Objective:To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods:This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children′s Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results:Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions:Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

Objective:To analyze the status quo and influencing factors of accidental prolapse of peripherally inserted central catheter (PICC) in children, so as to provide references for formulating preventive measures.Methods:Using the convenient sampling method, a total of 1 268 pediatric patients who underwent catheterization at Intravenous Catheter Nursing Studio of Beijing Children's Hospital, Capital Medical University from January to December 2021 were selected as the research objects to analyze the incidence of PICC accidental prolapse. Logistic regression was used to analyze the influencing factors of PICC accidental prolapse.Results:Of the 1 268 children included in this study, 29 were excluded from follow-up and 1 239 children were eventually included. A total of 1 339 PICCs were implanted in 1 239 children, and the incidence of PICC accidental prolapse was 5.60% (75/1 339). Logistic regression analysis showed that whether the children had skin rash, time, location and catheter indentation time were the influencing factors for the occurrence of PICC accidental prolapse ( P<0.05) . Conclusions:The incidence of children's PICC accidental prolapse is at a high level, which is affected by many factors. Nursing staff should formulate effective preventive measures according to the influencing factors of PICC accidental prolapse, reduce the occurrence of children's accidental catheterization and extend the retention time of PICC.

Background Zinc is a trace element essential for normal fetal heart development, and excess zinc can be toxic. The relationship between maternal and fetal zinc levels and the development of congenital heart disease (CHD) in the offspring is unclear. Objective To study the effects of maternal and neonatal zinc exposure levels on the risk of developing CHD in the offspring. Methods The data and biological samples of the study subjects were derived from the birth cohort established by Gansu Provincial Maternity and Child Care Hospital in Lanzhou from 2010 to 2012. Questionnaire surveys were conducted at baseline in the first trimester and at follow-up visits in the second trimester, the third trimester, and 42 d after delivery. Maternal venous blood during the third trimester and neonatal umbilical venous blood at delivery were collected, and information on their birth outcomes was extracted from medical records. Ninety-seven children with CHD diagnosed by echocardiography at birth and confirmed at the follow-up after 42 d were selected as the case group, and 194 healthy full-term infants were selected as the control group, 1∶2 matched for maternal age and geographical location from the database. The zinc concentrations in whole blood of pregnant mothers and umbilical cord blood of fetuses in both groups were measured by inductively coupled plasma mass spectrometry. According to the quartiles P₂₅ and P₇₅ of zinc levels in the whole blood of pregnant mothers and neonatal cord blood in the control group, zinc exposure was divided into three groups: low, medium, and high. After adjusting for maternal vaginal bleeding in early pregnancy, pre-pregnancy folic acid and vitamin supplementation, birth weight, and umbilical cerclage confounders, a multiple conditional logistic regression model was applied to analyze the associations between maternal whole blood and fetal umbilical cord blood zinc levels and the risk of CHD in the offspring, and a further subgroup analysis was performed by disease classification. Results The medians (P₂₅, P₇₅) of maternal whole blood zinc levels in the case group and the control group were 5.034 (3.456, 6.644) and 4.693 (3.411, 5.646) mg·L⁻¹, respectively, with significant differences between the two groups (P=0.029). The medians (P_25, P₇₅) of neonatal cord blood zinc level was 2.153 (1.479, 2.405) mg·L⁻¹ in the case group and 1.636 (1.304, 1.979) mg·L⁻¹ in the control group, with significant differences between the two groups (P<0.001). The zinc levels of maternal whole blood and neonatal cord blood in the simple CHD group were significantly higher than those in the control group (P<0.05). The multiple conditional logistic regression model showed that compared with the maternal medium zinc exposure level group (3.41-5.65 mg·L⁻¹), the risk of offspring CHD was 2.225 times of the high exposure level group (>5.65 mg·L⁻¹) (OR=2.225, 95%CI: 1.017-4.868). Compared with the neonatal medium zinc exposure level group (1.30-1.98 mg·L⁻¹), the neonatal high exposure level group (>1.98 mg·L⁻¹) also had an increased risk of CHD (OR=4.132, 95%CI: 1.801-9.480). The subgroup analysis results showed that compared with corresponding medium exposure level groups, the risk of simple CHD in the offspring of the maternal high zinc exposure level group was increased (OR=4.081, 95%CI: 1.427-11.669), and the risks of simple CHD (OR=7.122, 95%CI: 2.126-23.854) and complex CHD (OR=5.165, 95%CI: 1.859-14.346) of neonates of the neonatal high zinc exposure level group were increased. Conclusion Under the exposure levels of the study population, high concentrations of zinc exposure in pregnant mothers and neonates may be associated with the incidence of CHD.

Objective:To investigate the characteristics of clinical, muscle pathology and gene mutation in patients with nemaline myopathy caused by NEB gene mutation.Methods:The clinical and pathological data of patients with nemaline myopathy caused by NEB gene were collected from Neuromuscular Center of Jiaozuo People′s Hospital from January 1997 to January 2020. The next generation sequencing was preformed to detect NEB gene in all patients, and characteristics of gene mutation were analyzed.Results:Among the 11 patients, there were 8 males and 3 females, and 6 of them came from 2 families. The age of seeing a doctor ranged from 11 to 52 years, the age of onset was from 6 to 23 years, and the course of disease ranged from 5 to 35 years. Neurological examination showed that among the 11 patients, 8 patients had high palatal arch and long face. The muscle tone of both upperlimbs was normal, the tendon reflex was depressed, the proximal muscle strength was grade Ⅲ-Ⅴ, and the distal muscle strength was grade Ⅴ. The muscle tone of both lower extremities was reduced and the tendon reflex was absent. The proximal muscle strength was grade Ⅱ-Ⅳ and the distal muscle strength was grade Ⅲ-Ⅴ. No dysphagia or respiratory muscle involvement was found. Muscle biopsies were performed in 7 of the 11 patients, the pathological changes were muscle fibers of different sizes, circular atrophic muscle fibers and compensatory hypertrophic fibers, and occasionally denatured and necrotic muscle fibers were found. Different degrees of rod aggregation could be seen in all the 7 patients. Electron microscopic examination of 5 patients showed that there was rod aggregation between myofibrils, and most of them were located near the Z band, but no intranuclear rod was found. NEB gene was found in all 11 patients, and a total of 9 different mutation sites were detected, including 8 in exon region and 1 in intron region. Among them, c.21522+3A>G was found in 10 cases, c.1623delT was found in 3 cases and c.17611C>T was found in 3 cases. There was 1 case of c.4417C>T, c.2549delA, c.21065dupA, c.3520G>A, c.20943G>A, c.192G>A respectively.Conclusions:The clinical phenotype of nemaline myopathy caused by NEB gene has great heterogeneity. Muscle pathology shows that rod aggregation is an important basis for the diagnosis of this disease. Mutation c.21522+3A>G in intron is the most common mutation in this group of NEB gene. And the novel mutation sites of NEB gene are respectively c.17611C>T, c.2549delA, c.3520G>A, c.21065dupA, c.20943G>A and c.192G>A.

Objective:To investigate the clinical characteristics, skeletal muscle pathologies and gene variations of chronic progressive external ophthalmoplegia (CPEO).Methods:Sixteen patients with conformed CPEO, admitted to our hospital from January 1997 to December 2021, were chosen. Their clinical data such as onset age and course of diseases and muscle pathological examination results were collected and their gene variation characteristics were analyzed.Results:The initial symptom in all 16 patients was ptosis of varying degrees; 15 patients were with eye movement disorder, 6 with diplopia, 4 with proximal limb weakness, and 3 with dysphagia and dysarthria. Among the 16 patients, electromyography showed myogenic damage in 7 patients, myogenic combined with neurogenic damage in 1 patient, neurogenic damage in 1 patient, and normal in 7 patients. Skeletal muscle biopsies indicated that 14 patients were with ragged red fibers (RRF), 11 patients had cytochrome C oxidase (COX)-negative muscle fibers, 3 patients had a small amount of degenerated and necrotic myofibers with mononuclear phagocytic infiltration. Immunohistochemical staining indicated infiltration of CD8 and CD68 positive lymphocytes. Ten patients accepted genetic test, indicating 6 patients with single large fragment deletion of mitochondrial DNA (mtDNA), 1 patient with mtDNA point mutation, 1 patient with nucleosomal DNA (nDNA) point mutation, and 2 patients without pathogenicity variation clearly associated with clinical phenotype. Electron microscopy in 5 patients showed that abnormal mitochondrial aggregation was noted in 4 patients under the sarcolemma and among the myofibrils.Conclusion:In addition to ptosis and eye movement disorders, a small number of patients with CPEO may be accompanied by dysphagia and limb weakness; and single large fragment deletion of mtDNA is the main mutation form of CPEO.

Objective:To investigate the clinical characteristics, skeletal muscle pathologies and gene variations of chronic progressive external ophthalmoplegia (CPEO).Methods:Sixteen patients with conformed CPEO, admitted to our hospital from January 1997 to December 2021, were chosen. Their clinical data such as onset age and course of diseases and muscle pathological examination results were collected and their gene variation characteristics were analyzed.Results:The initial symptom in all 16 patients was ptosis of varying degrees; 15 patients were with eye movement disorder, 6 with diplopia, 4 with proximal limb weakness, and 3 with dysphagia and dysarthria. Among the 16 patients, electromyography showed myogenic damage in 7 patients, myogenic combined with neurogenic damage in 1 patient, neurogenic damage in 1 patient, and normal in 7 patients. Skeletal muscle biopsies indicated that 14 patients were with ragged red fibers (RRF), 11 patients had cytochrome C oxidase (COX)-negative muscle fibers, 3 patients had a small amount of degenerated and necrotic myofibers with mononuclear phagocytic infiltration. Immunohistochemical staining indicated infiltration of CD8 and CD68 positive lymphocytes. Ten patients accepted genetic test, indicating 6 patients with single large fragment deletion of mitochondrial DNA (mtDNA), 1 patient with mtDNA point mutation, 1 patient with nucleosomal DNA (nDNA) point mutation, and 2 patients without pathogenicity variation clearly associated with clinical phenotype. Electron microscopy in 5 patients showed that abnormal mitochondrial aggregation was noted in 4 patients under the sarcolemma and among the myofibrils.Conclusion:In addition to ptosis and eye movement disorders, a small number of patients with CPEO may be accompanied by dysphagia and limb weakness; and single large fragment deletion of mtDNA is the main mutation form of CPEO.

Objective:To evaluate the heterogeneity in pediatric ETV6-RUNX1 acute lymphoblastic leukemia (ALL) by gene expression profile and to study clinical characteristics in different clusters.Methods:An improved advanced fragment analysis (iAFA) technique was developed to detect 57 marker genes in 264 pediatric ALL patients treated in Beijing Children’s Hospital from August 2016 to June 2019. The 56 ALL patients with ETV6-RUNX1 positive were evaluated by clinical characteristics in gene expression profile, immunophenotype and early response of chemotherapy in different clusters.Results:The 56 ETV6-RUNX1-positive patients were clustered into 2 groups of E/R-1 (45, 80.4%) and E/R-2 (11, 19.6%) . Spearman coefficient was 0.788 and 0.901 in E/R-2 and E/R-1, respectively. The median of initial platelet counts was 104 (27-644) and 50 (8-390) ( P<0.01) in E/R-2 and E/R-1, respectively. The median of proportion of initial bone marrow immature cells was 0.830 (0.270-0.975) and 0.935 (0.445-0.990) ( P<0.05) in E/R-2 and E/R-1, respectively. The most specific immunophenotype at initial diagnosis, CD22 +CD34 +CD20 -CD117 -CD56 -, mainly gathered in E/R-2 ( P<0.001) . Patients negative of minimal residual disease detected by flow cytometry (MRD-FCM) at day 33 were 5 (55.6%) and 32 (88.9%) in E/R-2 and E/R-1, respectively. There was no significant difference in the original analysis ( P=0.064) but difference in sensitivity analysis ( P=0.035) . Nevertheless, patients negative of MRD detected by polymerase chain reaction (MRD-PCR) at day 33 were 7 (77.8%) and 36 (100%) in E/R-2 and E/R-1, respectively, with significant difference ( P=0.047) . Conclusion:Gene expression profile shows heterogeneous in ETV6-RUNX1 ALL, and the E/R-2 profile indicates that these patients may have a less tendency to thrombocytopenia at the initial diagnosis but have poorer response to induction chemotherapy and may influence further outcome.

OBJECTIVE: To explore the effects of bone marrow mesenchymal stem cells (BMSCs) in different concentrations on the balance of regulatory T cell/T-helper cell 17 (Treg/Th17). METHODS: BMSCs were isolated from SPF grade male Wistar rats with age of 3 weeks old and weight of 50 g. BMSCs were cultured and identified when they were expanded to the 4th generation. CD4⁺ T lymphocytes were isolated from SPF grade male Wistar rat with age of 6 weeks old and weight of 200 g and assayed for cell purity by flow cytometry. BMSCs were divided into 0.5-fold concentration group, basal concentration group, 2-fold concentration group and 4-fold concentration group by their concentrations of 1×10⁵/well, 2×10⁵/well, 4×10⁵/well and 8×10⁵/well, which were cultured with CD4⁺ T lymphocytes for 72 hours, respectively. Then the proportion of Treg cells and Th17 cells in each group was detected by flow cytometry, and cytokines were detected by cytometric bead array. RESULTS: The purities of BMSCs and CD4⁺ T lymphocytes were both higher than 95%. In the co-culture of BMSCs and CD4⁺ T lymphocytes, the proportions of Treg cells were statistically different among different concentration groups of BMSCs (F = 10.071, P = 0.001), in which BMSCs in 2-fold concentration group had the strongest ability to promote the Treg cells proliferation. The proportion of Treg cells in 2-fold concentration group was significantly higher than that in 0.5-fold concentration group, basal concentration group and 4-fold concentration group [(9.24±2.68)% vs. (3.87±0.38)%, (5.16±1.69)%, (3.86±0.36)%, all P < 0.01]. The level of interleukin-10 (IL-10) was lowest in 0.5-fold concentration group, and it was significantly lower than that in basal concentration group, 2-fold concentration group and 4-fold concentration group (ng/L: 39.80±14.48 vs. 148.43±64.49, 156.40±59.27, 126.92±42.95, all P < 0.05). Transforming growth factor-β (TGF-β) was the highest in basal concentration group, and it was significantly higher than that in 0.5-fold concentration group, 2-fold concentration group and 4-fold concentration group [ng/L: 3.17 (1.88, 5.74) vs. 0.71 (0.32, 1.38), 1.22 (0.47, 2.97), 0.52 (0.37, 1.23), all P < 0.05]. The proportions of Th17 cells were statistically different among the different concentration groups (F = 21.069, P = 0.000), with the highest proportion in basal concentration group which was significantly higher than that in 0.5-fold concentration group or 4-fold concentration group [(0.89±0.08)% vs. (0.64±0.15)%, (0.37±0.10)%, both P < 0.01], but no significant difference was found as compared with 2-fold concentration group [(0.83±0.06)%, P > 0.05]. However, the expressions of IL-17 and IL-6 were not different among the different concentration groups respectively (IL-17: χ² = 0.550, P = 0.760; IL-6: χ² = 0.010, P = 0.995). CONCLUSIONS BMSCs in moderate concentrations [(2-4)×10⁵/well] could promote proliferation both in Treg cells and Th17 cells, but no change could be found in higher concentrations of BMSCs (8×10⁵/well). However, the changes in related cytokines were not synchronized with Treg/Th17 cells.
Animals ; Cytokines/metabolism* ; Male ; Mesenchymal Stem Cells/metabolism* ; Rats ; Rats, Wistar ; T-Lymphocytes, Regulatory/metabolism* ; Th17 Cells/metabolism*

Algorithms ; Crystallography, X-Ray ; Disulfides ; chemistry ; Models, Molecular ; Protein Conformation ; Proteins ; chemistry

Objective To analyze preoperative risk factors of perioperative pulmonary hypertension crisis (PHC) for pregnant woman with severe pulmonary artery hypertension (PAH), and approach its clinical value. Methods A retrospective analysis was conducted. The clinical data from 152 pregnant women with severe PAH underwent cesarean delivery admitted to Beijing Anzhen Hospital from January 1st 2008 to December 31st 2016 was collected. The patients were divided into two groups according to with perioperative PHC or not. Through the case management system, age, height, weight, gestational age, pregnancy time, type of PAH, emergency or selective surgery, New York Heart Association (NYHA) cardiac function classification, and preoperative ultrasound left ventricular ejection fraction (LVEF), left ventricular diastolic final diameter (LVEDD), the pulmonary artery systolic pressure (sPAP) estimated by ultrasonic TI method, radial artery systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO2) without oxygen, oral sildenafil ingestion, having Swan-Ganz catheter placement or not, and whether used norepinephrine or not, as well as the occurrence of perioperative PHC and clinical outcomes were collected. Possible preoperative risk factors were compared between the two groups by single factor and multiple factors logistic regression analysis. The receiver-operating characteristic curve (ROC) was plotted to assess the diagnostic value of various risk factors.Results A total of 152 patients were screened. Ten patients got heart surgery under general anesthesia at the same time, and 4 patients experiencing cesarean section with general anesthesia were excluded. 138 patients were enrolled finally, 27 patients underwent perioperative PHC (19.57%), and 17 patients died with a mortality of 62.96%. Compared with non-PHC group, the patients in PHC group were older (years: 25.07±3.55 vs. 27.64±4.82), had a poor cardiac function (NYHA cardiac function classification: 3.22±0.64 vs. 2.85±0.53), a smaller LVEDD (mm: 38.78±4.76 vs. 43.91±9.67), lower SpO2 without oxygen (0.83±0.12 vs. 0.92±0.06) and oral sildenafil ingestion rate (29.63% vs. 56.76%), and higher sPAP estimated by ultrasonic TI method [mmHg (1 mmHg = 0.133 kPa): 113.41±24.73 vs. 99.35±21.10] and DBP (mmHg: 79.63±13.23 vs. 75.23±12.14), more having Swan-Ganz catheter placement (85.19% vs. 57.66%), more Eisenmenger syndrome (70.37% vs. 37.84%), and more emergency operation (48.15% vs. 23.42%, allP ≤ 0.1). The variables with statistically significant differences showed by single factor analysis were collected, and it was shown by multiple factors logistic regression analysis that LVEDD [odds ratio (OR) = 0.878, 95% confidence interval (95%CI) = 0.796-0.968,P = 0.009], whether oral taken sildenafil (OR = 0.161, 95%CI = 0.051-0.515,P = 0.002) or not, SpO2 at room air (OR = 0.882, 95%CI = 0.829-0.938,P = 0.000), Swan-Ganz catheter placement or not (OR = 6.186, 95%CI = 1.533-24.964,P = 0.010) were independent risk factors of perioperative PHC in pregnant women with severe PAH. It was shown by ROC curve analysis that the area under the ROC curve (AUC) of four factors mentioned above combined diagnosis for PHC was 0.878 (P = 0.000) with the sensitivity of 88.89% and specificity of 76.58%.Conclusions PHC is very dangerous for gravida with severe PAH, and the mortality rate is very high. LVEDD, oral sildenafil, SpO2 at room air, Swan-Ganz catheter placement or not were independent risk factors of perioperative PHC for severe PAH maternal. Four preoperative factors of perioperative PHC joint diagnosis accuracy were higher.