BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-yea...BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.展开更多
BACKGROUND Hereditary spherocytosis(HS)is a hereditary disease of hemolytic anemia that occurs due to the erythrocyte membrane defects.Dubin–Johnson syndrome(DJS),which commonly results in jaundice,is a benign heredi...BACKGROUND Hereditary spherocytosis(HS)is a hereditary disease of hemolytic anemia that occurs due to the erythrocyte membrane defects.Dubin–Johnson syndrome(DJS),which commonly results in jaundice,is a benign hereditary disorder of bilirubin clearance that occurs only rarely.The co-occurrence of HS and DJS is extremely rare.We recently diagnosed and treated a case of co-occurring HS and DJS.CASE SUMMARY A 21-year-old female patient presented to our department because of severe jaundice,severe splenomegaly,and mild anemia since birth.We eventually confirmed the diagnosis of co-occurring DJS and HS by next generation sequencing(NGS).The treatment of ursodeoxycholic acid in combination with phenobarbital successfully increased hemoglobin and reduced total bilirubin and direct bilirubin.CONCLUSION The routine application of NGS can efficiently render a definite diagnosis when inherited disorders are suspected.展开更多
BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine recept...BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.展开更多
BACKGROUND The co-infection of Chlamydia psittaci(C.psittaci)and Tropheryma whipplei(T.whipplei)is unusual,and the detection of pathogenic microorganisms is particularly important for patients with severe diseases or ...BACKGROUND The co-infection of Chlamydia psittaci(C.psittaci)and Tropheryma whipplei(T.whipplei)is unusual,and the detection of pathogenic microorganisms is particularly important for patients with severe diseases or poor experience in treatment.Early identification of pathogens can significantly improve the prognosis of the patients.Targeted next-generation sequencing(tNGS)is currently widely used in clinical practice for various infectious diseases,including respiratory infections,to achieve early,accurate,and rapid microbial diagnosis.CASE SUMMARY We report a case of a 40-year-old female patient with a history of contact with parrots who was diagnosed with C.psittaci and T.whipplei infection through bronchial lavage fluid targeted next generation sequencing.After moxifloxacin treatment,the patient's symptoms improved significantly,and the imaging changes were obviously resolved.CONCLUSION Coinfection with C.psittaci and T.whipplei is not common.In this case,timely and accurate identification of both pathogens was achieved using tNGS.Moreover,the efficacy of monotherapy with moxifloxacin was confirmed.展开更多
BACKGROUND Familial cases of autosomal recessive spastic ataxia of charlevoix-saguenay have not been reported in the Arabian Peninsula,although the consanguineous marriage rate is very high.We report the first family ...BACKGROUND Familial cases of autosomal recessive spastic ataxia of charlevoix-saguenay have not been reported in the Arabian Peninsula,although the consanguineous marriage rate is very high.We report the first family from the Arabian Peninsula harboring a novel frameshift mutation in the SACS gene.CASE SUMMARY A 33-year-old man presented to our neurology clinic with balance problems and weakness of distal upper and lower limbs.He was previously clinically diagnosed with Friedreich's ataxia.However,the severity of polyneuropathy and the electrodiagnostic studies(EDX)findings are atypical features of Friedreich’s ataxia,and the deterioration was attributed to diabetic neuropathy.Close examination of other family members identified cerebellar ataxia,lower-limb pyramidal signs,peripheral neuropathy,and magnetic resonance imaging findings characterized by pontine linear hypointensities.Genetic testing for Friedreich’s ataxia did not yield a diagnosis.Whole exome sequencing identified a novel frameshift germline mutation in the SACS gene termed c.5824_5827delTACT using the transcript NM_014363.5,which is predicted to cause premature termination of the sacsin protein at amino acid position 1942(p.Tyr1942Metfs*9)and disrupts the sacsin SRR3 and domains downstream from it.The mutation segregated with the disease in the family.CONCLUSION Our data add to the spectrum of mutations in the SACS gene and argues for a need to implement suitably integrated clinical and diagnostic services,including next generation sequencing technology,to better classify ataxia in this area of the world.展开更多
BACKGROUND Leptospira is an uncommon pathogen for adult severe community-acquired pneumonia and its nonspecific manifestations and limited diagnostic tests make it difficult to identify.Although conventional penicilli...BACKGROUND Leptospira is an uncommon pathogen for adult severe community-acquired pneumonia and its nonspecific manifestations and limited diagnostic tests make it difficult to identify.Although conventional penicillin remains efficacious to treat leptospirosis,failure in early diagnosis and treatment can lead to progression into a deadly syndrome with multiple organ dysfunction.Next generation sequencing is of great value to understand cases with infection of unknown cause,which could help in the diagnosis of uncertain Leptospira infection.CASE SUMMARY We recently managed a patient with fever,cough and dyspnea on admission that progressed into persistent adult respiratory distress syndrome,hemoptysis and hematuria after admission.In this case,the rare Leptospira infection was clouded by the positive influenza tests at admission,delaying early Leptospira-targeted antibiotics administration.Next generation sequencing,a novel molecular diagnostic tool,provided a key hint to uncover the crucial pathogen,Leptospira interrogans,further supported by the possible occupational exposure history.Subsequent conventional penicillin and mechanical respiratory support were administrated to cure the patient successfully without any sequela.CONCLUSION Clinicians must pay attention to possible exposure history and keep uncommon Leptospira in mind when managing pneumonia with unknown causes.展开更多
BACKGROUND Neonatal hyperbilirubinemia is a common problem faced by pediatricians.The role of genetic factors in neonatal jaundice has been gradually recognized.This study aims to identify genetic variants that influe...BACKGROUND Neonatal hyperbilirubinemia is a common problem faced by pediatricians.The role of genetic factors in neonatal jaundice has been gradually recognized.This study aims to identify genetic variants that influence the bilirubin level in five patients using next-generation sequencing(NGS).CASE SUMMARY Five neonates with severe hyperbilirubinemia were retrospectively studied.They exhibited bilirubin encephalopathy,hypothyroidism,ABO blood type incompatibility hemolysis,glucose-6-phosphate dehydrogenase(G6PD)deficiency and premature birth,respectively.A customized 22-gene panel was designed,and NGS was carried out for these neonates.Eight variations(G6PD c.G1388A,HBA2 c.C369G,ABCC2 c.C3825G,UGT1A1 c.G211A,SPTB c.A1729G,EPB41 c.G520A,c.1213-4T>G and c.A1474G)were identified in these five neonates.Genetic mutations of these genes are associated with G6PD deficiency,thalassemia,Dubin-Johnson syndrome,Gilbert syndrome,hereditary spherocytosis,and hereditary elliptocytosis.One of the neonates was found to have compound variants of the EPB41 splice site c.1213-4T>G and c.G520A(p.E174K),but no elliptocyte was seen on his blood smear of 4 years old.CONCLUSION Pathological factors of severe neonatal hyperbilirubinemia are complicated.Genetic variants may play an important role in an increased risk of neonatal hyperbilirubinemia,and severe jaundice in neonates may be related to a cumulative effect of genetic variants.展开更多
BACKGROUND Targeted treatments may greatly affect the natural history of urothelial carcinoma based on their pharmacokinetics. A phase II trial has explored the combination of cytotoxic chemotherapy with the anti-HER-...BACKGROUND Targeted treatments may greatly affect the natural history of urothelial carcinoma based on their pharmacokinetics. A phase II trial has explored the combination of cytotoxic chemotherapy with the anti-HER-2 monoclonal antibody trastuzumab in selected patients with metastatic bladder cancer, but it failed.CASE SUMMARY Here, we report a case of recurrent urothelial bladder carcinoma(UBC) in a patient who has undergone three operations, and further illuminate its diagnosis and treatment. The diagnosis of UBC was rendered according to the pathological indices. Next-generation sequencing on formalin fixed paraffin-embedded(FFPE)tissue was also performed and suggested HER2 gene amplification in the FFPE tissue. Based on HER2 gene amplification in FFPE, the patient was treated with chemotherapy in combination with trastuzumab after his third surgery.Fortunately, the patient got a clinically complete remission to trastuzumab for 34 mo.CONCLUSION There is not enough clinical evidence for incorporating trastuzumab in routine treatment of UBC. This case hinted that recurrent UBC patients with HER2 gene amplification may benefit from targeted trastuzumab. Further studies are needed to further investigate the status of HER2 gene and better determine trastuzumab in the management of UBC.展开更多
BACKGROUND Colorectal liver metastases(CLM)occur in 15%-30%of patients with colorectal cancer(CRC).Advancements in next generation sequencing(NGS)can provide more precise prognoses for cancer patients and help guide c...BACKGROUND Colorectal liver metastases(CLM)occur in 15%-30%of patients with colorectal cancer(CRC).Advancements in next generation sequencing(NGS)can provide more precise prognoses for cancer patients and help guide clinical treatment.However,the genetic variants that predict high sensitivity to neoadjuvant chemotherapy remain unclear,especially in patients with CLM.The aim of this study was to identify the relevant genetic variants in a single CLM patient and to summarize the current evidence on mutations and single nucleotide polymorphisms(SNPs)that objectively predict sensitivity to neoadjuvant chemotherapy.CASE SUMMARY A 76-year-old male patient,who was diagnosed as stage IV colon cancer with liver metastases,was found to have APC/TP53/KRAS mutations.He showed a good therapeutic response to 12 courses of oxaliplatin regimens combined with Bevacizumab.Genetic analysis of the patient identified 5 genes with 7 detected SNPs that may be related to a better response to chemotherapy drugs.In addition,a critical literature review was performed based on a standardized appraisal form after selecting the articles.Ultimately,21 eligible studies were appraised to assess the association between gene mutations and good prognosis.Mutations in KRAS,TP53,SMAD4,and APC were identified as being associated with a poor response to chemotherapy drugs,whereas mutations of CREBBP and POLD1 were associated with longer overall survival.CONCLUSION NGS can identify precise predictors of response to neoadjuvant chemotherapy,leading to improved outcomes for CRC patients.展开更多
Tests involving a large number of test cases and test scenarios are always time- and effort- intensive, and use ad hoc approaches. Test management is needed to control the complexity and the qual- ity of the testing o...Tests involving a large number of test cases and test scenarios are always time- and effort- intensive, and use ad hoc approaches. Test management is needed to control the complexity and the qual- ity of the testing of large software systems. The reporting mechanism is critical for monitoring the testing progress, analyzing test results, and evaluating the test effectiveness for a disciplined testing process throughout the testing lifecycle. This paper presents an XML-based report generation method for large sys- tem testing. The service-oriented architecture enables flexible test report generation, presentation, and ex- change to facilitate collaboration in a distributed environment. The results show that proper reporting can ef- fectively improve the visibility of the testing process and that this web-based approach is critical to enhance communication among multiple testing groups.展开更多
Epigenetic reprogramming of somatic cells into induced pluripotent stem cells （iPSCs） by overexpression of defined factors holds great promise for disease modeling and regen- erative medicine （Takahashi and Yamanak...Epigenetic reprogramming of somatic cells into induced pluripotent stem cells （iPSCs） by overexpression of defined factors holds great promise for disease modeling and regen- erative medicine （Takahashi and Yamanaka, 2006; Robinton and Daley, 2012）. However, the stochastic reprogramming process often results in variable pluripotency levels of iPSC lines as measured by their in vivo developmental potential, which poses a huge challenge to the applications of high quality iPSCs （Hanna et al., 2010）. The activation status of an imprinted Dlkl-Dio3 region has been identified as a molecular marker for pluripotency （Liu et al., 2010; Stadtfeld et al.,展开更多
Mining the data from the huge collection that are present in the database and uncovering the relationships between the item set are one of the key aspects of data mining technologies. Itinerary planning system with pe...Mining the data from the huge collection that are present in the database and uncovering the relationships between the item set are one of the key aspects of data mining technologies. Itinerary planning system with personalization in selecting the places to the users is one of the demanding features in most of the travel plan. In this work, the system is designed in such a way to provide the customized journey plan to the users and also the effective one to the back pack travelers. Here the Points of Interests are the places to visit in each destination for the number of days chosen by the travelers. In this system, the users are allowed to specify the desired POIs to visit for the selected destination and can make their customized travel plan effectively. This proposed system is designed to choose the customized places to visit and to plan travel for K-day itineraries. The most visited itineraries are saved and updated in the database. Association rules are used to find out the frequent places visited in each destination and to provide the reputed places to the users to plan the journey. Here the Weka tool is used to evaluate the performance of the algorithm and the rules that are generated for the given travel dataset. Data set is designed by considering several attributes that can take part during travel such as source, destination, travel cost, budget, etc. Statistical analysis is done to evaluate the performance of the proposed system and the list of features that are present in the system. During the analysis part, registered users, number of logins, frequent visits, and attributes are analyzed. Thus the system can be redefined further with the help of this statistical analysis. It is mostly used at the organization end to evaluate their performance and improve the features. Report is generated once the user has chosen their customized places to visit and all detailed description of journey is presented to the user. Report could be saved at the user end and they can use it for the future reference. Thus the goal of the system is to provide the customized travel with personalization in choosing POIs and to find the frequent places visited with desired amenities.展开更多
基金Changzhou High-level Medical Talents Training Project of the Health Commission of the Changzhou City,No.2022CZBJ079Changzhou Sci&Tech Program,No.CE20235064.
文摘BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.
基金Supported by the National Science and Technology Important and Special Project of China,No.2017ZX09304024
文摘BACKGROUND Hereditary spherocytosis(HS)is a hereditary disease of hemolytic anemia that occurs due to the erythrocyte membrane defects.Dubin–Johnson syndrome(DJS),which commonly results in jaundice,is a benign hereditary disorder of bilirubin clearance that occurs only rarely.The co-occurrence of HS and DJS is extremely rare.We recently diagnosed and treated a case of co-occurring HS and DJS.CASE SUMMARY A 21-year-old female patient presented to our department because of severe jaundice,severe splenomegaly,and mild anemia since birth.We eventually confirmed the diagnosis of co-occurring DJS and HS by next generation sequencing(NGS).The treatment of ursodeoxycholic acid in combination with phenobarbital successfully increased hemoglobin and reduced total bilirubin and direct bilirubin.CONCLUSION The routine application of NGS can efficiently render a definite diagnosis when inherited disorders are suspected.
基金Supported by Grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute,funded by the Ministry of Health&Welfare,Republic of Korea,No.RS-2022-KH129889.
文摘BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.
文摘BACKGROUND The co-infection of Chlamydia psittaci(C.psittaci)and Tropheryma whipplei(T.whipplei)is unusual,and the detection of pathogenic microorganisms is particularly important for patients with severe diseases or poor experience in treatment.Early identification of pathogens can significantly improve the prognosis of the patients.Targeted next-generation sequencing(tNGS)is currently widely used in clinical practice for various infectious diseases,including respiratory infections,to achieve early,accurate,and rapid microbial diagnosis.CASE SUMMARY We report a case of a 40-year-old female patient with a history of contact with parrots who was diagnosed with C.psittaci and T.whipplei infection through bronchial lavage fluid targeted next generation sequencing.After moxifloxacin treatment,the patient's symptoms improved significantly,and the imaging changes were obviously resolved.CONCLUSION Coinfection with C.psittaci and T.whipplei is not common.In this case,timely and accurate identification of both pathogens was achieved using tNGS.Moreover,the efficacy of monotherapy with moxifloxacin was confirmed.
文摘BACKGROUND Familial cases of autosomal recessive spastic ataxia of charlevoix-saguenay have not been reported in the Arabian Peninsula,although the consanguineous marriage rate is very high.We report the first family from the Arabian Peninsula harboring a novel frameshift mutation in the SACS gene.CASE SUMMARY A 33-year-old man presented to our neurology clinic with balance problems and weakness of distal upper and lower limbs.He was previously clinically diagnosed with Friedreich's ataxia.However,the severity of polyneuropathy and the electrodiagnostic studies(EDX)findings are atypical features of Friedreich’s ataxia,and the deterioration was attributed to diabetic neuropathy.Close examination of other family members identified cerebellar ataxia,lower-limb pyramidal signs,peripheral neuropathy,and magnetic resonance imaging findings characterized by pontine linear hypointensities.Genetic testing for Friedreich’s ataxia did not yield a diagnosis.Whole exome sequencing identified a novel frameshift germline mutation in the SACS gene termed c.5824_5827delTACT using the transcript NM_014363.5,which is predicted to cause premature termination of the sacsin protein at amino acid position 1942(p.Tyr1942Metfs*9)and disrupts the sacsin SRR3 and domains downstream from it.The mutation segregated with the disease in the family.CONCLUSION Our data add to the spectrum of mutations in the SACS gene and argues for a need to implement suitably integrated clinical and diagnostic services,including next generation sequencing technology,to better classify ataxia in this area of the world.
基金Basic Public Welfare Research Scheme of Zhejiang Province,No.GF19H030001.
文摘BACKGROUND Leptospira is an uncommon pathogen for adult severe community-acquired pneumonia and its nonspecific manifestations and limited diagnostic tests make it difficult to identify.Although conventional penicillin remains efficacious to treat leptospirosis,failure in early diagnosis and treatment can lead to progression into a deadly syndrome with multiple organ dysfunction.Next generation sequencing is of great value to understand cases with infection of unknown cause,which could help in the diagnosis of uncertain Leptospira infection.CASE SUMMARY We recently managed a patient with fever,cough and dyspnea on admission that progressed into persistent adult respiratory distress syndrome,hemoptysis and hematuria after admission.In this case,the rare Leptospira infection was clouded by the positive influenza tests at admission,delaying early Leptospira-targeted antibiotics administration.Next generation sequencing,a novel molecular diagnostic tool,provided a key hint to uncover the crucial pathogen,Leptospira interrogans,further supported by the possible occupational exposure history.Subsequent conventional penicillin and mechanical respiratory support were administrated to cure the patient successfully without any sequela.CONCLUSION Clinicians must pay attention to possible exposure history and keep uncommon Leptospira in mind when managing pneumonia with unknown causes.
文摘BACKGROUND Neonatal hyperbilirubinemia is a common problem faced by pediatricians.The role of genetic factors in neonatal jaundice has been gradually recognized.This study aims to identify genetic variants that influence the bilirubin level in five patients using next-generation sequencing(NGS).CASE SUMMARY Five neonates with severe hyperbilirubinemia were retrospectively studied.They exhibited bilirubin encephalopathy,hypothyroidism,ABO blood type incompatibility hemolysis,glucose-6-phosphate dehydrogenase(G6PD)deficiency and premature birth,respectively.A customized 22-gene panel was designed,and NGS was carried out for these neonates.Eight variations(G6PD c.G1388A,HBA2 c.C369G,ABCC2 c.C3825G,UGT1A1 c.G211A,SPTB c.A1729G,EPB41 c.G520A,c.1213-4T>G and c.A1474G)were identified in these five neonates.Genetic mutations of these genes are associated with G6PD deficiency,thalassemia,Dubin-Johnson syndrome,Gilbert syndrome,hereditary spherocytosis,and hereditary elliptocytosis.One of the neonates was found to have compound variants of the EPB41 splice site c.1213-4T>G and c.G520A(p.E174K),but no elliptocyte was seen on his blood smear of 4 years old.CONCLUSION Pathological factors of severe neonatal hyperbilirubinemia are complicated.Genetic variants may play an important role in an increased risk of neonatal hyperbilirubinemia,and severe jaundice in neonates may be related to a cumulative effect of genetic variants.
基金Supported by Zhejiang Natural Science Foundation-Zhejiang Mathematical and Physical Medical Association,No.SY19H310001
文摘BACKGROUND Targeted treatments may greatly affect the natural history of urothelial carcinoma based on their pharmacokinetics. A phase II trial has explored the combination of cytotoxic chemotherapy with the anti-HER-2 monoclonal antibody trastuzumab in selected patients with metastatic bladder cancer, but it failed.CASE SUMMARY Here, we report a case of recurrent urothelial bladder carcinoma(UBC) in a patient who has undergone three operations, and further illuminate its diagnosis and treatment. The diagnosis of UBC was rendered according to the pathological indices. Next-generation sequencing on formalin fixed paraffin-embedded(FFPE)tissue was also performed and suggested HER2 gene amplification in the FFPE tissue. Based on HER2 gene amplification in FFPE, the patient was treated with chemotherapy in combination with trastuzumab after his third surgery.Fortunately, the patient got a clinically complete remission to trastuzumab for 34 mo.CONCLUSION There is not enough clinical evidence for incorporating trastuzumab in routine treatment of UBC. This case hinted that recurrent UBC patients with HER2 gene amplification may benefit from targeted trastuzumab. Further studies are needed to further investigate the status of HER2 gene and better determine trastuzumab in the management of UBC.
基金National Natural Science Foundation of China,No.81972240.
文摘BACKGROUND Colorectal liver metastases(CLM)occur in 15%-30%of patients with colorectal cancer(CRC).Advancements in next generation sequencing(NGS)can provide more precise prognoses for cancer patients and help guide clinical treatment.However,the genetic variants that predict high sensitivity to neoadjuvant chemotherapy remain unclear,especially in patients with CLM.The aim of this study was to identify the relevant genetic variants in a single CLM patient and to summarize the current evidence on mutations and single nucleotide polymorphisms(SNPs)that objectively predict sensitivity to neoadjuvant chemotherapy.CASE SUMMARY A 76-year-old male patient,who was diagnosed as stage IV colon cancer with liver metastases,was found to have APC/TP53/KRAS mutations.He showed a good therapeutic response to 12 courses of oxaliplatin regimens combined with Bevacizumab.Genetic analysis of the patient identified 5 genes with 7 detected SNPs that may be related to a better response to chemotherapy drugs.In addition,a critical literature review was performed based on a standardized appraisal form after selecting the articles.Ultimately,21 eligible studies were appraised to assess the association between gene mutations and good prognosis.Mutations in KRAS,TP53,SMAD4,and APC were identified as being associated with a poor response to chemotherapy drugs,whereas mutations of CREBBP and POLD1 were associated with longer overall survival.CONCLUSION NGS can identify precise predictors of response to neoadjuvant chemotherapy,leading to improved outcomes for CRC patients.
基金Supported by the National Key Basic Research and Development (973) Program of China (No. 041250001)
文摘Tests involving a large number of test cases and test scenarios are always time- and effort- intensive, and use ad hoc approaches. Test management is needed to control the complexity and the qual- ity of the testing of large software systems. The reporting mechanism is critical for monitoring the testing progress, analyzing test results, and evaluating the test effectiveness for a disciplined testing process throughout the testing lifecycle. This paper presents an XML-based report generation method for large sys- tem testing. The service-oriented architecture enables flexible test report generation, presentation, and ex- change to facilitate collaboration in a distributed environment. The results show that proper reporting can ef- fectively improve the visibility of the testing process and that this web-based approach is critical to enhance communication among multiple testing groups.
基金supported by the grants from the "Strategic Priority Research Program" of the Chinese Academy of Sciences (No. XDA01020100 to Q.Z.)the China National Basic Research Program (No. 2012CBA01300 to Q.Z.)the National Science Foundation of China (No. 91319308 to Q.Z.,31201105 to L.L. and 31371516 to W.L.)
文摘Epigenetic reprogramming of somatic cells into induced pluripotent stem cells （iPSCs） by overexpression of defined factors holds great promise for disease modeling and regen- erative medicine （Takahashi and Yamanaka, 2006; Robinton and Daley, 2012）. However, the stochastic reprogramming process often results in variable pluripotency levels of iPSC lines as measured by their in vivo developmental potential, which poses a huge challenge to the applications of high quality iPSCs （Hanna et al., 2010）. The activation status of an imprinted Dlkl-Dio3 region has been identified as a molecular marker for pluripotency （Liu et al., 2010; Stadtfeld et al.,
文摘Mining the data from the huge collection that are present in the database and uncovering the relationships between the item set are one of the key aspects of data mining technologies. Itinerary planning system with personalization in selecting the places to the users is one of the demanding features in most of the travel plan. In this work, the system is designed in such a way to provide the customized journey plan to the users and also the effective one to the back pack travelers. Here the Points of Interests are the places to visit in each destination for the number of days chosen by the travelers. In this system, the users are allowed to specify the desired POIs to visit for the selected destination and can make their customized travel plan effectively. This proposed system is designed to choose the customized places to visit and to plan travel for K-day itineraries. The most visited itineraries are saved and updated in the database. Association rules are used to find out the frequent places visited in each destination and to provide the reputed places to the users to plan the journey. Here the Weka tool is used to evaluate the performance of the algorithm and the rules that are generated for the given travel dataset. Data set is designed by considering several attributes that can take part during travel such as source, destination, travel cost, budget, etc. Statistical analysis is done to evaluate the performance of the proposed system and the list of features that are present in the system. During the analysis part, registered users, number of logins, frequent visits, and attributes are analyzed. Thus the system can be redefined further with the help of this statistical analysis. It is mostly used at the organization end to evaluate their performance and improve the features. Report is generated once the user has chosen their customized places to visit and all detailed description of journey is presented to the user. Report could be saved at the user end and they can use it for the future reference. Thus the goal of the system is to provide the customized travel with personalization in choosing POIs and to find the frequent places visited with desired amenities.
