Very long chain acyl - CoA dehydrogenase deficiency (VLCADD) is a rare recessively inherited disorder of mitochondrial fatty acid β - oxidation. VLCADD is classfied into three types according the onset age and clinical manifestation: cardiomyopathic phenotype, hepatic phenotype and myopathic phenotype. The cardiomyopathic phenotype is most severe resulting in high mortality. The biochemical hallmark of the disease is elevation of C14:1 -camitine detected by tandem mass spectrometry .Enzyme analysis, molecular genetic analysis and fatty acid oxidation flux assay are used to make further diagnostic evaluation. Treatment regimens include avoidance of fasting, restriction of long - chain fat acid and supplementation of medium - chain triglycerides.

OBJECTIVETo investigate the clinical and laboratory features of very long chain acyl-CoA dehydrogenase deficiency ( VLCADD ) and the correlations between its genotype and phenotype.

METHODEleven patients diagnosed as VLCADD of Shanghai Jiaotong University School of Medicine seen from September 2006 to May 2014 were included. There were 9 boys and 2 girls, whose age was 2 d-17 years. Analysis was performed on clinical features, routine laboratory examination, and tandem mass spectrometry (MS-MS) , gas chromatography mass spectrometry (GC-MS) and genetic analysis were conducted.

RESULTAll cases had elevated levels of blood tetradecanoylcarnitine (C14:1) recognized as the characteristic biomarker for VLCADD. The eleven patients were classified into three groups: six cases in neonatal onset group, three in infancy onset group form patients and two in late onset group. Neonatal onset patients were characterized by hypoactivity, hypoglycemia shortly after birth. Infancy onset patients presented hepatomegaly and hypoglycemia in infancy. The two adolescent patients showed initial manifestations of exercise intolerance or rhabdomyolysis. Six of the eleven patients died at the age of 2-8 months, including four neonatal onset and two infant onset patients, with one or two null mutations. The other two neonatal onset patients were diagnosed since early birth through neonatal screening and their clinical manifestation are almost normal after treatments. Among 11 patients, seventeen different mutations in the ACADVL gene were identified, with a total mutation detection rate of 95.45% (21/22 alleles), including eleven reported mutations ( p. S22X, p. G43D, p. R511Q, p. W427X, p. A213T, p. C215R, p. G222R, p. R450H, p. R456H, c. 296-297delCA, c. 1605 + 1G > T) and six novel mutations (p. S72F, p. Q100X, p. M437T, p. D466Y, c. 1315delG insAC, IVS7 + 4 A > G). The p. R450H was the most frequent mutation identified in three alleles (13.63%, 3/22 alleles), followed by p. S22X and p. D466Y mutations which were detected in two alleles (9.09%, 2/22 alleles).

CONCLUSIONThe ACADVL gene mutations were heterozygous in our patients. The mortality of neonatal onset form and infant onset form is much higher than the late onset form patients, suggesting a certain correlation between the genotype and phenotype was found. The earlier diagnosis and treatment of VLCADD are of vital importance for the improvement of the prognosis of the patients.

Acyl-CoA Dehydrogenase, Long-Chain ; deficiency ; genetics ; Adolescent ; Age of Onset ; Alleles ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; China ; Female ; Genetic Testing ; Genotype ; Heterozygote ; Humans ; Infant ; Infant, Newborn ; Lipid Metabolism, Inborn Errors ; complications ; genetics ; Male ; Mitochondrial Diseases ; complications ; genetics ; Muscular Diseases ; complications ; genetics ; Mutation ; Neonatal Screening ; Phenotype ; Prognosis ; Rhabdomyolysis ; etiology ; Spectrum Analysis ; Tandem Mass Spectrometry

Objective To analyze gene mutations of a Niemann-Pick disease type C (NPC) proband,and carry out prenatal diagnosis for the family.Methods The coding regions of NPC1 gene in the proband (late-infantile form) and white blood cell (WBC) in peripheral blood of its parents were amplified by polymerase chain reaction and direct DNA sequencing in both directions was performed.The sequencing results were compared with human NPC1 gene sequence (NM_000271) in GenBank,and sequences of mutated exons were determined.Direct sequencing was used on 50 normal Chinese individuals' DNA samples (control) to exclude mutation's single nucleotide polymorphism (SNP).An inter-species alignment of homologous NPC1 proteins was performed using ClustalX 1.81 software.During the second pregnancy of the proband's mother,the amniotic fluid was obtained at 18 weeks of gestation and the amniocytes were cultured for gene mutation analysis.Neonate's DNA of WBC in peripheral blood was also extracted for NPC1 gene analysis.Results Mutation analysis of NPC1 gene revealed two novel heterozygous mutations (c.2284-2287 delCTCT and p.V959G) in the proband,which originated from her father and mother,respectively.These two mutations were absent in the control,suggesting that these mutations were not SNP.While comparing with the amino acid in NPC1 protein of human,mouse,rat,rabbit,cat and pig,it revealed that p.V959 belonged to a conservative amino acid region and the missense mutation of p.V959G may perturb the function of NPC protein.Neither mutation was found in DNA from amniotic fluid or from the cultivated amniocytes in the second pregnancy,suggesting a normal fetus.c.2284-2287 delCTCT and p.V959G mutation were not found in NPC1 gene analysis of WBC in peripheral blood of the neonate,which was consistent with the prenatal diagnosis.Conclusions PCR-direct sequencing could be used as genetic diagnosis for NPC proband and prenatal diagnosis for its family.The mutation p.V959G may be correlated to late infantile form of NPC.

OBJECTIVETo develop a resin composite incorporated with nano-antibacterial inorganic filler containing long-chain alkyl quaternary ammonium salt, and to measure its effect on human dental plaque microcosm biofilm.

METHODSA novel nano-antibacterial inorganic filler containing long-chain alkyl quaternary ammonium salt was synthesized according to methods introduced in previous research. Samples of the novel nano-antibacterial inorganic fillers were modified by a coupling agent and then added into resin composite at 0%, 5%, 10%, 15% or 20% mass fractions; 0% composite was used as control. A flexural test was used to measure resin composite mechanical properties. Results showed that a dental plaque microcosm biofilm model with human saliva as inoculum was formed. Colony-forming unit (CFU) counts, lactic acid production, and live/dead assay of biofilm on the resin composite were calculated to test the effect of the resin composite on human dental plaque microcosm biofilm.

RESULTSThe incorporation of nano-antibacterial inorganic fillers with as much as 15% concentration into the resin composite showed no adverse effect on the mechanical properties of the resin composite (P > 0.05). Resin composite containing 5% or more nano-antibacterial inorganic fillers significantly inhibited the metabolic activity of dental plaque microcosm biofilm, suggesting its strong antibacterial potency (P < 0.05).

CONCLUSIONThis novel resin composite exhibited a strong antibacterial property upon the addition of up to 5% nano-antibacterial inorganic fillers, thereby leading to effective caries inhibition in dental application.

Anti-Bacterial Agents ; pharmacology ; Biofilms ; drug effects ; Composite Resins ; chemistry ; Dental Caries ; prevention & control ; Dental Plaque ; Humans ; Lactic Acid ; Quaternary Ammonium Compounds ; pharmacology ; Saliva

Objective: To develop the Chinese primipara social capital scale (C-PSCS), and to evaluate its validity and reliability. Methods: The items of C-PSCS were developed based on Social Capital Scale by the World Bank and Social Network Scale. This scale was modified according to the characteristics of primiparas. We selected 10 experts who specialized in related field, and two rounds of seminars about content, cultural compatibility, primiparas' characteristics, and practicability. The finally C-PSCS included four dimensions: social trust, social reciprocity, social network, and social participation. Using purposive sampling to select 1 100 primiparas in their third trimesters (gestational weeks from 30 to 36 weeks). The validity analyses included content validity, construct validity and discriminant validity. The reliability analyses included Cronbach' α coefficient, and split-half reliability. Results: 1 035 questionnaires (94.09%) were qualified and the completion time was (13.23 ± 2.53) minutes. The total score of scale was 195.38 ± 45.98, and scores for social trust, social reciprocity, social network, and social participation were 30.26 ± 4.25, 22.84 ± 4.21, 34.23 ± 7.47, and 108.05 ± 41.96, respectively. The common factor cumulative variance contribution rates of each dimension were from 52.92% to 69.37%, which achieved more than 50% of the approved standard, and all the items held factor loading >0.5 in its relevant common factor, it had good construct validity. The scale had a good content validity, the r values between each dimensions and total scale were range from 0.57 to 0.81, P<0.01. For the high-score group, scores for social trust, social reciprocity, social network, and social participation dimensions were 32.89±3.19, 25.65±3.48, 38.27±6.59, 119.94±36.61, respectively, which were higher than low-score group (27.77±3.58, 20.18±2.91, 30.40±6.13, 96.76 ± 43.60), t-values were -24.23, -27.46, -19.90, and -9.24, respectively, P<0.001. It had good discriminant validity. The Cronbach'α coefficient for the total scale and four dimensions were from 0.76 to 0.86, and whose split-half reliability were from 0.68 to 0.84. Conclusion The validity and reliability of C-PSCS were excellent, and could be used to evaluate the social capital situation on the Chinese primiparas.

The purpose of this investigation was to develop Pluronic F-127 coated N-trimethyl chitosan nanoparticles(F-S NPs)of insulin as the model drug and asses their penetration of the mucosal barriers. Single factor screening was used to optimize the formulations of nanoparticles and the nanoparticles were characterized. Their particle size, Zeta potential, encapsulation efficiencies and drug loading were assayed to be(240. 6±6. 51)nm, (10. 42±1. 60)mV, (43. 39±2. 83)% and(3. 39±0. 57)%, respectively. The impact of PF-127 on mucin binding in vitro and nanoparticles′s transport in freshly obtained mucus were also evaluated. The mucin affinity of F-S NPs was significantly reduced when compared to that of the N-trimethyl chitosan nanoparticles(S NPs), i. e. , 28% of the latter. And F-S NPs was found to have an improved mucosal penetrating capability. Mucus-secreting HT29-MTX-E12(E12)cell monolayer was selected to investigate their cellular uptake. F-S NPs exhibited higher penetration coefficient than both free insulin and S NPs in mucus-secreting epithelium cells, i. e. , 16-fold and 1. 4-fold, respectively. Data suggest that F-S NPs be potential carriers to cross mucosal barriers and enhance the cellular uptake of insulin.

Objective: To study the effects of endoscopic submucosal dissection(ESD) on long-term quality of life (QOL) and gastric function of patients with distal early gastric cancer (EGC), compared with those of surgery. Methods: Patients with EGC who received ESD or surgical resection in Peking Union Medical College Hospital over 1 year ago were selected to be followed up. QLQ-C30, SF-36, EQ-5D and dyspeptic symptom rating scale were used to evaluate QOL. Five-hour gastric emptying rate was used to evaluate distal gastric function. Electronic gastroscopy was used to observe whether the anastomotic stoma was stenotic. According to the age at resection, 1 to 1 matching was performed between the distal 1/3 gastric ESD (E_P) group and the distal subtotal gastrectomy (S_P) group, and then the QOL and gastric function between the two groups were compared. Results: Twenty-five patients were included in group E_P and group S_P respectively. According to QLQ-C30, the scores of cognitive function were 83.3 (83.3, 83.3) in group E_P and 83.3 (83.3, 100.0) in group S_P (P=0.056). The proportion of patients with symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) between the two groups were not statistically different. There was no statistical difference in the scores of EQ-5D and SF-36 between the two groups. According to dyspeptic symptom rating scale, 56.0% patients in group E_Phad burning sensation, but only 28.0% in group S_P had this symptom (P=0.054). 20.0% of patients in group S_Preported nausea, while only 4.0% in group E_P had this symptom (P=0.084). Gastric emptying results showed that the proportion of patients with abnormal 5-hour gastric emptying rate was 31.8% in group E_P, while there was no abnormal emptying in group S_P (P=0.003). Gastroscopy results showed that one patient in group E_P had pyloric stenosis, but 5-hour gastric emptying rate was normal. All anastomotic stomas in group S_p were unobstructed. Conclusion ESD and surgical resection for distal EGC show similar long-term effects on QOL of patients. But the long-term gastric emptying function may decrease after distal gastric ESD.

Objective:To explore the endoscopic features of early gastric cancer (EGC) related to non-curative endoscopic resection, and to construct an assessment model to quantify the risk of non-curative resection.Methods:From August 2006 to October 2019, 378 lesions that underwent endoscopic resection and were diagnosed pathological as EGC in the Department of Gastroenterology, Peking Union Medical College Hospital were included in this case-control study.Seventy-eight (20.6%) non-curative resection lesions were included in the observation group, and 234 lesions which selected from 300 lesions of curative resection were included in the control group according to the difference of operation year ±1 with the observation group, and the ratio of 1∶3 of the observation group to the control group. Univariate and multivariate logistic regression analysis were performed to explore the risk factors for non-curative resection. The independent risk factor with the minimum β coefficient was assigned 1 point, and the remaining factors were scored according to the ratio of their β coefficient to the minimum. A predictive model was established to analyze the 378 lesions.The non-curative resection rates of lesions of different scores were calculated. Results:Univariate analysis showed that the lesion diameter, the location, redness, ulcer or ulcer scar, fold interruption, fold entanglement, and invasion depth observed with endoscopic ultrasonography (EUS) were associated with non-curative resection of EGC lesions ( P<0.05), and contact or spontaneous bleeding may be associated with non-curative resection ( P=0.068). Multivariate logistic regression analysis showed that submucosal involvement (VS confined to the mucosa: β=0.901, P=0.011, OR=2.46, 95% CI: 1.23-4.92), lesion diameter of 3-<5 cm (VS <3 cm: β=0.723, P=0.038, OR=2.06, 95% CI: 1.04-4.09), lesion diameter of ≥5 cm (VS <3 cm: β=2.078, P=0.003, OR=7.99, 95% CI: 2.02-31.66), location in the upper 1/3 of the stomach (VS lower 1/3: β=1.540, P<0.001, OR=4.66, 95% CI: 2.30-9.45), and fold interruption ( β=2.287, P=0.008, OR=1.93, 95% CI: 0.95-3.93) were independent risk factors for non-curative resection of EGC lesions. The factor of lesion diameter of 3-<5 cm and submucosal involvement were assigned 1 point respectively, location in the upper 1/3 of the stomach was assigned 2 points, diameter of ≥5 cm and fold interruption were assigned 3 points respectively, and other factors were assigned 0 point. Then the analysis of 378 lesions showed that the probability of non-curative resection at ≥2 points was 41.9% (37/93), 4 times as much as that at 0 [11.5% (25/217)]. Conclusion:EGC lesions with diameter ≥3 cm, located in the upper 1/3 of the stomach, interrupted folds or submucosal involvement are highly related to non-curative resection. The predictive model based on these factors achieves satisfactory efficacy, but it still needs further validation in larger cohorts.