Association between frailty and hepatic fibrosis in NAFLD among middle-aged and older adults: results from NHANES 2017-2020.

Background: Although previous studies found that frailty is prevalent in NAFLD patients with advanced liver fibrosis and cirrhosis, studies examining the relationship are spare. Aim: Our study aspires to investigate the potential correlation between the Frailty Index (FI) and hepatic fibrosis among middle-aged and older adults with NAFLD. Methods: Data from the 2017-2020.03 National Health and Nutrition Examination Survey (NHANES) were utilized for this study, with a final of 2,383 participants aged 50 years and older included. The quantification of frailty was executed employing a 49-item frailty index. The recognition of hepatic steatosis and fibrosis was accomplished through the utilization of the controlling attenuation parameter (CAP) and transient elastography (TE). The relationship between the FI and hepatic fibrosis were investigated employing univariable and multivariable-adjusted logistic regression analyses. A subgroup analysis was conducted, dividing the subjects based on gender, Body Mass Index (BMI), and the presence of hyperlipidemia. Results: The findings demonstrated a positive correlation between the FI and significant hepatic fibrosis in NAFLD, even after using multivariate logistic regression models adjusting for potential confounding factors (OR = 1.022, 95% CI, 1.004-1.041) and in tertiles (Q3vs Q1: OR = 2.004, 95% CI, 1.162-3.455). In the subgroup analysis, the correlation was more statistically significant in male (OR = 1.046, 95% CI, 1.022-1.071), under/normal weight (OR = 1.077, 95% CI, 1.009-1.150), overweight (OR = 1.040, 95% CI, 1.010-1.071), and subjects without hyperlipidemia (OR = 1.054, 95% CI, 1.012-1.097). The area under the Receiver Operating Characteristic (ROC) curve for the FI in assessing the existence of substantial fibrosis in NAFLD was 0.612 (95% CI, 0.596-0.628). Conclusion: This study demonstrated a positive correlation between significant hepatic fibrosis and frailty, particularly among males aged 50 years and older, who were non-obese and did not have hyperlipidemia with NAFLD. Additional studies are required to further validate these findings.

Defects in a liver-bone axis contribute to hepatic osteodystrophy disease progression.

Hepatic osteodystrophy (HOD) is a metabolic bone disease that is often associated with chronic liver disease and is marked by bone loss. Here, we demonstrate that hepatic expression of the phosphatase PP2Acα is upregulated during HOD, leading to the downregulation of expression of the hepatokine lecithin-cholesterol acyltransferase (LCAT). Loss of LCAT function markedly exacerbates the bone loss phenotype of HOD in mice. In addition, we found that alterations in cholesterol levels are involved in the regulation of osteoblast and osteoclast activities. We also found that LCAT improves liver function and relieves liver fibrosis in the mouse HOD model by promoting reversal of cholesterol transport from the bone to the liver. In summary, defects in a liver-bone axis occur during HOD that can be targeted to ameliorate disease progression.

Urinary levels of dimethoate, bisphenol A and benzo[a]pyrene in first-year students of Hohai University from different geographical regions.

BACKGROUND: The objective of this study was to detect the urinary levels of dimethoate, benzo(a) pyrene (BaP), and bisphenol A (BPA) in first-year Hohai University students with different geographic origins. METHODS: First-morning urine samples were collected from 540 healthy freshmen aged 17 to 19 years. Chemical levels were measured using ß-glucuronidase hydrolysis followed by a high-performance liquid chromatography-tandem mass spectrometry-based method. Geometric means (GMs) of these three chemicals are presented by body mass index (BMI) and location in a volume-based and creatinine-standardized way. RESULTS: GM concentrations of omethoate, BPA and 3-OHBaP were 9.47 µg/L (10.80 µg/g creatinine), 3.54 µg/L (4.04 µg/g creatinine) and 0.34 ng/L (0.39 ng/g creatinine), respectively. The GM concentration of omethoate in males was significantly higher than that in females. The individuals with a BMI higher than 23.9 had higher GM concentrations of omethoate, BPA, and 3-OHBaP. The inhabitants of Southwest China had significantly lower GM concentrations of omethoate, BPA, and 3-OHBaP than those who lived in other locations in China. CONCLUSION: The average level of environmental chemical accumulation in freshmen is lower in Southwest China and differs in youth who live in different regions. In addition, obesity is correlated with higher toxin levels in youth.

Vielanin P enhances the cytotoxicity of doxorubicin via the inhibition of PI3K/Nrf2-stimulated MRP1 expression in MCF-7 and K562 DOX-resistant cell lines.

BACKGROUND: Cancer cells that are resistant to structurally and mechanically unrelated anticancer drugs are said to have multidrug resistance (MDR). The overexpression of the ATP-binding cassette (ABC) transporter is one of the most important mechanisms of MDR. Vielanin P (VP), a dimeric guaiane from the leaves of Xylopia vielana, has the potential to reverse multidrug resistance. PURPOSE: To evaluate the meroterpenoid compound VP as a low cytotoxicity MDR regulator and the related mechanisms. METHODS: Cell viability was determined by CCK-8 and MTT assays. Apoptosis and the accumulation of doxorubicin (DOX) and 5(6)-carboxyfluorescein diacetate (CFDA) were determined by flow cytometry. We determined mRNA levels by quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels were analyzed by Western blotting and immunofluorescence. RESULTS: In the MCF-7 and K562 DOX-resistant cell lines, VP treatment (10 µM or 20 µM) enhanced the activity of chemotherapeutic agents. We found that VP selectively inhibited MRP1 mRNA but not MDR1 mRNA. VP enhanced DOX-induced apoptosis and reduced colony formation in the presence of DOX in drug-resistant cells. Moreover, VP increased the accumulation of DOX and the MRP1-specific substrate CFDA. In addition, VP reversed MRP1 protein levels and the accumulation of DOX and CFDA in MRP1-overexpressing MCF-7 and K562 cells. Thus, the mechanism of MDR reversal by VP is MRP1-dependent. Furthermore, we found that the inhibitory effect of VP on MRP1 is PI3K/Nrf2-dependent. CONCLUSION: These results support the potential therapeutic value of VP as an MDR-reversal agent by inhibiting MRP1 via PI3K/Nrf2 signaling.

Asperfuranones A-C, 3(2H)-furanone derivatives from the fungus Aspergillus sp. and the configuration reassignment of their eighteen analogues.

Three undescribed 3(2H)-furanone derivatives, asperfuranones A-C (1-3), along with one known compound (4) were isolated from the Aspergillus sp. strain obtained from the intestines of centipede. Their structures were determined by NMR and MS spectroscopic analyses, and the absolute configurations were established by the Snatzke's sector rules, modified Mosher's method and electronic circular dichroism (ECD) calculation. Meanwhile, the application of the sector rules led to the reassignment of the absolute configurations of 4 and other seventeen previously reported analogues (5-21).

[NSAIDs combined with radiotherapy to prevent heterotopic ossification after total hip arthroplasty].

OBJECTIVE: To investigate the preventive effects and differences of NSAIDs combined with radiotherapy, NSAIDs and radiotherapy for heterotopic ossification(HO) after total hip arthroplasty(THA). METHODS: From February 2015 to July 2016, 168 hips undergoing primary THA were divided into group A, B and C, and 163 patients were followed up (54 cases and 54 hips in group A, 55 cases and 55 hips in group B, 54 cases and 54 hips in group C). Among group A, 5 hips were primary osteoarthritis, 37 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 12 hips were secondary osteoarthritis due to acetabular dysplasia. Patients in group A received oral celecoxib (0.2 g, 2 times a day) for 2 weeks after operation. Among group B, 6 hips were primary osteoarthritis, 32 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 17 hips were secondary osteoarthritis due to acetabular dysplasia, all of which in group B were treated with preoperative single 7 Gy radiotherapy. Among group C, 5 hips were primary osteoarthritis, 35 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 14 hips were secondary osteoarthritis due to acetabular dysplasia. Patients in group C were treated with preoperative radiotherapy and celecoxib after operation. The side effects of gastrointestinal reactions were observed after operation, and the heterotopic ossification was evaluated by pelvic anterior and posterior X-ray (Brooker grading). RESULTS: The mean clinical and radiological follow-up was 21 months(12 to 30 months). In group A, 54 hips were followed up with 7 hips with heterotopic ossification, including 5 hips of Brooker I and 2 hips of Brooker II. In group B, 55 hips were successfully followed up, with 8 hips of heterotopic ossification occurred, including 6 hips of Brooker I, 2 hips of Brooker II. In group C, 54 hips were successfully followed up, with 5 hips of heterotopic ossification occurred , including 4 hips of Brooker I, 1 hip of Brooker II. There was no significant difference in efficacy among 3 groups (χ²=0.743, P=0.690) by chi-square test. The prevalence of side effects were as following: in group A, there were 6 hips with side effects;in group B, there were 6 hips with side effects;in group C, there were 7 hips with side effects. There was also no significant difference in side effects among 3 groups (χ²=0.135, P=0.935). CONCLUSIONS: The combined-therapy group has lower prevalence of HO than the NSAIDs group or radiotherapy group, but the statistical difference between them is not significant. NSAIDs is still the first choice to prevent HO after THA.

New triterpenoids with diverse side-chains from the barks of Melia Toosendan.

Nine new euphane- and apotirucallane-type triterpenoids (Toosendines A-I; 1-9), along with three known tirucallane-type compounds were isolated from the barks of Melia toosendan. Their structures were elucidated based on detailed spectroscopic analyses (HRESIMS, 1D/2D-NMR) and circular dichroism spectra. Results of bioactivities screening exhibited that compounds 1, 4 and 5 showed remarkable NO inhibitory activities in LPS-activated RAW 264.7 macrophages, meanwhile, compounds 1 and 4 showed moderate cytotoxicities against U2OS human cancer cell line.

[Analysis of perioperation complications of total hip arthroplasty in treating Crowe type IV developmental dysplasia of the hip].

OBJECTIVE: To evaluate the clinical effects of total hip arthroplasty (THA) for Crowe type IV developmental dysplasia of the hip (DDH) and analyze perioperative complications. METHODS: From March 2000 to March 2010, 19 patients (23 hips, of them, 4 patients with bilateral hips) with Crowe type IV DDH underwent THA. There were 5 males and 14 females, with average age of 61.3 years (ranged, 41 to 72 years). All hips were treated with small acetabular components combined with medial protrusion technique in acetabular reconstruction, as well as subtrochanteric shortening osteotomy in femur. Joint function of hips were evaluated according to Harris scoring. RESULTS: All patients were followed up with an average of 4.2 years (ranged, 1 to 8 years). Postoperative X-ray films showed all acetabular prosthesis were in true acetabulum. No loosening and nonunion were found in all patients. Harris scoring improved from preoperative 34.0 +/- 6.9 to postoperative 85.0 +/- 7.5. Complications occurred in 11 cases in the patients, including femoral split fracture in 3 cases, nerve injury in 3 cases, delayed union in 2 cases, dislocation in 3 cases. CONCLUSION: Total hip arthroplasty using small acetabular component, medial protrusion, femoral subtrochanteric shortening osteotomy technique for the Crowe type IV DDH can effectively restore hip function and leg length. But incidence of complications is high. The long-term follow-up is necessary for further study.

Effects of cake collapse caused by deposition of fractal aggregates on pressure drop during ceramic filtration.

A cake collapse model was developed by taking the combined effects of fractal dimension, relaxation ratio, coordination number, and aggregate diameter into consideration. The cake porosity including intraaggregate and interaggregate porosities was modeled successively by three typical coordination numbers (n = 6, 8, and 12). Accordingly, an inversion method made it possible to deduce the coordination number using the measured cake porosities, and the reverse-calculated value with minimum error and the corresponding relaxation ratios were applied as the parameters for the model. As a result, the profiles of intraaggregate and interaggregate porosities and cake porosity were respectively predicted in contrast to the integrated variation of the relaxation ratio and the fractal dimension. Furthermore, a comparison between the model predictions of the cake pressure drop gradients with and without aggregate compression was conducted to validate the presence of cake collapse. The results show that the predictions based on the proposed collapse model are in agreement with the experiments, and the coordination number is one of the key factors that must be incorporated into the cake collapse models.