Establishment of a prognosis predictive model for liver cancer based on expression of genes involved in the ubiquitin-proteasome pathway

BACKGROUND The ubiquitin-proteasome pathway(UPP)has been proven to play important roles in cancer.AIM To investigate the prognostic significance of genes involved in the UPP and develop a predictive model for liver cancer based on the expression of these genes.METHODS In this study,UPP-related E1,E2,E3,deubiquitylating enzyme,and proteasome gene sets were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)database,aiming to screen the prognostic genes using univariate and multivariate regression analysis and develop a prognosis predictive model based RESULTS Five genes(including autophagy related 10,proteasome 20S subunit alpha 8,proteasome 20S subunit beta 2,ubiquitin specific peptidase 17 like family member 2,and ubiquitin specific peptidase 8)were proven significantly correlated with prognosis and used to develop a prognosis predictive model for liver cancer.Among training,validation,and Gene Expression Omnibus sets,the overall survival differed significantly between the high-risk and low-risk groups.The expression of the five genes was significantly associated with immunocyte infiltration,tumor stage,and postoperative recurrence.A total of 111 differentially expressed genes(DEGs)were identified between the high-risk and low-risk groups and they were enriched in 20 and 5 gene ontology and KEGG pathways.Cell division cycle 20,Kelch repeat and BTB domain containing 11,and DDB1 and CUL4 associated factor 4 like 2 were the DEGs in the E3 gene set that correlated with survival.CONCLUSION We have constructed a prognosis predictive model in patients with liver cancer,which contains five genes that associate with immunocyte infiltration,tumor stage,and postoperative recurrence.

Novel mutation of SPG4 gene in a Chinese family with hereditary spastic paraplegia:A case report

BACKGROUND Hereditary spastic paraplegia(HSP)is a group of neurogenetic diseases of the corticospinal tract,accompanied by distinct spasticity and weakness of the lower extremities.Mutations in the spastic paraplegia type 4(SPG4)gene,encoding the spastin protein,are the major cause of the disease.This study reported a Chinese family with HSP caused by a novel mutation of the SPG4 gene.CASE SUMMARY A 44-year-old male was admitted to our hospital for long-term right lower limb weakness,leg stiffness,and unstable walking.His symptoms gradually worsened,while no obvious muscle atrophy in the lower limbs was found.Neurological examinations revealed that the muscle strength of the lower limbs was normal,and knee reflex hyperreflexia and bilateral positive Babinski signs were detected.Members of his family also had the same symptoms.Using mutation analysis,a novel heterozygous duplication mutation,c.1053dupA,p.(Gln352Thrfs*15),was identified in the SPG4 gene in this family.CONCLUSION A Chinese family with HSP had a novel mutation of the SPG4 gene,which is autosomal dominant and inherited as pure HSP.The age of onset,sex distribution,and clinical manifestations of all existing living patients in this family were analyzed.The findings may extend the current knowledge on the existing mutations in the SPG4 gene.

骨科大手术后静脉血栓栓塞症的危险因素研究

目的探讨骨科大手术患者术后静脉血栓栓塞症(VTE)的危险因素。方法选取2016年1月-2017年12月于山东中医药大学附属医院行骨科大手术的患者220例。其中术后3个月内并发VTE的102例患者作为观察组,选取同期未发生VTE的118例患者作为对照组。记录患者的各种危险因素,并采用Caprini血栓风险评估模型进行评分,分析危险因素与VTE之间的关系。结果两组患者的年龄、既往病史、纤维蛋白原、D-二聚体、同型半胱氨酸、手术体位、手术时间、输血史及输血量比较,差异有统计学意义(P<0.05);观察组Caprini血栓风险因素评分高于对照组(P<0.05);经多因素Logistic回归分析显示,既往病史、纤维蛋白原、D-二聚体、手术体位和手术时间是骨科大手术患者易栓的独立危险因素(P<0.05)。结论骨科大手术患者术后发生VTE是多种危险因素共同作用的结果,Caprini评分可较好地评估骨科大手术患者VTE发病的危险程度,而患者的既往病史、纤维蛋白原、D-二聚体、手术体位和手术时间是骨科大手术患者易栓的独立危险因素,应给予充分重视。

偏心叶轮对多翼离心风机气动性能和噪声影响的数值研究

由于多翼离心风机结构及应用条件的特殊性,其设计不能完全采用工业风机的设计方法和经验参数。本文通过不同位置偏心叶轮方案的设计,研究多翼离心风机偏心叶轮的最佳安装位置。与原型风机相比,采用优化的偏心叶轮设计方案,风机流量增加了1.43m3/min,效率提高了2.52%,噪声下降了1.2d B。通过对风机流场和声场的数值分析,指出偏心叶轮可以有效减小叶轮部分叶道内的旋涡,改善由于多翼离心风机强前弯叶片所导致的流道内的流动阻塞,使叶轮的部分通道内的进气状态得到改善,减少叶道内的流动分离,从而有效提高风机效率,降低风机噪声。

采用进气端叶片开槽降低多翼离心风机气动噪声的研究

叶轮是空调用离心风机风道系统的核心部分,对离心风机的气动性能和噪声有重要影响。本文设计了一种顶端开槽的多翼离心风机叶片,采用数值计算方法研究了叶片进气端开槽对空调用多翼离心风机气动性能和噪声的影响,通过实验测试验证了进气端开槽叶片的降噪效果。结果表明:采用叶片进气端开槽结构能够改善叶轮顶端间隙区域内低速流动状态,抑制叶轮通道内旋涡的扩展,有效降低风机宽频噪声。与原型多翼离心风机相比,采用叶片进气端开槽结构,在保持风量基本不变情况下,风机噪声下降了0.8dB。

Applications of metal–organic frameworks for green energy and environment: New advances in adsorptive gas separation, storage and removal

The separation of gas molecules with similar physicochemical properties is of high importance but practically entails a substantial energy penalty in chemical industry. Meanwhile, clean energy gases such as H_2 and CH_4 are considered as promising candidates for the replacement of traditional fossil fuels. However, the technologies for the storage of these gases are still immature. In addition, the release of anthropogenic toxic gases into the atmosphere is a worldwide threat of growing concern. Both in academia and industry, considerable research efforts have been devoted to developing advanced porous materials for the effective and energy-efficient separation, storage, or capture of the related gases. In contrast to conventional inorganic porous materials such as zeolites and activated carbons, metal–organic frameworks(MOFs) are considered as a type of promising materials for gas separation and storage. In this contribution, we review the recent research advance of MOFs in some relevant applications, including CO_2 capture, O_2 purification, separation of light hydrocarbons, separation of noble gases, storage of gases(CH_4,H_2, and C_2 H_2) for energy, and removal of some gaseous air pollutants(NH_3, NO_2, and SO_2). Finally, an outlook regarding the challenges of the future research of MOFs in these directions is given.

Micro RNA-185 regulates expression of lipid metabolism genes and improves insulin sensitivity in mice with non-alcoholic fatty liver disease

AIM:To assess the regulatory effect of micro RNA-185(mi R-185)on lipid metabolism and the insulin signalling pathway in human Hep G2 hepatocytes and a high-fat diet mouse model.METHODS:Quantitative reverse transcription-polymerase chain reaction was used to assess the m RNA levels of lipogenic genes after loss or gain of mi R-185.In addition,the amounts of insulin signalling intermediates were determined after transfection of Hep G2 cells with pre-mi R-185.RESULTS:Mi R-185 levels decreased in a time-and dose-dependent manner in response to palmitic acid in human Hep G2 hepatocytes.Transfection of Hep G2 cells with mi R-185 significantly decreased the m RNA levels of fatty acid synthase,3-hydroxy-3-methylglutaryl-Co A reductase,sterol-regulatory element binding protein-2,and sterol-regulatory element binding protein-1c,whereas inhibition of mi R-185 using an anti-mi R-185oligonucleotide produced the opposite effect in Hep G2cells.In a high-fat diet mouse model,the accumulation of lipids was significantly improved after treatment with mi R-185,compared with control animals.Induction of mi R-185 enhanced the insulin signalling pathway by upregulating the insulin-receptor substrate-2.CONCLUSION:These findings suggest that mi R-185plays an important role in regulating fatty-acid metabolism and cholesterol homeostasis in hepatocytes,as well as in improving insulin sensitivity,both in vitro and in vivo.

Connexin 32 and 43 promoter methylation in Helicobacter pylori-associated gastric tumorigenesis

AIM: To explore the mechanism of abnormal Connexin(Cx) 32 and Cx43 expression in the gastric mucosa after Helicobacter pylori(H. pylori) infection.METHODS: Biopsy specimens of gastric mucosa in different gastric carcinogenesis stages with H. pylori infection, that is, non-atrophic gastritis(NAG; n = 24), chronic atrophic gastritis(CAG; n = 25), intestinal metaplasia(IM; n = 28), dysplasia(DYS; n = 24), andgastric cancer(GC; n = 30), as well as specimens of normal gastric mucosa without H. pylori infection(NGM; n = 25), were confirmed by endoscopy and pathological examination. Cx32 and Cx43 mRNA expression was detected by real-time polymerase chain reaction(PCR). Cx32 and Cx43 promoter CpG island methylation status was determined by methylation-specific PCR(MSP), bisulfite PCR sequencing(BSP) and MassArray methods. RESULTS: The relative mRNA expression levels in the gastric mucosa of patients with NGM, NAG, CAG, IM, DYS and GC were 0.146 ± 0.011, 0.133 ± 0.026, 0.107 ± 0.035, 0.039 ± 0.032, 0.037 ± 0.01 and 0.03 ± 0.011 for Cx32; and 0.667 ± 0.057, 0.644 ± 0.051, 0.624 ± 0.049, 0.555 ± 0.067, 0.536 ± 0.058 and 0.245 ± 0.121 for Cx43, respectively, which were gradually decreasing and significantly different(GC vs NGM: P < 0.001 for Cx32, P < 0.001 for Cx43). The promoter methylation levels in the gastric mucosa from NGM to GC stages by MSP were 38.8% ± 9.0%, 43.1% ± 9.4%, 56.5% ± 3.1%, 64.4% ± 9.7%, 72.5% ± 4.2% and 79.6% ± 6.8% for Cx32; and 49.0% ± 3.9%, 58.1% ± 5.0%, 66.5% ± 7.9%, 74.0% ± 8.8%, 78.3% ± 3.6% and 88.7% ± 6.2% for Cx43, respectively, which were gradually increasing and significantly different(P = 0.039, P = 0.019). The promoter methylation levels by BSP and MassArray exhibited similar trends. Cx32 and Cx43 mRNA expression was negatively correlated with promoter methylation status and gastric carcinogenesis stages(P < 0.001, P = 0.016).CONCLUSION: Cx32 and Cx43 mRNA expression decreased gradually during H. pylori infection-associated gastric carcinogenesis, and it is associated with hypermethylation of these genes' promoter.

Clinical research of EX-PRESS drainage device and modified trabeculectomy combined with intravitreal conbercept treatment for neovascular glaucoma

AIM:To evaluate the efficacy and safety of modified trabeculectomy(experimental group) and implantation of EX-PRESS drainage device(control group),combined with intravitreal conbercept injection for neovascular glaucoma(NVG).METHODS:Totally 30 patients with NVG were selected from June 2014 to June 2017,and randomly divided into experimental group and control group.All patients were underwent intravitreal conbercept(0.5 mg/0.05 mL) treatment before surgery.Modified trabeculectomy was performed in MT group,while EX-PRESS drainage device implantation was performed in EX group.The success rates,best corrected visual acuity(BCVA),intraocular pressure(IOP),filtering bleb and complications were observed and compared.RESULTS:The differences of success rate,BCVA and filtering bleb were not statistically significant 12mo after the surgery(P>0.05),however,the difference of IOP at 1d,1wk,1,3,and 6mo after surgery was statistically significant(F_(time)=390.64,P_(time)<0.0001) between two groups.The interactions between two groups in the given time showed no significant difference(F_(intergroup×time)=0.181,P_(intergroup×time)=0.57),and also there was no significant difference in IOP between the two groups(F=3.16,P=0.09).The results of pairwise comparison at each time point showed no significant difference in IOP between 1d and 1wk,3 and 6,3mo and 12mo after surgery(P>0.05),while the results at other time point indicate statistical differences(P<0.05).CONCLUSION:The modified trabeculectomy and the implantation of EX-PRESS drainage device have clinical application value in reducing IOP and postoperative complications of refractory NVG.

Preliminary construction of evaluation indicator system for inpatients'nursing service needs in tertiary general hospital

Objectives:To construct a comprehensive evaluation indicator system for inpatients'nursing service needs in tertiary general hospital and to provide evidence for identifying and meeting the needs of inpatients'nursing services.Method:We used the Delphi method to conduct two rounds of expert consultations with 41 experts.Result:The indicator system consisting of 5 first-level indicators and 48 second-level indicators was preliminarily constructed.Conclusions:We formed an evaluation indicator system for inpatients'nursing service needs in tertiary general hospital and classified it into five categories:hospital environment,nursing attitude,nursing skills,information exchange,and emotional support.The indicator system is scientific and reliable.It can provide a basis for nursing staffs to identify and meet the needs of inpatients'care services.

Study on mechanism of Simiao Yong'an Decoction in treatment of deep venous thrombosis based on network pharmacology

Objective:To explore the mechanism of Simiao Yong'an Decoction in treating deep venous thrombosis based on the method of network pharmacology.Methods:Through TCMSP database,the effective components of each traditional Chinese medicine in Simiao Yong'an Decoction were obtained and their targets were predicted.The targets of deep venous thrombosis were collected by CTD database,and the key targets were obtained by intersection of the component targets and the disease targets;Protein-Protein Interaction(PPI)network was constructed by String database.The drugs-components-targets-disease network map was constructed by using the software of Cytoscape 3.7.2.GO function and KEGG pathway enrichment of Simiao Yong'an Decoction in the treatment of deep venous thrombosis were analyzed by using the plug-in of ClueGo.Results:121 effective components and 137 potential targets of Simiao Yong'an Decoction were obtained.There were 1172 targets of deep venous thrombosis.There were 214 biological processes analyzed by GO Biological Process and 72 pathways analyzed by KEGG analysis.Conclusion:Simiao Yong'an Decoction may act on ESR1,AR,PTGS2 and other key targets,as well as AGE-RAGE signaling pathway,PI3K-Akt signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,RLX signaling pathway and other pathways to treat deep venous thrombosis.

Application of diffusion kurtosis imaging technology in evaluating early mild traumatic brain injury

Objective To explore the value of magnetic resonance diffusion kurtosis imaging in diagnosing early tiny changes of brain tissue after mild traumatic brain injury.Methods A total of 22 patients with mild traumatic brain injury(study group)and 20 healthy subjects(control group)were enrolled in this study,and diffusion kurtosis imaging magnetic resonance scanning was employed in all subjects.fractional anisotropy,fractional anisotropy of kurtosis,mean kurtosis,axial kurtosis and radial kurtosis of diffusion kurtosis imaging parameters in the genu of corpus callosum,splenium corporis callosi,internal capsule,thalamus,putamen,cortex of frontal lobe,temporal lobe and parietal lobe at control group,the injured side and the mirror regions were measured,and the results were compared between the two groups.The receiver operating characteristic curve was used to evaluate the ability of different parameters in diagnosing mild traumatic brain injury.Results Compared with the control group,in the study group fractional anisotropy values of bilateral genu of corpus callosum,splenium corporis callosi,internal capsule and thalamus were significantly reduced,and fractional anisotropy of kurtosis values of bilateral thalamus and putamen were significantly reduced,and the differences were statistically significant(P<0.05).Compared with the control group,in the study group mean kurtosis and axial kurtosis values of bilateral genu of corpus callosum,posterior limb of Internal capsule,thalamus,putamen and cortex of temporal lobe were significantly reduced,while radial kurtosis values in the genu of corpus callosum,thalamus,cortex of frontal lobe,temporal lobe at the injured side were increased,and the differences were statistically significant(P<0.05).Conclusion DKI techniques can sensitively detect the early tiny pathologic changes of cerebral tissue in mild traumatic brain injury patients,which provide more imaging evidence for the clinical early diagnosis treatment and prognosis.

Clinicopathological Features of Nondiabetic Renal Diseases from Different Age Groups:An Observational Cross-sectional Study

Background:Diabetes mellitus (DM)has become the leading cause of chronic kidney disease (CKD).Nondiabetic renal diseases (NDRDs) have different clinicopathological features and prognosis from those of diabetic nephropathy.Our study sought to analyze the clinical and pathological features of NDRDs,in different age groups through a cross-sectional study. Methods:All patients with type 2 DM at our center who underwent renal biopsy between March 1997 and March 2017 were screened and divided into three groups by age:Group 1 (youth group),18-44 years old;Group 2 (middle-aged group),45-59 years old;and Group 3 (elderly group),≥60 years old.We analyzed the clinicopathological data and risk factors by univariate and multivariate logistic regression for NDRD of the patients to identify the features of NDRD in different age groups. Results:We included 982 patients in the final analysis.Patients with NDRD accounted for 64.4%of all patients.IgA nephropathy (IgAN) was the most common pathological pattern in young patients with NDRD,accounting for 26.3%.In the middle-aged group,the two most common pathological patterns were IgAN and membranous nephropathy.Membranous nephropathy was the most common pathological pattern in elderly patients with NDRD,accounting for 29.3%.Consistent with pathological features,glomerular hematuria is a risk factor for NDRD in Group 1 (odds ratio [OR],26.514;95%confidence interval [CI],2.503-280.910;P =0.006).On the other hand,rapidly increasing proteinuria or nephrotic syndrome is a risk factor for NDRD in Group 2 (OR,5.921;95% CI,2.061-17.013;P =0.001)and Group 3 (OR,90.409;95%CI,6.198-1318.826;P =0.001). Conclusions:This single-center study showed that the proportion and composition of NDRD differ among different age groups. Consistent with pathological features,some clinical indices such as hematuria and proteinuria showed different features among different age groups.

Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis

Background:Clinical outcomes of undifferentiated arthritis(UA)are diverse,and only 40%of patients with UA develop rheumatoid arthritis(RA)after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17(7.3%)patients failed to follow up during the study.Among the 217 patients who completed the study,83(38.2%)patients went into remission.UA patients who developed RA had a higher rheumatoid factor(RF)-positivity(42.9%vs.16.8%,χ^2=8.228,P=0.008),anti-cyclic citrullinated peptide(CCP)antibodypositivity(66.7%vs.10.7%,χ^2=43.897,P<0.001),and double-positivity rate of RF and anti-CCP antibody(38.1%vs.4.1%,χ^2=32.131,P<0.001)than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development(hazard ratio 18.017,95%confidence interval:5.803–55.938;P<0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

Clinical features and genotype-phenotype correlation analysis in patients with ATL1 mutations:A literature reanalysis

Background:The hereditary spastic paraplegias(HSPs)are a group of clinically and genetically heterogeneous disorders.Approximately 10% of the autosomal dominant(AD)HSPs(ADHSPs)have the spastic paraplegia 3A(SPG3A)genotype which is caused by ATL1 gene mutations.Currently there are more than 60 reported ATL1 gene mutations and the genotype-phenotype correlation remains unclear.The study aims to investigate the genotypephenotype correlation in SPG3A patients.Methods:We performed a reanalysis of the clinical features and genotype-phenotype correlations in 51 reported studies exhibiting an ATL1 gene mutation.Results:Most HSPs-SPG3A patients exhibited an early age at onset(AAO)of<10 years old,and showed an autosomal dominant pure spastic paraplegia.We found that 14% of the HSPs-SPG3A patients presented complicated phenotypes,with distal atrophy being the most common complicated symptom.The AAO of each mutation group was not statistically significant(P>0.05).The mutational spectrum associated with ATL1 gene mutation is wide,and most mutations are missense mutations,but do not involve the functional motif of ATL1 gene encoded atlastin-1 protein.Conclusions:Our findings indicate that there is no clear genotype-phenotype correlation in HSPs-SPG3A patients.We also find that exons 4,7,8 and 12 are mutation hotspots in ATL1 gene.

Fluorescein-based monitoring of RNA N^(6)-methyladenosine at single-nucleotide resolution

Dear Editor,N^(6)-methyladenosine(m^(6)A)emerges as an abundant chemical modification on RNAs,which enriches in distinct internal regions linked to divergent aspects of RNA fate(Zhao et al.,2017).Transcriptome-wide mapping of m^(6)A sites using high-throughput sequencing enables comparative analysis of cellular^(6)A dynamics on particular RNAs under both physiological and stress conditions(Dominissini et al.,2012;Meyer et al.,2015),yet is confined to low resolution of coverage and indistinction of adjacent m6A sites.

The distribution of hair in Han Chinese

Aim: To explore the characteristics of normal hair distribution in Han Chinese. Methods:A total of 146 healthy Han Chinese and 41 patients with androgenetic alopecia (AGA) were selected as research subjects. Digital photographs of the vertex, temporal, and occipital regions were taken after their hair was trimmed. An image analysis software was used to compute the number of follicular units (FUs) and hairs. Results: The mean FU density of the 146 healthy Han Chinese was 74.36 ± 13.33 units/cm2 and their mean hair density was 143.33 ± 28.08 hairs/cm2. There was no significant difference between males and females (P >0.05). The mean FU density in the occipital region of AGA patients was 77.78 ± 2.99 units/cm2 and their mean hair count was 148.12 ± 6.98 hairs/cm2. Both were lower than those of healthy Han Chinese, and the differences were statistically significant (P < 0.001). Two-hair FUs (52.62%) were the predominant type found in Han Chinese. Conclusion: The FU and hair densities of healthy Han Chinese are lower than those of whites and Africans. The study provides hair transplantation surgeons with information on hair distribution in Han Chinese. It also provides a quantitative basis for the area of donor site and transplantation density necessary for hair transplantation surgeries. The research findings provide some theoretical data for the hair distribution characteristics of Han Chinese. These data can contribute to the preoperative assessment, surgery planning, and postoperative outcome evaluation by hair transplantation surgeons.