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
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 pre...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.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
BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there ar...BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.展开更多
Objective: This analysis was conducted to clarify risk factors for chemotherapy-induced leukopenia (CIL) in lung cancer. Methods: A retrospective study was conducted on data from 358 patients with lung cancer who rece...Objective: This analysis was conducted to clarify risk factors for chemotherapy-induced leukopenia (CIL) in lung cancer. Methods: A retrospective study was conducted on data from 358 patients with lung cancer who received chemotherapy. Results: Among 358 cases of lung cancer who received chemotherapy, a total of 240 patients experienced CIL, rate was 67%. The demographic data including gender (P = 0.795), age (P = 0.134), presence of selected chronic comorbidities (P = 0.23) were not significantly different in the two groups. The weight loss rate, PS score, sub-normal pre-WBC level, sub-normal pre-PLT level, and the cycle of chemotherapy were significantly different between the groups (P < 0.05). Multivariate analysis revealed that the weight loss rate ≥5% (OR = 0.503), sub-normal pre-WBC level (OR = 11.807), the cycle of chemotherapy ≥3 (OR = 3.100) were main risk factors for CIL in lung cancer. Conclusion: Before treatment, weight loss rate is 5% or higher, chemotherapy has a cycle of 3 or more and sub-normal WBC level is independent risk factor of lung cancer after chemotherapy-induced leucopenia.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(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
BACKGROUND Chemotherapy-induced peripheral neuropathy(CIPN)is a severe and longlasting side effect caused by various anticancer agents that damage sensory,motor and autonomic nerves.It can cause maladaptive behaviors,...BACKGROUND Chemotherapy-induced peripheral neuropathy(CIPN)is a severe and longlasting side effect caused by various anticancer agents that damage sensory,motor and autonomic nerves.It can cause maladaptive behaviors,including disease severity,anxiety,depression,sleep disorders,falls,and social impairment.These disorders have physical,psychological and social effects on patients and can seriously influence their quality of life.AIM To investigate the current situation of psychosocial adaptation to the disease and its influencing factor in patients with CIPN.METHODS A convenience sampling method was used to select 233 patients with CIPN in our hospital from February to August 2021.In addition,a cross-sectional survey was conducted using a sociodemographic questionnaire,the Self-Report Psychosocial Adjustment to Illness Scale,and the European Organisation for the Research and Treatment of Cancer Quality of Life CIPN20(QLQ-CIPN20).Factors influencing psychosocial adaptation in patients with CIPN were analyzed by t-test or one-way analysis of variance,correlation analysis,multiple stepwise regression analysis,and structural equation models.RESULTS The psychosocial adaptation score of patients with CIPN was 52.51±13.18.Multivariate analysis showed that autonomic nerves,tumor stage,motor nerves,education level,availability of caregivers,semi-retirement status,CIPN grade were independent risk factors for patients with CIPN(P<0.05).Structural equation models showed that QLQ-CIPN20 mediated the relationship between CIPN grade,tumor stage,and psychosocial adaptation.CONCLUSION Patients with CIPN have poor psychosocial adaptation and are affected by a variety of physiological,psychological,and social factors.Patients’adaptive responses should be assessed,and targeted interventions implemented.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
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
With the clinical application of various chemotherapeutic drugs,the side effects are also followed.Diarrhea is one of the most serious side effects of chemotherapy.A large number of clinical and experimental studies h...With the clinical application of various chemotherapeutic drugs,the side effects are also followed.Diarrhea is one of the most serious side effects of chemotherapy.A large number of clinical and experimental studies have proven that traditional Chinese medicine has great prospects in relieving chemotherapy-related diarrhea.The article mainly discusses the mechanism of chemotherapy-related diarrhea and the prospect of traditional Chinese medicine in relieving the mechanism of chemotherapy-related diarrhea.展开更多
Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy. Neurokinin-1 receptor antagonists (NK1-RAs) have been incorporated in the contemporary management of CINV. However, clinica...Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy. Neurokinin-1 receptor antagonists (NK1-RAs) have been incorporated in the contemporary management of CINV. However, clinical studies on NK1-RAs have shown mixed results in reducing CINV risk. Most studies focused on the use of aprepitant (APR) and casopitant (CAS) in breast cancer patients receiving AC-type (doxorubicin and cyclophosphamide) chemotherapy. In this study, we compared the study design and clinical efficacies of these NK1-RAs in reducing CINV risk. Among the selected eight studies, 4 APR Randomized Controlled Trials (RCTs), 2 APR Observational Studies (OSs) and 2 CAS RCTs were identified. Patient-related characteristics such as the proportion of females (60.0% - 100.0%), age (46.5 - 59.5 years), histories of motion (5.6% - 47.0% in NK1-RA arms) and morning sicknesses (14.2% - 45.0% in NK1-RA arms) and types of antiemetic regimens;as well as chemotherapy-related characteristics such as the proportion of patients on AC chemotherapy (15.0% - 100.0%) varied greatly. In terms of efficacies, both APR and CAS improved overall CR and vomiting in majority of the studies. None of the studies, however, demonstrated that NK1-RA could provide adequate nausea control. To conclude, NK1-RAs are effective in improving vomiting and overall CR, but not useful in controlling nausea or attaining CC, the ideal CINV endpoint. A shift in paradigm is needed for future CINV research. As healthcare providers continue to strive for optimum CINV control in their patients, we hope this review can help them make better informed clinical decisions.展开更多
OBJECTIVE: To assess the efficacy and safety of Neiguan(PC6) acupoint acustimulation in preventing chemotherapy-induced nausea and vomiting(CINV),especially for patients with guideline-inconsistent CINV prophylaxis(GI...OBJECTIVE: To assess the efficacy and safety of Neiguan(PC6) acupoint acustimulation in preventing chemotherapy-induced nausea and vomiting(CINV),especially for patients with guideline-inconsistent CINV prophylaxis(GICP) due to personal reasons METHODS: From January 2021 to December 2021, 373 patients suffered from solid malignancy were recruited according to the inclusion criteria. Complete response(no emesis and no rescue medication use) rate during the overall phase(0-120 h of each chemo-cycle) was the primary assessment of CINV control. The Functional Living Index-Emesis(FLIE) questionnaire was investigated among these patients as a secondary 'quality of life' objective to assess the impact of CINV on patients' daily life by recording score of nausea and vomiting. RESULTS: With acustimulation of Neiguan(PC6) acupuncture point through a portable, noninvasive and user-friendly device, in terms of complete response rate and scores in nausea/vomiting by FLIE questionnaire, patients achieve a better outcome in highly emetogenic chemotherapy(HEC) induced CINV, especially GICP subgroup. Meanwhile, analysis also demonstrated this tendency existed in other patients with HEC/GCCP(guideline consistent CINV prophylaxis) and moderate emetogenic chemotherapy, although the difference was not significant. CONCLUSION: Considering advantages of Neiguan(PC6) acustimulation such as noninvasive, covered by medical insurance and few side effects, we believe it would be an ideal auxiliary tool in CINV control, especially in patients who receive highly emetogenic chemoprotocol and are reluctant to GCCP for economic reasons.展开更多
Objective: To observe the clinical efficacy and differences of the Zhuyu Juanbi formula delivered through ultrasound at Zusanli on patients with chemotherapy-induced peripheral neuropathy (CIPN) due to paclitaxel inje...Objective: To observe the clinical efficacy and differences of the Zhuyu Juanbi formula delivered through ultrasound at Zusanli on patients with chemotherapy-induced peripheral neuropathy (CIPN) due to paclitaxel injection. Methods: A total of 72 breast cancer patients with CIPN were randomly divided into two groups. The treatment group (36 cases) was treated with oral methylcobalamin plus ultrasonic medicine permeating Zhuyu Juanbi formulae, while the control group (36 cases) was treated with oral methylcobalamin alone. Following two 2 cycles of continuous treatment, the efficacy of peripheral neurotoxicity, TCM syndrome score, FACT/GOG-Ntx score, total neuropathy score, and safety indicators of gynecological cancer patients were observed in the two groups. Result: In the treatment of CIPN, the addition of ultrasonic medicine permeating Zhuyu Juanbi formulae was more effective than oral methylcobalamin alone in reducing peripheral neurotoxicity and improving the quality of life of patients. The difference between the two groups was statistically significant (P < 0.05), and ultrasound drug penetration Zhuyu Juanbi formulae significantly reduced the FACT/ GOG-Ntx score and TNS score in the treatment group. In terms of drug safety, it rarely caused adverse reactions such as grade 3 and 4 leukopenia, and the safety profile was therefore good. Conclusion: The combination of ultrasonic medicine permeating Zhuyu Juanbi formulae and methylcobalamin has been demonstrated to be an effective treatment for peripheral neurotoxicity in patients with PIPN. It has been shown to significantly improve the clinical symptoms of PIPN patients, improve the quality of life of patients, and have a good safety profile.展开更多
In the present paper, the authors analyze the academic theses of acupuncture for treatment of leucopenia induced by chemo or radio therapy. A total of 14 theses are retrieved and all written in Chinese. Quantitative m...In the present paper, the authors analyze the academic theses of acupuncture for treatment of leucopenia induced by chemo or radio therapy. A total of 14 theses are retrieved and all written in Chinese. Quantitative meta analysis is done for 4 studies of dichotomous data and 5 studies of continuous data. Both of them have positive results. Majority of these trials have methodological and/or reporting shortcomings. Overall, the existing evidence supports the value of acupuncture for the treatment of leucopenia induced by chemo or radio therapy. However, the evidence is still not fully convincing. There is an urgent need for well planned, large scale and multiple center studies to assess the effectiveness and cost effectiveness of acupuncture under real life conditions.展开更多
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 National Natural Science Foundation of China(No.82074348,No.82274491)the innovation and development joint project of Shandong Province Natural Science Foundation(ZR2023LZL009)the Jinan clinical medical science and technology innovation plan(No.202225014,202328072).
文摘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.
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Supported by the National Natural Science Foundation of China,No.82020108031,No.81973398,and No.82104290Guangdong Provincial Key Laboratory of Construction Foundation,No.2020B1212060034Guangdong Basic and Applied Basic Research Foundation,No.2022A1515012549 and No.2023A1515012667.
文摘BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.
文摘Objective: This analysis was conducted to clarify risk factors for chemotherapy-induced leukopenia (CIL) in lung cancer. Methods: A retrospective study was conducted on data from 358 patients with lung cancer who received chemotherapy. Results: Among 358 cases of lung cancer who received chemotherapy, a total of 240 patients experienced CIL, rate was 67%. The demographic data including gender (P = 0.795), age (P = 0.134), presence of selected chronic comorbidities (P = 0.23) were not significantly different in the two groups. The weight loss rate, PS score, sub-normal pre-WBC level, sub-normal pre-PLT level, and the cycle of chemotherapy were significantly different between the groups (P < 0.05). Multivariate analysis revealed that the weight loss rate ≥5% (OR = 0.503), sub-normal pre-WBC level (OR = 11.807), the cycle of chemotherapy ≥3 (OR = 3.100) were main risk factors for CIL in lung cancer. Conclusion: Before treatment, weight loss rate is 5% or higher, chemotherapy has a cycle of 3 or more and sub-normal WBC level is independent risk factor of lung cancer after chemotherapy-induced leucopenia.
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(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.
基金Supported by the Nursing Research Project Funding by the Affiliated Changzhou Second People's Hospital of Nanjing Medical University,No.2020HZD003.
文摘BACKGROUND Chemotherapy-induced peripheral neuropathy(CIPN)is a severe and longlasting side effect caused by various anticancer agents that damage sensory,motor and autonomic nerves.It can cause maladaptive behaviors,including disease severity,anxiety,depression,sleep disorders,falls,and social impairment.These disorders have physical,psychological and social effects on patients and can seriously influence their quality of life.AIM To investigate the current situation of psychosocial adaptation to the disease and its influencing factor in patients with CIPN.METHODS A convenience sampling method was used to select 233 patients with CIPN in our hospital from February to August 2021.In addition,a cross-sectional survey was conducted using a sociodemographic questionnaire,the Self-Report Psychosocial Adjustment to Illness Scale,and the European Organisation for the Research and Treatment of Cancer Quality of Life CIPN20(QLQ-CIPN20).Factors influencing psychosocial adaptation in patients with CIPN were analyzed by t-test or one-way analysis of variance,correlation analysis,multiple stepwise regression analysis,and structural equation models.RESULTS The psychosocial adaptation score of patients with CIPN was 52.51±13.18.Multivariate analysis showed that autonomic nerves,tumor stage,motor nerves,education level,availability of caregivers,semi-retirement status,CIPN grade were independent risk factors for patients with CIPN(P<0.05).Structural equation models showed that QLQ-CIPN20 mediated the relationship between CIPN grade,tumor stage,and psychosocial adaptation.CONCLUSION Patients with CIPN have poor psychosocial adaptation and are affected by a variety of physiological,psychological,and social factors.Patients’adaptive responses should be assessed,and targeted interventions implemented.
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.
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.
文摘With the clinical application of various chemotherapeutic drugs,the side effects are also followed.Diarrhea is one of the most serious side effects of chemotherapy.A large number of clinical and experimental studies have proven that traditional Chinese medicine has great prospects in relieving chemotherapy-related diarrhea.The article mainly discusses the mechanism of chemotherapy-related diarrhea and the prospect of traditional Chinese medicine in relieving the mechanism of chemotherapy-related diarrhea.
文摘Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy. Neurokinin-1 receptor antagonists (NK1-RAs) have been incorporated in the contemporary management of CINV. However, clinical studies on NK1-RAs have shown mixed results in reducing CINV risk. Most studies focused on the use of aprepitant (APR) and casopitant (CAS) in breast cancer patients receiving AC-type (doxorubicin and cyclophosphamide) chemotherapy. In this study, we compared the study design and clinical efficacies of these NK1-RAs in reducing CINV risk. Among the selected eight studies, 4 APR Randomized Controlled Trials (RCTs), 2 APR Observational Studies (OSs) and 2 CAS RCTs were identified. Patient-related characteristics such as the proportion of females (60.0% - 100.0%), age (46.5 - 59.5 years), histories of motion (5.6% - 47.0% in NK1-RA arms) and morning sicknesses (14.2% - 45.0% in NK1-RA arms) and types of antiemetic regimens;as well as chemotherapy-related characteristics such as the proportion of patients on AC chemotherapy (15.0% - 100.0%) varied greatly. In terms of efficacies, both APR and CAS improved overall CR and vomiting in majority of the studies. None of the studies, however, demonstrated that NK1-RA could provide adequate nausea control. To conclude, NK1-RAs are effective in improving vomiting and overall CR, but not useful in controlling nausea or attaining CC, the ideal CINV endpoint. A shift in paradigm is needed for future CINV research. As healthcare providers continue to strive for optimum CINV control in their patients, we hope this review can help them make better informed clinical decisions.
基金National and Natural Science Foundation of China:DGKZ Acts as a Potential Oncogene in Osteosarcoma Proliferation through Interaction with ERK1/2 and MYC Pathway (Grant Number 81972521)。
文摘OBJECTIVE: To assess the efficacy and safety of Neiguan(PC6) acupoint acustimulation in preventing chemotherapy-induced nausea and vomiting(CINV),especially for patients with guideline-inconsistent CINV prophylaxis(GICP) due to personal reasons METHODS: From January 2021 to December 2021, 373 patients suffered from solid malignancy were recruited according to the inclusion criteria. Complete response(no emesis and no rescue medication use) rate during the overall phase(0-120 h of each chemo-cycle) was the primary assessment of CINV control. The Functional Living Index-Emesis(FLIE) questionnaire was investigated among these patients as a secondary 'quality of life' objective to assess the impact of CINV on patients' daily life by recording score of nausea and vomiting. RESULTS: With acustimulation of Neiguan(PC6) acupuncture point through a portable, noninvasive and user-friendly device, in terms of complete response rate and scores in nausea/vomiting by FLIE questionnaire, patients achieve a better outcome in highly emetogenic chemotherapy(HEC) induced CINV, especially GICP subgroup. Meanwhile, analysis also demonstrated this tendency existed in other patients with HEC/GCCP(guideline consistent CINV prophylaxis) and moderate emetogenic chemotherapy, although the difference was not significant. CONCLUSION: Considering advantages of Neiguan(PC6) acustimulation such as noninvasive, covered by medical insurance and few side effects, we believe it would be an ideal auxiliary tool in CINV control, especially in patients who receive highly emetogenic chemoprotocol and are reluctant to GCCP for economic reasons.
文摘Objective: To observe the clinical efficacy and differences of the Zhuyu Juanbi formula delivered through ultrasound at Zusanli on patients with chemotherapy-induced peripheral neuropathy (CIPN) due to paclitaxel injection. Methods: A total of 72 breast cancer patients with CIPN were randomly divided into two groups. The treatment group (36 cases) was treated with oral methylcobalamin plus ultrasonic medicine permeating Zhuyu Juanbi formulae, while the control group (36 cases) was treated with oral methylcobalamin alone. Following two 2 cycles of continuous treatment, the efficacy of peripheral neurotoxicity, TCM syndrome score, FACT/GOG-Ntx score, total neuropathy score, and safety indicators of gynecological cancer patients were observed in the two groups. Result: In the treatment of CIPN, the addition of ultrasonic medicine permeating Zhuyu Juanbi formulae was more effective than oral methylcobalamin alone in reducing peripheral neurotoxicity and improving the quality of life of patients. The difference between the two groups was statistically significant (P < 0.05), and ultrasound drug penetration Zhuyu Juanbi formulae significantly reduced the FACT/ GOG-Ntx score and TNS score in the treatment group. In terms of drug safety, it rarely caused adverse reactions such as grade 3 and 4 leukopenia, and the safety profile was therefore good. Conclusion: The combination of ultrasonic medicine permeating Zhuyu Juanbi formulae and methylcobalamin has been demonstrated to be an effective treatment for peripheral neurotoxicity in patients with PIPN. It has been shown to significantly improve the clinical symptoms of PIPN patients, improve the quality of life of patients, and have a good safety profile.
文摘In the present paper, the authors analyze the academic theses of acupuncture for treatment of leucopenia induced by chemo or radio therapy. A total of 14 theses are retrieved and all written in Chinese. Quantitative meta analysis is done for 4 studies of dichotomous data and 5 studies of continuous data. Both of them have positive results. Majority of these trials have methodological and/or reporting shortcomings. Overall, the existing evidence supports the value of acupuncture for the treatment of leucopenia induced by chemo or radio therapy. However, the evidence is still not fully convincing. There is an urgent need for well planned, large scale and multiple center studies to assess the effectiveness and cost effectiveness of acupuncture under real life conditions.