Application of human bone marrow-derived mesenchymal stem cells in the treatment of radiation-induced gastrointestinal syndrome

Nuclear accidents and terrorism present a serious threat for mass casualty.Accidental or intended radiation exposure leads to radiation-induced gastrointestinal(GI)syndrome.However,currently there are no approved medical countermeasures for GI syndrome.Thus,developing novel treatments for GI syndrome is urgent.Mesenchymal stem cells(MSCs)derived from bone marrow are a subset of multipotent adult somatic stem cells that have the ability to undergo self-renewal,proliferation and pluripotent differentiation.MSCs have advantages over other stem cells;they can be easily isolated from patients or donors,readily expanded ex vivo,and they possess reparative and immunomodulatory properties.Moreover,MSCs have been shown to be powerful tools in gene therapy and can be effectively transduced with vectors containing therapeutic genes.Therefore,the therapeutic potential of MSCs has been brought into the spotlight for the clinical treatment of GI syndrome.In this review,we discuss the possible role of MSCs in radiation-induced GI syndrome.

Clinical Observation on Treatment of Post-operative Gastrointestinal Syndrome with Combined Acupuncture and Herbs

Objective： To observe the therapeutic effect of treating postoperative gastrointestinal syndrome with combined needles and herbs. Method： Altogether 117 in-patients were randomly allocated into the treatment group of 86 cases and control group of 31 cases. Point injection was mainly adopted in the treatment group plus Chinese herbal decoction, while Western medicine was adopted in the control group. And then the therapeutic effect of the two groups was compared. Result： The total effective rate of the treatment group and control group were 96.5% and 80.6% respectively, and the treatment course of the treatment group was significantly shorter than the control group （P 〈 0.01）. Conclusion： Combined needles and herbs have excellent effect in treating postoperative gastrointestinal syndrome and were superior to Western medicine.

Structural and functional characteristics of microbiota in oropharynx of sub-healthy children with gastrointestinal heat retention syndrome differentiated by traditional Chinese medicine

Objective:To explore the structural and functional characteristics of microbiota in oropharynx of subhealthy children with gastrointestinal heat retention syndrome(GHRS)differentiated by traditional Chinese medicine,and screen the biometric operational taxonomic units(OTUs)to assist the clinical diagnosis.Methods:We recruited children according to the“GHRS diagnostic scale”,collected their oropharyngeal swabs,and sequenced the 16 SrDNA V4 region.We described the bacterial structure with alpha-indexes,beta-distances,and relative abundances;moreover,we screened the differential genera/OTUs with Wilcoxon rank-sum test,Metagenome Seq analysis,and linear discriminant analysis effect size(LEf Se)analysis,in which biometric OTUs were selected to construct the receiver operating characteristic curve to verify the diagnostic value.The bacterial function was predicted with Kyoto Encyclopedia of Genes and Genomes pathways according to 16S rDNA gene by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.Results:The study population was composed of 10 children with GHRS and 10 healthy control children.GHRS children were more likely to overeat(gluttony,P=.033).Alpha-indexes,such as Sobs,abundancebased coverage estimator,Bootstrap,and Qstat,were significantly higher in the GHRS group,while betadistances did not exhibit any significant intergroup differences.There were 9 differently distributed nonpredominant genera between the groups in Wilcoxon rank-sum test,as well as 13 non-predominant genera in Metagenome Seq analysis and 3 non-predominant OTUs in LEfSe analysis.OTU44 and OTU196 were used to construct the receiver operating characteristic curve,and the area under curve was 0.92.Predicted functions showed that pathways related to oxidative phosphorylation and carbon metabolism were enriched in healthy control samples,while the pathway related to renin secretion was remarkably enriched in GHRS samples.Conclusion:Unique oropharyngeal microbial structure and function were identified in GHRS children.OTU44 and OTU196 were specific OTUs,which could be used as biomarkers of GHRS to assist clinical diagnosis.

Association between gastrointestinal heat retention syndrome and respiratory tract infections in children:A prospective cohort study

Objective:To explore the relationship between gastrointestinal heat retention syndrome and the incidence of pneumonia and recurrent respiratory tract infections(RRTIs)in children.Methods:A prospective cohort study was conducted in the pediatric outpatient department of Beijing Dongfang Hospital.Children without respiratory tract infections(RTIs)were consecutively recruited according to the selection criteria.A semi-structured questionnaire was used to record traditional Chinese medicine(TCM)symptoms and demographic and physiological characteristics.Gastrointestinal heat retention syndrome was considered to be a predisposing factor and was diagnosed according to a scale with reliability and validity.The participants were followed up for 12 months.Participants and their parents or guardians were contacted via clinical interviews and telephone every 6 months.Episodes of pneumonia and RTIs were recorded in detail.Results:A total of 420 children were included.Of participants,370(88.10%)were followed up for 12 months.The mean number of RTI episodes per participant was 5.37(95%CI:5.14 to 5.60).In total,186 participants in the gastrointestinal heat retention syndrome group and 184 participants in the nongastrointestinal heat retention syndrome group completed the 12-month follow-up period.The baseline of both groups was comparable.The incidence of RRTIs in children with gastrointestinal heat retention syndrome was 1.27(95%CI:1.01 to 1.59)times that in children without gastrointestinal heat retention syndrome.Logistic regression analysis revealed that abnormally increased appetite with frequent hunger,foul breath,dry stools,and dark red or purple fingerprints were positively correlated with the incidence of pneumonia.Irascibility and feverish feelings in the palms and soles were positively correlated with the occurrence of RRTI.Conclusions:Gastrointestinal heat retention syndrome is a risk factor for RRTIs in children.Studies with larger sample sizes and longer follow-up time are warranted to confirm the degree of causal risk associated with RTIs.

Exploring the association between gastrointestinal heat retention syndrome and adult chronic eczema: A caseecontrol study

Objective:To investigate the association between gastrointestinal heat retention syndrome(GHRS)and adult chronic eczema.Methods:This caseecontrol study compared GHRS/GHRS accompanied by damp-heat syndrome(GHRSDHS)and other patient characteristics between subjects with(cases)and without chronic eczema(controls)to identify potential factors associated with this condition.Semi-structured questionnaires were used to collect data via face-to-face interviews.Participants were recruited from Dongzhimen Hospital affiliated with Beijing University of Chinese Medicine.A logistic regression analysis was performed on the collected data,and odds ratios(ORs)were calculated.Results:A total of 168 cases and 172 controls were recruited.Among the cases of adult chronic eczema,there were 79 subjects with GHRS and 68 with GHRS-DHS.Sex(P=.02,OR=0.54,95%confidence interval[CI]:0.32-0.91),GHRS(P=.04,OR=1.90,95%CI:1.02-3.51),GHRS-DHS(P<.001,OR=4.89,95%CI:2.36-10.15),high sweet food consumption(P=.04,OR=2.03,95%CI:1.03-3.97),and mental stress(P=.01,OR=2.37,95%CI:1.26-4.47)were each found to be associated with chronic eczema.Furthermore,GHRS had a weak positive correlation with eczema EASI severity as measured by the eczema area and severity index(EASI)(P=003).Conclusion:GHRS/GHRS-DHS may be associated with adult chronic eczema.In the future,prospective cohort studies with larger samples should be conducted to investigate the cause and effect association between GHRS and adult chronic eczema.

Effect of gastrointestinal heat retention syndrome on gut microbiota in children with upper respiratory tract infection and lung-heat syndrome

Objective:Gastrointestinal heat retention syndrome(GHRS)is associated with lung-heat syndrome and is related to recurrent respiratory infection.Upper respiratory tract infection(URTI)lung heat syndrome is common in children.The study will explore the effect of GHRS on the structure and function of gut microbiota in children with URTI lung-heat syndrome.Methods:Participants were divided into both groups using the self-developed URTI scale and the“GHRS Diagnostic Scale$Pediatric Part”:GHRS-positive children(LS group)and GHRS-negative children(L group).General information,clinical symptoms,and stool were collected.We used 16S rRNA amplicon sequencing technology to determine the gene sequence of the V3eV4 region in feces and measure the gut microbiota of the both groups at the genus level.Results:A total of 23 children were included in the both groups.There were 12 cases in the LS group and 11 cases in the L group.There was no statistical difference between the both groups in age,gender,height,weight,and body mass index.The effective sequences shared by the both groups accounted for 85.66%of the total.In the gut microbiota,there was no difference in the a diversity and the b diversity between the both groups.Compared with the L group,the LS group had a significant increase in the relative abundance of the Ruminococcus gnavus group,Prevotella-9,Staphylococcus,and Actinomyces(P<.05).The functions of the both groups of microbiota primarily concentrate on metabolism,genetic information processing,and environmental information processing.The relative abundance of signaling molecules and interactions in the LS group were higher than that in the L group(P<.05).The redundancy analysis(RDA)showed that the URTI score had the greatest impact on the distribution of microbiota.Conclusion:GHRS may affect the development of URTI lung-heat syndrome by changing the relative abundances of gut microbiota.

Mesenchymal stem cell therapy for acute radiation syndrome: Innovative medical approaches in military medicine

After a radiological or nuclear event, acute radiation syndrome(ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on limited clinical data and remains inadequate. Efforts to develop medical innovations that address ARS complications are unlikely to be generated by the industry because of market uncertainties specific to this type of injury. A prospective strategy could be the integration of cellular therapy to meet the medical demands of ARS. The most clinically advanced cellular therapy to date is the administration of mesenchymal stem cells(MSCs). Results of currently published investigations describing MSC safety and efficacy in a variety of injury and disease models demonstrate the unique qualities of this reparative cell population in adapting to the specific requirements of the damaged tissue in which the cells integrate. This report puts forward a rationale for the further evaluation of MSC therapy to address the current unmet medical needs of ARS. We propose that the exploration of this novel therapy for the treatment of the multivariate complications of ARS could be of invaluable benefit to military medicine.

Mesenchymal stem cell therapy for acute radiation syndrome

Acute radiation syndrome affects military personnel and civilians following the uncontrolled dispersal of radiation,such as that caused by detonation of nuclear devices and inappropriate medical treatments.Therefore,there is a growing need for medical interventions that facilitate the improved recovery of victims and patients.One promising approach may be cell therapy,which,when appropriately implemented,may facilitate recovery from whole body injuries.This editorial highlights the current knowledge regarding the use of mesenchymal stem cells for the treatment of acute radiation syndrome,the benefits and limitations of which are under investigation.Establishing successful therapies for acute radiation syndrome may require using such a therapeutic approach in addition to conventional approaches.

Association between gastrointestinal symptoms and affectivity in patients with bipolar disorder

AIM To study if anxiety, depression and experience of stress are associated with gastrointestinal(GI) symptoms in patients with bipolar disorder.METHODS A total of 136 patients with bipolar disorder(mean age 49.9 years; 61% women) and 136 controls from the general population(mean age 51.0 years; 60% women) were included in the study. GI symptoms were assessed with The Gastrointestinal Symptom Rating Scale-irritable bowel syndrome(GSRS-IBS), level of anxiety and depression with The Hospital Anxiety and Depression Scale(HADS) and stress-proneness with Perceived Stress Questionnaire. Over a ten year period, all visits in primary care were retrospectively recorded in order to identify functional GI disorders.RESULTS In subjects with low total HADS-score, there were no significant differences in GI-symptoms between patients and controls(GSRS-IBS 7.0 vs 6.5, P = 0.513). In the patients with bipolar disorder there were significant correlations between all GSRS and HADS subscores for all symptom clusters except for "constipation" and "reflux". Factors associated to GI symptoms in the patient group were female sex(adjusted OR = 2.37, 95%CI: 1.07-5.24) and high HADS-Depression score(adjusted OR = 3.64, 95%CI: 1.07-12.4). These patients had also significantly more visits for IBS than patients with low HADS-Depression scores(29% vs 8%, P = 0.008). However, there was no significant differences in consulting behaviour for functional GI disorders between patients and controls(25% vs 17%, P = 0.108).CONCLUSION Female patients and patients with high HADS depression score reported significantly more GI symptoms, whereas patients with low HADS scores did not differ from control subjects.

Wireless capsule endoscopy

Wireless capsule endoscopy is a new technique that allows complete exploration of the small bowel without exlemal wires. Its role has been analyzed in many small bowel diseases such as obscure gastrointestinal bleeding, Crohn＇s disease and gastrointestinal polyposis syndromes with promising results. Studies on other pathologies （i.e. small bowel tumour, celiac disease） are under evaluation to define the role of this technique.

Clopidogrel and proton pump inhibitors-where do we stand in 2012?

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.