Objective:In critical care medicine, extubation is a pivotal step in the management of mechanically ventilated patients. Accurately determining the optimal timing for extubation is essential for minimizing complications and improving patient survival rates. However, reliable indicators to predict clinical outcomes following extubation remain scarce. This study aims to identify a novel and robust predictor of extubation success in critically ill patients, thereby providing clinicians with more precise decision-making support.Methods:This retrospective study analyzed data from adult patients who underwent mechanical ventilation and were evaluated for extubation across six intensive care units (ICUs) at Xiangya Third Hospital of Central South University between January 2019 and December 2021. Patients with a history of difficult airway, upper airway obstruction, or neuromuscular disorders affecting respiratory function were excluded. The primary outcome was the reintubation rate within 24 hours post-extubation. Categorical variables were analyzed using the chi-square test or Fisher’s exact test, while between-group differences were assessed with the Mann-Whitney U test. Significant predictors identified in univariate analysis were further evaluated via multivariate logistic regression. The diagnostic accuracy of the maximum inspiratory pressure/body mass index (MIP/BMI) ratio was determined using receiver operating characteristic (ROC) curve analysis, with the Youden index employed to establish the optimal cutoff value. Kaplan-Meier analysis and log-rank tests were used to compare extubation success rates between groups. Statistical analyses were performed using SPSS V28.0 and Stata v.16.0. Results:Diabetes comorbidity ( OR: 8.181, 95% CI: 1.659–40.338) and MIP/BMI ( OR: 0.140, 95% CI: 0.042–0.469) were identified as independent predictors of reintubation. The area under the ROC curve (AUROC) for MIP/BMI was 0.753, demonstrating good predictive accuracy. The optimal cutoff value for MIP/BMI was 1.26 cmH 2O/(kg·m 2), with a sensitivity of 55.3% and specificity of 92.3%. Kaplan-Meier analysis revealed a significantly higher reintubation rate in the low MIP/BMI group compared to the high MIP/BMI group ( P = 0.009), further validating its predictive utility. Conclusions:This study establishes MIP/BMI as a novel and clinically valuable predictor of extubation outcomes in critically ill patients. A cutoff value of 1.26 cmH 2O/(kg·m 2) was found to best predict successful extubation.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Diabetic foot ulcers are common in elderly people with diabetes.Ongoing research is aimed at unraveling the complicated molecular mechanisms underlying diabetic foot ulcers.The role of cellular aging in delayed healing of diabetic foot ulcers has been recognized.Analyzing the relationship between cellular aging and diabetic foot ulcers, examining how cellular aging delays the healing of diabetic foot wounds, and identifying treatment methods for the removal of senescent cells and for slowing down cellular senescence will provide new therapeutic targets and strategies for the development of drugs for diabetic foot ulcers.

Depression is a mental disease that seriously threatens life and health, and its pathogenesis is complicated. Recent studies have found that altitude is one of the important factors leading to depression. As an important transcription factor under hypoxic condition, hypoxia-inducible factor-1 regulates acute hypoxia, and upregulates neurotrophic factor and 5-hydroxytryptamine, thus exerting antidepressant effect by promoting brain metabolism; hypoxia-inducible factor-2 regulates chronic hypoxia, promotes inflammation and aggravates depression. This article focuses on the related research on hypoxia-inducible factors and pathogenesis of high altitude depression, to further explore the pathogenesis and prevent high altitude depression.

Objective: To establish an optimized path for health management of HBV infections among pregnant and lying-in women based on a Delphi method, so as to provide the evidence for intensifying the interruption of the mother-to-child transmission of HBV. Methods: Based on literature review and previous studies, the preliminary framework and contents of the optimized path for health management of HBV infections were constructed. Experts from epidemiology, clinical medicine and maternal and children healthcare were invited to participate in two-round Delphi consultations, and the preliminarily designed indicators were screened and revised. The score for feasibility of each indicator was calculated, and the weight of each indicator was estimated using a proportional distribution method. Results: Sixteen experts participated in the consultation, including 13 women. The participants had a mean age of (45.69±5.71) years, and a mean employment duration of (23.06±7.05) years. All participants had a degree of bachelor and above, and there were 14 experts with vice senior professional titles. The mean positive coefficient was 96.88% and the mean authority coefficient was 0.790 during the two-round expert consultations. There were significant differences in the coordination coefficient of importance, necessity and feasibility of indicators at all levels (P<0.05), and the coefficient of variation of the feasibility was all less than 0.250. The final optimized path for health management of HBV infections among pregnant and lying-in women included 6 primary indicators, 17 secondary indictors and 73 tertiary indicators. Among the primary indicators, delivery management (0.173 4), screening and evaluation (0.172 8) and pregnancy management (0.172 7) had a high weight. Conclusion A scientific and reliable optimized path is created for health management of HBV infections among pregnant and lying-in women, which has a potential value for improving the interruption of mother-to-child transmission of HBV.

Objective:To analyze the evolution of predominant Norovirus strain GⅡ.4 Sydney[P31] from 2017 to 2020 in China.Methods:Universal primers and next-generation sequencing technology were applied to establish Norovirus genogroup Ⅱ genome amplification method . Phylogenetic and key sites were analyzed on GⅡ.4 Sydney[P31] strains.Results:Among the 8 GⅡ.4 Sydney[P31] strains, 6 were successfully amplified and the genome sequences were obtained using the preliminarily established GⅡ genome amplification method . Phylogenetic analysis showed that the 6 strains obtained in this study from 2017-2020 strains grouped with the 2015-2019 GⅡ.4 Sydney[P31] reference strains in one cluster, and the Chinese strain GZ20133135 in 2013 and the 2012-2014 GⅡ.4 Sydney[P31] reference strains grouped into another one. A mutation Asp372Asn was found adjacent to the HBGA binding site Ⅱ. Epitope analysis showed that strains after 2017 have developed several aa mutations in A epitopes (297, 372, and 373), B epitopes (333), E epitopes (414), and H epitopes (309, 310), wherein the 2020 strains 20HN261 and 20HN253 have new changes in the A epitope (368) and G epitope (355) compared with the previous strains.Conclusions:The key mutation sites of the Chinese predominant Norovirus strain GⅡ.4 Sydney[P31] have been determined, which provides a scientific basis for tracking the emergence of new strains, and provides basic data for the development of vaccines against epidemic strains in China.

Objective:To study the clinical characteristics of children with adenovirus pneumonia complicated with liver injury and the understanding of clinicians.Methods:The children diagnosed with community-acquired adenovirus pneumonia were enrolled from January 1, 2013 to December 31, 2020. The clinical characteristics of the normal liver function group and the liver injured group were compared, and multivariate regression was applied.Results:Among the 3 294 enrolled children, 1 704 children had elevated alanine aminotransferase and/or aspartate aminotransferase on admission, and the liver function impairment rate was 51.7% (1 704/3 294), of which 1 671 cases were mildly injured (98.06%, 1 671/1 704), 28 cases were moderately injured (1.64%, 28/1 704), and 5 cases were severely injured (0.29%, 5/1 704). Compared with the normal liver function group, the proportion of male children in the liver injured group was higher (68.1% vs. 64.2%, P=0.017), and the age was younger[16(9, 30) months vs. 38(19, 53) months, P<0.001]. Children with liver injury were more likely to have wheezing (32.9% vs. 18.7%, P<0.001), shortness of breath (13.7% vs. 9.1%, P<0.001), and diarrhea (11.0% vs. 4.7%, P<0.001). The white blood cell counts, neutrophil counts and hemoglobin in the liver injured group were lower than those in the normal group, while the lymphocyte counts were higher than those in the normal group. The levels of creatine kinase, cardiac creatine kinase and lactate dehydrogenase were higher. The proportion of severe pneumonia in the liver injured group (26.9% vs. 11.2%, P<0.001) was higher than that in the normal liver function group, and the case fatality rate was significantly higher (1.47% vs. 0.25%, P<0.001). Comparing the probability of liver injury in children with mild and severe adenovirus pneumonia, it was found that the severe pneumonia group had more frequent liver injury (73.0% vs 46.6%, P<0.001), and both moderate and severe liver injury groups were higher than in the mild group. Further multivariate logistic regression analysis did not find a significant factor associated with the incidence of liver injury. Conclusions:The incidence of adenovirus pneumonia in children with liver injury was high, and mild injury is more common. Children with liver injury were younger, had more severe clinical symptoms such as wheezing and shortness of breath, and higher proportion of severe pneumonia and mortality. Among them, children with severe pneumonia had a higher proportion of liver injury, and moderate to severe injury was more common. The monitoring of children with different degrees of liver injury should be strengthened.

Objective:To clarify the evolutionary characteristics and key site variations of the GII.6[P7] genome of norovirus disease outbreak in China.Methods:Genome amplification and sequencing of 46 GII.6[P7] positive samples monitored from CaliciNet China from 2018 to 2021. Simultaneous integration of all ORF1 (GII. P7) and ORF2 (GII.6) sequences for Bayesian evolutionary analysis. And the use of Simplot for restructuring analysis.Results:According to Bayesian evolution analysis, GII. P7 polymerase has temporal evolutionary characteristics, with an average base replacement rate of 2.067× 10 -3 nucleotide substitution/site/year, and recombination with 4 different VP1 genotypes (GII.6, GII.7, GII.14, GII.20). In the capsid region, GII.6 noroviruses can be further divided into GII.6a, GII.6b and GII.6c subtypes. The 46 strains in this study belong to the GII.6a subtype, which are divided into the same cluster as the virus strain NHBGR59 circulating in China in 2015. Simplot analysis determined that the recombination site of the GII.6[P7] strain in this study was at the ORF1-2 junction. The amino acid site variation of VP1 mainly occurred at the end of P1.1 and the P2 region. Compared with the reference strain of GII.6a subtype, there was no variation in the receptor binding site. Conclusions:The GII.6[P7] recombinant strains of the norovirus outbreak from 2018 to 2021 in China all belong to the GII.6a[P7] subtype.

This paper reports 3 cases of acute hepatitis of unknown cause in children who met the case definition of WHO. Human adenovirus group C was detected in case 3, and the quantity of viral DNA was relatively high, which may be related to the liver function damage in the patient, but its role in pathogenesis needs further study to confirm.

There is an imbalance between the supply and demand of functional red blood cells (RBCs) in clinical appli-cations. This imbalance can be addressed by regenerating RBCs using several in vitro methods. Induced pluripotent stem cells (iPSCs) can handle the low supply of cord blood and the ethical issues in embryonic stem cell research, and provide a promising strategy to eliminate immune rejection. However, no complete single-cell level differentiation pathway exists for the iPSC-derived erythroid differentiation system. In this study, we used iPSC line BC1 to establish a RBC regeneration system. The 10X Genomics single-cell transcriptome platform was used to map the cell lineage and differentiation trajectory on day 14 of the regeneration system. We observed that iPSC differentiation was not synchronized during embryoid body (EB) culture. The cells (on day 14) mainly consisted of mesodermal and various blood cells, similar to the yolk sac hematopoiesis. We identified six cell classifications and characterized the regulatory transcription factor (TF) networks and cell–cell contacts underlying the system. iPSCs undergo two transformations during the differentiation trajectory, accompanied by the dynamic expression of cell adhesion molecules and estrogen-responsive genes. We iden-tified erythroid cells at different stages, such as burst-forming unit erythroid (BFU-E) and orthochromatic erythroblast (ortho-E) cells, and found that the regulation of TFs (e.g., TFDP1 and FOXO3) is erythroid-stage specific. Immune erythroid cells were identified in our system. This study provides systematic theoretical guidance for optimizing the iPSC-derived erythroid differentiation system, and this system is a useful model for simulating in vivo hematopoietic develo-pment and differentiation.