Newborn ornithine carbamyltransferase deficiency caused by new OTC gene mutations: a report of two cases and review of the literature on phenotype and genotype.

Background: Ornithine carbamyltransferase deficiency (OTCD) is the most common urea cycle disorder disease. Neonatal-type cases usually involve a serious condition, including the complete loss of ornithine carbamyltransferase (OTC) enzyme activities. Case Description: Case 1: A 3-day-old boy was hospitalized due to decreased muscle tone over three days, 10 hours of dyspnea, and two instances of convulsions. Diagnostic tests showed elevated blood ammonia levels, decreased citrulline concentration via mass spectrometry (MS/MS), and increased orotic acid observed by gas chromatography-mass spectrometry (GC/MS), while uracil was normal. Head ultrasound revealed abnormal brain parenchyma, indicating brain damage. Whole exon gene sequencing detected a new pathogenic mutation [c. 961T > C (p.Ser321Pro)] in the OTC gene, and the mother was identified as a carrier of this mutation. Case 2: A 3-day-old boy was admitted to our hospital because of "heart failure". The patient's blood ammonia was significantly increased; the MS/MS results showed that citrulline concentration decreased; the GC/MS results demonstrated that orotic acid was significantly increased; uracil was normal; and head magnetic resonance imaging (MRI) + diffusion-weighted imaging (DWI) + magnetic resonance spectroscopy (MRS) showed abnormal signals in the brain, with partial cystic malacia. Clinical exon gene sequencing showed that the 500 bp short interspersed nuclear elements (SINE) element may have been inserted into exon 5 of the OTC gene, which was inherited from his mother; this has not been reported previously in the literature. Although the blood ammonia of two patients decreased, they both died after giving up because of serious nervous system damage. In addition, a total of 62 neonatal OTCD patients were found in the literature. The clinical manifestations of these patients were not specific. The MS/MS results of 81% of neonatal OTCD patients showed that the concentration of citrulline was decreased. About 91% showed a significant increase in orotic acid, mutation sites were detected in 100% of the patients, and the prognosis was poor. Conclusions: This study improves our understanding of the clinical characteristics and OTC gene mutation sites of neonatal OTCD cases. c.961T>C and c.ins SINE? were identified as new mutations. The clinical manifestations of neonatal OTCD patients lack specificity, and the clinical and biochemical characteristics combined with gene detection are important for the diagnosis of OTCD.

Variations in length of stay among survived very preterm infants admitted to Chinese neonatal intensive care units.

BACKGROUND: This study aimed to describe length of stay (LOS) to discharge and site variations among very preterm infants (VPIs) admitted to 57 Chinese neonatal intensive care units (NICUs) and to investigate factors associated with LOS for VPIs. METHODS: This retrospective multicenter cohort study enrolled all infants < 32 weeks' gestation and admitted to 57 NICUs which had participated in the Chinese Neonatal Network, within 7 days after birth in 2019. Exclusion criteria included major congenital anomalies, NICU deaths, discharge against medical advice, transfer to non-participating hospitals, and missing discharge date. Two multivariable linear models were used to estimate the association of infant characteristics and LOS. RESULTS: A total of 6580 infants were included in our study. The overall median LOS was 46 days [interquartile range (IQR): 35-60], and the median corrected gestational age at discharge was 36 weeks (IQR: 35-38). LOS and corrected gestational age at discharge increased with decreasing gestational age. The median corrected gestational age at discharge for infants at 24 weeks, 25 weeks, 26 weeks, 27-28 weeks, and 29-31 weeks were 41 weeks, 39 weeks, 38 weeks, 37 weeks and 36 weeks, respectively. Significant site variation of LOS was identified with observed median LOS from 33 to 71 days in different hospitals. CONCLUSIONS: The study provided concurrent estimates of LOS for VPIs which survived in Chinese NICUs that could be used as references for medical staff and parents. Large variation of LOS independent of infant characteristics existed, indicating variation of care practices requiring further investigation and quality improvement.

Effects of mild-warming moxibustion on Bcl-2 and PKC expressions of peripheral blood in elderly people.

OBJECTIVE: To explore the anti-aging effects of mild-warming moxibustion on Bcl-2 and PKC expression in peripheral blood and general symptoms in elderly people. METHODS: A total of 61 elderly people and 30 non-elderly people were enrolled. The total effective rate of mild-warming moxibustion was assessed by symptom scores, and Bcl-2 and PKC expression in peripheral blood was detected by flow cytometry. RESULTS: The total effective rate in the mild-warming moxibustion group was significantly higher than in the blank control group (P < 0.01). Bcl-2 and PKC expression rates in peripheral blood in the blank control group were lower than in the normal control group (< 0.01), but higher after mild-warming moxibustion (P < 0.01). CONCLUSION: The anti-aging effects of mild-warming moxibustion may be due to increased Bcl-2 and PKC expression in peripheral blood in aged people.

Synthesis and structure-activity relationship of 7-(substituted)-aminomethyl-4-quinolone-3-carboxylic acid derivatives.

Gram-positive organisms have re-emerged as the major hospital pathogens, which make the unmet medical needs for antibacterial therapy even worse. In searching for potent agents against Gram-positive pathogens, novel 7-(substituted)-aminomethyl-quinolone-3-carboxylic acids were designed, synthesized, and evaluated for their antibacterial activities in vitro. Many 7-monoarylaminomethyl derivatives exhibited high potency against Gram-positive organisms compared to reference agents: vancomycin and pazufloxacin. Additionally, a few 7-monoalkylaminomethyl derivatives exhibited good activities against both Gram-positive and Gram-negative organisms.

Synthesis and antibacterial activity of substituted oxotriazolylphenyl oxazolidinones.

A series of 3-(4'-(2''-alkyl-3''-oxy-1'',2'',4''-triazolyl)-phenyl)-5-substituted oxazolidinones was designed and synthesized for in vitro antibacterial activity testing against fourteen Gram-negative and six Gram-positive standard organisms. The minimum inhibitory concentration (MIC) was determined by agar dilution at concentrations of 0.10, 0.20, 0.39, 0.78, 1.56, 3.13, 6.25 microg/mL. Different alkyl groups at the 2''-position played an important role in the activity against Gram-positive organisms. (S)-3-(4'-(2''-ethyl-3''-oxy-1'',2'',4''-triazolyl)-phenyl)-5-acetamidomethyloxazolidinone was active against Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus enteridis and Streptococcus nonhemolyticus, whereas 2''-methyl, 2''-propyl and 2''-n-butyl counterparts did not show activity at 6.25 microg/mL. Modification of the 5-substitutent of oxazolidinones also affected the activity against Gram-positive organisms. (S)-3-(4'-(2''-ethyl-3''-oxy-1'',2'',4''-triazolyl)-phenyl)-5-acetamidomethyloxazolidinones was approximately two fold more potent than 5-chloroacetamido, 5-dichloroacetamido and 5-trifluoroacetamido counterparts against Streptococcus enteridis. None of these compounds showed growth inhibition against fourteen Gram-negative organisms at 6.25 microg/mL.

Synthesis and in vitro evaluation of substituted phenyl-piperazinyl-phenyl oxazolidinones against Gram-positive bacteria.

With the incidence of linezolid-resistant Enterococcus faecalis, E. faecium and Staphylococcus aureus, modification of linezolid at the 5- and/or 3-positions led to the development of a series of 3-(methoxyl-phenyl)-piperazinyl-phenyl oxazolidinone analogues. These compounds were tested in vitro against six gram-positive standard organisms (S. aureus, S. epidermidis, S. pneumoniae, S. albus, Streptococcus enteridis and S. nonhemolyticus). 5-acetylaminomethyl oxazolidinones bearing fluorine at 3'-position of phenyl ring showed activities against several gram-positive bacteria (MIC: 3.13-6.25 mug/mL). The position of methoxyl group on the phenyl ring of piperazine group affected antibacterial spectrum. 3-(4'- (para-methoxyl-phenyl)-piperazinyl)-(3'-fluoro)-phenyl-5-acetylaminomethyl oxazolidinone was found active against 5 gram-positive organisms except S. nonhemolyticus, whereas 3-(4'-(ortho-methoxyl-phenyl)-piperazinyl)-(3'-fluoro)-phenyl-5-acetylaminomethyl oxazolidinone was found active only against 2 gram-positive organisms, namely S. albus, S. enteridis.

Synthesis and antibacterial activity of 7-(substituted)aminomethyl quinolones.

A series of 7-(substituted)aminomethyl quinolones was synthesized and evaluated for antibacterial activity. Derivatives with (monoalkyl)aminomethyl substituent at C-7 displayed high in vitro activities comparable to Lomefloxacin against gram-negative organisms, whereas those bearing a [(substituted)phenyl]aminomethyl side chain at C-7 demonstrated good activities against gram-positive organisms as potent as Lomefloxacin and Vancomycin.