Purpose: Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori. Materials and Methods: A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection. Results: A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively. Conclusions Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Liquiritigenin(LG)is a flavone of pharmacological importance,however,its application potential is severely limited due to its poor water solubility.LG could be disassociated slightly in water to form phenolate anion,therefore,better solubilization effect is expected by inclusion with cationic cyclodextrins(CCDs).In this work,four kinds of CCDs modified with amino groups at the primary face were synthesized,and their solid inclusion complexes with LG were successfully prepared by preparing their saturated solutions.The formation of the solid inclusion complexes was confirmed by scanning electron microscopy(SEM)and powder X-ray diffraction(PXRD),and their supramolecular binding behavior in solution was studied using multiple techniques.A 1∶1 inclusion stoichiometry of inclusion complexation was defined using Job plot by ultraviolet-visible(UV-vis)spectroscopy,and their binding stability constants(Ks)were determined as 2862.77,3494.70,6521.85 and 9599.48 L/mol using UV-vis spectroscopic titration,far more superior to that of nativeβ-CD(Ks=236.79 L/mol).This indicated that the amino side chains on CCDs could actively participate in the inclusion complexation through anion-cation interactions,significantly strengthening the host-guest binding between CCDs and LG.The inclusion modes were further elucidated based on proton and two-dimensional rotating-frame overhauser enhancement spectroscopy(2D-ROESY)nuclear magnetic resonance(NMR)experiments and molecular docking.Water solubility of LG was dramatically promoted up to 4.9 mg/mL,which was 70-fold higher than that of native LG.This study could draw inspiration for the binding and solubilization of phenols such as flavones by design of cationic macrocyclic molecules.

[Objective] To evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

Objective:To explore the relationship between mechanical ventilation based on volumetric guaranteed(VG)ventilation mode and weaning outcomes of neonatal respiratory distress syndrome(RDS).Methods:This study was a single-center prospective study,according to random number table method,129 neonatal with RDS who were admitted to our hospital from January 2022 to October 2024 were divided into control group(received pressure-controlled ventilation,n=64)and observation group(received pressure-controlled ventilation combined with VG,n=65).The duration of invasive ventilation,total duration of respiratory support,length of hospital stay,arterial blood gas parameters[partial pressure of carbon dioxide(PaCO2),pH value,partial pressure of oxygen(PaO2),PaO2/fraction of inspired oxygen(FiO2)],weaning time,extubation failure rate and incidence of complications were compared between the two groups.Results:The duration of invasive ventilation,the total duration of respiratory support,the weaning time and the length of hospital stay in the observation group were shorter than those in the control group,and the extubation failure rate and the incidence of complications were lower than those in the control group(P＜0.05).24 h,48 h after intervention,PaCO2 decreased,while pH value,PaO2 and PaO2/FiO2 increased.The PaCO2 in the observation group was lower than that in the control group,while the pH value,PaO2 and PaO2/FiO2 were higher than those in the control group(P＜0.05).Conclusion:Mechanical ventilation based on VG can shorten the mechanical ventilation time of neonatal with RDS,improve blood gas analysis indicators,and reduce weaning time,extubation failure rate and the risk of complications.

Objective To investigate the mechanism of action of circ-0058063 regulating ERK/MAPK signaling pathway on ferroptosis in esophageal cancer cells.Methods EC9706 cells were randomly divided into the Control group,the si-NC group,the si-circ-0058063 group,and the si-circ-0058063+ISO group.qRT-PCR was used to detect the expression of circ-0058063 in esophageal cancer tissues and cells;CCK-8 and clone formation assay were used to detect the cell proliferation ability.The levels of Fe2+,malondialdehyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in cells were detected.Western blot was used to detect the ERK/MAPK signaling pathway and the expression of ferroptosis-related protein in cells.Results The expression level of circ-0058063 in esophageal cancer tissue was significantly higher than that in adjacent tissues(P<0.05);the expression level of circ-0058063 in human esophageal cancer cell EC9706 was significantly higher than that in human normal esophageal epithelial cell HEEC(P<0.05).Compared with the Control group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063 group were significantly reduced(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly increased(P<0.05).Compared with the si-circ-0058063 group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063+ISO group were significantly increased(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly decreased(P<0.05).Conclusion Knockdown of circ-0058063 can inhibit the proliferation of esophageal cancer cells and induce ferroptosis,and its mechanism of action may be related to the inhibition of ERK/MAPK signaling pathway activation.

Myocardial fibrosis(MF)is the leading cause of car-diac insufficiency.Its complex pathogenesis and lack of effective treatment are key issues to be addressed in the cardiovascular field.Mitochondrial quality control system(MQC)is an impor-tant mechanism for eukaryotic cells to maintain the stability of mitochondrial form,quantity and quality.MQC disorders,which are characterized by low level of mitochondrial biogenesis,exces-sive mitochondrial oxidative stress,mitochondrial autophagy de-fect and mitochondrial dynamics disorder,play a crucial role in mediating the pathophysiological process of MF.Consequently,this article reviews the role of MQC in MF pathogenesis and the latest research,in order to better understand the molecular mech-anism of MF and provide reference for the development of more natural drugs in the future.

Objective:To investigate the rehabilitation effect of aerobic exercise combined with discharge rehabilita-tion guidance in patients with coronary heart disease(CHD).Methods:This randomized controlled study enrolled 225 CHD patients admitted in Huai'an First People's Hospital between June 2020 and June 2023.Patients were ran-domly divided into control group(n=112)and intervention group(n=113).Patients in the control group received discharge rehabilitation guidance intervention,while those in the intervention group received additional aerobic ex-ercise training.After 6-month intervention,cardiac function,pulmonary function,vascular endothelial function indexes,quality of life,exercise treadmill scores,walking distance and patient satisfaction with rehabilitation effect were compared between the two groups.Results:Compared to those in the control group after intervention,patients in the intervention group had significantly higher left ventricular ejection fraction(LVEF)[(69.82±7.92)％vs.(63.34±6.88)％],stroke volume(SV)[(74.74±8.09)ml vs.(68.03±7.70)ml],cardiac output(CO)[(4.85±0.82)L/min vs.(4.18±0.73)L/min],cardiac index(CI)[(3.05±0.64)L·min-1·m-2 vs.(2.42±0.59)L·min-1·m-2],forced vital capacity(FVC)[(2.88±0.59)L vs.(2.37±0.56)L],maximum oxygen uptake(VO2max)[(23.23±4.08)ml·kg-1·min-1 vs.(19.79±3.86)ml·kg-1·min-1],anaerobic threshold(AT)[(21.10±4.18)ml·kg-1·min-1 vs.(17.21±3.90)ml·kg-1·min-1],nitric oxide(NO)[(33.10±5.18)mg/L vs.(27.21±5.90)mg/L],scores of General Quality of Life Inventory 74(GQOLI-74)[(85.43±8.19)points vs.(79.67±7.86)points],Duke treadmill score(DTS)[(9.08±2.03)points vs.(7.14±1.78)points],6-min walking distance(6MWD)[(342.14±36.24)m vs.(317.21±34.90)m](P＜0.001 all),and significantly lower levels of von Willebrand factor(vWF)[(23.43±4.39)ng/L vs.(29.37±4.56)ng/L]and endothelin-1(ET-1)[(47.12±5.28)pg/ml vs.(52.79±5.96)pg/ml](P＜0.001 all).We detected significantly higher total satisfac-tion with rehabilitation effect(92.73％vs.78.18％,P=0.002)in intervention group.Conclusion:Aerobic exercise combined with discharge rehabilitation guidance had good rehabilitation effect in CHD patients.It could improve their cardiopulmonary function,vascular endothelial function,and prognosis quality of life,and increase patient sat-isfaction.

Objective:To investigate the rehabilitation effect of aerobic exercise combined with discharge rehabilita-tion guidance in patients with coronary heart disease(CHD).Methods:This randomized controlled study enrolled 225 CHD patients admitted in Huai'an First People's Hospital between June 2020 and June 2023.Patients were ran-domly divided into control group(n=112)and intervention group(n=113).Patients in the control group received discharge rehabilitation guidance intervention,while those in the intervention group received additional aerobic ex-ercise training.After 6-month intervention,cardiac function,pulmonary function,vascular endothelial function indexes,quality of life,exercise treadmill scores,walking distance and patient satisfaction with rehabilitation effect were compared between the two groups.Results:Compared to those in the control group after intervention,patients in the intervention group had significantly higher left ventricular ejection fraction(LVEF)[(69.82±7.92)％vs.(63.34±6.88)％],stroke volume(SV)[(74.74±8.09)ml vs.(68.03±7.70)ml],cardiac output(CO)[(4.85±0.82)L/min vs.(4.18±0.73)L/min],cardiac index(CI)[(3.05±0.64)L·min-1·m-2 vs.(2.42±0.59)L·min-1·m-2],forced vital capacity(FVC)[(2.88±0.59)L vs.(2.37±0.56)L],maximum oxygen uptake(VO2max)[(23.23±4.08)ml·kg-1·min-1 vs.(19.79±3.86)ml·kg-1·min-1],anaerobic threshold(AT)[(21.10±4.18)ml·kg-1·min-1 vs.(17.21±3.90)ml·kg-1·min-1],nitric oxide(NO)[(33.10±5.18)mg/L vs.(27.21±5.90)mg/L],scores of General Quality of Life Inventory 74(GQOLI-74)[(85.43±8.19)points vs.(79.67±7.86)points],Duke treadmill score(DTS)[(9.08±2.03)points vs.(7.14±1.78)points],6-min walking distance(6MWD)[(342.14±36.24)m vs.(317.21±34.90)m](P＜0.001 all),and significantly lower levels of von Willebrand factor(vWF)[(23.43±4.39)ng/L vs.(29.37±4.56)ng/L]and endothelin-1(ET-1)[(47.12±5.28)pg/ml vs.(52.79±5.96)pg/ml](P＜0.001 all).We detected significantly higher total satisfac-tion with rehabilitation effect(92.73％vs.78.18％,P=0.002)in intervention group.Conclusion:Aerobic exercise combined with discharge rehabilitation guidance had good rehabilitation effect in CHD patients.It could improve their cardiopulmonary function,vascular endothelial function,and prognosis quality of life,and increase patient sat-isfaction.

AIM To investigate the effects of Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction(GJHQHLRSD)on the pyroptosis,pathway of colonic epithelial cells in mouse models of ulcerative colitis(UC).METHODS Among the 63 C57BL/6J mice,13 were randomly selected and assigned to the model group,and the others were divided into the control group,the positive Sulfasalazine Enteric-Coated Tablets group(0.6 g/kg),and low,medium,and high dose GJHQHLRSD groups(3.9,7.8,15.6 g/kg),with 10 mice in each group.The UC mouse model was established using DSS,and the corresponding drugs were administered by gavage.The mice had their general condition observed;their disease activity index(DAI)score assessed;their colon length measured;their histopathological damage of the colon analyzed using HE staining;their colonic IL-1β,IL-8,and TNF-α levels measured by ELISA method;their colonic NLRP3,GSDMD,pro-IL-1β,pro-caspase-1,and IL-1βprotein expression detected by Western blot method;and their cell pyroptosis detected by TUNEL and GSDMD fluorescence double staining.RESULTS Compared with the control group,the model group exhibited significant decrease in body weight and a shortened colon length(P＜0.01);increases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);significant increase of colonic GSDMD and TUNEL positivity;indicating increased tissue damage and inflammatory response.Compared with the model group,the groups intervened with GJHQHLRSD showed a significant increase in body weight and colonic elongation(P＜0.05,P＜0.01);decreases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);a gradient decrease in positivity of GSDMD and TUNEL;indicating a significantly reduced colonic pathological damage.CONCLUSION GJHQHLRSD can improve the DSS-induced inflammatory reaction of colonic mucosa in UC mice,and its mechanism mainly involves the NLRP3/caspase-1,thereby the regulation of the cell pyroptosis process.