Interacting and joint effects of triglyceride-glucose index and hypertension on stroke risk in middle-aged and older Chinese adults: a population-based prospective cohort study.

Background: Triglyceride-glucose (TyG) index and hypertension were well-established risk factors for stroke. And TyG index was associated with hypertension. However, no prior study has investigated the interactive effects of the TyG index and hypertension on stroke. This study examined whether hypertension mediates associations of TyG index with incident stroke and the extent of interaction or joint relations of TyG index and hypertension with stroke in middle-aged and older Chinese adults. Methods: The China Health and Retirement Longitudinal Study (CHARLS) is an ongoing nationally representative prospective cohort study initiated in 2011. This cohort study included 9,145 middle-aged and older Chinese adults without stroke at baseline. The eposures were TyG index and the logarithmized product of hypertension, as determined during the baseline health examination. The main outcome was self-reported physician-diagnosed stroke which followed up from June 1, 2011, to June 30, 2018. Results: Of the 9,145 participants, 4,251 were men (46.5%); the mean (SD) age was 59.20 (9.33) years. During a median follow-up of 7.1 years, 637 (7.0%) participants developed stroke. In multivariable-adjusted models, the TyG index was significantly associated with the risk of hypertension [odds ratio (OR) per 1-SD increase, 1.29; 95% CI, 1.19-1.41] and stroke [hazard ratio (HR) per 1-SD increase, 1.16; 95% CI, 1.02-1.33]. Both multiplicative and additive interactions were observed between TyG index and hypertension on stroke (HR for multiplicative: 2.34, 95% CI, 1.57-3.48; Synergy index: 4.13, 95% CI, 2.73-6.25). Mediation analysis showed that 20.0% of the association between TyG index and stroke was mediated through hypertension. Conclusions: This study suggests a synergistic effect of TyG index and hypertension on stroke, and a small proportion of the association between TyG index and stroke was mediated by hypertension, indicating the benefit of coordinated control strategies for both exposures.

Prognostic value of aspartate aminotransferase/alanine aminotransferase ratio in hepatocellular carcinoma after hepatectomy.

BACKGROUND: The prognostic significance of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in hepatocellular carcinoma remains uncertain. The aim of the current study was to evaluate the association between the AST/ALT ratio and prognosis in patients with hepatocellular carcinoma after hepatectomy, and to explore the role of underlying liver diseases as mediators. METHODS: This retrospective study included patients with hepatocellular carcinoma who underwent hepatectomy between January 2014 and January 2018 at two Chinese hospitals. The maximally selected rank statistic and g-computation approach were used to quantify and visualize the association between the AST/ALT ratio and overall survival or recurrence-free survival. The role of mediators (chronic hepatitis B, hepatic steatosis and liver cirrhosis) was analysed. RESULTS: Among the 1519 patients (mean(s.d.) age at baseline, 50.5(11.3) years), 1309 (86.2%) were male. During a median follow-up of 46.0 months, 514 (33.8%) patients died and 358 (23.6%) patients experienced recurrence. The optimal cut-off value for the AST/ALT ratio was 1.4, and the AST/ALT ratio greater than or equal to 1.4 was independently associated with a 39.0% increased risk of death and a 30.0% increased risk of recurrence (overall survival: hazard ratio (HR), 1.39; 95% c.i. 1.15 to 1.68; recurrence-free survival: HR, 1.30; 95% c.i. 1.12 to 1.52) after adjusting for confounders. Chronic hepatitis B significantly mediated the association of the ratio of AST/ALT with both overall survival and recurrence-free survival (20.3% for overall survival; 20.1% for recurrence-free survival). CONCLUSION: The AST/ALT ratio greater than or equal to 1.4 was associated with shorter overall survival and recurrence-free survival in patients with hepatocellular carcinoma after hepatectomy, and chronic hepatitis B may play a role in their association.

Interacting and joint effects of triglyceride-glucose index (TyG) and body mass index on stroke risk and the mediating role of TyG in middle-aged and older Chinese adults: a nationwide prospective cohort study.

BACKGROUND: Individuals who are overweight or obese often develop insulin resistance, mediation of the association between body mass index (BMI) and stroke risk through the triglyceride-glucose index (TyG) seems plausible but has not been investigated. This study aims to examine whether TyG mediates associations of BMI with stroke risk and the extent of interaction or joint relations of TyG and BMI with stroke outcome. METHODS: The China Health and Retirement Longitudinal Study, initiated in 2011, is a nationally representative, ongoing prospective cohort study involving 8 231 middle-aged and older Chinese adults without a stroke history at baseline. Exposures examined include BMI and the TyG, the latter being the logarithmized product of fasting triglyceride and glucose concentrations. The primary study outcome is stroke incidence, as determined through self-reports, with a follow-up period extending from June 1, 2011, to June 30, 2018. RESULTS: Of the 8 231 participants, 3 815 (46.3%) were men; mean (SD) age was 59.23 (9.32) years. During a median follow-up of 7.1 years, 585 (7.1%) participants developed stroke. The TyG was found to mediate the association between BMI and incident stroke, proportions mediated were 16.3% for BMI in the 24.0-27.9 kg/m2 group and 53.8% for BMI ≥ 28.0 kg/m2 group. No significant multiplicative and additive interactions were found between BMI and TyG on incident stroke (Additive: RERI = 1.78, 95% CI - 1.29-4.86; Multiplicative, HR = 1.40, 95% CI 0.86-2.27). HRs for individuals with BMI ≥ 28.0 kg/m2 and quartile 4 of TyG compared with those with BMI < 24.0 kg/m2 and quartile 1 of TyG were 2.05 (95% CI 1.37-3.06) for incident stroke. Combining BMI and TyG enhanced predictive performance for stroke when compared to their individual (AUCBMI+TyG vs AUCBMI vs AUCTyG, 0.602 vs 0.581 vs 0.583). CONCLUSIONS: TyG appeared to be associated with stroke risk and mediates more than 50% of the total association between BMI and stroke in middle-aged and older Chinese adults. Public health efforts aiming at the reduction of body weight might decrease the stroke risk due to insulin resistance and the burden of stroke.

Changes in the triglyceride glucose-body mass index estimate the risk of stroke in middle-aged and older Chinese adults: a nationwide prospective cohort study.

BACKGROUND: Stroke was reported to be highly correlated with the triglyceride glucose-body mass index (TyG-BMI). Nevertheless, literature exploring the association between changes in the TyG-BMI and stroke incidence is scant, with most studies focusing on individual values of the TyG-BMI. We aimed to investigate whether changes in the TyG-BMI were associated with stroke incidence. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. The exposures were changes in the TyG-BMI and cumulative TyG-BMI from 2012 to 2015. Changes in the TyG-BMI were classified using K-means clustering analysis, and the cumulative TyG-BMI was calculated as follows: (TyG-BMI2012 + TyG-BMI2015)/2 × time (2015-2012). Logistic regressions were used to determine the association between different TyG-BMI change classes and stroke incidence. Meanwhile, restricted cubic spline regression was applied to examine the potential nonlinear association of the cumulative TyG-BMI and stroke incidence. Weighted quantile sum regression was used to provide a comprehensive explanation of the TyG-BMI by calculating the weights of FBG, triglyceride-glucose (TG), and BMI. RESULTS: Of the 4583 participants (mean [SD] age at baseline, 58.68 [9.51] years), 2026 (44.9%) were men. During the 3 years of follow-up, 277 (6.0%) incident stroke cases were identified. After adjusting for potential confounders, compared to the participants with a consistently low TyG-BMI, the OR for a moderate TyG-BMI with a slow rising trend was 1.01 (95% CI 0.65-1.57), the OR for a high TyG-BMI with a slow rising trend was 1.62 (95% CI 1.11-2.32), and the OR for the highest TyG-BMI with a slow declining trend was 1.71 (95% CI 1.01-2.89). The association between the cumulative TyG-BMI and stroke risk was nonlinear (Passociation = 0.017; Pnonlinearity = 0.012). TG emerged as the primary contributor when the weights were assigned to the constituent elements of the TyG-BMI (weight2012 = 0.466; weight2015 = 0.530). CONCLUSIONS: Substantial changes in the TyG-BMI are independently associated with the risk of stroke in middle-aged and older adults. Monitoring long-term changes in the TyG-BMI may assist with the early identification of individuals at high risk of stroke.

Adjuvant immune checkpoint inhibitors associated with higher recurrence-free survival in postoperative hepatocellular carcinoma (PREVENT): a prospective, multicentric cohort study.

BACKGROUND: Adjuvant therapy may improve survival of patients with hepatocellular carcinoma (HCC) after curative resection. This study compared safety and efficacy outcomes between patients at high risk of recurrence who received different types of adjuvant therapy or no such therapy after hepatic resection for HCC. METHODS: Recurrence-free survival (RFS), overall survival, and adverse events were compared among patients who received adjuvant immune checkpoint inhibitors (ICIs) alone, ICIs with tyrosine kinase inhibitors (TKIs), or no adjuvant therapy between 13 March 2019 and 19 March 2022. This study was registered on ClinicalTrials.gov (NCT05221398). RESULTS: Of the 517 patients in final analysis, 432 (83.6%) received no adjuvant therapy, 53 (10.2%) received ICIs alone, and 32 (6.2%) received adjuvant ICIs and TKIs. During median follow-up of 34.0 months (IQR 27.8 to 41.6 months), RFS was significantly longer among patients who received either type of adjuvant therapy (25.2 months, 95%CI 16.4-34.0) than among those who received none (16.1 months, 95%CI 12.9-19.4), and this difference remained significant after propensity score matching (HR 0.52, 95%CI 0.35-0.76, P = 0.004). Overall survival was unaffected by either type of adjuvant therapy, while significant difference was observed between patients who received adjuvant therapy or not after propensity score matching (HR 0.31, 95%CI 0.17-0.59, P = 0.005). The rate of grade 3 or 4 adverse events was similar between the two types of adjuvant therapy. CONCLUSIONS: ICIs alone or with TKIs may improve RFS of patients at high risk of HCC recurrence after curative resection.

Prognosis after hepatic resection of patients with hepatocellular carcinoma related to non-alcoholic fatty liver disease: meta-analysis.

BACKGROUND: Whether the safety and efficacy of hepatic resection differ between patients whose hepatocellular carcinoma (HCC) is related to non-alcoholic fatty liver disease (NAFLD) or has other aetiologies is unknown. A systematic review was performed to explore potential differences between such conditions. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies that reported hazard ratios (HRs) for overall and recurrence-free survival between patients with NAFLD-related HCC or HCC of other aetiologies. RESULTS: The meta-analysis involved 17 retrospective studies involving 2470 patients (21.5 per cent) with NAFLD-related HCC and 9007 (78.5 per cent) with HCC of other aetiologies. Patients with NAFLD-related HCC were older and had higher body mass index (BMI), but were less likely to have cirrhosis (50.4 per cent versus 64.0 per cent, P < 0.001). The two groups suffered similar rates of perioperative complications and mortality. Patients with NAFLD-related HCC had slightly higher overall survival (HR 0.87, 95 per cent c.i. 0.75 to 1.02) and recurrence-free survival (HR 0.93, 95 per cent c.i. 0.84 to 1.02) than those with HCC of other aetiologies. In the various subgroup analyses, the only significant finding was that Asian patients with NAFLD-related HCC had significantly better overall survival (HR 0.82, 95 per cent c.i. 0.71 to 0.95) and recurrence-free survival (HR 0.88, 95 per cent c.i. 0.79 to 0.98) than Asian patients with HCC of other aetiologies. CONCLUSION: The available evidence suggests that patients with NAFLD-related HCC have similar perioperative complications and mortality, but potentially longer overall and recurrence-free survival, compared with those with HCC of other aetiologies. Tailored surveillance strategies should be developed for patients with NAFLD without cirrhosis.

Long-term Effect of Hematopoietic Stem Cell Transplantation on the Quality of Life of Patients with ß-thalassemia Major in Guangxi, China - A Cross-sectional Study.

OBJECTIVE: The purpose of our study was to compare the quality of life (QOL) of patients with hematopoietic stem cell transplantation (HSCT) for more than 2 years for ß -thalassemia major (ß-TM) with that of ß-TM patients with conventional therapy (blood infusion and iron chelation) and that of the general population. METHODS: This was a cross-sectional comparative study on the QOL of 225 ß-TM patients treated with blood transfusion and iron chelation therapy, 133 ß-TM patients who had undergone HSCT or 270 ageand sex-matched healthy individuals from Guangxi, China. Child-self and parent-proxy reports of the PedsQL 4.0 Generic Core Scales were used to prospectively evaluate QOL. RESULTS: The incidence of acute GVHD was 14.3% (grade III-IV in 4.5% of patients), and that of chronic GVHD was 3.8%. This was lower than that of previous studies since the inclusion of anti-thymocyte globulin (ATG). Patients who underwent transplantation from a voluntary donor had higher QOL scores and lower rates of acute GVHD, chronic GVHD and comorbidities than those receiving stem cell sources from an HLA mismatched related donor (haploidentical donor). Transplants with PBSCs or UCBT, PBSCT+BMT, BMT, or BMT+UCBT as stem cell sources did not have any impact on QOL. The QOL of ß-TM patients was very similar to that of the general population. More complications (P<0.001), shorter post-transplantation time (P<0.001), and older age at HSCT (P=0.01) were associated with poorer child QOL (P=0.020). Additional analyses investigating QOL of ß-TM patients receiving conventional treatment with ß-TM revealed poorer outcomes than the cohort of transplanted patients. CONCLUSION: ß-TM patients can be cured by HSCT and regain QOL as good as that of the general population. ß-TM patients are suggested to undergo HSCT as soon as possible to avoid complications related to iron overload and blood infusion.

Lower risk of hepatocellular carcinoma with tenofovir than entecavir treatment in subsets of chronic hepatitis B patients: an updated meta-analysis.

BACKGROUND AND AIM: Previous smaller meta-analyses comparing the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) provided controversial results. This updated meta-analysis aimed to reliably identify any difference in the HCC incidence between TDF-treated or ETV-treated CHB patients in general or in specific subgroups. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies with hazard ratios (HRs) for HCC between TDF-treated and ETV-treated CHB patients. Retrieved dates ranged from January 2009 to October 2021. HRs with or without adjustment were pooled with random-effects model. RESULTS: Twenty-four comparative studies involving 37 771 CHB patients treated with TDF and 72 094 treated with ETV were included. TDF was associated with lower risk of HCC compared with ETV, with pooled unadjusted HR of 0.76 (95% confidence interval [CI]: 0.67-0.86) (24 studies) and adjusted HR of 0.81 (95% CI: 0.72-0.91) (21 studies). In propensity score matching cohorts, the TDF superiority was confirmed for unadjusted HR 0.83 (95% CI: 0.71-0.97) (14 studies) and was close to significance for adjusted HR (0.78, 95% CI: 0.58-1.04) (8 studies). Subgroup analyses showed that TDF was associated with lower HCC risk than ETV treatment in CHB patients who were from Asia (adjusted HR: 0.76, 95% CI: 0.66-0.87; 15 studies) or nucleos(t)ide naïve (adjusted HR:0.74, 95% CI: 0.65-0.84; 18 studies). CONCLUSION: Current evidence from a sizable population suggests that TDF is associated with significantly lower HCC risk compared with ETV treatment in patients who are from Asia and/or nucleos(t)ide naïve.

Quality of Life in Patients with ß-thalassemia Major: Short-term and Long-term Effects After Haematopoietic Stem Cell Transplantation.

BACKGROUND: Allogeneic haematopoietic stem cell transplantation (ALLO-HSCT) is a potentially curative approach to treat ß-thalassemia major (ß-TM). OBJECTIVE AND METHODS: To assess the quality of life (QOL) of patients with ß-TM after ALLO-HSCT, we searched PubMed, Embase, Web of Science, and MEDLINE for articles on the quality of life (QOL) of patients with ß-TM from 1 Feb 2020 to 31 Mar 2020. RESULTS: Our review revealed that the QOL of patients with ß-TM after ALLO-HSCT from a sibling donor is higher than that of patients that received blood infusion and iron-chelating therapy. Survivors of ALLO-HSCT have a QOL as good as that of a healthy population and the ability to return to normal life. However, studies thus far are limited to investigations with a few patients with ß-TM who received ALLO-HSCT of the bone marrow (BM) from a sibling donor or related donor. Graft vs. host disease, patient age, gender, sexual desire, health condition, psychological state, financial and employment stress, and social support contributed to a worse QOL after ALLO-HSCT. Medicine usage, physical therapy, and psychological intervention may help improve the decline in QOL related to ALLO-HSCT in patients with ß-TM. CONCLUSION: Doctors and nurses must focus on implementing medicine usage, physical therapy, and psychological intervention to improve the decline in QOL related to ALLO-HSCT.

Outcomes of Liver Resection for Metabolic Dysfunction-Associated Fatty Liver Disease or Chronic Hepatitis B-Related HCC.

AIMS: This study aims to determine differences in severity of background liver disease at hepatocellular carcinoma (HCC) diagnosis and long-term survival outcomes among patients undergoing liver resection for HCC in the background of metabolic dysfunction-associated fatty liver disease (MAFLD) compared to chronic hepatitis B (CHB) alone or concurrent CHB (CHB/MAFLD). METHODS: Patient demographics and comorbidities, clinicopathologic data, perioperative and long-term outcomes among patients who underwent liver resection for HCC were reviewed. Overall and recurrence-free survival were calculated with the Kaplan-Meier method, with the values compared using the log-rank test. RESULTS: From January 2014 to December 2018, 1325 patients underwent potential curative liver resection of HCC; 67 (5.0%), 176 (13.3%), and 1082 (81.7%) patients had MAFLD alone, CHB concurrent with MAFLD, and CHB alone, respectively. At HCC diagnosis, fewer MAFLD patients had cirrhosis, alpha fetoprotein concentration ≥ 400 ng/mL, tumor size ≥ 5 cm, mulinodular, microvascular invasion, receiving major hepatectomy, and receiving adjuvant transarterial chemoembolization. After a median follow-up of 47 months after liver resection, MAFLD (or MAFLD plus CHB/MAFLD) patients had significantly higher overall and recurrence-free survival than CHB patients before or after propensity score analysis (all P<0.05). CONCLUSION: Patients with HCC in the setting of MAFLD have less-severe background liver disease at HCC diagnosis and better long-term survival after curative liver resection compared to counterparts with CHB/MAFLD or CHB.

A miR-182 variant and risk of hepatocellular carcinoma in a southern Chinese population.

MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the posttranscriptional level and are involved in human carcinogenesis. The aim of the current study was to investigate the associations between miR-182 single nucleotide polymorphisms and HCC risk in a southern Chinese population. In this case-control study of 863 HCC patients and 908 cancer-free controls, we performed genotyping of miR-182 rs4541843 and assessed its association with HCC risk. We found that individuals carrying the AG/AA genotypes of miR-182 rs4541843 were significantly associated with an increased risk of HCC compared with those carrying the GG genotype (adjusted odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.07-2.76, P = 0.026). In the stratified analysis, this increased risk was more pronounced in the subgroups of older individuals (adjusted OR = 1.98, 95% CI = 1.04-3.76, P = 0.037), males (adjusted OR = 1.81, 95% CI = 1.09-2.99, P = 0.021), and never drinkers (adjusted OR = 1.84, 95% CI = 1.03-3.30, P = 0.041). Our results suggested that miR-182 polymorphism rs4541843 may contribute to the susceptibility to HCC. Our findings require validation in further studies with larger sample sizes.

Analysis of Clinicopathological Characteristics and Prognosis of Young Patients with Hepatocellular Carcinoma after Hepatectomy.

Background and Aims: This study was designed to analyze the effects of age and clinicopathological characteristics on prognosis of Chinese patients with hepatocellular carcinoma (HCC). Methods: The clinical data of 2032 HCC patients who were first diagnosed with HCC and underwent curative hepatectomy in our hospital between January 2006 and January 2011 were retrospectively analyzed. Results: Younger HCC patients (age <40 years, n=465) had a significantly higher hepatitis B infection rate, larger tumors, higher alpha-fetoprotein levels, higher preoperative liver function, and more frequent vascular invasions than older patients. Most younger patients were suitable for anatomical hepatectomy, and their tumors were found to be at a highly advanced stage. The recurrence-free survival and overall survival rates of younger HCC patients were significantly worse than those of older patients but this difference disappeared after propensity score matching. Multivariate analysis of pre-matched samples showed that age ≤40 years was one of the independent risk factors associated with poor overall survival. Conclusions: Younger patients showed different clinicopathological characteristics than older patients, such as higher rates of hepatitis B infection and advanced tumors. The recurrence-free survival and overall survival rates of younger HCC patients after hepatectomy may be similar to those of older patients.

Clinical significance of miR-1180-3p in hepatocellular carcinoma: a study based on bioinformatics analysis and RT-qPCR validation.

miRNAs play an indispensable role in human carcinogenesis. Dysregulated miR-1180-3p has been observed in several types of cancer, including hepatocellular carcinoma (HCC). This study intends to correlate the expression level of miR-1180-3p with clinical features and overall survival in HCC patients. The expression and clinical significance of miR-1180-3p, selected from GEO and TCGA databases, were verified using an RT-qPCR method. The target genes of miR-1180-3p were obtained using 3 miRNA target gene prediction databases, and their functions were analyzed using the online tool WebGestalt. miR-1180-3p expression was significantly upregulated in 88 HCC tissues compared with non-tumor liver tissues (0.004 ± 0.009 vs. 0.002 ± 0.002, t = - 2.099, P = 0.038). Additionally, we found that the expression levels of miR-1180-3p were significantly correlated with tumor number (χ2 = 9.157, P = 0.006) and MVI (χ2 = 11.354, P = 0.003). Based on Kaplan-Meier analysis, patients with high miR-1180 expression had a shorter overall survival than those with low miR-1180-3p expression (P = 0.002). Furthermore, multivariate Cox analyses indicated that miR-1180-3p expression was an independent prognostic factor for overall survival (HR = 13.36, 95% CI 1.16, 153.69, P = 0.038). In addition, a total of 733 target genes of miR-1180-3p were found from three prediction databases. The GO analyses demonstrated that the target genes were closely related to the proliferation and malignancy of tumors. The KEGG analysis showed that target genes were enriched in several key cancer-related signaling pathways, including the Pathways in cancer, the Ras signaling pathway, and the MAPK signaling pathway. In conclusion, we demonstrate that miR-1180-3p is upregulated in HCC and is associated with a poor prognosis. Thus, miR-1180-3p might be useful as a prognostic marker for HCC.

Development and validation of a nomogram for assessing survival in patients with hepatocellular carcinoma after hepatectomy.

BACKGROUND AND AIM: Assessing the average survival rate of patients with hepatocellular carcinoma (HCC) after hepatectomy is important for making critical decisions in everyday clinical practice. The present study aims to develop and validate a nomogram for assessing the overall survival probability for such patients. METHODS: The putative prognostic indicators for constructing the nomogram were identified using multivariable Cox regression and model selection based on the Akaike information criterion. The nomogram was subjected to internal and external validation. The nomogram endpoints were death within 1, 3, and 5 years. RESULTS: A consecutive sample of 522 HCC patients who underwent potentially curative hepatectomy was retrospectively analyzed. Age, Barcelona clinic liver cancer (BCLC) stage, tumor size, alanine transaminase, alpha fetal protein, and serum prealbumin were included in the final model. The nomogram's discriminative ability was good in the training set (C-index was 0.74 for 1 year, 0.73 for 3 years, 0.70 for 5 years) and was validated using both an internal bootstrap method (C-index was 0.73 for 1 year, 0.72 for 3 years, 0.69 for 5 years) and an external validating set (C-index was 0.72 for 1 year, 0.72 for 3 years, 0.69 for 5 years). The calibration plots for the endpoints showed optimal agreement between the nomogram's assessment and actual observations. CONCLUSIONS: The nomogram (an Excel-based tool) can be useful for assessing the probability of survival at 1, 3, and 5 years in patients with HCC after hepatectomy.

Association between Single-Nucleotide Polymorphism in MicroRNA Target Site of DDB2 and Risk of Hepatocellular Carcinoma in a Southern Chinese Population.

Damage-specific DNA-binding protein 2 (DDB2) is a DNA repair protein mainly involved in nucleotide excision repair, which plays a pivotal role in maintaining genomic stability. In this study, we evaluated the association of single-nucleotide polymorphism (SNP) rs1050244 in miRNA target site of DDB2 gene with risk of hepatocellular carcinoma (HCC) among 1073 HCC patients and 1119 cancer-free controls in a southern Chinese population. Our results showed that no statistically significant association was found between DDB2 rs1050244 and HCC risk. In further analysis stratified by age, sex, smoking, alcohol drinking, and HBV infection status, we found that individuals carrying the CT/TT genotypes of SNP rs1050244 had a significantly decreased risk of HCC compared with those with the CC genotype among non-HBV infected population (adjusted OR = 0.31, 95% CI = 0.13-0.72), and a significant interaction was found between this SNP and HBV infection (P interaction=0.002). Our results suggested that the DDB2 rs1050244 C>T polymorphism was associated with the decreased risk of HCC among non-HBV infected population. Further studies with larger sample sizes are needed to validate our findings.

Discovery of lixisenatide analogues as long-acting hypoglycemic agents using novel peptide half-life extension technology based on mycophenolic acid.

Noncovalent binding of peptides to human serum albumin protects against renal clearance and enzymatic degradation. Herein, we investigated the effect of mycophenolic acid (MPA) albumin binders for improving the stability of peptides. For proof-of-principle, the short acting glucagon-like peptide-1 (GLP-1) receptor agonist lixisenatide was selected and functionalized with different MPA albumin binders. In vitro, all lixisenatide analogues showed well preserved GLP-1 receptor activation potency. High performance affinity chromatography (HPAC) and ultrafiltration analyses indicated that DiMPA was able to confer high albumin affinity to lixisenatide and revealed that affinity is increased for DiMPA modified lixisenatide analogues containing OEG spacers. In db/db mice, the selected peptide 2c showed comparable efficacies to lixisenatide with respect to glucose-lowering and insulinotropic activities. Furthermore, the duration of action of glucose homeostasis of 2c was comparable to semaglutide in db/db mice. Importantly, DiMPA albumin binder did not bring significant toxicity of lixisenatide, as reflected by the comparable toxicity indexes in 2c and semaglutide groups after 2 weeks dosing in normal Kunming mice. Short-term study (21 days) conducted on db/db mice showed the better therapeutic efficacies of 2c than semaglutide on pancreas islets protection. Importantly, in chronic studies (84 days) on db/db mice, 2c exhibited a sustained improvement in glycaemic control, to a greater extent than that of semaglutide. Thus, we propose DiMPA modification as a novel and general method for development of long-acting GLP-1 receptor agonists for type 2 diabetes treatments, and 2c as a promising antidiabetic candidate.

Dose-Response Between Serum Prealbumin and All-Cause Mortality After Hepatectomy in Patients With Hepatocellular Carcinoma.

BACKGROUND: The relationship between serum prealbumin and the risk of all-cause mortality after hepatectomy in patients with hepatocellular carcinoma (HCC) needs to be evaluated. METHODS: We conducted a retrospective study. A Cox proportional hazards regression model was used to adjust for potential confounders. Prealbumin level was transformed by Z-scores and categorized into quartiles (Q1: <147 mg/L, Q2: 147-194 mg/L, Q3: 194-239 mg/L, Q4: >239 mg/L). We assessed the dose-response relationship between serum prealbumin and the risk of all-cause mortality using a restricted cubic spline model. RESULTS: Data were included from 2,022 HCC patients who underwent hepatectomy at Guangxi Medical University Cancer Hospital in China between January 2006 and January 2016. The adjusted hazard ratios (HRs) for increasing quartiles of serum prealbumin were 0.78 [95% confidence interval (CI): 0.64-0.95] for Q2, 0.66 (0.53-0.81) for Q3, and 0.51 (0.41-0.64) for Q4 in the Cox model (all P < 0.001). Serum prealbumin showed an L-shaped, non-linear dose-response relationship with the risk of all-cause mortality (P < 0.001). Among patients whose serum prealbumin was below 250 mg/L, risk of all-cause mortality decreased by 27% (95% CI: 18-36%) per increase of one standard deviation (69.8 mg/L) in serum prealbumin. CONCLUSIONS: Levels of serum prealbumin under 250 mg/L may be considered dangerous with respect to all-cause mortality after hepatectomy in HCC patients. Serum prealbumin may be useful as a prognostic marker in HCC patients undergoing hepatectomy.

Association between polymorphisms in MicroRNA target sites of RAD51D genes and risk of hepatocellular carcinoma.

RAD51D (RAD51L3) is a member of the RAD51 gene family which plays important roles in maintaining genomic stability and preventing DNA damage. This study is aimed to investigate the associations between RAD51D polymorphisms and the hereditary susceptibility of hepatocellular carcinoma (HCC). In this study we conducted a hospital-based case-control study including 805 cases (HCC patients) and 846 controls (nontumor patients) in Guangxi, China. A total of two Single-nucleotide polymorphisms (SNPs) rs12947947 and rs28363292 of RAD51D were selected and genotyped. Although we did not find two SNPs individually that had any significant main effect on risk of HCC, We found that the combined genotypes with 1-2 risk genotypes were associated with significantly increased overall risk of HCC (OR = 1.462, 95% CI = 1.050-2.036). According to the results of further stratification analysis, GT/GG genotype of rs28363292 increased HCC risk in zhuang people (OR = 3.913, 95% CI = 1.873-8.175) and nonhepatitis B virus (HBV) infection population (OR = 1.774, 95% CI = 1.060-2.969), the combined 1-2 risk genotypes increased the risk of HCC in zhuang people (OR = 2.817, 95% CI = 1.532-5.182) and non-HBV infected population (OR = 1.567, 95% CI = 1.042-2.358). Our results suggest that rs12947947 and rs28363292 polymorphisms may jointly contribute to the risk of HCC. Further large studies and functional studies are required to validate our findings.

Correlation between serum prealbumin and prognosis of patients with hepatocellular carcinoma after hepatectomy.

OBJECTIVE: To determine whether serum prealbumin levels are associated with long-term survival after hepatectomy in patients with primary hepatocellular carcinoma(HCC). METHODS: A consecutive sample of 526 patients with HCC who underwent potentially curative hepatectomy from August 2007 to August 2010 was retrospectively analyzed. Patients were classified as having normal or reduced serum prealbumin based on cut-off values of 200 or 182 mg/L. RESULTS: Multivariate analysis identified the preoperative level of serum prealbumin as an independent prognostic factor of long-term survival (P < 0.05): Survival was significantly better for those with normal levels than for those with reduced levels, based on either cut-off value. Similar results were observed in subgroup analyses based on the degree of cirrhosis, level of ɑ-fetoprotein and Barcelona Clinic Liver Cancer stage. CONCLUSIONS: Preoperative level of serum prealbumin may be useful for predicting long-term survival in patients with HCC after hepatectomy.