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Objective: To investigate the efficacy and safety of tocilizumab in the treatment of critically ill children with acute necrotizing encephalopathy (ANE). Methods: It is a retrospective cohort study. The children with ANE admitted to the pediatric intensive care unit of 4 Chinese tertiary hospitals from December 2022 to November 2023 were divided into conventional treatment group and tocilizumab group, and the comparison between groups was performed by using Mann - Whitney U test or Chi-square test. Results: Among 21 cases of severe ANE, there were 11 males with the onset age of 65 (27, 113) months. The duration from onset to PICU admission was 2 (1, 2) days. There were 13 cases of ultra-high fever (greater than 40 ℃), including 18 cases of convulsions, and 19 cases with a GCS score of less than 8 points. The causative agent was novel coronavirus Omicron in 7 cases and influenza A in 14 cases. All cases had central respiratory failure requiring mechanical ventilation. Of the 21 cases, 18 were shock, 15 were coagulopathy, 10 were kidney injury and 13 were liver dysfunction. Of these hospitalized patients, 8 children with ANE were treated with tocilizumab. Eight cases received continuous blood purification (CBP) treatment, 5 of them were combined with plasmapheresis. Serum cytokine levels were elevated in 21 children with ANE, including (interleukin, IL)-6 and IL-8 (61 (22, 1 513) and 68 (5, 296) ng/L). There were 14 cases (67%) deaths, including 11 cases in the conventional treatment group and 3 cases in the tocilizumab group. There was no significant difference in the mortality rate between the two groups ( P =0.056). Tocilizumab-related rash or other adverse events were not observed. Conclusions: The motality of critically ill ANE patients was high. The combination of Tocilizumab with conventional treatment did not reduce the motality of severe ANE patients, and no adverse reactions of tocilizumab were observed.

Objective: To investigate the risk factors of central nervous system (CNS) complications in children undergoing extracorporeal membrane oxygenation (ECMO) support. Methods: The clinical data, ECMO parameters, laboratory examination and outcome (follow-up to 90 d after discharge) of 82 children treated with ECMO in the pediatric intensive care unit (PICU) of Shanghai Children's Hospital from December 2015 to December 2021 were analyzed retrospectively in this study. The patients were divided into CNS complication group and non-CNS complication group. The ECMO mode, ECMO catheterization mode, clinical and laboratory indicators pre-ECMO and 24 h after ECMO initiation, in-hospital mortality and 90-day mortality were compared with Chi-square test, t test and nonparametric rank sum test. Kaplan-Meier method was used to draw survival curve, and Log-rank test was used to compare the difference in survival rate. The receiver operating characteristic (ROC) curve was used to evaluate the power of variables to predict CNS complications. Results: A total of 82 children were treated with ECMO, including 49 males and 33 females, aged 34 (8, 80) months. There were 18 cases suffering CNS complications, including cerebral hemorrhage in 8 cases, epilepsy in 6 cases, simple cerebral infarction in 3 cases, and cerebral hemorrhage combined with cerebral infarction in 1 case. Veno-arterial ECMO accounted for a greater proportion in CNS complication group (17/18 vs. 67% (43/64), χ 2 =4.02, P =0.045). A higher percentage of children with CNS complications underwent surgical cannulation compared to those in non-CNS complication group (16/18 vs. 53% (34/64), χ 2 =7.55, P =0.006). The laboratory results indicated that lower pre-ECMO pH value (7.24 (7.15, 7.28) vs. 7.35 (7.26, 7.45), Z =-3.65, P <0.001) and platelet count 24 h after ECMO initiation (66 (27, 135) ×10 9 /L vs. 107 (61, 157) ×10 9 /L, Z =-2.04, P =0.041) were associated with CNS complications. In the CNS complication group, 7 children died during hospitalization and 7 died during 90-day after admission, and there was no significant difference compared with those in the non-CNS complication group (7/18 vs. 31% (20/64), 7/18 vs. 34% (22/64), both P >0.05). The ROC curve analysis indicated that the area under the ROC curve for pre-ECMO pH value was 0.738 (95% CI 0.598-0.877), and the optimal cut-off value was 7.325. Conclusions: CNS complications in children undergoing ECMO support are common. Pre-ECMO pH value <7.325 is a risk factor for CNS complications. Reducing the veno-arterial ECMO and surgical cannulation can help reduce the occurrence of CNS complications.

Objective: To evaluate the effectiveness and safety of ultrasound-guided percutaneous cannulation for extracorporeal membrane oxygenation (ECMO) in children. Methods: In this retrospective observational study, 66 cases who underwent non-cardiac surgery ECMO in pediatric intensive care unit (PICU) of Shanghai Children's Hospital from May 2016 to April 2021 were collected. The demographics, model of ECMO support, type and size of arteriovenous cannulas, way of catheterization and complications were recorded and summarized. Patients were divided into percutaneous cannulation group and surgical cannulation group according to catheterization strategies. The demographics, duration of cannulation and ECMO support, ECMO weaning rate and hospital survival rate were compared among two groups. χ 2 and nonparametric rank sum test were used for comparison. Results: Among the 66 patients who received ECMO, 38 were male and 28 were female, with age 44.5 (12.0, 83.5) months and weight 15.0 (10.0, 25.0) kg; 21 patients underwent percutaneous cannulation, with a success rate of 95% (20 cases). Point-of-care ultrasound was performed for all percutaneous cannulation cases. The duration of percutaneous cannulation was significantly shorter than that of surgical cannulation (26.0 (23.3, 30.3) vs. 57.0 (53.8, 64.0) min, Z =6.31, P< 0.001). Successful percutaneous cannulation cases were aged 70.5 (23.8, 109.5) months, and their weight was 23.2 (13.6, 37.0) kg. Ten cases were initially given veno-venous (VV) ECMO support, and 10 cases were given veno-arterial (VA) ECMO support. ECMO arterial cannulas were sized from 8 F to 17 F, and venous cannulas sized from 10 F to 19 F. For VV-ECMO, the right internal jugular and femoral veins were used as vascular access, while VA-ECMO used right internal jugular vein-femoral artery or right femoral vein-left femoral artery approach. Only one patient suffered severe complication (superior vena cava perforation). There was no catheter-related bloodstream infection. Conclusion: Ultrasound-guided percutaneous cannulation for ECMO can be performed with a high rate of success and safety in children.

Objective: To investigate the efficacy of high flow nasal cannula (HFNC) in children with acute respiratory failure. Methods: A prospective study was conducted. A total of 153 patients aged from 1 to 14 years with acute respiratory failure were enrolled, who were admitted to pediatric intensive care unit (PICU) of Shanghai Children's Hospital from January 2018 to December 2019. HFNC success was defined as no need for invasive mechanical ventilation and successfully withdrawn from HFNC, while HFNC failure was defined as need for invasive mechanical ventilation. HFNC at a flow rate of 2 L/(kg·min) (maximum ≤ 60 L/min) with inhaled oxygen concentration (FiO 2 ) between 0.30 and 1.00 was applied to maintain percutaneous oxygen saturation (SpO 2 ) of 0.94-0.97. Parameters including arterial partial pressure of oxygen (PaO 2 ), partial pressure of carbon dioxide in artery (PaCO 2 ), SpO 2 and PaO 2 /FiO 2 were collected before and during the application of HFNC at 1 h, 6 h, 12 h, 24 h and 48 h, as well as over 48 h after HFNC withdrawn. Comparison between the groups was performed by student t test, Mann-Whitney U test or chi-square test. The sensitivity and specificity of the above parameters in predicting HFNC success were evaluated by receiver operating characteristic (ROC) curve. Results: A total of 153 children (70 males and 83 females) were enrolled. Among them, 131 (85.6%) cases were successfully weaned off from HFNC and 22 (14.4%) failed. The duration of HFNC was 57 (38, 95) hours in the successful group, and the PaO 2 /FiO 2 before HFNC application and after HFNC was withdrawn were 187 (170, 212) mmHg (1 mmHg=0.133 kPa) and 280 (262, 292) mmHg, respectively. The duration of HFNC in the failure group was 19 (9, 49) hours, and the PaO 2 /FiO 2 before HFNC application and after HFNC withdrawn were 176 (171, 189) mmHg and 159 (156, 161) mmHg, respectively. The values of PaO 2 /FiO 2 were significantly higher in the successful group than those in the failed group at using HFNC initially 1 h (196 (182, 211) vs. 174 (160, 178) mmHg, Z =-5.105, P< 0.01), 6 h (213 (203, 220) vs. 168 (157, 170) mmHg, Z =-6.772, P< 0.01), 12 h (226 (180, 261) vs. 165 (161, 170) mmHg, Z =-4.308, P< 0.01), 24 h (229 (195, 259) vs. 165 (161, 170) mmHg, Z =-4.609, P< 0.01) and 48 h (249 (216, 273) vs. 163 (158, 169) mmHg, Z =-4.628, P< 0.01) after the HFNC application, and over 48 h after HFNC was withdrawn (277 (268, 283) vs. 157 (154, 158) mmHg, Z =-3.512, P< 0.01). Moreover, the PaO 2 levels were significantly higher in the successful group than those in the failed group using HFNC initially at 1 h (73.7 (71.0, 76.7) vs. 70.0 (66.2, 71.2) mmHg, Z =-4.587, P< 0.01) and 6 h (79.0 (75.0, 82.0) vs. 71.0 (62.0, 72.0) mmHg, Z =-5.954, P< 0.01) after HFNC application. Also, the SpO 2 levels showed the same differences at 1 h (0.96 (0.95, 0.96) vs. 0.94 (0.92, 0.94), Z =-4.812, P< 0.01) and 6 h (0.96 (0.95, 0.97) vs. 0.94(0.91, 0.95), Z =-5.024, P< 0.01) after HFNC application. Forty eight hours after HFNC was withdrawn, the PaO 2 (88.0 (81.7, 95.0) vs. 63.7 (63.3, 66.0) mmHg, Z =-3.032, P< 0.01) and SpO 2 (0.96 (0.94, 0.98) vs. 0.91 (0.90, 0.92), Z =-3.957, P< 0.01) were also significantly higher in the successful group. Regarding the HFNC complications, there was one case with atelectasis and one with pneumothorax in the failure group. HFNC was used as sequential oxygen therapy after extubation in 79 children, successful in all. ROC curve showed that the area under curve of PaO 2 /FiO 2 in predicting HFNC success was 0.990, and the optimal cut-off value was 232 mmHg with the 95 %CI of 0.970-1.000 ( P< 0.01). Conclusions: HFNC could be used as a respiratory support strategy for children with mild to moderate respiratory failure and as a sequential oxygen therapy after extubation. The PaO 2 /FiO 2 when HFNC withdrow is the optimal index to evaluate the success of HFNC application.

Objective: To understand the current status of clinical guidelines and consensus for lung cancer chemotherapy, evaluate and analyze the quality of lung cancer chemotherapy treatment guidelines, and provide references for the revision and improvement of lung cancer chemotherapy clinical decision-making and guidelines. Methods: Search Pubmed, EMbase, Cochrane Library (Cochrane Library), China Knowledge Network, Wanfang Database, China Biomedical Literature Database and other related databases and clinical practice guidelines related to lung cancer chemotherapy, and screen the literatures according to the established inclusion exclusion criteria. Use the appraisal of guidelines for research and evaluation Ⅱ (AGREE Ⅱ) and reporting items for practice guidelines in healthcare (RIGHT) tools to compare and evaluate the quality of the included guides and the level of reporting specifications. Results: A total of 14 guidelines were included. The assessment results of AGREE Ⅱ showed that the average score of scope and purpose was 94 points, the average score of stakeholder involvement was 60 points, the average score of rigour of development was 43 points, the average score of clarity of presentation was 88 points, the average score of applicability was 50 points, the average score of editorial independence was 61 points. Seven guidelines were evaluated as A level, 6 guidelines were evaluated as B level, 1 guideline was evaluated as C level. The assessment results of RIGHT showed that, in addition to the basic information, the included guidelines have many deficiencies in 6 areas including background, evidence, recommendation, review and quality assurance, funding, declaration and management of interests and other information, and the normative gap between domestic and foreign guides was large. Conclusions: The overall quality of clinical guidelines for lung cancer chemotherapy is high, but the standardization needs to be strengthened. There is a big gap between the quality and standardization of domestic and foreign guides. Further developments of high-quality clinical practice guidelines and guidelines consistent with our country's actual situation are needed.

Objective: To compare the clinical features and outcomes of cancer-related and non-cancer-related sepsis in children who were admitted pediatric intensive care unit (PICU). Methods: The clinical history of patients with sepsis, who were admitted to PICU in Shanghai Children's Hospital, Shanghai Jiao Tong University from August 2016 to July 2019, were retrospectively reviewed. A total of 768 patients were divided into the cancer-related sepsis group (135 cases) and the non-cancer-related sepsis group (633 cases). The patients in the cancer-related group were further categorized into three subgroups including hematological malignancy (80 cases), solid tumor (43 cases) and hemophagocytic lymphohistiocytosis (HLH) (12 cases). The variables of clinical features, laboratory tests, pathogens, management strategies and in-hospital mortality were compared between the two groups by student t test, Mann-Whitney U test or Chi-square test. Results: The patients with cancer-related sepsis accounted for 17.6% of all patients (135/768). Regarding the site of initial infection, the incidence of gastrointestinal infection (43.0% (58/135) vs. 28.6% (181/633), χ(2)=10.718, P= 0.001), blood stream infection (29.6% (40/135) vs. 17.1% (108/633), χ(2)=11.297, P= 0.001) and skin and soft tissue infection (22.2% (30/135) vs. 4.1% (26/633), χ(2)=54.013, P< 0.01) were higher in the patients with cancer-related sepsis than in those with non-cancer-related sepsis. On first PICU admission, the levels of hemoglobin (71 (61, 83) vs. 106 (92, 116) g/L, Z= 13.594, P< 0.01), white blood cell (1.4 (0.3, 5.2) vs. 9.8 (5.8, 15.1)×10(9)/L, Z= 11.213, P< 0.01), platelet count (51 (15, 121) vs. 286 (192, 384)×10(9)/L, Z= 13.336, P< 0.01), CD19(+)cells (0.106 (0.008, 0.274) vs. 0.325 (0.224, 0.454), Z= 6.555, P< 0.01), and neutrophil (0.449 (0.170, 0.730) vs. 0.683 (0.537, 0.800), Z= 5.974, P< 0.01) were significantly lower in patients with cancer-related sepsis; however, the levels of C-reactive protein (82 (25, 155) vs. 36 (11, 86) mg/L, Z= -5.257, P< 0.01), procalcitonin (1.5 (0.3, 12.0) vs. 0.8 (0.2, 4.0) μg/L, Z= -2.767, P= 0.006), CD8(+)cells (0.329 (0.253, 0.514) vs. 0.209 (0.156, 0.275), Z= -5.699, P< 0.01), interleukin (IL) -6 (0.1 (0.1, 522.4) vs. 0.1 (0.1, 0.1) ng/L, Z= -2.747, P= 0.006), IL-8 (0.1 (0.1, 177.0) vs. 0.1 (0.1, 4.5) ng/L, Z= -2.087, P= 0.037), and IL-10 (0.1 (0.1, 42.7) vs. 0.1 (0.1, 6.6) ng/L, Z= -2.148, P= 0.032) were significantly higher in patients with cancer-related sepsis. Similarly, the rate of continuous renal replacement therapy (CRRT) (34.8% (47/135) vs. 16.9% (107/633), χ(2)=26.267, P< 0.01) and the use of intravenous immunoglobulin (IVIG) (83.0% (112/135) vs. 66.2% (419/633), χ(2)=14.667, P< 0.01) were significantly higher in cancer-related sepsis group. Moreover, the incidence of co-infection with fungi was also higher in cancer-related sepsis group (14.1% (19/135) vs. 0.5%(3/633), χ(2)=73.965, P< 0.01), and so was the number of multiple organ dysfunction (3 (2, 5) vs. 2 (1, 3), Z= -6.988, P< 0.01). Finally, the in-hospital mortality rate of cancer-related sepsis and non-cancer-related sepsis were 36.3% (49/135) and 9.3% (59/633), respectively, also significantly different (χ(2)=67.000, P< 0.01). There was no difference in the in-hospital mortality among children with hematologic tumors, solid tumors and HLH (35.0% (28/80) vs. 32.6% (14/43) vs. 7/12, χ(2)=2.838, P= 0.242). Conclusions: The site of initial infection, inflammatory markers on PICU admission, and co-infection pathogen during hospitalization are different between patients with cancer-related sepsis and non-cancer-related sepsis. Besides, the in-hospital mortality of cancer-related sepsis is about 4-fold that of non-cancer-related sepsis. The monitoring of clinical features and organ dysfunction, and timely treatment are crucial for cancer-related sepsis.

Objective: To explore the effectiveness and safety of continuous renal replacement therapy (CRRT) combined with extracorporeal membrane oxygenation (ECMO) on rescuing pediatric patients with cardiopulmonary failure. Methods: The medical records of patients treated with ECMO admitted to pediatric intensive care unit (PICU) in Shanghai Children's Hospital from December 2015 to November 2017 were retrospectively extracted. There were 14 patients treated with ECMO combined with CRRT (ECMO+ CRRT group) due to acute kidney injury (AKI) or fluid overload, while 11 cases treated with ECMO only. The demographics and clinical characteristics of patients, the indications, details and complications of ECMO and CRRT support, and the survival rates were analyzed. Results: A total of 25 cases including 15 boys and 10 girls with cardiopulmonary failure treated with ECMO were enrolled in this study, whose median age and body weight were 9 (1-117) months and 10 (2-42) kg. The median duration of ECMO support was 199.2 h, and the median duration of CRRT was 78.6 h. Among the 14 cases in ECMO + CRRT group, 12 cases were treated with CRRT connected to ECMO pipeline, and 2 other cases were treated with independently operated CRRT. The serum level of creatinine was significantly higher in ECMO+ CRRT group than that in ECMO group (53 (22- 126) vs. 29 (12- 92) μmol/L, Z= -2.208, P= 0.043). There was no significant difference in running time between ECMO+CRRT group and ECMO group ((257±203) vs. (122± 83) h, t =-2.062, P= 0.051). And the incidence of thrombocytopenia was higher in ECMO+CRRT group than that in ECMO group (10/14 vs . 3/11 , χ(2)=4.812, P= 0.028). There were no differences in the successful weaning rate and discharge survival rate between ECMO + CRRT and ECMO group (9 vs. 8, χ(2)= 0.203, P = 0.652 and 8 vs . 8, χ(2)= 0.659, P = 0.417, respectively). Conclusion: The combination of CRRT and ECMO is an effective and safe treatment to alleviate fluid overload and improve kidney function in pediatric patients with cardiopulmonary failure.

microRNA-184 (miR-184) is a small, non-coding, endogenic RNA molecule of 22 nucleotides in length. It is a highly conserved sequence throughout many different species. Multiple studies have demonstrated that miR-184 is an important factor in regulating gene expression at the post-transcriptional level. miR-184 plays vital roles in many biological processes, including development and differentiation in many tissues and organs. Meanwhile, the research on the physiological and pathological role of miR-184 in eyes draws more and more attention lately. Recent research indicates that miR-184 is highly expressed in the cornea and lens of mice. miR-184 plays crucial regulatory roles in several ocular diseases, such as neovascularization, keratoconus, endothelial dystrophy-iris hypoplasia-congenital cataract-stromal thinning syndrome, corneal squamous cell carcinoma, age-related macular degeneration and cataract. Here we summarize and discuss the recent findings of miR-184 in its gene structure, gene expression and regulation, biological function and its relevance with ocular diseases. (Chin J Ophthalmol, 2017, 53: 950-955) .

Objective: To describe the clinical features of bronchopulmonary infection with hypermastigotes., Methods: Two cases of bronchopulmonary infection with hypermastigotes were reported. The clinical features of another six cases from the Chinese literature were reviewed., Results: Bronchopulmonary infection with hypermastigotes mostly occurs in the hot and humid southern area. The symptoms are severe, with different manifestations such as chronic cough, asthma, pneumonia, and even lung abscess. Final diagnosis is made by the presence of hypermastigotes in smears of secretions from the respiratory tract. An antiprotozoal such as metronidazole is always effective., Conclusion: In patients with unexplained cough, asthma, and pneumonia or lung abscess which do not respond to ordinary therapy, rare pathogens such as hypermastigotes need to be considered.