Objective:To explore the application of the early clinical exposure concept-guided question-answer teaching model combined with the ORTCC (objectives, rules, training, check, and culture) model in endocrine teaching reform.Methods:Sixty-two students who interned at Beijing Anzhen Hospital of Capital Medical University from August 2022 to August 2023 were divided into control group and observation group according to the order of student number, with 31 students in each group. The control group received traditional teaching, while the observation group received early clinical exposure concept-guided question-answer teaching combined with the ORTCC model. At the end of the internship, the two groups were compared in terms of theoretical and practical assessment scores and comprehensive competency assessment scores. SPSS 22.0 was used to perform the t-test. Results:The theoretical assessment score of the control group was (87.00±3.86) points, while that of the observation group was (91.26±4.34) points, with a statistically significant difference between the two groups ( t=4.09, P<0.001). The observation group also showed significantly higher scores of clinical practice assessment and comprehensive competency assessment than the control group ( P<0.05). Conclusions:The combination of question-answer teaching guided by the early clinical exposure concept and the ORTCC model is helpful for endocrine interns to master theoretical knowledge and acquire clinical practical skills and comprehensive abilities, effectively improving the quality of internship teaching.

Objective:To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus.Methods:Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children′s Medical Center and Qingyuan People′s Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal.Results:Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses.Conclusions:Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for fetal duodenal obstruction (DO). METHODS: Fifty-one fetuses with DO identified by prenatal ultrasound were divided into DO only group and DO with other anomaly group. CMA was carried out on amniotic fluid or umbilical blood samples, and the outcome of pregnancy of all cases were followed up. RESULTS: Eight fetuses (15.7%) were found with genomic abnormalities, which included 3 chromosomal aneuploidies and 5 copy number variations (CNVs), including one 17q12 microduplication syndrome, one 13q21.33q31.1 microdeletion, one 13q21.32q22.3 deletion, one 13q21.2q31.1 deletion and one 1q43q44 duplication. EDNRB from 13q and HNF1B from 17q12 are candidate genes for fetal DO. No significant difference was found in the detection rate of pathogenic CNVs between the DO only and DO with other anomaly groups (9.5% vs.11.1%, P> 0.05). There were 39 live borns, 1 stillbirth, and 11 artificial abortions (8 with abnormal CMA results). CONCLUSION There is a correlation between fetal DO and abnormal copy number of the genome, for which prenatal diagnosis is necessary. CMA not only can detect microdeletions/microduplications, but also identify pathogenic genes, which can facilitate prenatal diagnosis, genetic counseling and prognosis for the fetus.
Chromosome Aberrations ; DNA Copy Number Variations ; Duodenal Obstruction/genetics* ; Female ; Fetus ; Humans ; Microarray Analysis ; Pregnancy ; Prenatal Diagnosis

Objective:To evaluate the value of whole exome sequencing (WES) in prenatal clinical application.Methods:A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed.Results:Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results.Conclusions:WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.

OBJECTIVE: To investigate the application value of whole exome sequencing technology in fetuses with congenital structural abnormalities. METHODS: The chromosomal abnormalities of 1147 families were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in late pregnancy or after birth were reanalyzed. Subgroups were divided according to the organs involved and whether single malformation or not. The gene regulatory network map was drawn by using string database and Cytoscape software. Fisher exact probability method was used to compare the difference of the diagnostic rate of pathogenic genes among the groups. RESULTS: A total of 160 fetal cases received positive molecular diagnosed, involving 178 variant sites of 125 pathogenic genes, including 8 cases (4.9%, 8/163) by data reanalysis, and the overall positive diagnosis rate was 13.9%. Diagnostic rate was highest in the group of skeletal malformation (31.5%, 39/124) and lowest in that with thoracic malformation (0, 0/32). The gene clusters of fetal edema and intrauterine growth restriction were independent, and were not associated with the major structural malformations. The probability of each parent carrying the same recessive gene variant was 0.03 (39/1146) and 0.08 (4/53) with positive family history. CONCLUSION For fetuses with congenital structural abnormalities that are negative for conventional genetic tests, 13.9% of phenotypic associated pathogenic/likely pathogenic genetic variants can be detected by whole exome sequencing technology. Its application value for prenatal diagnosis varies in fetus with different organs involved. Reanalysis of sequencing data for cases with new phenotypes in late pregnancy or after birth can further improve the molecular diagnosis rate. Further investigations are needed to explore the related genetic mechanisms.
Female ; Fetal Diseases ; Fetus/diagnostic imaging* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Technology ; Ultrasonography, Prenatal ; Whole Exome Sequencing

Objective:To explore and describe clinicopathological characteristics and prognosis of patients with double primary breast cancer (BC) and thyroid cancer (TC).Methods:Medical records of 98 patients diagnosed with double primary breast and thyroid cancer in National Cancer Center (NCC)/Cancer Hospital between January 1, 2001 and December 31, 2020 were retrospectively collected. All of the patients were followed up until January 1, 2021 to acquire survival data. Univariate survival analysis was conducted by Kaplan-Meier method, and multivariate survival analysis was carried out using the Cox proportional hazard model.Results:All of 98 patients in the group were women. The age at diagnosis of the first tumor ranged from 26-72 years old, and the median age was 47 years old. The BC recurring TC (breast methyl) group included 18 cases, TC recurring BC (methyl breast) group included 60 cases, BC and TC simultaneously occurred group (the two are diagnosed within 3 months) included 20 cases. There were statistically significant differences in breast cancer pathological grading, breast cancer postoperative radiotherapy, and combined with other tumors in breast methyl group, methyl breast group and the simultaneous group ( P<0.05). Among the 98 patients, 14 had recurrence and metastasis, and 7 died. The patients who died from tumors were all those with TC recurrence of BC. There were no statistically significant differences in the death, recurrence and metastasis of patients in the breast methyl group, methyl breast group and the simultaneous group ( P>0.05). Univariate analysis showed that BC stage and estrogen receptor (ER) were related to overall survival ( P<0.05), while the family history of BC, BC stage, and ER were not related with the recurrence and metastasis ( P<0.05). Multivariate analysis showed that BC family history, ER positive, and the order of tumor diagnosis (TC recurring BC) were independent influencing factors for the recurrence and metastasis ( P<0.05). Conclusion:ER negative is a poor prognostic factor for the double primary breast and thyroid cancer.

Objective:To explore and describe clinicopathological characteristics and prognosis of patients with double primary breast cancer (BC) and thyroid cancer (TC).Methods:Medical records of 98 patients diagnosed with double primary breast and thyroid cancer in National Cancer Center (NCC)/Cancer Hospital between January 1, 2001 and December 31, 2020 were retrospectively collected. All of the patients were followed up until January 1, 2021 to acquire survival data. Univariate survival analysis was conducted by Kaplan-Meier method, and multivariate survival analysis was carried out using the Cox proportional hazard model.Results:All of 98 patients in the group were women. The age at diagnosis of the first tumor ranged from 26-72 years old, and the median age was 47 years old. The BC recurring TC (breast methyl) group included 18 cases, TC recurring BC (methyl breast) group included 60 cases, BC and TC simultaneously occurred group (the two are diagnosed within 3 months) included 20 cases. There were statistically significant differences in breast cancer pathological grading, breast cancer postoperative radiotherapy, and combined with other tumors in breast methyl group, methyl breast group and the simultaneous group ( P<0.05). Among the 98 patients, 14 had recurrence and metastasis, and 7 died. The patients who died from tumors were all those with TC recurrence of BC. There were no statistically significant differences in the death, recurrence and metastasis of patients in the breast methyl group, methyl breast group and the simultaneous group ( P>0.05). Univariate analysis showed that BC stage and estrogen receptor (ER) were related to overall survival ( P<0.05), while the family history of BC, BC stage, and ER were not related with the recurrence and metastasis ( P<0.05). Multivariate analysis showed that BC family history, ER positive, and the order of tumor diagnosis (TC recurring BC) were independent influencing factors for the recurrence and metastasis ( P<0.05). Conclusion:ER negative is a poor prognostic factor for the double primary breast and thyroid cancer.

Background and Objectives: Stroke mimics are medical conditions producing stroke-like symptoms but eventually get diagnosed as non-stroke diseases. Epileptic seizure is a common type of stroke mimic. The purpose of this study is to investigate the application of emergency multimodal computed tomography (CT) in the diagnosis of epileptic seizure. Methods: We retrospectively reviewed the case group of patients with suspected stroke in the emergency stroke care service of the First Affiliated Hospital of Suzhou University from September 2017 to October 2019. We included those who underwent multimodal CT, including non-contrasted cranial CT, CT perfusion with CT angiography, and were ultimately diagnosed as epileptic seizures. Ten patients with acute anterior circulation ischemic stroke were assigned as controls. Results: A total of five cases met the inclusion criteria. Multimodal CT was completed within 2.25 to 3.50h from symptom onset. On CT perfusion, hyperperfusion was shown in four cases and slightly increased perfusion in one case with epileptic seizures. Cerebral blood flow and cerebral blood volume were significantly increased, while time to peak and mean transit time decreased in the regions of interest of the epileptic hemisphere when compared to either the non-affected hemisphere or the ischemic area in the control group (P<0.05). The abnormal perfusion areas did not follow vascular territory supply and CT angiography did not show vessel occlusion in the case group. Conclusion: Emergency multimodal CT could be used effectively to differentiate epileptic seizure from stroke.

Objective To establish the diagnostic model based on detection of serum biomarkers in pancreatic cancer (PC) associated diabetes.Methods From June 2013 to July 2014, at Ruijin Hospital, School of Medicine , Shanghai Jiao Tong University , 30 patients diagnosed with PC companied with new onset diabetic mellitus and 30 patients with new onset type 2 diabetic mellitus , were enrolled .Serum samples were examined by liquid chromatography-mass spectrometry ( LC-MS) for metabolomics analysis .Orthogonal partial least square ( OPLS ) was performed for raw data analysis to obtain the differentially expressed metabolites between two groups .The first 15 cases of each group were taken as training samples and the left as validation samples.The model was established using logistic regression via stepwise differentially expressed metabolites and clinical data input in training samples .The diagnostic efficiency of the model was verified in validating samples . Results Ten differentially expressed metabolites were identified in PC companied with new onset diabetic mellitus group and new onset type 2 diabetic mellitus group .The differentially expressed metabolites identified in positive ion mode were 3-ketosphingosine , arachidonoyl dopamine , phosphatidylethanolamine ( 18 :2 ) , ubiquinone-1 and valine .The differentially expressed metabolites identified in negative ion mode were C 16 sphingosine-1-phosphate, keto palmitic acid, isoleucine, N-succinyl-L-diaminopimelic acid and uridine.The diagnostic model was established in training samples:p=e(Xβ)/(1+e(Xβ)), ( Xβ) =-158.975-1.891 (age) +0.309 ( phosphatidylethanolamine 18:2 ) +1.035 ( C16 sphingosine-1-phosphate ) +0.084 (isoleucine) +1.1145 ( N-succinyl-L-diaminopimelic acid ).The area under curve ( AUC) of receiver operating characteristic (ROC) of this model was 0.982 in validation samples, the sensitivity and specificity were both 93.3％.Conclusion Serum metabolomics-based diagnostic approach is a promising method for screening PC from new onset diabetic mellitus .

OBJECTIVETo explore the genetic etiology of fetuses with ventricular septal defects (VSD) using chromosomal microarray analysis (CMA).

METHODSA total of 248 fetuses were divided into isolated VSD group, VSD with other cardiac and/or great vessels malformation group, VSD with extra-cardiac anomalies group (including malformation and sonographic soft markers), and VSD with both cardiac and extra-cardiac anomalies group. Standard karyotyping was carried out for all fetuses, and CMA was performed for 6 fetuses with an abnormal karyotype and a proportion of fetuses with a normal karyotype. All cases were followed up, and neonates were followed up until 1 year of age.

RESULTSChromosomal abnormalities were identified in 60 (24.2%) of the 248 fetuses. For 6 of the fetuses subjected to further CMA analysis, the origin of abnormal chromosomes were clarified, among which 2 have overlapped with the critical region of Wolf-Hirschhorn syndrome. Candidate genes for VSD included WHSC1, LBX1, LDB3 and BBS10. For 143 fetuses with a normal karyotype, CMA has identified pathogenic copy number variations (CNVs) in 11 cases (7.7%). These included 9 well-known microdeletion or microduplication syndromes, including 22q11.2 microdeletion, 17p11.2 microdeletion (Smith-Magenis syndrome), 17p13.3 microdeletion (Miller-Dieker syndrome), 1p36 microdeletion, 1q21.1 microduplication and 4q deletion. Candidate genes for VSD included TBX1, LZTR1, FAT1, AKAP10, SKI, PRDM26, GJA5, ERCC4 and YWHAE. For 48.7% of the fetuses with benign CNVs, spontaneously closure has occurred within the first year of life.

CONCLUSIONCMA may increase the detection rate of submicroscopic imbalances by 7.7%. No significant correlation between different groups of VSD and the pathogenic CNVs was observed. Whole-genome CMA should be recommended to the fetuses with VSD but a normal karyotype. Nearly half of VSDs with benign CNVs may close spontaneously within the first year of life.

Chromosome Aberrations ; Chromosome Deletion ; DNA Copy Number Variations ; Heart Septal Defects, Ventricular ; genetics ; Humans ; Infant ; Infant, Newborn ; Karyotyping ; Microarray Analysis ; methods ; Prenatal Diagnosis ; methods