[A clinical challenge of evaluation and management in children with genetic obesity].

Obesity is a growing global public health problem, while 40%-70% of obesity is determined by genetic factors. This article focuses on the classification, disease characteristics, diagnosis and progressive treatment of childhood genetic obesity. The prevention and control of childhood genetic obesity requires early detection of obese individuals and early screening of obesity causes. At the same time, clinicians are advised to propose individualized therapy and intervention measures based on multi-disciplinary opinions to improve the health of genetic obese children.

[Preliminary investigation of gender assignment in 46,XY disorders of sex development with severe male undermasculinisation].

Objective: To explore the feasibility of gender assignment in 46,XY disorders of sex development (DSD) with severe undermasculinisation mainly based on molecular diagnosis. Methods: A retrospective study of 45 patients of 46, XY DSD with severe undermasculinisation were admitted between November 2015 and October 2018 at Children's Hospital, Zhejiang University School of Medicine. The initial social gender were all female, of whom the external genital manifestations were Prader 0 to 2; the degree of masculinity was scored using external masculinisation score (EMS); the position and development of the gonads were examined by ultrasound, cystoscopy and laparoscopy, also including assessing the development of the Wolffian tube and the Müllerian tube. The level and ratio of testosterone to dihydrotestosterone before and after hCG stimulation were evaluated for the function of Leydig cell and 5α-reductase-2. Gender role scales and sandbox games were used to assess gender role behavior. Genital sensitivity to androgen stimulation was assessed; A panel including 163 genes related to gender development were determined by second-generation sequencing in all 45 patients. Finally, a multidisciplinary team (MDT) makes a gender assignment after a comprehensive analysis mainly based on the molecular etiological diagnosis. Results: Thirty-nine out of 45 patients (87%) had an identifiable genetic etiology, and the remaining 6 (13%) were negative for genetic testing. Forty-five patients had EMS less than or equal to 3 points. Sexual psychological assessment was performed in 39 patients, with male dominance in 24 (62%) and female dominance in 15 (38%). The gender assignment was 23 cases (51%) for male and 19 cases (42%) for female, and 3 cases (7%) were not completely determined. Conclusions: Molecular diagnosis provides a strong basis for appropriate gender assignment of 46, XY DSD children with severe undermasculinisation. Based on molecular diagnosis, each DSD should be analyzed by professional MDT to analyze the clinical symptoms/signs, gonadal development, gonad tumor risk, external genital morphology, sexual psychological assessment, potential fertility opportunities, parental views, Social and cultural factors, etc. make appropriate gender assignment.

LncRNA NBAT-1 is down-regulated in lung cancer and influences cell proliferation, apoptosis and cell cycle.

OBJECTIVE: To explore the expression and role of lncRNA NBAT-1 in lung cancer. PATIENTS AND METHODS: LncRNA NBAT-1 expression in lung cancer tissues and adjacent areas was detected via reverse transcriptase-polymerase chain reaction (RT-PCR). RAC1 protein was analyzed via Western blotting assay. Cell counting kit-8 (CCK-8) and flow cytometry were used to evaluate cell proliferation and apoptosis as well as cell cycle. RESULTS: The expression level of lncRNA NBAT-1 in cancer specimen was remarkably lower than that in adjacent areas. Furthermore, the low expression of lncRNA NBAT-1 had a significant correlation with patient's tumor size, differentiation degree of tumor cells and lymph node metastasis. The overexpression of lncRNA NBAT-1 could inhibit the proliferation and cell cycle, promote the apoptosis of A549 cells, and down-regulate the expression level of RAC1. CONCLUSIONS: The low expression of lncRNA NBAT-1 is involved in the progression of lung cancer.

[The preliminary report of a registration clinical trial of proton and heavy ion irradiation].

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions: IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.

[Advances in the research of pressure therapy for pediatric burn patients with facial scar].

Facial scar and deformation caused by burn injury severely affect physical and psychological well-being of pediatric burn patients, which needs medical workers and pediatric burn patients' family members to pay much attention to and to perform early rehabilitation treatment. Pressure therapy is an important rehabilitative strategy for pediatric burn patients with facial scar, mainly including wearing headgears and transparent pressure facemasks, which have their own features. To achieve better treatment results, pressure therapy should be chosen according to specific condition of pediatric burn patients and combined with other assistant therapies. Successful rehabilitation for pediatric burn patients relies on cooperation of both family members of pediatric burn patients and society. Rehabilitation knowledge should be provided to parents of pediatric burn patients to acquire their full support and cooperation in order to achieve best therapeutic effects and ultimately to rebuild physical and psychological well-being of pediatric burn patients.

[Value of intravoxel incoherent motion diffusion-weighted imaging in differential diagnosis of benign and malignant hepatic lesions and blood perfusion evaluation].

Objective: To investigate the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis and blood perfusion evaluation of benign and malignant hepatic lesions. Methods: A retrospective analysis was performed for 86 patients (96 lesions) with pathologically or clinically confirmed hepatic lesions or hepatic lesions diagnosed based on follow-up results, among whom 48 had malignant lesions (53 lesions) and 38 had benign lesions (43 lesions). The patients underwent conventional magnetic resonance (MR) plain scan, contrast-enhanced scan, and diffusion-weighted imaging (DWI) with different b values (b = 0, 50, 100, 150, 200, 400, 600, 800, 1 000, and 1 200 s/mm2) to determine the parameters of the double exponential model for intravoxel incoherent motion (IVIM): fast diffusion coefficient Dfast, slow diffusion coefficient Dslow, and percentage of fast-diffusion constituent F value. The patients were divided into groups according to the blood supply to lesions on conventional MR plain scan and contrast-enhanced scan, and there were 47 lesions in abundant blood supply group and 49 in poor blood supply group. The data for analysis were Dfast, Dslow, and F values of benign/malignant lesion groups and abundant/poor blood supply groups. The independent samples t-test was used for statistical analysis; the independent samples non-parametric test Mann-Whitney U test was used for the comparison of F value; the receiver operating characteristic (ROC) curve was used to evaluate the value of above parameters in the differentiation of benign and malignant lesions and blood supply evaluation. Results: Compared with the malignant lesion group, the benign lesion group had significantly higher Dslow, and F values (P< 0.001 orP= 0.001) and a higher Dfast value (P= 0.053). Compared with the poor blood supply group, the abundant blood supply group had significantly higher Dfast and F values (P< 0.001 orP= 0.001) and a higher Dslow value (P= 0.185). According to the ROC curve, the cut-off values of Dslow, Dfast, and F values in the diagnosis of benign/malignant hepatic lesions and evaluation of abundant/poor blood supply were 1.18×10-3mm2/s, 27.20×10-3mm2/s, 20.25%, 1.17×10-3mm2/s, 20.30×10-3mm2/s, and 17.80%, respectively, with sensitivities, specificities, accuracy, and areas under the ROC curve of 90.69%/92.45%/91.66%/0.938, 46.51%/73.58%/61.45%/0.589, 74.41%/50.94%/62.50%/0.653, 59.57%/57.14%/58.33%/0.559, 55.32%/63.26%/59.37%/0.618, and 93.61%/89.79%/90.62%/0.961, respectively. Conclusion: The parameter of the double exponential model for IVIM, Dslow value, has a certain value in the differential diagnosis of benign and malignant hepatic lesions, and F value can show blood perfusion in benign and malignant hepatic lesions without the need for contrast-enhanced scan, which provides a reference for the qualitative diagnosis of liver tumor.

Proliferation of myofibroblasts in the stroma of renal oncocytoma.

OBJECTIVES: Myofibroblasts are a vital component of stroma of many malignant neoplasms, but it is not yet established whether stromal myofibroblasts also exist in benign tumours such as oncocytoma of the kidney. MATERIALS AND METHODS: Histomorphological and immunohistochemical analysis of 16 renal oncocytomas diagnosed at Chang Gung Memorial Hospital, Taiwan, has been performed. RESULTS: Renal oncocytomas were composed of oncocytes, large cells with granular eosinophilic cytoplasm, arranged mostly in sheets, in tubulocystic or combined pattern. Few oncocytes appeared to be undergoing proliferation or apoptosis. MIB-1 and active caspase 3 indices were low, but higher in tumour than in surrounding non-tumour parenchyma (MIB-1: 0.93 +/- 0.09 versus 0.46 +/- 0.07, P < 0.001 and active caspase 3: 0.76 +/- 0.08 versus 0.41 +/- 0.09, P < 0.001). Wnt/beta-catenin signalling was not implicated in this neoplasm, as there was no loss of E-cadherin membranous localization or expression of intranuclear beta-catenin in the cells. Clumps of oncocytes were stained with periodic acid Schiff and had collagen I-, collagen III- and fibronectin-positive, but desmin- and human caldesmon-negative stromas. Importantly, alpha-smooth muscle actin (SMA)-immunostaining established the myofibroblastic nature of many of the stromal cells. Some of the myofibroblasts were also positive for MIB-1, indicating a proliferative role for them in the stroma. CONCLUSIONS: Renal oncocytomas were composed of two independent compartments: benign oncocytes and pronounced fibrotic stroma, which consisted of proliferating myofibroblasts (SMA- and MIB-1-positive) which were associated with excessive deposition of extracellular matrix (periodic acid Schiff-component, collagen I-, collagen III- and fibronectin-positive, and desmin- and human caldesmon-negative).

Prevalence of the metabolic syndrome in Zhejiang Chinese obese children and adolescents and the effect of metformin combined with lifestyle intervention.

OBJECTIVE: We aimed to evaluate the prevalence of metabolic syndrome (MS) in a group of obese children and adolescents in Zhejiang in the south of China, and to compare risk factors such as insulin resistance, adiponectin level and impaired glucose tolerance (IGT) etc with that of simple obese group (SOB) and non-obese healthy group, and also to evaluate the effect of metformin and lifestyle intervention in MS group by up to a 3-month follow-up. METHODS: Three hundred and forty eight moderately or severely obese adolescents aged between 7 and 16 years were enrolled. Oral glucose tolerance test (OGTT), biochemical indicators, blood pressure and body mass index (BMI) were assessed in all of them. Three subgroups were selected (MS group, SOB and healthy control). Adiponectin levels, Whole body insulin sensitive index (WBISI), homeostasis model of insulin resistance (HOMA-IR), plasma lipid and blood pressure were compared in these three groups. Thirty out of thirty-six MS subjects with age over 10 years received metformin treatment combined with lifestyle modification. RESULTS: (1) The prevalence of MS was 10.34% among all obese subjects, which increased with the severity of obesity and reached 22.1% in severely obese children and adolescents. The occurrence of more than one complication reached 72.13%. The incidence of type 2 diabetes and IGT were 1.44 and 1.44% respectively. (2) BMI, waist-to-hip ratio (WHR) and HOMA-IR increased stepwise in the control group, SOB and MS group, whereas serum adiponectin and WBISI decreased stepwise (all P<0.01). Systolic pressure, triglyceride, total cholesterol, low-density lipoprotein cholesterol and postprandial 2-h blood glucose in the MS group increased significantly compared to those in control and SOBs (all P<0.01). A correlation analysis showed that serum levels of adiponectin and WBISI were associated with the components of MS (all P<0.05). (3) After metformin and lifestyle intervention, clinical symptoms were ameliorated, serum adiponectin levels were actually increased and HOMA-IR was dropped in 20/30 MS children who had finished a 3-months follow-up (all P<0.01). CONCLUSION: The prevalence of MS in severely obese children and adolescents in Zhejiang area has reached a high level. Insulin resistance and hypoadiponectinemia were found in these MS children. Metformin combined with lifestyle modification was confirmed to be efficient and safe in treating the obese adolescents with MS.

Characterization of fusion partner genes in 114 patients with de novo acute myeloid leukemia and MLL rearrangement.

The fusion transcripts of MLL rearrangement [MLL(+)] in acute myeloid leukemia (AML) and their clinicohematologic correlation have not be well characterized in the previous studies. We used Southern blot analysis to screen MLL(+) in de novo AML. Reverse transcriptase-polymerase chain reaction was used to detect the common MLL fusion transcripts. cDNA panhandle PCR was used to identify infrequent or unknown MLL partner genes. MLL(+) was identified in 114 (98 adults) of 988 AML patients. MLL fusion transcripts comprised of 63 partial tandem duplication of MLL (MLL-PTD), 14 MLL-AF9, 9 MLL-AF10, 9 MLL-ELL, 8 MLL-AF6, 4 MLL-ENL and one each of MLL-AF1, MLL-AF4, MLL-MSF, MLL-LCX, MLL-LARG, MLL-SEPT6 and MLL-CBL. The frequency of MLL-PTD was 7.1% in adults and 0.9% in children (P<0.001). 11q23 abnormalities were detected in 64% of MLL/t11q23 and in none of MLL-PTD by conventional cytogenetics. There were no differences in remission rate, event-free survival and overall survival between adult MLL-PTD and MLL/t11q23 groups. Adult patients had a significantly poorer outcome than children. The present study showed that cDNA panhandle PCR can identify all rare or novel MLL partner genes. MLL-PTD was rare in childhood AML. MLL(+) adults had a poor outcome with no difference in survival between MLL-PTD and MLL/t11q23 groups.

Lack of BCL10 mutations in multiple myeloma and plasma cell leukemia.

To determine whether the BCL10 mutation plays a role in the oncogenesis of plasma cell dyscrasias, we used polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing analysis and examined the genomic BCL10 mutations in 57 patients with multiple myeloma or plasma cell leukemia and 52 normal bone marrow samples. We found three polymorphic sequence variants, either alone or in combination, at codons 5 and 8, and in intron 1 at base 58 of the BCL10 gene in 37 patients with plasma cell dyscrasia. Identical aberrant band shifts were also observed in 34 normal marrow samples. No polymorphic variants were identified in exon 2 or 3 in either patient or control samples, and no pathogenic mutations were detected. Patients with plasma cell dyscrasias in Taiwan appeared to have a higher frequency of polymorphisms at codon 5 and intron 1 at base 58, and a lower frequency at codons 8 and 213. Our results suggest that BCL10 is not involved in the oncogenesis of plasma cell dyscrasias.

[Use of heterogeneous acelluar dermal matrix and autologous overthin split-thickness skin for repair of deep burn at articular sites].

OBJECTIVE: To investigate the effect of heterogeneous (swine) acellular dermal matrix (s-ADM) and autologous overthin split-thickness skin (auto-OTS) composite grafting in repair of deep burns at articular sites. METHODS: From May 1999 to April 2000, 19 articular sites in 16 patients, including 14 males and 2 females, were treated. In all the 19 sites of deep burn, the total burn area varied from 2% to 48% and the full-thickness burn area varied from 1% to 35%. After the primary escharectomy (1 to 5 days later) and complete hemostasis, the s-ADM was utilized to cover the exposed articular sites and the auto-OTS was transferred on the surface of sutured s-ADM. The size of s-ADM applied to each patient varied from 25 cm2 to 150 cm2. Regular skin grafting was adopted elsewhere other than the articular site. The survival rate of all skin grafting was evaluated and pathological examination was performed. RESULTS: The survival rate of the composite skin was (90.80 +/- 18.34)%, which was obvious higher than the survival rate of contiguous granulosum skin grafting (P < 0.05) and almost the same with that of snip skin grafting(P > 0.05). The survived composite skin appeared as smooth and soft as normal skin, and the function of articular site almost recovered with neglectable hypertrophic scar. The pathological examination revealed that the normal cell grew into s-ADM with regularly arranged collagen fiber and neovascularization in the matrix. CONCLUSION: The combination of s-ADM and auto-OTS graft is cheap and effective method to cover wound and minimize hypertrophic scar.

Simultaneous occurrence of multiple aetiologies of polycythaemia: renal cell carcinoma, sleep apnoea syndrome, and relative polycythaemia in a smoker with masked polycythaemia rubra vera.

A 58 year old male heavy smoker presented with intracranial haemorrhage and erythrocytosis. Four aetiologies of polycythaemia--polycythaemia rubra vera (PRV), renal cell carcinoma, sleep apnoea syndrome, and relative polycythaemia--were found to be associated with the underlying causes of erythrocytosis. He did not fulfill the diagnostic criteria for PRV at initial presentation, but an erythropoietin independent erythroid progenitor assay identified the masked PRV, and the low post-phlebotomy erythropoietin concentration also suggested the likelihood of PRV evolution. This case demonstrates that a search for all the possible causes of erythrocytosis is warranted in patients who already have one aetiology of polycythaemia.

Aberration antigen expression in adult acute myelocytic leukemias.

Marrows from 58 newly diagnosed acute myelocytic leukemia (FAB-AML) patients were immunophenotyped by flow cytometry with 13 kinds of monoclonal antibodies. Marrows of 53.4% of the patients showed pure myeloid antigen expression (Ly-AML) and 34.5% displayed both myeloid and lymphocyte associated antigen expression (Ly+AML). In general, fluorescence intensity of lymphocyte associated antigen in Ly+AML was weaker than that of myeloid antigen. Myeloid and lymphoid marker cells distributed randomly in DNA-aneuploidy. It took more days to reach the first complete remission in Ly+AML. The aberration antigen expression in AML allows a sensitive detection of minimal residual leukemic cells in complete remission bone marrow and treatment stratification.