目的:基于SEER数据库的宫颈癌患者影响因素分析,分析影响宫颈癌预后的相关因素,为宫颈癌患者预后恢复及治疗提供科学参考依据。方法:利用SEER数据库初步筛查宫颈癌相关数据,从中下载所有符合研究的宫颈癌患者的不同病理分型的数据,选用...目的:基于SEER数据库的宫颈癌患者影响因素分析,分析影响宫颈癌预后的相关因素,为宫颈癌患者预后恢复及治疗提供科学参考依据。方法:利用SEER数据库初步筛查宫颈癌相关数据,从中下载所有符合研究的宫颈癌患者的不同病理分型的数据,选用第八期T,N,M分期对数据的T,N,M分期进行整理,标准化,筛选,筛选条件为患者第八期T,N,M分期明确,有符合要求的观察结局,如死亡或存活。通过筛查出的患者的不同病理分型的数据,运用SPSS26.0统计软件进行统计描述,采用Kaplan-Meier法。描绘生存曲线并估计患者的生存率,死亡率。生存时间分布的组间比较采用Log-Rank检验,对分析结果中P α = 0.05,以P Objective: Study on the prognostic risk model of cervical cancer patients based on SEER database, analyze the relevant factors affecting the prognosis of cervical cancer, and provide scientific reference for the prognosis recovery and treatment of cervical cancer patients. Methods: The SEER database was used to preliminarily screen the data related to cervical cancer, download the data of different pathological types of cervical cancer patients in line with the study, and select the eighth stage T, N, M to sort out, standardize and screen the T, N and M stages of the data. The screening conditions were that the eighth stage T, N and M stages of patients were clear, and there were satisfactory observed outcomes, such as death or survival. Through the data of different pathological types of patients screened, spss26 0 statistical software for statistical description, using Kaplan Meier method. Draw the survival curve and estimate the survival rate and mortality of patients. The inter group comparison of survival time distribution adopts log rank test to conduct multi factor Cox analysis on the variables with statistical significance of P α = 0.05, P < 0.05. Result: (1) Kaplan Meier univariate analysis: different pathological stages of T stage, N stage and M stage have an impact on the survival of patients, which is statistically significant (P < 0.05), and can affect the survival of patients to varying degrees. (2) Cox multivariate analysis: T stage, N stage and M stage were independent prognostic factors affecting the survival time of patients. Conclusion: Different T, N and M pathological stages of different cervical cancer patients can affect the prognosis of cervical cancer patients to varying degrees. They have a significant impact on the mortality and survival rate of cervical cancer patients, and can provide relevant basis for the development and improvement of the treatment scheme of cervical cancer.展开更多
In order to effectively predict the fracture of AA7075-T6 sheet, the forming limit curves of AA7075-T6 high-strength sheet were drawn according to Morciniak Kuczyski (M K) model and Lou Huh criterion, respectively. Th...In order to effectively predict the fracture of AA7075-T6 sheet, the forming limit curves of AA7075-T6 high-strength sheet were drawn according to Morciniak Kuczyski (M K) model and Lou Huh criterion, respectively. The errors between the predicted values of the two theoretical prediction models and experimental values were calculated by error analysis. The forming limit curves were verified by the punch stretch test to evaluate the prediction accuracy of M K model and Lou Huh criterion. The error analysis results show that the mean error of Lou Huh criterion with the optimal parameters for all tensile specimens is 25.04%, while the mean error of M K model for all tensile specimens is 74.24%. The prediction accuracy of Lou Huh criterion in predicting the fracture of AA7075-T6 sheet is higher. The punch stretch test results show that the forming limit curve drawn by Lou Huh criterion can effectively predict the fracture of AA7075-T6 sheet, but the prediction accuracy of M K model is relatively poor.展开更多
In the era of big data,traditional statistical inference methods are faced with great challenges.Taking the two-sample distribution test scenario of big data as an example,this paper proposes the BB-KS test based on m...In the era of big data,traditional statistical inference methods are faced with great challenges.Taking the two-sample distribution test scenario of big data as an example,this paper proposes the BB-KS test based on m out of n bootstrap for solving a single-machine memory and computing constraints.It is verified to the feasibility and effectiveness of the proposed test method through theoretical analysis and numerical simulation.The results show that the BB-KS test can improve the calculation efficiency of the test to a certain extent in the single machine scenario.展开更多
RNA contains diverse post-transcriptional modifications,and its catabolic breakdown yields numerous modified nucleosides requiring correct processing,but the mechanisms remain unknown.Here,we demonstrate that three RN...RNA contains diverse post-transcriptional modifications,and its catabolic breakdown yields numerous modified nucleosides requiring correct processing,but the mechanisms remain unknown.Here,we demonstrate that three RNA-derived modified adenosines,N6-methyladenosine(m6A),N6,N6-dimethyladenosine(m6,6A),and N6-isopentenyladenosine(i6A),are sequentially metabolized into inosine monophosphate(IMP)to mitigate their intrinsic cytotoxicity.展开更多
Ménétrier disease(MD)is a rare gastric disorder characterized by hypertrophy of the gastric mucosa,resulting in giant gastric folds,excessive mucus secretion,and significant protein loss.It is most common in...Ménétrier disease(MD)is a rare gastric disorder characterized by hypertrophy of the gastric mucosa,resulting in giant gastric folds,excessive mucus secretion,and significant protein loss.It is most common in middle-aged males,although cases have also been reported in children.This condition,also known as hyperplastic hypersecretory gastropathy,primarily affects the fundus and body of the stomach,leading to protein-losing gastropathy due to increased mucosal permeability.The exact pathogenesis of MD remains unclear;however,it has been linked to excessive transforming growth factor-alpha signaling via the epidermal growth factor receptor(EGFR),which promotes mucosal hyperplasia.Clinical manifestations include epigastric pain,nausea,vomiting,anorexia,weight loss,and peripheral edema due to protein-losing enteropathy.Diagnosis is based on clinical presentation,endoscopic findings,and histopathology revealing foveolar hyperplasia and glandular atrophy.Treatment options vary from symptomatic management with proton pump inhibitors and nutritional support to monoclonal antibodies targeting EGFR(e.g.,cetuximab)in severe cases.In refractory situations,gastrectomy may be required.This review highlights the current understanding,diagnostic approaches,and therapeutic strategies for MD.展开更多
The H9N2 subtype avian influenza virus(AIV)continues to propagate and undergo evolution within China,thereby posing a significant threat to the poultry industry.This study encompassed the collection of 436 samples and...The H9N2 subtype avian influenza virus(AIV)continues to propagate and undergo evolution within China,thereby posing a significant threat to the poultry industry.This study encompassed the collection of 436 samples and swabs in East China over the period spanning 2018 to 2019,from which 31 strains of the H9N2 subtype viruses were isolated and purified.We revealed that the HA and NA genes of the 31 isolates categorized within the Y280 branch,while the PB2 and M genes were associated with the G1 branch,and the remaining genes aligned with the F/98 branch.Despite this alignment,antigenic mapping demonstrated differences between the 2018 and 2019 strains,with the early vaccine strains displaying low serological reactivity toward these isolates.Notably,the CK/SH/49/19 isolate exhibited lethality in mice,characterized by a PB2 E627V mutation and a HA deletion at amino acid position 217.Mechanistically,in vitro studies showed that the influenza virus CK/SH/49/19 carrying PB2627V and HA 217M mutations displayed enhanced replication capacity,attributed to the heightened activity of the polymerase with PB2627V.Moreover,the absence of the amino acid at the HA 217 site obstructed viral adsorption and internalization,resulted in lower activation pH,and impeded the virus budding process.Critically,in vivo experiments revealed that CK/SH/49/19(PB2627V,HA 217Δ)triggered a robust activation of interferon response and interferon-stimulated genes.This study furnished a theoretical foundation for the scientific prevention and control strategies against H9N2 subtype avian influenza.展开更多
Objectives:Epigenetic changes,particularly N6-methyladenosine(m6A)modifications,play a pivotal role in cancer development.This study explored the role of ovarian tumor deubiquitinase 7B(OTUD7B)in esophageal squamous c...Objectives:Epigenetic changes,particularly N6-methyladenosine(m6A)modifications,play a pivotal role in cancer development.This study explored the role of ovarian tumor deubiquitinase 7B(OTUD7B)in esophageal squamous cell carcinoma(ESCC)in the context of m6A methylation and the hypoxia-inducible factor-1α(HIF-1α)pathway.Methods:The GSE179267 dataset was used to conduct differential gene expression analysis to identify key m6A-enriched genes.The Cancer Genome Atlas(TCGA),Cancer Cell Line Encyclopedia(CCLE),and Sequence-based RNA Adenosine Methylation Site Predictor(SRAMP)databases were used to evaluate the expression of OTUD7B in ESCC and its correlation with methyltransferase-like 14(METTL14)and HIF-1α.The m6A content in total RNA extracted from ESCC cells was assessed using a dot blot assay.Gene-specific m6A-PCR was used to quantify m6A modifications in OTUD7B mRNA.The functional role of OTUD7B was explored using clonogenic and Transwell assays.The effect of OTUD7B on HIF-1αubiquitination was detected using a co-immunoprecipitation assay.Results:OTUD7B was identified as a pivotal m6A-driven oncogene correlated with METTL14 and HIF-1α.METTL14 enhanced the mRNA stability and expression of OTUD7B through m6A methylation.OTUD7B overexpression counteracted the inhibitory effects of METTL14 knockdown on cell proliferation and invasion and stabilized HIF-1αby promoting deubiquitination.Conclusion:METTL14 plays a crucial role in the stabilization of OTUD7B through m6A methylation,thereby inhibiting the ubiquitin-proteasomal degradation of HIF-1αin ESCC.These findings highlight the potential of targeting the METTL14-OTUD7B axis as a therapeutic strategy for ESCC.展开更多
Background:Expression of mRNA is widely regulated by N6-methyladenosine(m6A).An increasing number of studies have shown that m6A methylation,facilitated by methyltransferase 3(METTL3),is crucial in the progression of ...Background:Expression of mRNA is widely regulated by N6-methyladenosine(m6A).An increasing number of studies have shown that m6A methylation,facilitated by methyltransferase 3(METTL3),is crucial in the progression of tumors.Previous reports have indicated the involvement of both METTL3 and c-Src kinase in the evolution of liver cancer.However,the potential connection between c-Src and the METTL3-mediated mechanism in liver cancer progression remains elusive.Methods:The correlation expression between c-Src and METTL3 between liver cancer patients and the control group was analyzed using the TCGA database,and was further demonstrated by Western blot and RT-qPCR.The functional roles of c-Src in METTL3-regulated liver cancer progression were investigated by cell proliferation assays and colony formation assays.The regulatory mechanism of METTL3 in c-Src expression was accessed by RNA-immunoprecipitation(RIP)-qPCR.Results:We demonstrated that c-Src kinase promoted liver cancer development,and the expression of SRC(encodes c-Src kinase)was positively correlated with METTL3 in liver cancer cases.We showed that SRC mRNA could be m6A-modified,and METTL3 regulated the transcription of SRC mRNA through interferon regulatory factor 1(IRF1).We revealed that IRF1,the expression of which was positively regulated byMETTL3,was a novel transcription factor of c-Src.Lastly,The pro-proliferative effect of METTL3 on hepatocellular carcinoma was mechanistically linked to IRF1/c-Src axis activation,as evidenced by our experimental data.Conclusion:Results suggested that the METTL3/IRF1/c-Src axis played potential oncogenic roles in liver cancer development and the axis may be a promising therapeutic target in the disease.展开更多
文摘目的:基于SEER数据库的宫颈癌患者影响因素分析,分析影响宫颈癌预后的相关因素,为宫颈癌患者预后恢复及治疗提供科学参考依据。方法:利用SEER数据库初步筛查宫颈癌相关数据,从中下载所有符合研究的宫颈癌患者的不同病理分型的数据,选用第八期T,N,M分期对数据的T,N,M分期进行整理,标准化,筛选,筛选条件为患者第八期T,N,M分期明确,有符合要求的观察结局,如死亡或存活。通过筛查出的患者的不同病理分型的数据,运用SPSS26.0统计软件进行统计描述,采用Kaplan-Meier法。描绘生存曲线并估计患者的生存率,死亡率。生存时间分布的组间比较采用Log-Rank检验,对分析结果中P α = 0.05,以P Objective: Study on the prognostic risk model of cervical cancer patients based on SEER database, analyze the relevant factors affecting the prognosis of cervical cancer, and provide scientific reference for the prognosis recovery and treatment of cervical cancer patients. Methods: The SEER database was used to preliminarily screen the data related to cervical cancer, download the data of different pathological types of cervical cancer patients in line with the study, and select the eighth stage T, N, M to sort out, standardize and screen the T, N and M stages of the data. The screening conditions were that the eighth stage T, N and M stages of patients were clear, and there were satisfactory observed outcomes, such as death or survival. Through the data of different pathological types of patients screened, spss26 0 statistical software for statistical description, using Kaplan Meier method. Draw the survival curve and estimate the survival rate and mortality of patients. The inter group comparison of survival time distribution adopts log rank test to conduct multi factor Cox analysis on the variables with statistical significance of P α = 0.05, P < 0.05. Result: (1) Kaplan Meier univariate analysis: different pathological stages of T stage, N stage and M stage have an impact on the survival of patients, which is statistically significant (P < 0.05), and can affect the survival of patients to varying degrees. (2) Cox multivariate analysis: T stage, N stage and M stage were independent prognostic factors affecting the survival time of patients. Conclusion: Different T, N and M pathological stages of different cervical cancer patients can affect the prognosis of cervical cancer patients to varying degrees. They have a significant impact on the mortality and survival rate of cervical cancer patients, and can provide relevant basis for the development and improvement of the treatment scheme of cervical cancer.
基金Project (51775481) supported by the National Natural Science Foundation of ChinaProject (E2019203418) supported by the Natural Science Foundation of Hebei Province, ChinaProject (ZD2017078) supported by the Science and Technology Plan of Hebei Higher School of Education Department, China。
文摘In order to effectively predict the fracture of AA7075-T6 sheet, the forming limit curves of AA7075-T6 high-strength sheet were drawn according to Morciniak Kuczyski (M K) model and Lou Huh criterion, respectively. The errors between the predicted values of the two theoretical prediction models and experimental values were calculated by error analysis. The forming limit curves were verified by the punch stretch test to evaluate the prediction accuracy of M K model and Lou Huh criterion. The error analysis results show that the mean error of Lou Huh criterion with the optimal parameters for all tensile specimens is 25.04%, while the mean error of M K model for all tensile specimens is 74.24%. The prediction accuracy of Lou Huh criterion in predicting the fracture of AA7075-T6 sheet is higher. The punch stretch test results show that the forming limit curve drawn by Lou Huh criterion can effectively predict the fracture of AA7075-T6 sheet, but the prediction accuracy of M K model is relatively poor.
文摘In the era of big data,traditional statistical inference methods are faced with great challenges.Taking the two-sample distribution test scenario of big data as an example,this paper proposes the BB-KS test based on m out of n bootstrap for solving a single-machine memory and computing constraints.It is verified to the feasibility and effectiveness of the proposed test method through theoretical analysis and numerical simulation.The results show that the BB-KS test can improve the calculation efficiency of the test to a certain extent in the single machine scenario.
文摘RNA contains diverse post-transcriptional modifications,and its catabolic breakdown yields numerous modified nucleosides requiring correct processing,but the mechanisms remain unknown.Here,we demonstrate that three RNA-derived modified adenosines,N6-methyladenosine(m6A),N6,N6-dimethyladenosine(m6,6A),and N6-isopentenyladenosine(i6A),are sequentially metabolized into inosine monophosphate(IMP)to mitigate their intrinsic cytotoxicity.
文摘Ménétrier disease(MD)is a rare gastric disorder characterized by hypertrophy of the gastric mucosa,resulting in giant gastric folds,excessive mucus secretion,and significant protein loss.It is most common in middle-aged males,although cases have also been reported in children.This condition,also known as hyperplastic hypersecretory gastropathy,primarily affects the fundus and body of the stomach,leading to protein-losing gastropathy due to increased mucosal permeability.The exact pathogenesis of MD remains unclear;however,it has been linked to excessive transforming growth factor-alpha signaling via the epidermal growth factor receptor(EGFR),which promotes mucosal hyperplasia.Clinical manifestations include epigastric pain,nausea,vomiting,anorexia,weight loss,and peripheral edema due to protein-losing enteropathy.Diagnosis is based on clinical presentation,endoscopic findings,and histopathology revealing foveolar hyperplasia and glandular atrophy.Treatment options vary from symptomatic management with proton pump inhibitors and nutritional support to monoclonal antibodies targeting EGFR(e.g.,cetuximab)in severe cases.In refractory situations,gastrectomy may be required.This review highlights the current understanding,diagnostic approaches,and therapeutic strategies for MD.
基金supported by National Natural Science Foundation of China[Grant number:32272992(JP),31772775(JP)]National Key Research and Development Program of China[Grant number:2021YFD1800205(JP)].
文摘The H9N2 subtype avian influenza virus(AIV)continues to propagate and undergo evolution within China,thereby posing a significant threat to the poultry industry.This study encompassed the collection of 436 samples and swabs in East China over the period spanning 2018 to 2019,from which 31 strains of the H9N2 subtype viruses were isolated and purified.We revealed that the HA and NA genes of the 31 isolates categorized within the Y280 branch,while the PB2 and M genes were associated with the G1 branch,and the remaining genes aligned with the F/98 branch.Despite this alignment,antigenic mapping demonstrated differences between the 2018 and 2019 strains,with the early vaccine strains displaying low serological reactivity toward these isolates.Notably,the CK/SH/49/19 isolate exhibited lethality in mice,characterized by a PB2 E627V mutation and a HA deletion at amino acid position 217.Mechanistically,in vitro studies showed that the influenza virus CK/SH/49/19 carrying PB2627V and HA 217M mutations displayed enhanced replication capacity,attributed to the heightened activity of the polymerase with PB2627V.Moreover,the absence of the amino acid at the HA 217 site obstructed viral adsorption and internalization,resulted in lower activation pH,and impeded the virus budding process.Critically,in vivo experiments revealed that CK/SH/49/19(PB2627V,HA 217Δ)triggered a robust activation of interferon response and interferon-stimulated genes.This study furnished a theoretical foundation for the scientific prevention and control strategies against H9N2 subtype avian influenza.
基金funded by the Doctoral Research Start-up Fund Project at Changzhi Medical College(grant number BS202118)Sichuan Science and Technology Program(grant number 2022YFS0631)Scientific and Technological Innovation Programs ofHigher Education Institutions in Shanxi(grant number 2021L348).
文摘Objectives:Epigenetic changes,particularly N6-methyladenosine(m6A)modifications,play a pivotal role in cancer development.This study explored the role of ovarian tumor deubiquitinase 7B(OTUD7B)in esophageal squamous cell carcinoma(ESCC)in the context of m6A methylation and the hypoxia-inducible factor-1α(HIF-1α)pathway.Methods:The GSE179267 dataset was used to conduct differential gene expression analysis to identify key m6A-enriched genes.The Cancer Genome Atlas(TCGA),Cancer Cell Line Encyclopedia(CCLE),and Sequence-based RNA Adenosine Methylation Site Predictor(SRAMP)databases were used to evaluate the expression of OTUD7B in ESCC and its correlation with methyltransferase-like 14(METTL14)and HIF-1α.The m6A content in total RNA extracted from ESCC cells was assessed using a dot blot assay.Gene-specific m6A-PCR was used to quantify m6A modifications in OTUD7B mRNA.The functional role of OTUD7B was explored using clonogenic and Transwell assays.The effect of OTUD7B on HIF-1αubiquitination was detected using a co-immunoprecipitation assay.Results:OTUD7B was identified as a pivotal m6A-driven oncogene correlated with METTL14 and HIF-1α.METTL14 enhanced the mRNA stability and expression of OTUD7B through m6A methylation.OTUD7B overexpression counteracted the inhibitory effects of METTL14 knockdown on cell proliferation and invasion and stabilized HIF-1αby promoting deubiquitination.Conclusion:METTL14 plays a crucial role in the stabilization of OTUD7B through m6A methylation,thereby inhibiting the ubiquitin-proteasomal degradation of HIF-1αin ESCC.These findings highlight the potential of targeting the METTL14-OTUD7B axis as a therapeutic strategy for ESCC.
基金supported by Natural Science Foundation of Hunan Province of China(project No.2022JJ40413)Outstanding Youth Project of Hunan Provincial Department of Education(project No.22B0814)+1 种基金Regional Consolidated Foundation ofHunan Province of China(project No.2023JJ50065)Natural Science Foundation of Hunan Province of China(project No.2023JJ50412).
文摘Background:Expression of mRNA is widely regulated by N6-methyladenosine(m6A).An increasing number of studies have shown that m6A methylation,facilitated by methyltransferase 3(METTL3),is crucial in the progression of tumors.Previous reports have indicated the involvement of both METTL3 and c-Src kinase in the evolution of liver cancer.However,the potential connection between c-Src and the METTL3-mediated mechanism in liver cancer progression remains elusive.Methods:The correlation expression between c-Src and METTL3 between liver cancer patients and the control group was analyzed using the TCGA database,and was further demonstrated by Western blot and RT-qPCR.The functional roles of c-Src in METTL3-regulated liver cancer progression were investigated by cell proliferation assays and colony formation assays.The regulatory mechanism of METTL3 in c-Src expression was accessed by RNA-immunoprecipitation(RIP)-qPCR.Results:We demonstrated that c-Src kinase promoted liver cancer development,and the expression of SRC(encodes c-Src kinase)was positively correlated with METTL3 in liver cancer cases.We showed that SRC mRNA could be m6A-modified,and METTL3 regulated the transcription of SRC mRNA through interferon regulatory factor 1(IRF1).We revealed that IRF1,the expression of which was positively regulated byMETTL3,was a novel transcription factor of c-Src.Lastly,The pro-proliferative effect of METTL3 on hepatocellular carcinoma was mechanistically linked to IRF1/c-Src axis activation,as evidenced by our experimental data.Conclusion:Results suggested that the METTL3/IRF1/c-Src axis played potential oncogenic roles in liver cancer development and the axis may be a promising therapeutic target in the disease.
