Objective:To explore the key targets and mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacological methods.Methods:The effective components and corresp...Objective:To explore the key targets and mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacological methods.Methods:The effective components and corresponding target proteins of Shengjiang Xiexin Decoction were screened by TCMSP,and the target of chemotherapy-induced diarrhea were screened by the GeneCards.R software was used to obtain the common targets of drugs and diseases,and the“component-target-disease”network diagram was constructed by Cytoscape3.8.0 software.The string datebase was used to draw the protein interaction(PPI)network,and the Bioconductor software was used to perform GO function and KEGG pathway enrichment analysis on effective targets.Result:The result showed that 216 components were screened and 276 effective targets were screened.There were 1764 chemotherapy-induced diarrhea targets.The 173 common targets were obtained through venn diagram.The GO function analysis found 2427 items of biological process,168 items of molecular function and 79 items of cellular component.The KEGG pathway analysis found 169 items.Conclusion:The PPI network found that STAT3、AKT1、MAPK3、JUN、MAPK1、RELA、IL6、etc.may be the key targets for Shengjiang Xiexin Decoction in treatment of chemotherapy-induced diarrhea.GO biological processes include DNA-binding transcription factor activity,cytokine receptor binding,cytokine activity,response to lipopolysaccharide,cellular response to chemical stress and so on.The KEGG pathways involved mainly include Toll-like receptor signaling pathway,TNF signaling pathway,inlfuenza A signaling pathway、hepatitise B signaling pathway and other pathways,that Play the role of anti-inflammatory and repair barrier.展开更多
Objective:To dig deeper into the traditional Chinese medicine treatment rules of chemotherapy-induced diarrhea with traditional Chinese medicine(TCM)inheritance computing platform system.Methods:Taking“traditional Ch...Objective:To dig deeper into the traditional Chinese medicine treatment rules of chemotherapy-induced diarrhea with traditional Chinese medicine(TCM)inheritance computing platform system.Methods:Taking“traditional Chinese medicine”,“chemotherapy”and“diarrhea”as the theme words,comprehensive search of the database of CNKI,Wanfang and VIP from its inception to November 2020 was conduct-ed.The formulas of external treatment of traditional Chinese medicine for chemotherapy-induced diarrhea were included and the association rule,clustering and factor analysis were carried out.Results:A total of 145 papers,57 prescriptions meeting the inclusion criteria were collected,among which high-frequency drugs including Baizhu(Atractylodis macrocephalae rhizoma),Fuling(Poria),Dangshen(Codonopsisradix),Huanglian(Coptidis rhizoma),Zhigancao(Glycyrrhizae radix et rhizoma praeparata cum melle)were the most commonly used.The confidence level was set as 0.7 and the support level was set as 10,12 core compatibility groups were obtained,and 6 categories were cluster analyzed.Conclusion:The principle of external treatment of chemotherapy-induced diarrhea is mainly“restore deficiency and benefiting qi”,“benefiting water infiltration and dampness”,“clearing heat”and“inducing astringency”.Prescription combination and new prescription combination based on traditional Chinese medicine(TCM)inheritance computing platform system can be used as reference for clinicians and applied in primary hospitals.展开更多
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-i...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.展开更多
Objective:This review aimed to map and summarize published studies that tested non-pharmacological management for chemotherapyinduced nausea and vomiting(CINV).Methods:We searched for eligible studies in 5 electronic ...Objective:This review aimed to map and summarize published studies that tested non-pharmacological management for chemotherapyinduced nausea and vomiting(CINV).Methods:We searched for eligible studies in 5 electronic databases and screened the retrieved studies using the inclusion and exclusion criteria.Data were then collated according to the types of interventions,measurement tool,and outcomes.Results:The search yielded 2343 records,of which 11 were included.Four categories of non-pharmacological CINV management were made;manipulative and body-based therapy(n=5 studies);mind–body therapy(n=3 studies);biologically based practice(n=1 study),and energy therapy(n=2 studies).Seven different scales were used to measure CINV.Nine studies repor ted improvement in CINV.Conclusions:This scoping review demonstrates the breadth of non-pharmacological management to address CINV.Various types of CINV scales were used to measure CINV severity.The management and scale can be utilized to improve nursing care,par ticularly in cancer care.展开更多
Kobuvirus comprises 6 officially recognized species,namely Aichivirus A-F,and can be further divided into 20 genotypes through VP1 gene phylogenetic analysis(https://ictv.global/report/chapter/picornaviridae/picornavi...Kobuvirus comprises 6 officially recognized species,namely Aichivirus A-F,and can be further divided into 20 genotypes through VP1 gene phylogenetic analysis(https://ictv.global/report/chapter/picornaviridae/picornaviridae/kobuvirus).Aichivirus A in human,Aichivirus B in bovine,Aichivirus C in porcine and caprine,Aichivirus D in yak have been proved to be associated with diarrhea(Chen Y S et al.2013;Yang et al.2015;Zhu et al.2016;Zhai et al.2017;Wang et al.2020;Abi et al.2022;Yan et al.2023).展开更多
Rotavirus is one of the pathogenic causes that induce diarrhea in young animals, especially piglets, worldwide. However, nowadays, there is no specific drug available to treat the disease, and the related vaccines hav...Rotavirus is one of the pathogenic causes that induce diarrhea in young animals, especially piglets, worldwide. However, nowadays, there is no specific drug available to treat the disease, and the related vaccines have no obvious efficiency in some countries. Via analyzing the pathogenesis of rotavirus, it inducing diarrhea is mainly due to disturb enteric nervous system, destroy gut mucosal integrity, induce intracellular electrolyte imbalance, and impair gut microbiota and immunity. Many studies have already proved that prebiotics and probiotics can mitigate the damage and diarrhea induced by rotavirus infection in hosts. Based on these, the current review summarizes and discusses the effects and mechanisms of prebiotics and probiotics on rotavirus-induced diarrhea in piglets. This information will highlight the basis for the swine production utilization of prebiotics and probiotics in the prevention or treatment of rotavirus infection in the future.展开更多
Diarrhea has become the leading cause of illness and death among infants and young children in developing countries.Clinically,patients with diarrhea showed damaged intestinal epithelial villi,usually accompanied by l...Diarrhea has become the leading cause of illness and death among infants and young children in developing countries.Clinically,patients with diarrhea showed damaged intestinal epithelial villi,usually accompanied by lactase deficiency.In this study,we evaluated the therapeutic effects of lactose-free milk powder on rats and children with diarrhea.Antibiotic-associated diarrhea(AAD)model was established by gavage with antibiotic mixture in SD rats,followed by administration of milk powder containing lactose or not.The results showed that lactose-free milk powder ameliorated A AD-related diarrhea symptoms,and accelerated the recovery from diarrhea.And 16S sequencing results indicated lactose-free milk powder contributed to increase theα-andβ-diversity of intestinal flora,and restore the intestinal microbiota disorder.In conclusion,our data demonstrate that lactose-free milk powder could alleviate diarrhea by restoring gut microbiota and intestinal barrier function.展开更多
BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea,which has been proposed as Linghu’s obesity-diarrhea syndrome(ODS);however,its molecular mechanisms are largely unknown.AIM To...BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea,which has been proposed as Linghu’s obesity-diarrhea syndrome(ODS);however,its molecular mechanisms are largely unknown.AIM To reveal the transcriptomic changes in the jejunum involved in ODS.METHODS In a cohort of 6 ODS patients(JOD group),6 obese people without diarrhea(JO group),and 6 healthy controls(JC group),high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes.In another cohort of 16 ODS patients(SOD group),16 obese people without diarrhea(SO group),and 16 healthy controls(SC group),serum diamine oxidase(DAO)and D-lactate(DLA)concentrations were detected to assess changes in intestinal barrier function.RESULTS The gene expression profiles of jejunal mucosa in the JO and JC groups were similar,with only 1 differentially expressed gene(DEG).The gene expression profile of the JOD group was significantly changed,with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group,129 of which overlapped.The enrichment analysis of these DEGs showed that the biological processes such as digestion,absorption,and transport of nutrients(especially lipids)tended to be up-regulated in the JOD group,while the biological processes such as rRNA processing,mitochondrial translation,antimicrobial humoral response,DNA replication,and DNA repair tended to be down-regulated in the JOD group.Eight DEGs(CDT1,NHP2,EXOSC5,EPN3,NME1,REG3A,PLA2G2A,and PRSS2)may play a key regulatory role in the pathological process of ODS,and their expression levels were significantly decreased in ODS patients(P<0.001).In the second cohort,compared with healthy controls,the levels of serum intestinal barrier function markers(DAO and D-LA)were significantly increased in all obese individuals(P<0.01),but were higher in the SOD group than in the SO group(P<0.001).CONCLUSION Compared with healthy controls and obese individuals without diarrhea,patients with Linghu’s ODS had extensive transcriptomic changes in the jejunal mucosa,likely affecting intestinal barrier function and thus contributing to the obesity and chronic diarrhea phenotypes.展开更多
BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented...BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.展开更多
BACKGROUND Dietary fiber is essential for human health and can help reduce the symptoms of constipation.However,the relationship between dietary fiber and diarrhea is,poorly understood.AIM To evaluate the relationship...BACKGROUND Dietary fiber is essential for human health and can help reduce the symptoms of constipation.However,the relationship between dietary fiber and diarrhea is,poorly understood.AIM To evaluate the relationship between dietary fiber and chronic diarrhea.METHODS This retrospective study was conducted using data from the United States National Health and Nutrition Examination Survey,conducted between 2005 and 2010.Participants over the age of 20 were included.To measure dietary fiber consumption,two 24-hour meal recall interviews were conducted.The independent relationship between the total amount of dietary fiber and chronic diarrhea was evaluated with multiple logistic regression and interaction analysis.RESULTS Data from 12829 participants were analyzed.Participants without chronic diarrhea consumed more dietary fiber than participants with chronic diarrhea(29.7 vs 28.5,P=0.004).Additionally,in participants with chronic diarrhea,a correlation between sex and dietary fiber intake was present:Women who consume more than 25 g of dietary fiber daily can reduce the occurrence of chronic diarrhea.CONCLUSION Dietary fiber can reduce the occurrence of chronic diarrhea.展开更多
BACKGROUND Accumulating evidence suggests that the gut microbiome is involved in the pathogenesis of insulin resistance(IR).However,the link between two of the most prevalent bowel disorders,chronic diarrhea and const...BACKGROUND Accumulating evidence suggests that the gut microbiome is involved in the pathogenesis of insulin resistance(IR).However,the link between two of the most prevalent bowel disorders,chronic diarrhea and constipation,and the triglyceride glucose(TyG)index,a marker of IR,has not yet been investigated.AIM To investigate the potential association between TyG and the incidence of chronic diarrhea and constipation.METHODS This cross-sectional study enrolled 2400 participants from the National Health and Nutrition Examination Survey database from 2009-2010.TyG was used as an exposure variable,with chronic diarrhea and constipation as determined by the Bristol Stool Form Scale used as the outcome variables.A demographic investigation based on TyG quartile subgroups was performed.The application of multivariate logistic regression models and weighted generalized additive models revealed potential correlations between TyG,chronic diarrhea,and constipation.Subgroup analyses were performed to examine the stability of any potential associations.RESULTS In the chosen sample,chronic diarrhea had a prevalence of 8.00%,while chronic constipation had a prevalence of 8.04%.In multiple logistic regression,a more prominent positive association was found between TyG and chronic diarrhea,particularly in model 1(OR=1.45;95%CI:1.17-1.79,P=0.0007)and model 2(OR=1.40;95%CI:1.12-1.76,P=0.0033).No definite association was observed between the TyG levels and chronic constipation.The weighted generalized additive model findings suggested a more substantial positive association with chronic diarrhea when TyG was less than 9.63(OR=1.89;95%CI:1.05-3.41,P=0.0344),and another positive association with chronic constipation when it was greater than 8.2(OR=1.74;95%CI:1.02-2.95,P=0.0415).The results of the subgroup analyses further strengthen the extrapolation of these results to a wide range of populations.CONCLUSION Higher TyG levels were positively associated with abnormal bowel health.展开更多
Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms.This disease presents with daily abdominal pain for at least 3 months related to defecation a...Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms.This disease presents with daily abdominal pain for at least 3 months related to defecation and associated with a change in the frequency of bowel movements and the shape of the stool.International surveys about this disease report a global prevalence of about 1.5%.A new amino acid based electrolyte solution has recently been commercialized for oral rehydration in diarrhea.It is composed of water,electrolytes,and five selected amino acids that function as sodium co-transporters without containing glucose.In recent years,some studies explored the effectiveness of the amino acid based electrolyte beverage in oncologic patients with gastrointestinal mucositis,reporting good results.Recently,a prospective study to evaluate the clinical impact of the amino acid based medical beverage was conducted in patients with diarrhea predominant irritable bowel syndrome.The research was based on a real-life methodology minimizing the disruption of the routine care.One hundred patients suffering from irritable bowel syndrome with diarrhea drank a solution based on selected amino acids twice a day for 2 wk.Each enrolled patient completed the study and showed a significant response rate with regard to stool consistency and pain reduction.Based on this data,we can hypothesize that the amino acid based oral rehydration solution could be a valid tool in the treatment of patients affected by irritable bowel syndrome with diarrhea.It is certainly necessary to plan highquality clinical trials comparing glucose based oral solutions and amino acid based solutions in patients with persisting diarrhea.Probably in the near future all oral rehydration solutions will contain amino acids.展开更多
Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is...Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.展开更多
Irritable bowel syndrome(IBS-D)with diarrhea is a common gastrointestinal functional disease in clinical practice,which seriously affects the quality of life of patients.Cur‐rently,Western medicine has poor therapeut...Irritable bowel syndrome(IBS-D)with diarrhea is a common gastrointestinal functional disease in clinical practice,which seriously affects the quality of life of patients.Cur‐rently,Western medicine has poor therapeutic effects,while traditional Chinese medi‐cine has unique advantages in relieving IBS-D symptoms and preventing recurrence.In recent years,especially with external treatment of traditional Chinese medicine,it has become a new treatment direction in clinical practice and has achieved good therapeutic effects.This article will provide a review of recent research on the treatment of IBS-D using traditional Chinese medicine external treatment methods.展开更多
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...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.展开更多
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 associ...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.展开更多
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 color...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.展开更多
Chemotherapy-induced peripheral neuropathy is a very frequent neurological complication in cancer. Oxaliplatin(OXA) is a platinum analogue used as a first-line agent in the treatment of colorectal cancer. OXA induce...Chemotherapy-induced peripheral neuropathy is a very frequent neurological complication in cancer. Oxaliplatin(OXA) is a platinum analogue used as a first-line agent in the treatment of colorectal cancer. OXA induced peripheral neuropathy(OIN) is the main toxicity both during and after the completion of chemotherapy that presents as two distinct syndromes: acute and chronic neuropathy. None of the neuroprotective agents previously tested had prevented or limited the acute and/or chronic OIN. MR309(previously developed as E-52862) is a novel selective sigma-1 receptor(S1R) antagonist with preclinical analgesic activity in OXA-induced neuropathic pain in animal models. This review analyzes the results of the recently published phase Ⅱ, randomized, double-blind, placebo-controlled clinical trial including 124 patients with colorectal cancer(CRC) treated with MR309. This study shows encouraging findings in the setting of neuroprotection against OIN with an acceptable safety profile. The study demonstrated MR309 usefulness in decreasing acute OIN, by reducing cold hypersensitivity experienced by patients, and pointed to the amelioration of chronic OIN by lowering the proportion of patients who developed severe chronic OIN. In addition, we provide a summary and discussion on the pathways that can be modulated by the S1R to explain the observed clinical benefits in the OIN.展开更多
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...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.展开更多
基金National Natural Science Foundation of China(No.81904001)Special Fund for Capital Health Development(No.2018-1-4061)+1 种基金National Administration of Traditional Chinese Medicine of China(No.2019-ZX-005)Hospital Project of China-Japan Friendship Hospital(No.2019-1-QN-56)。
文摘Objective:To explore the key targets and mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacological methods.Methods:The effective components and corresponding target proteins of Shengjiang Xiexin Decoction were screened by TCMSP,and the target of chemotherapy-induced diarrhea were screened by the GeneCards.R software was used to obtain the common targets of drugs and diseases,and the“component-target-disease”network diagram was constructed by Cytoscape3.8.0 software.The string datebase was used to draw the protein interaction(PPI)network,and the Bioconductor software was used to perform GO function and KEGG pathway enrichment analysis on effective targets.Result:The result showed that 216 components were screened and 276 effective targets were screened.There were 1764 chemotherapy-induced diarrhea targets.The 173 common targets were obtained through venn diagram.The GO function analysis found 2427 items of biological process,168 items of molecular function and 79 items of cellular component.The KEGG pathway analysis found 169 items.Conclusion:The PPI network found that STAT3、AKT1、MAPK3、JUN、MAPK1、RELA、IL6、etc.may be the key targets for Shengjiang Xiexin Decoction in treatment of chemotherapy-induced diarrhea.GO biological processes include DNA-binding transcription factor activity,cytokine receptor binding,cytokine activity,response to lipopolysaccharide,cellular response to chemical stress and so on.The KEGG pathways involved mainly include Toll-like receptor signaling pathway,TNF signaling pathway,inlfuenza A signaling pathway、hepatitise B signaling pathway and other pathways,that Play the role of anti-inflammatory and repair barrier.
基金National Natural Science Foundation of China Youth Science Foundation Project(No.81904001)Capital Health Development Scientific Research Project(No.first issue 2018-1-4061)+1 种基金State Administration of Traditional Chinese Medicine Clinical Collaboration Project of TCM and Western Medicine for Major and Intractable Diseases(No.2019-ZX-005)In-Hospital Project of China-Japan Friendship Hospital(No.2019-1-QN-56)。
文摘Objective:To dig deeper into the traditional Chinese medicine treatment rules of chemotherapy-induced diarrhea with traditional Chinese medicine(TCM)inheritance computing platform system.Methods:Taking“traditional Chinese medicine”,“chemotherapy”and“diarrhea”as the theme words,comprehensive search of the database of CNKI,Wanfang and VIP from its inception to November 2020 was conduct-ed.The formulas of external treatment of traditional Chinese medicine for chemotherapy-induced diarrhea were included and the association rule,clustering and factor analysis were carried out.Results:A total of 145 papers,57 prescriptions meeting the inclusion criteria were collected,among which high-frequency drugs including Baizhu(Atractylodis macrocephalae rhizoma),Fuling(Poria),Dangshen(Codonopsisradix),Huanglian(Coptidis rhizoma),Zhigancao(Glycyrrhizae radix et rhizoma praeparata cum melle)were the most commonly used.The confidence level was set as 0.7 and the support level was set as 10,12 core compatibility groups were obtained,and 6 categories were cluster analyzed.Conclusion:The principle of external treatment of chemotherapy-induced diarrhea is mainly“restore deficiency and benefiting qi”,“benefiting water infiltration and dampness”,“clearing heat”and“inducing astringency”.Prescription combination and new prescription combination based on traditional Chinese medicine(TCM)inheritance computing platform system can be used as reference for clinicians and applied in primary hospitals.
基金National Natural Science Foundation of China(grant numbers 82174143)the Innovative Team Project of Ordinary Universities in Guangdong Province(grant numbers 2022KCXTD016).
文摘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.
基金supported by the Institute of Research and Innovation of Universitas Muhammadiyah Yogyakarta(No.034/PEN-LP3M/II/2021)。
文摘Objective:This review aimed to map and summarize published studies that tested non-pharmacological management for chemotherapyinduced nausea and vomiting(CINV).Methods:We searched for eligible studies in 5 electronic databases and screened the retrieved studies using the inclusion and exclusion criteria.Data were then collated according to the types of interventions,measurement tool,and outcomes.Results:The search yielded 2343 records,of which 11 were included.Four categories of non-pharmacological CINV management were made;manipulative and body-based therapy(n=5 studies);mind–body therapy(n=3 studies);biologically based practice(n=1 study),and energy therapy(n=2 studies).Seven different scales were used to measure CINV.Nine studies repor ted improvement in CINV.Conclusions:This scoping review demonstrates the breadth of non-pharmacological management to address CINV.Various types of CINV scales were used to measure CINV severity.The management and scale can be utilized to improve nursing care,par ticularly in cancer care.
基金sponsored by the Southwest Minzu University Double World-Class ProjectChina(XM2023014)+3 种基金the Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System(SCCXTD-2020-18)the Key Laboratory of Veterinary Medicine of Universities of Sichuan Province of Chinathe Fundamental Research Funds for the Central UniversitiesSouthwest Minzu University China(ZYN2023043)。
文摘Kobuvirus comprises 6 officially recognized species,namely Aichivirus A-F,and can be further divided into 20 genotypes through VP1 gene phylogenetic analysis(https://ictv.global/report/chapter/picornaviridae/picornaviridae/kobuvirus).Aichivirus A in human,Aichivirus B in bovine,Aichivirus C in porcine and caprine,Aichivirus D in yak have been proved to be associated with diarrhea(Chen Y S et al.2013;Yang et al.2015;Zhu et al.2016;Zhai et al.2017;Wang et al.2020;Abi et al.2022;Yan et al.2023).
基金financially supported by 14^(th) Five-Year for Breeding Research Project of Sichuan Provincial Department of Science and Technology (2021YFYZ0008)。
文摘Rotavirus is one of the pathogenic causes that induce diarrhea in young animals, especially piglets, worldwide. However, nowadays, there is no specific drug available to treat the disease, and the related vaccines have no obvious efficiency in some countries. Via analyzing the pathogenesis of rotavirus, it inducing diarrhea is mainly due to disturb enteric nervous system, destroy gut mucosal integrity, induce intracellular electrolyte imbalance, and impair gut microbiota and immunity. Many studies have already proved that prebiotics and probiotics can mitigate the damage and diarrhea induced by rotavirus infection in hosts. Based on these, the current review summarizes and discusses the effects and mechanisms of prebiotics and probiotics on rotavirus-induced diarrhea in piglets. This information will highlight the basis for the swine production utilization of prebiotics and probiotics in the prevention or treatment of rotavirus infection in the future.
基金supported by the project of two children’s dairy products (201704810610483)。
文摘Diarrhea has become the leading cause of illness and death among infants and young children in developing countries.Clinically,patients with diarrhea showed damaged intestinal epithelial villi,usually accompanied by lactase deficiency.In this study,we evaluated the therapeutic effects of lactose-free milk powder on rats and children with diarrhea.Antibiotic-associated diarrhea(AAD)model was established by gavage with antibiotic mixture in SD rats,followed by administration of milk powder containing lactose or not.The results showed that lactose-free milk powder ameliorated A AD-related diarrhea symptoms,and accelerated the recovery from diarrhea.And 16S sequencing results indicated lactose-free milk powder contributed to increase theα-andβ-diversity of intestinal flora,and restore the intestinal microbiota disorder.In conclusion,our data demonstrate that lactose-free milk powder could alleviate diarrhea by restoring gut microbiota and intestinal barrier function.
文摘BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea,which has been proposed as Linghu’s obesity-diarrhea syndrome(ODS);however,its molecular mechanisms are largely unknown.AIM To reveal the transcriptomic changes in the jejunum involved in ODS.METHODS In a cohort of 6 ODS patients(JOD group),6 obese people without diarrhea(JO group),and 6 healthy controls(JC group),high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes.In another cohort of 16 ODS patients(SOD group),16 obese people without diarrhea(SO group),and 16 healthy controls(SC group),serum diamine oxidase(DAO)and D-lactate(DLA)concentrations were detected to assess changes in intestinal barrier function.RESULTS The gene expression profiles of jejunal mucosa in the JO and JC groups were similar,with only 1 differentially expressed gene(DEG).The gene expression profile of the JOD group was significantly changed,with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group,129 of which overlapped.The enrichment analysis of these DEGs showed that the biological processes such as digestion,absorption,and transport of nutrients(especially lipids)tended to be up-regulated in the JOD group,while the biological processes such as rRNA processing,mitochondrial translation,antimicrobial humoral response,DNA replication,and DNA repair tended to be down-regulated in the JOD group.Eight DEGs(CDT1,NHP2,EXOSC5,EPN3,NME1,REG3A,PLA2G2A,and PRSS2)may play a key regulatory role in the pathological process of ODS,and their expression levels were significantly decreased in ODS patients(P<0.001).In the second cohort,compared with healthy controls,the levels of serum intestinal barrier function markers(DAO and D-LA)were significantly increased in all obese individuals(P<0.01),but were higher in the SOD group than in the SO group(P<0.001).CONCLUSION Compared with healthy controls and obese individuals without diarrhea,patients with Linghu’s ODS had extensive transcriptomic changes in the jejunal mucosa,likely affecting intestinal barrier function and thus contributing to the obesity and chronic diarrhea phenotypes.
基金Supported by Eunice Kennedy Shriver National Institute of Child Health&Human Development of the National Institutes of Health,No.1K08HD079674-01 and 1R41HD092133-01National Institute of Allergy and Infectious Diseases,No.1A21AI169282and VA Research Career Scientist Award,No.1IK6BX004835.
文摘BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.
文摘BACKGROUND Dietary fiber is essential for human health and can help reduce the symptoms of constipation.However,the relationship between dietary fiber and diarrhea is,poorly understood.AIM To evaluate the relationship between dietary fiber and chronic diarrhea.METHODS This retrospective study was conducted using data from the United States National Health and Nutrition Examination Survey,conducted between 2005 and 2010.Participants over the age of 20 were included.To measure dietary fiber consumption,two 24-hour meal recall interviews were conducted.The independent relationship between the total amount of dietary fiber and chronic diarrhea was evaluated with multiple logistic regression and interaction analysis.RESULTS Data from 12829 participants were analyzed.Participants without chronic diarrhea consumed more dietary fiber than participants with chronic diarrhea(29.7 vs 28.5,P=0.004).Additionally,in participants with chronic diarrhea,a correlation between sex and dietary fiber intake was present:Women who consume more than 25 g of dietary fiber daily can reduce the occurrence of chronic diarrhea.CONCLUSION Dietary fiber can reduce the occurrence of chronic diarrhea.
文摘BACKGROUND Accumulating evidence suggests that the gut microbiome is involved in the pathogenesis of insulin resistance(IR).However,the link between two of the most prevalent bowel disorders,chronic diarrhea and constipation,and the triglyceride glucose(TyG)index,a marker of IR,has not yet been investigated.AIM To investigate the potential association between TyG and the incidence of chronic diarrhea and constipation.METHODS This cross-sectional study enrolled 2400 participants from the National Health and Nutrition Examination Survey database from 2009-2010.TyG was used as an exposure variable,with chronic diarrhea and constipation as determined by the Bristol Stool Form Scale used as the outcome variables.A demographic investigation based on TyG quartile subgroups was performed.The application of multivariate logistic regression models and weighted generalized additive models revealed potential correlations between TyG,chronic diarrhea,and constipation.Subgroup analyses were performed to examine the stability of any potential associations.RESULTS In the chosen sample,chronic diarrhea had a prevalence of 8.00%,while chronic constipation had a prevalence of 8.04%.In multiple logistic regression,a more prominent positive association was found between TyG and chronic diarrhea,particularly in model 1(OR=1.45;95%CI:1.17-1.79,P=0.0007)and model 2(OR=1.40;95%CI:1.12-1.76,P=0.0033).No definite association was observed between the TyG levels and chronic constipation.The weighted generalized additive model findings suggested a more substantial positive association with chronic diarrhea when TyG was less than 9.63(OR=1.89;95%CI:1.05-3.41,P=0.0344),and another positive association with chronic constipation when it was greater than 8.2(OR=1.74;95%CI:1.02-2.95,P=0.0415).The results of the subgroup analyses further strengthen the extrapolation of these results to a wide range of populations.CONCLUSION Higher TyG levels were positively associated with abnormal bowel health.
文摘Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms.This disease presents with daily abdominal pain for at least 3 months related to defecation and associated with a change in the frequency of bowel movements and the shape of the stool.International surveys about this disease report a global prevalence of about 1.5%.A new amino acid based electrolyte solution has recently been commercialized for oral rehydration in diarrhea.It is composed of water,electrolytes,and five selected amino acids that function as sodium co-transporters without containing glucose.In recent years,some studies explored the effectiveness of the amino acid based electrolyte beverage in oncologic patients with gastrointestinal mucositis,reporting good results.Recently,a prospective study to evaluate the clinical impact of the amino acid based medical beverage was conducted in patients with diarrhea predominant irritable bowel syndrome.The research was based on a real-life methodology minimizing the disruption of the routine care.One hundred patients suffering from irritable bowel syndrome with diarrhea drank a solution based on selected amino acids twice a day for 2 wk.Each enrolled patient completed the study and showed a significant response rate with regard to stool consistency and pain reduction.Based on this data,we can hypothesize that the amino acid based oral rehydration solution could be a valid tool in the treatment of patients affected by irritable bowel syndrome with diarrhea.It is certainly necessary to plan highquality clinical trials comparing glucose based oral solutions and amino acid based solutions in patients with persisting diarrhea.Probably in the near future all oral rehydration solutions will contain amino acids.
文摘Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.
文摘Irritable bowel syndrome(IBS-D)with diarrhea is a common gastrointestinal functional disease in clinical practice,which seriously affects the quality of life of patients.Cur‐rently,Western medicine has poor therapeutic effects,while traditional Chinese medi‐cine has unique advantages in relieving IBS-D symptoms and preventing recurrence.In recent years,especially with external treatment of traditional Chinese medicine,it has become a new treatment direction in clinical practice and has achieved good therapeutic effects.This article will provide a review of recent research on the treatment of IBS-D using traditional Chinese medicine external treatment methods.
基金supported by MSD Holding Co.,Ltd.The funding was only for the payment of using CHIRA database
文摘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.
基金supported by grants from the Demonstrative Research Platform of Clinical Evaluation Technology for New Anticancer Drugs(Grant Nos.18ZX09201-015 and 2017ZX09304015)the Innovation Fund for Medical Sciences of the Chinese Academy of Medical Sciences(Grant No.CIFMS,2016-I2M-1-001)。
文摘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.
文摘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.
文摘Chemotherapy-induced peripheral neuropathy is a very frequent neurological complication in cancer. Oxaliplatin(OXA) is a platinum analogue used as a first-line agent in the treatment of colorectal cancer. OXA induced peripheral neuropathy(OIN) is the main toxicity both during and after the completion of chemotherapy that presents as two distinct syndromes: acute and chronic neuropathy. None of the neuroprotective agents previously tested had prevented or limited the acute and/or chronic OIN. MR309(previously developed as E-52862) is a novel selective sigma-1 receptor(S1R) antagonist with preclinical analgesic activity in OXA-induced neuropathic pain in animal models. This review analyzes the results of the recently published phase Ⅱ, randomized, double-blind, placebo-controlled clinical trial including 124 patients with colorectal cancer(CRC) treated with MR309. This study shows encouraging findings in the setting of neuroprotection against OIN with an acceptable safety profile. The study demonstrated MR309 usefulness in decreasing acute OIN, by reducing cold hypersensitivity experienced by patients, and pointed to the amelioration of chronic OIN by lowering the proportion of patients who developed severe chronic OIN. In addition, we provide a summary and discussion on the pathways that can be modulated by the S1R to explain the observed clinical benefits in the OIN.
文摘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.