Efficacy of Tenofovir-Based Combination Therapy versus Tenofovir Monotherapy in Chronic Hepatitis B Patients Presenting with Suboptimal Responses to Pretreatment: A Meta-Analysis

Background/Aims. It remains unclear whether tenofovir disoproxil fumarate- (TDF-) based combination therapy produces better outcomes than TDF monotherapy in chronic hepatitis B (CHB) patients. The aim of this study was to compare the efficacy of the two regimens by performing a meta-analysis. Methods. A comprehensive literature search was performed on the comparison of TDF-based combination therapy and monotherapy for CHB patients in the PubMed, Embase, Web of Science, and the Cochrane Libraries. Both dichotomous and continuous variables were extracted and pooled outcomes were expressed as risk ratio (RR) or standard mean difference (SMD). Results. Nine eligible studies (1089 subjects in total) were included in our analysis. The proportion of patients with undetectable HBV DNA at 24, 48, and 96 weeks were similar between the two comparable groups (62.5% versus 70.9%, P=0.086; 78.1% versus 83.7%, P=0.118; 86.4% versus 87.9%, P=0.626, resp.). HBV DNA reduction, rates of ALT normalization, hepatitis B e antigen (HBeAg) loss, and HBeAg seroconversion were also similar between the two groups. Conclusions. On the current data, TDF-based combination therapy seemed to be no better than those achieved by monotherapy. Further studies are needed to verify this comparison

Identification of the C-Reactive Protein Interaction Network Using a Bioinformatics Approach Provides Insights into the Molecular Pathogenesis of Hepatocellular Carcinoma

Background/Aims: C reactive protein (CRP) levels are elevated in many diseases, including malignant tumors and cardiovascular disorders. In this study, the protein interaction network for CRP was evaluated to determine the importance of CRP and its interacting proteins in the molecular pathogenesis of hepatocellular carcinoma (HCC). Methods: Isobaric tags for relative and absolute quantitation (iTRAQ) and mass spectrometry were used to identify CRP interacting proteins in SMMC7721 cells. Moreover, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to evaluate enriched genes and pathways for differentially expressed genes using DAVID and WebGestalt. Co-immunoprecipitation and western blot analyses were employed to assess interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1. Results: In total, 52 proteins that interact with CRP were identified. A GO analysis suggested that most of the interacting proteins were involved in CRP complexes and regulated metabolic processes. A KEGG pathway analysis suggested that most CRP-interacting proteins contribute to the TRAIL signaling pathway, Class I PI3K/Akt signaling pathway, plasma membrane estrogen receptor signaling, Nectin adhesion pathway, and S1P1 pathway. Immunoprecipitation and western blot analyses revealed interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1. Conclusions: iTRAQ based proteomic profiling revealed the network of CRP interacting proteins. This network may activate the PI3K/Akt signaling pathway, thereby contributing to the pathogenesis of HCC

Healthy lifestyle and life expectancy free of major chronic diseases at age 40 in Chinese population: a prospective cohort study

Background: A healthy lifestyle has been associated with a longer life expectancy (LE). However, whether it also helps achieve gains in LE free of major non-communicable diseases (NCDs) and its share of total LE in Chinese adults remains unknown. Methods: We used data from China Kadoorie Biobank (CKB) of 451,233 adults aged 30-79 free of heart disease, stroke, cancer, chronic obstructive pulmonary disease (COPD), and asthma at baseline. Low-risk lifestyle factors included never smoking or quitting for reasons other than illness, no excessive alcohol use, being physically active, healthy eating habits, and healthy body shape. We built multistate life tables for individuals with different risk levels of lifestyle factors to calculate LE with and without diseases (cardiovascular diseases [CVDs], cancer, chronic respiratory diseases [CRDs, including COPD and asthma]) at age 40. For life table calculation, we used prevalence of lifestyle factors, transition rates, and hazard ratios (HRs) for three transitions (disease-free to disease onset, disease-free to death, and presence of disease to all-cause mortality). Findings: During a median follow-up of 11.1 years, we documented 111,002 new CVD cases, 24,635 cancer cases, 12,506 CRD cases, and 34,740 deaths. The adjusted HRs (95% confidence intervals [CIs]) of men adopting all five versus 0-1 low-risk factors was 0.56 (0.50, 0.63), 0.40 (0.20, 0.80), and 0.64 (0.50, 0.83) for baseline to disease, baseline to death, and disease to death, respectively; the corresponding values for women were 0.69 (0.64, 0.75), 0.57 (0.34, 0.94), and 0.57 (0.47, 0.69). The LE free of the three NCDs (95%CI) at age 40 for individuals with 0-1 low-risk factor was on average 23.9 (23.2, 24.6) years for men and 24.2 (23.5, 24.9) years for women. For individuals adopting all five low-risk factors, it was 30.2 (28.8, 31.6) years for men and 28.4 (27.2, 29.6) years for women, with an increase of 6.3 (5.1, 7.5) years (men) and 4.2 (3.6, 5.4) years (women). Correspondingly, the proportion of LE free of the three NCDs to total LE increased from 73.1% to 76.3% for men and from 67.6% to 68.4% for women. Interpretation: Our findings suggest that promoting healthy lifestyles through public health interventions could be associated with increased LE free of major NCDs and 'relative compression of morbidity' in the Chinese population

Duration-dependent impact of cardiometabolic diseases and multimorbidity on all-cause and cause-specific mortality: a prospective cohort study of 0.5 million participants

Background The association of incident cardiometabolic multimorbidity (CMM) with mortality risk is rarely studied, and neither are the durations of cardiometabolic diseases (CMDs). Whether the association patterns of CMD durations with mortality change as individuals progress from one CMD to CMM is unclear. Methods Data from China Kadoorie Biobank of 512,720 participants aged 30–79 was used. CMM was defined as the simultaneous presence of two or more CMDs of interest, including diabetes, ischemic heart disease, and stroke. Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the duration-dependent associations of CMDs and CMM with all-cause and cause-specific mortality. All information on exposures of interest was updated during follow-up. Results During a median follow-up of 12.1 years, 99,770 participants experienced at least one incident CMD, and 56,549 deaths were documented. Among 463,178 participants free of three CMDs at baseline, compared with no CMD during follow-up, the adjusted HRs (95% CIs) between CMM and all-cause mortality, mortality from circulatory system diseases, respiratory system diseases, cancer, and other causes were 2.93 (2.80–3.07), 5.05 (4.74–5.37), 2.72 (2.35–3.14), 1.30 (1.16–1.45), and 2.30 (2.02–2.61), respectively. All CMDs exhibited a high mortality risk in the first year of diagnosis. Subsequently, with prolonged disease duration, mortality risk increased for diabetes, decreased for IHD, and sustained at a high level for stroke. With the presence of CMM, the above association estimates inflated, but the pattern of which remained. Conclusion Among Chinese adults, mortality risk increased with the number of the CMDs and changed with prolonged disease duration, the patterns of which varied among the three CMDs

Electronic health record–based absolute risk prediction model for esophageal cancer in the Chinese population: model development and external validation

Background: China has the largest burden of esophageal cancer (EC). Prediction models can be used to identify high-risk individuals for intensive lifestyle interventions and endoscopy screening. However, the current prediction models are limited by small sample size and a lack of external validation, and none of them can be embedded into the booming electronic health records (EHRs) in China. Objective: This study aims to develop and validate absolute risk prediction models for EC in the Chinese population. In particular, we assessed whether models that contain only EHR-available predictors performed well. Methods: A prospective cohort recruiting 510,145 participants free of cancer from both high EC-risk and low EC-risk areas in China was used to develop EC models. Another prospective cohort of 18,441 participants was used for validation. A flexible parametric model was used to develop a 10-year absolute risk model by considering the competing risks (full model). The full model was then abbreviated by keeping only EHR-available predictors. We internally and externally validated the models by using the area under the receiver operating characteristic curve (AUC) and calibration plots and compared them based on classification measures. Results: During a median of 11.1 years of follow-up, we observed 2550 EC incident cases. The models consisted of age, sex, regional EC-risk level (high-risk areas: 2 study regions; low-risk areas: 8 regions), education, family history of cancer (simple model), smoking, alcohol use, BMI (intermediate model), physical activity, hot tea consumption, and fresh fruit consumption (full model). The performance was only slightly compromised after the abbreviation. The simple and intermediate models showed good calibration and excellent discriminating ability with AUCs (95% CIs) of 0.822 (0.783-0.861) and 0.830 (0.792-0.867) in the external validation and 0.871 (0.858-0.884) and 0.879 (0.867-0.892) in the internal validation, respectively. Conclusions: Three nested 10-year EC absolute risk prediction models for Chinese adults aged 30-79 years were developed and validated, which may be particularly useful for populations in low EC-risk areas. Even the simple model with only 5 predictors available from EHRs had excellent discrimination and good calibration, indicating its potential for broader use in tailored EC prevention. The simple and intermediate models have the potential to be widely used for both primary and secondary prevention of EC

Prevalence of urinary incontinence in middle-aged and elderly adults in 10 areas in China

Objective: To describe the population and area distribution differences in the prevalence of urinary incontinence in middle-aged and elderly adults in 10 areas in China. Methods: A total of 24 913 participants aged 45-95 years who completed the third resurvey of China Kadoorie Biobank during 2020-2021 were included. The prevalence of urinary incontinence was assessed by an interviewer-administered questionnaire, and urinary incontinence was classified as only stress urinary incontinence, only urgency urinary incontinence and mixed urinary incontinence. The prevalence of urinary incontinence and its subtypes were reported by sex, age and area, and the severity of urinary incontinence and treatment were described. Results: The average age of the participants was (65.4±9.1) years. According to the seventh national census data in 2020, the age-standardized prevalence rates of urinary incontinence was 25.4% in women and 7.0% in men. The age-standardized prevalence rates of only stress, only urgency and mixed incontinence were 1.7%, 4.2% and 1.2% in men and 13.5%, 5.8% and 6.1% in women, respectively. The prevalence rates of urinary incontinence and all subtypes in men and the prevalence of urinary incontinence and all subtypes except only stress urinary incontinence in women all increased with age ( P<0.001). After adjusting for age, the prevalence of urinary incontinence in both men and women were higher in rural area than in urban area ( P<0.001). The treatment rates in men and women with urinary incontinence were 15.4% and 8.5%, respectively. Conclusions: The prevalence of urinary incontinence was high in middle-aged and elderly adults in China, and the prevalence rate was higher in women than in men, but the treatment rate of urinary incontinence was low

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10−13), ALDH2/MYL2 (rs671, P = 3.40 × 10−11; rs12229654, P = 4.56 × 10−9), ITIH4 (rs2535633, P = 1.77 × 10−10) and NT5C2 (rs11191580, P = 3.83 × 10−8) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10−8) and an additional 14 at P < 1.0 × 10−3 with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity

Mixed H₂/H_∞ Optimal Voltage Control Design for Smart Transformer Low-Voltage Inverter

The smart transformer has been widely applied for the integration of renewables and loads. For the smart transformer application, the voltage control of low-voltage inverter is important for feeding the load. In this paper, a multi-objective optimization control design approach which comprehensively considers all aspects of indexes, such as linear quadratic (LQ) index, H∞ norm, and closed-loop poles placement, is proposed based on the linear matrix inequality (LMI) solution. The proposed approach is able to alleviate the weight of the designer from the tedious design process of the multiple resonant controllers and the selection of the weighting matrix for the LQ control. Besides that, some excellent performances such as fast recovering time, low total harmonic distortion (THD) and high robustness are achieved by the proposed approach. The THD are 0.5% and 1.7% for linear and non-linear loads, respectively. The voltage drop for linear load step is reduced to 10 V. The proposed approach is applied to a 5 kVA three-phase inverter to yield an optimal control law. Results from the simulation and experiment presented herein will illustrate and validate the proposed approach