[The role and mechanism of tumor metastasis-associated gene 1 in radiosensitivity of HeLa cells].

Objective: To determine the effect of tumor metastasis-associated gene 1 (MTA1) on the sensitivity of HeLa cells to radiotherapy, and to clarify its molecular mechanism. Methods: The transcriptome differences between MTA1 knocked down Hela cells and control cells were analyzed, and the differentially expressed genes (DEGs) was used to perform Gene-Set Enrichment Analysis (GSEA) and Gene Ontology (GO) cluster analysis. Flow cytometry was used to detect apoptosis in MTA1-overexpressed HeLa cells and control cells before and after 10 Gy X-ray irradiation. Cloning formation assay and real-time cellular analysis (RTCA) were used to monitor the cell proliferation before and after 2 Gy X-ray irradiation. To dissect the underlying molecular mechanisms of MTA1 affecting the sensitivity of radiotherapy, the proteins encoded by the DEGs were selected to construct a protein-protein interaction network, the expression of γ-H2AX was detected by immunofluorescence assay, and the expression levels of γ-H2AX, ß-CHK2, PARP and cleaved caspase 3 were measured by western blot. Results: By transcriptome sequencing analysis, we obtained 649 DEGs, of which 402 genes were up-regulated in MTA1 knockdown HeLa cells and 247 genes were down-regulated. GSEA results showed that DEGs associated with MTA1 were significantly enriched in cellular responses to DNA damage repair processes. The results of flow cytometry showed that the apoptosis rate of MTA1 over-expression group (15.67±0.81)% after 10 Gy X-ray irradiation was significantly lower than that of the control group [(40.27±2.73)%, P<0.001]. After 2 Gy X-ray irradiation, the proliferation capacity of HeLa cells overexpressing MTA1 was higher than that of control cells (P=0.024). The numbers of colon in MTA1 over-expression group before and after 2 Gy X-ray irradiation were (176±7) and (137±7) respectively, higher than (134±4) and (75±4) in control HeLa cells (P<0.05). The results of immunofluorescence assay showed that there was no significant expression of γ-H2AX in MTA1 overexpressed and control HeLa cells without X-ray irradiation. Western blot results showed that the expression level of ß-CHK2 in MTA1-overexpressing HeLa cells (1.04±0.06) was higher than that in control HeLa cells (0.58±0.25, P=0.036) after 10 Gy X-ray irradiation. The expression levels of γ-H2AX, PARP, and cleaved caspase 3 were 0.52±0.13, 0.52±0.22, and 0.63±0.18, respectively, in HeLa cells overexpressing MTA1, which were lower than 0.87±0.06, 0.78±0.12 and 0.90±0.12 in control cells (P>0.05). Conclusions: This study showed that MTA1 is significantly associated with radiosensitivity in cervical cancer HeLa cells. MTA1 over-expression obviously reduces the sensitivity of cervical cancer cells to X-ray irradiation. Mechanism studies initially indicate that MTA1 reduces the radiosensitivity of cervical cancer cells by inhibiting cleaved caspase 3 to suppress apoptosis and increasing ß-CHK2 to promote DNA repair.

The experiences of foreign-educated nurses in Japan: a systematic review.

AIM: To conduct a systematic review to understand the experiences of foreign-educated nurses in Japan. BACKGROUND: The experiences of foreign nurses in host countries, and the challenges they face, have been widely investigated around the world. However, no systematic review has focused on the experience of foreign-educated nurses in Japan. METHODS: A systematic literature review was conducted by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. Japan Medical Abstract Society, Citation Information by National Institute of Informatics, Cumulative Index to Nursing and Allied Health Literature, and PubMed databases were used for the literature search. Inclusion criteria were research articles published between 2013 and 2020 written in Japanese or English. A quality assessment was performed using Version 2018 of the Mixed Methods Appraisal Tool. Selected articles were read repeatedly, and relevant contents were extracted and summarized thematically. RESULTS: Twenty-five studies were selected for the review. The themes generated included (1) reasons for nurses to come to Japan, (2) experiences and current situations among the Economic Partnership Agreement nurses/nurse candidates living in Japan, and (3) experiences and current situation of nurses who had returned to their home countries. The second theme was classified into four categories: language and communication barriers, low pass rates for the national qualification exam, adaptation to workplaces and social environments, and psychological distress. CONCLUSION: Foreign nurses in Japan face various challenges and difficulties, even after they return to their home countries. Solving these problems may improve the wellbeing of foreign-educated nurses in Japan. IMPLICATIONS FOR NURSING POLICY: The results from the current review highlight the necessity for immediate intervention by policymakers to improve the current support system for Economic Partnership Agreement nurses/nurse candidates. A thorough pre-arrival orientation should be provided for the nurse candidates to able them to make a well-informed choice.

[Analysis on influencing factors of deaths from severe heat stroke in Shanghai, 2013-2017].

Objective: To explore the related factors of death from severe heat stroke in Shanghai from 2013 to 2017. Methods: The data of 1 152 patients with severe heat stroke who were divided into survival (n=1 037) and death (n=115) groups including gender, age and heat stroke type (heat cramp, heat exhaustion, heat apoplexy and the mixed type) were collected from meteorological bureau and case report system for high temperature heat stroke in Shanghai from 2013 to 2017. Meanwhile, the meteorological data of the onset date of severe heat stroke cases were collected, including maximum temperature, minimum temperature, daily temperature, relative humidity, air pressure, precipitation and wind speed. The differences of individual and meteorological factors between the two groups were compared, and multivariate logistic regression model was used to analyze the related factors of death from severe heat stroke. Results: Among 1 152 cases, the mean±SD of age was (56.29±18.95) years old, 843 (73.18%)were male, 962 (83.51%) were in the heat wave period; 322 cases (27.95%) were heat cramp, 170 cases (14.76%) were heat exhaustion, 533 cases (46.27%) were heat apoplexy and 114 cases (9.90%) were the mixed type. Daily average temperature ((32.81±1.99) ℃), daily maximum and minimum temperatures ((38.20±2.24) ℃ and (29.22±1.94) ℃) in survival group were lower than those in death group (all P values<0.001), which were (33.76±1.17) ℃, (39.19±1.31) ℃ and (29.72±1.66) ℃. Daily average relative humidity ((60.36±9.75)%) and daily minimum relative humidity ((41.26±9.71)%) in survival group were higher than those in death group(allP values <0.05), which were (54.59±6.89)% and (35.60±7.24)%. The results of logistic regression analysis suggested that compared with the cases with daily average humidity <60% and a mixed type heat stroke, the death OR (95%CI) values of cases with daily average humidity >60%, heat cramp, heat exhaustion and heat apoplexy were 0.31 (0.18,0.54), 0.13 (0.05,0.34), 0.68 (0.58,2.30) and 0.87 (0.48,1.58). Conclusion: The temperature, relative humidity and the type of heat stroke were the main related factors affecting the prognosis of severe heat stroke.

[Effects of MTA1 on biological behaviors of gastric cancer cells].

Objective: To study the effects of metastasis associated 1 (MTA1) on biological characteristics such as migration, invasion and proliferation of gastric cancer (GC) cells. Methods: pSilencer3.1-MTA1-siRNA vector was used to establish human gastric cancer BGC-823 cell lines with constitutive MTA1-knockdown. Boyden, wound healing, clony forming assay and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay were performed to identify the effects of MTA1-deficiency on the biological behaviors of BGC-823 cells in vitro. Simultaneously, MTA1 overexpressed BGC-823 cell line was established by pcDNA3-MTA1 plasmid transfection for reverse verification. In addition, the role of MTA1 in the tumorigenicity of gastric cancer BGC823 cells in vivo was examined by subcutaneous injection of BGC-823 cells expressing different MTA1 levels into nude mice. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to detect the expression levels of integrin ß1, cyclin D1 and uPAR in pSilencer3.1-MTA1-siRNA, pcDNA3-MTA1 transfected cells and control cells. Results: MTA1 knocked down or upregulated BGC-823 cell lines were successfully generated by transfecting pSilencer3.1-MTA1-siRNA or pcDNA3-MTA1 vector with lipofectamine 2000, respectively. The Boyden and wound healing experiments showed metastasis and invasion ability in MTA1 knocked down cells (25±2, 12±1) were significantly decreased when compared with those of control (78±2, 50±2) and MTA1-overexpressed groups (218±2, 269±3; P<0.05). The results of MTT assay and colony forming assay were significantly decreased when compared with those of showed that MTA1 overexpressed cells grew more rapidly and formed more colonies in vitro and induced worse malignant tumors in vivo, while MTA1 knocked down cells presented the reversed phenotype[control group (1 482.41±511.90) mm(3,) (1.39±0.29)g; MTA1 overexpressed group [(3 158.73±1 823.22) mm(3,) (2.23±0.51)g; MTA1-downregulated group (711.32±284.30)mm(3,) (0.87±0.21) g ; P<0.05)]. In addition, RT-PCR result showed that the expression level of MTA1 was positively correlated with the known metastasis-related genes (integrinß1, cyclinD1, uPAR). Conclusions: MTA1 promotes the invasion, migration and proliferation of human gastric cancer BGC-823 cells. On the contrary, down-regulation of MTA1 significantly inhibits tumorigenicity of BGC-823 cells and induces favorable phenotypes. MTA1 may promote the malignant phenotype of BGC-23 cells via regulating the expressions of integrinß1, cyclinD1 and uPAR.

[Acute effect of ambient air pollution on small airway lung functions among school children in Shanghai].

Objective: To study the acute effects of compound ambient air pollution on small airway lung functions among school children in Shanghai. Method: A longitudinal survey on lung functions was conducted among 233 school-children from three schools (A, B and C, located in innerring, mid-ring and outer-ring areas). Lung function test was performed once a week for 3 times respectively, among children in school A and B in Dec. 2013 and in school C in Dec. 2014. The fourth lung function test was tested in Jun. 2014 and May 2015 in the respective schools. Results: from the lung function would include items as: forced mid-expiratory flow at 25% of forced vital capacity (MEF(25%)), mid-expiratory flow at 50% of forced vital capacity (MEF(50%)), mid-expiratory flow at 75% of forced vital capacity (MEF(75%)) and mid-expiratory flow between 25% and 75% of the forced vital capacity (FEF(25%-75%)). Data regarding the daily air quality real-time of PM(2.5), PM(10), SO(2) and NO(2) in Dec. 2013, Dec. 2014, Jun. 2014 and May. 2015 from the three environmental monitoring spots and meteorological data from the Shanghai Meteorological Service system which were physically close to the three schools, were collected simultaneously. Linear mixed effect model was used to examine the levels of correlation between lung function indicators and ambient air pollutants. Results When confounding factors on meteorology and individuals were controlled, the lag effects and accumulated lag effects were found to have existed between the internal quarter rang (IQR) concentration of PM(2.5) and PM(10) in lag2 day and lag02 days, IQR concentration of SO(2) in lag02 day and IQR concentration of NO(2) lag0 day, when small airway lung functions like MEF(25%), MEF(50%), MEF(75%) and FEF(25%-75%)(P<0.05) were inspected. Results from the two air pollutants model analysis showed that SO(2) and NO(2) presenting interactive effects with PM(2.5), PM(10) and lag effects more significant than the individual SO(2) and NO(2), respectively (P<0.05). Conclusion: Contents on the ambient air pollutants as PM(2.5), PM(10), SO(2) and NO(2) were negatively associated with the lung functions in the small airways of children, in Shanghai.

DNA damage regulates ARID1A stability via SCF ubiquitin ligase in gastric cancer cells.

OBJECTIVE: The gene product of the AT-rich interactive domain 1A (SWI-like) gene (ARID1A) is a member of the SWI/SNF adenosine triphosphate-dependent chromatin-remodeling complexes, which plays an essential role in controlling gene expression and is also involved in cancer development. ARID1A is frequently mutated in a wild variety of cancers and function as a tumor suppressor in several kinds of cancers. ARID1A was down-regulated in gastric cancer, and associated poor patient prognosis. However, how ARID1A protein is regulated in gastric cancer remains largely unknown. MATERIALS AND METHODS: Here, we show that ARID1A protein is rapidly ubiquitinated and degradated in gastric cancer cells in response to DNA damage treatment. RESULTS: Using genetic and pharmacologic Cullin inactivation coupled with in vitro ubiquitination assay, we demonstrate that ARID1A is a substrate of the Cullin-SKP1-F-box protein (SCF) complexes. Moreover, gastric cancer cells with forced expression of ARID1A showed an increased sensitivity to DNA damage reagents. Thus, our data uncovered a previous unknown posttranscriptional regulation of ARID1A by SCF E3 ligase in gastric cancer cells in DNA damage response. CONCLUSIONS: These findings suggest ARID1A might be a promising drug target in gastric cancer treatment.

Insulin-like growth factor binding protein-3 (IGFBP-3) genetic variant and the risk of esophageal squamous cell carcinoma in a Chinese population.

Insulin-like growth factor binding protein-3 (IGFBP-3) exerts anti-proliferative or pro-apoptotic effects through IGF-dependent as well as IGF-independent mechanisms in vitro. The purpose of this study was to examine the association between genetic variants in IGFBP-3 (rs2270628) and the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population. Five hundred ESCC cases and 500 cancer-free controls of the Chinese Han population were involved in this study. The IGFBP-3 single-nucleotide polymorphism (SNP) rs2270628 was genotyped and the estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for its association with the risk of ESCC were determined using unconditional logistic regression analysis. Compared with the rs2270628 CC genotype, TT genotype was associated with a significantly increased ESCC risk with OR (95%CI) of 2.07 (1.05-4.09), but CT genotype was not (OR = 1.25, 95%CI =0.94-1.66). IGFBP-3 SNP rs2270628 may contribute to the risk of ESCC in the Chinese Han population.

The expression of angiopoietin-1 and -2 in the endometrium of women with abnormal bleeding induced by an intra-uterine device.

This study identified differences in expression of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) in the endometrium of 33 women with abnormal bleeding induced by an intra-uterine device (IUD; 23 proliferative phase, 10 secretory phase) compared with 28 control samples from normal endometria in women without an IUD fitted (12 proliferative phase, 16 secretory phase). Expression of Ang-1, Ang-2 and endothelial cell-specific tyrosine kinase receptor-2 (Tie-2) mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR), and Ang-1 and Ang-2 protein levels were detected by immunohistochemistry. The RT-PCR results showed significantly decreased Ang-1 expression in the endometrium from IUD patients during both phases compared with the control women. Expression of Tie-2 mRNA and the Ang-1:Ang-2 mRNA ratio were also significantly decreased in endometria from IUD patients in the secretory phase compared with the control women. Immunohistochemical analysis showed elevated Ang-2 protein levels in secretory phase endometrium from IUD patients compared with the control women. These results suggest that the angiopoietin/Tie-2 system promotes vascular remodelling in the endometrium and that changes in the expression of Ang-1, Ang-2 and Tie-2 may contribute to abnormal uterine bleeding in some IUD users.

Human cytomegalovirus glycoprotein genotypes in the genital tract tissue of tubal pregnancy patients.

This study investigated human cytomegalovirus (HCMV) glycoprotein genotypes in the genital tract tissue of 125 tubal pregnancy patients. The HCMV glycoprotein-B N-terminus (gBn, 54 - 485 NT), gB endoprotease cleavage site (gBclv, 1284 - 1600 NT) and glycoproteinH (gH, -58 - 213 NT) gene fragments were amplified by nested polymerase chain reaction and sequenced to identify gB and gH genotypes. Of 16 gBn-positive samples, four were gBn1, one was gBn2 and 11 were the gBn3 genotype. Of 13 positive gBclv samples, seven were gBclv1, two were gBclv2 and four were the gBclv3 genotype. Of 20 positive gH samples, 10 were gH1, six were gH2 and four were a combined gH1/gH2 genotype. In 10 of the samples that were positive for the gBn and gBclv genotypes, the gBn and gBclv genotypes were not consistent (four were gBclv1-gBn3). This study showed that: (i) HCMV infection with the gB1 - gB3 glycoprotein genotypes is present in tubal pregnancy; (ii) the gBclv and gBn genotypes are not strictly consistent; and (iii) intragenetic variability within the gB gene due to homologous recombination occurs frequently.

[The role of Anopheles anthropophagus in malaria transmission in in Xinyang City of Henan Province].

OBJECTIVE: To study the role of Anopheles anthropophagus in malaria transmission and transmission threshold so as to provide basis for vector surveillance and malaria control strategy. METHODS: Parasitological and entomological methods were used in the investigation at 5 villages of Xinyang City, Henan Province. RESULTS: From July to August, 1999, 74 febrile cases (10.9% of the total population) were examined. Among them 50 were infected, the incidence in the population of surveyed spots was 7.4%. Active detection was made in another randomly selected two villages and found that the parasite rate in the inhabitants was 2.0%, and the positive rate of IFA was 8.4%. Only vivax malaria was detected. An. anthropophagus and An. sinensis were collected, with An. anthropophagus as the predominant one in human dwellings. The estimated man-biting rate and the human blood index were 4.9388 and 0.7858 respectively. The vectorial capacity of An. anthropophagus was 5.5296. The critical man-biting rate of An. anthropophagus was 0.2407 as calculated by the formula (ma = -rlnP/abPh) according to Macdonald's model. The local man-biting rate was 20 times higher than that of the critical man-biting rate. CONCLUSION: The results demonstrated that An. anthropophagus is the principal vector in malaria transmission in the area. The findings imply that the critical man-biting rate is of practicable importance in vector surveillance.

Study of simplified measures for malaria surveillance in the late consolidation phase in China.

This paper presents the results of a study on simplified surveillance methods conducted in 23 pilot counties in 11 provinces and municipalities in China where reside 15 million people and malaria control has been in the late consolidation phase. Two simplified surveillance Schemes (A and B) taking treatment of clinical cases as the main measure were implemented in 1992-1994. The rate of annual blood examination for case detection was 1.0% in pilot Scheme A, while in areas of scheme B it was 0.3%. The implementation of both Scheme A and Scheme B, simplified or without treatment of infection foci and management of mobile populations, acquired satisfactory effects against malaria. Consequently, malaria incidence was declining steadily, only a few indigenous and introduced cases were detected. The parasite rate in residents and the IFA positive rate in children were very low. The results of pilot studies and cost-effectiveness analysis indicated that Scheme B is effective, rational and economic, and can be implemented to replace the routine surveillance measures in areas where malaria has been at the late consolidation phase in China.

Malaria and its control in the People's Republic of China.

Malaria is one of the major parasitic diseases in China. During the past 40 years, large scale malaria control activities were conducted in the country relying on primary health care nets and community participation. The control of malaria was implemented according to the principles of adopting integrated measures and repeated practices which are characterized by time- and locality-oriented approaches. As a result, remarkable success has been achieved. By the end of 1990, there were 117,000 malaria cases in China, with a morbidity of 0.0106%, which dropped by 95% in comparison with that in the 1950s. Most of the original hyper-endemic areas became meso- or hypo-endemic and for most of the previously meso- or hypo-endemic areas, the disease became sporadic. Malaria distribution and epidemic patterns also demonstrated great changes. The major experience comprises the integration of the malaria control program into the overall national health program, the mobilization of various sectors, including the community, the investigators and technical personnel in research institutions and control services to participate and cooperate in solving problems and difficulties encountered.

Pigments and antibiogram of transconjugants from nonpigmented mutants of Serratia marcescens.

Serratia marcescens produces a characteristic red pigment, prodigiosin, which is formed by the enzymatic coupling of 4-methoxy-2,2'-bipyrrole-5-bipyrrole-5-carboxaldehyde (MBC) and 2-methyl-3-amylpyrrole (MAP). Many clinical isolates which are resistant to multiple antibiotics are nonpigmented. However, the relationship of pigmentation (or nonpigmentation) to drug resistance of the strains has not yet been established. In this study we demonstrated the pigment synthesizing capability in the transconjugants obtained from nonpigmented mutants WF and 9-3-3 of S. marcescens under the condition of cell-to-cell contact. Mutant WF produces MAP while mutant 9-3-3 synthesized only MBC. After genetic transfer, the color of the recombinant colonies was red indicating the successful transfer of the pigment synthesizing capability. The antibiogram of the transconjugants indicated that they inherited the resistance characteristics to polymyxin B and chloramphenicol from their parent strains. further supportive evidence was obtained by spectroscopic and high performance liquid chromatographic analysis of the resulting pigments extracted from the pigmented transconjugants. The pigments produced by the transconjugants were similar, if not identical, to those produced by the wild type strain 08 and those synthesizes syntrophically. The possibility of simultaneous transfer of pigment synthesizing capability and drug resistance remains to be explored .