Critically ill with capillary leakage syndrome（CLS）presents with damaged vascular endothelial cells with glycocalyx degraded,which increases vascular permeability,and leads to the protein-rich fluid from the intravascular extravasate into the interstitial space.CLS can concomitant symptoms of hypovolemia and fluid overload.Fluid therapy is the most critical element in the treatment of CLS,but still lack of sufficient evidence to guide the choice of fluid management.Based on accurately hemodynamic monitoring,balanced salt or crystalloid + albumin or fresh frozen plasma may be input to ensure effective circulating blood volume.Albumin or fresh frozen plasma is particularly suitable for CLS patients failed to respond to crystalloids during the leakage period.In the later stage of leakage,conservative fluid management with “de-resuscitation”strategy was mainly used with diuretic and hemofiltration (renal replacement therapy/continuous renal replacement therapy) for attenuating fluid overload.Steroids and ulinastatin may be effective in CLS caused by sepsis.

Objective:To explore the risk factors of deaths caused by influenza-associated encephalopathy (IAE) in children.Methods:A case control study was conducted.The clinical data (including baseline fata, organ function indices, inflammatory factors, imaging data, treatment, and outcomes) of IAE children hospitalized in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from January 2020 to December 2023 were retrospectively analyzed.The children were divided into a survival group and a death group.The Logistic regression and receiver operating characteristic (ROC) curve were used to analyze the risk factors of death in IAE children.Results:A total of 46 cases were included, with an onset age of 74.8(46.0, 92.5) months.The main cause of IAE was influenza A virus infection, which was detected in 45 cases(97.8%), and 32 cases (69.6%) of them had H3N2.One child (2.2%) was infected by influenza B virus.Eight children died, showing a mortality of 17.4%.There was significant difference in Glasgow Coma Scale between the survival and death groups when they were admitted into the PICU [10 (9, 11) points vs.3 (3, 5) points] ( Z=-4.510, P<0.05).All patients in the death group had multiple organ dysfunction syndrome, respiratory failure and circulatory system failure.Serum procalcitonin (PCT)[15.7 (3.3, 37.4) μg/L], interleukin-6 (IL-6)[1 039.1 (319.3, 2 884.3) ng/L], and cerebrospinal fluid protein(CSFP)[13 050.0 (5 865.0, 21 100.0) mg/L] in the death group compared with those in the survival group [0.2 (0.1, 0.8) μg/L, 15.5 (7.9, 44.8) ng/L, 227.0 (190.0, 332.0) mg/L]were highly increased ( Z=-3.364, -4.088, -3.757, all P<0.001).Logistic regression analysis showed that PCT ( OR=0.660, P<0.05), IL-6 ( OR=1.014, P<0.05) and CSFP ( OR=1.001, P<0.05) were risk factors of death in IAE.The areas under the ROC curve for these three factors were 0.88 (95% CI: 0.77-0.97), 0.96 (95% CI: 0.86-1.00) and 0.93 (95% CI: 0.76-1.00), respectively.When a cutoff value of 2.50 μg/L, 269.67 ng/L and 5 240.00 mg/L was taken, PCT achieved a sensitivity of 0.875 and a specificity of 0.816, IL-6 achieved a sensitivity of 0.875 and specificity of 0.974, and CSFP achieved a sensitivity of 0.875 and specificity of 0.974, respectively. Conclusions:High levels of serum PCT, IL-6 and CSFP at PICU admission are risk factors of poor prognosis in children with IAE.

Critically ill with capillary leakage syndrome（CLS）presents with damaged vascular endothelial cells with glycocalyx degraded,which increases vascular permeability,and leads to the protein-rich fluid from the intravascular extravasate into the interstitial space.CLS can concomitant symptoms of hypovolemia and fluid overload.Fluid therapy is the most critical element in the treatment of CLS,but still lack of sufficient evidence to guide the choice of fluid management.Based on accurately hemodynamic monitoring,balanced salt or crystalloid + albumin or fresh frozen plasma may be input to ensure effective circulating blood volume.Albumin or fresh frozen plasma is particularly suitable for CLS patients failed to respond to crystalloids during the leakage period.In the later stage of leakage,conservative fluid management with “de-resuscitation”strategy was mainly used with diuretic and hemofiltration (renal replacement therapy/continuous renal replacement therapy) for attenuating fluid overload.Steroids and ulinastatin may be effective in CLS caused by sepsis.

Objective:To explore the risk factors of deaths caused by influenza-associated encephalopathy (IAE) in children.Methods:A case control study was conducted.The clinical data (including baseline fata, organ function indices, inflammatory factors, imaging data, treatment, and outcomes) of IAE children hospitalized in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from January 2020 to December 2023 were retrospectively analyzed.The children were divided into a survival group and a death group.The Logistic regression and receiver operating characteristic (ROC) curve were used to analyze the risk factors of death in IAE children.Results:A total of 46 cases were included, with an onset age of 74.8(46.0, 92.5) months.The main cause of IAE was influenza A virus infection, which was detected in 45 cases(97.8%), and 32 cases (69.6%) of them had H3N2.One child (2.2%) was infected by influenza B virus.Eight children died, showing a mortality of 17.4%.There was significant difference in Glasgow Coma Scale between the survival and death groups when they were admitted into the PICU [10 (9, 11) points vs.3 (3, 5) points] ( Z=-4.510, P<0.05).All patients in the death group had multiple organ dysfunction syndrome, respiratory failure and circulatory system failure.Serum procalcitonin (PCT)[15.7 (3.3, 37.4) μg/L], interleukin-6 (IL-6)[1 039.1 (319.3, 2 884.3) ng/L], and cerebrospinal fluid protein(CSFP)[13 050.0 (5 865.0, 21 100.0) mg/L] in the death group compared with those in the survival group [0.2 (0.1, 0.8) μg/L, 15.5 (7.9, 44.8) ng/L, 227.0 (190.0, 332.0) mg/L]were highly increased ( Z=-3.364, -4.088, -3.757, all P<0.001).Logistic regression analysis showed that PCT ( OR=0.660, P<0.05), IL-6 ( OR=1.014, P<0.05) and CSFP ( OR=1.001, P<0.05) were risk factors of death in IAE.The areas under the ROC curve for these three factors were 0.88 (95% CI: 0.77-0.97), 0.96 (95% CI: 0.86-1.00) and 0.93 (95% CI: 0.76-1.00), respectively.When a cutoff value of 2.50 μg/L, 269.67 ng/L and 5 240.00 mg/L was taken, PCT achieved a sensitivity of 0.875 and a specificity of 0.816, IL-6 achieved a sensitivity of 0.875 and specificity of 0.974, and CSFP achieved a sensitivity of 0.875 and specificity of 0.974, respectively. Conclusions:High levels of serum PCT, IL-6 and CSFP at PICU admission are risk factors of poor prognosis in children with IAE.

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

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.

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.

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.