The Associations between Healthy Eating Patterns and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Case-Control Study.

BACKGROUND: Although several epidemiological studies have identified an inverse association between healthy dietary patterns and metabolic dysfunction-associated steatotic liver disease (MASLD)/non-alcoholic fatty liver disease (NAFLD), little is known about the contribution of the food component to MASLD risk and the association between dietary patterns and severity of MASLD. This study aimed to investigate the association between healthy eating patterns and MASLD risk and severity of MASLD. METHODS: A case-control study including 228 patients diagnosed with MASLD and 228 controls was conducted. The modified Alternate Healthy Eating Index (AHEI), Dietary Approaches to Stop Hypertension (DASH) score, and Alternative Mediterranean Diet (AMED) score were evaluated based on information collected via a validated food-frequency questionnaire. MASLD was confirmed if participants presented with ultrasound-diagnosed fatty liver diseases along with at least one of five cardiometabolic risk factors and no other discernible cause. The logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of MASLD for dietary scores. RESULTS: Compared with participants in the lowest tertile, those in the highest tertile of AHEI had a 60% reduced risk of MASLD (OR: 0.40; 95% CI: 0.25-0.66). Similar associations were also observed for DASH and AMED, with ORs comparing extreme tertiles of 0.38 (95% CI: 0.22-0.66) and 0.46 (95% CI: 0.28-0.73), respectively. Further Stratified analysis revealed that the inverse associations between AHEI and DASH with MASLD risks were stronger among women than men, and the inverse associations between AMED and MASLD risks were more pronounced among participants with normal weight (OR: 0.22; 95% CI: 0.09-0.49). For components within the dietary score, every one-point increase in vegetable score and whole grain score within the AHEI was associated with an 11% (95% CI: 5-16%) and a 6% (95% CI: 0-12%) lower MASLD risk, respectively. Similar inverse associations with those scores were observed for the DASH and AMED. CONCLUSION: Greater adherence to healthy eating patterns was associated with reduced risk of MASLD, with vegetables and whole grains predominately contributing to these associations. These findings suggested that healthy eating patterns should be recommended for the prevention of MASLD.

Causal relationship between neuroticism and frailty: A bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have shown that neuroticism is associated with frailty, but the causal relationship between them remains unclear. METHODS: A two-sample Mendelian randomization (MR) study was conducted to explore the bidirectional causal relationship between neuroticism (n = 380,506 for the primary analysis, n = 79,004 for the validation) and frailty (n = 175,226) using publicly available genome-wide association study data. The inverse variance weighted (IVW), weighted median, and MR-Egger were used to obtain the causal estimates. Findings were verified through extensive sensitivity analyses and validated using another dataset. Multivariable MR (MVMR) analysis was performed to estimate the direct causal effects with adjustment of potential confounders. Two-step MR technique was then conducted to explore the mediators in the causal effects of neuroticism on frailty. RESULTS: Genetically-predicted higher neuroticism score was significantly correlated with higher frailty index (IVW beta: 0.53, 95%CI: 0.48 to 0.59, P = 9.3E-83), and genetically-determined higher frailty index was significantly associated with higher neuroticism score (IVW beta: 0.28, 95%CI: 0.21 to 0.35, P = 1.3E-16). These results remained robust across sensitivity analyses and were reproducible using another dataset. The MVMR analysis indicated that the causal relationships remained significant after adjusting for the potential confounding factors. Mediation analysis revealed that depression, years of schooling, and smoking were significantly mediated the causal effects of neuroticism on frailty. CONCLUSIONS: A bidirectional causal relationship existed between neuroticism and frailty. Our findings suggested that early intervention and behavioral changes might be helpful to reduce the neuroticism levels and prevent the development of frailty.

Integrated analysis of single-cell and bulk RNA-sequencing reveals tumor heterogeneity and a signature based on NK cell marker genes for predicting prognosis in hepatocellular carcinoma.

Background: Natural killer (NK) cells are a type of innate immune cell that recognize and eliminate tumor cells and infected cells, without prior sensitization or activation. Herein, we aimed to construct a predictive model based on NK cell-related genes for hepatocellular carcinoma (HCC) patients and assess the feasibility of utilizing this model for prognosis prediction. Methods: Single-cell RNA-seq data were obtained from the Gene Expression Omnibus (GEO) database to identify marker genes of NK cells. Univariate Cox and lasso regression were performed to further establish a signature in the TCGA dataset. Subsequently, qPCR and immunohistochemistry (IHC) staining were employed to validate the expression levels of prognosis signature genes in HCC. The effectiveness of the model was further validated using two external cohorts from the GEO and ICGC datasets. Clinical characteristics, prognosis, tumor mutation burden, immune microenvironments, and biological function were compared for different genetic subtypes and risk groups. Finally, molecular docking was performed to evaluate the binding affinity between the hub gene and chemotherapeutic drugs. Results: A total of 161 HCC-related NK cell marker genes (NKMGs) were identified, 28 of which were significantly associated with overall survival in HCC patients. Based on differences in gene expression characteristics, HCC patients were classified into three subtypes. Ten prognosis genes (KLRB1, CD7, LDB2, FCER1G, PFN1, FYN, ACTG1, PABPC1, CALM1, and RPS8) were screened to develop a prognosis model. The model not only demonstrated excellent predictive performance on the training dataset, but also were successfully validated on two independent external datasets. The risk scores derived from the model were shown to be an independent prognosis factor for HCC and were correlated with pathological severity. Moreover, qPCR and IHC staining confirmed that the expression of the prognosis genes was generally consistent with the results of the bioinformatic analysis. Finally, molecular docking revealed favorable binding energies between the hub gene ACTG1 and chemotherapeutic drugs. Conclusion: In this study, we developed a model for predicting the prognosis of HCC based on NK cells. The utilization of NKMGs as innovative biomarkers showed promise in the prognosis assessment of HCC.

The combined associations of depression and cognitive impairment with functional disability and mortality in older adults: a population-based study from the NHANES 2011-2014.

Objective: The present study aimed to explore the combined associations of depression and cognitive impairment with functional disability and mortality, and whether the joint effects of depression and cognitive impairment on mortality were influenced by functional disability. Methods: A total of 2,345 participants aged 60 and above from the 2011-2014 cycle of the National Health and Nutrition Examination Survey (NHANES) were included in the analyses. Questionnaires were used to evaluated depression, global cognitive function and functional disability (including disability in activities of daily living (ADLs), instrumental activities of daily living (IADLs), leisure and social activities (LSA), lower extremity mobility (LEM), and general physical activity (GPA)). Mortality status was ascertained up to December 31, 2019. Multivariable logistic regression was performed to investigate the associations of depression and low global cognition with functional disability. Cox proportional hazards regression models were conducted to evaluate the effect of depression and low global cognition on mortality. Results: Interactions between depression and low global cognition were observed when exploring associations of depression and low global cognition with IADLs disability, LEM disability, and cardiovascular mortality. Compared with normal participants, participants with both depression and low global cognition had the highest odds ratios of disability in ADLs, IADLs, LSA, LEM, and GPA. Besides, participants with both depression and low global cognition also had the highest hazard ratios of all-cause mortality and cardiovascular mortality, and these associations remained after adjusting for disability in ADLs, IADLs, LSA, LEM, and GPA. Conclusion: Older adults with both depression and low global cognition were more likely to have functional disability, and had the highest risk of all-cause mortality and cardiovascular mortality.

Identification of pseudo-immune tolerance for chronic hepatitis B patients: Development and validation of a non-invasive prediction model.

Background and aims: Patients with chronic hepatitis B (CHB) in the immune tolerant (IT) phase were previously thought to have no or slight inflammation or fibrosis in the liver. In fact, some CHB patients with normal ALT levels still experience liver fibrosis. This study aimed to develop and validate a non-invasive model for identifying pseudo-immune tolerance (pseudo-IT) of CHB by predicting significant liver fibrosis. Methods: This multi-center study enrolled a total of 445 IT-phase patients who had undergone liver biopsy for the training cohort (n = 289) and validation cohort (n = 156) during different time periods. A risk model (IT-3) for predicting significant liver fibrosis (Ishak score ≥ 3) was developed using high-risk factors which were identified using multivariate stepwise logistic regression. Next, an online dynamic nomogram was created for the clinical usage. The receiver operating characteristic (ROC) curve, net reclassification improvement and integrated discrimination improvement were used to assess the discrimination of the IT-3 model. Calibration curves were used to evaluate the models' calibration. The clinical practicability of the model was evaluated using decision curve analysis and clinical impact curves. Results: 8.8% (39 of 445) patients presented with significant liver fibrosis in this study. Aspartate aminotransferase (AST), hepatitis B e-antigen (HBeAg), and platelet (PLT) were included in the prediction model (IT-3). The IT-3 model showed good calibration and discrimination both in the training and validation cohorts (AUC = 0.888 and 0.833, respectively). The continuous NRI and IDI showed that the IT-3 model had better predictive accuracy than GPR, APRI, and FIB-4 (p < 0.001). Decision curve analysis and clinical impact curves were used to demonstrate the clinical usefulness. At a cut-off value of 106 points, the sensitivity and specificity were 91.7 and 70.2%, respectively. Conclusion: The IT-3 model proved an accurate non-invasive method in identifying pseudo-IT of CHB, which can help to formulate more appropriate treatment strategies.

Breastfeeding in infancy and mortality in middle and late adulthood: A prospective cohort study and meta-analysis.

BACKGROUND: Breastfeeding in infancy is associated with a lower risk of mortality among children, but the impact on mortality in middle and late adulthood remains unknown. OBJECTIVES: To assess the association between breastfeeding in infancy and mortality in middle and late adulthood. METHODS: We included 383,627 participants aged 40-73 from the UK Biobank (2006-2010) and followed up until 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality according to breastfeeding in infancy were estimated with Cox proportional hazards regression models. We further did a meta-analysis, including results from our present study and three other cohort studies (PROSPERO; number CRD42022348925). RESULTS: During a total of 4732,751 person-years of follow-up, 25,581 deaths were identified. Breastfeeding in infancy was associated with lower risks of mortality in middle and late adulthood, with adjusted HRs (95% CIs) of 0.95 (0.93-0.98) for all-cause mortality; 0.91 (0.87-0.96) for cardiovascular mortality and 0.94 (0.874-0.999) for respiratory mortality. Specifically, the association with mortality seemed to attenuate with age - stronger in middle-aged adults than in older adults. A similar association between breastfeeding in infancy and all-cause mortality was found in the meta-analysis. CONCLUSION: Breastfeeding in infancy is associated with a lower risk of mortality - even decades later - in middle and late adulthood.

Cross-sectional and longitudinal associations between body flexibility and sarcopenia.

BACKGROUND: The associations between body flexibility and sarcopenia were not well understood. This study aimed to explore the cross-sectional and longitudinal associations of flexibility with sarcopenia. METHODS: Our study selected participants aged 50-80 from the WELL-China cohort and the Lanxi cohort. Participants from the urban area of the Lanxi cohort were followed up 4 years later. Body flexibility was measured by the sit-and-reach test. Muscle mass was evaluated by dual-energy X-ray absorptiometry. Muscle strength was evaluated using handgrip strength. Sarcopenia was defined as having both low muscle mass and low muscle strength. We used multivariable logistic regressions to assess the cross-sectional associations of body flexibility with low muscle mass, low muscle strength and sarcopenia. We also used multivariable logistic regressions to explore the associations of baseline flexibility and 4-year changes in flexibility with incident low muscle mass, low muscle strength and sarcopenia. RESULTS: A total of 9453 participants were enrolled in the cross-sectional study, and 1233 participants were included in the longitudinal analyses. In the cross-sectional analyses, compared with low body flexibility, high body flexibility was inversely associated with low muscle mass (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50-0.68; P < 0.001), low muscle strength (OR, 0.62; 95% CI, 0.55-0.69; P < 0.001) and sarcopenia (OR, 0.52; 95% CI, 0.41-0.65; P < 0.001), and these associations did not differ in different age groups, sex or physical activity levels. In the longitudinal analyses, compared with participants with low body flexibility, participants with high body flexibility had lower risk of the incident low muscle strength (OR, 0.53; 95% CI, 0.38-0.74; P < 0.001) and sarcopenia (OR, 0.36; 95% CI, 0.21-0.61; P < 0.001), but not incident low muscle mass (OR, 0.59; 95% CI, 0.33-1.06; P = 0.076). Every 1-cm increase in flexibility during 4 years was associated with reduced risk of incident low muscle mass (OR, 0.96; 95% CI, 0.93-1.00; P = 0.025), low muscle strength (OR, 0.96; 95% CI, 0.94-0.98; P = 0.002) and sarcopenia (OR, 0.96; 95% CI, 0.93-0.99; P = 0.007). CONCLUSIONS: High flexibility was associated with reduced risk of incident low muscle strength and sarcopenia. Increases in flexibility were associated with reduced risk of incident low muscle mass, low muscle strength and sarcopenia. Flexibility exercises and monitoring the dynamic change of flexibility might be helpful in preventing sarcopenia among adults aged 50 years or over.

Is it possible to intervene early cirrhosis by targeting toll-like receptors to rebalance the intestinal microbiome?

Cirrhosis is a progressive chronic liver disease caused by one or more causes and characterized by diffuse fibrosis, pseudolobules, and regenerated nodules. Once progression to hepatic decompensation, the function of the liver and other organs is impaired and almost impossible to reverse and recover, which often results in hospitalization, impaired quality of life, and high mortality. However, in the early stage of cirrhosis, there seems to be a possibility of cirrhosis reversal. The development of cirrhosis is related to the intestinal microbiota and activation of toll-like receptors (TLRs) pathways, which could regulate cell proliferation, apoptosis, expression of the hepatomitogen epiregulin, and liver inflammation. Targeting regulation of intestinal microbiota and TLRs pathways could affect the occurrence and development of cirrhosis and its complications. In this paper, we first reviewed the dynamic change of intestinal microbiota and TLRs during cirrhosis progression. And further discussed the interaction between them and potential therapeutic targets to reverse early staged cirrhosis.

Efficacy predictors of third-generation cephalosporins in treating spontaneous bacterial peritonitis.

OBJECTIVE: Third-generation cephalosporins (3rd GCs) have recently become controversial as the first-line strategy for empirical spontaneous bacterial peritonitis (SBP) treatment. This study aimed to identify SBP treatment efficacy predictors of 3rd GCs. METHODS: In this retrospective cohort study, 279 cirrhosis patients with SBP who received 3rd GC monotherapy for initial empirical treatment from 2013 to 2019 were included. Nonresponse was defined as a decreased ascites polymorphonuclear (PMN) count < 25% from baseline after 48 hours of antibacterial treatment. Multivariate regression analysis was used to identify efficacy predictors of 3rd GCs in treating SBP. Kaplan-Meier analysis was used to evaluate survival data. RESULTS: The nonresponder group included 120 patients with no response, and the responder group included 159 patients with responses. The response rate to 3rd GCs was 57.0% among all patients. The common pathogens were Escherichia coli (40.6%), Staphylococcus (15.6%), Klebsiella pneumonia (12.5%), and Streptococcus (12.5%) in 32 ascites culture isolates. Nosocomial SBP (NSBP) (odds ratio [OR]: 2.371, 95% confidence interval [CI]: 1.323-4.249, P = .004), pneumonia (OR: 11.561, 95% CI: 1.876-71.257, P = .008), recurrent SBP (OR: 3.386, 95% CI: 1.804-6.357, P < .001), platelet count (≥113.5 × 109/L) (OR: 3.515, 95% CI: 1.973-6.263, P < .001), and ascites PMN count (≤0.760 × 109/L) (OR: 4.967, 95% CI: 2.553-9.663, P < .001) were independent predictors of nonresponse to 3rd GCs against SBP. Survival plot analysis at 30 days showed worse survival for the nonresponders (P = .003). CONCLUSION: NSBP, pneumonia, recurrent SBP, increased platelet count, and lower ascites PMN count were independent predictors of nonresponse to 3rd GC in treating SBP. Nonresponse to initial antibiotic treatment was associated with worse survival.

Associations between dietary magnesium intake and handgrip strength were modified by serum vitamin D level among the US elderly.

Objective: The present study aimed to evaluate the associations between dietary magnesium intake and handgrip strength, and whether these associations were affected by serum vitamin D status. Methods: A total of 2,127 participants aged 60 and above from the National Health and Nutrition Examination Survey (NHANES) of the 2011-2014 cycles were included in the analyses. Magnesium intake was obtained by 24-h dietary recalls and 30-day dietary supplement. Participants in the lowest sex-specific tertile of magnesium intake were defined as having low magnesium intake. Serum 25-hydroxyvitamin D [25(OH)D)] concentrations were examined by using ultra-high performance liquid chromatography tandem mass spectrometry and categorized into three levels: deficient, suboptimal, and sufficient. Handgrip strength was determined by using a dynamometer. Multivariable linear regression models were used to investigate the associations between dietary magnesium intake and handgrip strength. Results: Low magnesium intake was not associated with handgrip strength, but interactions between low magnesium intake and serum 25(OH)D level existed on handgrip strength. The stratified analyses found that only in participants with deficient serum 25(OH)D, low magnesium intake was associated with reduced handgrip strength. The combined analyses shown that participants with both low magnesium intake and deficient serum 25(OH)D had highest decrease of handgrip strength. Conclusion: Findings suggested that low magnesium intake was associated with reduced handgrip strength only in participants with deficient serum 25(OH)D. Increased magnesium intake was recommended for participants with deficient serum 25(OH)D in maintaining muscle strength.

Dietary Antioxidant Indices in Relation to All-Cause and Cause-Specific Mortality Among Adults With Diabetes: A Prospective Cohort Study.

Background: The potential beneficial effect of individual antioxidants on mortality has been reported. However, the association of overall intakes of dietary antioxidants with all-cause and cause-specific mortality among adults with diabetes remained unclear. Methods: A total of 4,699 US adults with diabetes were enrolled in 2003-2014 in the National Health and Nutrition Examination Survey (NHANES) and followed for mortality until 31 December 2015. The Dietary Antioxidant Quality Score (DAQS) and the Dietary Antioxidant Index (DAI), which indicate the total antioxidant properties, were calculated based on the intakes of vitamins A, C, E, zinc, selenium, and magnesium. The Cox proportional hazards regression models were used to investigate the associations of the DAQS or the DAI with all-cause and cause-specific mortality. Results: A total of 913 deaths occurred during 27,735 person-years of follow-up, including 215 deaths due to cardiovascular disease (CVD) and 173 deaths due to cancer. The higher intakes of antioxidant vitamins A, E, magnesium, and selenium were associated with lower all-cause mortality. The adjusted hazard ratios (HRs) (95% CIs) comparing the highest DAQS (5-6) to the lowest DAQS (0-2) were 0.70 (0.53-0.92) for all-cause mortality, 0.56 (0.35-0.90) for CVD mortality, and 0.59 (0.33-1.04) for cancer mortality. Consistent inverse associations were found between the DAI and mortality. Conclusion: Higher intake of overall dietary antioxidants was associated with lower risk of death from all-cause and CVD in adults with diabetes. Future dietary intervention studies are needed to determine whether increasing overall antioxidant micronutrients intake could prevent premature death among adults with diabetes.

Sarcopenia and sarcopenic obesity after cholecystectomy: A population-based study.

OBJECTIVE: The present study aimed to investigate the associations of cholecystectomy with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity. METHODS: This population-based study included data from 4,909 participants aged 18 to 80 years. History of cholecystectomy was diagnosed using abdominal ultrasonography. Muscle mass was evaluated using a dual-energy x-ray absorptiometry scan, and muscle strength was evaluated using an electronic hand dynamometer. Sarcopenia was defined as the presence of both low muscle mass and low muscle strength. Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Multivariable logistic regression models were performed to investigate the associations of cholecystectomy with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity. RESULTS: Participants with history of cholecystectomy were more likely than those without to have low muscle mass, low muscle strength, and sarcopenia. Furthermore, compared with cholecystectomy that occurred within 7 years (7 years is the median interval between cholecystectomy and the physical examination), participants with cholecystectomy that occurred more than 7 years ago had higher odds of sarcopenia. Finally, whether obesity was defined by BMI or body fat percentage, cholecystectomy was positively associated with sarcopenic obesity. CONCLUSIONS: Cholecystectomy is associated with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity.

Fas signaling in adipocytes promotes low-grade inflammation and lung metastasis of colorectal cancer through interaction with Bmx.

Obesity is a global public health issue. Obesity-related chronic low-grade inflammation (meta-inflammation) can lead to aberrant adipokine release and promote cardiometabolic diseases and obesity-related tumors. However, the mechanisms involved in the initiation of inflammatory responses in obesity and obesity-related tumors as well as metastasis are not fully understood. In this study, we found that the increased tumor necrosis factor-alpha (TNF-α) in adipocytes promoted the lung metastasis of MC38 colon cancer cells via Fas signaling. The release of TNF-α and interleukin (IL)-6 by Fas signaling in adipocytes was caused by the activation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways mediated by the interaction of Fas with Bmx, a non-receptor tyrosine kinase. Moreover, the Fas/Bmx complex is involved in the inflammation of adipocytes via Fas at the Tyr189 site and SH2 domain of Bmx. This is the first study to report the interaction between Fas and Bmx in adipocyte inflammation, which may provide clues for the development of potential new treatment strategies for obesity-related diseases.

Volatile Oil of Platycladus Orientalis (L.) Franco Leaves Exerts Strong Anti-inflammatory Effects via Inhibiting the IκB/NF-κB Pathway.

This study was designed to investigate the anti-inflammatory effects of volatile oil of Platycladus orientalis (L.) Franco leaves (VOPF) and the underlying molecular mechanisms by using the non-infectious inflammation rat models and infectious inflammation mouse models. Ear swelling and intraperitoneal capillary permeability in mice, and carrageenan-induced toe swelling and cotton ball-induced granuloma in rats were used to reveal anti-inflammatory effects of VOPF. Moreover, the lipopolysaccharide (LPS)-induced mouse model of acute lung injury was used to explore the anti-inflammatory mechanism of VOPF. The results showed that VOPF could significantly inhibit auricular swelling, intraperitoneal capillary permeability in mice, and reduce granuloma swelling and paw swelling in rats. Furthermore, it significantly alleviated the pathological damage of the lung tissue. In addition, VOPF could reduce the contents of IL-1ß and TNF-α and increase the content of IL-10 in the serum. It had little effect on the expression of p65 but reduced the phosphorylation level of p65 and IκB in NF-κB pathway. In conclusion, VOPF has anti-inflammatory effects and the mechanisms involve the down-regulation of the phosphorylation levels of p65 and IκB and blockage of the NF-κB signaling pathway.

The crosstalk between platelets and body fat: A reverse translational study.

BACKGROUND & AIMS: Our previous study found that platelet counts were positively associated with body fat percentage in human. In the present study, we conducted a reverse translational study to explore the role of platelets in modulating pre-adipocyte proliferation in mice. METHODS: Mouse pre-adipocyte cell line (3T3-L1) and human pre-adipocytes harvested from female subcutaneous fat were used. Pre-adipocytes were co-cultured with platelets or platelet releasate, which were isolated from mice or humans. The cell viability and proliferative ability of the pre-adipocytes were examined by MTT and flow cytometry assays. Western blotting analysis was used to determine the phosphorylation levels of proteins in the mTOR pathway. RESULTS: The number of platelets in the adipose tissues from obese mice was significantly higher than that from lean mice. Platelets and collagen-activated platelet releasate stimulated the proliferation of human pre-adipocytes and 3T3-L1 cells in vitro. Besides, platelets from obese mice were more potent in stimulating pre-adipocyte proliferation than those from lean control mice. Mechanistically, platelets enhanced pre-adipocyte proliferation through the acceleration of cell cycle progression from G0/G1 to S phase cell cycle progression. At the molecular level, platelets promoted pre-adipocyte proliferation through mTOR pathway-mediated upregulation of cyclin D1 expression. CONCLUSION: In conclusion, platelets and platelet releasate play an important role in the proliferation of pre-adipocytes. Our study may provide new clues and the molecular mechanism of the causal pathways between platelets and body fat to explain the finding we observed in population study.

Colonoscopic screening is associated with reduced Colorectal Cancer incidence and mortality: a systematic review and meta-analysis.

It is the great priority to detect colorectal cancer (CRC) as early as possible, finally to reduce the incidence and mortality of CRC. However, although colonoscopy is recommended in many consensuses, yet no one systematic review is conducted to figure out how colonoscopy could change the incidence and mortality. In our study, we conducted a comprehensive meta-analysis to evaluate the association between colonoscopy screening and the incidence or mortality of CRC. PubMed, EMBASE, and PMC database were systematically searched from their inception to June 2020. A total of 13 cohort and 16 case-control studies comprising 4,713,778 individuals were obtained in this review. Our results showed that colonoscopy was associated with a 52% RR reduction in incidence of CRC (RR: 0.48, 95% CI: 0.46-0.49) and 62% RR reduction in mortality of CRC (RR: 0.38, 95% CI: 0.36-0.40). Subgroup analysis of different interventions, study design, country, sample size, age or sex showed that the incidence and mortality reduction remained consistent, and colonoscopy screening had the same effect on people below and above 50. Our study indicated that colonoscopy could significantly reduce the incidence and mortality of CRC.

The threshold of alpha-fetoprotein (AFP) for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis.

OBJECTIVE: Hepatocellular carcinoma (HCC) has become a pressing health problem facing the world today due to its high morbidity, high mortality, and late discovery. As a diagnostic criteria of HCC, the exact threshold of Alpha-fetoprotein (AFP) is controversial. Therefore, this study was aimed to systematically estimate the performance of AFP in diagnosing HCC and to clarify its optimal threshold. METHODS: Medline and Embase databases were searched for articles indexed up to November 2019. English language studies were included if both the sensitivity and specificity of AFP in the diagnosis of HCC were provided. The basic information and accuracy data included in the studies were extracted. Combined estimates for sensitivity and specificity were statistically analyzed by random-effects model using MetaDisc 1.4 and Stata 15.0 software at the prespecified threshold of 400 ng/mL, 200 ng/mL, and the range of 20-100 ng/mL. The optimal threshold was evaluated by the area under curve (AUC) of the summary receiver operating characteristic (SROC). RESULTS: We retrieved 29,828 articles and included 59 studies and 1 review with a total of 11,731 HCC cases confirmed by histomorphology and 21,972 control cases without HCC. The included studies showed an overall judgment of at risk of bias. Four studies with AFP threshold of 400 ng/mL showed the summary sensitivity and specificity of 0.32 (95%CI 0.31-0.34) and 0.99 (95%CI 0.98-0.99), respectively. Four studies with AFP threshold of 200 ng/mL showed the summary sensitivity and specificity of 0.49 (95%CI 0.47-0.50) and 0.98 (95%CI 0.97-0.99), respectively. Forty-six studies with AFP threshold of 20-100 ng/mL showed the summary sensitivity and specificity of 0.61 (95%CI 0.60-0.62) and 0.86 (95%CI 0.86-0.87), respectively. The AUC of SROC and Q index of 400 ng/mL threshold were 0.9368 and 0.8734, respectively, which were significantly higher than those in 200 ng/mL threshold (0.9311 and 0.8664, respectively) and higher than those in 20-100 ng/mL threshold (0.8330 and 0.7654, respectively). Furthermore, similar result that favored 400 ng/mL were shown in the threshold in terms of AFP combined with ultrasound. CONCLUSION: AFP levels in serum showed good accuracy in HCC diagnosis, and the threshold of AFP with 400 ng/mL was better than that of 200 ng/mL in terms of sensitivity and specificity no matter AFP is used alone or combined with ultrasound.

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

Low muscle mass and low muscle strength associate with nonalcoholic fatty liver disease.

BACKGROUND: It is unclear whether low muscle mass and low muscle strength are independently or jointly associated with nonalcoholic fatty liver disease (NAFLD). Hence, the aim of the present study was to investigate the associations of NAFLD with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity. METHODS: A total of 5132 participants aged 18-80 years were recruited in this cross-sectional study. NAFLD was diagnosed using ultrasound. Muscle mass was evaluated using skeletal muscle mass index and muscle strength was evaluated using weight-adjusted hand grip strength. Sarcopenia was defined as the presence of both low muscle mass and low muscle strength. Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Multivariate logistic regression models were used to explore the associations of NAFLD with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity. RESULTS: Low muscle mass and low muscle strength were positively and independently associated with NAFLD (mass: odds ratio [OR], 2.57; 95% confidence interval [CI], 2.03-3.25; strength: OR, 1.47; 95% CI, 1.21-1.80). Compared with low muscle mass or low muscle strength alone, sarcopenia was associated with a higher risk of NAFLD (OR, 3.91; 95% CI, 2.90-5.28). Whether obesity was defined by body mass index (BMI) or waist circumference (WC), sarcopenic obesity was associated with a higher risk of NAFLD (BMI: OR, 10.42; 95% CI, 7.14-15.22; WC: OR, 11.64; 95% CI, 8.22-16.48) than sarcopenia or obesity alone. CONCLUSIONS: Low muscle mass and low muscle strength were positively and independently associated with NAFLD. When both were presented in the sarcopenic state, the risk of NAFLD was higher, and a concurrence of sarcopenia and obesity showed the highest risk of NAFLD.