Effects of Kangfuxin Solution (康复新液) Combined with Low-level Laser on Cytokines and Immune Function in Patients with Radiation-induced Oral Mucositis

Objective:To investigate the effect of Kangfuxin Solution(康复新液)combined with low-level laser therapy(LLLT)on cytokines and immune function in patients with radiation-induced oral mucositis.Methods:There were 84 nasopharyngeal carcinoma patients with oral mucositis after intensity-modulated radiation therapy(IMRT)were randomly divided into the control group(CG)and the observation group(OG),with 42 cases in each group.The CG was given LLLT,and the OG was treated with Kangfuxin Solution in addition to LLLT for 10 consecutive days.The healing time of oral mucosa,mucositis grading,oral pain scores,cytokines(interleukin-6,interleukin-1βand tumor necrosis factor-α)and T lymphocyte subsets were compared between the 2 groups before and after treatment.Results:The healing time of oral mucosa in the OG was(6.8±1.4)d,which was significantly shorter than(8.6±1.9)d in the CG(t=4.943,P<0.01).After treatment,the grading of oral mucositis in the OG was better than that in the CG,with a statistically significant difference(Z=2.942,P<0.05).The oral pain scores of the OG was lower than that in the CG at different time points after treatment,and the difference was statistically significant(t=8.207,11.017,P<0.01).After treatment,the levels of IL-6,IL-1βand TNF-αin peripheral blood of the OG were significantly lower than those in the CG(t=5.217,2.775,4.053,P<0.01).There were statistically significant differences in CD4+,CD8+and CD4+/CD8+between the OG and the CG after treatment(t=5.692,6.093,3.658,P<0.01).Conclusion:Kangfuxin Solution combined with LLLT can significantly shorten the healing time of oral mucosal,reduce the grading of oral mucositis,relieve oral pain,reduce inflammatory response and improve the immune function of patients.

Association between the nutritional status and radiation pharyngeal mucositis in patients with head and neck cancer during radiotherapy:A longitudinal study

Objective Radiation mucositis,especially pharyngeal mucositis,severely affects the oral intake of patients of head and neck cancer(HNC)during radiotherapy.Whether the nutritional status affects the severity of pharyngeal mucositis is currently unknown.This study investigated the incidence of malnutrition and radiation pharyngeal mucositis in patients with HNC during radiotherapy and analyzed the impact of the nutritional status on radiation pharyngeal mucositis.Methods Consecutive patients with HNC receiving radiotherapy were recruited for this longitudinal observational study.Data were collected at baseline(T_(1)),midtreatment(T_(2)),and at the end of treatment(T3).The Common Terminology Criteria for Adverse Events version 4.0 and the Global Leadership Initiative on Malnutrition criteria were used to assess pharyngeal mucositis and the nutritional status,respectively.Results There were 348 HNC patients who completed all assessments.The pharyngeal mucositis of patients with HNC was aggravated during radiotherapy(χ^(2)=553.521,P<0.001).At T3,56.0%of patients had moderate or severe pharyngeal mucositis.The proportion of patients with malnutrition increased significantly during treatment(21.3%at T_(1)vs 46.8%at T_(2)vs 76.1%at T3,χ^(2)=209.768,P<0.001).Both a multivariable analysis of generalized estimating equations and a logistic regression analysis showed that pharyngeal mucositis was associated with malnutrition.Conclusions Malnutrition was common in patients with HNC during radiotherapy,and it was closely related to pharyngeal mucositis.Joint interventions targeting nutrition and symptom management should be considered for patients with HNC.

A Review of Radiation-Induced Oral Mucositis in Traditional Chinese and Western Medicine Research

Radiation therapy is one of the main treatments for head and neck tumors,and radiationinduced oral mucositis(RIOM)is a common serious adverse effect of radiation therapy.We summarized the pathogenesis,prevention and treatment methods of RIOM related to traditional Chinese and Western medicine in recent years.The treatment of RIOM in traditional Chinese medicine should be based on clearing heat and detoxifying,nourishing Yin and promoting fluid,tonifying spleen and stomach,cooling blood and removing blood stasis.Osteopontin,immunoglobulin A and saliva flow tests may be effective clinical indicators in the future.Through analysis,the author believes that the use of integrated intervention of traditional Chinese and western medicine can better benefit patients,and the prevention and predictive diagnostic tools of RIOM should become the future focus of attention.

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.

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.

Management of pembrolizumab-induced steroid refractory mucositis with infliximab:A case report

BACKGROUND Pembrolizumab is an anti-programmed death receptor 1(PD-1)that was shown to have a tolerable safety profile with 17%of grade 3-4 drug-related adverse events,notable response rate of 16%with median duration of response of 8 mo,and median overall survival of 8 mo.Severe mucositis is a very rare complication with only two cases of grade 4 mucositis reported,and both cases had good response to intravenous methylprednisolone and subsequent oral prednisone tapering.We report the first case of pembrolizumab-induced severe mucositis that was refractory to steroid treatment.CASE SUMMARY An 80-year-old woman with a past medical history of recurrent right cheek nodular melanoma status post resection and new right lung metastatic melanoma on immunotherapy presented with dysphagia and odynophagia for 2 mo.She initially received 2 doses of ipilimumab 1 year ago with good outcome,but treatment was discontinued after developing severe diarrhea and rash.Pembrolizumab was then initiated 4 mo after disease progression.Significant improvement was noted after 3 doses.However,after 6 cycles of pembrolizumab,patient developed odynophagia and malnutrition.Improvement of symptoms was noted after discontinuation of pembrolizumab and initiation of steroids.3 mo later,patient developed pharyngeal swelling with hoarseness and new oxygen requirement due to impending airway obstruction while being on prednisone tapering regimen,finally ended up with intubation and tracheostomy.Histologic analysis of left laryngeal and epiglottis tissue showed granulation tissue with acute on chronic inflammation,negative for malignancy and infection.Patient achieved marked improvement after 2 doses of infliximab of 5 mg/kg every 2 wk while continuing on prednisone tapering course.CONCLUSION We report the first case of pembrolizumab-induced grade 4 mucositis that had limited recovery with prolonged steroid course but had rapid response with addition of infliximab.The patient had recurrent mucositis symptoms whenever steroids was tapered but achieved complete response after receiving two doses of infliximab while continuing to be on tapering steroids.The success of infliximab in this patient with pembrolizumab-induced severe mucositis presents a potentially safe approach to reduce prolonged steroid course and accelerate recovery in managing this rare complication.

High-potency sucralfate prevents and rapidly reverses chemo-radiation mucositis in a patient with stage 4b head and neck cancer

AIM:To study usefulness of high-potency sucralfate(HPS)in a patient with chemoradiation mucositis and discuss its mechanism of action.METHODS:HPS,a non-covalently cross-link of sucralfate,cations and bidentate anionic chelators,has a maintains a surface concentration of sucralfate 3 h following administration that is 7-23 fold that possible with standard-potency sucralfate.The accelerated mucosal healing and pain alleviation of HPS in patients with erosive esophageal reflux,prompted its use in this patient with chemoradiation mucositis of the oropharynx and alimentary tract.A literature-based review of the immuno-modulatory effects of sucralfate is discussed.RESULTS:Within 48 h of intervention:(1)there was complete disappearance of oral mucositis lesions;tenderness with(2)patient-reported disappearance of pain,nausea and diarrhea;patient required(3)no opiate analgesia and(4)no tube-feeding supplements to regular diet.Dysgeusia and xerostomia persisted.A modified Naranjo Questionnaire score of 10 supported the likelihood that HPS intervention caused the observed clinical effects.No adverse reactions noted.CONCLUSION:In this patient HPS was useful to treat chemo-radiation mucositis of the oropharynx and alimentary tract.HPS may directly or indirectly facilitate an immunomodulatory mechanism involving accelerated growth factor activation,which may be a new target for therapeutic intervention in such patients.

Effects of Yangyin Jiedu Decoction on Acute Oral Mucositis Caused by Radiation

[Objectives] The aim was to observe the clinical effect of Yangyin Jiedu Decoction for acute oral mucositis caused by radiotherapy for nasopharyngeal carcinoma( NPC). [Methods]Total 64 patients with non-keratinizing squamous cell carcinoma of nasopharynx were divided evenly and randomly into two groups,treatment group and control group. In the treatment group,the patients began to take Yangyin Jiedu Decoction one week before radiotherapy; while in the control group,the patients were treated with mixed solution of dexamethasone,lidocaine,recombinant human granulocyte colony stimulating factor and vitamin B12. From the beginning to the end of radiotherapy,the curative effect in the two groups was observed and compared. In addition,the levels of serum CRP,TGF-β1 and IL-6 were measured to detect the inflammatory response. [Results] The incidence of acute oral mucositis in the treatment group was significantly lower than that in the control group( P <0. 05). The effective rate was 96. 88% in the treatment group and 67. 74% in the control group. The levels of serum CRP,TGF-β1 and IL-6 in the treatment group were also lower than those in the control group. [Conclusions]Yangyin Jiedu Decoction has a good effect on prevention and treatment of acute radioactive oral mucositis and it is worthy of clinical application.

A Retrospective Match Controlled Study of Supersaturated Calcium Phosphate Oral Rinse vs. Supportive Care for Radiation Induced Oral Mucositis

Oral mucositis is a common morbidity induced by radiation therapy and chemo-radiotherapy for head and neck malignancies. This often results in treatment delays, premature treatment cessation and increased cost. New treatments of oral mucositis are emerging but effective remedies remain limited. Between February 2007 and May 2008, 21 patients with head and neck malignancies were treated with a supersaturated calcium phosphate oral rinse (Caphosol) that was performed for 4-10 times daily, each consisting of two one-minute rinses. There were 21 matched patients who received supportive care without the oral rinse. All patients in the two groups were treated with intensity modulated radiation therapy (IMRT) for average prescription doses of 66 Gy in 33 fractions. The effects of this rinse vs. supportive care on mucositis, PEG tube requirements, hospitalization, xerostomia, analgesic requirements and weight was respectively evaluated. We have observed statistically significant decreases in the incidence of radiation induced oral mucositis (p=0.0002) with WHO grade 3 (38% vs. 52%) and 4 mucositis (0% vs. 19%), need for PEG tube placement (33% vs. 57%) and hospitalization (0% vs 19%). There was also a favorable impact on the incidence of grade 3 (29% vs. 43%) xerostomia in the treated patients but it was statistically insignificant (p=0.58). Incremental costs related to treatment of oral mucositis were reduced considerably. Our data suggest that use of a supersaturated calcium phosphate oral rinse is an effective treatment for mucositis in patients undergoing IMRT. It may also be helpful in the reduction of hospitalization and PEG tube requirements.

Severe gastrointestinal mucositis following high dose melphalan therapy for multiple myeloma

Mucositis is a known complication following use of chemotherapy,but fatal mucositis is unusual and management of such cases may be challenging.Pathologically there is denudation of mucosa of gastrointestinal tract. Severe cases can develop ileus and even perforation of bowel wall.We report here a case of multiple myeloma who developed World Health Organization grade 4 gut mucositis following the use of high dose melphalan with the expulsion of"intestine-like"material.

Clinical relevance of the use of Dentoxol® for oral mucositis induced by radiotherapy: A phase II clinical trial

BACKGROUND Severe oral mucositis associated with cancer therapy is a frequent complication that may affect a patient's systemic condition,resulting in interruption and/or prolongation of cancer therapy.Dentoxol®is a medical solution in the form of a mouthwash that has been shown to result in statistically significant improvement in the prevention of severe oral mucositis.However,knowing the measures of the clinical significance of this therapy is important for accurate decision-making.To describe the clinical impact of Dentoxol®use in severe oral mucositis.METHODS Clinical significance was measured using the results obtained in a randomized controlled clinical trial previously conducted by the same group of researchers.The measures of clinical significance evaluated were the absolute risk or incidence,relative risk,absolute risk reduction,relative risk reduction,number needed to treat,and odds ratio.RESULTS The data obtained show that the impact of Dentoxol®on reducing the severity of oral mucositis has important clinical relevance.CONCLUSION The results of this study justify the incorporation of Dentoxol®mouth rinse into clinical protocols as a complement to cancer therapy to prevent and/or treat oral mucositis secondary to radiotherapy.

Protective Effect of <i>Camellia sinensis</i>on Methotrexate-Induced Small Intestinal Mucositis in Mice

Background: Green tea has been used as a daily beverage for several years. Anti-inflammatory effect of tea has also been depicted in different papers. Therefore we had set forward this study to examine the potential anti- inflammatory activity of green tea in small intestine mucositis experimental models. Aims: Evaluation of anti- inflammatory effects of green tea on mice. Materials and Methods: Green tea decoction (20%) was prepared by soaking 20 g of green tea in 100 ml boiled water separately, soaked for 2 minutes and thereafter filtered. In- flammatory activity was induced using methotrexate (2.75 g/kg/24 h sc), and a protecting effect of mucositis con- dition was investigated by vitamin E and Camellia sinensis decoction. Study Design: An experimental study was approved by an Animal Ethical Commitee. Results: Green tea decoction (20%) has shown significant anti-in- flammatory effects (65% and 70%) on methotrexate-induced acute mucositis model. In villous atrophy Green tea decoction (10% and 20%) has shown no protecting action at different intestinal segments. But at intestinal crypt hyperplasia, green tea decoction has shown 65.74%, as compared to mucositis group. An increase of apoptotic bodies were acchieved at MTX group, CS reduced this occurrence. Conclusion: Taken together, our data indi- cate that green tea (20%) has a potential anti-inflammatory compared vitamin E antioxidant action and cor- roborates with the current trend of tea being promoted as “health drink”. However more pharmacological and biochemical assays is necessary to elucidate mechanisms.

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.

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.

Application of the theory of“conducting fire back to its origin”in treating radiotherapy or chemotherapy induced oral mucositis

Oral mucositis is a common adverse reaction of radiotherapy and chemotherapy in cancer patients,which reduces the quality of life of patients and affects the progress of cancer treatment.Most of the patients with malignant tumor belong to the syndrome of deficiency in root case and excess in manifestation.When undergoing radiotherapy or chemotherapy,the patients’ministerial fire becomes hyperactive,which may cause oral mucositis.With the method of“conducting fire back to its origin”,ministerial fire can be led to vital gate,as well as recovering its physiological functions.In the treatment of oral mucositis,instead of attacking ministerial fire with too much heat-clearing herbs,we should,under the guidance of the theory of“conducting fire back to its origin”,differentiate the syndrome,and then we can use the methods of treatment of clearing and lowering heart fire,warmly invigorating spleen and stomach,nourishing liver and kidney,or warmly invigorating vital gate,to conduct ministerial fire back to vital gate.This article aims to provide theoretical reference for Traditional Chinese Medicine treatment of radiotherapy or chemotherapy induced oral mucositis.

Supersaturated Calcium Phosphate Rinse vs. Standard of Care for Mitigating Mucositis in Head and Neck Chemoradiation

Introduction: Oral mucositis (OM) can have a significant impact on patients’ quality of life, pain and treatment costs. Almost all patients receiving head and neck chemoradiation develop OM. Patients and Methods: Twenty patients were evaluated retrospectively for OM when undergoing head and neck chemoradiation. The control, soda/salt rinse, was compared to a powdered supersaturated calcium phosphate rinse (SSCPR), SalivaMAX. Results: The SSCPR group experienced a delay in the onset of OM, which was not statistically significant, and a marked reduction in peak OM that was statistically significant (p > 0.001). Conclusion: This retrospective study demonstrates that a powdered SSCPR is a safe and effective method of oral mucositis mitigation.

Development of Oral Dissolving Gelatin Beads Containing Allopurinol for the Prevention and Treatment of Mucositis

Oral dissolving gelatin beads (GBs) containing allopurinol (AP) were prepared by the seamless capsule method and their rheological properties were examined. The release profiles of both gelatin and AP from GBs were also investigated in limited dissolution medium. GBs containing AP provided an easy-to-handle dosage form, but the physical strength of the beads immediately decreased upon contact with physiological saline at 37℃. Gelatin was released from the outer layer of GBs in physiological saline, with almost all the gelatin dissolved after 5 min, together with approximately 30% of the AP contained in the inner layer of the GB. The oral administration of GBs likely results in immediate softening of the GB upon contact with saliva. The released AP acts directly at inflammation sites, in a manner similar following oral rinsing with an AP suspension. Therefore, GBs are a useful dosage form for preventing or treating localized problems in the oral cavity, such as mucositis.

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.

Observation on Efficacy of Lanzhou Formula (兰州方) with Bingpeng Powder (冰硼散) Mouthwash in Preventing and Treating Radiation-induced Oral Mucositis

Objective:To observe clinical efficacy of Lanzhou Formula(兰州方)with Bingpeng Powder(冰硼散)mouthwash in preventing and treating radiation-induced oral mucositis.Methods:A total of 200 patients with malignant tumors in the head and neck who received radiotherapy in our hospital from April 2018 to April 2020 were selected as research objects,and they were randomly divided into the study group and control group.The control group was given radiotherapy combined with mouthwash,which consisted of 500 mL of normal saline,125 mg of vitamin B12,400000 U of gentamicin and 1 g of lidocaine.The study group was given radiotherapy combined with Lanzhou Formula with Bingpeng Powder mouthwash.Incidences of radiation-induced oral mucositis,chewing and swallowing functions,and Karnofsky(KPS)scores were compared between the 2 groups.Results:At the end of the radiotherapy,there was no Grade 4 radiation-induced oral mucositis in the 2 groups.Compared with the control group,the radiation-induced oral mucositis in the study group basically belonged to Grade 1 and Grade 2,with a lower incidence of Grade 3(P<0.05).At the end of the radiotherapy,the chewing and swallowing functions in the 2 groups were decreased,but patients with 2-point chewing and swallowing functions in the study group were more than those in the control group,and patients with the 3-point were less than those in the control group(P<0.05).At the end of the radiotherapy,the KPS scores were decreased,but those in the study group were higher than those in the control group(P<0.05).Conclusion:During radiotherapy for patients with malignant tumors in the head and neck,Lanzhou Formula with Bingpeng Powder mouthwash can decrease the severity of radiation-induced oral mucositis,protect chewing and swallowing functions of patients to a certain extent,and improve the general condition of patients.It is worthy of clinical application and promotion.

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.