BACKGROUNDSH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive (AR) Charcot-Marie-Tooth (CMT) disease type 1, autosomal dominant (AD)-CMT1, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families.

METHODSA total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84 AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMT1 probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using polymerase chain reaction and Sanger sequencing. All these patients were out of 315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of pathogenic variants of PMP22, MFN2, MPZ, GJB1, GDAP1, HSPB1, HSPB8, EGR2, NEFL, and RAB7. Candidate variants were analyzed based on the standards and guidelines of American College of Medical Genetics and Genomics (ACMG). Clinical features were reevaluated.

RESULTSWe identified three novel heterozygous variants such as p.L95V (c.283C>G), p.L1048P (c.3143T>C), and p.V1105M (c.3313G>A) of SH3TC2 gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in silico and screening in the healthy control revealed that the three SH3TC2 variants were likely pathogenic, no second allele variants were discovered. According to the standards and guidelines of ACMG, the heterozygous SH3TC2 variants such as p.L95V, p.L1048P, and p.V1105M were considered to be of uncertain significance.

CONCLUSIONSSH3TC2, PMP2, and BSCL2 pathogenic variants might be rare in Chinese CMT patients. Further studies to confirm our findings are needed.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

No abstract available.
HMGB1 Protein* ; Pemphigus*

PURPOSE: Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research. MATERIALS AND METHODS: We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues. RESULTS: Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor–overexpressing PDX with clear cell histology (p=0.023). CONCLUSION: PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.
Animals ; Biology ; Cell Line ; Drug Therapy, Combination ; Eosine Yellowish-(YS) ; Epidermal Growth Factor ; Erlotinib Hydrochloride ; Female ; Hematoxylin ; Heterografts* ; Humans ; Mice ; Microsatellite Repeats ; Molecular Targeted Therapy ; Ovarian Neoplasms* ; Precision Medicine ; Translational Medical Research ; Tumor Burden

No abstract available.
Cranial Nerve Diseases* ; Lymphoma*

PURPOSE: Liver volumetry is a vital component in living donor liver transplantation to determine an adequate graft volume that meets the metabolic demands of the recipient and at the same time ensures donor safety. Most institutions use preoperative contrast-enhanced CT image-based software programs to estimate graft volume. The objective of this study was to evaluate the accuracy of 2 liver volumetry programs (Rapidia vs. Dr. Liver) in preoperative right liver graft estimation compared with real graft weight. METHODS: Data from 215 consecutive right lobe living donors between October 2013 and August 2015 were retrospectively reviewed. One hundred seven patients were enrolled in Rapidia group and 108 patients were included in the Dr. Liver group. Estimated graft volumes generated by both software programs were compared with real graft weight measured during surgery, and further classified into minimal difference (≤15%) and big difference (>15%). Correlation coefficients and degree of difference were determined. Linear regressions were calculated and results depicted as scatterplots. RESULTS: Minimal difference was observed in 69.4% of cases from Dr. Liver group and big difference was seen in 44.9% of cases from Rapidia group (P = 0.035). Linear regression analysis showed positive correlation in both groups (P < 0.01). However, the correlation coefficient was better for the Dr. Liver group (R² = 0.719), than for the Rapidia group (R² = 0.688). CONCLUSION: Dr. Liver can accurately predict right liver graft size better and faster than Rapidia, and can facilitate preoperative planning in living donor liver transplantation.
Donor Selection ; Humans ; Linear Models ; Liver ; Liver Transplantation ; Living Donors ; Organ Size ; Retrospective Studies ; Tissue Donors ; Tomography, X-Ray Computed ; Transplants*

OBJECTIVETo evaluate the efficacy and safety of cyclophosphamide as a second-line drug in the treatment of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.

METHODSSix children with anti-NMDAR encephalitis, who showed poor response to steroids and intravenous immunoglobulin, were given cyclophosphamide as a second-line immunotherapy. Follow-up was performed to evaluate the efficacy and safety of cyclophosphamide.

RESULTSAfter first-line immunotherapy for 1-4 weeks, the six patients had reduced psychiatric symptoms, seizures, and involuntary movements; three patients had an improved level of consciousness and were able to make simple conversations. However, all the patients still showed slow response, as well as cortical dysfunction symptoms such as aphasia, alexia, agraphia, acalculia, apraxia, and movement disorders. The six patients continued to receive cyclophosphamide as a sequential therapy. They were able to answer simple questions 7 days after treatment. Three school-aged patients were able to make simple calculation, had greatly improved reading and writing ability, and almost recovered self-care ability 2-3 weeks later. The cognitive function of the six patients was almost restored to the level before the onset of disease, and their living ability returned to normal 2-3 months later. During the treatment period, there were no adverse reactions or abnormal results of routine blood test and liver and kidney function tests.

CONCLUSIONSChildren with anti-NMDAR encephalitis should be given appropriate immunotherapy as soon as possible. Cyclophosphamide as a sequential therapy has good efficacy and safety.

Adolescent ; Anti-N-Methyl-D-Aspartate Receptor Encephalitis ; drug therapy ; physiopathology ; psychology ; Child ; Child, Preschool ; Cognition ; Cyclophosphamide ; therapeutic use ; Female ; Humans ; Immunotherapy ; Male

PURPOSE: Crohn's disease (CD) can involve any site of the gastrointestinal tract (GIT). However, the characteristics of upper GIT involvement in CD are unclear, especially in the Eastern pediatric population. This study aimed to estimate the prevalence of upper GIT involvement and identify the clinical features of Korean children with CD. METHODS: This was a retrospective multicenter cohort study that included 52 pediatric patients with CD who underwent esophagogastroduodenoscopy and biopsy. The clinical symptoms and endoscopic and histologic features of the upper GIT were identified according to the presence or absence of upper gastrointestinal symptoms. RESULTS: Among the 52 patients, upper GIT involvement was noted in 50.0% (26/52). The mean age at CD diagnosis was 14.1±2.1 years. Gastric ulcer was the most common lesion (19.2%) found on upper GIT endoscopy, followed by duodenal ulcers (15.4%). Chronic inflammation was the most common histopathologic feature (75.0%), followed by gastric erosion (17.3%). Granuloma was found in 9.6% of patients. Helicobacter pylori infection was identified in 5.8% of patients. Endoscopic and histologic findings were not significantly different, but the mean values of erythrocyte sedimentation rate (60.7±27.1 vs. 43.0±27.6 mm/h, p=0.037) and C-reactive protein (16.5±28.2 vs. 6.62±13.4 mg/dL, p=0.014) were significantly different between patients with and without upper gastrointestinal CD symptoms. CONCLUSION: Upper GIT involvement was relatively common in pediatric patients with CD irrespective of upper gastrointestinal symptoms, and H. pylori infection was relatively uncommon. The results of this study should aid the establishment of regional guidelines for upper GIT examination.
Biopsy ; Blood Sedimentation ; C-Reactive Protein ; Child ; Cohort Studies ; Crohn Disease* ; Diagnosis ; Duodenal Ulcer ; Endoscopy ; Endoscopy, Digestive System ; Gastrointestinal Tract ; Granuloma ; Helicobacter pylori ; Humans ; Inflammation ; Pediatrics ; Prevalence ; Retrospective Studies ; Stomach Ulcer ; Upper Gastrointestinal Tract*

PURPOSE: Crohn's disease (CD) can involve any site of the gastrointestinal tract (GIT). However, the characteristics of upper GIT involvement in CD are unclear, especially in the Eastern pediatric population. This study aimed to estimate the prevalence of upper GIT involvement and identify the clinical features of Korean children with CD. METHODS: This was a retrospective multicenter cohort study that included 52 pediatric patients with CD who underwent esophagogastroduodenoscopy and biopsy. The clinical symptoms and endoscopic and histologic features of the upper GIT were identified according to the presence or absence of upper gastrointestinal symptoms. RESULTS: Among the 52 patients, upper GIT involvement was noted in 50.0% (26/52). The mean age at CD diagnosis was 14.1±2.1 years. Gastric ulcer was the most common lesion (19.2%) found on upper GIT endoscopy, followed by duodenal ulcers (15.4%). Chronic inflammation was the most common histopathologic feature (75.0%), followed by gastric erosion (17.3%). Granuloma was found in 9.6% of patients. Helicobacter pylori infection was identified in 5.8% of patients. Endoscopic and histologic findings were not significantly different, but the mean values of erythrocyte sedimentation rate (60.7±27.1 vs. 43.0±27.6 mm/h, p=0.037) and C-reactive protein (16.5±28.2 vs. 6.62±13.4 mg/dL, p=0.014) were significantly different between patients with and without upper gastrointestinal CD symptoms. CONCLUSION: Upper GIT involvement was relatively common in pediatric patients with CD irrespective of upper gastrointestinal symptoms, and H. pylori infection was relatively uncommon. The results of this study should aid the establishment of regional guidelines for upper GIT examination.
Biopsy ; Blood Sedimentation ; C-Reactive Protein ; Child ; Cohort Studies ; Crohn Disease* ; Diagnosis ; Duodenal Ulcer ; Endoscopy ; Endoscopy, Digestive System ; Gastrointestinal Tract ; Granuloma ; Helicobacter pylori ; Humans ; Inflammation ; Pediatrics ; Prevalence ; Retrospective Studies ; Stomach Ulcer ; Upper Gastrointestinal Tract*

OBJECTIVETo summarize the clinical characteristics of peripheral blood, immune phenotypes, fusion genes and cytogenetics of patients with t(8;21) acute myeloid leukemia(AML) through the retrospective analysis of 586 patients with t(8;21) AML from 15 blood disease research centers in Northern area of China.

METHODSThe factors affecting prognosis of patients with t(8;21) AML were investigated by using univariate and multivariate COX regression.

RESULTSThe immune type of t(8;21) AML patients was mainly with HLA-DR, CD117, CD34, MPO, CD38, CD13and CD33(>95%), part of them with CD19and CD56; the most common accompanied mutation of t(8;21) AML patients was C-KIT mutation (37.8%); in addition to t(8;21) ectopic, the most common chromosomal abnormality was sex chromosome deletions (38.9%). The univariate analysis revealed a significant survival superiority of OS and PFS in t(8;21) AML patients of WBC≤3.5×10/L without C-KIT mutation, the newly diagnosed ones achieved HSCT(P<0.05), only survival superiority on OS in t(8;21) AML patients with extramedullary infiltration and CD19 positive; the results of multivariate analysis showed a significant survival superiority on OS and PFS in t(8;21) AML patients with WBC≤3.5×10/L(P<0.05).

CONCLUSIONThe clinical features of t(8;21) AML patients in China are similar to those in other countries, WBC≤3.5×10/L is a good prognostic factor while the C-KIT mutation is a poor one in t(8;21) AML patients.