Immortal Time Bias-Corrected Effectiveness of Traditional Chinese Medicine in Non-Small Cell Lung Cancer (C-EVID): A Prospective Cohort Study.

Background: Relatively little is known about the effect of traditional Chinese medicine (TCM) on prognosis of non-small cell lung cancer (NSCLC). Methods: In this nationwide, multicenter, prospective, cohort study, eligible patients aged 18-75 years with radical resection, and histologically confirmed stage II-IIIA NSCLC were enrolled. All patients received 4 cycles of standard adjuvant chemotherapy. Patients who received Chinese herbal decoction and (or) oral Chinese patent medicine for a cumulative period of not less than 6 months were defined as TCM group, otherwise they were considered as control group. The primary endpoint was DFS calculated using the Kaplan-Meier method. A time-dependent Cox proportional hazards model was used to correct immortal time bias. The secondary endpoints included DFS in patients of different characteristics, and safety analyses. This study was registered with the Chinese Clinical Trial Registry (ChiCTR1800015776). Results: A total of 507 patients were included (230 patients in the TCM group; 277 patients in the control group). The median follow-up was 32.1 months. 101 (44%) in the TCM group and 186 (67%) in the control group had disease relapse. The median DFS was not reached in the TCM group and was 19.4 months (95% CI, 14.2 to 24.6) in the control group. The adjusted time-dependent HR was 0.61 (95% CI, 0.47 to 0.78), equalling to a 39% reduction in the risk of disease recurrence with TCM. the number needed to treat to prevent one patient from relapsing was 4.29 (95% CI, 3.15 to 6.73) at 5 years. Similar results were observed in most of subgroups. Patients had a significant improvement in white blood cell decrease, nausea, decreased appetite, diarrhea, pain, and fatigue in the TCM group. Conclusion: TCM may improves DFS and has a better tolerability profile in patients with stage II-IIIA NSCLC receiving standard chemotherapy after complete resection compared with those receiving standard chemotherapy alone. Further studies are warranted.

Bioactivity, Compounds Isolated, Chemical Qualitative, and Quantitative Analysis of Cymbaria daurica Extracts.

Cymbaria daurica L. is widely used in traditional Mongolian medicine for the treatment of impetigo, psoriasis, pruritus, fetotoxicity, and diabetes. Therefore, the anti-inflammatory and α-glucosidase-inhibitory activities of four polar C. daurica extracts (water, n-butanol, ethyl acetate, and petroleum ether extract) were preliminarily evaluated to identify the active extracts. We also investigated the chemical composition of the active extracts by phytochemical analysis. The n-butanol and ethyl acetate extracts exhibited significant (p < 0.05) anti-inflammatory activities by inhibiting lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells. None of the tested extracts exhibited cytotoxic effects at the effective concentrations. The ethyl acetate extract significantly inhibited α-glucosidase activity, and the inhibition potency was equivalent to that of acarbose (p > 0.05). The n-Butanol extract presented the second highest inhibitory activity. As the n-butanol and ethyl acetate extracts were found to have potent anti-inflammatory and α-glucosidase-inhibitory activities, we separated and identified 10 compounds from the extracts. Among them, vanillic acid, cistanoside F, echinacoside, arenarioside, verbascoside, isoacteoside, and tricin were isolated from C. daurica for the first time. Further, 30 compounds from the n-butanol and ethyl acetate extracts of C. daurica were identified using UHPLC-Q-Exactive. The present study demonstrates for the first time that C. daurica contains phenylethanoid glycosides. In addition, this novel HPLC method was subsequently used for simultaneous identification of five compounds in the n-butanol and ethyl acetate extracts of C. daurica. This study provides a chemical basis for further characterization and utilization of C. daurica, which could be a potential source of novel anti-diabetic and anti-inflammatory agents.

Association between Chinese Medicine Therapy and Survival Outcomes in Postoperative Patients with NSCLC: A Multicenter, Prospective, Cohort Study.

OBJECTIVE: To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC). METHODS: This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome. RESULTS: Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307-0.567)]. A longer duration of CM therapy (6-12 months, 12-18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I-IIIA (HR=0.50, 95% CI: 0.37-0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33-0.71), DFS was even longer among CM treatment group patients. CONCLUSIONS: Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398).

[Analysis on prescription rules of Chen Baogui's prescriptions for treating epigastric fullness based on data mining].

To summary and analyze the prescription rules of Professor Chen Baogui, a famous traditional Chinese medicine (TCM) doctor, for treating epigastric fullness. Professor Chen Baogui's prescriptions for treating epigastric fullness were collected and the treatment data were input into traditional Chinese medicine inheritance support system (TCMISS) to analyze the rules of the prescriptions by using data mining methods. Based on the screened 214 cases, the treatment experience of Professor Chen Baogui for treating epigastric fullness was summarized and analyzed. It was found that Professor Chen gave priority to recuperation of Qi activity. The results of four properties and five tastes showed Professor Chen's medication compatibility rules: one was simultaneous use of cold and warm drugs, and the other was simultaneous use of pungent drugs for dispersion and bitter drugs for purgation. In drug use, the basic prescriptions had the efficacy of promoting Qi circulation and regulating viscera function, additionally with the drugs with functions of eliminating digestion and inducing stagnation, activating blood circulation to dissipate blood stasis, replenishing Qi and nourishing Yin, tranquilizing mind, strengthening muscles and bones according to the TCM syndrome type. The clinical experience of Professor Chen for treating epigastric fullness was objectively summarized with the help of TCMISS, which was significant for analyzing and inheriting academic thinking and medication experience from famous TCM doctors.

A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy.

Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of ~25 nm and vertical distance of ~1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.

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.

Anti-coxsackie virus B3 norsesquiterpenoids from the roots of Phyllanthus emblica.

Three new norsesquiterpenoid glycosides, 4'-hydroxyphyllaemblicin B (1) and phyllaemblicins E (2) and F (3), were isolated from the roots of Phyllanthus emblica, together with three known compounds, phyllaemblic acid (4), phyllaemblicin B (5), and phyllaemblicin C (6). Of these, 3 is a new norsesquiterpenoid dimer. The structures of 1-3 were established by spectroscopic data information and by acidic hydrolysis. The isolated compounds, together with two other known analogues, phyllaemblic acid methyl ester (7) and phyllaemblicin A (8), were evaluated for their antiviral activity toward coxsackie virus B3 (CVB3) by an in vitro cytopathic effect inhibitory assay. Compounds 5-7 exhibited strong anti-CVB3 activity.

[The study on the extraction and the antivirus activity of amylose extracted from Grateloupia filicina].

OBJECTIVE: To determine the activity of anti-Herpes simplex II virus (HSV-2) of amylose extracted from Grateloupia filicina. METHODS: Grateloupia filicina amylose was extracted by five kinds of abstraction methods and its suppression on Herpes simplex II virus was observed on cell level in three aspects: the drug activity of protecting cell, the drug influence of HSV-2 proliferation and the drug synthesis action of HSV-2. RESULTS: Grateloupia filicina had prominence anti-Herpes simplex II virus activity, IC50 of amylose extracted by water distilling and ethanol sedimentation was 5.80 microg/ml. CONCLUSION: It suggest that the antivirus activity happen in the stage of HSV-2 binding, adsorption and ingression with Vero cell.