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]

ObjectiveSepsis associated acute kidney injury （SA-AKI） is a critical clinical disease. The purpose of this study was to investigate the role and molecular mechanism of miR-4321 in the HK2 cellular damage induced by lipopolysaccharides （LPS）. MethodsRT-qPCR was conducted to detect the expression of miR-3165， miR-4270 and miR-4321 in LPS-induced HK2 cell model and cecal ligation and puncture （CLP）-induced renal injury model. In LPS-induced HK2 cell model， miR-4321-inhibitor was used to inhibit the miR-4321 expression. The effects of miR-4321 on cell proliferation， cell viability， cytokines and apoptosis-related protein levels were evaluated by CCK-8 analysis， EdU staining analysis and western blotting analysis， respectively. In CLP-induced renal injury model， miR-4321-Antago was used to intervene the miR-4321 expression. The changes of renal tissue structure were examined by H&E staining. The levels of serum creatinine and blood urea nitrogen （BUN） were measured by colorimetric method. ELISA was employed to assess the expression of interleukin-6 （IL-6）， interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in serum. IHC staining and western blotting were performed to determine the mTOR level and apoptosis-related protein expression in kidney tissues. Target genes of miR-4321 were predicted by Targetscan software and verified by dual-luciferase reporter assay. ResultsCompared with the control group， the miR-4321 expression was increased in LPS-induced HK2 cell model （n=3， t=7.154， P=0.001 3）. miR-4321 inhibitor promoted the proliferation and viability of HK2 cells， decreased the expression of LPS-induced IL-6， IL-1β and TNF-α and apoptosis-related proteins. In vivo experiments showed that miR-4321-Antago inhibited serum creatinine and BUN levels in CLP mice， improved renal injury， reduced levels of IL-1β， IL-6 and TNF-α， promoted the mTOR expression in renal tissues and inhibited the apoptosis-related protein expression. mTOR signaling pathway was believed the target gene of miR-4321. ConclusionInhibition of miR-4321 significantly alleviates SA-AKI， which may be achieved by increasing the expression of mTOR.

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Prospective Studies ; China ; Ischemia ; Aortic Aneurysm, Abdominal/surgery*

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective:To investigate the mechanism by which Fusobacterium nucleatum ( Fn) infection promotes TNF-α-induced inflammatory changes in colorectal cancer HCT116 cells. Methods:Fn-infected cells and TNF-α inflammation induction models were established and divided into 4 groups, namely uninfected control group, Fn-infected group, TNF-α induction group, and Fn+ TNF-α group. First, Fn was used to infect normal colonic epithelial cells hcoEPIC, colorectal cancer HCT116 and LoVo cells, the cell adhesion was detected 4 h later. Subsequently, HCT116 cells were induced with TNF-α for 3 h and then infected with Fn. After 24 h, the cell survival rate and cell damage were detected by CCK8 experiment and lactate dehydrogenase (LDH) viability assay. The ELISA method was further used to detect the expression of nuclear transcription factor NF-κB and cytokines IL-6, IL-8, and IL-1β in the cell and cell culture supernatant. Results:Fn has strong adhesion to colorectal cancer cells HCT116 and LoVo ( P<0.05), but basically does not show invasion. On the contrary, it has a higher invasion rate to normal colonic epithelial cells hcoEPIC after 24 h. Compared with the uninfected Fn group, the cell survival rate of the Fn-infected group was significantly reduced and the cell damage increased ( P<0.001). Three hours after TNF-α induction, Fn infection further promoted cell death and damage ( P<0.001). The expression of NF-κB in the Fn infection and TNF-α alone treatment group was significantly higher than that of the uninfected group ( P<0.001, P<0.05), and the NF-κB expression in the Fn+ TNF-α group was significantly higher than that of the control group and the single treatment group ( P<0.001). In the Fn infection and TNF-α treatment groups, the expressions of IL-6 and IL-8 were significantly higher than those in the uninfected group ( P<0.001), and IL-1β did not change significantly ( P>0.05). The expressions of IL-6, IL-8 and IL-1β in the Fn+ TNF-α group were significantly higher than those in the normal control group and the single treatment group ( P<0.05). Conclusions:Fusobacterium nucleatum can preferentially adhere to colorectal cancer cell HCT116, further promote TNF-α-induced cell damage and death, the expression and release of NF-κB and its downstream pro-inflammatory cytokines IL-6, IL-8, IL-1β.

Objective: Motion-corrected averaging with a single-shot technique was introduced for faster acquisition of late-gadoliniumenhancement (LGE) cardiovascular magnetic resonance (CMR) imaging while free-breathing. We aimed to evaluate the image quality (IQ) of free-breathing motion-corrected single-shot LGE (moco-ss-LGE) in patients with hypertrophic cardiomyopathy (HCM). Materials and Methods: Between April and December 2019, 30 patients (23 men; median age, 48.5; interquartile range [IQR], 36.5–61.3) with HCM were prospectively enrolled. Breath-held single-shot LGE (bh-ss-LGE) and free-breathing mocoss-LGE images were acquired in random order on a 3T MR system. Semi-quantitative IQ scores, contrast-to-noise ratios (CNRs), and quantitative size of myocardial scar were assessed on pairs of bh-ss-LGE and moco-ss-LGE. The mean ± standard deviation of the parameters was obtained. The results were compared using the Wilcoxon signed-rank test. Results: The moco-ss-LGE images had better IQ scores than the bh-ss-LGE images (4.55 ± 0.55 vs. 3.68 ± 0.45, p < 0.001). The CNR of the scar to the remote myocardium (34.46 ± 11.85 vs. 26.13 ± 10.04, p < 0.001), scar to left ventricle (LV) cavity (13.09 ± 7.95 vs. 9.84 ± 6.65, p = 0.030), and LV cavity to remote myocardium (33.12 ± 15.53 vs. 22.69 ± 11.27, p < 0.001) were consistently greater for moco-ss-LGE images than for bh-ss-LGE images. Measurements of scar size did not differ significantly between LGE pairs using the following three different quantification methods: 1) full width at half-maximum method; 23.84 ± 12.88% vs. 24.05 ± 12.81% (p = 0.820), 2) 6-standard deviation method, 15.14 ± 10.78% vs. 15.99 ± 10.99% (p = 0.186), and 3) 3-standard deviation method; 36.51 ± 17.60% vs. 37.50 ± 17.90% (p = 0.785). Conclusion Motion-corrected averaging may allow for superior IQ and CNRs with free-breathing in single-shot LGE imaging, with a herald of free-breathing moco-ss-LGE as the scar imaging technique of choice for clinical practice.

Objective: Motion-corrected averaging with a single-shot technique was introduced for faster acquisition of late-gadoliniumenhancement (LGE) cardiovascular magnetic resonance (CMR) imaging while free-breathing. We aimed to evaluate the image quality (IQ) of free-breathing motion-corrected single-shot LGE (moco-ss-LGE) in patients with hypertrophic cardiomyopathy (HCM). Materials and Methods: Between April and December 2019, 30 patients (23 men; median age, 48.5; interquartile range [IQR], 36.5–61.3) with HCM were prospectively enrolled. Breath-held single-shot LGE (bh-ss-LGE) and free-breathing mocoss-LGE images were acquired in random order on a 3T MR system. Semi-quantitative IQ scores, contrast-to-noise ratios (CNRs), and quantitative size of myocardial scar were assessed on pairs of bh-ss-LGE and moco-ss-LGE. The mean ± standard deviation of the parameters was obtained. The results were compared using the Wilcoxon signed-rank test. Results: The moco-ss-LGE images had better IQ scores than the bh-ss-LGE images (4.55 ± 0.55 vs. 3.68 ± 0.45, p < 0.001). The CNR of the scar to the remote myocardium (34.46 ± 11.85 vs. 26.13 ± 10.04, p < 0.001), scar to left ventricle (LV) cavity (13.09 ± 7.95 vs. 9.84 ± 6.65, p = 0.030), and LV cavity to remote myocardium (33.12 ± 15.53 vs. 22.69 ± 11.27, p < 0.001) were consistently greater for moco-ss-LGE images than for bh-ss-LGE images. Measurements of scar size did not differ significantly between LGE pairs using the following three different quantification methods: 1) full width at half-maximum method; 23.84 ± 12.88% vs. 24.05 ± 12.81% (p = 0.820), 2) 6-standard deviation method, 15.14 ± 10.78% vs. 15.99 ± 10.99% (p = 0.186), and 3) 3-standard deviation method; 36.51 ± 17.60% vs. 37.50 ± 17.90% (p = 0.785). Conclusion Motion-corrected averaging may allow for superior IQ and CNRs with free-breathing in single-shot LGE imaging, with a herald of free-breathing moco-ss-LGE as the scar imaging technique of choice for clinical practice.

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.
China ; Female ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; Pregnancy ; Respiratory Distress Syndrome, Newborn ; Retrospective Studies

OBJECTIVETo express and purify the mouse endothelial cell-targeted recombinant Notch ligand protein mD1R, and to investigate its effect on hematopoiesis after carbon tetrachloride damage.

METHODSPCR was performed to clone and construct the expression vector pET22b(+)-mD1R. The mD1R successfully transformed into E. coli was induced by IPTG, and purified with Ni-beads affinity chromatography. The target protein was detected by SDS-PAGE. The fluorescence-activated cell sorting analysis (FACS), cell adhesion test, immunofluorescence staining and quantitative real-time PCR were employed to detect the endothelial cell-targeted and Notch signaling-activated biological characteristics of mD1R. The carbon tetrachloride mouse model was established to observe the effects of mD1R on the hematopoietic stem cell (HSC), myeloid cells and lymphoid cells by flow cytometry. The LinScal-1c-Kit cells were sorted by magnetic bead, FACS was performed to analyze the cell cycle, and RT-PCR was employed to observe the expression of interleukin (IL)-10.

RESULTSThe prokaryotic expression vector was successfully cloned and constructed. The purity and the activity were confirmed in mD1R recombinant protein. The purified mD1R activated the Notch signaling pathway of hematopoietic stem cells in carbon tetrachloride damaged mouse, and internally elevated the number of HSC and long-term HSC to 2.96-fold and 6.18-fold. In addition, mD1R improved the amplification of the myeloid progenitor cells and the myeloid-derived suppressor cells, particularly the granulocyte/monocyte into blood. Mechanistically, the further analyses suggested that Notch pathway could increase the proliferation of HSC and enhance expression of IL-10 after stress injury.

CONCLUSIONSA new and activated recombinant Notch ligand protein has been obtained successfully to communicate hematopoietic stem cells and hematopoietic microenvironment. The Notch- mediated intrinsic hematopoiesis has been regulated by the anti-inflammatory factor after stress injury.