Ammonia plays an important role in cellular metabolism.However,ammonia is considered a toxic product.In bone marrow-derived mesenchymal stem cells,multipotent stem cells with high expression of glutamine synthetase(GS...Ammonia plays an important role in cellular metabolism.However,ammonia is considered a toxic product.In bone marrow-derived mesenchymal stem cells,multipotent stem cells with high expression of glutamine synthetase(GS)in bone marrow,ammonia and glutamate can be converted to glutamine via glutamine synthetase activity to support the proliferation of MSCs.As a major nutritional amino acid for biosynthesis,glutamine can activate the Akt/mTOR/S6k pathway to stimulate cell proliferation.The activation of mTOR can promote cell entry into S phase,thereby enhancing DNA synthesis and cell proliferation.Our studies demonstrated that mesenchymal stem cells can convert the toxic waste product ammonia into nutritional glutamine via GS activity.Then,the Akt/mTOR/S6k pathway is activated to promote bone marrow-derived mesenchymal stem cell proliferation.These results suggest a new therapeutic strategy and potential target for the treatment of diseases involving hyperammonemia.展开更多
Chronic inflammation,through a variety of mechanisms,plays a key role in the occurrence and development of digestive system malignant tumors(DSMTs).In this study,we feature and provide a comprehensive understanding of...Chronic inflammation,through a variety of mechanisms,plays a key role in the occurrence and development of digestive system malignant tumors(DSMTs).In this study,we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation.The development and evaluation of cancer prevention strategies is a longstanding process.Cancer prevention,especially in the early stage of life,should be emphasized throughout the whole life course.Issues such as the time interval for colon cancer screening,the development of direct-acting antiviral drugs for liver cancer,and the Helicobacter pylori vaccine all need to be explored in long-term,large-scale experiments in the future.展开更多
The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of ...The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.展开更多
Dear Editor, Androgen Insensitivity Syndrome （AIS） is an X-linked recessive genetic disorder presenting as male pseudohermaphroditism with gender ambiguity or reversal. According to the reaction to androgens, subje...Dear Editor, Androgen Insensitivity Syndrome （AIS） is an X-linked recessive genetic disorder presenting as male pseudohermaphroditism with gender ambiguity or reversal. According to the reaction to androgens, subjects with AIS can exhibit varying degrees of feminization, mainly in two forms.展开更多
Objective: To conduct a hierarchical classification analysis of the nonreportable results of noninvasive prenatal testing in an attempt to reduce failure rates and provide pregnant women with accurate information to a...Objective: To conduct a hierarchical classification analysis of the nonreportable results of noninvasive prenatal testing in an attempt to reduce failure rates and provide pregnant women with accurate information to alleviate their anxiety.Methods: In this study,30,039 singleton pregnancies who underwent noninvasive prenatal testing in a single center from May 2019 to April 2022 were collected,and 811 samples with initial noninvasive prenatal testing failure were retrospectively analyzed.Grouping was based on the reasons for initial test failure;tracking the noninvasive prenatal testing results and prenatal diagnosis results(if any)of the“z-scores in the gray area”group and analyzing the possible influencing factors of the“low fetal fraction”group in the pre-experimental and experimental period by using one-way analysis of variance,Mann-Whitney U test,and χ^(2) test;and tracking the pregnancy outcomes of the test failures samples to analyze the risk of perinatal complications and adverse pregnancy outcomes of the different types of test failures.Results: None of the samples'initial inconclusive results because of z-scores in the gray area were found to have chromosomal aneuploidy.However,pregnancy complications(P=0.018)and a high likelihood of adverse pregnancy outcomes(P=0.048)may still occur.Maternal gestational age(P<0.001),body mass index(P<0.001),library concentration(P<0.001),and fetal gender(P<0.001)were considered to be the associated factors for the initial low fetal fraction results.This may be associated with pregnancy complications(P<0.001)and a high likelihood of adverse pregnancy outcomes(P=0.034).The body mass index(P=0.015)and time between draws(P=0.001)were associated with the second test’s success.The incidence of low fetal fraction samples was more frequent with blood collection tubes of the G type than with the K type(P<0.001).Conclusion: Initial inconclusive results because of z-scores in the gray area did not imply an increased risk of aneuploidy,but vigilance is needed for an increased risk of pregnancy complications and adverse pregnancy outcomes.Because of the low fetal fraction,the initial absence of results may be related to the assay method,as well as the effect of blood collection tubes and the need to be alert to the risk of pregnancy complications and adverse pregnancy outcomes.展开更多
We describe the prenatal diagnosis and fetal phenotype of partial trisomy 12 （pl2-pter） transmitted from a maternal reciprocal translocation 6;12. Genetic analysis of umbilical cord blood of a 27-year-old woman, gra...We describe the prenatal diagnosis and fetal phenotype of partial trisomy 12 （pl2-pter） transmitted from a maternal reciprocal translocation 6;12. Genetic analysis of umbilical cord blood of a 27-year-old woman, gravida 4, para 1 at 35 weeks＇ gestation due to a tricuspid regurgitation and orbital hypertelorism by sonography revealed an unusual karyotype of 46, XY, der （6） t （6;12） （p24;p12） mat. The pregnancy was terminated at 37 gestational weeks. The proband postnatally displayed by dysmorphic features of a round flat face with prominent cheeks and high forehead, hypertelorism, a short nose, a broad and depressed nasal bridge, anteverted nares, a deformed philtrum, an open mouth, thin upper vermilion and broad everted lower lip, low-set ears and aural atresia, broad hands with simian creases, and a short neck. By anatomy, the fetal was found to have right artery catheter vagus, congenital cataract, no turbinate and external auditory canal. Through the karoytpye-phynotpye analysis on the present patient and a review of other reported cases, we believed that the case was the first report, which expanded the database of partial trisomy 12p, and was of benefit for future clinical genetic counseling. At the same time, this study supported the viewpoint that phenotypic variability depends on the type and extent of the associated partial monosomy展开更多
Osteosarcoma (OS) is the most common histological form of primary bone cancer in childhood cancer and young adults. At present, OS is widely investigated because of the interaction between the tumor and bone microenvi...Osteosarcoma (OS) is the most common histological form of primary bone cancer in childhood cancer and young adults. At present, OS is widely investigated because of the interaction between the tumor and bone microenvironment and the effect of such interaction on OS progression and metastasis.1 The connective tissue growth factor (CTGF), also known as cellular communication network factor 2 (CCN2), is a secreted extracellular matrix-associated protein. CTGF is as active as the regulators of signaling activities of several different pathways and an orchestrator of their cross-talk.2 Therefore, we conducted experiments to investigate the effects of CTGF on OS tumor progress and the cross-talk with stromal cells in the tumor microenvironment.展开更多
The flow-through hybridization and gene chip(FHGC)was developed to used in clinical molecular diagnostics for thalassemia,human papillomavirus(HPV),and other dis-eases.FHGC could improve hybridization efficiency and r...The flow-through hybridization and gene chip(FHGC)was developed to used in clinical molecular diagnostics for thalassemia,human papillomavirus(HPV),and other dis-eases.FHGC could improve hybridization efficiency and reduce hands-on time,thus improving precision,repro-ducibility,and traceability.Multiple genotypes can be detected simultaneously without incurring high costs.^(1)During the experiment,the polymerase chain reaction(PCR)product or buffer forced through the membrane matrix,PCR products are apprehended by a probe attached to the membrane.展开更多
基金supported by the National Natural Science Foundation of China(No.81602492)the National Science Fund for Excellent Young Scholars National Science Fund for Excellent Young Scholars(No.32122052)National Natural Science Foundation Regional Innovation and Development(No.U19A2003).
文摘Ammonia plays an important role in cellular metabolism.However,ammonia is considered a toxic product.In bone marrow-derived mesenchymal stem cells,multipotent stem cells with high expression of glutamine synthetase(GS)in bone marrow,ammonia and glutamate can be converted to glutamine via glutamine synthetase activity to support the proliferation of MSCs.As a major nutritional amino acid for biosynthesis,glutamine can activate the Akt/mTOR/S6k pathway to stimulate cell proliferation.The activation of mTOR can promote cell entry into S phase,thereby enhancing DNA synthesis and cell proliferation.Our studies demonstrated that mesenchymal stem cells can convert the toxic waste product ammonia into nutritional glutamine via GS activity.Then,the Akt/mTOR/S6k pathway is activated to promote bone marrow-derived mesenchymal stem cell proliferation.These results suggest a new therapeutic strategy and potential target for the treatment of diseases involving hyperammonemia.
基金Supported by the Open Project Fund of Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases,No.SS202204.
文摘Chronic inflammation,through a variety of mechanisms,plays a key role in the occurrence and development of digestive system malignant tumors(DSMTs).In this study,we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation.The development and evaluation of cancer prevention strategies is a longstanding process.Cancer prevention,especially in the early stage of life,should be emphasized throughout the whole life course.Issues such as the time interval for colon cancer screening,the development of direct-acting antiviral drugs for liver cancer,and the Helicobacter pylori vaccine all need to be explored in long-term,large-scale experiments in the future.
基金supported by the National Natural Science Foundation of China(81760037)Yunling Scholar Project of Yunnan Province(YNWR-YLXZ-2019-0005)+1 种基金Hunan Provincial Innovation Platform and Talent Program(2018SK4004)Hunan Provincial Natural Science Foundation(2019JJ80048).
文摘The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.
文摘Dear Editor, Androgen Insensitivity Syndrome （AIS） is an X-linked recessive genetic disorder presenting as male pseudohermaphroditism with gender ambiguity or reversal. According to the reaction to androgens, subjects with AIS can exhibit varying degrees of feminization, mainly in two forms.
基金funded by the Key Project on Science and Technology Program of Fujian Health Commission(No.2021ZD01002)the Natural Science Foundation of Xiamen,China(Grant No.3502Z20227299)+1 种基金the General Science and Technology Project of Xiamen,China(Grant No.3502Z20224014)the Medical Innovation Project of Fujian Province(Grant No.2021CXB025).
文摘Objective: To conduct a hierarchical classification analysis of the nonreportable results of noninvasive prenatal testing in an attempt to reduce failure rates and provide pregnant women with accurate information to alleviate their anxiety.Methods: In this study,30,039 singleton pregnancies who underwent noninvasive prenatal testing in a single center from May 2019 to April 2022 were collected,and 811 samples with initial noninvasive prenatal testing failure were retrospectively analyzed.Grouping was based on the reasons for initial test failure;tracking the noninvasive prenatal testing results and prenatal diagnosis results(if any)of the“z-scores in the gray area”group and analyzing the possible influencing factors of the“low fetal fraction”group in the pre-experimental and experimental period by using one-way analysis of variance,Mann-Whitney U test,and χ^(2) test;and tracking the pregnancy outcomes of the test failures samples to analyze the risk of perinatal complications and adverse pregnancy outcomes of the different types of test failures.Results: None of the samples'initial inconclusive results because of z-scores in the gray area were found to have chromosomal aneuploidy.However,pregnancy complications(P=0.018)and a high likelihood of adverse pregnancy outcomes(P=0.048)may still occur.Maternal gestational age(P<0.001),body mass index(P<0.001),library concentration(P<0.001),and fetal gender(P<0.001)were considered to be the associated factors for the initial low fetal fraction results.This may be associated with pregnancy complications(P<0.001)and a high likelihood of adverse pregnancy outcomes(P=0.034).The body mass index(P=0.015)and time between draws(P=0.001)were associated with the second test’s success.The incidence of low fetal fraction samples was more frequent with blood collection tubes of the G type than with the K type(P<0.001).Conclusion: Initial inconclusive results because of z-scores in the gray area did not imply an increased risk of aneuploidy,but vigilance is needed for an increased risk of pregnancy complications and adverse pregnancy outcomes.Because of the low fetal fraction,the initial absence of results may be related to the assay method,as well as the effect of blood collection tubes and the need to be alert to the risk of pregnancy complications and adverse pregnancy outcomes.
文摘We describe the prenatal diagnosis and fetal phenotype of partial trisomy 12 （pl2-pter） transmitted from a maternal reciprocal translocation 6;12. Genetic analysis of umbilical cord blood of a 27-year-old woman, gravida 4, para 1 at 35 weeks＇ gestation due to a tricuspid regurgitation and orbital hypertelorism by sonography revealed an unusual karyotype of 46, XY, der （6） t （6;12） （p24;p12） mat. The pregnancy was terminated at 37 gestational weeks. The proband postnatally displayed by dysmorphic features of a round flat face with prominent cheeks and high forehead, hypertelorism, a short nose, a broad and depressed nasal bridge, anteverted nares, a deformed philtrum, an open mouth, thin upper vermilion and broad everted lower lip, low-set ears and aural atresia, broad hands with simian creases, and a short neck. By anatomy, the fetal was found to have right artery catheter vagus, congenital cataract, no turbinate and external auditory canal. Through the karoytpye-phynotpye analysis on the present patient and a review of other reported cases, we believed that the case was the first report, which expanded the database of partial trisomy 12p, and was of benefit for future clinical genetic counseling. At the same time, this study supported the viewpoint that phenotypic variability depends on the type and extent of the associated partial monosomy
基金supported by the National Natural Science Foundation of China(No.81102035,and 82060388)Doctor Foundation of Guizhou Provincial People's Hospital(No.GZSYBS[2019]08)+2 种基金Guizhou High-level Innovative Talents Project(No.QKPT[2017]5724-6)Guizhou Department and Platform Talents(No.[2017]5735-31)Science and Technology Department of Guizhou Province(No.QKHJC[2021-396]).
文摘Osteosarcoma (OS) is the most common histological form of primary bone cancer in childhood cancer and young adults. At present, OS is widely investigated because of the interaction between the tumor and bone microenvironment and the effect of such interaction on OS progression and metastasis.1 The connective tissue growth factor (CTGF), also known as cellular communication network factor 2 (CCN2), is a secreted extracellular matrix-associated protein. CTGF is as active as the regulators of signaling activities of several different pathways and an orchestrator of their cross-talk.2 Therefore, we conducted experiments to investigate the effects of CTGF on OS tumor progress and the cross-talk with stromal cells in the tumor microenvironment.
基金supported by the National Natural Science Foundation of China(No.82060388)Science and Technology Department of Guizhou Province(No.QKHJC-ZK[2021-396],QKHJC[2020]1Y424)+2 种基金Healthcare Commission of Guizhou Province(China)(No.GZWJKJ2019-1-192,GZWJKJ2021-310)Guiyang Science and Technology Bureau Guizhou,China(No.ZKH2022-4-3)Guizhou Department and Platform Talents(China)(No.[2018]5766-1).
文摘The flow-through hybridization and gene chip(FHGC)was developed to used in clinical molecular diagnostics for thalassemia,human papillomavirus(HPV),and other dis-eases.FHGC could improve hybridization efficiency and reduce hands-on time,thus improving precision,repro-ducibility,and traceability.Multiple genotypes can be detected simultaneously without incurring high costs.^(1)During the experiment,the polymerase chain reaction(PCR)product or buffer forced through the membrane matrix,PCR products are apprehended by a probe attached to the membrane.
