内镜热损伤术后息肉样结节瘢痕的病理性质及处理策略探讨

目的 总结内镜热损伤治疗术后息肉样结节瘢痕(PNS)的病理性质和发生机制,并探讨处理策略。方法 选择2015年3月-2019年3月于该科行内镜氩等离子体凝固术(APC)、内镜下黏膜切除术(EMR)和内镜黏膜下剥离术(ESD)治疗胃黏膜增生性病变的患者,回顾性分析发生PNS的7例患者的诊治及随访资料。同时,在中国知网(CNKI)、万方数据知识服务平台、中国生物医学数据库等中国数据库以及PubMed、Science Direct Online (SDOL)等国外数据库中检索相关文献,总结PNS的病理特征及随访结果。结果 临床资料:该科内镜治疗黏膜增生性病变后PNS发生率为1.21%(7/579),男5例,女2例,病变均位于胃窦。4例追加了ESD,术后标本切缘病理阴性,但随访复查中,手术瘢痕处再次发现息肉样结节。另外3例PNS未追加治疗,其中1例术后3个月发现息肉样结节,未作处理,术后6个月复查结节消失。文献检索结果:中文数据库无相关文献,在Science Direct Online (SDOL)和PubMed中检索到2篇相关文献,1篇为ESD术后发生PNS的个案报道,另一篇为多中心研究,前一篇文献资料包含在后一篇文献中。多中心研究文献显示:ESD术后PNS总体发病率为1.23%,各中心PNS发病率为0.15%~11.40%,所有发生PNS的患者原发病变均位于胃远端,长期随访无恶性肿瘤复发,17.86%的病例PNS于平均随访18个月后消失。结论 只要原发病变根治性切除,PNS在组织学上仅显示为再生和增生性组织,应被视为良性病变,除定期复查外,不需任何干预,即使内镜下切除,仍有可能复发。

KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients

AIM:To investigate gene mutations and DNA mismatch repair(MMR) protein abnormality in Chinese colorectalcarcinoma(CRC) patients and their correlations with clinicopathologic features.METHODS:Clinical and pathological information for 535 patients including 538 tumors was reviewed and recorded.Mutation analyses for exon 2 of KRAS gene and exon 15 of BRAF gene were performed by Sanger sequencing except that in 9 tumors amplification refractory mutation system PCR was used.Expression of MMR proteins including MHL1,MSH2,MSH6 and PMS2 was evaluated by immunohistochemistry.Correlations of KRAS and BRAF mutation status and the expression status of MMR proteins with age,gender,cancer stage,location,and histology were analyzed.Correlations between KRAS or BRAF mutations and MMR protein expression were also explored.RESULTS:The overall frequencies of KRAS and BRAF mutations were 37.9% and 4.4%,respectively.KRAS mutations were more common in patients ≥ 50 years old(39.8% vs 22% in patients < 50 years old,P < 0.05).The frequencies of BRAF mutants were higher in tumors from females(6.6% vs males 2.8%,P < 0.05),located in the right colon(9.6% vs 2.1% in the left colon,1.8% in the rectum,P < 0.01),with mucinous differentiation(9.8% vs 2.8% without mucinous differentiation,P < 0.01),or being poorly differentiated(9.5% vs 3.4% well/moderately differentiated,P < 0.05).MMR deficiency was strongly associated with proximal location(20.5% in the right colon vs 9.2% in the left colon and 5.1% in the rectum,P < 0.001),early cancer stage(15.0% in stages Ⅰ-Ⅱ vs 7.7% in stages Ⅲ-Ⅳ,P < 0.05),and mucinous differentiation(20.2% vs 9.2% without mucin,P < 0.01).A higher frequency of MLH1/PMS2 loss was found in females(9.2% vs 4.4% in males,P < 0.05),and MSH2/MSH6 loss tended to be seen in younger(<50 years old) patients(12.0% vs 4.0% ≥ 50 years old,P < 0.05).MMR deficient tumors were less likely to have KRAS mutations(18.8% vs 41.7% in MMR proficient tumors,P < 0.05) and tumorswith abnormal MLH1/PMS2 tended to harbor BRAF mutations(15.4% vs 4.2% in MMR proficient tumors,P < 0.05).CONCLUSION:The frequency of sporadic CRCs having BRAF mutation,MLH1 deficiency and MSI in Chinese population may be lower than that in the Western population.

Incorporating the magnetic alignment of GO composites into Pebax matrix for gas separation

The mixed matrix membranes(MMMs) were developed by incorporating graphite oxide(GO) flakes functionalized with iron oxide(Fe_3O_4) into Pebax matrix. The Pebax/Fe_3O_4–GO MMMs were used to separate CO_2/CH_4 and CO_2/N_2 gas mixture. The results showed that the MMMs with magnetic alignment presented the better gas separation performance than that of random arrangement of Pebax/Fe_3O_4–GO mixed matrix membranes. The reason was that the Fe_3O_4–GO flakes arranged magnetically in the membrane played a multiple role in improving the performance of MMMs. Firstly, under the action of the magnetic field,the magnetic alignment of Fe_3O_4–GO flakes in Pebax matrix constructed the shorter transfer path for gas molecule, increasing the CO_2 permeability. Secondly, the hydroxyl groups in GO flakes and the presence of Fe_3O_4 have stronger binding force for water, improving the CO_2 solubility selectivity. Thirdly, the better interaction between the magnetic alignment of GO composites and polymer matrix, reduced the interface defects. Especially, the optimum gas separation performance was obtained at the Fe_3O_4–GO flakes content of 3 wt% in Pebax matrix at vertical arrangement with selectivity of 47 and 75 for CO_2/CH_4 and CO_2/N_2, respectively, and CO_2 permeability of 538 Barrer at 0.2 MPa and room temperature.

奥施康定联合即释吗啡片治疗癌痛的效果及对患者生存质量的影响

目的探究为癌痛患者实施奥施康定联合即释吗啡片治疗的临床效果及对患者生存质量的影响。方法将100例癌因为恶性肿瘤引发癌痛的患者随机分为临床观察组与一般对照组,对于对照组患者我们使用奥施康定进行治疗,对于观察组患者为其采用奥施康定联合即释吗啡片治疗。治疗前后采用视VAS评分量表对治疗效果进行评估,同时采用QLQ-C30评分系统对对患者治疗前后的生存质量进行评估,并同时比较两组患者的不良反应发生率。结果患者在进行治疗前各种评分量表均无显著性差异,但经治疗后观察组患者的疼痛抑制效果及生活质量均显著优于对照组,且观察组患者的不良反应发生率远低于对照组。结论对癌痛患者实施奥施康定联合即释咖啡片止痛治疗有助于提高患者的生活质量临床疗效显著,值得进行推广。

脑转移瘤治疗方法的选择和疗效分析

目的研究分析脑转移瘤治疗更适合的治疗方案。方法将我们所在医院2016年03月至2018年03月接收的117例脑转移瘤患者作为研究对象,根据其治疗方案的不同分为Ⅰ、Ⅱ、Ⅲ组,每组39例。研究分析Ⅰ、Ⅱ、Ⅲ组患者治疗后的治疗效果和生存率。结果Ⅱ、Ⅲ组的患者治疗后6、12、18个月的治疗效果和生存率均显著高于Ⅰ组,Ⅲ组患者治疗后12、18个月治疗效果和生存率显著高于Ⅱ组,差异显著(P<0.05)。结论WBRT+SRT+化疗的治疗方案能够有效提高脑转移癌患者的治疗效果和生存率,是脑转移瘤更适合的治疗方案,值得临床推广。

Long non-coding RNA MALAT1 in hematological malignancies and its clinical applications

Metastasis-associated lung adenocarcinoma transcript 1(MALAT1)is a well-established oncogenic long non-coding RNA,the higher expression of which is strongly correlated with cancer events such as tumorigenesis,progression,metastasis,drug resistance,and treatment outcome in solid cancers.Recently,a series of studies has highlighted its potential role in hematological malignancies in terms of these events.Similar to solid cancers,MALAT1 can regulate various target genes via sponging and epigenetic mechanisms,but the miRNAs sponged by MALAT1 differ from those identified in solid cancers.In this review,we systematically describe the role and underlying mechanisms of MALAT1 in multiple types of hematological malignancies,including regulation of cell proliferation,metastasis,stress response,and glycolysis.Clinically,MALAT1 expression is related to poor treatment outcome and drug resistance,therefore exhibiting potential prognostic value in multiple myeloma,lymphoma,and leukemia.Finally,we discuss the evaluation of MALAT1 as a novel therapeutic target against cancer in preclinical studies.

Charge-changing cross section measurements of 300 MeV/nucleon^(28)Si on carbon and data analysis

Charge-changing cross section(σcc)measurements via the transmission method have recently seen significant progress with the aim of determining the charge radii of exotic nuclei.In this work,we report a newσcc measurement of 304(9)MeV/nucleon^(28)Si on carbon at the second Radioactive Ion Beam Line in Lanzhou(RIBLL2)and describe the data analysis procedure in detail.This procedure is essential for evaluating the systematic uncertainty in the transmission method.The determinedσcc of 1125(11)mb is found to be consistent with the existing data at similar energies.The present work will serve as a reference forσcc determinations at RIBLL2.

Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer

Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity.Dendritic cell(DCs)vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality.Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world.Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years,their efficacy is still unsatisfactory overall.Therefore,there is an urgent unmet clinical need for lung cancer treatment.Here,we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm,2 medical centers,pilot study initiated by the investigator(ChiCTR-ONC 16009100,NCT02956551).The patients enrolled were patients with heavily treated metastatic lung cancer.Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis.A total of 12 patients were enrolled in this study.A total of 85 vaccine treatments were administered with a median value of 5 doses/person(range:3-14 doses/person).In total,12-30 peptide-based neoantigens were selected for each patient.AIl treatment-related adverse events were grade 1-2 and there were no delays in dosing due to toxic effects.The objective effectiveness rate was 25%;the disease control rate was 75%;the median progression-free survival was 5.5 months and the median overall survival was 7.9 months.This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.

Dynamic microstructure evolution and mechanical properties of dilute Mg-Al-Ca-Mn alloy during hot rolling

The dynamic microstructure and texture of dilute Mg-0.50Al-0.71Ca-0.33Mn(wt.%) during hot rolling at two slab temperatures were investigated by electron backscattered diffraction(EBSD) and high resolution transmission electron microscopy(HRTEM). The results show that the development of the rolling microstructures is to first form {10–12} extension twins in the original grains, thereby forming the extension-twinned regions, and then to further form {10–11}-{10–12} double twins and kinks in the extension-twinned regions, and finally to form continuous dynamic recrystallized(continuous DRXed)grains in the double twins and the cross parts of the shear-deformed coarse extension-twinned regions.These extension twins, double twins and kinks show a decisive effect on the formation of rolling texture.The number of {10–11}-{10–12} double twins and resultant the continuous DRX process are strongly affected by the rolling slab temperature and the reduction thickness per pass. By optimizing the rolling conditions, texture and microstructures of the multi-pass rolled Mg-Al-Ca-Mn alloy sheets are successfully modified. Although the total alloy content is only 1.5 wt.%, these Mg-Al-Ca-Mn alloy sheets show much higher strength than the commercial Mg-3Al-1 Zn(wt.%)(AZ31B) sheet.

Combined inhibition of Notch and FLT3 produces synergistic cytotoxic effects in FLT3/ITD^(+)acute myeloid leukemia

Internal tandem duplication(ITD)mutations of FMS-like tyrosine kinase-3(FLT3)are the most frequent genetic alterations in acute myeloid leukemia(AML)and predict a poor prognosis.FLT3 tyrosine kinase inhibitors(TKIs)provide short-term clinical responses,but the long-term prognosis of FLT3/ITD^(+)AML patients remains poor.Notch signaling is important in numerous types of tumors.However,the role of Notch signaling in FLT3/ITD^(+)AML remains to be elucidated.In the current study,we found that Notch signaling was activated upon FLT3-TKI treatment in FLT3/ITD^(+)cell lines and primary cells.As Notch signaling can be blocked byγ-secretase inhibitors(GSIs),we examined the combinatorial antitumor efficacy of FLT3-TKIs and GSIs against FLT3/ITD^(+)AML and explored the underlying molecular mechanisms.As a result,we observed synergistic cytotoxic effects,and the treatment preferentially reduced cell proliferation and induced apoptosis in FLT3/ITD^(+)AML cell lines and in primary AML cells.Furthermore,the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in an FLT3/ITD^(+)patient-derived xenograft AML model.Mechanistically,differential expression analysis suggested that CXCR3 may be partially responsible for the observed synergy,possibly through ERK signaling.Our findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD^(+)AML.

Concurrent Analysis and Design of Structure and Its Periodic Material

The specific good properties of cellular materials and composite materials, such as low density and high permeability, make the optimal design of such materials necessary and at- tractive. However, the given materials for the structures may not be optimal or suitable, since the boundary condition and applied loads vary in practical applications; hence the macro-structure and its material micro-structure should be considered simultaneously. Although abundant studies have been reported on the structural and material optimization at each level, very few of them considered the mutual coordination on both scales. In this paper, two FE models are built for the macro-structure and the micro-structure, respectively; and the effective elastic properties of the periodic micro-structure are blended into the analysis of macro-structure by the homogenization theory. Here, a topological optimum is obtained by gradually re-distributing the constituents within the micro-structure and updating the topological shape at the macro-structure until converges are achieved on both scales. The mutual coordination between the roles of micro-scale and macro-scale is considered. Some numerical examples are presented, which illustrate that the proposed optimization algorithm is effective and highly efficient for the micro-structure design and macro-structure optimization. For the composite design, one can see reasonable effects of the stiffness of base materials on the resultant topologies.