising potential in the management of HCC, in terms of developing novel prognostic biomarkers and therapies for HCC. Exploring the clinical application of targeted RNA methylation may provide new insights and approaches for the management of HCC. Further research in this field is warranted to fully understand the functional roles and underlying mechanisms of RNA methylation in HCC. In this review, we described the multifaceted functional roles and potential mechanisms of RNA methylation in HCC. Moreover, the prospects of clinical application of targeted RNA methylation for HCC management are discussed, which may provide the basis for subsequent in-depth research on RNA methylation in HCC.

The oncogenic mechanisms of the Janus kinase-signal transducer and activator of transcription pathway in digestive tract tumors.

Digestive tract tumors are heterogeneous and involve the dysregulation of multiple signaling pathways. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway plays a notable role in the oncogenesis of digestive tract tumors. Typically activated by pro-inflammatory cytokines, it regulates important biological processes, such as cell growth, differentiation, apoptosis, immune responses, and inflammation. The aberrant activation of this pathway manifests in different forms, including mutations in JAKs, overexpression of cytokine receptors, and sustained STAT activation, and contributes to promoting the malignant characteristics of cancer cells, including uncontrolled proliferation, resistance to apoptosis, enhanced invasion and metastasis, angiogenesis, acquisition of stem-like properties, and drug resistance. Numerous studies have shown that aberrant activation of the JAK-STAT pathway is closely related to the development and progression of digestive tract tumors, contributing to tumor survival, angiogenesis, changes in the tumor microenvironment, and even immune escape processes. In addition, this signaling pathway also affects the sensitivity of digestive tract tumors to chemotherapy and targeted therapy. Therefore, it is crucial to comprehensively understand the oncogenic mechanisms underlying the JAK-STAT pathway in order to develop effective therapeutic strategies against digestive tract tumors. Currently, several JAK-STAT inhibitors are undergoing clinical and preclinical trials as potential treatments for various human diseases. However, further investigation is required to determine the role of this pathway, as well as the effectiveness and safety of its inhibitors, especially in the context of digestive tract tumors. In this review, we provide an overview of the structure, classic activation, and negative regulation of the JAK-STAT pathway. Furthermore, we discuss the pathogenic mechanisms of JAK-STAT signaling in different digestive tract tumors, with the aim of identifying potential novel therapeutic targets. Video Abstract.

HCC prediction models in chronic hepatitis B patients receiving entecavir or tenofovir: a systematic review and meta-analysis.

BACKGROUND: Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk. METHODS: We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk. Subgroup and meta-regression analyses of discrimination and calibration were conducted. Sensitivity analysis was conducted to validate the stability of the results. RESULTS: We identified ten prediction models in 23 studies. The pooled 3-, 5-, and 10-year AUROC varied from 0.72 to 0.84, 0.74 to 0.83, and 0.76 to 0.86, respectively. REAL-B, AASL-HCC, and HCC-RESCUE achieved the best discrimination. HCC-RESCUE, PAGE-B, and mPAGE-B overestimated HCC development, whereas mREACH-B, AASL-HCC, REAL-B, CAMD, CAGE-B, SAGE-B, and aMAP underestimated it. All models were able to identify people with a low risk of HCC accurately. HCC-RESCUE and aMAP recognized over half of the population as low-risk. Subgroup analysis and sensitivity analysis showed similar results. CONCLUSION: Considering the predictive performance of all four aspects, we suggest that HCC-RESCUE was the best model to utilize in clinical practice, especially in primary care and low-income areas. To confirm our findings, further validation studies with the above four components were required.

Changing incidence of hepatitis B and persistent infection risk in adults: a population-based follow-up study from 2011 in China.

BACKGROUND: This study aimed to estimate hepatitis B incidence and chronicity risk in rural adults in China under the background of eliminating viral hepatitis. METHODS: Hepatitis B surface antigen (HBsAg) screening was conducted every 2 years in demonstration areas since 2011. Individuals with baseline HBsAg-negative were included. Incidence was calculated as the number of HBsAg-positive cases divided by the total person-times. HBsAg-positive individuals were followed up to study the persistent infection (> 6 months), chronic infection (> 12 months), and recovery with hepatitis B surface antibody (anti-HBs). The chi-square test and cox proportional regression analysis were performed. RESULTS: There were 8,942 incident cases over 2,138,532 person-years, yielding an average incidence of 0.42 per 100 person-years. HBV incidence decreased rapidly in both genders and all age groups and then kept stable. Male gender, low population density, low gross domestic product per capita, and islanders were associated with higher incidence. Of the positive cases, 4,989 (55.8%) patients were followed up. The persistent infection, chronic infection, and recovery with anti-HBs rates were 32.3%, 31.0%, and 31.4%, respectively. Persistent or chronic infection was more common in younger adults and males, while seroconversion had no concern with gender or age. CONCLUSIONS: HBV incidence in adult rural residents was decreasing and stayed low. The chronicity rate was relatively high and protective antibodies were induced in only one third. The importance of population-based screening and vaccination for susceptible individuals should be addressed.

Age and Serum Creatinine Can Differentiate Wilson Disease Patients with Pseudonormal Ceruloplasmin.

Methods: We retrospectively screened individuals with serum Cp ≥ 140 mg/L from 1032 WD patients who were hospitalised for the first time. Logistic regression analyses were performed in a case-control study between the WD cohort and another liver disease cohort to explore the independent risk factors for WD diagnosis and establish a regression model to identify them. The follow-up medical records of the WD cohort were subjected to mixed-effects model analysis in a longitudinal study to discover factors associated with Cp normalisation. Results: Eighty-six WD patients and their 353 medical records and another 98 non-WD liver disease patients were included in the present study. Cp normalisation was significantly associated with the copper burden and liver function indexes, such as urinary copper, γ-glutamyltransferase, and albumin (p ≤ 0.001). Logistic regression analysis showed that age and serum creatinine (p ≤ 0.001) were independent risk factors associated with WD. The AUC value of the regression model in the total cohort was 0.926 (p ≤ 0.001). At a cutoff value of ≥0.617 and ≥-1, the positive and negative predictive values were both 90.8% for WD. Conclusion: Increased serum Cp in WD patients is related to excessive copper burden and hepatic injury, and common tests can effectively distinguish WD patients from other liver injury patients.

Indole-3-carbinol ameliorates necroptosis and inflammation of intestinal epithelial cells in mice with ulcerative colitis by activating aryl hydrocarbon receptor.

Ulcerative colitis (UC) is a disease characterized by inflammation and disruption of the intestinal epithelial barrier. Necroptosis plays a critical role in disease progression. Indole-3-carbinol (I3C), a natural dietary agonist of aryl hydrocarbon receptor (AHR), has shown alleviating effects on UC. However, its mechanisms of action have not been comprehensively elucidated. Therefore, we aimed at investigating the protective role of I3C in DSS-induced colitis mice models. I3C significantly ameliorated body weight loss, colon length shortening and colonic pathological damage in colitis mice, reduced disease activity index (DAI) and histological (HI) scores, as well as alleviated colonic necroptosis and inflammation. In vitro, I3C attenuated necroptosis and inflammation of colonoids and NCM460 cells. AHR, activated by I3C, inhibits activation of receptor-interacting protein kinase 1 (RIPK1) and the subsequent assembly of necrosome in a time-dependent manner, as well as suppressing NF-κB activation and decreasing TNF-α, IL-1ß, IL-6 and IL-8 expression. Silencing of AHR aggravated necroptosis and inflammation of NCM460 cells, and did not be ameliorated by I3C. Furthermore, AHR activation induces the expression of inhibitor of apoptosis proteins (IAPs) and the ubiquitination of RIPK1. In conclusion, I3C exerts a protective effect in DSS-induced colitis mice models by alleviating the necroptosis and inflammation of IECs through activating AHR.

The role of fibrosis index FIB-4 in predicting liver fibrosis stage and clinical prognosis: A diagnostic or screening tool?

This review evaluates the ability of the fibrosis index based on four factors (FIB-4) identifying fibrosis stages, long-time prognosis in chronic liver disease, and short-time outcomes in acute liver injury. FIB-4 was accurate in predicting the absence or presence of advanced fibrosis with cut-offs of 1.0 and 2.65 for viral hepatitis B, 1.45 and 3.25 for viral hepatitis C, 1.30 (<65 years), 2.0 (≥65 years), and 2.67 for non-alcoholic fatty liver disease (NAFLD), respectively, but had a low-to-moderate accuracy in alcoholic liver disease (ALD) and autoimmune hepatitis. It performed better in excluding fibrosis, so we built an algorithm for identifying advanced fibrosis by combined methods and giving work-up and follow-up suggestions. High FIB-4 in viral hepatitis, NAFLD, and ALD was associated with significantly high hepatocellular carcinoma incidence and mortality. Additionally, FIB-4 showed the ability to predict high-risk varices with cut-offs of 2.87 and 3.91 in cirrhosis patients and predict long-term survival in hepatocellular carcinoma patients after hepatectomy. In acute liver injury caused by COVID-19, FIB-4 had a predictive value for mechanical ventilation and 30-day mortality. Finally, FIB-4 may act as a screening tool in the secondary prevention of NAFLD in the high-risk population.

Population-based active screening strategy contributes to the prevention and control of tuberculosis.

Despite the achievements obtained worldwide in the control of tuberculosis in recent years, many countries and regions including China still face challenges such as low diagnosis rate, high missed diagnosis rate, and delayed diagnosis of the disease. The discovery strategy of tuberculosis in China has changed from "active discovery by X-ray examination" to "passive discovery by self-referral due to symptoms", and currently the approach is integrated involving self-referral due to symptoms, active screening, and physical examination. Active screening could help to identify early asymptomatic and untreated cases. With the development of molecular biology and artificial intelligence-assisted diagnosis technology, there are more options for active screening among the large-scale populations. Although the implementation cost of a population-based active screening strategy is high, it has great value in social benefits, and active screening in special populations can obtain better benefits. Active screening of tuberculosis is an important component of the disease control. It is suggested that active screening strategies should be optimized according to the specific conditions of the regions to ultimately ensure the benefit of the tuberculosis control.

Altered gut microbiota correlate with different immune responses to HAART in HIV-infected individuals.

BACKGROUND: Although gut microbiota dysbiosis has been reported in HIV infected individuals recently, the relationship between the gut microbiota and immune activation in patients with different immune responses to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (healthy controls) and 58 HIV-infected individuals, including 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and < 200 CD4+ T-cell counts/µl after 2 years of HIV-1 viral suppression respectively) without comorbidities. RESULTS: Metagenome sequencing revealed that HIV-infected immunological responders and immunological non-responders could not recover completely from the gut microbiota dysbiosis. At a 97% similarity level, the relative abundances of Fusobacterium, Ruminococcus gnavus and Megamonas were greater, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacterium rectale and Roseburia were more depleted in the IR and INR groups than those in the healthy controls. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8 + CD57+ T-cell counts. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundances of genera Ruminococcus and Fusobacterium but were negatively correlated with the genus Faecalibacterium. The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than those in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of CD8 + CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8 + CD57+ T-cell counts. CONCLUSIONS: Gut microbiota dysbiosis may be one of the factors contributing to different immune responses and treatment outcomes to HAART.

Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan. RESULTS: The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13-22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31-8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10-1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI, 1.11-88.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

The Burden of Chronic Hepatitis C in China From 2004 to 2050: An Individual-Based Modeling Study.

The launch of new direct-acting antivirals (DAAs) is expected to substantially reduce the burden of hepatitis C virus (HCV) in China. However, the effect of these changes has not yet been modeled in China. Therefore, we aim to predict the burden of HCV-related diseases in China by simulating different scenarios that incorporate recent therapeutic advances of HCV and China's current screening strategy. We developed an individual-based microsimulation Markov model that simulated disease progression of HCV-infected patients in China from 2004 to 2050. We simulated four scenarios with different assumptions about treatment, including a natural history scenario, a pre-DAAs scenario, a DAA treatment for all patients with a METAVIR fibrosis score ≥F3 (DAAs [≥F3]) scenario, and a DAAs (≥F0) scenario. The introduction of DAAs is predicted to have great impacts on the burden of HCV in China, particularly under the DAAs (≥F0) scenario in which we rapidly expand DAAs to all HCV-infected patients (≥F0) in 2021. Under this scenario, prevalence of chronic HCV is expected to peak at 10.75 million (95% confidence interval [CI], 8.30-12.85) around 2020 and then decrease to 7.92 million (95% CI, 5.41-10.08) in 2050. Conclusion: If the future increasing burden of HCV-related diseases is to be averted, China needs to start launching the new DAA treatment and rapidly increase the number of patients treated. However, to maximize the benefits of new DAAs, expanded screening is necessary to identify more cases that require treatment in the short term. Without these changes, the HCV burden in China will remain high in the future.

Both gut microbiota and cytokines act to atherosclerosis in ApoE-/- mice.

BACKGROUND: Several studies have suggested a role for the gut microbiome and cytokines in atherosclerosis development, but combined analyses of the changes of the gut microbiota and cytokines have not been explored previously. METHODS: We treated ApoE-/- and wild-type mice with a high-fat diet for 12 weeks. The gut microbiome and cytokine composition were analyzed using 16S ribosomal DNA sequencing and RayBio Quantibody Arrays, respectively. GO and KEGG analysis were performed to rationalize the potential mechanisms involved in the process of atherosclerosis. RESULTS: Gut bacterial characteristics in ApoE-/- mice were clearly separated and 21 gut bacterial clades were detected by the LEfSe analysis showing significant differences during the development of atherosclerosis. The relative abundance of Verrucomicrobia, Bacteroidaceae, Bacteroides, and Akkermansia showed significant positive correlations with serum total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Additionally, the relative abundance of Ruminococcaceae was positive with the level of HDL and the abundance of Rikenellaceae showed a negative relationship with the level of TG and LDL. Thirteen differentially expressed proteins were identified with P-value < 0.05. CXCL5, FGF2, and E-Selectin were significantly negatively associated with Akkermansia and Verrucomicrobia. Additionally, CXCL5 was significantly negatively correlated with Bacteroides and Bacteroidaceae. Three "cellular component" subcategories, 24 ″molecular function" subcategories, 752 ″biological process" subcategories and 29 statistically remarkable KEGG pathway categories were identified. CONCLUSIONS: Gut microbiota changes of the mice having atherosclerosis and their relationship with the inflammatory status could be one of the major etiological mechanisms underlying atherosclerosis.

A system dynamics modelling simulation based on a cohort of hepatitis B epidemic research in east China community.

Hepatitis B constitutes a severe public health challenge in China. The Community-based Collaborative Innovation hepatitis B (CCI-HBV) project is a national epidemiological study of hepatitis B and has been conducting a comprehensive intervention in southern Zhejiang since 2009.The comprehensive intervention in CCI-HBV areas includes the dynamic hepatitis B screening in local residents, the normalised treatment for hepatitis B infections and the upcoming full-aged hepatitis B vaccination. After two rounds of screening (each round taking for 4 years), the initial epidemiological baseline of hepatitis B in Qinggang was obtained, a coastal community in east China. By combining key data and system dynamics modelling, the regional hepatitis B epidemic in 20 years was predicted.There were 1041 HBsAg positive cases out of 12 228 people in Round 1 indicating HBV prevalence of 8.5%. Of the 13 146 people tested in Round 2, 1171 people were HBsAg positive, with a prevalence of 8.9%. By comparing the two rounds of screening, the HBV incidence rate of 0.192 per 100 person-years was observed. By consulting electronic medical records, the HBV onset rate of 0.533 per 100 person-years was obtained. We generated a simulated model to replicate the real-world situation for the next two decades. To evaluate the effect of interventions on regional HBV prevalence, three comparative experiments were conducted.In this study, the regional hepatitis B epidemic in 20 years was predicted and compared with HBV prevalence under different interventions. Owing to the existing challenges in research methodology, this study combined HBV field research and simulation to provide a system dynamics model with close-to-real key data to improve prediction accuracy. The simulation also provided a prompt guidance for the field implementation.

Establishment and development of national community-based collaborative innovation demonstration areas to achieve the control target of hepatitis B in China.

BACKGROUND: The major infectious diseases of hepatitis B has constituted an acute public health challenge in China. An effective and affordable HBV control model is urgently needed. A national project of Community-based Collaborative Innovation HBV (CCI-HBV) demonstration areas has optimized the existing community healthcare resources and obtained initial results in HBV control. METHODS: Based on the existing community healthcare network, CCI-HBV project combined the community health management and health contract signing service for long-staying residents in hepatitis B screening. Moreover, HBV field research strategy was popularized in CCI-HBV areas. After screening, patients with seropositive results were enrolled in corresponding cohorts and received treatment at an early stage. And the uninfected people received medical supports including health education through new media, behavior intervention and HBV vaccinations. In this process, a cloud-based National Information Platform (NIP) was established to collect and store residents' epidemiological data. In addition, a special quality control team was set up for CCI project. RESULTS: After two rounds of screening, HBsAg positive rate dropped from 5.05% (with 5,173,003 people screened) to 4.57% (with 3,819,675 people screened), while the rate of new HBV infections was 0.28 per 100 person-years in the fixed cohorts of 2,584,322 people. The quality control team completed PPS sampling simultaneously and established the serum sample database with 2,800,000 serum samples for unified testing. CONCLUSIONS: CCI-HBV project has established a large-scale field research to conduct whole-population screening and intervention. We analyzed the HBsAg prevalence and new infection rate of HBV in the fixed population for the epidemic trend and intervention effect. The purpose of CCI-HBV project is to establish and evaluate a practical model of grid management and field strategy, to realize the new goal to control hepatitis B in China. To provide policymakers with a feasible model, our results are directly applicable. TRIAL REGISTRATION: The project was funded by the Major Projects of Science Research for the 11th and 12th five-year plans of China, entitled "The prevention and control of AIDS, viral hepatitis and other major infectious diseases", Grant Nos. 2009ZX10004901, 2011ZX10004901, 2013ZX10004904, 2014ZX10004007 and 2014ZX10004008.

Pneumonia Mortality in Children Aged <5 Years in 56 Countries: A Retrospective Analysis of Trends from 1960 to 2012.

BACKGROUND: Pneumonia is now the second leading cause of death for children aged <5 years worldwide. However, analyses of the long-term evolution of under-5 mortality from pneumonia are still scarce in the literature. We aimed to explore long-term trends of under-5 mortality from pneumonia in 56 countries from 1960 to 2012. METHODS: Data on under-5 mortality from pneumonia were extracted from the World Health Organization mortality database. Long-term trends were assessed for 56 countries and for 4 national income transition groups. We also used joinpoint regression analysis to detect distinct period segments of long-term trends and estimate the annual percent of changes of each period segment. RESULTS: The average mortality rate from pneumonia for children aged 0-4 years in 56 countries declined from 163.0 per 100000 children (95% confidence interval [CI], 119.4 to 212.8) in 1960 to 9.9 per 100000 children (95% CI, 6.4 to 13.4) in 2012, with an average annual percent of change of -5.6% (95% CI, -7.2% to -3.9%). The temporal trends of childhood mortality were different between national income transition groups. CONCLUSIONS: Our findings suggest a striking overall downward trend in under-5 mortality from pneumonia between 1960 and 2012. However, the rate and absolute terms of decline differ by national income transition group. These variable patterns between national income transition groups may inform further intervention setting and priority setting.

Hepatitis B virus infection in hilly/mountainous regions of southeastern China: a locality-dependent epidemiology.

BACKGROUND: The overall prevalence of hepatitis B virus (HBV) infection in China is declining. The purpose of this study was to use a community-based epidemiological study to update the infection status of hepatitis B virus (HBV) in mountainous regions of China, and to evaluate the impact of the Expanded Program of Immunization (EPI) on HBV transmission. METHODS: In total, 10,383 participants were selected by multi-stage stratified random cluster sampling in two mountainous regions, Xianju and Anji, in Zhejiang province, China. RESULTS: The positive rates of hepatitis B virus surface antigen (HBsAg), anti-HBV core antigen (anti-HBc), and anti-HBV surface antigen (anti-HBs) were 9.5%, 33.9%, and 51.0%, respectively. Positive HBV markers were more frequently detected in males than in females (P < 0.01). The alanine aminotransferase (ALT) levels were elevated (>38 IU/L) in 15.3% of the HBsAg-positive and 6.3% of the HBsAg-negative subjects. The α-fetoprotein (AFP) level was elevated in 0.8% of the HBsAg-positive participants who were older than 30 years old. CONCLUSIONS: The epidemiology of HBV infection is location dependent. The prevalence of HBV infection in the mountainous regions is higher than the national levels. Moreover, HBV infection in women of childbearing age is up to 10%, which represents a main factor for continuous HBV transmission.

Tuberculosis in China: A longitudinal predictive model of the general population and recommendations for achieving WHO goals.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) remains a major public health challenge. China accounts for more than 10% of the global TB burden, and effective modelling of TB trends remains limited. METHODS: We used data drawn primarily from two Chinese nation-wide cross-sectional epidemiological surveys combined with data from China's National Disease Reporting Network to construct an eight-state Markov model that simulates TB prevalence. By adjusting the relevant parameters, we evaluated which characteristics have the greatest bearing upon prevalence and efficacy of the response measures. RESULTS: If current trends continue, the prevalence of TB in China will enter an 8-year period of decline from approximately 390 to 200 cases per 100 000 population and stabilize at 163 cases per 100 000 population, which is a figure well above the World Health Organization (WHO) goal of eliminating TB by 2050. We find that the proportion of notified cases in the population, the rate of progression from latent to active and the overall treatment success rate are the chief factors affecting disease progression. CONCLUSION: We suggest a 90-90-90 strategy, wherein the proportion of notified cases in the population reaches 90%, the risk of progression from latent to active is decreased by 90% compared with the current level and the overall treatment success rate is increased to 90%. This strategy could reduce TB prevalence to less than 10 cases per 100 000 population within 5 years and to 1.77 cases per 100 000 population within 50 years.

Tissue transglutaminase 2 exerts a tumor-promoting role in hepatitis B virus-related hepatocellular carcinoma.

Hepatitis B virus (HBV) infection is a major risk factor which can lead to development of hepatocellular carcinoma (HCC). Tissue transglutaminase-2 (TG2) has been shown to be critical for cancer progression. However, how TG2 promotes the progression of HBV-related HCC remains unknown. In this study, we aimed to explore the expression and function of TG2 on HBV-related HCC progression. The expression levels of TG2 were examined in a series of HBV-related HCC tissues and a panel of HCC cell lines. The effects of TG2 knockdown on the proliferation and migration of HBV-related cells were determined. TG2 expression was found to be significantly upregulated in HBV-related HCC tissues. TG2 expression was higher in HBV-related HCC cell lines than HBV-unrelated HCC cell lines. Moreover, inhibition of TG2 in HCC cell lines HepG2.2.15 and Hep3B could inhibit cell proliferation, migration, and invasion in vitro. Our results indicated that TG2 could serve as a promising target for treatment of HBV-related HCC patients.

Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis.

Conflicting evidence exists with regard to the relationship between maternal infection during pregnancy and the risk of autism spectrum disorder (ASD) in offspring. The aim of this meta-analysis was to systematically assess this relationship. To identify relevant studies, we conducted systematic searches in PubMed and Embase of scientific articles published through March 2016. Random-effects models were adopted to estimate overall relative risk. A total of 15 studies (2 cohort and 13 case-control studies) involving more than 40,000 ASD cases were included in our meta-analysis. Our results showed that maternal infection during pregnancy was associated with an increased risk of ASD in offspring (OR=1.13, 95% confidence interval (CI): 1.03-1.23), particularly among those requiring hospitalization (OR=1.30, 95% CI: 1.14-1.50). Subgroup analyses suggested that risk may be modulated by the type of infectious agent, time of infectious exposure, and site of infection. These findings indicate that maternal infection during pregnancy increases the risk of ASD in offspring. Possible mechanisms may include direct effects of pathogens and, more indirectly, the effects of inflammatory responses on the developing brain.

Use of antipsychotics and risk of myocardial infarction: a systematic review and meta-analysis.

AIM: There is emerging concern that antipsychotics may be associated with an increased risk of myocardial infarction (MI). A previous review identified five observational studies that did not provide an accurate estimate of the association between antipsychotic drug use and MI risk. More recent studies have produced variable results. METHODS: We performed a systematic review and meta-analysis of observational studies to determine whether antipsychotic use affects the risk for MI. Our analysis included all observational studies that compared MI incidence among patients receiving antipsychotics vs. no treatment. RESULTS: Nine observational studies were included in the analysis. The odds for developing MI were 1.88-fold higher (odds ratio (OR) 1.88, 95% confidence interval (CI) 1.39, 2.54) in antipsychotic users compared with individuals who had not taken antipsychotics. Subgroup analyses found an OR of 2.48 (95% CI 1.66, 3.69) among patients with schizophrenia and an OR of 2.64 (95% CI 2.48, 2.81) among short term (<30 days) antipsychotic users. CONCLUSION: The findings of this meta-analysis support an increased risk of MI in antipsychotic drug users. The present systematic review expands previous knowledge by demonstrating an increased and more pronounced risk in short term users.