The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findin...The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findings,highlighting the role of mitochondrial dysfunction in the pathogenesis of T2DM.By examining the molecular mechanisms through which these tRNA variants contribute to disease progression,the study introduces new targets for therapeutic strategies.We discuss the broader implications of these results,emphasizing the importance of understanding mitochondrial genetics in addressing T2DM.展开更多
BACKGROUND The coronavirus disease 2019(COVID-19)virus has been a world-known pan-demic since February 2020.Multiple variances had been established;the most common variants in Israel were omicron and delta.AIM To anal...BACKGROUND The coronavirus disease 2019(COVID-19)virus has been a world-known pan-demic since February 2020.Multiple variances had been established;the most common variants in Israel were omicron and delta.AIM To analyze and compare laboratory values in the"omicron"and"delta"variants of the coronavirus by conducting follow-up examinations and laboratory audits on COVID-19 patients admitted to our institution.METHODS A retrospective study,two groups,50 patients in each group.Patients examined positive for COVID-19 were divided into groups according to the common variant at the given time.We reviewed demographic data and laboratory results such as complete blood count and full chemistry,including electrolytes and coagulation parameters.RESULTS The mean age was 52%,66.53±21.7 were female.No significance was found comparing laboratory results in the following disciplines:Blood count,hemo-globin,and lymphocytes(P=0.41,P=0.87,P=0.97).Omicron and delta variants have higher neutrophil counts,though they are not significantly different(P=0.38).Coagulation tests:Activated paritial thromoplastin test and international normalized ratio(P=0.72,P=0.68).We found no significance of abnormality for all electrolytes.CONCLUSION The study compares laboratory results of blood tests between two variants of the COVID-19 virus–omicron and delta.We found no significance between the variants.Our results show the need for further research with larger data as well as the need to compare all COVID-19 variants.展开更多
Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure ...Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.展开更多
Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between geneti...Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.展开更多
Amino acids are the primary form of nitrogen utilization in higher plants,mainly transported by amino acid transporters.In this study,we analyzed the natural variation of amino acid transporter-like 4(OsATL4)in rice g...Amino acids are the primary form of nitrogen utilization in higher plants,mainly transported by amino acid transporters.In this study,we analyzed the natural variation of amino acid transporter-like 4(OsATL4)in rice germplasm resources,identified its spatiotemporal expression characteristics,determined its substrate transport,and validated its function using transgenic plants.We found that the promoter sequence of OsATL4 varied across 498 rice varieties.The expression level of OsATL4 was higher in japonica rice,which was negatively correlated with tiller number and grain yield.OsATL4 was highly expressed in the basal part,leaf sheath,stem,and young panicle,with its two splicing variants localized to the cell membrane.OsATL4a(the long splicing variant)had a high affinity for transporting Ser,Leu,Phe,and Thr,while OsATL4b(the short splicing variant)had a high affinity for transporting Ser,Leu,and Phe.Blocking OsATL4 promoted axillary bud outgrowth,rice tillering,and grain yield,whereas overexpression lines exhibited the opposite phenotype.Exogenous application of low concentrations of Ser promoted axillary bud outgrowth in overexpression lines,while high concentrations of Ser inhibited it.Conversely,the mutant lines showed the opposite response.Altered expression of OsATL4 might affect the expression of genes in nitrogen,auxin,and cytokinin pathways.We propose that two splicing variants of OsATL4 negatively regulate rice tillering and yield by mediating the transport of amino acids,making it a significant target for high-yield rice breeding.展开更多
Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk....Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.展开更多
Soybean(Glycine max)is an important and valuable crop,providing oil and proteins for both humans and animals.Seed weight is a key trait that determines soybean yields;however,the genes and mechanisms controlling seed ...Soybean(Glycine max)is an important and valuable crop,providing oil and proteins for both humans and animals.Seed weight is a key trait that determines soybean yields;however,the genes and mechanisms controlling seed weight remain poorly understood.Here,we used genome-wide association study(GWAS)and joint linkage mapping to identify a ubiquitin-specific protease,GmSW17.1,which regulates 100-seed weight in soybean.Two natural allelic variants of GmSW17.1 resulted in significantly different 100-seed weight,with GmSW17.1T conferring heavier seeds.We used CRISPR/Cas9 technology to knock out GmSW17.1,resulting in lighter and smaller seeds;however,these mutants produced more seeds than the wild type,resulting in similar overall yields.Owing to the increased number of seeds,we determined that GmSW17.1 is highly transcribed in developing seeds,and its encoded protein physically interacts in the nucleus with GmSGF11,which plays a crucial role in the deubiquitinating pathway.Analysis of genomic sequences from more than 1714 soybean accessions suggested that the natural allele GmSW17.1T was selected during the domestication and genetic improvement,resulting in its rapid expansion in cultivated soybean.These findings provide important insights into the role of GmSW17.1 in 100-seed weight and offer valuable clues for the molecular breeding of soybean.展开更多
AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 m...AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.展开更多
Due to the diversity and unpredictability of changes in malicious code,studying the traceability of variant families remains challenging.In this paper,we propose a GAN-EfficientNetV2-based method for tracing families ...Due to the diversity and unpredictability of changes in malicious code,studying the traceability of variant families remains challenging.In this paper,we propose a GAN-EfficientNetV2-based method for tracing families of malicious code variants.This method leverages the similarity in layouts and textures between images of malicious code variants from the same source and their original family of malicious code images.The method includes a lightweight classifier and a simulator.The classifier utilizes the enhanced EfficientNetV2 to categorize malicious code images and can be easily deployed on mobile,embedded,and other devices.The simulator utilizes an enhanced generative adversarial network to simulate different variants of malicious code and generates datasets to validate the model’s performance.This process helps identify model vulnerabilities and security risks,facilitating model enhancement and development.The classifier achieves 98.61%and 97.59%accuracy on the MMCC dataset and Malevis dataset,respectively.The simulator’s generated image of malicious code variants has an FID value of 155.44 and an IS value of 1.72±0.42.The classifier’s accuracy for tracing the family of malicious code variants is as high as 90.29%,surpassing that of mainstream neural network models.This meets the current demand for high generalization and anti-obfuscation abilities in malicious code classification models due to the rapid evolution of malicious code.展开更多
AIM:To describe the clinical,electrophysiological,and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant.MET...AIM:To describe the clinical,electrophysiological,and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant.METHODS:The patient underwent a complete ophthalmologic examination including best-corrected visual acuity,anterior segment and dilated fundus,visual field,spectral-domain optical coherence tomography(OCT)and electroretinogram(ERG).The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result.Then we reviewed the characteristics of the patients reported with the same variant.RESULTS:A 30-year male presented with severe early retinal degeneration who complained night blindness,decreased visual acuity,vitreous floaters and amaurosis fugax.The best corrected vision was 0.04 OD and 0.12 OS,respectively.The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye.Autofluorescence shows bilateral symmetrical hypo-autofluorescence.ERG revealed that the amplitudes of a-and b-wave were severely decreased.Multifocal ERG showed decreased amplitudes in the local macular area.A homozygous missense variant c.146C>T(chr14:68191267)was found.The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied.CONCLUSION:An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported.The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.展开更多
Aim: To detect risk and preventive factors associated with the Omicron variant infection in university students, a combination of a web-based survey and multivariate logistic regression analysis was introduced as the ...Aim: To detect risk and preventive factors associated with the Omicron variant infection in university students, a combination of a web-based survey and multivariate logistic regression analysis was introduced as the front-line initiatives by the school health practitioners. Design: Questionnaire survey. Methods: The school-wide web-based questionnaire survey was conducted among our university students as a part of the annual health check-up in April, 2023. The positive outcome was confined to the first symptomatic COVID-19 onset during the Omicron variant outbreak. Results: In this self-administered survey, risk or protective associations were merely estimated statistically in university students (n = 5406). In measured factors, karaoke and club/group activities could maintain the statistical significance in adjusted odds ratios (ORs) as relative risk factors, and science course, measles/ rubella (MR) vaccination, and COVID-19 vaccination remained as relative protective factors in adjusted OR analyses. Club/group activities with member gathering and karaoke sing-along sessions in university students may frequently have WHO’s three Cs. These risk factors are still important topics for the infection control of COVID-19 in university students. Together with some recent reports from other researchers, the significant protective role of MR vaccine in our survey warrants further clinical investigation. If the breakthrough infection continuously constitutes the majority of infection, real data in test-negative case-control or web-based questionnaire design continue to be important for statistical analysis to determine the minimal requirement of our strategies which may be equivalent to or replace COVID-19 vaccines.展开更多
Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and mole...Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.展开更多
Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms an...Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms and respiratory decline were finally explained by the diagnosis of West Nile-encephalitis. During her admission, the isolated peaked T-waves indicated the underlying stress-induced cardiomyopathy. The absence of all other causes of hyperacute T-waves, their subsequent resolution with the resolution of infection and improvement in wall motion abnormalities, further supported the association. This case highlights the importance of considering hyperacute T-waves in an approach towards the diagnosis of WNV-encephalitis related atypical variant of stress-induced cardiomyopathy.展开更多
Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the ...Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.展开更多
BACKGROUND Pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree.The clear cell variant of PMEC is exceptionally uncommon and presents not...BACKGROUND Pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree.The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges,primarily attributable to its morphological similarity to other tumors containing clear cells.CASE SUMMARY A 22-year-old male,formerly in good health,came in with a two-month duration of persistent cough and production of sputum.Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus,which resulted in complete atelectasis of the left lung.Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor,charac-terized by clear cell morphology in most of the tumor cells.The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection.Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion,leading to a definitive pathological diagnosis of the clear cell variant of PMEC,staged as T2N0M0.After surgery,the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period.CONCLUSION This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male.The patient underwent successful left lower lobe sleeve resection.This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy,underscoring the importance of precise diagnosis and personalized treatment strategies.展开更多
BACKGROUND The Columbia classification identified five histological variants of focal segmental glomerulosclerosis(FSGS).The prognostic significance of these variants remains controversial.AIM To evaluate the relative...BACKGROUND The Columbia classification identified five histological variants of focal segmental glomerulosclerosis(FSGS).The prognostic significance of these variants remains controversial.AIM To evaluate the relative frequency,clinicopathologic characteristics,and medium-term outcomes of FSGS variants at a single center in Pakistan.METHODS This retrospective study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan on all consecutive adults(≥16 years)with biopsy-proven primary FSGS from January 1995 to December 2017.Studied subjects were treated with steroids as a first-line therapy.The response rates,doubling of serum creatinine,and kidney failure(KF)with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis,and Chi-square tests as appropriate.Data were analyzed by SPSS version 22.0.P-value≤0.05 was considered significant.RESULTS A total of 401 patients were diagnosed with primary FSGS during the study period.Among these,352(87.7%)had a designated histological variant.The not otherwise specified(NOS)variant was the commonest,being found in 185(53.9%)patients,followed by the tip variant in 100(29.1%)patients.Collapsing(COL),cellular(CEL),and perihilar(PHI)variants were seen in 58(16.9%),6(1.5%),and 3(0.7%)patients,respectively.CEL and PHI variants were excluded from further analysis due to small patient numbers.The mean follow-up period was 36.5±29.2 months.Regarding response rates of variants,patients with TIP lesions achieved remission more frequently(59.5%)than patients with NOS(41.8%)and COL(24.52%)variants(P<0.001).The hazard ratio of complete response among patients with the COL variant was 0.163[95%confidence interval(CI):0.039-0.67]as compared to patients with NOS.The TIP variant showed a hazard ratio of 2.5(95%CI:1.61-3.89)for complete remission compared to the NOS variant.Overall,progressive KF was observed more frequently in patients with the COL variant,43.4%(P<0.001).Among these,24.53%of patients required kidney replacement therapy(P<0.001).The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57(95%CI:1.87-113.49)as compared to patients with the TIP variant.CONCLUSION In conclusion,histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.展开更多
English idiom variant refers to the form of idiom created by means of altering some original components,structures,or meanings of the former idioms.The nonce variant of English idioms can be analyzed from the followin...English idiom variant refers to the form of idiom created by means of altering some original components,structures,or meanings of the former idioms.The nonce variant of English idioms can be analyzed from the following three aspects:reasons for formation of nonce variant,types into which it could be divided,and rhetorical functions it is capable of producing.Through the analysis of these three aspects,it is almost likely for language-users to realize the importance and modes of idiom’s renovation,get a better understanding of English idioms,and thus utilize English idioms more skillfully.展开更多
BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries....BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.Data was collected and analyzed on Excel sheet.RESULTS In total,358 individuals were included,including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer.The prevalence of breast cancer susceptibility gene(BRCA)1/2 pathogenic variants was 8.63%(19/220)in patients with breast cancer,and 15.1%(5/33)in those with ovarian cancer.Among the 25 of 220 patients with breast cancer tested by next-generation sequencing,3 patients had pathogenic variants other than BRCA1/2.The highest risk was observed in those aged 40 years with breast cancer and a positive family history,where the BRCA1/2 prevalence was 20.1%(9/43).Among the unaffected subjects,31.1%(14/45)had the same BRCA1/2 pathogenic variants in their corresponding relatives.Among the subjects referred because of a positive family history of cancer without known hereditary factors,5.35%(3/56)had pathogenic variants of BRCA1 and BRCA2.The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.CONCLUSION This study showed a 8.63%prevalence of pathogenic variants in patients with breast cancer and a 15.1%prevalence in patients with ovarian cancer.Among the relatives of patients with BRCA1/2 pathogenic variants,31%tested positive for the same variant,while 5.3%of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.展开更多
1|INTRODUCTION The first case of severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)was reported in Wuhan,China,in December 2019.The virus spread worldwide within a few weeks of its outbreak,resulting in cor...1|INTRODUCTION The first case of severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)was reported in Wuhan,China,in December 2019.The virus spread worldwide within a few weeks of its outbreak,resulting in coronavirus disease(COVID‐19)[1,2].In March 2020,the World Health Organization(WHO)declared the COVID‐19 outbreak,a global pandemic.展开更多
Objective: To study the expression of CD44 correlation with the ability ofmetastasis of tumor cells in gastric carcinoma, to find the correlation of the concentration ofsoluble CD 44 Variant 6 (sCD44v6) and the histol...Objective: To study the expression of CD44 correlation with the ability ofmetastasis of tumor cells in gastric carcinoma, to find the correlation of the concentration ofsoluble CD 44 Variant 6 (sCD44v6) and the histologic expression of CD44 Variant 6 (CD44v6) in tumorswith the clinico- pathologic features, and to make serum concentration of the CD44v6 and theexpression of CD44v6 may be useful an indicator as an early diagnosis, invasion, metastasis, andprognosis. Methods: Serum samples were obtained from 70 patients with primary gastric carcinomabefore surgery and 20 patients after surgery. Serum levels of CD44v6 were determined with aquantitative- enzyme- link-immuno- adsorbent assay. The expression of CD44v6 in tumors was examinedby immuno-histo-chemical staining. Results: Both the serum concentration of CD44v6 and itsexpression in tumors were positively related to the depth of invasion of the tumor, lymph nodemetastasis, clinical stage, and diffuse type gastric carcinoma, but not to the tumor size. The serumlevel of CD44v6 in patients with gastric cancer was significantly higher than that in control. Theserum concentration of CD44v6 was markedly lowered after curative surgery (F<0. 001), and the serumlevel of CD44v6 was higher in patients with gastric cancer with CD44v6 positive tumor cells than inthose with CD44v6 negative tumor cells. The serum level of CD44v6 was a prognostic indicator inpatients with diffuse type gastric carcinoma, as was the histological expression of CD44v6.Conclusion: CD44v6 of gastric cancer and serum concentration of CD44v6 seems to be correlated to theprogression of diffuse type gastric carcinoma metas- tasis and clinical stage. An elevated level ofsCD44v6 may serve as an indicator of lymph node metastasis (especially early metastasis) and badprognosis in pa tients with gastric carcinoma.展开更多
文摘The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findings,highlighting the role of mitochondrial dysfunction in the pathogenesis of T2DM.By examining the molecular mechanisms through which these tRNA variants contribute to disease progression,the study introduces new targets for therapeutic strategies.We discuss the broader implications of these results,emphasizing the importance of understanding mitochondrial genetics in addressing T2DM.
文摘BACKGROUND The coronavirus disease 2019(COVID-19)virus has been a world-known pan-demic since February 2020.Multiple variances had been established;the most common variants in Israel were omicron and delta.AIM To analyze and compare laboratory values in the"omicron"and"delta"variants of the coronavirus by conducting follow-up examinations and laboratory audits on COVID-19 patients admitted to our institution.METHODS A retrospective study,two groups,50 patients in each group.Patients examined positive for COVID-19 were divided into groups according to the common variant at the given time.We reviewed demographic data and laboratory results such as complete blood count and full chemistry,including electrolytes and coagulation parameters.RESULTS The mean age was 52%,66.53±21.7 were female.No significance was found comparing laboratory results in the following disciplines:Blood count,hemo-globin,and lymphocytes(P=0.41,P=0.87,P=0.97).Omicron and delta variants have higher neutrophil counts,though they are not significantly different(P=0.38).Coagulation tests:Activated paritial thromoplastin test and international normalized ratio(P=0.72,P=0.68).We found no significance of abnormality for all electrolytes.CONCLUSION The study compares laboratory results of blood tests between two variants of the COVID-19 virus–omicron and delta.We found no significance between the variants.Our results show the need for further research with larger data as well as the need to compare all COVID-19 variants.
基金supported by the project“Protection of biodiversity of Italian poultry breeds—TuBAvI”,funded in the framework of the PSRN 2014–2020,submeasure 10.2“Support for sustainable conservation,use and development of genetic resources in agriculture”.
文摘Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.
基金funded by the National Key R&D Program of China(Grant Nos.2018YFC1313100 and 2018YFC1313102)the National Natural Science Foundation of China(Grant No.81773539)+1 种基金Collaborative Innovation Center for Cancer Personalized Medicinethe Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).
文摘Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.
基金supported by the National Natural Science Foundation of China (32060064/32260498)the Guizhou Provincial Excellent Young Talents Project of Science and Technology (Qiankehepingtairencai-YQK (2023)002)+6 种基金the Guizhou Provincial Science and Technology Projects (Qiankehejichu-ZK (2021)General 128Qiankehejichu-ZK (2022)Key 008Qiankehechengguo (2024)General 116Qiankehepingtairencai-BQW (2024)001,qiankehepingtai-YWZ (2024)004)the Key Laboratory of Molecular Breeding for Grain and Oil Crops in Guizhou Province (Qiankehezhongyindi (2023)008)the Key Laboratory of Functional Agriculture of Guizhou Provincial Department of Education (Qianjiaoji (2023)007)the Qiandongnan Science and Technology Support Project (Qiandongnan Kehe Support (2023)06).
文摘Amino acids are the primary form of nitrogen utilization in higher plants,mainly transported by amino acid transporters.In this study,we analyzed the natural variation of amino acid transporter-like 4(OsATL4)in rice germplasm resources,identified its spatiotemporal expression characteristics,determined its substrate transport,and validated its function using transgenic plants.We found that the promoter sequence of OsATL4 varied across 498 rice varieties.The expression level of OsATL4 was higher in japonica rice,which was negatively correlated with tiller number and grain yield.OsATL4 was highly expressed in the basal part,leaf sheath,stem,and young panicle,with its two splicing variants localized to the cell membrane.OsATL4a(the long splicing variant)had a high affinity for transporting Ser,Leu,Phe,and Thr,while OsATL4b(the short splicing variant)had a high affinity for transporting Ser,Leu,and Phe.Blocking OsATL4 promoted axillary bud outgrowth,rice tillering,and grain yield,whereas overexpression lines exhibited the opposite phenotype.Exogenous application of low concentrations of Ser promoted axillary bud outgrowth in overexpression lines,while high concentrations of Ser inhibited it.Conversely,the mutant lines showed the opposite response.Altered expression of OsATL4 might affect the expression of genes in nitrogen,auxin,and cytokinin pathways.We propose that two splicing variants of OsATL4 negatively regulate rice tillering and yield by mediating the transport of amino acids,making it a significant target for high-yield rice breeding.
文摘Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.
基金supported by Research and Application of Technological Innovation in Inner Mongolia Soybean Industry (2023DXZD0002)the National Natural Science Foundation of China (32201756)+4 种基金the National Key Research and Development Program of China (2021YFD1201600)the Agricultural Science and Technology Innovation Program (ASTIP)of Chinese Academy of Agricultural Sciences (CAAS-ZDRW202109,01-ICS-05)the earmarked fund for CARS (CARS-04-PS01)Scientific Innovation 2030 Project (2022ZD0401703)the National Science Foundation for Post-doctoral Scientists of China (2021 M703554).
文摘Soybean(Glycine max)is an important and valuable crop,providing oil and proteins for both humans and animals.Seed weight is a key trait that determines soybean yields;however,the genes and mechanisms controlling seed weight remain poorly understood.Here,we used genome-wide association study(GWAS)and joint linkage mapping to identify a ubiquitin-specific protease,GmSW17.1,which regulates 100-seed weight in soybean.Two natural allelic variants of GmSW17.1 resulted in significantly different 100-seed weight,with GmSW17.1T conferring heavier seeds.We used CRISPR/Cas9 technology to knock out GmSW17.1,resulting in lighter and smaller seeds;however,these mutants produced more seeds than the wild type,resulting in similar overall yields.Owing to the increased number of seeds,we determined that GmSW17.1 is highly transcribed in developing seeds,and its encoded protein physically interacts in the nucleus with GmSGF11,which plays a crucial role in the deubiquitinating pathway.Analysis of genomic sequences from more than 1714 soybean accessions suggested that the natural allele GmSW17.1T was selected during the domestication and genetic improvement,resulting in its rapid expansion in cultivated soybean.These findings provide important insights into the role of GmSW17.1 in 100-seed weight and offer valuable clues for the molecular breeding of soybean.
基金Supported by Shenzhen Science and Technology Program,Shenzhen,China(No.JCYJ20200109145001814,No.SGDX20211123120001001)the National Natural Science Foundation of China(No.81970790)Sanming Project of Medicine in Shenzhen(No.SZSM202011015).
文摘AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.
基金support this work is the Key Research and Development Program of Heilongjiang Province,specifically Grant Number 2023ZX02C10.
文摘Due to the diversity and unpredictability of changes in malicious code,studying the traceability of variant families remains challenging.In this paper,we propose a GAN-EfficientNetV2-based method for tracing families of malicious code variants.This method leverages the similarity in layouts and textures between images of malicious code variants from the same source and their original family of malicious code images.The method includes a lightweight classifier and a simulator.The classifier utilizes the enhanced EfficientNetV2 to categorize malicious code images and can be easily deployed on mobile,embedded,and other devices.The simulator utilizes an enhanced generative adversarial network to simulate different variants of malicious code and generates datasets to validate the model’s performance.This process helps identify model vulnerabilities and security risks,facilitating model enhancement and development.The classifier achieves 98.61%and 97.59%accuracy on the MMCC dataset and Malevis dataset,respectively.The simulator’s generated image of malicious code variants has an FID value of 155.44 and an IS value of 1.72±0.42.The classifier’s accuracy for tracing the family of malicious code variants is as high as 90.29%,surpassing that of mainstream neural network models.This meets the current demand for high generalization and anti-obfuscation abilities in malicious code classification models due to the rapid evolution of malicious code.
基金Supported by Shenzhen Science and Technology Program,Shenzhen,China(No.JCYJ20200109145001814,No.SGDX20211123120001001)the National Natural Science Foundation of China(No.81970790)Sanming Project of Medicine in Shenzhen(No.SZSM202011015).
文摘AIM:To describe the clinical,electrophysiological,and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant.METHODS:The patient underwent a complete ophthalmologic examination including best-corrected visual acuity,anterior segment and dilated fundus,visual field,spectral-domain optical coherence tomography(OCT)and electroretinogram(ERG).The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result.Then we reviewed the characteristics of the patients reported with the same variant.RESULTS:A 30-year male presented with severe early retinal degeneration who complained night blindness,decreased visual acuity,vitreous floaters and amaurosis fugax.The best corrected vision was 0.04 OD and 0.12 OS,respectively.The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye.Autofluorescence shows bilateral symmetrical hypo-autofluorescence.ERG revealed that the amplitudes of a-and b-wave were severely decreased.Multifocal ERG showed decreased amplitudes in the local macular area.A homozygous missense variant c.146C>T(chr14:68191267)was found.The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied.CONCLUSION:An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported.The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.
文摘Aim: To detect risk and preventive factors associated with the Omicron variant infection in university students, a combination of a web-based survey and multivariate logistic regression analysis was introduced as the front-line initiatives by the school health practitioners. Design: Questionnaire survey. Methods: The school-wide web-based questionnaire survey was conducted among our university students as a part of the annual health check-up in April, 2023. The positive outcome was confined to the first symptomatic COVID-19 onset during the Omicron variant outbreak. Results: In this self-administered survey, risk or protective associations were merely estimated statistically in university students (n = 5406). In measured factors, karaoke and club/group activities could maintain the statistical significance in adjusted odds ratios (ORs) as relative risk factors, and science course, measles/ rubella (MR) vaccination, and COVID-19 vaccination remained as relative protective factors in adjusted OR analyses. Club/group activities with member gathering and karaoke sing-along sessions in university students may frequently have WHO’s three Cs. These risk factors are still important topics for the infection control of COVID-19 in university students. Together with some recent reports from other researchers, the significant protective role of MR vaccine in our survey warrants further clinical investigation. If the breakthrough infection continuously constitutes the majority of infection, real data in test-negative case-control or web-based questionnaire design continue to be important for statistical analysis to determine the minimal requirement of our strategies which may be equivalent to or replace COVID-19 vaccines.
文摘Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.
文摘Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms and respiratory decline were finally explained by the diagnosis of West Nile-encephalitis. During her admission, the isolated peaked T-waves indicated the underlying stress-induced cardiomyopathy. The absence of all other causes of hyperacute T-waves, their subsequent resolution with the resolution of infection and improvement in wall motion abnormalities, further supported the association. This case highlights the importance of considering hyperacute T-waves in an approach towards the diagnosis of WNV-encephalitis related atypical variant of stress-induced cardiomyopathy.
文摘Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.
基金Hunan Provincial Natural Science Foundation of China,No.2022JJ40246The Hunan Cancer Hospital Climb Plan,No.2021NSFC-B005.
文摘BACKGROUND Pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree.The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges,primarily attributable to its morphological similarity to other tumors containing clear cells.CASE SUMMARY A 22-year-old male,formerly in good health,came in with a two-month duration of persistent cough and production of sputum.Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus,which resulted in complete atelectasis of the left lung.Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor,charac-terized by clear cell morphology in most of the tumor cells.The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection.Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion,leading to a definitive pathological diagnosis of the clear cell variant of PMEC,staged as T2N0M0.After surgery,the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period.CONCLUSION This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male.The patient underwent successful left lower lobe sleeve resection.This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy,underscoring the importance of precise diagnosis and personalized treatment strategies.
文摘BACKGROUND The Columbia classification identified five histological variants of focal segmental glomerulosclerosis(FSGS).The prognostic significance of these variants remains controversial.AIM To evaluate the relative frequency,clinicopathologic characteristics,and medium-term outcomes of FSGS variants at a single center in Pakistan.METHODS This retrospective study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan on all consecutive adults(≥16 years)with biopsy-proven primary FSGS from January 1995 to December 2017.Studied subjects were treated with steroids as a first-line therapy.The response rates,doubling of serum creatinine,and kidney failure(KF)with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis,and Chi-square tests as appropriate.Data were analyzed by SPSS version 22.0.P-value≤0.05 was considered significant.RESULTS A total of 401 patients were diagnosed with primary FSGS during the study period.Among these,352(87.7%)had a designated histological variant.The not otherwise specified(NOS)variant was the commonest,being found in 185(53.9%)patients,followed by the tip variant in 100(29.1%)patients.Collapsing(COL),cellular(CEL),and perihilar(PHI)variants were seen in 58(16.9%),6(1.5%),and 3(0.7%)patients,respectively.CEL and PHI variants were excluded from further analysis due to small patient numbers.The mean follow-up period was 36.5±29.2 months.Regarding response rates of variants,patients with TIP lesions achieved remission more frequently(59.5%)than patients with NOS(41.8%)and COL(24.52%)variants(P<0.001).The hazard ratio of complete response among patients with the COL variant was 0.163[95%confidence interval(CI):0.039-0.67]as compared to patients with NOS.The TIP variant showed a hazard ratio of 2.5(95%CI:1.61-3.89)for complete remission compared to the NOS variant.Overall,progressive KF was observed more frequently in patients with the COL variant,43.4%(P<0.001).Among these,24.53%of patients required kidney replacement therapy(P<0.001).The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57(95%CI:1.87-113.49)as compared to patients with the TIP variant.CONCLUSION In conclusion,histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.
基金sponsored by the teaching program“English Grammar”(Fund No.209/1541801009).
文摘English idiom variant refers to the form of idiom created by means of altering some original components,structures,or meanings of the former idioms.The nonce variant of English idioms can be analyzed from the following three aspects:reasons for formation of nonce variant,types into which it could be divided,and rhetorical functions it is capable of producing.Through the analysis of these three aspects,it is almost likely for language-users to realize the importance and modes of idiom’s renovation,get a better understanding of English idioms,and thus utilize English idioms more skillfully.
文摘BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.Data was collected and analyzed on Excel sheet.RESULTS In total,358 individuals were included,including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer.The prevalence of breast cancer susceptibility gene(BRCA)1/2 pathogenic variants was 8.63%(19/220)in patients with breast cancer,and 15.1%(5/33)in those with ovarian cancer.Among the 25 of 220 patients with breast cancer tested by next-generation sequencing,3 patients had pathogenic variants other than BRCA1/2.The highest risk was observed in those aged 40 years with breast cancer and a positive family history,where the BRCA1/2 prevalence was 20.1%(9/43).Among the unaffected subjects,31.1%(14/45)had the same BRCA1/2 pathogenic variants in their corresponding relatives.Among the subjects referred because of a positive family history of cancer without known hereditary factors,5.35%(3/56)had pathogenic variants of BRCA1 and BRCA2.The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.CONCLUSION This study showed a 8.63%prevalence of pathogenic variants in patients with breast cancer and a 15.1%prevalence in patients with ovarian cancer.Among the relatives of patients with BRCA1/2 pathogenic variants,31%tested positive for the same variant,while 5.3%of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.
文摘1|INTRODUCTION The first case of severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)was reported in Wuhan,China,in December 2019.The virus spread worldwide within a few weeks of its outbreak,resulting in coronavirus disease(COVID‐19)[1,2].In March 2020,the World Health Organization(WHO)declared the COVID‐19 outbreak,a global pandemic.
基金Supported by a grant from Science and Technology Committee of Jiangsu Province(457-99064)
文摘Objective: To study the expression of CD44 correlation with the ability ofmetastasis of tumor cells in gastric carcinoma, to find the correlation of the concentration ofsoluble CD 44 Variant 6 (sCD44v6) and the histologic expression of CD44 Variant 6 (CD44v6) in tumorswith the clinico- pathologic features, and to make serum concentration of the CD44v6 and theexpression of CD44v6 may be useful an indicator as an early diagnosis, invasion, metastasis, andprognosis. Methods: Serum samples were obtained from 70 patients with primary gastric carcinomabefore surgery and 20 patients after surgery. Serum levels of CD44v6 were determined with aquantitative- enzyme- link-immuno- adsorbent assay. The expression of CD44v6 in tumors was examinedby immuno-histo-chemical staining. Results: Both the serum concentration of CD44v6 and itsexpression in tumors were positively related to the depth of invasion of the tumor, lymph nodemetastasis, clinical stage, and diffuse type gastric carcinoma, but not to the tumor size. The serumlevel of CD44v6 in patients with gastric cancer was significantly higher than that in control. Theserum concentration of CD44v6 was markedly lowered after curative surgery (F<0. 001), and the serumlevel of CD44v6 was higher in patients with gastric cancer with CD44v6 positive tumor cells than inthose with CD44v6 negative tumor cells. The serum level of CD44v6 was a prognostic indicator inpatients with diffuse type gastric carcinoma, as was the histological expression of CD44v6.Conclusion: CD44v6 of gastric cancer and serum concentration of CD44v6 seems to be correlated to theprogression of diffuse type gastric carcinoma metas- tasis and clinical stage. An elevated level ofsCD44v6 may serve as an indicator of lymph node metastasis (especially early metastasis) and badprognosis in pa tients with gastric carcinoma.