Elaidic acid-induced intestinal barrier damage led to gut-liver axis derangement and triggered NLRP3 inflammasome in the liver of SD rats

Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks.The results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and Desulfovibrionaceae.Plus,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the liver.Overall,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage.

Application of ultrasound-guided balloon occlusion in cesarean section in 130 cases of sinister placenta previa

Objective:To investigate the clinical utility of ultrasound-guided balloon occlusion in cesarean section in patients with sinister placenta previa.Methods:The Interventional and Ultrasound Departments of the authors’center assisted obstetrics to complete cesarean section in cases of sinister placenta previa.A total of 130 patients with implanted sinister placenta previa were diagnosed using obstetrical ultrasound and magnetic resonance imaging(MRI).Before cesarean section,the balloon was positioned in the bilateral radial or abdominal aorta.Immediately after delivery of the fetus,the balloon was temporarily filled to transiently seal the target vessel.According to the obstetrician’s assessment of hemostasis,the balloon was withdrawn at the appropriate time.Among the 130 patients,there was one case of abdominal aortic occlusion,with 129 cases blocked by the bilateral common iliac artery.Results:All 130 cases were successfully blocked,with an average blocking time of<15 min,while intraoperative blood loss was 800–1500 ml.Conclusion:Ultrasound-guided balloon blocking treatment before cesarean section can mitigate the dangers of placenta previa and significantly reduce blood loss with no exposure to X-ray radiation.Thus,the technique merits serious consideration.

TNFα inhibitor C87 sensitizes EGFRvⅢ transfected glioblastoma cells to gefitinib by a concurrent blockade of TNFα signaling

Objective: More than half of human glioblastomas show EGFR gene amplification and mutation, but EGFR inhibitors have not been effective in treating EGFR-positive glioblastoma patients.The mechanism behind this type of primary resistance is not well understood.The aim of this study was to investigate gefitinib resistance in glioblastoma, and explore ways to circumvent this significant clinical problem.Methods: MTT method was used to test the cell viability after EGFR-positive glioblastoma cells were treated with indicated drugs;real-time quantitative PCR method was included to detect the TNFα mRNA levels in glioma tissues and cell lines.ELISA was introduced to measure the TNFα protein levels in cell culture supernatant of glioblastoma cells treated with gefitinib.Western blot was used to detect the activity change of intracellular kinases in drug-treated glioblastoma cells.Two mouse xenograft tumor models were carried out to evaluate the in vivo effects of a combination of EGFR and TNFα inhibitors.Results: We found that glioblastoma resistance to gefitinib may be mediated by an adaptive pro-survival TNFα-JNK-Axl signaling axis, and that high TNFα levels in the glioblastoma microenvironment may further intensify primary resistance.A combination of the TNFα-specific small-molecule inhibitor C87 and gefitinib significantly enhanced the sensitivity of glioblastoma cells to gefitinib in vitro and in vivo.Conclusions: Our findings provide a possible explanation for the primary resistance of glioblastoma to EGFR inhibitors and suggest that dual blockade of TNFα and EGFR may be a viable therapeutic strategy for the treatment of patients with chemotherapy-refractory advanced glioblastoma.

使用双侧闪光灯摄影比色技术对上颌中切牙进行比色的可行性研究（英文）

目的:研究使用数码相机双侧闪光灯摄影比色技术对上颌中切牙进行比色的可行性,并了解青年人上颌左右中切牙的颜色差异。方法:采用数码相机和双侧闪光灯获取155例志愿者的两侧上颌中切牙的数码照片。利用计算机软件对每颗牙齿照片的的L(明度)、a(红绿色度)和b(黄蓝色度)的颜色坐标进行测量。采用可靠性内相关系数(ICC)比较每颗右上颌中切牙两次拍照之间的色彩差异,检验该技术的一致性。采用配对样本t检验对左右上颌中切牙的L、a、b值分别进行统计学分析,比较左右上颌中切牙的颜色差异。结果:L、a、b的ICC检验值均在良好的可信度范围内(0.75~1.00)。左右两侧上颌中切牙的红绿色度a在切端、中部和颈部均有明显差异,明度L仅在两侧上颌中切牙的切端具有明显差异,黄蓝色度b仅在两侧上颌中切牙的牙颈部有明显差异。结论:使用双侧闪光灯摄影比色技术在牙齿比色过程中可以输出稳定的结果,具有较高的可信度;青年人左右两侧上颌中切牙的颜色并不是完全相同的。

非编码RNA在宫颈癌组织中的表达及临床意义

目的分析非编码RNA长链非编码RNA(LINC00982)及微小RNA(hsa-miR-1246)在子宫颈癌组织中的表达情况,旨在为宫颈癌的诊断提供新的生物标志物和潜在的治疗靶点。方法收集云南大学附属医院2021年1月至2021年10月收治的21例因子宫肌瘤等良性病变行全子宫切除术患者的正常宫颈组织样本(对照组)和43例经病理学诊断为子宫颈癌患者的宫颈癌组织样本(实验组),运用实时荧光定量PCR(RT-qPCR)检测并比较2组间LINC00982及hsa-miR-1246的表达情况。结果(1)与人正常子宫颈组织相比,子宫颈癌组织中LINC00982-1/2的表达下调(P<0.05),而hsa-miR-1246表达上调(P<0.05);(2)高分化宫颈癌组织中LINC00982-1/2及hsa-miR-1246的表达量低于中低分化宫颈癌组织(P<0.05);(3)Ⅲ/Ⅳ期人宫颈癌组织中LINC00982-1/2及hsa-miR-1246的表达量高于Ⅰ/Ⅱ期(P<0.05);(4)腺癌组织中LINC00982-1的表达量低于鳞状细胞癌(P<0.05),但腺癌与鳞状细胞癌中LINC00982-2两者比较,差异无统计学意义(P>0.05),而hsamiR-1246的表达量则高于鳞状细胞癌(P<0.05);(5)LINC00982-1/2表达量随SCCA的增高而下降(P<0.05),而hsa-miR-1246表达量随SCCA的增高而增高;(6)肿瘤直径>4 cm的组织中,LINC00982-1/2及hsa-miR-1246的表达量高于肿瘤直径≤4 cm者。结论LINC00982在宫颈癌组织中低表达;hsa-miR-1246在宫颈癌组织中高表达;且子宫颈癌组织中LINC00982-1/2及hsa-miR-1246表达与组织分化程度、病理分期、病理类型、SCCA的高低及肿瘤直径密切相关。

ALK融合基因阳性非小细胞肺癌脑转移的靶向治疗进展

间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)基因融合在非小细胞肺癌(non-small cell lung cancer,NSCLC)中发生率约为2%~7%,此类肺癌更易出现脑转移,严重影响患者生存质量,缩短患者的生存期。近年来,随着ALK-酪氨酸激酶抑制剂(ALK-tyrosine kinase inhibitor,ALK-TKI)的不断研发,ALK-NSCLC脑转移患者的生存期显著延长。本文对ALK-TKI治疗肺癌脑转移的研究进展进行综述,旨在为临床工作提供参考和借鉴。

阿来替尼治疗ALK基因融合重排NSCLC脑转移瘤的临床疗效分析

目的:探讨阿来替尼治疗ALK融合重排非小细胞肺癌(non-small cell lung cance,NSCLC)脑转移患者的疗效及不良反应。方法:回顾性分析2016年8月至2019年10月天津医科大学肿瘤医院34例以脑转移为首发的ALK基因融合重排NSCLC患者的临床资料,其中13例(38.2%)患者接受阿来替尼单药一线治疗。男性7例(53.8%),女性6例(46.2%),中位年龄51(35~72)岁。应用Kaplan-Meier分析其生存情况。结果:阿来替尼治疗ALK基因融合重排肺癌脑转移瘤,颅内中位无进展生存期(median pro-gression-free survival,m PFS)为24.5个月。药物不良反应较轻。结论:在颅内可测量病灶得到局部治疗的基础上,阿来替尼作为ALK基因融合重排NSCLC脑转移患者的一线治疗方案,显著延长患者无进展生存期(progression-free survival,PFS)。

5-氟尿嘧啶和卡培他滨对中国患者的心脏毒性:一项前瞻性研究

背景与目的已有许多研究报道5-氟尿嘧啶(5-Fluorouracil,5-FU)和卡培他滨相关的心脏毒性,严重程度从无症状心电图(electrocardiography,ECG)异常到严重心肌梗塞而不同。目前为止,对中国恶性肿瘤患者的这种心脏毒性尚无研究。本研究旨在前瞻性地对多个中心招募的癌症患者进行5-FU和卡培他滨相关心脏毒性的发生率和临床表现进行评估。方法在完成研究的527例患者中,196例接受基于5-FU的化疗,331例接受基于卡培他滨的化疗并以其为一线或辅助治疗。在治疗期间和长达28 d的随访期间对所发生的不良反应进行记录。疗效测量指标包括心电图、心肌酶、心肌肌钙蛋白、脑钠肽和超声心动图。使用单因素分析和logistic回归方法进行亚组分析和鉴定与两种药物的心脏毒性相关的显著性独立变量。结果 527例患者中有161例(30.6%)出现心脏毒性。卡培他滨组的心脏毒性发生率为33.8%(112/331),显著高于5-FU组25%(49/196)的发生率(P=0.0042)。110/527患者(20.9%)发生心律失常,105/527(19.9%)发生缺血性改变,而只有20/527患者(3.8%)出现心力衰竭,6/527患者(1.1%)出现心肌梗塞。既往的心脏病、高血压、卡培他滨为基础的化疗和治疗时间被确定为与心脏毒性相关的显著风险因素。优势比分别为15.7(心脏病史vs.无病史)、1.86(卡培他滨vs. 5-FU)、1.06(5–8个化疗周期vs. 1–4个化疗周期)和1.58(高血压vs.无高血压)。结论氟嘧啶类药物在中国人群中引起的心脏毒性可能在临床实践中被低估。建议密切监测患者,尤其是对心脏毒性高风险的患者。可能的风险因素包括治疗持续时间、基于卡培他滨的化疗、既往心脏病史和高血压史。

Microsurgery vs. radiosurgery for the treatment of multiple metastases in the brain: a retrospective cohort study

Objective:Multiple brain metastases are a severe condition for cancer patients.To date,no general consensus exists regarding the optimal treatment procedure for multiple brain metastases.Radiotherapy is the most commonly used treatment option.The role of surgical resection for multiple brain metastases is unclear.The aim of this study was to compare the outcomes of patients with multiple brain metastases treated with either surgery or stereotactic radiosurgery(SRS).Methods:The medical records of 279 consecutive adult patients with multiple brain metastases treated with either surgery(26 patients)or SRS(253 patients)were retrospectively reviewed.Propensity score matching was conducted to correct for discrepancies in the baseline characteristics,and 78 patients(26 receiving surgery and 52 receiving SRS)were chosen for comparison of outcomes,such as overall survival,local tumor control rate,and symptom improvement.Results:The tumor size in the surgery group was significantly greater than that in the SRS group after propensity score matching.However,the neurological recovery rate,incidence of leptomeningeal metastasis after surgery,1-year local tumor control rate,and overall survival were not significantly different between groups.Conclusions:Our data demonstrate that surgery and radiosurgery have identical overall survival and local tumor control rates in patients with 2 to 4 brain metastases.Although SRS remains the primary and standard option for patients with brain metastasis,surgery offers several distinct advantages,such as establishing a diagnosis or relieving mass effects,and may additionally be beneficial in carefully selected patients with 2–4 brain metastases.

The integrated risk assessment and zoning of meteorological disaster in Heilongjiang Province of China

This paper describes studies on the integrated risk assessment and zoning of meteorological disaster in Heilongjiang Province,in northeastern China,by using information-diffusion theory and cluster method with 35 years of summer temperature and precipitation data from 74 meteorological stations from 1971 through 2005.The information-diffusion theory has been used extensively in risk assessment,yet almost no one has done research about risk assessment by information-diffusion theory based on meteorological disaster standards.Some research results are as follows:the risk probability of low temperature and cold damage in the northern region is higher than that in the southern region;the risk probability of general low temperature and cold damage in the southwestern region is the highest;the risk probability of serious low temperature and cold damage in the northern region is the highest,followed by the central and southeast region;the high-risk region of arid disaster in Heilongjiang Province was primarily located in the southwestern,central,and southern parts of the province;the high-intensity arid disaster was located in the south-eastern region;the high-risk region of flood in Heilongjiang Province was primarily located from the southwest and then across the central part to the western part of Heilongjiang Province;the high-intensity flood disasters were located in almost every part of Heilongjiang Province.We can conclude from the integrated meteorological disaster risk zoning that the high-risk region of mete-orological disaster is primarily located in the southern and northern part of the province,the moderate-risk region is distributed in the central southern region and western region,the low-risk region is located in the eastern part,and the light-risk region is located in the central western part of Heilongjiang Province.

指向深度教学的教师课程能力提升

深度教学是一种将知识打开、内化、再外化,从而使教学内容真正被展开和加工,并能够为学生所吸收理解,最终应用于其成长实践的过程。深度教学是教师应然达到的一种教学状态,但我国教师教师往往未能实现深度教学,主要是因为教师课程能力不足,导致教学的深度不够。因此,深度教学需要教师课程能力的提升,教师应提升课程能力使其最终指向深度教学。从客观上看,我国教师课程能力整体存在着课程自觉意识的缺失、课程内容呈现的符号化、课程改革的稚化等问题。通过养成课程反省思维,建立有信念感的意义教学;实现课程迁移应用,建立高阶思维下的启发式教学;关注课程实效,实现与知识密切相关的创新型教学,是提升教师课程能力的有效策略,也是实现深度教学的必由路径。

Microsurgical Treatment of Meningiomas Invading the Sagittal or Transverse Sinuses

OBJECTIVE To analyze our management strategy and results of treating patients affected by meningiomas invading the sagittal or transverse sinuses.METHOOS Review of data from 35 patients with pathologically confirmed meningiomas（29 of the sagittal sinus and 6 of the transverse sinus） surgically treated between from July 1999 and June 2003, including clinical manifestations, mode of diagnosis and curative effect of microsurgery etc. For our surgical decision-making, meningiomas were classified into six types based on the degree of sinus involvement.RESULTS A Simpson＇s Grade Ⅰ resection was achieved in 27 cases （77.1%）, Grade Ⅱ in 6 （17.1%） and Grade Ⅲ in 2 （5.7%）. No patients died after the operations. The recurrence rate in the study overall was 2.9%, with a follow-up period from 3 to 6 years.CONCLUSION Application of microsurgical techniques, protection of the sinus, avoidance of damages to the cerebral cortex, veins of the central sulcus, as well as other veins from the tumor, are the major factors for increasing the rate of total resection, reducing complications and improving the quality of life for the patients with meningiomas invading the sagittal or transverse sinuses.

A robust method for identification of plant SUMOylation substrates in a library-based reconstitution system

Dear Editor,SUMOylation,which transfers a small ubiquitin-like protein to the lysine residues of target proteins,is an important type of posttranslational modification in eukaryotic cells.This modification plays a critical role in plant development and stress responses(Miura and Hasegawa,2010);thus,the efficient identification of SUMOylation substrates in plant cells is a fundamental issue in the field.In Arabidopsis,hundreds of SUMOylated proteins have been identified by a mass spectrometry(MS)approach in which modified targets in transgenic plants harboring an H89R variant of SUMO1 are enriched via affinity chromatography and a four-residue footprint is left on the substrates after trypsin digestion for MS analysis(Miller et al.,2010).Given that antibodies generated against SUMO molecules are not very specific,it is impractical to catch endogenous SUMO moieties via antibody-based one-step purification.Thus,it is difficult to obtain SUMOylation substrates via existing approaches in plant species that cannot be efficiently transformed.Given that SUMOylation is highly reversible(Yates et al.,2016),another problem is that the modification may be removed quickly during sample preparation.In addition,based on the efficiency and sensitivity of affinity enrichment and MS,substrates with low protein levels may be missed in the analyses.

Genetic and immunologic characteristics of colorectal cancer patients with KRAS mutations and predictive significance of tumor immune microenvironment in adjuvant chemotherapy

Colorectal cancer(CRC)is one of the most common cancers around the world,and it is one of the leading causes of cancer-related death.1 Although anti-EGFR therapy and immune checkpoint inhibitor(ICl)therapy are becoming more and more important for colorectal therapy,however,clinical outcomes of current treatments for metastatic CRC,especially with ICls,have been shown to be affected by the status of KRAS.Therefore,KRAS mutation status detection has become a very important diagnostic factor for managing metastatic CRC patients.

Biomedical applications of mRNA nanomedicine

As an attractive alternative to plasmid DNA, messenger RNA （mRNA） has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.

In situ construction of ligand nano-network to integrin αvβ3 for angiogenesis inhibition

Angiogenesis occurs during the process of tumor growth,invasion and metastasis,and is essential for the survival of solid tumors.As an integrin significantly ove rexpressed in human tumor vascular endothelial cells,αvβ3 is a suitable targeting site for anti-angiogenesis of tumor.We designed and prepared a selfassembling peptide(SAP)with the ability to targeting αvβ3 and self-assembly.SAP formed nanoparticles in solution and transformed into nanofibrous network once specifically binding to integrin αvβ3 on the surface of human umbilical vein endothelial cells(HUVECs).The SAP network stably anchored on HUVECs over 24h,which consequently resulted in high-efficient inhibition of vascularization.In vitro anti-angiogenesis experiment displayed that the inhibition rate of tube-formation reached 94.9%.In vivo anti-angiogenesis array based on chick chorioallantoic membrane(CAM)model exhibited that the SAP had an inhibition rate up to 63.1%.These results indicated the outstanding anti-angiogenic ability of SAP,potentially for tumor therapy.

Beta-adrenergic signaling on neuroendocrine differentiation, angiogenesis, and metastasis in prostate cancer progression

Prostate cancer is a complex, heterogeneous disease that mainly affects the older male population with a high-mortality rate. The mechanisms underlying prostate cancer progression are still incompletely understood. Beta-adrenergic signaling has been shown to regulate multiple cellular processes as a mediator of chronic stress. Recently, beta-adrenergic signaling has been reported to affect the development of aggressive prostate cancer by regulating neuroendocrine differentiation, angiogenesis, and metastasis. Here, we briefly summarize and discuss recent advances in these areas and their implications in prostate cancer therapeutics. We aim to provide a better understanding of the contribution of beta-adrenergic signaling to the progression of aggressive prostate cancer.

Two new species of Flavoperla(Plecoptera:Perlidae)from China

In this paper,two new species are described and illustrated from China:Flavoperla separata Liu,Li&Shali,sp.nov.from Hubei and Shaanxi Provinces and F.qinlinga Liu,Li&Li,sp.nov.from Shaanxi and Sichuan Provinces,with the discussion of their congeners.All type specimens are deposited in the Entomological Museum of China Agricultural University(CAU)and the Henan Institute of Science and Technology(HIST).

Cardiotoxicity of 5-fluorouracil and capecitabine in Chinese patients: a prospective study

Background:5-Fluorouracil(5-FU)and capecitabine-associated cardiotoxicity ranging from asymptomatic electro-cardiography(ECG)abnormalities to severe myocardial infarction has been reported in a number of studies,but such cardiotoxicity in Chinese patients with malignant diseases has not been investigated to date.In the present study,we aimed to prospectively evaluate the incidence rates and clinical manifestations of 5-FU-and capecitabine-associated cardiotoxicity in cancer patients recruited from multiple centers in China.Methods:Among the 527 patients who completed the study,196 received 5-FU-based chemotherapy and 331 received capecitabine-based chemotherapy as either first-line or adjuvant therapy.Adverse events were reported during the treatment and up to 28 days of follow-up.Outcome measures included ECG,myocardial enzymes,cardiac troponin,brain natriuretic peptide and echocardiography.Univariate analysis and logistic regression were performed for subgroup analysis and identification of significant independent variables that are associated with cardiotoxicity of both agents.Results:In total,161 of 527 patients(30.6%)experienced cardiotoxicity.The incidence rate of cardiotoxicity was 33.8%(112/331)in the capecitabine group,which was significantly higher than the rate of 25%(49/196)in the 5-FU group(P=0.0042).110/527 patients(20.9%)suffered arrhythmia,105/527(19.9%)developed ischemic changes,while only 20/527 patients(3.8%)presented heart failure and 6/527 patients(1.1%)had myocardial infarction.Pre-existing cardiac disease,hypertension,capecitabine-based chemotherapy and duration of treatment were identified as sig-nificant risk factors associated with cardiotoxicity.The odds ratio were 15.7(prior history of cardiac disease versus no history),1.86(capecitabine versus 5-FU),1.06(5-8 versus 1-4 chemotherapy cycles)and 1.58(hypertension versus no hypertension),respectively.Conclusions:Cardiotoxicity induced by fluoropyrimidines in the Chinese population may be underestimated in clini-cal practice.Close monitoring of patients is recommended,especially for those patients at high risk for cardiotoxicity.Possible risk factors are duration of treatment,capecitabine-based chemotherapy,pre-existing cardiac diseases and hypertension.Trial registration This study was initiated on January 22,2014 and has been retrospectively registered with the registra-tion number ChiCTR1800015434 .

Ultrathin tellurium nanosheets for simultaneous cancer thermo-chemotherapy

The emerging two-dimensional monoelemental materials(2D Xenes)have been commonly supposed as promising drug delivery carriers,photothermal and photodynamic therapeutic agents,biosensors,theranostics,and some other candidates for biomedical applications.Here,high-performance and bioactive ultrathin 2D Tellurium nanosheets(Te NSs)are prepared by a simple but efficient liquid-phase exfoliation approach.The as-obtained Te NSs possess a mean size of~90 nm and a mean thickness of~5.43 nm.The pegylation Te NSs(Te-PEG NSs)possess excellent biocompatibility and stability.The Te-PEG NSs could generate local hyperthermia with a remarkable photothermal conversion efficiency of about 55%under 808 nm laser irradiation.Additionally,Te-PEG NSs exhibit an extremely high loading capacity of chemo drug(~162%)owing to their ultra-high surface area and tumor microenvironment-triggered drug release superiority.The results of in vivo experiments show that the Te-PEG NSs have higher tumor elimination efficiency via the combination of photothermal and chemotherapy,comparing to any other single therapeutic modalities.Therefore,our work not only highlights the promising potentials of tellurene as an ideal anti-cancer platform but also expands the application of 2D Te for cancer nanomedicine.