Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor

BACKGROUND Targeting DNA damage response(DDR)pathway is a cutting-edge strategy.It has been reported that Schlafen-11(SLFN11)contributes to increase chemosensitivity by participating in DDR.However,the detailed mechanism is unclear.AIM To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 defects.METHODS To reach the purpose,eight esophageal squamous carcinoma cell lines,142 esophageal dysplasia(ED)and 1007 primary esophageal squamous cell carcinoma(ESCC)samples and various techniques were utilized,including methylationspecific polymerase chain reaction,CRISPR/Cas9 technique,Western blot,colony formation assay,and xenograft mouse model.RESULTS Methylation of SLFN11 was exhibited in 9.15%of(13/142)ED and 25.62%of primary(258/1007)ESCC cases,and its expression was regulated by promoter region methylation.SLFN11 methylation was significantly associated with tumor differentiation and tumor size(both P<0.05).However,no significant associations were observed between promoter region methylation and age,gender,smoking,alcohol consumption,TNM stage,or lymph node metastasis.Utilizing DNA damaged model induced by low dose cisplatin,SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways,while inhibiting the ATM/CHK2 signaling pathway.Epigenetic silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor(AZD0156),both in vitro and in vivo.CONCLUSION SLFN11 is frequently methylated in human ESCC.Methylation of SLFN11 is sensitive marker of ATM inhibitor in ESCC.

Testis-specific Fankl gene in knockdown mice produces oligospermia via apoptosis

Fankl is exclusively expressed in the testis from the meiosis phase to the haploid phase of spermatogenesis. In this study, we examined the function of Fankl by establishing a Fankl-knockdown transgenic mouse model. The apoptotic statuses of the testes of the transgenic mice were tested using the terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） method. The FANK1 consensus DNA-binding sequence was identified using cyclic amplification of sequence target （CAST） analysis. Differentially expressed genes were examined using microarray analysis. A reduction in sperm number and an increase in apoptotic spermatocytes were observed in Fankl-knockdown mice, and the apoptotic cells were found to be primarily spermatogonia and spermatocytes. The CAST results demonstrated that the consensus DNA-binding sequence was AAAAAG, in which the percentage occurrence of each base at each position ranged from 55 to 86%. This sequence was present in the promoter regions of 10 differentially expressed genes that were examined using microarray analysis. In total, 17 genes were differentially expressed with changes in their expression levels greater than twofold. The abnormal expression of Fankl target genes that were regulated directly or indirectly by Fankl reduced the number of sperm in the knockdown mice. Thus, FANK1 may Dlav a pivotal role in sDermato^enesis as a transcription factor.Fankl is exclusively expressed in the testis from the meiosis phase to the haploid phase of spermatogenesis. In this study, we examined the function of Fankl by establishing a Fankl-knockdown transgenic mouse model. The apoptotic statuses of the testes of the transgenic mice were tested using the terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） method. The FANK1 consensus DNA-binding sequence was identified using cyclic amplification of sequence target （CAST） analysis. Differentially expressed genes were examined using microarray analysis, A reduction in sperm number and an increase in apoptotic spermatocytes were observed in Fankl-knockdown mice, and the apoptotic cells were found to be primarily spermatogonia and spermatocytes. The CAST results demonstrated that the consensus DNA-binding sequence was AAAAAG, in which the percentage occurrence of each base at each position ranged from 55 to 86%. This sequence was present in the promoter regions of 10 differentially expressed genes that were examined using microarray analysis. In total, 17 genes were differentially expressed with changes in their expression levels greater than twofold. The abnormal expression of Fankl target genes that were regulated directly or indirectly by Fankl reduced the number of sperm in the knockdown mice. Thus, FANK1 may play a pivotal role in spermatogenesis as a transcription factor.

Efficacy of different antibiotics in treatment of children with respiratory mycoplasma infection

BACKGROUND Respiratory infections in children are common pediatric diseases caused by pathogens that invade the respiratory system.Children are considerably susceptible to Mycoplasma pneumoniae infection.There has been widespread clinical attention on treatment strategies for this disease.AIM To analyze the clinical efficacy of different antibiotics in treating pediatric respiratory mycoplasma infections.METHODS We included 106 children with a confirmed diagnosis of respiratory mycoplasma infection who were admitted to our hospital from April 2017 to July 2019 and grouped them using a random number table.Among them,53 children each received clarithromycin or erythromycin.The clinical efficacy of both drugs was evaluated and compared.We performed the multiplex polymerase chain reaction(MP-PCR)test and determined the MP-PCR negative rate in children after the end of the treatment course.We compared the incidence of toxic and side effects,including nausea,diarrhea,and abdominal pain;further,we recorded the length of hospitalization,antipyretic time,and drug costs.Additionally,we evaluated and compared the compliance of the children during treatment.RESULTS The erythromycin group showed a significantly higher total effective rate of clinical treatment than the clarithromycin group.MP-PCR test results showed that the clarithromycin group had a significantly higher MP-PCR negative rate than the erythromycin group.Moreover,children in the clarithromycin group had shorter fever time,shorter hospital stays,and lower drug costs than those in the erythromycin group.The clarithromycin group had a significantly higher overall drug adherence rate than the erythromycin group.The incidence of toxic and side effects was significantly lower in the clarithromycin group than in the erythromycin group(P<0.05).CONCLUSION Our findings indicate that clarithromycin has various advantages over erythromycin,including higher application safety,stronger mycoplasma clearance,and higher medication compliance in children;therefore,it can be actively promoted.

Prediction of syphilis incident rate and number in China based on the GM(1,1)grey model

Objective:To explore the feasibility of using grey model GM(1,1)model to predict syphilis,and to provide a theoretical basis for the health sector to develop corresponding strategies.Methods:GM(1,1)model was used to construct and simulate the incident rate and case number of syphilis in China from 2009 to 2018 to predict the change trend.Results:The GM(1,1)prediction model of syphilis incident rate was x^(1)(k+1)=929.367901 e(0.029413k)-906.297901.The GM(1,1)prediction model for the number of syphilis patients was x^(1)(k+1)=1060.278025 e(0.034280k)-1029.639925.For syphilis incidence model,the posterior difference ratio was 0.19819 and the probability of small error was 1.For the syphilis incident number model,the posterior difference ratio was 0.18450 and the probability of small error was 1.The above models have good fitting accuracy with excellent grade level and can be predicted by extrapolation and predicted that the syphilis incidence in 2019-2021 may be 36.15 per 100,000,37.23 per 100,000 and 38.34 per 100,000,respectively.From 2019 to 2021,the number of incident syphilis cases in China may be 503,406,520,962 and 539,130,respectively.Conclusion:The GM(1,1)model can well fit and predict the change trend of syphilis incidence in time series.The prediction model showed that the incidence of syphilis may continue to increase and the number of syphilis cases per year may continue to increase substantially.More effort is needed to strengthen the prevention and treatment of venereal disease,reduce venereal harm to the population and improve the early detection rate of syphilis.

Immune Responses and Histopathological Changes in Rabbits Immunized with Inactivated SARS Coronavirus

To evaluate the immunogenicity of inactivated SARS coronavirus(SARS-CoV),three groups of rabbits were immunized three times at 2-week intervals with inactivated vaccine + adjuvant,adjuvant,and normal saline respectively.Eight batchs of serum were sampled from the auricular vein at day 7 to day 51,and specific IgG antibody titers and neutralizing antibody titers were detected by indirect ELISA and micro-cytopathic effect neutralizing test.Antibody specificity was identified by proteinchip assay.Histopathological changes were detected by H&E staining.The results showed that,rabbits in the experimental group immunized with inactivated SARS-CoV all generated specific IgG antibodies with neutralizing activity,which suggested the inactivated SARS-CoV could preserve its antigenicity well and elicit an effective humoral immune responses.The peak titer value of specific IgG antibody and neutralizing antibody reached 1:40960 and 1:2560 respectively.In the experimental group,no obvious histopathological changes was detected in the H&E stained slides of heart,spleen,kidney and testis samples,but the livers had slight histopathological changes,and the lungs presented remarkable histopathological changes.These findings are of importance for SARS-CoV inactivated vaccine development.

The incidence and prediction of tuberculosis in China

Objective:To explore the incidence trend of tuberculosis in China from 2009 to 2018,and make a short-term prediction,so as to provide reference for scientific formulation of prevention and control measures for tuberculosis and rational allocation of control and prevention resources.Methods:The grey model GM(1,1)model was used to build and predict the incidence of tuberculosis in China by extracting the data from 2009 to 2018 from the Statistical Yearbook of China.Results:The GM(1,1)prediction model was established to predict the incidence of tuberculosis.The GM(1,1)prediction model for tuberculosis incidence was x^(1)(k+1)=-2572.122087 e(-0.029096k)+2653.212087.The grey GM(1,1)prediction model for pulmonary tuberculosis case number was x^(1)(k+1)=-4092.009372 e(-0.024334k)+4199.703172.The above two models with high fitting accuracy were used to predict that the incidence of tuberculosis in 2019-2021 would be 56.77/100,000,55.14/100,000 and 53.56/100,000,respectively.The model predicted that the number of incident tuberculosis cases may be 790,242,771,245 and 752,704 from 2019 to 2021 in China,respectively.Conclusion:The projection shows that the incidence of tuberculosis may decrease,but the annual incident number of tuberculosis is still very high.We should continue to strengthen the prevention and standardized treatment of tuberculosis,and improve the early detection and treatment rates.