Crimean-Congo hemorrhagic fever (CCHF) is a severe illness with high fatality.Cases are reported in several countries in Africa,Europe,the Middle East,and Asia.Phylogenetic analyses based on the virus S (nucleocapsid)...Crimean-Congo hemorrhagic fever (CCHF) is a severe illness with high fatality.Cases are reported in several countries in Africa,Europe,the Middle East,and Asia.Phylogenetic analyses based on the virus S (nucleocapsid),M (glycoprotein),and L (polymerase) genome segments sequences indicate distinct geographic lineages exist but their specific genetic characteristics require elucidation.In this work we collected all full length S segment sequences and generated a phylogenetic tree based on the alignment of these 62 samples.We then analyzed the alignment using entries from AAIndex,the Amino Acid Index database,to identify amino acid mutations that performed significant changes in charge,pka,hydropathy and side chain volume.Finally,we mapped these changes back to the tree and alignment to identify correlated mutations or sites that characterized a specific lineage.Based on this analysis we are able to propose a number of sites that appear to be important for virus function and which would be good candidates for experimental mutational analysis studies.展开更多
Newcastle disease (ND) virus is a leading threat to commercial and domestic poultry in Pakistan. The virus infects and constitutes irreversible impairment to the nervous system, damages the respiratory system, and mar...Newcastle disease (ND) virus is a leading threat to commercial and domestic poultry in Pakistan. The virus infects and constitutes irreversible impairment to the nervous system, damages the respiratory system, and marks severe gastrointestinal lesions leading to heavy mortality in short-living birds and substantial losses in layers and breeders. The continuous emergence and evolution of the virus made it inclined to evade the humoral response and indirectly the circumvention of artificial active immunization. Newcastle disease is caused by the orthoavula genus of the paramyxoviridae family and has shown high genetic diversity even in their genotypes while information regarding enzootic trends of the virus is scanty in Pakistan. A total of 40 tracheal samples of NDV were collected from different commercial broiler farms and 11 isolates of NDV were identified. In the current study, we determined the genetic diversity of the Newcastle disease virus based on the partial sequencing of the fusion protein gene available in the NCBI database. Genetic analysis showed that seven isolates belonged to class I genotype VII and four belonged to class II genotype II. Interestingly, two isolates had epidemiological connections with vaccine-like class II genotype II. Our findings, concerning the recent outbreaks of class I genotype VII and class II genotype II of NDV in vaccinated commercial flocks, suggest possible potential partial mutations in the fusion protein gene. Genetic diversity and formation of the new cleavage site in an important neutralizing protein of wild strain are linked with the potency of artificial active immunization and a major cause of vaccine failure.展开更多
AIM:To compare the differences between dideoxy sequencing/KRAS StripAssay/pyrosequencing for detection of KRAS mutation in Chinese colorectal cancer (CRC) patients.METHODS:Formalin-f ixed, paraff in-embedded (FFPE) sa...AIM:To compare the differences between dideoxy sequencing/KRAS StripAssay/pyrosequencing for detection of KRAS mutation in Chinese colorectal cancer (CRC) patients.METHODS:Formalin-f ixed, paraff in-embedded (FFPE) samples with tumor cells ≥ 50% were collected from 100 Chinese CRC patients at Beijing Cancer Hospital. After the extraction of genome DNA from FFPE samples, fragments contained codons 12 and 13 of KRAS exon 2 were amplified by polymerase chain reaction and analyzed by dideoxy sequencing, the KRAS Strip Assay and pyrosequencing. In addition, the sensitivities of the 3 methods were compared on serial dilutions (contents of mutant DNA: 100%,50%,20%, 5%,10%, 5%,1%,0%) of A549 cell line DNA (carrying the codon 12 Gly>Ser mutation) into wild-type DNA (human normal intestinal mucosa). The results of dideoxy sequencing,the KRAS StripAssay and pyrosequencing were analyzed by Chromas Software, Collector forKRAS Strip Assay and the pyrosequencing PyroMarkTM Q24 system, respectively.RESULTS: Among 100 patients, KRAS mutations were identif ied in 34%, 37% and 37% of patients by dideoxy sequencing, the KRAS StripAssay and pyrosequencing, respectively. The sensitivity was highest with the KRAS Strip Assay (1%), followed by pyrosequencing (5%), and dideoxy sequencing was lowest (15%). Six different mutation types were found in this study with 3 main mutations Gly12 Asp (GGT>GAT), Gly12 Val (GGT>GTT) and Gly13 Asp (GGC>GAC). Thirty-three patients were identifi ed to have KRAS mutations by the 3 methods, and a total of 8 patients had conflicting results between 3 methods: 4 mutations not detected by dideoxy sequencing and the KRAS StripAssay were identified by pyrosequencing; 3 mutations not detected by dideoxy sequencing and pyrosequencing were identif ied by the KRAS StripAssay; and 1 mutation not detected by pyrosequencing was conf irmed by dideoxy sequencing and the KRAS StripAssay. Among these discordant results, the results identif ied by dideoxy sequencing were consistent either with the KRAS StripAssay or with pyrosequencing, which indicated that the accuracy of dideoxy sequencing was high. CONCLUSION: Taking a worldwide view of reports and our results,dideoxy sequencing remains the most popular method because of its low cost and high accuracy.展开更多
In this paper,based on the observation data of air temperature during 1951-2009 in Shenyang,the interannual and interdecadal variation of annual average temperature,maximum and minimum temperature in Shenyang were con...In this paper,based on the observation data of air temperature during 1951-2009 in Shenyang,the interannual and interdecadal variation of annual average temperature,maximum and minimum temperature in Shenyang were conducted the statistical analysis by means of linear trend estimation and mutation detection by using Mann-Kendall method.As was demonstrated in the results,the annual average temperature,maximum and minimum temperature in Shenyang showed an upward trend,whose linear tendency rate was 0.231,0.181 and 0.218 respectively.The increment trend of annual average temperature,maximum and minimum temperature was extremely clear.The increase in minimum temperature was more significant than that in mean temperature and maximum temperature.The abrupt change point of annual mean temperature in Shenyang appeared in 1981;the abrupt change point of annual mean maximum temperature appeared in 1994;the annual mean minimum temperature underwent mutation in 1978.展开更多
BACKGROUND Colorectal cancer(CRC)remains a major global health burden due to its high incidence and mortality,with treatment efficacy often hindered by tumor hetero-geneity,drug resistance,and a complex tumor microenv...BACKGROUND Colorectal cancer(CRC)remains a major global health burden due to its high incidence and mortality,with treatment efficacy often hindered by tumor hetero-geneity,drug resistance,and a complex tumor microenvironment(TME).Lactate metabolism plays a pivotal role in reshaping the TME,promoting immune eva-sion and epithelial-mesenchymal transition,making it a promising target for novel therapeutic strategies and prognostic modeling in CRC.AIM To offer an in-depth analysis of the role of lactate metabolism in CRC,high-lighting its significance in the TME and therapeutic response.METHODS Utilizing single-cell and transcriptomic data from the Gene Expression Omnibus and The Cancer Genome Atlas,we identified key lactate metabolic activities,particularly in the monocyte/macrophage subpopulation.RESULTS Seven lactate metabolism-associated genes were significantly linked to CRC prognosis and used to construct a predictive model.This model accurately forecasts patient outcomes and reveals notable distinct patterns of immune infiltration and transcriptomic profiles mutation profiles between high-and low-risk groups.High-risk patients demonstrated elevated immune cell infiltration,increased mutation frequencies,and heightened sensitivity to specific drugs(AZD6482,tozasertib,and SB216763),providing a foundation for personalized treatment approaches.Additionally,a nomogram integrating clinical and metabolic data effectively predicted 1-,3-,and 5-year survival rates.CONCLUSION This report underscored the pivotal mechanism of lactate metabolism in CRC prognosis and suggest novel avenues for therapeutic intervention.展开更多
Climate change and anthropogenic activities have driven significant terrestrial water storage changes(TWSC)in the Three Rivers Source Region(TRSR),exerting profound impacts on freshwater availability across China and ...Climate change and anthropogenic activities have driven significant terrestrial water storage changes(TWSC)in the Three Rivers Source Region(TRSR),exerting profound impacts on freshwater availability across China and broader Asia.However,long-term TWSC characterization remains challenging due to limited observational data in this alpine region.Here,we integrate GRACE observations(2002-2020),ERA5-Land reanalysis,and GLDAS data to reconstruct TWSC using two methods:(1)the water balance method(PER)and(2)the component summation method(SS),applied to three input datasets(ERA5-Land,GLDAS,and their average,GLER).Comparative analysis reveals that the SS method applied to GL-ER yields the highest consistency with GRACE-derived TWSC.Using this optimal approach,we extend the analysis to 1951~2020,uncovering spatiotemporal TWSC patterns.Although annual TWSC trends appear negligible due to strong seasonality,we introduce the intra-year TWSC fluctuation(TWSCF)index to quantify cumulative variability.A significant(p<0.05)transition occurred in 1980,with TWSCF shifting from a declining trend(-0.39 mm/yr)to an increasing trend(0.56 mm/yr),primarily driven by soil moisture changes.However,Hurst exponent analysis suggests this upward trend may not persist.Drought and vegetation assessments indicate concurrent wetting and greening in the TRSR.TWSC correlates strongly with meteorological drought,acting as a reliable drought indicator while its linkage with vegetation dynamics suggests a potential contribution to greening.Our findings provide a robust framework for understanding long-term TWSC evolution and its hydrological-ecological interactions under climate change.展开更多
Charcot-Marie-Tooth （CMT） disease is the most common inherited peripheral neuropathic disorder. CMT is clinically and genetically heterogeneous. To date, 27 genes associated with the disease have been cloned. The pr...Charcot-Marie-Tooth （CMT） disease is the most common inherited peripheral neuropathic disorder. CMT is clinically and genetically heterogeneous. To date, 27 genes associated with the disease have been cloned. The present study carried out clinical classification according to clinical, electrophysiological and pathological features, conducted inheritance classification according to inheritance patterns, and performed mutation analysis of 13 CMT disease genes （PMP22, CX32, HSPB1, MNF2, MPZ, HSPB8, GDAP1, NFL, EGR2, SIMPLE, RAB7, LMNA, MTMR2） in 57 Chinese probands with CMT. Five cases of AD-CMT1 and 13 cases of sporadic CMT1 were diagnosed as CMT1A; five cases of X-CMT1, one case of X-CMT2 and one case of sporadic CMT1 were diagnosed as CMTXl; four cases of AD-CMT2 were diagnosed as CMT2F; one case of AD-CMT2 and one case of sporadic CMT2 were diagnosed as CMT2A2; one case of AD-CMT2 was diagnosed as CMT2L; one case of AD-CMT2 was diagnosed as CMT2J; one case of AR-CMT1 was diagnosed as CMT4A. Among the 57 CMT probands, seven genotypes were determined among 34 patients, with a detection rate of 59.6%. The results indicated that the clinical classification and inheritance classification are indispensable for selecting potential disease genes for mutation detection, and for efficient molecular diagnosis.展开更多
AIM: To analyze the metallochaperone antioxidant-1 (Atox1) gene sequence in Wilson disease patients. METHODS: Mutation analysis of the four exons of the Atox1 gene including the intron- exon boundaries was performed i...AIM: To analyze the metallochaperone antioxidant-1 (Atox1) gene sequence in Wilson disease patients. METHODS: Mutation analysis of the four exons of the Atox1 gene including the intron- exon boundaries was performed in 63 Wilson disease patients by direct sequencing. RESULTS: From 63 selected patients no mutations were identified after the entire coding region including the intron- exon boundaries of Atox1 were sequenced. One known polymorphism within the Atox1 gene (5’UTR -99 T>C) in 31 (49%) of the Wilson patients as well as one previously undescribed variation (5’UTR -68 C>T) in 2 of the Wilson patients could be detected. Statistical analyses revealed that the existence of a variation within the Atox1- gene showed a tendency towards an earlier onset of the disease. CONCLUSION: Based on the data of this study, no major role can be attributed to Atox1 in the pathophysiology or clinical variation of Wilson disease.展开更多
A measure of the“goodness”or efficiency of the test suite is used to determine the proficiency of a test suite.The appropriateness of the test suite is determined through mutation analysis.Several Finite State Machi...A measure of the“goodness”or efficiency of the test suite is used to determine the proficiency of a test suite.The appropriateness of the test suite is determined through mutation analysis.Several Finite State Machine(FSM)mutants are produced in mutation analysis by injecting errors against hypotheses.These mutants serve as test subjects for the test suite(TS).The effectiveness of the test suite is proportional to the number of eliminated mutants.The most effective test suite is the one that removes the most significant number of mutants at the optimal time.It is difficult to determine the fault detection ratio of the system.Because it is difficult to identify the system’s potential flaws precisely.In mutation testing,the Fault Detection Ratio(FDR)metric is currently used to express the adequacy of a test suite.However,there are some issues with this metric.If both test suites have the same defect detection rate,the smaller of the two tests is preferred.The test case(TC)is affected by the same issue.The smaller two test cases with identical performance are assumed to have superior performance.Another difficulty involves time.The performance of numerous vehicles claiming to have a perfect mutant capture time is problematic.Our study developed three metrics to address these issues:FDR/|TS|,FDR/|TC|,and FDR/|Time|;In this context,most used test generation tools were examined and tested using the developed metrics.Thanks to the metrics we have developed,the research contributes to eliminating the problems related to performance measurement by integrating the missing parameters into the system.展开更多
Based on data of temperature and precipitation in Huanren County from 1953 to 2010, linear trend analysis and mutation detection of temperature and precipitation sequence were carried out using linear trend, Mann-Kend...Based on data of temperature and precipitation in Huanren County from 1953 to 2010, linear trend analysis and mutation detection of temperature and precipitation sequence were carried out using linear trend, Mann-Kendall detection and dryness of the de Martonne method. The results showed that during 1953-2010, annual average temperature, annual average maximum and minimum temperature in Huanren County showed an increasing trend; annual precipitation showed a decreasing trend; there was a downward trend in annual dryness. The mutation of annu- al average temperature, annual average maximum and minimum temperature appeared in 1978, 1987 and 1982 respectively; there was no mutation of annual precipitation and dryness. On the whole, the climate of Huanren County tended to be warm and dry over the past 58 years.展开更多
[Objective]The research aimed to study the variation of rainfall data from Guilin Weather Station during 1957-2007.[Method]Based on the daily rainfall data in Guilin during 1957-2007,the trend,period and mutation of p...[Objective]The research aimed to study the variation of rainfall data from Guilin Weather Station during 1957-2007.[Method]Based on the daily rainfall data in Guilin during 1957-2007,the trend,period and mutation of precipitation in Guilin in 51 years were analyzed by using the trend analysis,wavelet analysis and Mann-Kendall non-parameter statistics test method.[Result]The rainfall in Guilin in 51 years presented the rising trend.The rainfall variation was same in the first,second and third quarters of most years,except in the individual year.The rainfall in the fourth quarter had the decrease trend,and the variation was obvious in each year.It illustrated that the rainfall variation in winter was very unstable and had the decrease trend in recent years.But as a whole,the variation of total rainfall in Guilin wasn’t obvious and had the rise trend.It illustrated that the climate variation in Guilin in 51 years wasn’t obvious.The wavelet analysis showed that the rainfall variation in Guilin had 15-year big period and the small period of 2-3 years.Mann-Kendall non-parameter statistics test showed that the mutation situation of total rainfall in Guilin in 51 years wasn’t obvious.But the mutation situations in the second and third quarters were more.The variation in recent 10 years was the most obvious.Maybe it was affected by the global climate variation.[Conclusion]The research provided the theory basis for analyzing the climate variation in Guilin.展开更多
Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectom...Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectomy was performed on two of the three展开更多
AIM:To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes,and to explore the relationship between ACF and colorectal adenoma even...AIM:To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes,and to explore the relationship between ACF and colorectal adenoma even carcinoma. METHODS: DNA from 35 CRC, 15 adenomas, 34 ACF and 10 normal mucus was isolated by means of microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene was performed. RESULTS: K-ras gene mutation frequency in ACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/15), and 14.3% (5/35) respectively, showing no difference (P 】 0.05) in K-ras gene mutation among three pathologic procedures. The K-ras gene mutation in adenoma, carcinoma and 4 ACF restricted in codon 12 (GGT GAT), but the other 2 mutations from ACF located in codon 13 (GGC GAC). K-ras gene mutation was found more frequently in older patients and patients with polypoid cancer. No mutation in codon 61 was found in the three tissue types. Mutation rate of APC gene in adenoma and carcinoma was 22.9% (8/35) and 26.7% (4/15), which was higher than ACF (2.9%) (P 【0.05). APC gene mutation in carcinoma was not correlated with age of patients, location, size and differentiation of tumor. CONCLUSION: ACF might be a very early morphological lesion in the tumorogenesis of colorectal tumor. The morphological feature and gene mutation status was different in ACF and adenoma. ACF is possibly putative microadenoma that might be the precursor of adenoma. In addition, the development of a subgroup of colorectal carcinomas might undergo a way of normal epithelium ACF carcinomas .展开更多
BACKGROUND Schwannomas,also known as neurinomas,are tumors that derive from Schwann cells.Gastrointestinal schwannomas are extremely rare,but the stomach is the most common site.Gastric schwannomas are usually asympto...BACKGROUND Schwannomas,also known as neurinomas,are tumors that derive from Schwann cells.Gastrointestinal schwannomas are extremely rare,but the stomach is the most common site.Gastric schwannomas are usually asymptomatic.Endoscopy and imaging modalities might offer useful preliminary diagnostic information.However,to diagnose schwannoma,the immunohistochemical positivity for S-100 protein is essential,whereas CD117,CD34,SMA,desmin,and DOG-1 are negative.CASE SUMMARY A 45-year-old female was found to have a gastric mass during a medical examination,which was diagnosed as a gastric schwannoma.We performed endoscopic full-thickness resection and endoscopic purse-string suture.Pathology and immunohistochemical staining confirmed the diagnosis of gastric schwannoma through the positivity of S-100 protein.Furthermore,to exclude the misdiagnosis of gastrointestinal stromal tumor,we performed a mutational detection of the c-Kit and PDGFRA genes.Postoperative follow-up revealed that the patient recovered well.CONCLUSION Immunohistochemical staining is essential for the diagnosis of schwannoma.Endoscopic full-thickness resection is an effective treatment method for gastric schwannoma.展开更多
BACKGROUND The totally implantable venous access port(TIVAP)is an important device in patients for injecting blood products,parenteral nutrition or antineoplastic chemotherapy.Metastatic spread at the site of the inse...BACKGROUND The totally implantable venous access port(TIVAP)is an important device in patients for injecting blood products,parenteral nutrition or antineoplastic chemotherapy.Metastatic spread at the site of the insertion of a TIVAP is extremely rare.CASE SUMMARY We report the case of 33-year-old male with advanced gastrointestinal stromal tumor(GIST)who underwent radical tumor resection after neoadjuvant imatinib therapy.However,a solitary GIST metastasis at the site of a TIVAP insertion developed during adjuvant imatinib treatment.Mutational analysis showed secondary mutation in KIT exon 13(V564 A),which is resistant to imatinib treatment.To our knowledge,this is the first case report of a patient with advanced GIST developing GIST metastasis at the site of a TIVAP insertion.CONCLUSION This case highlights that when a patient with advanced,high metastatic GIST requires TIVAP insertion,we should realize that there is a risk of developing tumor metastasis at the site of a TIVAP insertion.展开更多
The CRISPR-Cas system has revolutionized modern life sciences,enabling groundbreaking applications ranging from functional genomics to therapeutic development.Despite its transformative potential,significant technical...The CRISPR-Cas system has revolutionized modern life sciences,enabling groundbreaking applications ranging from functional genomics to therapeutic development.Despite its transformative potential,significant technical limitations persist in current computational tools for quantifying editing efficiency-particularly concerning data processing capabilities,analytical throughput,and operational flexibility.This research presents SuperDecode,a novel computational framework designed to address these methodological constraints.The SuperDecode offers key advantages,including local processing capabilities,large-size sequencing files,batch-processing,and diversified operational functions.展开更多
AIM： To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer （HNPCC） families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands...AIM： To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer （HNPCC） families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands. METHODS： Thirty-one independent Chinese HNPCC families were collected in Zhejiang Province. All of them met Chinese HNPCC criteria. Clinical data about patient gender, site of colorectal cancer, age of onset, history of multiple colorectal cancer, associated extracolonic cancer were recorded. PCR and denaturing high performance liquid chromatography （DHPLC） were employed to screen the mutations. Sequencing analysis was used to find out the exact mutation site and characteristics of the samples showing abnormal DHPLC profiles. RESULTS： One hundred and thirty-six malignant neoplasms were found in 107 patients including 14 multiple cancers. One hundred and six of the 136 neoplasms （77.9%） were diagnosed as colorectal cancer, with an average age of onset at 48.57 ±29.00 years. Gastric cancer was the most common extracolonic cancer （10.3%） in these families. Twenty-three different sequence variations in hMLHI and hMSH2 genes were detected in these 17 families. Fifteen sequence variations were located in the exons, including 5 SNPs, 3 silent mutations, 3 missense mutations, 2 nonsense mutations and 2 frameshift mutations. The latter seven mutations seemed to be pathogenic. CONCLUSION： Germline mutations of hMLH1 and hMSH2 genes are identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC criteria. Chinese HNPCC families have some particular clinical characteristics, such as a left-sided predominance, less synchronous or metachronous colorectal cancer, and frequent occurrence of gastric cancer.展开更多
The speckle-type POZ protein （SPOP） is a tumor suppressor in prostate cancer （PCa）. SPOP somatic mutations have been reported in up to 15% of PCa of those of European descent. However, the genetic roles of SPOP in...The speckle-type POZ protein （SPOP） is a tumor suppressor in prostate cancer （PCa）. SPOP somatic mutations have been reported in up to 15% of PCa of those of European descent. However, the genetic roles of SPOP in African American （AA）-PCa are currently unknown. We sequenced the SPOP gene to identify somatic mutations in 49 AA prostate tumors and identified three missense mutations （p.Y87C, p.F102S, and p.G111E） in five AA prostate tumors （10%） and one synonymous variant （p.11061） in one tumor. Intriguingly, all of mutations and variants clustered in exon six, and all of the mutations altered conserved amino acids. Moreover, two mutations （p.F102S and p.G111E） have only been identified in AA-PCa to date. Quantitative real-time polymerase chain reaction analysis showed a lower level of SPOP expression in tumors carrying SPOP mutations than their matched normal prostate tissues. In addition, SPOP mutations and novel variants were detected in 5 of 27 aggressive PCa and one of 22 less aggressive PCa （P 〈 0.05）. Further studies with increased sample size are needed to validate the clinicopathological significance of these SPOP mutations in AA-PCa.展开更多
AIM： To establish the role of human T Cell Factor-4 （hTCF-4） gene exons 3-9 mutation status in association with sporadic rectal cancer with microsatellite instability （MSI）. METHODS： Microsatellite markers were ...AIM： To establish the role of human T Cell Factor-4 （hTCF-4） gene exons 3-9 mutation status in association with sporadic rectal cancer with microsatellite instability （MSI）. METHODS： Microsatellite markers were genotyped in 93 sporadic rectal cancer patients. Eleven cases were found to be high-frequency MSI （MSI-H）. Sequence analysis of the coding region of the exons 3-9 of hTCF-4 gene was carried out for the 11 MSI-H cases and 10 controls （5 microsatellite stability （MSS） cases and 5 cases with normal mucosa）. The sequencing and MSI identification were used. RESULTS： Several novel mutations and variants were revealed. In exon 4, one is a 4-position continuous alteration which caused amino acid change from Q131T and S132I （391insA, 392 G 〉 A, 393 A 〉 G and 395delC） and another nucleotide deletion （395delC） is present in MSI-H cases （5/10 and 4/10, respectively） but completely absent in the controls.CONCLUSION： Novel mutations in exon 4 of hTCF-4 gene were revealed in this study, which might be of importance in the pathogenesis of sporadic rectal cancer patients with MSI-H.展开更多
It is of utmost necessity to understand the dynamics of regional active accumulated temperature(AAT)to cope with the negative impacts of global warming on agroforestry development and food security and to provide a re...It is of utmost necessity to understand the dynamics of regional active accumulated temperature(AAT)to cope with the negative impacts of global warming on agroforestry development and food security and to provide a real-time and effective reference basis for regional agroforestry planning.The daily temperature data from 30 meteorological stations in Sichuan Province from 1970 to 2020,and sea surface temperature(SST)index data from the Atlantic Multiphase Oscillation(AMO)and Pacific Decadal Oscillation(PDO)were used for the study.Sichuan Province was divided into the western region(WS)and the eastern region(ES),considering 1000 m above sea level as the boundary.The spatiotemporal characteristics of≥0℃ and≥10℃ active accumulated temperature(AAT0,AAT10)in WS and ES were analyzed comprehensively using 5-day average sliding,empirical orthogonal function(EOF),ensemble empirical mode decomposition(EEMD),and multiple mutation tests.The results show that(1)AAT0 and AAT10 of WS ranged from 3034℃ to 3586℃ and 1971℃ to 2636℃,respectively,while the AAT0 and AAT10 of ES ranged from 5863℃ to 6513℃ and 4847℃ to 5875℃,respectively.The period around 1997 was a significant abrupt change,and the AAT in the province generally increased during the subsequent time period(2)AAT in the study area is mainly driven by the fluctuations of AMO,as reflected by the low-to-high variation of AAT coinciding with the jump of the cold-to-warm phase of AMO.Considering different time scale fluctuations in the past 51 years,the major cycle for both AAT0 and AAT10 in WS is 3.40 a,while the major cycles in ES are 3.64 a and 3.19 a,respectively with a sub-cycle of 7.29 a.AAT fluctuation has an insignificant periodic characteristic of 25.50 a on the interdecadal scale(3)The spatial heterogeneity of AAT in WS is prominent and is mainly reflected by the significantly warm conditions in the south of the WS region and relatively slight warm conditions in the north,as well as by the isolated cooling area in the form of"freezing point",i.e.,Xiaojin county.In contrast,the spatial variability of AAT in ES is more or less consistent,with the warming areas concentrated in the foothills of the western edge of the basin and a slight increase in AAT observed in the central part of the basin.展开更多
文摘Crimean-Congo hemorrhagic fever (CCHF) is a severe illness with high fatality.Cases are reported in several countries in Africa,Europe,the Middle East,and Asia.Phylogenetic analyses based on the virus S (nucleocapsid),M (glycoprotein),and L (polymerase) genome segments sequences indicate distinct geographic lineages exist but their specific genetic characteristics require elucidation.In this work we collected all full length S segment sequences and generated a phylogenetic tree based on the alignment of these 62 samples.We then analyzed the alignment using entries from AAIndex,the Amino Acid Index database,to identify amino acid mutations that performed significant changes in charge,pka,hydropathy and side chain volume.Finally,we mapped these changes back to the tree and alignment to identify correlated mutations or sites that characterized a specific lineage.Based on this analysis we are able to propose a number of sites that appear to be important for virus function and which would be good candidates for experimental mutational analysis studies.
文摘Newcastle disease (ND) virus is a leading threat to commercial and domestic poultry in Pakistan. The virus infects and constitutes irreversible impairment to the nervous system, damages the respiratory system, and marks severe gastrointestinal lesions leading to heavy mortality in short-living birds and substantial losses in layers and breeders. The continuous emergence and evolution of the virus made it inclined to evade the humoral response and indirectly the circumvention of artificial active immunization. Newcastle disease is caused by the orthoavula genus of the paramyxoviridae family and has shown high genetic diversity even in their genotypes while information regarding enzootic trends of the virus is scanty in Pakistan. A total of 40 tracheal samples of NDV were collected from different commercial broiler farms and 11 isolates of NDV were identified. In the current study, we determined the genetic diversity of the Newcastle disease virus based on the partial sequencing of the fusion protein gene available in the NCBI database. Genetic analysis showed that seven isolates belonged to class I genotype VII and four belonged to class II genotype II. Interestingly, two isolates had epidemiological connections with vaccine-like class II genotype II. Our findings, concerning the recent outbreaks of class I genotype VII and class II genotype II of NDV in vaccinated commercial flocks, suggest possible potential partial mutations in the fusion protein gene. Genetic diversity and formation of the new cleavage site in an important neutralizing protein of wild strain are linked with the potency of artificial active immunization and a major cause of vaccine failure.
文摘AIM:To compare the differences between dideoxy sequencing/KRAS StripAssay/pyrosequencing for detection of KRAS mutation in Chinese colorectal cancer (CRC) patients.METHODS:Formalin-f ixed, paraff in-embedded (FFPE) samples with tumor cells ≥ 50% were collected from 100 Chinese CRC patients at Beijing Cancer Hospital. After the extraction of genome DNA from FFPE samples, fragments contained codons 12 and 13 of KRAS exon 2 were amplified by polymerase chain reaction and analyzed by dideoxy sequencing, the KRAS Strip Assay and pyrosequencing. In addition, the sensitivities of the 3 methods were compared on serial dilutions (contents of mutant DNA: 100%,50%,20%, 5%,10%, 5%,1%,0%) of A549 cell line DNA (carrying the codon 12 Gly>Ser mutation) into wild-type DNA (human normal intestinal mucosa). The results of dideoxy sequencing,the KRAS StripAssay and pyrosequencing were analyzed by Chromas Software, Collector forKRAS Strip Assay and the pyrosequencing PyroMarkTM Q24 system, respectively.RESULTS: Among 100 patients, KRAS mutations were identif ied in 34%, 37% and 37% of patients by dideoxy sequencing, the KRAS StripAssay and pyrosequencing, respectively. The sensitivity was highest with the KRAS Strip Assay (1%), followed by pyrosequencing (5%), and dideoxy sequencing was lowest (15%). Six different mutation types were found in this study with 3 main mutations Gly12 Asp (GGT>GAT), Gly12 Val (GGT>GTT) and Gly13 Asp (GGC>GAC). Thirty-three patients were identifi ed to have KRAS mutations by the 3 methods, and a total of 8 patients had conflicting results between 3 methods: 4 mutations not detected by dideoxy sequencing and the KRAS StripAssay were identified by pyrosequencing; 3 mutations not detected by dideoxy sequencing and pyrosequencing were identif ied by the KRAS StripAssay; and 1 mutation not detected by pyrosequencing was conf irmed by dideoxy sequencing and the KRAS StripAssay. Among these discordant results, the results identif ied by dideoxy sequencing were consistent either with the KRAS StripAssay or with pyrosequencing, which indicated that the accuracy of dideoxy sequencing was high. CONCLUSION: Taking a worldwide view of reports and our results,dideoxy sequencing remains the most popular method because of its low cost and high accuracy.
基金Supported by the Infrastructure Project of China Meteorological Administration(CMA) in 2010~~
文摘In this paper,based on the observation data of air temperature during 1951-2009 in Shenyang,the interannual and interdecadal variation of annual average temperature,maximum and minimum temperature in Shenyang were conducted the statistical analysis by means of linear trend estimation and mutation detection by using Mann-Kendall method.As was demonstrated in the results,the annual average temperature,maximum and minimum temperature in Shenyang showed an upward trend,whose linear tendency rate was 0.231,0.181 and 0.218 respectively.The increment trend of annual average temperature,maximum and minimum temperature was extremely clear.The increase in minimum temperature was more significant than that in mean temperature and maximum temperature.The abrupt change point of annual mean temperature in Shenyang appeared in 1981;the abrupt change point of annual mean maximum temperature appeared in 1994;the annual mean minimum temperature underwent mutation in 1978.
基金Supported by Henan Province Science and Technology Research Project,No.232102310043Henan Provincial Science and Technology Research and Development Plan Joint Fund,No.222103810047Key Scientific Research Project Plan of Colleges and Universities in Henan Province,No.22A320033.
文摘BACKGROUND Colorectal cancer(CRC)remains a major global health burden due to its high incidence and mortality,with treatment efficacy often hindered by tumor hetero-geneity,drug resistance,and a complex tumor microenvironment(TME).Lactate metabolism plays a pivotal role in reshaping the TME,promoting immune eva-sion and epithelial-mesenchymal transition,making it a promising target for novel therapeutic strategies and prognostic modeling in CRC.AIM To offer an in-depth analysis of the role of lactate metabolism in CRC,high-lighting its significance in the TME and therapeutic response.METHODS Utilizing single-cell and transcriptomic data from the Gene Expression Omnibus and The Cancer Genome Atlas,we identified key lactate metabolic activities,particularly in the monocyte/macrophage subpopulation.RESULTS Seven lactate metabolism-associated genes were significantly linked to CRC prognosis and used to construct a predictive model.This model accurately forecasts patient outcomes and reveals notable distinct patterns of immune infiltration and transcriptomic profiles mutation profiles between high-and low-risk groups.High-risk patients demonstrated elevated immune cell infiltration,increased mutation frequencies,and heightened sensitivity to specific drugs(AZD6482,tozasertib,and SB216763),providing a foundation for personalized treatment approaches.Additionally,a nomogram integrating clinical and metabolic data effectively predicted 1-,3-,and 5-year survival rates.CONCLUSION This report underscored the pivotal mechanism of lactate metabolism in CRC prognosis and suggest novel avenues for therapeutic intervention.
基金funded by the Postdoctoral Research Startup Foundation of University of Jinan(Grant No.100389917).
文摘Climate change and anthropogenic activities have driven significant terrestrial water storage changes(TWSC)in the Three Rivers Source Region(TRSR),exerting profound impacts on freshwater availability across China and broader Asia.However,long-term TWSC characterization remains challenging due to limited observational data in this alpine region.Here,we integrate GRACE observations(2002-2020),ERA5-Land reanalysis,and GLDAS data to reconstruct TWSC using two methods:(1)the water balance method(PER)and(2)the component summation method(SS),applied to three input datasets(ERA5-Land,GLDAS,and their average,GLER).Comparative analysis reveals that the SS method applied to GL-ER yields the highest consistency with GRACE-derived TWSC.Using this optimal approach,we extend the analysis to 1951~2020,uncovering spatiotemporal TWSC patterns.Although annual TWSC trends appear negligible due to strong seasonality,we introduce the intra-year TWSC fluctuation(TWSCF)index to quantify cumulative variability.A significant(p<0.05)transition occurred in 1980,with TWSCF shifting from a declining trend(-0.39 mm/yr)to an increasing trend(0.56 mm/yr),primarily driven by soil moisture changes.However,Hurst exponent analysis suggests this upward trend may not persist.Drought and vegetation assessments indicate concurrent wetting and greening in the TRSR.TWSC correlates strongly with meteorological drought,acting as a reliable drought indicator while its linkage with vegetation dynamics suggests a potential contribution to greening.Our findings provide a robust framework for understanding long-term TWSC evolution and its hydrological-ecological interactions under climate change.
基金the National Natural Science Foundation of China, No. 81071001, 30600200the Natural Science Foundation of Hu-nan Province, No. 2006JJ30009
文摘Charcot-Marie-Tooth （CMT） disease is the most common inherited peripheral neuropathic disorder. CMT is clinically and genetically heterogeneous. To date, 27 genes associated with the disease have been cloned. The present study carried out clinical classification according to clinical, electrophysiological and pathological features, conducted inheritance classification according to inheritance patterns, and performed mutation analysis of 13 CMT disease genes （PMP22, CX32, HSPB1, MNF2, MPZ, HSPB8, GDAP1, NFL, EGR2, SIMPLE, RAB7, LMNA, MTMR2） in 57 Chinese probands with CMT. Five cases of AD-CMT1 and 13 cases of sporadic CMT1 were diagnosed as CMT1A; five cases of X-CMT1, one case of X-CMT2 and one case of sporadic CMT1 were diagnosed as CMTXl; four cases of AD-CMT2 were diagnosed as CMT2F; one case of AD-CMT2 and one case of sporadic CMT2 were diagnosed as CMT2A2; one case of AD-CMT2 was diagnosed as CMT2L; one case of AD-CMT2 was diagnosed as CMT2J; one case of AR-CMT1 was diagnosed as CMT4A. Among the 57 CMT probands, seven genotypes were determined among 34 patients, with a detection rate of 59.6%. The results indicated that the clinical classification and inheritance classification are indispensable for selecting potential disease genes for mutation detection, and for efficient molecular diagnosis.
基金German Research Foundation DFG Junior-Grant Faculty of Medicine, University of Heidelberg
文摘AIM: To analyze the metallochaperone antioxidant-1 (Atox1) gene sequence in Wilson disease patients. METHODS: Mutation analysis of the four exons of the Atox1 gene including the intron- exon boundaries was performed in 63 Wilson disease patients by direct sequencing. RESULTS: From 63 selected patients no mutations were identified after the entire coding region including the intron- exon boundaries of Atox1 were sequenced. One known polymorphism within the Atox1 gene (5’UTR -99 T>C) in 31 (49%) of the Wilson patients as well as one previously undescribed variation (5’UTR -68 C>T) in 2 of the Wilson patients could be detected. Statistical analyses revealed that the existence of a variation within the Atox1- gene showed a tendency towards an earlier onset of the disease. CONCLUSION: Based on the data of this study, no major role can be attributed to Atox1 in the pathophysiology or clinical variation of Wilson disease.
文摘A measure of the“goodness”or efficiency of the test suite is used to determine the proficiency of a test suite.The appropriateness of the test suite is determined through mutation analysis.Several Finite State Machine(FSM)mutants are produced in mutation analysis by injecting errors against hypotheses.These mutants serve as test subjects for the test suite(TS).The effectiveness of the test suite is proportional to the number of eliminated mutants.The most effective test suite is the one that removes the most significant number of mutants at the optimal time.It is difficult to determine the fault detection ratio of the system.Because it is difficult to identify the system’s potential flaws precisely.In mutation testing,the Fault Detection Ratio(FDR)metric is currently used to express the adequacy of a test suite.However,there are some issues with this metric.If both test suites have the same defect detection rate,the smaller of the two tests is preferred.The test case(TC)is affected by the same issue.The smaller two test cases with identical performance are assumed to have superior performance.Another difficulty involves time.The performance of numerous vehicles claiming to have a perfect mutant capture time is problematic.Our study developed three metrics to address these issues:FDR/|TS|,FDR/|TC|,and FDR/|Time|;In this context,most used test generation tools were examined and tested using the developed metrics.Thanks to the metrics we have developed,the research contributes to eliminating the problems related to performance measurement by integrating the missing parameters into the system.
基金Supported by the Project of Meteorological Bureau of Benxi City,China(BQ2010002)
文摘Based on data of temperature and precipitation in Huanren County from 1953 to 2010, linear trend analysis and mutation detection of temperature and precipitation sequence were carried out using linear trend, Mann-Kendall detection and dryness of the de Martonne method. The results showed that during 1953-2010, annual average temperature, annual average maximum and minimum temperature in Huanren County showed an increasing trend; annual precipitation showed a decreasing trend; there was a downward trend in annual dryness. The mutation of annu- al average temperature, annual average maximum and minimum temperature appeared in 1978, 1987 and 1982 respectively; there was no mutation of annual precipitation and dryness. On the whole, the climate of Huanren County tended to be warm and dry over the past 58 years.
基金Supported by Guangxi Scientific and Technological Project(Guikegong 0816006-10)Scientific Research Item of Guangxi Science and Technology Agency(Guikeneng 0801Z004)
文摘[Objective]The research aimed to study the variation of rainfall data from Guilin Weather Station during 1957-2007.[Method]Based on the daily rainfall data in Guilin during 1957-2007,the trend,period and mutation of precipitation in Guilin in 51 years were analyzed by using the trend analysis,wavelet analysis and Mann-Kendall non-parameter statistics test method.[Result]The rainfall in Guilin in 51 years presented the rising trend.The rainfall variation was same in the first,second and third quarters of most years,except in the individual year.The rainfall in the fourth quarter had the decrease trend,and the variation was obvious in each year.It illustrated that the rainfall variation in winter was very unstable and had the decrease trend in recent years.But as a whole,the variation of total rainfall in Guilin wasn’t obvious and had the rise trend.It illustrated that the climate variation in Guilin in 51 years wasn’t obvious.The wavelet analysis showed that the rainfall variation in Guilin had 15-year big period and the small period of 2-3 years.Mann-Kendall non-parameter statistics test showed that the mutation situation of total rainfall in Guilin in 51 years wasn’t obvious.But the mutation situations in the second and third quarters were more.The variation in recent 10 years was the most obvious.Maybe it was affected by the global climate variation.[Conclusion]The research provided the theory basis for analyzing the climate variation in Guilin.
文摘Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectomy was performed on two of the three
基金This subject is supported by the Fund for Returned Scientists and Scholars,[1999]363.Chinese Ministry of Education.
文摘AIM:To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes,and to explore the relationship between ACF and colorectal adenoma even carcinoma. METHODS: DNA from 35 CRC, 15 adenomas, 34 ACF and 10 normal mucus was isolated by means of microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene was performed. RESULTS: K-ras gene mutation frequency in ACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/15), and 14.3% (5/35) respectively, showing no difference (P 】 0.05) in K-ras gene mutation among three pathologic procedures. The K-ras gene mutation in adenoma, carcinoma and 4 ACF restricted in codon 12 (GGT GAT), but the other 2 mutations from ACF located in codon 13 (GGC GAC). K-ras gene mutation was found more frequently in older patients and patients with polypoid cancer. No mutation in codon 61 was found in the three tissue types. Mutation rate of APC gene in adenoma and carcinoma was 22.9% (8/35) and 26.7% (4/15), which was higher than ACF (2.9%) (P 【0.05). APC gene mutation in carcinoma was not correlated with age of patients, location, size and differentiation of tumor. CONCLUSION: ACF might be a very early morphological lesion in the tumorogenesis of colorectal tumor. The morphological feature and gene mutation status was different in ACF and adenoma. ACF is possibly putative microadenoma that might be the precursor of adenoma. In addition, the development of a subgroup of colorectal carcinomas might undergo a way of normal epithelium ACF carcinomas .
文摘BACKGROUND Schwannomas,also known as neurinomas,are tumors that derive from Schwann cells.Gastrointestinal schwannomas are extremely rare,but the stomach is the most common site.Gastric schwannomas are usually asymptomatic.Endoscopy and imaging modalities might offer useful preliminary diagnostic information.However,to diagnose schwannoma,the immunohistochemical positivity for S-100 protein is essential,whereas CD117,CD34,SMA,desmin,and DOG-1 are negative.CASE SUMMARY A 45-year-old female was found to have a gastric mass during a medical examination,which was diagnosed as a gastric schwannoma.We performed endoscopic full-thickness resection and endoscopic purse-string suture.Pathology and immunohistochemical staining confirmed the diagnosis of gastric schwannoma through the positivity of S-100 protein.Furthermore,to exclude the misdiagnosis of gastrointestinal stromal tumor,we performed a mutational detection of the c-Kit and PDGFRA genes.Postoperative follow-up revealed that the patient recovered well.CONCLUSION Immunohistochemical staining is essential for the diagnosis of schwannoma.Endoscopic full-thickness resection is an effective treatment method for gastric schwannoma.
基金the National Natural Science Foundation of China,No.815729311.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,No.ZYJC18034。
文摘BACKGROUND The totally implantable venous access port(TIVAP)is an important device in patients for injecting blood products,parenteral nutrition or antineoplastic chemotherapy.Metastatic spread at the site of the insertion of a TIVAP is extremely rare.CASE SUMMARY We report the case of 33-year-old male with advanced gastrointestinal stromal tumor(GIST)who underwent radical tumor resection after neoadjuvant imatinib therapy.However,a solitary GIST metastasis at the site of a TIVAP insertion developed during adjuvant imatinib treatment.Mutational analysis showed secondary mutation in KIT exon 13(V564 A),which is resistant to imatinib treatment.To our knowledge,this is the first case report of a patient with advanced GIST developing GIST metastasis at the site of a TIVAP insertion.CONCLUSION This case highlights that when a patient with advanced,high metastatic GIST requires TIVAP insertion,we should realize that there is a risk of developing tumor metastasis at the site of a TIVAP insertion.
文摘The CRISPR-Cas system has revolutionized modern life sciences,enabling groundbreaking applications ranging from functional genomics to therapeutic development.Despite its transformative potential,significant technical limitations persist in current computational tools for quantifying editing efficiency-particularly concerning data processing capabilities,analytical throughput,and operational flexibility.This research presents SuperDecode,a novel computational framework designed to address these methodological constraints.The SuperDecode offers key advantages,including local processing capabilities,large-size sequencing files,batch-processing,and diversified operational functions.
基金Supported by the Subdivisional Project of the "863" High Technology Research and Program of China, No. 2001AA227111
文摘AIM： To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer （HNPCC） families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands. METHODS： Thirty-one independent Chinese HNPCC families were collected in Zhejiang Province. All of them met Chinese HNPCC criteria. Clinical data about patient gender, site of colorectal cancer, age of onset, history of multiple colorectal cancer, associated extracolonic cancer were recorded. PCR and denaturing high performance liquid chromatography （DHPLC） were employed to screen the mutations. Sequencing analysis was used to find out the exact mutation site and characteristics of the samples showing abnormal DHPLC profiles. RESULTS： One hundred and thirty-six malignant neoplasms were found in 107 patients including 14 multiple cancers. One hundred and six of the 136 neoplasms （77.9%） were diagnosed as colorectal cancer, with an average age of onset at 48.57 ±29.00 years. Gastric cancer was the most common extracolonic cancer （10.3%） in these families. Twenty-three different sequence variations in hMLHI and hMSH2 genes were detected in these 17 families. Fifteen sequence variations were located in the exons, including 5 SNPs, 3 silent mutations, 3 missense mutations, 2 nonsense mutations and 2 frameshift mutations. The latter seven mutations seemed to be pathogenic. CONCLUSION： Germline mutations of hMLH1 and hMSH2 genes are identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC criteria. Chinese HNPCC families have some particular clinical characteristics, such as a left-sided predominance, less synchronous or metachronous colorectal cancer, and frequent occurrence of gastric cancer.
文摘The speckle-type POZ protein （SPOP） is a tumor suppressor in prostate cancer （PCa）. SPOP somatic mutations have been reported in up to 15% of PCa of those of European descent. However, the genetic roles of SPOP in African American （AA）-PCa are currently unknown. We sequenced the SPOP gene to identify somatic mutations in 49 AA prostate tumors and identified three missense mutations （p.Y87C, p.F102S, and p.G111E） in five AA prostate tumors （10%） and one synonymous variant （p.11061） in one tumor. Intriguingly, all of mutations and variants clustered in exon six, and all of the mutations altered conserved amino acids. Moreover, two mutations （p.F102S and p.G111E） have only been identified in AA-PCa to date. Quantitative real-time polymerase chain reaction analysis showed a lower level of SPOP expression in tumors carrying SPOP mutations than their matched normal prostate tissues. In addition, SPOP mutations and novel variants were detected in 5 of 27 aggressive PCa and one of 22 less aggressive PCa （P 〈 0.05）. Further studies with increased sample size are needed to validate the clinicopathological significance of these SPOP mutations in AA-PCa.
基金the National Natural Science Foundation of China, No. 39925032
文摘AIM： To establish the role of human T Cell Factor-4 （hTCF-4） gene exons 3-9 mutation status in association with sporadic rectal cancer with microsatellite instability （MSI）. METHODS： Microsatellite markers were genotyped in 93 sporadic rectal cancer patients. Eleven cases were found to be high-frequency MSI （MSI-H）. Sequence analysis of the coding region of the exons 3-9 of hTCF-4 gene was carried out for the 11 MSI-H cases and 10 controls （5 microsatellite stability （MSS） cases and 5 cases with normal mucosa）. The sequencing and MSI identification were used. RESULTS： Several novel mutations and variants were revealed. In exon 4, one is a 4-position continuous alteration which caused amino acid change from Q131T and S132I （391insA, 392 G 〉 A, 393 A 〉 G and 395delC） and another nucleotide deletion （395delC） is present in MSI-H cases （5/10 and 4/10, respectively） but completely absent in the controls.CONCLUSION： Novel mutations in exon 4 of hTCF-4 gene were revealed in this study, which might be of importance in the pathogenesis of sporadic rectal cancer patients with MSI-H.
基金the National Natural Science Foundation of China(Grant No.51779114)。
文摘It is of utmost necessity to understand the dynamics of regional active accumulated temperature(AAT)to cope with the negative impacts of global warming on agroforestry development and food security and to provide a real-time and effective reference basis for regional agroforestry planning.The daily temperature data from 30 meteorological stations in Sichuan Province from 1970 to 2020,and sea surface temperature(SST)index data from the Atlantic Multiphase Oscillation(AMO)and Pacific Decadal Oscillation(PDO)were used for the study.Sichuan Province was divided into the western region(WS)and the eastern region(ES),considering 1000 m above sea level as the boundary.The spatiotemporal characteristics of≥0℃ and≥10℃ active accumulated temperature(AAT0,AAT10)in WS and ES were analyzed comprehensively using 5-day average sliding,empirical orthogonal function(EOF),ensemble empirical mode decomposition(EEMD),and multiple mutation tests.The results show that(1)AAT0 and AAT10 of WS ranged from 3034℃ to 3586℃ and 1971℃ to 2636℃,respectively,while the AAT0 and AAT10 of ES ranged from 5863℃ to 6513℃ and 4847℃ to 5875℃,respectively.The period around 1997 was a significant abrupt change,and the AAT in the province generally increased during the subsequent time period(2)AAT in the study area is mainly driven by the fluctuations of AMO,as reflected by the low-to-high variation of AAT coinciding with the jump of the cold-to-warm phase of AMO.Considering different time scale fluctuations in the past 51 years,the major cycle for both AAT0 and AAT10 in WS is 3.40 a,while the major cycles in ES are 3.64 a and 3.19 a,respectively with a sub-cycle of 7.29 a.AAT fluctuation has an insignificant periodic characteristic of 25.50 a on the interdecadal scale(3)The spatial heterogeneity of AAT in WS is prominent and is mainly reflected by the significantly warm conditions in the south of the WS region and relatively slight warm conditions in the north,as well as by the isolated cooling area in the form of"freezing point",i.e.,Xiaojin county.In contrast,the spatial variability of AAT in ES is more or less consistent,with the warming areas concentrated in the foothills of the western edge of the basin and a slight increase in AAT observed in the central part of the basin.
