The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to...The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.展开更多
Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the pr...Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.展开更多
Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of ...Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease(CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.展开更多
Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CD...Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CDI),have worse outcomes of CDI-including higher rates of colectomy and death,and experience higher rates of recurrence.However,it is still not clear whether C.difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment.The burden of CDI has increased dramatically over the past decade,with severe outbreaks described in many countries,which have been attributed to a new and more virulent strain.A parallel rise in the incidence of CDI has been noted in patients with IBD.IBD patients with CDI tend be younger,have less prior antibiotic exposure,and most cases of CDI in these patients represent outpatient acquired infections.The clinical presentation of CDI in these patients can be unique-including diversion colitis,enteritis and pouchitis,and typical findings on colonoscopy are often absent.Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation,and the prognostic implications of CDI in these patients,it is recommended to test all IBD patients hospitalized with a disease flare for C.difficile.Treatment includes general measures such as supportive care and infection control measures.Antibiotic therapy with either oral metronidazole,vancomycin,or the novel antibiotic-fidaxomicin,should be initiated as soon as possible.Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI.The aim of this paper is to review recent data on CDI in IBD:role in pathogenesis,diagnostic methods,optional treatments,and outcomes of these patients.展开更多
Ulcerative colitis and Crohn’s disease,commonly known as inflammatory bowel disease(IBD),draw attention from specialists of various disorders,including gastroenterology,psychiatry,and radiology.The involvement of a c...Ulcerative colitis and Crohn’s disease,commonly known as inflammatory bowel disease(IBD),draw attention from specialists of various disorders,including gastroenterology,psychiatry,and radiology.The involvement of a cortical influence in the brain-gut axis as well as the interaction of the hypothalamic-pituitary-adrenal axis and the peripheral nervous system provide an initial explanation of the psychological symptoms associated with IBD.The involvement of structures the limbic system,such as the anterior cingulate cortex,the prefrontal cortex,and the amygdala,paves the way for the discovery of the mechanisms underlying depression depression,anxiety,alexithymia,personality traits,and other psychological impairments following the onset of IBD.Psychiatric therapy in IBD patients is almost as important as the gastroenterological approach and consists of pharmacological treatment and psychotherapy.Neither of the available psychiatric treatment methods is considered the golden standard because both methods have side effects,and psychotropic medication can provoke the worsening of IBD symptoms.Thus,both approaches must be applied with awareness of the possibility of side effects.We suggest that psychiatrists and gastroenterologists work together to reach a consensus on IBD therapy to ensure success and to reduce side effects and relapse to the lowest possible rates.展开更多
Inflammatory bowel disease(IBD)is believed to develop via a complex interaction between genetic,environmental factors and the mucosal immune system.Crohn’s disease and ulcerative colitis are two major clinical forms ...Inflammatory bowel disease(IBD)is believed to develop via a complex interaction between genetic,environmental factors and the mucosal immune system.Crohn’s disease and ulcerative colitis are two major clinical forms of IBD.MicroRNAs(miRNAs)are a class of small,endogenous,noncoding RNA molecules,and evolutionary conserved in animals and plants.It controls protein production at the post-transcriptional level by targeting mRNAs for translational repression or degradation.MiRNAs are important in many biological processes,such as signal transduction,cellular proliferation,differentiation and apoptosis.Considerable attention has been paid on the key role of miRNAs in autoimmune and inflammatory disease,especially IBD.Recent studies have identified altered miRNA profiles in ulcerative colitis,Crohn’s disease and inflammatory bowel diseaseassociated colorectal cancer.In addition,emerging data have implicated that special miRNAs which suppress functional targets play a critical role in regulating key pathogenic mechanism in IBD.MiRNAs were found involving in regulation of nuclear transcription factor kappa B pathway(e.g.,miR-146a,miR-146b,miR-122,miR-132,miR-126),intestinal epithelial barrier function(e.g.,miR-21,miR-150,miR-200b)and the autophagic activity(e.g.,miR-30c,miR-130a,miR-106b,miR-93,miR-196).This review aims at discussing recent advances in our understanding of miRNAs in IBD pathogenesis,their role as disease biomarkers,and perspective for future investigation and clinical application.展开更多
Tumor necrosis factor-α(TNF-α)inhibitors are biological agents introduced in the late 1990s for the treatment of different immune-mediated diseases as inflammatory bowel disease,rheumatoid arthritis and psoriasis.Th...Tumor necrosis factor-α(TNF-α)inhibitors are biological agents introduced in the late 1990s for the treatment of different immune-mediated diseases as inflammatory bowel disease,rheumatoid arthritis and psoriasis.The most commonly used TNF-αantagonists are infliximab,adalimumab,and certolizumab pegol,and though highly effective in lowering inflammation,the efficacy must be weighed against the potential for adverse events.The treatment-induced immunosuppression is suspected to increase the risk of infections,including the risk of reactivation of latent tuberculosis,as the TNF-αcytokine plays an important role in the immune function.In this topic highlight a short overview of the infection risk associated with TNF-αinhibiter therapy is outlined with a focus on the overall risk of serious infections,mycobacterial infection and latent viral infections.展开更多
Pneumonia and acute respiratory distress syndrome are common and important causes of respiratory failure in the intensive care unit with a significant impact on morbidity, mortality and health care utilization despite...Pneumonia and acute respiratory distress syndrome are common and important causes of respiratory failure in the intensive care unit with a significant impact on morbidity, mortality and health care utilization despite early antimicrobial therapy and lung protective mechanical ventilation. Both clinical entities are characterized by acute pulmonary inflammation in response to direct or indirect lung injury. Adjunct anti-inflammatory treatment with corticosteroids is increasingly used, although the evidence for benefit is limited. The treatment decisions are based on radiographic, clinical and physiological variables without regards to inflammatory state. Current evidence suggests a role of biomarkers for the assessment of severity, and distinguishing sub-phenotypes (hyperinflammatory versus hypo-inflammatory) with important prognostic and therapeutic implications. Although many inflammatory biomarkers have been studied the most common and of interest are C-reactive protein, procalcitonin, and pro-inflammatory cytokines including interleukin 6. While extensively studied as prognostic tools (prognostic enrichment), limited data are available for the role of biomarkers in determining appropriate initiation, timing and dosing of adjunct anti-inflammatory treatment (predictive enrichment)展开更多
BACKGROUND Osteoarthritis is a chronic degenerative disease with an incidence of 50%in people over 65 years old and 80%in people over 80 years old worldwide.It is the second leading reason of loss of working capacity ...BACKGROUND Osteoarthritis is a chronic degenerative disease with an incidence of 50%in people over 65 years old and 80%in people over 80 years old worldwide.It is the second leading reason of loss of working capacity after cardiovascular diseases and severely affects the society and families.Therefore,finding biological markers related to the diagnosis and treatment of osteoarthritis is of great significance in clinical practice.AIM To observe the changes and clinical value of serum inflammatory factors and miR-145 expression in patients with osteoarthritis before and after treatment.METHODS Eighty-three patients with knee osteoarthritis(observation group)who were admitted to our hospital from April 2013 to June 2015,and 60 healthy people(control group)during the same period were selected.After 4 wk of treatment,the levels of miR-145,tumor necrosis factor(TNF)-α,interleukin(IL)-6,and IL-10 were compared between the control group and the observation group before treatment.The correlation of miR-145,TNF-α,IL-6,and IL-10 levels with visual analogue scale(VAS),Lysholm,and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores was assessed by Pearson correlation analysis.The correlation of the expression of miR-145,TNF-α,IL-6,and IL-10 with Kellgren-Lawrence(K-L)grades was assessed by Spearman correlation analysis.The critical levels of miR-145,TNF-α,IL-6,and IL-10 in distinguishing different K-L grades were determined by receiver operating characteristic(ROC)curve analysis.RESULTS The expression level of miR-145 in the observation group was significantly higher than that in the control group before treatment(P<0.05).After treatment,the expression level of miR-145 in the observation group was significantly lower than that before treatment(P<0.05).The levels of TNF-αand IL-6 in the observation group were significantly higher than those in the control group(P<0.05),and the level of IL-10 was significantly lower than that in the control group(P<0.05).After treatment,the levels of TNF-αand IL-6 in the observation group were significantly lower than those before treatment(P<0.05),and IL-I0 level was significantly higher than that before treatment(P<0.05).VAS and WOMAC scores were both positively correlated with miR-145,TNF-α,and IL-6(P<0.05),and negatively correlated with IL-10(P<0.05),while Lysholm scores were negatively correlated with miR-145,TNF-α,and IL-6(P<0.05),and positively correlated with IL-10(P<0.05).K-L grades were positively correlated with miR-145,TNF-α,and IL-6(P<0.05),and negatively correlated with IL-10(P<0.05).The area under the ROC curve(AUC)and specificity of TNF-αin differentiating K-L grades I-II were the highest,which were 0.785 and 97.45%,respectively,and miR145 had the highest sensitivity of 94.59%;the AUC and sensitivity of IL-6 in differentiating K-L grades II-III were the highest,which were 0.766 and 97.30%,respectively,and TNF-αhad the highest specificity of 86.68%.CONCLUSION MiR-145 and inflammatory factors have certain diagnostic value in osteoarthritis,and they are expected to become potential indicators for the diagnosis and evaluation of osteoarthritis in the future.展开更多
Inflammatory bowel disease(IBD)incidence has been increasing steadily,most dramatically in the Western developed countries.Treatment often includes lifelong immunosuppressive therapy and surgery.There is a critical ne...Inflammatory bowel disease(IBD)incidence has been increasing steadily,most dramatically in the Western developed countries.Treatment often includes lifelong immunosuppressive therapy and surgery.There is a critical need to reduce the burden of IBD and to discover medical therapies with better efficacy and fewer potential side-effects.Repurposing of treatments originally studied in other diseases with similar pathogenesis is less costly and time intensive than de novo drug discovery.This study used a treatment repurposing methodology,the literature-related discovery and innovation(LRDI)text mining system,to identify potential treatments(developed for non-IBD diseases)with sufficient promise for extrapolation to treatment of IBD.By searching for desirable patterns of twenty key biomarkers relevant to IBD(e.g.,inflammation,reactive oxygen species,autophagy,barrier function),the LRDI-based query retrieved approximately 9500 records from Medline.The most recent 350 records were further analyzed for proof-of-concept.Approximately 18%(64/350)met the criteria for discovery(not previously studied in IBD human or animal models)and relevance for application to IBD treatment.Many of the treatments were compounds derived from herbal remedies,and the majority of treatments were being studied in cancer,diabetes,and central nervous system disease,such as depression and dementia.As further validation of the search strategy,the query identified ten treatments that have just recently begun testing in IBD models in the last three years.Literature-related discovery and innovation text mining contains a unique search strategy with tremendous potential to identify treatments for repurposing.A more comprehensive query with additional key biomarkers would have retrieved many thousands more records,further increasing the yield of IBD treatment repurposing discovery.展开更多
Purpose: Based on the National Natural Science Foundation of China, we collect and sort out the literature published in approximately the last 30 years, which use prescriptions in Synopsis of the Golden Chamber to tre...Purpose: Based on the National Natural Science Foundation of China, we collect and sort out the literature published in approximately the last 30 years, which use prescriptions in Synopsis of the Golden Chamber to treat pelvic inflammatory disease (PID). This study provides theoretical basis for the treatment of PID;we recommend this achievement to colleagues. Method: Firstly, we searched and collected the literatures from last three decades in CNKI, Wanfang and VIP databases, which are about classical prescriptions treating endometriosis. Then, by screening all the literatures, we obtained the clinical research literatures and individual case reports. Finally, we went through the internal quality of the two categories of literatures to get the dominant prescriptions. Using a retrospective study of evidence-based medicine research, we comprehensively collect literature, standardize the disease spectrum, classify the evidence, and then evaluate the internal quality. Results: We refine 4 prescriptions which commonly are used in the treatment of PID;in other words, they are also the clinical symptoms of PID: Gui Zhi Fu Ling Wan symptom, which manifests blood stasis and cold-damp stagnancy;Dang Gui Shao Yao San symptom, which manifests disharmony of liver and spleen, qi-blood stasis and damp obstruction;Da Huang Mu Dan Tang symptom, which manifests the gathering toxic heat and qi-blood stasis;Yi Yi Fu Zi Bai Jiang San symptom, which manifests the internal toxic heat and qi-blood injury. Conclusion: This study is gospel for the patients with recurrent episodes of PID who can’t often use antibiotics. At the same time, it is also a green therapeutics which Chinese ancients dedicated to human medicine.展开更多
Objectives To investigate the effects of preoperative smoking and smoking cessation time on preoperative peripheral blood inflammatory indexes and postoperative hospitalization outcomes in male patients with lung canc...Objectives To investigate the effects of preoperative smoking and smoking cessation time on preoperative peripheral blood inflammatory indexes and postoperative hospitalization outcomes in male patients with lung cancer and surgery therapy.Methods We retrospectively enrolled 637 male patients who underwent curative-intent lung cancer resection between January 2014 and December 2016.Patients were classified as the current smokers,the never smokers,and the ex-smokers based on their smoking history,and the ex-smokers were allocated into five subgroups according to their smoking cessation times(CeT):CeT W6 weeks,6weeks<CeT W lyear,lyear<CeT<5years,5years<CeT<lOyears,CeT>10years.The preoperative peripheral blood white blood cells(WBCs),albumin,neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),intraoperative blood loss,30-day mortality,in-hospital days,hospitalization costs,intensive care un辻(ICU),admission days and placement time of closed thoracic drainage tube were compared among difTerent groups.Results There were significant differences in WBC(F=S.275,P<0.001)and albumin(F=2,470,P<0.05)among patients of current smokers,ex-smokers with different smoking cessation time,and never-smokers.The blood WBC count in current smokers(7.7 X 109/L)was significantly higher than that in ex・smokers(7.0 X 109/L)and never-smokers(5.9 X 109/L)(t=-2.145,P<0.05;t=-6.073,P<0.01,respectively).The level of peripheral blood albumin in current smokers(41.1 g/L)was lower than that in ex・smokers(42.1 g/L)and neve—smokers(43.2 g/L)(t=2.323,P<0.05;t=3.995,P<0.01,respectively).The level of peripheral blood NLR in current smokers(3.7)was higher than that in ex-smokers(3.1)and never smokers(2.8)(t—-1.836,P<0.05;t=-2.889,P<0.01,respectively).There was no significant difference in WBC,albumin and NLR among five subgroups of different smoking cessation time.No significant difference was observed in intraoperative blood loss,30-day mortality,hospitalization costs,hospital stay,ICU stay and placement time of closed thoracic drainage tube among groups either.Conclusion Smoking increases the preoperative inflammatory indexes in peripheral blood of lung cancer patients.Smoking cessation has beneficial effect on reducing levels of these inflammatory indexes,which may be not impacted by the time length of smoking cessation.Therefore,lung cancer patients should be encouraged to quit smoking at any time.展开更多
Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases that often involve organs other than those of the gastrointestinal tract. Immune-related extraintestinal manifestations (EIMs) are usu...Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases that often involve organs other than those of the gastrointestinal tract. Immune-related extraintestinal manifestations (EIMs) are usually related to disease activity, but sometimes may take an independent course. Globally, about one third of patients develop these systemic manifestations. Phenotypic classification shows that certain subsets of patients are more susceptible to developing EIMs, which frequently occur simultaneously in the same patient overlapping joints, skin, mouth, and eyes. The clinical spectrum of these manifestations varies from mild transitory to very severe lesions, sometimes more incapacitating than the intestinal disease itself. The great majority of these EIMs accompany the activity of intestinal disease and patients run a higher risk of a severe clinical course. For most of the inflammatory EIMs, the primary therapeutic target remains the bowel. Early aggressive therapy can minimize severe complications and maintenance treatment has the potential to prevent some devastating consequences.展开更多
The most common and aggressive type of brain tumor is glioblastoma multiforme (GBM). The prognosis for GBM remains poor with a five-year survival rate between 1% and 2%. The prospects for patients with recurrent GBM (...The most common and aggressive type of brain tumor is glioblastoma multiforme (GBM). The prognosis for GBM remains poor with a five-year survival rate between 1% and 2%. The prospects for patients with recurrent GBM (RGBM) are much worse, with the majority dying within 6 months. This publication provides a brief description of the treatment of 11 GBM patients treated with sodium phenylbutyrate (PB) in combination with pazopanib, m-TOR inhibitors, and other agents. The treatment was associated with tolerable side effects and resulted in objective responses in 54.5% of cases (complete response 18.2%, partial response 36.3%) and 27.3% cases of stable disease. The preferable treatment regimen consisted of PB, pazopanib, dasatinib, everolimus, and bevacizumab (BVZ). For various reasons not all patients were compliant with the treatment regimen. In patients who strictly complied with the treatment plan, all responded as CR or PR. Based on preliminary findings, the authors propose further phase I/II clinical trials with PB in combination with pazopanib, dasatinib, everolimus, and BVZ in patients with RGBM who failed standard surgery, radiation therapy and chemotherapy. With proper dose reductions, the treatment appears to be well-tolerated. Molecular profiling of patient subgroups with favorable genomic signatures may help to select patients for future studies.展开更多
Despite a decrease in incidence over past decades,gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic ...Despite a decrease in incidence over past decades,gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.展开更多
AIM: To evaluate fecal calprotectin (FC) as a surrogate marker of treatment outcome of relapse of inflammatory bowel disease (IBD) and, to compare FC with fecal myeloperoxidase (MPO) and fecal eosinophil protein X (EP...AIM: To evaluate fecal calprotectin (FC) as a surrogate marker of treatment outcome of relapse of inflammatory bowel disease (IBD) and, to compare FC with fecal myeloperoxidase (MPO) and fecal eosinophil protein X (EPX). METHODS: Thirty eight patients with IBD, comprising of 27 with ulcerative colitis (UC) and 11 with Crohn’s disease (CD) were investigated before treatment (inclusion), and after 4 and 8 wk of treatment. Treatment outcomes were evaluated by clinical features of disease activity and endoscopy in UC patients, and disease activity in CD patients. In addition, fecal samples were analyzed for FC by enzyme-linked immunosorbent assay (ELISA), and for MPO and EPX with radioimmunoassay (RIA). RESULTS: At inclusion 37 of 38 (97%) patients had elevated FC levels (> 94.7 μg/g). At the end of the study, 31 of 38 (82%) patients fulfilled predefined criteria of a complete response [UC 21/27 (78%); CD 10/11 (91%)]. Overall, a normalised FC level at the end of the study predicted a complete response in 100% patients, whereas elevated FC level predicted incomplete response in 30%. Normalised MPO or EPX levels predicted a complete response in 100% and90% of the patients, respectively. However, elevated MPO or EPX levels predicted incomplete response in 23% and 22%, respectively. CONCLUSION: A normalised FC level has the potential to be used as a surrogate marker for successful treatment outcome in IBD patients. However, patients with persistent elevation of FC levels need further evaluation. FC and MPO provide superior discrimination than EPX in IBD treatment outcome.展开更多
The frequency of diagnosis of inflammatory bowel disease(IBD) has increased in younger populations.For this reason,pregnancy in patients with IBD is a topic of interest,warranting additional focus on disease managemen...The frequency of diagnosis of inflammatory bowel disease(IBD) has increased in younger populations.For this reason,pregnancy in patients with IBD is a topic of interest,warranting additional focus on disease management during this period.The main objective of this article is to summarize the latest findings and guidelines on the management of potential problems from pregnancy to the breastfeeding stage.Fertility is decreased in patients with active IBD.Disease remission prior to conception will likely decrease the rate of pregnancy-related complications.Most of the drugs used for IBD treatment are safe during both pregnancy and breastfeeding.Two exceptions are methotrexate and thalidomide,which are contraindicated in pregnancy.Antitumor necrosis factor agents are not advised during the third trimester as they exhibit increased transplacental transmission and potentially cause immunosuppression in the fetus.Radiological and endoscopic examinations and surgical interventions should be performed only when absolutely necessary.Surgery increases the fetal mortality rate.The delivery method should be determined with consideration of the disease site and presence of progression or flare up.Treatment planning should be a collaborative effort among the gastroenterologist,obstetrician,colorectal surgeon and patient.展开更多
Significant progress has been achieved in the treatment of metastatic colorectal cancer(mCRC)patients during the last 20 years.There are currently numerous treatments available for the first-line treatment of mCRC.Sop...Significant progress has been achieved in the treatment of metastatic colorectal cancer(mCRC)patients during the last 20 years.There are currently numerous treatments available for the first-line treatment of mCRC.Sophisticated molecular technologies have been developed to reveal novel prognostic and predictive biomarkers for CRC.The development of next-generation sequencing and wholeexome sequencing,which are strong new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of customized treatment,has resulted in tremendous breakthroughs in DNA sequencing technology in recent years.The appropriate adjuvant treatments for mCRC patients are determined by the tumor stage,presence of high-risk pathologic characteristics,microsatellite instability status,patient age,and performance status.Chemotherapy,targeted therapy,and immunotherapy are the main systemic treatments for patients with mCRC.Despite the fact that these novel treatment choices have increased overall survival for mCRC,survival remains optimal for individuals with non-metastatic disease.The molecular technologies currently being used to support our ability to practice personalized medicine;the practical aspects of applying molecular biomarkers to regular clinical practice;and the evolution of chemotherapy,targeted therapy,and immunotherapy strategies for the treatment of mCRC in the front-line setting are all reviewed here.展开更多
AIM To examine the efficacy and safety of thalidomide and thalidomide analogues in induction and maintenance of remission in patients with inflammatory bowel disease(IBD).METHODS A literature search was performed in t...AIM To examine the efficacy and safety of thalidomide and thalidomide analogues in induction and maintenance of remission in patients with inflammatory bowel disease(IBD).METHODS A literature search was performed in the following databases: PubM ed, EMBASE, Web of Science, Ovid and the Cochrane Library, and Chinese databases such as the China National Knowledge Infrastructure, China Science and Technology Journal Database(VIP), Wanfang Data. The randomized controlled analysis was performed to assess the effects of thalidomide therapy on inflammatory bowel disease for patients who did show good response with other therapies. RESULTS Three studies(n = 212) met the inclusion criteria were used in this Meta-analysis. No difference was found between thalidomide/thalidomide analogues and placebo in the induction of remission(RR = 1.36, 95%CI: 0.83-2.22, P = 0.22), the induction of clinical response(RR = 1.14, 95%CI: 0.75-1.72, P = 0.54) and the induction of adverse events(RR = 1.41, 95%CI: 0.99-2.02, P = 0.06).CONCLUSION Currently, there is not enough evidence to support use of thalidomide or its analogue for the treatment in patients of any age with IBD. However, it warrants a reanalysis when more data become available.展开更多
文摘The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.
基金supported by the GRF RGC&CRF,Hong Kong(Grant Nos.:475012 and C5045-20 EF)HMRF,Hong Kong(Grant No.:03141386)+3 种基金ITF,Hong Kong(Grant No.:ITS/209/12)UGC Direct Grant 2011,2012,2021.032HKOG Trust Fund 2011,2014,2019the National Natural Science Foundation of China(Grant Nos.:81974225 and 82201823)。
文摘Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.
文摘Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease(CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.
文摘Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CDI),have worse outcomes of CDI-including higher rates of colectomy and death,and experience higher rates of recurrence.However,it is still not clear whether C.difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment.The burden of CDI has increased dramatically over the past decade,with severe outbreaks described in many countries,which have been attributed to a new and more virulent strain.A parallel rise in the incidence of CDI has been noted in patients with IBD.IBD patients with CDI tend be younger,have less prior antibiotic exposure,and most cases of CDI in these patients represent outpatient acquired infections.The clinical presentation of CDI in these patients can be unique-including diversion colitis,enteritis and pouchitis,and typical findings on colonoscopy are often absent.Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation,and the prognostic implications of CDI in these patients,it is recommended to test all IBD patients hospitalized with a disease flare for C.difficile.Treatment includes general measures such as supportive care and infection control measures.Antibiotic therapy with either oral metronidazole,vancomycin,or the novel antibiotic-fidaxomicin,should be initiated as soon as possible.Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI.The aim of this paper is to review recent data on CDI in IBD:role in pathogenesis,diagnostic methods,optional treatments,and outcomes of these patients.
文摘Ulcerative colitis and Crohn’s disease,commonly known as inflammatory bowel disease(IBD),draw attention from specialists of various disorders,including gastroenterology,psychiatry,and radiology.The involvement of a cortical influence in the brain-gut axis as well as the interaction of the hypothalamic-pituitary-adrenal axis and the peripheral nervous system provide an initial explanation of the psychological symptoms associated with IBD.The involvement of structures the limbic system,such as the anterior cingulate cortex,the prefrontal cortex,and the amygdala,paves the way for the discovery of the mechanisms underlying depression depression,anxiety,alexithymia,personality traits,and other psychological impairments following the onset of IBD.Psychiatric therapy in IBD patients is almost as important as the gastroenterological approach and consists of pharmacological treatment and psychotherapy.Neither of the available psychiatric treatment methods is considered the golden standard because both methods have side effects,and psychotropic medication can provoke the worsening of IBD symptoms.Thus,both approaches must be applied with awareness of the possibility of side effects.We suggest that psychiatrists and gastroenterologists work together to reach a consensus on IBD therapy to ensure success and to reduce side effects and relapse to the lowest possible rates.
文摘Inflammatory bowel disease(IBD)is believed to develop via a complex interaction between genetic,environmental factors and the mucosal immune system.Crohn’s disease and ulcerative colitis are two major clinical forms of IBD.MicroRNAs(miRNAs)are a class of small,endogenous,noncoding RNA molecules,and evolutionary conserved in animals and plants.It controls protein production at the post-transcriptional level by targeting mRNAs for translational repression or degradation.MiRNAs are important in many biological processes,such as signal transduction,cellular proliferation,differentiation and apoptosis.Considerable attention has been paid on the key role of miRNAs in autoimmune and inflammatory disease,especially IBD.Recent studies have identified altered miRNA profiles in ulcerative colitis,Crohn’s disease and inflammatory bowel diseaseassociated colorectal cancer.In addition,emerging data have implicated that special miRNAs which suppress functional targets play a critical role in regulating key pathogenic mechanism in IBD.MiRNAs were found involving in regulation of nuclear transcription factor kappa B pathway(e.g.,miR-146a,miR-146b,miR-122,miR-132,miR-126),intestinal epithelial barrier function(e.g.,miR-21,miR-150,miR-200b)and the autophagic activity(e.g.,miR-30c,miR-130a,miR-106b,miR-93,miR-196).This review aims at discussing recent advances in our understanding of miRNAs in IBD pathogenesis,their role as disease biomarkers,and perspective for future investigation and clinical application.
文摘Tumor necrosis factor-α(TNF-α)inhibitors are biological agents introduced in the late 1990s for the treatment of different immune-mediated diseases as inflammatory bowel disease,rheumatoid arthritis and psoriasis.The most commonly used TNF-αantagonists are infliximab,adalimumab,and certolizumab pegol,and though highly effective in lowering inflammation,the efficacy must be weighed against the potential for adverse events.The treatment-induced immunosuppression is suspected to increase the risk of infections,including the risk of reactivation of latent tuberculosis,as the TNF-αcytokine plays an important role in the immune function.In this topic highlight a short overview of the infection risk associated with TNF-αinhibiter therapy is outlined with a focus on the overall risk of serious infections,mycobacterial infection and latent viral infections.
文摘Pneumonia and acute respiratory distress syndrome are common and important causes of respiratory failure in the intensive care unit with a significant impact on morbidity, mortality and health care utilization despite early antimicrobial therapy and lung protective mechanical ventilation. Both clinical entities are characterized by acute pulmonary inflammation in response to direct or indirect lung injury. Adjunct anti-inflammatory treatment with corticosteroids is increasingly used, although the evidence for benefit is limited. The treatment decisions are based on radiographic, clinical and physiological variables without regards to inflammatory state. Current evidence suggests a role of biomarkers for the assessment of severity, and distinguishing sub-phenotypes (hyperinflammatory versus hypo-inflammatory) with important prognostic and therapeutic implications. Although many inflammatory biomarkers have been studied the most common and of interest are C-reactive protein, procalcitonin, and pro-inflammatory cytokines including interleukin 6. While extensively studied as prognostic tools (prognostic enrichment), limited data are available for the role of biomarkers in determining appropriate initiation, timing and dosing of adjunct anti-inflammatory treatment (predictive enrichment)
文摘BACKGROUND Osteoarthritis is a chronic degenerative disease with an incidence of 50%in people over 65 years old and 80%in people over 80 years old worldwide.It is the second leading reason of loss of working capacity after cardiovascular diseases and severely affects the society and families.Therefore,finding biological markers related to the diagnosis and treatment of osteoarthritis is of great significance in clinical practice.AIM To observe the changes and clinical value of serum inflammatory factors and miR-145 expression in patients with osteoarthritis before and after treatment.METHODS Eighty-three patients with knee osteoarthritis(observation group)who were admitted to our hospital from April 2013 to June 2015,and 60 healthy people(control group)during the same period were selected.After 4 wk of treatment,the levels of miR-145,tumor necrosis factor(TNF)-α,interleukin(IL)-6,and IL-10 were compared between the control group and the observation group before treatment.The correlation of miR-145,TNF-α,IL-6,and IL-10 levels with visual analogue scale(VAS),Lysholm,and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores was assessed by Pearson correlation analysis.The correlation of the expression of miR-145,TNF-α,IL-6,and IL-10 with Kellgren-Lawrence(K-L)grades was assessed by Spearman correlation analysis.The critical levels of miR-145,TNF-α,IL-6,and IL-10 in distinguishing different K-L grades were determined by receiver operating characteristic(ROC)curve analysis.RESULTS The expression level of miR-145 in the observation group was significantly higher than that in the control group before treatment(P<0.05).After treatment,the expression level of miR-145 in the observation group was significantly lower than that before treatment(P<0.05).The levels of TNF-αand IL-6 in the observation group were significantly higher than those in the control group(P<0.05),and the level of IL-10 was significantly lower than that in the control group(P<0.05).After treatment,the levels of TNF-αand IL-6 in the observation group were significantly lower than those before treatment(P<0.05),and IL-I0 level was significantly higher than that before treatment(P<0.05).VAS and WOMAC scores were both positively correlated with miR-145,TNF-α,and IL-6(P<0.05),and negatively correlated with IL-10(P<0.05),while Lysholm scores were negatively correlated with miR-145,TNF-α,and IL-6(P<0.05),and positively correlated with IL-10(P<0.05).K-L grades were positively correlated with miR-145,TNF-α,and IL-6(P<0.05),and negatively correlated with IL-10(P<0.05).The area under the ROC curve(AUC)and specificity of TNF-αin differentiating K-L grades I-II were the highest,which were 0.785 and 97.45%,respectively,and miR145 had the highest sensitivity of 94.59%;the AUC and sensitivity of IL-6 in differentiating K-L grades II-III were the highest,which were 0.766 and 97.30%,respectively,and TNF-αhad the highest specificity of 86.68%.CONCLUSION MiR-145 and inflammatory factors have certain diagnostic value in osteoarthritis,and they are expected to become potential indicators for the diagnosis and evaluation of osteoarthritis in the future.
文摘Inflammatory bowel disease(IBD)incidence has been increasing steadily,most dramatically in the Western developed countries.Treatment often includes lifelong immunosuppressive therapy and surgery.There is a critical need to reduce the burden of IBD and to discover medical therapies with better efficacy and fewer potential side-effects.Repurposing of treatments originally studied in other diseases with similar pathogenesis is less costly and time intensive than de novo drug discovery.This study used a treatment repurposing methodology,the literature-related discovery and innovation(LRDI)text mining system,to identify potential treatments(developed for non-IBD diseases)with sufficient promise for extrapolation to treatment of IBD.By searching for desirable patterns of twenty key biomarkers relevant to IBD(e.g.,inflammation,reactive oxygen species,autophagy,barrier function),the LRDI-based query retrieved approximately 9500 records from Medline.The most recent 350 records were further analyzed for proof-of-concept.Approximately 18%(64/350)met the criteria for discovery(not previously studied in IBD human or animal models)and relevance for application to IBD treatment.Many of the treatments were compounds derived from herbal remedies,and the majority of treatments were being studied in cancer,diabetes,and central nervous system disease,such as depression and dementia.As further validation of the search strategy,the query identified ten treatments that have just recently begun testing in IBD models in the last three years.Literature-related discovery and innovation text mining contains a unique search strategy with tremendous potential to identify treatments for repurposing.A more comprehensive query with additional key biomarkers would have retrieved many thousands more records,further increasing the yield of IBD treatment repurposing discovery.
文摘Purpose: Based on the National Natural Science Foundation of China, we collect and sort out the literature published in approximately the last 30 years, which use prescriptions in Synopsis of the Golden Chamber to treat pelvic inflammatory disease (PID). This study provides theoretical basis for the treatment of PID;we recommend this achievement to colleagues. Method: Firstly, we searched and collected the literatures from last three decades in CNKI, Wanfang and VIP databases, which are about classical prescriptions treating endometriosis. Then, by screening all the literatures, we obtained the clinical research literatures and individual case reports. Finally, we went through the internal quality of the two categories of literatures to get the dominant prescriptions. Using a retrospective study of evidence-based medicine research, we comprehensively collect literature, standardize the disease spectrum, classify the evidence, and then evaluate the internal quality. Results: We refine 4 prescriptions which commonly are used in the treatment of PID;in other words, they are also the clinical symptoms of PID: Gui Zhi Fu Ling Wan symptom, which manifests blood stasis and cold-damp stagnancy;Dang Gui Shao Yao San symptom, which manifests disharmony of liver and spleen, qi-blood stasis and damp obstruction;Da Huang Mu Dan Tang symptom, which manifests the gathering toxic heat and qi-blood stasis;Yi Yi Fu Zi Bai Jiang San symptom, which manifests the internal toxic heat and qi-blood injury. Conclusion: This study is gospel for the patients with recurrent episodes of PID who can’t often use antibiotics. At the same time, it is also a green therapeutics which Chinese ancients dedicated to human medicine.
基金Fund supported by the National Key R&D Program of China(No.2018YFC2001800)~~。
文摘Objectives To investigate the effects of preoperative smoking and smoking cessation time on preoperative peripheral blood inflammatory indexes and postoperative hospitalization outcomes in male patients with lung cancer and surgery therapy.Methods We retrospectively enrolled 637 male patients who underwent curative-intent lung cancer resection between January 2014 and December 2016.Patients were classified as the current smokers,the never smokers,and the ex-smokers based on their smoking history,and the ex-smokers were allocated into five subgroups according to their smoking cessation times(CeT):CeT W6 weeks,6weeks<CeT W lyear,lyear<CeT<5years,5years<CeT<lOyears,CeT>10years.The preoperative peripheral blood white blood cells(WBCs),albumin,neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),intraoperative blood loss,30-day mortality,in-hospital days,hospitalization costs,intensive care un辻(ICU),admission days and placement time of closed thoracic drainage tube were compared among difTerent groups.Results There were significant differences in WBC(F=S.275,P<0.001)and albumin(F=2,470,P<0.05)among patients of current smokers,ex-smokers with different smoking cessation time,and never-smokers.The blood WBC count in current smokers(7.7 X 109/L)was significantly higher than that in ex・smokers(7.0 X 109/L)and never-smokers(5.9 X 109/L)(t=-2.145,P<0.05;t=-6.073,P<0.01,respectively).The level of peripheral blood albumin in current smokers(41.1 g/L)was lower than that in ex・smokers(42.1 g/L)and neve—smokers(43.2 g/L)(t=2.323,P<0.05;t=3.995,P<0.01,respectively).The level of peripheral blood NLR in current smokers(3.7)was higher than that in ex-smokers(3.1)and never smokers(2.8)(t—-1.836,P<0.05;t=-2.889,P<0.01,respectively).There was no significant difference in WBC,albumin and NLR among five subgroups of different smoking cessation time.No significant difference was observed in intraoperative blood loss,30-day mortality,hospitalization costs,hospital stay,ICU stay and placement time of closed thoracic drainage tube among groups either.Conclusion Smoking increases the preoperative inflammatory indexes in peripheral blood of lung cancer patients.Smoking cessation has beneficial effect on reducing levels of these inflammatory indexes,which may be not impacted by the time length of smoking cessation.Therefore,lung cancer patients should be encouraged to quit smoking at any time.
文摘Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases that often involve organs other than those of the gastrointestinal tract. Immune-related extraintestinal manifestations (EIMs) are usually related to disease activity, but sometimes may take an independent course. Globally, about one third of patients develop these systemic manifestations. Phenotypic classification shows that certain subsets of patients are more susceptible to developing EIMs, which frequently occur simultaneously in the same patient overlapping joints, skin, mouth, and eyes. The clinical spectrum of these manifestations varies from mild transitory to very severe lesions, sometimes more incapacitating than the intestinal disease itself. The great majority of these EIMs accompany the activity of intestinal disease and patients run a higher risk of a severe clinical course. For most of the inflammatory EIMs, the primary therapeutic target remains the bowel. Early aggressive therapy can minimize severe complications and maintenance treatment has the potential to prevent some devastating consequences.
文摘The most common and aggressive type of brain tumor is glioblastoma multiforme (GBM). The prognosis for GBM remains poor with a five-year survival rate between 1% and 2%. The prospects for patients with recurrent GBM (RGBM) are much worse, with the majority dying within 6 months. This publication provides a brief description of the treatment of 11 GBM patients treated with sodium phenylbutyrate (PB) in combination with pazopanib, m-TOR inhibitors, and other agents. The treatment was associated with tolerable side effects and resulted in objective responses in 54.5% of cases (complete response 18.2%, partial response 36.3%) and 27.3% cases of stable disease. The preferable treatment regimen consisted of PB, pazopanib, dasatinib, everolimus, and bevacizumab (BVZ). For various reasons not all patients were compliant with the treatment regimen. In patients who strictly complied with the treatment plan, all responded as CR or PR. Based on preliminary findings, the authors propose further phase I/II clinical trials with PB in combination with pazopanib, dasatinib, everolimus, and BVZ in patients with RGBM who failed standard surgery, radiation therapy and chemotherapy. With proper dose reductions, the treatment appears to be well-tolerated. Molecular profiling of patient subgroups with favorable genomic signatures may help to select patients for future studies.
文摘Despite a decrease in incidence over past decades,gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.
基金Grants from the Medical Faculty, Uppsala University, Uppsala, Sweden
文摘AIM: To evaluate fecal calprotectin (FC) as a surrogate marker of treatment outcome of relapse of inflammatory bowel disease (IBD) and, to compare FC with fecal myeloperoxidase (MPO) and fecal eosinophil protein X (EPX). METHODS: Thirty eight patients with IBD, comprising of 27 with ulcerative colitis (UC) and 11 with Crohn’s disease (CD) were investigated before treatment (inclusion), and after 4 and 8 wk of treatment. Treatment outcomes were evaluated by clinical features of disease activity and endoscopy in UC patients, and disease activity in CD patients. In addition, fecal samples were analyzed for FC by enzyme-linked immunosorbent assay (ELISA), and for MPO and EPX with radioimmunoassay (RIA). RESULTS: At inclusion 37 of 38 (97%) patients had elevated FC levels (> 94.7 μg/g). At the end of the study, 31 of 38 (82%) patients fulfilled predefined criteria of a complete response [UC 21/27 (78%); CD 10/11 (91%)]. Overall, a normalised FC level at the end of the study predicted a complete response in 100% patients, whereas elevated FC level predicted incomplete response in 30%. Normalised MPO or EPX levels predicted a complete response in 100% and90% of the patients, respectively. However, elevated MPO or EPX levels predicted incomplete response in 23% and 22%, respectively. CONCLUSION: A normalised FC level has the potential to be used as a surrogate marker for successful treatment outcome in IBD patients. However, patients with persistent elevation of FC levels need further evaluation. FC and MPO provide superior discrimination than EPX in IBD treatment outcome.
文摘The frequency of diagnosis of inflammatory bowel disease(IBD) has increased in younger populations.For this reason,pregnancy in patients with IBD is a topic of interest,warranting additional focus on disease management during this period.The main objective of this article is to summarize the latest findings and guidelines on the management of potential problems from pregnancy to the breastfeeding stage.Fertility is decreased in patients with active IBD.Disease remission prior to conception will likely decrease the rate of pregnancy-related complications.Most of the drugs used for IBD treatment are safe during both pregnancy and breastfeeding.Two exceptions are methotrexate and thalidomide,which are contraindicated in pregnancy.Antitumor necrosis factor agents are not advised during the third trimester as they exhibit increased transplacental transmission and potentially cause immunosuppression in the fetus.Radiological and endoscopic examinations and surgical interventions should be performed only when absolutely necessary.Surgery increases the fetal mortality rate.The delivery method should be determined with consideration of the disease site and presence of progression or flare up.Treatment planning should be a collaborative effort among the gastroenterologist,obstetrician,colorectal surgeon and patient.
文摘Significant progress has been achieved in the treatment of metastatic colorectal cancer(mCRC)patients during the last 20 years.There are currently numerous treatments available for the first-line treatment of mCRC.Sophisticated molecular technologies have been developed to reveal novel prognostic and predictive biomarkers for CRC.The development of next-generation sequencing and wholeexome sequencing,which are strong new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of customized treatment,has resulted in tremendous breakthroughs in DNA sequencing technology in recent years.The appropriate adjuvant treatments for mCRC patients are determined by the tumor stage,presence of high-risk pathologic characteristics,microsatellite instability status,patient age,and performance status.Chemotherapy,targeted therapy,and immunotherapy are the main systemic treatments for patients with mCRC.Despite the fact that these novel treatment choices have increased overall survival for mCRC,survival remains optimal for individuals with non-metastatic disease.The molecular technologies currently being used to support our ability to practice personalized medicine;the practical aspects of applying molecular biomarkers to regular clinical practice;and the evolution of chemotherapy,targeted therapy,and immunotherapy strategies for the treatment of mCRC in the front-line setting are all reviewed here.
文摘AIM To examine the efficacy and safety of thalidomide and thalidomide analogues in induction and maintenance of remission in patients with inflammatory bowel disease(IBD).METHODS A literature search was performed in the following databases: PubM ed, EMBASE, Web of Science, Ovid and the Cochrane Library, and Chinese databases such as the China National Knowledge Infrastructure, China Science and Technology Journal Database(VIP), Wanfang Data. The randomized controlled analysis was performed to assess the effects of thalidomide therapy on inflammatory bowel disease for patients who did show good response with other therapies. RESULTS Three studies(n = 212) met the inclusion criteria were used in this Meta-analysis. No difference was found between thalidomide/thalidomide analogues and placebo in the induction of remission(RR = 1.36, 95%CI: 0.83-2.22, P = 0.22), the induction of clinical response(RR = 1.14, 95%CI: 0.75-1.72, P = 0.54) and the induction of adverse events(RR = 1.41, 95%CI: 0.99-2.02, P = 0.06).CONCLUSION Currently, there is not enough evidence to support use of thalidomide or its analogue for the treatment in patients of any age with IBD. However, it warrants a reanalysis when more data become available.
