AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.M...AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.METHODS We retrospectively reviewed all patients at our centerwith metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea(increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were used.RESULTS A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients(14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids(1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients(56%) had ongoing diarrhea despite highdose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients(88%) developed steroidrefractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were reported.CONCLUSION In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course.展开更多
AIM： To investigate whether NSAIDs/ASA lesions in the colon can histologically be diagnosed on the basis of ischemic necrosis similar to biopsy-based diagnosis of NSAIDs/ASA- induced erosions and ulcers of the stomac...AIM： To investigate whether NSAIDs/ASA lesions in the colon can histologically be diagnosed on the basis of ischemic necrosis similar to biopsy-based diagnosis of NSAIDs/ASA- induced erosions and ulcers of the stomach. METHODS： In the period between 1997 and 2002, we investigated biopsy materials obtained from 611 patients （415 women, 196 men, average age 60.5 years） with endoscopic focal erosions, ulcerations, strictures or diaphragms in the colon. In the biopsies obtained from these lesions, we always established the suspected diagnosis of NSA/D-inducecl lesions whenever necroses of the ischemic type were found. Together with the histological report, we enclosed a questionnaire to investigate the use of medication. The data provided by the questionnaire were then correlated with the endoscopic findings, the location, number and nature of the lesions, and the histological findings. RESULTS： At the time of their colonoscopy, 86.1% of the patients had indeed been taking NSAID/ASA medication for years （43.9%） or months （29.5%）. The most common indication for the use of these drugs was pain （64.3%）, and the most common indication for colonoscopy was bleeding （55.5%）. Endoscopic inspection revealed multiple erosions and/or ulcers in 60.6%, strictures in 15.8%, and diaphragms in 3.0% of the patients. The lesions were located mainly in the right colon including the transverse colon （79.9%）. A separate analysis of age and sex distribution, endoscopic and histological findings for NSAIDs alone, ASA alone, combined NSAID/ASA, and for patients denying the use of such drugs, revealed no significant differences among the groups. CONCLUSION： This uncontrolled retrospective study based on the histological finding of an ischemic necrosis shows that the histologically suspected diagnosis of NSAID-induced lesions in the colon is often correct. The true diagnostic validity of this finding and the differentiation from ischemic colitis should, however, be investigated in a prospective controlled study.展开更多
BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS).Crohn's disease(CD...BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS).Crohn's disease(CD)is a major differential diagnosis of CEAS,because these diseases share some clinical features.Therefore,there is a need to develop a convenient screening test to distinguish CEAS from CD.AIM To examine whether prostaglandin E major urinary metabolites(PGE-MUM)can serve as a biomarker to distinguish CEAS from CD.METHODS This was a transactional study of 20 patients with CEAS and 98 patients with CD.CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2 A1.We measured the concentration of PGEMUM in spot urine by radioimmunoassay,and the concentration was compared between the two groups of patients.We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic(ROC)curve analysis.RESULTS Twenty Japanese patients with CEAS and 98 patients with CD were enrolled.PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD(median 102.7 vs 27.9μg/g×Cre,P<0.0001).One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS[95%confidence interval(CI)3.2-16.7].A logistic regression analysis revealed that the association was significant even after adjusting confounding factors(adjusted odds ratio 29.6,95%CI 4.7-185.7).ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9μg/g×Cre with 95.0%sensitivity and 79.6%specificity.CONCLUSION PGE-MUM measurement is a convenient,non-invasive and useful test for the distinction of CEAS from CD.展开更多
AIM: To study the effects of amphetamine, an indirect- acting adrenomimetic compound on the indomethacin- induced gastric ulcerations in rats. METHODS: Male Wistar-Bratislava rats were randomly divided into four group...AIM: To study the effects of amphetamine, an indirect- acting adrenomimetic compound on the indomethacin- induced gastric ulcerations in rats. METHODS: Male Wistar-Bratislava rats were randomly divided into four groups: Group 1 (control), received an ulcerogenic dose of indomethacin (50 μmol/kg) and Groups 2, 3 and 4, treated with amphetamine (10, 25 and 50 μmol/kg). The drug was administered simulta- neously with indomethacin and once again 4 h later. The animals were sacrificed 8 h after indomethacin treatment. The stomachs were opened and the inci- dence, the number of lesions and their severity were evaluated. The results were expressed as percentage and as mean ± standard error (mean ± SE). RESULTS: The incidence of ulceration in the control group was 100%. Amphetamine, at doses of 10, 25 and 50 μmol/kg, lowered the incidence to 88.89%, 77.78% and 37.5% respectively. The protection ratio was posi- tive: 24.14%, 55.17% and 80.6% respectively. The total number of ulcerations/rat was 12.44 ± 3.69 in the con- trol group. It decreased to 7.33 ± 1.89, 5.33 ± 2.38 and 2.25 ± 1.97 under the effects of the above-mentioned doses of amphetamine. CONCLUSION: Amphetamine affords a significant dose-dependent protection against the indomethacin- induced gastric ulcerations in rats. It is suggested that the adrenergic system is involved in the gastric mucosa protection.展开更多
Aims: Steadily the clinicians of our team in inflammatory bowel disease encounter ulcerative colitis patients that develop deep ulcers during their treatment. Currently, these practitioners are only equipped with thei...Aims: Steadily the clinicians of our team in inflammatory bowel disease encounter ulcerative colitis patients that develop deep ulcers during their treatment. Currently, these practitioners are only equipped with their grade of expertise in inflammatory domains to decide what new therapy maybe use in such cases. Encouraged by the limited knowledge of this frequent pathology, we seek to determine the molecular conditions underlying the recurrent formation of deep ulcerations in certain group of patients. Method: The goal of this strategy is to expose differences between groups of patients based on similarities computed by random walk graph kernels and performing functional inference on those differences. Results: We apply the methodology to a cohort of eleven miRNA microarrays of ulcerative colitis patients. Our results showed how the group of ulcerative colitis patients with presence of deep ulcers is topologically more similar (0.35) than ulcerative colitis patients (0.18) to control. Such topological constraint drove functional inference to complete the information that clinicians need. Conclusions: Our analyses reveal highly interpretable in the guidance of practitioners to eventually correct initial therapies of ulcerative colitis patients that develop deep ulcers. The methodology can provide them with useful molecular hypotheses necessaries prior to make any decision on the newest course of the treatment.展开更多
Genital ulceration is the loss of integrity of the mucous membranes (or genital skin) leaving the dermis uncovered and almost always accompanied by satellite lymphadenopathies. Beyond a month of evolution, it is said ...Genital ulceration is the loss of integrity of the mucous membranes (or genital skin) leaving the dermis uncovered and almost always accompanied by satellite lymphadenopathies. Beyond a month of evolution, it is said to be chronic. Sexually transmitted diseases are infections due to microbial agents among which parasites, bacteria, viruses and fungi that can be associated with each other to varying degrees. Sexually transmitted infections must be mentioned before any genital ulceration. Hence the interest of the case that we report of chronic anogenital ulcerations complicating a polymicrobial pelvic infection in a patient immunocompromised to HIV. The physical examination reveals a hypogastric sensitivity to deep palpation, the presence of a superinfected anogenital ulceration exposing the deep dermis covered with purulent serosities interesting the labia minora, the posterior vaginal fork, the anal region, the clitoris and an extension of the lesions to the gluteal fold is observed. We found a satellite lymphadenopathy in the right inguinal fold. The screening finds the HIV1 positive serology with a viral load of 28,000 copies, the herpes simplex 1&2 and Chlamydia trachomatis serologies were all positive. The genital samples are marked by the presence of bacterial vaginosis with Candida Albicans and Gardnerella Vaginalis, the presence of urogenital mycoplasmas of the Ureaplasma Urealyticum The pelvic ultrasound was in favor of a bilateral adnexitis. A protocol was put in place: the first step consisted of seat baths, antifungi and antibiotics administration: fluconazole 150 mg and tinidazole 2 g in single doses, then josamycin 1 g/24h in two doses per os for two weeks. The second stage consists of the administration of doxycycline 200 mg for 21 days, Aciclovir 500 mg for 10 days, and the administration of ARV (Tenofovir + Lamivudine + Dolutegravir) or one tablet daily. The evolution is marked by a progressive healing of the clitoris, the labia majora and labia minora, the posterior vaginal fork. In case of chronicity, a biopsy in search of a tumor process is not mandatory when there is a satisfactory response to treatment and good healing. The patient’s death two weeks after the beginning of ARV treatment, can be explained by a probable immune reconstitution syndrome.展开更多
Acute myeloblastic leukemia (AML) is a highly fatal malignant bone marrow disease. Physicians, dentists and all other healthcare professionals should be aware of sinister oral signs and symptoms in order to early diag...Acute myeloblastic leukemia (AML) is a highly fatal malignant bone marrow disease. Physicians, dentists and all other healthcare professionals should be aware of sinister oral signs and symptoms in order to early diagnosis and referral of patients. Here we report a case of AML who presented with oral ulcers. Ulcers developed after a parrot bite, which initially misled the physicians. Unfortunately our patient did not survive, but early diagnosis and prompt investigation and treatment can be life-saving in many other similar cases.展开更多
Background: Diabetic foot together with open wounds in distal type peripheral arterial disease constitutes a challenge in therapeutic planning. Ozone therapy may unveil new horizons in management. Case Report: A 67-ye...Background: Diabetic foot together with open wounds in distal type peripheral arterial disease constitutes a challenge in therapeutic planning. Ozone therapy may unveil new horizons in management. Case Report: A 67-year-old woman with diabetes mellitus was applied with open wounds at the bottom of her foot with purulent discharge, with a decision for above ankle amputation. She had had numerous interventions for her wounds including metatarsal amputations due to osteomyelitis and had been on an intense treatment including antibiotics, insulin, antihypertensives and antiaggregants. Angiogram revealed diffuse peripheral arterial disease in lower extremities. All medication but antihypertensives was stopped. She received major medical ozone application as 2000 gamma/session i.v. for 2 weeks, external ozone sac application starting from 60 and dropping to 30 gamma/session for 3 weeks and ozone insuflation 40 gamma/session for 10 sessions. Her purulent discharge ceased after the third session and the atonic debris of the wounds exfoliated, the wounds healed from the base towards the surface of the skin. She was then put on cilostazol and clopidogrel therapy. Conclusion: By being one of the known strongest bactericide, virucide, and fungicide elements, medical ozone therapy stimulates and upregulates the antioxidant system of the body with its hormesis effects. After the cessation of all circulatory system supporting medication (as their interaction with ozone is not clear yet), appropriate ozone therapy may bring new horizons for patients when all classically known methods of treatment have been completed, before assigning the patients for amputation.展开更多
Helicobacter pylori(H.pylori)infection plays a critical role in gastric diseases,impacting the microbiota structure in gastric and duodenal ulcers.In their study,Jin et al utilized metagenomic sequencing to analyze mu...Helicobacter pylori(H.pylori)infection plays a critical role in gastric diseases,impacting the microbiota structure in gastric and duodenal ulcers.In their study,Jin et al utilized metagenomic sequencing to analyze mucosal samples from patients with ulcers and healthy controls,revealing significant changes in microbial diversity and composition.This article reviews their findings,emphasizing H.pylori’s role in gastric ulcers and the need for further research on its impact on duodenal ulcers.We evaluate the study’s strengths and limitations,suggesting future research directions to enhance our understanding of H.pylori’s contribution to ulcerative diseases.展开更多
Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic ...Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)present a significant clinical challenge due to their high prevalence and profound impact on morbidity.Ultrasound-assisted wound debridement(UAWD)has emerged as a potential therape...BACKGROUND Diabetic foot ulcers(DFUs)present a significant clinical challenge due to their high prevalence and profound impact on morbidity.Ultrasound-assisted wound debridement(UAWD)has emerged as a potential therapeutic modality to improve healing outcomes in DFU management.AIM To evaluate the efficacy of UAWD in treating DFUs on wound closure rates,treatment duration,and quality of life outcomes.METHODS This systematic review and meta-analysis followed PRISMA guidelines,systematically searching PubMed,Embase,Web of Science,and the Cochrane Library with no date restrictions.Randomized controlled trials(RCTs)that evaluated the efficacy of UAWD in DFU treatment were included.Data were independently extracted by two reviewers,with discrepancies resolved through consensus or third-party consultation.The risk of bias was assessed using the Cochrane tool.χ2 and I2 statistics assessed heterogeneity,informing the use of fixed or random-effects models for meta-analysis,supplemented by sensitivity analysis and publication bias assessment through funnel plots and Egger's test.RESULTS From 1255 articles,seven RCTs met the inclusion criteria.The studies demonstrated that UAWD significantly reduced DFU healing time(standardized mean difference=-0.78,95%CI:-0.97 to-0.60,P<0.001)and increased healing rates(odds ratio=9.96,95%CI:5.99 to 16.56,P<0.001)compared to standard care.Sensitivity analysis confirmed the stability of these results,and no significant publication bias was detected.CONCLUSION UAWD is a promising adjunctive treatment for DFUs,significantly reducing healing times and increasing healing rates.These findings advocate for the integration of UAWD into standard DFU care protocols.展开更多
Gastric ulcer(GU)is a common digestive system disease.Acupuncture,as one of the external treatments of traditional Chinese medicine(TCM),has the characteristics of multi-target,multi-pathway and multi-level action in ...Gastric ulcer(GU)is a common digestive system disease.Acupuncture,as one of the external treatments of traditional Chinese medicine(TCM),has the characteristics of multi-target,multi-pathway and multi-level action in the treatment of GU.The relationship between meridian points and Zang-fu is an important part of the theory of TCM,which is crucial for the diagnosis and treatment of diseases.There is an external and internal link between acupoints and Zang-fu.The pathological reaction of Zang-fu can manifest as acupoint sensitization,while stimulation of acupoints can play a therapeutic role in the internal Zang-fu.Therefore,the acupoint has the functions of reflecting and treating diseases.This review explores the tender points on the body surface of patients with GU and the rules of acupoint selection.In addition,Zusanli(ST36),as one of the most used acupoints of the stomach meridian,was selected to show the mechanisms behind acupoint stimulation in the treatment of GU in greater detail,specifically in the well-studied model of the stress GU(SGU).Hence,the mechanisms of acupuncture at ST36 and points commonly used in combination with ST36 to treat SGU are discussed further.Treatment effects can be achieved through anti-inflammatory and antioxidant activities,gastric mucosal injury repair,and interaction with the brain-gut axis.In summary,this review provides evidence for a comprehensive understanding of the phenomena and mechanism of acupoint functions for GU.展开更多
Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,de...Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,despite the lack of supporting evidence.This highlights the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease.By analyzing existing data from less than a dozen previously published studies,a novel,evidence-based pathogenesis was constructed,implicating colonic epithelial hydrogen peroxide as a causal factor in the development of this disease.This newly identified mechanism informed the creation of a ground-breaking class of therapeutics,known as reducing agents,which have demon-strated remarkable success in resolving colonic inflammation and restoring colonic health in patients with refractory ulcerative colitis.This paper outlines the timeline of these publications and reinterprets the findings within the context of contemporary biomedical science.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of li...BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of life of UC patients and may lead to deterioration of the patient’s condition.UC drugs combined with anti-anxiety and antidepression drugs can alleviate symptoms of both depression and UC.Brain-derived neurotrophic factor(BDNF)precursor(proBDNF)/p75 neurotrophin receptor(p75NTR)/sortilin and BDNF/tropomyosin receptor kinase B(TrkB)signalling balance is essential for maintaining brain homeostasis and preventing the development of depressive behaviours.AIM To explore the mechanism by which Wuling powder regulates the proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of UC with depre-ssion.METHODS Depression was established in C57BL/6J mice via chronic restraint stress,and the UC model was induced with dextran sodium sulfate(DSS).In the treatment stage,mesalazine(MS)was the basic treatment,Wuling powder was the experimental treatment,and fluoxetine was the positive control drug for treating depression.Changes in intestinal mucosal inflammation,behaviour,and the proBDNFp75NTR/sortilin and BDNF/TrkB pathways were evaluated.RESULTS In the depression groups,Wuling powder decreased the immobility time,increased the distance travelled in the central zone and the total distance travelled,and restored balance in the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways.In the DSS and chronic restraint stress+DSS groups,immobility time increased,distance travelled in the central zone and total distance travelled decreased,activity of the proBDNF/p75NTR/sortilin pathway was upregulated,and activity of the BDNF/TrkB pathway was downregulated,indicating that mice with UC often have comorbid depression.Compared with those of MS alone,Wuling powder combined with MS further decreased the colon histopathological scores and the expression levels of tumor necrosis factor-alpha and interleukin-6 mRNAs.CONCLUSION This study confirmed that Wuling powder may play an antidepressant role by regulating the balance of the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways and further relieve intestinal inflammation in UC.展开更多
Neurosurgical patients,including those with severe traumatic brain injury,spinal cord injury,stroke,or raised intracranial pressure,are at heightened risk for stress ulcers and aspiration pneumonitis,leading to signif...Neurosurgical patients,including those with severe traumatic brain injury,spinal cord injury,stroke,or raised intracranial pressure,are at heightened risk for stress ulcers and aspiration pneumonitis,leading to significant morbidity and mortality.These patients are typically managed through both pharmacological interventions[e.g.,proton pump inhibitors(PPIs),histamine 2(H2)antagonists,sucralfate]and non-pharmacological measures(e.g.,nasogastric decompression,patient positioning)to mitigate adverse outcomes.The pathogenesis of stress ulcers in neurosurgical patients is multifactorial,but the routine use of stress ulcer prophylaxis remains controversial.While gastric acid suppression with H2 rece-ptor antagonists and PPIs is commonly employed,concerns have arisen regarding the association between elevated gastric pH,bacterial colonization,and ventilator-associated pneumonia.The lack of comprehensive data on gastroprotection in critically ill neurosurgical patients,who face a greater risk than non-neurosurgical counterparts,further complicates this issue.Recent studies,such as one by Gao et al on the efficacy of vonoprazan-amoxicillin dual therapy in elderly patients,highlight the potential of novel therapies,but the influence of pre-existing conditions like Helicobacter pylori infection remains unclear.Non-pharmacological interventions,including nasogastric decompression and early enteral nutrition,are critical in improving outcomes but require further research to refine strategies.This editorial underscores the need for tailored approaches and encourages further investigation into optimal gastroprotective strategies for neurosurgical patients.展开更多
BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear f...BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.展开更多
Peptic ulcer(PU)is characterized by inflammation,necrosis,and erosion of the gastrointestinal mucosa caused by various pathogenic factors,leading to ulcer formation.The stomach and duodenum are the most commonly affec...Peptic ulcer(PU)is characterized by inflammation,necrosis,and erosion of the gastrointestinal mucosa caused by various pathogenic factors,leading to ulcer formation.The stomach and duodenum are the most commonly affected sites.Bletilla striata,a traditional Chinese medicinal herb,contains diverse chemical constituents and exhibits multiple pharmacological effects.As a key component in various traditional Chinese medicine compound formulations,it has demonstrated notable clinical efficacy.Moreover,it has a solid research foundation and broad application prospects in the treatment of gastrointestinal diseases.This paper systematically elaborates on the clinical efficacy and mechanisms of action of Bletilla striata in the treatment of PUs,drawing from ancient medical literature and traditional formula applications to provide support for clinical use.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thio...BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.METHODS This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to 2022.Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab.We evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine withdrawal.RESULTS There were 62 UC participants with mean age of 43.4 years and 42%were females.All participants received vedolizumab as maintenance therapy with 67.7%withdrew thiopurine.Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies detected.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial.While thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.展开更多
OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-perf...OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.展开更多
BACKGROUND Hydroxyurea,an antimetabolite,is frequently prescribed for various hemato-logical disorders,and its common side effects include gastrointestinal problems,cutaneous or mucosal lesions and pyrexia/fever.CASE ...BACKGROUND Hydroxyurea,an antimetabolite,is frequently prescribed for various hemato-logical disorders,and its common side effects include gastrointestinal problems,cutaneous or mucosal lesions and pyrexia/fever.CASE SUMMARY This study reports the case of a 67-year-old woman who developed recurrent abdominal pain after 10 years of continuous hydroxyurea therapy for primary thrombocythemia.Colonoscopy revealed an ileocecal ulcer.After discontinuing hydroxyurea therapy for 6 months,follow-up colonoscopy showed a significant reduction in the ulceration.CONCLUSION We consider cecal ulcers as a rare complication of hydroxyurea therapy which typically resolves upon stopping the drug.展开更多
文摘AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.METHODS We retrospectively reviewed all patients at our centerwith metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea(increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were used.RESULTS A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients(14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids(1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients(56%) had ongoing diarrhea despite highdose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients(88%) developed steroidrefractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were reported.CONCLUSION In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course.
文摘AIM： To investigate whether NSAIDs/ASA lesions in the colon can histologically be diagnosed on the basis of ischemic necrosis similar to biopsy-based diagnosis of NSAIDs/ASA- induced erosions and ulcers of the stomach. METHODS： In the period between 1997 and 2002, we investigated biopsy materials obtained from 611 patients （415 women, 196 men, average age 60.5 years） with endoscopic focal erosions, ulcerations, strictures or diaphragms in the colon. In the biopsies obtained from these lesions, we always established the suspected diagnosis of NSA/D-inducecl lesions whenever necroses of the ischemic type were found. Together with the histological report, we enclosed a questionnaire to investigate the use of medication. The data provided by the questionnaire were then correlated with the endoscopic findings, the location, number and nature of the lesions, and the histological findings. RESULTS： At the time of their colonoscopy, 86.1% of the patients had indeed been taking NSAID/ASA medication for years （43.9%） or months （29.5%）. The most common indication for the use of these drugs was pain （64.3%）, and the most common indication for colonoscopy was bleeding （55.5%）. Endoscopic inspection revealed multiple erosions and/or ulcers in 60.6%, strictures in 15.8%, and diaphragms in 3.0% of the patients. The lesions were located mainly in the right colon including the transverse colon （79.9%）. A separate analysis of age and sex distribution, endoscopic and histological findings for NSAIDs alone, ASA alone, combined NSAID/ASA, and for patients denying the use of such drugs, revealed no significant differences among the groups. CONCLUSION： This uncontrolled retrospective study based on the histological finding of an ischemic necrosis shows that the histologically suspected diagnosis of NSAID-induced lesions in the colon is often correct. The true diagnostic validity of this finding and the differentiation from ischemic colitis should, however, be investigated in a prospective controlled study.
基金Supported by the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development(AMED),No.15ek0109053h0002 to Matsumoto Tby grants from the Japan Society for the Promotion of Science(JSPS)KAKENHI,No.25460953,to Umeno J,Esaki M,and Matsumoto T
文摘BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS).Crohn's disease(CD)is a major differential diagnosis of CEAS,because these diseases share some clinical features.Therefore,there is a need to develop a convenient screening test to distinguish CEAS from CD.AIM To examine whether prostaglandin E major urinary metabolites(PGE-MUM)can serve as a biomarker to distinguish CEAS from CD.METHODS This was a transactional study of 20 patients with CEAS and 98 patients with CD.CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2 A1.We measured the concentration of PGEMUM in spot urine by radioimmunoassay,and the concentration was compared between the two groups of patients.We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic(ROC)curve analysis.RESULTS Twenty Japanese patients with CEAS and 98 patients with CD were enrolled.PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD(median 102.7 vs 27.9μg/g×Cre,P<0.0001).One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS[95%confidence interval(CI)3.2-16.7].A logistic regression analysis revealed that the association was significant even after adjusting confounding factors(adjusted odds ratio 29.6,95%CI 4.7-185.7).ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9μg/g×Cre with 95.0%sensitivity and 79.6%specificity.CONCLUSION PGE-MUM measurement is a convenient,non-invasive and useful test for the distinction of CEAS from CD.
文摘AIM: To study the effects of amphetamine, an indirect- acting adrenomimetic compound on the indomethacin- induced gastric ulcerations in rats. METHODS: Male Wistar-Bratislava rats were randomly divided into four groups: Group 1 (control), received an ulcerogenic dose of indomethacin (50 μmol/kg) and Groups 2, 3 and 4, treated with amphetamine (10, 25 and 50 μmol/kg). The drug was administered simulta- neously with indomethacin and once again 4 h later. The animals were sacrificed 8 h after indomethacin treatment. The stomachs were opened and the inci- dence, the number of lesions and their severity were evaluated. The results were expressed as percentage and as mean ± standard error (mean ± SE). RESULTS: The incidence of ulceration in the control group was 100%. Amphetamine, at doses of 10, 25 and 50 μmol/kg, lowered the incidence to 88.89%, 77.78% and 37.5% respectively. The protection ratio was posi- tive: 24.14%, 55.17% and 80.6% respectively. The total number of ulcerations/rat was 12.44 ± 3.69 in the con- trol group. It decreased to 7.33 ± 1.89, 5.33 ± 2.38 and 2.25 ± 1.97 under the effects of the above-mentioned doses of amphetamine. CONCLUSION: Amphetamine affords a significant dose-dependent protection against the indomethacin- induced gastric ulcerations in rats. It is suggested that the adrenergic system is involved in the gastric mucosa protection.
文摘Aims: Steadily the clinicians of our team in inflammatory bowel disease encounter ulcerative colitis patients that develop deep ulcers during their treatment. Currently, these practitioners are only equipped with their grade of expertise in inflammatory domains to decide what new therapy maybe use in such cases. Encouraged by the limited knowledge of this frequent pathology, we seek to determine the molecular conditions underlying the recurrent formation of deep ulcerations in certain group of patients. Method: The goal of this strategy is to expose differences between groups of patients based on similarities computed by random walk graph kernels and performing functional inference on those differences. Results: We apply the methodology to a cohort of eleven miRNA microarrays of ulcerative colitis patients. Our results showed how the group of ulcerative colitis patients with presence of deep ulcers is topologically more similar (0.35) than ulcerative colitis patients (0.18) to control. Such topological constraint drove functional inference to complete the information that clinicians need. Conclusions: Our analyses reveal highly interpretable in the guidance of practitioners to eventually correct initial therapies of ulcerative colitis patients that develop deep ulcers. The methodology can provide them with useful molecular hypotheses necessaries prior to make any decision on the newest course of the treatment.
文摘Genital ulceration is the loss of integrity of the mucous membranes (or genital skin) leaving the dermis uncovered and almost always accompanied by satellite lymphadenopathies. Beyond a month of evolution, it is said to be chronic. Sexually transmitted diseases are infections due to microbial agents among which parasites, bacteria, viruses and fungi that can be associated with each other to varying degrees. Sexually transmitted infections must be mentioned before any genital ulceration. Hence the interest of the case that we report of chronic anogenital ulcerations complicating a polymicrobial pelvic infection in a patient immunocompromised to HIV. The physical examination reveals a hypogastric sensitivity to deep palpation, the presence of a superinfected anogenital ulceration exposing the deep dermis covered with purulent serosities interesting the labia minora, the posterior vaginal fork, the anal region, the clitoris and an extension of the lesions to the gluteal fold is observed. We found a satellite lymphadenopathy in the right inguinal fold. The screening finds the HIV1 positive serology with a viral load of 28,000 copies, the herpes simplex 1&2 and Chlamydia trachomatis serologies were all positive. The genital samples are marked by the presence of bacterial vaginosis with Candida Albicans and Gardnerella Vaginalis, the presence of urogenital mycoplasmas of the Ureaplasma Urealyticum The pelvic ultrasound was in favor of a bilateral adnexitis. A protocol was put in place: the first step consisted of seat baths, antifungi and antibiotics administration: fluconazole 150 mg and tinidazole 2 g in single doses, then josamycin 1 g/24h in two doses per os for two weeks. The second stage consists of the administration of doxycycline 200 mg for 21 days, Aciclovir 500 mg for 10 days, and the administration of ARV (Tenofovir + Lamivudine + Dolutegravir) or one tablet daily. The evolution is marked by a progressive healing of the clitoris, the labia majora and labia minora, the posterior vaginal fork. In case of chronicity, a biopsy in search of a tumor process is not mandatory when there is a satisfactory response to treatment and good healing. The patient’s death two weeks after the beginning of ARV treatment, can be explained by a probable immune reconstitution syndrome.
文摘Acute myeloblastic leukemia (AML) is a highly fatal malignant bone marrow disease. Physicians, dentists and all other healthcare professionals should be aware of sinister oral signs and symptoms in order to early diagnosis and referral of patients. Here we report a case of AML who presented with oral ulcers. Ulcers developed after a parrot bite, which initially misled the physicians. Unfortunately our patient did not survive, but early diagnosis and prompt investigation and treatment can be life-saving in many other similar cases.
文摘Background: Diabetic foot together with open wounds in distal type peripheral arterial disease constitutes a challenge in therapeutic planning. Ozone therapy may unveil new horizons in management. Case Report: A 67-year-old woman with diabetes mellitus was applied with open wounds at the bottom of her foot with purulent discharge, with a decision for above ankle amputation. She had had numerous interventions for her wounds including metatarsal amputations due to osteomyelitis and had been on an intense treatment including antibiotics, insulin, antihypertensives and antiaggregants. Angiogram revealed diffuse peripheral arterial disease in lower extremities. All medication but antihypertensives was stopped. She received major medical ozone application as 2000 gamma/session i.v. for 2 weeks, external ozone sac application starting from 60 and dropping to 30 gamma/session for 3 weeks and ozone insuflation 40 gamma/session for 10 sessions. Her purulent discharge ceased after the third session and the atonic debris of the wounds exfoliated, the wounds healed from the base towards the surface of the skin. She was then put on cilostazol and clopidogrel therapy. Conclusion: By being one of the known strongest bactericide, virucide, and fungicide elements, medical ozone therapy stimulates and upregulates the antioxidant system of the body with its hormesis effects. After the cessation of all circulatory system supporting medication (as their interaction with ozone is not clear yet), appropriate ozone therapy may bring new horizons for patients when all classically known methods of treatment have been completed, before assigning the patients for amputation.
文摘Helicobacter pylori(H.pylori)infection plays a critical role in gastric diseases,impacting the microbiota structure in gastric and duodenal ulcers.In their study,Jin et al utilized metagenomic sequencing to analyze mucosal samples from patients with ulcers and healthy controls,revealing significant changes in microbial diversity and composition.This article reviews their findings,emphasizing H.pylori’s role in gastric ulcers and the need for further research on its impact on duodenal ulcers.We evaluate the study’s strengths and limitations,suggesting future research directions to enhance our understanding of H.pylori’s contribution to ulcerative diseases.
基金Supported by the King Salman Center for Disability Research,No.KSRG-2023-407.
文摘Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.
基金Hubei Province Top Medical Youth Talent Program,Wuhan Knowledge Innovation Special Basic Research Project,No.2023020201020558Clinical Research Project of Affiliated Hospital of Guangdong Medical University,No.LCYJ2021B004 and No.LCYJ2019B010Science and Technology Plan Project of Zhanjiang,No.2022A01191.
文摘BACKGROUND Diabetic foot ulcers(DFUs)present a significant clinical challenge due to their high prevalence and profound impact on morbidity.Ultrasound-assisted wound debridement(UAWD)has emerged as a potential therapeutic modality to improve healing outcomes in DFU management.AIM To evaluate the efficacy of UAWD in treating DFUs on wound closure rates,treatment duration,and quality of life outcomes.METHODS This systematic review and meta-analysis followed PRISMA guidelines,systematically searching PubMed,Embase,Web of Science,and the Cochrane Library with no date restrictions.Randomized controlled trials(RCTs)that evaluated the efficacy of UAWD in DFU treatment were included.Data were independently extracted by two reviewers,with discrepancies resolved through consensus or third-party consultation.The risk of bias was assessed using the Cochrane tool.χ2 and I2 statistics assessed heterogeneity,informing the use of fixed or random-effects models for meta-analysis,supplemented by sensitivity analysis and publication bias assessment through funnel plots and Egger's test.RESULTS From 1255 articles,seven RCTs met the inclusion criteria.The studies demonstrated that UAWD significantly reduced DFU healing time(standardized mean difference=-0.78,95%CI:-0.97 to-0.60,P<0.001)and increased healing rates(odds ratio=9.96,95%CI:5.99 to 16.56,P<0.001)compared to standard care.Sensitivity analysis confirmed the stability of these results,and no significant publication bias was detected.CONCLUSION UAWD is a promising adjunctive treatment for DFUs,significantly reducing healing times and increasing healing rates.These findings advocate for the integration of UAWD into standard DFU care protocols.
基金funded by National Key Research and Development Program of China(No.2022YFC3501705)National Natural Science Foundation of China general projects(No.82274066)Shanghai Science and Technology Innovation Project(No.22S21901200).
文摘Gastric ulcer(GU)is a common digestive system disease.Acupuncture,as one of the external treatments of traditional Chinese medicine(TCM),has the characteristics of multi-target,multi-pathway and multi-level action in the treatment of GU.The relationship between meridian points and Zang-fu is an important part of the theory of TCM,which is crucial for the diagnosis and treatment of diseases.There is an external and internal link between acupoints and Zang-fu.The pathological reaction of Zang-fu can manifest as acupoint sensitization,while stimulation of acupoints can play a therapeutic role in the internal Zang-fu.Therefore,the acupoint has the functions of reflecting and treating diseases.This review explores the tender points on the body surface of patients with GU and the rules of acupoint selection.In addition,Zusanli(ST36),as one of the most used acupoints of the stomach meridian,was selected to show the mechanisms behind acupoint stimulation in the treatment of GU in greater detail,specifically in the well-studied model of the stress GU(SGU).Hence,the mechanisms of acupuncture at ST36 and points commonly used in combination with ST36 to treat SGU are discussed further.Treatment effects can be achieved through anti-inflammatory and antioxidant activities,gastric mucosal injury repair,and interaction with the brain-gut axis.In summary,this review provides evidence for a comprehensive understanding of the phenomena and mechanism of acupoint functions for GU.
文摘Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,despite the lack of supporting evidence.This highlights the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease.By analyzing existing data from less than a dozen previously published studies,a novel,evidence-based pathogenesis was constructed,implicating colonic epithelial hydrogen peroxide as a causal factor in the development of this disease.This newly identified mechanism informed the creation of a ground-breaking class of therapeutics,known as reducing agents,which have demon-strated remarkable success in resolving colonic inflammation and restoring colonic health in patients with refractory ulcerative colitis.This paper outlines the timeline of these publications and reinterprets the findings within the context of contemporary biomedical science.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of life of UC patients and may lead to deterioration of the patient’s condition.UC drugs combined with anti-anxiety and antidepression drugs can alleviate symptoms of both depression and UC.Brain-derived neurotrophic factor(BDNF)precursor(proBDNF)/p75 neurotrophin receptor(p75NTR)/sortilin and BDNF/tropomyosin receptor kinase B(TrkB)signalling balance is essential for maintaining brain homeostasis and preventing the development of depressive behaviours.AIM To explore the mechanism by which Wuling powder regulates the proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of UC with depre-ssion.METHODS Depression was established in C57BL/6J mice via chronic restraint stress,and the UC model was induced with dextran sodium sulfate(DSS).In the treatment stage,mesalazine(MS)was the basic treatment,Wuling powder was the experimental treatment,and fluoxetine was the positive control drug for treating depression.Changes in intestinal mucosal inflammation,behaviour,and the proBDNFp75NTR/sortilin and BDNF/TrkB pathways were evaluated.RESULTS In the depression groups,Wuling powder decreased the immobility time,increased the distance travelled in the central zone and the total distance travelled,and restored balance in the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways.In the DSS and chronic restraint stress+DSS groups,immobility time increased,distance travelled in the central zone and total distance travelled decreased,activity of the proBDNF/p75NTR/sortilin pathway was upregulated,and activity of the BDNF/TrkB pathway was downregulated,indicating that mice with UC often have comorbid depression.Compared with those of MS alone,Wuling powder combined with MS further decreased the colon histopathological scores and the expression levels of tumor necrosis factor-alpha and interleukin-6 mRNAs.CONCLUSION This study confirmed that Wuling powder may play an antidepressant role by regulating the balance of the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways and further relieve intestinal inflammation in UC.
文摘Neurosurgical patients,including those with severe traumatic brain injury,spinal cord injury,stroke,or raised intracranial pressure,are at heightened risk for stress ulcers and aspiration pneumonitis,leading to significant morbidity and mortality.These patients are typically managed through both pharmacological interventions[e.g.,proton pump inhibitors(PPIs),histamine 2(H2)antagonists,sucralfate]and non-pharmacological measures(e.g.,nasogastric decompression,patient positioning)to mitigate adverse outcomes.The pathogenesis of stress ulcers in neurosurgical patients is multifactorial,but the routine use of stress ulcer prophylaxis remains controversial.While gastric acid suppression with H2 rece-ptor antagonists and PPIs is commonly employed,concerns have arisen regarding the association between elevated gastric pH,bacterial colonization,and ventilator-associated pneumonia.The lack of comprehensive data on gastroprotection in critically ill neurosurgical patients,who face a greater risk than non-neurosurgical counterparts,further complicates this issue.Recent studies,such as one by Gao et al on the efficacy of vonoprazan-amoxicillin dual therapy in elderly patients,highlight the potential of novel therapies,but the influence of pre-existing conditions like Helicobacter pylori infection remains unclear.Non-pharmacological interventions,including nasogastric decompression and early enteral nutrition,are critical in improving outcomes but require further research to refine strategies.This editorial underscores the need for tailored approaches and encourages further investigation into optimal gastroprotective strategies for neurosurgical patients.
基金Supported by Xi’an Science and Technology Plan Project,No.23YXYJ0162Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project,No.TZKN-CXRC-16+2 种基金Project of Shaanxi Administration of Traditional Chinese Medicine,No.SZYKJCYC-2025-JC-010Shaanxi Province Key Research and Development Plan Project-Social Development Field,No.S2025-YF-YBSF-0391the Science and Technology Innovation Cultivation Program of Longhua Hospital affiliated to Shanghai University of Chinese Medicine,No.YD202220。
文摘BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.
基金Supported by National Science and Technology Major Project,No.2024ZD0521002The Innovation Team Project of Traditional Chinese Medicine of Liaoning Province,No.LNZYYCXTD-CCCX-003+1 种基金General Program of the National Natural Science Foundation of China,No.82074296Construction Project of Inheritance Studios of Famous Chinese Medicine Experts in China,No.[2022]No.75.
文摘Peptic ulcer(PU)is characterized by inflammation,necrosis,and erosion of the gastrointestinal mucosa caused by various pathogenic factors,leading to ulcer formation.The stomach and duodenum are the most commonly affected sites.Bletilla striata,a traditional Chinese medicinal herb,contains diverse chemical constituents and exhibits multiple pharmacological effects.As a key component in various traditional Chinese medicine compound formulations,it has demonstrated notable clinical efficacy.Moreover,it has a solid research foundation and broad application prospects in the treatment of gastrointestinal diseases.This paper systematically elaborates on the clinical efficacy and mechanisms of action of Bletilla striata in the treatment of PUs,drawing from ancient medical literature and traditional formula applications to provide support for clinical use.
基金Supported by Takeda Australia,No.IISR-2016-101883.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.METHODS This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to 2022.Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab.We evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine withdrawal.RESULTS There were 62 UC participants with mean age of 43.4 years and 42%were females.All participants received vedolizumab as maintenance therapy with 67.7%withdrew thiopurine.Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies detected.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial.While thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.
基金the Guangdong Provincial Basic and Applied Basic Research Project:Mechanistic Study on the Regulation of Inflammatory Microenvironment and Improvement of Ulcerative Colitis by Lingnan Traditional Medicine Ficus Pandurata Hance through Wilms'Tumor 1-associating Protein-Mediated RNA Methyltransferase Promoting Toll Like Receptor 4 m6A Modification(2023A1515011699)the Zhongshan Medical Research Project:Mechanistic Study on the Action of Xiahuo Pingwei San in the Treatment of Ulcerative Colitis(2022A020446)。
文摘OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.
基金Supported by National Natural Science Foundation of China,No.82370604Major Science and Technology innovation Project of Fujian Province,No.2023Y9269Natural Science Foundation of Fujian Province,China,No.2023J01239.
文摘BACKGROUND Hydroxyurea,an antimetabolite,is frequently prescribed for various hemato-logical disorders,and its common side effects include gastrointestinal problems,cutaneous or mucosal lesions and pyrexia/fever.CASE SUMMARY This study reports the case of a 67-year-old woman who developed recurrent abdominal pain after 10 years of continuous hydroxyurea therapy for primary thrombocythemia.Colonoscopy revealed an ileocecal ulcer.After discontinuing hydroxyurea therapy for 6 months,follow-up colonoscopy showed a significant reduction in the ulceration.CONCLUSION We consider cecal ulcers as a rare complication of hydroxyurea therapy which typically resolves upon stopping the drug.
