Objective:To explore the factors affecting the prognosis of severe pediatric acute respiratory distress syndrome (ARDS) after receiving extracorporeal membrane oxygenation (ECMO) support.Methods:It was a multicenter prospective observational study. A total of 95 children with severe ARDS who were treated with ECMO salvage therapy from January 2018 to December 2022 in 9 pediatric ECMO centers in China were enrolled in the study. The general data, disease severity, organ function, comprehensive treatment and prognosis were recorded, and they were divided into survival group and death group according to the outcome at discharge. T test, chi-square test, multivariate Logistic regression and mixed linear model were used to analyze the relationship among baseline before ECMO treatment, some important indicators (pediatric critical scores, platelet count, albumin, fibrinogen, etc) during ECMO treatment and prognosis. Results:Among the 95 children with severe ARDS who received ECMO, 55 (58%) were males and 40 (42%) were females, aged 36.9 (0.5, 72.0) months. Twelve children (13%) were immunodeficient. Sixty-eight (72%) children were treated with venous artery (VA) mode and 27 (28%) with venous vein (VV) mode. The discharge survival rates of overall, VA, and VV mode children were 51% (48/95), 47% (32/68), and 59% (16/27), respectively. The number of immunodeficient children in the death group was higher, and there were lower pediatric critical scores, platelet count, albumin, fibrinogen and arterial oxygen partial pressure/fraction of inspired oxygen (PaO 2/FiO 2), higher ventilator driving pressure (ΔP), oxygenaion index (OI), and longer ARDS duration before ECMO (all P<0.05). There were no statistically significant differences in other indicators, including age, gender, weight, and ECMO mode among different prognostic groups (all P>0.05). High ΔP, high OI, low P/F, and low albumin were high-risk factors affecting prognosis(all P<0.05). After further grouping, it was found that ΔP≥25 cmH 2O (1 cmH 2O=0.098 kPa), P/F≤67 mmHg (1 mmHg=0.133 kPa) and OI≥35 were the thresholds for predicting poor prognosis ( P<0.05). From 24 h after ECMO, there were significant differences in ΔP, P/F and OI between the dead group and the survival group (all P<0.05), and the differences gradually increased with the ECMO process. The platelet level was significant from 7 days after ECMO ( P<0.05) and gradually expanded. Blood lactate levels showed a significant difference between the 2 groups on before and after ECMO ( P<0.05) and gradually increased from 24 h after ECMO. Conclusions:The risk factors affecting the prognosis of severe ARDS in ECMO include high ΔP, high OI, low P/F and low albumin purification therapy before ECMO. The gradual decrease of ΔP, OI and increase of P/F from 24 h of ECMO predicted a good prognosis, while the gradual increase of lactate after ECMO application showed a poor prognosis.

Objective To investigate the association between four single nucleotide polymorphisms(SNP)(rs9340 in MAPK1,rs14804 in NRAS,rs712 and rs7973450 in KRAS)in the 3'UTR of ERK1/2 signaling pathway-related genes and non-small cell lung cancer(NSCLC).Methods A total of 478 NSCLC patients and 480 healthy controls were enrolled in this study.Four SNPs were genotyped by using TaqMan assays.The association between the four SNPs and NSCLC was analyzed.Results The distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the non-small cell squamous cell carcinoma(SCC)group(P = 0.009),suggesting that the G allele of rs9340 may be a protective factor for non-small cell lung squamous cell carcinoma(OR = 0.67,95%CI:0.50～0.91).In addition,in the<50 years age group,the distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the NSCLC group(P = 5.07×10-4),indicating that the G allele of rs9340 may be a protective factor for NSCLC(OR = 0.46,95%CI:0.29～0.72).Conclusion The SNP rs9340 in MAPK1 may be associated with the risk of NSCLC.

Objective:To evaluate the effect of obesity on in-hospital prognosis of patients with mechanical ventilation in PICU.Methods:We enrolled 301 patients who received mechanical ventilation treatment in PICU at Chongqing Medical University Affiliated Children′s Hospital, between June 2015 and June 2020, and stratified them into obese group(49 cases), overweight group(96 cases)and normal weight group(156 cases). Obesity was determined by reference to the growth and development standards published by the World Health Organization.Indicators included PICU hospital mortality, duration of mechanical ventilation, length of stay in the PICU, length of stay in hospital and the rates of duration of mechanical ventilation>21 days, re-intubation, tracheotomy, ventilator-associated pneumonia, central venous catheter infection, deep venous thrombosis and pressure ulcers were observed.The influence of obesity on hospitalized prognosis of children in PICU was analyzed.Results:In obesity group, overweight group and normal weight group, PICU hospital mortality(2.0%, 10.4%, 12.2%), the rate of tracheal reintubation(14.3%, 5.2%, 9.0%), the rate of tracheotomy (2.0%, 1.0%, 2.6%), the rate of deep venous thrombosis(8.2%, 3.1%, 5.8%), and the rate of pressure ulcers(4.1%, 7.3%, 1.9%) did not have significant difference(all P>0.05). No ventilator-associated pneumonia and central venous catheter infection occurred in three groups.There were no significant differences in the PICU hospital mortality, duration of mechanical ventilation, length of stay in the PICU, length of stay in hospital among the three groups(all P>0.05). Obesity was not an independent risk factor for in-hospital death in PICU patients on mechanical ventilation( B=1.975, SE=1.038, OR=7.206, 95% CI 0.942~55.127, P=0.057). Conclusion:Obesity does not prolong the duration of mechanical ventilation, length of stay in PICU and total length of stay in hospital, as well as not increase the rate of duration of mechanical ventilation>21 days, re-intubation, tracheotomy, ventilator-associated pneumonia, central venous catheter infection, deep venous thrombosis and pressure ulcers.Obesity is not an independent influencing factor for in-hospital death in patients with mechanical ventilation in PICU.

Objective:To explore the risk factors for mortality in pediatric acute respiratory distress syndrome (PARDS) requiring extracorporeal membrane oxygenation (ECMO) support.Methods:Clinical data of 109 patients with severe PARDS supported by ECMO, who were hospitalized in 6 ECMO centers in China from September 2012 to February 2020, were retrospectively analyzed. They were divided into survival group and death group according to the prognosis. Chi-square test and rank sum test were used to compare the variables between the two groups, including the demographic data, laboratory examination results, clinical data before and after ECMO, and other supportive treatment. Univariate and multivariate Logistic regression models were used to analyze the prognostic risk factors.Results:In these 109 cases, 54 died and 55 survived. Compared with the survival group, the death group had higher incidences of acute kidney injury (AKI) (48.1% (26/54) vs. 21.8% (12/55) , χ2=8.318, P=0.004) and coagulation dysfunction (22.2% (12/54) vs. 7.3% (4/55) , χ2=4.862, P=0.027), and higher rate of renal replacement therapy (48.1% (26/54) vs. 21.8% (12/55) , χ2=9.694, P=0.008) during ECMO support. Logistic regression analysis showed that continuous renal replacement therapy (CRRT) and AKI were independent risk factors for death in patients with severe PARDS requiring ECMO support ( HR=3.88,95% CI 1.04-14.52, HR=4.84,95% CI 1.21-19.46, both P<0.05). Conclusion:AKI and CRRT are independent risk factors for predicting mortality in patients with severe PARDS requiring ECMO support.

Objective: To investigate the effects of direct-acting antiviral agents (DAA) therapy on the frequency of myeloid-derived suppressor cells (MDSC) and their subset of monocytic myeloid-derived suppressor cells (M-MDSC) in chronic hepatitis C (CHC) patients. Methods: A total of 32 treatment-naive CHC patients and 16 healthy controls were recruited at Third Affiliated Hospital of Sun Yat-Sen University from June 2016 to June 2017. The peripheral blood mononuclear cells (PBMC) were separated from the peripheral blood of patients with CHC before DAA therapy, at four weeks after DAA therapy, at 12 weeks after DAA therapy and 12 weeks after the end of DAA therapy. The frequencies of MDSC and M-MDSC were detected by the flow cytometer. The t test, U test and chi-square test was employed to analyze the data. Results: All the 32 treatment-naive patients achieved the rapid virological response and no virological breakthrough was observed. Before DAA therapy, the frequency of MDSC in CHC patients was 2.18%, which was higher than healthy individuals (0.60%; Z=-4.593, P<0.01), and positively correlated with the plasma levels of hepatitis C virus (HCV) RNA (r=0.688, P<0.01) and aspartate aminotransferase (r=0.735, P<0.01). After four weeks of DAA therapy, the frequency of MDSC decreased significantly to 1.07%, with no statistical significance compared to the controls (Z=-1.221, P>0.05). However, at 12 weeks after DAA therapy, the MDSC frequency increased, with statically significance compared to the controls (1.64% vs 0.60%, Z=-3.117, P=0.002). At 12 weeks after the end of DAA therapy, the MDSC frequency had decreased to 1.29% again, with no statistical significance compared to the controls (Z=-1.387, P=0.664). The changes of M-MDSC frequency were slightly different. Before DAA therapy, the frequency of M-MDSC in CHC patients was higher compared to healthy controls (1.66% vs 0.81%, Z=-2.745, P<0.01). The frequencies of M-MDSC were 0.91%, 1.09% and 1.10% at four, 12 weeks after DAA and 12 weeks after the end of DAA therapy, respectively. The differences were not statistically significant compared to the controls (Z=-0.589, -1.028 and -0.486, respectively, all P>0.05). Conclusion Immune status of the peripheral MDSC and M-MDSC can return to normal after DAA therapy in CHC patients.

Objective To investigate the effect and significance of the traditional Chinese medicine tetrandrine(TET) prenatal intervention on the expression of RhoA protein and Rho kinase ROCK1 in the fetal lung of congenital diaphragmatic hernia (CDH) rat model.Methods SD female rats with 9.5 d of gestation were randomly divided into the control group,CDH group and TET group.The CDH group and TET intervention group were administered with nitrofen by gavage for establishing CDH model.The TET intervention was given on 16.5 d of gestation.The fetal rat lungs were taken by cesarean section on 21.5 d of gestation and the lung weight/body ratio(Lw/Bw) was measured.The lung development and small pulmonary arterial morphologic changes in HE staining in all groups were observed with microscopy.The protein expression of RhoA and Rho kinase ROCK1were respectively examined by immunohistochemistry and Western blot.Results In the CDH group,the lungs had obvious maldevelopment and the fetal lung development in the TET group was close to that in the control group.The lung development indicators of Lw/Bw,PAA％,and lung vascular remodeling indicators of lumen area and vascular total area ratio(LA％) in the CDH group were significantly lower than those in the control group(2.11±0.36 vs.4.24±0.31;33.60±3.12 vs.58.81 ±2.92;38.58±2.15 vs.61.20±3.23,P＜0.05),the indicators of Lw/Bw.PAA％ and LA％ after TET intervention were significantly improved compared with the CDH group(3.61±0.24 vs.2.11±0.36;42.46±3.68 vs.33.60±3.12;56.07±3.32 vs.38.58±2.15,all P ＜0.05);the ratio of small pulmonary artery wall thickness to vascular external diameter (WT％) and the medium thickness percentage (MT％) in CDH group were significantly higher than those in the control group(26.64±2.41 vs.13.50±1.45 and 25.98±2.79 vs.16.47±2.07,P＜0.05),WT％ and MT％ in the TET group were obviously lower than those in the CDH group (16.02±2.35 vs.26.64± 2.41 and 17.96 ± 1.95 vs.25.98 ± 2.79,P＜0.05).The immunohistochemistry and Western blot detection indicated that the expressions of RhoA and ROCK1 from low to high were the control group ＜TET group ＜ CDH group.Conclusion Pulmonary hypoplasia and lung vascular remodeling exist in fetal rats with CDH and Rho/Rho kinase signaling pathway may be involved in the process.Prenatally giving TET may play the lung protective effect by regulating the Rho/Rho signal pathway.

Objective To evaluate the efficacy and safety of remifentanil (RF) for analgesia of post-operative children with congenital heart disease in pediatric intensive care unit.Methods A total of 250 patients were enrolled and divided into 5 groups by random numerical table method.Patients in group RF1, RF2,RF3,SF and M was treated with at the doses of reminfentanil 1-3 μg/(kg·h),3-6 μg/(kg·h), 6-9 μg/(kg·h),sufentanil 0.08 μg/(kg·h) and morphine 20 μg/(kg·h) respectively.All the analgesias were given intravenously with midazolam 2 μg / ( kg·min) for sedative.We recorded the faces pain scale, Ramsay,vital signs(mean arterial pressure,heart rate),blood gas analysis,cortisol,ventilation time,times of contemporary sedation drugs and incidence of side effects in 24 hours after operation(1 h,4 h,8 h,12 h,24 h).Results The analgesic satisfaction in group M were lower than those in the other four groups at 1 h,4 h (P＜0.05),and the analgesic satisfaction in group RF3 were higher than those in group RF1 and RF2 at 1 h, 4 h,8 h(P＜0.05).Compared with group M and SF,group RF1,group RF2 and group RF3 had a more sta-ble hemodynamics (mean arterial pressure,heart rate).The times of contemporary sedative in group M were maximum among the 5 groups.The incidence of low blood pressure in group M was higher than those in the other four groups(P=0.06),while the incidence of respiratory depression in group RF3 was the most(P=0.06).There were also no significant differences in blood gas analysis,cortisol and ventilation time among each group.Conclusion The efficacy of remifentanil is superior to morphine.Compared with sufentanil and morphine,remifentanil has less influence on hemodynamics. We recommend the dose of remifentanil 3-6 μg/(kg·h),compound with midazolam 2 μg/(kg·min),which is more reliable and durable.

Objective: To assess the value of urine soluble triggering receptor expressed on myeloid cells-1(sTREM-1) in early diagnosis and prognosis of sepsis associated acute kidney injury (AKI). Methods: This was a case-control study. A total of 62 patients with sepsis during November 2016 to June 2017 were collected, who were divided into non-AKI sepsis (n= 49) and AKI sepsis (n=13) groups according to the serum creatinine (SCr) or urine output, sepsis with shock (n=22) and sepsis without shock (n=40) groups according to the presence of shock, survival (n=47) and death (n=15) groups according to the mortality. Twenty healthy children were recruited in control group, whose urine sTREM-1 were used as reference value. Urine and blood specimens were detected on admission (within 12 h), at 24 h and 48 h after admission. Student's t-test and Mann-Whitney U test were used for statistical analysis. Results: On admission, the level of urine sTREM-1 were significantly higher in sepsis patients than in healthy controls (96.8 (71.3, 105.8) vs. 68.6 (60.6, 71.1)ng/L, Z=4.708, P<0.05). Comparing of sTREM-1 in different groups showed that the levels were higher in AKI sepsis patients than in the non-AKI ones ((106±5) vs. (86±18) ng/L, t=6.670, P<0.05), higher in the sepsis with shock group than in sepsis without shock group ((98±11) vs. (86± 20) ng/L, t=3.059, P<0.05), and also higher in death group than in survival group ((101±12) vs. (87±18) ng/L, t=3.615, P<0.05). The area under the receiver operating characteristic (AUROC) of urine sTREM-1 in predicting sepsis associated AKI was 0.814 (95%CI: 0.708-0.920), which was higher than that in predicting shock, increased serum creatinine, hyperlipidemia or hyperbilirubinemia (0.530, 0.425, 0.429 and 0.443, respectively). The optimal sTREM-1 cut-off point for predicting sepsis associated kidney injury was 96.5 ng/L, with specificity and sensitivity of 100% and 57.1%. The odds ratio(OR) of urine sTREM-1 was 0.879 with a significance of 0.005 after adjusting shock, prognosis, serum creatinine, lactate and total bilirubin level, indicating that the urine sTREM-1 was an independent risk factor of sepsis associated AKI. Conclusion Urine sTREM-1 can be used as an early diagnostic biomarker for sepsis associated AKI, with advantage of noninvasiveness and convenience. Trial registration: Chinese Clinical Trial Registry, ChiCTR-DDD-17010743.

Objective To investigate the protective effect of rosiglitazone on the rats with high altitude pulmonary edema.Methods Thirty-six SD rats were randomly (random number) divided into 6 groups (n =6 each):control group (Control),hypobaric hypoxia model group (HH),rosiglitazone groups (RSG) which were administered with 3 different doses [RSG-L:5 mg/ (kg · d),RSG-M:10 mg/ (kg·d),RSG-H:20 mg/ (kg· d)],dexamethasone group [Dex,4 mg/ (kg· d)].Rats were injected intraperitoneally with different doses of rosiglitazone (RSG),dexamethasone (Dex) or vehicle (Control and HH) for 3 days before placed in simulated altitude of 6 000 m hypobaric hypoxia animal chamber where the temperature and pressure were constant.After 72 h in the chamber,each rat was anesthetized.The water content of lung was determined with wet/dry weight ratio.Bronchoalveolar lavage fluid was measured by bradford method.The contents of GSH was measured by micro-ezymed labeled method.The contents of MDA was measured by TBA method.The enzymatic activities of SOD was measured by WST-1 method.The changes of the TNF-α,IL-6 and IL-10 in serum were determined by ELISA.Light microscope was used to observe the pathological changes of lung tissue.Results Compared with Control group,the wet/dry weight ratio of lung (5.08 ± 0.24) and total protein content of BALF (351.06 ± 44.55) μg/mL increased significantly (P ＜ 0.01) in HH group.There were red blood cells in the alveolar and interstitium,pink fluid exudation in the alveolar,the alveolar septum enhancement,and a large number of inflammatory cell infiltration;the SOD activity (10.65 ± 0.94) U/mgprot and the content of GSH (1.63 ±0.20) μmol/gprot in lung tissue were significantly decreased (P ＜ 0.01),the contents of MDA (2.1 5 ± 0.18) nmol/mgprot increased significantly (P ＜ 0.01),TNF-o (56.92 ± 2.87) pg/mL and IL-6 (217.80 ±48.01) pg/mL levels in serum were significantly increased (P ＜0.01),and IL-10 (76.85 ± 16.72) pg/mL level decreased (P ＜ 0.05).Compared with the HH group,the wet/dry ratio of lung and total protein content of BALF in different doses of rosiglitazone group significantly decreased (P ＜ 0.01),the pathological changes of the lung tissue was significantly improved,SOD activity and the content of GSH in lung tissue was significantly increased (P ＜ 0.01),the content of MDA decreased (P ＜ 0.01),The levels of TNF-α and IL-6 in serum were significantly decreased (P ＜ 0.01),while the IL-10 level was significantly increased (P ＜ 0.01).Conclusion Rosiglitazone could protect the high altitude pulmonary edema by alleviating the oxidative stress and inflammatory response.

Objective To obtain the recombinant corticotropin releasing hormone (CRH) protein with soluble, high purity protein through optimizing prokaryotic expression condition and purifying glutathione thiol transferase (GST)-CRH protein. Methods To detect the expression of soluble CRH protein through grope of the host strain GST-CRH temperature of induction expression, the host strain concentration (OD600), IPTG concentration and induction time, the purification of GST-CRH was performed by GST-CRH agarose gel. Western Blot assay was used for the expression identification of the target protein. Results The optimal conditions for the induction of CRH protein were determined: temperature of 30 ℃, IPTG induced concentration 0.1 mmol/L, bacteria density (OD600) 0.8, the induction time of 8 hours, purified GST-CRH>95% fusion protein was obtained. Conclusion The optimal expression conditions of GST-CRH are obtained, and the soluble protein of high purity GST-CRH is also obtained.