No association between hepatitis C virus infection and risk of colorectal cancer: a systematic review and meta-analysis of cohort studies.

Background and aim: There is still uncertainty regarding whether hepatitis C virus (HCV) infection is associated with colorectal cancer (CRC). This study aims to investigate the potential association between HCV infection and CRC through a systematic review and meta-analysis of cohort studies. Methods: PubMed, Embase, and Web of Science were systematically searched from the beginning of their inception to October 2023 to find relevant cohort studies on the association between HCV infection and CRC risk. The random-effect, generic inverse variance method was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC outcome among individuals with HCV infection. We also performed subgroup and sensitivity analysis. Results: A total of 8 cohort studies involving 1,939,164 participants were included in this meta-analysis. The result from the meta-analysis suggested that there was no statistically significant association between HCV and the risk of developing CRC (HR = 0.99, 95% CI: 0.82-1.88, p = 0.88) with low statistical heterogeneity (I2 = 28%, p = 0.20). Subgroup analyses that were conducted based on study design, diagnosis of HCV infection, and publication year yielded similar results. Analyses of subgroups based on study areas revealed that there was no significant association between HCV infection and CRC risk in Asia (n = 2, HR = 0.96, 95% CI: 0.71-1.29, p = 0.79; I2 = 26%), Europe (n = 3, HR = 1.06, 95% CI: 0.83-1.37, p = 0.63; I2 = 0%), and North America (n = 2, HR = 1.10, 95% CI: 0.87-1.38, p = 0.44; I2 = 0%); however, a negative correlation was found in Oceania (n = 1, HR = 0.43, 95% CI: 0.22-0.84, p = 0.01). Sensitivity analysis further reinforce the stability of our conclusion. Conclusion: Our cohort-based meta-analysis showed insufficient evidence to support the association between HCV infection and an increased risk of CRC. To gain a clearer insight into the potential association between these two conditions, it would be beneficial to conduct large, well-designed, high-quality prospective cohort studies that consider different ethnic populations and potential confounding factors.Systematic review registration: PROSPERO, identifier [CRD42023472688], https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023472688.

Assessment of macro, trace and toxic element intake from rice: differences between cultivars, pigmented and non-pigmented rice.

Pigmented and non-pigmented rice varieties (grown in different areas) were collected in China, Yunnan, to investigate the content of macro-, trace elements and potentially toxic elements (PTEs), and to assess the health risk associated with dietary intake. The order of elemental concentrations in rice was Mn > Zn > Fe > Cu > Se for trace elements, P > K > Mg > Ca > Na for macro elements, and Cr > As > Cd for PTEs. Rice with a high concentration of essential elements also associated with a high content of PTEs. In addition, higher content of Cr, Mn and Na were found in pigmented rice. The health risk assessment showed that the daily intake of all elements was below the tolerable limit (UL). Moreover the intake of Fe, Zn and Se was far from sufficient for the nutrient requirement. The PTEs in rice dominated the health risk. Of concern is that this rice consumption is likely to contribute to carcinogenic risks in the long term and that adults are at higher health risk from pigmented rice compared to non-pigmented rice. This study confirms that the lack of essential micronutrients in rice and the health risk associated with rice diets should remain a concern.

The reporting quality of randomized controlled trials in pharmacotherapy for pituitary adenomas.

BACKGROUND: Medical therapy has become an increasingly important intervention owing to improvements in the multidisciplinary care for pituitary adenomas (PAs). This study aimed to assess the reporting quality of randomized controlled trials (RCTs) on PAs pharmacotherapy. METHODS: RCTs evaluating the efficacy of pharmacotherapy in PAs published in English between January 1, 1974, and December 31, 2022, were searched for and collected from PubMed and MEDLINE. The 2010 Consolidated Standards for Test Reports (CONSORT) statement-based 28 items overall quality score (OQS) was used to evaluate the overall quality of each report. RESULTS: Twenty-seven related RCTs including 1816 patients were retrieved. The median OQS score was 12 (range, 6-19) on a scale of 0 to 28. Important items, such as background, objectives, participants, interventions, and outcomes, were sufficiently reported in 100% (27/27) of the articles. Statistical methods were adequately described in 93% (25/27) of patients. However, RCTs underreported identification as randomized trials in the title (3/27, 11%), sample size, allocation concealment, implementation, ancillary analysis method, and Diagram and Ancillary analyses (1/27, 4%). The OQS of published RCTs has significantly increased since 2010 (P = .012). The multivariate final model showed significant associations between higher OQS and publication since 2010 and enrollment of more than 100 patients. CONCLUSIONS: The overall reporting quality of RCTs on pharmacotherapy in PAs was poor, based on the 2010 CONSORT statement. However, we noticed an improvement in the OQS over the years and identified the factors associated with a better report. Increased effort is necessary to raise awareness of these issues among writers, readers, reviewers, and editors.

Characteristics of changes in plasma proteome profiling after sleeve gastrectomy.

Bariatric surgery (BS), recognized as the most effective intervention for morbid obesity and associated metabolic comorbidities, encompasses both weight loss-dependent and weight loss-independent mechanisms to exert its metabolic benefits. In this study, we employed plasma proteomics technology, a recently developed mass spectrometric approach, to quantitatively assess 632 circulating proteins in a longitudinal cohort of 9 individuals who underwent sleeve gastrectomy (SG). Through time series clustering and Gene Ontology (GO) enrichment analysis, we observed that complement activation, proteolysis, and negative regulation of triglyceride catabolic process were the primary biological processes enriched in down-regulated proteins. Conversely, up-regulated differentially expressed proteins (DEPs) were significantly associated with negative regulation of peptidase activity, fibrinolysis, keratinocyte migration, and acute-phase response. Notably, we identified seven proteins (ApoD, BCHE, CNDP1, AFM, ITIH3, SERPINF1, FCN3) that demonstrated significant alterations at 1-, 3-, and 6-month intervals post SG, compared to baseline. These proteins play essential roles in metabolism, immune and inflammatory responses, as well as oxidative stress. Consequently, they hold promising potential as therapeutic targets for combating obesity and its associated comorbidities.

Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma.

Ascomylactam C (AsC) is a new 13-membered-ring macrocyclic alkaloid, which was first isolated and identified in 2019 from the secondary metabolites of the mangrove endophytic fungus Didymella sp. CYSK-4 in the South China Sea. AsC has been found to have a broad-spectrum cytotoxic activity. However, the antitumor effects in vivo and mechanisms of AsC remain unclear. The aim of this study was to describe the effects of AsC on lung cancer and melanoma cells and to explore the antitumor molecular mechanism of AsC. In vitro, we used plate colony formation experiments and demonstrated the ability of AsC to inhibit low-density tumor growth. An Annexin V/PI cell apoptosis detection experiment revealed that AsC induced tumor cell apoptosis. In vivo, AsC suppressed the tumor growth of LLC and B16F10 allograft significantly in mice, and promoted the infiltration of CD4+ T and CD8+ T cells in tumor tissues. Mechanistically, by analyses of Western blotting, immunofluorescence and ELISA analysis, we found that AsC increased ROS formation, induced endoplasmic reticulum (ER) stress, activated the protein kinase RNA-like ER kinase (PERK)/eukaryotic translation initiation factor (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway, and induced immunogenic cell death (ICD) of tumor cells. Our results suggest that AsC may be a potentially promising antitumor drug candidate.

LincRNA01703 Facilitates CD81+ Exosome Secretion to Inhibit Lung Adenocarcinoma Metastasis via the Rab27a/SYTL1/CD81 Complex.

Metastasis, a major cause of cancer-related mortality worldwide, frequently occurs early in the diagnosis of lung adenocarcinoma (LUAD). However, the precise molecular mechanisms governing the aggressive metastatic behavior of LUAD remain incompletely understood. In this study, we present compelling evidence indicating that the long noncoding RNA linc01703 is significantly downregulated in metastatic lung cancer cells. Intriguingly, in vivo experiments revealed that Linc01703 exerted a profound inhibitory effect on lung cancer metastasis without discernible impact on the in vitro proliferation or invasion capacities of LUAD cells. Mechanistically, Linc01703 enhanced the interaction between Rab27a, SYTL1, and CD81, consequently promoting the secretion of CD81+ exosomes. These exosomes, in turn, suppressed the infiltration of immune cells within the tumor microenvironment, thereby impeding LUAD metastasis. Importantly, our analysis of lung cancer tissues revealed a correlation between reduced CD81 expression and an unfavorable patient prognosis. Collectively, our findings suggest that Linc01703 functions as a metastasis suppressor by facilitating the secretion of CD81+ exosomes through the formation of the Rab27a/SYTL1/CD81 complex.

Skeletal muscle-specific DJ-1 ablation-induced atrogenes expression and mitochondrial dysfunction contributing to muscular atrophy.

BACKGROUND: DJ-1 is a causative gene for Parkinson's disease. DJ-1-deficient mice develop gait-associated progressive behavioural abnormalities and hypoactive forearm grip strength. However, underlying activity mechanisms are not fully explored. METHODS: Western blotting and quantitative real-time polymerase chain reaction approaches were adopted to analyse DJ-1 expression in skeletal muscle from aged humans or mice and compared with young subjects. Skeletal muscle-specific-DJ-1 knockout (MDKO) mice were generated, followed by an assessment of the physical activity phenotypes (grip strength, maximal load capacity, and hanging, rotarod, and exercise capacity tests) of the MDKO and control mice on the chow diet. Muscular atrophy phenotypes (cross-sectional area and fibre types) were determined by imaging and quantitative real-time polymerase chain reaction. Mitochondrial function and skeletal muscle morphology were evaluated by oxygen consumption rate and electron microscopy, respectively. Tail suspension was applied to address disuse atrophy. RNA-seq analysis was performed to indicate molecular changes in muscles with DJ-1 ablation. Dual-luciferase reporter assays were employed to identify the promoter region of Trim63 and Fbxo32 genes, which were indirectly regulated by DJ-1 via the FoxO1 pathway. Cytoplasmic and nuclear fractions of DJ-1-deleted muscle cells were analysed by western blotting. Compound 23 was administered into the gastrocnemius muscle to mimic the of DJ-1 deletion effects. RESULTS: DJ-1 expression decreased in atrophied muscles of aged human (young men, n = 2; old with aged men, n = 2; young women, n = 2; old with aged women, n = 2) and immobilization mice (n = 6, P < 0.01). MDKO mice exhibited no body weight difference compared with control mice on the chow diet (Flox, n = 8; MDKO, n = 9). DJ-1-deficient muscles were slightly dystrophic (Flox, n = 7; MDKO, n = 8; P < 0.05), with impaired physical activities and oxidative capacity (n = 8, P < 0.01). In disuse-atrophic conditions, MDKO mice showed smaller cross-sectional area (n = 5, P < 0.01) and more central nuclei than control mice (Flox, n = 7; MDKO, n = 6; P < 0.05), without alteration in muscle fibre types (Flox, n = 6; MDKO, n = 7). Biochemical analysis indicated that reduced mitochondrial function and upregulated of atrogenes induced these changes. Furthermore, RNA-seq analysis revealed enhanced activity of the FoxO1 signalling pathway in DJ-1-ablated muscles, which was responsible for the induction of atrogenes. Finally, compound 23 (an inhibitor of DJ-1) could mimic the effects of DJ-1 ablation in vivo. CONCLUSIONS: Our results illuminate the crucial of skeletal muscle DJ-1 in the regulation of catabolic signals from mechanical stimulation, providing a therapeutic target for muscle wasting diseases.

Quantitative Diagnosis of Nonalcoholic Fatty Liver Disease with Ultrasound Attenuation Imaging in a Biopsy-Proven Cohort.

RATIONALE AND OBJECTIVES: To evaluate the performance of attenuation imaging (ATI) based on ultrasound for detection of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This prospective study was approved by our institutional review board (B2021-092R). Written informed consent was obtained from all patients. This study included 60 patients who had clinical suspicion of NAFLD and were referred for liver biopsy after ATI and controlled attenuation parameter (CAP) examinations between September 2020 and December 2021. The histologic hepatic steatosis was graded. The area under curve (AUC) analysis was performed. RESULTS: The success rate of the ATI examination was 100%. The intraobserver reproducibility of ATI was 0.981. The AUCs of ATI for detecting ≥S1, ≥S2, and S3 were 0.968 (cut-off value of 0.671 dB/cm/MHz), 0.911 (cut-off value of 0.726 dB/cm/MHz), and 0.766 (cut-off value of 0.757 dB/cm/MHz), respectively. The AUCs of CAP for detecting ≥S1, ≥S2, and S3 were 0.916 (cut-off value of 258.5 dB/m), 0.872 (cut-off value of 300.0 dB/m), and 0.807 (cut-off value of 315.0 dB/m), respectively. The diagnostic values showed no significant difference between ATI and CAP in detecting ≥S1, ≥S2, and S3 (P = .281, P = .254, and P = .330, respectively). The ATI had significant correlations with high-density lipoprotein cholesterol (P < .001), and with triglycerides (P = .015). CONCLUSION: ATI showed good feasibility and diagnostic performance in the detection of varying degrees of hepatic steatosis in NAFLD patients.

Comparison of Venous Blood Gas and Biochemical Parameters in Sunda Pangolin (Manis javanica) and Chinese Pangolin (Manis pentadactyla) before and after Isoflurane Anesthesia.

Venous blood gas analytes are commonly examined in animals, and the results may be important when evaluating the overall health status of an animal. Pangolins are critically endangered mammals, and there is limited information on their physiological reference values in the literature. The aim of this study was to analyze venous blood gas and biochemical parameters before and during isoflurane anesthesia in wild healthy Sunda and Chinese pangolins. The results obtained showed that the blood gas index trends of the two pangolin species before and after isoflurane anesthesia were the same. After anesthesia, the partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), total carbon dioxide (CO2), mean blood bicarbonate (HCO3-), extracellular fluid compartment (BEecf) base excess and the mean blood glucose (Glu) levels of both pangolin species showed a significant increase compared to the pre-anesthesia period. In contrast, the mean blood potassium (K+), lactate (Lac) and mean blood pH levels were significantly lower. No significant differences in the mean blood sodium (Na+) or blood ionized calcium (iCa) levels were observed during anesthesia. This study is important for future comparisons and understanding the health status of this endangered species.

Diagnosis and genetic analysis of a case with Bardet-Biedl syndrome caused by compound heterozygous mutations in the BBS12 gene.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy, which is caused by mutations mainly in genes encoding BBSome complex and IFT complex. Here, we reported a 21-year-old female with BBS characterized by three primary features including obesity, retinitis pigmentosa sine pigmento and bilateral renal cysts. She also had some secondary features such as diabetes mellitus, nonalcoholic fatty liver disease, subclinical hypothyroidism and mild conductive hearing damage. Whole exome sequencing revealed two compound heterozygous mutations in exon 2 of the BBS12 gene (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) in this patient. Sanger sequencing showed that her father and mother carried c.188delC (p.T63fs) and c.1993_1995del (p.665_665del) variants, respectively, while her parents were free of BBS-related symptoms. In conclusion, this case reported two novel mutations (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) of the BBS12 gene in a girl presented with BBS, which provides novel genetic resources for studies of the disease. Meanwhile, the BBS case shows the entire development progress from her birth to adulthood, which helps facilitate clinicians' understanding of BBS.

A novel model for detecting advanced fibrosis in patients with nonalcoholic fatty liver disease.

AIMS: The study aimed to develop a novel noninvasive model to detect advanced fibrosis based on routinely available clinical and laboratory tests. MATERIALS AND METHODS: A total of 309 patients who underwent liver biopsy were randomly divided into the estimation group (n = 201) and validation group (n = 108). The model was developed using multiple regression analysis in the estimation group and further verified in the validation group. Diagnostic accuracy was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: The model was named NAFLD Fibrosis Index (NFI): -10.844 + 0.046 × age - 0.01 × platelet count + 0.19 × 2h postprandial plasma glucose (PG) + 0.294 × conjugated bilirubin - 0.015 × ALT + 0.039 × AST + 0.109 × total iron binding capacity -0.033 × parathyroid hormone (PTH). The area under the ROC curve (AUC) of NFI was 0.86 (95% CI: 0.79-0.93, p < 0.001) in the estimation group and 0.80 (95% CI: 0.69-0.91, p < 0.001) in the validation group, higher than NFS, FIB4, APRI, and BARD, and similar to FibroScan (NFI AUC = 0.77, 95% CI: 0.66-0.89, p = 0.001 vs. FibroScan AUC = 0.76, 95% CI: 0.62-0.90, p = 0.002). By applying the low cut-off value (-2.756), advanced fibrosis could be excluded among 49.3% and 48% of patients in the estimation group (sensitivity: 93.1%, NPV: 97.9%, specificity: 55.2%, and PPV: 26.0%) and validation group (sensitivity: 81.3%, NPV: 94.2%, specificity: 53.3%, and PPV: 23.2%), respectively, allowing them to avoid liver biopsy. CONCLUSIONS: The study has established a novel model for advanced fibrosis, the diagnostic accuracy of which is superior to the current clinical scoring systems and is similar to FibroScan.

Postprandial glucose is correlated with an increasing risk of liver fibrosis in Chinese patients with nonalcoholic fatty liver disease.

AIM: Type 2 diabetes (T2DM) is closely related to nonalcoholic fatty liver disease (NAFLD) and is an important risk factor for the progression of liver fibrosis, but the role of 2-h postprandial blood glucose (PPG) as a biomarker in this process remains unclear. This study was designed to investigate the relationship between PPG and liver fibrosis in Chinese NAFLD populations with or without T2DM. METHODS: This study included three independent NAFLD populations: 1) 618 inpatients with T2DM or pre-diabetes, 2) 255 patients with T2DM or pre-diabetes who underwent liver biopsy, and 3) a prospective community-based cohort without diabetes who completed a median of 4.22 years follow-up. The degree of liver fibrosis was assessed by liver fibrosis stage in subjects with a liver biopsy, and by NAFLD fibrosis score (NFS) in subjects without liver biopsy. RESULTS: In the first population, PPG {OR 0.02, [95% CI (0.01-0.03)], P< 0.001} was positively correlated with NFS. In the second population, an increasing PPG was associated with increase in the proportion of advanced liver fibrosis (P = 0.012). Multivariate line regression revealed that PPG {OR 0.03 [95% CI (0.00-0.06)], P = 0.049}was positively associated with liver fibrosis stages. In the third population, PPG {OR 0.103, [95% CI (0.011-0.194) P = 0.028} at baseline was positively associated with NFS at follow-up. Furthermore, changes in PPG were significantly associated with NFS change after follow-up. We did not find a similar association between fasting glucose or HbA1c and liver fibrosis. CONCLUSIONS: PPG was independently associated with the severity of liver fibrosis in the Chinese NAFLD population.

An artificial intelligence-based risk prediction model of myocardial infarction.

BACKGROUND: Myocardial infarction can lead to malignant arrhythmia, heart failure, and sudden death. Clinical studies have shown that early identification of and timely intervention for acute MI can significantly reduce mortality. The traditional MI risk assessment models are subjective, and the data that go into them are difficult to obtain. Generally, the assessment is only conducted among high-risk patient groups. OBJECTIVE: To construct an artificial intelligence-based risk prediction model of myocardial infarction (MI) for continuous and active monitoring of inpatients, especially those in noncardiovascular departments, and early warning of MI. METHODS: The imbalanced data contain 59 features, which were constructed into a specific dataset through proportional division, upsampling, downsampling, easy ensemble, and w-easy ensemble. Then, the dataset was traversed using supervised machine learning, with recursive feature elimination as the top-layer algorithm and random forest, gradient boosting decision tree (GBDT), logistic regression, and support vector machine as the bottom-layer algorithms, to select the best model out of many through a variety of evaluation indices. RESULTS: GBDT was the best bottom-layer algorithm, and downsampling was the best dataset construction method. In the validation set, the F1 score and accuracy of the 24-feature downsampling GBDT model were both 0.84. In the test set, the F1 score and accuracy of the 24-feature downsampling GBDT model were both 0.83, and the area under the curve was 0.91. CONCLUSION: Compared with traditional models, artificial intelligence-based machine learning models have better accuracy and real-time performance and can reduce the occurrence of in-hospital MI from a data-driven perspective, thereby increasing the cure rate of patients and improving their prognosis.

Protective Effect of Casticin on Experimental Skin Wound Healing of Rats.

INTRODUCTION: The wound is known as damage to the skin structure by external stimuli, such as cut, bruises, and burn, which typically leaves the internal tissue exposed. The wound repair process when hampered leads to an excessive burden on the healthcare setting. Therefore, there is an urgent need to develop effective agents that can promote the wound healing process. In the present study, we intended to investigate the pharmacological benefit of Casticin (CST), a polymethylflavone against wound. METHODS: The wound in Wistar rats was induced by a surgical procedure. After surgery, the wound was examined for wound size over a period and for the expression of cyclooxygenase-2 and induced collagen III expressions. The effect of CST was examined on tumor necrosis factor α, interferon gamma, interleukin (IL)-10, transforming growth factor beta, and IL-7 by real-time polymerase chain reaction. The expression of matrix metalloproteinases (MMP)-2 and MMP-9 and its natural inhibitor (tissue inhibitors of metalloproteinases, TIMP1), level of macrophages, and lymphocytes were also quantified. The effect of CST was determined also on apoptosis of rats' splenocytes. RESULTS: CST significantly enhances wound healing of rat postsurgery, with maximum activity achieved in the case of a 60 µM treated group. The expression of cyclooxygenase-2 was found reduced together with an increase in collagen III, tumor necrosis factor α, interferon gamma, IL-10, transforming growth factor beta, and IL-7 in the CST group. The levels of MMP-2 and MMP-9 were also found reduced together with an increase in TIMP1 level in CST-treated group. The levels of CD4+, CD8+, and CD11b+ cells at the wound site 24 and 120 h postsurgery was also found reduced in CST-treated group. However, it showed no apoptosis in murine splenocytes. CONCLUSIONS: Collectively, CST can promote the wound healing process by modulation of inflammation and immune response, which induces tissue remodeling.

Identifying drug-related attributes to personalise antihypertensive agents: the outcome report of patients receiving metoprolol therapy.

BACKGROUND: Currently, numerous antihypertensive drugs from different pharmacological classes are available; however, blood pressure control is achieved in only less than a third of patients treated for hypertension. Moreover, providing optimal and personalised treatment for hypertension is challenging. Therefore, in this study, we propose a 'drug-related attributes' sensitive spectrum. This novel concept can assist clinicians in selecting an optimal antihypertensive drug and improve blood pressure control after examining the attributes of a patient. METHODS: We collected clinical data on attributes related to hypertension and its therapy of inpatients from West China Hospital who received metoprolol therapy and constructed the sensitive spectrum using data-visualisation tools. RESULTS: Our analysis revealed that haematocrit, haemoglobin, serum creatinine, serum cystatin C, serum urea, age, sex, systolic pressure, diastolic pressure, pulse pressure, and heart rate are metoprolol-related attributes. CONCLUSION: Our study showed that all metoprolol-related attributes identified are reasonable and helpful in improving the personalisation of metoprolol therapy. The proposed drug-related attributes spectrum can help personalise antihypertensive medication. Moreover, data-visualisation tools can be effectively used to mine the drug-related attributes sensitive spectrum.

Acute Effects of Sleeve Gastrectomy on Glucose Variability, Glucose Metabolism, and Ghrelin Response.

PURPOSE: This study aims to examine the changes of glucose metabolism, glucose variability (GV), and ghrelin secretion within 1 week following SG in Chinese patients with obesity. MATERIALS AND METHODS: Forty-nine patients with obesity (15 with type 2 diabetes) were enrolled to undergo SG. Within 1 week before and after surgery, liquid meal tests were performed in all subjects, and continuous glucose monitoring (CGM) was performed in diabetic patients. Blood samples were collected at 0, 15, 30, 45, 60, 120, and 180 min for glucose, C-peptide, insulin, and ghrelin analysis in liquid meal test. Mean amplitude of glucose excursions (MAGE), standard deviations (SD), and percent time-in-range (%TIR) determined by CGM were analyzed. RESULTS: Both in diabetic and non-diabetic groups, significant decrease was observed in glucose, insulin, C-peptide, and ghrelin. Homeostasis model assessment-insulin resistance and liver fat content was decreased. In diabetic group, MAGE and SD were decreased significantly, and the percent time-in-range was higher. The decrease in blood glucose was positively correlated with the decrease in ghrelin concentration in non-diabetic group. CONCLUSION: Within 1 week after SG, both glucose metabolism and glucose variability were improved significantly. Suppression of ghrelin secretion postoperatively might be a driver of this early improved glycemia homeostasis.

Performance of liver stiffness measurements obtained with FibroScan is affected by glucose metabolism in patients with nonalcoholic fatty liver disease.

BACKGROUND: The performance of liver stiffness measurements (LSMs) obtained using FibroScan can be affected by several factors, and cut-off values are different for fibrosis caused by various aetiologies. The study aims to evaluate the diagnostic accuracy of LSM in nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism and investigate whether the LSM value would be affected by metabolic indicators. METHODS: The study involved 91 NAFLD patients with abnormal glucose metabolism who underwent liver biopsy. The diagnostic accuracy of LSM value was evaluated by the receiver operator characteristic (ROC) curves, with the biopsy results taken as the gold standard. Multivariate linear regression and subgroup analysis were performed to determine the correlated indicators. RESULTS: The areas under the ROC curves (AUROCs) of LSM values for detecting fibrosis stage ≥1, 2, 3 and 4 were 0.793 (95% confidence interval [CI]: 0.695-0.871), 0.764 (95% CI: 0.663-0.846), 0.837 (95% CI: 0.744-0.906) and 0.902 (95% CI: 0.822-0.955), with cut-off values of 6.3, 7.6, 8.3 and 13.8 kPa, respectively. Multivariate linear regression demonstrated that haemoglobin A1c (HbA1c, ß = 0.205, P = 0.026) and alanine aminotransferase (ALT, ß = 0.192, P = 0.047) were independently associated with the LSM value after adjustment for fibrosis stage, ballooning and inflammation grade from liver biopsy. Subgroup analysis demonstrated that LSM values were slightly higher in patients with HbA1c ≥7% than in those with HbA1c < 7% and in patients with body mass index (BMI) ≥30 kg/m2 than in those with BMI < 30 kg/m2. CONCLUSIONS: FibroScan was valuable for the evaluation of liver fibrosis in NAFLD patients with abnormal glucose metabolism. FibroScan is recommended to evaluate severe fibrosis, especially to exclude advanced fibrosis. Glucose metabolism state may affect LSM values.

Diagnosis of Fibrosis Using Blood Markers and Logistic Regression in Southeast Asian Patients With Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of fibrosis. Liver biopsy remains the gold standard for the confirmation of fibrosis in NAFLD patients. Effective and non-invasive diagnosis of advanced fibrosis is essential to disease surveillance and treatment decisions. Herein we used routine medical test markers and logistic regression to differentiate early and advanced fibrosis in NAFLD patients from China, Malaysia, and India (n 1 = 540, n 2 = 147, and n 3 = 97) who were confirmed by liver biopsy. Nine parameters, including age, body mass index, fasting blood glucose, presence of diabetes or impaired fasting glycemia, alanine aminotransferase, γ-glutamyl transferase, triglyceride, and aspartate transaminase/platelet count ratio, were selected by stepwise logistic regression, receiver operating characteristic curve (ROC), and hypothesis testing and were used for model construction. The area under the ROC curve (auROC) of the model was 0.82 for differentiating early and advanced fibrosis (sensitivity = 0.69, when specificity = 0.80) in the discovery set. Its diagnostic ability remained good in the two independent validation sets (auROC = 0.89 and 0.71) and was consistently superior to existing panels such as the FIB-4 and NAFLD fibrosis score. A web-based tool, LiveFbr, was developed for fast access to our model. The new model may serve as an attractive tool for fibrosis classification in NAFLD patients.

Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism.

BACKGROUND: Pioglitazone is a promising therapeutic method for nonalcoholic fatty liver disease (NAFLD) patients with or without type 2 diabetes. However, there is remarkable variability in treatment response. We analyzed our previous randomized controlled trial to examine the effects of gender and other factors on the efficacy of pioglitazone in treating Chinese nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism. METHODS: This is a post hoc analysis of a previous randomized, parallel controlled, open-label clinical trial (RCT) with an original purpose of evaluating the efficacy of berberine and pioglitazone on NAFLD. The total population (n = 185) was randomly divided into three groups: lifestyle intervention (LSI), LSI + pioglitazone (PGZ) 15 mg qd, and LSI + berberine (BBR) 0.5 g tid, respectively, for 16 weeks. The study used proton magnetic resonance spectroscopy (1H-MRS) to assess liver fat content. RESULTS: As compared with LSI, PGZ + LSI treatment further decreased liver fat content in women (- 15.24% ± 14.54% vs. - 8.76% ± 13.49%, p = 0.025), but less decreased liver fat content in men (- 9.95% ± 15.18% vs. - 12.64% ± 17.78%, p = 0.046). There was a significant interaction between gender and efficacy of pioglitazone before and after adjustment for age, smoking, drinking, baseline BMI, BMI change, treatment adherence, baseline liver fat content, and glucose metabolism. CONCLUSION: The study recommends pioglitazone plus lifestyle intervention for Chinese NAFLD female patients with abnormal glucose metabolism. TRIAL REGISTRATION: Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease, NCT00633282 . Registered on 3 March 2008, https://register.clinicaltrials.gov .

Osteocalcin and Non-Alcoholic Fatty Liver Disease: Lessons From Two Population-Based Cohorts and Animal Models.

Osteocalcin regulates energy metabolism in an active undercarboxylated/uncarboxylated form. However, its role on the development of non-alcoholic fatty liver disease (NAFLD) is still controversial. In the current study, we investigated the causal relationship of circulating osteocalcin with NAFLD in two human cohorts and studied the effect of uncarboxylated osteocalcin on liver lipid metabolism through animal models. We analyzed the correlations of serum total/uncarboxylated osteocalcin with liver steatosis/fibrosis in a liver biopsy cohort of 196 participants, and the causal relationship between serum osteocalcin and the incidence/remission of NAFLD in a prospective community cohort of 2055 subjects from Shanghai Changfeng Study. Serum total osteocalcin was positively correlated with uncarboxylated osteocalcin (r = 0.528, p < .001). Total and uncarboxylated osteocalcin quartiles were inversely associated with liver steatosis, inflammation, ballooning, and fibrosis grades in both male and female participants (all p for trend <.05). After adjustment for confounding glucose, lipid, and bone metabolism parameters, the male and female participants with lowest quartile of osteocalcin still had more severe liver steatosis, with multivariate-adjusted odds ratios (ORs) of 7.25 (1.07-49.30) and 4.44 (1.01-19.41), respectively. In the prospective community cohort, after a median of 4.2-year follow-up, the female but not male participants with lowest quartile of osteocalcin at baseline had higher risk to develop NAFLD (hazard ratio [HR] = 1.90; 95% confidence interval [CI] 1.14-3.16) and lower chance to achieve NAFLD remission (HR = 0.56; 95% CI 0.31-1.00). In wild-type mice fed a Western diet, osteocalcin treatment alleviated hepatic steatosis and reduced hepatic SREBP-1 and its downstream proteins expression. In mice treated with osteocalcin for a short term, hepatic SREBP-1 expression was decreased without changes of glucose level or insulin sensitivity. When SREBP-1c was stably expressed in a human SREBP-1c transgenic rat model, the reduction of lipogenesis induced by osteocalcin treatment was abolished. In conclusion, circulating osteocalcin was inversely associated with NAFLD. Osteocalcin reduces liver lipogenesis via decreasing SREBP-1c expression. © 2020 American Society for Bone and Mineral Research (ASBMR).