New cycloalkyl[b]thiophenylnicotinamide-based α-glucosidase inhibitors as promising anti-diabetic agents: Synthesis, in silico study, in vitro and in vivo evaluations.

In the present study, a series of cycloalkyl[b]thiophenylnicotinamide derivatives against α-glucosidase were synthesized, and evaluated for their in vitro and in vivo anti-diabetic potential. Most of the synthetic analogues exhibited superior α-glucosidase inhibitory effects than the standard drug acarbose (IC50 = 258.5 µM), in which compound 11b with cyclohexyl[b]thiophene core demonstrated the highest activity with an IC50 value of 9.9 µM and showed higher selectivity towards α-glucosidase over α-amylase by 7.4-fold. Fluorescence quenching experiment confirmed the direct binding of 11b with α-glucosidase, kinetics study revealed that 11b was a mixed-type inhibitor, and its binding mode was analyzed using molecular docking. Moreover, analogs compounds 6a-9b, 11b, 12b did not show in vitro cytotoxicity against LO2 and HepG2 cells. Finally, compound 11b exhibited in vivo hypoglycemic activity by reducing the blood glucose levels in sucrose-loaded rats.

The analgesic efficacy of pericapsular nerve group block in patients with intertrochanteric femur fracture: A randomized controlled trial.

BACKGROUND: The aim of this study is to evaluate analgesic efficacy of pericapsular nerve group (PENG) block in patients with intertrochanteric femur fracture (IFF). METHODS: This double-blinded randomized controlled trial in patients with IFF scheduled for proximal femoral nail antirotation (PFNA) between December 2020 and November 2021. The primary outcome was VAS scores during exercising at 6 h after surgery; secondary outcomes were pain during exercising and rest, intraoperative dose of remifentanil, cumulative dose of postoperative fentanyl, postoperative analgesia satisfaction scores, and ratio of quadriceps weakness. RESULTS: A total of 50 patients were randomly divided into PENG block group (n = 25) or fascia iliaca compartment block (FICB) group (n = 25). Exercising VAS scores at 6 h after surgery were significantly lower in PENG block group than that in FICB group (2 (2, 4) vs. 6 (4, 7), P < 0.001). The intraoperative dose of remifentanil and cumulative dose of postoperative fentanyl by patient-controlled intravenous analgesia within 24 h after surgery in PENG block group were significantly lower than in FICB group (both P < 0.001). Postoperative analgesia satisfaction scores in PENG block group were significantly higher than those in FICB group (P = 0.016). The ratio of quadriceps weakness at 6 h after surgery was significantly higher in FICB group than PENG block group (48% vs. 0%, P < 0.001). CONCLUSIONS: Compared to FICB, ultrasound-guided PENG block may provide better postoperative pain relief in patients with IFF, with less pronounced quadriceps weakness.

Machine learning algorithms based on proteomic data mining accurately predicting the recurrence of hepatitis B-related hepatocellular carcinoma.

BACKGROUND AND AIM: Over 10% of hepatocellular carcinoma (HCC) cases recur each year, even after surgical resection. Currently, there is a lack of knowledge about the causes of recurrence and the effective prevention. Prediction of HCC recurrence requires diagnostic markers endowed with high sensitivity and specificity. This study aims to identify new key proteins for HCC recurrence and to build machine learning algorithms for predicting HCC recurrence. METHODS: The proteomics data for analysis in this study were obtained from the Clinical Proteomics Tumor Analysis Consortium (CPTAC) database. We analyzed different proteins based on cases with or without recurrence of HCC. Survival analysis, Cox regression analysis, and area under the ROC curves (AUROC > 0.7) were used to screen for more significant differential proteins. Predictive models for HCC recurrence were developed using four machine learning algorithms. RESULTS: A total of 690 differentially expressed proteins between 50 relapsed and 77 non-relapsed hepatitis B-related HCC patients were identified. Seven of these proteins had an AUROC > 0.7 for 5-year survival in HCC, including BAHCC1, ESF1, RAP1GAP, RUFY1, SCAMP3, STK3, and TMEM230. Among the machine learning algorithms, the random forest algorithm showed the highest AUROC values (AUROC: 0.991, 95% CI 0.962-0.999) for identifying HCC recurrence, followed by the support vector machine (AUROC: 0.893, 95% Cl 0.824-0.956), the logistic regression (AUROC: 0.774, 95% Cl 0.672-0.868), and the multi-layer perceptron algorithm (AUROC: 0.571, 95% Cl 0.459-0.682). CONCLUSIONS: Our study identifies seven novel proteins for predicting HCC recurrence and the random forest algorithm as the most suitable predictive model for HCC recurrence.

Lifestyle Interventions for Non-Obese Patients Both with, and at Risk, of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease occurring in non-obese subjects (the so-called non-obese NAFLD) is a highly prevalent but neglected liver condition, which is closely associated with metabolic disorders and suboptimal lifestyles. Landmark studies have shown that lifestyle interventions are potentially beneficial in decreasing the risk of developing non-obese NAFLD and in ameliorating NAFLD in non-obese individuals with pre-existing NAFLD. Lifestyle interventions usually refer to changes in eating habits and physical activity, both of which have a powerful effect on non-obese NAFLD and on risk factors for non-obese NAFLD. However, to date, patients and health-care professionals have a poor awareness and understanding of non-obese NAFLD and the beneficial effects of lifestyle interventions in this patient population. The aim of this narrative review is to briefly discuss the evidence for the effects of lifestyle changes and what changes are needed amongst medical personnel and other stakeholders in order to raise awareness of non-obese NAFLD.

Differential Diagnosis of COVID-19 Pneumonia From Influenza A (H1N1) Pneumonia Using a Model Based on Clinicoradiologic Features.

Objectives: Both coronavirus disease 2019 (COVID-19) pneumonia and influenza A (H1N1) pneumonia are highly contagious diseases. We aimed to characterize initial computed tomography (CT) and clinical features and to develop a model for differentiating COVID-19 pneumonia from H1N1 pneumonia. Methods: In total, we enrolled 291 patients with COVID-19 pneumonia from January 20 to February 13, 2020, and 97 patients with H1N1 pneumonia from May 24, 2009, to January 29, 2010 from two hospitals. Patients were randomly grouped into a primary cohort and a validation cohort using a seven-to-three ratio, and their clinicoradiologic data on admission were compared. The clinicoradiologic features were optimized by the least absolute shrinkage and selection operator (LASSO) logistic regression analysis to generate a model for differential diagnosis. Receiver operating characteristic (ROC) curves were plotted for assessing the performance of the model in the primary and validation cohorts. Results: The COVID-19 pneumonia mainly presented a peripheral distribution pattern (262/291, 90.0%); in contrast, H1N1 pneumonia most commonly presented a peribronchovascular distribution pattern (52/97, 53.6%). In LASSO logistic regression, peripheral distribution patterns, older age, low-grade fever, and slightly elevated aspartate aminotransferase (AST) were associated with COVID-19 pneumonia, whereas, a peribronchovascular distribution pattern, centrilobular nodule or tree-in-bud sign, consolidation, bronchial wall thickening or bronchiectasis, younger age, hyperpyrexia, and a higher level of AST were associated with H1N1 pneumonia. For the primary and validation cohorts, the LASSO model containing above eight clinicoradiologic features yielded an area under curve (AUC) of 0.963 and 0.943, with sensitivity of 89.7 and 86.2%, specificity of 89.7 and 89.7%, and accuracy of 89.7 and 87.1%, respectively. Conclusions: Combination of distribution pattern and category of pulmonary opacity on chest CT with clinical features facilitates the differentiation of COVID-19 pneumonia from H1N1 pneumonia.

Ultrasound-guided, direct suprainguinal injection for fascia iliaca block for total hip arthroplasty: A retrospective study.

BACKGROUND: Peripheral regional block combined with general anesthesia might be a preferable anesthetic regimen for elderly patients undergoing total hip arthroplasty. AIM: To investigate whether ultrasound-guided, direct suprainguinal injection for fascia iliaca block accelerated recovery after general anesthesia and relieved postoperative pain after total hip arthroplasty. METHODS: Patients who underwent total hip arthroplasty under general anesthesia in 2015 or 2019 at The Second Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. The patients were grouped based on whether preoperative suprainguinal fascia iliaca block was performed or not. The time to tracheal extubation and time spent in the post-anesthesia care unit (PACU), intraoperative remifentanil dosage, fentanyl consumption in the PACU, postoperative cumulative fentanyl consumption within 48 h after operation, visual analogue scale at rest and during movement on the first and second days after surgery, and adverse reactions were compared. RESULTS: Thirty-one elderly patients who underwent total hip arthroplasty were included in the study (block group, n = 16; no-block group, n = 15). The visual analog scale scores at rest and during movement on the first and second days were significantly lower in the block group than in the no-block group (all P < 0.05). Compared with the no-block group, the intraoperative remifentanil dosage was lower, the time to tracheal extubation and the time spent in the PACU were shorter in the block group (all P < 0.01). Fentanyl consumption in the PACU and postoperative cumulative fentanyl consumption in 48 h after operation were lower in the block group (all P < 0.01). The incidence of dizziness was higher in the no-block group than in the block group (P = 0.037). CONCLUSION: Ultrasound-guided, direct suprainguinal injection for fascia iliaca block led to faster recovery after general anesthesia and early postoperative pain relief in elderly patients undergoing total hip arthroplasty.

Gene-Focused Networks Underlying Phenotypic Convergence in a Systematically Phenotyped Cohort With Heterogeneous Intellectual Disability.

The broad spectrum of intellectual disability (ID) patients' clinical manifestations, the heterogeneity of ID genetic variation, and the diversity of the phenotypic variation represent major challenges for ID diagnosis. By exploiting a manually curated systematic phenotyping cohort of 3803 patients harboring ID, we identified 704 pathogenic genes, 3848 pathogenic sites, and 2075 standard phenotypes for underlying molecular perturbations and their phenotypic impact. We found the positive correlation between the number of phenotypes and that of patients that revealed their extreme heterogeneities, and the relative contribution of multiple determinants to the heterogeneity of ID phenotypes. Nevertheless, despite the extreme heterogeneity in phenotypes, the ID genes had a specific bias of mutation types, and the top 44 genes that ranked by the number of patients accounted for 39.9% of total patients. More interesting, enriched co-occurrent phenotypes and co-occurrent phenotype networks for each gene had the potential for prioritizing ID genes, further exhibited the convergences of ID phenotypes. Then we established a predictor called IDpred using machine learning methods for ID pathogenic genes prediction. Using10-fold cross-validation, our evaluation shows remarkable AUC values for IDpred (auc = 0.978), demonstrating the robustness and reliability of our tool. Besides, we built the most comprehensive database of ID phenotyped cohort to date: IDminer http://218.4.234.74:3100/IDminer/, which included the curated ID data and integrated IDpred tool for both clinical and experimental researchers. The IDminer serves as an important resource and user-friendly interface to help researchers investigate ID data, and provide important implications for the diagnosis and pathogenesis of developmental disorders of cognition.

Regulatory effect of a Chinese herbal medicine formula on non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a major cause of chronic liver disease. The Chinese herbal medicine (CHM) Dachaihu decoction (DCHD) has been proved to treat NAFLD with good efficacy in previous studies. Based on the TCM principle of formula formation, we divided DCHD into soothing liver part, invigorating spleen part, and dredging intestine part. Marshall officially proposed the concept of "intestinal-hepatic axis", which systematically explains the interactions between the intestine and liver. We hypothesized that the effect of CHM on NAFLD is achieved by regulating the liver and intestine. Thus, we aimed to investigate the possible effect of a CHM formula on NAFLD in a rat model. AIM: To investigate the effects of a CHM formula (a decoction of Chinese thorowax root, scutellaria root, and white peony root) on NAFLD and its regulatory effect on the "intestinal-liver" axis. METHODS: Sixty rats were randomly divided into control, model, pioglitazone hydrochloride (PH), and CHM (a decoction of Chinese thorowax root, scutellaria root, and white peony root) groups. An NAFLD rat model was established using a high-fat high-fructose diet for 16 wk. From the 13th week, rats were administered with PH or a decoction of Chinese thorowax, scutellaria, and white peony root (CHM group) for 4 wk. Rats in the control group and model group were administered with an equal volume of distilled water. At the end of the study, blood was collected via the abdominal aorta. Liver tissues were harvested and any morphological changes were observed by hematoxylin-eosin (HE) staining, Oil red O staining, and Masson staining. In addition, blood lipids, liver function markers, and triglyceride (TG) in liver tissues were analyzed. The levels of transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), Toll-like receptor-4 (TLR4), and nuclear factor-kappa B (NF-кB) in liver tissues and secreted immunoglobulin A (sIgA) in intestinal tissues were analyzed by ELISA, and protein and mRNA expression of occludin and zonula occludens-1 (ZO-1) in the intestine were measured using Western blot and reverse transcription-quantitative polymerase chain reaction, respectively. The endotoxin level in plasma was detected by endpoint chromogenic assay. RESULTS: Compared to the normal control group, the liver coefficient, serum TG, total cholesterol (TC), low density lipoprotein (LDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), blood glucose, plasma endotoxin, and the levels of TG, TNF-α, TGF-ß, NF-kB, and TLR4 in liver tissues increased significantly in the model group, while serum high density lipoprotein (HDL), intestinal sIgA, and protein and mRNA expression of occludin and ZO-1 decreased significantly in the model group (P < 0.01). PH and CHM attenuated the elevated liver coefficient, serum TG, TC, LDL, AST, and ALT, blood glucose, plasma endotoxin, and the levels of TG, TNF-α, TGF-ß, NF-kB, and TLR4 in liver tissues and increased serum HDL levels compared to the model group (P < 0.01). Intestinal sIgA and the protein and mRNA expression of intestinal occludin and ZO-1 were significantly increased in the PH group compared to the model and CHM groups (P < 0.01). CONCLUSION: The decoction of Chinese thorowax root, scutellaria root, and white peony root is beneficial in regulating lipid metabolism and liver function, which indicates that it has a good effect on the liver. To a certain extent, this CHM formula can affect both the liver and intestine, while its effect on the liver is superior to that on the intestine.

Long non-coding RNA Igf2as controls hepatocellular carcinoma progression through the ERK/MAPK signaling pathway.

Long non-coding RNAs (lncRNAs) serve an important role in numerous human diseases, including cancer. Abnormal expression of lncRNAs has been associated with a number of tumor types; however, the underlying mechanisms through which lncRNA functions have yet to be elucidated. The present study primarily focuses on insulin-like growth factor 2 antisense 1 (Igf2as), a lncRNA reported to be differentially expressed in hepatocellular carcinoma (HCC). Reverse transcription-quantitative polymerase chain reaction analysis was used to determine the level of Igf2as in HCC cells and tissues. Flow cytometry was used to determine the level of cell apoptosis following Igf2as suppression and western blot analysis was used to identify altered protein expression levels. The results demonstrated that Igf2as was upregulated in HCC cells and tissues, and that the inhibition of Igf2as using a targeted small interfering RNA (si-Igf2as), significantly decreased cell proliferation and increased apoptosis. Western blot analysis identified that the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway was inhibited in cells transfected with si-Igf2as. In addition, cell migration was markedly reduced by the knockdown of Igf2as. These results suggest that lncRNA Igf2as may control hepatocellular progression primarily through the regulation of the ERK/MAPK signaling pathway.

[Study on Simultaneous Mercury and Lead Detection in Water Samples with PGNAA-XRF].

Prompt gamma neutron activation analysis (PGNAA) technology is used in heavy metals measurement. It is found that the detection accuracy of lead (Pb) is impacted heavily by mercury (Hg), because of thermal neutron cross section of mercury is much bigger than lead. In this paper, a new combined detection method was proposed to improve the lead measurement accuracy in situ environmental water rejects analysis by PGNAA-XRF. Thus, a combined measurement facility was developed to analyze the mercury and lead in water simultaneously. The geometry of set-up is determined by a series of simulations with the MCNP code to improve the detection efficiency of the prompt gamma-ray intensity (Iγ) and characteristic X-ray fluorescence intensity (IX) of element. The ideal sample height and cavity are 33 and 16 cm, respectively. The influence of the relationship between Iγ, IX and different concentration (ｃi) of Hg and Pb was researched by MCNP calculations, respectively. The simulation results showed that there were good linear relationships between Iγ, IX and ｃi, respectively. The empirical formula of combined detection method was proposed based on the above calculations. The limits of detection for Hg and Pb with the combined measurement instrument were 3.89 and 4.80 mg·kg-1, respectively. It is a significant increase in performance of the mercury and lead detection simultaneously.

[Synthesis and fluorescence properties of SrZn(WO4)2:Tb3+, Ce3+ phosphors].

SrZn(1-x) (WO4)2:xTb3+, yCe3+ green fluorescent phosphors for near ultraviolet excitation were prepared using chemical co-precipitation. The phases of different doping ratio samples were characterized by the X-ray diffraction (XRD). The emission spectrum and excitation spectrum of samples were characterized by fluorescence spectroscopy (PL). The luminescence properties of the rare-earth Tb3+ ion doped and Ce3+ and Tb3+ ion codoped samples were discussed. XRD analysis shows that the main diffraction peaks of samples were consistent with the standard card (JCPDS 08-0490 and the JCPDS 15-0774) of the diffraction peak data. This showed that the doping rare earth ions did not change matrix lattice structure. The excitation spectrum showed that the excitation spectrum peaks at 223 nm which is assigned to the 7F-7D absorption transitions of Tb3+. The emission spectrum excited by 223 nm exhibits sharp lines peaking at 543 nm which was assigned to the 5D4-7F5 transitions of the Tb3+ ions. With Tb3+ and Ce3+ co-doping, the spectrum didn't change much. The intensity of fluorescence reached the strongest when the concentration of Tb3+:Ce3+ arrived at 0.06:0.02 which may means that there was energy transfer between the ions of Ce3+ and Tb3+.

Mesenchymal stem cells with overexpression of midkine enhance cell survival and attenuate cardiac dysfunction in a rat model of myocardial infarction.

INTRODUCTION: Elevated midkine (MK) expression may contribute to ventricular remodeling and ameliorate cardiac dysfunction after myocardial infarction (MI). Ex vivo modification of signaling mechanisms in mesenchymal stem cells (MSCs) with MK overexpression may improve the efficacy of cell-based therapy. This study sought to assess the safety and efficacy of MSCs with MK overexpression transplantation in a rat model of MI. METHODS: A pLenO-DCE vector lentivirus encoding MK was constructed and infected in MSCs. MSC migration activity and cytoprotection was examined in hypoxia-induced H9C2 cells using transwell insert in vitro. Rats were randomized into five groups: sham, MI plus injection of phosphate buffered saline (PBS), MSCs, MSCs-green fluorescent protein (MSCs-GFP) and MSCs-MK, respectively. Survival rates were compared among groups using log-rank test and left ventricular function was measured by echocardiography at baseline, 4, 8 and 12 weeks. RESULTS: Overexpression of MK partially prevented hypoxia-induced MSC apoptosis and exerted MSC cytoprotection to anoxia induced H9C2 cells. The underlying mechanisms may be associated with the increased mRNA and protein levels of vascular endothelial growth factor (VEGF), transformation growth factor-ß (TGF-ß), insulin-like growth factor 1 (IGF-1) and stromal cell-derived factor 1 (SDF-1a) in MSCs-MK compared with isolated MSCs and MSCs-GFP. Consistent with the qPCR results, the culture supernatant of MSCs-MK had more SDF-1a (9.23 ng/ml), VEGF (8.34 ng/ml) and TGF-ß1 (17.88 ng/ml) expression. In vivo, a greater proportion of cell survival was observed in the MSCs-MK group than in the MSCs-GFP group. Moreover, MSCs-MK administration was related to a significant improvement of cardiac function compared with other control groups at 12 weeks. CONCLUSIONS: Therapies employing MSCs with MK overexpression may represent an effective treatment for improving cardiac dysfunction and survival rate after MI.

The ginsenoside Rg1 prevents transverse aortic constriction-induced left ventricular hypertrophy and cardiac dysfunction by inhibiting fibrosis and enhancing angiogenesis.

BACKGROUND: Ginsenoside Rg1, an important and active ingredient of Panax ginseng, has been shown to exert cardioprotective effects in vivo. The present study aimed to test the hypothesis that ginsenoside Rg1 attenuates cardiac dysfunction in a transverse aortic constriction (TAC)-induced left ventricular hypertrophy in vivo via proangiogenic and antifibrotic effects. METHODS: This study investigated the effects of ginsenoside Rg1 in a rat model of TAC-induced left ventricular hypertrophy. Cardiac function was assessed by echocardiography. The antifibrotic and proangiogenic effects were assessed by histopathology and mRNA expression of procollagen I, III, and vascular endothelial growth factor (VEGF) through quantitative real-time PCR. The expression of phosphorylation of Akt, p38 mitogen-activated protein kinase (MAPK), hypoxia inducible factor-1 (HIF-1), and VEGF proteins were examined by Western blotting. RESULTS: Ginsenoside Rg1 treatment significantly decreased TAC-induced myocardial fibrosis and left ventricular hypertrophy, and preserved cardiac function. Ginsenoside Rg1 administration enhanced angiogenesis by increasing the expression of HIF-1 and VEGF. These cardioprotective effects of ginsenoside Rg1 are partially related to the activation of phospho-Akt and inhibition of p38 MAPK. CONCLUSIONS: Ginsenoside Rg1 exhibited protective effect against TAC-induced left ventricular hypertrophy and cardiac dysfunction, which is potentially associated with phospho-Akt activation and p38 MAPK inhibition.