Purpose To investigate the activity of language network with brain function connection network analysis method using MRI order statistics correlation coefficient, and to explore the temporal reliability and functional asymmetry, and provide the theoretical foundation for clinical researches of resting-state language network.Materials and Methods Twenty-five healthy volunteers were scanned three times in resting state. All data were processed using 32 bit Matlab 7.11.0 and DPARSF. The two main language functional areas, Broca and Wernicke, were selected as the regions of interest. The functional connectivity of language network was analyzed with order statistics correlation coefficient.Results Based on the functional connectivity diagrams using seed analysis method, the asymmetry index and intra-class correlation were obtained. The functional connectivity of resting-state language network based on order statistics correlation coefficient was similar to that using the traditional correlation coefficient methods. Conclusion The temporal reliability of resting-state language network can provide a reference value for clinical research of language disorders, as well as the clinical diagnosis and treatment of the language disorders or mental diseases caused by abnormal functional asymmetry of language network.

Objective To investigate the feasibility of new criteria for evaluating the radiotherapeutic effect on esophageal cancer by barium meal (BM) combined with CT scans.Methods A total of 189 patients who were diagnosed with esophageal cancer (confirmed by biopsy) from January 2004 to December 2010 were enrolled as subjects.All patients underwent BM and CT scans before and after radiotherapy.The maximal esophageal wall thickness (EWT) and changes in the volumes of regional lymph nodes measured by CT scans were analyzed.New criteria for evaluating the short-term radiotherapeutic effect on esophageal cancer was studied considering the analysis results as well as the BM-based criteria for evaluating short-term radiotherapeutic effect and follow-up results.Results The BM-based evaluation criteria were still useful,but had certain limitations.There were 115 patients who had regional lymph node metastasis as detected by CT scans before radiotherapy,and they were divided into complete remission (CR) group and partial remission (PR) group according to BM results after radiotherapy; the local control rate (LCR) of CR group was significantly higher than that of PR group,but there was no significant difference in survival rate (SR) between the two groups.There were 65 patients who had no regional lymph node metastasis,and they were also divided into CR group and PR group according to BM results after radiotherapy;the LCR and SR of CR group were significantly higher than those of PR group.In summary,the patients who had a CR as evaluated by BM and had the maximal EWT of ≤ 1.20 cm and the volumes of residual lymph nodes of ≤ 1.00 cm3 on CT were defined as CR ; the patients who had a PR as evaluated by BM or had the maximal EWT of ＞ 1.20 cm or those who had a CR evaluated by BM and had the maximal EWT of ≤ 1.20 cm and the volumes of residual lymph nodes of ＞ 1.00 cm3 on CT were defined as PR.The cases evaluated by BM as no remission (NR) or showing metastasis were defined as NR or progressive disease.There were significant differences in LCR and SR between the CR group and PR group determined by the new criteria.Conclusions Simply using BM to evaluate the short-term radiotherapeutic effect on esophageal cancer has certain limitations; instead,the evaluation based on both BM and CT scans is more accurate.

Objective To investigate the parameters of diffusion?weighted magnetic resonance imaging ( DWMRI) for prediction of the efficacy of chemoradiotherapy ( CRT) for esophageal squamous cell carcinoma ( ESCC) , to determine the optimal time point and threshold for prediction, and to provide a basis for clinical practice. Methods From 2010 to 2011, 38 patients with ESCC were consecutively enrolled as subjects. All patients received three?dimensional conformal radiotherapy with 60 Gy in 30 fractions for 6 weeks. They also received concurrent or consolidation chemotherapy ( FP or TP scheme ) as adjuvant treatment. Patients received DWMRI scans before radiotherapy and at weeks 1?6 during radiotherapy. The apparent diffusion coefficient ( ADC ) values and tumor lengths obtained from serial DWMRI scans were recorded and analyzed. Comparison was made by paired t test. Repeated measurements were analyzed by analysis of variance ( ANOVA) and multivariate ANOVA. The prognosis was predicted by the Logistic model. The effectiveness analysis and threshold screening were performed using the receiver operating characteristic (ROC) curve. Results In all patients, 20(52?6%) had complete response (CR) and 18(47?4%) had partial response ( PR) . There were no significant differences in the ADC values before radiotherapy and at weeks 1?6 during radiotherapy between patients with CR and PR ( 1?82 vs. 1?42;1?92 vs. 1?49;2?06 vs. 1?67;2?35 vs. 1?79;2?62 vs. 2?11;2?71 vs. 2?18;2?96 vs. 2?28×10-3 mm2/s;P=0?006,0?003,0?012, 0?001,0?003,0?008,0?002) . The ADC value at third week during radiotherapy was the only independent prognostic factor for short?term treatment outcomes in patients with ESCC ( OR=0?134, P=0?007) . These results were also supported by the multivariate ANOVA analyses. The analysis of the ROC curve showed that at the third week during radiotherapy, the area under the ADC curve was the largest ( A z=0?857) and the diagnostic effectiveness was the best;the threshold value, sensitivity, and specificity were 2?02×10-3 mm2/s, 80?0%, and 92?9%, respectively. Eight patients who had tumor out of control or recurrence within 1 year after treatment had the ADC curve fall down at the end of the fifth week and the reduction of tumor length substantially slow down from the fifth week. Conclusions DWMRI is an effective imaging approach for monitoring tumor response to CRT in patients with ESCC. The ADC value at the end of the third week during radiotherapy may be the optimal time point for prediction of treatment outcomes. The reduction in the ADC value or non?reduction in tumor length at the end of the treatment indicates a high risk of recurrence.

Objective: To evaluate the safety of enterovirus 71（EV71）inactivated vaccines produced by Wuhan Institute of Bio Products through learning the incidence of adverse events following immunization（AEFI）in children aged 6 months to 3 years old after vaccination. Methods: According to the national requirement for vaccine safety monitoring program，data of AEFI cases after inoculated EV71 vaccines from September 2017 to October 2018 in Zhejiang Province was collected by combining active and passive monitoring. Demographic characteristics，space distribution，dose and incidence of AEFI were analyzed. Results: A total of 107 503 children were included in this study，of which 27 173 were actively monitored and 80 330 were passively monitored. The monitoring results showed that 288 cases of AEFI occurred after inoculated EV71 vaccines，the reported incidence rate was 267.90/100 000. Of 288 cases，266 cases had common reactions（247.43/100 000），14 cases had abnormal reactions（13.02/100 000）and 8 cases had complications（7.44/100 000）；145 cases were passively monitored（180.51/100 000）and 143 cases were actively monitored（526.26/100 000）；150 cases were males and 138 cases were females，with the males to females ratio of 1.09∶1. The AEFI of EV71 vaccines were reported in all the cities of Zhejiang Province，with Jinhua，Taizhou and Hangzhou ranking the top three and accounting for 50.69% of all the reported cases. About 202 cases of AEFI（70.14%）occurred after the first dose of EV71 vaccines，and 163 cases（56.60%）occurred on the day of inoculation.Most of common reactions were fever，swelling and sclerosis. The harm of the reported abnormal reactions was mild，with 8 cases of anaphylactic rash and no other serious abnormal reactions were found. Conclusion The reported incidence rate of AEFI of the domestic EV71 vaccine in children aged from 6 months to 3 years is 267.90/100 000，without serious abnormal reactions，suggesting that the EV71 vaccine is safe.

OBJECTIVETo explore the origin and mechanism of small supernumerary marker chromosomes (sSMC) in order to facilitate genetic counseling.

METHODSChromosome karyotypes of two fetuses and their immediate family members were analyzed by conventional G banding. High-throughput whole genome sequencing was used to determine the origin of sSMCs.

RESULTSFetus 1 was shown to have a karyotype of 47,XY,+mar but with normal FISH and B ultrasound findings. Its father also had a 47,XY,+mar karyotype with normal FISH results and clinical phenotype. High-throughput genome sequencing revealed that fetus 1 and its father were both 46,XY,dup(21)(q11.2;q21.1) with a 6.2 Mb duplication of the long arm of chromosome 21. The fetus was born with normal phenotype and developed well. Its grandmother also had a karyotype of 46,XX,t(15;21)(q13;p13) with normal FISH result and clinical phenotype. The karyotypes of its mother and grandfather were both normal. Analysis of fetus 2 showed a 47,XY,+mar karyotype with normal FISH results. High-throughput genome sequencing suggested a molecular karyotype of 46,XX. The fetus was born with normal phenotype and developed well. The karyotypes of its parents were both normal.

CONCLUSIONConsidering their variable origins, identification of sSMC should combine conventional G banding analyses with high-throughput whole genome sequencing for precise delineation of the chromosomes.

Adult ; Amniotic Fluid ; chemistry ; Chromosome Banding ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Cytogenetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genetic Markers ; Humans ; In Situ Hybridization, Fluorescence ; Infant, Newborn ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis ; Young Adult

OBJECTIVETo track and analyze two false positive cases from non-invasive prenatal testing for potential fetal aneuploidy.

METHODSThe two cases, respectively reported to have XO (+++) and T18 (1/20) XO(+), were analyzed with conventional karyotyping, fluorescence in situ hybridization (FISH) and massively parallel genomic sequencing (MPS).

RESULTSThe first fetus, who was suspected for XO(+++), was verified to have super female syndrome (47,XXX/46,XX) due to confined placental mosaicism by karyotyping of amniotic fluid cells, FISH analysis of placenta and massively parallel sequencing (MPS) of fetal tissue. The second fetus, suspected to have trisomy 18 (1/20) XO(+), was verified to have Turner syndrome by karyotyping, FISH and MPS analyses of umbilical cord blood cells. And the karyotype was 45,X[48]/46, X, der(X) del(X) (p11.21) del(X) (q13.3)[62].

CONCLUSIONNon-invasive prenatal testing carries a risk for false positive diagnosis of fetal sex chromosome and trisomy 18. Combined cytogenetic and molecular techniques are required to ensure an accurate diagnosis.

Adult ; Aneuploidy ; Chromosome Aberrations ; Diagnostic Errors ; False Positive Reactions ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Pregnancy ; Prenatal Diagnosis ; Young Adult

OBJECTIVE: To delineate cytogenetic and molecular abnormalities of a fetus carrying a de novo 46,X,der(X),t(X;Y)(p22.3;p11.2). METHODS: G-banded karyotyping and next-generation sequencing (NGS) were used to analyze the fetus, his father and sister. Single nucleotide polymorphism-based arrays (SNP-array), multiple PCR and fluorescence in situ hybridization (FISH) were utilized to verify the result. RESULTS: G-banded karyotyping at 320 bands showed that the fetus had a normal karyotype, while NGS has identified a 3.58 Mb microdeletion at Xp22.33 and a Y chromosomal segment of about 10 Mb at Yp11.32p11.2. With the sequencing results, high-resolution karyotyping at 550-750 bands level has determined the fetus to be 46,X,der(X)t(X;Y)(p22.3;p11.2). The result was confirmed by PCR amplification of the SRY gene, FISH and SNP-array assays. The karyotypes of his father and sister were both normal. His sister also showed no amplification of the SRY gene, and her NGS results were normal too, suggesting that the karyotype of the fetus was de novo. CONCLUSION Combined karyotyping, NGS, SNP-array, PCR and FISH assay can facilitate diagnosis of XX disorder of sex development.
Chromosomes, Human, X ; genetics ; Disorders of Sex Development ; genetics ; Female ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Translocation, Genetic

Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.

Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with multiple pterygium syndrome (MPS). METHODS: A child with MPS who was treated at the Orthopedics Department of Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University on August 19, 2020 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were also collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing of her parents and bioinformatic analysis. RESULTS: The child, an 11-year-old female, had a complain of "scoliosis found 8 years before and aggravated with unequal shoulder height for 1 year". WES results revealed that she has carried a homozygous c.55+1G>C splice variant of the CHRNG gene, for which both of her parents were heterozygous carriers. By bioinformatic analysis, the c.55+1G>C variant has not been recorded by the CNKI, Wanfang data knowledge service platform and HGMG databases. Analysis with Multain online software suggested that the amino acid encoded by this site is highly conserved among various species. As predicted with the CRYP-SKIP online software, the probability of activation and skipping of the potential splice site in exon 1 caused by this variant is 0.30 and 0.70, respectively. The child was diagnosed with MPS. CONCLUSION The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient.
Humans ; Child ; Female ; Abnormalities, Multiple/genetics* ; Malignant Hyperthermia/genetics* ; Skin Abnormalities/genetics* ; Heterozygote ; Mutation ; Receptors, Nicotinic/genetics*