Noninvasive models for the prediction of liver fibrosis in patients with chronic hepatitis B.

OBJECTIVE: To evaluate the diagnostic accuracy of aspartate aminotransferase(AST)/ alanine transaminase (ALT), AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4) and gamma-glutamyl transpeptidase to platelet count ratio (GPR) for hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS: A total of 1210 CHB patients who underwent liver biopsy were divided into two groups: patients with no significant fibrosis (control group) and patients with significant fibrosis, and routine laboratory tests were retrospectively included. Logistic regression models were used for the prediction, and the area under the receiver operating characteristic (AUROC) was used to assess the diagnostic accuracy. RESULTS: A total of 631 (52.1%) and 275 (22.7%) patients had significant fibrosis (≥ S2) and advanced fibrosis (≥ S3), respectively. The GPR showed significantly higher diagnostic accuracy than that of APRI, FiB-4, and AST/ALT to predict ≥ S2(significant fibrosis) and ≥ S3 fibrosis(advanced fibrosis), with an AUROC was 0.69 (95%CI: 0.66-0.71) and 0.72 (0.69-0.75), respectively. After stratified by the status of HBeAg ( positive or negative), GPR, APRI, and FiB-4 showed improved predicting performance for significant fibrosis and advanced fibrosis in HBeAg positive patients, with the most significant improvement was shown for GPR in predicting significant fibrosis (AUROC = 0.74, 95%CI: 0.70-0.78). CONCLUSIONS: Among the four noninvasive models, GPR has the best performance in the diagnosis of hepatic fibrosis in CHB patients and is more valuable in HBeAg-positive patients.

Decoding the gene regulatory network of endosperm differentiation in maize.

The persistent cereal endosperm constitutes the majority of the grain volume. Dissecting the gene regulatory network underlying cereal endosperm development will facilitate yield and quality improvement of cereal crops. Here, we use single-cell transcriptomics to analyze the developing maize (Zea mays) endosperm during cell differentiation. After obtaining transcriptomic data from 17,022 single cells, we identify 12 cell clusters corresponding to five endosperm cell types and revealing complex transcriptional heterogeneity. We delineate the temporal gene-expression pattern from 6 to 7 days after pollination. We profile the genomic DNA-binding sites of 161 transcription factors differentially expressed between cell clusters and constructed a gene regulatory network by combining the single-cell transcriptomic data with the direct DNA-binding profiles, identifying 181 regulons containing genes encoding transcription factors along with their high-confidence targets, Furthermore, we map the regulons to endosperm cell clusters, identify cell-cluster-specific essential regulators, and experimentally validated three predicted key regulators. This study provides a framework for understanding cereal endosperm development and function at single-cell resolution.

Synthesis, Quality Control and Preliminary Activity Evaluation of a New Compound HM475.

Based on the principle of molecular splicing and theory of traditional Chinese medicine pairs, a new multi-active compound (HM475) was synthesized by connecting metformin with honokiol, and its structure was characterized, which not only reduced the toxicity of raw materials, but also maintained the original activity, and had a certain significance in research and innovation. At the same time, quality control and preliminary activity evaluation were carried out, and the effect of HM475 on neuroinflammation was further explored, which provided a new idea for drug development of neurodegenerative diseases.

Efficacy and safety of elbasvir/grazoprevir treatment for Chinese patients with hepatitis C virus genotype 1b: a retrospective study.

OBJECTIVES: To determine the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) treatment in Chinese patients with GT1b chronic hepatitis virus C (HCV) infections. METHODS: In this retrospective study, 49 treatment-naive patients with chronic GT1b HCV infection were treated with GZR (100 mg) plus EBR (50 mg) for 12 weeks. The viral response was the primary endpoint and fibrosis stage changes during and after treatment, as well as the incidence of treatment-emergent adverse events (TEAE) were secondary endpoints. RESULTS: After 2-week EBR/GZR treatment, the virologic response rate was 85.1% (80/94) and reached 100% (94/94) after 8 and 12 weeks of therapy. Sustained virologic response (SVR) rates were 100% at the 12, 24 and 48-week follow-ups. Multivariate analysis revealed that the baseline viral load of HCV RNA may affect the rapid 2-week virologic response (OR: 0.36, 95% CI: 0.14-0.92, P=0.034), but did not influence efficacy during further treatment or follow-ups. Fifteen patients with ≥1 TEAE (16.0%) were observed and 7 (7.4%) and 8 (8.5%) patients had mild ALT or AST elevations (1.1-2.5× BL), but no serious drug-related AEs occurred. Liver stiffness measurement (LSM), the AST to platelet ratio index (APRI) and the fibrosis index based on 4 factor (FIB4) scores were consistently reduced, especially in patients with high baseline assessments after 12 weeks' treatment and during follow-ups. CONCLUSIONS: A 12-week EBR/GZR regimen shows high efficacy and safety in Chinese patients with GT1b HCV infections.

Rational Design of Photothermal and Anti-Bacterial Foam With Macroporous Structure for Efficient Desalination of Water.

With the environmental deterioration and the rise in demand for sustainability, the lack of freshwater resources has emerged as a global concern. To address this issue, the desalination of water using solar evaporation is centered on as a promising approach. In this study, we designed a light and photothermal liquefied-chitin-based polyurethane foam to achieve efficient water evaporation benefiting from their powerful solar spectral absorption, low thermal conductivity, quick transportation of water, hierarchically porous structures, and anti-biofouling natures. Moreover, because of the introduction of nano-silver, the newly developed foam exhibits considerable antibacterial ability and improved photothermal performance. Notably, the low thermal conductivity of the foam can reduce the loss of absorbed solar heat, whereas its large porous structure provides a smooth water transport channel. More importantly, with the assistance of heat, polyacrylamide hydrogels adhering along with the pores rapidly absorb and desorb water molecules, promoting the evaporation of water and improving solar energy conversion efficiency. Ultimately, under irradiation by one sunlight, the proposed material demonstrated a water evaporation rate and solar photothermal conversion efficiency of 2.44 kg m-2 h-1 and 153.2%, respectively.

Differentiating Pu-erh raw tea from different geographical origins by 1 H-NMR and U-HPLC/Q-TOF-MS combined with chemometrics.

Pu-erh tea is believed to be a beneficial beverage for health due to its many kinds of pharmacological effects. Nevertheless, detailed information related to differences in metabolites of Pu-erh raw tea from different geographical origins remains scarce. In this study, 43 elements were found in water-soluble components of Pu-erh raw tea by highly sensitive ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (U-HPLC/Q-TOF-MS). The characteristic groups of 29 metabolites from nondestructive proton nuclear magnetic resonance (1 H-NMR) spectroscopy were assigned. The variables contributed largely to the origin classification, mainly including valine, threonine, chlorogenic acid, quinic acid, epiafzelechin, and gallic acid ester, were screened out by sparse partial least squares discriminant analysis (sPLS-DA) method. This study provided a feasible and rapid technique for distinguishing Pu-erh tea from different areas by 1 H-NMR combined with sPLS-DA.

Safety of locating the tip of a medium-long catheter at the axillary front and clavicle midline: A protocol for systematic review and meta-analysis.

BACKGROUND: Medium-long catheters are being used more and more widely in clinical practice, but we still do not know the impact of different placements, but this is an important clinical issue that cannot be ignored. OBJECTIVE: At present, the tip positioning of the mid-length catheter mainly includes the anterior part of the axilla and the midclavicular line. Different positioning may have different effects. Therefore, we did this research to confirm which positioning is more safety. METHODS: We systematically searched the Chinese and English databases: PubMed, Embase, CENTRAL, CINAHL, Web of Science, China Knowledge Network, China Biomedical Literature Database, VIP, Wan Fang. Literature screening, data extraction, and quality evaluation were carried out by 2 researchers, and finally, use Stata to carry out meta-analysis. RESULTS: This study is ongoing and the results will be submitted to a peer-reviewed journal for publication. ETHICS AND DISSEMINATION: Ethical approval is not applicable, since this is an overview based on published articles. PROTOCOL REGISTRATION NUMBER: INPLASY2020110042.

Synthesis, Characterization and Biological Evaluation of Magnolol and Honokiol Derivatives with 1,3,5-Triazine of Metformin Cyclization.

Herein, we sought to evaluate the contribution of the 1,3,5-triazine ring through the metformin cyclization unit to the biological activity of magnolol and honokiol-conjugates. One of the phenolic OH groups of magnolol or honokiol was replaced by a 1,3,5-triazine ring to further explore their synthesis and medicinal versatility. In this study, a robust procedure of three steps was adopted for the synthesis of magnolol and honokiol derivatives by alkylation of potassium carbonate with a 1,3,5-triazine ring. To our knowledge, this is the first report to connect one of the phenolic OH positions of magnolol or honokiol to a 1,3,5-triazine ring cyclized by metformin. The structural characterization of three new compounds was carried out via spectroscopic techniques, i.e., 13C NMR, 1H NMR, and HRMS. Surprisingly, these compounds showed no cytotoxicity against RAW 264.7 macrophages but significantly inhibited the proliferation of MCF-7 (human breast cancer cells), HepG2 (human hepatoma cells), A549 (human lung carcinoma cells), and BxPC-3 (human pancreatic carcinoma cells) tumor cell lines. Furthermore, the compounds also significantly inhibited the release of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in the lipopolysaccharide (LPS)-activated mouse cells (RAW 264.7). Among them, compound 2 demonstrated promising broad-spectrum antiproliferative potential with half inhibitory concentration (IC50) values ranging from 5.57 to 8.74 µM and it significantly decreased caspase-3 and Bcl-2 expression in HepG2 cells. These interesting findings show that derivatization of magnolol and honokiol with 1,3,5-triazine affects and modulates their biological properties.

Rapid identification model based on decision tree algorithm coupling with 1H NMR and feature analysis by UHPLC-QTOFMS spectrometry for sandalwood.

Sandalwood is one of the most valuable woods in the world. However, today's counterfeits are widespread, it is difficult to distinguish authenticity. In this paper, similar genus (Dalbergia and Pterocarpus) and confused species (Gluta sp.) of sandalwood were quickly and efficiently identified. Rapid identification model based on 1H NMR and decision tree (DT) algorithm was firstly developed for the identification of sandalwood, and the accuracy was improved by introducing the AdaBoost algorithm. The accuracy of the final model was above 95%. And the feature components between different species of sandalwood were further explored using UHPLC-QTOFMS and NMR spectrometry. The results showed that 183 compounds were identified, among which 99 were known components, 84 were unknown components. The 1H NMR and 13C NMR signals of 505 samples were assigned, among them, 14 compounds were attributed, characteristic chemical shift intervals with great differences in the model were analysed. Furthermore, the fragmentation pattern of different compounds from sandalwood, in both positive and negative ion ESI modes, was summarized. The results showed a potential and rapid tool based on DT, NMR spectroscopy and UHPLC-QTOFMS, which had performed great potential for rapid identification and feature analysis of sandalwood.

A novel metformin derivative showed improvement of lipid metabolism in obese rats with type 2 diabetes.

In this study, we investigated the lipid metabolism regulatory activity of a novel metformin derivative (MD568) and its potential mechanism of action in obese rats with type 2 diabetes mellitus (T2 DM). Previous gene chip analysis of 3T3-L1 cells have shown that MD568 regulates the transcription of genes involved in the peroxisome proliferator-activated receptor (PPAR) signalling pathway, fatty acid metabolism, and glycerolipid metabolism. In this study, obese T2 DM rats were treated with MD568 (200 mg/kg) for 8 weeks. Results showed that MD568 significantly reduced the body weight gain, plasma glucose, insulin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. MD568 treatment also improved the insulin resistance of obese T2 DM model rats. In particular, in white adipose tissue, MD568 inhibited the excessive volume increment of adipose cells by down-regulating the protein levels of CCAAT/enhancer-binding protein-α (C/EBP-α) and PPAR-γ, as well as the transcription of their target lipid metabolism-related genes. In the liver, MD568 inhibited hepatic fatty lesions and interfered with hepatic gluconeogenesis by regulating the expression of lipid metabolism-related genes and glycogen-related kinases. In conclusion, our results suggest that the newly synthesized MD568 affects the maintenance of lipid homeostasis in obese type 2 diabetic rats.

Lipidomics Analysis of Timosaponin BII in INS-1 Cells Induced by Glycolipid Toxicity and Its Relationship with Inflammation.

Anemarrhena asphodeloides Bunge is a traditional Chinese medicine. The timosaponin BII is one of the most abundant and widely studied active ingredients in Anemarrhena asphodeloides Bunge. Related studies have shown that timosaponin BII has potential value for development and further utilization. The protective effect of timosaponin BII on islet ß cells under type 2 diabetes was investigated in the glycolipid toxic INS-1 cell model and possible biomarkers were explored by lipidomics analysis. Timosaponin BII was isolated from Anemarrhena asphodeloides Bunge by polyamide resin and Sephadex LH-20. Then, the glycolipid toxicity INS-1 cell model was established to investigate the protective effect of timosaponin BII. The results showed that timosaponin BII could significantly influence the levels of malondialdehyde (MDA) and glutathione (GSH), thereby restoring the insulin secretion ability and cell viability of model cells. Lipidomics analysis was combined with multivariate statistical analysis for marker selection. The four most common pathological and pharmacological lipid markers were phosphatidylserine (PS), suggesting that timosaponin BII had protective effects on model cells related to the reduction oxidative stress and macrophage inflammation. RAW264.7 macrophages were stimulated by LPS to establish a model of inflammation and study the effect of timosaponin BII on the nodes of NOD-like receptor P3 (NLRP3) inflammasome pathway in the model cells. In conclusion, timosaponin BII may have the effect of protecting INS-1 pancreatic ß cells through reducing IL-1ß (interleukin-1ß) production by inhibiting the NLRP3 inflammasome in macrophage and restoring the insulin secretion ability and cell viability by reducing oxidative stress.

Droxinostat, a Histone Deacetylase Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cell Lines via Activation of the Mitochondrial Pathway and Downregulation of FLIP.

BACKGROUND: The current chemotherapeutic outcomes for hepatocellular carcinoma (HCC) are not encouraging, and long-term survival of this patient group remains poor. Recent studies have demonstrated the utility of histone deacetylase inhibitors that can disrupt cell proliferation and survival in HCC management. However, the effects of droxinostat, a type of histone deacetylase inhibitor, on HCC remain to be established. METHODS: The effects of droxinostat on HCC cell lines SMMC-7721 and HepG2 were investigated. Histone acetylation and apoptosis-modulating proteins were assessed via Western blot. Proliferation was examined with 3-(4, 5 dimetyl-2-thiazolyl)-2, 5-diphenyl 2H-tetrazolium bromide, cell proliferation, and real-time cell viability assays, and apoptosis with flow cytometry. RESULTS: Droxinostat inhibited proliferation and colony formation of the HCC cell lines examined. Hepatoma cell death was induced through activation of the mitochondrial apoptotic pathway and downregulation of FLIP expression. Droxinostat suppressed histone deacetylase (HDAC) 3 expression and promoted acetylation of histones H3 and H4. Knockdown of HDAC3 induced hepatoma cell apoptosis and histone H3 and H4 acetylation. CONCLUSIONS: Droxinostat suppresses HDAC3 expression and induces histone acetylation and HCC cell death through activation of the mitochondrial apoptotic pathway and downregulation of FLIP, supporting its potential application in the treatment of HCC.

The synergistic effect of organic silicone quaternary ammonium salt and 5-fluorouracil on hepatocellular carcinoma in vitro and in vivo.

Hepatocellular carcinoma (HCC) is the third most common type of cancer worldwide, causing over 370,000 deaths per year, with approximately half of them in China. Chemotherapy is the optimal treatment for patients with advanced HCC, although chemoresistance has become a significant obstacle to successful liver cancer surgery. In this paper, we have assessed the characteristics of drugs to explore the effects of individual and combined action of organic silicone quaternary ammonium salt (Jieyoushen) and 5-fluorouracil (5-FU). The results of MTT assays showed that single and combined action of Jieyoushen and 5-FU can inhibit the proliferation of liver carcinoma cell lines in a dose-dependent and time-dependent manner, respectively. Electron microscopy and Hoechst 33342 staining showed characteristic apoptotic bodies in apoptotic cells treated with Jieyoushen and 5-FU. Flow cytometry results indicated that the percentage of cells at G0/G1 phase gradually increased, whereas it gradually decreased during the S phase after treatment. Taken together, these results suggest that the combination of Jieyoushen with 5-FU exerts a synergistic anticancer effect on HCC growth and that targeted therapeutic strategies may improve HCC sensitivity to chemotherapy.

Correlations of P21-activated kinase 1 expression to clinicopathological features of gastric carcinoma and patients' prognosis.

BACKGROUND AND OBJECTIVE: Recent studies proved that P21-activated kinase 1 (PAK1) is highly expressed in many kinds of tumor and plays an important role in genesis, development, and metastasis of tumor. We aimed to detect the expression of PAK1 in gastric carcinoma and to analyze its relationship with clinicopathological features and prognosis of gastric carcinoma. METHODS: Tissue microarray and immunohistochemical staining were performed to detect PAK1 in paraffin specimens of 189 gastric carcinomas, 54 paracancer tissues, 40 lymph nodes and 30 healthy tissues. Clinicopathologic features and follow-up data of the patients were analyzed by the Chi2 test and the Kaplan-Meier method. RESULTS: Positive rate of PAK1 was 73.0% in gastric carcinoma, 57.4% in paracancer tissues and 23.3% in healthy controls (Chi2 = 29.364, P < 0.05). Expression of PAK1 was significantly correlated with tumor size, tumor differentiation, lymph node metastasis, Lauren classification and invasive depth (all P < 0.05). The positive rate of PAK1 was significantly higher in primary gastric carcinomas than in metastatic lymph nodes (75.0% vs. 52.5%, Chi2 = 4.381, P < 0.05). Survival analysis using the Kaplan-Meier method showed that the expression of PAK1 was a predictor for poor prognosis of the patients with gastric carcinoma (Chi2 = 6.857, P < 0.01). CONCLUSIONS: Expression of PAK1 is an early molecular event in the tumorigenesis of gastric carcinoma. It is also closely correlated the development of gastric carcinoma and the patients' prognosis.

[Relationship between Ets-1 expression and angiogenesis, clinicopathological features and survival of patients with gastric carcinoma].

OBJECTIVE: To investigate the expression of Ets-1 in gastric carcinoma, para-cancerous tissue and metastatic lymph nodes, and to determine the relationship between Ets-1 expression and clinicopathological features, angiogenesis and survival of patients with gastric carcinoma. METHODS: Gastric carcinoma tissue microarray was used to determine Ets-1 protein expression by SP immunohistochemical staining in 189 advanced gastric cancer, 54 papacancerous tissues, 41 metastatic lymph nodes and 32 control tissues. RESULTS: The positive rates for Ets-1 expression of the carcinoma, paracancerous and control tissues were 71.4%, 29.6% and 18.8%, respectively, with a significant difference among the three groups (P < 0.01). In the cancer tissues, the positive rate of Ets-1 protein expression was significantly associated with depth of invasion and lymph node metastasis (P < 0.01), but not associated with degree of differentiation, Lauren's histological type, sex, age, and size of tumor (P > 0.05). The positive rates for Ets-1 expression of the 41 gastric cancer and 41 metastatic lymph nodes were significantly different (P < 0.05). In metastatic lymph nodes, the positive rate for Ets-1 expression was higher. The MVD in Ets-1 positive tumors was higher than that in the Ets-1 negative tumors, with a significant difference (P < 0.05). Kaplan-Meier survival analysis showed that the survival time of Ets-1-negative patients was longer than that of Ets-1-positive patients (P < 0.05). Cox regression analysis showed that Ets-1 expression was not an independent prognostic factor of gastric carcinoma. CONCLUSION: A higher expression of Ets-1 is involved in carcinogenesis, development, invasion, and metastasis of gastric cancer. Ets-1 plays an important role in angiogenesis in gastric cancer. Ets-1 is a useful marker for predicting the outcome for patients with gastric carcinoma, though it is not an independent prognostic indicator.

[Epidemiological study on status of Helicobacter pylori in children and teenagers in Wuwei city, Gansu province].

OBJECTIVE: To investigate the prevalence of Helicobacter pylori (Hp) infection among children aged 3 to 18 years old of Wuwei city, Gansu province. METHODS: The study was based upon a personal questionnaire and a determination of Hp antigen using the Hp stool antigen test (HpSA) method. A total of 938 subjects and 96 families were selected in Wuwei city. Eighty children and teenagers with a definite positive Hp stool antigen test were examined by serum Western blotting method. RESULTS: The prevalence of Hp was 72.3% (678/938) with no age difference. Prevalence of Hp infection was correlated with type of dwelling, occupation of parents, drinking water source, kindergarten attendance, consumption of raw vegetables, a poor oral hygiene and breast feeding etc. According to the multivariate analysis, drinking water source, kindergarten attendance and consumption of raw vegetables were most strongly associated with prevalence of Hp in children and adolescents. The infection rate of parents whose children were infected with Hp was higher than that of those whose children were not infected [82.3% (121/147) vs 47.4% (18/38), chi(2) = 19.736, P < 0.05]. The antibody responses of 57 samples (71.3%) from 80 children were of type I Hp and 23 samples (28.7%) type II. CONCLUSIONS: Hp infective rate is high in Wuwei city. The data support maternal-child and sibling-sibling transmission as the primary transmission routes of Hp. The results of serological analysis confirm that the majority of Wuwei Hp infection is of type I.