Z1, a novel DENV2 NS5 RdRp small molecular inhibitor, inhibits DENV2 replication and infection / 中国药理学通报

Aim To screen novel NS5 inhibitors a-gainst dengue virus ( DENV) replication. Methods His-tagged DENV2 NS5 RNA-dependent polymerase ( NS5 RdRp ) was expressed and purified in BL21 cells. The binding ability of the small molecules to NS5 polymerase was determined by SPR assay. The activity of dengue inhibition by Z1 was determined by CPE, LDH and plaque assay. RNA synthesis was as-sessed by Real-time PCR. The dsRNA synthesis and viral proteins were detected by immunofluorescence as-say. The level of viral proteins was examined by West-ern blot. The stage of DENV life cycle was evaluated by time of drug-addition assay. Results A small mo-lecular Z1 was discovered, which could bind to NS5 RdRp. Z1 inhibited DENV2 RNA replication, synthe-sis of dsRNA and protein synthesis in post-entry stage of dengue life-cycle. Cell based assay confirmed that Z1 inhibited DENV-induced cell death with EC50 val-ues of 4. 75μmol·L-1 . Conclusions The novel NS5 inhibitor Z1, inhibits DENV2 RNA replication, protein synthesis and release of progeny virus, which may be severed as an anti-DENV2 antiviral drug for further de-velopment.

Contents of serum albumin after surgical operation in children with acute intussusception / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the changes of serum albumin contents after operation and investigate whether post-operational serum albumin contents are correlated with the disease severity in children with acute intussusception.</p><p><b>METHODS</b>Serum albumin contents were measured using the automatic biochemistry analyzer in 32 children with mild acute intussusception and 21 children with severe acute intussusception 1 day after surgical operation. After 5 days combined treatment, serum albumin contents were re-examined. Thirty healthy children severed as the control group. The correlation between post-operational serum albumin contents and critical illness scores was evaluated.</p><p><b>RESULTS</b>Serum albumin contents in the mild (34.2+/-6.5 g/L; P<0.05) and the severe intussusception groups (25.8+/-7.5 g/L; P<0.01) 1 day after operation were significantly lower than those in the control group (37.1+/-4.1 g/L). There were significant differences in serum albumin contents between the mild and the severe intussusception groups (P<0.05). Five days after operation, serum albumin contents in the mild intussusception group significantly increased (37.1+/-11.4 g/L; P<0.05), while serum albumin contents in the severe intussusception group did not differ from those 1 day after operation. There was a positive correlation between serum albumin contents on the 1st day after operation and the critical illness scores (r=0.879, P<0.01).</p><p><b>CONCLUSIONS</b>Serum albumin contents decreased on the 1st day after operation and were correlated with the disease severity in children with acute intussusception. Hypoalbuminemia lasted for a longer period in severe cases. The post-operational measurement of serum albumin contents may be useful in the evaluation of the severity for children with acute intussusception.</p>

Risk factors for death in children with septic shock / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To identify the risk factors for death in children with septic shock.</p><p><b>METHODS</b>Clinical data of 53 children with septic shock admitted to the Yuying Children's Hospital between January 2006 and July 2008 were retrospectively studied. Risk factors for death were assessed using univariate analysis and logistic regression analysis.</p><p><b>RESULTS</b>Nineteen cases died out of 53 children with septic shock. Univariate analysis and logistic regression analysis showed that arterial blood pH value<7.0 (OR=89.66), hypotension (OR=84.00), the pediatric critical illness score<70 (OR=60.00), the number of organ dysfunction>or=3 (OR=38.98), incompletion of volume resuscitation within 6 hrs after shock (OR=26.41), and no administration of effective antibiotics within 1 hr after shock (OR=11.43) and of vasoactive drugs (OR=75.68) were risk factors for death in children with septic shock.</p><p><b>CONCLUSIONS</b>A low arterial blood pH value (<7.0), hypotension, a pediatric critical illness score (<70) and the number of organ dysfunction>or=3 are related to a high mortality in children with septic shock. If the volume resuscitation can be completed within 6 hrs after shock, effective antibiotics can be administered within 1 hr after shock, and vasoactive drugs can be used properly, the outcome of children with septic shock may be improved.</p>

Clinical analysis of community-acquired Pseudomonas aeruginosa septic shock / 中华儿科杂志

<p><b>OBJECTIVE</b>This study sought to analyze the clinical manifestations and intervention of fulminant septic shock in community-acquired Pseudomonas aeruginosa septicemia.</p><p><b>METHODS</b>We retrospectively reviewed the medical records for diagnosis, antibiotic therapy, clinical course of septic shock, respiratory support, laboratory data etc.</p><p><b>RESULTS</b>Eight of nine cases with P. aeruginosa septic shock died. Fever (nine cases) and cough (three cases) or diarrhea (3 cases) were the 2 most common initial symptoms, three cases developed skin gangrenosum later. Pseudomonas aeruginosa infection was not considered in any of the cases before death or blood culture showed positive result. Only 3 cases were initially treated with susceptible antibiotic regimen but no anti pseudomonas combination therapy was applied, susceptible antibiotic monotherapy was applied in 7 cases after transfer to the ICU. The mean latency of shock occurrence was 5.1 hours (range 0 to 21 hours) after admission, the mean duration from the occurrence of shock to death was 13.8 hours (range, 1 - 32 hours). All the patients were transfer red to ICU for shock, the appropriate resuscitation of shock patients was delayed by 49.3 minutes (range 25 - 80 minutes) by transfer. Only two cases were diagnosed and treated for shock on admission; after transferred to ICU, only 5 patients were diagnosed as having shock, and only 3 received anti-shock treatment. Eight of the patients died of persistent shock. In 6 patients who died, mechanical ventilation was not applied until cardiac arrest occurred. All the patients had hypoalbuminaemia, elevated serum C-reactive protein concentration, leukopenia and 6 cases had DIC.</p><p><b>CONCLUSION</b>The initial presentation of the cases with community-acquired Pseudomonas aeruginosa septicemia was nonspecific with fever and cough or diarrhea. Clinicians often underestimated the severity of the infection, few patients received effective antimicrobial therapy. The authors suggest that an anti-pseudomonas antibiotic should be included in the initial empiric antibiotic regimen to cover P. aeruginosa high-risk patients; the front-line clinician should be educated for early recognition and aggressive resuscitation of P infection. aeruginosa septicemia.</p>

Three cases of enterovirus 71 infection with pulmonary edema or pulmonary hemorrhage as the early clinical manifestation / 中华儿科杂志

<p><b>OBJECTIVE</b>To recognize the clinical features of the enterovirus 71 (EV71) infection with pulmonary edema or pulmonary hemorrhage as a fulminant and often fatal illness.</p><p><b>METHODS</b>We retrospectively reviewed the medical records of the three cases with EV71 infection for clinical manifestation, laboratory data, medications, outcome etc.</p><p><b>RESULTS</b>All the cases were infants and they all died. These infants had no skin or mucosal lesions, however, they had sudden onset of cyanosis and tachypnea 1 to 2 days after the onset of the febrile disease with vomiting. All these 3 cases were misdiagnosed and were treated for shock on admission. Pulmonary hemorrhage was not considered in any of the cases on admission. All the cases received tracheal intubation when foamy secretions were discharged from mouth and nose of the patients and notable cyanosis was noted. After intubation, all had pink foamy fluid flew out from the endotracheal tube. The patients had hyperglycemia and limb weakness, two had tachycardia, and hypertension was found in one case. Chest X-ray showed bilateral or unilateral widespread air space opacity, but the cardiac size and shape were normal. All the patients had leucocytosis. EV71 infection was confirmed by detection of specific sequences of the virus in throat swab and tracheal secretions samples and in one case in cerebrospinal fluid sample.</p><p><b>CONCLUSION</b>Pulmonary edema or pulmonary hemorrhage occurred in the 3 cases with EV71-infected infants. The initial presentation was often nonspecific with fever and vomiting, and sudden appearances of cyanosis, tachypnea, tachycardia, hypertension or hypotension, limb weakness may suggest pulmonary edema or hemorrhage. Excessive fluid resuscitation may deteriorate the illness, on the contrary, fluid restriction and inotropic agents, and early intubation with positive pressure mechanical ventilation may be the proper treatment.</p>

Clinical Analysis of 7 Children with Fatal Virus Encephalopathy / 实用儿科临床杂志

Objective To explore clinic manifestations and laboratory investgation of virus encephalopathy.Methods The clinical course,cerebrospinal fluid(CSF),hepatic dysfunction,computerized tomography of 7 cases treated in our hospital from October 1999 to March 2005 were retrospectively reviewed.Results Seven cases of virus encephalopathy were typically associated with a suddent onset of high fever,severe convulsion,rapidly progressive coma,marked elevations of alanine aminotransferase(AST) and aspartate transaminase(ALT).Four cases died,3 cases had severe sequelae.Blood ammonemia was normal,brain CT scans revealed peripheral or basal nuclei low-density areas.Conclusion Children with a sudden onset of high fever,severe convulsions,rapidly progressive coma may have a poor prognosis.

Changes of Serum Gastrin,Plasma Motilin and Somatostatin in Critically Ill Children and Those Clinical Significances / 实用儿科临床杂志

Objective To explore the changes of serum gastrin(GAS),plasma motilin(MTL) and somatostatin(SST) in critically ill children with gastrointestinal dysfunction(GID).Methods According to pediatric critical illness score,75 cases were divided into greatly critical group(score90).Fifty cases of greatly critical and critical group were divided into GID group and non-GID group.The levels of serum GAS,plasma MTL and SST were detected on an empty stomach at acute stage and convalescence stage,comparing with those of normal control group,and then,the relationship between the levels of serum GAS,plasma MTL,SST and GID,the severity of disease were analyzed.Results At acute stage,the levels of serum GAS and plasma MTL of greatly critical group and critical group were higher than those of normal control group,the levels of plasma SST of greatly critical group and critical group were lower than that of normal control group,the more severe condition of critical children,the higher level of serum GAS and plasma MTL,the lower level of plasma SST.At convalescence stage,the level of serum GAS and plasma MTL of the greatly critical group and critical group decreased and the level of plasma SST increased.The levels of serum GAS and plasma MTL of GID group were higher than those of non-GID group,but the level of plasma SST of GID group was lower than that of non-GID group.Conclusion The level of serum GAS,plasma MTL and SST can be used to assess the severity of illness and prognosis,judge the change of disease and determine the efficacy of treatment programs,and detect gastrointestinal functional lesion.

Severity of Systemic Inflammatory Response to Type B Epidemic Encephalitis and Blood Tumor Necrosis Factor Complicated with Respiratory Failure / 实用儿科临床杂志

Objective To study the severity of systemic inflammatory response to type B epidemic encephalitis and blood tumor necrosis factor complicated with respiratory failure.Methods Fourteen children with type B epidemic encephalitis were divided into two groups;6 cases in group one with respiratory failure were given mechanical ventilation and the other 8 cases had normal respiration.Breat-hing pattern,respiratory rate,GCS scores,daily dosage of sedatives were observed before endotracheal intubation;while heart rate,temperature,WBC,CRP,TNF were measured.Results Patients in respiratory failure group were given a small dosage of Luminal;there was no significant difference in GCS between two groups treated with compound Wintermin.The heart rate,temperature,WBC,CRP,TNF levels in respiratory failure group were significantly higher than those in normal respiratory group.Conclusions The severity of systemic inflammatory response is more severe in epidemic type B encephalitis with respiratory failure than the controls.Significant increase in blood TNF may be an important factors to cause peripheral respiratory failure.