Background:Peptic ulcer bleeding(PUB)represents the leading etiology of acute upper gastrointestinal bleeding.Currently,endoscopy within 24 hours after admission is recommended for patients with acute upper gastrointestinal bleeding,but the optimal timing remains uncertain.Aims:To investigate the impact of endoscopic timing on the prognosis of patients with PUB.Methods:A retrospective analysis was conducted on PUB patients presenting with gastrointestinal bleeding symptoms who underwent gastroscopy within 24 hours after admission at Huizhou First Hospital from January 2019 to December 2022.According to the endoscopic timing after admission,patients were divided into urgent endoscopy group(≤8 hours after admission)and early endoscopy group(8-24 hours after admission).The 30-day rebleeding rate,rate of adverse in-hospital outcomes,length of hospital stay,hospitalization cost,and blood transfusion rate were compared between the two groups.Results:A total of 608 PUB patients were enrolled.The 30-day rebleeding rate was 6.6%.No significant differences in 30-day rebleeding rate,rate of adverse in-hospital outcomes,length of hospital stay and blood transfusion rate were found between the urgent endoscopy group and early endoscopy group(all P>0.05).However,hospitalization cost was significantly higher in urgent endoscopy group(P=0.002).In 376 patients with high-risk ulcer,the 30-day rebleeding rate was 10.4%.High-risk ulcer patients receiving urgent endoscopy demonstrated significantly lower 30-day rebleeding rate(7.3%vs.13.7%,P=0.042)and rate of adverse in-hospital outcomes(4.1%vs.10.4%,P=0.019),while there were no significant differences in length of hospital stay,hospitalization cost,and blood transfusion rate between the two subgroups(all P>0.05).Conclusions:Urgent endoscopy within 8 hours after admission does not reduce the 30-day rebleeding rate and rate of adverse in-hospital outcomes in patients with PUB.However,patients with high-risk ulcer may benefit from urgent endoscopy within 8 hours after admission.

[Objective]To explore the effect and potential mechanism of quercetin on polarization of lipopolysaccharide(LPS)-induced primary microglia.[Methods]Primary rat microglia were isolated and cultured,and then randomly divided into control group,model group and quercetin low-dose,medium-dose,high-dose groups.In model group,microglial activation was induced with LPS.In the quercetin groups,microglia were pretreated with quercetin at concentrations of 20,40 and 80 μmol·L-1 for 1 hour,followed by the addition of LPS to the culture medium for an additional 24 hours.Cell viability was assessed by using the CCK-8 assay.The nitric oxide(NO)content in the supernatant was measured by the Griess assay.Microglia activation was detected by ionized calcium binding adapter molecule 1(Iba1)/CD68 immunofluorescence staining.The expression levels of CD86,inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,CD206,arginase-1(Arg-1),chitinase like protein 1/2(Ym1/2),IL-10 and transforming growth factor-β(TGF-β)mRNA were determined by Real time-quantitative polymerase chain reaction(RT-qPCR).Network pharmacology and molecular docking methods were employed to predict the potential mechanisms of quercetin in regulating microglia polarization.The protein expression levels of CD86,iNOS,CD206,Arg-1,phosphophorylated-phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K),phosphophorylated-protein kinase B(p-Akt)/protein kinase B(Akt),phosphophorylated-nuclear factor-κB(p-NF-κB)/nuclear factor-κB(NF-κB)and phosphophorylated-inhibitor of NF-κB α(p-IκB-α)/inhibitor of NF-κB α(IκB-α)were determined by Western blot.[Results]Compared with LPS group,the NO release and CD68 mean fluorescence intensity of microglia in quercetin groups were significantly reduced(P<0.01),indicating that quercetin inhibited LPS-induced activation of primary microglia.Quercetin inhibited the mRNA and protein expression of CD86 and iNOS(P<0.05,P<0.01),and decreased the mRNA expression of pro-inflammatory factors TNF-α,IL-1β and IL-6(P<0.05,P<0.01).Additionally,quercetin promoted the mRNA and protein expression of CD206 and Arg-1(P<0.05,P<0.01),and upregulated the mRNA expression of anti-inflammatory factors Ym1/2,IL-10 and TGF-β(P<0.05,P<0.01).These findings indicated that quercetin promoted the transformation of LPS-induced primary microglia from the M1 type to the M2 type,thereby inhibiting neuroinflammation.The results of network pharmacology and molecular docking indicated that the regulation of microglia polarization by quercetin may be through the PI3K/Akt/NF-κB signaling pathway.In vitro experimental results showed that compared with LPS group,the protein expression levels of p-NF-κB and p-IκB-α in quercetin medium and high dose groups were significantly reduced(P<0.01),and the protein expression of p-PI3K and p-Akt was significantly increased(P<0.05,P<0.01).[Conclusion]Quercetin inhibited LPS-induced microglia inflammatory response and promoted microglia polarization to the M2 type,and the mechanism may be related to its regulation of the PI3K/Akt/NF-κB signaling pathway.

Background:Peptic ulcer bleeding(PUB)represents the leading etiology of acute upper gastrointestinal bleeding.Currently,endoscopy within 24 hours after admission is recommended for patients with acute upper gastrointestinal bleeding,but the optimal timing remains uncertain.Aims:To investigate the impact of endoscopic timing on the prognosis of patients with PUB.Methods:A retrospective analysis was conducted on PUB patients presenting with gastrointestinal bleeding symptoms who underwent gastroscopy within 24 hours after admission at Huizhou First Hospital from January 2019 to December 2022.According to the endoscopic timing after admission,patients were divided into urgent endoscopy group(≤8 hours after admission)and early endoscopy group(8-24 hours after admission).The 30-day rebleeding rate,rate of adverse in-hospital outcomes,length of hospital stay,hospitalization cost,and blood transfusion rate were compared between the two groups.Results:A total of 608 PUB patients were enrolled.The 30-day rebleeding rate was 6.6%.No significant differences in 30-day rebleeding rate,rate of adverse in-hospital outcomes,length of hospital stay and blood transfusion rate were found between the urgent endoscopy group and early endoscopy group(all P>0.05).However,hospitalization cost was significantly higher in urgent endoscopy group(P=0.002).In 376 patients with high-risk ulcer,the 30-day rebleeding rate was 10.4%.High-risk ulcer patients receiving urgent endoscopy demonstrated significantly lower 30-day rebleeding rate(7.3%vs.13.7%,P=0.042)and rate of adverse in-hospital outcomes(4.1%vs.10.4%,P=0.019),while there were no significant differences in length of hospital stay,hospitalization cost,and blood transfusion rate between the two subgroups(all P>0.05).Conclusions:Urgent endoscopy within 8 hours after admission does not reduce the 30-day rebleeding rate and rate of adverse in-hospital outcomes in patients with PUB.However,patients with high-risk ulcer may benefit from urgent endoscopy within 8 hours after admission.

[Objective]To explore the effect and potential mechanism of quercetin on polarization of lipopolysaccharide(LPS)-induced primary microglia.[Methods]Primary rat microglia were isolated and cultured,and then randomly divided into control group,model group and quercetin low-dose,medium-dose,high-dose groups.In model group,microglial activation was induced with LPS.In the quercetin groups,microglia were pretreated with quercetin at concentrations of 20,40 and 80 μmol·L-1 for 1 hour,followed by the addition of LPS to the culture medium for an additional 24 hours.Cell viability was assessed by using the CCK-8 assay.The nitric oxide(NO)content in the supernatant was measured by the Griess assay.Microglia activation was detected by ionized calcium binding adapter molecule 1(Iba1)/CD68 immunofluorescence staining.The expression levels of CD86,inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,CD206,arginase-1(Arg-1),chitinase like protein 1/2(Ym1/2),IL-10 and transforming growth factor-β(TGF-β)mRNA were determined by Real time-quantitative polymerase chain reaction(RT-qPCR).Network pharmacology and molecular docking methods were employed to predict the potential mechanisms of quercetin in regulating microglia polarization.The protein expression levels of CD86,iNOS,CD206,Arg-1,phosphophorylated-phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K),phosphophorylated-protein kinase B(p-Akt)/protein kinase B(Akt),phosphophorylated-nuclear factor-κB(p-NF-κB)/nuclear factor-κB(NF-κB)and phosphophorylated-inhibitor of NF-κB α(p-IκB-α)/inhibitor of NF-κB α(IκB-α)were determined by Western blot.[Results]Compared with LPS group,the NO release and CD68 mean fluorescence intensity of microglia in quercetin groups were significantly reduced(P<0.01),indicating that quercetin inhibited LPS-induced activation of primary microglia.Quercetin inhibited the mRNA and protein expression of CD86 and iNOS(P<0.05,P<0.01),and decreased the mRNA expression of pro-inflammatory factors TNF-α,IL-1β and IL-6(P<0.05,P<0.01).Additionally,quercetin promoted the mRNA and protein expression of CD206 and Arg-1(P<0.05,P<0.01),and upregulated the mRNA expression of anti-inflammatory factors Ym1/2,IL-10 and TGF-β(P<0.05,P<0.01).These findings indicated that quercetin promoted the transformation of LPS-induced primary microglia from the M1 type to the M2 type,thereby inhibiting neuroinflammation.The results of network pharmacology and molecular docking indicated that the regulation of microglia polarization by quercetin may be through the PI3K/Akt/NF-κB signaling pathway.In vitro experimental results showed that compared with LPS group,the protein expression levels of p-NF-κB and p-IκB-α in quercetin medium and high dose groups were significantly reduced(P<0.01),and the protein expression of p-PI3K and p-Akt was significantly increased(P<0.05,P<0.01).[Conclusion]Quercetin inhibited LPS-induced microglia inflammatory response and promoted microglia polarization to the M2 type,and the mechanism may be related to its regulation of the PI3K/Akt/NF-κB signaling pathway.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Background:Peptic ulcer bleeding(PUB)is the main cause of acute upper gastrointestinal bleeding.Currently,endoscopic examination within 24 hours is recommended for patients with acute upper gastrointestinal bleeding,but the optimal timing within 24 hours remains uncertain.Aims:To study the impact of endoscopic timing on the prognosis of patients with PUB.Methods:A retrospective analysis was conducted on patients who presented to Huizhou First Hospital with symptoms of gastrointestinal bleeding(hematemesis,melena,and bloody stools)from 2019 to 2022 and were diagnosed with PUB by gastroscopy within 24 hours.Their basic clinical data were collected.According to the endoscopic timing after admission,they were divided into urgent endoscopy group(≤8 hours after admission)and emergent endoscopy group(8-24 hours after admission).The 30-day rebleeding rate,the rates of adverse in-hospital outcomes,hospitalization costs,length of hospital stay,and blood transfusion rates were compared between the two groups.Results:A total of 608 patients were included in this study.The 30-day rebleeding rate was 6.6%.No significant differences in the 30-day rebleeding rate(5.3%vs.7.5%,P=0.275),the rate of adverse in-hospital outcomes in was(3.8%vs.7.2%,P=0.071),length of hospital stay and blood transfusion rate were found between the urgent endoscopy group emergent endoscopy group The hospitalization cost in the urgent endoscopy group was significantly higher than that in the emergent endoscopy group(P=0.002).There were 376 patients with high-risk ulcers.The 30-day rebleeding rate was 10.4%and the rate of adverse in-hospital outcomes was 7.2%.The 30-day rebleeding rate(7.3%vs.13.7%,P=0.042),the rate of adverse in-hospital outcomes(4.1%vs.10.4%,P=0.019)in the urgent endoscopy group were significantly lower than those in the emergent endoscopy group.There were no significant differences in hospitalization cost,length of hospital stay,and blood transfusion rate between the two groups.Conclusions:Urgent endoscopy within 8 hours after admission in patients with PUB does not reduce the 30-day rebleeding rate and the rate of adverse in-hospital outcomes.However,patients with high-risk ulcers seem more likely to benefit from emergency endoscopy within 8 hours.

Background:Peptic ulcer bleeding(PUB)is the main cause of acute upper gastrointestinal bleeding.Currently,endoscopic examination within 24 hours is recommended for patients with acute upper gastrointestinal bleeding,but the optimal timing within 24 hours remains uncertain.Aims:To study the impact of endoscopic timing on the prognosis of patients with PUB.Methods:A retrospective analysis was conducted on patients who presented to Huizhou First Hospital with symptoms of gastrointestinal bleeding(hematemesis,melena,and bloody stools)from 2019 to 2022 and were diagnosed with PUB by gastroscopy within 24 hours.Their basic clinical data were collected.According to the endoscopic timing after admission,they were divided into urgent endoscopy group(≤8 hours after admission)and emergent endoscopy group(8-24 hours after admission).The 30-day rebleeding rate,the rates of adverse in-hospital outcomes,hospitalization costs,length of hospital stay,and blood transfusion rates were compared between the two groups.Results:A total of 608 patients were included in this study.The 30-day rebleeding rate was 6.6%.No significant differences in the 30-day rebleeding rate(5.3%vs.7.5%,P=0.275),the rate of adverse in-hospital outcomes in was(3.8%vs.7.2%,P=0.071),length of hospital stay and blood transfusion rate were found between the urgent endoscopy group emergent endoscopy group The hospitalization cost in the urgent endoscopy group was significantly higher than that in the emergent endoscopy group(P=0.002).There were 376 patients with high-risk ulcers.The 30-day rebleeding rate was 10.4%and the rate of adverse in-hospital outcomes was 7.2%.The 30-day rebleeding rate(7.3%vs.13.7%,P=0.042),the rate of adverse in-hospital outcomes(4.1%vs.10.4%,P=0.019)in the urgent endoscopy group were significantly lower than those in the emergent endoscopy group.There were no significant differences in hospitalization cost,length of hospital stay,and blood transfusion rate between the two groups.Conclusions:Urgent endoscopy within 8 hours after admission in patients with PUB does not reduce the 30-day rebleeding rate and the rate of adverse in-hospital outcomes.However,patients with high-risk ulcers seem more likely to benefit from emergency endoscopy within 8 hours.

Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.
Humans ; Fibroblast Growth Factors ; Phosphatidylinositol 3-Kinases/metabolism* ; Central Nervous System/metabolism* ; Signal Transduction/physiology* ; Alzheimer Disease

Transcription factors, the proteins with special structures, can bind to specific sites and regulate specific expression of target genes. NAC (NAM, ATAF1/2, CUC1/2) transcription factors, unique to plants, are composed of a conserved N-terminal domain and a highly variable C-terminal transcriptional activation domain. NAC transcription factors are involved in plant growth and development, responses to biotic and abiotic stresses and other processes, playing a regulatory role in flower development. In this paper, we reviewed the studies about NAC transcription factors in terms of discovery, structure, and regulatory roles in anther development, other floral organ development and flowering time. This review will provide a theoretical basis for deciphering the regulatory mechanism and improving the regulatory network of NAC transcription factors in flower development.
Flowers/genetics* ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/metabolism* ; Plants/metabolism* ; Transcription Factors/metabolism*

Objective:To analyze the radiotherapy-related factors affecting the survival of non-small cell lung cancer (NSCLC) patients complicated with malignant pleural effusion (MPE)(MPE-NSCLC).Methods:From 2007 to 2019, 256 patients pathologically diagnosed with MPE-NSCLC received primary treatment. Among them, 117 cases were enrolled in this study. All patients were divided into two groups according to the radiation dose (<63 Gy and≥63 Gy). Propensity score matching (PSM) was performed to further adjust the confounding factors (Calipers value=0.1). The impact of radiotherapy-related factors on the overall survival (OS) was analyzed by Kaplan—Meier method, log-rank test and Cox’s regression model. Results:Primary tumor radiotherapy significantly prolonged the OS ( P<0.001). The radiation dose escalation (36.0-44.1 Gy, 45.0-62.1 Gy, 63.0-71.1 Gy) of primary tumor significantly prolonged the OS ( P<0.001). The corresponding median OS were 5, 13 and 18 months, respectively. Before the PSM, univariate analysis suggested that radiation dose ≥63 Gy, gross tumor volume (GTV)<157.7 cm 3 and stations of metastatic lymph node (S-mlN)≤5 were significantly associated with better OS (all P<0.05) and T 4N 3 was significantly associated with worse OS ( P=0.018). After the PSM, univariate analysis indicated that radiation dose ≥63 Gy was significantly associated with better OS ( P=0.013) and S-mlN ≤5 had a tendency to prolong the OS ( P=0.098). Prior to the PSM, multivariate analysis showed that radiation dose ≥63 Gy was an independent favorable factor of OS ( HR=0.566, 95% CI 0.368-0.871, P=0.010) and GTV<157.7 cm 3 had a tendency to prolong the OS ( HR=0.679, 95% CI 0.450-1.024, P=0.065). After the PSM, multivariate analysis revealed that radiation dose ≥63 Gy was still an independent favorable factor of OS ( HR=0.547, 95% CI 0.333~0.899, P=0.017). No ≥grade 4 radiation toxicity occurred. The incidence rates of grade 3 radiation esophagitis and pneumonitis were 9.4% and 5.1%, respectively. Conclusion:For MPE-NSCLC, radiotherapy dose of primary tumor may play a key role in improving OS on the basis of controllable MPE.