As a symbiotic microbial community within the human body,the gut microbiota plays a crucial role in modulating various physiological processes,including metabolism,immunity,and endocrine function.During allogeneic hematopoietic stem cell transplantation(allo-HSCT),the hematopoietic and immune systems undergo significant changes,which are also influenced by the gut microbiota.Specifically,regarding hematopoietic function,the gut microbiota facilitates the multi-lineage differentiation of hematopoietic stem cells via NOD1-STATs and TLRs-MyD88 signaling pathways,and promotes rapid granulomonocytic lineage differentiation under infection stress.Consequently,early-stage primary graft dysfunction following transplantation may be associated with gut microbiota dysbiosis.In terms of immune function,the gut microbiota enhances the expression of antigen-presenting molecules on intestinal epithelial cells,thereby initiating acute graft-versus-host disease(aGVHD)in the gastrointestinal tract.Moreover,the gut microbiota regulates intestinal immune function through metabolites such as short-chain fatty acids,bile acids,and indole derivatives.Dysbiosis of the gut microbiota can lead to disrup-tion of the intestinal mucus barrier and immune barrier functions,further promoting the onset and progression of aGVHD in the gastrointestinal tract.Therefore,targeting the gut microbiota has emerged as an attractive therapeutic strategy and has been clinically applied.Notably,fecal microbiota transplantation combined with immunosuppressive therapy has shown significant efficacy in alleviating clinical severity and improving prognosis in steroid-refractory aGVHD,demonstrating high safety and manageable adverse reactions,representing a novel breakthrough in its treatment.

Allogeneic haematopoietic stem cell transplantation(allo-HSCT)is the most effective curative treatment for hematologic malignancies.Its efficacy hinges on eliminating primary hematological disorders and restoring bone marrow hematopoiesis during conditioning,as well as leveraging the graft-versus-leukemia(GVL)effect.However,acute graft-versus-host disease(aGVHD)remains a significant complication following allo-HSCT,substantially affecting patient survival and quality of life.Current preclinical studies focus on strategies to mitigate aGVHD while preserving adequate GVL effects to improve transplant outcomes.This review summarizes recent preclinical research findings in this field,emphasizing the regulatory roles and specific molecular mechanisms of T cells,antigen-presenting cells,myeloid-derived suppressor cells,and mesenchymal stem cells in aGVHD.It further highlights the latest therapeutic strategies for aGVHD from preclinical studies,aiming to provide valuable insights for researchers and clinicians to develop more effective therapeutic targets and strategies.

Circadian rhythms,a result of the long-term evolution of organisms adapting to the Earth′s environment,play a crucial regulatory role in biological activities.Disruptions in circadian rhythms have been iden-tified as potential carcinogenic risk factors,closely linked to the pathological states of digestive system diseases,and significantly contribute to the occurrence and progression of digestive system tumors.These rhythms not only influence the regulation of cell cycles,proliferation,and apoptosis of tumor cells but also profoundly affect their migratory abilities,immune functions,and drug resistance.This article focuses on the specific regulatory mechanisms of circadian rhythm genes in relation to digestive system tumors and comprehensively summarizes research findings on the anti-tumor effects of traditional Chinese medicine targeting these circadian clock genes.The aim is to provide new avenues for target selection and prognostic evaluation in the treatment of digestive system tumors.

Objective To explore the effects of long non-coding RNA LINC01772 on cell cycle,apoptosis and radiotherapy sensitivity of A549.Methods A549 cells were resuscitated and cultured for experimental pur-pose.The effects of LINC01772 knockdown on cell viability,cell cycle progression,and apoptosis were assessed using CCK-8 assays and flow cytometry,and apoptosis-related proteins were analyzed using western blotting.CCK-8 and clonogenic assays were used to measure the changes in the sensitivity of A549 cells to radiotherapy following various radiation doses,and flow cytometry to examine alterations in the cell cycle and apoptosis post-radiation treatment.Results Following lentiviral transfection that reduced LINC01772 levels in A549 cells,a significant decrease in cell viability(P<0.01)was observed alongside an increase in apoptosis(P<0.01).Notably,expres-sions of Bad and Cleaved Caspase-3 were significantly elevated(P<0.01),while Bcl-2 expression was markedly decreased(P<0.01).After exposure to different radiation doses,a dose-dependent reduction in A549 cell viability was noted(P<0.01),accompanied by a significant impairment of clonogenic ability(P<0.01),G2/M phase arrest within the cell cycle(P<0.01),and an increased incidence of apoptosis(P<0.01).Conclusion Inhibiting long non-coding RNA LINC01772 expression substantially diminishes cellular viability in A549 cells,enhances apoptotic processes,disrupts their cycling mechanisms,and augments their sensitivity to radiotherapy,suggesting that this non-coding RNA may serve as a potential target for enhancing lung cancer radiotherapy.

Objective The study aimed to investigate whether montelukast sodium could alleviate airway inflammatory responses in asthmatic mice by affecting the PHD2/HIF-1α pathway.Methods An allergic asthma model was established by ovalbumin(OVA)induction,and 18 female BALB/c mice were randomly divided into a control group(Con group),an asthma group(OVA group),and an asthma group with montelukast sodium intervention(30 mg/kg montelukast sodium by oral administration 1 h before OVA challenge,Mon group).HE staining was used to analyze the pathological changes in the lungs of mice.Blood cell analyzer and kits were used to determine the number of inflammatory cells and the levels of cytokines,the content of lactic acid and pyruvic acid in the lungs,respectively.RT-PCR and Western blot were used to detect the mRNA and protein expression of HIF-1α,PHD2,E-cad and p120 in the lungs of mice.Results Compared with the Con group,there was a significant increase in the number of eosinophils,lymphocytes,neutrophils and monocytes,the levels of IL-5,IL-13,complement factor D(CFD)and contents of lactate and pyruvate in the lungs of mice in the OVA group.Lung HIF-1α,PHD2,p120 and E-cad mRNA levels were reduced,meanwhile HIF-1α and PHD2 protein expression were upregulated but E-cad and p120 protein expression were downregulated(all with P<0.05).After montelukast sodium intervention,the number of eosinophils and monocytes and CFD expression were significantly decreased in the lungs of Mon group,the contents of lactate and pyruvate were basically restored to normal,and the mRNA and protein expression of HIF-1α,PHD2,p120 and E-cad were effectively improved.Conclusion Montelukast sodium could alleviate the airway inflammatory responses in the lungs of asthmatic mice by regulating the PHD2/HIF-1α signaling pathway.

Objective To investigate the impact of pomegranate peel polyphenols(PPP)on the malignant biological behavior of colon cancer cells through modulation of the miR-138-5p/hypoxia-inducible factor-1α(HIF-1α)pathway.Methods Quantitative real-time PCR(qRT-PCR)was employed to measure the expression levels of miR-138-5p and HIF-1α mRNA in the normal colon epithelial cell line FHC and three colorectal cancer cell lines:SW480,HCT116,and Caco-2.SW480 cells were divided into six groups:a blank control group,a negative control(mimics NC)group,a miR-138-5p mimics group,three different concentrations of PPP treatment groups(0.5 mg/mL,1 mg/mL,and 2 mg/mL),a PPP+inhibitor NC group at 2 mg/mL,and a PPP+miR-138-5p inhibitor group at 2 mg/mL.The effects on cell proliferation,invasion,and migration,as well as changes in apoptosis and related proteins including B-cell lymphoma 2(Bcl-2),migration invasion enhancer 1(MIEN1),and Cyclin D1,were evaluated separately.Additionally,the targeting relationship between miR-138-5p and HIF-1α was validated.The expression levels of miR-138-5p,HIF-1α mRNA,and protein were assessed in each experimental group.Results The expression levels of miR-138-5p were highest in FHC cells and lowest in SW 480 cells,while the expression levels of HIF-1α mRNA showed an opposite trend,being lowest in FHC cells and highest in SW 480 cells(P<0.05).Compared with the control group,different concentrations of PPP significantly promoted cell apoptosis,upregulated miR-138-5p expression,inhibited cell proliferation,invasion,and migration,and downregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein,with significant differences between groups(P<0.05).Compared with the mimics NC group,the miR-138-5p mimics group significantly enhanced cell apoptosis,upregulated miR-138-5p expression,inhibited cell proliferation,invasion,and migration,and downregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein(P<0.05).Compared with the 2 mg/mL PPP+inhibitor NC group,the 2 mg/mL PPP+miR-138-5p inhibitor group significantly suppressed cell apoptosis,downregulated miR-138-5p expression,promoted cell proliferation,invasion,and migration,and upregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein(P<0.05).These results indicate a targeted relationship between miR-138-5p and HIF-1α(P<0.05).Conclusion PPP inhibits the malignant biological behavior of colon cancer cells through upregulation of the miR-138-5p/HIF-1α pathway.

Objective To investigate the influencing factors of antibiotic-associated diarrhea(AAD)following congenital heart disease(CHD)surgery in pediatric patients,develop a nomogram-based predictive model,and validate its efficacy.Methods A retrospective analysis was conducted on the clinical data of pediatric patients who underwent CHD surgery in the Pediatric Intensive Care Unit(PICU)of a tertiary hospital in Guang-dong Province from July 2022 to July 2024.Patients were categorized into an AAD group and a non-AAD group.Univariate and multivariate logistic regression analyses were performed to identify risk factors for AAD occurrence following CHD surgery.A risk prediction model was developed,and a nomogram was constructed.The predictive performance of the model was evaluated using the Receiver Operating Characteristic(ROC)curve to calculate the area under the curve(AUC),the Hosmer-Lemeshow goodness-of-fit test,calibration curves,and clinical decision curve analysis.External validation of the model was conducted using data from patients in the Surgical Intensive Care Unit(SICU).Results The incidence of AAD following CHD surgery was 48.52%(229 out of 472 cases).Risk factors for AAD included the combined use of antibiotics,mechanical ventilation,elevated C-reactive protein levels,prolonged surgical duration,and extended antibiotic usage time(all with OR>1,P<0.05).Conversely,probiotic administration was identified as a protective factor(OR<1,P<0.05).The predictive model demon-strated excellent discrimination,as evidenced by the ROC curve areas:0.922(95%CI:0.894～0.951)in the modeling group,0.886(95%CI:0.838～0.915)in the internal validation group,and 0.862(95%CI:0.784～0.941)in the external validation group.Additionally,the model exhibited satisfactory calibration,as indicated by the Hosmer-Lemeshow test results:χ2=7.96,P=0.538 in the modeling group;χ2=4.24,P=0.895 in the inter-nal validation group;and χ2=9.923,P=0.270 in the external validation group.Furthermore,the model provided significant clinical utility.Conclusions Combined antibiotic use,duration of antibiotic therapy,mechanical ventilation,surgical duration,C-reactive protein(CRP)levels,and probiotic administration are key factors influ-encing the occurrence of AAD.The risk prediction model developed based on these variables demonstrates robust predictive performance and can serve as a valuable reference for the development and implementation of preventive and therapeutic strategies in clinical practice.

Objective To investigate the impact of noise isolation through the use of noise-cancelling headphones on the quality of postoperative recovery following esophageal or gastric endoscopic submucosal dissec-tion.Methods This is a prospective,parallel-group,randomized controlled clinical trial.Patients aged 18 years or older,regardless of gender and with ASA physical status Ⅰ-Ⅳ,who underwent elective esophageal or gastric endoscopic submucosal dissection under general anesthesia with endotracheal intubation from August 2023 to February 2024 were randomly assigned to either a control group or an observation group using a random number table.In the observation group,noise-cancelling headphones were used to reduce intraoperative noise intensity during general anesthesia,while the control group did not receive any noise isolation measures.The study recorded the average noise intensity during surgery and the proportion of intraoperative time with noise intensity≥70 dB.The primary outcome was the quality of recovery at 24 hours postoperatively,assessed using the 15-item Quality of Recovery Scale(QoR-15).Secondary outcomes included QoR-15 scores at 48 hours postoperatively,resting and movement-evoked pain scores measured by the Visual Analog Pain Scale(VAS)immediately after extubation,upon leaving the resuscitation room,and at 24 and 48 hours postoperatively,as well as analgesic drug consumption during surgery and within 48 hours postoperatively.Additionally,sleep quality was evaluated using the Pittsburgh Sleep Quality Index(PSQI)at 48 hours postoperatively.Results Compared with the control group,the observation group exhibited a significant increase in QoR-15 score at 24 hours post-surgery[(123.43±5.92)vs.(119.75±6.62),t=3.211,P=0.002].The resting VAS score[1(0,3)vs.2(2,3),Z=-3.755,P<0.001]and movement-evoked VAS score[2(1,3)vs.3(2,3),Z=-2.959,P=0.003]of the observation group immediately after extubation were significantly lower than those of control group.There was no significant difference in resting and movement-evoked VAS scores between the two groups when leaving the resuscitation room or at 24 and 48 hours after surgery(P>0.05).The intraoperative fentanyl consumption was significantly lower in the observation group compared to the control group[(0.23±0.05)vs.(0.27±0.06),t=3.515,P=0.01].There were no significant differences in remifentanil consumption during surgery or in the frequency of rescue analgesia with flurbiprofen axetil within 48 hours post-surgery(P>0.05).Postoperative PSQI scores were significantly lower in the observation group compared to the control group[(5.40±2.57)vs.(6.63±3.23),t=2.313,P=0.022].Conclusion The use of noise-cancelling headphones for intraoperative noise isolation is a safe and effective strategy that enhances postop-erative recovery quality,alleviates postoperative pain,and decreases the overall consumption of analgesic drugs in patients undergoing endoscopic submucosal dissection of esophageal and gastric lesions under general anesthesia.

Objective To assess the clinical efficacy and safety of rectal mucosal columnar suturing(Block technique)in combination with lauromacrogol injection for the treatment of female rectocele.Methods This retro-spective study analyzed 90 female patients with rectocele who were treated at Sir Run Run Hospital,Nanjing Medical University,from January 2022 to December 2023.Patients were categorized into three groups according to their surgical treatments:Block combined with lauromacrogol injection(BP group,n=30),Block alone(B group,n=30),and Procedure for Prolapse and Hemorrhoids(PPH,H group,n=30).The study compared general clinical data,perioperative indicators,Longo′s Obstructed Defecation Syndrome(Longo′s ODS)scores,the degree of recto-cele before and after surgery,anorectal manometry parameters,surgical efficacy,and perioperative complications among the three groups.Results The intraoperative blood loss in Group H was significantly higher compared to Groups B and BP(P<0.05).In terms of the 24-hour postoperative VAS score and hospital stay duration,Group BP demonstrated superior outcomes relative to Groups H and B(P<0.05).Preoperatively,there were no significant differences among the three groups regarding Longo′s ODS score,rectocele depth,resting anal pressure,or residual anal pressure(P>0.05).Postoperatively,Group BP exhibited significantly better Longo′s ODS scores and rectocele depth compared to Groups B and H(P<0.05).Although no significant differences were observed in postoperative resting and residual anal pressures among the three groups(P>0.05),the values in Group BP were closer to the normal range.The overall efficacy rate in Group BP was 93.3%,which was higher than the 73.3%in Group B and 66.7%in Group H(P<0.05).There was no significant difference in the complication rate across the three groups(P>0.05).Conclusions Block combined with lauromacrogol injection is a safe and effective treatment for female rectocele,demonstrating superior efficacy compared to both PPH and Block alone.This method not only effectively restores the physiological anatomy of the female rectum but also significantly improves clinical symptoms.

Objective To evaluate the effects of lysine inositol vitamin B12 oral solution in conjunction with recombinant human growth hormone(rhGH)on bone mineral density(BMD)and insulin-like growth factor-1(IGF-1)levels in children with idiopathic short stature.Methods A total of 92 children diagnosed with idiopathic dwarfism at the Affiliated Hospital of Chengde Medical College between August 2021 and March 2024 were recruited and randomly divided into two groups using a random number table method.The rhGH group received recombinant human growth hormone(rhGH)at a dose of 0.15 U/kg/day,while the comprehensive treatment group received lysyl myo-inositol and vitamin B12 oral solution in addition to rhGH.Growth and development indices,IGF-1 levels,bone metabolism markers,serum calcium,serum phosphorus,and vitamin D levels were compared between the two groups.Additionally,adverse reactions were monitored and recorded for both groups.Results Comparison of growth and development indicators in children with idiopathic dwarfism before treatment between the two groups showed no significant difference(P>0.05).After 12 months of treatment,both groups exhibited increased growth rates,height standard deviation scores,and body mass indices compared to pre-treatment levels,with the com-bined group showing significantly higher values than the rhGH group(P<0.05).Similarly,there was no signifi-cant difference in IGF-1 levels between the two groups before treatment(P>0.05).However,at 6 and 12 months post-treatment,IGF-1 levels were significantly higher in both groups compared to baseline,with the combined group demonstrating significantly greater increases than the rhGH group(P<0.05).Regarding bone metabolism parameters,blood calcium,blood phosphorus,and vitamin D levels,no significant differences were observed between the two groups prior to treatment(P>0.05).At 12 months post-treatment,bone mineral density,bone alkaline phosphatase(BAP),typeⅠprocollagen amino-terminal propeptide(PINP),blood calcium,blood phos-phorus,and vitamin D levels were significantly higher in both groups compared to pre-treatment levels,with the combined group showing significantly greater improvements than the rhGH group(P<0.05).Cumulative adverse effects did not differ significantly between the integrated group and the rhGH group(P>0.05).Conclusion The combination of lysine,inositol,vitamin B12 oral solution and rhGH enhances bone metabolism and promotes growth in children with idiopathic short stature.