Clinical outcome and prognostic factors of T4N0M0 colon cancer after R0 resection:A retrospective study

BACKGROUND Paradoxically,patients with T4N0M0(stage II,no lymph node metastasis)colon cancer have a worse prognosis than those with T2N1-2M0(stage III).However,no previous report has addressed this issue.AIM To screen prognostic risk factors for T4N0M0 colon cancer and construct a prognostic nomogram model for these patients.METHODS Two hundred patients with T4N0M0 colon cancer were treated at Tianjin Medical University General Hospital between January 2017 and December 2021,of which 112 patients were assigned to the training cohort,and the remaining 88 patients were assigned to the validation cohort.Differences between the training and validation groups were analyzed.The training cohort was subjected to multi-variate analysis to select prognostic risk factors for T4N0M0 colon cancer,followed by the construction of a nomogram model.RESULTS The 3-year overall survival(OS)rates were 86.2%and 74.4%for the training and validation cohorts,respectively.Enterostomy(P=0.000),T stage(P=0.001),right hemicolon(P=0.025),irregular review(P=0.040),and carbohydrate antigen 199(CA199)(P=0.011)were independent risk factors of OS in patients with T4N0M0 colon cancer.A nomogram model with good concordance and accuracy was constructed.CONCLUSION Enterostomy,T stage,right hemicolon,irregular review,and CA199 were independent risk factors for OS in patients with T4N0M0 colon cancer.The nomogram model exhibited good agreement and accuracy.

Comparative efficacy and safety between endoscopic submucosal dissection,surgery and definitive chemoradiotherapy in patients with cT1N0M0 esophageal cancer

BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the comparative efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC remain unclear.AIM To compare the efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC.METHODS We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th,2022.We analyzed demographic,medical recorded,histopathologic characteristics,imaging and endoscopic,and follow-up data.The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments.Inverse probability of treatment weighting(IPTW)was used to minimize potential confounding factors.RESULTS We retrospectively analyzed patients who underwent ESD(n=99)or surgery(n=220)or d-CRT(n=16)at the Sun Yat-sen University Cancer Center from 2017 to 2019.The median follow-up time for the ESD group,the surgery group,and the d-CRT group was 42.0 mo(95%CI:35.0-60.2),45.0 mo(95%CI:34.0-61.75)and 32.5 mo(95%CI:28.3-40.0),respectively.After adjusting for background factors using IPTW,the highest 3-year overall survival(OS)rate and 3-year recurrence-free survival(RFS)rate were observed in the ESD group(3-year OS:99.7% and 94.7% and 79.1%;and 3-year RFS:98.3%,87.4% and 79.1%,in the ESD,surgical,and d-CRT groups,respectively).There was no difference of severe complications occurring between the three groups(P≥0.05).Multivariate analysis showed that treatment method,histology and depth of infiltration were independently associated with OS and RFS.CONCLUSION For cT1N0M0 EC,ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery,with a similar rate of severe complications occurring.

m6A RNA甲基化调控因子在食管腺癌中的表达谱及其临床意义研究

目的:探讨N6-甲基腺苷(m6A)RNA甲基化调控因子在食管腺癌中的表达模式及其预后价值,构建基于m6A调控因子的风险模型,用于预测患者生存并寻找新的治疗靶点。方法:从TCGA数据库获取81名食管腺癌患者和11名对照患者的RNA-seq数据及临床预后信息。使用Limma包分析m6A RNA甲基化调控因子的表达与临床病理特征间的关系,采用Cox回归和LASSO算法构建包含五个m6A因子的风险模型。结果:17个m6A因子在食管腺癌组织中的表达显著高于正常组织。YTHDC2、EIF3A与T、N分期,IGF22BP1与远处转移相关。Cox分析和LASSO回归确定RBMX、HNRNPA2B1、WTAP、VIRMA四个预后因子并构建风险模型。Kaplan-Meier分析显示,高风险患者生存率显著低于低风险组。结论:m6A因子的表达与食管腺癌患者的临床特征密切相关,所构建的风险模型为预后预测和个性化治疗提供了新参考。

干扰RNA METTL14对大鼠肺成纤维细胞向肌成纤维细胞转化的影响

目的探究干扰RNA甲基转移酶样蛋白14(methyltransferase-like 14,METTL14)在转化因子β1(transforming growth factorβ1,TGF-β1)诱导的大鼠肺成纤维细胞向肌成纤维细胞转移中的作用。方法大鼠肺成纤维细胞中构建METTL14小干扰RNA(small interfering RNA METTL14,si-METTL14)序列(si-METTL14-122、si-METTL14-300、si-METTL14-450)及对照siRNA(Negative control siRNA,si-NC)。建立TGF-β1(20 ng/mL)诱导肺成纤维细胞向肌成纤维细胞转化模型,转染si-NC及si-METTL14序列至肺成纤维细胞,检测METTL14、肌成纤维细胞标志物Ⅰ型胶原蛋白α1(collagen typeⅠalpha 1,COL1A1)、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)及肌成纤维细胞转化负向调控因子Smad家族7号蛋白(Smad family member 7,Smad7)的mRNA和蛋白水平。结果si-METTL14有效沉默肺成纤维细胞METTL14表达水平。肌成纤维细胞转化模型组中METTL14表达显著升高(P<0.05)。与control组相比,TGF-β1诱导model组COLIA1、α-SMA表达显著升高,Smad7表达显著降低,转染si-METTL14抑制COLIA1、α-SMA表达,促进Smad7表达(P<0.05)。结论METTL14抑制TGF-β1诱导大鼠肺成纤维细胞向肌成纤维细胞转化,且可能与METTL14上调Smad7表达有关。

Effect of toroidal mode coupling on explosive dynamics of m/n=3/1 double tearing mode

The CLT code was used to quantitatively study the impact of toroidal mode coupling on the explosive dynamics of the m/n=3/1 double tearing mode.The focus of this study was on explosive reconnection processes,in which the energy bursts and the main mode no longer dominates when the separation between two rational surfaces is relatively large in the medium range.The development of higher m and n modes is facilitated by a relatively large separation between two rational surfaces,a small q_(min)(the minimum value of the safety factor),or low resistivity.The relationships between the higher m and n mode development,explosive reconnection rate,and position exchange of 3/1 islands are summarized for the first time.Separation plays a more important role than q_(min)in enhancing the development of higher m and n modes.At a relatively large separation,the good development of higher m and n modes greatly reduces the reconnection rate and suppresses the development of the main mode,resulting in the main mode not being able to develop sufficiently large to generate the position changes of 3/1 islands.

Learning Sequential and Structural Dependencies Between Nucleotides for RNA N6-Methyladenosine Site Identification

N6-methyladenosine(m6A)is an important RNA methylation modification involved in regulating diverse biological processes across multiple species.Hence,the identification of m6A modification sites provides valuable insight into the biological mechanisms of complex diseases at the post-transcriptional level.Although a variety of identification algorithms have been proposed recently,most of them capture the features of m6A modification sites by focusing on the sequential dependencies of nucleotides at different positions in RNA sequences,while ignoring the structural dependencies of nucleotides in their threedimensional structures.To overcome this issue,we propose a cross-species end-to-end deep learning model,namely CR-NSSD,which conduct a cross-domain representation learning process integrating nucleotide structural and sequential dependencies for RNA m6A site identification.Specifically,CR-NSSD first obtains the pre-coded representations of RNA sequences by incorporating the position information into single-nucleotide states with chaos game representation theory.It then constructs a crossdomain reconstruction encoder to learn the sequential and structural dependencies between nucleotides.By minimizing the reconstruction and binary cross-entropy losses,CR-NSSD is trained to complete the task of m6A site identification.Extensive experiments have demonstrated the promising performance of CR-NSSD by comparing it with several state-of-the-art m6A identification algorithms.Moreover,the results of cross-species prediction indicate that the integration of sequential and structural dependencies allows CR-NSSD to capture general features of m6A modification sites among different species,thus improving the accuracy of cross-species identification.

H9N2亚型禽流感病毒M1和NA基因在昆虫细胞中的表达

为通过昆虫细胞表达出H9N2亚型禽流感病毒M1和NA蛋白,并鉴定其免疫活性,利用PCR技术扩增H9N2亚型禽流感病毒M1和NA基因,以pFastBacDual为转移载体构建重组转移载体pFastBacDual-M1和pFastBacDual-NA;将阳性重组转移载体分别转化至DH10Bac感受态细胞,得到重组杆粒rBacmid-M1和rBacmid-NA;将重组杆粒分别转染Sf9昆虫细胞,获得含M1和NA基因的重组杆状病毒rBV-M1和rBV-NA;运用IFA和Western-blot鉴定M1和NA蛋白的表达情况,同时以NA蛋白为包被抗原,运用间接ELISA方法鉴定NA蛋白的反应活性。结果显示,IFA鉴定均出现特异性绿色荧光,Western-blot检测M1和NA蛋白大小分别约为28和52 ku,ELISA检测NA蛋白对抗H9N2阳性血清有很高的反应值。结果表明,M1和NA蛋白可在昆虫细胞中特异性表达且具有反应原性。本试验为进一步研发H9N2亚型禽流感诊断技术和疫苗奠定了基础。

Comparative Study of the Physicochemical Quality of the Waters of the Méné River (Sassandra Watershed, Ivory Coast) in the Dry Season and in the Rainy Season

The study carried out on the waters of the Méné River led to an overall assessment of its water quality during the dry season and the rainy season. The analysis focused on eight (8) water samples taken from the river during a period of dry season (January-February) and a period of rainy season (June and September). The various physicochemical parameters were measured according to Afnor standardized methods. The readings of temperature, turbidity, pH and conductivity made it possible to account for the disturbances occurring in water quality. A temporal variation correlated with the seasons (dry or rainy) is noted. Turbidity depends on the concentration of suspended solids (SS) in the water and drained particles and therefore on the seasons. Just like the temperature, the conductivity changes with the season. The waters of the Méné River are generally acidic. The results obtained show that there is a low level of pollution by chlorides, phosphates, nitrites and nitrates. A slight pollution of the waters of Méné in organic matter (chemical oxygen demand values are less than 25 mg∙L−1 during dry season and 32.33 ± 4.73 mg∙L−1 during rainy season) was observed. The concentrations of metallic trace elements such as iron, manganese and aluminum indicate significant pollution of these waters by these elements. Overall, the waters of the Méné River are of satisfactory quality because all the physicochemical parameters analyzed have values below standards during the dry season as well as during the rainy season with the exception of COD and a few metallic trace elements.

因子von Neumann代数上的非线性(m,n)导子

设m和n是任意固定的非零整数,且(m+n)(m-n)≠0,M是一个因子von Neumann代数,δ是M上的一个映射(没有可加性或连续性假设).用矩阵分块方法证明了:若对任意的A,B∈M,有mδ(AB)+nδ(BA)=mδ(A)B+mAδ(B)+nδ(B)A+nBδ(A),则δ是一个可加导子.

人高致病性禽流感病毒H5N1安徽株HA、M2蛋白双顺反子表达载体的构建及表达研究

将我国分离的人H5N1亚型禽流感病毒A/Anhui/1/2005作为研究对象,扩增其HA和M2基因片段并克隆至DNA疫苗表达载体pVRC中,构建成真核表达质粒。为提高HA的表达量,按照人偏爱密码子将HA基因进行优化改造,经全基因合成后插入真核表达载体pVRC,以β-actin蛋白为内参比证明了优化后的HA蛋白表达效果明显提高。将M2基因和优化后的HA基因共同克隆入双顺反子表达载体pIRES中,获得同时表达HA或M2的双顺反子真核表达质粒;通过Western blot和间接免疫荧光检测方法,确认构建的重组质粒在真核细胞中成功地表达了目的蛋白HA和M2。通过上述结果为进一步开展人高致病性禽流感病毒安徽株HA和M2基因的功能与致病性研究及使用表达HA和M2蛋白进行新型人用禽流感双价疫苗研发奠定基础。

肺炎支原体肺炎患儿外周血及小鼠模型miRNAs差异表达

目的研究miRNAs在肺炎支原体肺炎患儿血中淋巴细胞以及在小鼠感染模型肺组织中的表达差异。方法通过miRNA芯片技术筛选24例肺炎支原体肺炎患儿和24例健康儿童血液淋巴细胞中差异表达的miRNAs,通过实时定量PCR法验证芯片检测结果的准确性,并构建支原体呼吸道感染小鼠模型,通过实时定量PCR法验证小鼠肺组织中相关miRNA的表达差异。结果在支原体肺炎患儿血液淋巴细胞中筛选出表达上调的miRNA 105个,下调的133个(P<0.05),通过PCR进一步证实患儿外周血及小鼠模型肺组织中miR-126、miR-181、miR-146a相对表达升高,miR-155相对表达降低,与芯片结果一致。结论 miR-126、miR-181、2017-12-18接收miR-146a、miR-155在肺炎支原体患儿外周血淋巴细胞及小鼠模型肺组织中存在差异表达,它们可能通过调控炎症因子的释放,参与肺炎支原体导致的免疫炎症反应。

H1N2亚型猪流感病毒HA、NP、NA、M和NS基因的克隆与序列分析

对3株H1N2亚型猪流感病毒（SIV）：Sw／GX／17／05、Sw／HN／I／05和Sw／GX／13／06的血凝素（HA）、核蛋白（NP）、神经氨酸酶（NA）、基质蛋白（M）和非结构蛋白（NS）基因进行克隆和序列分析。结果显示：3株分离毒株HA、NP、NA、M和NS基因之间核苷酸同源性分别为91．3％～98．0％、98．4％～98．8％、97．4％～98．3％、98．8％～99．8％和98．1％～98．4％。遗传进化分析显示：分离毒株与美国分离的三源基因重排HIN2sIV具有较近的亲缘关系；在HA、NP、M和NS基因进化树中，3株分离毒株均位于古典H1N1亚型SIV群，在NA基因进化树中，3株分离毒株则位于人流感病毒群。HA和NA基因推导氨基酸序列分别与代表毒株古典H1N1SIVA／swine／Maryland／23239／1991（H1N1）和人H3N2流感病毒A／BuenosAires／4459／96（H3N2）比较分析显示：HA（95．4％～96．1％）和NA（96．6％～97．2％）具有较高的氨基酸同源性；糖基化位点、抗原位点和受体结合位点（HA）处氨基酸存在一定的差异，这些氨基酸差异对病毒生物学特性的影响有待于进一步研究。

SARS-CoV毒株E、M、N和S基因分子变异研究

目的通过对SARS-CoV毒株基因序列的变异分析,揭示SARS-CoV毒株出现和流行与基因进化的关系。方法对广东地区SARS-CoV毒株进行序列分析,其余毒株序列从GenBank检索,采用DNAstar5.0软件,对检索的SARS-CoV的E、M、N、S基因核苷酸序列进行比对和分析;并结合临床资料对变异毒株进行流行病学分析。结果以果子狸冠状病毒(SZ-3)为基准,102株人类毒株中,6株毒株E基因的4个氨基酸发生置换,两株毒株发生缺失变异;果子狸毒株M基因的第5位丝氨酸置换为人类毒株甘氨酸并减少1个糖蛋白位点,此外M基因有38株毒株发生8个氨基酸置换变异;6株毒株N基因发生氨基酸置换,3株毒株发生缺失变异;人类毒株S基因中9个氨基酸全部发生变异并增加1个糖蛋白位点,与果子狸毒株不同比例占0.72%(9/1255);部分毒株中S基因的27个氨基酸在发生置换变异,7株毒株发生缺失变异。结论冠状病毒S基因中9个氨基酸置换和1个糖蛋白位点影响,可能导致人类SARS-CoV毒株出现和SARS流行;SARS流行持续和传播扩大与S基因进化变异相一致。所以认为,SARS-CoV毒株S基因变异可能在SARS出现和流行中发挥极其重要的作用。

碱土金属氧化物阳离子~2MO^+(M=Ca,Sr,Ba)参与N_2O与CO反应的理论研究

本文采用UB3LYP/6-311G(2d)+SDD//CCSD(T)/6-311+G(2d)+SDD方法,计算研究了气相中碱土金属氧化物阳离子2 MO+(M=Ca,Sr,Ba)参与N2O(X1∑+)+CO(X1∑+)→N2(X1∑g+)+CO2(X1∑g+)的反应机理.通过计算亲氧性得到在三种氧化物阳离子中只有2 CaO+从N2O得到O原子并传递给CO的过程是热力学允许的.碱土金属氧化物阳离子2 MO+参与主题反应的机理通过以下两种方式进行,其一为2 MO+从N2O获取O原子生成2 MO2+,进而向CO提供O原子得到2 MO+和CO2,该过程为催化反应机理;其二为2 MO+先与N2O复合生成中间体IM1,之后IM1继续与CO复合生成中间体IM2′,经过一系列反应过程最终生成2 MO+,N2和CO2.通过对两种反应过程的热力学性质和动力学因素分析得到,2 MO+(M=Ca,Sr,Ba)参与反应N2O(X1∑+)+CO(X1∑+)→N2(X1∑g+)+CO2(X1∑g+)的机理为后一路径,所得结果与实验观测相符.

[Si(S_2Ph)_n]^(m±)(n=1～3)化合物稳定性的ab initio和DFT研究

采用ａｈ ｉｎｉｔｉｏ ＨＦ及密度泛函（ＤＦＴ）Ｂ３ＬＹＰ方法对［Ｓｉ（Ｓ２Ｐｈ）ｎ］ｍ± （ｎ＝１～３）的稳定结构以及结合能进行系统的理论计算，分析了该配合物体系 稳定存在的可能性，并运用完全均衡校正法对基函数重叠误差（ＢＳＳＥ）进行了校 正，同时对配合物分子轨道进行了分析，为实验研究提供了有参考价值的理论结 果．

选择性颈清扫对T1,2N0M0舌癌患者预后影响的Meta分析

目的评价选择性颈清扫对T1,2N0M0舌癌患者预后的影响。材料与方法检索国内外已公开发表的关于选择性颈清扫对T1,2N0M0舌癌患者预后影响的对照研究,应用Meta分析进行统计学处理。结果(1)选择性颈清扫对术后复发的影响:符合标准的文献7篇,总样本数742,其中选择性颈清扫组291人,观察组451人。Meta分析结果:选择性颈清扫组相对于观察组的复发优势比OR=0.41,95%可信区间(0.22,0.75),具有统计学意义。(2)选择性颈清扫对术后生存的影响:符合标准的文献5篇,总样本数614,其中选择性颈清扫组222人,观察组392人。Meta分析结果:选择性颈清扫组相对于观察组的生存优势比OR=1.61,95%可信区间(1.14,2.27),具有统计学意义。结论选择性颈清扫可减少T1,2N0M0舌癌患者术后的复发并能延长生存期。

新型Al组分渐变结构的N极性GaN基HEMT中二维电子气研究

提出了一种含有Al N插入层的新型Al组分渐变的N极性Ga N基高电子迁移率晶体管(HEMT)结构,并通过自洽求解一维薛定谔方程和泊松方程,仿真研究了该新型N极性HEMT结构的二维电子气特性。结果表明采用该新型N极性HEMT结构其体载流子浓度峰值与普通Al组分渐变N极性HEMT结构相比提高了12%。同时定义了Al组分从大到小渐变层和从小到大渐变层厚度之比R及最大值xmax,仿真表明二维电子气面密度随R增大而减小,而xmax超过0.4后二维电子气面密度出现饱和趋势。

基于提升方案的整数Deslauriers-Dubuc(m,n)插值小波变换结合SPIHT应用于图象无损压缩编码性能的研究

研究了基于提升方案的 Deslauriers- Dubuc( m ,n)插值小波变换结合 SPIHT应用于图象无损压缩编码的性能 .实验结果表明 ,基于提升方案和整数运算的插值小波变换是整 -整可逆变换 ,适于快速的 ,渐进性的直至无损图象压缩 .无损压缩性能远好于 Huffm an、Win Rar、Raw+ Win Zip、JPEGL S.以 ( 4,4)插值小波为例平均而言压缩比分别比上述编码方法提高了 63 % ,49% ,46% ,3 4%左右 .由于实现的可逆小波变换是基于整数运算的 ,可由加法和移位完成 ,运算速度快 。

人NMDA受体主亚基M3-M4环基因片段的高效表达、纯化与鉴定

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