OBJECTIVES: Prolonged invasive mechanical ventilation is associated with increased risks of severe complications such as retinopathy of prematurity and bronchopulmonary dysplasia. Although neonatal intensive care unit (NICU) follow the principle of early extubation, extubation failure rates remain high, and reintubation may further increase the risk of adverse outcomes. This study aims to identify risk factors and short-term prognosis associated with first extubation failure in neonates, to provide evidence for effective clinical intervention strategies. METHODS: Clinical data of neonates who received invasive ventilation in the NICU of Children's Hospital of Nanjing Medical University from January 1, 2019, to December 31, 2021, were retrospectively collected. Neonates were divided into a successful extubation group and a failed extubation group based on whether reintubation occurred within 72 hours after the first extubation. Risk factors and short-term outcomes related to extubation failure were analyzed. RESULTS: A total of 337 infants were included, with 218 males (64.69%). Initial extubation failed in 34 (10.09%) infants. Compared with the successful extubation group, the failed extubation group had significantly lower gestational age [(31.37±5.14) weeks vs (34.44±4.07) weeks], age [2.5 (1.00, 8.25) h vs 5 (1.00, 22.00) h], birth weight [(1 818.97±1128.80) g vs (2 432.18±928.94) g], 1-minute Apgar score (6.91±1.90 vs 7.68±2.03), and the proportion of using mask oxygenation after extubation (21% vs 46%) (all P<0.05). Conversely, compared with the successful extubation group, the failed extubation group had significantly higher rates of vaginal delivery (59% vs 32%), caffeine use during mechanical ventilation (71% vs 38%), dexamethasone use at extubation (44% vs 17%), the highest positive end-expiratory pressure level within 72 hours post-extubation [6(5.00, 6.00) cmH₂O vs 5 (0.00, 6.00) cmH₂O] (1 cmH₂O=0.098 kPa), the highest FiO₂ within 72 hours post-extubation [(34.35±5.95)% vs (30.22±3.58)%], and duration of noninvasive intermittent positive pressure ventilation after extubation [0.5 (0.00, 42.00) hours vs 0 (0, 0) hours] (all P<0.05). Multivariate analysis identified gestational age <28 weeks (OR=5.570, 95% CI 1.866 to 16.430), age at NICU admission (OR=0.959, 95% CI 0.918 to 0.989), and a maximum FiO₂≥35% within 72 hours post-extubation (OR=4.541, 95% CI 1.849 to 10.980) as independent risk factors for extubation failure (all P<0.05). Additionally, the failed extubation group exhibited significantly higher incidences of necrotizing enterocolitis grade II or above, moderate-to-severe bronchopulmonary dysplasia, severe bronchopulmonary dysplasia, retinopathy of prematurity, treatment abandonment due to poor prognosis, and discharge on home oxygen therapy (all P<0.05). Total hospital length of stay and total hospitalization costs were also significantly increased in the failed extubation group (all P<0.05). CONCLUSIONS Gestational age <28 weeks, younger age at NICU admission, and FiO₂≥35% after extubation are high-risk factors for first extubation failure in neonates. Extubation failure markedly increases the risk of adverse clinical outcomes.
Humans ; Infant, Newborn ; Male ; Female ; Airway Extubation/adverse effects* ; Risk Factors ; Retrospective Studies ; Respiration, Artificial/methods* ; Intensive Care Units, Neonatal ; Prognosis ; Gestational Age ; Bronchopulmonary Dysplasia ; Infant, Premature ; Treatment Failure ; Intubation, Intratracheal

The angiogenic response is essential for the repair of ischemic brain tissue. Integrin α6 (Itga6) expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures; however, its role in post-ischemic angiogenesis remains poorly understood. In this study, we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization, reduced pericyte coverage on microvessels, and accelerated breakdown of microvascular integrity in the peri-infarct area. In vitro, endothelial cells with ITGA6 knockdown display reduced proliferation, migration, and tube-formation. Mechanistically, we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis. Importantly, the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels, leading to improved functional recovery. Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis, and may represent a promising therapeutic target for promoting recovery after stroke.
Animals ; Nitric Oxide Synthase Type III/metabolism* ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Integrin alpha6/genetics* ; Endothelial Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Stroke/pathology* ; Vascular Remodeling/physiology* ; Vascular Endothelial Growth Factor A/metabolism* ; Mice, Knockout ; Signal Transduction/physiology* ; Mice, Inbred C57BL ; Male ; Neovascularization, Physiologic/physiology*

Diabetic kidney disease(DKD)is one of the most important complications of diabetes.In recent years,domestic and foreign studies have found that mammalian target protein of rapamycin(mTOR)related signaling pathway is a classic pathway involved in the regulation of autophagy,which can achieve the therapeutic effect of DKD by targeting the autophagy pathway,and plays a crucial role in the prevention and treatment of DKD.In this paper,we reviewed the mechanism of mTOR-related signaling pathway targeted autophagy in the prevention and treatment of DKD,in order to provide a new reference and basis for clinical prevention and treatment of DKD.

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.

Objective To propose a method for classifying small bowel capsule endoscopy images by combining the Swin Transformer network with an improved Adapt-RandAugment data augmentation approach,aiming to enhance the accuracy and efficiency of small bowel lesion classification and recognition.Methods An Adapt-RandAugment data augmentation approach was formulated based on the RandAugment data enhancement sub-strategy and the principles of no feature loss and no distortion when enhancing small bowel capsule endoscopy images.In the publicly available Kvasir-Capsule dataset of small bowel capsule endoscopic images,the Adapt-RandAugment data augmentation approach was trained based on the Swin Transformer network,and the convolutional neural networks ResNet152 and DenseNet161 were used as the benchmarks to validate the combined Swin Transformer network and Adapt-RandAugment data augmentation approach for small bowel capsule endoscopy image classification.Results The proposed algorithm gained advantages over ResNet152 and DenseNet161 networks in the indicators,which had the macro average precision(MAC-PRE),macro average recall(MAC-REC),macro average F1 score(MAC-Fi-S)being 0.383 2,0.314 8 and 0.290 5 respectively,the micro average precision(MIC-PRE),micro average recall(MIC-REC)and micro average F1 score(MIC-Fi-S)all being 0.755 3,and the Matthews correlation coe-fficient(MCC)being 0.452 3.Conclusion The proposed small bowel capsule endoscopy image classification method based on Swin Transformer network and Adapt-RandAugment data augmentation approach behaves well in classified recognition efficiency and accuracy.[Chinese Medical Equipment Journal,2024,45(6):9-16]

Objective To investigate the risk factors and adverse prognosis associated with initial non-invasive ventilation(NIV)failure in very low birth weight infants(VLBWI)with gestational age<32 weeks.Methods A retrospective collection of clinical data from preterm infants admitted to the neonatal intensive care unit(NICU)in 28 tertiary hospitals in Jiangsu Province from January 2019 to December 2021 was conducted.Based on the outcomes of initial NIV,the infants were divided into a successful group and a failure group to analyze the risk factors for NIV failure and adverse prognosis.Results A total of 817 infants were included,with 453 males(55.4%)and 139 failures(17.0%).The failure group had lower gestational age,birth weight,and 1-minute and 5-minute Apgar scores compared to the successful group(P<0.05).The failure group also had a higher proportion of respiratory distress syndrome(RDS)diagnosed upon NICU admission,higher maximum positive end-expiratory pressure during NIV,and higher percentages of reaching the required maximum fraction of inspired oxygen(FiO2)≥30%,≥35%,and≥40%throughout the initial NIV process compared to the successful group(P<0.05).Gestational age(OR=0.671,95%CI:0.581-0.772),RDS(OR=1.955,95%CI:1.181-3.366),and FiO2≥30%(OR=2.053,95%CI:1.106-4.044)were identified as risk factors for initial NIV failure in these infants with gestational age<32 weeks(P<0.05).The failure group had higher incidences of complications such as pulmonary infections,pneumothorax,retinopathy of prematurity,moderate to severe bronchopulmonary dysplasia,and severe intraventricular hemorrhage during hospitalization,as well as longer hospital stays and higher total costs compared to the successful group(P<0.05).Conclusions Smaller gestational age,a diagnosis of RDS in the NICU,and achieving a maximum FiO2≥30%during the initial NIV process are risk factors for initial NIV failure in infants with gestational age<32 weeks.Initial NIV failure significantly increases the risk of adverse outcomes in this population.

Eleven compounds were isolated from the ethyl acetate fraction of the 95% aqueous ethanol extract of the roots of Sophora tonkinensis by silica gel, ODS, Sephadex LH-20 column chromatography, and semi-preparative RP-HPLC. Their structures were identified as 7-hydroxy-8-isopentenylchromone (1), furo[2,3-f]-1,3-benzodioxole-7-carboxylic acid (2), 6-[3-(2′,4′-dihydroxyphenyl)acryloyl]-7-hydroxy-2,2-dimethyl-8-(3-methyl-2-butenyl)-2H-benzopyran (3), flemichapparin B (4), tectorigenin (5), genistein (6), 6-hydroxy-1,3-benzodioxole-5-carboxylic acid (7), vanillic acid (8), protocatechuic acid (9), 2,4-dihydroxybenzoic acid (10), and p-hydroxybenzoic acid (11) through extensive spectroscopic data (IR, UV, HR-ESI-MS, and NMR spectra). Among them, compounds 1 and 2 were new compounds. In addition, compound 3 showed significant α-glucosidase and protein tyrosine phosphatase-1B (PTP1B) inhibitory activities with IC₅₀ values of 5.595 and 0.320 μmol·L^-1, respectively.

Objective To investigate factors influencing the occurrence of early haematoma expansion(HE)in patients with spontaneous intracerebral hemorrhage(sICH),to develop a predictive model and evaluate its predictive efficacy.Methods A retrospective cohort of 238 patients with sICH,admitted to General Hospital of Western Theater Command between January 2017 and December 2022,was analyzed.Patients were categorized into two groups based on the criteria of HE exceeding 33%in relative volume or 6 ml in absolute volume:HE group(n=62)and non-haematoma expansion(NHE)group(n=176).Clinical characteristics,laboratory findings,Non-contrast Computed Tomography(NCCT)imaging,and Glasgow Coma Scale(GCS)scores were compared between the two groups.Multifactorial logistic regression analysis was employed to identify risk factors for HE and to model the probability of its occurrence.The R language rms package was utilized to construct a nomogram model for predicting HE in sICH patients,Additionally,the related clinical,NCCT,and GCS models were constructed.The predictive efficacy of each model for HE in sICH patients was evaluated using area under Receive Operative Characteristic(ROC)curve(AUC),and the clinical application value of each model was assessed using accuracy,sensitivity,specificity,and Jordon's index.The Delong test was applied to analyze differences in the predictive values of the models.Results Significant differences in satellite sign,vortex sign,and history of anticoagulant treatment were observed between two groups(P<0.05).Multifactorial logistic regression analysis revealed independent risk factors for HE in sICH patients,including the first CT examination time,homogeneity,history of anticoagulant medication,volume,maximal diameter,hypodensity sign,island sign,satellite sign,and vortex sign(P<0.05).The AUCs for the constructed clinical model,NCCT model,GCS model and nomogram model in predicting the occurrence of HE in sICH patients were 0.672,0.706,0.518 and 0.754,respectively.The nomogram model demonstrated higher accuracy,sensitivity,Jordon's index and AUC compared with those in the clinical and NCTT models.Conclusions The first CT examination time,homogeneity,history of anticoagulant treatment,volume,maximum diameter,hypodensity sign,island sign,satellite sign,and vortex sign are independent predictors of early HE in sICH patients.The nomogram model,constructed with the above parameters,demonstrated high predictive efficacy for HE and holds potential for clinical application.

In recent years,the rapid development of medical information technology has made it critical to analyze large-scale diagnosis and therapeutic data and extract rules based on real medical environment.This has become an essential approach for marketing evaluation and regulatory decision-making of drugs and devices both domestically and internationally.Real world study(RWS),as a novel methodology for clinical evaluation of drugs in the field of drug utilization research(DUR),have presented opportunities and challenges for observational studies in assessing actual efficacy or effectiveness.However,despite being a popular methodological approach among scholars in the field,there are still limitations and deficiencies when analyzing population medication characteristics in RWS.Systematic evaluation research methods have not yet been established,leading to inadequate generation of real-world evidence(RWE).The research design,methodological pathways,evaluation indicators,confounding factors,and bias management involved in DUR based on real-world data(RWD)were reviewed in this artical with the intention of providing guidance for further exploration into DUR.

Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P＜0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P＜0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.