Efficacy and Safety of Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People's Republic of China: a Systematic Review and Meta-Analysis.

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.

Physiological role for S-nitrosylation of RyR1 in skeletal muscle function and development.

Excitation-contraction coupling in skeletal muscle myofibers depends upon Ca2+ release from the sarcoplasmic reticulum through the ryanodine receptor/Ca2+-release channel RyR1. The RyR1 contains ∼100 Cys thiols of which ∼30 comprise an allosteric network subject to posttranslational modification by S-nitrosylation, S-palmitoylation and S-oxidation. However, the role and function of these modifications is not understood. Although aberrant S-nitrosylation of multiple unidentified sites has been associated with dystrophic diseases, malignant hyperthermia and other myopathic syndromes, S-nitrosylation in physiological situations is reportedly specific to a single (1 of ∼100) Cys in RyR1, Cys3636 in a manner gated by pO2. Using mice expressing a form of RyR1 with a Cys3636→Ala point mutation to prevent S-nitrosylation at this site, we showed that Cys3636 was the principal target of endogenous S-nitrosylation during normal muscle function. The absence of Cys3636 S-nitrosylation suppressed stimulus-evoked Ca2+ release at physiological pO2 (at least in part by altering the regulation of RyR1 by Ca2+/calmodulin), eliminated pO2 coupling, and diminished skeletal myocyte contractility in vitro and measures of muscle strength in vivo. Furthermore, we found that abrogation of Cys3636 S-nitrosylation resulted in a developmental defect reflected in diminished myofiber diameter, altered fiber subtypes, and altered expression of genes implicated in muscle development and atrophy. Thus, our findings establish a physiological role for pO2-coupled S-nitrosylation of RyR1 in skeletal muscle contractility and development and provide foundation for future studies of RyR1 modifications in physiology and disease.

IGF-1 Induces Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells by Promoting SOX4 via the MAPK/ERK Pathway.

Tissue engineering envisions functional substitute creation for damaged tissues. Insulin-like growth factor-1 (IGF-1) plays roles in bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation (OD), and we investigated its specific mechanism. BMSCs were cultured and OD was induced. Surface antigens (CD105, CD90, CD44, CD45, CD34) were identified by flow cytometry. Adipogenic, chondrogenic, and osteogenic differentiation abilities of BMSCs were observed. BMSCs were cultured in osteogenic medium containing 80 ng/mL IGF-1 for 3 weeks. Alkaline phosphatase activity, calcification level, osteogenic factor (runt related protein 2 [RUNX2], osteocalcin [OCN], osterix [OSX]), total (t-) ERK1/2 and phosphorylated- (p-) ERK1/2 levels, and SRY-related high-mobility-group box 4 (SOX4) levels were assessed by alkaline phosphatase staining and Alizarin Red staining, Western blot, and reverse transcription-quantitative polymerase chain reaction. The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway inhibitor (PD98059) was used to inhibit the MAPK/ERK pathway in IGF-1-treated BMSCs. Small interfering-SOX4 was transfected into BMSCs to down-regulate SOX4. IGF-1 increased alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels in BMSCs, indicating that IGF-1 induced rat BMSC OD. SOX4, and p-ERK1/2 and t-ERK1/2 levels were elevated in IGF-1-induced BMSCs, which were annulled by PD98059. PD98059 partly averted IGF-1-induced rat BMSC OD. SOX4 levels, alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels were reduced after SOX4 down-regulation, showing that downregulation of SOX4 averted the effect of IGF-1 on inducing rat BMSC OD. IGF-1 induced rat BMSC OD by stimulating SOX4 via the MAPK/ERK pathway.

The ligand binding domain of a type IV pilus chemoreceptor PilJ has a different fold from that of another PilJ-type receptor McpN.

Bacterial chemoreceptors sense the extracellular signals and regulate bacterial motilities, biofilm formation, etc. The periplasmic ligand binding domains of chemoreceptors occur as different structural folds and recognize a diversity of chemical molecules. In Pseudomonas aeruginosa (PAO1), two bacterial chemoreceptors, McpN (PA2788) and PilJ (PA0411), are proposed to both contain a PilJ-like ligand-binding domain (LBD) (Pfam motif PF13675) and involved in nitrate chemotaxis and type IV pilus-mediated motility, respectively. The LBDs of McpN and PilJ consist of 135 and 263 residues, respectively, and share very low sequence identity, suggesting they might occur as different structures. Here, we found that PilJ-LBD folded into an HBM module, the same as the sensor domains of McpS-LBD and TorS-LBD, but it differed from that of McpN-LBD. We also observed a trimer in SEC and AUC and proposed a trimeric model based on the crystal structure. Based on the sequence, we classified the Pfam containing McpN-LBD and PilJ-LBD into three classes: sPilJ (single PilJ) represented by McpN-LBD with only one PilJ domain, dPilJ (dual PilJ) that contained dual PilJ domains, and hPilJ (hybrid PilJ) that comprises of a PilJ domain and another non-PilJ domain. Our work indicates a significant structural difference between the ligand binding domains of PilJ and McpN and will help our further study on both kinds of chemoreceptors.

A Green High-k Dielectric from Modified Carboxymethyl Cellulose-Based with Dextrin.

Many crucial components inside electronic devices are made from non-renewable, non-biodegradable, and potentially toxic materials, leading to environmental damage. Finding alternative green dielectric materials is mandatory to align with global sustainable goals. Carboxymethyl cellulose (CMC) is a bio-polymer derived from cellulose and has outstanding properties. Herein, citric acid, dextrin, and CMC based hydrogels are prepared, which are biocompatible and biodegradable and exhibit rubber-like mechanical properties, with Young modulus values of 0.89 MPa. Hence, thin film CMC-based hydrogel is explored as a suitable green high-k dielectric candidate for operation at low voltages, demonstrating a high dielectric constant of up to 78. These fabricated transistors reveal stable high capacitance (2090 nF cm-2) for ≈±3 V operation. Using a polyelectrolyte-type approach and poly-(2-vinyl anthracene) (PVAn) surface modification, this study demonstrates a thin dielectric layer (d ≈30 nm) with a small voltage threshold (Vth ≈-0.8 V), moderate transconductance (gm ≈65 nS), and high ON-OFF ratio (≈105). Furthermore, the dielectric layer exhibits stable performance under bias stress of ± 3.5 V and 100 cycles of switching tests. The modified CMC-based hydrogel demonstrates desirable performance as a green dielectric for low-voltage operation, further highlighting its biocompatibility.

A study on the influencing factors of corporate digital transformation: empirical evidence from Chinese listed companies.

In an era where digital technology is reshaping business landscapes, understanding the factors that drive corporate digital transformation is essential. In this paper we explore these influencing factors, focusing on Chinese A-share listed companies from 2007 to 2021. Our approach involved a comprehensive analysis of multiple variables through regression techniques to determine their impact on digital transformation. The findings reveal the drive for reform in the digital transformation endeavours of enterprises. Notably, companies with higher gearing, overhead, and accounts receivable ratios exhibit a stronger inclination towards digital transformation. Conversely, enterprises in monopolistic industries and those at the inception stage of their life cycle show less propensity for such transformation. The findings of this research not only shed light on the strategic decisions behind digital transformation in response to financial and competitive challenges but also provide actionable insights for policymakers and business strategists. This study underscores the importance of contextualizing digital transformation efforts within the unique framework of industry characteristics and company development phases.

Driving forces of digital transformation in chinese enterprises based on machine learning.

With advanced science and digital technology, digital transformation has become an important way to promote the sustainable development of enterprises. However, the existing research only focuses on the linear relationship between a single characteristic and digital transformation. In this study, we select the data of Chinese A-share listed companies from 2010 to 2020, innovatively use the machine learning method and explore the differences in the predictive effects of multi-dimensional features on the digital transformation of enterprises based on the Technology-Organization-Environment (TOE) theory, thus identifying the main drivers affecting digital transformation and the fitting models with stronger predictive effect. The study found that: first, by comparing machine learning and traditional linear regression models, it is found that the prediction ability of ensemble earning method is generally higher than that of tradition measurement method. For the sample data selected in this research, XGBoost and LightGBM have strong explanatory ability and high prediction accuracy. Second, compared with the technical driving force and environmental driving force, the organizational driving force has a greater impact. Third, among these characteristics, equity concentration and executives' knowledge level in organizational dimension have the greatest impact on digital transformation. Therefore, enterprise managers should always pay attention to the decision-making role of equity concentration and executives' knowledge level. This study further enriches the literature on digital transformation in enterprises, expands the application of machine learning in economics, and provides a theoretical basis for enterprises to enhance digital transformation.

Study on the impact of digital transformation on the innovation potential based on evidence from Chinese listed companies.

Digital transformation has emerged as a powerful force in reshaping the business landscape and enabling organizations to enhance their capabilities. One critical aspect of this change is how it impacts an enterprise's innovation ability. To explore this question, we select data regarding China's A-share listed enterprises from 2007 to 2021 as the research sample. We employ crawler technology to gather keywords related to "digital transformation" from annual reports, portraying detailed journeys of enterprises' digital transformation. Through descriptive statistics and multiple covariance tests, a linear relationship is established between digital transformation and innovation ability. Benchmark regression is conducted and a robustness test is utilized to determine the robustness of the benchmark regression. The mechanism, heterogeneity, and moderating effects of this study are also tested. The results reveal that digital transformation makes a significant positive contribution to the innovation capability of enterprises. Meanwhile, among different types of enterprises, the impact of digital transformation on enterprise innovation capability shows heterogeneity. In terms of the impact mechanism, digital transformation can enhance the innovation output of enterprises by reducing the agency cost and improving the risk-taking level of enterprises, so as to further improve the innovation capability of enterprises. The research results of this paper provide essential theoretical support for the digital transformation of enterprises and the government's formulation of enterprises' digitalization strategies. More profoundly, it provides significant reference for how to further promote the digital transformation of Chinese enterprises.

Optimizing Typha biochar with phosphoric acid modification and ferric chloride impregnation for hexavalent chromium remediation in water and soil.

Considering the persistent and covert nature of heavy metal soil contamination, the sustainable development of ecological environments and food safety is at significant risk. Our study focuses on remediating soils contaminated with chromium (Cr); we introduce an advanced remediation material, iron oxide phosphoric acid-loaded activated biochar (HFBC), synthesized through pyrolysis. This HFBC displays greater microporosity, fewer impurities, and enhanced efficiency for the remediation process. Our research utilized a comprehensive set of analytical techniques, including Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Photoelectron Spectroscopy (XPS), alongside adsorption studies to elucidate the Cr removal mechanism. The effectiveness of HFBC in remediation was influenced by several factors: the pH level, dosage of HFBC, the initial concentration of Cr, and the ambient temperature. Our results indicated an optimal chromium (VI) adsorption capacity of 55.5 mg/g by HFBC at a pH of 6.0 and a temperature of 25 °C, with the process adhering to the pseudo-second-order kinetic model and the Langmuir adsorption isotherm, thus suggesting spontaneity in the uptake method. Moreover, this mechanism encompasses both adsorption and reduction reactions. Using HFBC in pot experiments with cabbage indicated not only an increase in soil pH and cation exchange capacity (CEC), but also a surge in bacterial community abundance. Significant reductions in bioavailable chromium were also recorded. Interestingly, HFBC addition bolstered the growth of cabbage, while concurrently diminishing chromium accumulation within the plant, particularly notable as the HFBC application rate increased. In summation, the HFBC produced in our study has demonstrated convincing efficacy in removing chromium from aqueous solutions and soil. Moreover, the positive agronomic implications of its use, such as enhanced plant growth and reduced heavy metal uptake by plants, indicate its high potential for operational value in the domain of environmental remediation of heavy metals.

The value of MRI-based radiomics for evaluating early parotid gland injury in primary Sjögren's syndrome.

OBJECTIVE: This study aimed to evaluate the value of machine learning models (ML) based on MRI radiomics in diagnosing early parotid gland injury in primary Sjögren's syndrome (pSS). METHODS: A total of 164 patients (114 in the training cohort and 50 in the testing cohort) with pSS (n=82) or healthy controls (HC) (n=82) were enrolled. Itksnap software was used to perform two-dimensional segmentation of the bilateral parotid glands on T1-weighted (T1WI) and fat-suppressed T2-weighted imaging (fs-T2WI) images. A total of 1548 texture features of the parotid glands were extracted using radiomics software. A radiomics score (Radscore) was constructed and calculated. A t-test was used to compare the Radscore between the two groups. Finally, five machine learning models were trained and tested to identify early pSS parotid injury, and the performance of the machine learning models was evaluated by calculating the acceptance operating curve (ROC) and other parameters. RESULTS: The Radscores between the pSS and HC groups showed significant statistical differences (p<0.001). Among the five machine learning models, the Extra Trees Classifier (ETC) model performed high predictive efficacy in identifying early pSS parotid injury, with an AUC of 0.87 in the testing set. CONCLUSION: MRI radiomics-based machine learning models can effectively diagnose early parotid gland injury in primary Sjögren's syndrome.

Genome analysis of Shewanella putrefaciens 4H revealing the potential mechanisms for the chromium remediation.

Microbial remediation of heavy metal polluted environment is ecofriendly and cost effective. Therefore, in the present study, Shewanella putrefaciens stain 4H was previously isolated by our group from the activated sludge of secondary sedimentation tank in a dyeing wastewater treatment plant. The bacterium was able to reduce chromate effectively. The strains showed significant ability to reduce Cr(VI) in the pH range of 8.0 to 10.0 (optimum pH 9.0) and 25-42 ℃ (optimum 30 ℃) and were able to reduce 300 mg/L of Cr(VI) in 72 h under parthenogenetic anaerobic conditions. In this paper, the complete genome sequence was obtained by Nanopore sequencing technology and analyzed chromium metabolism-related genes by comparative genomics The genomic sequence of S. putrefaciens 4H has a length of 4,631,110 bp with a G + C content of 44.66% and contains 4015 protein-coding genes and 3223,  2414, 2343 genes were correspondingly annotated into the COG, KEGG, and GO databases. The qRT-PCR analysis showed that the expression of chrA, mtrC, and undA genes was up-regulated under Cr(VI) stress. This study explores the Chromium Metabolism-Related Genes of S. putrefaciens 4H and will help to deepen our understanding of the mechanisms of Cr(VI) tolerance and reduction in this strain, thus contributing to the better application of S. putrefaciens 4H in the field of remediation of chromium-contaminated environments.

Outcomes following KRASG12C inhibitor treatment in patients with KRASG12C-mutated solid tumors: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of FDA-approved KRASG12C inhibitors in patients with KRASG12C-mutated solid tumors. METHODS: We searched PubMed, EMBASE, Cochrane Library, and major international conferences for clinical trials published in English up to March 6, 2023. Clinical trials investigating sotorasib or adagrasib and reporting the clinical outcomes of the objective response rate (ORR), disease control rate (DCR), or incidence rate of grade ≥ 3 adverse events (AEs) were eligible. The primary endpoint was the ORR. Secondary endpoints included the DCR, incidence rate of grade ≥ 3 AEs, and odds ratio (OR) of the ORR between patients with or without co-mutation. The Random-effects model was applied for the outcomes of interest. RESULTS: 18 studies with 1224 patients were included in this meta-analysis. The pooled ORR, DCR, and incidence rate of grade ≥ 3 AEs were 31 % (95 % CI, 25-37 %), 86 % (95 % CI, 82-89 %), and 29 % (95 % CI, 23-36 %), respectively. KRASG12C-mutated NSCLC patients with a co-mutation of KEAP1 exhibited a worse ORR than those with wild-type KEAP1 (OR: 0.35, 95 % CI: 0.16-0.77). CONCLUSIONS: This study provided a comprehensive understanding of the efficacy and safety of KRASG12C inhibitors in treating solid tumors and identified KEAP1 mutation as a potential predictive biomarker of inferior response in patients treated with KRASG12C inhibitors. These findings may assist in the design of future clinical trials for identifying populations that may benefit from KRASG12C inhibitor treatment.

Antitumor effect of exopolysaccharide from Lactiplantibacillus plantarum WLPL09 on melanoma mice via regulating immunity and gut microbiota.

Exopolysaccharide (EPS-09) from L. plantarum WLPL09 was systemically investigated for the antitumor effect in B16F10 melanoma bearing mice model. The results showed that administraion of EPS-09 (200 mg/kg) could sigificantly inhibit the tumor growth of melanoma bearing mice, with a inhibition rate of 42.53 %. Meanwhile, compared to the Model group, high dose of EPS-09 (200 mg/kg) administraion could increase the spleen index (P = 0.10), promote the splenic lymphocytes proliferation under the stimulation of ConA and LPS with a proliferation rate of 120.58 % and 169.88 %, respectively, enhance the amount of CD4+ and CD8+ T cells (P < 0.0001, P = 0.0149) in tumor tissue, as well as the serum content of cytokines, i.e., TNF-α, IFN-γ, IL-2 (P < 0.05) and IL-6 (P = 0.039) of B16F10 melanoma bearing mice. The transcriptional level analysis revealed that EPS-09 (200 mg/kg) administraion could sigificantly (P < 0.05) upregulate the transcription of apoptosis raleted genes, i.e., P53, Caspase-3 and Caspase-9, and the ratio of Bax/Bcl-2, downregulate the transcription of angiogenesis markers, i.e., Vegf and Fgf2 compared with Model group. Furthermore, administration of EPS-09 could increase the abundance of phylum Firmicutes, family Ruminococcaceae and Lachnospiraceae, and genus Ruminococcus, but reduce the abundance of genus Prevotella, Akkermansia and Oscillospira. Taken together, these results indicate that administration of EPS-09 can induce apoptosis of tumor cell, inhibit tumor angiogenesis, improve the immunity, regulate the intestinal microbiota composition of B16F10 melanoma bearing mice, and play positive roles in the antitumor activity against melanoma.

A Universal Additive Design Strategy to Modulate Solvation Structure and Hydrogen Bond Network toward Highly Reversible Fe Anode for Low-Temperature All-Iron Flow Batteries.

Aqueous all-iron redox flow batteries (RFBs) are promising competitors for next-generation grid-scale energy storage applications. However, the high-performance operation of all-iron RFBs in a wider temperature range is greatly hindered by inferior iron plating/stripping reaction and low solid-liquid transition temperature at Fe anode. Herein, a universal electrolyte additive design strategy for all-iron RFBs is reported, which realizes a highly reversible and dendrite-free Fe anode at low temperatures. Quantum chemistry calculations first screen several organic molecules with oxygen-containing functional groups and identify N,N-Dimethylacetmide (DMAc) as a potential candidate with low cost, high solubility, and strong interactions with Fe2+ and H2 O. Combined experimental characterizations and theoretical calculations subsequently demonstrate that adding DMAc into the FeCl2 solution effectively reshapes the primary solvation shell of Fe2+ via the Fe2+ -O (DMAc) bond and breaks hydrogen-bonding network of water through intensified H-bond interaction between DMAc and H2 O, thereby affording the Fe anode with enhanced Fe/Fe2+ reversibility and lower freezing point. Consequently, the assembled all-iron RFB achieves an excellent combination of high power density (25 mW cm-2 ), long charge-discharge cycling stability (95.59% capacity retention in 103 h), and preeminent battery efficiency at -20 °C (95% coulombic efficiency), which promise a future for wider temperature range operation of all-iron RFBs.

Research Advances in Targeted Drug Delivery System / 医药导报

In recent years,due to the development of disciplines such as molecular biology,cell biology,and materials science,the research of targeted therapy drugs has become a hot spot.Compared with conventional drugs,targeted therapy drugs can selectively increase the concentration and effectively reduce the toxic side effects of drugs in target tissues,which is an ideal way of drug delivery.Nanomaterial is receiving more attention for its superior performance in animals.The application and develop-ment of nanocrystals in targeted drug delivery systems has effectively broken the limitation of insoluble drugs and plays an indis-pensable role in drug delivery systems.In this paper,we briefly reviewed the characteristics and classification of targeted therapy drugs and the application of nanocrystals in pharmaceutical research to provide a reference for the related research.

Analysis of Residue and Transfer Status and Risk Assessment of Plant Growth Regulator Paclobutrazol in Shenmai Granules / 医药导报

Objective To analyze the residual status,transfer behavior,and risk of paclobutrazole in the national mar-ket of Shenmai granules.Methods GC-MS/MS determined the residual amount of paclobutrazol in Shenmai granules,and ANOVA analyzed the distribution characteristics of sample residuals.The transfer rule of paclobutrazol from Ophiopogonis Radix to Shenmai granules was investigated by simulating the production process,and chronic exposure assessment was performed using the point evaluation model.Results The established method can accurately determine the residual amount of paclobutrazol in Shenmai granules.The residual amount of paclobutrazol in 85 batches of Shenmai granules ranged from 0.001 3 to 0.015 8 mg·kg-1,and there was a statistical difference in the residual amount among different enterprise samples.The transfer rate of paclobutrazol from decoction pieces to preparations was 29.8%.The chronic risk quotient(HQc)of paclobutrazol residues in Shenmai granules was 0.000 7%,far lower than 1.Conclusion There is a general presence of paclobutrazol residues in Shenmai granules.The risk assessment results show that the normal dosage of Shenmai granules does not pose an unacceptable risk to the general population.The residual distribution characteristics and process transfer rules can provide a reference for safety risk control in production enterprises.

Research progress on surgical evaluation system for congenital heart disease / 中国胸心血管外科临床杂志

@#The surgical difficulty of congenital heart disease varies greatly. To ensure the safety of surgery and maximize the benefits of patients, various congenital heart surgery scoring systems have been used to evaluate the risk of different complex congenital cardiac operations. However, the complete correction of cardiac anatomical malformations is a common surgical challenge. Recent studies have shown that the correction is closely related to perioperative mortality and postoperative complications, and a new scoring system for the degree of cardiac anatomical malformations has been proposed. Therefore, this review summarizes the literature and discusses different evaluative methods of congenital heart surgery, aiming to optimize the surgical evaluation system for congenital heart surgery, enhance the quality of surgery and improve the prognosis of patients.

Aucubin inhibits the proliferation of human hepatocellular carcinoma cells line HepG2 / 基础医学与临床

Objective To investigate the effects of aucubin(AU)on the proliferation,apoptosis,and cell cycle of human liver cancer cells line HepG2 and its mechanism of action.Methods HepG2 cells were cultured in vitro,CCK-8 method was applied to screen the optimal dosage concentration of AU.HepG2 cells were randomly grouped into a control group,an AU 12.5 mg/L group(AU L group),an AU 62.5 mg/L group(AU H group),and an AU H+Akt pathway agonist(SC79)group(AU H+SC79 group).The cell proliferation was observed in each group;5-Ethynyl-2′-deoxyuridine(EDU)method was applied to detect cell proliferation;Flow cytometry was applied to detect cell apoptosis and cell cycle;Western blot was applied to detect the expression levels of phosphorylated pro-tein kinase B(p-Akt),Akt,p-MDM2,MDM2,p-p53,and p53 proteins.Results AU concentrations of 12.5 and 62.5 mg/L were selected for subsequent experiments.Compared with 0 mg/L AU,the proliferation of 12.5 and 62.5 mg/L AU cells was obviously reduced(P＜0.05);Compared with the control group,the number of suspended and exfoliated cells in the AU L and AU H groups gradually increased.Cells shrunk and became round.The propor-tion of G0/G1 phase cells,the proportion of EDU positive staining cells increased and the expression level of p-Akt/Akt and p-MDM2/MDM2 proteins decreased.The proportions of S and G2/M phase cells,the rate of cell apoptosis,and the expression level of p-p53/p53 protein all increased(P＜0.05).Compared with the AU H group,the above changes in the AU H+SC79 group were recovered(P＜0.05).After AU treatment,the tumor vol-ume and weight of transplanted nude mice decreased.Conclusions AU may inhibit the proliferation of liver cancer cells,induce cell cycle arrest and apoptosis by regulating the Akt/MDM2/p53 signaling pathway.

Application value of multiplexed sensitivity encoding diffusion weighted imaging in neck MRI scanning / 实用放射学杂志

Objective To explore the feasibility of the multiplexed sensitivity encoding diffusion weighted imaging(MUSE-DWI)sequence in neck MRI,and to compare with traditional single-shot echo-planar imaging diffusion weighted imaging(SS-EPI-DWI)sequence.Methods Thirty healthy volunteers underwent MUSE-DWI and SS-EPI-DWI sequences scanning in neck.Two groups of images were independently scored by two radiologists for magnetic sensitivity artifact,chemical shift artifact,geometric distortion and overall image quality.The noise,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the regions of interest(ROI)of the two groups of images were measured and compared on the nasopharyngeal fossa layer,parotid gland layer,glottic layer and thyroid layer.Results Qualitative analysis showed that the image quality scores of MUSE-DWI sequence were significantly better than those of SS-EPI-DWI sequence in terms of magnetic sensitivity artifact,chemical shift artifact,geometric distortion and overall image quality(P<0.001).Quantitative analysis showed that the noise values of ROIs of MUSE-DWI sequence were significantly lower than those of SS-EPI-DWI sequence(P<0.001).The SNR and CNR of ROIs of MUSE-DWI sequence were higher than those of SS-EPI-DWI sequence(P<0.001).Conclusion MUSE-DWI sequence can significantly reduce geometric distortion,magnetic sensitivity artifact and chemical shift artifact,and SNR and CNR of images are significantly increased compared with SS-EPI-DWI sequence,which is more suitable for neck MRI scanning.