Integration of scRNA-Seq and Bulk RNA-Seq to analyze the heterogeneity ofcolorectal cancer immune cells and establish a molecular risk model

Background:Colorectal cancer(CRC)is a highly heterogeneous malignant tumor that significantly impacts clinical diagnosis and treatment.Single-cell RNA sequencing is an innovative method for exploring tumor heterogeneity and understanding its role at cellular and genetic levels.Method:The colorectal cancer Single-cell RNA sequencing data were analysed on the immune.RNA-seq data in bulk form was utilized to assess the major genes of the immune cell subsets linked to CRC.We conducted an analysis of the abundance of immune cells in the microenvironment of CRC,and also performed weighted gene co-expression network analysis.Gene set enrichment analysis helped perform two analytical procedures of subtype groups.Furthermore,Least absolute shrinkage and selection operator regression was employed to analyse and screen for a gene signature.Finally,quantitative PCR Was performed to detect the expression levels of signature genes in CRC.Results:The Single-cell RNA sequencing(GSE146771)dataset was integrated to obtain 9 cell clusters.The Single-sample gene set enrichment analysis showed that the related gene expression of T-cell subsets of different functional statuses could vary greatly between patients with GSE146771.Immune cell analysis of TCGA-CRC indicated an improved overall survival rate for patients with elevated Th2 cell abundance.Five-gene signature(Risk Score=-0.205×CDC25C-0.231×GSTCD-0.010×KPNA2-0.002×KIF15-0.171×ORC1)was developed by weighted correlation network analysis,and lasso Cox regression.Then,the risk prediction efficacy of the signature was validated in four GSE datasets.Furthermore,the expression of five genes was reduced in CRC tissue by quantitative PCR.Conclusion:Five-gene signature based on CRC heterogeneity was developed as a prognosis predictor,which can serve as a potential treatment target.

Survival and prognostic factors of non-small cell lung cancer patients with postoperative locoregional recurrence treated with radical radiotherapy

Background: Locoregional recurrence remains the challenge for long-term survival of non-small cell lung cancer(NSCLC) patients after radical surgery, and curative-intent radiotherapy could be a treatment choice. This study aimed to assess the survival and prognostic factors of patients with postoperative locoregionally recurrent NSCLC treated with radical radiotherapy.Methods: We reviewed medical records of 74 NSCLC patients with postoperative locoregional recurrence who received radical radiotherapy between April 2012 and February 2016 at Sun Yat-sen University Cancer Center(Guangzhou, China). The efficacy and safety of radical radiotherapy were analyzed. The probability of survival was estimated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to identify prognostic factors.Results: Grade 3/4 adverse events included neutropenia(8 cases, 10.8%), esophagitis(7 cases, 9.5%), pneumonitis(1 case, 1.4%), and vomiting(1 case, 1.4%).The 2-year overall survival, progression-free survival, local recurrencefree survival(LRFS), and distant metastasis-free survival(DMFS) rates of all patients were 84.2,42.5,70.0, and 50.9%,respectively. Univariate and multivariate analyses showed that a higher biological effective dose(BED) of radiation was associated with longer LRFS [hazard ratios(HR)=0.317,95% confidence interval(CI) = 0.112-0.899, P = 0.016] and that wild-type epidermal growth factor receptor(EGFR) was associated with longer DMFS compared with EGFR mutation(HR = 0.383,95% CI=0.171-0.855, P = 0.019).Conclusions: Radical radiotherapy is effective and well-tolerated in NSCLC patients with postoperative locoregional recurrence. High BED is a predictor for long LRFS, and the presence of wild-type EGFR is a predictor for long DMFS.

Experimental study on mechanical properties of methane-hydrate-bearing sediments

Mechanical properties of methane hydrate- bearing-sediments （MHBS） are basic parameters for safety analysis of hydrate exploration and exploitation. Young＇s modulus, cohesion, and internal friction angle of hydrate- bearing sediments synthesized in laboratory, are investigated using tri-axial tests. Stress-strain curves and strength parameters are obtained and discussed for different compositions and different hydrate saturation, followed by empirical expressions related to the cohesion, internal friction angle, and modulus of MHBS. Almost all tested MHBS samples exhibit plastic failure. With the increase of total saturation of ice and methane hydrate （MH）, the specimens＇ internal friction angle decreases while the cohesion increases.

非小细胞肺癌术后局部复发患者接受根治性放疗的生存及预后因素

背景与目的局部复发是影响根治性手术后非小细胞肺癌(non?small cell lung cancer,NSCLC)患者长期生存的重要因素之一,而根治性放疗可作为解决这一问题的可选治疗方案。本研究旨在评价接受根治性放疗的NSCLC术后局部复发患者的生存和预后因素。方法回顾2012年4月至2016年2月期间,在中山大学肿瘤防治中心接受根治性放疗的74例NSCLC术后局部复发患者的病历资料,分析根治性放疗的疗效和安全性。采用Kaplan-Meier法估算患者生存率,并用log-rank检验进行比较,采用Cox回归模型进行单、多因素分析。结果 3/4级不良事件包括中性粒细胞减少(8例,10.8%)、放射性食管炎(7例,9.5%)、放射性肺炎(1例,1.4%)和呕吐(1例,1.4%)。所有患者的2年总生存率、无进展生存率、局部无复发生存(local recurrence?free survival,LRFS)率和无远处转移生存(distant metastasis?free survival,DMFS)率分别为84.2%、42.5%、70.0%和50.9%。单因素和多因素分析显示,较高的生物等效剂量(biological effective dose,BED)与较长的LRFS相关(风险比[hazard ratios,HR]=0.317,95%置信区间[confidence interval,CI]:0.112–0.899,P=0.016),与表皮生长因子受体(epidermal growth factor receptor,EGFR)突变型患者相比,EGFR野生型患者的DMFS较长(HR=0.383,95%CI:0.171–0.855,P=0.019)。结论对于NSCLC术后局部复发患者应用根治性放疗治疗是安全有效的。BED与LRFS呈正相关,EGFR野生型患者DMFS较长。

Electroacupuncture pretreatment exhibits antidepressive effects by regulating hippocampal proteomics in rats with chronic restraint stress

The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and electroacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment at Baihui（GV20） and Yintang（GV29） acupoints was performed daily（1 m A, 2 Hz, discontinuous wave, 20 minutes） prior to restraint for 28 days. Open field tests and body weight measurements were carried out to evaluate the depressive symptoms at specific time points. On day 28, the crossing number, rearing number, and body weights of the model group were significantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and absolute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins（COG） database. Twenty-seven differential proteins（uncharacteristic proteins expected） were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related proteins exist in nerve cells.

Stability analysis of seabed strata and casing structure during the natural gas hydrates exploitation by depressurization in horizontal wells in South China Sea

Natural gas hydrates(NGHs)are a new type of clean energy with great development potential.However,it is urgent to achieve safe and economical NGHs development and utilization.This study established a physical model of the study area using the FLAC^(3D) software based on the key parameters of the NGHs production test area in the South China Sea,including the depressurization method,and mechanical parameters of strata,NGHs occurrence characteristics,and the technological characteristics of horizontal wells.Moreover,this study explored the law of influences of the NGHs dissociation range on the stability of the overburden strata and the casing structure of a horizontal well.The results are as follows.With the dissociation of NGHs,the overburden strata of the NGHs dissociation zone subsided and formed funnelshaped zones and then gradually stabilized.However,the upper interface of the NGHs dissociation zone showed significant redistribution and discontinuity of stress.Specifically,distinct stress concentration and corresponding large deformation occurred in the build-up section of the horizontal well,which was thus prone to suffering shear failure.Moreover,apparent end effects occurred at the end of the horizontal well section and might cause the deformation and failure of the casing structure.Therefore,it is necessary to take measures in the build-up section and at the end of the horizontal section of the horizontal well to prevent damage and ensure the wellbore safety in the long-term NGHs exploitation.

Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for Thymoma-associated Severe Aplastic Anemia: a Case Report

THYMOMA, a relatively rare epithelial neoplasm with unique clinical and pathologic features, is the most usual diagnosis for a mass located in the mediastinum. It is often associated withautoimmune disorders. The myastnema gravls ano pure red cell aplasia are the most common disorders, with the incidences of 40% and 5%, respectively, while the incidence of aplastic anemia is only about 0-1.4%. 1 Thymectomy is hard to perform on patients with severe aplastic anemia（SAA） due to severe pancytopenia.

Design of Tough, yet Strong, Heat-resistant PLA/PBAT Blends with Reconfigurable Shape Memory Behavior by Engineering Exchangeable Covalent Crosslinks

Polylactide(PLA)has often been blended with biodegradable poly(butylene adipate-co-terephthalate)(PBAT)to improve its toughness.However,the strength and heat resistance of PLA are always sacrificed.Herein,exchangeable hydroxyl-ester crosslinks are constructed in PLA/PBAT blends by successively introducing a tertiary amine-containing polyol,bis-(2-hydroxyethyl)amino-tris(hydroxymethyl)methane(BTM)and 4,4’-diphenylmethane diisocyanate(MDI)via reactive blending.BTM can react with both PLA and PBAT by transesterification,generating PLA or PBAT chains with terminal or pendant hydroxyl groups,which can then react with MDI to form networks.With internal catalysis of tertiary amine moiety in BTM,transesterification between the residual hydroxyl groups and ester bonds can occur at high temperatures,endowing the PLA/PBAT network with vitrimeric properties.Owning to the transesterification and chain extension reactions with MDI between PLA and PBAT,the interfacial adhesion is greatly improved.As a result of the excellent interfacial adhesion and the network structure,the prepared PLA/PBAT blends show greatly enhanced heat resistance and toughness(more than 40 times that of PLA)while maintaining high stiffness comparable to PLA.Furthermore,the prepared PLA/PBAT blends exhibit promising reconfigurable shape memory behavior.The present work provides a new and facile way to achieve high-performance and functional biodegradable polymeric materials.

Habitat suitability modeling based on remote sensing to realize time synchronization of species and environmental variables

Aims Remote sensing(RS)is a technical method for effectively capturing real-world data on a large scale.We aimed to(i)realize the time synchronization of species and environmental variables,and extract variables related to the actual growth of species based on RS in habitat suitability modeling,and(ii)provide a reference for species management.Methods Taking invasive species Ambrosia artemisiifolia in China as an example for habitat suitability modeling.Temperature and precipitation variables were calculated from the land surface temperature provided by the moderate-resolution imaging spectroradiometer(MODIS),and climate station data,respectively.Besides,other variables that directly affect the growth or reproduction of A.artemisiifolia were also included,such as the relative humidity of the previous year’s flowering period(RHPFP),and the effective UV irradiance reaching the Earth’s surface(UVI).The random forest method was selected to model the habitat suitability.The environmental variables and samples were divided into four-time periods(i.e.1990–2000,2001–2005,2006–2010 and 2011–2016)based on sampling time.Variables from the long-time series of RS(1990–2016)and WorldClim(1960–1990)were also modeled.Important Findings It was feasible to extract environmental variables from RS for habitat suitability modeling,and was more accurate than that based on the variables from WorldClim.The potential distribution of A.artemisiifolia in 1990–2000 and 2006–2010 was smaller than that in 2001–2005 and 2011–2016.The precipitation of driest months(bio14),precipitation coefficient of variation(bio15),RHPFP and UVI were the important environmental variables that affect the growth and reproduction of A.artemisiifolia.The results indicated that the time synchronization of species and environmental variables improved the prediction accuracy of A.artemisiifolia,which should be considered in habitat suitability modeling(especially for annual species).This study can provide an important reference for the management and prevention of the spread of A.artemisiifolia.