Objective:To preliminarily explore the association of pregnancy factors with cow's milk protein allergy in infants.Methods:This study was based on data from a subcohort of a study called ge-netic susceptibility to cow's milk allergy in Chinese children,including infants born in Peking University People's Hospital between March 1,2020,and December 31,2020.The infants were divided into a cow's milk protein allergy(CMPA)group and a control group according to whether they had developed cow's milk protein allergy at the age of 1 year.We retrospectively collected the clinical data of infants and their mothers before and during pregnancy,and analyzed the association of multiple factors during pregnancy with cow's milk protein allergy in infants.Results:A total of 278 infants were enrolled in this study,including 52 infants with CMPA and 226 infants without CMPA.Among them,there were 143 boys and 135 girls.The proportion of male infants in the CMPA group(69.2％)was higher than that in the control group(47.3％),and the difference was statistically significant(P=0.004).There were no significant differences in the distribution of birth weight,gestational age at birth,low-birth-weight in-fants,premature,umbilical cord entangle neck,and neonatal asphyxia between the CMPA group and the control group(P＞0.05).The proportion of mothers complicated with autoimmune diseases,anemia or antibiotics exposure during pregnancy in the CMPA group was higher than that in the control group,and there were statistical differences between the two groups(P＜0.05).There was no significant difference in the distribution of other pregnancy complications between the two groups(P＞0.05),such as eclamp-sia/preeclampsia,chronic hypertension/gestational hypertension,diabetes/gestational diabetes,thyroid diseases,and so on.There was no significant difference in the overall distribution of some blood routine indexes during pregnancy between the CMPA group and the control group(P＞0.05).Multivariate Lo-gistic regression analysis showed that male infant,mothers complicated with autoimmune diseases or ane-mia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.Conclusion:Male infant,mothers complicated with autoimmune diseases or anemia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.

Objective:To evaluate the effect of statins combined with PCSK9 inhibitors on coronary artery atherosclerotic plaque, as well as to verify the lipid-lowering effect of the combined therapy.Methods:A computerized search of PubMed, Embase, Web of Science, Cochrane Library, Wanfang, and CNKI databases was conducted to retrieve published literature from inception to December 20, 2022. The English search terms utilized included "PCSK9 inhibitors," "Alirocumab," "Evolocumab," "plaque," "IVUS," and "OCT." The corresponding Chinese search terms were "PCSK9 inhibitors," "plateau," "intravascular ultrasound," and "optical coherence tomography." The literature that examined the effect of statins alone or in combination with PCSK9 inhibitors on coronary atherosclerotic plaques using intravascular ultrasound or optical coherence tomography was identified. The collected data were subsequently processed using Review Manager (Revman) version 5.4.Results:In the final analysis, nine studies involving 1912 patients were included. The analysis results revealed that compared with statins alone, statins combined with PCSK9 inhibitors significantly reduced the percentage of atherosclerotic volume ( MD: -2.08 mm 3, 95% CI: -2.94 to -1.23 mm 3, P < 0.001), accelerated the regression of atherosclerotic volume ( MD: -1.13 mm 3, 95% CI: -1.49 to -0.77 mm 3, P < 0.001), slightly, but not significantly, reduced the overall atherosclerotic volume ( MD: -6.42 mm 3, 95% CI: -14.34-1.51 mm 3, P = 0.110). Nevertheless, the combined therapy contributed to a significant reduction in atherosclerotic volume ( MD: -5.16 mm 3, 95% CI: -7.09 to -3.23 mm 3, P < 0.001) and significantly increased the fiber cap thickness of thin cap plaques ( MD: 8.46 μm, 95% CI: 5.13-11.79 μm, P < 0.001). Additionally, this combined therapy significantly lowered blood lipid levels. Conclusion:The combination of statins and PCSK9 inhibitors can significantly improve the characteristics and phenotype of atherosclerotic plaques and significantly reduce blood lipid levels. For patients with high cardiovascular risk, it is recommended to initiate treatment with statins combined with PCSK9 inhibitors as soon as possible and maintain it for a long time to ensure more benefits.

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]

Background::Hyperglycemia frequently induces apoptosis in endothelial cells and ultimately contributes to microvascular dysfunction in patients with diabetes mellitus (DM). Previous research reported that the expression of integrins as well as their ligands was elevated in the diseased vessels of DM patients. However, the association between integrins and hyperglycemia-induced cell death is still unclear. This research was designed to investigate the role played by integrin subunit β5 (ITGB5) in hyperglycemia-induced endothelial cell apoptosis.Methods::We used leptin receptor knockout (Lepr-KO) ( db/ db) mice as spontaneous diabetes animal model. Selective deletion of ITGB5 in endothelial cell was achieved by injecting vascular targeted adeno-associated virus via tail vein. Besides, we also applied small interfering RNA in vitro to study the mechanism of ITGB5 in regulating high glucose-induced cell apoptosis. Results::ITGB5 and its ligand, fibronectin, were both upregulated after exposure to high glucose in vivo and in vitro. ITGB5 knockdown alleviated hyperglycemia-induced vascular endothelial cell apoptosis and microvascular rarefaction in vivo. In vitro analysis revealed that knockdown of either ITGB5 or fibronectin ameliorated high glucose-induced apoptosis in human umbilical vascular endothelial cells (HUVECs). In addition, knockdown of ITGB5 inhibited fibronectin-induced HUVEC apoptosis, which indicated that the fibronectin-ITGB5 interaction participated in high glucose-induced endothelial cell apoptosis. By using RNA-sequencing technology and bioinformatic analysis, we identified Forkhead Box Protein O1 (FoxO1) as an important downstream target regulated by ITGB5. Moreover, we demonstrated that the excessive macroautophagy induced by high glucose can contribute to HUVEC apoptosis, which was regulated by the ITGB5-FoxO1 axis. Conclusion::The study revealed that high glucose-induced endothelial cell apoptosis was positively regulated by ITGB5, which suggested that ITGB5 could potentially be used to predict and treat DM-related vascular complications.

Objective:To investigate the relationship between gestational weight gain (GWG) in twin pregnancies and adverse perinatal outcomes.Methods:This retrospective study included twin pregnant women with live births at≥25 weeks of gestation and their offspring, who delivered at Peking University People's Hospital from January 2012 to October 2022. Total GWG was standardized according to gestational age and categorized into three groups based on the 2009 Institute of Medicine (IOM) guidelines: insufficient GWG (GWG below IOM recommendations), appropriate GWG (GWG within IOM recommendations), and excessive GWG (GWG above IOM recommendations). Comparisons between data of the three groups used analysis of variance, Kruskal-Wallis test or Bonferroni correction or Chi-square partitions. Multivariable logistic regression models and generalized estimating equations with logistic regression models were used to analyze the independent effects of GWG on maternal and neonatal outcomes. Results:A total of 794 twin pregnant women and their 1 588 live-born neonates were included in the study. There were 360 women (45.3%) with appropriate GWG, 356 (44.8%) with insufficient GWG, and 78 (9.8%) with excessive GWG. Both insufficient and excessive GWG were associated with an increased risk of preterm birth [adjusted ORs of 1.39 (95% CI: 1.04-1.88) and 1.70 (95% CI: 1.05-2.78), respectively]. Insufficient GWG was associated with an increased risk of gestational diabetes mellitus (adjusted OR=1.42, 95% CI: 1.00-2.01) and low birth weight infants (adjusted OR=2.04, 95% CI: 1.57-2.66). Insufficient GWG was also associated with a reduced risk of eclampsia or preeclampsia (adjusted OR=0.50, 95% CI: 0.33-0.75), cesarean section (adjusted OR=0.48, 95% CI: 0.30-0.77), discordant twin growth (adjusted OR=0.56, 95% CI: 0.37-0.85), and large for gestational age infants (adjusted OR=0.46, 95% CI: 0.35-0.61). Excessive GWG was associated with an increased risk of eclampsia or preeclampsia (adjusted OR=2.85, 95% CI: 1.65-4.91), and large for gestational age infants (adjusted OR=2.49, 95% CI: 1.60-3.86), while with a decreased risk of low birth weight infants (adjusted OR=0.42, 95% CI: 0.27-0.65). Conclusions:More than half of the twin pregnancies have GWG outside the recommended range of the IOM guidelines. Both insufficient and excessive GWG are associated with adverse perinatal outcomes, particularly an increased risk of preterm birth.

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

Objective:We compared the clinical outcomes between β-blocker with angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in patients with acute myocardial infarction (AMI) without left ventricular systolic dysfunction.Methods:A total of 750 patients who were diagnosed as AMI without left ventricular systolic dysfunction and successfully received percutaneous coronary intervention (PCI) in TEDA International Cardiovascular Hospital from October 2016 to September 2017 were collected retrospectively. We divided the patients into two groups: β-blocker + ACEI group (BB+ ACEI group, n=666) and β-blocker + ARB group (BB+ ARB group, n=84) according to discharge medications. The clinical datas were gathered and the end-point events were followed up. K-M curve was used to describe cumulative survival rate of the two groups. We used Cox regression analysis to compare the clinical outcomes of the two groups. Results:The occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) (8.3% vs 3.4%, HR=2.377, 95% CI: 1.006-5.616, P=0.048), all-cause death (3.6% vs 0.4%, HR=12.951, 95% CI: 1.947-86.159, P=0.008) and non-fatal myocardial infarction (3.6% vs 0.8%, HR=5.231, 95% CI: 1.193-22.934, P=0.028) in the BB+ ARB group was significantly higher than those in the BB+ ACEI group followed up for 13 months. However, there was no difference between the two groups in the incidence of stroke (1.2% vs 1.4%, HR=0.922, 95% CI: 0.117-7.276, P=0.516) and target vessel revascularization (3.6% vs 1.6%, HR=1.607, 95% CI: 0.384-6.729, P=0.516). The cumulative survival rate of BB+ ACEI group was higher than that of BB+ ARB group, with statistically significant difference ( P<0.05). Conclusions:Compared with β-blocker combined with ARB, β-blocker combined with ACEI are more beneficial to reduce the incidence of MACCE, all-cause death and non-fatal myocardial infarction in AMI patients without left ventricular systolic dysfunction after PCI.

OBJECTIVE: This study aimed to examine the associations of daytime napping with incident risks of cardiovascular diseases (CVDs) and hypertension (HTN). METHODS: Data for napping and CVD outcomes in 25 provinces were collected from baseline (2010) and three waves of follow-up (2012-2017) investigations of the China Family Panel Studies. Cox frailty models with random intercepts for the surveyed provinces were used to assess the longitudinal effects of daytime napping on CVD and HTN. RESULTS: Compared with non-nappers, 30+ min nappers had higher risks of CVD and HTN, while no significant associations were observed among < 30 min nappers. Incident risks among 30- to < 60-min nappers increased by 22% [hazard ratio (HR) 1.22, 95% confidence interval ( CI) 1.08-1.39] for CVD and 21% (1.21, 1.04-1.41) for HTN, respectively, with corresponding HRs of CVD and HTN of 1.27 (1.09-1.47) and 1.38 (1.16-1.65) among ≥ 60 min nappers. Nap-associated CVD risks varied by subgroups, with stronger associations in participants with lower body mass index (< 24 kg/m ²), physically inactive persons, smokers, and participants with longer nighttime sleep (≥ 7 h/night). Significant effects of daytime napping were observed on rural and northern residents only, highlighting great regional variations in CVD risks associated with napping habits. CONCLUSIONS This cohort study revealed strong evidence that long daytime napping (≥ 30 min) is associated with an increased incidence of cardiovascular events.
Adult ; Cardiovascular Diseases/etiology* ; China/epidemiology* ; Cohort Studies ; Female ; Humans ; Hypertension/etiology* ; Incidence ; Longitudinal Studies ; Male ; Middle Aged ; Risk Factors ; Sleep/physiology* ; Time Factors

Objective To analyze the clinical features and clinical significance of patients with inflammatory bowel disease (IBD) complicated by thrombosis.Methods From March 14th,2001 to February sixth 2017,at Nanjing General Hospital of Nanjing Military Command,27 IBD patients with thrombosis diagnosed by clinical symptoms,endoscopy,imaging and pathology were enrolled.During the same period,81 gender and age matched IBD patients without thrombosis were included in the control group.The basic data,information of IBD diagnosis and treatment and thrombotic events of patients were collected and analyzed.T-test and Chi-square test were performed for statistical analysis.Binary logistics regression was used for risk factors analysis.Results The mean age of diagnosis of IBD patients with thrombosis was (44.8 ± 15.8) years,which was higher than that of the IBD patients of control group ((36.0 ± 14.4) years),and the difference was statistically significant (t =2.69,P =0.008).Among 27 IBD patients with thrombosis,arterial thrombosis was 51.9％ (14/27),deep venous thrombosis of the lower extremity veins was 29.6％ (8/27),portal venous system involved was 11.1％ (3/27),pulmonary embolism was 3.7％ (1/27) and disseminated intravascular coagulation accounted for 7.4％ (2/27).Nine patients (33.3％,9/27) underwent surgery six months before the diagnosis of thrombosis.The results of binary logistic regression indicated that the age of diagnosis and vascular catheterization were independent risk factors for thrombosis in IBD patients (odds ratio (OR) =1.04,95％ confidence interval (CI) 1.01 to 1.07,P=0.01;0R=5.64,95％ CI 1.39 to 22.96,P=0.02).After medicine treatment or surgery,81.5％ (22/27) of the patients improved,9.1％ (2/22) were worse and 13.6％ (3/22) died.Conclusion Screening and prevention of thrombosis should be paid attention in IBD patients with a history of vascular catheterization,at active phase and older age when diagnosed.

BACKGROUND: Bone defects are one of the most important challenges that surgeons have to manage in total knee arthroplasty. The reasonable treatment method can guarantee the effect of the repair operation. OBJECTIVE: To review the relevant literatures concerning bone defects treated by primary total knee arthroplasty and revision total knee arthroplasty, and to analyze the optimal managements for different types of bone defects. METHODS: Relevant literatures were identified in China National Knowledge Infrastructure, Wanfang data, Vip, PubMed, Medline, and Web of Science. The key words were "total knee arthroplasty, total knee replacement, revision total knee arthroplasty, bone loss, bone defect, bone deficiency, management". The included studies were analyzed and summarized. RESULTS AND CONCLUSION: (1) Sixty-two studies regarding total knee arthroplasty for bone defects were included, without recognized standards on the type of bone defects. AORI is the most widely used classification for bone defects. (2) Pre-operated detailed evaluation including laboratory and radiographic examination, and accurate diagnosis are the key to success. (3) Management of bone defect was similar in tibia and femur, but there is still no standard classification and management of patellar bone defect. (4) Using stem fixation whenever a femoral or tibial component is revised can improve clinical outcome. (5) Through detailed evaluation, accurate diagnose and appropriate classification of bone defect, selection, according to the characteristics of different strategies, the age of the patient and the needs of life, can get a good clinical result.