Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

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.

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.

microRNA(miRNA)is a 22nt long sin-gle-stranded non-coding RNA that is involved in a variety of physiological and pathological processes.Bronchial asthma is a heterogeneous disease,and airway inflammation is one of the important mecha-nisms of its pathogenesis.Asthma can be classified into different types based on the different immune mechanisms involved in its pathogenesis,and the mechanism of airway inflammation also varies be-tween different types of asthma.This article reviews the research progress of miRNA in asthma airway inflammation and endotype,and explores the pathogenesis and treatment prospects of miRNA in asthma airway inflammation and endotype.

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.

Background::Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.Methods::Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4-knockdown ( Atf4+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Results::CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes ( TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C hi monocytes and gMacs. Conclusion::ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.

Objective:To understand the current situations and existing problems of pediatric emergency in Shanghai city and provide a basis for the construction and management of pediatric emergency.Methods:The questionnaire survey was used to investigate the current situations of pediatric emergency department in secondary and tertiary public hospitals in Shanghai city.Results:A total of 28 questionnaires were delivered, and 28 were responded.Six of the 28 hospitals had no administratively independent pediatric emergency or no separate pediatric emergency area.Of the 22 hospitals, each had an average of 9.7 professional emergency pediatricians, with the exception of one secondary hospital that lacked professional emergency pediatricians.Professional emergency pediatricians accounted for an average of 70.0% of all pediatricians.Of the 22 hospitals, 18(81.8%) were open 24 hours a day.Fourteen(63.6%) had independent triage.Eight children′s emergency rooms(36.4%) were shared with adults.Among the 22 hospitals, 20 hospitals filled in the annual total number of pediatric emergency visits, and the total number of pediatric emergency visits ranged from 2 791 to 467 428, with an average of 93 966.65.Conclusion:There are still some problems in the development of pediatric emergency department in secondary and tertiary public hospitals in Shanghai city, such as insufficient human resources, substandard personnel training, incomplete equipment and lack of critical first-aid techniques.Therefore, the construction and management of pediatric emergency department still need to be improved.

Objective: To observe the effects of ginger-partitioned moxibustion at Shenque (CV8) and Guanyuan (CV4) on the expression levels of endocrine-related molecules and their receptors in rats with primary dysmenorrhea (PD) due to cold-dampness stagnation, thus to explore their analgesic mechanisms. Methods: Thirty-two female Wistar rats were divided into a normal group, a model group, a ginger-partitioned moxibustion group, and a Western medicine group according to the random number table method, with 8 rats in each group. Except for rats in the normal group, all other rats were treated with oxytocin combined with ice-water bath to establish the rat models of PD due to cold-dampness stagnation. After successful modeling, rats in the normal group and the model group did not receive treatment; rats in the ginger-partitioned moxibustion group received treatments with ginger-partitioned moxibustion at Shenque (CV8) and Guanyuan (CV4); rats in the Western medicine group received ibuprofen by intragastric administration. The writhing response of rats was compared among groups, and the serum levels of prostaglandin F2α (PGF2α), estrogen (estradiol, E2), progesterone (P), and the mRNA expression of PGF2α and E2 receptors in the uterine tissues were detected. Results: No writhing behavior was observed in the normal group; compared with the normal group, the serum PGF2α and E2 levels in the model group were increased (P<0.01), while the P level was decreased (P<0.01), and the mRNA expression levels of the uterine PGF2α and E2 receptors were increased (P<0.01, P<0.05). Compared with the model group, the writhing behavior latency was prolonged, and the writhing response score was decreased in the ginger-partitioned moxibustion group and the Western medicine group (P<0.01); the serum PGF2α and E2 levels in the ginger-partitioned moxibustion group and the Western medicine group were decreased, while the P level was increased (P<0.05 or P<0.01); the mRNA expression levels of the uterine PGF2α and E2 receptors in the ginger-partitioned moxibustion group and the Western medicine group were decreased (P<0.05). Compared with the Western medicine group, the ginger-partitioned moxibustion group showed a prolonged writhing behavior latency, reduced writhing response score (P<0.05), and decreased serum E2 level (P<0.05), while no statistical differences in the serum PGF2α and P levels, or the mRNA expression levels of uterine PGF2α and E2 receptors (P>0.05).Conclusion: The analgesic effect of ginger-partitioned moxibustion on PD due to cold-dampness stagnation may be related to regulating the mRNA expression levels of PGF2α and E2 receptors in the uterine tissues.

Biomarkers of sepsis play critical roles in diagnosis, early recognition of organ dysfunction, risk stratification, prognostication, and therapeutic strategy.The dysregulated inflammatory response is reflected drastic changes in pathogen-associated molecular patterns and damage-associated molecular patterns, presented the changes of gene expression and epigenetic modification, metabolic reprogramming and immune dysfunction of immune cells.Sepsis is classified into hyperinflammatory phenotype and immunosuppression phenotype.Biomarker exploration is also conductive to understand the heterogeneity of sepsis and developing the individualized treatment strategies.This issue focused on novel immune-associated biomarkers for prognostic prediction that could be useful to optimize patient management.

Objective:To describe the treatment strategies in children with septic shock in China.Methods:A questionnaire was prepared and 368 pediatric intensivists from the Pediatric Critical Care Physician Branch of Chinese Medical Doctor Association were surveyed about the treatment of pediatric septic shock from April to June 2017.Results:Surveys were received from 87.2%(68/78) institutions and 368 questionnaires (response-rate 45.1%) were included.59.2% and 77.7% of the respondents chose debridement surgery and fluid drainage as source control intervention.Antibiotics were used within 1 hour of shock in 90.8% of respondents.98.4% of respondents chose normal saline, 72.3% of respondents chosen albumin, and 53.8% of respondents chosen plasma for fluid resuscitation.When no venous access was available during shock resuscitation, 57.1% of respondents preferred intraosseous access.79.3% and 83.2% of the respondents used the adjuvant therapy such as glucocorticoids and intravenous immunoglobulin.96.7%, 85.3% and 22.0% of respondents were likely to provide oxygen and mechanical ventilation, continuous renal replacement, and extracorporeal membrane oxygenation as organ support, respectively.Additionally, 322 (88.7%), 188 (51.1%), and 85 (23.1%) respondents chose the "best advice" options to simulated clinical cases of fluid resuscitation, inotropic agents, and vasoactive agents, respectively.In the simulated cases of vasoactive drugs and inotropic drugs, 69.3% and 24.2% of the respondents chose fluid resuscitation strategy, respectively.In cases of fluid resuscitation, 49.7% (183/368) of respondents reported performing fluid responsiveness and volume status assessment, and instruments used in the assessment included bedside echocardiography[39.4% (145/368)], bioreactance[10.3% (38/368)], transpulmonary thermodilution devices[6.3% (23/368)]. Pediatricians who received advanced life support courses for children ( P=0.006) and intensive care specialist training center training ( P=0.002) were more likely to choose the " best recommendation" option than those who did not attend the training. Conclusion:The current status of pediatric septic shock treatment strategies in China are active source control intervention, antibiotic use and organs support, and increased awareness of non-invasive hemodynamic monitoring.However, there may be excessive fluid infusion and inappropriate use of plasma, glucocorticoids and intravenous immunoglobulin.Different training and continuing education may improve rational treatment strategies.