Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

Prognostic impact of inflammatory and nutritional biomarkers in pancreatic cancer

Pancreatic cancer is usually associated with a poor prognosis.Surgery is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outcomes are necessary.Lu et al recently published a retrospective,single centre cohort study evaluating the impact of seven nutritional and inflammatory markers in pancreatic cancer surgical patients:The albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),nutritional risk index,and the geriatric nutritional risk index.A significant correlation was found between the PNI,SII,NLR,and PLR and a hospital discharge of less than 15 days.In a univariable analysis,PNI,SII,NLR and PLR were significantly related to recurrence-free survival and,in a multivariable analysis PNI was associated with overall survival.Various meta-analyses corroborate the results in terms of prognosis but individual studies are discordant on their usefulness.Besides,the cut-off values for these markers vary significantly between studies and there are no clinical trials comparing them to identify the most relevant ones.These are limitations when implementing nutritional and inflammatory biomarkers into clinical practice and further studies are needed in order to answer these questions.

Gut virome:New key players in the pathogenesis of inflammatory bowel disease

Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the intes-tine.While the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immunological response,environmental exposure,particularly the gut microbiota,and genetic suscept-ibility represents the major determinants.The gut virome is a group of viruses found in great frequency in the gastrointestinal tract of humans.The gut virome varies greatly among individuals and is influenced by factors including lifestyle,diet,health and disease conditions,geography,and urbanization.The majority of research has focused on the significance of gut bacteria in the progression of IBD,although viral populations represent an important component of the microbiome.We conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.

Biologics in the management of pediatric inflammatory bowel disease:When and what to choose

Pediatric inflammatory bowel disease(PIBD)is a chronic inflammatory disorder of the gastrointestinal tract,with rising global incidence and prevalence.Over the past two decades,biologics have added to the therapeutic armamentarium and revolutionized the approach to treatment of inflammatory bowel disease.The available biologics include monoclonal antibodies which target inflammatory cytokines(anti-tumor necrosis factor alpha,anti-interleukin 12/23)or recruitment of leucocytes to the gastrointestinal tract(anti-alpha4beta7 integrin)and small molecules(Janus kinase inhibitors,sphingosine 1-phosphate-inhibitors)which modify the proinflammatory signaling.Considering their potential disease-modifying ability,recent pediatric guidelines from the West have advocated upfront use of biologics in appropriate clinical scenarios as a top-down approach rather than the conventional step-up approach.Although real-world studies are available regarding the clinical efficacy of biologics in PIBD,there is paucity of long-term outcome and safety data in children.Also,little information is available about the best approach in the newly industrialized-developing countries where PIBD is rising but at the same time,infections are prevalent and resources are limited.In this review,we summarize the efficacy and safety profile of biologics and small molecule drugs and discuss the challenges in the management of PIBD,especially in the developing world,and future directions.

Genetic factors that predict response and failure of biologic therapy in inflammatory bowel disease

Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.

Cardiovascular involvement in multisystem inflammatory syndrome in children and midterm follow-up from a pediatric tertiary center in India

BACKGROUND In multisystem inflammatory syndrome in children(MIS-C)with coronavirus disease 2019,there was paucity of data from low-income and middle-income countries on cardiovascular involvement and its longitudinal outcomes.We planned to estimate the pattern of cardiovascular involvement among children with MIS-C and its mid-term outcomes.AIM To determine association between cardiovascular abnormalities and clinical and laboratory parameters.To study the time-line for resolution of various abnormalities.METHODS In this prospective study done in a tertiary care hospital,270 were recruited from June 2020 to January 2022.Baseline demographic data and clinical presentation were recorded.Laboratory parameters and echocardiography were done at admission.Follow-up was done at 2 weeks,3 months,6 months and 1 year after diagnosis.Descriptive statistics were used for parametric and non-parametric data.Risk factors were identified by multivariate regression analysis.RESULTS The 211(78.2%)had cardiac involvement and 102 needed intensive care unit(ICU)admission.Cardiovascular abnormalities observed were shock 123(45.6%),coronary dilatation 28(10.4%),coronary aneurysm 77(28.5%),left ventricular(LV)dysfunction 78(29.3%),mitral regurgitation(MR)77(28.5%)and pericardial effusion 98(36.3%).Coronary artery aneurysm/dilatation during follow-up at 2 weeks and 1 year were 25.7%and 0.9%respectively.Multivariate regression analysis revealed breathlessness[odds ratio(OR)=3.91,95%CI:1.25-12.21,P=0.019]and hi-flow nasal cannula(HFNC)support(OR=8.5,95%CI:1.06-68.38,P=0.044)as predictors of cardiovascular involvement.Higher mean age(OR=1.16,95%CI:1.02-1.32,P=0.026),breathlessness(OR=4.99,95%CI:2.05-12.20,P<0.001),gallop(OR=4.45,95%CI:0.41-2.52,P=0.016),MR(OR=3.61,95%CI:1.53-8.53,P=0.004)and invasive ventilation(OR=4.01,95%CI:1.28-12.58,P=0.017)were predictive of LV dysfunction.Altered sensorium(OR=4.96,95%CI:2.23-11.02,P<0.001),headache(OR=6.61,95%CI:1.46-29.92,P=0.014),HFNC(OR=7.03,95%CI:2.04-24.29,P=0.002),non-rebreathing mask usage(OR=21.13,95%CI:9.00-49.61,P<0.001)and invasive ventilation(OR=5.64,95%CI:1.42-22.45,P=0.014)were risk factors for shock.Anemia was a risk factor for coronary involvement(OR=3.09,95%CI:1.79-5.34,P<0.001).CONCLUSION Significant number of children with MIS-C had cardiovascular involvement contributing to higher ICU management.Although shock resolved quickly,resolution of ventricular function and coronary abnormalities were slower,and hence warrants a structured long-term follow-up protocol.

The genetics of pediatric inflammatory bowel disease:Towards precision medicine

Pediatric inflammatory bowel disease(IBD)is a chronic and heterogeneous disease.IBD is commonly classified into Crohn’s disease and ulcerative colitis.It is linked to serious symptoms and complications.The onset of IBD commonly occurs during adolescence.Despite the significant number of cases globally(~5 million),the causes of pediatric IBD,which constitutes 25%of IBD patients,are not yet fully understood.Apart from environmental factors,genetic factors contribute to a higher risk of developing IBD.The predisposition risk of IBD can be investigated using genetic testing.Genetic mechanisms of pediatric IBD are highly complex which resulted in difficulty in selecting effective treatment or patient management.Genetic variation of IBD would serve as a basis for precision medicine and allow for the discovery of more robust treatment avenues for this condition in pediatric patients.This review aims to discuss the genetics of pediatric IBD,and current development in the screening,diagnosis,and treatment based on genetic profiling of pediatric IBD subjects toward more personalized management of this disease.

Prognostic value of inflammatory markers in predicting recurrencefree survival in gastrointestinal stromal tumor patients:A nomogram-based approach

BACKGROUND There are currently no relevant studies at home or abroad that combine inflammatory indicators and nomograms to predict the prognosis of gastrointestinal stromal tumor(GIST)patients after surgery.The purpose of this study was to investigate the predictive value of related inflammatory indicators[systemic immune-inflammation index(SII),neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR)and monocyte/Lymphocyte ratio(MLR)]in patients undergoing GIST surgery,incorporating relevant risk factors to establish a nomogram prediction model,with the aim of better predicting the prognosis of GIST patients.AIM To explore the relationships between the SII,NLR,PLR,and MLR and postoperative recurrence in patients with GIST.METHODS This study retrospectively included patients who underwent GIST surgery from January 2014 to January 2017 and analyzed the potential relationships between the preoperative SII,NLR,PLR,and MLR and clinicopathological features.The independent risk factors influencing the prognosis of GIST patients were obtained via multivariate regression analysis,and a nomogram model based on the independent risk factors was established.RESULTS Among the 124 GIST patients included in the present study,31(25%)experienced recurrence within 5 years.Kaplan-Meier survival analysis revealed a correlation between the MLR and PLR and tumor size(P=0.016 and P=0.002,respectively).The preoperative SII,MLR,NLR,and PLR were significantly associated with recurrence-free survival(RFS)(P<0.05).The multivariate analysis results identified the PLR,MLR,and targeted therapy as independent prognostic factors for patient outcomes.CONCLUSION Preoperative MLR and PLR,which are independent risk factors for GIST recurrence,were correlated with RFS.Nomograms based on the PLR,MLR and targeted therapy can be used for clinical treatment.

Patient and physician factors contributing to delays in inflammatory bowel diseases:Enhancing timely diagnosis

In this article,we comment on the article by Blüthner et al.The article provides a comprehensive analysis of the factors contributing to the late detection of Crohn’s disease and ulcerative colitis within a German cohort.It highlights the conse-quences on patient outcomes,particularly disease progression and the increased risk of developing complications.The study identifies specific predictors asso-ciated with both patient-related and physician-related delays,offering a detailed exploration of the initial approach.Additionally,the article delves into the distinct patterns observed in the German population,stressing the unique aspects of diagnostic delays that may differ from those reported in other regions.This detailed examination offers valuable insights into the specific challenges faced within the German healthcare system and underscores the necessity of targeted interventions to facilitate early diagnosis.The importance of improved screening tools,patient education,and better healthcare infrastructure is emphasized as crucial steps toward improving patient care in inflammatory bowel disease.

Artificial intelligence-driven strategies for managing renal and urinary complications in inflammatory bowel disease

In this editorial,we discuss the article by Singh et al published in World Journal of Nephrology,stating the need for timely adjustments in inflammatory bowel disease(IBD)patients'long-term management plans.IBD is chronic and lifelong,with recurrence and remission cycles,including ulcerative colitis and Crohn's disease.It's exact etiology is unknown but likely multifactorial.Related to gut flora and immune issues.Besides intestinal symptoms,IBD can also affect various extrain-testinal manifestations such as those involving the skin,joints,eyes and urinary system.The anatomical proximity of urinary system waste disposal to that of the alimentary canal makes early detection and the differentiation of such symptoms very difficult.Various studies show that IBD and it's first-line drugs have nephro-toxicity,impacting the patients'life quality.Existing guidelines give very few references for kidney lesion monitoring.Singh et al's plan aims to improve treatment management for IBD patients with glomerular filtration rate decline,specifically those at risk.Most of IBD patients are young and they need lifelong therapy.So early therapy cessation,taking into account drug side effects,can be helpful.Artificial intelligence-driven diagnosis and treatment has a big potential for management improvements in IBD and other chronic diseases.

Inflammatory Bowel Disease and Dementia:Evidence Triangulation from a Meta-Analysis of Observational Studies and Mendelian Randomization Study

Objective Observational studies have found associations between inflammatory bowel disease(IBD)and the risk of dementia,including Alzheimer’s dementia(AD)and vascular dementia(VD);however,these findings are inconsistent.It remains unclear whether these associations are causal.Methods We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia.Mendelian randomization(MR)analysis based on summary genome-wide association studies(GWASs)was performed.Genetic correlation and Bayesian colocalization analyses were used to provide robust genetic evidence.Results Ten observational studies involving 80,565,688 participants were included in this metaanalysis.IBD was significantly associated with dementia(risk ratio[RR]=1.36,95%CI=1.04-1.78;I2=84.8%)and VD(RR=2.60,95%CI=1.18-5.70;only one study),but not with AD(RR=2.00,95%CI=0.96-4.13;I^(2)=99.8%).MR analyses did not supported significant causal associations of IBD with dementia(dementia:odds ratio[OR]=1.01,95%CI=0.98-1.03;AD:OR=0.98,95%CI=0.95-1.01;VD:OR=1.02,95%CI=0.97-1.07).In addition,genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia.Conclusion Our study did not provide genetic evidence for a causal association between IBD and dementia risk.The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.

Evaluating large language models as patient education tools for inflammatory bowel disease:A comparative study

BACKGROUND Inflammatory bowel disease(IBD)is a global health burden that affects millions of individuals worldwide,necessitating extensive patient education.Large language models(LLMs)hold promise for addressing patient information needs.However,LLM use to deliver accurate and comprehensible IBD-related medical information has yet to be thoroughly investigated.AIM To assess the utility of three LLMs(ChatGPT-4.0,Claude-3-Opus,and Gemini-1.5-Pro)as a reference point for patients with IBD.METHODS In this comparative study,two gastroenterology experts generated 15 IBD-related questions that reflected common patient concerns.These questions were used to evaluate the performance of the three LLMs.The answers provided by each model were independently assessed by three IBD-related medical experts using a Likert scale focusing on accuracy,comprehensibility,and correlation.Simultaneously,three patients were invited to evaluate the comprehensibility of their answers.Finally,a readability assessment was performed.RESULTS Overall,each of the LLMs achieved satisfactory levels of accuracy,comprehensibility,and completeness when answering IBD-related questions,although their performance varies.All of the investigated models demonstrated strengths in providing basic disease information such as IBD definition as well as its common symptoms and diagnostic methods.Nevertheless,when dealing with more complex medical advice,such as medication side effects,dietary adjustments,and complication risks,the quality of answers was inconsistent between the LLMs.Notably,Claude-3-Opus generated answers with better readability than the other two models.CONCLUSION LLMs have the potential as educational tools for patients with IBD;however,there are discrepancies between the models.Further optimization and the development of specialized models are necessary to ensure the accuracy and safety of the information provided.

New perspectives and prospects for the next generation of combination therapy in inflammatory bowel disease

This article comments on the letter by Lowell et al,which addresses the next generation of combination therapy for inflammatory bowel disease(IBD).As the understanding of the pathogenesis of IBD continues to improve,treatment strategies are evolving rapidly.The letter examines the current status and future directions of combination therapy for IBD,focusing on approaches that combine biologics with immunomodulators and the emerging dual-biologic therapy(DBT).The traditional combination of biologics and immunomodulators has demonstra-ted preliminary efficacy by enhancing the effects of biologics through immunomo-dulation.However,concerns regarding long-term safety warrant careful evalua-tion.Recent trials,including DUET-Crohn's disease and DUET-ulcerative colitis,have shown promising potential for the broader adoption of DBT.Nevertheless,comprehensive data on efficacy and safety,as well as the effective integration of supportive treatments,remain essential to establish new paradigms for the next generation of IBD care.

Effect of negative mood,serum inflammatory factors,miR-155,and brain-derived neurotrophic factor

BACKGROUND Abdominal postoperative patients are susceptible to postoperative depression resulting from pain and stress,which can hinder their rehabilitation.Acupuncture has shown potential to relieve this condition.AIM To analyze the mechanism by which acupuncture relieves postoperative depression in patients post-abdominal surgery.METHODS Abdominal postoperative patients with depression between January 2015 and December 2023 at the First Affiliated Hospital of Heilongjiang University of Chinese Medicine were enrolled.Patients were divided into two groups using the random throwing method:Observation(250 cases,fluoxetine hydrochloride+acupuncture treatment)and control(250 cases,fluoxetine hydrochloride treatment).Changes in negative emotions Hamilton Depression Scale 24,serum inflammatory factors[tumor necrosis factorα,interleukin(IL)-1β,IL-6],miR-155 expression levels,and BDNF levels were assessed.RESULTS Significant improvements were observed in the observation group compared to the control group in all assessed parameters after six weeks(P<0.05).This suggests that the combination of fluoxetine hydrochloride and acupuncture may be more effective in managing postoperative depression than medication alone.CONCLUSION Acupuncture complies with the principle of traditional Chinese medicine syndrome differentiation and ensures the pertinence and effectiveness of treatment.In addition,it not only actively improves depressive symptoms but also effectively regulates the serum level of inflammatory factors.

L-arginine administration exacerbates myocardial injury in diabetics via prooxidant and proinflammatory mechanisms along with myocardial structural disruption

BACKGROUND L-arginine(L-Arg)is one of the most widely used amino acids in dietary and pharmacological products.However,the evidence on its usefulness and dose limitations,especially in diabetics is still controversial.AIM To investigate the effects of chronic administration of different doses of L-Arg on the cardiac muscle of type 2 diabetic rats.METHODS Of 96 male rats were divided into 8 groups as follows(n=12):Control,0.5 g/kg L-Arg,1 g/kg L-Arg,1.5 g/kg L-Arg,diabetic,diabetic+0.5 g/kg L-Arg,diabetic+1 g/kg L-Arg,and diabetic+1.5 g/kg L-Arg;whereas L-Arg was orally administered for 3 months to all treated groups.RESULTS L-Arg produced a moderate upregulation of blood glucose levels to normal rats,but when given to diabetics a significant upregulation was observed,associated with increased nitric oxide,inflammatory cytokines,and malonaldehyde levels in diabetic rats treated with 1 g/kg L-Arg and 1.5 g/kg L-Arg.A substantial decrease in the antioxidant capacity,superoxide dismutase,catalase,glutathione peroxidase,reduced glutathione concentrations,and Nrf-2 tissue depletion were observed at 1 g/kg and 1.5 g/kg L-Arg diabetic treated groups,associated with myocardial injury,fibrosis,α-smooth muscle actin upregulation,and disruption of desmin cardiac myofilaments,and these effects were not noticeable at normal treated groups.On the other hand,L-Arg could significantly improve the lipid profile of diabetic rats and decrease their body weights.CONCLUSION L-Arg dose of 1 g/kg or more can exacerbates the diabetes injurious effects on the myocardium,while 0.5 g/kg dose can improve the lipid profile and decrease the body weight.

Laparoscopic hepatectomy using indocyanine green attenuates postoperative inflammatory response for hepatocellular carcinoma:A propensity score matching analysis

BACKGROUND Improving the intraoperative and postoperative performance of laparoscopic hepatectomy was quite a challenge for liver surgeons.AIM To determine the benefits of indocyanine green(ICG)fluorescence imaging in patients with hepatocellular carcinoma(HCC)who underwent laparoscopic hepatectomy during and after surgery.METHODS We retrospectively collected the clinicopathological data of 107 patients who successfully underwent laparoscopic hepatectomy at Zhongshan Hospital(Xiamen),Fudan University from June 2022 to June 2023.Whether using the ICG fluorescence imaging technique,we divided them into the ICG and non-ICG groups.To eliminate statistical bias,a 1:1 propensity score matching analysis was conducted.The comparison of perioperative outcomes,including inflammationrelated markers and progression-free survival,was analyzed statistically.RESULTS Intraoperatively,the ICG group exhibited lower blood loss,a shorter surgical time,lower hepatic inflow occlusion(HIO)frequency,and a shorter total HIO time.Postoperatively,the participation of ICG resulted in a shorter duration of hospitalization(6.5 vs 7.6 days,P=0.03)and postoperative inflammatory response attenuation(lower neutrophil-lymphocyte ratio on the first day after surgery and platelet-lymphocyte ratio on the third day,P<0.05).Although the differences were not significant,the levels of all inflammation-related markers were lower in the ICG group.The rates of postoperative complications and the survival analyses,including progression-free and overall survivals showed no significant difference between the groups.CONCLUSION The involvement of ICG fluorescence imaging may lead to improved perioperative outcomes,especially postoperative inflammatory response attenuation,and ultimately improve HCC patients’recovery after surgery.

Lymphogranuloma venereum proctosigmoiditis misdiagnosed as inflammatory bowel disease: A case report

BACKGROUND There has been a rise in the number of cases diagnosed as lymphogranuloma venereum(LGV),caused by the transmission of Chlamydia trachomatis,specifi-cally serotypes L1,L2,and L3,mostly in men who have sex with men(MSM).LGV can clinically manifest as rectal discomfort,bleeding,and mucoid discharge mimicking inflammatory bowel disease(IBD).Therefore,the role of a wholesome collection of patient history along with gaining patient trust and ease in reporting different elements of their life—whether social or sexual history-could greatly guide physician’s investigations leading to timely and more efficient diagnosis.CASE SUMMARY A 38-year-old male presenting with symptoms of rectal bleeding,mucoid dis-charge,and abdominal pain during the past month.Initial treatment for hemo-rrhoids given at an outpatient clinic did not improve the patient’s complaints warranting further examinations,whereby endoscopy revealed the presence of mucosal edema and ulcerations in the rectosigmoid area rendering IBD a plau-sible diagnosis theoretically,but practically refuted due to the negative biopsy results,and positive result of nucleic acid amplification testing of the rectal swab sample for Chlamydia trachomatis.The latter results are in accordance with the diagnosis of LGV proctosigmoiditis.Accordingly,medical therapy with doxycy-cline was instituted,which yielded a notable symptomatic relief,and an education on safe sexual practices.INTRODUCTION Chlamydia trachomatis is a gram-negative bacterium with 15 different serotypes that can be categorized based on their resulting infection:Trachoma,anogenital infection,and lymphogranuloma venereum(LGV).LGV is sexually transmitted disease mostly by oral or anal sex due to the contraction of serotypes L1,L2,and L3 of this bacterium with a rising number of cases in homosexual males who engage in sexual activity[1,2].Moreover,there has been an evident link between patients diagnosed with LGV and a positive history of human immunodeficiency virus[3].Diagnosing a patient with LGV can be challenging due to the unpredictable and varied nature of clinical symptoms[1].Its most common presentations consisting of rectal pain,hematochezia,tenesmus,or mucous discharge can closely mimic those of inflam-matory bowel disease(IBD),similarly for the severe inflammatory changes found in rectal biopsy results contributing to the struggle in forming differential diagnosis[2,4,5].The latter hence marks the importance of detailed and wholesome collection of the patient’s history to aid physicians in giving greater consideration to LGV as a differential diagnosis.For this,we herein depict the case of a 38 years old male patient who was diagnosed with LGV after revisiting the patient’s sexual history.

A cross-sectional study of the association between dietary inflammatory index and glaucoma prevalence in a US population

AIM:To assess the relationship between dietary inflammatory index(DII)and prevalence of glaucoma among individuals aged 40y and above in the United States.METHODS:Participants were drawn from 2 cycles of the National Health and Nutrition Examination Survey(NHANES,2005-2008)for a cross-sectional study.DII was calculated from 24-hour dietary recall questionnaire conducted by experienced researchers and data analyzed in R according to the NHANES user guide,“Stratified Multi-stage Probability Sampling”.The relationship between DII and glaucoma was evaluated by multi-factor logistic regression analysis and the existence of a non-linear association examined by restricted cubic spline(RCS)analysis.RESULTS:A total of 5359 subjects were included and the cross-sectional analysis weighted to represent the US population of 109 million.DII was elevated in glaucoma patients(P<0.001)and smoking and alcohol use contributed to significant differences(P<0.001).DII correlated negatively with Healthy Eating Index(HEI)-2015(Spearman rank correlation coefficient,r=-0.49).RCS analysis showed a linear relationship between DII and glaucoma risk(P of non-linear relationship=0.575).CONCLUSION:An increased DII is strongly associated with high risk of glaucoma and diet-induced inflammation should be controlled to delay glaucoma progression.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge,as chronic local inflammation can largely impair bone healing.Here,we used magnesium silicate nanospheres(MSNs)to load microRNA-146a-5p(miR-146a)to fabricate a nanobiomaterial,MSN+miR-146a,which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells(hDPSCs).In addition,miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages(BMMs)under lipopolysaccharide(LPS)stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6(TRAF6),and MSNs could simultaneously promote M2 polarization of BMMs.MiR-146a was also found to inhibit osteoclast formation.Finally,the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel.Collectively,the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oralmaxillofacial bone defects.