Purpose: Whether a dilated intrahepatic bile duct (IHBD) has any effect on the prognosis of choledochal cyst (CC) remains controversial. We aimed to summarize the clinical characteristics and prognosis of CC with IHBD dilatation. Methods: One hundred ninety-two children diagnosed with CC were identified, including 127 without IHBD dilatation (group A) and 65 with IHBD dilatation (group B). A retrospective analysis was performed to explore the clinical characteristics and prognosis of CC with IHBD dilatation based on clinical indices, symptoms, and complications. Results: Compared with group A, incidences of jaundice and fever were higher in group B (P = 0.010 and P = 0.033). Preoperative total bilirubin, direct bilirubin, and indirect bilirubin were increased in group B compared to group A (P = 0.005, P < 0.001, and P = 0.014), as were preoperative ALT, AST, γ-GT, and total bile acid (P = 0.006, P = 0.025, P < 0.001, and P = 0.024). The risk of liver fibrosis or cirrhosis was significantly increased for group B compared with group A (P = 0.012) and also occurred earlier in group B (P = 0.006). In the dilated IHBDs, 95.4% (62 of 65) recovered to normal, and more than half of dilated IHBDs (37 of 65) recovered to normal in 1 week. Conclusion Most IHBDs can recover to normal postoperatively in a short time, and proactive treatment is recommended for CC patients with IHBD dilatation for significant abnormal liver functions.

Objective: To investigate clinical, molecular genetic characteristics, and treatment outcomes of 3 children with sitosterolemia. Methods: Three cases of children presented with multiple xanthomas during June 2016 to June 2017 were included. The clinical manifestations, laboratory examinations and follow-up data were retrospectively analyzed. DNA was extracted from peripheral blood and analyzed with whole exome sequencing(WES). All the detected variants were confirmed by Sanger sequencing. Plasma plant sterol concentrations were measured by gas chromatography-mass spectrometry. Results: Three cases of children including 1 boy and 2 girls presented with multiple linear and intertriginous xanthomas around skin of the joint areas at the age from 15 months to 6 years and 2 months. Total cholesterol of the 3 cases was elevated to 14.45, 15.47 and 15.85 mmol/L (3.36-6.46), and low density lipoprotein cholesterol was 9.02, 13.54 and 12.47 mmol/L (< 3.36) respectively. Genetic analysis with WES revealed that 2 cases carried compound heterozygous variants in ABCG5 gene, 1 case carried compound heterozygous variants in ABCG8 gene. Two reported variants (p. N437K, p.R446X) and one novel variant (p.Q251X) of ABCG5 were identified in case 2 and 3. Two novel ABCG8 variants (p.R263Q, c.1528_1530delATC) were found in case 1. All these children had extremely high plasma plant sterol levels, thus the diagnosis of sitosterolemia was confirming. The campesterol level was 111.35, 102.86 and 58.91 μmol/L(0.01-10.00), the stigmasterol was 14.97, 29.43 and 17.79 μmol/L (0.10-8.50) and the sitosterol was 231.20, 177.66 and 114.20 μmol/L (1.00-15.00) respectively. The total serum cholesterol levels of three children decreased to nomal after the patients were placed on the low plant sterol/low cholesterol diet. The xanthomas regressed gradually, and almost disappeared after 8 months of treatment in case 1 and 3. Conclusions Children with sitosterolemia presented with skin xanthomas around the joint areas. The level of total cholesterol, low density lipoprotein cholesterol and plant sterols increased obviously. One novel variant (p.Q251X) of ABCG5 and 2 novel variants (p.R263Q, c.1528_1530delATC) of ABCG8 were identified. Children with sitosterolemia responded well to a low plant sterols/low cholesterol diet.

Objective To investigate the characteristics of glycogen storage disease type IV (GSD IV) clinically, in laboratory tests and in gene mutation. Methods The clinical manifestations, biochemical indexes, activity of chitotriosidase, and the follow-up of the treatment in 5 cases of GSD IV were analyzed. Results Five patients (3 boys and 2 girls) aged 4 months - 5 years presented hepatosplenomegaly and elevated liver enzyme levels for 2 months at hospital visit. Two patients had motor developmental delay and weakness but their creatine kinase (CK) level were normal. Glycogen storage and liver fibrosis were observed in the liver biopsy in 4 patients. Target sequencing found that all 5 children carried the complex heterozygous mutation of the GBE1 gene with 2 reported mutations(p.R515C,p.R524Q)and 7 novel mutations.The novel mutation contains 5 missense mutations (p.I460T, p.F76S, p.F538V, p.L650R, p.W455R), one insertion mutations (c.141_142insGCGC), and one large fragment deletion (exon 3-7). Therefore, diagnosis of liver type of GSD IV was confirmed in those children. Two patients died of liver cirrhosis. The liver transplantation was performed due to liver cirrhosis in one patient whose chitotriosidase activity increased obviously before transplantation and decreased significantly after the transplantation and liver enzyme levels were returned to normal 4 months after transplantation. In the other two patients their growth and liver enzyme levels were normal;one had not received special treatments while the other was treated with raw corn starch and level of chitotriosidase was normal. Conclusions The clinical manifestations of GSD IV are heterogeneous. Target sequencing can be used for fast and noninvasive diagnosis of GSD IV. Chitotriosidase activity is useful in the prognosis assessment for GSD IV.

OBJECTIVETo determine the genetic etiology and clinical characteristics of 2 boys featuring development delay (DD).

METHODSRoutine chromosomal banding was performed to analyze the karyotypes of the patients and their parents. Single nucleotide polymorphism array (SNP array) analysis was employed to identify pathogenic deletion/duplication of chromosomes, and quantitative real-time PCR (qPCR) was performed to confirm the results.

RESULTSPatient 1 showed a global developmental delay, especially impaired language development, seizures, behavioral problems belonging to the autism spectrum and mild facial dysmorphism. Patient 2 mainly presented with severely delayed speech and moderate intellectual disability, but did not have obvious facial dysmorphism and autistic-like behavior. The diagnosis of 22q13 syndrome was established based on identification of a heterozygous microdeletion at chromosome 22q13.33 in both patients (69 kb and 587 kb, respectively) by the SNP array analysis. Both patients had deletions of SHANK3 and ACR, which are located at the end of 22q. Quantitative real-time PCR verified that the deletion of SHANK3 gene in both patients were de novo in origin.

CONCLUSIONTwo cases of 22q13 deletion syndrome have been diagnosed by SNP array analysis. Deletion of SHANK3 gene may be the major contributor to the clinical manifestations of the patients. SNP array analysis can facilitate discovery of microdeletions, which has played an important role in the diagnosis and genetic counseling for the family.

Objective To investigate the clinical, laboratory and genetic features of glycogen storage disease(GSD)IXc. Methods Five patients suspected as liver GSD were included in our study. DNA was extracted from peripheral blood of all the patients and diagnoses were made after target sequencing to nearly 2700 disease causing genes. All detected mutations were confirmed in the probands and their parents. Further analysis was based on clinical features, routine laboratory examinations and treatment. Results All the 5 patients manifested with severe hepatomegaly, hypoglycemia, moderately to severely elevated liver enzyme levels, hypertriglyceridemia and growth retardation. Four cases showed poor exercise tolerance but with normal creatine kinase (CK) levels. None of the patients showed liver cirrhosis. Growth velocity and hepatomegaly was improved after the uncooked corn starch treatment was initiated. In the 5 patients, 6 different pathogenic or likely pathogenic mutations in the PHKG2 gene were identified, including one reported mutation (p.E157K) and five novel mutations (p.E56X, p.R185X, c.79_88delinsTCTGGTCG, c.761delC,p.R279C). The p.E157K was the most frequently mutation identified (6/12, 50%). Conclusions The p.E157K mutation is the hot mutation in our small cohort. Main clinical features of our patients include fasting hypoglycemia, impaired liver function,short statures and poor exercise tolerance, without developing liver cirrhosis.

Objective: To investigate the clinical and laboratory features of three children with late-onset type Ⅱ glycogen storage disease(GSD) who presented with hypertrophic cardiomyopathy and to analyze the effect of five mutations identified on the acid-α-glucosidase (GAA) activity and stability. Method: Three cases of children with muscle weakness were included in this study.GAA activity was analyzed in Dried Blood Spot of the patients.DNA was extracted from peripheral blood in all the patients and their parents and subjected to polymerase chain reaction and directly sequencing of GAA gene.Five mutant pcDNA3.1-myc-his-GAA expression plasmids(p.G478R, p.P361L, p.P266S, p.Q323X, p.R672Q) were constructed and transient instantaneously transfected into 293T cells to analyze the enzyme activity and stability of GAA. Result: All the three children had the onset of disease at 3 years or 1.5 years of age.They presented with developmental delay, muscle weakness and hypertrophic cardiomyopathy.GAA activity of 3 patients was 2.65, 3.55 and 1.51 pmol(punch·h)(8.00-98.02)respectively. Genetic analysis found 5 mutations (p.G478R, p. P361L, p. P266S, p. Q323X, p. R672Q), and all of these 3 cases had clinical manifestations and were diagnosed as late-onset type Ⅱ glycogen storage disease.Five mutant pcDNA3.1-myc-his-GAA expression plasmids were transfected into 293T cells.Five mutant enzyme activities were found to be only 9.9%-22.5% of the wild-type enzyme activity and the protein expression of the five mutants was 32.0%-63.9% compared with the wild type. Conclusion This study reports 3 children with late-onset GSD Ⅱ accompanied by hypertrophic cardiomyopathy and compensatory stage of cardiac function in addition to limb muscle weakness.Five pathogenic mutations were identified, and these 5 mutations result in decreased GAA activity and GAA expression by in vitro functional analysis.

Objective To investigate the effect of statin on trabecular bone microstructure by using trabecular bone score (TBS), a new type of bone microstructure evaluation index. Methods A total of 253 middle and aged patients hospitalized in the First Affiliated Hospital of Nanjing Medical University between January 2014 and March 2016 were retrospectively analyzed. According to whether statin was used or not, patients were divided into two groups: 90 patients in the statin use group (statin was use for more than 1 year) and 163 in the control group (not taken any statin). Serum biochemical indicators, such as triacylglycerol, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, alkaline phosphatase, fasting blood glucose and 25 hydroxy vitamin D, were compared between the two groups. Dual energy X-ray absorptiometry (DXA) was used to measure the bone mineral density (BMD) of lumbar spine and femoral neck. TBS was calculated with TBS iNsight? software, and the DXA image of lumbar spine were analyzed. Results Values of total cholesterol and low density lipoprotein cholesterol were significantly lower in statin group compared with those of control group (P<0.001), while no significant differences in other biochemical indicators between two groups (P>0.05). There was higher lumbar spine BMD statin group compared to that of control group (g/cm2:1.04 ± 0.19 vs. 0.96 ± 0.14, P<0.01). There was higher lumbar spine BMD and higher TBS (1.31±0.09 vs. 1.26±0.09, P<0.01) in statin group than that of control group. There was no difference in the femoral neck BMD between the two groups (P>0.05). Conclusion Statin increases lumbar spine BMD and improves trabecular bone microstructure in middle and aged people.

Objective To investigate the clinical significance of measuring resting energy expenditure (REE) for guiding an accurate nutritional support in elderly bedridden patients with nasal feeding.Methods The REE of 32 elderly bedridden patients with nasal feeding was assessed by using the Cosmed K4b2 portable telemetric gas analysis system.The waist-hip ratio, serum levels of albumin, transferrin, prealbumin and retinol-binding protein were determined to assess comprehensive nutrition status.The energy intakes were calculated, and the correlation of REE and the difference between the energy intakes and consumption with nutritional index were analyzed.Results The resting energy expendture was lower in the patients with waist-hip ratio≥0.95 than in patients with waist-hip ratio ＜0.95 (t=3.622, P＜0.01).The waist-hip ratio was reduced and serum albumin and transferrin levels were decreased along with the increase of REE in elderly patients (r=-0.55,-0.36 and-0.593, respectively, P=0.001, 0.043, ＜0.001).The difference between the energy intake and expenditure was higher in patients with waist-hip ratio≥0.95 than those with waist-hip ratio＜0.95 (t =5.643, P＜ 0.001).Serum albumin, prealbumin, transferrin and retinol-binding protein levels were increased along with the increase of the difference between the energy intake and expenditure, which showed the positive correlations (r=0.525, 0.409, 0.624, 0.414, respectively,P=0.002, 0.02, ＜0.001, 0.019).Conclusions Precise determination of REE and energy intake guided by REE are the important guarantees for the reasonable nutrition support in the elderly.

Objective To assess the association between interleukin-10-1082 (IL-10-1082) gene polymorphisms and susceptibility of gastric cancer in the Chinese population.Methods Cochrane systematic evaluation was adopted for the analysis.Articles published in Medline,Embase,Cochrane library,CBM,CJFD and CSJD from 1966 to 2012 were retrieved.Case control studies on the correlation between the 1L-10-1082 polymorphism and gastric cancer in Chinese population were collected.Gastric cancer patients were in the gastric cancer group,and healthy individuals were in the control group.Two researchers extracted data and evaluated the quality of literatures independently.Meta analysis was performed to detect whether there were differences between the gastric cancer group and the control group about the distribution of genotypes of IL-10-1082 gene (GG,AA,AG,AA,alleles G and A).The heterogeneity was analyzed using the Q test or I2 test.Fixed effect model or random effect model was adopted,and the results of the meta analysis were presented with odds ratio (OR) and 95％ confidence interval (95％ CI).Results Thirteen literatures including 5252 patients were included in the analysis.There were 2077 patients in the gastric cancer group and 3175 patients in the control group.The results of meta analysis showed that population with the genotypes GG and AG have higher risk of having gastric cancer when compared with population with the genotype AA (OR =1.76,95％ CI 1.33-2.33 ; OR =2.08,95％ CI 1.62-2.66,P ＜0.05).Population with the allele G have higher risk of having gastric cancer when compared with population with allele A (OR =1.67,95％ CI 1.31-2.13,P ＜ 0.05).Conclusion The genotypes GG,AG and the allele G of IL-10-1082 gcne of the Chincse population are significantly associated with the increased risk of gastric cancer.