Regulatory B cells(Breg) are a subgroup of B lymphocytes and characterized by their immunosuppressive capacity. The regulation of immune response by Breg plays a critical role in the mouse and human immune systems. Previous studies on Breg mainly focus on autoimmune diseases and tumors, but in recent years, the role of Breg in chronic infectious diseases has attracted attention. This review summarized the phenotypes, modes of action and the role of Breg in the process of chronic infectious diseases aiming to provide a new sight for research on immunotherapy for chronic infectious diseases.

Objective To detect the expression pattern of microRNA in A549 cells treated by lipopolysaccharide, study the expression of miRNA-1247-3P in A549 cells under LPS treatment and explore the possible mechanism of miRNA-1247-3P in A549 cells under LPS treatment. Methods A549 cells were divided into experimental and control groups. Immunocytochemical method and RT-PCR were used to detect the changes of SP-A and SP-C. The expression of miRNAs were detected using miRNAs array in different groups. The key miR-1247-3P was collected to detect the changes of miR-1247-3P in all groups using quantitative real-time polymerase chain reaction. Results Compared with control group, the expressions of SP-A and SP-C were significantly decreased in the experimental groups (P < 0.05). MiRNA array showed that 31 miRNAs were up-regulated and 3 miRNAs were down-regulated. Compared with control group, the expression of miR-1247-3P was significantly increased in the experimental groups (P < 0.05). Conclusion The increased expression of miR-1247-3P may play an important role in the pathogenesis of ARDS.

Objective:To investigate the effects of probiotics on the stabilization of blood glucose and its mechanism in children with severe infectious pneumonia.Methods:Eighty children with severe infectious pneumonia admitted to PICU were enrolled in the clinical trial prospectively.They were divided into two groups by random.Forty patients given probiotics were regarded as treatment group,the others not given probiotics were considered to be controlled group,in addition to the regular therapy.Blood glucose,plasma H2 S,D-lactate and acetic acid,propionic acid and butyric acid concentrations in stools were measured respectively at the beginning of the treatment and on day 8 after the treatment.At the same time the changes of blood glucose,fluctuation of them and prognosis were examined.Results:There was no significance in all the parameters of the two groups at the beginning of the treatment (P ＞ 0.05).The levels of plasma H2S and acetic acid,butyric acid in the stools of the probiotics group was (24.6 ± 7.4) μmol/L,(32.8 ± 8.6) μmol/g,(15.2 ± 5.2) μmoL/g on the day 8 respectively;but the concentration of these parameters in the control group was (20.9 ± 7.4) μ mol/L,(28.6 ± 7.9) μmol/g,(12.9 ± 5.0) μmoL/g.Meanwhile the level of D-lactate in patients given probiotics (1.25 ± 0.39) μg/ ml was significantly lower than that the control group (1.45 ± 0.4) μg/ml.The blood glucose (6.1 ± 2.7) mmol/L was lower than than in the other group (7.4 ± 2.7) mmol/L on day 8.And a higher recov ery rate was found in probiotic group.Furthermore,blood glucose and H2S,acetic acid levels expressed negative correlation at 8 day;but positive correlations were found between blood glucose and D-lactate (P ＜ 0.05).Conclusion:Application of probiotics to children with severe infectious pneumonia can moderate the structure of enterobacteria,reinforce the intestinal barrier and elevate the levels of plasma H2S and had positive effects on the stabilization of blood glucose and prognosis.

Objective To investigate the clinical efficacy and safety of nebulization treatment for childhood respiratory virus infection with human recombinant interferon α-1b.Methods A randomized,controlled clinical re-search was designed.375 subjects with children respiratory tract virus infection were randomly divided into the treat-ment group(250 cases) and control group(125 cases).In addition to conventional therapy,the treatment group with recombinant human interferon α-1b and the control group with ribavirin were executed by using nebulization treat-ment.Results A total of 357 subjects were statistically included in the trail.Sore throat,cough,wheezes,rale of lung disappearing time and the days of hospitalization of treatment group were significantly different(u=5.83,6.51,6.33, 7.39,5.57,6.62,all P<0.01) compared with the control group;The treatment group in the cure rate and total effec-tive rate was significantly higher(χ2 =7.85,25.71,all P<0.01),and no obvious adverse reactions were reported. Conclusion Nebulization treatment of childhood respiratory virus infection with human recombinant interferon α-1b is safe and effective.The method of operation is simple and thus its application is worth promoting in clinic.

Objective To explore the therapeutic mechanism of in response to kainic acid－induced epilepsy in mice. Methods Sixty mice Were randomly divided into control group,model group and loW－dose Sirolimus group, medium－dose and high－dose Sirolimus groups. Prevention and therapeutic administration Were used in the Sirolimus loW,medium and high dose groups. One Week before model establishment,intraperitoneal injection of Sirolimus 1 mg／kg,3 mg／kg and 9 mg／kg Were given once a day,but the model group and the control group Were injected intra﹣peritoneally the same dose of 9 g／L saline. One Week after the preventive administration,all mice except the control group,Were intraperitoneally injected 30 mg／kg kainate solution,and the control group Was injected an equal dose of 9 g／L saline. Mice Were treated 1 Week after the establishment of the models. The number of mice With epileptic symp﹣toms and the number of epileptic seizures,the seizure time and the average number of episodes Were recorded,the Mor﹣ris Water maze test Was performed on the mice,and the arrival time,sWimming distance and number of crossing times of the mice Were collected. The expression levels of mTOR pathWay－related protein gene and the number of apoptotic cells in hippocampus Were detected in hippocampus of mice. Results Epilepsy symptoms appeared earlier in the model group after modeling,and the epileptoid－like symptoms Were significantly delayed in each group(P﹦0. 001 9). The epilepsy grading model group Was significantly higher than that of other groups. The mouse seizure time on the 6th day after modeling Was significantly higher than that on the 3rd day after modeling. The time required for the model epileptic mouse to reach the platform and the sWimming length Was significantly more than that of the control group( P ﹦0. 000 1),While the number of the mice traversing the platform Was significantly loWer(P﹦0. 000 2),and the admi﹣nistration group Was significantly relieved. The gene expression levels of mTOR pathWay key proteins mTOR and S6 in the hippocampus of mice in the model group Were significantly up－regulated(P﹦0. 000 1). Simultaneously,different doses of Sirolimus could significantly doWn － regulate PI3K,AKT,mTOR,and S6 gene expression levels( P ﹦0. 000 1). Compared With the control group,the gray ratios of p－PI3K,p－AKT,p－mTOR and p－S6 and normal PI3K,AKT,mTOR and S6 protein in the model group Were significantly higher(P﹦0. 000 1),and Sirolimus Was also observed. It Was significantly doWn－regulated after administration(P﹦0. 000 1). Conclusions Sirolimus can signifi﹣cantly inhibit the over－activation of mTOR signaling pathWay in the hippocampal region of kainic acid－induced epi﹣lepsy mice,thereby alleviating the symptoms of epilepsy in mice and increasing learning and memory.

Objective:To explore the relationship between different admission sources and outcomes at children in pediatric intensive care unit(PICU).Methods:The clinical data of children admitted to PICU of Henan Provincial People′s Hospital from January 1, 2021 to December 31, 2021 were collected.The children were divided into emergency group, outpatient group, ward transfer group and out-hospital transfer group according to different admission sources, and the influence of different admission sources on the outcome of children was analyzed.Results:A total of 413 children were included in the study.There were 141 cases(34.14%)in emergency group, 14 cases(3.39%)in outpatient group, 115 cases(27.85%)in ward transfer group and 143 cases(34.62%)in out-hospital transfer group.There were significant differences among the four groups in terms of age, length of hospital stay, PCIS score, type of disease, duration of mechanical ventilation and outcome of children( P<0.05). There was no significant difference in gender among the four groups( P=0.328). Among the 143 children of out-hospital transfer group, 92 cases(64.3%)were admitted during the day and 51 cases(35.7%)were admitted in the night.There was no significant difference in age, gender, duration of mechanical ventilation, PCIS score, length of hospital stay and outcome of children between two groups( P>0.05). The independent risk factors for mortality of children in out-hospital transfer group were length of hospital stay( OR=0.717, 95% CI 0.582-0.883, P=0.002), gender( OR=13.185, 95% CI 2.044-85.061, P=0.007), duration of mechanical ventilation>1 day( OR=23.524, 95% CI 3.294-168.026, P=0.002)and PCIS score≤80( OR=6.000, 95% CI 1.637-21.985, P=0.007). Conclusion:PICU children in our hospital mainly come from emergency, ward transfer and out-hospital transfer.The patients transferred from other hospitals were the most critically ill and had the worst outcome, suggesting that we need to develop and popularize referral standards for critically ill children and establish a transport system so that children can receive timely referral and effective treatment, so as to reduce the risk of death of referred children as far as possible.

Objective:To investigate the relationship between the biochemical parameters, the pulmonary pathologic injury and the immune mechanism of severe sepsis in infant porcine, and the intervention effect of Shenfu injection.Methods:Panamanian infant porcine (2-3 months old) were divided into sham operation group (Sham group; intravenous injection of normal saline), lipopolysaccharide (LPS) induced severe sepsis model group (LPS group; intravenous injection of LPS 1 mg/kg, and continuing at 0.5 mg·kg -1·h -1 for 12 hours), and Shenfu injection intervention group (SF group; intravenous injection of Shenfu injection 10 mL/kg at the same time of modeling, twice a day) according to the random number table method, with 5 in each group. Forty-eight hours after the challenge, the changes of C-reactive protein (CRP), procalcitonin (PCT), oxygenation index (PaO 2/FiO 2), base excess (BE), blood lactate (Lac) and other biochemical indexes were detected with blood sampling; the number of neutrophils [myeloperoxidase positive (MPO +)] and their activated subsets CD11b + CD64 +, M1 macrophages (CD80 + CD64 +), CD4 + and CD8 + T cells were analyzed in peripheral blood by flow cytometry. The levels of plasma cytokines were detected by enzyme linked immunosorbent assay (ELISA). The pathological damage of lung tissue was observed by hematoxylin-eosin (HE) staining. The mRNA expression of lung injury related molecules and their receptors, chemokines, cytokines, vascular endothelial related molecules and tight junction protein were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results:Compared with Sham group, the levels of CRP, PCT and Lac in LPS group significantly increased, and PaO 2/FiO 2 and BE significantly decreased. In the peripheral blood, CD80 + CD64 + macrophages, CD11b + CD64 + and MPO + neutrophils, CD4 +, CD8 + T cells and tumor necrosis factor-α (TNF-α) significantly decreased, but interleukin-10 (IL-10) and vascular endothelial cell growth factor (VEGF) significantly increased; the mRNA expressions of high mobility group protein B1 (HMGB1), receptor for advanced glycation end products (RAGE), angiopoietin 2/angiopoietin 1 (Ang2/Ang1) significantly increased, Toll like receptor 9 (TLR9), chemokines (CXCL9 and CXCL10), TNF-α, IL-27, Tek tyrosine kinase 2 (TIE2), vascular endothelial cadherin (VE-CAD) and Occludin significantly decreased in lung tissue. HE staining showed inflammatory cell infiltration and exudation in the alveolar cavity, alveoli consolidation, thickening of the alveolar interstitial layer and emphysema. Compared with LPS group, Lac in SF group significantly decreased (mmol/L: 4.2±1.0 vs. 6.3±1.1, P < 0.05), while BE and PaO 2/FiO 2 significantly increased [BE (mmol/L): -6.4±2.6 vs. -11.6±2.5, PaO 2/FiO 2 (mmHg, 1 mmHg = 0.133 kPa): 180±36 vs. 105±35, both P < 0.05]; the percentage of CD80 + CD64 + macrophages, CD11b + CD64 + and MPO + neutrophils significantly increased [CD80 + CD64 +: (7.13±2.01)% vs. (3.80±0.46)%, CD11b + CD64 +: (8.33±2.55)% vs. (2.15±0.47)%, MPO +: (21.22±2.33)% vs. (8.31±0.46)%, all P < 0.05]; the mRNA expressions of HMGB1 and RAGE decreased to some extent [HMGB1 mRNA (2 -ΔΔCT): 1.81±0.45 vs. 2.23±0.85, RAGE mRNA (2 -ΔΔCT): 6.69±3.48 vs. 11.60±6.91, both P < 0.05], the mRNA expressions of CXCL9 and TIE2 increased to a certain extent [CXCL9 mRNA (2 -ΔΔCT): 1.06±0.63 vs. 0.50±0.12, TIE2 mRNA (2 -ΔΔCT): 1.42±0.68 vs. 0.27±0.16, both P < 0.05]; the pathological damage of lung tissue were significantly alleviated. Conclusions:The increased abnormality of BE, Lac, and PaO 2/FiO 2, the immune exhausting and paralysis may be important factors leading to the fatal lung injury in infant porcine with severe sepsis. The possible mechanism is that the excessive activation of HMGB1 and its receptor RAGE, the suppression of TLR9 and corresponding chemokine and inflammatory factors lead to increased endothelial damage and decreased tight connection, which in turn induces capillary leakage. The intervention of immune disorders by Shenfu injection in the severe pneumonia accompanied by sepsis may be related to elevated M1 macrophages and activated neutrophils in the peripheral blood, inhibition of HMGB1 and its receptor RAGE mRNA expression, and elevated CXCL9 and TIE2 expression.

Community acquired pneumonia(CAP)has a high morbidity and mortality rate, and can bring a heavy social and economic burden.Its etiology is complex.How to identify high-risk children, early diagnosis, prognosis prediction are the focus of clinical research.Early identification and active intervention of high-risk children who need hospitalization or admission to pediatric intensive care unit by using score scales and biomarkers are crucial to improve the survival rate.This review summarized the assessment of severity and prognosis of CAP in children by different score scales and biomarkers.

Objective:To measure the predictive value of miR-424 on the risk of sepsis complicated with acute respiratory distress syndrome(ARDS), and to explore its correlation with the prognosis of ARDS children.Methods:A prospective study was conducted.The data of children with sepsis (some complicated with ARDS), who were treated in Henan Provincial People′s Hospital (People′s Hospital, Zhengzhou University) were collected from February 2020 to February 2021.The incidence of ARDS and the fatality rate of ARDS children were recorded.Children were divided into survival group and death group according to whether death or not.The expression of miR-424 in peripheral blood mononuclear cells was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Pearson correlation analysis was made to investigate the relationship between the expression level of miR-424 and Pediatric Critical Illness Score(PCIS), Sequential Organ Failure Assessment(SOFA) score, oxygenation index(P/F ratio), C-reactive protein(CRP), procalcitonin (PCT), interleukin 6 (IL-6) and interleukin 8 (IL-8). The factors affecting the prognosis of ARDS children were analyzed by multivariate Logistic regression.Receiver operating characteristic curve(ROC)was used to assess the accuracy of miR-424 in early diagnosis of sepsis complicated with ARDS, and to measure the predicative value of miR-424 on the risk of death in sepsis patients with ARDS. Results:A total of 121 sepsis patients were included in this study, and 36 cases of them were complicated with ARDS.The expression level of miR-424(0.56±0.17)in the blood of sepsis patients complicated with ARDS was significantly lower than that of sepsis patients without ARDS (0.98±0.26)( t=8.776, P<0.001). The expression of miR-424 was negatively co-rrelated with IL-6( r=-0.627, P<0.01), IL-8 ( r=-0.651, P<0.01) and CRP( r=-0.472, P<0.05)in sepsis patients with ARDS.The expression of miR-424 was positively correlated with PCIS score( r=0.330, P<0.05), P/F ratio ( r=0.592, P<0.001) and albumin ( r=0.496, P<0.05) in sepsis patients with ARDS.The ROC showed that miR-424 [area under curve(AUC)=0.908, 95% CI: 0.856-0.960] could differentiate sepsis patients with ARDS from those without ARDS.Compared with that of the survival group(0.63±0.15), miR-424 of the death group decreased significantly(0.42±0.14)( t=3.890, P<0.05). The decreased miR-424 (AUC=0.845, 95% CI: 0.696-0.995)indicated an increased risk of death in children with ARDS.Multivariate Logistic regression analysis showed that miR-424( OR=0.001, P=0.033)and albumin ( OR=0.553, P=0.040) were independent risk factors for death in ARDS children. Conclusions:miR-424 can help with early diagnosis of sepsis complicated with ARDS, and can be used as a predictor of the prognosis of sepsis children complicated with ARDS.

Objective:To analyze clinical factors related to nosocomial infection in children with extracorporeal membrane oxygenation(ECMO)support.Methods:General data, infection data and relevant factors in children with ECMO support in Bayi Children′s Hospital, the 7 th Medical Center of People′s Liberation Army General Hospital and Henan Provincial People′s Hospital from September 2012 to February 2020 were reviewed.Relevant factors of nosocomial infection in them were analyzed. Results:Among 163 cases, 36(22.1%) children supported with ECMO had infections during the period of ECMO, and 72 pathogenic microorganisms were detected, including 67 bacteria (33 Acinetobacter baumannii, 21 Klebsiella pneumoniae, and 6 Pseudomonas aeruginosa) and 5 fungi.Pathogens from the respiratory system, blood system, urinary tract and abdominal cavity were detected in 45 cases(62.5%), 25 cases (34.7%), 1 case (1.4%), and 1 case (1.4%), respectively.Drug sensitivity analysis of the Acinetobacter baumannii showed that it was the extensively resistant strain.Compared with uninfected children supported with ECMO, ECMO support time[(10.0±6.7) d], hospitalization[(34.0±25.3) d], hospitalization cost[(234 368±113 234) yuan], preoperative oxygenation index(52.8±23.0) and lactate value[(9.6±5.9) mmol/L]were significantly higher in nosocomial infection ones[(4.6±3.2) d, (24.3±19.8) d, (161 416±65 847) yuan, 35.6±10.4, (5.6±5.4) mmol/L] supported with ECMO (all P<0.05). There was no significant difference in the mortality between 2 groups ( P>0.05). In addition, lactate level (9.8 mmol/L) and oxygenation index (36.0±12.7) were significantly higher in died children(2.7 mmol/L, 22.1±10.4) with nosocomial infection during the period of ECMO support than those of survivors (all P<0.05). Multivariate Logistic regression analysis showed that ECMO support time( OR=7.054, 95% CI: 2.206-25.525) and preoperative lactate value( OR=2.250, 95% CI: 1.378-4.611) were independent risk factors of nosocomial infection. Conclusions:Correcting underlying diseases of ECMO supporting and shortening the duration of ECMO can reduce the incidence and mortality of nosocomial infection in children who are supported with ECMO.