OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a child with Acid-labile subunit deficiency (ALS). METHODS: A male child diagnosed with ALS at Dongguan Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Clinical data of his family was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and Sanger sequencing was used for family verification of candidate variants. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was classified. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2020-6). RESULTS: The patient, a 5-year-and-7-month-old boy, presented with short stature and delayed bone age. Endocrine examinations showed decreased serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP3). WES revealed that he has harbored compound heterozygous variants of the IGFALS gene, namely c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31. Sanger sequencing verified that the variants were inherited from his father and mother, respectively. According to the ACMG guidelines, c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 variants were classified as likely pathogenic (PVS1+PM2_supporting). Based on the pre-set literature search strategy, 11 research literature on ALS were retrieved, which involved a total of 33 families and 62 patients. Combined with the patient in this study, 31 IGFALS gene variants were identified among the 63 patients, which mainly consisted of missense variants (20 types), with variant sites concentrated in exon 2. The main clinical features were short stature in conjunct with delayed puberty, with a significant genotype-phenotype correlation. CONCLUSION The IGFALS gene variants NM_004970.2: c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 may be the genetic etiology in this family. This study has expanded the variant spectrum of the IGFALS gene and provided valuable information for the diagnosis, genetic counseling and clinical treatment of the disease.
Humans ; Male ; Phenotype ; Child, Preschool ; Carrier Proteins/genetics* ; Glycoproteins/deficiency* ; Exome Sequencing ; Female ; Mutation ; Insulin-Like Growth Factor I/metabolism* ; Growth Disorders/genetics*

Objective:To analyze the reasons of misdiagnosed cases in the intraoperative frozen pathological diagnosis of breast disease and explore effective measures and practices for targeted and standardized quality control.Methods:A retrospective analysis was conducted on 2 421 cases of breast intraoperative frozen pathological examination performed at Renmin Hospital of Wuhan University from Apr. 2020 to Dec. 2021. The results of intraoperative frozen pathological examination were compared with postoperative pathological results to calculate the overall concordance rate and misdiagnosis rate. Pathological classification and causative analysis were performed for misdiagnosed cases. Standardized management was implemented to address the identified issues, and an analysis was conducted on 2248 cases from Feb. 2022 to Nov. 2023 to compare the overall concordance rate and misdiagnosis rate before and after management.Results:The comparison between intraoperative rapid frozen pathology diagnosis and postoperative paraffin pathology diagnosis showed that among the 2 421 breast specimens, there were 2 377 cases (98.18%) with concordant results and 44 cases of misdiagnosis, resulting in a misdiagnosis rate of 1.82%. The pathological types of 44 misdiagnosed cases were analyzed, among which 10 cases were lymph node metastatic carcinoma, 5 were lobar tumors, 3 were intraductal papillary tumors, 7 were carcinoma in situ and common hyperplasia each, and 4 were carcinoma in situ, sclerosing adenopathy, and other invasive carcinoma each. Through the analysis of causes, it was found that poor slide quality, the need for immunohistochemistry assistance, careless slide reading, missed critical lesions, and other factors contributed to misdiagnosis, with variations in the causes of misdiagnosis among different pathological types. After implementing standardized management, the overall concordance rate significantly improved (98.93%) and the misdiagnosis rate significantly decreased (1.07%) .Conclusions:Intraoperative frozen pathological diagnosis is of great significance in the treatment of breast diseases. The targeted standardized quality control can help early detection and solve problems, reduce the differences between different doctors and technicians, and improve the accuracy of intraoperative frozen pathological diagnosis.

Objective:To analyze the reasons of misdiagnosed cases in the intraoperative frozen pathological diagnosis of breast disease and explore effective measures and practices for targeted and standardized quality control.Methods:A retrospective analysis was conducted on 2 421 cases of breast intraoperative frozen pathological examination performed at Renmin Hospital of Wuhan University from Apr. 2020 to Dec. 2021. The results of intraoperative frozen pathological examination were compared with postoperative pathological results to calculate the overall concordance rate and misdiagnosis rate. Pathological classification and causative analysis were performed for misdiagnosed cases. Standardized management was implemented to address the identified issues, and an analysis was conducted on 2248 cases from Feb. 2022 to Nov. 2023 to compare the overall concordance rate and misdiagnosis rate before and after management.Results:The comparison between intraoperative rapid frozen pathology diagnosis and postoperative paraffin pathology diagnosis showed that among the 2 421 breast specimens, there were 2 377 cases (98.18%) with concordant results and 44 cases of misdiagnosis, resulting in a misdiagnosis rate of 1.82%. The pathological types of 44 misdiagnosed cases were analyzed, among which 10 cases were lymph node metastatic carcinoma, 5 were lobar tumors, 3 were intraductal papillary tumors, 7 were carcinoma in situ and common hyperplasia each, and 4 were carcinoma in situ, sclerosing adenopathy, and other invasive carcinoma each. Through the analysis of causes, it was found that poor slide quality, the need for immunohistochemistry assistance, careless slide reading, missed critical lesions, and other factors contributed to misdiagnosis, with variations in the causes of misdiagnosis among different pathological types. After implementing standardized management, the overall concordance rate significantly improved (98.93%) and the misdiagnosis rate significantly decreased (1.07%) .Conclusions:Intraoperative frozen pathological diagnosis is of great significance in the treatment of breast diseases. The targeted standardized quality control can help early detection and solve problems, reduce the differences between different doctors and technicians, and improve the accuracy of intraoperative frozen pathological diagnosis.

Objective:To study the feasibility of magnetic resonance imaging(MRI)technique with amide proton transfer(APT)in predicting the prognosis of cerebral stroke.Methods:A total of 71 patients with acute cerebral stroke who admitted to the Nanjing First Hospital,Nanjing Medical University from September 2022 to May 2023 were selected.All of them underwent the test of National Institute of Health Stroke Scale(NIHSS),and received the MRI examination with chemical exchange saturation transfer(CEST).According to the modified Rankin scale(mRS)values of 1-month follow-up,they were divided into favorable recovery group(mRS<2,44 cases)and poor group(mRS≥2,27 cases).The asymmetric magnetization transfer ratio(MTRasym)image(APT)was obtained by analyzing data with special software.And then,the difference(△APTw)of APT values between ischemic zone and contralateral normal tissue was further calculated.The △APTw values of two groups were compared and analyzed,and the Pearson correlation analysis was adopted to analyze the correlation among △APTw,NIHSS and mRS.The receiver operating characteristics(ROC)curve was drawn,and the area under curve(AUC)of ROC curve was calculated.Results:There were significant positive correlations among △APTw,NIHSS and mRS scores(R2=0.659,0.522,P<0.001),and the differences of △APTW,NIHSS and mRS scores between the favorable recovery group and poor group were significant(t=5.73,6.36,13.92,P<0.05),respectively.The AUC value was 0.886,and the sensitivity and specificity of prediction were respectively 77.8%and 95.5%.The positive and negative predictive values were respectively 91.3%and 87.5%.Conclusion:APT imaging technique has feasibility in predicting the prognosis of acute cerebral ischemic stroke.

OBJECTIVE: To explore the genetic basis for a Chinese patient featuring cleidocranial dysplasia(CCD). METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and his parents. Whole exome sequencing (WES) was carried out for the patient, and suspected variant was verified by Sanger sequencing. RESULTS: WES has identified a missense c.460G>T (p.Val154Phe) (GRCh37/hg19) variant of the RUNX2 gene. The variant was located in the Runt domain, a highly conserved region (PM1); it was not present in either the Genome Aggregation Database or the 1000 Genomes Project (PM2), and was predicted to have a deleterious effect on the gene product by multiple in silico prediction tools (PP3); the clinical phenotype of the patient was highly consistent with that of cleidocranial dysplasia (PP4). Furthermore, the variant was unreported in medical literature and was absent in both parents (PS2). Based on the American College of Medical Genetics and Genomics guidelines, the c.460 G>T variant of RUNX2 gene was predicted to be pathogenic (PS2+PM1+PM2+PP3+PP4). CONCLUSION The c.460G>T (p.Val154Phe) variant of the RUNX2 gene probably underlay the clinical phenotype in the patient. Above finding has enabled accurate diagnosis and expanded the spectrum of RUNX2 variants.
China ; Cleidocranial Dysplasia/genetics* ; Core Binding Factor Alpha 1 Subunit/genetics* ; Humans ; Mutation ; Whole Exome Sequencing

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the prenatal diagnosis of a fetus with structural anomaly detected by ultrasonography. METHODS: The fetus and its parents were subjected to chromosomal karyotyping and CMA analysis. RESULTS: The fetus was found to carry a 46,XN,t(8;11)(q21.2;q13) translocation which was inherited from its mother. CMA has found no copy number variations (CNVs) in both parents but a de novo 2.00 Mb microdeletion in the fetus at 8q13.3. CONCLUSION CMA is capable of detecting microdeletions and microduplications in fetuses with translocations detected by karyotyping analysis.
Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 8 ; DNA Copy Number Variations ; Female ; Fetus ; Humans ; Karyotyping ; Microarray Analysis ; Pregnancy ; Prenatal Diagnosis

Objective: To understand the longitudinal changes of refractive errors in adolescent myopia screening in the suburb of Shanghai, and to provide reference for targeted measures of myopia prevention and intervention. Methods: By using the cluster sampling method, 1 346 students were selected from two primary schools in a town in the suburb of Shanghai. Physical development indicators and refractive examination parameters of non ciliary muscle paralysis, and uncorrected visual acuity in 2017 and 2020 were collected from the Shanghai adolescent refractive development file. Longitudinal change of spherical equivalent (SE) refractive were assessed. A linear regression model was used to examine the relationship between the rate of SE change with characteristics of the students. Results: The average annual incidence of myopia was 16.36%, and the SE degrees of the left and right eyes of myopia students decreased by 225 degrees for three years. Girls (right eye Z=-4.33; left eye Z=-3.75, P<0.01), newly-onset myopia and persistent myopia (right eye Z=634.45; left eye Z=638.85, P<0.01) was a key for the rapid progress of refractive power. Conclusion The proportion of students with severe low vision is relatively high, and the apparent shifts toward more hyperopia in myopia students call for effective prevention and control programs based on changes in refractive to slow the progression of adolescent myopia.

Objective:To explore the effect of transitional nursing on medicine-taking compliance and insight of first hospitalized female schizophrenic patients.Methods:Seventy female cases who met ICD-10 diagnostic criteria that were discharged after stable treatment were randomly divided into intervention group and control group, 35 cases for each group.The medicine-taking compliance of the two groups was evaluated by the Morisky medication adherence scale, and the treatment effect was evaluated by the Insight and Treatment Attitude Questionnaire (ITAQ).The follow-up period was two months after discharge with four assessment points.Results:The Morisky scores in intervention group at the end of 1 week[ (4.7±1.2) vs. (4.0±0.8) ], 2 weeks[ (5.1±1.2) vs. (3.8±1.1) ], 1 month[ (5.1±1.5) vs. (3.5±1.2) ]and 2 months[ (5.8±1.2) vs. (3.3±1.0) ]were higher than those in control group (F=52.74, P＜0.001).The ITAQ scores in intervention group at the end of 1 week[ (3.4±2.1) vs. (2.9±1.4) ], 2 weeks[ (5.5±3.2) vs. (3.7±2.5) ], 1 month[ (4.6±2.7) vs. (4.5±2.7) ]and 2 months[ (6.9±3.4) vs. (3.9±2.6) ]were also higher than those in control group (F=7.12, P=0.010).Conclusion:Transitional nursing can improve the medicine-taking compliance and rehabilitation effect of first hospitalized female schizophrenic patients.

Objective To investigate the effects and mechanism of evodiamine on the proliferation and apoptosis of osteosarcoma MG-63 cells.Methods MG-63 cells were cultured with evodiamine for 24 hours,and the cell proliferation was evaluated by methyl thiazolyl tetrazolium (MTT) assay.Cell cycle arrest,apoptosis and intracellular Ca2+ accumulation were evaluated by flow cytometry.BALB/C mice model of osteosarcoma was established to investigate the tumor inhibitory effect of evodiamine on human osteosarcoma.Wnt/β-catenin signaling protein expressions in osteosarcoma cells were detected by Western blotting.Results As concentration of evodiamine increasing (0.25 μmol/L,0.5 μmol/L,1.0 μmol/L,2.0 μmol/L and 4.0 μmol/L),the inhibition rate of MG-63 ceils increased [(4.18 ± 1.26)％,(15.49 ± 2.26)％,(40.55 ± 6.57)％,(49.87 ±7.69)％ and (60.42 ±8.29)％].The difference was statistically significant between 2.0 μmol/L group and the control group (t =-2.66,P ＜ 0.05).MG-63 cells were cultured with 2.0 μmol/L evodiamine for 24 hours,and the apoptotic rate was (64.67 ± 8.63) ％,the proportion of S phase cells was (85.33 ± 9.31)％,the fluorescence of Ca2+ was 97.33 ± 21.31.The corresponding data of the control group were (4.94 ± 0.81) ％,(43.67 ± 8.92) ％ and 28.67 ± 8.92,the differences were statistically significant (t =-11.90,P ＜ 0.05;t =-7.22,P ＜ 0.05;t =-6.65,P ＜ 0.05).On mice model,the tumor weight of evodiamine group and the control group was (2.15 ±0.35)g and (4.29 ±0.49)g respectively,the difference was statistically significant (t =7.95,P ＜ 0.05).Comparing with the control group (1.00 ± 0.00),evodiamine decreased the expression of β-catenin protein (0.72 ± 0.36) and increased the expressions of Bax (1.15± 0.27) and Caspase-3 (1.46 ± 0.18) protein,and the differences were statistically significant (t =-3.05,P ＜ 0.05;t =-6.42,P ＜ 0.05;t =-5.85,P ＜ 0.05).Conclusion Evodiamine inhibits proliferation and induces apoptosis of human osteosarcoma MG-63 cells by blocking Wnt/β-catenin signaling.

BACKGROUND:Silk fibroin, as a kind of high-performance biomaterial, has been widely used to construct scaffolds in bone tissue engineering. However, whether silk fibroin itself holds osteoinductive ability has not been reported yet. OBJECTIVE:To investigate the impact of different concentrations of silk fibroin solution on the proliferation and differentiation of rat bone marrow mesenchymal stem cel s (BMSCs) in vitro. METHODS:Silk fibroin and BMSCs were respectively isolated from silkworm cocoon and rat tibia, and were identified. Then, BMSCs were cultured in different concentrations of silk fibroin solution (0.01%, 0.05%and 0.1%), and the cell proliferation and the alkaline phosphatase activity were detected at different time points. RESULTS AND CONCLUSION:FTIR spectra of the sample extracted from silkworm cocoon showed distinct absorption peaks at 1 653 (amide I), 1 530.5 (amide II) and 1 212.3 cm-1 (amide III), which could be confirmed to be silk fibroin. Thus generated BMSCs showed long fusiform or astral morphology, positive for representative markers (CD29, CD44 and CD90) relating to mesenchymal stem cells, and could differentiate into osteocytes, chondrocytes and adipocytes under specific induction conditions, which further confirmed the extracted cells were BMSCs. Compared with the control group (without silk fibroin), 0.05% silk fibroin not only significantly promoted the cell adhesion, migration and proliferation, but also enhanced the alkaline phosphatase activity (P<0.01). With the increasing of the silk fibroin concentrations, the osteodifferentiation capacity of the BMSCs was progressively improved within the range of 0-0.05%and then declined at 0.01%of silk fibroin solutions. These results suggest that silk fibroin can promote osteogenesis, thus providing scientific evidence for developing silk fibroin-based tissue-engineered scaffolds.