Objective:To investigate the association between small vulnerable newborn (SVN) phenotypes and the risk of neurodevelopmental delay at the age of 1 year.Methods:A prospective cohort study was conducted. A total of 25 860 singleton infants from "The Born in Guangzhou Cohort Study" who completed the Gesell developmental scale assessment at 1 year of age between January 2013 and June 2025 were included. Maternal sociodemographic characteristics, and other information were collected using a self-administered questionnaire, and maternal pregnancy-related information and neonatal birth data were extracted from medical records. Global developmental delay (GDD) was defined as a developmental quotient below 86 in ≥3 domains of the Gesell developmental scale, which assesses the adaptive, gross motor, fine motor, language, and personal-social domains. The random forest algorithm was employed for missing data imputation. Based on prematurity, small for gestational age (SGA), and low birth weight (LBW), newborns were categorized into 6 phenotypes: preterm-SGA-LBW, preterm-appropriate for gestational age (AGA)-LBW, preterm-AGA-nonLBW, term-SGA-LBW, term-LBW-only or term-SGA-only, and term-AGA-nonLBW phenotype. Among these, the first 5 were classified as SVN phenotypes, and the last one served as the reference group. Inter-group comparisons were performed using analysis of variance (ANOVA), χ2 tests, or Kruskal-Wallis test, as appropriate.?? Multivariable robust Poisson regression models were applied to analyze the association of different SVN phenotypes with the risks of GDD and developmental delays in specific domains, with stratified analyses by sex. Results:Among the 25 860 infants, 13 719 (53.1%) were male and 12 141 (46.9%) were female. The gestational age at birth was 39.4 (38.6, 40.0) weeks. The overall detection rate of GDD at 1 year of age was 3.7% (962/25 860). The rates of delay across developmental domains, in descending order, language in 8 134 cases (31.5%), gross motor in 4 488 cases (17.4%), personal-social in 1 271 cases (4.9%), adaptive in 1 262 cases (4.9%), and fine motor in 621 cases (2.4%). Compared with the reference group, preterm-AGA-LBW, preterm-SGA-LBW, preterm-AGA-noneLBW, and term-SGA-LBW phenotypes were all associated with an increased risk of GDD, with the adjusted RR (95% CI) of 6.07(5.01-7.35), 4.81(3.11-7.46), 2.10(1.54-2.88) and 1.89(1.29-2.76) respectively.The preterm-AGA-noneLBW phenotype was all associated with an increased risk of delay in gross motor, language and personal-social functional domains (all P<0.05). The term-SGA-LBW phenotype was associated with an increased risk of delay in gross motor, fine motor and personal-social functional domains (all P<0.01). Whereas the term-LBW-only or term-SGA-only phenotype showed no statistically association with developmental delay in any functional domain (all P≥0.05). Conclusion:The combined classification based on gestational age and birth weight helps identify infants at high risk for neurodevelopmental delay at 1 year of age, suggesting that it may offer a reference for the rational allocation of clinical resources.

Objective:To investigate the association between small vulnerable newborn (SVN) phenotypes and the risk of neurodevelopmental delay at the age of 1 year.Methods:A prospective cohort study was conducted. A total of 25 860 singleton infants from "The Born in Guangzhou Cohort Study" who completed the Gesell developmental scale assessment at 1 year of age between January 2013 and June 2025 were included. Maternal sociodemographic characteristics, and other information were collected using a self-administered questionnaire, and maternal pregnancy-related information and neonatal birth data were extracted from medical records. Global developmental delay (GDD) was defined as a developmental quotient below 86 in ≥3 domains of the Gesell developmental scale, which assesses the adaptive, gross motor, fine motor, language, and personal-social domains. The random forest algorithm was employed for missing data imputation. Based on prematurity, small for gestational age (SGA), and low birth weight (LBW), newborns were categorized into 6 phenotypes: preterm-SGA-LBW, preterm-appropriate for gestational age (AGA)-LBW, preterm-AGA-nonLBW, term-SGA-LBW, term-LBW-only or term-SGA-only, and term-AGA-nonLBW phenotype. Among these, the first 5 were classified as SVN phenotypes, and the last one served as the reference group. Inter-group comparisons were performed using analysis of variance (ANOVA), χ2 tests, or Kruskal-Wallis test, as appropriate.?? Multivariable robust Poisson regression models were applied to analyze the association of different SVN phenotypes with the risks of GDD and developmental delays in specific domains, with stratified analyses by sex. Results:Among the 25 860 infants, 13 719 (53.1%) were male and 12 141 (46.9%) were female. The gestational age at birth was 39.4 (38.6, 40.0) weeks. The overall detection rate of GDD at 1 year of age was 3.7% (962/25 860). The rates of delay across developmental domains, in descending order, language in 8 134 cases (31.5%), gross motor in 4 488 cases (17.4%), personal-social in 1 271 cases (4.9%), adaptive in 1 262 cases (4.9%), and fine motor in 621 cases (2.4%). Compared with the reference group, preterm-AGA-LBW, preterm-SGA-LBW, preterm-AGA-noneLBW, and term-SGA-LBW phenotypes were all associated with an increased risk of GDD, with the adjusted RR (95% CI) of 6.07(5.01-7.35), 4.81(3.11-7.46), 2.10(1.54-2.88) and 1.89(1.29-2.76) respectively.The preterm-AGA-noneLBW phenotype was all associated with an increased risk of delay in gross motor, language and personal-social functional domains (all P<0.05). The term-SGA-LBW phenotype was associated with an increased risk of delay in gross motor, fine motor and personal-social functional domains (all P<0.01). Whereas the term-LBW-only or term-SGA-only phenotype showed no statistically association with developmental delay in any functional domain (all P≥0.05). Conclusion:The combined classification based on gestational age and birth weight helps identify infants at high risk for neurodevelopmental delay at 1 year of age, suggesting that it may offer a reference for the rational allocation of clinical resources.

Objective To explore the pathogenic mechanisms of Legionella pneumophila(L.pneumophila)infection inhibiting the fusion of endosome-lysosome fusion in mouse macrophages.Methods Twelve C57 mice were randomly divided into control group and L.pneumophila infection group(n=6 each).After anesthesia,an equal volume of physiological saline or L.pneumophila solution was administered nasally.Body weight changes were monitored for 3 consecutive days,and the lungs were extracted to assess injury.Hematoxylin and eosin(HE)staining and immunohistochemical staining were performed to observe the pathological characteristics of lung tissue in both groups.Transcriptome sequencing was utilized to analyze differentially expressed genes(DEGs)and associated signaling pathways in lung tissues.Mouse bone marrow macrophages(BMDMs)were isolated and co-cultured with L.pneumophila,with infection status confirmed by immunofluorescence staining.Transcriptome sequencing was employed to analyze DEGs and enriched related signaling pathways before and after infection.Core genes involved in the post-infection signaling pathway were identified,and the consistency of their mRNA expression levels in vivo and in vitro was verified using RT-qPCR.The expression of relevant proteins was detected by Western Blotting,and bacterial proliferation assays were conducted to evaluate the intracellular replication of L.pneumophila.Results Compared with control group,the body weight of mice in L.pneumophila infection group significantly decreased(P<0.001)on the second and third day post-infection.Edema and red hepatoid degeneration were observed in both left and right lung tissues,with lesion areas spreading from the hilum to the lung periphery.HE staining revealed increased inflammatory cell infiltration in the alveolar spaces,thickening of alveolar septa and increased fibrin exudation in L.pneumophila infection group.Immunohistochemistry results showed a significant increase in myeloperoxidase(MPO)activity in the lung tissue infected mice(P<0.001).Transcriptome sequencing identified 2550 DEGs,with 1444 up-regulated genes and 1106 down-regulated genes.KEGG enrichment analysis indicated that these DEGs were mainly involved in pathways related to tumor necrosis factor,rheumatoid arthritis,Rap1,PI3K-Ak,and phagosome pathways.Immunofluorescence results showed in vitro proliferation of L.pneumophila within mouse BMDMs.Transcriptome sequencing identified 2550 DEGs,including 1677 up-regulated genes and 873 down-regulated genes.KEGG enrichment analysis showed that enrichment in pathway related to transcription dysregulation in cancer,PI3K-Akt and phagosome pathways.Thirteen core genes,including tubulin β1(Tubb1),were identified from the overlap between mouse lung tissue and BMDMs.RT-qPCR results demonstrated a significant decrease in Tubb1 expression in both lung tissue and BMDMs infected with L.pneumophila(P<0.001).Western Blotting results revealed significant decreases in Rab7,Tubb1,and LAMP2 protein expression(P<0.05),and increases in iNOS and MPO expression(P<0.05).Intracellular proliferation experiments indicated that L.pneumophila gradually increased within BMDMs over time.Conclusion The potential mechanism of L.pneumophila infection in mouse macrophages involves the down-regulation of Rab7/Tubb1/LAMP2 which inhibits the endosome-lysosome fusion.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

20-hydroxyeicosatetraenoic acid(20-HETE)and epoxyeicosatrienoic acids(EETs)are products of enzyme metabolism of arachidonic acid(AA)by cytochrome P450(CYP).20-HETE is mainly produced by CYP4A,CYP4F metabolism of AA,which has a certain toxic effect on the cardiovascular and cerebrovascular system.EETS is mainly produced by CYP2J,CYP2C metabolizes AA,which has a certain protective effect on the cardiovascular and cerebrovascular system.This article reviews the effects and mechanisms of drugs related to AA-CYP-HETE/EETs metabolic pathway on cardiovascular diseases such as myocardial hypertrophy,hypertension,heart failure,and myocardial infarction,in order to provide a reference for the clinical use of cardiovascular diseases and provide ideas and directions for the basic research and development of cardiovascular disease treatment drugs.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1⁺ SCs). Darbepoetin alpha (a long-acting EPO analog, EPO_anlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin^- Sca-1⁺ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPO_anlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin^- Sca-1⁺ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1⁺ SCs.
Animals ; Mice ; Ventricular Remodeling ; Erythropoietin ; Myocardial Infarction ; Heart ; Stem Cells

BackgroundSleep disorder can adversely affect human physical and mental health， with important implications for socioeconomic development. And higher vocational college students are subject to various pressures and stimuli exerted by academic studies， job seeking and family socioeconomic status， which may contribute to the onset insomnia symptom or sleep disorder. ObjectiveTo discuss the sleep status and influencing factors among higher vocational college students， and to provide references for improving their sleep status. MethodsIn January and February， 2022， a stratified random sampling method was utilized to enroll 3 300 students from five higher vocational colleges in Wenjiang district of Chengdu city. All the participants were assessed using Insomnia Severity Index （ISI）， Patient Health Questionnaire Depression Scale-9 item （PHQ-9） and Generalized Anxiety Disorder Scale-7 （GAD-7）. Pearson correlation analysis was conducted to test the correlation of ISI with PHQ-9 and GAD-7 scores， and the Logistic regression analysis was performed to identify the influencing factors of insomnia symptom in higher vocational college students. ResultInsomnia symptom was detected in 81.90% （2 497 / 3 300） of higher vocational college students. The detection rate of insomnia symptom among vocational college students yielded statistical difference in terms of gender， family socioeconomic status， being an only child or having siblings， degree of psychological pressure exerted by academic studies or job seeking， amount of hours spent on Internet per day， frequency of physical exercise， and the presence or absence of anxiety symptom and depression symptom （χ²=21.032， 22.172， 8.983， 75.939， 36.781， 32.350， 54.512， 86.561， P<0.01 or 0.05）. Among higher vocational college students， ISI score was positively correlated with GAD-7 and PHQ-9 scores （r=0.620， 0.714， P<0.01）， and GAD-7 score was positively correlated with PHQ-9 score （r=0.824， P<0.01）. Gender， family socioeconomic status， degree of psychological pressure exerted by academic studies or job seeking， amount of hours spent on Internet per day， frequency of physical exercise， and the presence or absence of anxiety symptom and depression symptom were effective factors in predicting the insomnia symptom in higher vocational college students （P<0.01 or 0.05）. ConclusionFemale gender， average and below average family socioeconomic status， moderate-to-severe degree of psychological pressure exerted by academic studies or job seeking， spending 2~5 h， 5~7 h or >7 h on Internet per day， inadequate physical exercise and presence of depressive symptom are the risk factors for insomnia symptom in higher vocational college students.［Funded by Sichuan Provincial Primary Health Development Research Center in 2022， North Sichuan Medical College （number， SWFZ22-C-89）］

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy