Objective: We present our preliminary experience of using a homemade transumbilical single-port access for performing transumbilical single port access (SPA) laparoscopic surgery for gastrointestinal disease and its perioperative nutritional management.Methods: During Nov.2009-Dec.2009,five patients received SPA surgery and nutritional management following the protocol of fast track surgery.A patient with stomach GIST received partial gastrectomy,a patient with ascending colon lymphoma received right hemicolectomy,a patient with rectal cancer received anterior resection,a patient with jejunum GIST received partial small bowel resection,and a patient with early gastric cancer received distal subtotal gastrectomy (D1+α). Results: Transumbilical SPA surgery were successfully done in five patients without conversion.The mean length of incision was 3 cm,the mean time for operation was 138 (60-240)min,and the mean blood loss was 50 (10-100)ml.All patients could mobilize and orally drink on the 1st day after operation,have soft diet the 3st days after operation,their mean postoperative hospital stay was 4 days.No complication occurred.Mean body weight loss was 2.6 kg on discharge compared with at admission.Conclusion: Transumbilical SPA surgery with the protocol of fast-track surgery had advantages including shorter incision,less trauma,faster recovery,and less body weight loss.

A series of novel 4-substituted-3-nitrobenzamide derivatives were designed and synthesized. The structures of the target compounds were confirmed with 1H NMR, 13C NMR, MS and element analysis. Anti-tumor activities against HCT-116, MDA-MB435 and HL-60 cell lines in vitro were evaluated by SRB assay. The results indicated most of the target compounds exhibited potent anti-tumor activity. Compound 4a showed the most potent inhibitory activities against three cancer cell lines with the GI50 values of 1.904-2.111 micromol x L(-1). Compounds 4g, 41-4n exhibited more potent inhibitory activities against MDA-MB435 and HL-60 cell lines with the GI50 values of 1.008-3.586 micromol x L(-1) and 1.993-3.778 micromol x L(-1), respectively. The structure-activity relationship of these compounds is discussed preliminarily.

A series of [1,3]dioxolo[4,5-f]isoindolone derivatives were designed, synthesized and evaluated as inhibitors of acetylcholinesterases (AChE). Furthermore, their effects on memory impairment of mice induced by scopolamine were investigated with step-through test. The results suggested that most of the target compounds exhibited potential inhibition on AChE with IC50 values at micromolar range. Compounds I1 (IC50 value of 0.086 μmol · L(-1)) and I2 (IC50 value of 0.080 μmol · L(-1)) showed the strongest AChE inhibitory activity, which are equipotent to donepezil (IC50 value of 0.094 μmol · L(-1)). Moreover, compounds I1-I4 could improve the memory impairment induced by scopolamine in mice.

Objective To investigate the epidemiologic characteristics and risk factors for congenital hypothyroidism (CH) in Beijing between the years 1989 and 2014.Methods Information on neonatal screening,and diagnoses and treatment of CH from 1989 to 2014 were obtained from the database of the Beijing Neonatal Screening Center.The screening parameter was thyroid-stimulating hormone (thyrotropin;TSH),which was measured by radioimmunoassay (RIA) from 1989 to 1995,enzyme-linked immunosorbent assay (ELISA) from 1996 to 2003,and time-resolved fluorescence immunoassay (DELFIA(R))from 2004 to 2014.The cutoff value of each screening method was set as the international standard for the corresponding years (20 mIU/L from 1989 to 1995 and 10 mIU/L from 1996 to 2014).CH was diagnosed using "The Technical Specification of Diagnosis and Treatment of Phenylketonuria and Congenital Hypothyroidism",published in 2010 by the Ministry of Health of the People's Republic of China.Data on live birth infants were obtained from Beijing obstetric quality reports.The incidence of CH using different screening methods was compared,and trends in annual incidence were analyzed.To exclude the influence of different screening methods,data from the years 2004 to 2014 were used to identify the risk factors for CH.Results Between 1989 and 2014,the incidence of CH in Beijing was 36.7 per 100 000 individuals,with permanent CH (PCH) and transient CH (TCH) having incidences of 16.4 per 100 000 and 15.9 per 100 000,respectively.The annual incidence of CH increased from 11.2 per 100 000 in 1989 to 51.0 per 100 000 in 2014 (x2119.02,P＜0.001),with PCH increasing from 5.6 to 16.0 per 100 000 (x2=34.38,P＜0.001) and TCH increasing from 5.6 to 13.0 per 100 000 (x2=26.93,P＜0.001).Among the PCH cases,70.44％ (255/362) were thyroid dysgenesis or ectopic glands,while the other 29.56％ (107/362) were dyshormonogenesis.Between 2004 and 2014,the incidence of CH in females (51.7/100 000) was higher than in males (37.0/100 000),and it was higher in post-term (334.5/100 000) and preterm births (77.8/100 000) than that in term births (41.4/100 000).It was also higher in the low birth weight (87.7/100 000) than the normal (42.4/100 000)and high birth weight (42.6/100 000) populations.Conclusions Between 1989 and 2014,there was a tendency towards an increase in the overall incidence of CH,and the incidence of both PCH and TCH in Beijing.Female sex,preterm birth,older gestational age,low birth weight,and preterm birth were risk factors affecting the incidence of CH in Beijing.

Objective To investigate the epidemiologic characteristics and risk factors for congenital hypothyroidism (CH) in Beijing between the years 1989 and 2014.Methods Information on neonatal screening,and diagnoses and treatment of CH from 1989 to 2014 were obtained from the database of the Beijing Neonatal Screening Center.The screening parameter was thyroid-stimulating hormone (thyrotropin;TSH),which was measured by radioimmunoassay (RIA) from 1989 to 1995,enzyme-linked immunosorbent assay (ELISA) from 1996 to 2003,and time-resolved fluorescence immunoassay (DELFIA(R))from 2004 to 2014.The cutoff value of each screening method was set as the international standard for the corresponding years (20 mIU/L from 1989 to 1995 and 10 mIU/L from 1996 to 2014).CH was diagnosed using "The Technical Specification of Diagnosis and Treatment of Phenylketonuria and Congenital Hypothyroidism",published in 2010 by the Ministry of Health of the People's Republic of China.Data on live birth infants were obtained from Beijing obstetric quality reports.The incidence of CH using different screening methods was compared,and trends in annual incidence were analyzed.To exclude the influence of different screening methods,data from the years 2004 to 2014 were used to identify the risk factors for CH.Results Between 1989 and 2014,the incidence of CH in Beijing was 36.7 per 100 000 individuals,with permanent CH (PCH) and transient CH (TCH) having incidences of 16.4 per 100 000 and 15.9 per 100 000,respectively.The annual incidence of CH increased from 11.2 per 100 000 in 1989 to 51.0 per 100 000 in 2014 (x2119.02,P＜0.001),with PCH increasing from 5.6 to 16.0 per 100 000 (x2=34.38,P＜0.001) and TCH increasing from 5.6 to 13.0 per 100 000 (x2=26.93,P＜0.001).Among the PCH cases,70.44％ (255/362) were thyroid dysgenesis or ectopic glands,while the other 29.56％ (107/362) were dyshormonogenesis.Between 2004 and 2014,the incidence of CH in females (51.7/100 000) was higher than in males (37.0/100 000),and it was higher in post-term (334.5/100 000) and preterm births (77.8/100 000) than that in term births (41.4/100 000).It was also higher in the low birth weight (87.7/100 000) than the normal (42.4/100 000)and high birth weight (42.6/100 000) populations.Conclusions Between 1989 and 2014,there was a tendency towards an increase in the overall incidence of CH,and the incidence of both PCH and TCH in Beijing.Female sex,preterm birth,older gestational age,low birth weight,and preterm birth were risk factors affecting the incidence of CH in Beijing.

Objective:To investigate the characteristics of congenital hypothyroidism (CH) in premature infants and analyze the predictors of transient congenital hypothyroidism(TCH) and permanent CH (PCH).Methods:A retrospective study was conducted on the preterm infants with CH born in Beijing from January 2008 to June 2018. They were screened, diagnosed and treated by the Beijing Neonatal Disease Screening Center. They were assigned into TCH and PCH groups according to the clinical prognosis. Univariate analysis and Logistic regression analyses were used to determine the predictors of PCH, and the receiver operating characteristic curve (ROC) was drawn to determine the best cut-off point.Results:A total of 2 216 892 newborns were screened, 15 382 were initially screened positive, the median time of screening was 4(4,10) d after birth, and the median time of postnatal reexamination was 30(22,42) d after birth, 14 576 newborns were reexamined, the reexamination rate was 94.8%. A total of 92 preterm infants were diagnosed with CH, of which 60 were TCH, accounting for 65.2%; 28 were PCH, accounting for 30.4%; and 4 were lost to follow-up, accounting for 4.3%. Univariate analysis showed that in the PCH group, the abnormal rate of thyroid B-ultrasound, levothyroxine (LT4) dose at 1-year old, thyrotropin (TSH) level at 2 years old, LT4 dose at 2 years old, LT4 dose and free thyroxine (FT4) level at 3 years old were higher than those in the TCH group. Logistic regression analysis revealed that abnormal B-ultrasound ( OR=12.184,95% CI 2.270~65.403), and elevated TSH level at 2 years old ( OR=2.033,95% CI 1.280~3.228),increased LT4 dose at 3 year old ( OR=21.435,95% CI 3.439~133.584) are the risk factors for PCH. The maximum area under ROC curve was 0.798 at 3 years old (95% CI 0.680~0.916), the best cut-off point was 1.3 μg/(kg·d) for the 3-year-old drug dose; followed by 2-year-old TSH level, which was 0.683 (95% CI 0.548~0.817), the best cut-off point was 4.51 μIU/ml. Conclusions:TCH accounted for a large proportion of preterm infants with CH. During the follow-up, the increased LT4 dose at 3 years old and the elevated TSH level at 2 years old were the early predictors of PCH.

Objective:To explore the clinical characteristics of pediatric glucose transporter type 1 deficiency syndrome (GLUT1 DS), evaluate the efficacy and safety of ketogenic diet therapy (KDT).Methods:Clinical data of 19 children with GLUT1 DS admitted to Children′s Hospital of Fudan University, Tianjin Children′s Hospital, Shenzhen Children′s Hospital, Children′s Hospital of Nanjing Medical University and Jiangxi Provincial Children′s Hospital between 2015 and 2019 were collected retrospectively. The first onset symptom, main clinical manifestations, cerebrospinal fluid features and genetic testing results of patients were summarized, the efficacy and safety of ketogenic diet treatment were analyzed. Results:Among the 19 cases, 13 were males and 6 females. The age of onset was 11.0 (1.5-45.0) months,the age of diagnosis was 54.0 (2.8-132.0) months. Epilepsy was the first onset symptom of 13 cases. Different forms of tonic-clonic seizures were the most common types of epilepsy (7 cases with generalized tonic-clonic seizures, 5 cases with focal tonic or clonic seizures, 4 cases with generalized tonic seizures). Antiepileptic drugs were effective in 4 cases. Paroxysmal motor dysfunction was present in 12 cases and ataxia was the most common one. All patients had different degrees of psychomotor retardation. Among 17 patients received cerebrospinal fluid examination, cerebrospinal fluid (CSF) glucose level was lower than 2.2 mmol/L and CSF glucose/glycemic index was<0.45 in 16 cases, only 1 case presented normal CSF glucose level (2.3 mmol/L) and normal CSF glucose/glycemic index(0.47). SLC2A1 gene mutations were found in 16 patients, missense, frameshift and nonsense mutations were the common types with 5 cases, 5 cases and 3 cases respectively. All 19 patients were treated with ketogenic diet, which was effective in 18 cases in seizure control, 11 cases in dyskinesia improvement and 18 cases in cognitive function improvement. No serious side effects were reported in any stage of KDT.Conclusions:The diagnosis of GLUT1 DS is often late. It is necessary to improve the early recognition of the disease and perform CSF glucose detection and genetic testing as early as possible. The KDT is an effective and safe treatment for GLUT1 DS, but a small number of patients have not response to diet therapy.

OBJECTIVE3-Methylcrotonyl-coenzyme A carboxylase deficiency (MCCD) is an autosomal recessive inborn error of leucine catabolism. The cases suspected as MCCD detected by neonatal screening are not rare. The aim of the study was to investigate the clinical outcomes in cases suspected as MCCD by neonatal screening. The second aim was to investigate the mutation spectrum of MCC gene in Chinese population and hotspot mutation.

METHODForty-two cases (male 33, female 9) , who had higher blood 3-hydroxy-isovalerylcarnitine (C5-OH) levels(cut-off <0.6 µmol/L) detected by neonatal screening using MS/MS, were recruited to this study during Sept.2011 to Mar.2013. The C5-OH concentrations were [0.84 (0.61-20.15) µmol/L] in 42 cases at the screening recall. Five cases were firstly diagnosed as maternal MCCD, 6 cases as benign MCCD and 31 cases were suspected as MCCD. To follow up the height, weight, mental development, blood C5-OH concentrations and urinary 3-methylcrotonyl-glycine (3-MCG) and 3-hydroxy isovalerate (3-HIVA) in order to investigate the clinical outcome. The MCCC1 and MCCC2 gene mutation were analyzed for some cases. The novel gene variants were evaluated, and the influence of novel missense variants on the protein structure and function were predicted by PolyPhen-2, SIFT, UniProt and PDB software.

RESULT(1) Forty-two cases had no symptoms, their physical and mental development were normal in the last visit at the median ages of 29 months, the oldest age of follow up was nearly 9 years. (2) Gene mutation analysis was performed for 29 cases with informed consent signed by parents.Fourteen different mutations were identified in 19 cases. The mutations in MCCC1 gene accounted for 86%, the most common mutation was c.ins1680A, (accounted for 40%). Nine kinds of novel variant were detected including 211AG>CC/p.Q74P, c.295G>A/p.G99S, c.764A>C/p.H255P, c.964G>A/p. E322K, c.1331G>A/p.R444H, c.1124delT, c.39_58del20, c.1518delG, c.639+2T>A.Other 3 kinds of mutation in MCCC1 gene and 2 kinds of mutation in MCCC2 gene have been reported previously; the amino acid of mutant positions of five kinds of novel missense variant are almost highly conserved. These missense variants were predicted to cause change of human MCC protein side chain structure by changing hydrogen bonding, size of amino acid residue and electric charge, and predicted to damage the protein function possibly according to PolyPhen-2 and PDB analysis. So these novel variants may be disease-causing mutations. No mutation were detected in 10 cases. (3) Blood concentrations of C5-OH when screening, recall and end of follow-up in maternal MCCD was 3.50 (1.63-11.43), 1.84 (1.00-9.30), 0.27 (0.26-5.81) µmol/L. There was a significant downward trend.In contrast, benign MCCD group was 8.20 (3.60-9.60), 9.67 (3.88-20.15), 23.0 (5.87-49.10) µmol/L.It showed a rising trend. Children's urinary 3-MCG of benign MCCD group was found abnormally elevated in 4 cases (100%) when they were recalled.

CONCLUSIONA certain number of cases with MCCD or suspected as MCCD in this study had no symptoms and normal physical and mental development after follow-up to oldest age of nearly 9 years. The mutation in MCCC1 gene is common, nine novel mutations were found, c.ins1680A may be a hotspot mutation in Chinese population. The urinary GC/MS analysis and blood MS/MS analysis for mother should be routinely performed for all cases with high blood C5-OH level detected by neonatal screening.

Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Carbon-Carbon Ligases ; blood ; deficiency ; genetics ; Carnitine ; analogs & derivatives ; blood ; Child ; Child, Preschool ; DNA Mutational Analysis ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; Neonatal Screening ; Tandem Mass Spectrometry ; Urea Cycle Disorders, Inborn ; blood ; diagnosis ; enzymology ; genetics