Diffusion-induced lithium isotopic heterogeneity in olivines from peridotites of an oceanized mantle lithosphere at the Yunzhug ophiolite (central Tibet).

This paper reports lithium concentrations and isotopic compositions of olivines in the oceanized subcontinental lithospheric mantle (SCLM) peridotites of the Tibetan Yunzhug ophiolite. The results show systematic Li isotope changes with distance from the rim of olivine grains. δ7Li values of olivine in dunites decrease from + 10.46 to + 1.33‰ with increasing distance to olivine rim from 26.15 to 124.71 µm. A negative correlation of δ7Li and Li content in olivine from dunite and harzburgite indicates recent diffusive ingress of Li into the peridotites. The extremely heavy Li isotopic composition requires the seawater or seawater alteration endmember in the mixing model, and reveals Li diffusion from seawater into olivine. As in dunites, olivines in a harzburgite sample show similar variations in δ7Li as a function of distance from the grain rim (e.g., 6.01 to 1.73 in sample 14YZ13). We suggest that the behavior of Li in the oceanized SCLM peridotites may be controlled by Li diffusion from seawater, as Li activity in the liquid state is higher than the solid state in transporting Li through the olivines in the peridotites. This study supports that seawater Li diffusion is one of the important factors for the heterogeneity of mantle Li isotopes in ophiolites.

Artificial intelligence differentiates abdominal Henoch-Schönlein purpura from acute appendicitis in children.

OBJECTIVE: This study aims to construct an artificial intelligence (AI) model capable of effectively discriminating between abdominal Henoch-Schönlein purpura (AHSP) and acute appendicitis (AA) in pediatric patients. METHODS: A total of 6965 participants, comprising 2201 individuals with AHSP and 4764 patients with AA, were enrolled in the study. Additionally, 53 laboratory indicators were taken into consideration. Five distinct artificial intelligence (AI) models were developed employing machine learning algorithms, namely XGBoost, AdaBoost, Gaussian Naïve Bayes (GNB), MLPClassifier (MLP), and support vector machine (SVM). The performance of these prediction models was assessed through receiver operating characteristic (ROC) curve analysis, calibration curve assessment, and decision curve analysis (DCA). RESULTS: We identified 32 discriminative indicators (p < .05) between AHSP and AA. Five indicators, namely the lymphocyte ratio (LYMPH ratio), eosinophil ratio (EO ratio), eosinophil count (EO count), neutrophil ratio (NEUT ratio), and C-reactive protein (CRP), exhibited strong performance in distinguishing AHSP from AA (AUC ≥ 0.80). Among the various prediction models, the XGBoost model displayed superior performance evidenced by the highest AUC (XGBoost = 0.895, other models < 0.89), accuracy (XGBoost = 0.824, other models < 0.81), and Kappa value (XGBoost = 0.621, other models < 0.60) in the validation set. After optimization, the XGBoost model demonstrated remarkable diagnostic performance for AHSP and AA (AUC > 0.95). Both the calibration curve and decision curve analysis suggested the promising clinical utility and net benefits of the XGBoost model. CONCLUSION: The AI-based machine learning model exhibits high prediction accuracy and can differentiate AHSP and AA from a data-driven perspective.

A strong short-duration convection near Poyang Lake in daytime of warm season.

Poyang Lake (PL), the biggest freshwater lake in China, is situated in the East Asian Monsoon region, and has an important impact on local convection. In general, PL can result in convection in local region when it is a heat source in nighttime of warm season. However, at around noon on 4 May 2020 (PL is a cold source), a convection was triggered about 20 km west of PL, and rapidly enhanced and resulted in lightning when approaching PL, and then quickly weakened and disappeared after entering the main body of PL. In order to explore the convection formation, several observational data and the Weather Research and Forecasting model were applied in this study. Results show that when the convection approaches PL, its rapid enhancement is induced by PL, and after entering the main body of PL, its quick weakening is also resulted from PL. However, the initiation of the convection is mainly induced by the local topography west of PL under a favorable large-scale background. Mechanism analysis indicates that the strong low-level convergence near the west shore of PL associated with lake-land breeze is responsible for the rapid enhancement of the convection, and the low-level divergence over the main body of PL associated with the lake-land breeze and the increase of the low-level stability induced by cooling of PL jointly result in the quick weakening of the convection. The prevailing southerly wind in low level passes through the local topography (Meiling Mountain) west of PL, and is divided into southwesterly wind (flow around Meiling) and southerly wind (flow over Meiling), and they converge in the north of Meiling, triggering the convection. This study is not only important to deepen the understanding of PL affecting regional weather, but also helpful for improving the refined forecasting of convection near PL.

Repair of fingertip defect with reverse digital artery island flap and repair of donor site with digital dorsal advancement flap.

Objective: The reverse digital artery island flap (RDAF) is widely used in repairing fingertip skin defects based on its good appearance and practicability. However, the donor area of the flap needs skin grafting, which can lead to complications. This retrospective study explored the clinical application of digital dorsal advance flap (DDAF) in repairing the donor site of the reverse digital artery island flap. Method: From June 2019 to February 2022, 17 patients with a soft tissue defect of the finger had been restored with the reverse digital artery island flap, and at the same time, the donor area was repaired with digital dorsal advance flap (DDAF). The sensitivity, the active range of motion (ROM) and patient satisfaction were assessed after the operation. Results: All flaps survived completely without skin grafting with only one linear scar. The sensory and motor functions of all patients recovered well. Assessment based on the Michigan Hand Outcomes Questionnaire (MHQ) showed satisfactory functional recovery for all patients. Conclusions: Reconstruction using RDAF combined with DDAF represents an effective alternative for repairing fingertip skin defects.

hASCs-derived exosomal miR-155-5p targeting TGFßR2 promotes autophagy and reduces pyroptosis to alleviate intervertebral disc degeneration.

Background: Intervertebral disc degeneration (IDD) is a complex chronic disease involving nucleus pulposus cells (NPCs) senescence, apoptosis, autophagy and extracellular matrix (ECM) degradation. In this study, we aimed to investigate the role of human adipose tissue stem cells (hASCs)-derived exosomal miR-155-5p targeting TGFßR2 in IDD and the mechanisms involved. Then miRNA sequencing was performed, and hASCs-derived Exo (hASCs-Exo) was extracted and characterized. Methods: First, NPCs were treated with different concentrations of LPS. Then miRNA sequencing was performed, and hASCs-Exo was extracted and characterized. NPCs were treated with PBS or autophagy inhibitor 3-MA. NPCs were transfected with miR-155-5p mimic, si-TGFßR2 and negative control. Cell viability, apoptosis, ROS, caspase-1+PI, pyroptosis markers, inflammatory cytokines, autophagy markers, Aggrecan, MMP13, and Akt/mTOR pathway-related factors were measured. Bioinformatics prediction and dual-luciferase were performed to verify the binding sites of miR-155-5p to TGFßR2. Finally, we validated the role of hASCs-derived exosomal miR-155-5p on IDD in vivo. Results: LPS promoted pyroptosis of NPCs, and inhibited autophagy and ECM synthesis. MiR-155-5p was characterized as an inflammation-related miRNA in NPCs. HASCs-derived exosomal miR-155-5p inhibited pyroptosis of NPCs and promoted autophagy and ECM synthesis. After bioinformatics prediction and verification, it was found that miR-155-5p targeted TGFßR2. Moreover, miR-155-5p targeted TGFßR2 to promote autophagy and inhibit pyroptosis in NPCs. In vivo experiments revealed that hASCs-derived exosomal miR-155-5p alleviated IDD in rats. Conclusions: HASCs-derived exosomal miR-155-5p alleviated IDD by targeting TGFßR2 to promote autophagy and reduce pyroptosis. Our study may provide a new therapeutic target for IDD. Translational Potential of this Article: HASCs-derived exosomal miR-155-5p is expected to be a biomarker for clinical treatment of IDD. Our study may provide a new therapeutic target for IDD.

ST8SIA6-AS1 contributes to hepatocellular carcinoma progression by targeting miR-142-3p/HMGA1 axis.

Hepatocellular carcinoma (LIHC) accounts for 90% of all liver cancers and is a serious health concern worldwide. Long noncoding RNAs (lncRNAs) have been observed to sponge microRNAs (miRNAs) and participate in the biological processes of LIHC. This study aimed to evaluate the role of the ST8SIA6-AS1-miR-142-3p-HMGA1 axis in regulating LIHC progression. RT-qPCR and western blotting were performed to determine the levels of ST8SIA6-AS1, miR-142-3p, and HMGA1 in LIHC. The relationship between ST8SIA6-AS1, miR-142-3p, and HMGA1 was assessed using luciferase assay. The role of the ST8SIA6-AS1-miR-142-3p-HMGA1 axis was evaluated in vitro using LIHC cells. Expression of ST8SIA6-AS1 and HMGA1 was significantly upregulated, whereas that of miR-142-3p was markedly lowered in LIHC specimens and cells. ST8SIA6-AS1 accelerated cell growth, invasion, and migration and suppressed apoptosis in LIHC. Notably, ST8SIA6-AS1 inhibited HMGA1 expression by sponging miR-142-3p in LIHC cells. In conclusion, sponging of miR-142-3p by ST8SIA6-AS1 accelerated the growth of cells while preventing cell apoptosis in LIHC cells, and the inhibitory effect of miR-142-3p was abrogated by elevating HMGA1 expression. The ST8SIA6-AS1-miR-142-3p-HMGA1 axis represents a potential target for the treatment of patients with LIHC.

Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism.

Liver fibrosis is a chronic liver disease with the presence of progressive wound healing response caused by liver injury. Currently, there are no approved therapies for liver fibrosis. Exosomes derived from human adipose mesenchymal stem cells (hADMSCs-Exo) have displayed a prominent therapeutic effect on liver diseases. However, few studies have evaluated therapeutic effect of hADMSCs-Exo in liver fibrosis and cirrhosis, and its precise mechanisms of action remain unclear. Herein, we investigated anti-fibrotic efficacy of hADMSCs-Exo in vitro and in vivo, and identified important metabolic changes and the detailed mechanism through transcriptomic and metabolomic profiling. We found hADMSCs-Exo could inhibit the proliferation of activated hepatic stellate cells through aggravating apoptosis and arresting G1 phase, effectively inhibiting the expression of profibrogenic proteins and epithelial-to-mesenchymal transition (EMT) in vitro. Moreover, it could significantly block collagen deposition and EMT process, improve liver function and reduce liver inflammation in liver cirrhosis mice model. The omics analysis revealed that the key mechanism of hADMSCs-Exo anti-hepatic fibrosis was the inhibition of PI3K/AKT/mTOR signaling pathway and affecting the changes of metabolites in lipid metabolism, and mainly regulating choline metabolism. CHPT1 activated by hADMSCs-Exo facilitated formation and maintenance of vesicular membranes. Thus, our study indicates that hADMSCs-Exo can attenuate hepatic stellate cell activation and suppress the progression of liver fibrosis, which holds the significant potential of hADMSCs-Exo for use as extracellular nanovesicles-based therapeutics in the treatment of liver fibrosis and possibly other intractable chronic liver diseases.

Novel Therapeutic Mechanism of Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis via Upregulation of BTG2.

Background: Osteoarthritis (OA) is a debilitating and degenerative joint disease, which is characterized by progressive destruction of articular cartilage. Mesenchymal stem cells (MSCs) have been implicated in the treatment of OA. However, the function of adipose-derived MSCs (AD-MSCs) in OA and its underlying mechanism remain obscure. Aim: We aimed to explore the function of AD-MSCs in OA and investigate its potential regulatory mechanism. Methods: A guinea pig model of OA was constructed. AD-MSCs injected into the articular cavity of OA guinea pigs were viewed by in vivo bioluminescence imaging. The effect of AD-MSCs on the gonarthritis of OA guinea pigs was evaluated through both macroscopic and microscopic detections. The detailed molecular mechanism was predicted by GEO databases and bioinformatics tools and then verified via mechanism experiments, including ChIP assay, DNA pulldown assay, and luciferase reporter assay. Results: AD-MSCs had a significant positive therapeutic effect on the gonarthritis of the OA model, and the overall effects of it was better than that of sodium hyaluronate (SH). B-cell translocation gene 2 (BTG2) was significantly downregulated in the articular cartilage of the OA guinea pigs. Furthermore, BTG2 was positively regulated by Krüppel-like factor 4 (KLF4) in AD-MSCs at the transcriptional level. AD-MSCs performed an effect on KLF4 expression at the transcriptional levels. Conclusion: AD-MSCs suppresses OA progression through KLF4-induced transcriptional activation of BTG2. Our findings revealed an AD-MSCs-dominated therapeutic method for OA.

The prognostic significance of inflammation-immunity-nutrition score on postoperative survival and recurrence in hepatocellular carcinoma patients.

Background: Inflammation, immunity, and nutrition status play important roles in tumorigenesis, progression, and metastasis. This study aimed to evaluate the prognostic value of Inflammation-Immunity-Nutrition Score (IINS) for overall survival (OS) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC) undergoing radical surgery. Methods: A total of 204 HCC patients who met the criteria were included in this retrospective study: 144 in the prediction model and 60 in the validation model. IINS was constructed based on the sum of classification scores of preoperative high-sensitivity C-reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The associations between the IINS group and the clinicopathologic characteristics were analyzed using Pearson's χ2 test or Fisher's exact test. Multivariate Cox regression analysis was used to evaluate variables significant on univariate analysis. Kaplan-Meier survival curves were conducted to investigate the prognostic values of IINS, Alpha-fetoprotein (AFP) and IINS-AFP classification. The prognostic performances of all the potential prognostic factors were further compared by receiver operating characteristic (ROC) curve, and time-dependent ROC curve. The internal validation and external validation were used to ensure the credibility of this prediction model. Results: The patients were divided into low and high IINS groups according to the median of IINS. According to multivariate Cox regression analyses, the Barcelona Clinic Liver Cancer (BCLC) Stage (P=0.003), AFP (P=0.013), and IINS (P=0.028) were independent prognostic factors for OS, and BCLC Stage (P=0.009), microvascular invasion (P=0.030), and IINS (P=0.031) were independent prognostic factors for PFS. High IINS group were associated with significantly worse OS and PFS compared with low IINS group (P<0.001; P=0.004). In terms of clinical prognosis, IINS-AFP classification was good in group I, moderate in group II, and poor in group III. Group I had a longer OS (P<0.001) and PFS (P=0.008) compared with group II and III. ROC analysis revealed that IINS-AFP classification had a better prognostic performance for OS (AUC: 0.767) and PFS (AUC: 0.641) than other predictors, excluding its slightly lower predictive power for PFS than IINS. The time-dependent ROC curves also showed that both IINS (12-month AUC: 0.650; 24-month AUC: 0.670; 36-month AUC: 0.880) and IINS-AFP classification (12-month AUC: 0.720; 24-month AUC: 0.760; 36-month AUC: 0.970) performed well in predicting OS for HCC patients. Furthermore, the internal validation and external validation proved that IINS had good predictive performance, strong internal validity and external applicability, and could be used to establish the prediction model. Conclusion: Inflammation-immunity-nutrition score could be a powerful clinical prognostic indicator in HCC patients undergoing radical surgery. Furthermore, IINS-AFP classification presents better prognostic performance than IINS or AFP alone, and might serve as a practical guidance to help patients adjust treatment and follow-up strategies to improve future outcomes.

Weighted gene co-expression network analysis reveals prognostic and diagnostic significance of PAQR4 in patients with early and late hepatocellular carcinoma.

Background: This study aimed to reveal novel markers for prognostic and diagnostic prediction of hepatocellular carcinoma (HCC). Methods: We applied The Cancer Genome Atlas (TCGA) data to screen differentially expressed genes (DEGs). We identified hub modules and genes using weighted gene co-expression network analysis (WGCNA). After verification with the GSE36376 dataset, hub genes were further identified. The expression of progestin and adipoQ receptor 4 (PAQR4) was confirmed in HCC by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic and prognosis value of PAQR4 was assessed. The expression of PAQR4 was verified using the GSE76427 dataset. Results: A total of 803 DEGs were obtained between HCC and normal tissue. Through WGCNA, 7 hub modules were screened, among which the blue module was selected to identify the hub genes associated with the HCC. After overlapping all the DEGs with 837 genes of the blue module, we obtained 466 DEGs that were defined as hub genes. Among the hub genes, 239 were related to staging. After verifying with the GSE36376 dataset, PAQR4 was identified as the real hub gene of HCC. The results of qRT-PCR revealed that PAQR4 was upregulated between HCC and normal tissue. Furthermore, PAQR4 was related to the diagnosis and prognosis of patients with HCC. Moreover, the GSE76427 verification results of PAQR4 were consistent with our integration and qRT-PCR results. Ultimately, high expression of PAQR4 was significantly related to cell cycle, DNA replication, and the p53 signaling pathway. Conclusions: The PAQR4 gene may be associated with the prognosis and diagnosis of HCC.

Gynura segetum-induced liver injury leading to acute liver failure: a case report and literature review.

BACKGROUND: Gynura segetum (GS) is widely used in medical care and in community settings in China as the herbal remedy. It is widely thought to have antiphlogistic properties and pain relief in traditional Chinese medicine. It has been reported that GS can cause chronic drug-induced liver injury (DILI), manifested as hepatic sinusoid obstruction syndrome (HOSO). But case reports of acute DILI developing acute liver failure (ALF) due to GS are extremely rare. CASE PRESENTATION: We report a case of a 63-year-old female patient with hepatolithiasis for more than 6 years. There were no deterioration of liver function and no history of viral liver disease, autoimmune liver disease, blood transfusion or surgical allergy before operation. ALF and grade II liver encephalopathy occurred after partial hepatectomy. To follow up the medical history, the patient has been taking GS (Tusanqi) for a year and a half. The causality assessment was done by the updated Roussel Uclaf Causality Assessment Method, and the possibility of DILI caused by GS as highly probable for the score was 6 points. Excluding other causes, a diagnosis of DILI-associated ALF was established. After symptomatic support and artificial liver support system (ALSS) treatment, the clinical symptoms and signs of the patients were significantly improved. After discharge, the liver function of the patients returned to normal. CONCLUSIONS: Based on this rare case of severe liver injury, we recommend that timely prevention, identification, and appropriate management of DILI is essential for patients with a history of taking GS and other hepatotoxic drugs, and careful monitoring of liver function for patients with DILI could avoid ALF as far as possible.

Prognostic value of inflammation-immunity-nutrition score in patients with hepatocellular carcinoma treated with anti-PD-1 therapy.

BACKGROUND: There are no validated biomarkers that can predict the clinical benefit of immune checkpoint blockers against the programmed cell death protein 1 (PD-1) treatments in hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic value of inflammation-immunity-nutrition score (IINS) in patients with HCC treated with anti-PD-1 therapy. METHODS: A consecutive series of 101 HCC patients treated with PD-1 inhibitors in Sichuan Provincial People's Hospital between January 2018 and August 2020 were enrolled in the retrospective study. IINS (0-6) was constructed based on pretreatment high-sensitivity C-reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The patients were divided into high and low IINS groups according to IINS values. Prognostic values of each variable were evaluated with univariate and multivariate time-dependent Cox regression analyses. Survival curves were calculated and compared using the Kaplan-Meier method and log-rank test. The prognostic performance of IINS was further compared with that of other traditional prognostic indicators by receiver operating characteristic (ROC) curve and the areas under the ROC curve. RESULTS: Patients with low IINS had longer overall survival (OS) (HR: 4.711, 95% CI: 1.80-12.37, p = .001) and progression-free survival (HR: 3.411, 95% CI: 1.79-6.51, p < .0001) than those with high IINS. The multivariate analysis identified IINS (HR: 3.746, 95% CI: 1.05-13.38, p = .042) and tumor number (HR: 5.111, 95% CI: 1.075-24.299, p = .04) as independent prognostic factors. According to ROC analysis, IINS (AUC =0.729, 95% CI: 0.597-0.861, p = .002) presented better prognostic performance than other traditional prognostic indicators. The area of the IINS-CA19-9 under the ROC curve (AUC) was higher than that of the IINS or CA19-9 levels for the prediction of OS. CONCLUSION: The results suggest that IINS may be an independent prognostic indicator for HCC patients treated with anti-PD-1 therapy. IINS-CA19-9 classification may be more effective in predicting clinical benefit of anti-PD-1 therapy in HCC patients.

Long non-coding RNA PVT1/microRNA miR-3127-5p/NCK-associated protein 1-like axis participates in the pathogenesis of abdominal aortic aneurysm by regulating vascular smooth muscle cells.

The long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) has been implicated in the progression of abdominal aortic aneurysms (AAA). However, the detailed mechanism requires further analysis. Our study was aimed at interrogating the mechanism of PVT1 in an H2O2-induced AAA model in vitro. The expression of lncRNA PVT1, microRNA miR-3127-5p, and NCK-associated protein 1-like (NCKAP1L) was examined in AAA tissues and H2O2-treated vascular smooth muscle cells (VSMCs). Cell proliferation was assayed using Cell Counting Kit-8 (CCK8) and 5-Bromodeoxyuridine (BrdU) assays. Meanwhile, 5-Ethynyl-2'-deoxyuridine (EdU) staining was performed to assess cell apoptosis and caspase-3 activity. IL-1ß and caspase-1 expression was also assessed using Western blotting to determine inflammasome activation in H2O2-treated VSMCs. Luciferase reporter assays addressed the possible interaction between miR-3127-5p and PVT1 or NCKAP1L, which was predicted by starBase analysis. PVT1 and NCKAP1L expression was elevated in AAA tissues and induced the AAA model in vitro, whereas miR-3127-5p showed the opposite trend. Functionally, PVT1 silencing promoted cell proliferation and reduced the apoptotic rate and inflammasome activation in H2O2-treated VSMCs. Mechanical investigation demonstrated that PVT1 acted as a sponge of miR-3127-5p to modulate NCKAP1L expression, resulting in suppression of VSMC proliferation, induction of apoptosis, and activation of inflammation. In conclusion, PVT1 participates in AAA progression through the miR-3127-5p/NCKAP1L axis and may be a promising biosignature and therapeutic target for AAA.

LncRNA H19 secreted by umbilical cord blood mesenchymal stem cells through microRNA-29a-3p/FOS axis for central sensitization of pain in advanced osteoarthritis.

OBJECTIVE: To explore the molecular mechanism of umbilical cord blood mesenchymal stem cells (UCBMSCs) in the treatment of advanced osteoarthritis pain. METHODS: Normal healthy rats were selected to establish advanced osteoarthritis (OA) model, and the rats were randomly divided into control group, intravenous group, intracavitary group and intrathecal group. The intravenous group received intravenous injection of UCBMSCs, intracavitary group received intra-articular injection of UCBMSCs, and intrathecal group received subarachnoid injection of UCBMSCs. The pain behavior and serum pro-inflammatory factor levels were evaluated before and after treatment. microRNA-29a-3p and FOS mRNA in spinal dorsal horn was detected using qPCR, the phosphorylation of c-fos protein and NR1, NR2B, ERK and PKCg was detected using Western blot, and the level of LncRNA H19 was detected using qPCR. RESULTS: LncRNA H19 was enriched in the exosomes of UCBMSCs. microRNA-29a-3p was the target gene of LncRNA H19, while FOS was the downstream target of microRNA-29a-3p. Pain and inflammation of rats in the intrathecal group improved best, and the phosphorylation levels of c-fos and NR1, NR2B, ERK and PKCg in the spinal dorsal horn of the intrathecal group decreased. LncRNA H19 regulated the central sensitization of astrocytes through microRNA-29a-3p/FOS axis. CONCLUSION: Intrathecal injection of umbilical cord blood mesenchymal stem cells can improve the pain and central sensitization of advanced osteoarthritis through LncRNA H19/microRNA-29a-3p/FOS axis.

Repression of MicroRNA-124-3p Alleviates High-Fat Diet-Induced Hepatosteatosis by Targeting Pref-1.

Nonalcoholic fatty liver disease (NAFLD) is the common disease in the liver, which is associated with metabolic syndrome and hepatocellular carcinoma. Accumulated evidence establishes that small non-coding microRNAs (miRNAs) contribute to the initiation and progression of NAFLD. However, the molecular repertoire of miRNA in NAFLD is still largely unknown. Here, using an integrative approach spanning bioinformatic analysis and functional approaches, we demonstrate that miR-124-3p participates in the development of NAFLD by directly targeting preadipocyte factor-1 (Pref-1). In response to high-fat diet (HFD), expression of miR-124-3p was increased in the liver. Inhibition of miR-124-3p expression led to a dramatic reduction of triglyceride contents in hepatocytes, in parallel with decreased inflammatory factors. Mechanistically, miR-124-3p directly controls the transcription of Pref-1, a secretory factor that has been proved to resist metabolic syndrome. Our work identifies a novel molecular axis in hepatosteatosis, and highlights miR-124-3p/Pref-1 as potential targets for clinical interventions of NAFLD.

The mechanism of curcumin post-treatment relieving lung injuries by regulating miR-21/TLR4/NF-κB signalling pathway.

OBJECTIVE: To investigate the mechanism by which curcumin prevents lung injury in a rat model of limb ischaemia-reperfusion injury. METHODS: Rats were randomized into four groups (n = 20): control group (sham group); ischaemia-reperfusion group (I/R group); curcumin group (I/R+Cur group); and inhibitor of agomir-21 group (I/R+Cur+antagomir-21 group). At 3 h after reperfusion, lung tissues were collected for histopathology and immunohistochemistry to determine the apoptosis index (AI). Lung injury score (LIS) and lung wet/dry (W/D) ratio were determined. Lung microRNA-21 (miR-21) mRNA levels were measured using reverse transcription-polymerase chain reaction. Toll-like receptor 4 (TLR4) and nuclear factor kappa-B p65 (NF-κB p65) protein levels were measured by Western blot analysis. Tumour necrosis factor (TNF)-α and interleukin (IL)-1ß levels were determined by enzyme-linked immunosorbent assays. RESULTS: In the I/R group, the W/D, LIS, AI, miR-21 mRNA, TLR4, NF-κB p65, TNF-α and IL-1ß were significantly increased and the PaO2 was decreased compared with the sham group. Evidence of lung injury was observed in the I/R group and this was alleviated in the I/R+Cur group. An inhibitor of miR-21 (antagomir-21) reversed the protective effects of curcumin. CONCLUSION: Curcumin post-treatment can alleviate the lung injuries induced by limb ischaemia-reperfusion via downregulating the levels of miR-21 mRNA.

Effects of cyclosporin A pre-treatment combined with etomidate post-treatment on lung injury induced by limb ischemia-reperfusion in rats.

OBJECTIVES: To investigate the influence of cyclosporin A (CsA) pre-treatment and etomidate (ETO) post-treatment on lung injury induced by limb ischemia-reperfusion (I/R) in rats. METHODS: Rats were randomly divided into five groups: sham, I/R, I/R+CsA, I/R+ETO, and I/R+CsA+ETO. Limb I/R lung injury was established by bilateral clamping of the femoral arteries for 2 hours. Following reperfusion for 3 hours, blood gas analysis was performed. Pathological changes were assessed using immunohistochemistry. The apoptosis index (AI) and wet/dry weight ratio (W/D) were calculated. Levels of Fas protein and FasL mRNA were assessed by western blotting and RT-PCR, respectively. Tumor necrosis factor (TNF)-α and interleukin (IL)-1ß were detected by ELISA. RESULTS: I/R resulted in decreased PaO2 but increased AI, W/D, Fas, FasL mRNA, TNF-α and IL-1ß. Scattered punctate apoptosis and necrosis were observed by immunohistochemistry. Compared with the I/R group, the I/R+ETO and I/R+CsA groups showed increased SpO2, decreased AI, W/D, Fas, FasL mRNA, TNF-α and IL-1ß, and decreased numbers of apoptotic and necrotic cells. Combined treatment with CsA+ETO resulted in more dramatic changes in these parameters. CONCLUSIONS: ETO post-treatment and CsA pretreatment reduced lung injury induced by limb I/R in rats. The mechanism may be related to synergistic inhibition of Fas/FasL signaling.

Risk factors for sleep quality disturbances in patients with lumbar spinal stenosis before operation.

PURPOSE: We aimed to explore the risk factors of preoperative sleep quality in patients with lumbar spinal stenosis (LSS) and the association of sleep-related beliefs with sleep quality in these patients. METHODS: Sleep quality and related risk factors of sleep quality disturbances in patients with LSS preoperatively were assessed by questionnaires. Pittsburgh Sleep Quality Index (PSQI) for sleep quality, Oswestry Disability Index (ODI) for clinical outcomes, Visual Analog Scale for Pain (VAS Pain), Self-Rating Anxiety Scale (SAS) for anxiety level, and Dysfunctional Beliefs and Attitudes about Sleep (DBAS-16) for sleep-related beliefs were assessed. Bivariate logistic regression analysis was used to assess the risk factors of sleep quality disturbances. RESULTS: A total of 227 patients were enrolled, mean age 64 years (SD 13.1), 119 women (52%). The incidence of sleep quality disturbances in patients was 37% (83/227). Increased DBAS-16 scores (OR = 0.781; 95% CI, 0.725-0.841; p < 0.001) significantly decreased the probability of developing sleep quality disturbances, while increased anxiety levels (OR = 1.241; 95% CI, 1.152-1.337; p < 0.001) significantly increased the probability of developing sleep quality disturbances in patients. Factors including educational level, increased age, sex, preoperative length of stay, VAS Pain scores, and ODI scores showed no significant association and were therefore excluded from the model. CONCLUSIONS: High levels of anxiety and mistaken sleep-related beliefs were risk factors of sleep quality disturbances in patients with LSS before surgery. The more mistaken sleep-related beliefs were, the greater the probability of sleep disturbances.