The mechanism of radiotherapy or chemotherapy-induced oral mucositis is not yet clear.And model establishment is needed in further study.In order to summarize the methods of model establishment and make a comparison,l...The mechanism of radiotherapy or chemotherapy-induced oral mucositis is not yet clear.And model establishment is needed in further study.In order to summarize the methods of model establishment and make a comparison,literature databases including Web of Science、Pubmed and CNKI were searched for related researches from January 2015 to January 2021.Hamsters,mice,rats,guinea pigs and miniature pigs were chosen to be modeling animals and modeling methods could be classified into:chemotherapy,chemotherapy combined with superficial mucosal irritation,radiotherapy,radiotherapy combined with superficial mucosal irritation and chemoradiotherapy.Advantages and disadvantages had been analyzed in this study to provide reference for following studies.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the crit...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.展开更多
Background A series of public health preventive measures has been widely implemented in Beijing to control the corona-virus disease-19(COVID-19)pandemic since January 2020.An evaluation of the effects of these prevent...Background A series of public health preventive measures has been widely implemented in Beijing to control the corona-virus disease-19(COVID-19)pandemic since January 2020.An evaluation of the effects of these preventive measures on the spread of other respiratory viruses is necessary.Methods Respiratory specimens collected from children with acute respiratory infections were tested by NxTAGTN,respiratory pathogen panel assays during January 2017 and December 2020.Specimens characterized as rhinoviruses(RVs)were sequenced to identify the RV species and types.Then,the epidemiology results of respiratory pathogens in 2020 were compared with those from 2017 to 2019 using SPSS statistics 22.0.Results The positive rates of adenovirus(ADV),influenza virus(flu),RVs,and respiratory syncytial virus(RSV)dropped abruptly by 86.31%,94.679c,94.59%,and 92.17%,respectively,from February to May 2020,compared with the average level in the same period during 2017-2019.Positive rates of RVs then steeply increased from June 2020(13.77%),to an apex(37.25%)in August 2020,significantly higher than the average rates(22.51%)in August 2017-2019(7^=0.005).The increase,especially in group>3 years,was accompanied by the reopening of schools and kindergartens after the 23rd and 24th week of 2020 in Beijing.Conclusions Whereas the abrupt drop in viral pathogen positive rates from February to May 2020 revealed the remarkable effects of the COVID-19 preventive measures,the sharp increase in positive rates of RVs from the 23rd week of 2020 might be explained by the reopening of schools and kindergartens in Beijing.展开更多
Background:Patients carrying the HongKongαα(HKαα)allele and-α3.7/αααanti-4.2 could be misdiagnosed as-α3.7/ααby the current conventional thalassemia detection methods,leading to inaccurate genetic counselin...Background:Patients carrying the HongKongαα(HKαα)allele and-α3.7/αααanti-4.2 could be misdiagnosed as-α3.7/ααby the current conventional thalassemia detection methods,leading to inaccurate genetic counseling and an incorrect prenatal diagnosis.This study was aimed to accurately analyze the genotypes of HKααcarriers and-α3.7/αααanti-4.2.Methods::Samples were collected in our hospital from July 2017 to October 2019.Twenty-four common types of Chinese thalassemia were screened by gap-polymerase chain reaction(Gap-PCR)and reverse dot blot(RDB).Anti-4.2 multiplex-PCR was used to confirm carriers of theαααanti-4.2 duplication with-α3.7 deletion.Two-round nested PCR and multiplex ligation-dependent probe amplification(MLPA)were applied to accurately identify and confirm their genotypes.For data analysis,we used descriptive statistics and Fisher’s exact tests.Results::Two thousand five hundred and forty-four cases were identified as thalassemia in 5488 peripheral blood samples.The results showed thatα,β,andαβcompound thalassemia were identified in 1190(46.78%),1286(50.55%),and 68(2.67%)cases,respectively.A total of 227 samples from thalassemia patients were identified as-α3.7/ααby Gap-PCR,and the genotypes of two samples were uncertain.There was a difference between Gap-PCR and combined groups(Gap-PCR combined with nested PCR and MLPA)in detecting HKαα(P<0.05).Among the 229 patients,20 patients were identified as HKααcarriers and one was identified as-α3.7/ααα anti-4.2 by two-round nested PCR and MLPA,including 15 patients with HKαα/αα,three with HKαα/αα and β-thalassemia coinheritance,one with HKαα/-SEA,one with HKαα/-α4.2 andβ-thalassemia coinheritance,and one with-α3.7/αααanti-4.2 and β-thalassemia coinheritance.Conclusions::αααanti-4.2 and HKααgenotypes of patients carrying-α3.7 need to be detected to reduce the misdiagnosis rate of patients carrying HKααand-α3.7/αααanti-4.2 alleles.More accurate genetic counseling can be provided in the clinic using nested PCR combined with MLPA.展开更多
Neuroscientists have emphasized visceral influences on consciousness and attention,but the potential neurophysiological pathways remain under exploration.Here,we found two neurophysiological pathways of heartbrain int...Neuroscientists have emphasized visceral influences on consciousness and attention,but the potential neurophysiological pathways remain under exploration.Here,we found two neurophysiological pathways of heartbrain interaction based on the relationship between oxygen-transport by red blood cells(RBCs)and consciousness/attention.To this end,we collected a dataset based on the routine physical examination,the breaking continuous flash suppression(b-CFS)paradigm,and an attention network test(ANT)in 140 immigrants under the hypoxic Tibetan environment.We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention.The results showed that RBC function,via two independent neurophysiological pathways,not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control.Importantly,consciousness played a fundamental role in executive function which might be associated with the level of perceived stress.These results indicated the important role of oxygen-transport in heart-brain interactions,in which the related stress response affected consciousness and executive control.The findings provide new insights into the neurophysiological schema of heartbrain interactions.展开更多
In the article titled,"Diagnosis of the accurate genotype of HKaa carriers in patients with thalassemia using multiplex ligation-dependent probe amplification combined with nested polymerase chain reaction"p...In the article titled,"Diagnosis of the accurate genotype of HKaa carriers in patients with thalassemia using multiplex ligation-dependent probe amplification combined with nested polymerase chain reaction"published in pages 1175-1181,Issue 10,Vol.133 of Chinese Medical Journal,the author and aliation section should be corrected as follows.展开更多
Objective:The aim is to study the effects of metformin on the expression of 70 kDa ribosomal protein S6 kinase(P70S6k),insulin receptor substrate 1(IRS-1),and IRS-1Ser307 phosphorylation in human luteinized granulosa ...Objective:The aim is to study the effects of metformin on the expression of 70 kDa ribosomal protein S6 kinase(P70S6k),insulin receptor substrate 1(IRS-1),and IRS-1Ser307 phosphorylation in human luteinized granulosa cells.Methods:Granulosa cells in the experimental group were cultured in M199 medium containing 0.1 mmol/L metformin for 24 h and those in control group were cultured in M199 medium.The expression levels of P70S6k and IRS-1 mRNA were detected by reverse-transcriptiom polymerase chain reaction(RT-PCR)and real-time PCR.P70S6k,IRS-1,p-ser307-IRS-1,and p-thr389-P70S6k protein expression levels were detected by immunofluorescence and western blotting.Results:P70S6k mRNA level was higher and IRS-1 was significantly lower in the experimental group than those in the control group.IRS-1 and p-ser307-IRS-1 were expressed in cell plasma,and P70S6k and p-thr389-P70S6k were expressed in cell nucleus.The results of Western blot analysis indicated that the expression levels of P70S6k,p-thr389-P70S6k,IRS-1,and p-ser307-IRS-1 proteins had significant difference between the experimental group and the control group.Compared to the control group,the relative intensity illustrated that the expression levels of P70S6K and p-thr389-P70S6k significantly increased in the experimental group;however,those of IRS-1 and p-ser307-IRS-1 proteins significantly decreased.Conclusion:Metformin can inhibit the P70S6k mRNA and protein expression levels in the granulosa cells and improve insulin sensitivity by regulating IRS-1 expression through Akt/P70S6k/IRS-1-dependent pathway.展开更多
基金National Natural Science Foundation of China(No.81973693)。
文摘The mechanism of radiotherapy or chemotherapy-induced oral mucositis is not yet clear.And model establishment is needed in further study.In order to summarize the methods of model establishment and make a comparison,literature databases including Web of Science、Pubmed and CNKI were searched for related researches from January 2015 to January 2021.Hamsters,mice,rats,guinea pigs and miniature pigs were chosen to be modeling animals and modeling methods could be classified into:chemotherapy,chemotherapy combined with superficial mucosal irritation,radiotherapy,radiotherapy combined with superficial mucosal irritation and chemoradiotherapy.Advantages and disadvantages had been analyzed in this study to provide reference for following studies.
基金Supported by National Natural Foundation of China,No.821742232019 Chinese and Western Medicine Clinical Collaborative Capacity Building Project for Major Difficult Diseases,No.2019-ZX-005。
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.
基金This work was supported by grants from The Pediatric Medical Coordinated Development Center of the Beijing Hospitals Authority(No.XTZD20180505)Beijing Municipal Commission of Health and Family(No.2060399 PXM2017_026268_00005_00254486).
文摘Background A series of public health preventive measures has been widely implemented in Beijing to control the corona-virus disease-19(COVID-19)pandemic since January 2020.An evaluation of the effects of these preventive measures on the spread of other respiratory viruses is necessary.Methods Respiratory specimens collected from children with acute respiratory infections were tested by NxTAGTN,respiratory pathogen panel assays during January 2017 and December 2020.Specimens characterized as rhinoviruses(RVs)were sequenced to identify the RV species and types.Then,the epidemiology results of respiratory pathogens in 2020 were compared with those from 2017 to 2019 using SPSS statistics 22.0.Results The positive rates of adenovirus(ADV),influenza virus(flu),RVs,and respiratory syncytial virus(RSV)dropped abruptly by 86.31%,94.679c,94.59%,and 92.17%,respectively,from February to May 2020,compared with the average level in the same period during 2017-2019.Positive rates of RVs then steeply increased from June 2020(13.77%),to an apex(37.25%)in August 2020,significantly higher than the average rates(22.51%)in August 2017-2019(7^=0.005).The increase,especially in group>3 years,was accompanied by the reopening of schools and kindergartens after the 23rd and 24th week of 2020 in Beijing.Conclusions Whereas the abrupt drop in viral pathogen positive rates from February to May 2020 revealed the remarkable effects of the COVID-19 preventive measures,the sharp increase in positive rates of RVs from the 23rd week of 2020 might be explained by the reopening of schools and kindergartens in Beijing.
基金This work was supported by a grant from the Department of Science and Technology of Sichuan province,China(No.30504010332).
文摘Background:Patients carrying the HongKongαα(HKαα)allele and-α3.7/αααanti-4.2 could be misdiagnosed as-α3.7/ααby the current conventional thalassemia detection methods,leading to inaccurate genetic counseling and an incorrect prenatal diagnosis.This study was aimed to accurately analyze the genotypes of HKααcarriers and-α3.7/αααanti-4.2.Methods::Samples were collected in our hospital from July 2017 to October 2019.Twenty-four common types of Chinese thalassemia were screened by gap-polymerase chain reaction(Gap-PCR)and reverse dot blot(RDB).Anti-4.2 multiplex-PCR was used to confirm carriers of theαααanti-4.2 duplication with-α3.7 deletion.Two-round nested PCR and multiplex ligation-dependent probe amplification(MLPA)were applied to accurately identify and confirm their genotypes.For data analysis,we used descriptive statistics and Fisher’s exact tests.Results::Two thousand five hundred and forty-four cases were identified as thalassemia in 5488 peripheral blood samples.The results showed thatα,β,andαβcompound thalassemia were identified in 1190(46.78%),1286(50.55%),and 68(2.67%)cases,respectively.A total of 227 samples from thalassemia patients were identified as-α3.7/ααby Gap-PCR,and the genotypes of two samples were uncertain.There was a difference between Gap-PCR and combined groups(Gap-PCR combined with nested PCR and MLPA)in detecting HKαα(P<0.05).Among the 229 patients,20 patients were identified as HKααcarriers and one was identified as-α3.7/ααα anti-4.2 by two-round nested PCR and MLPA,including 15 patients with HKαα/αα,three with HKαα/αα and β-thalassemia coinheritance,one with HKαα/-SEA,one with HKαα/-α4.2 andβ-thalassemia coinheritance,and one with-α3.7/αααanti-4.2 and β-thalassemia coinheritance.Conclusions::αααanti-4.2 and HKααgenotypes of patients carrying-α3.7 need to be detected to reduce the misdiagnosis rate of patients carrying HKααand-α3.7/αααanti-4.2 alleles.More accurate genetic counseling can be provided in the clinic using nested PCR combined with MLPA.
基金supported by the National Natural Science Foundation of China(31660274,31771247,and 31600907)the Reformation and Development Funds for Local Region Universities from the Chinese Government in 2020(00060607,ZCJK 2020-11).
文摘Neuroscientists have emphasized visceral influences on consciousness and attention,but the potential neurophysiological pathways remain under exploration.Here,we found two neurophysiological pathways of heartbrain interaction based on the relationship between oxygen-transport by red blood cells(RBCs)and consciousness/attention.To this end,we collected a dataset based on the routine physical examination,the breaking continuous flash suppression(b-CFS)paradigm,and an attention network test(ANT)in 140 immigrants under the hypoxic Tibetan environment.We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention.The results showed that RBC function,via two independent neurophysiological pathways,not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control.Importantly,consciousness played a fundamental role in executive function which might be associated with the level of perceived stress.These results indicated the important role of oxygen-transport in heart-brain interactions,in which the related stress response affected consciousness and executive control.The findings provide new insights into the neurophysiological schema of heartbrain interactions.
文摘In the article titled,"Diagnosis of the accurate genotype of HKaa carriers in patients with thalassemia using multiplex ligation-dependent probe amplification combined with nested polymerase chain reaction"published in pages 1175-1181,Issue 10,Vol.133 of Chinese Medical Journal,the author and aliation section should be corrected as follows.
基金supported by the Science Technology Research Project of Higher Education of Ningxia Province(NGY2016125)the Open Project of Key Laboratory of Fertility Preservation and Maintenance,Ministry of Education(XY201518)。
文摘Objective:The aim is to study the effects of metformin on the expression of 70 kDa ribosomal protein S6 kinase(P70S6k),insulin receptor substrate 1(IRS-1),and IRS-1Ser307 phosphorylation in human luteinized granulosa cells.Methods:Granulosa cells in the experimental group were cultured in M199 medium containing 0.1 mmol/L metformin for 24 h and those in control group were cultured in M199 medium.The expression levels of P70S6k and IRS-1 mRNA were detected by reverse-transcriptiom polymerase chain reaction(RT-PCR)and real-time PCR.P70S6k,IRS-1,p-ser307-IRS-1,and p-thr389-P70S6k protein expression levels were detected by immunofluorescence and western blotting.Results:P70S6k mRNA level was higher and IRS-1 was significantly lower in the experimental group than those in the control group.IRS-1 and p-ser307-IRS-1 were expressed in cell plasma,and P70S6k and p-thr389-P70S6k were expressed in cell nucleus.The results of Western blot analysis indicated that the expression levels of P70S6k,p-thr389-P70S6k,IRS-1,and p-ser307-IRS-1 proteins had significant difference between the experimental group and the control group.Compared to the control group,the relative intensity illustrated that the expression levels of P70S6K and p-thr389-P70S6k significantly increased in the experimental group;however,those of IRS-1 and p-ser307-IRS-1 proteins significantly decreased.Conclusion:Metformin can inhibit the P70S6k mRNA and protein expression levels in the granulosa cells and improve insulin sensitivity by regulating IRS-1 expression through Akt/P70S6k/IRS-1-dependent pathway.
