The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development ...The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development in the developed countries is the result of a close interaction between the basic sciences and clinical genetics. In China, however, clinical genetics has not received due emphasis and medical genetics is still not recognized as one of the medical specialties. This is in marked contrast to the situation in the West. It is high time to acknowledge that medical genetics is a medical specialty and to promote clinical genetics service in qualified hospitals in our country.展开更多
Cardiovascular diseases are affected by multiple factors like genetic as well as environmental hence they reveal factorial nature. The evidences that genetic factors are susceptible for developing cardiovascular disea...Cardiovascular diseases are affected by multiple factors like genetic as well as environmental hence they reveal factorial nature. The evidences that genetic factors are susceptible for developing cardiovascular diseases come from twin studies and familial aggregation. Different ethnic populations reveal differences in the prevalence coronary artery disease(CAD) pointing towards the genetic susceptibility. With progression in molecular techniques different developments have been made to comprehend the disease physiology. Molecular markers have also assisted to recognize genes that may provide evidences to evaluate the role of genetic factors in causation of susceptibility towards CAD. Numerous studies suggest the contribution of specific "candidate genes", which correlate with various roles/pathways that are involved in the coronary heart disease. Different studies have revealed that there are large numbers of genes which are involved towards the predisposition of CAD. However, these reports are not consistent. One of the reasons could be weak contribution of genetic susceptibility of these genes. Genome wide associations show different chromosomal locations which dock, earlier unknown, genes which may attribute to CAD. In the present review different ApoAI-CⅡI-AIV gene clusters have been discussed.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
Compounds isolated from Epimedium include the total flavonoids of Epimedium,icariin,and its metabolites(icaritin,icariside Ⅰ,and icariside Ⅱ),which have similar molecular structures.Modern pharmacological research a...Compounds isolated from Epimedium include the total flavonoids of Epimedium,icariin,and its metabolites(icaritin,icariside Ⅰ,and icariside Ⅱ),which have similar molecular structures.Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects,especially in improving sexual function,hormone regulation,anti-osteoporosis,immune function regulation,anti-oxidation,and anti-tumor activity.To date,we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system.However,their actions in other tissues have been reviewed in recent years.This review critically focuses on the Epimedium,its bioactive compounds,and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system.Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.展开更多
Renal cell carcinoma(RCC),which accounts for about 90 percent of kidney cancers,has a distinct metabolic reprogramming profile characterized by increased aerobic glycolysis(Warburg effect),abnormal accumulation of lip...Renal cell carcinoma(RCC),which accounts for about 90 percent of kidney cancers,has a distinct metabolic reprogramming profile characterized by increased aerobic glycolysis(Warburg effect),abnormal accumulation of lipids,and impaired mitochondrial function.Recent advances in high-throughput proteomic and metabolomic technologies have revolutionized our understanding of the pathophysiology of RCC,allowing for the systematic identification of disease-specific molecular signatures,elucidation of drug resistance mechanisms,and possible targets for intervention.The review focuses on the use of proteomic and metabolomic technologies in renal cell carcinoma and the research progress on related biomarkers,and is expected to provide useful information for the early detection and treatment of RCC.展开更多
BACKGROUND Perinatal depression affects 10%-20%of pregnant women and subsequently influences maternal health and fetal development.Concerns over the safety of antidepressants during pregnancy have prompted the explora...BACKGROUND Perinatal depression affects 10%-20%of pregnant women and subsequently influences maternal health and fetal development.Concerns over the safety of antidepressants during pregnancy have prompted the exploration of nutritional interventions as adjunct therapies.This study evaluated the impact of combining preconception and prenatal supplementation with myo-inositol,probiotics,and trace elements on mood,quality of life,and fetal development in depressed mothers.This retrospective cohort study included 314 pregnant women who were diag-nosed with mild to moderate depression,as determined by a Zung self-rating depression scale score of less than 69.The participants were divided into an intervention group(n=161)receiving myo-inositol,probiotics,and trace elements and a control group(n=153)without supplementation.Supplementation comm-enced 3 months before conception and continued through pregnancy.Psychiatric symptoms and quality of life were evaluated using the positive and negative affect schedule-now,state-trait anxiety inventory,Patient Health Ques-tionnaire-8,and World Health Organization Quality of life Assessment:Brief Version scales preconception and postpartum.Fetal development metrics were assessed via ultrasound,and neonatal outcomes were recorded.RESULTS The intervention group presented significant reductions in gestational diabetes mellitus(13.04%vs 23.53%,P=0.016)and gestational hypertension(3.73%vs 9.15%,P=0.049).Higher levels of inositol,iron,zinc,and probiotics were observed near term in the intervention group.Postpartum mood assessments indicated lower anxiety and depression scores for the intervention group,with significant improvements in the positive and negative affect schedule-now(P=0.002),trait anxiety(P=0.002),and Patient Health Questionnaire-8(P=0.018)scores.The World Health Organization Quality of life Assessment:Brief Version scores improved in the psychological(P=0.041)and environmental(P=0.009)domains postpartum.Fetal biparietal diameter and femoral length were greater in the intervention group alongside better neonatal body length and reduced neonatal unit admissions(2.48%vs 7.84%,P=0.031).CONCLUSION Combined supplementation with myo-inositol,probiotics,and trace elements from preconception through pregnancy may reduce pregnancy-related complications,enhance mood and quality of life,and improve fetal growth metrics.展开更多
Enhancer of zeste homolog 2(EZH2)is a key epigenetic regulatory protein and enzyme catalytic subunit of the polycomb repressor complex 2(PRC2),responsible for catalyzing the trimethylation of histone H3K27 and subsequ...Enhancer of zeste homolog 2(EZH2)is a key epigenetic regulatory protein and enzyme catalytic subunit of the polycomb repressor complex 2(PRC2),responsible for catalyzing the trimethylation of histone H3K27 and subsequent repression of gene transcription.Abnormal EZH2 expression or mutation is associated with various cancers,particularly lymphoma,and breast and prostate cancer.EZH2 has been investigated as an important target in cancer therapy and potential EZH2-targeted drugs have been developed.This article reviews the research progress on the mechanism of transcriptional regulation of EZH2 and the development and clinical use of some inhibitors targeting EZH2.展开更多
BACKGROUND Although the relationship between somatic DNA polymerase epsilon(POLE)exonuclease domain mutations(EDMs)and colorectal cancer(CRC)is well established,the role of POLE non-EDMs in CRC remains unclear.AIM To ...BACKGROUND Although the relationship between somatic DNA polymerase epsilon(POLE)exonuclease domain mutations(EDMs)and colorectal cancer(CRC)is well established,the role of POLE non-EDMs in CRC remains unclear.AIM To identify POLE non-EDMs and EDMs in CRC,and to determine their associations with accompanying mutations and microsatellite instability(MSI).METHODS In this retrospective study,next-generation sequencing was performed using a targeted colon cancer panel(Qiagen,DHS-003Z)on 356 CRC patients.Of these,191 patients were found to carry POLE mutations.For these patients,MSI status was assessed using both real-time PCR(EasyPGX^(■)Ready MSI kit)and immunohistochemistry,and accompanying somatic mutations were investigated.RESULTS POLE mutations were identified in 53.65%of the CRC patients.Among the POLE-mutant patients,87.96%were classified as pMMR(MSI-L),and 12.04%as dMMR(MSI-H).The most frequently observed POLE non-EDM variant was exon 34 c.4337_4338delTG p.V1446fs*3.The POLE EDMs were present in exon 14,with two specific variants p.Y458F(0.52%)and p.Y468N(0.52%).The most common pathogenic variants accompanying the POLE mutations were in MLH3,MSH3,KRAS,PIK3CA,and BRAF genes.POLE mutations were associated with a high mutational burden and MSI in CRC,particularly in the dMMR phenotype.This association suggests that POLE mutations may serve as important biomarkers for understanding the genetic profile of the disease and may be used in the clinical management of CRC.CONCLUSION POLE mutations,especially non-EDMs,are frequent in MSI-L CRC and often co-occur with MLH3,MSH3,KRAS,PIK3CA,and BRAF,highlighting their potential role in tumor biology and as biomarkers for personalized treatment.Functional validation and multicenter studies are needed.展开更多
Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion...Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion of CAG repeats disrupts the genetic stability of animal models,which is detrimental to disease research.Methods:In this study,we established a mouse model in which CAG repeats do not undergo microsatellite instability(MSI)across generations.A humanized ATXN2 cDNA with four CAA interruptions within 73 CAG expansions was inserted into the Rosa26 locus of C57BL/6J mice.A 23 CAG control mouse model was also generated to verify ATXN2 integration and expression.Results:In our model,the number of CAG repeats remained stable during transmission,with no CAG repeat expansion observed in 64 parent-to-offspring transmissions.Compared with SCA2-Q23 mice,SCA2-Q73 mice exhibited progressive motor impairment,reduced Purkinje cell count and volume(indicative of cell atrophy),and muscle atrophy.These observations in the mice suggest that the behavioral and neuropathological phenotypes may reflect the features of SCA2 patients.RNA-seq analysis of the gastrocnemius muscle in SCA2-Q73 mice showed significant changes in muscle differentiation and development gene expression at 56 weeks,with no significant differences at 16 weeks compared to SCA2-Q23 mice.The expression level of the Myf6 gene significantly changed in the muscles of aged mice.Conclusion:In summary,the establishment of this model not only provides a stable animal model for studying CAG transmission in SCA2 but also indicates that the lack of long-term neural stimulation leads to muscle atrophy.展开更多
Individuals with congenital absence of the vas deferens(CAVD)may transmit cystic fibrosis(CF)-causing variants of the cystic fibrosis transmembrane conductance regulator(CFTR)gene to their offspring through assisted r...Individuals with congenital absence of the vas deferens(CAVD)may transmit cystic fibrosis(CF)-causing variants of the cystic fibrosis transmembrane conductance regulator(CFTR)gene to their offspring through assisted reproductive technology(ART).We aimed to delineate the spectrum and estimate the prevalence of CF-causing variants in Chinese individuals with CAVD through a cohort analysis and meta-analysis.CFTR was sequenced in 145 Chineseindividuals with CAVD.CFTR variants were classified as CF-causing or non-CF-causing variants regarding clinical significance.A comprehensive genotype analysis was performed in Chinese individuals with CAVD,incorporating previous studies and our study cohort.The prevalence of CF-causing variants was estimated through meta-analysis.In our cohort,56 differentCFTR variants were identified in 108(74.5%)patients.Twenty variants were categorized as CF-causing and were detected in 28(19.3%)patients.A comprehensive genotype analysis of 867 patients identified 174 differentCFTR variants.Sixty-four were classified as CF-causing variants,56.3%of which had not been previously reported in Chinese patients with CF.Meta-analysis showed that 14.8%(95%confidence interval[CI]:11.0%-18.9%)CAVD cases harbored one CF-causing variant,and 68.6%(95%CI:65.1%-72.0%)CAVD cases carried at least one CFTR variant.Our study underscores the urgent need for extensiveCFTR screening,including sequencing of whole exons and flanking regions and detection of large rearrangements and deep intronic CF-causing variants,in Chinese individuals with CAVDbefore undergoing ART.The established CF-causing variants spectrum may aid in the development of genetic counseling strategies and preimplantation diagnosis to prevent the birth of a child with CF.展开更多
BACKGROUND The special physiological changes during pregnancy pose a huge challenge to the diagnosis of cervical cancer in pregnancy(CCIP).However,due to the poor prognosis of advanced-stage CCIP,there is currently no...BACKGROUND The special physiological changes during pregnancy pose a huge challenge to the diagnosis of cervical cancer in pregnancy(CCIP).However,due to the poor prognosis of advanced-stage CCIP,there is currently no consensus or guideline for diagnosis and treatment.CASE SUMMARY In this case report,we presented the case of a 30-year-old woman at 30 weeks of gestation who presented with irregular vaginal bleeding and was admitted to a local hospital at 35 weeks of gestation with a sudden gush of fluid and underwent a C-section.During the surgery,a rotten fish-like solid mass in the lower segment of the posterior wall of the uterus was excised for biopsy.The patient was referred to our hospital because she experienced heavy vaginal bleeding 13 days after one chemotherapy session.The solid mass was initially misdiagnosed as uterine clearcell carcinoma at local hospital but later confirmed as cervical adenosquamous carcinoma by a multidisciplinary team.Three months posttreatment,she succumbed to multiple tumor metastases.The infant was healthy at the latest 2-year follow-up.CONCLUSION Obstetricians should expand differential diagnoses when obstetric factors cannot explain symptoms of persistent vaginal bleeding during pregnancy.Atypical and insidious clinical presentations are often concealed by physiological changes during pregnancy,which may increase the difficulty of diagnosis and result in misdiagnosis.展开更多
BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-Eu...BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-European populations remains unclear.AIM To investigate HLA genotypes associated with the development of ADAs in Taiwan Region of China inflammatory bowel disease(IBD)patients treated with biologics.METHODS In this multicenter study,IBD patients treated with anti-tumor necrosis factor(TNF),anti-integrin,or anti-interleukin(IL)-12/23 therapies from April 2022 to June 2024 were enrolled.All participants underwent next-generation sequencing for HLA genotyping.ADA levels were measured via enzyme linked immunosorbent assay.HLA allele frequencies were compared between ADA-positive and ADA-negative groups,and against general Taiwan Region of China population data.RESULTS Ninety-five IBD patients were included:58 received anti-TNF therapy(38 infliximab,20 adalimumab),27 antiintegrin,and 10 anti-IL-12/23.ADAs occurred only in the anti-TNF group(n=22):19 infliximab(50%)and 3 adalimumab(15%).No ADAs developed in patients on anti-integrin or anti-IL-12/23 agents.HLA-C*03:04:01 was significantly associated with anti-infliximab ADAs(31.6%vs 0%,P=0.02),and HLA-B*15:18:01 with anti-adalimumab ADAs(66.7%vs 0%,P=0.016).HLA-DQA1*05 was not associated with ADA formation.Frequencies of HLA-C*03:04:01(8.4%vs 10.5%)and HLA-B*15:18:01(1.6%vs 0.6%)in IBD patients were comparable to those in the general population.ADA titers were inversely correlated with serum drug levels.CONCLUSION In Taiwan Region of China IBD patients,HLA-C*03:04:01 and HLA-B*15:18:01 were significantly associated with ADA development to infliximab and adalimumab,respectively.HLA-DQA1*05 was not predictive,highlighting ethnic differences in genetic predisposition to immunogenicity.展开更多
Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this region.Identification of cis-or trans...Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this region.Identification of cis-or trans-acting mutations contributing to the diverse extent of fetal hemoglobin(Hb F)might illustrate the underlying mechanism ofγ-β-globin switching.Here,we recruit a cohort of 1142β-thalassemia patients and dissect the natural variants in the wholeβ-globin gene cluster through a targeted next-generation sequencing panel.A previously unreported SNP rs7948668,predicted to disrupt the binding motif of IKAROS as a key component of chromatin remodeling complexes,is identified to be significantly associated with higher levels of Hb F and age at onset.Gene-editing on this SNP leads to the elevation of Hb F in both HUDEP-2 and primary CD34+cells while the extent of elevation is amplified in the context ofβ-thalassemia mutations,indicating epistasis effects of the SNP in the regulation of Hb F.Finally,we perform ChIP-qPCR and 4C assays to prove that this variant disrupts the binding motif of IKAROS,leading to enhanced competitiveness of HBG promoters to locus control regions.This study highlights the significance of common regulatory SNPs and provides potential targets for treatingβ-hemoglobinopathy.展开更多
Chorionic gonadotropinα(Cgα)functions as the shared subunit for thyroid-stimulating hormone subunitβ(Tshβ),luteinizing hormone subunitβ(Lhβ),and follicle-stimulating hormone subunitβ(Fshβ).While theseβ-subuni...Chorionic gonadotropinα(Cgα)functions as the shared subunit for thyroid-stimulating hormone subunitβ(Tshβ),luteinizing hormone subunitβ(Lhβ),and follicle-stimulating hormone subunitβ(Fshβ).While theseβ-subunits have been extensively studied using effective gene knockout models in zebrafish,the biological role of Cgαremains elusive.In this study,cgα-deficient zebrafish generated via transcription activator-like effector nucleases(TALENs)exhibited viability but displayed pronounced developmental abnormalities,including growth retardation,hyperpigmentation,reduced thyroxine(T4)levels,and defective anterior swim bladder inflation during juvenile stages.In adults,cgαdeficiency led to disrupted gonadal development,impaired secondary sex characteristics(SSCs),and severely impacted reproductive behavior in both female and male fish.Notably,both testicular and ovarian differentiation were observed in cgα-deficient fish and lhβ^(−/−);fshβ^(−/−)mutants.Gonadal sex differentiation in cgα-deficient zebrafish exhibited a pronounced shift toward testicular fate upon additional disruption of fshβ(cgα^(−/−);fshβ^(−/−)),marked by elevated anti-Müllerian hormone(amh)expression,or following loss of follicle-stimulating hormone receptor(fshr)(cgα^(−/−);fshr^(−/−)).In vitro assays in Chinese hamster ovary(CHO)cells revealed increased cAMP response element(CRE)promoter activity following transfection with constructs encoding Fshr,Fshβ/Fshr,or Cgα/Fshβ/Fshr.Collectively,the phenotypes observed in cgα-deficient fish recapitulate those of thyrotropin-and gonadotropin-disrupted models,highlighting the essential role of Cgαin thyroid and gonadal function.Importantly,these findings uncover the role of Fsh signaling in maintaining proper ovarian differentiation in zebrafish,including Cgα-independent Fshβactivity and the constitutive functionality of Fshr.展开更多
BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to th...BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.展开更多
Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe o...Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.展开更多
MicroRNAs are small non-coding RNAs which regulate gene expression in a post-transcriptional manner. Although the first study was published about 15 years ago, knowledge about their role in regulation of cell prolifer...MicroRNAs are small non-coding RNAs which regulate gene expression in a post-transcriptional manner. Although the first study was published about 15 years ago, knowledge about their role in regulation of cell proliferation, differentiation, apoptosis and immunity has been greatly advanced recently. Their association with formation, angiogenesis, metastasis and chemotherapy resistance of minors has become one of the core issues in epigenetics of cancer. Here, we summarize the latest findings concerning microRNAs involved in dif- ferent signal pathways leading to colorectal cancer, introduce some new potential microRNAs as biomarkers in diagnosis and prognosis, and analyze its application in the treatment of cancer.展开更多
【Abstract】factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immu...【Abstract】factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffinembedded blocks of adjacent normal specimens from the cases,along with normal esophageal tissue from 80 healthy subjects.RESULTS:Positive expression of p53 protein was detected in 56.2%(45/80)of ESCC cases,and in none of the normal esophageal tissue of the control group(P【0.001).Furthermore,73.8%(59/80)of ESCC cases and 43.8%(35/80)of controls had positive expression of p21 protein(P【0.001).Cigarette smoking was significantly associated with p53 over-expression in ESCC cases(P=0.010,OR=3.64;95%CI:1.32-10.02).p21 over-expression was associated with poorer clinical outcome among the ESCC patients(P=0.009).CONCLUSION:Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran.Furthermore,p21 over-expression was found to be associated with poor prognosis,specifically in the operable ESCC patients.展开更多
文摘The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development in the developed countries is the result of a close interaction between the basic sciences and clinical genetics. In China, however, clinical genetics has not received due emphasis and medical genetics is still not recognized as one of the medical specialties. This is in marked contrast to the situation in the West. It is high time to acknowledge that medical genetics is a medical specialty and to promote clinical genetics service in qualified hospitals in our country.
文摘Cardiovascular diseases are affected by multiple factors like genetic as well as environmental hence they reveal factorial nature. The evidences that genetic factors are susceptible for developing cardiovascular diseases come from twin studies and familial aggregation. Different ethnic populations reveal differences in the prevalence coronary artery disease(CAD) pointing towards the genetic susceptibility. With progression in molecular techniques different developments have been made to comprehend the disease physiology. Molecular markers have also assisted to recognize genes that may provide evidences to evaluate the role of genetic factors in causation of susceptibility towards CAD. Numerous studies suggest the contribution of specific "candidate genes", which correlate with various roles/pathways that are involved in the coronary heart disease. Different studies have revealed that there are large numbers of genes which are involved towards the predisposition of CAD. However, these reports are not consistent. One of the reasons could be weak contribution of genetic susceptibility of these genes. Genome wide associations show different chromosomal locations which dock, earlier unknown, genes which may attribute to CAD. In the present review different ApoAI-CⅡI-AIV gene clusters have been discussed.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
基金supported by the National Nature Science Foundation of China(NSFC,No.31960156,No.31660338,No.31760627,and No.32270848)Collaborative Innovation Center of Chinese Ministry of Education(2020-39),Science and Technology Support Program of Guizhou Province(QKH[2021]111,QKH[2020]4Y192,QKH[2018]5772-006,and QKH[2019]5406)Science and Technology Fund of Guizhou Provincial Health Commission(gzwkj2022-019).
文摘Compounds isolated from Epimedium include the total flavonoids of Epimedium,icariin,and its metabolites(icaritin,icariside Ⅰ,and icariside Ⅱ),which have similar molecular structures.Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects,especially in improving sexual function,hormone regulation,anti-osteoporosis,immune function regulation,anti-oxidation,and anti-tumor activity.To date,we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system.However,their actions in other tissues have been reviewed in recent years.This review critically focuses on the Epimedium,its bioactive compounds,and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system.Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
基金National Natural Science Foundation of China(3236016631760321).
文摘Renal cell carcinoma(RCC),which accounts for about 90 percent of kidney cancers,has a distinct metabolic reprogramming profile characterized by increased aerobic glycolysis(Warburg effect),abnormal accumulation of lipids,and impaired mitochondrial function.Recent advances in high-throughput proteomic and metabolomic technologies have revolutionized our understanding of the pathophysiology of RCC,allowing for the systematic identification of disease-specific molecular signatures,elucidation of drug resistance mechanisms,and possible targets for intervention.The review focuses on the use of proteomic and metabolomic technologies in renal cell carcinoma and the research progress on related biomarkers,and is expected to provide useful information for the early detection and treatment of RCC.
文摘BACKGROUND Perinatal depression affects 10%-20%of pregnant women and subsequently influences maternal health and fetal development.Concerns over the safety of antidepressants during pregnancy have prompted the exploration of nutritional interventions as adjunct therapies.This study evaluated the impact of combining preconception and prenatal supplementation with myo-inositol,probiotics,and trace elements on mood,quality of life,and fetal development in depressed mothers.This retrospective cohort study included 314 pregnant women who were diag-nosed with mild to moderate depression,as determined by a Zung self-rating depression scale score of less than 69.The participants were divided into an intervention group(n=161)receiving myo-inositol,probiotics,and trace elements and a control group(n=153)without supplementation.Supplementation comm-enced 3 months before conception and continued through pregnancy.Psychiatric symptoms and quality of life were evaluated using the positive and negative affect schedule-now,state-trait anxiety inventory,Patient Health Ques-tionnaire-8,and World Health Organization Quality of life Assessment:Brief Version scales preconception and postpartum.Fetal development metrics were assessed via ultrasound,and neonatal outcomes were recorded.RESULTS The intervention group presented significant reductions in gestational diabetes mellitus(13.04%vs 23.53%,P=0.016)and gestational hypertension(3.73%vs 9.15%,P=0.049).Higher levels of inositol,iron,zinc,and probiotics were observed near term in the intervention group.Postpartum mood assessments indicated lower anxiety and depression scores for the intervention group,with significant improvements in the positive and negative affect schedule-now(P=0.002),trait anxiety(P=0.002),and Patient Health Questionnaire-8(P=0.018)scores.The World Health Organization Quality of life Assessment:Brief Version scores improved in the psychological(P=0.041)and environmental(P=0.009)domains postpartum.Fetal biparietal diameter and femoral length were greater in the intervention group alongside better neonatal body length and reduced neonatal unit admissions(2.48%vs 7.84%,P=0.031).CONCLUSION Combined supplementation with myo-inositol,probiotics,and trace elements from preconception through pregnancy may reduce pregnancy-related complications,enhance mood and quality of life,and improve fetal growth metrics.
基金supported by the National Natural Science Foundation of China(32360166,31760321).
文摘Enhancer of zeste homolog 2(EZH2)is a key epigenetic regulatory protein and enzyme catalytic subunit of the polycomb repressor complex 2(PRC2),responsible for catalyzing the trimethylation of histone H3K27 and subsequent repression of gene transcription.Abnormal EZH2 expression or mutation is associated with various cancers,particularly lymphoma,and breast and prostate cancer.EZH2 has been investigated as an important target in cancer therapy and potential EZH2-targeted drugs have been developed.This article reviews the research progress on the mechanism of transcriptional regulation of EZH2 and the development and clinical use of some inhibitors targeting EZH2.
文摘BACKGROUND Although the relationship between somatic DNA polymerase epsilon(POLE)exonuclease domain mutations(EDMs)and colorectal cancer(CRC)is well established,the role of POLE non-EDMs in CRC remains unclear.AIM To identify POLE non-EDMs and EDMs in CRC,and to determine their associations with accompanying mutations and microsatellite instability(MSI).METHODS In this retrospective study,next-generation sequencing was performed using a targeted colon cancer panel(Qiagen,DHS-003Z)on 356 CRC patients.Of these,191 patients were found to carry POLE mutations.For these patients,MSI status was assessed using both real-time PCR(EasyPGX^(■)Ready MSI kit)and immunohistochemistry,and accompanying somatic mutations were investigated.RESULTS POLE mutations were identified in 53.65%of the CRC patients.Among the POLE-mutant patients,87.96%were classified as pMMR(MSI-L),and 12.04%as dMMR(MSI-H).The most frequently observed POLE non-EDM variant was exon 34 c.4337_4338delTG p.V1446fs*3.The POLE EDMs were present in exon 14,with two specific variants p.Y458F(0.52%)and p.Y468N(0.52%).The most common pathogenic variants accompanying the POLE mutations were in MLH3,MSH3,KRAS,PIK3CA,and BRAF genes.POLE mutations were associated with a high mutational burden and MSI in CRC,particularly in the dMMR phenotype.This association suggests that POLE mutations may serve as important biomarkers for understanding the genetic profile of the disease and may be used in the clinical management of CRC.CONCLUSION POLE mutations,especially non-EDMs,are frequent in MSI-L CRC and often co-occur with MLH3,MSH3,KRAS,PIK3CA,and BRAF,highlighting their potential role in tumor biology and as biomarkers for personalized treatment.Functional validation and multicenter studies are needed.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:CIFMS,2021-I2M-1-024The Joint Fund for the Department of Science and Technology of Yunnan Province-Kunming Medical University,Grant/Award Number:202201AY070001-007+1 种基金Open Research Fund Project of Yunnan Provincial Key Laboratory of Pharmacology of Natural Medicines,Grant/Award Number:YKLPNP-G2403The Science and Technology Leading Talent Program of Yunnan Province,Grant/Award Number:202405AB350002。
文摘Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion of CAG repeats disrupts the genetic stability of animal models,which is detrimental to disease research.Methods:In this study,we established a mouse model in which CAG repeats do not undergo microsatellite instability(MSI)across generations.A humanized ATXN2 cDNA with four CAA interruptions within 73 CAG expansions was inserted into the Rosa26 locus of C57BL/6J mice.A 23 CAG control mouse model was also generated to verify ATXN2 integration and expression.Results:In our model,the number of CAG repeats remained stable during transmission,with no CAG repeat expansion observed in 64 parent-to-offspring transmissions.Compared with SCA2-Q23 mice,SCA2-Q73 mice exhibited progressive motor impairment,reduced Purkinje cell count and volume(indicative of cell atrophy),and muscle atrophy.These observations in the mice suggest that the behavioral and neuropathological phenotypes may reflect the features of SCA2 patients.RNA-seq analysis of the gastrocnemius muscle in SCA2-Q73 mice showed significant changes in muscle differentiation and development gene expression at 56 weeks,with no significant differences at 16 weeks compared to SCA2-Q23 mice.The expression level of the Myf6 gene significantly changed in the muscles of aged mice.Conclusion:In summary,the establishment of this model not only provides a stable animal model for studying CAG transmission in SCA2 but also indicates that the lack of long-term neural stimulation leads to muscle atrophy.
基金supported by the National Natural Science Foundation of China(grant No.82171588)the Fundamental Research Funds for the Central Institutes(grant No.2023GJZD01).
文摘Individuals with congenital absence of the vas deferens(CAVD)may transmit cystic fibrosis(CF)-causing variants of the cystic fibrosis transmembrane conductance regulator(CFTR)gene to their offspring through assisted reproductive technology(ART).We aimed to delineate the spectrum and estimate the prevalence of CF-causing variants in Chinese individuals with CAVD through a cohort analysis and meta-analysis.CFTR was sequenced in 145 Chineseindividuals with CAVD.CFTR variants were classified as CF-causing or non-CF-causing variants regarding clinical significance.A comprehensive genotype analysis was performed in Chinese individuals with CAVD,incorporating previous studies and our study cohort.The prevalence of CF-causing variants was estimated through meta-analysis.In our cohort,56 differentCFTR variants were identified in 108(74.5%)patients.Twenty variants were categorized as CF-causing and were detected in 28(19.3%)patients.A comprehensive genotype analysis of 867 patients identified 174 differentCFTR variants.Sixty-four were classified as CF-causing variants,56.3%of which had not been previously reported in Chinese patients with CF.Meta-analysis showed that 14.8%(95%confidence interval[CI]:11.0%-18.9%)CAVD cases harbored one CF-causing variant,and 68.6%(95%CI:65.1%-72.0%)CAVD cases carried at least one CFTR variant.Our study underscores the urgent need for extensiveCFTR screening,including sequencing of whole exons and flanking regions and detection of large rearrangements and deep intronic CF-causing variants,in Chinese individuals with CAVDbefore undergoing ART.The established CF-causing variants spectrum may aid in the development of genetic counseling strategies and preimplantation diagnosis to prevent the birth of a child with CF.
基金Supported by National Key Research and Development Program of China,No.2021YFC2701603.
文摘BACKGROUND The special physiological changes during pregnancy pose a huge challenge to the diagnosis of cervical cancer in pregnancy(CCIP).However,due to the poor prognosis of advanced-stage CCIP,there is currently no consensus or guideline for diagnosis and treatment.CASE SUMMARY In this case report,we presented the case of a 30-year-old woman at 30 weeks of gestation who presented with irregular vaginal bleeding and was admitted to a local hospital at 35 weeks of gestation with a sudden gush of fluid and underwent a C-section.During the surgery,a rotten fish-like solid mass in the lower segment of the posterior wall of the uterus was excised for biopsy.The patient was referred to our hospital because she experienced heavy vaginal bleeding 13 days after one chemotherapy session.The solid mass was initially misdiagnosed as uterine clearcell carcinoma at local hospital but later confirmed as cervical adenosquamous carcinoma by a multidisciplinary team.Three months posttreatment,she succumbed to multiple tumor metastases.The infant was healthy at the latest 2-year follow-up.CONCLUSION Obstetricians should expand differential diagnoses when obstetric factors cannot explain symptoms of persistent vaginal bleeding during pregnancy.Atypical and insidious clinical presentations are often concealed by physiological changes during pregnancy,which may increase the difficulty of diagnosis and result in misdiagnosis.
基金Supported by Ministry of Science and Technology,Taiwan,No.MOST 111-2314-B-002-226Taiwan University Hospital,Hsin-Chu Branch,No.112-BIH017The Liver Disease Prevention and Treatment Research Foundation,Taiwan.
文摘BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-European populations remains unclear.AIM To investigate HLA genotypes associated with the development of ADAs in Taiwan Region of China inflammatory bowel disease(IBD)patients treated with biologics.METHODS In this multicenter study,IBD patients treated with anti-tumor necrosis factor(TNF),anti-integrin,or anti-interleukin(IL)-12/23 therapies from April 2022 to June 2024 were enrolled.All participants underwent next-generation sequencing for HLA genotyping.ADA levels were measured via enzyme linked immunosorbent assay.HLA allele frequencies were compared between ADA-positive and ADA-negative groups,and against general Taiwan Region of China population data.RESULTS Ninety-five IBD patients were included:58 received anti-TNF therapy(38 infliximab,20 adalimumab),27 antiintegrin,and 10 anti-IL-12/23.ADAs occurred only in the anti-TNF group(n=22):19 infliximab(50%)and 3 adalimumab(15%).No ADAs developed in patients on anti-integrin or anti-IL-12/23 agents.HLA-C*03:04:01 was significantly associated with anti-infliximab ADAs(31.6%vs 0%,P=0.02),and HLA-B*15:18:01 with anti-adalimumab ADAs(66.7%vs 0%,P=0.016).HLA-DQA1*05 was not associated with ADA formation.Frequencies of HLA-C*03:04:01(8.4%vs 10.5%)and HLA-B*15:18:01(1.6%vs 0.6%)in IBD patients were comparable to those in the general population.ADA titers were inversely correlated with serum drug levels.CONCLUSION In Taiwan Region of China IBD patients,HLA-C*03:04:01 and HLA-B*15:18:01 were significantly associated with ADA development to infliximab and adalimumab,respectively.HLA-DQA1*05 was not predictive,highlighting ethnic differences in genetic predisposition to immunogenicity.
基金supported by the National Natural Science Foundation of China(U20A20353 to X.Xu and 81900185 to Y.Ye).
文摘Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this region.Identification of cis-or trans-acting mutations contributing to the diverse extent of fetal hemoglobin(Hb F)might illustrate the underlying mechanism ofγ-β-globin switching.Here,we recruit a cohort of 1142β-thalassemia patients and dissect the natural variants in the wholeβ-globin gene cluster through a targeted next-generation sequencing panel.A previously unreported SNP rs7948668,predicted to disrupt the binding motif of IKAROS as a key component of chromatin remodeling complexes,is identified to be significantly associated with higher levels of Hb F and age at onset.Gene-editing on this SNP leads to the elevation of Hb F in both HUDEP-2 and primary CD34+cells while the extent of elevation is amplified in the context ofβ-thalassemia mutations,indicating epistasis effects of the SNP in the regulation of Hb F.Finally,we perform ChIP-qPCR and 4C assays to prove that this variant disrupts the binding motif of IKAROS,leading to enhanced competitiveness of HBG promoters to locus control regions.This study highlights the significance of common regulatory SNPs and provides potential targets for treatingβ-hemoglobinopathy.
基金supported by the National Natural Science Foundation,China(32230108 to Z.Y.)National Key Research and Development Program,China(2022YFF1000300 to Z.Y.and 2022YFD2401800 to G.Z.)Foundation of Hubei Hongshan Laboratory(2021hszd021 to Z.Y.and 2021hskf013 to G.Z.)。
文摘Chorionic gonadotropinα(Cgα)functions as the shared subunit for thyroid-stimulating hormone subunitβ(Tshβ),luteinizing hormone subunitβ(Lhβ),and follicle-stimulating hormone subunitβ(Fshβ).While theseβ-subunits have been extensively studied using effective gene knockout models in zebrafish,the biological role of Cgαremains elusive.In this study,cgα-deficient zebrafish generated via transcription activator-like effector nucleases(TALENs)exhibited viability but displayed pronounced developmental abnormalities,including growth retardation,hyperpigmentation,reduced thyroxine(T4)levels,and defective anterior swim bladder inflation during juvenile stages.In adults,cgαdeficiency led to disrupted gonadal development,impaired secondary sex characteristics(SSCs),and severely impacted reproductive behavior in both female and male fish.Notably,both testicular and ovarian differentiation were observed in cgα-deficient fish and lhβ^(−/−);fshβ^(−/−)mutants.Gonadal sex differentiation in cgα-deficient zebrafish exhibited a pronounced shift toward testicular fate upon additional disruption of fshβ(cgα^(−/−);fshβ^(−/−)),marked by elevated anti-Müllerian hormone(amh)expression,or following loss of follicle-stimulating hormone receptor(fshr)(cgα^(−/−);fshr^(−/−)).In vitro assays in Chinese hamster ovary(CHO)cells revealed increased cAMP response element(CRE)promoter activity following transfection with constructs encoding Fshr,Fshβ/Fshr,or Cgα/Fshβ/Fshr.Collectively,the phenotypes observed in cgα-deficient fish recapitulate those of thyrotropin-and gonadotropin-disrupted models,highlighting the essential role of Cgαin thyroid and gonadal function.Importantly,these findings uncover the role of Fsh signaling in maintaining proper ovarian differentiation in zebrafish,including Cgα-independent Fshβactivity and the constitutive functionality of Fshr.
基金Supported by the Research Grants of the National Research,Development and Innovation Office,No.K125377,No.K134863 and No.K143549New National Excellence Program of the Ministry of Human Capacities,No.UNKP-20-5-SZTE-161,No.UNKP-22-3-SZTE-233,No.UNKP-23-5-SZTE-719,No.UNKP-22-4-SZTE-296 and No.UNKP-22-3-SZTE-278+1 种基金Janos Bolyai Research Grant,No.BO/00723/22the Géza Hetényi Research Grant by Albert Szent-Györgyi Medical School,University of Szeged.
文摘BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.
基金Acknowledgment This work was supported by the National High Tech- nology Research and Development Program of China （Grants 2004AA216090 and 2002BA711A08）, National Basic Research Program of China （Grant 2004Cb518805）, the Natural National Science Foundation of China （Grant 30470960） and the China Medical Board of New York.
文摘Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.
基金supported by the Huazhong University of Science and Technology (No. 24510101 and 25510026)
文摘MicroRNAs are small non-coding RNAs which regulate gene expression in a post-transcriptional manner. Although the first study was published about 15 years ago, knowledge about their role in regulation of cell proliferation, differentiation, apoptosis and immunity has been greatly advanced recently. Their association with formation, angiogenesis, metastasis and chemotherapy resistance of minors has become one of the core issues in epigenetics of cancer. Here, we summarize the latest findings concerning microRNAs involved in dif- ferent signal pathways leading to colorectal cancer, introduce some new potential microRNAs as biomarkers in diagnosis and prognosis, and analyze its application in the treatment of cancer.
基金Supported by The National Institute of Genetic Engineering and Biotechnology,Projects No.291,316Digestive Diseases Research Center of Tehran University of Medical Sciences
文摘【Abstract】factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffinembedded blocks of adjacent normal specimens from the cases,along with normal esophageal tissue from 80 healthy subjects.RESULTS:Positive expression of p53 protein was detected in 56.2%(45/80)of ESCC cases,and in none of the normal esophageal tissue of the control group(P【0.001).Furthermore,73.8%(59/80)of ESCC cases and 43.8%(35/80)of controls had positive expression of p21 protein(P【0.001).Cigarette smoking was significantly associated with p53 over-expression in ESCC cases(P=0.010,OR=3.64;95%CI:1.32-10.02).p21 over-expression was associated with poorer clinical outcome among the ESCC patients(P=0.009).CONCLUSION:Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran.Furthermore,p21 over-expression was found to be associated with poor prognosis,specifically in the operable ESCC patients.
