Severe hand, foot and mouth disease (HFMD) may lead to the high mortality due to brainstem encephalitis, encephalomyelitis, pulmonary edema/pulmonary hemorrhage and cardiopulmonary failure in children. Some patients are complicated with severe gastrointestinal dysfunction, manifested as abdominal distension, intestinal paralysis, bleedy stool, haematemesis. "Catecholamine storm" and viral systemic inflammatory response syndrome may be the main mechanisms for gastrointestinal dysfunction. It is important to focus on the monitoring of gastrointestinal dysfunction of severe HFMD. Preventing and avoiding iatrogenic damage of gastrointestinal dysfunction are main treatment strategies.

Multidrug-resistant organisms are growing worldwide public health problem and few therapeutic options remain available.The traditional antimicrobials (glycopeptides) for multidrug-resistant Grampositive infections are declining in efficacy.New antimicrobials that are presently available are linezolid,daptomicin and tigecycline,which have well-defined indications for severe multidrug-resistant organisms infections.Unfortunately,the therapies available for multidrug-resistant Gram-negatives including carbapenem-resistant Pseudomonas aeruginosa,Acinetobacter baumannii and Enterobacteriaceae are limited to colistin and tigecycline only.Distribution of multidrug-resistant organisms are changing in recent years.Strains of multidrug-resistant organisms were dominated by Gram-negative bacteria in most hospital particularly in intensive care unit.Multidrug-resistant/pandrug-resistant Pseudomonas aeruginosa,Acinetobacter baumannii are increasing rapidly in trend.Strategy that includes surveillance,infection control procedures,isolation and antimicrobial principle should be emphasized and implemented to reduce multidrug-resistant organism diffusion.

Pediatric acute liver failure has a high mortality.Liver transplantation is the only definite treatment.Extracorporeal liver support can be employed as a strategy for bridging to transplantation or recovery.There are three types of device for temporary support:biological,non-biological (also called artificial) and bio-artificial (hybrid techniques).Early non-biological device including hemodialysis,hemoperfusion/plasma perfusion and plasmapheresis have improved biochemical efficacy,but there are little data for clinical end points.Continuous blood purification and the combination of various non-biological methods such as the molecular adsorbent recirculatory system and Prometheus(R) are new extracorporeal blood purification therapy.The results of many experimental and clinical trials have improved the efficacy of the above mentioned methods.

MicroRNAs are small,single-stranded and non-coding RNAs.MicroRNAs modulates gene expression by binding themselves to complementary sites of target genes.It had been discovered that micmRNAs modulate sepsis in multiple levels.Through targeting Ca2+/calmodulin-dependent protein kinase Ⅱ,miR-152 and miR-148 impair innate response and antigen presentation,and also suppress proliferation of antigen specific CD4 + T cells; miR-29 family regulate cellular immunity through setting the threshold in thymic involution; MicroRNA-17-92 plays a causative role in B cell lineage; miR-146 and miR-155 down-regulate proinflammatory cytokines through suppressing components of pattern recognition receptors,while miR-132 through acetylcholinesterase degeneration.miR-124 degenerates mRNA of glucocorticoid receptorαand results in glucocorticoid resistant in treatment of sepsis.Immune regulation of microRNAs in sepsis is briefly described in this paper.

Hemodynamics is monitoring a series of physiological and pathological parameter changes such as blood flow,the chamber pressure of the heart,pressure or resistance of cardiovascular and cardiopulmonary system.Traditional hemodynamic monitoring in septic shock manily includes central venous pressure,cardiac index,blood lactate and pH.In recent years,expanded non-invasive or invasive monitoring technologies include central venous or mixed venous oxygen saturation,continuous ultrasound associated with underlying cardiac output monitoring and pulse indicator continuous cardiac output.Macro-hemodynamic,metabolic and microcirculatory parameters constitute a new hemodynamics network.In order to properly assess the patient's blood volume and circulation function and to overcome the limitations of a single parameter,it is need to emphasize analysis and integration of the various parameters.

According to the hemodynamic changes,circulatory failure is divided into warm shock and cold shock,and severe circulatory failure often co-exist in both conditions in children.Circulatory failure in children is characterized by rapid change on hemodynamic status,pathologic vasodilation,relative or absolute hypovolemia,myocardial depression,altered blood flow distribution,and metabolic disorders.Therapeutic strategies include improving cardiac output and tissue perfusion,achieving SVO2＞70％ and cardiac index to 3.3～6.0 L/( min· m2 ),ensuring the intravascular blood volume and cardiac load.

Objective To investigate the effects of erythropoietin (EPO) on neuron apoptosis and expression of caspase-3 after excitotoxic brain injury induced by ibotenic acid (Ibo) in mice during different developmental stages.Methods A total of 144 healthy KM mice aged 7 d (n =48),21 d (n =48) and 42 d (n =48) were selected,and those of the same age were randomly (random number) divided into 3 groups:sham surgery group (n =16),Ibo group (n =16) and EPO treated group (n =16).Brain injury model was established by Ibo 1μl (5 μg) injected into left hippocampus.In EPO treated group,intraperitoneal injection of 5000 U/ (kg · d) EPO was performed for 3 consecutive days after injection of 1 μl Ibo into left hippocampus.Mice in sham surgery group and Ibo control group were treated with saline in the same dose instead.The pathological changes of neurons in hippocampus were observed 3 d after modeling in each group with Nissl staining,the level and activity of caspase-3 in hippocampus were determined by ABCELISA and spectrophotometry.Result After modeling,degeneration and death of neurons in hippocampuswith substantially decrease in number of intact neurons were found under light microscopy in Ibo group in comparison with sham surgery group.However,compared with the Ibo group,pathological changes in EPO treated group were less serious.The level of caspase-3 in Ibo control group was significantly higher than that in sham surgery group (P＜0.05),and the level of caspase-3 in EPO treated group was significantly lower than that in Ibo group (P ＜ 0.05).Conclusions The level of caspase-3 is significantly up-regulated in hippocampus of mice with Ibo-induced brain injury,leading to neuron apoptosis.EPO mitigates brain injury and plays a role of protection on brain function,suggesting the mechanism is attributed to decrease in caspase-3.

Sepsis is the leading cause of acute kidney injury (AKI) in pediatric intensive care unit.Development of AKI during sepsis increased patient morbidity,predicts higher mortality and days of stay in the intensive care unit.The mechanisms behind AKI in sepsis remain controversial but were believed to be complex and multi-factorial.The pathophysiology of AKI in sepsis involved intrarenal hemodynamic changes,endothelial dysfunction,infiltration of inflammatory cytokines.The new markers of neutrophil gelatinase-associated lipocalin as the representative is helpful for early diagnosis of AKI.Renal replacement therapy (RRT)is the main treatment of sepsis related AKI.At present,the model,dose and exact timing of RRT is not well defined.A widely accepted viewpoint is that the injury stage of RIFLE diagnostic criteria and fluid overload up to 10％ ～ 20％ is the beginning of the most appropriate chance of RRT.

The presence and persistence of systemic and lung inflammation in children with acute respiratory distress syndrome (ARDS) is the basis for the use of corticosteroids as a therapeutic agent.The trial of ARDS treated with high-dose short-course corticosteroids showed no benefit,even increase motality.At present,the results of randomized controlled trial and meta-analysis suggested that low-dose and replacement-dose methylprednisolone [1-2 mg/(kg· d)] or equivalent types of corticosteroids may decrease the fatality rate,reduce staying days in ICU and the duration of mechanical ventilation.Use of corticosteroids for ARDS in children is still lack of multicenter randomized controlled trial.

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.