The PNPLA3 rs738409 C>G variant interacts with changes in body weight over time to aggravate liver steatosis, but reduces the risk of incident type 2 diabetes.

AIMS/HYPOTHESIS: The rs738409 C>G variant of the patatin-like phospholipase domain containing 3 gene (PNPLA3) increases the risk of non-alcoholic fatty liver disease (NAFLD) with no predisposition for insulin resistance. In this study, we aimed to investigate the influence of PNPLA3 polymorphisms on liver fat content (LFC) and glucose metabolic variables, and the associations between these, during the natural course of body weight changes in a Chinese adult cohort. METHODS: The LFC, measured using a quantitative ultrasound method, was prospectively monitored in 2189 middle-aged and elderly adults from the Shanghai Changfeng Study, together with changes in body weight and metabolic variables. General linear models were used to detect interactive effects between the PNPLA3 rs738409 genotype and 4 year changes in body weight on liver steatosis and glucose metabolism. RESULTS: The PNPLA3 homozygous GG genotype dissociated the changes in the LFC and OGTT 2 h post-load blood glucose (PBG) in relation to 4 year changes in body weight. PNPLA3 GG genotype carriers showed greater increases in the LFC and serum alanine aminotransferase (ALT) but lower PBG elevation and incident diabetes than PNPLA3 wild-type (CC) genotype carriers exhibiting the same degree of body weight increase. The interactions between the PNPLA3 genotype and changes in body weight on the LFC (false discovery rate [FDR]-adjusted pinteraction = 0.044) and ALT (FDR-adjusted pinteraction = 0.044) were significant. Subgroup analyses showed that the effect of the PNPLA3 GG genotype on changes in the LFC and PBG was only observed in metabolically unhealthy participants with insulin resistance or abdominal obesity. CONCLUSIONS/INTERPRETATION: The PNPLA3 GG genotype interacted with changes in body weight to aggravate liver steatosis but reduced the risk of incident type 2 diabetes in metabolically unhealthy participants.

Prediction of renal allograft chronic rejection using a model based on contrast-enhanced ultrasonography.

OBJECTIVE: To evaluate the application of contrast-enhanced ultrasonography (CEUS) for the diagnosis of renal allograft chronic rejection (CR). METHODS: A total of 104 patients who were suspected to have AR or CR were enrolled in this study (derivation group, n = 66; validation group, n = 38). Before biopsy, all patients received an ultrasound examination. RESULTS: In the CR group, rising time (RT) and time to peak (TTP) of medulla (RTm and TTPm, respectively) were significantly longer compared to those in the AR group. The kidney volume was significantly decreased in the CR group but was increased in the AR group. In the derivation group, age, change in kidney volume, and TTPm were identified as independent predictors by multivariate analysis. Based on the multivariate analysis results and area under receiver operating characteristic (ROC) curves (AUROCs) of individual markers, we constructed a new index as follows: P = -5.424 + 0.074 × age -9.818 × kidney volume change + 0.115 × TTPm; New Index = eP /(1 + eP ). The new index discriminates CR from AR and had better AUROCs than any other parameters. CONCLUSION: In conclusion, the new index provides a new diagnosis model for CR.

Serum ferritin levels are associated with insulin resistance in Chinese men and post-menopausal women: the Shanghai Changfeng study.

Associations between ferritin and insulin sensitivity have been described in recent studies. The possible association showed conflicting results by sex and menopausal status. We aimed to investigate the cross-sectional association of ferritin levels with insulin resistance and ß-cell function. A total of 2518 participants (1033 men, 235 pre-menopausal women and 1250 post-menopausal women) were enrolled from the Changfeng Study. A standard interview was conducted, as well as anthropometric measurements and laboratory analyses, for each participant. The serum ferritin level was measured using electrochemiluminescence immunoassay. Insulin resistance and ß-cell function indices were derived from a homeostasis model assessment. The results showed that the serum ferritin levels were 250·4 (sd 165·2), 94·6 (sd 82·0) and 179·8 (sd 126·6) ng/ml in the men, pre-menopausal and post-menopausal women, respectively. In fully adjusted models (adjusting for age, current smoking, BMI, waist:hip ratio, systolic blood pressure, diastolic blood pressure, TAG, HDL-cholesterol, LDL-cholesterol, log urine albumin:creatinine ratio, leucocytes, alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transpeptidase), serum ferritin concentrations are significantly associated with insulin resistance in men and post-menopausal females, and the null association was observed in pre-menopausal females. Interestingly, an increased ß-cell function associated with higher ferritin was observed in post-menopausal participants, but not in male participants. In conclusion, these results suggested that elevated serum ferritin levels were associated with surrogate measures of insulin resistance among the middle-aged and elderly male and post-menopausal women, but not in pre-menopausal women.

Relationship between non-high-density lipoprotein cholesterol and carotid atherosclerosis in normotensive and euglycemic Chinese middle-aged and elderly adults.

BACKGROUND: We investigate whether non-high-density lipoprotein cholesterol (non-HDL-C) provides a better estimate of cardiovascular risk than other lipid profiles in normotensive and euglycemic middle-aged and elderly adults. METHODS: A total of 512 males and 958 females were enrolled from the Changfeng Study. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral carotid intima-media thicknesses (CIMTs) were measured using ultrasonography, and the presence of carotid plaques was assessed. RESULTS: The mean values of non-HDL-C were 3.4 ± 0.8 mmol/l and 3.6 ± 0.9 mmol/l for male and female subjects, respectively. Compared with female subjects with non-HDL-C in the first quartile, female subjects with non-HDL-C in the fourth quartile had 1.317-fold increased risks for carotid plaques after adjusting for conventional cardiovascular disease (CVD) risk factors and increasing quartiles of all lipid levels. Non-HDL-C was positively associated with the CIMT after adjusting for CVD risk factors in female subjects (ß = 0.062, P = 0.034). CONCLUSIONS: These results suggest that non-HDL-C is independently associated with carotid atherosclerosis in normotensive and euglycemic females.

The association of liver fat content and serum alanine aminotransferase with bone mineral density in middle-aged and elderly Chinese men and postmenopausal women.

BACKGROUND: Recent studies have linked non-alcoholic fatty liver disease (NAFLD) to a reduced bone mineral density (BMD). We aimed to detect the quantitative association of liver fat content (LFC) and serum alanine aminotransferase (ALT) with BMD in a middle-aged and elderly Chinese population. METHODS: The lumbar spine, hip and whole body BMDs were measured using dual-energy x-ray absorptiometry (Lunar iDXA, GE Healthcare) in 1659 Chinese (755 men and 1028 postmenopausal women) from Shanghai Changfeng community. Liver fat content was quantified via an ultrasound quantitative method. Multivariate linear regression analyses were carried out to determine the independent association of LFC and serum ALT with BMD and bone metabolic biomarkers. We also attempted to investigate the synergistic association between LFC and ALT as risk factors for bone mineral loss in Chinese. RESULTS: Subjects with higher LFC had significantly lower BMD at all skeletal sites. Univariate correlation analysis showed that both LFC and ALT were inversely associated with BMD at the spine (r = -0.116, P < 0.001 and r = -0.102, P = 0.005), hip (r = -0.095, P = 0.014 and r = -0.075, P = 0.041) and whole body sites (r = -0.134, P < 0.001 and r = -0.164, P < 0.001) in men. After confounders were controlled for, LFC and ALT remained associated with BMD and bone formation biomarkers in men, but not postmenopausal women. When both NAFLD and elevation of ALT were present, there was a significant synergistic worsening of the BMDs at all bone sites. CONCLUSIONS: Liver fat content and serum ALT were inversely correlated with BMD in middle-aged and elderly men. The underlying mechanism might relate to a reduction in osteoblast activity. Elevation of the hepatotoxic biomarker ALT may indicate high risk for osteoporosis in patients with NAFLD.

Serum ferritin levels are associated with carotid atherosclerosis in Chinese postmenopausal women: the Shanghai Changfeng Study.

Postmenopausal women are at increased risk of CVD: the increased serum ferritin level may be involved in the pathogenesis. The aim of the present study is to investigate the relationship of ferritin and carotid atherosclerosis in postmenopausal women. A total of 1178 postmenopausal women (mean age, 60·8 years) were enrolled from the Changfeng Study. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral CIMT (carotid intima-media thickness) were measured using ultrasonography, and the presence of carotid plaques was assessed. Serum ferritin was measured using electrochemiluminescence immunoassay. The results showed that serum ferritin was 181·9 (sd 65·8) ng/ml in the postmenopausal women. Multivariate, linear, stepwise regression analysis demonstrated that age (standardised ß = 0·233, P< 0·001), alanine transaminase (standardised ß = 0·194, P< 0·001), log homeostasis model assessment index for insulin resistance (standardised ß = 0·181, P< 0·001), TAG (standardised ß = 0·083, P= 0·003), Hb (standardised ß = 0·080, P= 0·004) and PPG (2-h glucose levels following a 75-g oral glucose challenge) (standardised ß = 0·079, P= 0·004) were independently associated with serum ferritin. Compared with the ferritin level of subjects in the first quartile, that in the fourth quartile had greater CIMT, and higher prevalence of carotid plaque. After adjusting for conventional CVD risk factors, Hb, leucocytes, log urine albumin:creatinine ratio and liver function, the ferritin level of postmenopausal women in the fourth quartile had a 1·587-fold increased risk of carotid plaques relative to those in the lowest quartile. In conclusion, these results suggest that serum ferritin is independently and positively associated with carotid atherosclerosis in postmenopausal women and that ferritin may be implicated in atherosclerosis.

Serum 25-hydroxyvitamin D levels are associated with carotid atherosclerosis in normotensive and euglycemic Chinese postmenopausal women: the Shanghai Changfeng study.

BACKGROUND: The role of serum 25-hydroxyvitamin D (25 (OH) D) in atherogenesis is unclear. We investigated whether the 25 (OH) D is independently associated with the carotid intima-media thickness (CIMT) and carotid plaques in normotensive and euglycemic postmenopausal women. METHODS: A total of 671 normotensive and euglycemic postmenopausal women (mean age, 58.8 years) were enrolled from the Changfeng Study. A standard interview, anthropometrics measurements and laboratory analyses were performed for each participant. Bilateral CIMTs were measured using ultrasonography, and the presence of carotid plaques was assessed. The serum 25 (OH) D was measured using electrochemiluminescence immunoassay. RESULTS: Serum 25 (OH) D was 43.6 ± 18.2 nmol/L in the postmenopausal women. Compared with subjects with 25 (OH) D in the first, second and third quartiles, subjects with 25 (OH) D in the fourth quartile had decreased CIMT and prevalence of carotid plaque (0.684 ± 0.009 mm vs 0.719 ± 0.009 mm, 0.708 ± 0.009 mm and 0.709 ± 0.009 mm; 10.8% vs 19.0%, 14.8% and 16.8%, respectively). After adjusting for conventional CVD risk factors, PTH, liver and renal function, postmenopausal women with 25 (OH) D in the fourth quartile still had lower CIMT than those in the first, second and third quartiles (p = 0.039) and the subjects in the fourth quartile had a 0.421-fold decreased risk of carotid plaques relative to those in the lowest quartile (95% confidence interval 0.209 to 0.848). CONCLUSIONS: These results suggest serum 25 (OH) D is independently and inversely associated with carotid atherosclerosis in postmenopausal women with normal blood pressure and normal glucose tolerance.

Chitin/calcite composite extracted from shell waste as a low-cost adsorbent for removal of tetracycline and ciprofloxacin: Effects and mechanisms.

Recently, water contamination caused by the misuse of antibiotics has become a growing concern. In this study, an economical chitin/calcite composite (CCA) was extracted from crab shell waste, and the effects and mechanisms of its removal of ciprofloxacin (CIP) and tetracycline (TC) from aqueous solution were investigated. The functional groups of chitin and the metal phase of calcite gave CCA the ability to remove antibiotics. Experiments on kinetics, isothermal adsorption, thermodynamics, co-removal, and reusability were conducted to systematically explore the adsorption performances of CCA toward antibiotics. The pseudo-second-order (FSO) and Langmuir models suited the data obtained from experiments best and displayed a good fit for the chemisorption and a certain homogeneity of adsorption sites. At 25 °C, the maximum adsorption capacities (Qmax) toward CIP and TC were 228.86 and 150.76 mg g-1, respectively. The adsorption mechanisms of CCA with TC and CIP are pH dependent since pH can affect the surface charge of CCA and the form in which CIP and TC are existing. The X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) demonstrated that the keto-O and carboxyl groups of CIP and the carbonyl, hydroxyl, and amido groups of TC could be responsible for the binding with the calcite and the functional groups of chitin through surface complexation, cation bridge and hydrogen bonding.

Structural design of La2(CO3)3 loaded magnetic biochar for selective removal of phosphorus from wastewater.

High levels of phosphorus released into the environment can cause eutrophication issues in wastewater, therefore discharge concentrations of such element are regulated in many countries. This study addresses the pressing need for effective phosphorus removal methods by developing a novel La2(CO3)3 and MnFe2O4 loaded biochar composite (LMB). A remarkable adsorption capacity towards the three forms of phosphorus from wastewater, including phosphate, phosphite, and etidronic acid monohydrate (as a representative of organic phosphorus), was exhibited by LMB (88.20, 16.35, and 15.95 mg g-1, respectively). The high saturation magnetization value (50.17 emu g-1) highlighted the easy separability and recyclability of the adsorbent. The adsorption process was well described by the Langmuir isotherm model and the pseudo-second-order kinetic model, which mainly involved chemisorption. Characterization results confirm the effective loading of La2(CO3)3 with ligand exchange and electrostatic attraction identified as the primary mechanisms. Importantly, the LMB demonstrated exceptional selectivity for phosphorus in wastewater samples containing various substances, exhibiting minimal interference from competing ions (Cl-, NO3-, SO42-, and CO32-). These findings enhance the understanding of LMB's application in efficient wastewater phosphorus removal. Holding significant promise in wastewater remediation, the LMB acts as an effective adsorbent, contributing substantially to the prevention and control of various types of phosphorus pollutants, thereby mitigating wastewater eutrophication.

Differentiating Benign From Malignant Ovarian Masses With Solid Components: Diagnostic Performance of CEUS Combined With IOTA Simple Rules and O-RADS.

OBJECTIVE: This study aimed to apply the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR), the Ovarian-Adnexal Reporting and Data System (O-RADS) and contrast-enhanced ultrasound (CEUS) in an identical cohort of Chinese patients and to analyze their performance in discrimination of ovarian masses with solid components. METHODS: This was a two-center retrospective study that included a total of 94 ovarian lesions in 86 women enrolled from January 2018 to February 2023. The lesions were classified by using the IOTA terminology and CEUS was performed for the lesions exhibiting solid components on ultrasonography, IOTA SR and O-RADS were applied, and CEUS images were analyzed retrospectively. We assessed the time to wash-in, time to peak intensity (PI), PI compared to myometrium, and time to wash-out, and observed statistically significant differences between benign and malignant lesions in the first three parameters. CEUS characteristics were employed to determine CEUS scores for benign (score 0) and malignant (score 3) lesions. Subsequently, the lesions were reassessed based on the IOTA SR and O-RADS classifications and CEUS scores. The sensitivity, specificity, and area under the receiver-operating-characteristics curve (AUC) of the different models were also determined. RESULTS: Among the 94 ovarian lesions, 46 (48.9%) were benign and 48 (51.1%) were malignant. It was found that in the 60 lesions to which the SR could be applied, the sensitivity, specificity, and AUC was 0.900, 0.667, and 0.783, respectively. The sensitivity, specificity, and AUC of O-RADS was observed to be 1.000, 0.283 and 0.641, respectively. When SR and O-RADS were combined with CEUS, their sensitivity, specificity, and AUC values were increased to 0.917, 0.891, 0.904, and 0.958, 0.783, 0.871, respectively. CONCLUSION: IOTA SR and O-RADS exhibited relatively low specificity in differentiating malignant from benign ovarian lesions with the solid components, and their diagnostic performance can be significantly improved when combined with CEUS.

Comparison of contrast-enhanced ultrasound, IOTA simple rules and O-RADS for assessing the malignant risk of sonographically appearing solid ovarian masses.

PURPOSE: To explore the diagnostic accuracy of ovarian solid tumors by 2D ultrasound and contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: We retrospectively evaluated the CEUS characteristics of prospectively enrolled 16 benign and 19 malignant ovarian solid tumors. We performed International Ovarian Tumor Analysis (IOTA) simple rules and Ovarian-Adnexal Reporting and Data System (O-RADS) for all lesions, and evaluated their characteristics on CEUS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of IOTA simple rules, O-RADS and CEUS in the diagnosis of ovarian solid malignancies were calculated. RESULTS: The combination of time to wash-in earlier than or equal to the myometrium, time to PI earlier than or equal to the myometrium and the intensity at peak were higher than or equal to myometrium with sensibility of 0.947, specificity of 0.938, and PPV of 0.947, NPV of 0.938 which were higher than IOTA simple rules and O-RADS. According to the definition of ovarian solid tumor, the diagnostic accuracy of O-RADS 3 and CEUS were both 100%, CEUS improved the accuracy of O-RADS 4 from 47.4% to 87.5%, the accuracy of solid smooth CS 4 in O-RADS 5 and CEUS were both 100%, CEUS improved the accuracy of solid irregular in O-RADS 5 from 70% to 87.5%. CONCLUSION: For ovarian solid tumors that are difficult to distinguish between benign and malignant, the introduction of CEUS on the basis of 2D classification criteria can significantly improve the diagnostic accuracy.

Presence of sarcopenia identifies a special group of lean NAFLD in middle-aged and older people.

BACKGROUND: Sarcopenia, the age-related loss of muscle mass and function, is closely associated and frequently concomitant with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the clinical features of the sarcopenic NAFLD patients from middle-aged and older people. METHODS: A total of 1305 patients with NAFLD from the Shanghai Changfeng Study were included for analysis. Sarcopenia was diagnosed based on the height-adjusted appendicular skeletal muscle mass (ASM/height2). We comprehensively analyzed the metabolic phenotype, carotid artery condition, liver fibrosis score, and serum metabolomic profile of each participant. RESULTS: Among the middle-aged and older population, 68.1% of patients with sarcopenia and NAFLD were lean. Sarcopenia was independently associated with increased risk of carotid plaque (OR, 2.22; 95%CI 1.23-4.02) and liver fibrosis (OR, 2.07; 95%CI 1.24-3.44), and the sarcopenic lean NAFLD patients were characterized by a higher risk of carotid plaque (p = 0.008) and liver fibrosis (p = 0.001) than the non-sarcopenic lean NAFLD patients, despite their lower BMI and similar prevalence of metabolic syndrome and diabetes. Further serum metabolomic examination indicated that the sarcopenic lean NAFLD patients presented a distinct metabolomic profile prone to carotid plaque and liver fibrosis, with upregulated serum valine, N-acetylneuraminyl-glycoproteins, lactic acid, small LDL triglycerides and VLDL5 components, and reduced components of HDL4. A sarcopenic characterization score based on above metabolites was established and could also predict increased risk of carotid plaque and liver fibrosis. CONCLUSION: The presence of sarcopenia identifies a special subgroup of lean NAFLD with increased risk of cardiovascular disease and liver fibrosis clinically.

Renal function-dependent association of serum uric acid with metabolic syndrome and hepatic fat content in a middle-aged and elderly Chinese population.

The effect of uric acid (UA) on the pathogenesis of metabolic disorders is highly dependent on its physicochemical properties, and hyperuricaemia associated with different conditions may have different clinical meanings. The aim of the present study was to investigate the association of serum UA levels with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) in a middle-aged and elderly population with normal and impaired renal function. The cross-sectional study was performed on 1141 participants (426 men, 715 women; mean age 62 years) enrolled from the Shanghai Changfeng community. Each participant underwent a standard interview, with anthropometric and laboratory measurements. Hepatic fat content (HFC) was determined by a newly established quantitative ultrasound method. Univariate correlation analysis showed that serum UA was associated with all components of metabolic syndrome and HFC (r = 0.193, P < 0.001), especially in participants with a normal estimated glomerular filtration rate (eGFR; r = 0.255, P < 0.001). Logistic regression analysis demonstrated an independent association of serum UA with metabolic syndrome and NAFLD in participants with normal renal function, but not in those with eGFR < 90 mL/min per 1.73 m(2) . Furthermore, multivariate linear analysis showed that UA levels were independently associated with HFC (P = 0.003), but only in participants with normal eGFR. Elevated serum UA is independently associated with metabolic syndrome and NAFLD in patients with normal renal excretory function. However, in those with renal insufficiency, hyperuricaemia has no association with metabolic disorders.

NAFLD-related gene polymorphisms and all-cause and cause-specific mortality in an Asian population: the Shanghai Changfeng Study.

BACKGROUND: The PNPLA3 and TM6SF2 gene variants have been found to cause NAFLD with a favourable cardiovascular risk profile. AIMS: To investigate the effects of the NAFLD risk alleles on the all-cause and cause-specific mortality in 5581 Chinese adults. METHODS: The genome-wide genotypes were detected using a genotyping array and serum lipoprotein profiles were examined using 1H NMR platform. Liver fat content (LFC) was measured using a quantitative ultrasound method. The vital status was determined using official registration data. RESULTS: Genome-wide association analysis showed that a series of variants in PNPLA3 were associated with LFC, including rs738409 C>G variant (P = 8.6 × 10-7 ). Further analyses validated the associations of TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants with NAFLD. During 29 425.1 person-years of follow-up, the overall mortality was 816 per 100 000 person-years, where 299 deaths were attributable to cardiovascular disease and 85 to liver disease. The PNPLA3 rs738409 C>G variant was independently associated with increased liver-specific mortality (P for trend = 0.034) but reduced cardiovascular mortality (P for trend = 0.047). A composite genetic-predisposition score of PNPLA3, TM6SF2, and MBOAT7 risk alleles presented similar opposite effects on liver-specific and cardiovascular mortality. Moreover, interactions of the NAFLD risk alleles with adiposity for liver-specific mortality were found (Pinteraction  < 0.05). The reduced serum VLDL1 concentration was responsible for the increased liver-specific mortality related to NAFLD risk alleles. CONCLUSION: The PNPLA3 rs738409 C>G variant and its combination with TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants increase liver-specific mortality but reduce cardiovascular mortality in overweight/obese Chinese.

Liver fat content is independently associated with microalbuminuria in a normotensive, euglycaemic Chinese population: a community-based, cross-sectional study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is associated with microalbuminuria (MA) in patients with diabetes/pre-diabetes. Whether this association is mediated by blood glucose and blood pressure (BP) remains unclear. This study investigated whether liver fat content (LFC) was associated with MA in a normotensive and non-diabetic population. DESIGN: A cross-sectional substudy. SETTINGS: LFC was determined from the hepatic/renal echogenicity ratio at ultrasound. MA was defined as an albumin-to-creatinine ratio (ACR) of 30-300 µg/mg (early- morning urine sample). Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate LFC as a predictor of MA. PARTICIPANTS: Between May 2010 and June 2011, this cross-sectional, community-based study enrolled residents from Shanghai (China), aged ≥40 years and with normal glucose tolerance and BP. RESULTS: A total of 550 residents (median age, 57 years; 174 men) were enrolled and stratified according to LFC quartiles. ACR (p<0.001) and MA prevalence (p=0.012) increased across the LFC quartiles. Multivariable logistic regression showed that the OR for MA (per SD increase in LFC) was 1.840 (95% CI 1.173 to 2.887, p=0.008) after adjustment for potential confounders including age, gender, waist-hip ratio, blood urea nitrogen, systolic and diastolic BP, fasting blood glucose, postprandial glucose, low-density lipoprotein-cholesterol, triglycerides, high-density lipoprotein-cholesterol, total cholesterol, estimated glomerular filtration rate and lipid-lowering drugs. The ROC analysis revealed that the optimal LFC cut-off value for predicting MA was 6.82%. CONCLUSION: LFC is independently associated with MA in normotensive, euglycaemic middle-aged and elderly Chinese individuals. Screening for MA in people with NAFLD might facilitate early intervention to minimise kidney disease risk.

Sarcopenia, sarcopenic overweight/obesity and risk of cardiovascular disease and cardiac arrhythmia: A cross-sectional study.

BACKGROUND: Sarcopenia is an age-dependent skeletal muscle disorder that is common in patients with heart failure. The current study aimed to investigate the associations of sarcopenia with carotid atherosclerosis, cardiovascular disease and cardiac arrhythmia in a middle-aged and elderly population without clinical heart failure. METHODS: A total of 2432 participants (992 men and 1440 women) from Shanghai Changfeng Study were included for analysis. The degree of sarcopenia was measured using height-adjusted appendicular skeletal muscle mass (ASM/height2). Carotid plaques were detected by carotid artery ultrasonography, and myocardial ischemia, infarction and cardiac arrhythmia were diagnosed based on electrocardiogram, past history and clinical manifestations. RESULTS: Sarcopenia was associated with higher prevalence of carotid atherosclerosis (26.4% vs 20.4%, P = 0.027), myocardial infarction (4.0% vs 1.1%, P = 0.001), and premature ventricular contraction (4.0% vs 2.0%, P = 0.034) in the participants with normal body weight, and higher prevalence of carotid atherosclerosis (45.0% vs 31.2%, P = 0.016), myocardial infarction (10.0% vs 4.3%, P = 0.020) and atrial fibrillation (7.5% vs 1.3%, P < 0.001) in those with overweight/obese status. After adjustment for age, gender, cigarette smoking, alcohol drinking, menopausal status in women and other metabolic and inflammatory confounding factors, sarcopenia was independently associated with the risk of myocardial infarction in the whole population, and the risk of atrial fibrillation in the overweight/obese participants (all P < 0.05). Compared with nonsarcopenic lean participants, the risk of myocardial infarction was gradually increased in sarcopenic lean (OR 3.08 [1.28-7.45], P = 0.012) and sarcopenic overweight/obese participants (OR 4.07 [1.31-12.62], P = 0.015). For the atrial fibrillation, the participants with either sarcopenia or overweight/obesity alone showed no higher risk. However, concomitant sarcopenia and overweight/obesity was associated with approximately 5-fold risk of atrial fibrillation (OR 5.68 [1.34-24.12], P = 0.019) after multiple adjustment. CONCLUSION: Sarcopenia is associated with myocardial infarction and atrial fibrillation in middle-aged and elderly adults without clinical heart failure.

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).

Analysis of contrast-enhanced ultrasound features of hepatocellular adenoma according to different pathological molecular classifications.

OBJECTIVE: To explore the specific contrast-enhanced ultrasound (CEUS) features of hepatocellular adenomas (HCA) according to their pathological molecular classifications. METHODS & MATERIALS: In this retrospective study, fifty-three histopathologically proved HCA lesions (mean size, 39.7±24.9 mm) were included. Final histopathological diagnosis of HCA lesions were identified by surgical resection (n = 51) or biopsy (n = 2) specimens. CEUS imaging features were compared among four subgroups according to World Health Organization (WHO) 2019 pathological molecular classifications standards. Analysis of variance (ANOVA) were used for statistical analysis of continuous variables. Fisher's exact test were used for categorical variables. The sensitivity (SE), specificity (SP), and accuracy of CEUS feature in diagnosis of each HCA subtype were calculated and compared. RESULTS: Final histopathological diagnosis included HNF-1α inactivated HCAs (H-HCA, n = 12), ß-catenin activated HCAs (B-HCA, n = 8), inflammatory HCAs (I-HCA, n = 31), and unclassified HCAs (U-HCA, n = 2). During arterial phase of CEUS, all HCAs were hyper-enhanced, 66.6% (8/12) of H-HCAs and 50% (4/8) of B-HCAs displayed complete hyperenhancement, whereas 58.0% (18/31) of I-HCAs showed centripetal filling hyperenhancement pattern (P = 0.016). Hyper-enhanced subcapsular arteries could be detected in 64.5% (20/31) I-HCAs during early arterial phase. During portal venous and late phase, sustained hyper- or iso-enhancement were observed in 91.7% (11/12) of H-HCAs, while most of I-HCAs (61.3%, 19/31) and B-HCAs (7/8, 87.5%) were hypo-enhanced (P = 0.000). Central unenhanced areas were most commonly observed in I-HCAs (29.0%, 9/31) (P = 0.034). CONCLUSION: Depending on its unique imaging features including enhancement filling pattern, hyper-enhanced subcapsular artery and presence of washout, CEUS might provide helpful diagnostic information for preoperative prediction of various HCA molecular subtypes.

The PNPLA3 rs738409 C>G variant influences the association between low skeletal muscle mass and NAFLD: the Shanghai Changfeng Study.

BACKGROUND: Age-related skeletal muscle loss and patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphisms are both associated with increased liver steatosis and fibrosis in the absence of obesity. AIM: To investigate the influence of PNPLA3 polymorphism on the relationship between skeletal muscle loss and non-alcoholic fatty liver disease (NAFLD). METHODS: Liver fat content was measured using a quantitative ultrasound method, and liver fibrosis was assessed by NAFLD fibrosis, BARD and FIB-4 scores in 3969 Chinese adults. The degree of sarcopenia was measured by weight-adjusted appendicular skeletal muscle mass (ASM% = appendicular skeletal muscle mass(kg)/body weight(kg)  100%). RESULTS: The NAFLD proportion increased from 19.9% to 41.2% in men and 26.3% to 42.3% in women with decreasing ASM% quartiles (P < 0.001). Low ASM% was inversely associated with NAFLD in PNPLA3 CC (odds ratio [OR]: men, 0.735 [0.610-0.885] and women, 0.812 [0.718-0.918], both P = 0.001) and CG (OR: men, 0.673 [0.573-0.790] and women, 0.798 [0.713-0.893], both P < 0.001) but not GG genotype carriers. The association remained significant after adjustment for age, cigarette smoking, fat mass, interaction between fat mass and ASM%, obesity, diabetes and all components of metabolic syndrome. Subgroup analyses found that PNPLA3 GG gene variant did not increase the risk for NAFLD in individuals with low ASM% regardless of obesity status. Low ASM% also increased risk for liver fibrosis (all P < 0.05), which became insignificant after multiple adjustments. CONCLUSIONS: Low ASM% is associated with NAFLD and liver fibrosis. Dissociation of sarcopenia and NAFLD was found in PNPLA3 GG genotype carriers. A stratification based on PNPLA3 genotypes might facilitate personalised treatment for NAFLD.

Prediction of Renal Allograft Acute Rejection Using a Novel Non-Invasive Model Based on Acoustic Radiation Force Impulse.

Point shear wave elastography based on acoustic radiation force impulse is a novel technology used to quantify tissue stiffness by measuring shear wave speed. A total of 115 kidney transplantation recipients were consecutively enrolled in this prospective study. The patients were subdivided into two groups using 1 mo post-transplantation as the cutoff time for determining the development of acute rejection (AR). Shear wave speed was significantly higher in the AR group than in the non-AR group. We created a model called SEV, comprising shear wave speed, estimated glomerular filtration rate and kidney volume change, that could successfully discriminate patients with or without AR. The area under the receiver operating characteristic curve of SEV was 0.89, which was higher than values for other variables; it was even better in patients within 1 mo post-transplantation (0.954), but was lower than the estimated glomerular filtration rate in patients after 1 mo post-transplantation. Therefore, the SEV model may predict AR after renal transplantation with a high degree of accuracy, and it may be more useful in the early post-operative stage after renal transplantation.