Fluid management is a key component in the treatment of pediatric acute respiratory distress syndrome (PARDS).Its primary goal is to maintain hemodynamic stability and improve tissue perfusion while avoiding complications such as worsening pulmonary edema and other adverse effects due to fluid overload.In children with shock who require fluid resuscitation,fluid management must balance the necessity of early resuscitation with the need for de-resuscitation in later stages,necessitating the development of an individualized and precise assessment and management strategy.This review integrates clinical practice with the latest evidence to explore the pathophysiological characteristics of PARDS,strategies for fluid resuscitation,key monitoring indicators, indications and contraindications for fluid resuscitation,as well as the management of common issues,current controversies, and future directions.

The development of polysaccharide conjugate vaccines, which convert polysaccharide antigens into T-cell-dependent immunogens through covalent conjugation with protein carriers, represents a critical strategy for enhancing immune protection in infants and young children. Globally licensed conjugate vaccines currently employ carrier proteins including Tetanus Toxoid, Diphtheria Toxoid, and Cross-Reacting Material 197. Recent advances have focused on three key areas: novel carrier protein discovery, optimized conjugation strategies, and evaluation of immune interference during co-administration of multivalent formulations. These efforts aim to achieve broader serotype coverage, prolonged protective efficacy, and simplified immunization schedules. This review synthesizes recent progress in carrier protein development, encompassing vaccine design principles, manufacturing processes, safety profiles, and epidemiological effectiveness. Furthermore, it critically examines current selection criteria for carrier proteins, their clinical applications, and persistent challenges, providing strategic insights to inform future conjugate vaccine development and immunization policy optimization in China.

Objective To explore the mechanism of electroacupuncture in alleviating hyperlipidemia in a rat model by modulating mammalian target of rapamycin complex 1(mTORC1)-mediated lipophagy in hepatocytes.Methods A total of 30 SD rats were randomly divided into blank(n=6)and modeling groups(n=24)using the random number table method.A hyperlipidemic rat model was established by feeding rats a high-fat diet(feeding for 8 weeks).After successful modeling,the modeling group was randomly divided into the model,electroacupuncture,mTORC1 inhibitor,and electroacupuncture+mTORC1 agonist groups,with six rats in each group.Except for the blank group,all other rats were fed with high fat diet.Rats in the electroacupuncture and electroacupuncture+mTORC1 agonist groups received electroacupuncture intervention at bilateral"Fenglong"(ST40)acupoints(dilatational wave 2 Hz/100 Hz,current intensity 1 mA)for 30 min once daily.Rats in the mTORC1 inhibitor group received intraperitoneal injections of the mTORC1 inhibitor,rapamycin(2 mg/kg),once daily.Rats in the electroacupuncture+mTORC1 agonist group received intraperitoneal injections of the mTORC1 agonist MHY1485(10 mg/kg)once daily.The interventions were administered for five consecutive days per week for 4 weeks.Upon completion of the intervention,the following analyses were performed:serum contents of total cholesterol(TC),triglycerides(TAG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),free fatty acids(FFA),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were measured using a fully automated biochemical analyzer.Hepatic histopathological changes and lipid deposition were observed using hematoxylin-eosin and oil red O staining.The liver condition was observed and the liver index was calculated.Hepatic TC and TAG levels were measured using an enzyme-linked immunosorbent assay.The ultrastructure of the liver tissue was observed using transmission electron microscopy,and the mean fluorescence intensity of perilipin 2(PLIN2)and microtubule-associated protein 1 light chain 3(LC3)-Ⅱ in the liver tissue was detected using immunofluorescence.Protein expression of LC3-Ⅱ/LC3-Ⅰ,phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR,and mTORC1 in liver tissue was detected using Western blotting.Results Compared to the blank group,the model group rats showed increased serum TC,TAG,LDL-C,ALT,AST,and FFA levels,along with decreased HDL-C levels(P<0.05).The liver index and hepatic TC and TAG levels were also elevated(P<0.05).Histological examination of liver tissue revealed substantial lipid accumulation,numerous lipid droplets within hepatocytes,abnormal mitochondrial morphology,and scarce autophagic vacuole.The mean fluorescence intensity of PLIN2 increased,whereas that of LC3-Ⅱ decreased(P<0.05).Additionally,the LC3-Ⅱ/LC3-Ⅰ ratio was reduced,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression were increased(P<0.05).Compared to the model group,rats in the mTORC1 inhibitor and electroacupuncture groups exhibited decreased serum TC,TAG,LDL-C,ALT,AST,and FFA levels(P<0.05),along with a reduced liver index and hepatic TC and TAG levels(P<0.05).Histological examination showed markedly attenuated lipid accumulation and visible autophagic vacuole in the hepatocytes.The mean fluorescence intensity of PLIN2 decreased,whereas that of LC3-Ⅱ increased(P<0.05).Moreover,the LC3-Ⅱ/LC3-Ⅰ ratio increased,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression decreased(P<0.05).In comparison with both the electroacupuncture and mTORC1 inhibitor groups,the electroacupuncture+mTORC1 agonist group demonstrated increased serum TAG,TC,LDL-C,ALT,AST,and FFA levels(P<0.05)as well as elevated liver index and hepatic TC and TAG levels(P<0.05).Liver tissues exhibited aggravated lipid deposition and absence of autophagic vacuole in liver cells.The mean fluorescence intensity of PLIN2 was enhanced,whereas that of LC3-Ⅱ was reduced(P<0.05).Furthermore,the LC3-Ⅱ/LC3-Ⅰ ratio decreased,and the p-mTOR/mTOR ratio and mTORC1 protein expression increased(P<0.05).Conclusion Electroacupuncture at"Fenglong"(ST40)may improve blood lipid levels in hyperlipidemic rats by inhibiting mTORC1 and promoting hepatocyte lipophagy.

The development of polysaccharide conjugate vaccines, which convert polysaccharide antigens into T-cell-dependent immunogens through covalent conjugation with protein carriers, represents a critical strategy for enhancing immune protection in infants and young children. Globally licensed conjugate vaccines currently employ carrier proteins including Tetanus Toxoid, Diphtheria Toxoid, and Cross-Reacting Material 197. Recent advances have focused on three key areas: novel carrier protein discovery, optimized conjugation strategies, and evaluation of immune interference during co-administration of multivalent formulations. These efforts aim to achieve broader serotype coverage, prolonged protective efficacy, and simplified immunization schedules. This review synthesizes recent progress in carrier protein development, encompassing vaccine design principles, manufacturing processes, safety profiles, and epidemiological effectiveness. Furthermore, it critically examines current selection criteria for carrier proteins, their clinical applications, and persistent challenges, providing strategic insights to inform future conjugate vaccine development and immunization policy optimization in China.

Objective To explore the mechanism of electroacupuncture in alleviating hyperlipidemia in a rat model by modulating mammalian target of rapamycin complex 1(mTORC1)-mediated lipophagy in hepatocytes.Methods A total of 30 SD rats were randomly divided into blank(n=6)and modeling groups(n=24)using the random number table method.A hyperlipidemic rat model was established by feeding rats a high-fat diet(feeding for 8 weeks).After successful modeling,the modeling group was randomly divided into the model,electroacupuncture,mTORC1 inhibitor,and electroacupuncture+mTORC1 agonist groups,with six rats in each group.Except for the blank group,all other rats were fed with high fat diet.Rats in the electroacupuncture and electroacupuncture+mTORC1 agonist groups received electroacupuncture intervention at bilateral"Fenglong"(ST40)acupoints(dilatational wave 2 Hz/100 Hz,current intensity 1 mA)for 30 min once daily.Rats in the mTORC1 inhibitor group received intraperitoneal injections of the mTORC1 inhibitor,rapamycin(2 mg/kg),once daily.Rats in the electroacupuncture+mTORC1 agonist group received intraperitoneal injections of the mTORC1 agonist MHY1485(10 mg/kg)once daily.The interventions were administered for five consecutive days per week for 4 weeks.Upon completion of the intervention,the following analyses were performed:serum contents of total cholesterol(TC),triglycerides(TAG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),free fatty acids(FFA),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were measured using a fully automated biochemical analyzer.Hepatic histopathological changes and lipid deposition were observed using hematoxylin-eosin and oil red O staining.The liver condition was observed and the liver index was calculated.Hepatic TC and TAG levels were measured using an enzyme-linked immunosorbent assay.The ultrastructure of the liver tissue was observed using transmission electron microscopy,and the mean fluorescence intensity of perilipin 2(PLIN2)and microtubule-associated protein 1 light chain 3(LC3)-Ⅱ in the liver tissue was detected using immunofluorescence.Protein expression of LC3-Ⅱ/LC3-Ⅰ,phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR,and mTORC1 in liver tissue was detected using Western blotting.Results Compared to the blank group,the model group rats showed increased serum TC,TAG,LDL-C,ALT,AST,and FFA levels,along with decreased HDL-C levels(P<0.05).The liver index and hepatic TC and TAG levels were also elevated(P<0.05).Histological examination of liver tissue revealed substantial lipid accumulation,numerous lipid droplets within hepatocytes,abnormal mitochondrial morphology,and scarce autophagic vacuole.The mean fluorescence intensity of PLIN2 increased,whereas that of LC3-Ⅱ decreased(P<0.05).Additionally,the LC3-Ⅱ/LC3-Ⅰ ratio was reduced,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression were increased(P<0.05).Compared to the model group,rats in the mTORC1 inhibitor and electroacupuncture groups exhibited decreased serum TC,TAG,LDL-C,ALT,AST,and FFA levels(P<0.05),along with a reduced liver index and hepatic TC and TAG levels(P<0.05).Histological examination showed markedly attenuated lipid accumulation and visible autophagic vacuole in the hepatocytes.The mean fluorescence intensity of PLIN2 decreased,whereas that of LC3-Ⅱ increased(P<0.05).Moreover,the LC3-Ⅱ/LC3-Ⅰ ratio increased,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression decreased(P<0.05).In comparison with both the electroacupuncture and mTORC1 inhibitor groups,the electroacupuncture+mTORC1 agonist group demonstrated increased serum TAG,TC,LDL-C,ALT,AST,and FFA levels(P<0.05)as well as elevated liver index and hepatic TC and TAG levels(P<0.05).Liver tissues exhibited aggravated lipid deposition and absence of autophagic vacuole in liver cells.The mean fluorescence intensity of PLIN2 was enhanced,whereas that of LC3-Ⅱ was reduced(P<0.05).Furthermore,the LC3-Ⅱ/LC3-Ⅰ ratio decreased,and the p-mTOR/mTOR ratio and mTORC1 protein expression increased(P<0.05).Conclusion Electroacupuncture at"Fenglong"(ST40)may improve blood lipid levels in hyperlipidemic rats by inhibiting mTORC1 and promoting hepatocyte lipophagy.

Fluid management is a key component in the treatment of pediatric acute respiratory distress syndrome (PARDS).Its primary goal is to maintain hemodynamic stability and improve tissue perfusion while avoiding complications such as worsening pulmonary edema and other adverse effects due to fluid overload.In children with shock who require fluid resuscitation,fluid management must balance the necessity of early resuscitation with the need for de-resuscitation in later stages,necessitating the development of an individualized and precise assessment and management strategy.This review integrates clinical practice with the latest evidence to explore the pathophysiological characteristics of PARDS,strategies for fluid resuscitation,key monitoring indicators, indications and contraindications for fluid resuscitation,as well as the management of common issues,current controversies, and future directions.

Objective:To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories.Methods:The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory.Results:In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%).Conclusions:A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

Objective:To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China.Methods:A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results:A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality ( OR=1.04, 1.09, 0.67, 95% CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions:Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.