Lymphovenous anastomosis and complex decongestive therapy for severe deformed lymphedema with recurrent infection:A case report

BACKGROUND Lower extremity lymphedema is a common complication following treatment for gynecological malignancies.Its incidence rate can reach up to 70%,affecting~20 million people worldwide.However,specialized treatment centers are scarce,and there is a lack of consensus on treatment approaches.Furthermore,there are even fewer reports on the systematic and effective treatment of severe lymphedema with malformations.Effective management of this condition remains a significant challenge for clinicians.CASE SUMMARY A 40-year-old woman developed bilateral leg swelling 6 years after receiving treatment for endometrial cancer.Since August 2018,she experienced>30 episodes of lymphangitis.Upon presentation,she exhibited bilateral leg swelling and deformation,with four large swellings in the posterior thigh that impeded movement,and pain in the limbs.Skin manifestations included lichenoid lesions and features of deep sclerosis.Radionuclide lymphoscintigraphy confirmed the diagnosis of lower limb lymphedema.After 6 mo of complex decongestive therapy(CDT)and three lymphaticovenous anastomosis(LVA)treatments,the patient lost 49 kg in weight.She also experienced a maximum circumference reduction of 35.2 cm in the left lower limb and 37.5 cm in the right lower limb.The leg pain disappeared,her swelling significantly decreased,and she regained the ability to walk,cycle,and run normally.CONCLUSION The combined application of CDT and LVA therapy demonstrates significant positive effects in the treatment of severe,deformed stage III lymphedema.

Review:Cell therapy in congestive heart failure

Congestive heart failure （CHF） has emerged as a major worldwide epidemic and its main causes seem to be the aging of the population and the survival of patients with post-myocardial infarction. Cardiomyocyte dropout （necrosis and apoptosis） plays a critical role in the progress of CHF; thus treatment of CHF by exogenous cell implantation will be a promising medical approach. In the acute phase of cardiac damage cardiac stem cells （CSCs） within the heart divide symmetrically and/or asymmetrically in response to the change of heart homeostasis, and at the same time homing of bone marrow stem cells （BMCs） to injured area is thought to occur, which not only reconstitutes CSC population to normal levels but also repairs the heart by differentiation into cardiac tissue. So far, basic studies by using potential sources such as BMCs and CSCs to treat animat CHF have shown improved ventricular remodelling and heart function. Recently, however, a few of randomized, double-blind, placebo-controlled clinical trials demonstrated mixed results in heart failure with BMC therapy during acute myocardial infarction.

Congestive Heart Failure: Treatment of Symptoms or Causes

This paper is based on the author’s 20+ years of experience treating patients with congestive heart failure (CHF) as a cardiologist. In the 20+ years, 64 patients were treated, including both with reduced and preserved left ventricular function. Most patients had a 4 - 5 days hospitalization in their first admission with one readmission (1.6%) over seven years. This paper will help us understand the physiology and pathophysiology of congestive heart failure, especially how to use beta blockers and diuretics. It will shorten the length of hospitalization and lower the readmission rate and cost of CHF treatment. This paper will help us to open another research direction for CHF.

Effectiveness of six-step complex decongestive therapy for treating upper limb lymphedema after breast cancer surgery

BACKGROUND Complex decongestive therapy(CDT)is currently recommended as the standard treatment for lymphedema.CDT is a four-step detumescence therapy that can effectively treat upper limb lymphedema after breast cancer surgery,and is considered non-invasive,painless and without side effects.AIM To determine the effectiveness of a six-step CDT involving a foam granule bandage for the treatment of upper extremity lymphedema pressure after breast cancer surgical intervention.METHODS The study included 100 patients with upper extremity lymphedema after breast cancer surgery.The surgical methods were mastectomy plus axillary lymph node dissection and breast preservation plus sentinel lymph node biopsy.The study population was further divided into the experimental group and control group with 50 cases in each group.The control group was given conventional CDT(four-step method),which included skin care,freehand lymphatic drainage,foam granule pressurized bandage,and functional exercise.In the experimental group,a six-step CDT method was applied that involved a foam particle bandage combined with air wave pressure therapy in addition to the four steps of conventional CDT.Patients in both groups were given one course of treatment daily(20 times),and the changes in body moisture and subjective symptoms were measured before and after treatment,preoperatively and 20 times after treatment.RESULTS No statistically significant differences in 50-Hz bioelectrical impedance and extracellular moisture ratio were observed between the two groups before treatment,suggesting comparability of the baseline data.After treatment,the 50-Hz bioelectrical impedance of the experimental group was significantly higher than that in the control group,and the extracellular moisture ratio was significantly lower than that in the control group.A comparison of the differences between the two groups before and after treatment indicated that the treatment effect in the experimental group was better than that in the control group.After 20 treatments,according to subjective evaluations,the tightness and swelling of the limbs in the experimental group were significantly reduced as compared with those in the control group.CONCLUSION The six-step CDT method can effectively reduce lymphedema,promote lymphatic circulation,and alleviate the subjective symptoms of patients,and thereby improve the quality of life and treatment compliance among patients.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Real-world evidence on the efficacy and safety of vonoprazanamoxicillin dual therapy for Helicobacter pylori treatment in elderly patients

BACKGROUND A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of Helicobacter pylori(H.pylori).While substantial research supports the efficacy and safety of vonoprazan and amoxicillin(VA)dual therapy in the general population,there is still a lack of studies specifically focusing on its safety in elderly patients.AIM To evaluate efficacy and safety of VA dual therapy as first-line or rescue treatment for H.pylori in elderly patients.METHODS As a real-world retrospective study,data were collected from elderly patients aged 60 years and above who accepted VA dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1000 mg thrice daily for 14 days)for H.pylori eradication in the Department of Gastroenterology at Peking University First Hospital between June 2020 and January 2024.H.pylori status was evaluated by^(13)C-urease breath test 6 weeks after treatment.All adverse events(AEs)during treatment were recorded.RESULTS In total,401 cases were screened.Twenty-one cases were excluded due to loss to follow-up,lack of re-examination,or unwillingness to take medication.The total of 380 included cases comprised 250 who received VA dual therapy as first-line treatment and 130 who received VA dual therapy as rescue treatment.H.pylori was successfully eradicated in 239 cases(95.6%)in the first-line treatment group and 116 cases(89.2%)in the rescue treatment group.The overall incidence of AEs was 9.5%for both groups.Specifically,9.2%of patients experienced an AE in the first-line treatment group and 10.0%in the rescue treatment group.Five patients discontinued treatment due to AE,with a discontinuation rate of 1.3%.No serious AE occurred.CONCLUSION The VA dual therapy regimen as a first-line treatment and a rescue therapy was effective and safe for elderly patients aged 60 and older.

Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

Current status of drug therapy for chronic hepatitis B

In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.Prevention and treatment of HBV are key measures to reduce complications.At present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a challenge.Anti-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’compliance.We will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.

Antiviral therapy for hepatitis B virus infection is beneficial for the prognosis hepatocellular carcinoma

In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.

Summary of the current guidelines for managing iatrogenic colorectal perforations and the evolving role of endoluminal vacuum therapy

Colonoscopy represents a safe procedure that is widely used in medical practice either to diagnose or treat various gastrointestinal diseases.During the last few years,the incidence rate of perforations in colonoscopic procedures has increased,especially in therapeutic colonoscopies.The recent advancements in endoscopic techniques and gastrointestinal tumoral resection procedures such as endoscopic mucosal resection,endoscopic full-thickness resection,and endoscopic submucosal dissection(ESD)could be a risk factor for this increased risk.The incidence rate of mortality of serious colonoscopic perforations is 7.1%.The management plan for these perforations starts with conservative treatment in mild cases,endoscopic closure,and surgical management in severe cases.Recently,endoluminal vacuum therapy was found to be effective in the management of colorectal perforations and this has been reported in multiple case reports.This editorial provides an overview of the current guidelines for the management of iatrogenic colorectal perforations.These insights are from the perspectives of endoscopists and gastroenterologists.We also present a management algorithm based on the guidelines of the European Society of Gastrointestinal Endoscopy,the American Gastroenterological Association,and the World Society of Emergency Surgery.We also discussed in brief the use of endoluminal vacuum therapy in colorectal perforations.

Advancing treatment strategies:Insights from network meta-analysis of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.

Current perspectives and the future of disease-modifying therapies in type 1 diabetes

Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.

Root canal therapy combined with endoscopic sinus surgery for odontogenic sinusitis:Efficacy comparison in a cohort study

BACKGROUND Odontogenic maxillary sinusitis,often triggered by dental issues like periapical periodontitis,significantly contributes to chronic sinusitis,mainly affecting adults around 50 years old,emphasizing the need for a multidisciplinary diagnostic and treatment approach.AIM To investigate the therapeutic effect and clinical value of root canal therapy combined with nasal endoscopic surgery compared with simple root canal the-rapy in the treatment of severe odontogenic maxillary sinusitis caused by peria-pical periodontitis.METHODS The clinical data,diagnosis,and treatment of 200 patients with severe odonto-genic maxillary sinusitis caused by periapical periodontitis from October 2020 to October 2021 were analyzed retrospectively.Among them,63 patients were treated with simple root canal therapy as the control group,and 137 patients were treated with root canal therapy combined with nasal endoscopic surgery as the observation group.The therapeutic effect,Lund-Kennedy endoscopic score,paranasal sinus Lund-Mackay score,complication rate,recurrence rate,and patient satisfaction were compared between the two groups.RESULTS First,we compared the effective rates:23 cases were cured,22 were improved,and 8 were ineffective in the control group,yielding a total effective rate of 84.90%.Meanwhile,97 cases were cured,34 improved,and 6 were ineffective in the observation group,resulting in a total effective rate of 95.62%.The observation group had a higher total effective rate compared with the control group(P<0.05).Second,we compared the Lund–Kennedy endoscopic score.Before treatment,no significant difference(P>0.05)was observed in this score between the two groups.After treatment,the Lund–Kennedy endoscopic score decreased in both groups.The Lund–Kennedy endoscopic score of the observation group at 3 and 6 mo after treatment was lower compared to that of the control group(P<0.05).Third,we compared the Lund–Mackay score of paranasal sinuses.Before treatment,there was no significant difference in this score between the two groups(P>0.05).After treatment,the Lund–Mackay scores of paranasal sinuses decreased in both groups.The Lund–Mackay scores of paranasal sinuses in the observation group at 3 and 6 mo after treatment were lower compared to those of the control group(P<0.05).Fourth,we compared the incidence and recurrence rate of complications.Three months after treatment,no significant difference was found in the incidence and recurrence rate of complications between the observation group(6.56%)and the control group(9.52%)(P>0.05).However,6 mo after treatment,the incidence and recurrence rate of complications in the observation group(2.91%)was significantly higher compared to that of the control group(12.69%)(P<0.05).Fifth,we compared patient satisfaction.Six months after treatment,the patient satisfaction of the observation group(93.43%)was significantly better than that of the control group(84.12%)(P<0.05).CONCLUSION Root canal therapy combined with nasal endoscopic surgery has a good therapeutic effect on severe odontogenic maxillary sinusitis caused by periapical periodontitis,and it can reduce the injury of maxillary sinus mucosa and bone,and significantly reduce the incidence of complications and recurrence rate.Meanwhile,it has high patient satisfaction and remarkable therapeutic effect,which is suggested to be popularized and applied in clinic.

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.

Evaluating Wharton’s jelly-derived stem cell therapy in autism:Insights from a case study

Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder affecting over 2%of the global population,marked by social communication deficits and repetitive behaviors.Kabatas et al explored the efficacy and safety of Wharton’s jelly-derived mesenchymal stem cell(WJ-MSC)therapy in a 4-year-old child with ASD.Using the childhood autism rating scale and Denver II develop-mental screening test,significant improvements were seen after six WJ-MSC sessions,with no adverse events over 2 years.Despite promising results,the study’s single-case design limits generalizability.Larger,multi-center trials are needed to validate the findings and assess long-term effects of WJ-MSC therapy in ASD.

Effectiveness of complex decongestive therapy in management of breast cancer associated lymphedema

Background:To assess the edema relief effects of complex decongestive therapy(CDT)in patients with breast cancer associated lymphedema after axillary lymph node dissection(ALND).Methods:58 breast cancer patients with unilateral arm lymphedema after breast cancer ALND were enrolled.The patients were divided into three groups based on the difference of circumference between the affected and unaffected extremity:group 1,mild lymphedema in circumference difference;group 2,moderate lymphedema,and group 3,severe lymphedema.These patients received four weeks of CDT and self-administered home therapy.Arm circumference was measured before,right after CDT,3 months and 12 months of follow-up.Results:In the first group,the circumference difference was 1.53±0.73 cm prior to CDT,and 0.32±0.59 cm right after CDT,and the difference was statistically significant(P<0.001).At the 1-year-follow-up,we got an even higher value than the pre-CDT one,however,there was no significant difference(P=0.175).At the end of CDT,the circumference difference of the third group was 4.52±2.58 cm,significantly lower than the baseline level(8.76±3.07 cm)(P<0.001).In the third group,the reduction of circumference difference was persisted for 12 months.Conclusion:The effects of CDT were maintained for 12 months,while there were differences in progress of circumference difference among the three groups.The effects of patients with severe initial edema(>5 cm increased)last longer.

Therapeutic Efficacy of Complex Decongestive Therapy in the Treatment of Elephantiasis of the Lower Extremities

Objective To evaluate the therapeutic efficacy of complex decongestive therapy in the treatment of elephantiasis of the lower extremities.Methods Seventeen patients with unilateral lower limb elephantiasis were included in the study(5 with primary lymphedema and 12 with secondary lymphedema).All patients were treated with one course(4 weeks)of complex decongestive therapy.Changes inextracellular fluid(ECF),BMI,circumferences,and skin properties including skin stiffness(SF),percent water content(PWC),and trans-epidermal water loss(TEWL)were measured before and after treatment.Results The“elephantiasis-like”appearance of the affected limb was greatly improved after treatment.The ECF,BMI,and circumferences were significantly decreased after treatment(P<0.001)with an average ECF of 2.97±1.82 L,BMI of 1.638±2.647 kg/m^2,and circumference of 6.58±2.79 cm.The values of PWC,TEWL,and SFwere 50.5%±10.6%,18.55±10.2 g/m^2 h,and 0.161±0.176 N,respectively,before treatment and 36.05%±7%,8.3±2.07 g/m^2h,and 0.086±0.038 N,respectively,after treatment,there by showing significant decreases(P<0.05).Conclusion Complex decongestive therapy is effective in the treatment of advanced stages of chronic lymphedema.

Neoadjuvant therapy for pancreas cancer: Past lessons and future therapies

Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.

Study on Apoptosis and Expression of P53, Bcl-2,Bax in Cardiac Myocytys of Congestive Heart Failure Induced by Ventricular Pacing

The apoptosis and the expression of p53, bcl-2 and Bax in myocytes of chronic rapid ventricular pacing-induced congestive heart failure (CHF) in rabbits were investigated. The CHF rabbit model (P, n=7) was established by chronic rapid ventricular pacing for 3 weeks. By using TUNEL technique the apoptosis in the myocytes in the rabbit model was studied and the expression of p53, bcl-2 and Bax in myocytes was detected by using immunohistochemical method. Sham-operated (C, n=9) group served as control group. The results showed that there were about 4033± 884.56 apoptotic cells/10 6 myocytes in P group, but no apoptotic cells were found in C group. Myocytes positive for p53 immunoreactivity (18.86±8.48 vs 5.06±0.87, P<0.01) and positive for Bax immunoreactivity (7.15±1.91 vs 0.43±0.09, P<0.01) were increased in P group as compared with those in C group, while the myocytes positive for bcl-2 immunoreactivity (7.08±1.05 vs 14.97±4.47, P<0.01) and the ratio of bcl-2/Bax were decreased in P group as compared with those in C group. Apoptosis was involved in the development of CHF induced by continuously rapid ventricular pacing in rabbit. The expression of p53 and Bax was increased, while the expression of bcl-2 was inhibited. These might play an important role in the acceleration of the apoptosis.

When combination therapy isn't working: Emerging therapies for the management of inflammatory bowel disease

Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.