Genomes of cultivated and wild Capsicum species provide insights into pepper domestication and population differentiation.

Pepper (Capsicum spp.) is one of the earliest cultivated crops and includes five domesticated species, C. annuum var. annuum, C. chinense, C. frutescens, C. baccatum var. pendulum and C. pubescens. Here, we report a pepper graph pan-genome and a genome variation map of 500 accessions from the five domesticated Capsicum species and close wild relatives. We identify highly differentiated genomic regions among the domesticated peppers that underlie their natural variations in flowering time, characteristic flavors, and unique resistances to biotic and abiotic stresses. Domestication sweeps detected in C. annuum var. annuum and C. baccatum var. pendulum are mostly different, and the common domestication traits, including fruit size, shape and pungency, are achieved mainly through the selection of distinct genomic regions between these two cultivated species. Introgressions from C. baccatum into C. chinense and C. frutescens are detected, including those providing genetic sources for various biotic and abiotic stress tolerances.

Integrated proteomic and metabolomic analyses reveal significant changes in chloroplasts and mitochondria of pepper (Capsicum annuum L.) during Sclerotium rolfsii infection.

Infection by Sclerotium rolfsii will cause serious disease and lead to significant economic losses in chili pepper. In this study, the response of pepper during S. rolfsii infection was explored by electron microscopy, physiological determination and integrated proteome and metabolome analyses. Our results showed that the stomata of pepper stems were important portals for S. rolfsii infection. The plant cell morphology was significantly changed at the time of the fungal hyphae just contacting (T1) or surrounding (T2) the pepper. The chlorophyll, carotenoid, and MDA contents and the activities of POD, SOD, and CAT were markedly upregulated at T1 and T2. Approximately 4129 proteins and 823 metabolites were clearly identified in proteome and metabolome analyses, respectively. A change in 396 proteins and 54 metabolites in pepper stem tissues was observed at T1 compared with 438 proteins and 53 metabolites at T2. The proteins and metabolites related to photosynthesis and antioxidant systems in chloroplasts and mitochondria were disproportionally affected by S. rolfsii infection, impacting carbohydrate and amino acid metabolism. This study provided new insights into the response mechanism in pepper stems during S. rolfsii infection, which can guide future work on fungal disease resistance breeding in pepper.

The trend of direct medical costs and associated factors in patients with chronic hepatitis B in Guangzhou, China: an eight-year retrospective cohort study.

BACKGROUND: Although the expenses of liver cirrhosis are covered by a critical illness fund under the current health insurance program in China, the medical costs associated with hepatitis B virus (HBV) related diseases is not well addressed. In order to provide evidence to address the problem, we investigated the trend of direct medical costs and associated factors in patients with chronic HBV infection. METHODS: A retrospective cohort study of 65,175 outpatients and 12,649 inpatients was conducted using a hospital information system database for the period from 2008 to 2015. Generalized estimating equations (GEE) were applied to explore associations between annual direct medical costs and corresponding factors, meanwhile quantile regression models were used to evaluate the effect of treatment modes on different quantiles of annual direct medical costs stratified by medical insurances. RESULTS: The direct medical costs increased with time, but the proportion of antiviral costs decreased with CHB progression. Antiviral costs accounted 54.61% of total direct medical costs for outpatients, but only 6.17% for inpatients. Non-antiviral medicine costs (46.06%) and lab tests costs (23.63%) accounted for the majority of the cost for inpatients. The direct medical costs were positively associated with CHB progression and hospitalization days in inpatients. The direct medical costs were the highest in outpatients with medical insurance and in inpatients with free medical service, and treatment modes had different effects on the direct medical costs in patients with and without medical insurance. CONCLUSIONS: CHB patients had a heavy economic burden in Guangzhou, China, which increased over time, which were influenced by payment mode and treatment mode.

Integration of mRNA and miRNA profiling reveals the heterosis of three hybrid combinations of Capsicum annuum varieties.

Capsicum annuum is also known as chili which is one of the most important vegetable crops grown in the world. Breeding new varieties with heterosis could improve the quality of pepper, increase yield, growth potential, disease resistance, adaptability, and seed viability. To investigate the heterosis among three cross combinations of different parents, the mRNA-miRNA integrated analysis was performed. A total number of 22,659,009 to 36,423,818 clean data were generated from mRNA-seq with 81 libraries, and the unique mapped reads were from 35,495,567 (86.81%) to 46,466,622 (88.95%). The plant-hormone signal transduction pathway (40 genes) was detected with a higher DEG number. The SAUR32L, GID1, PYR1, EIN2. ERF1, PR1, JAR1-like, IAA from this pathway play a key role in plant development. From the miRNA-seq, the number of clean reads was ranging from 12,132,221 to 25,632,680. A total of 220 miRNAs were predicted in this study, and all of them were identified as novel miRNA. The top three candidate KEGG pathways of miRNA were ribosome signaling pathway (13 miRNAs), spliceosome pathway (13 miRNAs), and plant hormone signal transduction pathways (10 miRNAs). With the mRNA and miRNA integrated analysis, we found some key genes were regulated by some miRNAs. Among them, the scarecrow-like 6 protein can be up or down regulated by mir8, mir120, mir184, mir_214, mir125, and mir130. The function of Della protein was regulated by mir24, mir74, mir94, mir139, and mir190. This study contributes to understanding how heterosis regulates the traits, such as crop production, fruit weight, and fruit length.

Accuracy of Self-Reported Hypertension, Diabetes, and Hyperlipidemia among Adults of Liwan, Guangzhou, China.

BACKGROUND: We aimed to determine the accuracy of self-reported diabetes, hypertension, and hyperlipidemia in Chinese adults and examine factors that affect the accuracy of self-reports. METHODS: This representative cross-sectional survey was conducted in Liwan District, Guangzhou City, Southeast China. Self-reported data were collected using a structured questionnaire. Biometrical data were recorded, including blood lipid, blood glucose and arterial blood pressure levels. Sensitivity, specificity, and κ values of self-reports were used as measurements of accuracy or agreements. The Robust Poisson-GEE was applied to determine the association of participants' characteristics with the accuracy of self-reports. RESULTS: Self-reported and biometrical data of 1278 residents aged 18 yr and older (693 women and 585 men) were used to calculate three measures of agreement. The agreement between self-reports and biomedical measurements was substantial for both hypertension and diabetes (κ=0.77 and 0.76), but only slight for hyperlipidemia (κ=0.06). Similarly, the sensitivity was higher for hypertension and diabetes (72.3% and 71.2%) than for hyperlipidemia (6.8%), while the specificity was high overall (≥98%). The factors associated with an accurate self-reported diagnosis in respondents with disease included having undergone blood pressure measurement (for hypertension) or blood glucose measurement (for diabetes) in the past 6 month, having attended health knowledge lectures in the past year and having social health insurances (for hypertension), and having undergone physical discomfort in the past 2 weeks (for hypertension and diabetes). CONCLUSION: The accuracy of self-reported hypertension and diabetes was high, whereas that of self-reported hyperlipidemia was lower among the population.

A novel single-base mutation in CaBRI1 confers dwarf phenotype and brassinosteroid accumulation in pepper.

Dwarfing is the development trend of pepper breeding. It is of great practical and scientific value to generate new dwarf germplasms, and identify new genes or alleles conferring dwarf traits in pepper. In our previous study, a weakly BR-insensitive dwarf mutant, E29, was obtained by EMS mutagenesis of the pepper inbred line 6421. It can be used as a good parent material for breeding new dwarf varieties. Here, we found that this dwarf phenotype was controlled by a single recessive gene. Whole-genome resequencing, dCAPs analysis, and VIGs validation revealed that this mutation was caused by a nonsynonymous single-nucleotide mutation (C to T) in CaBRI1. An enzyme activity assay, transcriptome sequencing, and BL content determination further revealed that an amino-acid change (Pro1157Ser) in the serine/threonine protein kinase and catalytic (S_TKc) domain of CaBRI1 impaired its kinase activity and caused the transcript levels of two important genes (CaDWF4 and CaROT3) participating in BR biosynthesis to increase dramatically in the E29 mutant, accompanied by significantly increased accumulation of brassinolide (BL). Therefore, we concluded that the novel single-base mutation in CaBRI1 conferred the dwarf phenotype and resulted in brassinosteroid (BR) accumulation in pepper. This study provides a new allelic variant of the height-regulating gene CaBRI1 that has theoretical and practical values for the breeding of the plants suitable for the facility cultivation and mechanized harvesting of pepper varieties.

Latent profile analysis of anxiety disorder among left-behind children in rural Southern China: a cross-sectional study.

OBJECTIVES: Previous studies have used latent profile analysis (LPA) to examine rural left-behind children's anxiety. Further study is needed to identify the heterogeneous characteristics of rural left-behind children's anxiety and explore the related factors. SETTING: A cross-sectional survey using a school-based sample was conducted in January 2018 in Qingxin district, Qingyuan city, Guangdong province. PARTICIPANTS: 1026 left-behind children (effective response rate of the questionnaire: 95.39%). MAIN OUTCOME MEASURES: Profile latent classes (LC) and anxiety disorder. RESULTS: The LPA identified three anxiety LC: 'low anxiety' (56.6%), 'medium anxiety' (34.8%) and 'severe anxiety' (8.6%). The multinomial logistic regression model was used to predict the relationship between personal, family, school factors and anxiety. We found that the variables directly related to lower anxiety classes included age (12-14 years), harmonious or fair relationship with classmates, no neglect, harmonious parental relationship and the duration of mother migration <6 months. CONCLUSIONS: These findings suggested the need for careful consideration of differences in anxieties among rural left-behind children. Identifying latent subgroups may provide an empirical basis for teachers and public health practitioners to implement anxiety intervention efforts.

Influence of school-level factors and anxiety on injury-prone children / 中国学校卫生

Objective@#To understand the characteristics of injuries among rural children, and to determine the relationships between school-level factors with anxiety among injury-prone children, to provide a reference for making effective measures to prevent and control the injuries.@*Methods@#A cross-sectional survey was conducted in the Qingxin District of Qingyuan City. Six primary schools and middle schools were randomly selected from two towns. A total of 5 250 students in grades 3-9 were investigated. Students filled out the questionnaire themselves. Screen for Child Anxiety Related Emotional Disorders (SCARED) was used to assess anxiety.@*Results@#Among the 770 rural children who suffered injuries during the past year, the leading cause of injury was falling(44.62%), falling at home(29.61%), getting injuried in low limbs(29.45%), getting injuried by oneself (41.00%) and mainly unintentional injuries(68.66%) . About 35.06% of children reported anxiety symptoms. Approximately 14.94% of children were injury-prone type. Significant differences in educational stage, boarding school, fighting involvement, and somatization/panic between injury-prone children were found in control group(P<0.05). The robust Poisson-GEE model showed that primary school students in high grade and middle grade, fighting with classmates, somatic/panic associated with injury risk (PR value was 2.11, 1.75, 1.58 and 1.58, respectively).@*Conclusion@#Injury-prone children in rural are affected by school-level factors as well as anxiety symptoms. In addition to safety education, mental health promotion and prevention of school bullying should be adopted in schools.

Blocking Polysulfides and Facilitating Lithium-Ion Transport: Polystyrene Sulfonate@HKUST-1 Membrane for Lithium-Sulfur Batteries.

Minimizing the shuttle effect of polysulfides (PS) is crucial for practical applications of lithium-sulfur (Li-S) batteries. However, the trade-off between effective suppression of the shuttle effect and fast redox reaction kinetics is inevitable for separator-based Li-S batteries. Herein, via a self-confined solid-conversion process, we develop a polystyrene sulfonate (PSS)-threaded well-intergrown HKUST-1 (Cu3(BTC)2) (BTC: 1,3,5-benzenetricarboxylic acid)-coated Celgard separator (PSS@HKUST-1/Celgard, PHC) for high-performance Li-S batteries. The PHC membrane favors the interception and accommodation of long-chain PS. Notably, enormous sulfonate groups of the three-dimensional PSS networks in PSS@HKUST-1 membrane significantly facilitate lithium-ion transport, which guarantee fast redox kinetics. The PHC separator demonstrates efficient inhibition of PS (i.e., 4 orders of magnitude lower in PS permeation rate) with fast Li+ transportation (i.e., 71% higher in ionic conductivity) than the Celgard separator. When applying the PHC membrane in Li-S batteries with conventional sulfur/super P carbon cathode, highly reversible capacity with an average fading rate of 0.05% per cycle is maintained for 500 cycles at 0.5 C, excellent rate performance up to 5 C, and high areal capacity over 7 mA h cm-2 are also achieved. This work paves a new way for addressing the trade-off between suppressing the PS shuttle effect and fast kinetic reaction for separator-based Li-S batteries.

Identification and characterization of novel microRNAs for fruit development and quality in hot pepper (Capsicum annuum L.).

MicroRNAs (miRNAs) are non-coding small RNAs which play an important regulatory role in various biological processes. Previous studies have reported that miRNAs are involved in fruit development in model plants. However, the miRNAs related to fruit development and quality in hot pepper (Capsicum annuum L.) remains unknown. In this study, small RNA populations from different fruit ripening stages and different varieties were compared using next-generation sequencing technology. Totally, 59 known miRNAs and 310 novel miRNAs were identified from four libraries using miRDeep2 software. For these novel miRNAs, 656 targets were predicted and 402 of them were annotated. GO analysis and KEGG pathways suggested that some of the predicted miRNAs targeted genes involved in starch sucrose metabolism and amino sugar as well as nucleotide sugar metabolism. Quantitative RT-PCR validated the contrasting expression patterns between several miRNAs and their target genes. These results will provide an important foundation for future studies on the regulation of miRNAs involved in fruit development and quality.

Cost-Effectiveness Comparison Between the Response-Guided Therapies and Monotherapies of Nucleos(t)ide Analogues for Chronic Hepatitis B Patients in China.

BACKGROUND AND OBJECTIVE: Nucleos(t)ide analogue (NA) monotherapies are typically used as the primary treatment for chronic hepatitis B (CHB) patients, including lamivudine (LAM), telbivudine (TBV), adefovir (ADV), entecavir (ETV) and tenofovir (TDF). For high-resistance NAs (LAM, TBV, ADV), they can generate excellent clinical outcomes by using response-guided therapy; however, their pharmacoeconomic profiles remain unclear in China. We aimed to evaluate the cost effectiveness between response-guided therapies and monotherapies of NAs for Chinese hepatitis B e-antigen (HBeAg)-positive and -negative CHB patients. METHODS: We constructed a Markov model to simulate CHB progression associated with 12 treatment strategies using effectiveness and cost data from the published literature. We measured the lifetime costs, quality adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity (especially to extend the range of the TDF price) and probabilistic sensitivity analyses were used to explore the uncertainties of the model. RESULTS: For both HBeAg-positive and -negative patients, no treatment strategy generated the lowest lifetime costs (US$31,185-US$31,338) and QALYs (7.54-7.58). ETV and TDF monotherapies were not dominated by other treatments, whereas, the ICER of ETV monotherapy was the lowest (US$6112/QALY-US$8533/QALY). For each high-resistance NA, compared with its monotherapy, the ICERs of its response-guided therapies were below the willingness-to-pay threshold of US$22,833/QALY. Additionally, TDF monotherapy was the preferred treatment when its price dropped to US$1820/year or lower. CONCLUSION: Among 12 treatment strategies evaluated, ETV monotherapy is the most cost-effective treatment for treatment-naive CHB patients in China. The response-guided therapies of high-resistance NAs are more cost-effective than their monotherapies.

The Role of Interferon Lambda 3 Genetic Polymorphisms in Response to Interferon Therapy in Chronic Hepatitis B Patients: An Updated Meta-Analysis.

CONTEXT: Polymorphisms of the interferon lambda 3 (IFNL3) gene have been proposed to be associated with drug-induced clearance of the hepatitis C virus (HCV). However, the role of IFNL3 polymorphisms in the prediction of treatment on chronic hepatitis B (CHB) patients have yielded controversial results. The aim of this study was to clarify the role of IFNL3 polymorphisms (rs12979860, rs8099917, and rs12980275) in the treatment response of CHB patients to interferon (IFN). EVIDENCE ACQUISITION: EMBASE and PUBMED/MEDLINE were searched to identify relevant studies from January 2009 to March 2015. The search used the keyword "interferon lambda 3" or "IFNL3," combined with the following terms: "interferon therapy," "hepatitis," and "polymorphisms." Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were used to assess the strength of the associations between the polymorphisms and the response to IFN therapy. RESULTS: Nine studies of 1602 CHB patients receiving IFN treatment were included. Under the random-effects model, patients expressing the variant rs12980275 showed a significantly increased response to IFN therapy (OR = 2.85; 95% CI = 1.14 - 4.60). In the subgroup analyses by antiviral agents, the patients carrying the rs8099917T allele in the IFN-only treatment group showed a significantly increased response to IFN therapy (OR for the dominant model = 2.03; 95% CI = 1.24 - 3.31), whereas those in the mixed treatment group showed a significantly decreased response (OR for the dominant model = 0.30; 95% CI = 0.10 - 0.90). CONCLUSIONS: This study supports the idea that the IFNL3 gene is an important predictor of the response of CHB patients to IFN therapy.

Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF. METHODS: Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF. RESULTS: In the base-case analysis, the lowest lifetime cost and the best cost-effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 × gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively. CONCLUSIONS: For Chinese chronic hepatitis B patients, ETV is still the most cost-effective strategy over TDF and other nucleos(t)ide analogs, with a threshold of $20,466 USD/QALY gained.

Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.

BACKGROUND/AIM: Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). METHODS: To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. RESULTS: In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. CONCLUSION: ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.

Smoking behaviors before and after implementation of a smoke-free legislation in Guangzhou, China.

BACKGROUND: According to the partial smoke-free legislation implemented on 1 September 2010 in Guangzhou, China, smoke-free did not cover all indoor areas. Some places have a full smoking ban (100 % smoke-free), other places have a partial smoking ban, and homes have no ban. This study aimed to compare the smoking behaviors before and after implementation of a smoke-free legislation. METHOD: A repeated cross-sectional survey was conducted on smoking-related behaviors with a total of 4,900 respondents before, and 5,135 respondents after the legislation was instituted. For each wave of the survey, a three-stage stratified sampling process was used to obtain a representative sample. Pearson's Chi-square test was used to determine differences of smoking prevalence and quit ratio between the two samples. Logistic regression models were used to examine the associations of a smoke-free legislation with smoking behaviors. RESULTS: The overall daily smoking rate declined significantly from 20.8 % to 18.2 % (p < 0.05), especially among those aged 15-24 years. The quit ratios increased significantly (from 14.5 % to 17.9 %), but remained low among 15-44 year olds. The overall self-reported smoking behaviors in locations with a full smoking ban decreased significantly from 36.4 % to 24.3 % with the greater drops occurring in cultural venues, public transport vehicles, and government offices. Smoking in places with partial smoking bans remained high (89.6 % vs. 90.4 %), although a slight decrease was observed in some of these areas. The implementation of a smoke-free legislation did not lead to more smoking in homes (91.0 % vs 89.4 %), but smoking in homes remained high. CONCLUSIONS: These findings highlight the urgent need for a comprehensive smoke-free legislation covering all public places in Guangzhou, simultaneously educational interventions and campaigns promoting voluntary changes in home smoking need to occur.

Dose-response relations between second-hand smoke exposure and depressive symptoms among middle-aged women.

A growing body of evidence indicates a strong association between smoking and depression. However, little is known about the possible effects of second-hand smoke (SHS) exposure on depression. This study aimed to examine the potential dose-response relation between SHS exposure and depressive symptoms among non-smoking middle-aged women. A cross-sectional survey was conducted using a stratified three-stage sampling method. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression Scale with a cut-off point of 16. Self-reported SHS exposure was defined as non-smokers׳ inhalation of the smoke exhaled from smokers on at least one day a week. The multivariable logistic regression analysis was completed with adjustment for potential confounders. Among 1280 middle-aged women, 19.4% were classified as having depressive symptoms. There was a 104% increased odds of depressive symptoms corresponding to SHS exposure in general (OR=2.04, 95% CI 1.48-2.79) using no exposure as reference. There were significant positive relations between SHS exposure in general and depressive symptoms in a dose-response manner. These significant trends were observed consistently whether SHS exposure occurred in homes or workplaces. Our findings suggest that long-term and regular SHS exposure is associated with a significant, dose-dependent increase in risk of depressive symptoms.

Cost-effectiveness analysis of antiviral therapies for hepatitis B e antigen-positive chronic hepatitis B patients in China.

BACKGROUND AND OBJECTIVE: Several antiviral therapies are now available for patients with chronic hepatitis B (CHB), but the most cost-effective strategy for Chinese patients is unclear. The aim of this study was to estimate the long-term cost effectiveness of the antiviral treatments (lamivudine, adefovir, telbivudine and entecavir) for hepatitis B e antigen (HBeAg)-positive CHB patients in China. METHODS: A Markov model was used to simulate the life-time (41-year time span) costs and effectiveness associated with antiviral treatments from the perspective of Chinese healthcare. Relative model parameters were derived from Chinese population studies. Costs and effectiveness were discounted at 5 %. The highest retail prices for generic and branded drug prices were also considered. Probabilistic sensitivity analysis and one-way sensitivity analysis were used to explore model uncertainties. RESULTS: In the base-case analysis, the least quality-adjusted life years (QALYs) were obtained with adefovir as the reference strategy. Lamivudine generated the highest incremental cost-effectiveness ratio (ICER), with an additional US$35,000 needed to gain one additional QALY for generic drugs and US$36,000 for branded drugs. Entecavir had the lowest ICER of US$7,600 and US$9,100, respectively. The projected 10-year cumulative incidences of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC) and mortality for entecavir were lower than the other strategies. In probabilistic sensitivity analyses, entecavir was the preferred option at a threshold of US$18,924 per QALY. CONCLUSIONS: In patients with HBeAg-positive CHB in China, entecavir is a cost-effective option compared with other therapies for CHB.

Familial correlations of onset age of hepatocellular carcinoma: a population-based case-control family study.

BACKGROUND: There was lack of evidence for familial aggregation in onset age of hepatocellular carcinoma (HCC) in Chinese population. We conducted a population-based case-control family study to examine familial correlation of age of HCC onset in Taixing, China. METHODS: A total of 202 cases and 202 matched controls as well as their relatives were included in the study. Lifetime cumulative risks of HCC were estimated using the Kaplan-Meier approach. Cross ratios (CRs) were obtained from stratified Cox proportional hazard models, to assess the familial correlation of onset age. RESULTS: The mean age of HCC onset was decreased as increasing number of HCC cases in a family. The onset age was the earliest for first-degree relatives, intermediate for second-degree relatives, and latest for non-blood relatives (spouse) (log-rank test, P<0.01). The onset age was significantly correlated between probands and their relatives. In stratified Cox proportional hazard models, the CRs for the probands versus their fathers, mothers, siblings and uncles/aunts were 6.25 (95% confidence interval (CI): 1.84-21.25), 9.81 (95% CI: 1.24-77.56), 6.22 (95% CI: 1.37-28.36) and 3.24 (95% CI: 1.26-8.33), respectively. After adjustment for hepatitis B virus infection, the CRs remained significant. CONCLUSION: This current study suggested a significant correlation of onset age for HCC among blood relatives. Familial HCC cases yielded earlier age of onset and their relatives have higher HCC risk in early age, highlighting intensive surveillance should be start at an earlier age for individuals with family history of HCC.