热休克蛋白保护缺血再灌注损伤的研究进展

热休克蛋白(HSP)是近年来的研究热点,是一个高度保守的蛋白分子,广泛存在于原核生物和真核生物体内。当机体暴露于高温等各种应激条件下,就会刺激热休克蛋白的表达,从而保护机体功能。文章主要就热休克蛋白对心脏、肾脏、肝脏、脑和睾丸缺血再灌注损伤的保护作用进行系统性阐述。

Noncoding RNAs in gastric cancer: Research progress and prospects

Noncoding RNAs(nc RNAs) have attracted much attention in cancer research field. They are involved in cellular development, proliferation, differentiation and apoptosis. The dysregulation of nc RNAs has been reported in tumor initiation, progression, invasion and metastasis in various cancers, including gastric cancer(GC). In the past few years, an accumulating body of evidence has deepened our understanding of nc RNAs, and several emerging nc RNAs have been identified, such as PIWI-interacting RNAs(pi RNAs) and circular RNAs(circ RNAs). The competing endogenous RNA(ce RNA) networks include m RNAs, micro RNAs, long nc RNAs(lnc RNAs) and circ RNAs, which play critical roles in the tumorigenesis of GC. This review summarizes the recent hotspots of nc RNAs involved in GC pathobiology and their potential applications in GC. Finally, we briefly discuss the advances in the ce RNA network in GC.

CD133:A cancer stem cells marker, is used in colorectal cancers

Colorectal cancer is one of the most common malignant tumors worldwide. A model of cancer development involving cancer stem cells has been put forward because it provides a possible explanation of tumor hierarchy. Cancer stem cells are characterized by their proliferation, tumorigenesis, differentiation, and selfrenewal capacities, and chemoradiotherapy resistance. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of cancer stem cell markers, such as CD133, have been of great interest. CD133, a five-transmembrane glycoprotein, is widely used as a marker to identify and isolate colorectal cancer stem cells. This marker has been investigated to better understand the characteristics and functions of cancer stem cells. Moreover, it can also be used to predict tumor progression, patient survival, chemoradiotherapy resistance and other clinical parameters. In this review, we discuss the use of CD133 in the identification of colorectal cancer stem cell, which is currently controversial. Although the function of CD133 is as yet unclear, we have discussed several possible functions and associated mechanisms that may partially explain the role of CD133 in colorectal cancers. In addition, we focus on the prognostic value of CD133 in colorectal cancers. Finally, we predict that CD133 may be used as a possible target for colorectal cancer treatment.

KRAS mutation testing in metastatic colorectal cancer

The KRAS oncogene is mutated in approximately 35%-45% of colorectal cancers, and KRAS mutational status testing has been highlighted in recent years. The most frequent mutations in this gene, point substitutions in codons 12 and 13, were validated as negative predictors of response to anti-epidermal growth factor receptor antibodies. Therefore, determining the KRAS mutational status of tumor samples has become an essential tool for managing patients with colorectal cancers. Currently, a variety of detection methods have been established to analyze the mutation status in the key regions of the KRAS gene; however, several challenges remain related to standardized and uniform testing, including the selection of tumor samples, tumor sample processing and optimal testing methods. Moreover, new testing strategies, in combination with the mutation analysis of BRAF , PIK3CA and loss of PTEN proposed by many researchers and pathologists, should be promoted. In addition, we recommend that microsatellite instability, a prognostic factor, be added to the abovementioned concomitant analysis. This review provides an overview of KRAS biology and the recent advances in KRAS mutation testing. This review also addresses other aspects of status testing for determining the appropriate treatment and offers insight into the potential drawbacks of mutational testing.

Resistance to apoptosis should not be taken as a hallmark of cancer

In the research community, resistance to apoptosis is often considered a hallmark of cancer. However, pathologists who diagnose cancer via microscope often see the opposite. Indeed, increased apoptosis and mitosis are usually observed simultaneously in cancerous lesions. Studies have shown that increased apoptosis is associated with cancer aggressiveness and poor clinical outcome. Furthermore, overexpression of Bcl-2, an antiapoptotic protein, is linked with better survival of cancer patients. Conversely, Bax, CD95, Caspase-3, and other apoptosis-inducing proteins have been found to promote carcinogenesis. This notion of the role of apoptosis in cancer is not new; cancer cells were found to be short-lived 88 years ago. Given these observations, resistance to apoptosis should not be considered a hallmark of cancer.

内镜下逆行阑尾炎治疗术治疗急性非复杂性阑尾炎疗效的Meta分析

目的评价内镜下逆行阑尾炎治疗术治疗急性非复杂性阑尾炎的临床价值。方法通过计算机检索PUBMED、CNKI数据库、Web of Knowledge、Cochrane图书馆对照试验注册库和万方数据库从建库至2018年6月的有关内镜下逆行阑尾炎治疗术治疗急性非复杂性阑尾炎的相关文献,采用Cochrane协作网提供的RevMan 5.0版软件进行统计处理,对纳入资料的异质性进行分析,计算OR^值或MD值及其95%可信区间(95%CI)。结果按照入选标准,纳入了8项临床试验,共537例患者。Meta分析结果显示,内镜下逆行阑尾炎治疗术治疗急性非复杂性阑尾炎住院时间短(MD=-2.11,95%CI:-3.10^-1.11,P<0.05)、并发症发生率低(OR^=0.27,95%CI:0.13~0.56,P<0.05)、手术时间短(MD=-23.46,95%CI:-29.97^-16.96,P<0.05)。结论目前的研究结果显示,内镜下逆行阑尾炎治疗术是一种安全有效地治疗急性非复杂性阑尾炎的内镜治疗方法,可有效缩短患者的手术时间、住院时间和降低并发症发生率,具有临床推广及应用价值。

ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer

AIM: To determine the influence of excision repair cross complementing group 1 (ERCC1 ) codon 118 polymorphism and mRNA level on the clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy. METHODS: Eighty-nine gastric cancer patients treated with oxalipatin-based adjuvant chemotherapy were included in this study. ERCC1 codon 118 C/T polymorphism was tested by polymerase chain reaction-ligation detection reaction (PCR-LDR) method in peripheral blood lymphocytes of those patients; and the intratumoral ERCC1 mRNA expression was measured using reverse transcription PCR in 62 patients whose tumor tissue specimens were available. RESULTS: No significant relationship was found between ERCC1 codon 118 polymorphism and ERCC1 mRNA level. The median relapse-free and overall survival period was 20.1 mo and 28.4 mo, respectively. The relapse-free and overall survivals in patients with low levels of ERCC1 mRNA were significantly longer than those in patients with high levels (P < 0.05), while there was no significant association found between ERCC1 118 genotypes and the disease prognosis. Multivariate analysis also showed that ERCC1 mRNA level was a potential predictor for relapse and survival in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy (P < 0.05). CONCLUSION: ERCC1 codon 118 polymorphism has no signifi cant impact on ERCC1 mRNA expression, and the intratumoral ERCC1 mRNA level but not codon 118 polymorphism may be a useful predictive parameter for the relapse and survival of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

MLH1 promoter germline-methylation in selected probands of Chinese hereditary non-polyposis colorectal cancer families

AIM: To detect the MLH1 gene promoter germline- methylation in probands of Chinese hereditary non- polyposis colorectal cancer (HNPCC), and to evaluate the role of methylation in MLH1 gene promoter and molecular genetics in screening for HNPCC. METHODS: The promoter germline methylation of MLH1 gene was detected by methylation-specific PCR (MSP) in 18 probands from unrelated HNPCC families with high microsatellite-instability (MSI-H) phenotype but without germline mutations in MSH2, MLH1 and MSH6 genes. At the same time, 6 kindreds were col- lected with microsatellite-stability (MSS) phenotype but without germline mutations in MSH2, MLH1 and MSH6 genes as controls. The results of MSP were confirmed by clone sequencing. To ensure the reliability of the results, family H65 with nonsense germline mutation at c.2228C > A in MSH2 gene was used as the negative control and the cell line sw48 was used as the known positive control along with water as the blank control. Immunochemical staining of MLH1 protein was per- formed with Envision two-step method in those patients with aberrant methylation to judge whether the status of MLH1 gene methylation affects the expression of MLH1 protein. RESULTS: Five probands with MLH1 gene promoter methylation were detected in 18 Chinese HNPCC fami- lies with MSI-H phenotype but without germline muta- tions in MSH2, MLH1 and MSH6 genes. Two of the five probands from families H10 and H29 displayed exhaus- tive-methylation, fulfilling the Japanese criteria (JC) and the Amsterdam criteria (AC), respectively. The other 3 probands presented part-methylation fulfilling the AC. Of the 13 probands with unmethylation phenotype, 8 ful- filled the JC and the Bethesda guidelines (BG), 5 fulfilled the AC. The rate of aberrant methylation in MLH1 gene in the AC group (22.2%, 4/18) was higher than that in the JC/BG groups (5.6%, 1/18) in all HNPCC families with MSI-H phenotype but without germline mutations in MSH2, MLH1 and MSH6 genes. However, no proband with methylation in MLH1 gene was found in the families with MSS phenotype and without germline mutations in MSH2, MLH1 and MSH6 genes. No expression of MLH1 protein was found in tumor tissues from two patients with exhaustive-methylation phenotype, whereas posi- tive expression of MLH1 protein was observed in tumor tissues from patients with partial methylation phenotype (excluding family H42 without tumor tissue), indicating that exhaustive-methylation of MLH1 gene can cause defective expression of MLH1 protein. CONCLUSION: Methylation phenotype of MLH1 gene is correlated with microsatellite phenotype of MMR genes, especially with MSI-H. Exhaustive-methylation of MLH1 gene can silence the expression of MLH1 pro- tein. MLH1 promoter methylation analysis is a promis- ing tool for molecular genetics screening for HNPCC.

Three novel missense germline mutations in different exons of MSH6 gene in Chinese hereditary non-polyposis colorectal cancer families

AIM: To investigate the germline mutations of MSH6 gene in probands of Chinese hereditary non-polyposis colorectal cancer (HNPCC) families fulfilling different clinical criteria. METHODS: Germline mutations of MSH6 gene were detected by PCR-based DNA sequencing in 39 unrelated HNPCC probands fulfilling different clinical criteria in which MSH2 and MLH1 mutations were excluded. To further investigate the pathological effects of detected missense mutations, we analyzed the above related MSH6 exons using PCR-based sequencing in 137 healthy persons with no family history. The clinicopathological features were collected from the Archive Library of Cancer Hospital, Fudan University and analyzed. RESULTS: Four germline missense mutations distributed in the 4th, 6th and 9th exons were observed. Of them, three were not found in international HNPCC databases and did not occur in 137 healthy controls, indicating that they were novel missense mutations. The remaining mutation which is consistent with the case H14 at c.3488A>T of exon 6 of MSH6 gene was also found in the controls, the rate was approximately 3.65% (5/137) and the type of mutation was not found in the international HNPCC mutational and SNP databases, suggesting that this missense mutation was a new SNP unreported up to date. CONCLUSION: Three novel missense mutations and a new SNP observed in the probands of Chinese HNPCC families, may play an important role in the development of HNPCC.

Polarization-controlled dual resonant lattice Kerker effects

The generalized Kerker effects have attracted increasing interests in recent years due to their abilities to manipulate the far-field properties of metasurfaces.However,the dual-polarized generalized Kerker effect enabling different tailoring of orthogonally-polarized electromagnetic waves has not yet been reported.Herein,we demonstrate polarization-controlled dual resonant lattice Kerker effects in periodic silicon nanodisks.By varying the incident angle,the electric dipole and magnetic dipole surface lattice resonances can spectrally overlap,causing zero reflectance and unitary transmittance,i.e.,the resonant lattice Kerker effect.The incident angle for achieving this effect can be tuned differently for s-and p-polarizations over large regions by varying the nanodisk size or the lattice periods.The proposed dual-polarized resonant lattice Kerker effects open up avenues for polarization-controlled manipulation of the phase and wavefront of light with metasurfaces.

MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1

MicroRNAs （miRNAs） that exert function by posttran- scriptional suppression have recently brought insight in our understanding of the role of non.protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer （CRC） and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues （NCTs）, and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phe- nocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potentialtumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.

Insights into measurements of water-soluble ions in PM_(2.5)and their gaseous precursors in Beijing

To better understand the characteristics and transformation mechanisms of secondary inorganic aerosols,hourly mass concentrations of water-soluble inorganic ions(WSIIs)in PM_(2.5)and their gaseous precursors were measured online from 2016 to 2018 at an urban site in Beijing.Seasonal and diurnal variations in water-soluble ions and gaseous precursors were discussed and their gas-particle conversion and partitioning were also examined,some related parameters were characterized.The(TNH_(3))Rich was also defined to describe the variations of the excess NH_(3)in different seasons.In addition,a sensitivity test was carried out by using ISORROPIA II to outline the driving factors of gas-particle partitioning.In Beijing,the relative contribution of nitrate to PM_(2.5)has increased markedly in recent years,especially under polluted conditions.In the four seasons,only a small portion of NO_(2)in the atmosphere was converted into total nitrate(TNO_(3)),and more than 80%of TNO_(3)occurred in the form of nitrate due to the abundant ammonia.The concentration of total ammonia(TNH_(3))was much higher than that required to neutralize acid gases,and most of the TNH_(3)occurred as gaseous NH_(3).The nitrous acid(HONO)concentration was highly correlated with NH_(3)concentration and had increased significantly in Beijing compared with previous studies.The total chloride(TCl)was the highest in winter,andε(Cl^(-))was more sensitive to variations in the ambient temperature(T)and relative humidity(RH)thanε(NO_(3)^(-)).

人工卵巢的研究进展

卵巢作为女性的生殖器官,具有分泌类固醇激素和生育功能。随着人类寿命的延长,女性一生中约三分之一的时间处于绝经状态,而绝经后的相关并发症对女性的生活质量构成严重影响。近年来,组织工程卵巢逐渐成为研究热点,为相关临床问题提供了有希望的解决方案。本文从人工卵巢所需的条件、因素、功能和应用等展开综述,为卵巢功能的重塑或替代提供参考。

Correction to:MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1

CORRECTION TO:PROTEIN CELL(2014)5(11):851-861 HTTPS://DOI.ORG/10.1007/S13238-014-0093-5 In the original publication the display of Fig.1 is in correct.The correct Fig.1 is available in this correction.

An investigation on patient dose in screen-film diagnostic radiology in Lhasa City,Xizang Autonomous Region,China

This study aimed to investigate patient dose in diagnostic screen-film radiographic examinations in the city of Lhasa,China.Seven out of the twenty-six hospitals registered with the Lhasa Health Bureau were included in the investigation.The entrance surface air Kerma(ESAK)of seven conventional screen-film radiology X-ray equipment in these hospitals was measured with a QA dosimeter in September 2012.The X-ray examinations were divided into three categories:PA(posterior-anterior)chest,upper/lower limb,and AP(anterior-posterior)lumbar spine.For each category,ESAKs were calculated and analyzed.The mean ESAK was 0.6 mGy for PA chest,0.3 mGy for upper/lower limb,and 1.8 mGy for AP lumbar spine.In addition,the mean ESAK value recorded for PA chest X-ray examinations exceeded the corresponding value recommended by the International Atomic Energy Agency(0.4 mGy).

Effects of 3-aminobenzamide on poly(ADP-ribose)polymerase expression,apoptosis and cell cycle progression of HeLa cells after X-ray irradiation

The aim of this paper is to study the changes of apoptosis and cell cycle progression in HeLa cells after the poly(ADP-ribose)polymerase(PARP)was inhibited by its inhibitor 3-aminobenzamide(3-AB)and the mechan-isms of PARP action on HeLa cells damaged by irra-diation.Flow cytometry(FCM)was used to examine the PARP expression and the percentage of apoptotic cells and cell cycle progression.The percentage of HeLa cells with positive expression of PARP protein 2,4,8 and 12 h after administrated with 3-AB was significantly lower than that of the control(P<0.01).The percentages of apoptotic cells in the 3-AB plus irradiation group at the time points of 2,8,12 and 24 h after 2 Gy irradiation were higher than that in the irradiation group(P<0.01 or P<0.05)and the percentage of G2 cells decreased signifi-cantly(P<0.01 or P<0.05).It indicates that 3-AB can rapidly inhibit PARP expression of HeLa cells,promote cell apoptosis and block G2 arrest induced by irradiation.