Progress in diagnosis and treatment of small cell lung cancer with integrated traditional Chinese and Western medicine

Lung cancer is one of the most common major diseases that seriously threaten human health,lung cancer includes small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC).Although patients with SCLC account for about 20%of the total number of patients with lung cancer,the mortality rate is much higher than that of patients with NSCLC.Integrated traditional Chinese and Western medicine has obvious advantages in the treatment of patients with SCLC.According to the relevant literature reports on the treatment of SCLC in recent years,this article will summarize the research progress of integrated traditional Chinese and western medicine in the treatmentof SCLC from the aspects of traditional Chinese medicine(TCM)combined with surgery,chemotherapy,radiotherapy,and molecular targeted therapy.

Progress in research of single-flavor Chinese medicine extracts in treatment of non-small cell lung cancer

Lung cancer is one of the diseases with high morbidity and mortality,and non-small cell lung cancer accounts for a large proportion of it.Traditional Chinese medicine has a long history in treating tumors.More and more researchers have paid more attention to it.At present,many studies have proved that traditional Chinese medicine extracts such as astragalus,turmeric,ginseng,coix seed,and gallbladder can inhibit tumor cell proliferation,and have synergistic effects when used in combination with radiotherapy and chemotherapy Its mechanism of action is mostly related to regulating the cell cycle,inhibiting the expression of cancer-related genes,and inducing apoptosis.It is believed that with the development of purification technology,Chinese medicine extracts will play a greater role.

Plasma Vitamin D Levels And Vitamin D Receptor Polymorphisms Are Associated with Survival of Non-small Cell Lung Cancer

Objective：Vitamin D and its receptor（VDR） involve in multiple cellular processes and play an important role in the initiation and progression of malignancy.Thus we hypothesized that plasma vitamin D levels and single nucleotide polymorphisms（SNPs） in VDR may be of prognostic significance in non-small cell lung cancer（NSCLC）.Methods：We examined plasma 25-hydroxyvitamin D [25（OH）D] levels in 87 patients diagnosed with NSCLC using enzyme-linked immunosorbent assay（ELISA） and genotyped seven potentially functional SNPs in VDR in 568 NSCLC patients on Illumina Golden Gate platform.Results：Patients with higher plasma 25（OH）D levels had worse survival than patients with lower ones（P for trend = 0.048）.The SNPs of rs1544410 and rs739837 were independently associated with NSCLC survival（adjusted HR = 1.61,95% CIs = 1.06-2.45 for rs739837 AA vs AC/CC and adjusted HR = 1.51,95% CIs = 1.06-2.16 for rs1544410 AG/AA vs GG）.A joint effect was observed between rs1544410 and rs739837 and the risk of death elevated as the number of unfavourable genotypes patients carried increased（P for trend = 0.003）.There were no significant associations between VDR polymorphisms and plasma 25（OH）D levels.Conclusion：Our findings indicate that plasma 25（OH）D levels and genetic variants of VDR may serve as prognostic markers for NSCLC in this Chinese population.

Clinical Observation on Treatment of NonParvicellular Carcinoma of the Lung with Jin Fu Kang Oral Liquid

Jin Fu Kang Oral Liquid ([symbol: see text]), made of traditional Chinese drugs for supplementing qi and nourishing yin, was developed according to the common symptoms in lung carcinoma with deficiency of both qi and yin. Of the 96 cases in the Jin Fu Kang group, 1 case got complete remission (CR) after treatment, 8 cases partial remission (PR), 52 cases no change (NC), PR + NC covering 63.5%. Of the 52 cases in the group of Jin Fu Kang plus chemotherapy, 11 cases got PR after treatment, 26 cases NC, PR + NC covering 71.2%. Of the 25 cases in the chemotherapy group, 4 cases got PR after treatment, 11 cases NC, PR + NC covering 60.0%. The results show that the therapeutic effectiveness in the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy was better than that in the chemotherapy group. The one-year survival rate and the two-year survival rate after treatment in the Jin Fu Kang group were 67.3% and 67.3% respectively; 66.7% and 66.7% in the group of Jin Fu Kang plus chemotherapy; and 40.3% and 0.0% in the chemotherapy group. The improvement of clinical symptoms, increase of body weight and improvement of health situation (KPS marks) after treatment in both the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy were better than that in the chemotherapy group. Some indicators of immunology and hemogram after treatment were greatly improved in the Jin Fu Kang group, worse in the chemotherapy group, but no obvious improvement in the group of Jin Fu Kang plus chemotherapy.

Efficacy and safety of Kang’ai injection adjunct with TP chemotherapy for the treatment of non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials

Background:Combination therapy with traditional Chinese medicine and chemotherapy was proposed as a therapeutic strategy for non-small cell lung cancer patients.Therefore,we performed a systematic review and metaanalysis of randomized controlled trials to assess effects of this combination therapy on non-small cell lung cancer.To evaluate the efficacy and safety of the Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy in the treatment of non-small cell lung cancer.Methods:A randomized controlled study of the Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy in the databases of China National Knowledge Infrastructure Database,WanFang Database,VIP Database,Sino-Med Database,PUBMED,EMBASE and Cochrane library was searched by computer.The literatures published from the database establishment to July 1,2020 were included in the search scope.After 2 evaluators independently evaluated and cross checked the quality of the study,Revman 5.3 was used to meta analyze the clinical effect of the Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy on patients with non-small cell lung cancer.Results:A total of 1,370 lung cancer patients were included in 20 RCTs.The results of meta-analysis showed that there were significant differences between the 2 groups in clinical efficacy(RR=1.32,95%CI(1.20,1.44)),quality of life(RR=1.44,95%CI(1.32,1.57)),immune function(MD=0.53,95%CI(0.23–0.83)),adverse reactions(RR=0.49,95%CI(0.41,0.58)).Conclusion:The Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy is effective and safe in the treatment of non-small cell lung cancer,and has great prospects for further development.However,the quality of evidence was very low-to-moderate.Considering the poor quality of evidence,we are not very confident in the results.We look forward to more research and update results in the future and improve the evidence quality.

The Therapeutic Effects of the Radiotherapy Plus TCM Treatment Observed in Senile Non-Parvicellular Lung Cancer Patients at the Late Stage

47 senile non-parvicellular lung cancer patients at stage Ⅲ or Ⅳ were randomly divided into a treatment group (26 cases) treated by radiotherapy plus traditional Chinese medicine (TCM) and a control group (21 cases) treated only by radiotherapy for observation of the therapeutic effects.The patients in the treatment group orally took Chinese medicine during and after the radiotherapy.There was no obvious difference in short-term therapeutic effects between the two groups,but the long-term curative effects in the treatment group was obviously superior to that in the control group (P<0.05 or P<0.01).Conclusion:radiotherapy plus TCM can prolong the survival period for senile non-parvicellular lung cancer patients.

Effect of TCM Combined with Chemotherapy on Immune Function and Quality of Life of Patients with Non-small Cell Lung Cancer inStage Ⅲ-Ⅳ

Objective: To observe and compare the effect of traditional Chinese medicine (TCM) combined with chemotherapy (CT) on immune function and quality of life (QOL)of patients with non-small cell lung cancer (NSCLC) in stage Ⅲ-Ⅳ. Methods: One hundred cases with stage Ⅲ-Ⅳ NSCLC were randomly divided into two groups. The treated group (n=50) received CT combined with TCM, and the control group received CT alone. The percentage of T lymphocyte subset in peripheral blood and the change of natural killer (NK) cell count were observed after treatment. The QOL and tolerance of CT were also compared between the two groups after treatment. Results: In the treated group, CD3 cell count, CD4 cell count, CD4/ CDg ratio and NK cell activity were higher than those in control group, while CD8 cell count in the treated group was lower than that in the control group (P<0.05), and QOL and tolerance of CT in the treated group were also better (P<0.05). Conclusion: TCM combined with CT could raise the patients' ability in tolerating CT in stage Ⅲ-ⅣNSCLC.

Modulating the crosstalk between macrophage and Th17: potential mechanism of natural products on acute lung injury

Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in ICU patients.Lung injury is a common organ damage observed in sepsis patients.Macrophages and Th17 cells,as crucial components of innate and adaptive immunity,play pivotal roles in the development of sepsis-induced acute lung injury(ALI).This review summarizes the alterations and mechanisms of macrophages and Th17 cells in sepsis-induced ALI.By focusing on the“cross-talk”between macrophages and Th17 cells,this review aims to provide a solid theoretical foundation for further exploring the therapeutic targets of traditional Chinese medicine formulas in the treatment of sepsis complicated with ALI,thereby offering insights and guidance for the clinical application of traditional Chinese medicine in managing sepsis-associated ALI.

Traditional Chinese medicines for non-small cell lung cancer: Therapies and mechanisms

The most common subtype of lung cancer is non-small cell lung cancer(NSCLC), which has a poor prognosis and seriously threatens the health of human beings. The multidisciplinary comprehensive treatment model has gradually become the mainstream of NSCLC treatment. Traditional Chinese medicine(TCM) can be used effectively either as an adjunctive therapy or alone throughout the NSCLC therapy,which has a significant impact on survival, quality of life, and reduction of toxicity. Therefore, this paper reviewed the theoretical basis, the latest clinical application, and combined treatment mechanisms in order to explore the advantage stage of TCM treatment and the synergistic therapeutic mechanisms.

Retrospective Clinical Study on Integrated Chinese and Western Medicine in Treatment of Limited-Stage Small Cell Lung Cancer

Objective: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival(PFS) and overall survival(OS) of limited-stage small-cell lung cancer(LS-SCLC) patients after the first-line chemoradiotherapy. Methods: The data of 67 LS-SCLC patients who received combined treatment of Chinese medicine(CM) and Western medicine(WM) between January 2013 and May 2020 at the outpatient clinic of Guang’anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method(Kaplan–Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. Results: The median PFS in the CM and WM combination treatment group and the WM group were 19 months(95% CI: 12.36–25.64) vs. 9 months(95% CI: 5.96–12.04), respectively, HR=0.43(95% CI: 0.27–0.69, P <0.001). The median OS in the CM and WM combination group and the WM group were 34.00 months(95% CI could not be calculated) vs. 18.63 months(95% CI: 16.43–20.84), respectively, HR=0.40(95% CI: 0.24–0.66, P<0.001). Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months(P<0.001). Conclusion: The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone.(Registration No. Chi CTR2200056616)

自拟健脾除积方联合信迪利单抗及化疗对晚期非小细胞肺癌患者的影响

目的:探讨自拟健脾除积方联合信迪利单抗及化疗对晚期非小细胞肺癌患者疾病控制率、中医症候积分及不良反应的影响。方法:选取2020年10月—2022年10月在我院就诊的102例晚期非小细胞肺癌患者,随机分为观察组和对照组,每组各51例,对照组在吉西他滨+顺铂化疗的基础上给予信迪利单抗,观察组在对照组基础上联合自拟健脾除积方治疗。比较两组患者临床疗效、治疗前后中医症候积分、肿瘤标志物水平及不良反应。结果:观察组有效率和疾病控制率明显高于对照组(P<0.05);观察组和对照组治疗后中医症候积分均显著低于治疗前;治疗后,观察组中医症候积分显著低于对照组(P<0.05)。两组治疗后血清铁蛋白(SF)、鳞状细胞癌抗原(SCCA)及癌胚抗原(CEA)水平均显著低于同组治疗前,观察组SF、SCCA、CEA水平均显著低于对照组。观察组白细胞计数减少、恶心、呕吐症状总发生率显著低于对照组(P<0.05)。结论:自拟健脾除积方联合信迪利单抗对晚期非小细胞肺癌患者治疗效果较好,可改善患者中医症候,具有较高的安全性。

参芪补肺汤联合孟鲁司特钠片治疗非小细胞肺癌术后慢性咳嗽的临床研究

目的观察参芪补肺汤联合孟鲁司特钠片治疗非小细胞肺癌(NSCLC)术后慢性咳嗽的临床疗效。方法将100例NSCLC术后慢性咳嗽患者按照随机数字表法分为2组,对照组50例予孟鲁司特钠片治疗,治疗组50例在对照组治疗基础上联合参芪补肺汤治疗。2组均治疗4周。比较2组治疗前后咳嗽症状、莱彻斯特咳嗽生命质量问卷(LCQ-MC)评分、肺功能指标[用力肺活量(FVC)、第1 s用力呼气容积(FEV_(1))、FEV_(1)/FVC、呼气峰流量(PEF)]、炎症指标[白细胞介素8(IL-8)、肿瘤坏死因子α(TNF-α)、降钙素原(PCT)、白细胞介素6(IL-6)]、中医证候评分,并统计2组不良反应发生率、复发率和疗效。结果治疗组总有效率98.00%(49/50),对照组总有效率82.00%(41/50),治疗组临床疗效优于对照组(P<0.05)。2组治疗后日间与夜间咳嗽症状评分均较本组治疗降低(P<0.05),且治疗组治疗后均低于对照组(P<0.05),2组治疗后LCQ-MC评分均升高(P<0.05),且治疗组治疗后高于对照组(P<0.05)。2组治疗后FVC、FEV_(1)、FEV_(1)/FVC、PEF均较本组治疗前升高(P<0.05),且治疗组治疗后均高于对照组(P<0.05)。2组治疗后IL-8、TNF-α、PCT、IL-6均较本组治疗降低(P<0.05),且治疗组治疗后均低于对照组(P<0.05)。2组治疗后中医证候各项评分均较本组治疗前降低(P<0.05),且治疗组治疗后均低于对照组(P<0.05)。治疗组不良反应发生率4.00%(2/50),对照组不良反应发生率18.00%(9/50),治疗组不良反应发生率低于对照组(P<0.05)。治疗组复发率4.08%(2/49),对照组24.39%(10/41),治疗组复发率低于对照组(P<0.05)。结论参芪补肺汤联合孟鲁司特钠片治疗NSCLC术后慢性咳嗽患者疗效显著,能够有效缓解咳嗽症状,改善患者肺功能,提升LCQ-MC评分,且不良反应发生率与复发率降低,具有临床应用价值。

Effects of Combined Chinese Drugs and Chemotherapy in Treating Advanced Non-small Cell Lung Cancer

Objective:To evaluate the efficacy and side effects of combined Chinese drugs and chemotherapy in treating advanced non-small cell lung cancer(NSCLC).Methods:Sixty-three patients with stageⅢB andⅣNSCLC hospitalized from October 2001 to October 2008 were enrolled and assigned to two groups using a randomizing digital table,with 33 patients in the treatment group and 30 in the control group. They were all treated with the Navelbine and Cisplatin(NP) chemotherapy,but to the treatment group the Chinese drugs Sh...

Pharmacological Effects of Serum Containing Chinese Medicine Bushen Huayu Jiedu Compound Recipe (补肾化瘀解毒复方) in Lung Cancer Drug-resistance Cells

Objective： To explore the pharmacologic effects of Chinese medicine Bushen Huayu Jiedu Compound Recipe （补肾化瘀解毒复方,BSHYJDR） in drug-resistance cells of lung cancer. Methods： Human lung adenocarcinoma A549/DDP cell strain was selected, serum pharmacology and flow cytometer （FCM） method were adopted, $180 tumor-bearing mice and normal mice were given, through gastrogavage, different doses of a decocted concentration of BSHYJDR. Serum from the abdominal aorta was taken to observe the effect of drug-serum on cisplatin （DDP） concentration, free Ca^2＋ concentration and the expression of lung drug-resistance protein LRP-56 in A549/DDP cells. Results： Compared with the drug-resistance group, the intracellular DDP concentration in the group taking a high dose and the normal group of Chinese medicine showed significant difference （P〈0.05）, while no significant difference was found in the low-dose group （P〉0.05）. Compared with the drug-resistance group, the Ca^2＋ concentration in cells and the expression of LRP in lung cancer drug-resistance cells A549/DDP of the high-dose group, the low-dose group and the normal group of Chinese medicine were significantly different （all P〈0.01）, the LRP expression of the normal group was obviously higher than that of the drug-resistance group （P〈0.05）. Cenclusien： It was indicated that serum containing Chinese medicine BSHYJDR in the tumor-bearing mice and the normal mice had certainly different, tumor-bearing mice serum containing could improve drug concentration in lung cancer drug-resistance cells, prevent the inflow and release of Ca^2＋, and inhibit the expression of the drug-resistance gene in the lung cancer drug-resistance cells, which might be the mechanism of BSHYJDR in enhancing the efficacy in reversing and inhibiting tumor.

Clinical Observation on the Combined Treatment of 57 Cases of Non-small Cell Lung Cancer Using Argon-Helium Cryosurgery and Chinese Herbal Medicine

Objective： To observe the clinical effect of the combined therapy using argon-helium cryosurgery （Ar-He knife） and Chinese herbal medicine in treating non-small cell lung cancer （NSCLC）. Methods： Fifty-seven patients of NSCLC were treated with the combined therapy and observed. Results： The treatment was successfully completed in all patients with mild adverse reactions. The effective rate was 83.8% 3 months after the operation, 79.6% 6 months after the operation, and 77.3% 12 months after the operation, with median survival of 9 months. The survival rate after 12 months was 46.67% （21/45）, 34.62% （9/26） after 18 months, and 36.36% （4/11） after 24 months. Conclusion： Argon-helium cryosurgery therapy is superior in its assured orientation, quick tumor load deprivation and less post- operational reaction. Combined with Chinese herbal medication, Argon-helium cryosurgery therapy can prolong survival time, relieve clinical symptoms, and elevate the quality of life in NSCLC patients, and is thus worthy of promotion.

The Treatment of Non-Small Cell Lung Cancer by Interstitial 1-125 Seeds Implantation Combined with Chemotherapy and Chinese Medicine

Objective： To investigate the effects of brachytherapy with computed tomography-guided percutaneous radioactive 1-125 seeds interstitial implantation （ISI） synchronized chemotherapy and Chinese medicine （CM） for the treatment of advanced stage of non-small cell lung cancer （NSCLC）. Methods： Ninety patients diagnosed with NSCLC by biopsy were randomly assigned to three groups： the synchronized therapy group （A）, the chemotherapy plus CM-treated group （B）, and the chemotherapy-treated group （C）; a 2-month course of treatment was administered to them all. The effectiveness of treatment was evaluated based on tumor size, tumor markers （carcinoembryonic, squamous cell carcinoma-associated antigen, and cytokeratin 19 fragment）, clinical symptoms, and quality of life （QOL） in patients. Results： The total effective rates of Groups A to C were 83.33%, 46.67%, and 43.33%, respectively. The tumor markers were reduced obviously in Group A, showing significant difference compared with those in the other two groups. Additionally, QOL was elevated and cancer-related symptoms were alleviated more significant in Group A than those in Group C （all P〈0.05）. Conclusion： The synchronized therapy of 1-125 implantation with chemotherapy and CM was a safe therapeutic method and can be regarded as a new mode for treatment of advanced-stage NSCLC.

Chinese Medicine Treatment Prolonged Survival in Small Cell Lung Cancer Patients:A Clinical Observation

Objective To evaluate the effect of Chinese medicine(CM)treatment on survival time and quality of life(QOL)in patients with small cell lung cancer(SCLC).Methods This was an exploratory and prospective clinical observation.Patients diagnosed with SCLC receiving CM treatment were included and followed up every 3 months.The primary outcome was overall survival(OS),and the secondary outcomes were progression-free survival(PFS)and QOL.Results A total of 136 patients including 65 limited-stage SCLC(LS-SCLC)patients and 71 extensive-stage SCLC(ES-SCLC)patients were analyzed.The median OS of ES-SCLC patients was 17.27 months,and the median OS of LS-SCLC was 40.07 months.The survival time was 16.27 months for SCLC patients with brain metastasis,9.83 months for liver metastasis,13.43 months for bone metastasis,and 18.13 months for lung metastasis.Advanced age,pleural fluid,liver and brain metastasis were risk factors,while longer CM treatment duration was a protective factor.QOL assessment indicated that after 6 months of CM treatment,scores increased in function domains and decreased in symptom domains.Conclusion CM treatment might help prolong OS of SCLC patients.Moreover,CM treatment brought the trend of symptom amelioration and QOL improvement.These results provide preliminary evidence for applying CM in SCLC multi-disciplinary treatment.

Multidisciplinary and Comprehensive Chinese Medicine for Advanced Non-Small Cell Lung Cancer Patients:A Retrospective Study of 855 Cases

Objective To investigate the effects of multidisciplinary and comprehensive Chinese medicine(CM)treatments on progression-free survival(PFS)and median survival time(MST)in patients with advanced non-small cell lung cancer(NSCLC)and identify factors that influence progression and prognosis.Methods Clinical data of 855 patients with advanced NSCLC who received multidisciplinary and comprehensive CM treatments at Longhua Hospital from January 2009 to December 2018 were retrospectively analyzed.Univariate analysis was performed by the Kaplan-Meier method and log-rank sequential inspection.Multivariate analysis of significant variables from the univariate analysis was performed with Cox regression modeling.Key factors correlated to progression and prognosis were screened out,and a Cox proportional hazard model was established to calculate the prognostic index.Results The PFS and MST of 855 advanced NSCLC patients were 9.0 and 26.0 months,respectively.The 1-,2-,3-,and 5-year survival rates were 79.2%,54%,36.2%,and 17.1%,respectively.Gender,pathologic type,and clinical stage were independent prognostic risk factors;surgical history,radiotherapy,treatment course of Chinese patent medicine,intravenous drip of Chinese herbal preparation,duration of oral administration of Chinese herbal decoction(CHD),and intervention measures were independent prognostic protective factors.Gender was an independent risk factor for progression,while operation history and oral CHD administration duration were independent protective factors(all P<0.05).Women with stage IIIb–IIIc lung adenocarcinoma had the best outcomes.Conclusions Female patients have lower progression risk and better prognoses than male patients,younger patients have higher progression risk but better long-term prognoses than the elderlys,and patients with lower performance status scores are at lower risk for progression and have better prognoses.Comprehensive CM treatments could significantly reduce progression risk,improve prognosis,and prolong survival time for patients with advanced NSCLC.This treatment mode offers additional advantages over supportive care alone.

Comprehensive Treatment with Chinese Medicine in Patients with Advanced Non-Small Cell Lung Cancer: A Multicenter, Prospective, Cohort Study

Objective： To determine whether additional Chinese medicine（CM） could prolong survival and improve the quality of life（QOL） in patients with advanced non-small cell lung cancer（NSCLC） compared with Western medicine（WM） alone. Methods： This was a multicenter, prospective cohort study. A total of 474 hospitalized patients with stage Ⅲ–Ⅳ NSCLC were recruited and divided into 2 groups. Patients in the WM group received radiotherapy, chemotherapy, and optimal supportive therapy according to the National Comprehensive Cancer Network（NCCN） guidelines. In the integrative medicine（IM） group, individualized CM（Chinese patent medicines and injections） and WM were administered. The primary end point was overall survival, and the secondary end points were time to disease progression, adverse events, and QOL. Follow-up clinical examinations and chest radiography were performed every 2 months. Results： The median survival was 16.60 months in the IM group and 13.13 months in the WM group（P〈0.01）. The incidences of loss of appetite, nausea, and vomiting in the IM group were significantly lower than those in the WM group（P〈0.05）. The QOL based on Functional Assessment of Cancer Therapy-Lung in the IM group was markedly higher than that in the WM group at the fourth course（P〈0.05）. Conclusions： Additional CM may prolong survival and improve the QOL patients with NSCLC. The adverse effects of radio-and chemotherapy may be attenuated as CM is used in combination with conventional treatments.