Efficacy of salvage surgery versus re-irradiation for isolated regional lymph node recurrence in patients with nasopharyngeal carcinoma.

BACKGROUND: To compare the clinical characteristics and prognoses of patients with isolated regional lymph node recurrent nasopharyngeal carcinoma (irrNPC) who underwent surgery or re-irradiation treatment. METHODS: We retrospectively reviewed 124 irrNPC patients who underwent initial radiotherapy between January 2010 and December 2020. The staging of regional lymph node recurrence was as follows: 75.8% for rN1, 14.5% for rN2, and 9.7% for rN3. Fifty-five patients underwent regional lymph node surgery (Surgery group), and sixty-nine patients received salvage radiotherapy with or without chemotherapy (Re-irradiation group). The survival rate was compared using Kaplan‒Meier analysis and evaluated by the log-rank test. Cox proportional hazard models were used to analyze prognostic factors. RESULTS: The median follow-up time was 70 months, the 5-year overall survival (OS) was 74%, and the median survival time was 60.8 months. There were no significant differences in 5-year OS (75.6% vs. 72.4%, P = 0.973), regional recurrence-free survival (RRFS, 62.7% vs. 71.1%, P = 0.330) or distant metastasis-free survival (DMFS, 4.2% vs.78.7%, P = 0.677) between the Surgery group and Re-irradiation group. Multivariate analysis revealed age at recurrence, radiologic extra-nodal extension (rENE) status, and recurrent lymph node (rN) classification as independent prognostic factors for OS. The rENE status was an independent prognostic factor for DMFS. Subgroup analysis of the Surgery group revealed that the rN3 classification was an adverse prognostic factor for OS. Age at recurrence ≥ 50 years, GTV-N dose, and induction chemotherapy were found to be independent prognostic factors for OS, RRFS, and DMFS, respectively, in the Re-irradiation group. CONCLUSIONS: For NPC patients with isolated regional lymph node recurrence after initial radiotherapy, those who underwent surgery had survival prognosis similar to those who underwent re-radiotherapy with or without chemotherapy. A prospective study is needed to validate these findings.

Hepatitis B virus infection as a risk factor for chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Currently, several studies have observed that chronic hepatitis B virus infection is associated with the pathogenesis of kidney disease. However, the extent of the correlation between hepatitis B virus infection and the chronic kidney disease risk remains controversial. METHODS: In the present study, we searched all eligible literature in seven databases in English and Chinese. The random effects model was used to conduct a meta-analysis. Quality of included studies was assessed using the Newcastle-Ottawa Quality Scale. RESULTS: In this analysis, a total of 31 studies reporting the association between hepatitis B virus infection and chronic kidney disease risk were included. The results showed a significant positive association between hepatitis B virus infection and the risk of chronic kidney disease (pooled OR, 1.20; 95% CI, 1.12-1.29), which means that hepatitis B virus increases the risk of developing chronic kidney disease. CONCLUSION: This study found that hepatitis B virus infection was associated with a significantly increased risk of chronic kidney disease. However, the current study still cannot directly determine this causal relationship. Thus, more comprehensive prospective longitudinal studies are needed in the future to provide further exploration and explanation of the association between hepatitis B virus and the risk of developing chronic kidney disease.

Development and validation of an online dynamic nomogram based on the atherogenic index of plasma to screen nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), a common liver disease worldwide, can be reversed early in life with lifestyle and medical interventions. This study aimed to develop a noninvasive tool to screen NAFLD accurately. METHODS: Risk factors for NAFLD were identified using multivariate logistic regression analysis, and an online NAFLD screening nomogram was developed. The nomogram was compared with reported models (fatty liver index (FLI), atherogenic index of plasma (AIP), and hepatic steatosis index (HSI)). Nomogram performance was evaluated through internal and external validation (National Health and Nutrition Examination Survey (NHANES) database). RESULTS: The nomogram was developed based on six variables. The diagnostic performance of the present nomogram for NAFLD (area under the receiver operator characteristic curve (AUROC): 0.863, 0.864, and 0.833, respectively) was superior to that of the HSI (AUROC: 0.835, 0.833, and 0.810, respectively) and AIP (AUROC: 0.782, 0.773, and 0.728, respectively) in the training, validation, and NHANES sets. Decision curve analysis and clinical impact curve analysis presented good clinical utility. CONCLUSION: This study establishes a new online dynamic nomogram with excellent diagnostic and clinical performance. It has the potential to be a noninvasive and convenient method for screening individuals at high risk for NAFLD.

Characteristics and interplay of esophageal microbiota in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal microbiota may influence esophageal squamous cell carcinoma (ESCC) pathobiology. Therefore, we investigated the characteristics and interplay of the esophageal microbiota in ESCC. METHODS: We performed 16S ribosomal RNA sequencing on paired esophageal tumor and tumor-adjacent samples obtained from 120 primarily ESCC patients. Analyses were performed using quantitative insights into microbial 2 (QIIME2) and phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2). Species found to be associated with ESCC were validated using quantitative PCR. RESULTS: The microbial diversity and composition of ESCC tumor tissues significantly differed from tumor-adjacent tissues; this variation between subjects beta diversity is mainly explained by regions and sampling seasons. A total of 56 taxa were detected with differential abundance between the two groups, such as R. mucilaginosa, P. endodontalis, N. subflava, H. Pylori, A. Parahaemolyticus, and A. Rhizosphaerae. Quantitative PCR confirmed the enrichment of the species P. endodontalis and the reduction of H. Pylori in tumor-adjacent tissues. Compared with tumor tissue, a denser and more complex association network was formed in tumor-adjacent tissue. The above differential taxa, such as H. Pylori, an unclassified species in the genera Sphingomonas, Haemophilus, Phyllobacterium, and Campylobacter, also participated in both co-occurrence networks but played quite different roles. Most of the differentially abundant taxa in tumor-adjacent tissues were negatively associated with the epidermal growth factor receptor (EGFR), erb-b2 receptor tyrosine kinase 2 (ERBB2), erb-b2 receptor tyrosine kinase 4 (ERBB4), and fibroblast growth factor receptor 1 (FGFR1) signaling pathways, and positively associated with the MET proto-oncogene, receptor tyrosine kinase (MET) and phosphatase and tensin homolog (PTEN) signaling pathways in tumors. CONCLUSION: Alterations in the microbial co-occurrence network and functional pathways in ESCC tissues may be involved in carcinogenesis and the maintenance of the local microenvironment for ESCC.

A novel inflammation-related prognostic biomarker for predicting the disease-free survival of patients with colorectal cancer.

BACKGROUND: To develop and evaluate the prognostic value of a comprehensive inflammatory biomarker for postoperative colorectal cancer (CRC) patients. METHODS: A total of 646 CRC patients were recruited between August 2017 and December 2019 from Fujian Medical University Union Hospital, with follow-up data up to 2021. The least absolute shrinkage and selection operator method (LASSO) was used to select inflammation indicators in order to construct a comprehensive biomarker (named NSAP). The Cox regression model was utilized to analyze the association between the NSAP and the disease-free survival (DFS) of CRC. Predictive performance and clinical utility of prognostic models were evaluated by area under the curve (AUC) and decision curve analyses (DCAs). RESULTS: During a median follow-up of 23 months, 95 clinical outcomes were observed, with a 1-year survival rate is 89.47%. A comprehensive inflammatory biomarker (NSAP) was established based on four blood indicators (including neutrophil-to-lymphocyte ratio (NLR), neutrophil×monocyte-to-lymphocyte ratio (SIRI), albumin-to-globulin ratio (AGR), and platelet-to-lymphocytes ratio (PLR)). Patients with a lower NSAP had significantly associated with better DFS of CRC (HR=0.53, 95%CI 0.32-0.89). Moreover, compared to a previously established model, the traditional TNM staging system or/and tumor markers, the nomogram based on NSAP displayed more excellent predictive ability (0.752 vs 0.597, 0.711 and 0.735, P < 0.05). DCAs also demonstrated that the established nomogram had better utility for decision making. CONCLUSIONS: Our study suggests that NSAP may be a useful comprehensive prognostic biomarker for predicting the DFS of CRC patients. The nomogram based on NSAP can be considered a valuable tool to estimate the prognosis of patients with CRC.

Association of meat consumption with NAFLD risk and liver-related biochemical indexes in older Chinese: a cross-sectional study.

BACKGROUND: Non-alcohol fatty liver disease (NAFLD) is the most common liver disease and an unhealthy lifestyle can lead to an increased risk of NAFLD. The present study aims to evaluate the association of meat consumption with NAFLD risk and liver-related biochemical indexes in middle-aged and elderly Chinese. METHODS: A cross-sectional study was conducted in individuals who were 45 years or older and underwent a physical examination from April 2015 to August 2017 in Southeast China. To evaluate associations between meat intake and NAFLD risk, inverse probability of treatment weighting and subgroup analyses were performed with logistic regressions. Spearman's rank correlation was carried out to examine the relationship between meat consumptions and liver-related biochemical indexes. RESULTS: High consumptions of red meat (28.44-49.74 and > 71.00 g/day) (ORadjusted = 1.948; P < 0.001; ORadjusted = 1.714; P = 0.002) was positively associated with NAFLD risk on inverse probability of treatment weighting analysis, adjusting for smoking, tea intake, weekly hours of physical activity and presence of hypertension, dyslipidemia and diabetes. Exposure-response relationship analysis presented that red meat intake was positively associated with NAFLD risk. Significant associations of red meat intakes with serum levels of γ-glutamyl transferase, alanine transaminase, aspartate aminotransferase, total triglyceride and high-density lipoprotein cholesterol were found (rs = 0.176; P < 0.001; rs = 0.128; P < 0.001; rs = 0.060; P = 0.016; rs = 0.085; P = 0.001; rs = - 0.074; P = 0.003). CONCLUSIONS: These findings suggest that the reduction of meat consumption may decrease NAFLD risk and should warrant further investigations.

Identifying potential biomarkers of nonalcoholic fatty liver disease via genome-wide analysis of copy number variation.

BACKGROUND: The prevalence of Non-alcoholic fatty liver disease (NAFLD) is increasing and emerging as a global health burden. In addition to environmental factors, numerous studies have shown that genetic factors play an important role in the development of NAFLD. Copy number variation (CNV) as a genetic variation plays an important role in the evaluation of disease susceptibility and genetic differences. The aim of the present study was to assess the contribution of CNV to the evaluation of NAFLD in a Chinese population. METHODS: Genome-wide analysis of CNV was performed using high-density comparative genomic hybridisation microarrays (ACGH). To validate the CNV regions, TaqMan real-time quantitative PCR (qPCR) was utilized. RESULTS: A total of 441 CNVs were identified, including 381 autosomal CNVs and 60 sex chromosome CNVs. By merging overlapping CNVs, a genomic CNV map of NAFLD patients was constructed. A total of 338 autosomal CNVRs were identified, including 275 CNVRs with consistent trends (197 losses and 78 gains) and 63 CNVRs with inconsistent trends. The length of the 338 CNVRs ranged from 5.7 kb to 2.23 Mb, with an average size of 117.44 kb. These CNVRs spanned 39.70 Mb of the genome and accounted for ~ 1.32% of the genome sequence. Through Gene Ontology and genetic pathway analysis, we found evidence that CNVs involving nine genes may be associated with the pathogenesis of NAFLD progression. One of the genes (NLRP4 gene) was selected and verified by quantitative PCR (qPCR) method with large sample size. We found the copy number deletion of NLRP4 was related to the risk of NAFLD. CONCLUSIONS: This study indicate the copy number variation is associated with NAFLD. The copy number deletion of NLRP4 was related to the risk of NAFLD. These results could prove valuable for predicting patients at risk of developing NAFLD.

Physical activity intervention for non-diabetic patients with non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease nowadays. Changes in diet and lifestyle have led to a dramatic increase in the prevalence of NAFLD around the world. This meta-analysis is to investigate the efficacy of physical activity intervention on liver-specific endpoints in the population with NAFLD, including hepatic enzyme, serum lipid, glucose metabolism and intra-hepatic lipid. METHODS: PubMed and China National Knowledge Infrastructure (CNKI) databases were searched for randomized clinical trials of physical activity intervention on NAFLD patients through April 20th, 2019. Effect sizes were reported as standardized mean difference (SMD) and 95% confidence intervals (CI). Quality of included studies was assessed according to the Cochrane risk of bias tool. Meta-analyses were conducted using random-effect or fixed-effect models depending on the significance of heterogeneity. Subgroup analyses according to types and duration of physical activity were conducted to investigate clinical variability. RESULTS: Nine studies with a cumulative total of 951 participants met selection criteria. Physical activity was found associated with small reductions in hepatic enzyme parameters: ALT (SMD -0.17, 95% CI:-0.30 to - 0.05), AST (SMD -0.25, 95% CI: - 0.38, - 0.13) and GGT (SMD -0.22, 95% CI: - 0.36, - 0.08). Significant small improvements were also found in serum lipid parameters including TC (SMD = - 0.22, 95% CI: - 0.34, - 0.09), TG (SMD = - 0.18, 95% CI: - 0.31 to - 0.06) and LDL-C (SMD = - 0.26, 95% CI: - 0.39 to - 0.13). Significant improvement was also found in intra-hepatic lipid content (SMD = - 0.21, 95% CI: - 0.36 to - 0.06) There was no difference between physical intervention group and control group in HDL and three glucose metabolism parameters. Subgroup analysis suggested both aerobic exercise alone and resistance exercise alone can improve most liver function and longer period of exercise generally had better improvement effect. CONCLUSIONS: Our findings suggest that physical activity alone can only slightly improve hepatic enzyme levels, most serum lipid levels and intra-hepatic lipid content in non-diabetic patients with NAFLD.

The role of hepatitis B infection in anti-tuberculosis drug-induced liver injury: a meta-analysis of cohort studies.

Drug-induced liver injury (DILI) is a common adverse drug reaction leading to the interruption of tuberculosis (TB) therapy. We aimed to identify whether the hepatitis B virus (HBV) infection would increase the risk of DILI during first-line TB treatment. A meta-analysis of cohort studies searched in PubMed, Web of Science and China National Knowledge Infrastructure was conducted. Effect sizes were reported as risk ratios (RRs) and 95% confidence intervals (CIs) and calculated by R software. Sixteen studies with 3960 TB patients were eligible for analysis. The risk of DILI appeared to be higher in TB patients co-infected with HBV (RR 2.66; 95% CI 2.13-3.32) than those without HBV infection. Moreover, patients with positive hepatitis B e antigen (HBeAg) were more likely to develop DILI (RR 3.42; 95% CI 1.95-5.98) compared to those with negative HBeAg (RR 2.30; 95% CI 1.66-3.18). Co-infection with HBV was not associated with a higher rate of anti-TB DILI in latent TB patients (RR 4.48; 95% CI 0.80-24.99). The effect of HBV infection on aggravating anti-TB DILI was independent of study participants, whether they were newly diagnosed with TB or not. Besides, TB and HBV co-infection patients had a longer duration of recovery from DILI compared to non-co-infected patients (SMD 2.26; 95% CI 1.87-2.66). To conclude, the results demonstrate that HBV infection would increase the risk of DILI during TB therapy, especially in patients with positive HBeAg, and close liver function monitoring is needed for TB and HBV co-infection patients.

Analysis of lifetime death probability for major causes of death among residents in China.

BACKGROUND: Cumulative mortality rate and cumulative mortality risk are two commonly used indicators to measure the impact and severity of diseases. However, they are calculated during a defined life span and assume the subject does not die from other causes. This study aims to use a new indicator, lifetime death probability (LDP), to estimate the lifetime death probabilities for the top five leading causes of death in China and explore the regional differences and trends over time. METHODS: LDPs were calculated using a probability additive formula and abridged life tables. RESULTS: In 2014, LDPs for heart disease, cerebrovascular disease, malignancy, respiratory disease, and injury and poisoning were 24.4, 23.7, 19.2, 15.5, and 5.3%, respectively. The LDPs for heart disease and malignancy increased by 7.3 and 0.5%, respectively, compared to those from 2004 to 2005. In contrast, the LDPs for cerebrovascular and respiratory disease decreased by 1.0 and 3.9%, respectively, compared to those in 2004-2005. Across the eastern, central and western regions, malignancy had the highest LDP in the eastern region, cerebrovascular and heart diseases in the central region, and respiratory diseases, and injury and poisoning in the western region. CONCLUSIONS: LDP is an effective indicator for comparing health outcomes and can be applied for future disease surveillance. Heart disease and malignancy were the two most common causes of death in China, but with regional differences. There is a need to implement targeted measures to prevent chronic diseases in different regions.

Circulating Iron Levels Interaction with Central Obesity on the Risk of Nonalcoholic Fatty Liver Disease: A Case-Control Study in Southeast China.

OBJECTIVES: We aimed to evaluate the associations between body iron stores and the risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese population and explore whether this effect may be modified by other factors. METHODS: A 1: 1 frequency-matched case-control study was conducted, including 482 NAFLD cases and 490 gender- and age-matched controls. Serum levels of ferritin, hepcidin, and C-reactive protein were measured. RESULTS: Multivariate logistic regression analysis showed that hepcidin was not associated with NAFLD risk; however, elevated serum ferritin was significantly associated with increased risk of NAFLD (adjusted OR 1.619, 95% CI 1.158-2.267), and hepcidin:ferritin ratio was significantly associated with decreased risk of NAFLD -(OR-adjusted 0.702, 95% CI 0.501-0.984). When stratified by gender, a significant association was found between elevated serum ferritin and hepcidin:ferritin ratio and NAFLD only for women (ORadjusted 2.131, 95% CI 1.151-3.944 and ORadjusted 0.414, 95% CI 0.219-0.781, respectively). A significant multiplicative interaction between central obesity and elevated serum hepcidin was observed (p < 0.05). CONCLUSIONS: Elevated serum ferritin and hepcidin:ferritin ratio are associated with NAFLD in a Chinese population. Although serum hepcidin is not associated with NAFLD, it may augment the risk effect of central obesity on NAFLD.

Oolong tea consumption and its interactions with a novel composite index on esophageal squamous cell carcinoma.

BACKGROUND: No previous study has investigated the association between oolong tea consumption and esophageal squamous cell carcinoma (ESCC), we aim to elucidate the association between oolong tea consumption and ESCC and its joint effects with a novel composite index. METHODS: In a hospital-based case-control study, 646 cases of ESCC patients and 646 sex and age matched controls were recruited. A composite index was calculated to evaluate the role of demographic characteristics and life exposure factors in ESCC. Unconditional logistic regression was used to calculate the point estimates between oolong tea consumption and risk of ESCC. RESULTS: No statistically significant association was found between oolong tea consumption and ESCC (OR = 1.39, 95% CI: 0.94-2.05). However, drinking hot oolong tea associated with increased risk of ESCC (OR = 1.60, 95% Cl: 1.06-2.41). Furthermore, drinking hot oolong tea increased ESCC risk in the high-risk group (composite index> 0.55) (OR = 3.14, 95% CI: 1.93-5.11), but not in the low-risk group (composite index≤0.55) (OR = 1.16, 95% CI: 0.74-1.83). Drinking warm oolong tea did not influence the risk of ESCC. CONCLUSIONS: No association between oolong tea consumption and risk of ESCC were found, however, drinking hot oolong tea significantly increased the risk of ESCC, especially in high-risk populations.

[Case-control study of the relationship between dietary fatty acids intake and non-alcoholic fatty liver disease in Nanping City, 2015-2017].

OBJECTIVE: To explore the relationship between different kinds of dietary fatty acids intake and non-alcoholic fatty liver disease(NAFLD). METHODS: A 1↿ frequency matched case-control study was conducted among 546 NAFLD patients diagnosed by ultrasound as case group, 546 people without NAFLD randomly selected and matched by sex and age(±5) as control group from April 2015 to August 2017 in Nanping first hospital. The data was obtained from participants using structured questionnaires during face-to-face interviews. Information on dietary intake was collected using semi-quantitative food frequency questionnaires. Residual method was used to derive energy-adjusted variable, unconditional Logistic regression was used to estimate odds ratios(OR) and their 95% CI. RESULTS: The NAFLD group consumed a significantly higher amount of fatty acid(FAs), saturated fatty acid(SFAs), mono-unsaturatedfattyacids(MUFAs), poly-unsaturated fatty acids(PUFAs), n-3 PUFAs, n-6 PUFAs, C16↿, C18↿, C16↿, C18↿, C18↿ and C18↿. Multivariate unconditional Logistic regression analysis indicated that daily intake of total fatty acids, MUFAs, n-6 PUFAs, C18↿, C18↿ more than 98. 96 g/d, 38. 83 g/d, 26. 23 g/d, 33. 55 g/d and 24. 91 g/d respectively, were the risk factors for NAFLD. The adjusted ORs and 95% CI were 2. 26(1. 49-3. 44), 1. 93(1. 29-2. 88), 5. 13(3. 40-7. 76), 1. 82(1. 22-2. 79) and 5. 24(3. 40-7. 76). Daily intake of C20↿, C22↿ in 0. 07-0. 09 g/d, 0. 01-0. 02 g/d were the protective factors for NAFLD. The adjusted ORs and 95% CI were 0. 58(0. 39-0. 85) and 0. 64(0. 43-0. 94). CONCLUSION: Daily intake of total fatty acids, MUFAs, n-6 PUFAs, C18↿, C18↿ more than 98. 96, 38. 83, 26. 23, 33. 55 and 24. 91 g/d respectively, were the risk factors for NAFLD. Daily intake of C20↿, C22↿ in 0. 07-0. 09 g/d, 0. 01-0. 02 g/d respectively, were the protective factors for NAFLD.

Multiple MicroRNAs Ameliorate Hepatocyte Steatosis and Injury by Suppressing FABP1 Expression.

BACKGROUND/AIMS: Liver fatty acid-binding protein (FABP1) is a key regulator of hepatic lipid metabolism. MicroRNAs (miRNAs) are thought to be involved in nonalcoholic fatty liver disease (NAFLD), and the underlying mechanism is largely unclear. We investigated whether miRNAs influence hepatocyte steatosis by regulating the FABP1 gene. METHODS: Candidate FABP1-targeting miRNAs were evaluated using luciferase reporter assay. FABP1 expression was measured using western blotting and quantitative reverse transcription-PCR. Intracellular lipid accumulation was measured based on Oil Red O staining and intracellular triglyceride content. Hepatocyte injury was evaluated based on culture supernatant levels of alanine aminotransferase, aspartate aminotransferase, and intracellular adenosine triphosphate, and mitochondrial membrane potential. RESULTS: Dicer1 knockdown significantly elevated FABP1 expression. In total, 68 miRNAs potentially targeting FABP1 were selected; of these, miR-3941, miR-4517, and miR-4672 directly targeted the FABP1 3' untranslated region. Mimics of the three miRNAs substantially repressed FABP1 expression at translational level and led to HepG2 cell resistance to steatosis and cell injury induced by free fatty acids mixture, which rescue of FABP1 overexpression reversed. CONCLUSION: Our findings identify a novel mechanism by which miRNAs protect against hepatocyte steatosis and injury by downregulating FABP1 expression.

Hepatitis B Virus X Protein Induces Hepatic Steatosis by Enhancing the Expression of Liver Fatty Acid Binding Protein.

UNLABELLED: Hepatitis B virus (HBV) has been implicated as a potential trigger of hepatic steatosis although molecular mechanisms involved in the pathogenesis of HBV-associated hepatic steatosis still remain elusive. Our prior work has revealed that the expression level of liver fatty acid binding protein 1 (FABP1), a key regulator of hepatic lipid metabolism, was elevated in HBV-producing hepatoma cells. In this study, the effects of HBV X protein (HBx) mediated FABP1 regulation on hepatic steatosis and the underlying mechanism were determined. mRNA and protein levels of FABP1 were measured by quantitative RT-PCR (qPCR) and Western blotting. HBx-mediated FABP1 regulation was evaluated by luciferase assay, coimmunoprecipitation, and chromatin immunoprecipitation. Hepatic lipid accumulation was measured by using Oil-Red-O staining and the triglyceride level. It was found that expression of FABP1 was increased in HBV-producing hepatoma cells, the sera of HBV-infected patients, and the sera and liver tissues of HBV-transgenic mice. Ectopic overexpression of HBx resulted in upregulation of FABP1 in HBx-expressing hepatoma cells, whereas HBx abolishment reduced FABP1 expression. Mechanistically, HBx activated the FABP1 promoter in an HNF3ß-, C/EBPα-, and PPARα-dependent manner, in which HBx increased the gene expression of HNF3ß and physically interacted with C/EBPα and PPARα. On the other hand, knockdown of FABP1 remarkably blocked lipid accumulation both in long-chain free fatty acids treated HBx-expressing HepG2 cells and in a high-fat diet-fed HBx-transgenic mice. Therefore, FABP1 is a key driver gene in HBx-induced hepatic lipid accumulation via regulation of HNF3ß, C/EBPα, and PPARα. FABP1 may represent a novel target for treatment of HBV-associated hepatic steatosis. IMPORTANCE: Accumulating evidence from epidemiological and experimental studies has indicated that chronic HBV infection is associated with hepatic steatosis. However, the molecular mechanism underlying HBV-induced pathogenesis of hepatic steatosis still remains to be elucidated. In this study, we found that expression of liver fatty acid binding protein (FABP1) was dramatically increased in the sera of HBV-infected patients and in both sera and liver tissues of HBV-transgenic mice. Forced expression of HBx led to FABP1 upregulation, whereas knockdown of FABP1 remarkably diminished lipid accumulation in both in vitro and in vivo models. It is possible that HBx promotes hepatic lipid accumulation through upregulating FABP1 in the development of HBV-induced nonalcoholic fatty liver disease. Therefore, inhibition of FABP1 might have therapeutic value in steatosis-associated chronic HBV infection.

Independent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China.

BACKGROUND: The purpose of this study was to explore the effects of CYP2C19 gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population. METHODS: A 1:2 frequency-matched case control study of 285 patients and 570 controls was conducted from June 2010 to May 2011 in AnXi of Fujian province, China. Environmental factors were investigated using a self-administered questionnaire and genotypes were determined using polymerase chain reaction restriction fragment length polymorphism based methods. Unconditional logistic regression models were used for statistical evaluation. RESULTS: Current or former smoking, consumption of pickled vegetables or hot beverages/food, having a first degree relative with ESCC and history of reflux esophagitis were significantly associated with increased ESCC risk, whereas tea drinking and consumption of fresh vegetables and fruits were significantly associated with decreased risk. The CYP2C19*2 GA/AA genotype was significantly more prevalent in ESCC patients and individuals with at least one copy of the CYP2C19*2 A allele had a 3.19-fold increased risk (adjusted 95% confidence interval (CI): 2.21-4.61, P < 0.001) of ESCC compared with those without this allele. We found no significant associations between CYP2C19*3 genotypes and ESCC. The Cyp2C19*2 polymorphism appeared to have a multiplicative joint effect with tea drinking and hot beverage/food consumption (gene-tea drinking: P(interaction) = 0.042; hot beverage/food consumption: P(interaction) = 6.98 × 10(-6)) and an additive joint effect with pickled vegetable consumption (interaction contrast ratio = 1.96, 95% CI: 0.12-3.80). CONCLUSIONS: Our findings suggest that the CYP2C19*2 polymorphism plays an important role in the development of ESCC in the Chinese population, modified by tea drinking and consumption of pickled vegetables or hot beverages/food. Further studies are warranted to confirm our results.

Spatial-temporal analysis of hepatitis B in Fujian Province, China in 2012-2021.

Background: Fujian Province has one of the highest reported incidences of hepatitis B virus infection in China. This study aimed to provide a theoretical framework for preventing and controlling hepatitis B in Fujian Province, and to assess the trends and the spatial-temporal distribution patterns of hepatitis B in this region. Methods: Data on hepatitis B cases were extracted from the National Notifiable Infectious Disease Surveillance System. Spatial autocorrelation analysis, trend surface analysis, and spatial-temporal scanning statistics were used to identify the spatial and aggregation patterns at the county level. The Joinpoint was used to assess the reported incidence trends. Results: The average reported incidence of hepatitis B in Fujian from 2012 to 2021 was 14.46/10,000 population, with 583,262 notified cases. The age-adjusted reported incidence of hepatitis B decreased from 17.44/10,000 population in 2012 to 11.88/10,000 population in 2021, with an average reduction in the annual percentage change of 4.5%. There were obvious spatial-temporal aggregation characteristics in hepatitis B cases, and a high-incidence area was located in eastern Fujian. Spatio-temporal scanning statistics revealed four levels of aggregation of hepatitis B reporting rates. The first level of aggregation area included Minhou, Gulou, Jin'an, Taijiang, and nine other districts and counties. Conclusion: The incidence of hepatitis B is declining in Fujian Province. Spatial clusters of hepatitis B cases in Fujian Province were identified, and high-risk areas in eastern Fujian still exist. Closely monitoring the general patterns in the occurrence of hepatitis B and implementing focused control and preventative strategies are important.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma.

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

The roles of HBV infection and host factors in ultrasound-diagnosed fatty liver: a case-control study.

BACKGROUND/AIMS: The present study is to evaluate the roles of HBV infection, host factors and their interactions in the development of ultrasound-diagnosed fatty liver in Fujian province of China, a highly HBV endemic area. METHODOLOGY: From June 2007 to May 2008, 527 ultrasound-diagnosed fatty liver patients and 1042 controls were ultrasonically diagnosed in this hospital-based case-control study. Their demographic, anthropometric, biochemical, behavioral factors and HBV markers were compared, and factors associated with fatty liver were determined by multivariate logistic regression analysis. RESULTS: Multivariate ORs and 95% confidence intervals (Cls) of fatty liver were 3.96 (2.10-7.48) for HBsAg positivity, 2.97 (1.78-4.94) for HBsAg negativity with antibodies positivity (either anti-HBe or anti-HBc or both), 1.66 (1.10-2.51) for low alcohol consumption, 7.09 (4.28- 11.75) for obesity, 3.19 (1.75-5.81) for reduced high density lipoprotein cholesterol (HDL-C), 2.17 (1.00-4.72) for elevated fasting plasma glucose (FPG), 2.71 (1.72-4.27) for hypertriglyceridemia, 9.19 (4.32-19.57) for hypertension, and 2.89 (1.86-4.48) for hyperuricemia. Furthermore, synergistic interactions on the additive model were observed between HBV infection and obesity, hypertriglyceridemia, reduced HDL-C, and hyperuricemia with regard to the risk of fatty liver. CONCLUSIONS: Ultrasound-diagnosed fatty liver in Fujian province of China is closely associated with HBV infection, low alcohol consumption, obesity, and other features of the metabolic syndrome. In addition, HBV infection was synergistic with obesity, hypertriglyceridemia, reduced HDL-C, and hyperuricemia as far as the risk of fatty liver concerned.

Effect of Percutaneous Endoscopic Gastrostomy on Quality of Life after Chemoradiation for Locally Advanced Nasopharyngeal Carcinoma: A Cross-Sectional Study.

(1) Background: Prophylactic percutaneous endoscopic gastrostomy (PEG) maintained nutritional status and improved survival of patients with locally advanced nasopharyngeal carcinoma (LA-NPC). However, the role of PEG in patients' quality of life (QoL) is still controversial. We aimed to investigate the effect of PEG on the QoL of patients with LA-NPC without progression. (2) Methods: Patients with LA-NPC between 1 June 2010 and 30 June 2014 in Fujian Cancer Hospital were divided into PEG and non-PEG groups. The QoL Questionnaire core 30 (QLQ-C30), incidence of adverse effects, weight, and xerostomia recovery were compared between the two groups of patients without progression as of 30 June 2020. (3) Results: No statistically significant difference in the scores of each QLQ-C30 scale between the two groups (p > 0.05). The incidence of xerostomia was higher in the PEG group than in the non-PEG group (p = 0.044), but the association was not seen after adjusting for gender, age, T, and N stage (OR: 0.902, 95%CI: 0.485−1.680). No significant difference in the incidence of other adverse effects as well as in weight and dry mouth recovery (p > 0.05). (4) Conclusion: PEG seems not to have a detrimental effect on long-term Qol, including the self-reported swallowing function of NPC patients without progressive disease.