初诊Ⅳ期肺癌患者中性粒细胞/淋巴细胞比值与营养不良风险的相关性分析

背景与目的 恶性肿瘤患者往往伴随营养不良,与预后密切相关。中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)作为体内炎症的指标,能够预测多种疾病的营养不良风险,然而其与肺癌患者营养不良的关系尚不明确。本研究旨在分析NLR与初诊Ⅳ期肺癌患者营养不良风险的关系,并进一步确定NLR的截断值以更好地预测患者营养不良的风险。方法 回顾性分析2019年5月至2021年2月天津医科大学总医院肿瘤内科收治的209例初诊Ⅳ期肺癌患者,应用营养风险筛查2002 (nutritional risk screening 2002,NRS 2002)量表对其营养状况进行评估,同时收录患者人口学信息、病理、卡氏体能状态(Karnofsky performance status,KPS)评分、体重指数、合并疾病及临床生化指标的资料。分析NLR与营养不良风险的关系,并采用受试者工作特征(receiver operating characteristic,ROC)曲线来确定预测营养不良风险的最佳NLR临界值。应用多因素Logistic回归进一步评估NLR与营养不良风险之间的关系。结果 初诊Ⅳ期肺癌患者存在营养不良风险的比率为36.36%(76/209)。对NLR与NRS 2002营养不良风险评分进行分析发现,NLR与营养不良风险评分呈正相关(r=0.765,P<0.001)。通过ROC曲线分析,确定初诊Ⅳ期肺癌患者营养不良风险的最佳截断值NLR为3.94 [曲线下面积(area under the curve,AUC)=0.747,95%CI:0.678-0.815,P<0.001],敏感性为55%,特异性为86%,阳性预测值为68%,阴性预测值为77%。相比于NLR≤3.94组的患者,NLR>3.94组的患者更容易发生营养不良(69.49%vs 23.33%,P<0.001),并且NLR为初诊Ⅳ期肺癌患者营养不良风险的独立危险因素。结论 NLR在初诊Ⅳ期肺癌患者中与营养不良风险有关,NLR可作为Ⅳ期肺癌患者营养风险筛查的指标之一。

Hydroxysafflor yellow A induced ferroptosis of Osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway

Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis.Since there is no permanent therapy for this condition,it is necessary to develop a cure.Therefore,this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A(HYSA)in osteosarcoma cell lines(MG63).In this investigational study,MG63 cells were utilized.Microarray experiments,quantitative polymerase chain reaction(qPCR),immunofluorescent staining,extracellular acidification rate(ECAR),oxygen consumption rate(OCR),glucose consumption,lactate production,and ATP levels,proliferation assay,5-Ethynyl-2′-deoxyuridine(EDU)staining,and Western blot were performed.In MG63 cells,HYSA lowered cell proliferation and metastasis rates,suppressed EDU cell number,and enhanced caspase-3/9 activity levels.HYSA reduced the Warburg effect and induced ferroptosis(FPT)in MG63 cells.Inhibiting ferroptosis diminished HYSA’s anti-cancer activities in MG63 cells.The stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA’s anti-cancer activities in MG63 cells.HIF-1αis one target spot for HYSA in a model of osteosarcoma cancer(OC).HYSA altered HIF-1α’s thermophoretic activity;following binding with HYSA,HIF-1α’s melting point increased from~55°C to~60°C.HYSA significantly enhanced the thermal stability of exogenous WT HIF-1αwhile not affecting Mut HIF-1α,suggesting that ARG-311,GLY-312,GLN-347,and GLN-387 may be involved in the interaction between HIF-1αand HYSA.Conclusively,our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 pathway.HYSA is a possible therapeutic option for OC or other cancers.

BRAF融合在非小细胞肺癌中的研究进展

在晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)中,鼠类肉瘤病毒癌基因同源物B1(V-Raf murine sarcoma viral oncogene homolog B1,BRAF)突变恶性程度高、预后差,目前达拉非尼联合曲美替尼被批准用于BRAF V600突变患者的一线治疗。BRAF除了突变外,还可以发生融合,随着基因检测的发展,BRAF融合的检出逐渐增多,但是对于BRAF融合的治疗缺乏有效的治疗策略。本文从BRAF融合的临床特点、作用机制、临床治疗等方面进行综述,加强对BRAF基因融合的认识,为BRAF融合在NSCLC患者的治疗方面提供理论依据。

2例免疫检查点抑制剂联合化疗引发2型糖尿病个案报道

免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)已经成为肿瘤治疗的重要手段,其在临床中的应用越来越广泛。ICIs引起的不良反应逐渐被认识,其中免疫治疗相关性糖尿病是罕见的不良反应,最常见的是1型糖尿病。随着ICIs联合化疗在肺癌患者中广泛应用,治疗过程中出现2型糖尿病的患者逐渐被发现,但是这部分患者后续继续应用ICIs维持治疗对血糖、ICIs治疗过程的影响尚不清楚。本文报道2例ICIs联合化疗期间新发的2型糖尿病,其中1例患者转为1型糖尿病,旨在增加对免疫治疗相关性糖尿病的认识。

聚乙二醇和聚丙烯酸钠对纳米碳酸钙口服制剂的改性评估研究

目的利用聚乙二醇(PEG)和聚丙烯酸钠(PAAS)对球形纳米碳酸钙进行表面改性,并应用于肠道除铅的体外效果分析。方法用复方分解法制备球形纳米碳酸钙,分散剂PEG和PAAS进行表面改性,采用粒径与电位分析、扫描电镜、透射电镜、X射线粉末衍射法、红外光谱分析等表征手段对改性的纳米碳酸钙及其粉体的结构特征进行检测,并用原子吸收光谱仪考察其在模拟肠液的体外除铅效果。结果改性纳米碳酸钙中PEG/PAAS比例为1∶1时所制备的纳米碳酸钙粒径、电位、分散性、晶体稳定性最佳,4 h左右能将铅离子浓度降低至30μg/L以下,达到满意的除铅效果,与微米碳酸钙比较两者差异有统计学意义(P<0.05)。结论经PEG和PAAS改性后的纳米碳酸钙性质稳定,无毒,可进一步制成口服制剂应用于人体肠道除铅。

胆红素吸附治疗高胆红素血症的疗效分析

目的观察高胆红素血症患者行胆红素吸附治疗的临床疗效。方法选取2015—2017年在中南大学湘雅医院血液净化中心行胆红素吸附治疗的高胆红素血症患者,共10例。其中,男性8例,女性2例;平均年龄(57±18)岁。结果 10例患者共行18次胆红素吸附治疗,其中显效1例,有效8例,无效2例,总有效率为80%。治疗后胆红素降低(P <0.05),对转氨酶、肌酐、尿素、尿酸的清除无作用(P>0.05),对白蛋白、血常规、凝血常规、E7A无影响(P>0.05)。结论胆红素吸附在治疗以血清胆红素升高为主的高胆红素血症患者效果较好,安全性高。若合并有自发性腹膜炎、肝肾综合征、肝性脑病等并发症的危重患者,则应联合多种人工肝治疗模式。

腕部桡动脉-头静脉内瘘通畅的影响因素研究

目的分析影响终末期肾脏疾病(ESRD)维持性血液透析患者自体动静脉瘘(AVF)通畅性的因素。方法选取2016年12月-2018年1月于中南大学湘雅医院肾内科行腕部桡动脉-头静脉标准内瘘手术ESRD患者195例。分析其人口统计学资料、临床资料、生化指标及术后应用抗凝治疗是否与AVF通畅相关。结果195例患者随访1年,8例患者失访,4例患者死亡,行肾移植手术者12例,29例患者出现术后并发症。AVF的1年生存率为91.6%。多因素Cox比例风险模型分析中,抗凝史[H^R=3.412(95%CI:1.225,9.503),P=0.019]是AVF通畅的影响因素。结论术后应用抗凝治疗会降低AVF的1年通畅率。

Clinicopathological features and trend changes of gastric carcinoma in Southern China

AIM:To investigate the clinicopathological features of gastric carcinoma in southern China and disease trends changes over the last 18 years.METHODS:We designed a retrospective study in the Department of Gastrointestinal Surgery,the first affiliated hospital,Sun Yat-sen University.A total of 2100adult patients with definitely diagnosed,histologically proven gastric carcinomas treated with radical gastrectomy from 1994 to 2013 were examined retrospectively.In all cases patient age,gender,tumor location,Borrmann type,histopathological type and grade,and pTNM stage were identified and recorded.The information was obtained from hospital records.The data were analyzed with Stata12.0 software.RESULTS:In this study,the mean age of patients was 57 years with a range from 19-89 years.A higher incidence was found in patients over 60 years of age.In the study population,67.38%of patients were male and 32.62%were female.Women had a higher disease incidence than men in patients less than 40 years of age(P<0.001).No obvious change of patient age and gender was observed in the last 18 years.The rates of disease by location were the following:antrum(44.57%),followed by fundus/body(24.95%)and cardia/gastroesophageal junction(23.00%).The mean tumor diameter was 5.57 cm,and advanced gross type BorrmannⅢwas most common.Most patients were at advanced stages when first diagnosed,and patients with early stage disease were relatively rare.More early stage patients were detected in recent years,especially after 2000(P<0.001).Gastric carcinoma has different features in young and old patients.The young patients had the following features:more frequently female,tumors in the antrum,larger tumor size,poorly differentiated carcinoma,high rate of metastasis to other sites and advanced stages(P<0.05).CONCLUSION:In southern China,gastric carcinoma was more frequent in old men and young women.Young and old patients should be treated differently for having different features.

Vagina vasorum dissection during D2 lymphadenectomy for gastric carcinoma

AIM: To explore the relationship between metastasis and vagina vasorum in the progress of gastric carcinoma and to find some facts and references for gastric surgeons. METHODS: One hundred and seven specimens of left or right gastric arteries (55 left and 52 right) were gathered from 59 patients undergoing radical gastrectomy for gastric carcinoma. All the frozen specimens were cut into 3 μm-thick sections and stained with hematoxylin-eosin (HE) and immunohistochemical method separately. Cytokeratin (CK) and mesothelial cells (MC) were stained with immunohistochemical method. Cancer cells inside vagina vasorum were detected and the structure of artery wall was observed under microscope. RESULTS: Metastatic cancer cells or tubercles were found inside vagina vasorum in some stage Ⅲ or Ⅳ specimens, but not in stageⅠor Ⅱ specimens. Tumor cells in vagina vasorum were CK positive in 26 specimens of 14 tumors. Among them, stage Ⅲ was found in 4 specimens of 2 tumors, and stage Ⅳ in 22 specimens of 12 tumors. None of these specimens was positive for MC. The positive rate of CK increased with TNM staging. Compared with the lower part, tumors in the upper and middle parts of stomach were more likely to metastasize into vagina vasorum. CONCLUSION: Vagina vasorum dissection should be performed during D2 lymphadenectomy for TNM stage Ⅲ or Ⅳ gastric carcinoma.

Bile Acid Effects on Placental Damage in Intrahepatic Cholestasis of Pregnancy

Aims: The abnormal increase of bile acid is found in intrahepatic cholestasis of pregnancy (ICP). It also can be observed the damage of placental tissue in ICP. The aim of this study was to find the associations of the bile acid in umbilical vein and the damage of placental tissue. Methods: Thirty women diagnosed with ICP and fifty normal pregnant women between September 2015 and September 2017 at Nanshan District Maternity & Child Healthcare Hospital of Shenzhen were included in this study. The glycocholic acid (GA), total bile acids (TBA), total bilirubin (TB), direct bilirubin (DB) and albumin level in umbilical vein were measured by cycle enzyme method in ICP and control group. The placental damage was analyzed by morphologic study using hematoxylin dyes in two groups. The correlation between the level of the bile acid in the umbilical vein and the damage of the placenta was assessed using SPSS software. Results: The GA, TBA, TB, DB and albumin level in umbilical vein were significantly higher in ICP than those of pregnant women, respectively. The placental villis were expanded and the structure was destroyed in ICP. The vessel was damaged and the cell trophoblast hyperplasia in ICP. It also can be seen that there was obvious nodules and a typical fibrous necrotic substance in ICP but not in control group. There is a positive correlation between the level of the TBA in the umbilical vein and the damage of the placenta in ICP. Conclusion: The TBAs were significantly higher in umbilical vein and were related to the placental damage in ICP.

Research on Extension Evaluation of Rural Road Maintenance Quality Based on Game Theory

The importance of rural highway maintenance is self-evident, and it is also a basic work of the highway operation department. Selecting an appropriate evaluation method can timely and accurately find the pavement diseases, and improve the timeliness of pavement repair. To improve the accuracy of pavement quality comprehensive evaluation, based on the game theory, the improved extension evaluation method was combined with subjective and objective weight determination methods in this paper, to propose a comprehensive weight determination method with a good operability. The results show that the improved extension evaluation method provides a feasible scheme for rural highway maintenance quality evaluation

The inhibitory effect of SEMA3C/3D mutations on Neuro-2a cells migration and axonal growth in patients with Hirschsprung′s disease

Objective:To explore the effect and mechanism of SEMA3C/3D mutations on axonal growth of neurons and cell migration in Hirschsprung′s disease(HSCR)patients.Methods:HEK293 Tcells were transfected with wild-type and mutant SEMA3C/3D plasmids.The supernatants that contained SEMA3C/3D-AP fusion proteins were collected and added into the Neuro-2acells.The changes in the cell morphology were observed by immunofluorescence staining.The expression and phosphorylation levels of cofilin,ERM and CRMP2 were determined by western blotting.The cell migration rate was measured by transwell assay.Results:Compared with wild-type SEMA3D,SEMA3D-P615T mutant suppressed cofilin phosphorylation in Neuro-2a cells(P <0.05).The neural cells treated by five mutant SEMA3C/3D-AP fusion proteins presented different levels of axon atrophy,growth cone collapse,and sometimes,loss of normal structure.SEMA3C-S329 G,SEMA3C-V337M and SEMA3D-P615T mutants cells exhibited a significantly reduced migration rate as compared with wild-type SEMA3C/3D treated cells(P <0.01).Conclusion:SEMA3C and SEMA3 D mutations in HSCR patients could lead to the inhibition of Neuro-2a cells′migration and axonal growth.The mechanism of SEMA3 DP615T mutant might be related to down-regulation of the expression of p-cofilin,which consequently lead to cytoskeleton structure collapse and migrating ability decrease.Our study might provide important clues for the pathogenesis of HSCR.

Recent advances in developing active targeting and multi-functional drug delivery systems via bioorthogonal chemistry

Bioorthogonal chemistry reactions occur in physiological conditions without interfering with normal physiological processes.Through metabolic engineering,bioorthogonal groups can be tagged onto cell membranes,which selectively attach to cargos with paired groups via bioorthogonal reactions.Due to its simplicity,high efficiency,and specificity,bioorthogonal chemistry has demonstrated great application potential in drug delivery.On the one hand,bioorthogonal reactions improve therapeutic agent delivery to target sites,overcoming off-target distribution.On the other hand,nanoparticles and biomolecules can be linked to cell membranes by bioorthogonal reactions,providing approaches to developing multi-functional drug delivery systems(DDSs).In this review,we first describe the principle of labeling cells or pathogenic microorganisms with bioorthogonal groups.We then highlight recent breakthroughs in developing active targeting DDSs to tumors,immune systems,or bacteria by bioorthogonal chemistry,as well as applications of bioorthogonal chemistry in developing functional bio-inspired DDSs(biomimetic DDSs,cell-based DDSs,bacteria-based and phage-based DDSs)and hydrogels.Finally,we discuss the difficulties and prospective direction of bioorthogonal chemistry in drug delivery.We expect this review will help us understand the latest advances in the development of active targeting and multi-functional DDSs using bioorthogonal chemistry and inspire innovative applications of bioorthogonal chemistry in developing smart DDSs for disease treatment.

Carbon coated LaFe_(0.92)Pd_(0.08)O_(3) composites for catalytic transfer hydrogenation:Balance in the ability of substrates adsorption and conversion

Catalytic transfer hydrogenation(CTH)is a green and efficient pathway for selective hydrogenation of unsaturated aldehydes and ketones.However,managing the abilities of solid catalysts to adsorb substrates and to convert them into desired products is a challenging task.Herein,we report the synthesis of carbon coated LaFe_(0.92)Pd_(0.08)O_(3) composites(LFPO-8@C)for CTH of benzaldehyde(BzH)into benzyl alcohol(BzOH),using isopropanol(IPA)as hydrogen source.The coating with carbon improves the ability to adsorb/transfer reactants from solution to active sites,and the doping of Pd2+at Fe3+site strengthens the ability of LaFeO_(3) to convert BzH into BzOH.A balanced point between them(i.e.,abilities to adsorb BzH and to convert BzH into BzOH)is obtained at LFPO-8@C,which exhibits a BzOH formation rate of 3.88 mmol·gcat^(-1)·h^(-1) at 180℃ for 3 h,which is 1.50 and 2.72 times faster than those of LFPO-8 and LaFeO_(3)@C.A reaction mechanism is proposed,in which the acidic sites(e.g.,Fe^(4+),oxygen vacancy)are used for the activation of C=O bond of BzH and O-H bond of IPA,and the basic sites(e.g.,lattice oxygen)for the activation ofα-H(O-H)bond of IPA.

Catalytic combustion of volatile organic compounds using perovskite oxides catalysts—a review

With the rapid development of industry,volatile organic compounds(VOCs)are gaining attention as a class of pollutants that need to be eliminated due to their adverse effects on the environment and human health.Catalytic combustion is the most popular technology used for the removal of VOCs as it can be adapted to different organic emissions under mild conditions.This review first introduces the hazards of VOCs,their treatment technologies,and summarizes the treatment mechanism issues.Next,the characteristics and catalytic performance of perovskite oxides as catalysts for VOC removal are expounded,with a special focus on lattice distortions and surface defects caused by metal doping and surface modifications,and on the treatment of different VOCs.The challenges and the prospects regarding the design of perovskite oxides catalysts for the catalytic combustion of VOCs are also discussed.This review provides a reference base for improving the performance of perovskite catalysts to treat VOCs.

自发短路反应原位构筑锌离子传导界面层稳定锌负极

水系锌离子电池具有高安全性、大容量、低成本、环境友好等优点,在大型储能系统中显示出巨大的潜力.然而,金属锌负极上枝晶的生长、析氢腐蚀、钝化等问题严重阻碍了锌离子电池的应用.在锌负极表面构筑一层界面层被证明是一种简单有效的方法.目前已经报道的无机界面涂层材料如纳米Ca CO_(3)、无定形Ti O_(2)等,主要通过物理作用机械阻隔枝晶,但这些材料本身不具有锌离子的导电性,无法化学调控锌离子的传输.本文采用ZnxV_(2)O_(5)·n H_(2)O(Zn VO)作为界面改性材料,将锌离子电池常用的正极材料层状钒氧化物应用于锌负极的界面保护,通过V_(2)O_(5)·n H_(2)O与金属锌之间的自发短路反应,在锌负极表面上原位构建了Zn VO材料的锌离子导电界面层.与无修饰的锌负极相比,Zn VO涂覆后的锌负极,在减少电解液与锌负极直接接触的同时引导锌离子的传输,表现出更好的电化学性能.其中,锌对称电池的循环寿命提高了10倍以上.

Ambient flash sintering of reduced graphene oxide/zirconia composites:Role of reduced graphene oxide

Fabrication of graphene/ceramic composites commonly requires a high-temperature sintering step with long times as well as a vacuum or inert atmosphere,which not only results in property degradation but also significant equipment complexity and manufacturing costs.In this work,the ambient flash sintering behavior of reduced graphene oxide/3 mol% yttria-stabilized ZrO_(2)(rGO/3 YSZ) composites utilizing rGO as both a composite component and a conductive additive is reported.When the sintering condition is carefully optimized,a dense and conductive composite can be achieved at room temperature and in the air within 20 s.The role of the rGO in the FS of the rGO/3 YSZ composites is elucidated,especially with the assistance of a separate investigation on the thermal runaway behavior of the rGO.The work suggests a promising fabrication route for rGO/ceramic composites where the vacuum and furnace are not needed,which is of interest in terms of simplifying the fabrication equipment for energy and cost savings.

Single-cell analysis of angiotensin-converting enzyme II expression in human kidneys and bladders reveals a potential route of 2019 novel coronavirus infection

Background::Since 2019,a novel coronavirus named 2019 novel coronavirus(2019-nCoV)has emerged worldwide.Apart from fever and respiratory complications,acute kidney injury has been observed in a few patients with coronavirus disease 2019.Furthermore,according to recent findings,the virus has been detected in urine.Angiotensin-converting enzyme II(ACE2)has been proposed to serve as the receptor for the entry of 2019-nCoV,which is the same as that for the severe acute respiratory syndrome.This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.Methods::We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders.The Pearson correlation coefficients between ACE2 and all other genes were first generated.Then,genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.Results::Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule(PT)cells of the kidney.ACE2 expression was found in 5.12%,5.80%,and 14.38%of the proximal convoluted tubule cells,PT cells,and proximal straight tubule cells,respectively,in three published kidney cell atlas datasets.In addition,ACE2 expression was also confirmed in 12.05%,6.80%,and 10.20%of cells of the proximal convoluted tubule,PT,and proximal straight tubule,respectively,in our own two healthy kidney samples.For the analysis of public data from three bladder samples,ACE2 expression was low but detectable in bladder epithelial cells.Only 0.25%and 1.28%of intermediate cells and umbrella cells,respectively,had ACE2 expression.Conclusion::This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.

Microstructure and Wear Properties of Fe-based Amorphous Coatings Deposited by High-velocity Oxygen Fuel Spraying

Fe-based powder with a composition of Fe_（42.87）Cr_（15.98）Mo_（16.33）C_（15.94）B_（8.88）（at.%）was used to fabricate coatings by high-velocity oxygen fuel spraying.The effects of the spraying parameters on the microstructure and the wear properties of the Fe-based alloy coatings were systematically studied.The results showed that the obtained Fe-based coatings with a thickness of about 400μm consisted of a large-volume amorphous phase and some nanocrystals.With increasing the fuel and oxygen flow rates,the porosity of the obtained coatings decreased.The coating deposited under optimized parameters exhibited the lowest porosity of 2.8%.The excellent wear resistance of this coating was attributed to the properties of the amorphous matrix and the presence of nanocrystals homogeneously distributed within the matrix.The wear mechanism of the coatings was discussed on the basis of observations of the worn surfaces.