Niacin, a broad-spectrum lipid-regulating agent, can significantly lower plasma triglyceride and raise the high density lipoprotein-cholesterol.Extended-release niacin added to statins monotherapy could further modify the lipid profile and reduce residual cardiovascular risk.This combination therapy provides a safe, effective and economical treatment for clinicians and may be superior to other drugs combined with statins.

Objective To construct human apolipoprotein O (apolipoprotein O, ApoO) expression vector and obtain recombinant fusion protein thioredoxin (Trx)-ApoO by pET prokaryotic expression system. Methods The ApoO gene fragment from the human liver cDNA library was amplified by PCR. The resulting product was cloned into pET-32a(+) vector and sequenced. The confirmed cDNA was cloned into plasmid E.coli DH10B and then transformed into E.coli BL 21 (DE3) where it was induced to express protein by isopropyl β-D-1-thiogalactopyranoside (IPTG).The fusion protein was purified by Ni-NTA resin. Results The ApoO gene was cloned by PCR and a 519 bp DNA fragment was shown on the agarose electrophoresis. The cloned gene was sequenced and demonstrated to have the same sequence as that of human ApoO gene in GenBank which justified a successful construction of recombinant plasmid. ApoO cDNA gene fragment was induced by IPTG, and a 34 kD recombinant fusion protein Trx-ApoO was tested on sodium dodecyl sulfate polyacrylamide (SDS-PAGE). Conclusion Human ApoO gene is successfully cloned and its recombinant fusion protein Trx-ApoO is expressed.

Objective To explore the effectiveness,feasibility and suitability of the guideline for nasogastric tube feeding in adult patients.Methods Based on the Ottawa Model of Research Use as framework,we screened relevant evidence from guidelines,and developed new nasogastric tube feeding nursing procedure.Nursing knowledge,the rate of compliance to new procedure and the incidence of complications of nasogastric tube feeding were used to evaluate the clinical effects of the guideline.Results Nurses' knowledge increased significantly(P＜0.05).Nurses had a high degree of implementation of the new procedure,with the rate of over 85％.Compared with the control group,the rate of complications of nasogastric tube feeing in the experimental group was lower than that in the control group.Especially,the rates of reflux and aspiration were significantly lower(P＜0.05).Both rates of tube shedding and skin damage in the intervention group were decreased significantly(P＜0.05).Conclusion The nasal feeding nursing guideline in our clinical scenarios has its effectiveness,feasibility and suitability.

Objective To evaluate the practicability of CHROMagar orientation medium combined with simple biochemical tests for identification of common oxidase-negtive gram-negative bacilli.Methods The CHROMagar orientation medium was used together with biochemical tests including indole test , ornithine decarboxylase test and lysine decarboxylase test for identification of common oxidase -negtive gram-negative bacilli.The sensitivity, specificity, likelihood ratio, Youden index and Kappa value of the diagnostic assays were evaluated .McNemar test was performed to evaluate facticity, accuracy and cost of the method in com-parison with the Vitek-2 system as reference method .Results The identification of oxidase-negtive gram-negative bacilli from 318 bacterial strains showed that the sensitivities and specificities of CHROMagar orien-tation mediumm in combination with simple biochemical tests to Serratia marcescens, Stenotrophomonas mal-tophilia and Acinetobacter baumannii reached 100%, and for Escherichia coli, Enterobacter aerogenes and Klebsiella pneumoiae were above 90%.The specificities for identification of Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii and Proteus mirabilis were all above 90%, but the sensitivities were around 75%-90%.Kappa values of the assays were above 0.85, howerer, which was only 0.5947 for Citrobacter freundii.McNemar test showed that all P values were above 0.05, and cost of the assays was reduced by 90%.Conclusion CHROMagar orientation medium in combination with simple biochemical tests is a cost-effective assay for identification of common oxidase-negtive gram-negative bacilli .

Metabolic associated fatty liver disease (MAFLD) is currently one of the most important liver diseases worldwide, and its incidence rate is increasing year by year. This article summarizes the current research status of medical treatment of MAFLD, including lifestyle changes and individualized drug treatment. Lifestyle changes include diet management, exercise intervention, biological clock adjustment, and psychological intervention, and individualized drug treatment includes insulin sensitizer, vitamin E, weight-loss and lipid-lowering drugs, liver-protecting and transaminase-lowering drugs, and traditional Chinese medicine treatment. At the same time, multidisciplinary treatment is the trend of clinical treatment of MAFLD.

OBJECTIVETo delineate the mutation spectrum of phenylalanine hydroxylase (PAH) gene among patients affected with phenylalanine hydroxylase deficiency (PAHD) in Henan Province of China, and to explore the correlation between the genotype and the phenotype.

METHODSA total of 155 affected children were recruited. Potential mutation of the PAH gene were analyzed by direct sequencing. The genotype-phenotype correlation was analyzed by matching the expected and observed phenotypes.

RESULTSOver 72 mutations and 108 genotypes have been identified. There were 7 homozygous mutations, including 1 case with EX6-96A>G/EX6-96A>G, 1 with R241C/R241C, 1 with R413P/R413P, and 4 with R243Q/R243Q. Among these, 6 patients have presented classic PKU phenotypes, except for a R241C/R241C genotype which has led to mild PKU. In 104 patients carrying compound PAH mutations, 52 were classic, 34 were mild and 39 had mild HPA. Patients who were heterozygous for EX6-96A>G/R241C, R243Q/A434D, EX6-96A>G/R413P and EX6-96A>G/ R241C were found with both the classic PKU and mild PKU phenotypes. Common mutations associated with mild HPA have included R53H, R243Q, V399V and H107R. The common mutations associated with mild PKU included R243Q, R241C, EX6-96A>G, and IVS4-1G>A. The prevalent mutations in classic PKU were R243Q, EX6-96A>G and V399V. The consistency between prediction of the biochemical genotype and observed phenotype was 77.78%, especially in classic PKU, the consistency was up to 82.14%. Significant correlations were disclosed between pretreatment levels of phenylalanine and AV sum (r=-0.6729, P < 0.01).

CONCLUSIONThe mutation spectrum of PAH gene in Henan seems to differ from that of other regions. Independent assortment of mutant alleles may result in a complex genotype-phenotype correlation, but the genotypes of PAHD patients have correlated with the phenotype.

Female ; Genotype ; Humans ; Male ; Mutation ; Phenotype ; Phenylalanine Hydroxylase ; genetics ; Phenylketonurias ; genetics

Objective: To study the prevalence, clinical and genetic characteristics of primary carnitine deficiency (PCD). Methods: From January 2013 to December 2017, 720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry. Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed. Dietary guidance and L-carnitine supplementation were provided to the parents. Growth and intelligence development were surveyed during follow-up. Results: In total 21 neonates and 6 mothers were diagnosed with PCD, which yielded an incidence of 1 in 34 317. Eighteen SLC22A5 mutations were detected, which included 4 novel mutations, namely c. 1484T>C, c. 394-1G>T, c. 431T>C and c. 265-266insGGCTCGCCACC. Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations. Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations. Common mutations included c. 1400C>G (42.3%), c. 760C>T (11.5%) and c. 51C>G (7.7%). During the 8 ~ 42 month follow-up, neonates with PCD showed no clinical symptoms but normal growth. Blood level of free carnitine was raised in all mothers after the treatment. Conclusion The incidence of neonatal PCD in Henan is 1 in 34 317, with the most common mutation being c. 1400C>G. Above finding has enriched the spectrum of SLC22A5 gene mutations.

The association between circadian rhythm and metabolic diseases has attracted more and more attention in recent years. A large number of clinical studies have shown that people who often stay up late or work in shifts have a significantly higher risk of nonalcoholic fatty liver disease than those with regular work and rest. Based on current research findings, this article reviews the mechanism of action of circadian rhythm genes in nonalcoholic fatty liver disease from the five aspects of lipid metabolism, glucose metabolism, intestinal flora, oxidative stress, and endoplasmic reticulum stress.

Objective:To explore the genetic basis for a child featuring tetrahydrobiopterin deficiency and global developmental delay.Methods:Clinical and laboratory examinations were carried out for the child. Genomic DNA of the patient was subjected to high-throughput sequencing to identify genetic variants associated with hyperphenylalaninemia. Candidate variants were verified by Sanger sequencing.Results:The result of blood tandem mass spectrometry showed that the Phenylalanine in the blood was 642.7 μmol/l, and the ratio of Phenylalanine/Tyrosine was 5.42. Analysis of urinary pterin: neopterin 0.09 mmol/mol Cr, biopterin 0.04 mmol/mol Cr, biopterin% 77%, which suggested tetrahydrobiopterin deficiency. The parents of the proband were first cousins. DNA sequencing revealed that the proband has harbored homozygous c. 353A>T variants in exon 2 of the GCH1 gene, for which his great grandmother, grandfather, mother, uncle, father and elder brother were heterozygous carriers with normal phenotype and no clinical symptoms associated with dopa responsive dystonia. Conclusion:The homozygous c. 353A>T variant of the GCH1 gene probably underlay the tetrahydrobiopterin deficiency in this pedigree of consanguineous marriage.

Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.