Effects of commercially produced almond by-products on chemotherapy-induced mucositis in rats

AIM To determine if almond extracts reduce the severity of chemotherapy-induced mucositis as determined through biochemical,histological and behavioural markers.METHODS Intestinal mucositis is a debilitating condition characterized by inflammation and ulceration of the gastrointestinal mucosa experienced by cancer patients undergoing chemotherapy.Certain bioactive plant products have shown promise in accelerating mucosal repair and alleviating clinical symptoms.This study evaluated almond extracts for their potential to reduce the severity of chemotherapy-induced mucositis in Dark Agouti rats.Female Dark Agouti rats were gavaged(days 3-11) with either PBS,almond hull or almond blanched water extract at two doses,and were injected intraperitoneally with 5-fluorouracil(5-FU-150 mg/kg) or saline on day 9 to induce mucositis.Burrowing behavior,histological parameters and myeloperoxidase activity were assessed.RESULTS Bodyweight was significantly reduced in rats that received 5-FU compared to saline-treated controls(P < 0.05).Rats administered 5-FU significantly increased jejunal and ileal MPO levels(1048%; P < 0.001 and 409%; P < 0.001),compared to healthy controls.Almond hull extract caused a pro-inflammatory response in rats with mucositis as evidenced by increased myeloperoxidase activity in the jejunum when compared to 5-FU alone(rise 50%,1088 ± 96 U/g vs 723 ± 135 U/g,P = 0.02).Other extractrelated effects on inflammatory activity were minimal.5-FU significantly increased histological severity score compared to healthy controls confirming the presence of mucositis(median of 9.75 vs 0; P < 0.001).The extracts had no ameliorating effect on histological severity score in the jejunum or ileum.Burrowing behavior was significantly reduced in all chemotherapy-treated groups(P = 0.001).The extracts failed to normalize burrowing activity to baseline levels.CONCLUSION Almond extracts at these dosages offer little beneficial effect on mucositis severity.Burrowing provides a novel measure of affective state in studies of chemotherapyinduced mucositis.

Therapeutic potential of the citrus flavonoid hesperidin and its aglycone hesperetin against chemotherapy-induced toxicity

Chemotherapy-induced toxicity(CIT)remains a major concern in cancer patients undergoing chemotherapy.New approaches to ameliorate the side effects of chemotherapy are urgently needed.Recently,the nutritional value of citrus fruits has attracted wide attention.Hesperidin and its aglycone hesperetin are the main active components in citrus fruits.Hesperidin and hesperetin have a wide range of pharmacological activities,including antioxidant and anti-inflammatory properties.This review aims to provide insights into the potential application of citrus flavonoids in CIT and summarize the underlying mechanisms of hesperidin and hesperetin in alleviating CIT.We have collected and collated relevant scientific articles on hesperidin and hesperetin and their treatment of CIT from different scientific databases.Hesperidin and its glycosides can reduce the toxicity of chemotherapeutic drugs,and their therapeutic effects are mainly through anti-inflammatory and antioxidant effects.At present,modern medical treatment is the main treatment method for CIT,but hesperidin,as an extract of food and medicinal materials,can greatly alleviate CIT.While killing tumor cells,chemotherapeutic drugs also damage normal cells leading to toxic effect on various organs.The pathological mechanism of CIT has not been fully elucidated,but current evidences indicate that cellular stress plays a key role.The citrus flavonoids hesperidin and hesperetin have the protective effect against CIT,highlighting its potential as an adjuvant in chemotherapy regimens.Hesperidin may also have synergistic anti-tumor activity with chemotherapeutic agents.We believe that more functional foods and anti-CIT drugs based on natural foods will be developed.

Modified Pulsatilla decoction alleviates 5-fluorouracil-induced intestinal mucositis by modulating the TLR4/MyD88/NF-κB pathway and gut microbiota

BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.

Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

AIM To investigate the effects of orally gavaged aqueous rhubarb extract(RE) on 5-fluorouracil(5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats(n = 8/group) were gavaged daily(1 mL) with water, high-dose RE(HDR; 200 mg/kg) or low-dose RE(LDR; 20mg/kg) for eight days. Intestinal mucositis was induced(day 5) with 5-FU(150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase(MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA. RESULTS B o d y w e i g h t w a s s i g n i f i c a n t l y r e d u c e d i n r a t s administered 5-FU compared to healthy controls(P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels(≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity(by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness(by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats(19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis.CONCLUSION In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal inflammation, manifesting from 5-FU-induced intestinal mucositis.

Research progress and comparison of the establishment of animal models of radiotherapy or chemotherapy-induced oral mucositis

The mechanism of radiotherapy or chemotherapy-induced oral mucositis is not yet clear.And model establishment is needed in further study.In order to summarize the methods of model establishment and make a comparison,literature databases including Web of Science、Pubmed and CNKI were searched for related researches from January 2015 to January 2021.Hamsters,mice,rats,guinea pigs and miniature pigs were chosen to be modeling animals and modeling methods could be classified into:chemotherapy,chemotherapy combined with superficial mucosal irritation,radiotherapy,radiotherapy combined with superficial mucosal irritation and chemoradiotherapy.Advantages and disadvantages had been analyzed in this study to provide reference for following studies.

Glycine supplementation reduces the severity of chemotherapy-induced oral mucositis in hamsters

Objective: Oral mucositis (OM) is a devastating toxicity associated with cytotoxic cancer therapy. The OM pathogenesis and the complex interactions occur in response to tissue insult. Application of this evolving model has aided in the development of mechanistically based therapies for the prevention and treatment of mucositis. The present study was to assess the effects of glycine supplementation on chemotherapy-induced oral mucositis. Methods: In a hamster cheek pouch model of chemotherapy-induced oral mucositis, one group of 20 animals received systemic glycine supplementation for 7 days, while another similar control group did not. Clinical mucositis severity and neutrophil infiltrate (on histology) were assessed by blinded examiners. Free radical production was measured as malondialdehyde (MDA) levels. Results: As compared to control animals, glycine-treated animals demonstrated a highly significant reduction in clinical severity of oral mucositis, neutrophil infiltrate, and MDA levels (p < 0.001 for all). Conclusions: Glycine supplementation reduces the severity of chemotherapy-induced oral mucositis in an animal model. This effect is at least partly mediated through inhibition of the inflammatory response and reduced production of damaging free radicals.

Liu-Jun-Zi decoction alleviates chemotherapy-induced anorexia by regulating gut microbiota and TLR4/MyD88/NF-κB p65 signaling pathway

Background:Liu-Jun-Zi decoction(LJZD),a classical nourishing formula in China,has been proven to be effective in treating chemotherapy-induced anorexia.In this study,the mechanism of LJZD in alleviating chemotherapy-induced anorexia was discussed from the aspects of regulating gut microbiota,repairing intestinal barrier injury and inhibiting inflammatory pathways.Methods:A rat model of chemotherapy-induced anorexia was established using cisplatin.The study evaluated the therapeutic effects of LJZD by observing the weight,food intake,and intestinal pathology of rats.The impact of LJZD on gut microbiota and metabolites,specifically short-chain fatty acids,was investigated through gut microbiota analysis and targeted metabolomics.The anti-inflammatory and intestinal protective effects of LJZD were assessed by examining the expression of intestinal tight junction proteins associated with the inflammatory pathway.Results:LJZD alleviated cisplatin-induced inflammation and intestinal barrier disruption,as evidenced by upregulated expression of tight junction protein 1(TJ-1)and occludin,along with reduced serum levels of interleukin 6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and lipopolysaccharide.Additionally,LJZD alleviated microbiota imbalance and regulated the levels of short-chain fatty acids,especially increased the relative abundance of Coriobacteriales Incertae Sedis,Lactabacillus johnsonii F19785,Parasutterella,and reduced the Tyzzerella.In the hypothalamus,LJZD exerts suppressive effects on the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)p65 signaling pathway,leading to a downregulation in the transcriptional activity of IL-6 and IL-1β,as well as Interleukin 6 receptors(IL-6R)and Interleukin-1βreceptors(IL-1R1)mRNA expression levels.Conclusion:In summary,LJZD alleviate chemotherapy-induced anorexia by modulating the gut microbiota,repairing the intestinal mechanical barriers,and suppressing the TLR4/MyD88/NF-κB p65 signaling pathway.

Guicao Baidu decoction in mitigating chemotherapy-induced myocardial injury:case report and mechanism investigation

To observe the effects of GuiCaoBaiDu Decoction(GCBD)on chemotherapy especially doxorubicin(DOX)-induced myocardial cardiotoxicity(DIC)and explore the mechanisms.The present study presents a case demonstrating the preventive and therapeutic effects of GCBD on myocardial injury following chemotherapy.Then network pharmacology was employed to predict the targets of GCBD.Subsequently,a DOX-induced apoptosis model of H9C2 cardiomyocytes was established and co-cultured with serum containing GCBD serum.The viability and myocardial enzyme levels were evaluated using CCK8 assay and ELISA assay,TUNEL was using for apoptosis test.The GCBD effect was confirmed by tests of ROS andα-actinin levels,evaluation of mitochondrial morphology,and BAX co-localization with mitochondria.Furthermore,the expression levels of apoptosis-related molecules were determined via Western blotting.Additionally,a mouse model exhibiting DOX-induced cardiac functional impairment was generated and subsequently treated with GCBD.Myocardial enzyme level was tested at first,then echocardiography was tested,myocardial apoptosis in mice was observed through HE staining while related proteins were detected using IHC.Network pharmacological analyses revealed that GCBD exerts its effects on BAX,Caspase7,and other related molecules.Initially,we demonstrated the effective amelioration of DIC in cardiomyocyte viability,LDH/CK levels,α-actinin and ROS levels,and apoptosis by GCBD through improvements in TUNEL test,mitochondrial morphology and WB.The efficacy of GCBD in enhancing cardiac function in DIC mice has been validated through animal experiments.Taken together,our study showed that GCBD could significantly alleviate DOX induced myocardial injury by regulating mitochondrial apoptosis.The utilization of GCBD can effectively contribute to the prevention and treatment of chemotherapy-induced myocardial injury when anthracycline chemotherapy is employed in clinical practice.

Computed tomography enterography-based radiomics for assessing mucosal healing in patients with small bowel Crohn's disease

BACKGROUND Mucosal healing(MH)is the major therapeutic target for Crohn's disease(CD).As the most commonly involved intestinal segment,small bowel(SB)assessment is crucial for CD patients.Yet,it poses a significant challenge due to its limited accessibility through conventional endoscopic methods.AIM To establish a noninvasive radiomic model based on computed tomography enterography(CTE)for MH assessment in SBCD patients.METHODS Seventy-three patients diagnosed with SBCD were included and divided into a training cohort(n=55)and a test cohort(n=18).Radiomic features were obtained from CTE images to establish a radiomic model.Patient demographics were analysed to establish a clinical model.A radiomic-clinical nomogram was constructed by combining significant clinical and radiomic features.The diagnostic efficacy and clinical benefit were evaluated via receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA),respectively.RESULTS Of the 73 patients enrolled,25 patients achieved MH.The radiomic-clinical nomogram had an area under the ROC curve of 0.961(95%confidence interval:0.886-1.000)in the training cohort and 0.958(0.877-1.000)in the test cohort and provided superior clinical benefit to either the clinical or radiomic models alone,as demonstrated by DCA.CONCLUSION These results indicate that the CTE-based radiomic-clinical nomogram is a promising imaging biomarker for MH and serves as a potential noninvasive alternative to enteroscopy for MH assessment in SBCD patients.

Early esophageal cancer with mucosal bridging in the resting room: A case report

BACKGROUND Patients diagnosed with esophageal mucosal bridges often experience symptoms such as chest pain and dysphagia,which pose considerable challenges for endo-scopic surgical interventions.CASE SUMMARY We present a case involving early-stage esophageal cancer discovered in a resting room,notable for the rare manifestation of esophageal mucosal bridging.Following a comprehensive multidisciplinary discussion and the development of a treatment strategy,we proceeded with endoscopic submucosal dissection for the patient.During the procedure,we encountered operational challenges due to the presence of a diverticulum and a partial absence of the muscularis propria.To facilitate the retraction of a portion of the resected specimen,we utilized dental floss.Ultimately,we successfully excised the entire lesion.After a three-day period of fasting with a water-only diet,subsequent iodine water cholan-giography did not indicate any perforations,and the patient was advised to transition to a liquid diet.The patient was discharged five days post-operation.A follow-up endoscopy conducted three months later revealed scar-like changes in the mid-esophagus,with the patient reporting no significant discomfort.CONCLUSION In summary,although esophageal mucosal bridges are rarely documented,they should be considered in the differential diagnosis of mechanical dysphagia.Furthermore,endoscopic therapy represents a feasible approach for their mana-gement.

Role of duodenal mucosal resurfacing in controlling diabetes in rats

BACKGROUND The duodenum plays a significant role in metabolic regulation,and thickened mucous membranes are associated with insulin resistance.Duodenal mucosal resurfacing(DMR),a new-style endoscopic procedure using hydrothermal energy to ablate this thickened layer,shows promise for enhancing glucose and lipid metabolism in type 2 diabetes(T2D)patients.However,the mechanisms driving these improvements remain largely unexplored.AIM To investigate the mechanisms by which DMR improves metabolic disorders using a rat model.METHODS Rats with T2D underwent a revised DMR procedure via a gastric incision using a specialized catheter to abrade the duodenal mucosa.The duodenum was evaluated using histology,immunofluorescence,and western blotting.Serum assays measured glucose,lipid profiles,lipopolysaccharide,and intestinal hormones,while the gut microbiota and metabolomics profiles were analyzed through 16S rRNA gene sequencing and ultra performance liquid chromatography-mass spectrum/mass spectrum,severally.RESULTS DMR significantly improved glucose and lipid metabolic disorders in T2D rats.It increased the serum levels of cholecystokinin,gastric inhibitory peptide,and glucagon-like peptide 1,and reduced the length and depth of duodenal villi and crypts.DMR also enhanced the intestinal barrier integrity and reduced lipopolysaccharide translocation.Additionally,DMR modified the gut microbiome and metabolome,particularly affecting the Blautia genus.Correlation analysis revealed significant links between the gut microbiota,metabolites,and T2D phenotypes.CONCLUSION This study illustrates that DMR addresses metabolic dysfunctions in T2D through multifaceted mechanisms,highlighting the potential role of the Blautia genus on T2D pathogenesis and DMR’s therapeutic impact.

Efficacy-cost analysis of endoscopic mucosal resection and cold snare polypectomy:A propensity score matching analysis

BACKGROUND Although substantial evidence supports the advantages of cold snare polypectomy(CSP)in terms of polypectomy efficacy and reduced postoperative adverse events,few studies have examined the cost differences between CSP and traditional endoscopic mucosal resection(EMR)for the treatment of intestinal polyps.AIM To compare the efficacy-cost of EMR and CSP in the treatment of intestinal polyps.METHODS A total of 100 patients with intestinal polyps were included in the retrospective data of our hospital from April 2022 to May 2023.According to the treatment methods,they were divided into EMR(n=46)group and CSP(n=54)group.The baseline data of the two groups were balanced by 1:1 propensity score matching(PSM),and the cost-effectiveness analysis was performed on the two groups after matching.The recurrence rate of the two groups of patients was followed up for 1 year,and they were divided into recurrence group and non-recurrence group according to whether they recurred.Multivariate logistic regression analysis was used to screen out the influencing factors affecting the recurrence of intestinal polyps after endoscopic resection.RESULTS Significant disparities were observed in the number of polyps and smoking background between the two groups before PSM(P<0.05).Following PSM,the number of polyps and smoking history were well balanced between the EMR and CSP groups.The direct cost incurred by the CSP group was markedly higher than that incurred by the EMR group.Concurrently,the cost-effectiveness ratio in the CSP group was substantially reduced when juxtaposed with that in the EMR group(P<0.05).Upon completion of the 1-year follow-up,the rate of recurrence after endoscopic intestinal polypectomy was 38.00%.Multivariate methods revealed that age≥60 years,male sex,number of polyps≥3,and pathological type of adenoma were risk factors for recurrence after endoscopic intestinal polypectomy(all P<0.05).CONCLUSION CSP was more cost-effective for the treatment of intestinal polyps.An age≥60 years,male sex,having a number of polyps≥3,and pathological type of adenoma are independent influencing factors for recurrence.

Relationship between gastric mucosal atrophy by endoscopy and non-ampullary duodenal epithelial tumors

BACKGROUND The pathogenesis of non-ampullary duodenal epithelial tumors(NADETs)is not fully understood.NADETs that express gastric-type mucin phenotypes(GNADETs)are noteworthy because of their high malignancy.Gastric foveolar metaplasia,from which G-NADETs originate,protects the duodenal mucosa from gastric acidity.As gastric acid secretion is affected by endoscopic gastric mucosal atrophy(EGMA),we hypothesized that EGMA would be associated with GNADETs.AIM To evaluate the association between EGMA and the occurrence of G-NADETs.METHODS This cross-sectional retrospective study investigated the relationship between EGMA and NADETs in 134 patients.The duodenum was divided into parts 1(bulb),2(superior duodenal angle to the papilla),and 3(anal side of the papilla to the horizontal part).The effects of gastric acidity and presence of Brunner’s glands were considered.EGMA was divided into types C(no or mild atrophy)and O(severe atrophy).Mucin phenotype expressions in NADETs were divided into gastric,intestinal,gastrointestinal,and unclassifiable.RESULTS When NADETs were classified according to EGMA,105 were classified as type C and 29 as type O.G-NADETs were present in 11.9%(16 cases)of all cases,and all 16 cases were of type C.Among G-NADETs,93.8%(15 cases)were present in part 1 or 2.There was an association between G-NADETs and type C in part 1,and 50.0%(eight of 16 cases)of G-NADETs were associated with a current or previous Helicobacter pylori infection status.Additionally,all eight cases occurred in part 1.CONCLUSION G-NADETs were significantly associated with type C.Gastric acidity and Brunner's gland growth may be associated with G-NADETs.

Effect of Modulen vs budesonide on clinical response and mucosal healing in Crohn’s patients

BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD.However,their effects on the small bowel(SB)mucosa remain underexplored.AIM To prospectively assess clinical and mucosal responses to Modulen vs budesonide in adults with CD,using SB capsule endoscopy.METHODS Thirty patients were divided into two groups:Modulen+home-based diet(21 patients)and budesonide(9 patients)for an eight-week intervention followed by four weeks of follow-up.Clinical,laboratory,and endoscopic responses were evaluated.The mucosal changes were assessed through SB capsule endoscopy.RESULTS Results indicated significant clinical improvement in the Modulen group with reduced CD activity index(P=0.041)and improved inflammatory bowel disease questionnaire score(P=0.016).Moreover,Modulen was associated with a signifi-cant SB mucosal improvement,evidenced by a decrease in Lewis score(P=0.027).No significant changes were observed in calprotectin or other laboratory parame-ters.Conversely,budesonide exhibited more modest clinical effects,but it improved calprotectin,hemoglobin,and C-reactive protein levels(P=0.051,P=0.014,and P=0.038,respectively).The capsule endoscopy did not reveal a significant mucosal response in the budesonide group.CONCLUSION Both interventions have a role in CD treatment.Yet,their effects differ and may complement each other:Modulen yields clinical and mucosal improvements,while budesonide primarily leads mainly to laboratory improvements.

Patterns of antiemetic prophylaxis for chemotherapy-induced nausea and vomiting in China

Background： Few studies have attempted to evaluate the use of antiemetic therapy for chemotherapyinduced nausea and vomiting （CINV） at a national level in China or to assess how treatment regimens adhere to current guidelines. Methods： We searched the China Health Insurance Research Association （CHIRA） Database to identify patients with cancer who were 〉 18 years old and received either moderately or highly emetogenie chemotherapy （MEC and HEC, respectively） between 2008 and 2012. Patients＇ characteristics as well as usage of specific antiemetic regimens were analyzed using descriptive statistics. Results： Of the 14,548 patients included in the study, 6,477 received HEC while 8,071 were treated with MEC. Approximately 89.9% used antiemetics prophylactically to prevent acute CINV and 71.5% for delayed CINV while 9.0% were prescribed antiemetics as rescue therapy. A significantly lower proportion of patients treated with HEC received prophylactic antiemetic therapy for delayed CINV as compared to those treated with MEC （59.4% vs. 81.3 %; P〈0.001）. The HEC group had a slightly lower proportion of patients using a mixed regimen containing a 5-HT3 antagonist to prevent both acute and delayed CINV than the MEC group （P〈0.012）; however, a higher proportion received a mixed regimen containing eorticosteroids （P≤0.007）. Although more than half of the patients in the HEC group took three antiemeties to prevent acute and delayed CINV, these rates were significantly lower than those of the MEC group （both P〈0.001）. Finally, analysis of the regimens used revealed that there is over-utilization of drugs within the same class of antiemetic. Conclusions： These findings indicate that more attention is needed for treatment of delayed CINV, in terms of both overall use and the components of a typical treatment regimen.

Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia: a case–control study

The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition （P=0.002）, duration of mucositis （P= 0.003） and the average grade of mucositis （P= 0.03）. The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering： from leukaemia.

Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation

BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation,restoring the mucosal barrier,and regulating gut microbiota.

Current management of chemotherapy-induced neutropenia in adults:key points and new challenges

Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.

Anti-Colorectal Cancer Chemotherapy-Induced Diarrhoea: Current Treatments and Side-Effects

Chemotherapy-induced diarrhoea (CID) is a common side-effect experienced by patients being treated with a variety of antineoplastic agents. Approximately 80% of patients undergoing chemotherapeutic treatment for colorectal and other gastrointestinal cancers present with CID;moreover, about 5% of early deaths associated with combination anti-cancer chemotherapy are due to CID. Chronic post-treatment diarrhoea amongst cancer survivors can persist for more than 10 years greatly effecting long-term quality of life. Gastrointestinal toxicities such as diarrhoea and vomiting are amongst the primary contributors to dose reductions and delays throughout anti-cancer treatment, presenting a significant hurdle in clinical management of anti-cancer regimes and often result in sub-optimum treatment. However, little is known about pathophysiological mechanisms underlying CID. This work provides a review of chemotherapy-induced diarrhoea, current management guidelines, and shortcomings of current treatments as well as emerging and already existing anti-diarrhoeal treatments potentially suitable for CID.

Chemotherapy-induced neurotoxicity in the treatment of gynecological cancers:State of art and an innovative approach for prevention

Chemotherapy-induced peripheral neuropathy(CIPN)is a common side effect that occurs in 20%of ovarian cancer patients treated with the combination of carboplatin/paclitaxel(CP).This toxicity is directly correlated with the dose of paclitaxel administered.Several studies have investigated whether different formulations of taxane can induce this side effect at a lower rate,but,unfortunately,no significant improvement was obtained.CIPN can be disabling in the daily lives of patients and can cause dose reduction or early termination of the treatment.Neuropathy can last for months and even years after its onset.Moreover,patients responsive to CP treatment are candidates for a reintroduction of the same drugs when disease relapse occurs,and residual neuropathy can affect the continuation of treatment.There are no approved drugs that mitigate or prevent the onset of CIPN.In this review,we summarize the evidence regarding the incidence of CIPN with different taxane formulations,regimen schedules and prevention systems.In particular,the Hilotherm®Chemo care device is a regional cooling system that lowers the temperature of the hands and feet to reduce the flow of chemotherapy into the capillaries.We used hilotherapy during chemotherapy infusion to prevent the onset of CIPN.Updated data from 44 ovarian cancer patients treated with 6 cycle of CP show that hilotherapy was well tolerated;only two patients(4.5%)stopped hilotherapy because of cold intolerance,and only one patient(2.2%)experienced grade≥2 CIPN.