Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

The heterogeneity of sepsis plays critical roles in determining the response of clinical intervention and the outcome of sepsis.Based on the host-response revealed from multiomics,the new idea of the endotype of sepsis was revealed from multiple perspectives,such as transcriptome,proteome,epigenome,and exosome signature spectrum,etc.In recent years,in the field of sepsis endotype,the research of clinical subtype,metabolic subtype,and immune subtype is booming.This concept has gradually penetrated into multiple aspects,including the diagnosis,severity assessment,patients screening for clinical research,and the reference for individualized clinical treatment.It brings a new perspective for clinical individualized treatment of sepsis.

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.

Hemophagocytic lymphohistiocytosis（HLH）/macrophage activation syndrome（MAS）are hyperinflammatory diseases that primarily affect children.The main pathophysiological mechanism involves the reduction or lack of T lymphocyte and natural killer cell function，leading to abnormal proliferation and activation of lymphocytes and macrophages，resulting in cytokine storm and organ dysfunction.The main manifestations are high fever，cytopenia，hepatosplenomegaly，elevated ferritin，liver failure，and coagulation dysfunction,with a mortality rate that can exceed 50%.In recent years，HLH/MAS has developed new immunotherapy methods based on the treatment of traditional immunosuppressive agents.This article focused on the clinical research and treatment of new immunotherapy methods.

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 evaluate the efficacy and safety of intensity modulated radiotherapy (IMRT) and programmed death-1 (PD-1) immunotherapy combined with single-agent chemotherapy for patients with local failure of esophageal cancer after initial radical chemoradiotherapy.Methods:Clinical data of 80 patients with local failure of esophageal cancer after initial radical chemoradiotherapy treated with IMRT or PD-1 immunotherapy combined with single-agent chemotherapy in People's Hospital of Xinghua between June 2014 and June 2023 were retrospectively analyzed. IMRT was delivered at 1.8-2.0 Gy per fraction, 5 fractions per week, with a total dose of 45.0-60.0 Gy in 40 patients (IMRT group). The other 40 patients received PD-1 immunotherapy combined with single-agent chemotherapy (PD-1 immunotherapy combined with single-agent chemotherapy group). Kaplan-Meier method was used for univariate analysis and the cumulative survival probability. Log-rank test was used for survival significance test. Cox proportional hazards model was used for multivariate analysis of related factors affecting overall survival (OS), progression-free survival (PFS) and local control (LC).Results:By December 2023, the follow-up rate was 100%. The 1- and 2-year OS rates in the IMRT group were 66.1% and 18.9%, with a median OS time of 10.1 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year OS rates were 72.3% and 36.9%, with a median OS time of 12.4 months. There was a significant difference in OS rates between two groups ( χ2=3.89, P=0.049). The 1- and 2-year PFS rates in the IMRT group were 47.4% and 31.6%, with a median PFS time of 8.5 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year PFS rates were 70.0% and 64.2%, with a median PFS time of 11.9 months. There was no significant difference in the PFS rates between two groups ( χ2=2.66, P=0.103). The 1- and 2-year LC rates in the IMRT group were 68.6% and 62.3%, with a median LC time of 8.9 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year LC rates were 72.8% and 66.7%, with a median LC time of 12.0 months. There was no significant difference in LC rates between two groups ( χ2=0.18, P=0.672). Grade 2 radiation esophagitis and radiation pneumonitis developed in 82.5% (33/40) and 32.5% (13/40) in the IMRT group, respectively. The incidence of grade 1-2 peripheral blood leukopenia was 40.0% (16/40), 50.0% (20/40) for grade 1-2 peripheral blood thrombocytopenia, 27.5% (11/40) for moderate to severe anemia, and 20.0% (8/40) for grade 1-2 thyroid dysfunction in the PD-1 immunotherapy combined with single-agent chemotherapy, respectively. Single- and multi-factor analysis showed that the failure site ( χ2=9.01, P=0.011) and short-term efficacy ( χ2=7.78, P=0.005) were the independent prognostic factors affecting OS. The short-term efficacy was the independent prognostic factor for PFS ( χ2=31.63, P<0.001). The short-term efficacy was the independent prognostic factors affecting LCS ( χ2=17.64, P=0.001) too. Conclusion:For the patients with local failure of esophageal cancer after initial radical chemoradiotherapy, the combination of PD-1 immunotherapy with single-agent chemotherapy yields better survival prognosis than re-irradiation alone, but it is still necessary to pay attention to the related drug toxicities.

Objective:To survey the child health service capacity of community health service institutions in Shenzhen city.Methods:This was a cross-sectional study. An online survey was conducted among 559 community health service centers, stations and clinics in Shenzhen from January 23, 2024 to February 3, 2024. The questionnaire contents included the development of child health management, vaccination, diagnosis and treatment of common diseases in children, management of children′s chronic diseases, appropriate technology, availability of children′s special drug dosage forms, provision of special Chinese patent medicine and appropriate technology of traditional Chinese medicine for children, referral and remote consultation in 2019 and 2023. The reasons of unavailable service items were asked in the questionnaire and the questionnaire also contained an open-ended question about the suggestions for improving the capacity of child health services.Results:A total of 559 valid questionnaires were collected, accounting for 64.48% (559/867) of the community health service centers, stations and health clinics in Shenzhen in 2023. Compared to 2019, there was a significant increase in the rate of pediatric health services provided in 2023, including the diagnosis and treatment of common diseases in children under 6 years (96.06%, 537 institutions), nebulized inhalation therapy (96.60%, 540 institutions), influenza and other respiratory pathogen detection (90.70%, 507 institutions), rotavirus and other intestinal pathogen detection (34.53%, 193 institutions), allergen detection (81.75%, 457 institutions), blood oxygen saturation monitoring (84.44%, 472 institutions), pediatric-specific formulations of Western medicine (90.52%, 506 institutions), pediatric-specific formulations of traditional Chinese medicine (89.27%, 499 institutions), appropriate Chinese medicine techniques (88.19%, 493 institutions), relatively fixed referral hospitals (95.17%, 532 institutions), and remote consultation service (19.14%, 107 institutions); and the differences were statistically significant ( P<0.01). The reasons for unavailable service items were lack of space and personnel for the basic public health services, lack of space, personnel and a deficiency in knowledge and technical capabilities for diagnostic tests, and lack of equipment and personnel for remote consultation service. Suggestions made by 394 respondent institutions (70.48%) for further improvement included: conducting and strengthening various training (44.42%, 175/394), consultation and teaching by expert visiting (18.53%, 73/394), increasing the space and equipment (9.39%, 37/394), and further study at higher-level units (98.88%, 35/394). Conclusions:The child health services have been greatly improved in community health service institutions in Shenzhen, but there are still rooms for further improvement such as the ability of child health management, vaccination, chronic disease managements and provision of remote consultation.

Sepsis, leukemia/cancer and severe trauma/ surgery always contribute to severe coagulation dysfunction in children.The anticoagulation management during extracorporeal membrane pulmonary oxygenation(ECMO)is quite difficult because of complications such as bleeding or embolism and received more attention.How to dynamically balance anticoagulation with bleeding and thrombosis is crucial in ECMO support.This review summarized advances on prevention and management of coagulation disorder, and the optimizing of monitoring coagulation during ECMO.

Objective:To analyze the difference of clinical characteristics and outcomes of infants with moderate and severe pediatric acute respiratory distress syndrome(PARDS)diagnosed according to baseline oxygenation index(OI) in pediatric intensive care unit(PICU).Methods:Second analysis of the data collected from the "Efficacy of pulmonary surfactant (PS) in the treatment of children with moderate and severe ARDS" program.Retrospectively compare of the differences in clinical data such as general condition, underlying diseases, OI, mechanical ventilation, PS administration and outcomes among infants with moderate and severe PARDS divided by baseline OI who admitted to PICUs at 14 participating tertiary hospitals from 2016 to December 2021.Results:Among the 101 cases, 55 cases (54.5%) were moderate and 46 cases (45.5%) were severe PARDS.The proportion of male in the severe group (50.0% vs.72.7%, P=0.019) and the pediatric critical illness score(PCIS)[72 (68, 78) vs.76 (70, 80), P=0.019] were significantly lower than those in the moderate group, while there was no significant difference regarding age, body weight, etiology of PARDS and underlying diseases.The utilization rate of high-frequency ventilator in the severe group was significantly higher than that in the moderate group (34.8% vs.10.9%, P=0.004), but there was no significant difference in PS use, fluid load and pulmonary complications.The 24 h OI improvement (0.26±0.33 vs.0.04±0.34, P=0.001) and the 72 h OI improvement[0.34 (-0.04, 0.62) vs.0.15 (-0.14, 0.42), P=0.029)]in the severe group were significantly better than those in the moderate group, but there was no significant difference regarding mortality, length of hospital stay and intubation duration after diagnosis of PARDS between the two groups. Conclusion:In moderate and severe(divided by baseline OI) PARDS infants with invasive mechanical ventilation, children in severe group have better oxygenation improvement in the early stage after PARDS identified and are more likely to receive high frequency ventilation compared to those in moderate group.Baseline OI can not sensitively distinguish the outcomes and is not an ideal index for PARDS grading of this kind of patient.

Objective:To investigate the status quo and related issues of reception of pediatric patients by general practitioners in community health centers in Longhua District of Shenzhen through qualitative and quantitative studies.Methods:In qualitative study, 10 general practitioners (GPs) from community health centers in Longhua District of Shenzhen were selected by the purpose sampling method for personal in-depth interviews. The interview contents were recorded and transcribed, then coded by Nvivo software. Theme frame analysis method was used for data sorting and theme extraction. Based on the results of qualitative interviews, the questionnaire was developed and distributed through the electronic questionnaire platform. The contents of the questionnaire included general information, the situation of pediatric patient reception in community health centers, the willingness and ability of GPs to receive children, the existing problems and the measures to promote receiving pediatric patients in community health centers.Results:The results of personal in-depth interviews with 10 GPs showed that the obtained information reached saturation. Through repeated reading, induction and analysis of the interview data, four themes were extracted: ① GPs in community health centers received a large number of pediatric outpatients with common diseases; ② GPs in community health centers are willing to receive child patients, but they were lack of ability; ③ there were many problems of pediatric patients reception in community health centers; ④ training and incentive policies would help to promote child patient reception in community health centers. A total of 223 electronic questionnaires were collected, 219 of which were valid for analysis. All the community health centers in Longhua District received pediatric patients, the number accounted for 20%-60% of the total outpatients; 84.5%(185/219)of the responders were willing to receive child patients, 65.8% (144/219)of them assumed that the consulting ability was average. The main problems for GPs to receive pediatric patients were "insufficient training" (76.7%,168/219) and "lack of consulting ability" (55.3%,121/219). The important measures to promote GPs to receive child patients were to improve their own clinical competence (94.1%,206/219), to have clinical faculty with pediatric background mentoring at the community health center (74.9%,164/219), to improve the supporting facilities (42.9%,94/219) and continuous professional support (38.8%,85/219).Conclusion:The status quo of pediatric patient reception in the community of Shenzhen Longhua District is generally satisfactory. The main problems in this aspect are insufficient training for general practitioners and lack of clinical competence, which should be strengthened and improved in the future.