Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis

BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.

Emerging role of exosomes in ulcerative colitis: Targeting NOD-like receptor family pyrin domain containing 3 inflammasome

Ulcerative colitis(UC)is a chronic recurrent inflammatory bowel disease.Despite ongoing advances in our understanding of UC,its pathogenesis is yet unelu-cidated,underscoring the urgent need for novel treatment strategies for patients with UC.Exosomes are nanoscale membrane particles that mediate intercellular communication by carrying various bioactive molecules,such as proteins,RNAs,DNA,and metabolites.The NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome is a cytosolic tripartite protein complex whose activation induces the maturation and secretion of proinflammatory cytokines interleukin-1β(IL-1β)and IL-18,triggering the inflammatory response to a pathogenic agent or injury.Growing evidence suggests that exosomes are new modulators of the NLRP3 inflammasome,with vital roles in the pathological process of UC.Here,recent evidence is reviewed on the role of exosomes and NLRP3 inflammasome in UC.First,the dual role of exosomes on NLRP3 inflammasome and the effect of NLRP3 inflammasome on exosome secretion are summarized.Finally,an outlook on the directions of exosome-NLRP3 inflammasome crosstalk research in the context of UC is proposed and areas of further research on this topic are high-lighted.

Helicobacter pylori infection alters gastric microbiota structure and biological functions in patients with gastric ulcer or duodenal ulcer

BACKGROUND Helicobacter pylori(H.pylori)infection is closely associated with gastrointestinal diseases.Our preliminary studies have indicated that H.pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer(GU)or duodenal ulcer(DU).AIM To investigate the contributions of H.pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases.METHODS Patients with H.pylori infection and either GU or DU,and healthy individuals without H.pylori infection were included.Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing.The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed.RESULTS Compared with that in the healthy individuals,the gastric mucosal microbiota in the H.pylori-positive patients with GU was dominated by H.pylori,with signi-ficantly reduced biodiversity.The intergroup differential functions,which were enriched in the H.pylori-positive GU patients,were all derived from H.pylori,particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones.A significant enrichment of the uibE gene was detected in the synthesis pathway.There was no significant difference in microbial diversity between the H.pylori-positive DU patients and healthy controls.CONCLUSION H.pylori infection significantly alters the gastric microbiota structure,diversity,and biological functions,which may be important contributing factors for GU.

Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab:A case report

BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

Are we ready to use new endoscopic scores for ulcerative colitis?

For ulcerative colitis(UC),the variability in inflammatory activity along the colon poses a challenge in management.The focus on achieving endoscopic healing in UC is evident,where the UC Endoscopic Index of Severity and Mayo Endoscopic Subscore are commonly used for evaluation.However,these indices primarily consider the most severely affected region.Liu et al recent study validates the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting(TIGER)score offering a comprehensive assessment of inflammatory activity across diverse segments of the colon and rectum and a reliable index correlating strongly with UC Endoscopic Index of Severity and moderately with Mayo Endoscopic Subscore(MES).Despite recommendation,certain aspects warrant further invest-igation.Fecal calprotectin,an intermediate target,correlates with TIGER and should be explored.Determining TIGER scores defining endoscopic remission and response,evaluating agreement with histological activity,and assessing inter-endoscopist agreement for TIGER require scrutiny.Exploring the correlation between TIGER and intestinal ultrasound,akin to MES,adds value.

Five commonly used traditional Chinese medicine formulas in the treatment of ulcerative colitis:A network meta-analysis

BACKGROUND Currently,traditional Chinese medicine(TCM)formulas are commonly being used as adjunctive therapy for ulcerative colitis in China.Network meta-analysis,a quantitative and comprehensive analytical method,can systematically compare the effects of different adjunctive treatment options for ulcerative colitis,providing scientific evidence for clinical decision-making.AIM To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis(UC)in clinical practice through a network metaanalysis.METHODS Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1,2022.Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard.The methodological quality of the studies was assessed using ReviewManager(RevMan)5.4,and a funnel plot was constructed to test for publication bias.ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures.RESULTS A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study.The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients.Adjuvant treatment with Baitouweng decoction(BTWT)showed a significant effect[mean difference=36.22,95%confidence interval(CI):7.63 to 65.76].For the reduction of tumor necrosis factor in patients with UC,adjunctive therapy with BTWT(mean difference=−9.55,95%CI:−17.89 to−1.41),Shenlingbaizhu powder[SLBZS;odds ratio(OR)=0.19,95%CI:0.08 to 0.39],and Shaoyao decoction(OR=−23.02,95%CI:−33.64 to−13.14)was effective.Shaoyao decoction was more effective than BTWT(OR=0.12,95%CI:0.03 to 0.39),SLBZS(OR=0.19,95%CI:0.08 to 0.39),and Xi Lei powder(OR=0.34,95%CI:0.13 to 0.81)in reducing tumor necrosis factor and the recurrence rate of UC.CONCLUSION TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.

Exploring the autophagy-related pathogenesis of active ulcerative colitis

BACKGROUND The pathogenesis of ulcerative colitis(UC)is complex,and recent therapeutic advances remain unable to fully alleviate the condition.AIM To inform the development of novel UC treatments,bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC.METHODS The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria.Differential analysis was conducted to obtain differentially expressed genes(DEGs).Au-tophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes(DEARGs)associated with active UC.DEARGs were then subjected to KEGG,GO,and DisGeNET disease enrichment analyses using R software.Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm.The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs,and the top five targets in the Dgree ranking were designated as core targets.RESULTS A total of 4822 DEGs were obtained,of which 58 were classified as DEARGs.SERPINA1,BAG3,HSPA5,CASP1,and CX3CL1 were identified as core targets.GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy.KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways.Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion.Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls.CONCLUSION Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

Perforated gastric ulcer causing mediastinal emphysema: A case report

BACKGROUND Mediastinal emphysema is a condition in which air enters the mediastinum between the connective tissue spaces within the pleura for a variety of reasons.It can be spontaneous or secondary to chest trauma,esophageal perforation,medi-cally induced factors,etc.Its common symptoms are chest pain,tightness in the chest,and respiratory distress.Most mediastinal emphysema patients have mild symptoms,but severe mediastinal emphysema can cause respiratory and circulatory failure,resulting in serious consequences.CASE SUMMARY A 75-year-old man,living alone,presented with sudden onset of severe epigastric pain with chest tightness after drinking alcohol.Due to the remoteness of his residence and lack of neighbors,the patient was found by his nephew and brought to the hospital the next morning after the disease onset.Computed tomography(CT)showed free gas in the abdominal cavity,mediastinal emph-ysema,and subcutaneous pneumothorax.Upper gastrointestinal angiography showed that the esophageal mucosa was intact and the gastric antrum was perforated.Therefore,we chose to perform open gastric perforation repair on the patient under thoracic epidural anesthesia combined with intravenous anesthesia.An operative incision of the muscle layer of the patient's abdominal wall was made,and a large amount of subperitoneal gas was revealed.And a continued incision of the peritoneum revealed the presence of a perforation of approx-imately 0.5 cm in the gastric antrum,which we repaired after pathological examination.Postoperatively,the patient received high-flow oxygen and cough exercises.Chest CT was performed on the first and sixth postoperative days,and the mediastinal and subcutaneous gas was gradually reduced.CONCLUSION After gastric perforation,a large amount of free gas in the abdominal cavity can reach the mediastinum through the loose connective tissue at the esophageal hiatus of the diaphragm,and upper gastrointestinal angiography can clarify the site of perforation.In patients with mediastinal emphysema,open surgery avoids the elevation of the diaphragm caused by pneumoperitoneum compared to laparoscopic surgery and avoids increasing the mediastinal pressure.In addition,thoracic epidural anesthesia combined with intravenous anesthesia also avoids pressure on the mediastinum from mechanical ventilation.

Small-diameter acellular porcine corneal stroma for peripheral corneal ulceration treatment

AIM:To evaluate the clinical efficacy of small-diameter acellular porcine corneal stroma(SAPS)for the treatment of peripheral corneal ulceration(PCU).METHODS:This retrospective clinical study included 18 patients(18 eyes)with PCU between April 2018 and December 2020.All patients had PCU and underwent lamellar keratoplasty with SAPS.Observation indicators included preoperative and postoperative best-corrected visual acuity(BCVA)and transparency of SAPS.The infection control rate in the surgical eye-lesion area was also calculated.RESULTS:Eighteen patients underwent lamellar keratoplasty with SAPS to treat PCU.None of the patients experienced rejection after 6mo(18/18)and 12mo(16/16)of follow-up.The BCVA(0.47±0.30)at the 6mo followup after operation was significantly improved compared with the baseline(0.99±0.80),and the difference was statistically significant(Z=-3.415,P<0.05).The BCVA at the 12mo follow-up after operation was not statistically significant compared to the 6mo(Z=0,P=1).With time,the SAPS graft gradually became transparent.At the 6mo(18/18)and 12mo(16/16)follow-up,none of the patients had recurrent corneal infection.CONCLUSION:SAPS is clinically effective in the treatment of PCU,improving the patient’s BCVA and reducing the incidence of rejection after keratoplasty.

Multivariate analysis of oral mucosal ulcers during orthodontic treatment

BACKGROUND Orthodontic treatment can easily cause local soft tissue reactions in the oral cavity of patients under mechanical stress,leading to oral mucosal ulcers and affecting their quality of life.At present,only limited literature has explored the factors leading to oral ulcers in orthodontic treatment,and these research results are still controversial.AIM To investigate the current status and related factors of oral mucosal ulcers during orthodontic treatment,aiming to provide a valuable reference for preventing this disease in clinical practice.METHODS A total of 587 patients who underwent orthodontic treatment at the Peking University School of Stomatology and Hospital of Stomatology between 2020 and 2022 were selected and allocated to an observation or control group according to the incidence of oral mucosal ulcers during orthodontic therapy.A questionnaire survey was constructed to collect patient data,including basic information,lifestyle and eating habits,treatment details,mental factors,and trace element levels,and a comparative analysis of this data was performed between the two groups.RESULTS A logistic regression model with oral ulcers as the dependent variable was established.The regression results showed that age(≥60 years:odds ratio[OR]:6.820;95%confidence interval[CI]:2.226–20.893),smoking history(smoking:OR:4.434;95%CI:2.527–7.782),toothbrush hardness(hard:OR:2.804;95%CI:1.746–4.505),dietary temperature(hot diet:OR:1.399;95%CI:1.220–1.722),treatment course(>1 year:OR:3.830;95%CI:2.203–6.659),and tooth brushing frequency(>1 time per day:OR:0.228;95%CI:0.138–0.377)were independent factors for oral mucosal ulcers(P<0.05).Furthermore,Zn level(OR:0.945;95%CI:0.927–0.964)was a protective factor against oral ulcers,while the SAS(OR:1.284;95%CI:1.197–1.378)and SDS(OR:1.322;95%CI:1.231–1.419)scores were risk factors.CONCLUSION Age≥60 years,smoking history,hard toothbrush,hot diet,treatment course for>1 year,tooth brushing frequency of≤1 time per day,and mental anxiety are independent risk factors for oral mucosal ulcers.Therefore,these factors should receive clinical attention and be incorporated into the development and optimization of preventive strategies for reducing oral ulcer incidence.

Global trends in publications regarding macrophages-related diabetic foot ulcers in the last two decades

BACKGROUND Diabetic foot ulcers(DFUs)are one of the most severe and popular complications of diabetes.The persistent non-healing of DFUs is the leading cause of amputation,which causes significant mental and financial stress to patients and their families.Macrophages are critical cells in wound healing and perform essential roles in all phases of wound healing.However,no studies have been carried out to systematically illustrate this area from a scientometric point of view.Although there have been some bibliometric studies on diabetes,reports focusing on the investigation of macrophages in DFUs are lacking.AIM To perform a bibliometric analysis to systematically assess the current state of research on macrophage-related DFUs.METHODS The publications of macrophage-related DFUs from January 1,2004,to December 31,2023,were retrieved from the Web of Science Core Collection on January 9,2024.Four different analytical tools:VOSviewer(v1.6.19),CiteSpace(v6.2.R4),HistCite(v12.03.07),and Excel 2021 were used for the scientometric research.RESULTS A total of 330 articles on macrophage-related DFUs were retrieved.The most published countries,institutions,journals,and authors in this field were China,Shanghai Jiao Tong University of China,Wound Repair and Regeneration,and Aristidis Veves.Through the analysis of keyword co-occurrence networks,historical direct citation networks,thematic maps,and trend topics maps,we synthesized the prevailing research hotspots and emerging trends in this field.CONCLUSION Our bibliometric analysis provides a comprehensive overview of macrophage-related DFUs research and insights into promising upcoming research.

Role of second look endoscopy in endoscopic submucosal dissection and peptic ulcer bleeding:Meta-analysis of randomized controlled trials

BACKGROUND Second-look endoscopy(SLE)to prevent recurrent bleeding in patients with peptic ulcer disease(PUD)and those undergoing endoscopic submucosal dissection(ESD)is routinely being performed.Conflicting evidence exists regarding efficacy,risk,benefit,and cost-effectiveness.AIM To identify the role and effectiveness of SLE in ESD and PUD,associated rebleeding and PUD-related outcomes like mortality,hospital length of stay,need for endoscopic or surgical intervention and blood transfusions.METHODS A systematic review of literature databases PubMed,Cochrane,and Embase was conducted from inception to January 5,2023.Randomized controlled trials that compared patients with SLE to those who did not have SLE or evaluated the role of prophylactic hemostasis during SLE compared to other conservative interventions were included.The study was conducted per PRISMA guidelines,and the protocol was registered in PROSPERO(ID CRD42023427555:).RevMan was used to perform meta-analysis,and Mantel-Haenszel Odds ratio(OR)were generated using random effect models.RESULTS A total of twelve studies with 2687 patients were included in our systematic review and meta-analysis,of which 1074 patients underwent SLE after ESD and 1613 patients underwent SLE after PUD-related bleeding.In ESD,the rates of rebleeding were 7%in the SLE group compared to 4.4%in the non-SLE group with OR 1.65,95%confidence intervals(CI)of 0.96 to 2.85;P=0.07,whereas it was 11%in the SLE group compared to 13%in the non-SLE group with OR 0.895%CI:0.50 to 1.29;P=0.36.The mean difference in the blood transfusion rates in the SLE and no SLE group in PUD was OR 0.01,95%CI:-0.22 to 0.25;P=0.91.In SLE vs non-SLE groups with PUD,the OR for Endoscopic intervention was 0.29,95%CI:0.08 to 1.00;P=0.05 while it was OR 2.03,95%CI:0.95 to 4.33;P=0.07,for surgical intervention.The mean difference in the hospital length of stay was-3.57 d between the SLE and no SLE groups in PUD with 95%CI:-7.84 to 0.69;P=0.10,denoting an average of approximately 3 fewer days of hospital stay among patients with PUD who underwent SLE.For mortality between SLE and non-SLE groups in PUD,the OR was 0.88,95%CI:0.45 to 1.72;P=0.70.CONCLUSION SLE does not confer any benefit in preventing ESD and PUD-associated rebleeding.SLE also does not provide any significant improvement in mortality,need for interventions,or blood transfusions in PUD patients.SLE decreases the hospital length of stay on average by 3.5 d in PUD patients.

Gastrointestinal Ulcers Treatment: Plants and Recipes Used by Herbalists of Abomey-Calavi and Cotonou Districts, Southern Benin

This study set out to identify plants and recipes used by herbalists in the municipalities of Abomey-Calavi and Cotonou to treat gastrointestinal ulcers and to characterize the distribution of their knowledge. An ethno-pharmacological survey was carried out in which informants who agreed freely were interviewed using a semi-structured questionnaire. A total of 85 herbalists were surveyed. The data were processed with Microsoft Excel to calculate the relative frequencies of citation of the various species mentioned by the herbalists and various indices including Simpson’s Index were adapted to test the distribution of their knowledge. Multiple regression and correspondence analysis were performed using R studio. Our results revealed that the Dendi, Ifè and Mina, all equitable in their knowledge of anti-ulcer plants, are likely to know more than the other ethnic groups. On the other hand, respondents practicing Islam are more likely to know many antiulcer plants than those practicing Vodoun and Christianity. This constant distribution of knowledge of anti-ulcer plants among the Dendi, Ifè and Mina, three different ethnic groups seems normal and attests to the fusion between these different ethnic groups in view of this knowledge. A total of 70 anti-ulcer recipes, made from 71 species of medicinal plants or non-floristic resources were recorded. Vitellaria paradoxa, Parkia biglobosa and Ocimum gratissimum were the top 03 most frequently cited in descending order of frequency. All the species cited are grouped into 44 botanical families among which the Fabaceae, Lamiaceae and Sapotaceae were strongly represented. Benin’s flora abounds in a diversity of medicinal plant species known to herbalists in Abomey-Calavi and Cotonou for the treatment of gastrointestinal ulcers. The results of this study constitute a good archive for the selection of plant species for in-depth studies with a view to formulating improved traditional medicines for gastrointestinal ulcers.

Portraying Diabetic Foot Ulcers: Comparative Evaluation of Diabetic Foot Infections versus Diabetic Foot Ulcers

Background: Confusion often arises in caring for diabetic foot infections and ulcers, especially with antimicrobials;we aim to shed light on this entity and alert healthcare workers to its stewardship. Methods: Records were reviewed between February 2016 and September 2023. Data for patients diagnosed with diabetes and foot ulcers, infected or not, were examined following ICD 9 search terms. Records for patients were included if they were prediabetic/diabetic adults with foot ulcers, more than 18 years old, and on antidiabetic treatment. Patients were excluded if they insulin resistant, with normal HgbA1c levels, wheel-chair dependent, bed-bound, non-diabetic patients, diabetic patients who had vascular lower limb surgery earlier to ulcers, diabetic patients who had aortocoronary bypass, deep venous thrombosis within six months, malignancy, and severe clinical depression. A modified IWGDF/IDSA guidelines definitions for DFI and DFU was considered. Statistical analysis was done using R programming. Statistical methods were employed as appropriate, and a significant P-value was considered for P Results: Most characteristics were well balanced between DFI and DFU, on imaging osteomyelitis and tissue swelling were significantly more in DFI. Endovascular radiological procedures showed angiograms to be considerably more in DFI, while angioplasty was more in DFU, in addition to smoking. Bacteremia was uncommon, and swab cultures were mostly polymicrobial in both ulcers;no clear association with blood bacteria was detected with the polymicrobial growth, though few were concordant. Antimicrobials prescribed for both ulcers were not statistically different except for carbapenems, which were more in DFI (P Conclusion: Attention should be paid to best practices while caring for diabetic ulcers. These include swab culture interpretations, the use of antimicrobials, and plan management according to DFI or DFU to utilize either local care or combination with antimicrobials.

Theoretical Assessment of Environmental Factors and Untreated Infectious Individuals in the Transmission Dynamics of Buruli ulcer

Buruli ulcer is the third most common mycobacterial disease worldwide, posing a significant public health burden, especially in impoverished regions of West and Central Africa, such as Benin. The management of Buruli ulcer (BU) in Africa is often hindered by limited resources, delays in treatment, and inadequate medical facilities. Additionally, a portion of the population does not seek hospital care, which facilitates the continued presence of the pathogen in the environment. This paper aims to investigate the role of environmental factors in the transmission of Buruli ulcer. We develop a mathematical model to describe the dynamics of Buruli ulcer transmission, incorporating the presence of the bacterium in the environment. Theoretical results are presented to demonstrate that the model is well-posed. We compute the equilibria, including the disease-free equilibrium and the endemic equilibrium, and study their stability. To achieve this, we derive a threshold parameter called the basic reproduction number ℛ0, which determines whether the disease will persist in a human population. If ℛ0is less than one, the disease will eventually die out;if ℛ0is greater than one, the disease will persist. Sensitivity analysis is performed to understand the impact of various parameters on the dynamics of Buruli ulcer transmission and to identify the parameters that influence the basic reproduction number ℛ0. Finally, numerical simulations are conducted to validate the theoretical results obtained from the mathematical analysis.

Albizzia chinensis(Osbeck)Merr extract YS ameliorates ethanol-induced acute gastric ulcer injury in rats by regulating NRF2 signaling pathway

Background:Around the world,there is a high incidence of gastric ulcers.YS,an extract from the Chinese herb Albizzia chinensis(Osbeck)Merr,has potential therapeutic applications for gastrointestinal diseases.Here we elucidated the protective effect and underlying mechanism of action of YS on gastric ulcer in rats injured by ethanol.Methods:The ethanol-i nduced gastric ulcer rat model was used to assess the protective effect of YS.A pathological examination of gastric tissue was performed by H&E staining.GES-1 cells damaged by hydrogen peroxide were used to simulate oxidative damage in gastric mucosal epithelial cells.Endogenous NRF2 was knocked down using small interfering RNA.Immunoprecipitation was used to detect ubiquitination of NRF2.Co-i mmunoprecipitation was used to detect the NRF2-Keap1 interaction.Results:YS(10 and 30 mg/kg,i.g.)significantly reduced the ulcer index,decreased MDA level,and increased SOD and GSH levels in gastric tissues damaged by ethanol.YS promoted NRF2 translocation from cytoplasm to nucleus and enhanced the NQO1 and HO-1 expression levels in injured rat gastric tissue.In addition,YS regulated NQO1 and HO-1 via NRF2 in H_(2)O_(2)-i nduced oxidative injured GES-1 cells.Further studies on the underlying mechanism indicated that YS reduced the interaction between NRF2 and Keap1 and decreased ubiquitylation of NRF2,thereby increasing its stability and expression of downstream factors.NRF2 knockdown abolished the effect of YS on MDA and SOD in GES-1 cells treated with H_(2)O_(2).Conclusion:YS reduced the NRF2-Keap1 interaction,promoting NRF2 translocation into the nucleus,which increasing the transcription and translation of NQO1 and HO-1 and improved the antioxidant capacity of rat stomach.

Tofacitinib for ulcerative colitis: A promising treatment option

A single center retrospective clinical study revealed the efficacy and safety of tofa-citinib in the treatment of ulcerative colitis(UC).This study has clinical reference value but also has some limitations.Previous studies,including this clinical trial,have shown that tofacitinib could be a promising treatment option for UC,but further clinical research is required to prove this point.

Improving pressure ulcer care in intensive care units:Evaluating the impact of bundled care and silver nanoparticle dressings

BACKGROUND Pressure ulcer(PU)are prevalent among critically ill trauma patients,posing substantial risks.Bundled care strategies and silver nanoparticle dressings offer potential solutions,yet their combined effectiveness and impact on patient satisfaction remain insufficiently investigated.AIM To assess the impact of bundled care along with silver nanoparticle dressing on PUs management and family satisfaction in critically ill trauma patients.METHODS A total of 98 critically ill trauma patients with PUs in intensive care unit(ICU)were included in this study.Patients were randomly assigned to either the control group(conventional care with silver nanoparticle dressing,n=49)or the intervention group(bundled care with silver nanoparticle dressing,n=49).The PU Scale for Healing(PUSH)tool was used to monitor changes in status of pressure injuries over time.Assessments were conducted at various time points:Baseline(day 0)and subsequent assessments on day 3,day 6,day 9,and day 12.Family satisfaction was assessed using the Family Satisfaction ICU 24 ques-tionnaire.RESULTS No significant differences in baseline characteristics were observed between the two groups.In the intervention group,there were significant reductions in total PUSH scores over the assessment period.Specifically,surface area,exudate,and tissue type parameters all showed significant improvements compared to the control group.Family satisfaction with care and decision-making was notably higher in the intervention group.Overall family satisfaction was significantly better in the intervention group.CONCLUSION Bundled care in combination with silver nanoparticle dressings effectively alleviated PUs and enhances family satisfaction in critically ill trauma patients.This approach holds promise for improving PUs management in the ICU,benefiting both patients and their families.

Tilapia Head Glycolipid Alleviates Indomethacin-Induced Gastric Ulcer via Regulating Oxidative Stress and Inflammation Through COX/PGE2 Signaling Pathway in Adult Rats

The aim of this experiment was to investigate the ameliorative effect and molecular mechanism of tilapia head glycolipid(TH-GL)on indomethacin(IDM)-induced gastric ulcer in male Sprague Dawley(SD)rats.The gastric ulcer model was established by oral administration of 30mgkg^(-1) IDM after 7 days of TH-GL or omeprazole(OME)administration in rats.Then the macroscopic gastric injury symptoms,gastric mucosa protective factor cyclooxygenase 1(COX-1),cyclooxygenase 2(COX-2),prostaglandin E_(2)(PGE_(2)),the levels of oxidative stress,and inflammatory cytokine expression levels in the rats were analyzed.The experimental results showed that multiple ulcers appeared on the gastric surface of the rats in the model group.Compared to the model group,TH-GL significantly alleviated gastric ulcers and reduced the gastric damage index in rats.In addition,TH-GL significantly promoted the expression of constitutive enzyme COX-1 while inhibited the expression of inducible enzyme COX-2,and make PGE2 maintain at normal levels.TH-GL also inhibited oxidative stress and inflammatory responses,increased superoxide dismutase(SOD)activity and glutathione(GSH)content,decreased the level of malondialdehyde(MDA)and the content of pro-inflammatory factor.In conclusion,these results suggested that TH-GL could maintain the expression levels of COX-1 and PGE2 while inhibit the expression of COX-2 in the gastric of rat and then prevent IDM-induced gastric ulcer,which may be related to the regulation of oxidative stress and inflammatory response.Therefore,TH-GL might be a new option for the prevention of gastric diseases induced by IDM.

Outcome and risk factors of ulcer healing after gastric endoscopic submucosal dissection: A systematic review and meta-analysis

BACKGROUND Endoscopic submucosal dissection(ESD)is widely utilized for the treatment of large adenomas,submucosal lesions,and early gastric cancer.A significant arti-ficial ulcer typically forms after ESD.Delayed or incomplete healing of these ulcers can result in complications such as delayed bleeding and perforation.However,a comprehensive review of the outcomes and risk factors related to ulcer healing following ESD is currently lacking.AIM To assess ulcer healing outcomes and identify risk factors associated with delayed ulcer healing.RESULTS Our analysis included 12 studies,involving a total of 3430 patients.The meta-analysis revealed an overall healing rate of 65.55%for ulcers following ESD[odds ratio(OR)=2.71;95%confidence interval(CI):2.45-3.00].The healing rate within eight weeks was 48.32%(OR=0.76;95%CI:0.35-1.66),while the rate beyond eight weeks was 88.32%(OR=6.73;95%CI:3.82-11.87).Risk factors included Helicobacter pylori(H.pylori)infection(OR:=5.32;95%CI:1.90-14.87;P=0.001),ulcer size(OR=2.08;95%CI:1.19-3.61;P=0.01),lesion site(OR=2.08;95%CI:1.19-3.11),and pathological type(OR=1.64;95%CI:1.06-2.52).Diabetes(OR=0.56;95%CI:0.05-5.80;P=0.63)and duration of operation(OR=1.00;95%CI:0.99-1.01;P=0.96)were not significant factors.CONCLUSION The healing rate of ulcers following ESD is high after eight weeks.Risk factors affecting the healing process include H.pylori infection,ulcer size,lesion site,and pathological type.