Hemodynamic parameters and diabetes mellitus in community-dwelling middle-aged adults and elders: a community-based study.

Hemodynamic parameters have been correlated with stroke, hypertension, and arterial stenosis. While only a few small studies have examined the link between hemodynamics and diabetes mellitus (DM). This case-control study enrolled 417 DM patients and 3475 non-DM controls from a community-based cohort. Peak systolic velocity (PSV), end-diastolic velocity (EDV), blood flow velocity (MFV), pulsatility index (PI), and the resistance index (RI) of the common carotid arteries were measured by color Doppler ultrasonography. Generalized linear regression analyses showed that as compared to the non-DM controls, the age-sex-adjusted means of PSV, EDV, and MFV were - 3.28 cm/sec, - 1.94 cm/sec, and - 2.38 cm/sec, respectively, lower and the age-sex-adjusted means of RI and PI were 0.013 and 0.0061, respectively, higher for the DM cases (all p-values < 0.0005). As compared to the lowest quartiles, the multivariable-adjusted ORs of DM for the highest quartiles of PSV, EDV, MFV, RI, and PI were 0.59 (95% confidence interval [CI] 0.41-0.83), 0.45 (95% CI 0.31-0.66), 0.53 (95% CI 0.37-0.77), 1.61 (95% CI 1.15-2.25), and 1.58 (95% CI 1.12-2.23), respectively. More importantly, the additions of EDV significantly improved the predictabilities of the regression models on DM. As compared to the model contained conventional CVD risk factors alone, the area under the receiver operating curve (AUROC) increased by 1.00% (95% CI 0.29-1.73%; p = 0.0059) and 0.80% (95% CI 0.15-1.46%; p = 0.017) for models that added EDV in continuous and quartile scales, respectively. Additionally, the additions of PSV and MFV also significantly improved the predictabilities of the regression models (all 0.01 < p-value < 0.05). This study reveals a significant correlation between DM and altered hemodynamic parameters. Understanding this relationship could help identify individuals at higher risk of DM and facilitate targeted preventive strategies to reduce cardiovascular complications in DM patients.

Predictability of Cardiovascular Risk Scores for Carotid Atherosclerosis in Community-Dwelling Middle-Aged and Elderly Adults.

Background: The assessment of future risk of cardiovascular diseases (CVD) is strongly recommended for all asymptomatic adults without CVD history. Carotid atherosclerosis (CA) is a preclinical phenotype of CVDs. However, data on estimated future CVD risks with respect to preclinical atherosclerosis are limited. This community-based study aimed to assess the relationships between predicted CVD risks and CA. Methods: We enrolled 3908 subjects aged 40-74 years without CVD history and calculated their 10-year CVD risks using the Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE). Carotid plaque (CP) at the extracranial carotid arteries was determined by high-resolution B-mode ultrasonography and further classified into mild or advanced CA. Results: The means of FRS for CP-negative and mild and advanced CA were 9.0%, 14.4%, and 22.1%, respectively (p-value < 0.0001). The corresponding values for PCE score were 4.8%, 8.8%, and 15.0%, respectively (p-value < 0.0001). The odds ratios (ORs) of having CP per 5.0% increase in FRS and PCE score were 1.23 (95% CI, 1.19-1.28) and 1.36 (95% CI, 1.28-1.44), respectively. The corresponding values of having advanced CA were 1.24 (95% CI, 1.19-1.29) and 1.38 (95% CI, 1.30-1.48), respectively. Among the models of FRS or PCE plus other conventional CVD risk factors, the FRS + age model had the highest discrimination for the presence of CP (AUROC, 0.7533; 95% CI, 0.7375-0.7691) as well as for the presence of advanced CA (AUROC, 0.8034; 95% CI, 0.7835-0.8232). The calibration of the FRS + age models for the presences of CP and advanced CA was excellent (χ2 = 8.45 [p = 0.49] and 10.49 [p = 0.31], respectively). Conclusions: Estimated future CVD risks were significantly correlated with risks of having CA. Both FRS and PCE had good discrimination for the presences of CP and advanced CA.

Common Genetic Variants of Response to Hepatitis B Vaccines Correlate with Risks of Chronic Infection of Hepatitis B Virus: A Community-Based Case-Control Study.

Hepatitis B (HB) vaccination effectively reduces the risks of chronic infection with the hepatitis B virus (HBV). It is unknown whether there is a common genetic determinant for response to the HB vaccine and susceptibility to chronic HBV infection. This case-control study, which included 193 chronic HBV carriers and 495 non-carriers, aimed to explore the effects of the most significant single nucleotide polymorphisms (SNPs) in response to the HB vaccine on the risks of chronic HBV infection. Out of 13 tested SNPs, the genotype distributions of four SNPs at the human leukocyte antigen (HLA) class II region, including rs34039593, rs614348, rs7770370, and rs9277535, were significantly different between HBV carriers and non-carriers. The age-sex-adjusted odds ratios (OR) of chronic HBV infection for rs34039593 TG, rs614348 TC, rs7770370 AA, and rs9277535 AA genotypes were 0.51 (95% confidence interval [CI], 0.33-0.79; p = 0.0028), 0.49 (95% CI, 0.32-0.75; p = 6.5 × 10-4), 0.33 (95% CI, 0.18-0.63; p = 7.4 × 10-4), and 0.31 (95% CI, 0.14-0.70; p = 0.0043), respectively. Multivariable analyses showed that rs614348 TC and rs7770370 AA genotypes were significantly independent protectors against chronic HBV infection. The multivariable-adjusted ORs for subjects with none, either one, or both of the protective genotypes were 1.00 (referent), 0.47 (95% CI: 0.32-0.71; p = 3.0 × 10-4), and 0.16 (95% CI: 0.05-0.54; p = 0.0032), respectively. Among eight HBeAg-positive carriers, only one of them carried a protective genotype. This study shows that response to the HB vaccine and susceptibility to chronic HBV infection share common genetic determinants and indicates that HLA class II members are the main responsible host genetic factors.

Effects of a 12-week walking intervention on circulating lipid profiles and adipokines in normal weight and abdominal obese female college students.

Background/objectives: Regular exercise such as aerobic exercise has been shown to reduce the risk of some diseases such as cardiovascular disease (CVD). However, only few studies have investigated the impact of regular aerobic exercise on non-obese and overweight/obese persons. Therefore, this study was designed to compare the effect of a 12-week 10,000 steps a day walking intervention on the body composition, serum lipids, adipose tissue function, and obesity-associated cardiometabolic risk between normal weight and overweight/obese female college students. Methods: Ten normal weight (NWCG) and 10 overweight/obese (AOG) individuals were recruited in this study. Both groups performed a regular 10,000 steps a day walk for 12 weeks. Their blood pressure, body mass index, waist-to-hip ratio, and blood lipid profiles were evaluated. Moreover, serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay. Results: Our results revealed that triglyceride (TG), TG/high-density lipoprotein cholesterol (HDL-C) ratio and leptin were significantly reduced in the AOG group after the 12-week walking intervention. However, total cholesterol, HDL-C, and adiponectin/leptin ratio were significantly increased in the AOG group. There was little or no change in these variables in the NWCG group after the 12-week walking intervention. Conclusions: Our study demonstrated that a 12-week walking intervention may help improve cardiorespiratory fitness and obesity-associated cardiometabolic risk by decrease resting heart rate, modulating blood lipid profiles, and inducing adipokine alterations in obese individuals. Therefore, our research encourages obese young adults to improve their physical health by participating in a 12-week walking program of 10,000 steps a day.

A systematic analysis of the global and regional burden of colon and rectum cancer and the difference between early- and late-onset CRC from 1990 to 2019.

The burden of colorectal cancer (CRC) varies substantially across different geographical locations. However, there was no further quantitative analysis of regional social development and the disease burden of CRC. In addition, the incidence of early- and late-onset CRC has increased rapidly in developed and developing regions. The main purpose of this study was to investigate the trends in CRC burden across different regions, in addition to the epidemiological differences between early and late-onset CRC and their risk factors. In this study, estimated annual percentage change (EAPC) was employed to quantify trends in age-standardized incidence rate (ASIR), mortality rate, and disability-adjusted life-years. Restricted cubic spline models were fitted to quantitatively analyze the relationship between trends in ASIR and Human Development Index (HDI). In addition, the epidemiological characteristics of early- and late-onset CRC were investigated using analyses stratified by age groups and regions. Specifically, meat consumption and antibiotic use were included to explore the differences in the risk factors for early- and late-onset CRC. The quantitative analysis showed that the ASIR of CRC was exponentially and positively correlated with the 2019 HDI in different regions. In addition, the growing trend of ASIR in recent years varied substantially across HDI regions. Specifically, the ASIR of CRC showed a significant increase in developing countries, while it remained stable or decreased in developed countries. Moreover, a linear correlation was found between the ASIR of CRC and meat consumption in different regions, especially in developing countries. Furthermore, a similar correlation was found between the ASIR and antibiotic use in all age groups, with different correlation coefficients for early-onset and late-onset CRC. It is worth mentioning that the early onset of CRC could be attributable to the unrestrained use of antibiotics among young people in developed countries. In summary, for better prevention and control of CRC, governments should pay attention to advocate self-testing and hospital visits among all age groups, especially among young people at high risk of CRC, and strictly control meat consumption and the usage of antibiotics.

Associations of genetic markers of diabetes mellitus with carotid atherosclerosis: a community-based case-control study.

BACKGROUND: Diabetes mellitus (DM) is a well-established determinant of atherosclerosis and cardiovascular diseases (CVD). Recently, genome-wide association studies (GWAS) identified several single nucleotide polymorphism (SNP) significantly correlated with DM. The study aimed to explore the relationships of the top significant DM SNPs with carotid atherosclerosis (CA). METHODS: We used a case-control design and randomly selected 309 cases and 439 controls with and without, respectively, carotid plaque (CP) from a community-based cohort. Eight recent GWAS on DM in East Asians reported hundreds of SNPs with genome-wide significance. The study used the top significant DM SNPs, with a p-value < 10-16, as the candidate genetic markers of CA. The independent effects of these DM SNPs on CA were assessed by multivariable logistic regression analyses to control the effects of conventional cardio-metabolic risk factors. RESULTS: Multivariable analyses showed that, 9 SNPs, including rs4712524, rs1150777, rs10842993, rs2858980, rs9583907, rs1077476, rs7180016, rs4383154, and rs9937354, showed promising associations with the presence of carotid plaque (CP). Among them, rs9937354, rs10842993, rs7180016, and rs4383154 showed significantly independent effects. The means (SD) of the 9-locus genetic risk score (9-GRS) of CP-positive and -negative subjects were 9.19 (1.53) and 8.62 (1.63), respectively (p < 0.001). The corresponding values of 4-locus GRS (4-GRS) were 4.02 (0.81) and. 3.78 (0.92), respectively (p < 0.001). The multivariable-adjusted odds ratio of having CP for per 1.0 increase in 9-GRS and 4-GRS were 1.30 (95% CI 1.18-1.44; p = 4.7 × 10-7) and 1.47 (95% CI 1.74-9.40; p = 6.1 × 10-5), respectively. The means of multi-locus GRSs of DM patients were similar to those of CP-positive subjects and higher than those of CP-negative or DM-negative subjects. CONCLUSIONS: We identified 9 DM SNPs showing promising associations with CP. The multi-locus GRSs may be used as biomarkers for the identification and prediction of high-risks subjects for atherosclerosis and atherosclerotic diseases. Future studies on these specific SNPs and their associated genes may provide valuable information for the preventions of DM and atherosclerosis.

Combined effects of hypertension, hyperlipidemia, and diabetes mellitus on the presence and severity of carotid atherosclerosis in community-dwelling elders: A community-based study.

BACKGROUND: Hypertension, hyperlipidemia, and diabetes mellitus (DM) are common cardiovascular disease (CVD) comorbidities and well-known major determinants of atherosclerosis. However, their combined effects and relative contributions have not been well explored. This study aimed to characterize the characteristics of carotid atherosclerosis and dissect the relative effects of these common CVD comorbidities on the presence and severity of carotid atherosclerosis in community-dwelling elderly individuals. METHODS: We enrolled 817 elders from communities in northern Taiwan. We evaluated their cardiovascular risk profiles and scanned their extracranial carotid arteries using high-resolution ultrasonography systems. RESULTS: The prevalence rates for hypertension, hyperlipidemia, and DM were 45.4%, 37.1%, and 16.8%, respectively. Sixty-two (7.6%) and 188 (23.0%) elderly had all three and two of these common CVD comorbidities, respectively. The prevalent rates of carotid plaque and moderate-to-severe atherosclerosis were 62.9% and 35.5%, respectively. The percentages of one or more common CVD comorbidities in elders with carotid plaque and moderate-to-severe atherosclerosis were 78.2% and 83.1%, respectively. Multivariate analyses showed that the number of common CVD comorbidities was the most predictive determinant. Multivariable-adjusted odds ratios (ORs) per comorbidity for the presence of carotid plaque and advanced carotid atherosclerosis were 1.52 (95% CI, 1.28-1.81) and 1.57 (95% CI, 1.28-1.93), respectively. Models containing hypertension and DM were the second most predictive. Combinatory analyses showed distinct relationship patterns between carotid atherosclerosis and hypertension, hyperlipidemia, and DM. Hypertension was significantly correlated with higher ORs for the presence of carotid plaque and advanced carotid atherosclerosis but not for hyperlipidemia. CONCLUSION: Carotid plaques are highly prevalent in community-dwelling elders. The number of common CVD comorbidities was the most predictive determinant of carotid plaques and advanced carotid atherosclerosis. Our results indicate that to reduce the impact of atherosclerotic diseases, blood pressure controls precede the control of blood lipids and glucose in the community-dwelling elders.

Goji Ferment Ameliorated Acetaminophen-Induced Liver Injury in vitro and in vivo.

This study aimed to investigate the hepatoprotective effects of lyophilized powder of goji ferment (LPGF) against acetaminophen (APAP)-induced hepatic damage in Hep3B cells and in mice. Eleven strains of lactic acid bacteria (LAB) were selected and their hepatoprotection against APAP-induced cellular damage in Hep3B cell line was evaluated. Four strains of LAB, including BCRC11652 (Leuconostoc mesenteroides subsp. mesenteroides), BCRC14619 (Lactobacillus gasseri), KODA-1 (Pediococcus acidilactici), and KODA-2 (Limosilactobacillus fermentum), have hepatoprotective potential against APAP in vitro. Goji significantly stimulated the growth of individual and combined strains of LAB and the optimal fermented condition was the treatment of goji at 10% (w/w) for 24 h. The prepared lyophilized powder of goji ferment (LPGF) containing fifteen combinations of LAB strains was used to explore their hepatoprotection in vitro. LPGF containing all combinations of LAB strains, except for KODA-2, significantly restored APAP-reduced cell viability and improved APAP-increased cellular levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In mice model, LPGF containing BCRC11652, BCRC14619, and KODA-2 was chosen to evaluate its hepatoprotection against APAP-induced liver injury. LPGF at diverse doses have a tendency but no significant improvement on APAP-reduced body weight gain and liver weight. LPGF significantly decreased APAP-increased serum ALT and AST levels in a dose-dependent manner. At the end of experiment, LPGF significantly and dose-dependently reversed APAP-reduced activities of GSH and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase in hepatic tissue. Overall, LPGF was demonstrated to exhibit hepatoprotection against APAP-induced liver injury in vitro and in vivo.

Association of Common Variants in OLA1 Gene with Preclinical Atherosclerosis.

Reactive oxygen species impair the blood vessels, leading to the initiation of atherosclerosis, and migration and proliferation of vascular smooth muscle cells and neovascularization by endothelial cells of vasa vasorum are essential for atherosclerosis development. Obg-like ATPase 1 (OLA1), a negative regulator in cellular responses to oxidative stress, binds to breast cancer susceptibility gene 1 (BRCA1), which protects vascular endothelial and smooth muscle cells against reactive oxygen species. However, it is not known whether OLA1 is genetically correlated with atherosclerosis. Here, we conducted two independent population-based case-control studies to explore the effects of variants in OLA1 genes on preclinical atherosclerosis. A total of 564 and 746 subjects who had thicker and normal carotid intima-media thickness (cIMT), respectively, were enrolled. Among 55 screened SNPs, rs35145102, rs201641962, rs12466587, rs4131583, and rs16862482 in OLA1 showed significant associations with cIMT. SNP rs35145102 is a 3'-utr variant and correlates with the differential expression of OLA1 in immune cells. These five genetic markers form a single closely linked block and H1-ATTGT and H2-GCCTC were the top two most prevalent 5-locus haplotypes. The H1 + H1 genotype negatively and H1 + H2 genotype positively correlated with thicker cIMT. The five identified SNPs in the OLA1 gene showed significant correlations with cIMT. Furthermore, we found that OLA1 was required for migration and proliferation of human aortic endothelial and smooth muscle cells and regulated vascular tube formation by human aortic endothelial cells. Therefore, these genetic variants in the OLA1 gene may serve as markers for risk prediction of atherosclerotic diseases.

Fructus Zanthoxyli extract improves glycolipid metabolism disorder of type 2 diabetes mellitus via activation of AMPK/PI3K/Akt pathway: Network pharmacology and experimental validation.

OBJECTIVE: This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli (FZ) against type 2 diabetes mellitus (T2DM) based on network pharmacology and experimental validation. METHODS: Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry, and gas chromatography-mass spectrometry were used to identify the constituents of FZ. Next, the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases (including Gene Expression Omnibus database and Swiss Target Prediction online database), and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the pathway was verified by in vitro experiments, and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM. RESULTS: A total of 43 components were identified from FZ, and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM. The dug component-target network indicated that PPARA, PPARG, PIK3R3, JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM. Interestingly, the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. In vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in HepG2 cells. Moreover, FZ treatment was able to promote the AMPK and PI3K/Akt expressions in HepG2 cells. CONCLUSION: Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.

The Anti-Proliferative and Apoptotic Effects of Rutaecarpine on Human Esophageal Squamous Cell Carcinoma Cell Line CE81T/VGH In Vitro and In Vivo.

The overall five-year survival rate for patients with esophageal cancer is low (15 to 25%) because of the poor prognosis at earlier stages. Rutaecarpine (RTP) is a bioalkaloid found in the traditional Chinese herb Evodia rutaecarpa and has been shown to exhibit anti-proliferative effect on tumor cells. However, the mechanisms by which RTP confer these effects and its importance in esophageal squamous cell carcinoma treatment remain unclear. Thus, in the present study, we first incubated human esophageal squamous cell carcinoma cell line, CE81T/VGH, with RTP to evaluate RTP's effects on tumor cell growth and apoptosis. We also performed a xenograft study to confirm the in vitro findings. Furthermore, we determined the expression of p53, Bax, bcl-2, caspase-3, caspase-9, and PCNA in CE81T/VGH cells or the tumor tissues to investigate the possible mechanisms. All the effects of TRP were compared with that of cisplatin. The results showed that RTP significantly inhibits CE81T/VGH cell growth, promotes arrest of cells in the G2/M phase, and induces apoptosis. Consistently, the in vivo study showed that tumor size, tumor weight, and proliferating cell nuclear antigen protein expression in tumor tissue are significantly reduced in the high-dose RTP treatment group. Furthermore, the in vitro and in vivo studies showed that RTP increases the expression of p53 and Bax proteins, while inhibiting the expression of Bcl-2 in cancer cells. In addition, RTP significantly increases the expression of cleaved caspase-9 and cleaved caspase-3 proteins in tumor tissues in mice. These results suggest that RTP may trigger the apoptosis and inhibit growth in CE81T/VGH cells by the mechanisms associated with the regulation of the expression of p53, Bax, Bcl-2, as well as caspase-9 and caspase-3.

Serum soluble programmed cell death 1 levels predict spontaneous functional cure in inactive carriers with chronic hepatitis B.

BACKGROUND: Hepatitis B surface antigen (HBsAg) seroclearance is the most important milestone indicating favourable clinical outcomes in patients with chronic hepatitis B (CHB). However, it is difficult to achieve due to the impaired HBV-specific immunity, such as programmed cell death 1 (PD-1)-associated T cell exhaustion. We assessed soluble PD-1 (sPD-1) as a novel seromarker for predicting spontaneous HBsAg loss. METHODS: Serial serum levels of sPD-1 were evaluated in 1046 untreated hepatitis B e antigen (HBeAg)-seronegative individuals who had achieved undetectable serum HBV DNA. Multiple regression analyses were applied to assess associations among baseline and subsequent sPD-1 levels, HBsAg decline during follow-up, and spontaneous HBsAg seroclearance. RESULTS: A total of 390 individuals achieved spontaneous HBsAg seroclearance during 6464.4 person-years of follow-up. Baseline sPD-1 levels were inversely associated with baseline HBsAg levels (qHBsAg) as well as a greater decline in qHBsAg during follow-up. Incidence rates of HBsAg seroclearance were 11.5, 61.7, 96.7 and 151.0 per 1000 person-years for sPD-1 levels of ≥4000, 536-3999, 125-535 and <125 pg/mL, respectively (Ptrend  < 0.0001). Compared with baseline sPD-1 levels ≥4000 pg/mL, the rate ratio (95% CI) of HBsAg seroclearance was 2.1 (1.1-3.9), 3.0 (1.6-5.5) and 5.1 (2.8-9.5), for baseline sPD-1 levels of 536-3999, 125-535 and <125 pg/mL, respectively, after adjustment for sex, age and serum alanine aminotransferase and HBsAg levels. CONCLUSION: sPD-1 level is a novel marker which independently predicts spontaneous HBsAg seroclearance of HBeAg-negative inactive CHB patients with undetectable HBV DNA. (word count: 234, <250).

Prevalences of diabetes mellitus and carotid atherosclerosis and their relationships in middle-aged adults and elders: a community-based study.

BACKGROUND/PURPOSE: Atherosclerosis and diabetes mellitus (DM) are both severe chronic diseases that cause huge burdens on patients' families and societies. Connections between the two diseases have brought high attention recently, however, population-based study with large sample size was few. The study aimed to explore the relationship between carotid atherosclerosis and DM. METHODS: We enrolled 3908 adults aged 40-74 years from communities and measured their cardio-metabolic profiles and scanned their carotid arteries bilaterally. RESULTS: The overall prevalence rates of carotid plaque and DM were 34.4 and 10.7%, respectively. The age-specific prevalence rates of DM and carotid plaque were nearly linearly correlated in both sexes (both Pearson's correlation coefficient r > 0.97). The prevalence rates of carotid plaque, total plaque number ≥3, maximum diameter stenosis ≥30%, and plaque score ≥3 were 53.6, 24.8, 19.1, and 28.6%, respectively, in DM patients and were 32.1, 9.4, 9.8, and 11.2%, respectively, in non-DM controls. After adjustment for other conventional risk factors, the multivariable-adjusted OR of having carotid plaque was 1.60 (95% CI 1.27-2.01) and were 2.06 (95% CI 1.55-2.75), 1.33 (95% CI 0.99-1.78), and 2.03 (95% CI 1.55-2.65) for total plaque number ≥3, maximum diameter stenosis ≥30%, and plaque score ≥3, respectively. CONCLUSION: We demonstrated that prevalences of DM were linearly correlated with prevalences of carotid plaque and DM patients had higher prevalence rates of carotid plaque and more advanced carotid atherosclerosis than non-DM controls. Our results indicated the need to address the role of DM in atherosclerosis development.

Detection and genetic characterization of the novel torque teno virus group 6 in Taiwanese general population.

Torque teno virus (TTV) is one of the most common human viruses and can infect an individual with multiple genotypes chronically and persistently. TTV group 6 is a recently discovered phylogenetic group first isolated from eastern Taiwan indigenes, but whether the TTV group 6 was also prevalent in the general population still unknown. One hundred and three randomly collected blood samples from general population and 66 TTV positive DNA samples extracted from Taiwan indigenes were included. A group-6-specific PCR was developed for re-screen over TTV positive samples. Two TTV group 6 positive samples from general population were cloned and sequenced for identifying mix-infected TTVs and confirming their classification by maximum-likelihood and Bayesian inference phylogeny. TTV group 6 can be detected in 4.5% (4/89) and 7.6% (5/66) of TTV positive samples from Taiwanese general population and eastern Taiwan indigenes, respectively. Sample VC09 was mix-infected with TTV groups 3 and 6. Sample VC99 was mix-infected with TTV groups 3, 4 and 6. A highly diverse triple overlapping region was observed, which may represent a unique phenomenon of TTV. The group-6-specific PCR can successfully detect TTV group 6. TTV group 6 may be prevalent worldwide regardless of the geographic region and/or ethnic groups.

Genetic variants associated with serum alanine aminotransferase levels among patients with hepatitis C virus infection: A genome-wide association study.

Information on genetic variants associated with elevated serum alanine aminotransferase (ALT) levels remains limited. A genome-wide association study was performed to identify single-nucleotide polymorphisms (SNPs) associated with ALT levels. The ALT-associated SNP was further evaluated for hepatocellular carcinoma (HCC) risk. A cohort of 892 anti-HCV seropositive patients was used for genome-wide SNP array to examine the associations with baseline ALT levels. SNPs <10-5 were further tested for associations with serial ALT levels then validated in 486 anti-HCV seropositives. Multinomial logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals of SNPs associated with ALT. The SNP was evaluated for HCC risk by using Cox's proportional hazards models. After quality control, 803 participants with 564,464 SNPs were included in the analysis. Of these, 12 SNPs were associated with ALT (p < 10-5 ). Among the participants, 158 (19.7%) had ALT persistently ≤15 U/L, 327 (40.7%) ever >15 U/L but never >45 U/L, and 318 (39.6%) ever >45 U/L during follow-up. The rs568800 was associated with serial ALT levels, and this was replicated in the external population significantly (p < .05). The A allele (vs C) of rs568800 was associated with ALT >15 U/L but ≤45 U/L and ALT >45 U/L, with the adjusted ORs of 1.41 (1.11-1.78) and 1.86 (1.34-2.60), respectively. The adjusted HRs for HCC were 2.09 (0.90-4.89) for AC and 2.64 (1.13-6.17) for AA (CC as a reference). In conclusion, the rs568800 was associated with serum ALT levels and HCC risk. Clinical utility should be evaluated among patients who have received antivirals.

Compound Cocktail Inhibits Influenza Viral Pneumonia via Phospholipase Cγ1 Phosphorylation-Related Necroptosis and Partial Autophagy in Natural Killer Cells.

Influenza viral infections are prone to global outbreaks and cause pneumonia in affected populations. High morbidity and mortality caused by pneumonia occur during an influenza pandemic. Antivirals or control of inflammation is the primary means of influenza treatment. A compound cocktail composed of arctiin, daidzein, glycyrrhizic acid, and liquiritin inhibited mouse pneumonia resulting from a PR8 viral infection and caused a weight gain after oral administration. Natural killer cell activating receptors, both Ly49D and Ly49H in the lungs, were increased in the treatment in mice. In H3N2 virus-infected natural killer-92MI cells, the cocktail treatment had different effects on phosphorylation sites of phospholipase Cγ1 (PLCγ1) and killed infected cells through necroptosis or late apoptosis, in which RIP3 was increased and both caspase-3 and phosphorylated-JNK in the cells were downregulated. Acid phosphatase activity in viral-infected natural killer-92MI cells was induced by the compound cocktail treatment, which could be related to the p62 decrease in natural killer-92MI cells. In addition, an autophagic flux induction was observed in alveolar basal epithelial cells (A549). Protein p65, but not phosphorylated-p65, was significantly decreased by the treatment. Our results indicate that the compound cocktail strengthened the phosphorylation of PLCγ1-related necroptosis and partial autophagy in natural killer cells, which could yield an inhibitory effect on viral pneumonia in influenza.