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 study the early predictors of refractory septic shock (RSS) in neonates.Methods:From July 2020 to December 2021, clinical data of neonates with septic shock admitted to the Neonatal Department of our hospital were retrospectively reviewed. According to the maximum septic shock score (SSS) during clinical course, the neonates were assigned into RSS group and non-RSS group. Perinatal data, laboratory results and hemodynamic parameters at diagnosis were compared between the two groups. Multiple logistic regression analysis was used to identify independent risk factors of RSS and septic shock-related death. Receiver operating characteristic (ROC) curve was constructed to evaluate the early predictors of poor prognosis.Results:A total of 130 neonates were enrolled, including 54 in RSS group and 76 in non-RSS group. Compared with the non-RSS group, the RSS group had significantly lower pH, base excess (BE), stroke volume index (SVI), cardiac output (CO) and cardiac index (CI).Meanwhile, the RSS group had significantly higher mean arterial pressure (MAP) to CI ratio (MAP/CI) and SSS [including bedside SSS (bSSS), computed SSS (cSSS) and modified version of cSSS (mcSSS)] (all P<0.05). Multiple logistic regression analysis showed that increased MAP/CI was an independent predictor of RSS. The cut-off value of MAP/CI was 11.6 [sensitivity 62%, specificity 87%, positive predictive value (PPV) 79% and negative predictive value (NPV) 77%], with an area under the curve (AUC) of 0.734. Increased mcSSS was an independent predictor of septic shock-related death. The cut-off value of mcSSS was 5.8 (sensitivity 83%, specificity 72%, PPV 21% and NPV 97%), with an AUC of 0.845. Conclusions:Increased MAP/CI (≥11.6) and mcSSS (≥5.8) may be early predictors of RSS and septic shock-related death in neonates.

Objective To investigate the effect of amygdalin on the permeability increase of microvascular endothelial cells(PMVEC)induced by influenza A virus FM1 and its mechanism.Methods The PMVEC cells were randomly divided into control group,model group(100 TCID50 FM1),amygdalin low-dose group(100 TCID50 FM1+4.0 mg·mL-1 amygdalin),amygdalin medium-dose group(100 TCID50 FM1+8.0 mg·mL-1 amygdalin),amygdalin high-dose group(100 TCID50 FM1+16.0 mg·mL-1 amygdalin)and 740Y-P group(100 TCID50 FM1+16.0 mg·mL-1 amygdalin+50 μmol·L-1 PI3K activator 740Y-P).Methyl thiazolyl tetrazolium(MTT)method,Transwell method,enzyme linked immunosorbent assay(ELISA)method and Western blot method were used to detect cell proliferation,cell permeability,inflammatory factor expression level and protein expression level in each group,respectively.Results Interleukin-6(IL-6)levels in control,model,amygdalin-L,amygdalin-M,amygdalin-H groups were(50.12±3.16),(93.12±5.61),(80.33±6.24),(70.05±5.46)and(61.03±4.68)pg·mL-1,respectively;the levels of tumor necrosis factor-α(TNF-α)in each group were(101.31±9.24),(167.05±10.31),(142.02±10.13),(125.34±9.87)and(112.44±8.05)pg·mL-1,respectively.The cell transepithelial resistance(TER)of control,model,amygdalin-L,amygdalin-M,amygdalin-H and 740Y-P groups were(53.01±4.17),(24.98±2.66),(30.01±3.49),(36.84±3.25),(46.23±4.31),(30.21±3.16)Ω × cm2;phosphorylated phosphatidylinositol-3 hydroxy kinase(p-PI3K)protein levels in each group were 0.34±0.04,1.01±0.09,0.80±0.08,0.61±0.07,0.43±0.05,0.87±0.09,respectively;phosphorylated mammalian target of repamycin(p-mTOR)levels in each group were 0.27±0.03,0.82±0.10,0.60±0.06,0.42±0.03,0.31±0.02 and 1.01±0.12,respectively.Compared model group with control group;compared amygdalinp-L,-M,-H groups with model group;compared amygdalinp-H group with 740Y-P group,the differences of the above indicators were all statistically significant(all P＜0.05).Conclusion Amygdalin may decrease the permeability of PMVEC cells induced by influenza virus FM1 by inhibiting PI3K/AKT/mTOR pathway.

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

OBJECTIVE: To establish an efficient protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into functional midbrain dopaminergic progenitor cells (DAPs) in vitro. METHODS: hiPSCs were induced to differentiate into DAPs in two developmental stages. In the first stage (the first 13 days), hiPSCs were induced into intermediate cells morphologically similar to primitive neuroepithelial cells (NECs) in neural induction medium containing a combination of small molecule compounds. In the second stage, the intermediate cells were further induced in neural differentiation medium until day 28 to obtain DAPs. After CM-DiI staining, the induced DAPs were stereotactically transplanted into the right medial forebrain bundle (MFB) of rat models of Parkinson's disease (PD). Eight weeks after transplantation, the motor behaviors of PD rats was evaluated. Immunofluorescence assay of brain sections of the rats was performed at 2 weeks after transplantation to observe the survival, migration and differentiation of the transplanted cells in the host brain microenvironment. RESULTS: hiPSCs passaged stably on Matrigel showed a normal diploid karyotype, expressed the pluripotency markers OCT4, SOX2, and Nanog, and were positive for alkaline phosphatase. The primitive neuroepithelial cells obtained on day 13 formed dense cell colonies in the form of neural rosettes and expressed the neuroepithelial markers (SOX2, Nestin, and PAX6, 91.3%-92.8%). The DAPs on day 28 highly expressed the specific markers (TH, FOXA2, LMX1A and NURR1, 93.3-96.7%). In rat models of PD, the hiPSCs-DAPs survived and differentiated into TH⁺, FOXA2⁺ and Tuj1⁺ neurons at 2 weeks after transplantation. Eight weeks after transplantation, the motor function of PD rats was significantly improved as shown by water maze test (P < 0.0001) and apomorphine-induced rotation test (P < 0.0001) compared with rats receiving vehicle injection. CONCLUSION HiPSCs can be effectively induced to differentiate into DAPs capable of differentiating into functional neurons both in vivo and in vitro. In rat models of PD, the transplanted hiPSCs-DAPs can survive for more than 8 weeks in the MFB and differentiate into multiple functional neurocytes to ameliorate neurological deficits of the rats, suggesting the potential value of hiPSCs-DAPs transplantation for treatment of neurological diseases.
Humans ; Rats ; Animals ; Induced Pluripotent Stem Cells ; Cell Differentiation/physiology* ; Neurons ; Parkinson Disease ; Mesencephalon ; Cells, Cultured

Objective:To study the predictive value of vasoactive-inotropic score (VIS), fluid overload (FO) and lactate level for the outcome of preterm infants with refractory septic shock.Methods:Preterm infants diagnosed with refractory septic shock and required hydrocortisone treatment in our Department from January 2016 to December 2021 were analyzed retrospectively. Preterm infants were assigned into three gestational age groups (<28 weeks, 28-31 weeks, 32-36 weeks). According to the outcome of the disease, the children were further divided into good prognosis group and poor prognosis group. The relationship between the maximum VIS, FO and the mean lactic acid before hydrocortisone and the outcome of refractory septic shock was analyzed by receiver operating characteristic (ROC) curve, the cut-off point of ROC curve was calculated to obtain the predictive efficacy of the three indicators for the outcome of refractory septic shock in preterm infants.Results:A total of 50 preterm infants with refractory septic shock and received hydrocortisone treatment were enrolled, including 20 in the good prognosis group and 30 in the poor prognosis group. There were no significant differences in the maximum VIS, FO and mean lactic acid before hydrocortisone treatment between the two groups of gestational age of <32 weeks ( P> 0.05). The maximum VIS, FO and mean lactic acid of gestational age of 32-36 weeks in the poor prognosis group were higher than those in the good prognosis group, VIS: 56.1±15.7 vs. 37.1±12.9, FO (%): 108.2 (78.6,137.7) vs. 55.5 (10.3, 100.7), and mean lactic acid (mmol/L): 8.3 (4.6, 12.0) vs. 4.8 (-0.8, 10.5), all P<0.05. The area under the ROC curve of the mean lactic acid was the largest, the cut-off value was 4.1 mmol/L, and the Youden index was 1.732. Conclusions:VIS, FO and lactate level are difficult to be used for determining the outcome of refractory septic shock in preterm infants of <32 weeks. While the mean lactic acid has the best predictive performance in preterm infants of 32-36 weeks.

OBJECTIVE: To investigate the causes of ineffectiveness of platelet transfusion with monoclonal antibody solid phase platelet antibody test (MASPAT) matching in patients with allogeneic hematopoietic stem cell transplantation and explore the strategies of platelet transfusion. METHODS: A case of donor-specific HLA antibodies (DSA) induced by transfusion which ultimately resulted in transplantation failure and ineffective platelet transfusion with MASPAT matching was selected, and the causes of ineffective platelet transfusion and platelet transfusion strategy were retrospectively analyzed. RESULTS: The 32-year-old female patient was diagnosed as acute myeloid leukemia (high risk) in another hospital with the main symptoms of fever and leukopenia, who should be admitted for hematopoietic stem cell transplantation after remission by chemotherapy. In the course of chemotherapy, DSA was generated due to platelet transfusion, and had HLA gene loci incompatible with the donor of the first transplant, leading to the failure of the first transplant. The patient received platelet transfusion for several times before and after transplantation, and the results showed that the effective rate of MASPAT matched platelet transfusion was only 35.3%. Further analysis showed that the reason for the ineffective platelet transfusion was due to the missed detection of antibodies by MASPAT method. During the second hematopoietic stem cell transplantation, the DSA-negative donor was selected, and the matching platelets but ineffective transfusion during the primary transplantation were avoided. Finally, the patient was successfully transplanted and discharged from hospital. CONCLUSIONS DSA can cause graft failure or render the graft ineffective. For the platelet transfusion of patients with DSA, the platelet transfusion strategy with matching type only using MASPAT method will miss the detection of antibodies, resulting in invalid platelet transfusion.
Female ; Humans ; Adult ; Platelet Transfusion ; Antibodies, Monoclonal ; Retrospective Studies ; HLA Antigens ; Hematopoietic Stem Cell Transplantation

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*

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.
Adult ; Female ; Humans ; Male ; Alcohol Drinking ; Diseases in Twins/genetics* ; Hypertension/genetics* ; Twins, Dizygotic/genetics* ; Twins, Monozygotic/genetics*