Hemodynamic monitoring in shock is one of the core challenges in sepsis management.This article systematically explores how to optimize hemodynamic management in septic shock from three perspectives:assessment of fluid responsiveness and tolerance,monitoring of arterial and venous blood pressure,and macro- and microcirculatory monitoring.Firstly,fluid responsiveness assessment is the foundation of fluid therapy,but it must be combined with fluid tolerance to avoid fluid overload.Secondly,the refined evaluation of arterial and venous pressure changes,from macrocirculation to microcirculation,provides a more comprehensive perspective for hemodynamic management.Thirdly,the transition from cardiac output to microcirculatory flow is critical for optimizing oxygen delivery,requiring dynamic adjustment of treatment through both invasive and non-invasive techniques,while also considering the relationship between cardiac output and oxygen delivery and their impact on tissue oxygenation.By integrating these monitoring approaches,individualized and precise treatment for septic shock patients can be achieved,thereby improving outcomes.

Hemodynamic monitoring in shock is one of the core challenges in sepsis management.This article systematically explores how to optimize hemodynamic management in septic shock from three perspectives:assessment of fluid responsiveness and tolerance,monitoring of arterial and venous blood pressure,and macro- and microcirculatory monitoring.Firstly,fluid responsiveness assessment is the foundation of fluid therapy,but it must be combined with fluid tolerance to avoid fluid overload.Secondly,the refined evaluation of arterial and venous pressure changes,from macrocirculation to microcirculation,provides a more comprehensive perspective for hemodynamic management.Thirdly,the transition from cardiac output to microcirculatory flow is critical for optimizing oxygen delivery,requiring dynamic adjustment of treatment through both invasive and non-invasive techniques,while also considering the relationship between cardiac output and oxygen delivery and their impact on tissue oxygenation.By integrating these monitoring approaches,individualized and precise treatment for septic shock patients can be achieved,thereby improving outcomes.

Abstract: Although respiratory tract viral infections in children mainly cause respiratory diseases, severe respiratory viral infections are closely associated with infections, inflammation, or dysfunction of the nervous system. Common respiratory viruses such as human respiratory syncytial virus, influenza virus, coronaviruses, and human metapneumovirus can lead to severe neurological complications including encephalitis, acute disseminated encephalomyelitis, cerebellitis, Guillain-Barré syndrome, acute flaccid myelitis, and necrotizing encephalopathy, posing a threat to life. The outbreak of the SARS-CoV-2 epidemic has continuously increased the incidence and mortality of neurological complications in critically ill children. Therefore, this article will discuss the neuroinvasive mechanisms and neurological manifestations of respiratory viral infections in children, aiming to enhance early recognition of neurological complications related to respiratory viral infections in children by healthcare professionals and to minimize the harm of complications to children's health.

Objective:To investigate the effects of insulin-like growth factor-binding protein 3(IGFBP3),which is carried in exosomes released by cisplatin(DDP)-tolerant human lung adenocarcinoma(LUAD)A549/DDP cells,on differentiation of macrophages and its effect on DDP resistance of A549 cells.Methods:The parental A549 and A549/DDP cells were cultured in vitro,and the IC50 values were calculated after treatment with different concentrations of DDP for 48 h.The supernatants of A549 or A549/DDP cells culture were collected,and the exosomes were isolated using ultracentrifugation and named A-exo or A/D-exo,respectively.THP-1 cells were induced to differentiate into M0-type macrophages with PMA(15 μg/mL),mixed with A549 cells at a ratio of 1∶1,and then inoculated in the axillae of nude mice;on the day of tumor cell inoculation,the tumor cells were injected with PBS,A-exo,and A/D-exo at the inoculation site of the tumor cells,respectively,and at the same time,the treatment was carried out by intraperitoneal injection of DDP 1 time every 4 d.On the 35th day of the tumor loading in mice,the recruitment of human CD11b+CD206+or CD11b+CD86+macrophages in transplanted tumor tissues was detected by flow cytometry(FCM).Antibody microarrays were used to screen for proteins carried by A-exo or A/D-exo and validated by detecting the amount of IGFBP3 protein in A-exo and A/D-exo by ELISA method.A549 or A549/DDP cells were treated with different concentrations of rhIGFBP3,and the effects of rhIGFBP3 on the proliferation or migration ability of the cells were detected by MTS assay and Transwell assay,respectively.M0-type macrophages were treated with rhIGFBP3 for 4 d,and the culture supernatant was collected;the effects of different concentrations of rhIGFBP3 on the production of TGF-β and TNF-α content by M0-type macrophages were detected by ELISA;in addition,A549 cells were treated with rhIGFBP3 or culture supernatant of M0-type macrophages pretreated with rhIGFBP3,and again detected the IC50 value of DDP on A549 cells.Results:The IC50 value of DDP on A549/DDP cells was significantly higher than that of A549 cells(P<0.01);A/D-exo significantly promoted the growth of A549 cells xenograft tumors(P<0.05)and facilitated the recruitment of CD11b+CD206+macrophages into tumor tissues(P<0.05),compared with PBS and A-exo groups.Exosomes A-exo and A/D-exo were successfully obtained;high levels of IGFBP3 were carried in A/D-exo compared with A-exo.The analysis showed that the expression level of IGFBP3 was significantly up-regulated in patients with LUAD,and the overall survival rate of patients with high expression of IGFBP3 was reduced compared with those with low expression of IGFBP3.High concentration of rhIGFBP3(100 ng/mL)had a significant pro-proliferative effect on either A549 or A549/DDP cells(both P<0.05),but there was no statistically significant effect on the migratory ability of A549 or A549/DDP cells.High concentrations of rhIGFBP3(100 ng/mL)induced TGF-β1 production by M0-type macrophages(P<0.05),but not TNF-α production.The IC50 value of DDP on A549 cells was significantly increased(P<0.05)after treatment with culture supernatant of M0-type macrophages pretreated with IGFBP3(but not rhIGFBP3).Conclusion:A549/DDP cells mediate M2-type macrophage differentiation and promote secondary drug resistance in A549 cells by secreting IGFBP3-rich exosomes.

Objective:To provide support for efficient aeromedical support to aircrews by preliminarily investigating the current situation of asthenopia in civil aviation aircrews and analyzing its influencing factors.Methods:A cross-sectional study was used. Seventeen items of Asthenopia Survey Questionnaire (ASQ-17), that was developed by the asthenopia research team of Eye Hospital of Wenzhou Medical University, was conducted on aircrews of China Southern Airlines Co., Ltd. from September 23, 2022 to December 29, 2022. The situation and risk factors of asthenopia, as well as the symptoms mentioned in ASQ-17 were evaluated and analyzed in civil aviation aircrews. The risk factors of asthenopia were analyzed by multivariate Logistic regression analysis.Results:A total of 556 questionnaires were collected, and 516 were valid, with an effective recovery rate of 92.8%. The detection rate of asthenopia in civil aviation aircrews was 31.40%. There were significant differences in the detection rate of asthenopia between genders and the groups with and without ametropia and among the job types of aircrews ( χ2=10.07, 8.34, 11.83, P=0.002, 0.004, 0.003), but there was no significant difference in the detection rate of asthenopia between age groups (<40 years and ≥40 years) and whether corneal refractive surgery of aircrews (both P>0.05). There were significant differences in the detection rate of asthenopia among the aircrews with varying durations of close-up eye use, different sleep qualities and severities of anxiety even depression ( χ2=16.33, 36.34, 62.65, P=0.003,<0.001,<0.001), with an increasing trend in the detection rates of asthenopia corresponding to the prolonged durations of close-up eye use, the decreased sleep quality and the aggravated anxiety even depression. Multivariate Logistic regression analysis showed that job types, duration of close-up eye use, sleep quality, anxiety even depression and ametropia were the main risk factors for the occurrence of asthenopia ( OR=1.881-5.824, P=0.007-0.040). The results of ASQ-17 showed that the top 3 eyes symptoms of asthenopia in civil aviation aircrews were dry eyes, eyes soreness and periocular discomfort, with an average score of 18.06 on the ASQ-17. Conclusions:The detection rate of asthenopia in civil aviation aircrews is relatively high. The causes of asthenopia include dry eyes, excessive close-up eye use, ametropia and psychological factors according to the preliminary analysis. Aviation physicians should provide scientific and reasonable advice and intervention on the risk factors of asthenopia, with the aim of providing professional support for the visual health of aircrews.

Objective:To analyze the clinical situation of critically ill children with Montgomery T-tube，aiming to summarize the characteristics of T-tube application in pediatric and the experience of postoperative airway management in PICU.Methods:The etiology，clinical characteristics，complications and ICU admissions of patients with Montgomery T-tube admitted to the Pediatric Hospital of Fudan University from April 2019 to December 2021 were analyzed，and the application of T-tube in patients with critical conditions requiring long-term mechanical ventilation was described in the light of clinical experience.Results:During the study period,seven children were admitted to the PICU after T-tube insertion,including three males and four females,aged 9~75 months.Five children received mechanical ventilation.Among them,there were five cases with congenital laryngeal malformations,one case with tracheoesophageal fistula,and one case with laryngeal papilloma.The main complications were sputum blockage,infection,and granulation proliferation.One child died of secretion blockage,while the other children were successfully evacuated from the T-tube.The longest retention time of the T-tube was 367 days.Five patients experienced hoarseness after removing the T-tube,and upon re-examination with fiberoptic bronchoscopy,no recurrence of subglottic stenosis was observed.There was no respiratory distress or wheezing,and there were no abnormalities observed during regular outpatient follow-up after discharge.After discharge,the quality of life of the six surviving children improved compared to preoperative,and they all resumed oral feeding.There were no complaints of swallowing difficulties or aspiration during outpatient follow-up.But they were all combined with malnutrition.Conclusion:The Montgomery T-tube is a secure and dependable airway stent utilized for airway remodeling and the maintenance of airway patency following interventional surgery.For critically ill children,early management of airway clearance and infection prevention are imperative.

AIM:To test and compare the perceptual eye position and fixation stability of adolescents with emmetropia and adolescents with low myopia, investigating the characteristics of the perceptual eye position and fixation stability of adolescents with low myopia.METHODS: Cross-sectional study. A total of 132 adolescents(264 eyes)who visited in the ophthalmology clinic of our hospital from April to December 2023 were randomly selected as the research subjects. Participants were categorized into normal control group(n=45, 90 eyes), simple low myopia group(n=45, 90 eyes)and low myopia with anisometropia group(n=42, 84 eyes)according to their refractive status and were underwent assessments for perceptual eye position and fixation stability.RESULTS: Compared with the normal control group, the static and dynamic horizontal perceptual eye position deviation of the simple low myopia group and the low myopia with anisometropia group were significantly increased(P<0.05). Compared with the simple low myopia group, the static and dynamic horizontal perceptual eye position deviation of the low myopia with anisometropia group were significantly increased(P<0.05). There was no significant difference in static and dynamic vertical perceptual eye position deviation among the three groups(P>0.05); compared with the normal control group, the horizontal and vertical fixation stability of the simple low myopia group and the low myopia with anisometropia group were significantly worse(all P<0.01), but there was no differences in the simple low myopia group and the low myopia with anisometropia group(P >0.05).CONCLUSION: Abnormalities are observed in perceptual eye position and fixation stability function in adolescents with low myopia compared with those adolescents with emmetropia, even at best corrected visual acuity. The occurrence of anisometropia could lead to an increased degree of horizontal perceptual eye position displacement.

Objective:To analyze clinical characteristics of patients within 48 hours in pediatric intensive care unit（PICU）,and investigate causes and prognosis of extubation failure in reintubation children.Methods:A single-center retrospective study was conducted.Patients who were reintubated within 48 hours after extubation in PICU at Children's Hospital of Fudan University from January 1，2019 to December 31，2022 were retrospectively enrolled.Patients with unplanned extubation for various reasons which include re-intubation due to surgery and replacement of tracheal intubation were excluded.We analyzed the clinical characteristics，causes of extubation failure and prognosis.Main outcome measures included principal diagnosis，pediatric critical illness score（PCIS），the reason of intubation，the glasgow coma scale（GCS），the direct cause of reintubation，aeration time，hospitalization period，outcomes at PICU discharge and whether to extubate successfully.Results:During the study period，a total of 2 652 patients were extubated in PICU,and a total of 87 children were enrolled.Finally，63（72.4%）patients survived at PICU，nine（10.3%）patients died in hospital，and 15（17.2%）patients were discharged automatically.In the survival group，38（60.3%）patients were decannulated and 25（39.7%）patients underwent tracheotomy.The top three principal diagnosis in 87 cases were central nervous system disease[34（39.1%）cases]，lower airway disease[18（20.7%）cases] and sepsis[nine（10.3%）cases].Of the 87 children，28（32.2%）patients were reintubated due to central respiratory failure，21（24.1%）patients were reintubated due to lower airway disease，20（23.0%）patients were reintubated due to upper airway obstruction，14（16.1%）patients were reintubated due to cough weakness and/or swallowing disturbance，and four（4.6%）patients were reintubated for other reasons.In children with mechanical ventilation duration ≥7 days before first extubation，central nervous system diseases were the most common primary diseases，and it accounts for 55.6%.Central respiratory failure was the main direct cause of reintubation，accounting for 40.0%，and more patients(40.0%) had GCS scores＜8 before the first intubation.Compared with the successful decannulation group，the extubation failure group had the higher proportion of children with GCS＜8（32.7% vs.10.5%， P＜0.05），the longer median duration of mechanical ventilation before the first extubation[239（123，349）h vs.68.5（19，206）h， P＜0.05]and the longer median length of ICU stay[38（23，54）d vs.24（12，43）d， P＜0.05].After comparing the three groups including survival group，in-hospital death group and automatic discharge group，the PCIS score of the survival group was the highest，and the in-hospital death group was the lowest( P＜0.05). Conclusion:The rate of reintubation at 48 h after extubation in PICU is 3.3%.The immediate causes of reintubation mainly included central respiratory failure，lower airway disease，upper airway obstruction，cough weakness and/or dysphagia.The mortality rate of reintubation in critically ill children is high and the prognosis is poor.

Objective: Scavenger receptor class B type I (SR-BI) is primarily known for its role in the selective uptake of cholesteryl esters (CEs) from high-density lipoproteins (HDLs). Here we investigated whether SR-BI deficiency is associated with other potentially relevant changes in the plasma lipidome than the established effect of HDL-cholesterol elevation. Methods: Targeted ultra-high-performance liquid chromatography-tandem mass spectrometry was utilized to measure lipid species in plasma from female wild-type and SRBI knockout mice. Results: SR-BI deficiency was associated with a reduction in the average CE fatty acid length (−2%; p<0.001) and degree of CE fatty acid unsaturation (−18%; p<0.001) due to a relative shift from longer, polyunsaturated CE species CE (20:4), CE (20:5), and CE (22:6) towards the mono-unsaturated CE (18:1) species. Sphingomyelin (SM) levels were 64% higher (p<0.001) in SR-BI knockout mice without a parallel change in (lyso)phosphatidylcholine (LPC) concentrations, resulting in an increase in the SM/LPC ratio from 0.102±0.005 to 0.163±0.003 (p<0.001). In addition, lower LPC lengths (−5%; p<0.05) and fatty acid unsaturation degrees (−20%; p<0.01) were detected in SR-BI knockout mice. Furthermore, SR-BI deficiency was associated with a 4.7-fold increase (p<0.001) in total plasma ceramide (Cer) levels, with a marked >9-fold rise (p<0.001) in Cer (d18:1/24:1) concentrations. Conclusion We have shown that SR-BI deficiency in mice not only impacts the CE concentrations, length, and saturation index within the plasma compartment, but is also associated with plasma accumulation of several Cer and SM species that may contribute to the development of specific hematological and metabolic (disease) phenotypes previously detected in SR-BI knockout mice.

OBJECTIVE To optimize the preparation of Xiakucao Kaiyin Granules(XKG)and control the quality of its intermedi-ates.METHODS The physical characteristics of spray dry powder of XKG were determined by powder evaluation method,and the physical fingerprint composed of 9 secondary physical quality indexes,such as bulk density,tap density,angle of repose and Hausner ratio,was established to determine the stability of the previous process and the quality consistency of spray dry powder.Taking the parti-cle forming rate,dissolution rate,moisture absorption rate and angle of repose as evaluation indexes,dry granulation was carried out,and the auxiliary materials of XKG were screened.The mixture design experiment combined with G1-entropy weight method and neural network method were used to optimize the proportion of the selected excipients,and the best preparation technology of XKG was deter-mined by comparing the two methods.The physical fingerprint of particles was established to evaluate the consistency of particle quality among different batches.RESULTS The similarity of physical fingerprints of 9 batches of spray dry powder was greater than 0.970,and the physical properties were stable.The comprehensive score of the best proportion of auxiliary materials obtained through the anal-ysis of mixture design was higher than that obtained by neural network modeling and optimization,so it was finally determined that the proportion of medicine and auxiliary materials of XKG was 7:3 and 29%maltodextrin and 71%lactose were added for dry granulation.The similarity of physical fingerprints of five batches of granule was greater than 0.994.CONCLUSION The estab-lished physical fingerprint of intermediates can be used to control the quality process of XKG,and the optimized prescription of XKG can improve the physical properties of granules and improve the consistency of granule quality.