Adenovirus,respiratory syncytial virus,influenza virus type A and B,cytomegalovirus and EB virus are the mainly etiology of severe pneumonia in children.New type of virus,such as influenza-H1N1 virus,avian influenza virus(H5N1 or H7N9) can also be epidemic in pediatric population.Ribavirin is effective drugs in the treatment of respiratory syncytial virus and adenovirus pneumonia.Acyclovir or ganciclovir is used for EB virus or immune deficiency and irnmunosuppressive patients with CMV pneumonia.Current opinin strongly recommend treatment with oral oseltamivir as soon as possible in influenza and seasonal influenza.Oseltamivir reduces the severity,duration of the symptoms of influenza,and reduces the frequency of secondary illnesses and exacerbation of underlying conditions.Zanamivir and peramivir may be effective in patients infected with influenza virus,including oseltamivir-resistant virus.Some Chinese medicine such as maxingshigan-yinqiaosan can obtain similar effect of oseltamivir in treatment of influenza virus infection.

Early goal-directed therapy ( EGDT ) emerged as a novel approach for reducing septic shock mortality and the EGDT protocol requires invasive patient monitoring to guide resuscitation with intra-venous fluids.EGDT was incorporated into guidelines published by the international Surviving Sepsis Cam-paign,but remains controversial.Recently,large randomized trials showed that EGDT did not significantly de-crease mortality in patients with septic shock compared with usual care.Fliud resuscitation and monitoring is the most important in septic shock.Therefore the EGDT is still valuable in present stage.Further,development practical methods for accurately assessing optimal fluid administration is needed.

The improvement of oxygenation basis on prone positioning in acute respiratory distress syndrome (ARDS) includes increased end-expiratory lung volume,improved ventilation-perfusion (V/Q) matching,and drainage of secretions.Randomized controlled trials report that prone position ventilation in patients with ARDS tends to reduce mortality rates,especially when used in conjunction with lung protective strategies and greater prone positioning durations.At present,the available data suggest that early prone positioning may provide benefit to ARDS with severe hypoxemia.keeping in mind that a risk of positioning-related complications will have to be taken into account when weighing the risk to benefit for patient with ARDS.There is still limited information available of prone position ventilation application in pediatric ARDS.

Objective To investigate the association of immunological indicators with the severity and prognosis of pediatric patients with severe sepsis.Methods We enrolled 82 pediatric patients with severe sepsis admitted to pediatric intensive care unit (PICU) at Shanghai Children′s Hospital between March 2013 and February 2017 as septic group.Fifteen healthy children served as control group.The blood samples were collected within 24 hours after admission and on day 7 after treatment.The levels of immunoglobulin (IgG,IgM and IgA) were analyzed by automatic special protein analyzer,and the proportion of T-lymphocyte subgroup (CD3+,CD4+,CD8+ and CD19+) and natural killer (NK) cells (CD16+ and CD56+) in peripheral blood were detected by flow-cytometry.Results The levels of IgG,IgM and IgA had no statistical differences between septic group and control group(P>0.05).Interestingly,the proportion of NK cells in pediatric patients with severe sepsis was significantly lower compared to the control group,and the number of NK cells was significantly increased after 7 days treatment compared with that within 24 hours after admission[(3.7±1.9)% vs.(11.5±1.9)%,P<0.05].In addition,the proportions of T-lymphocyte subgroups including CD3+,CD4+ and CD8+ were significantly decreased in patients of septic group compared with control group[(62.8±8.5)% vs.(70.9±2.3)%,(33.3±7.0)% vs.(39.8±1.8)% and(22.6±2.8)% vs.(34.8±15.6)%,respectively,all P<0.05].Moreover,the proportions of NK cells,CD3+ and CD4+ T lymphocytes subsets in peripheral blood of patients with severe sepsis were positively associated with pediatric critical illness score(P<0.05),and negatively associated with pediatric risk of mortality score Ⅲ and the number of dysfunction organs(all P<0.05).Furthermore,the proportions of NK cells and CD3+ and CD4+ T lymphocytes in peripheral blood of non-survivor with severe sepsis were significantly lower than those in the survivor[(1.5±0.5)% vs.(4.7±1.4)%,(55.1±5.0)% vs.(66.4±7.4)%,(29.7±5.2)% vs.(35.0±7.2),P< 0.05].Conclusion The proportion of NK cells and CD3+ and CD4+ T lymphocytes subsets in peripheral blood decreases in pediatric patients with severe sepsis,which is associated with severity and prognosis of severe sepsis.

Objective To investigta e the efficayc of bedside plasma exchange( PE) combined con-tinuous veno-venous hemodiafiltration ( CVVHDF ) in childer n with critical hemo lty ic uremic syndrome ( HUS) .Method s Eight patients with HUS from Pediatric Intensive Care Unit of Shanghai Ch ildren′s Hos-pitalw ere included in the present stuyd .The seveir ty of children was gar ded accordni g to peid atric critiac l ill-ness soc re and pediatric riks ofs core mortalityⅢ.Four of them received continuuo s blood purification treat-me nt.Meanwhile,the clinical manifestation and outcom e of HUS weer analyzed.Results Eight children with HUS weer ni itially trae ted with diuretic and blood transfusion for 12-24 hours.Four ac ses who deteriora-ted aggressively were ep rofr med PE and CVVHDF.Plasauto iQ21 and Prisma flex wereu sed with Pir sma TPE 2000 membrna e plasma separator and AN69 M60 membrane filter respectively.All the 4 patients with critical HUS survived after bedside continuous blood purification treatment.Clinical symptoms and serum bio-chemistry were improved sing ificantly as follows.The average levels of serum creatinine and lactate dehydro-genase decreased obviously(318μmol/L vs.162μmol/L;1 963 U/L vs.407 U/L,respectively).In addi-tion,platelet count increased significantly(40 ×109/L vs.97 ×109/L) .Eventually,symptoms disappeared in these 4 patients.Conclusion The combined therapy of PE and CVVHDF in HUS could stabilize fluid acid-base equilibrium,prevent hemolysis and improve the renal function.

Objective To study the changes of P-selectin and E-selectin in pediatric patients with critical illness ,and analyze their relationship with the severity and prognosis of diseases.Methods Forprospective study,42 critically ill patients admitted in pediatric intensive care unit (PICU ) from September,2012 to March,2013 as critically ill group were enrolled,and blood specimens were collected with 24 hours after admission.Another 42 cases blood samples were collected from children's physical examination as control group.The severity of the critically ill patients were evaluated by Pediatric Critical illness Score (PICS)and Pediatric risk of score mortality (PRISM)-III.The levels of serum P-selectin and serum E-selectin were measured by double antibody sandwich enzyme-linked immunoassay (ABC-ELISA). Results P-selectin and E-selectin in control group children and critically ill patients group were (37.23 ± 8.99)ng/mL,(36.24 ±17.82)ng/mL,and (107.24 ±35.53)ng/mL,(114.93 ±40.17)ng/mL, respectively.There were statistical differences between two groups (P=0.000).The levels of P-selectin and E-selectin in acute phase were higher than that of levels in recovery phase in critically ill group (P =0.000).Negative correlation was observed between P-selectin concentration and the PCIS score (r =-0.673,P=0.000),as well as E-selectin (r=-0.548,P=0.000).P-selectin level and E-selectin level based upon PRISMⅢ≥10 group were significantly higher than they in PRISMⅢ <10 group (P=0.003,P=0.014).In critically ill children,the differences in P-selectin,E-selectin were significant higher in death patients (P=0.003;P =0.000).Compared with the non-sepsis illness group,the level of P-selectin and E-selectin in the severe sepsis patients were significantly higher (P =0.04,P =0.025 ). Conclusions The levels of P-selectin and E-selectin are closely related to the severity and prognosis in critically ill children.Measuring the level of P-selectin and E-selectin could be used as a judegment the severity and to understand pathological physiological process.

Objective To investigate the changes of epithelial neutrophil activating peptide-78 (ENA-78) in the serum of patients with critical illness,and to analyze the relationship between the severity and prognosis.Methods Prospective case-control study was performed,and 42 cases of critically ill patients admitted to Pediatric Intensive Care Unit,Children's Hospital Affiliated to Shanghai Jiaotong University from Sep.to Nov.2013 were selected as critically ill group,blood specimens were collected within 24 hours and 7 days after their admission.Another 42 cases of blood samples were collected during physical examinations in this hospital as control group.The severity of critically ill patients were graded by Pediatric Critical Illness Score (PICS) and Pediatric Risk of Score Mortality (PRISM) Ⅲ,and the serum ENA-78 was measured by double antibody sandwich enzyme-linked immunoassay.Results 1.The level of ENA-78 in the control group was (0.44 ± 0.28) ng/L; ENA-78 in acute phase and recovery phase of critically ill group were (2.85 ± 0.89)ng/L and (1.00 ± 0.64)ng/L,respectively,there were statistical differences between control group and critically ill group,acute phase group and recovery phase group (all P =0.000).2.The negative correlation was observed between ENA-78 concentration and PCIS score(r =-0.724,P =0.000).ENA-78 in PRISM Ⅲ ≥ 10 group was significantly higher than that in PRISM Ⅲ＜ 10 group(P =0.000).The ENA-78 between death group and the survival group was significantly different(P =0.000).3.ENA-78 in patients with severe infection was higher than that in the non-infectious cases(P =0.000).4.With the organ dysfunction expanded ENA-78 rose accordingly,and the difference was statistically significant (P =0.000).Conclusions The level of ENA-78 is different in critically ill patients in children.It can provide reference of assessing the severity of disease and predicting prognosis by determing the ENA-78 level.

Obej ctive Abnormal proliferation of T cells plays an important role in the development of autoimmune diseases. The article aimed to study the inhibitory effect of small molecule compound BD691 on T cell proliferation and its mechanism. Methods Human peripheral blood T-lymphocytes were isolated and purified by the immunomagnetic microbeads,then T cells were ac-tivated with anti-CD3/CD28 mAbs or alloantigen.The inhibitory effect of BD691 on activated T cell proliferation, the cytotoxic effect BD891 on resting T cells and the expression of activated T cells marker CD25 were measured by flow cytometry.Furthermore, ELISA was used to detect the secretion of cytokines associated with T cell differentiation. Results BD691 significantly inhibited the prolif-eration of T cells being stimulated by anti-CD3/CD28 mAb or alloantigen in a dose-dependent manner, and IC50 values are (8.5 ± 1.5)μmol/L and (7.2 ±1.3)μmol/L, respectively.However, BD691 had no obvious cytotoxic effects on resting T cells and periph-eral blood mononuclear cells, even at a high concentration ( up to 100μmol/L) .In T cells which were not activated by anti-CD3/CD28 mAb, the percentage of CD25+T cells is only 1.6%of the total cells, while the number increased to 68% after activating treatment.Mean-while, in T cells which were activated by 0, 3.3, 10, 30μmol/L BD691, no obvious change of CD25 expression were observed, while immunosuppressant FK506 (0.1μmol/L) significantly decreased the expression of CD25 +T cells (14.9%).In unactivated T cells, 95.6%cells were at G0/G1 phase, while after activation, the percentage of cells at G0/G1 phase reduced to 57.7%.In addition, BD691 inhibited the secretion of IFN-γ, IL-6 and IL-17 in activated T cells, but had no effects on the secretion of IL-2, IL-4 and IL-10. Co nclusion BD691 exerts no effects on T cell activation, but it inhibits T cell proliferation by inducing T cell cycling arrest at G0/G1 phase.Moreover, BD691 inhibits the secretion of key cytokines (such as IFN-γ, IL-6, IL-17) closely related to the differ-entiation of Th1 and Th17 cells.The results suggest that BD 691 is a potential lead compound to develop a new immunosuppressant for the inhibition of abnormal proliferation and differentiation of T cells.

Objective Benzothiazole derivative BD960 has immunosuppressive activity after cell -based assays for high-throughput screening.The paper aimed to investigate the involved mechanism of BD960 on T cell proliferation. Methods Human peripheral blood T-lymphocytes were isolated and purified by the immunomagnetic microbeads.Then the T cells were activated by anti-CD3/anti-CD28 mAbs or alloantigen.The effect of BD960 on activa-ted T cell proliferation, the cytotoxic effect BD960 on resting T cells and the expression of activated T cells marker CD25 were measured by flow cytometer.Cytokine levels, including IL-2, IL-4, IL-6, IL-10, IL-17A and IFN-γ, were determined by ELISA. Results BD960 significantly inhibited the proliferation of T cells stimulated by anti-CD3/anti-CD28 mAb or alloantigen in a dose-dependent manner.The IC50 value is (2.3 ±0.3)μmol/L or (2.5 ±0.3)μmol/L, respectively.Moreover, BD960 had no obvious cytotoxic effects on rest-ing T cells and peripheral blood mononuclear cells, even at a high concentration ( up to 100μmol/L) .The ratio of CD25 expression on T cell was 69.7%after stimulated by Anti-CD3/CD28 mAbs with 72 h, the concentration (0.625、2.5、10)μmol/L of BD960 also had no potent effects on the ratio, but 0.1μmol/L FK506 could inhibit CD25 expression as low as 9.4%.The G0/G1 phase of activated T cells was 58.5%after stimulated by BD960 with 96 h.BD960 could induce cell cycle arrest at the G0/G1 phase in activated T cells with the increase of concentration and RAPA in the concentration of 0.1 μmol/L was 91.5%.In addition, BD960 (0.625、2.5、10)μmol/L could inhibit the secretion of IFN-γ, IL-6 and IL-17 in activated T cells with the increase of concentration, without any effects on the secretion of IL-2, IL-4 and IL-10. Conclusion BD960 not only exerts the inhibition on the late stage of T cell activation of cell proliferation but also inhibits the secretion of inflammatory cytokines, such as IL-6, IL-17 and IFN-γ, while the mechanism of BD960 on T cell proliferation was not the same as FK506.As a result, BD960 has the potential to be the lead compound to develop a new immunosuppressant.

Objective: To investigate the incidence and prognosis of hypophosphatemia in critically ill children treated with continuous blood purification (CBP). Methods: The medical records of the critically ill patients, who were treated with CBP, admitted to pediatric intensive care unit (PICU) of Shanghai Children's Hospital from May 2014 to April 2017 were retrospectively analyzed. The serum phosphorus levels were tested before CBP, at 48-72 h during CBP, at the end of CBP and on the next day after CBP finished. Phosphorus supplement was given to the children with severe hypophosphatemia. Results: A total of 85 patients met the inclusion criteria. The serum phosphorus levels at the 4 indicated time points were (1.4±0.5), (0.7±0.3), (0.8±0.3), (0.9±0.4) mmol/L, respectively (F=45.21, P<0.05). Among the children, 66 cases (78%) had hypophosphatemia during CBP. The incidences of moderate and severe hypophosphatemia were 32 (48%) and 9 (14%), respectively. There were 41 patients with CBP replacement rates of (35-49) ml/(kg·h), while 44 patients with CBP replacement rates of 50-70 ml/(kg·h). There were significant differences at 48-72 h during CBP, the end of CBP and on the next day after CBP ((0.8±0.4) vs. (0.5±0.2), (1.0±0.3) vs. (0.6±0.2), and (1.1±0.4) vs. (0.8±0.2) mmol/L; t=7.672, 4.060, 14.440, P<0.05). Atotal of 9 cases were treated with sodium glycerophosphate. Among the 85 children, 24 (28%) patients died while 61 (72%) survived. There were no significant differences between the two groups in serum phosphorus levels at the indicated time points ((1.4±0.5) vs. (1.4±0.5), (0.7±0.3) vs. (0.7±0.3), (0.7±0.3) vs. (0.8±0.3), and (1.0±0.3) vs. (0.9±0.3) mmol/L, respectively, P>0.05). Conclusions Hypophosphatemia is prone to occur during CBP, which probably related to the replacement rate. There was no significant relationship between hypophosphatemia and mortality in critically ill children after giving phosphorus supplementation.