Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

BACKGROUND: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. METHODS: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: 2·67; NFS: 0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226. FINDINGS: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62-0·81) for histology, 0·76 (0·70-0·83) for LSM-VCTE, 0·74 (0·64-0·82) for FIB-4, and 0·70 (0·63-0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression. INTERPRETATION: Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases. FUNDING: Innovative Medicines Initiative 2

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis.

BACKGROUND Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. METHODS This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: 2·67; NFS: 0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226. FINDINGS Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62-0·81) for histology, 0·76 (0·70-0·83) for LSM-VCTE, 0·74 (0·64-0·82) for FIB-4, and 0·70 (0·63-0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression. INTERPRETATION Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases. FUNDING Innovative Medicines Initiative 2

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

BackgroundHistologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.MethodsThis was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0–4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0–2 vs F3 vs F4; LSM: 2·67; NFS: 0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.FindingsOf 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44–63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33–91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62–0·81) for histology, 0·76 (0·70–0·83) for LSM-VCTE, 0·74 (0·64–0·82) for FIB-4, and 0·70 (0·63–0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.InterpretationSimple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases

Advanced Materials for High Biocompatible Hydrogel System

Hydrogels are gels with water as the dispersion medium and three-dimensional porous polymer networks cross-linked chemically or physically [...

Organochlorine Pesticides in Surface Water of Jiuxi Valley, China: Distribution, Source Analysis, and Risk Evaluation

Residual levels of 11 organochlorine pesticides (OCPs) in surface water of Jiuxi Valley were determined during spring and autumn at nine sampling points to assess their contamination and potential risks. The water samples were extracted by solid-phase extraction (SPE), and OCPs were analyzed by gas chromatograph equipped with a 63Ni-ECD detector. The investigation results indicated that the concentration of total OCPs varied from 4.07 to 13.5 ng·L−1 with an average value of 7.15 ng·L−1 in spring, and from 12.5 to 30.1 ng·L−1 with an average value of 19.9 ng·L−1 in autumn. Jiuxi Valley was slightly contaminated by OCPs, and the concentrations of ΣHCHs and ΣDDTs in the river were at relatively low levels. HCHs were the main pollutant in spring, and also in autumn, and α-HCH was the main component of the HCH isomers at most sampling points. Source analysis indicated that local use of lindane or input of fresh γ-HCH contributed to the presence of HCHs. New inputs were the major sources of DDTs, aldrin, heptachlor, and endrin. The OCP levels of this investigation were within the standard limits set by a majority of the water quality standards and guidelines of China, WHO, European Union, and Canada. However, although the γ-HCH concentrations at all sampling sites, endrin concentrations at all sampling sites, and β-HCH concentrations at most sampling sites were below the human health water quality standard, and the levels of other tested OCPs (α-HCH, p,p′-DDD, p,p′-DDE, p,p′-DDT, aldrin, and heptachlor) exceeded the value of EPA-recommended water quality criteria for human health, which indicated potential risks to human health around the region

Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis

Abstract Background Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. Methods The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Results Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Conclusion Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro

A hybrid contact approach for modeling soil-structure interaction using the material point method

The grid-based multi-velocity field technique has become increasingly popular for simulating the Material Point Method (MPM) in contact problems. However, this traditional technique has some shortcomings, such as (1) early contact and contact penetration can occur when the contact conditions are unsuitable, and (2) the method is not available for contact problems involving rigid-nonrigid materials, which can cause numerical instability. This study presents a new hybrid contact approach for the MPM to address these limitations to simulate the soil and structure interactions. The approach combines the advantages of point-point and point-segment contacts to implement contact detection, satisfying the impenetrability condition and smoothing the corner contact problem. The proposed approach is first validated through a disk test on an inclined slope. Then, several typical cases, such as granular collapse, bearing capacity, and deformation of a flexible retaining wall, are simulated to demonstrate the robustness of the proposed approach compared with FEM or analytical solutions. Finally, the proposed method is used to simulate the impact of sand flow on a deformable structure. The results show that the proposed contact approach can well describe the phenomenon of soil-structure interaction problems

Irisin protects macrophages from oxidized low density lipoprotein-induced apoptosis by inhibiting the endoplasmic reticulum stress pathway

Irisin is a newly discovered myokine which can relieve metabolic disorders and resist atherosclerosis. The effects of irisin on ox-LDL-induced macrophage apoptosis and endoplasmic reticulum stress-related pathways were observed in vitro. RAW264.7 macrophages were cultured in vitro and pretreated with irisin at 20, 40 and 80 ng/ml for 30 min, followed by culture with 100 mg/L ox-LDL and 5 mg/L tunicamycin (TM) for 12 h. The cell viability and apoptosis were detected by MTT assay and annexin V-FITC double staining. The nuclear translocation of activating transcription factor 6 (ATF6) was detected by immunofluorescence assay. Western blot was used to detect the expressions of p-PERK, p-eIF2α, C/EBP homologous protein (CHOP) and Bcl-2. Irisin reduced lipid accumulation in macrophages in a concentration-dependent pattern and significantly inhibited apoptosis induced by ox-LDL and TM. Compared with ox-LDL and TM groups, the expressions of CHOP, p-PERK and p-eIF2α in the irisin group significantly decreased, the translocation of ATF6 from cytoplasm to nucleus was significantly weakened, and Bcl-2 expression significantly increased. Irisin can alleviate the apoptosis of macrophages induced by ox-LDL, which may be achieved by inhibiting the PERK/eIF2α/CHOP and ATF6/CHOP endoplasmic reticulum stress signaling pathways. Keywords: Irisin, Endoplasmic reticulum stress, Macrophage, Apoptosi

Intermolecular reductive heck reaction of unactivated aliphatic alkenes with organohalides

A general intermolecular reductive Heck reaction of organohalides with both terminal and internal unactivated aliphatic alkenes has been first realized in high yield with complete anti-Markovnikov selectivity. The challenging vinyl bromides, aryl chlorides, and polysubstituted internal alkenes were first applied. More than 100 remote carbofunctionalized alkyl carboxylic acid derivatives were rapidly synthesized from easily accessible starting materials. The synthesis of drug molecules has further demonstrated the wide synthetic utility of this scalable strategy. Preliminary mechanistic studies are consistent with the proposed catalytic cycle.We gratefully acknowledge funding from the National Natural Science Foundation of China (21602104), Natural Science Foundation of Jiangsu Province, China (BK 20160986), and the Starting Funding of Research (3983500176) from Nanjing Tech University

Universal Coating from Electrostatic Self-Assembly to Prevent Multidrug-Resistant Bacterial Colonization on Medical Devices and Solid Surfaces

We provide a facile and scalable strategy for preparing gold nanoparticles (AuNPs)-based antibacterial coating on a variety of surfaces through electrostatic self-assembly. AuNPs conjugated with 4,6-diamino-2-pyrimidinethiol (DAPT, not antibacterial by itself), AuDAPT, can form stable coating on different substrates made from polyethylene (PS), polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), polydimethylsiloxane (PDMS), and SiO₂ in one step. Such a coating can efficiently eradicate pathogenic Gram-negative bacteria and even multidrug-resistant (MDR) mutants without causing any side-effect such as cytotoxicity, hemolysis, coagulation, and inflammation. We show that immobilized AuDAPT, instead of AuDAPT released from the substrate, is responsible for killing the bacteria and that the antimicrobial components do not enter into the environment to cause secondary contamination to breed drug resistance. Advantages for such coating include applicability on a broad range of surfaces, low cost, stability, high antibacterial efficiency, good biocompatibility, and low risk in antibiotics pollution; these advantages may be particularly helpful in preventing infections that involve medical devices