Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

OBJECTIVE: To explore the clinical manifestations and genetic characteristics of a child with Leukoencephalopathy with ataxia (LKPAT) caused by a CLCN2 gene variant. METHODS: A retrospective analysis was conducted on the clinical data of a child admitted to Hunan Children's Hospital in June 2024 due to "intermittent convulsions for 13 days". Peripheral blood samples were collected from the child and his parents for whole exome sequencing, followed by Sanger sequencing validation and pathogenicity analysis of candidate variants. Literature searches were performed using the keywords "CLCN2 gene" "chloride channel-2" "leukoencephalopathy with ataxia/LKPAT" "leukoencephalopathy" in both Chinese and English on CNKI, Wanfang, and PubMed databases. The search time was set from the establishment of the databases to July 31, 2024. Childhood-onset LKPAT literature was screened and analyzed. This study was approved by the Medical Ethics Committee of Hunan Children's Hospital (Ethics No. HCHLL-2024-351). RESULTS: The child was a 7-month-and-26-day-old male infant born to consanguineous parents, presenting with epileptic seizures and borderline development. Cranial MRI revealed symmetrical long T₂ signal shadows in the posterior limb of the internal capsule, cerebral peduncle, pons, and middle peduncle of the cerebellum. Video electroencephalogram (EEG) showed an abnormal childhood EEG with one focal seizure. Whole exome sequencing revealed a homozygous c.2201dup (p.Glu735Ter) variant in the CLCN2 gene of the child. Sanger sequencing confirmed that the variant was inherited from both parents. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), this variant was classified as pathogenic (PVS1+PM3_Supporting+PM2_Supporting). A total of 8 relevant literature were retrieved, together with the present case, 16 childhood-onset LKPAT patients were cumulatively reported, which consisted of 9 males and 7 females. Twelve CLCN2 gene variants were involved, including 2 nonsense variants, 3 missense variants, 7 frameshifting variants, 2 c.61dup variants, and 5 c.1709G>A variants. The initial symptoms of the 16 patients included headache, ataxia, epileptic seizures, spasticity, developmental delay, lower back pain, hearing impairment, and intention tremor. Three patients had onset of the disease before the age of one, of which 2 had epileptic seizures as the initial symptom. CONCLUSION The homozygous variant CLCN2: c.2201dup (p.Glu735Ter) is considered the pathogenic cause of LKPAT in this child, marking the first childhood-onset case reported in China. Genetic testing has facilitated the diagnosis of childhood-onset LKPAT and expanded the spectrum of CLCN2 gene mutations.
Humans ; Chloride Channels/genetics* ; Male ; CLC-2 Chloride Channels ; Leukoencephalopathies/genetics* ; Infant ; Ataxia/genetics* ; Homozygote ; Mutation ; Retrospective Studies ; Exome Sequencing ; Genetic Testing ; Female

AIM To study the chemical constituents of dichloromethane fraction from Hypericum perforatum L.METHODS The dichloromethane fraction from H.perforatum was isolated and purified by silica gel,ODS,Sephadex LH-20,semi-preparative HPLC and etc.The structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eleven compounds were isolated and identified as hypernorpoleketone A(1),α-onocerin(2),(3R)-thunberginol C(3),2-geranyloxy-1-(2-methylpropanoyl)-phloroglucinol(4),4,6-dihydroxy-2-O-(3″,7″-dimethyl-2″,6″-octadienyl)-1-(2′-methylbutanoyl)benzene(5),norhyperpalum G(6),garsubellin A(7),garsubellin B(8),(2″R/S)-kellerine C(9),kobusone(10),eriodictyol(11).CONCLUSION Compound 1 is a new compound.Compounds 2-3 are isolated from the plants of family Guttiferae for the first time.Compounds 4-10 are isolated from this plant for the first time.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To investigate the clinical characteristics,coexisting gene mutations and prognosis of acute myeloid leukemia(AML)patients with GATA2 gene mutation.Methods:The clinical data of 370 newly diagnosed AML patients treated in our hospital from January 2008 to January 2021 was analyzed retrospectively,the next-generation sequencing technology was used to detect the mutated genes in those patients.The clinical characteristics of AML patients with GATA2 mutations,the co-mutated genes of GATA2 mutations,and the effect of GATA2 mutation on prognosis were analyzed.Results:A total of 23 patients(6.2％)with GATA2 mutation was detected in 370 AML patients.Compared with GATA2 non-mutation group,patients in GATA2 mutation group were mostly normal karyotypes(P=0.037)and in low-risk cytogenetic stratification(P=0.028).The incidence of CEBPAdm and NRAS in GATA2 mutation group was significantly higher than that in GATA2 non-mutation group(P=0.010,P=0.009).There were no statistically significant differences between the two groups in terms of sex,age,white blood cell count(WBC),platelet count,hemoglobin,bone marrow(BM)blast,induction chemotherapy regimen and CR rate(P＞0.05).Among the 23 patients with GATA2 mutation,the most common co-mutated genes were CEBPAdm,NRAS(both 39.1％),NPM1,FLT3,TET2,WT1(all 17.4％),ASXL1 and IDH1(both 13.0％).Survival analysis showed that there was no statistical difference in 5-year overall survival(OS)and leukemia-free survival(LFS)rates between patients with and without GATA2 mutations in whole cohort(n=370)(P=0.306,P=0.308).Among 306 patients without CEBPAdm,the 5-year OS and LFS rates in GATA2 mutation group showed an increasing trend compared with GATA2 non-mutation group,but the difference was not statistically significant(P=0.092,P=0.056).Among 64 patients with CEBPAdm,there was no statistically significant difference in 5-year OS rate between the GATA2 mutation group and the GATA2 non-mutation group(P=0.104),but the 5-year LFS rate of the GATA2 mutation group was significantly decreased(P=0.047).Among the 23 patients with GATA2 mutation,16 cases received the"3+7"induction regimen,of which 12 cases received allogeneic hematopoietic stem cell transplantation(allo-HSCT);7 cases received the"DCAG"induction regimen,of which 3 cases received allo-HSCT.The CR rate was not statistically different between the"3+7"regimen group and the"DCAG"regimen group(P=1.000).The 5-year OS rate and LFS rate in the transplantation group were significantly higher than the chemotherapy group(P=0.021,P=0.020).Conclusion:GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification,and it is significantly associated with CEBPAdm and NRAS co-mutations.The prognostic significance of GATA2 is influenced by CEBPAdm.The choice of"3+7"or"DCAG"induction regimen in patients with GATA2 mutation does not affect their CR rate,while the choice of allo-HSCT can significantly improved the prognosis compared with chemotherapy only.

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q₁) of blood selenium, the ORs (95%CI) of Q₃ and Q₄ blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (P_nonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.
Aged, 80 and over ; Female ; Humans ; Selenium ; Cohort Studies ; Cross-Sectional Studies ; Metals/analysis* ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*

Prostaglandin E
Angiotensin II ; Animals ; Humans ; Hypertension/chemically induced* ; Mice ; Mice, Inbred C57BL ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle

OBJECTIVE: To report on the clinical, metabolic and genetic characteristics of a child with carnitine palmitoyl transferase 1A (CPT1A) deficiency. METHODS: Clinical data and the level of acylcarnitine for a child who initially presented as epilepsy were analyzed. Genomic DNA was extracted from peripheral blood samples of the child and her parents and subjected to next-generation sequencing (NGS). RESULTS: Mass spectrometry of blood acylcarnitine indicated increased carnitine 0 (C0) and significantly increased C0/ (C16+C18). DNA sequencing revealed that the child has carried compound heterozygous variants of the CPT1A gene, namely c.1846G>A and c.2201T>C, which were respectively inherited from her mother and father. CONCLUSION CPT1A presenting initially as epilepsy was unreported previously. Analysis of blood acylcarnitine C0 and C0/ (C16 + C18) ratio and NGS are necessary for the identification and diagnosis of CPT1A deficiency. The c.1846G>A and c.2201T>C variants of the CPT1A gene probably underlay the disease in this child. Above finding has also enriched the spectrum of CPT1A gene variants.
Carnitine/blood* ; Carnitine O-Palmitoyltransferase/genetics* ; Child ; DNA Mutational Analysis ; Female ; Humans ; Hypoglycemia/genetics* ; Lipid Metabolism, Inborn Errors/genetics*

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

Objective:To explore the relationship between the expression level of micro RNA-133a(miR-133a) and the indexes of heart failure in patients with ischemic heart failure and its clinical application value.Methods:From January 2018 to September 2019, the clinical data of 80 patients diagnosed as ischemic heart failure in Shenyang Fourth People′s Hospital were analyzed prospectively.According to the classification of New York Heart Association(NYHA), 20 cases were divided into NYHA class Ⅰ group, class Ⅱ group, class Ⅲ group and class Ⅳ group, and 20 healthy people in the same period were selected as the healthy control group.The concentration of brain natriuretic peptide (BNP) in peripheral blood was detected by automatic immune analyzer, the indexes of cardiac function were detected by echocardiography, the expression of miR-133a in serum was detected by qRT-PCR, the difference of expression concentration of miR-133a in different functional grades was compared, and the correlation between the concentration of miR-133a and BNP and the indexes of echocardiography was analyzed.Results:The expression of miR-133a in healthy control group(0.167±0.024), NYHA Ⅰ group(0.289±0.012), NYHA Ⅱ group (0.415±0.034), NYHA Ⅲ group(0.981±0.217) and NYHA Ⅳ group(1.238±0.249) was statistically significant( F=106.4, P<0.001). Pearson correlation analysis showed that miR-133a was positively correlated with BNP in NYHAⅡ, Ⅲ and Ⅳ grade( r=0.815, 95% CI: 0.582-0.924, P<0.001; r=0.465, 95% CI: 0.029-0.753, P<0.05; r=0.749, 95% CI: 0.459-0.895, P<0.001). MiR-133 was negatively correlated with EF( r=-0.811, 95% CI: -0.875--0.719, P<0.001), positively correlated with LVPW, LV and EDV( r=0.331, 95% CI: 0.120-0.513, P<0.01; r=0.845, 95% CI: 0.764-0.896, P<0.001; r=0.705, 95% CI: 0.572-0.803, P<0.001). Conclusion:The expression of miR-133a in patients with ischemic heart failure is increased, which is related to the index of cardiac dysfunction, and has certain diagnostic and prognostic value.