Genome-Wide Association Study of Hepatocellular Carcinoma in Southern Chinese Patients with Chronic Hepatitis B Virus Infection

One of the most relevant risk factors for hepatocellular carcinoma (HCC) development is chronic hepatitis B virus (HBV) infection, but only a fraction of chronic HBV carriers develop HCC, indicating that complex interactions among viral, environmental and genetic factors lead to HCC in HBV-infected patients. So far, host genetic factors have incompletely been characterized. Therefore, we performed a genome-wide association (GWA) study in a Southern Chinese cohort consisting of 95 HBV-infected HCC patients (cases) and 97 HBV-infected patients without HCC (controls) using the Illumina Human610-Quad BeadChips. The top single nucleotide polymorphisms (SNPs) were then validated in an independent cohort of 500 cases and 728 controls. 4 SNPs (rs12682266, rs7821974, rs2275959, rs1573266) at chromosome 8p12 showed consistent association in both the GWA and replication phases (ORcombined = 1.31–1.39; pcombined = 2.71×10−5–5.19×10−4; PARcombined = 26–31%). We found a 2.3-kb expressed sequence tag (EST) in the region using in-silico data mining and verified the existence of the full-length EST experimentally. The expression level of the EST was significantly reduced in human HCC tumors in comparison to the corresponding non-tumorous liver tissues (P<0.001). Results from sequence analysis and in-vitro protein translation study suggest that the transcript might function as a long non-coding RNA. In summary, our study suggests that variations at chromosome 8p12 may promote HCC in patients with HBV. Further functional studies of this region may help understand HBV-associated hepatocarcinogenesis

The Spill-Over Impact of the Novel Coronavirus-19 Pandemic on Medical Care and Disease Outcomes in Non-communicable Diseases: A Narrative Review

OBJECTIVES: The coronavirus-19 (COVID-19) pandemic has claimed more than 5 million lives worldwide by November 2021. Implementation of lockdown measures, reallocation of medical resources, compounded by the reluctance to seek help, makes it exceptionally challenging for people with non-communicable diseases (NCD) to manage their diseases. This review evaluates the spill-over impact of the COVID-19 pandemic on people with NCDs including cardiovascular diseases, cancer, diabetes mellitus, chronic respiratory disease, chronic kidney disease, dementia, mental health disorders, and musculoskeletal disorders. METHODS: Literature published in English was identified from PubMed and medRxiv from January 1, 2019 to November 30, 2020. A total of 119 articles were selected from 6,546 publications found. RESULTS: The reduction of in-person care, screening procedures, delays in diagnosis, treatment, and social distancing policies have unanimously led to undesirable impacts on both physical and psychological health of NCD patients. This is projected to contribute to more excess deaths in the future. CONCLUSION: The spill-over impact of COVID-19 on patients with NCD is just beginning to unravel, extra efforts must be taken for planning the resumption of NCD healthcare services post-pandemic

Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma

© 2014 American Cancer Society. BACKGROUND A current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy with concurrent cisplatin plus adjuvant cisplatin and fluorouracil (PF). In this randomized trial, the authors evaluated the potential therapeutic benefit from changing to an induction-concurrent chemotherapy sequence, replacing fluorouracil with oral capecitabine, and/or using accelerated rather than conventional radiotherapy fractionation. METHODS Patients with stage III through IVB, nonkeratinizing NPC were randomly allocated to 1 of 6 treatment arms. The protocol was amended in 2009 to permit confining randomization to the conventional fractionation arms. The primary endpoint was progression-free survival. Secondary endpoints included overall survival and safety. RESULTS In total, 803 patients were accrued, and 706 patients were randomly allocated to all 6 treatment arms. Comparisons of induction PF versus adjuvant PF did not indicate a significant improvement. Unadjusted comparisons of induction cisplatin and capecitabine (PX) versus adjuvant PF indicated a favorable trend in progression-free survival for the conventional fractionation arm (P = .045); analyses that were adjusted for other significant factors and fractionation reflected a significant reduction in the hazards of disease progression (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.36-0.80) and death (HR, 0.42; 95% CI, 0.25-0.70). Unadjusted comparisons of induction sequences versus adjuvant sequences did not reach statistical significance, but adjusted comparisons indicated favorable improvements by induction sequence. Comparisons of induction PX versus induction PF revealed fewer toxicities (neutropenia and electrolyte disturbance), unadjusted comparisons of efficacy were statistically insignificant, but adjusted analyses indicated that induction PX had a lower hazard of death (HR, 0.57; 95% CI, 0.34-0.97). Changing the fractionation from conventional to accelerated did not achieve any benefit but incurred higher toxicities (acute mucositis and dehydration). CONCLUSIONS Preliminary results indicate that the benefit of changing to an induction-concurrent sequence remains uncertain; replacing fluorouracil with oral capecitabine warrants further validation in view of its convenience, favorable toxicity profile, and favorable trends in efficacy; and accelerated fractionation is not recommended for patients with locoregionally advanced NPC who receive chemoradiotherapy.postprin

Associations of Problematic Internet Use, Weight-Related Self-Stigma, and Nomophobia with Physical Activity: Findings from Mainland China, Taiwan, and Malaysia

Insufficient physical activity is a common problem for university students because they may engage in sedentary lifestyle owing to excessive time spent on their smartphones and social media use. This may result in problematic internet use (PIU) and nomophobia (fear of not having a mobile phone). Moreover, prior evidence shows that weight-related self-stigma is an important factor contributing to low physical activity. Therefore, the present study examined the associations between PIU, nomophobia, and physical activity among university students across mainland China, Taiwan, and Malaysia. Participants (3135 mainland Chinese, 600 Taiwanese, and 622 Malaysian) completed the Bergen Social Media Addiction Scale (BSMAS), Smartphone Application-Based Addiction Scale (SABAS), Nomophobia Questionnaire (NMPQ), Weight Self-Stigma Questionnaire (WSSQ), and International Physical Activity Questionnaire Short Form (IPAQ-SF). The measurement invariance of the assessed questionnaires was supported across the three regions. The present findings analyzed using partial least squares structural equation modeling showed that (i) greater nomophobia was associated with higher levels of physical activity, (ii) greater weight-related self-stigma was associated with higher levels of physical activity, and (iii) greater nomophobia was associated with greater weight-related self-stigma. Although the present findings suggest the possibility that experiencing some level of nomophobia or weight-related self-stigma appears to help improve physical activity, it is not recommended that these be encouraged, but reducing PIU should be targeted as a means to improve physical activit

The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

<p>Abstract</p> <p>Background</p> <p>Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints.</p> <p>Methods</p> <p>Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation.</p> <p>Results</p> <p>By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (<it>p </it>< 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated.</p> <p>Conclusion</p> <p>This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.</p

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe