Sepsis cardiomyopathy (SIC) is sepsis complicated with heart dysfunction，and its definition，pathogenesis，diagnostic criteria and therapeutic measures have not been well established.The reported prevalence of SIC varied from 10% to 70% and the diagnosis based on the measures of heart function and biological markers.The most important indicator is reduced left heart ejection fraction.Currently，it is believed that SIC should avoid rapid high-dose liquid treatment on the basis of infection treatment.The use of inotropic drugs needs to consider the improvement of myocardial contractility and avoid inducing arrhythmia and adverse effects on vascular resistance.The appropriate timing of extracorporeal membrane oxygenation support is still be challenged.The review focusesd on the fluid management and progress，vasoactive drug therapy and mechanical assistance，and the development of novel targeted drugs in SIC.

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Objective:To investigate the effects of therapeutic plasma exchange(TPE)as adjuvant therapy in children with myasthenia gravis(MG)in pediatric intensive care unit(PICU).Methods:A retrospective study was conducted in 7 children with MG admitted to PICU at Shanghai Children′s Hospital from January 2016 to December 2019.TPE was performed on unsatisfactory effect of acetylcholinesterase inhibitors, glucocorticoids or IVIG.The TPE dose was 50-70 mL/kg for 2 to 3 times for each case.The clinical symptoms, anti-acetylcholine antibody(AChR-Ab)level and prognosis were measured before and after TPE.Results:Seven children with myasthenia gravis admitted to PICU from January 2016 to December 2019, including 4 cases of systemic myasthenia gravis(1 case of myasthenia crisis with respiratory failure)and 3 cases of ocular myasthenia gravis.The AChR-Ab level decreased from 1.66(0.99, 3.33)nmol/L before TPE to 0.66(0.40, 10.97)nmol/L after TPE( Z=-2.545, P=0.011). The symptoms of muscle weakness and blepharoptosis were partially or completely relieved in 7 cases.There were no significantly changes in the levels of circulating immune complex, complement C3, CD4 + , CD8 + and NK cells before and after TPE(all P>0.05). During the process of TPE, 2 cases had mild rash, and 1 case had hypotensive shock, which were recovered after timely treatment.After TPE, the fibrin levelsdecreased from 1.90(1.40, 2.40)g/L to 1.10(1.00, 1.30)g/L( Z=-3.092, P=0.002). Conclusion:TPE reduce the AChR-Ab levels and improve the short-term symptoms in children with myasthenia gravis who have failed conventional treatment.TPE may be an optional therapy for pediatric severe MG.

Objective To investigate the features and incidence of severe anti-N-methyl-D-aspartate receptor ( NMDAR) encephalitis in pediatric intensive care unit ( PICU) treated with therapeutic plasma exchange(TPE). Methods A retrospective study was conducted of children with severe anti NMDAR encephalitis admitted to PICU of Shanghai Children′s Hospital from July 2015 to June 2018. Demographic data,therapeutic regimens,clinical and laboratory data were analyzed. The one dose of replacement plasma was 50-70 ml/kg. The laboratory biomarkers, anti-NMDAR in serum and cerebrospinal fluid ( CSF) were measured before and after TPE treatment. Results Thirteen cases with anti-NMDAR encephalitis were analyzed. The main clinical features were seizures, unconsciousness, motor dysfunctions organ dysfunction included respiratory failure in 3 (23. 1%) patients and shock in 4 (30. 8%) cases. The average levels of PICU stays were[11. 0(5. 5,19. 0)] days. The conventional therapy included methylprednisolone,intrave-nous immunoglobulin (IVIG),antiepileptic,and immune-suppressants. Seven patients received conventional treatment,and 6 (46. 2%) cases combined TPE after unsatisfactory effect on 3 to 7 days conventional treat-ment. TPE dosage was 50-70 ml/kg body weight per times for 3-5 dosages. The Glasgow coma score(GCS) and pediatric risk of mortality Ⅲ( PRISM Ⅲ) of children after TPE treatment were signifcantly improved compared with those before TPE treatment[ GCS:7. 5(6. 0,9. 3) vs. 12. 5 (11. 5,13. 5),PRISM Ⅲ:15. 5 (9. 5,17. 5) vs. 11. 0(4. 5,12. 3),all P<0. 05]. The levels of anti-NMDAR antibody in both serum and CSF decreased significantly after TPE(all P<0. 05). Three cases (50. 0%) had anaphylaxis during TPE. Conclusion TPE could decease the levels of anti-NMDAR antibody in CSF and serum,improve psychiatric and neurologic symptoms. TPE may be a potential therapy in pediatric severe NMDAR encephalitis.

Objective To analyze the effects on control rate and the outcome of pulmonary function in children with bronchial asthma (abbreviated asthma) who were received the two years standardized treatment and management,and to explore the sensitive parameters of control effects in children with asthma.Methods Using the retrospective analysis,asthmatic children were selected from January 2014 to January 2015 in Beijing Children's Hospital,allergy and asthma outpatient clinics.All the patients were received asthma control treatment and management according to GINA guidelines (2014 version).They were assessed on asthma control level at one year and two years follow up visits respectively and their pulmonary function were evaluated at the same time.According to response status to therapy and adjustment of step up and down,children were divided into two groups,the stable control group and the difficult to control group.The parameters of sex,age,asthma,combined with rhinitis,allergen sensitization and pulmonary function were compared between the two groups.Results A total of 149 patients were enrolled in this study.The treatment levels were 20.2％,67.1％ and 12.7％ respectively at grade 2,grade 3 and ≥ 4 grade.After Treatment management for one year and two years,the asthma control level were assessed as good control was 81.8％ and 83.2％ respectively (P ＜ 0.05) Each parameter of pulmonary function excepted FEV1/FVC at the one year visit point after treatment and management was significantly higher than that at enrollment (P ＜ 0.05).After two years of treatment and management,PEF％ pred and FEF25 ％ pred was higher than that at first follow up visit (P ＜ 0.05).There were no significantly different on the distribution of sex,age,course of asthma,allergic rhinitis,allergen sensitization and initial control treatment level between the stable control and the difficult to control groups.Asthma control stability status assessment and analysis at the one year follow up visits showed that PEF％ pred was significantly higher in the group of stable control than that in group of difficult to control (97.3 ± 14.3 vs 93.1 ± 15.1,P ＜ 0.05).Asthma control stability starus assessment and analysis at two years follow up visits showed that the positive rate of allergen sensitization was significantly lower in the group of stable control than that in group of difficult to control (P ＜ 0.05),while FEV1/FVC was significantly higher in the group of stable control than that in group of difficult to control (81.0 ± 9.47vs77.4 ± 8.95,P＜0.05).Conclusion School age children asthma control level were improved with longer time regular treatment and management as well as the pulmonary function improvement.Multiple allergenic sensitization and lower PEF％ pred value and FEV1/FVC are suggestive parameters for children with difficult to control asthma.

Objective To investigate the prognostic value of heart-type fatty acid-binding protein (H-FABP)in pediatric patients with severe sepsis and septic shock. Methods A prospective observational study was carried out in consecutive pediatric patients with severe sepsis and septic shock admitted between October 2016 and September 2017. Data of patient's demographics, clinical characteristics, blood biochemical markers including H-FABP, N-terminal B-type natriuretic peptide (NT-BNP), creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTnl), Lactate dehydrogenase (LDH) and Lactic acid (Lac), complications and survival status were collected and analyzed. The receiver operating characteristic (ROC) curve was mainly used to evaluate the power of a continuous variable for 28-day survival rate, and Kaplan-Meier analysis was used to compare 28-day survival curves in pediatric patients with severe sepsis and septic shock. Results A total of 78 cases with severe sepsis (n=33) and septic shock (n=45) were enrolled in this study. There were 64 survival cases and 14 non-survivor within 28 days after admission. The plasma levels of H-FABP, NT-BNP, LDH, CK-MB were significantly higher in non-survivor than those in survivor (49.10±65.14) vs. (5.06±4.29) ng/ml; (131.63±130.91) vs. (37.30±29.24) U/L; (2 403.88±415.97) vs.(2 971.57±279.49) U/L; (5 872.93±6 383.28)pg/ml vs. (1 656.86±2 715.73) pg/ml; respectively, all P＜0.05). The area under the receiver operating characteristic curve (AUC) of H-FABP was 0.858 (95％ confidence interval [CI]: 0.716-1.0; P=0.002), which was superior to CK-MB (AUC=0.841,95％CI: 0.696-0.986; P=0.003);LDH (AUC=0.818, 95％CI: 0.610-1.000; P =0.005) and NT-BNP (AUC=0.728, 95％CI: 0.535-0.921;P=0.045). A Kaplan-Meier curve showed a significantly lower survival rate in patients with H-FABP greater than 7.7 ng/mL than the patients with H-FABP less than 7.7 ng/mL. Conclusions H-FABP is an effective prognostic indicator in pediatric patients with severe sepsis and septic shock with superiority to traditional myocardial enzyme.

Objective To assess the clinical benefits of continuous blood purification(CBP) in severe enterovirus 71(EV71)-associated hand,foot and mouth disease (HFMD) in children.Methods We retro-spectively analyzed the medical records of pediatric patients with EV71-associated HFMD admitted to PICU in Shanghai Children's Hospital from January 2012 to December 2016.Severity of EV71-associated HFMD was graded in the accordance with the expert consensus on severe EV71-infected HFMD.According to the severity,the patients with stage 2 HFMD were treated with standard management,and the patients with stage 3-4 HFMD were treated with continuous veno-venous hemodiafiltration(CVVHDF) as an adjuvant therapy. Patient demographics,clinical characteristics,cardiovascular function indexes,outcome and complications of CVVHDF were collected and analyzed.Results A total of 76 patients with severe EV71-associated HFMD were enrolled in this study.Among them,there were 21 patients with stage 3-4 HFMD,and 17 cases were treated with CVVHDF as an adjuvant therapy with a survival rate of 82.4 %(14/17).The median time of CVVHDF treatment was 48(36,64)h.The plasma levels of angiotensin Ⅱ[185.9(125.2,800.0) ng/L vs. 106.0(90.8,232.5) ng/L],aldosterone[165.7(94.0,353.3) ng/L vs. 103.3(84.3,144.3)ng/L],rennin [1.12(0.74,3.45) μg/(L·h) vs. 0.79(0.52,1.25) μg/(L·h) ],adrenaline[169.8(145.5,244.6) ng/L vs. 148.0(109.0,208.1) ng/L],dopamine[152.7(97.0,191.1) ng/L vs. 96.0(68.0,160.9) ng/L], and lactate[3.50(2.75,3.90) mmol/L vs. 1.30(0.95,1.90) mmol/L] were significantly decreased after CVVHDF treatment(all P<0.05,respectively).The fever,heart rate,systolic blood pressure,left ventricular ejection fraction and cardiac index of the patients were significantly improved after treatment(all P<0.05, respectively).Conclusion CBP is an important rescue therapy for patients with severe EV71-infected HFMD, which results in rapidly improving fever,cardiovascular function and stabling the levels of vasoactive mediators.

Critical ill with cardiac and respiratory failure receiving extracorporeal membrane oxygenation ( ECMO ) often have comorbid of acute kidney injury and fluid overload. Continuous renal replacement therapy ( CRRT) is required. A variety of methods for combining ECMO and CRRT can be chosen. There are three major ways:performing CRRT through independent venous accessin-line connection ( connection of the hemofilter alone to the ECMO circuit ) , and a CRRT device connected to the ECMO circuit. The combination of ECMO and CRRT appears to be a safe and effective technique. The technique difficulties in concurrent extracorporeal life support system include CRRT device connection ways with ECMO by measuring intra-circuit pressure, anticoagulant use and monitoring access-related complications. The most important management is the CRRT inlet and outlet pressures deviating from the safety range at high ECMO circuit.