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Retinal dehydrogenase 5 (RDH5) is an important enzyme in the visual cycle. Several studies have reported that the RDH family may play crucial roles in tumor prognosis. However, the role of RDH5 in tumor prognosis is still unclear. We examined the mRNA level of RDH5 by using q-PCR in hepatocellular carcinoma (HCC) and adjacent non-cancerous tissues. The proliferation rate of HCC cells was detected by MTS assay, and the invasive ability was examined by transwell and scratch wound assays. The YAP protein localization and expression were visualized by immunofluorescence in two different cell lines. CpG islands in the promoter region were predicted by using the methprimer database. Clinical characteristics of a patient cohort data came from The Cancer Genome Atlas database. RDH5 was significantly downregulated in hepatocellular carcinoma tissues, and low RDH5 expression was associated with metastasis and poor patient prognosis. Functional assays revealed that the RDH5 promoter is methylated in HCC cell lines. Moreover, overexpressing RDH5 can suppress metastasis by reversing the epithelial-mesenchymal transition (EMT) process, and RDH5 also inhibits cell proliferation in HCC cell lines. Furthermore, suppressing RDH5 can activate the Hippo/YAP signaling pathway and promote the nuclear translocation of YAP. Clinical data demonstrated that RDH5 is an independent prognostic factor in HCC. In our study, we provided the first evidence that RDH5 plays a crucial role in suppressing proliferation and metastasis, and the RDH5 promoter is methylated in hepatocellular carcinoma. And as an important regulator, RDH5 can suppress the Hippo/YAP signaling pathway. Taken together, it revealed that RDH5 might be a potential therapeutic target in HCC patients.

Objective To study the use of Chinese medicine (CM) in cancer patients in southern China. Methods A total of 1,950 cancer patients finished questionnaires in four provinces in southern China. The survey included socio-demographic and clinical characteristics of participants, dosage forms, efficacy, and side effects. Results The study results showed that cancer patients with higher education (>12 years) were more likely to accept the treatment of Chinese herbs. There were 54.61% (1,065 cases) of patients chose Chinese herbs for the initial treatment and 14.46% (282 cases) chose Chinese herbs as monotherapy. Most patients (54.51%, 1,063 cases) continuously used CM for more than 6 months, and a few of them (212 cases) used CM for up to 3 years. All kinds of dosage forms of CM had been used, including CM decoction, CM patent prescription and CM injection. Concerning the efficacy in the view of patients, 40.31% (786 cases) believed that it would be effective to take Chinese herbs before they starting the anti-cancer treatment, and the percentage increased to 81.08% after 1-month CM treatment. The effect of Chinese herbs was mainly demonstrated by symptom relief and improvement of quality of life, and 8.31% (162 cases) of patients experienced control of tumor growth and decreased tumor markers. Furthermore, only 14.31% (279 cases) participants reported that they experienced side effects during CM treatment. Conclusion This large scale investigation reflects the current situation of domestic CM usage objectively and comprehensively, which might provide new ways for cancer treatment.

Early diagnosis and treatment of gastric precancerous lesions (GPL) are key factors for reducing the incidence and morbidity of gastric cancer. The study is aimed at examining GPL in mice induced by N-methyl-N-nitroso-urea (MNU) and to illustrate the underlying mechanisms of tumorigenesis. In this study, we utilized an in vivo MNU-induced GPL mouse model, and histopathological changes of the gastric mucosa were observed by hematoxylin and eosin (H&E-stain) and alcian blue (AB-PAS-stain). The level of miR-194-5p in the gastric mucosa was determined by real-time polymerase chain reaction. We used transmission electron microscopy to observe the effects of MNU on gastric chief cells and parietal cells. We performed immunohistochemical detection of HIF-1α, vWF, Ki-67, and P53, while the changes in the protein expression of key genes in LKB1-AMPK and AKT-FoxO3 signaling pathways were detected by western blot analysis. We demonstrated that the miR-194-5p expression was upregulated under hypoxia in GPL gastric tissues, and that a high miR-194-5p expression level closely related with tumorigenesis. Mechanistically, miR-194-5p exerted the acceleration of activities related to metabolic reprogramming through LKB1-AMPK and AKT-FoxO3 pathways. Furthermore, similar to miR-194-5p, high expression levels of AMPK and AKT were also related to the metabolic reprogramming of GPL. Moreover, we revealed the correlation between the expression levels of miR-194-5p, p-AMPKα, p-AKT, and FoxO3a. These findings suggest that miR-194-5p/FoxO3 pathway is important for the reversal of metabolic reprogramming in GPL. Thus, exploring strategies to regulate the miR-194-5p/FoxO3a pathway may provide an efficient strategy for the prevention and treatment of GPL.

The tumor prescriptions contained in Dictionary of Tumor Formulas, Compendium of Good Tumor Formulas, Chinese Pharmacopoeia, Ministry of Health Drug Standards for Chinese Medicine Formulas and National Compilation of Standards for Proprietary Chinese Medicines were selected and organized to construct a database for tumor prescriptions, and the data mining techniques were applied to investigate the prescription regularity of colorectal cancer prescriptions. The formula data were extracted after screening in strict accordance with the inclusion and exclusion criteria, and were then analyzed with Microsoft Excel 2010 for frequency statistics, Apriori block provided by SPSS Clementine 12.0 software for correlation rule analysis, and arules and arulesViz packages in R 4.0.2 software for correlation rule visualization. In addition, SPSS 18.0 software was used for cluster analysis and factor analysis, in which cluster analysis was performed by Ochiai algorithm with bicategorical variables in systematic clustering method and factor analysis was performed mainly with principal component analysis. A total of 285 prescriptions were included in the statistical analysis, and the frequency statistics showed that 43 herbs had been used more than 16 times. The association rules analysis showed that 26 high-frequency me-dicine pair rules were obtained, and the association rules for those dispelling evil spirits, strengthening the body, resolving stasis, dispelling dampness, etc. were visualized. In the cluster analysis, we generated a dendrogram from which 7 groups of traditional Chinese medicines with homogeneity were extracted. 10 common factors were obtained in the factor analysis. The types of herbal medicines involved in the colorectal cancer prescription included anti-cancer antidotes, strengthening and tonifying medicines, blood-regulating medicines, and expectorant medicines, corresponding to the treatment for eliminating evil spirits, strengthening, resolving stasis, and expectorating dampness. The prescriptions for anti-cancer detoxification were normally based on the pairs composed of Scutellaria barbata-Hedyotis diffusa and Sophora flavescens, Sargentodoxa cuneata, S. barbata, often combined with stasis relieving drug and dampness eliminating drug, reflecting the characteristics of treatment for both toxicity and stasis, dampness and toxicity simultaneously. The prescriptions for strengthening the righteousness and tonifying the deficiency were composed of Astragalus membranaceus and Atractylodes macrocephala mainly, exerting the effect of benefiting Qi, strengthening the spleen and drying dampness, tonifying kidney and essence, tonifying blood and invigorating blood. Meanwhile, anti-cancer detoxification medicines shall be reduced as much as possible. The compatibility of the medicines for the intestinal tract reflected the principle of using the right medicine for the right condition and eliminating evil spirits or strengthening the body, as appropriate.

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). 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. 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. 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)

Background Resveratrol (Res) inhibits ovarian cancer (OC) cell growth but its in vivo anti-OC effects are unclear due to the low bioavailability of systemically administered Res. Intraperitoneal administration may overcome this therapeutic dilemma because it makes Res directly affect the abdominal tumors. Ethanol and DMSO are common Res solvents, while their reliability and safety for long-term in vivo treatment remain unknown. Methods A rat orthotopic OC model was established using the rat NUTU-19 OC cell line. Res dissolved in 10% ethanol or 0.2% DMSO was injected intraperitoneally (20 mg/kg/day) into tumor-free and tumor-bearing rats for 2 weeks. The tumors were collected for gross, morphological and molecular examinations, and blood and ascitic samples were obtained for a CA125 ELISA. Res concentration in ovarian tissues was determined by high performance liquid chromatography (HPLC). Results The average tumor weight (0.187±0.065 g) of the Res-in-DMSO group was lower than that of untreated (0.426±0.091 g; P

Cisplatin (DDP) is the first-line chemotherapeutic agent against lung cancer. However, the therapeutic effect of DDP loses over time due to the acquired drug resistance in non-small cell lung cancer (NSCLC) cells. In recent years, the role of the traditional Chinese medicine (TCM) cordycepin (Cor) in cancer treatment has been attracting attention. However, the effects of Cor on DDP resistance in NSCLC are unclear. In the present study, we aimed to investigate the effects of Cor in combination with DDP on cell proliferation and apoptosis in NSCLC and explore possible underlying mechanisms. The cell proliferation and apoptosis were analyzed in NSCLC parental (A549) and DDP-resistant (A549DDP) cells treated with DDP alone or in combination with Cor both in vitro and in vivo. Different genes and signaling pathways were investigated between DDP-sensitive and DDP-resistant A549 cells by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The perturbations of the MAPK and PI3K-AKT signaling pathways were evaluated by Western blot analysis. Our data showed that Cor markedly enhanced DDP inhibition on cell proliferation and promotion of apoptosis compared to the DDP-alone group in both A549 and A549DDP cells. The synergic actions were associated with activation of AMPK; inhibition of AKT, mTOR, and downstream P709S6K; and S6 phosphorylation in the AKT pathway compared with DDP alone. Collectively, combination of Cor and DDP has a synergistic effect in inhibiting proliferation and promoting apoptosis of NSCLC cells in the presence or absence of DDP resistance. The antitumor activity is associated with activation of AMPK and inhibition of the AKT pathway to enhance DDP inhibition on NSCLC. Our results suggested that Cor in combination with DDP could be an additional therapeutic option for the treatment of DDP-resistant NSCLC.

Background Limited treatment strategies are available for squamous-cell lung cancer (SQLC) patients. Few studies have addressed whether immune-related genes (IRGs) or the tumor immune microenvironment can predict the prognosis for SQLC patients. Our study aimed to construct a signature predict prognosis for SQLC patients based on IRGs. Methods We constructed and validated a signature from SQLC patients in The Cancer Genome Atlas (TCGA) using bioinformatics analysis. The underlying mechanisms of the signature were also explored with immune cells and mutation profiles. Results A total of 464 eligible SQLC patients from TCGA dataset were enrolled and were randomly divided into the training cohort (n = 232) and the testing cohort (n = 232). Eight differentially expressed IRGs were identified and applied to construct the immune signature in the training cohort. The signature showed a significant difference in overall survival (OS) between low-risk and high-risk cohorts (P < 0.001), with an area under the curve of 0.76. The predictive capability was verified with the testing and total cohorts. Multivariate analysis revealed that the 8-IRG signature served as an independent prognostic factor for OS in SQLC patients. Naive B cells, resting memory CD4 T cells, follicular helper T cells, and M2 macrophages were found to significantly associate with OS. There was no statistical difference in terms of tumor mutational burden between the high-risk and low-risk cohorts. Conclusion Our study constructed and validated an 8-IRG signature prognostic model that predicts clinical outcomes for SQLC patients. However, this signature model needs further validation with a larger number of patients.

Traditional Chinese medicine (TCM) is an important part of the treatment of primary liver cancer (PLC) in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical practice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the methodological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.

On November 3, 2014, in Bethesda, MD, the Office of Cancer Complementary and Alternative Medicine of the National Cancer Institute held a meeting to examine the potential utility and feasibility of establishing an international consortium for Chinese medicine and cancer. There is significant interest in the West in using components of Chinese medicine (CM) —such as botanicals and herbal medicines, acupuncture and acupressure, and qigong—in the field of oncology, as potential anticancer agents, for symptom management, and to improve quality of life. The proposal for a consortium on CM came from the Chinese Academy of Chinese Medical Sciences, with the aims of improving scientific communications and collaborations and modernizing the studies of CM for cancer. The US National Cancer Institute’s Office of Cancer Complementary and Alternative Medicine agreed to work with Chinese Academy of Chinese Medical Sciences to explore the feasibility of establishing an international consortium for Chinese medicine and cancer. At the meeting, participants from the United States, China, Canada, Australia, and Korea discussed issues in CM and cancer research, treatment, and management, including potential mechanisms of action, proof of efficacy, adverse effects, regulatory issues, and the need for improving the quality of randomized clinical trials of CM treatments and supportive care interventions. Presented in these proceedings are some of the main issues and opportunities discussed by workshop participants.

s Background Pain is a common symptom in cancer patients. Acupuncture is a suggested treatment for a wide range of clinical conditions, usually for its beneficial effects on pain control. Si guan xue (the four points) have been widely used in clinical practice, and has shown that it is highly effective, effective in obtaining qi, shows strong acupuncture stimulation, and is simple to manipulate and safe to use. Therefore, the aim of this study is to test the protocol and safety of acupuncture at the si guan xue in the management of cancer pain. Methods This is a single-blind, randomized controlled pilot trial. 42 patients with moderate to severe cancer pain were randomly assigned to three different arms with seven sessions of treatment; that is, treatment arm 1 (the si guan xue arm, n = 14), treatment arm 2 (the si guan xue plus commonly used acupoints arm, n = 14) and the control arm (the commonly used acupoints arm n = 14). Primary outcomes included acupuncture relieving cancer pain, and patients’ subjective improvement as measured by the Patient Global Impression of Change (PGIC). Secondary outcomes included the scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Karnofsky’s Performance Status (KPS). Results The analysis showed that the cancer pain reduction in treatment arm 2 was most prominent on day 5 when compared with the control arm (P0.05). Furthermore, no serious adverse events were observed. Conclusions These results indicate that acupuncture at the si guan xue plus commonly used acupoints tends to be effective in reducing cancer pain. However, the sample size was small, and a future multi-centre study with a larger sample size is warranted. Trial registration ChiCTR-IOR-15007471 (Retroactively registered on 28 NOV 2015)

Compared with organic-counterpart or micro-counterpart, nanothermites have attracted substantial interests owing to their exhibited outstanding properties. A common goal of a great amount of studies in nanothermite-based energetic materials is to enhance the reaction properties. Thermite planar geometry structural systems have been the promising structures because they are very tunable to control the alternating layered geometry and thickness of fuel and oxidizer. In this article, the planar interfacial contact Al/Fe2O3 nanolaminate thermite systems were studied to explore the effects of variations in preheating temperature, preheating rate and the initial distance between participating fuel and oxidizer on reaction properties and products characterizations by using the classic molecular dynamics simulations. According to the results, ignition delay and reaction time decrease with increasing the preheating temperature. The ignition delay and reaction time decrease from hundreds of picoseconds to a few tens of picoseconds. Additionally, higher heating rate results in higher energized structure, and much more energy was absorbed during heating period leading to a much shorter ignition delay. Reaction will start when the initial distance among reactants is shorter than a certain distance after passing through the ignition delay. Analyses also show the majority number of triangular structure for Fe2Al clusters and a small amount of tetrahedral structure for Fe3Al clusters during thermite reaction.

Background Altered cellular metabolism is considered to be one of the hallmarks of cancer (Coller, Am J Pathol 184:4–17, 2014; Kim and Bae, Curr Opin Hematol 25:52–59, 2018). However, few studies have investigated the role of metabolism in the development of gastric precancerous lesions (GPLs). Weipiling (WPL), a traditional Chinese medicine formula for treatment of GPLs. In this study, we evaluated the amelioration of GPLs by WPL and investigated the possible role of WPL in regulating glucose metabolism. Methods Firstly, the major components of WPL are chemically characterized by HPLC analytical method. In this study, we chose the Atp4a−/− mouse model (Spicer etal., J Biol Chem 275:21555–21565, 2000) for GPL analysis. Different doses of WPL were administered orally to mice for 10 weeks. Next, the pathological changes of gastric mucosa were assessed by the H&E staining and AB-PAS staining. In addition, TUNEL staining was used to evaluate apoptosis, and we further used immunohistochemically labelled CDX2, MUC2, ki-67, PTEN, and p53 proteins to assess the characteristic changes of gastric mucosa in precancerous lesions. The levels of such transporters as HK-II, PKM2, ENO1, MPC1, and LDHA were determined by Western blot analysis. Finally, we assessed the expression of mTOR, HIF-1α, AMPK, Rheb, TSC1 and TSC2 protein in the gastric mucosa of Atp4a−/−mice. Results In this work, we evaluated the protective effect of WPL on gastric mucosa in mice with precancerous lesions. The aberrant apoptosis in gastric mucosa of gastric pre-cancerous lesions was controlled by WPL (P). Furthermore, WPL suppressed the expression of CDX2, MUC2, ki-67, PTEN and p53, as the levels of these proteins decreased significantly compared with the model group (P<0.05). In parallel, WPL significantly suppressed the expression of transporters, such as HK-II, PKM2, ENO1, MPC1 and LDHA (P). In addition, mTOR, HIF-1a, AMPK, Rheb, TSC1 and TSC2 protein levels in gastric mucosa of Atp4a−/− mice in the high- and low-dose WPL groups were significantly lower than those in the model group (P), while the expression of TSC1 and TSC2 protein was significantly higher (P). Conclusions Conclusively, WPL could ameliorate GPLs in Atp4a−/− mice by inhibiting the expression of transporters and suppressing the aberrant activation of mTOR/HIF-1α.

HOXA transcript at the distal tip (HOTTIP), a long noncoding RNA, is upregulated in pancreatic ductal adenocarcinoma (PDAC), but the HOTTIP-mediated oncogenic pathway is not fully understood. We identified canonical HOTTIP-HOXA13 targets, CYP26B1, CLIC5, CHI3L1 and UCP2-responsible for cell growth and cell invasion. Genome-wide analysis revealed that 38% of HOTTIP-regulated genes contain H3K4me3 and HOTTIP enrichment at their promoters, without HOXA13 binding. HOTTIP complexes with WDR5-MLL1 to trans-activate oncogenic proteins CYB5R2, SULT1A1, KIF26A, SLC1A4, and TSC22D1 by directly inducing H3K4me3 at their promoters. The WDR5, MLL1, and H3K4me3 levels at their promoters and their expression levels are sensitive to HOTTIP expression. These results indicate the importance of the noncanonical trans-acting HOTTIP-WDR5-MLL1 pathway in the HOTTIP regulatory mechanism by promoting oncogenic protein expression. Furthermore, HOTTIP is regulated by miR-497 in PDAC cells, but HOTTIP is negatively correlated with miR-497 levels in PDAC tissues. In conclusion, HOTTIP is upregulated in PDAC due to the loss of the inhibitory miR-497; HOTTIP promotes PDAC progression through the canonical HOTTIP-HOXA13 axis. A novel noncanonical trans-acting HOTTIP-WDR5-MLL1-H3K4me3 pathway is also delineated.

To observe the influence of fire needle stimulation at Sihua acupoints combined with chemotherapy on Th1/Th2 imbalance and performance status in the patients with advanced non-small cell lung cancer (NSCLC) so as to investigate its immunological mechanism underlying the improvement of lung cancer.Sixty eligible NSCLC inpatients were randomly assigned to a control group and a treatment group (Compared with the results before treatment, the levels of IL-2 and IFN-γ concentration increased obviously and the levels of IL-4 and IL-10 concentration as well as KPS score decreased significantly in the treatment group and the control group after treatment (allFire needle stimulation at Sihua acupoints improves the function of Th1 cells, and reduces the function of Th2 cells. As a result, the balance between Th1 and Th2 has been modified and the deterioration degree of the performance status been alleviated in the patients after chemotherapy.

Gefitinib is one of commonly used first-line treatment options for patients with positive EGFR mutation in non-small cell lung cancer (NSCLC). However, most patients with gefitinib treatment relapse over time due to the loss of drug sensitivity. Compound Kushen injection (CKI) has been used to treat lung cancer, including EGFR-mutated NSCLC. In this report, we examined the anti-cancer and drug sensitivity increased activities of CKI in gefitinib less sensitive NSCLC cell lines H1650 and H1975. Bioinformatics analysis was applied to uncover gene regulation and molecular mechanisms of CKI. Our results indicated that when associating with gefitinib in a dose-dependent fashion, CKI demonstrated the ability to inhibit the proliferation and to increase the sensitivity to gefitinib treatment in gefitinib less sensitive cell lines. This could be the results of down regulation of the PI3K/Akt/mTOR pathway and up regulation of autophagy, which were identified as the potential primary targets of CKI to increase gefitinib treatment effect.

Objective To preliminarily observe miRNA gene profiles in benefit serum of advanced non-small cell lung cancer (NSCLC) treated by TCM combined Western medicine (WM) , and to seek for molecular markers for its efficacy monitoring and prediction. Methods Recruited were 5 advanced NSCLC patients who received TCM combined WM treatment and obtained efficacy benefit ( as the treatment group) , 3 advanced NSCLC patients who received early treatment ( as the lung cancer group) , and 3 healthy subjects (as the control group). Serum samples were collected and total RNA was extracted using Trizol method. Using microRNA PCR ARRAY chip technology (product of Exiqon Company) , differentially miRNA expression profiling in serum between the lung cancer group and the control group, and between the treatment group and the lung cancer group were detected. Benefit miRNA expression profiling was ob- tained based on cluster analysis and comparative analysis. Results After tested by miRNA PCR ARRAY and managed by data analysis, a total of 42 miRNAs with more than 2 folds difference were screened in the lung cancer group and the control group, including 29 up-regulated and 12 down-regulated miRNAs. Be- sides, miR-10b-5p, miR-21-5p, miR-182-5p, miR-361-3p, and miR-382-5p were statistically different (P0. 05). A total of 45 miRNAs with more than 2 folds difference were screened in the treatment group and the lung cancer group, including 12 up-regulated and 33 down-regulated miRNAs. Fifteen miRNAs were statistically different including miR-137-3p, miR-182-5p, miR-376a-3p, miR-382-5p, miR-409-3p, miR-10a-5p, miR-21-5p, miR-29a-3p, miR-141-3p, miR-150-5p, miR-200c-3p, miR-342-3p, miR-365a-3p, miR-375, miR- 502-3p (P0.05). Totally 22 miRNAs were screened in the treatment group with more than 2 folds differ- ence as compared with the lung cancer group and with less than or equivalent to 2 folds difference as com- pared with the control group, including 7 up-regulated and 15 down-regulated miRNAs, of which, miR-127- 3p, miR-182-5p, miR-382-5p, miR-409-3p, miR-10a-5p, miR-21-5p, miR-141-3p, miR-342-3p were statistically different (P0. 05). Conclusion miRNAs including miR-21-5p, miR-182-5p, miR-382-5p are promising to become molecular markers for efficacy monitoring and prediction of advanced NSCLC treated by TCM combined WM, which provides reference for individualized treating advanced NSCLC.

Lung cancer is the leading cause of cancer death worldwide. Chemotherapy is one of the most effective strategies for lung cancer treatment. However, the side effects of chemotherapy limit the application of chemotherapeutic agents. The β-Asarone, a low-toxicity natural compound from a traditional Chinese medicinal herb, has been demonstrated to display anticancer activities in multiple cancer types. However, the anticancer activities of β-Asarone in lung cancer have not been shown, and the underlying molecular mechanisms are still unclear. In the current study, we show that β-Asarone displays a dose-dependent inhibitory effect on the viability of lung cancer cells. Additionally, β-Asarone significantly suppresses the cell migration, invasion, and adhesion of lung cancer cells. Moreover, β-Asarone induces apoptosis associated with the activation of caspase-9 and caspase-3, the upregulation of XAF1, Puma, Bax (Ser184) and Bad (Ser112), the downregulation of XIAP, Bcl-2 and Survivin, the translocation of Bax, Bad, phospho-Bax (Ser184), phospho-Bad (Ser112) and cytochrome C and the reduction of the mitochondrial membrane potential. Mechanistically, our study shows that β-Asarone inhibits Wnt/β-catenin signaling. Rescuing the activation of Wnt/β-catenin signaling overcomes β-Asarone-induced anticancer effects. Taken together, our data provide the first evidence of the anticancer effects of β-Asarone in lung cancer, demonstrates that the inhibition of Wnt/β-catenin signaling could be critical for β-Asarone-induced anticancer effects. Our study thus suggests a potential application of β-Asarone as an anticancer agent in the clinical treatment of lung cancer.

BACKGROUND Aplysia ras homology member I/ARHI is known as ovarian cancer suppressor gene and potential inhibitor of signal transducer and activator of transcription 3/STAT3 signaling. Resveratrol suppresses growth and STAT3 activation of ovarian cancer cells, while its influence in ARHI expression remains unknown. OBJECTIVE The current study aims to elucidate the status of ARHI expression and its relevance with growth suppression and STAT3 inactivation of resveratrol-treated cells. METHODS ARHI expression patterns of three ovarian cancer cell lines (human CAOV-3, OVCAR-3 and rat NUTU-19) without and with 100 μM resveratrol treatment were checked by immunocytochemical staining, Western blotting and RT-PCR. The involvement of ARHI in the growth inhibition and STAT3 inactivation of resveratrol-treated OVCAR-3 cells was investigated by transfection of ARHI-specific siRNA. RESULTS ARHI is expressed in low levels in three ovarian cancer cell lines, which is upregulated upon resveratrol treatment accompanied with growth arrest, extensive apoptosis, increased autophagic activity and inactivated STAT3 signaling. Specific siRNA transfection efficiently knocked down ARHI expression in resveratrol-treated CAOV-3 and OVCAR-3 cells and increased the total cell number in limited extents (P> 0.05) in comparison with that of resveratrol-treated ovarian cancer cells without any transfection or transfected with mock oligonucleotides. ARHI knockdown failed to prevent resveratrol-caused STAT3 inactivation and cell crisis. CONCLUSION ARHI upregulation is another molecular event caused by resveratrol and one of the elements related with resveratrol's anti-ovarian cancer efficacy. Resveratrol may inactivate STAT3 signaling of ovarian cancer cells in ARHI unrelated pattern(s).

The Chinese medicine formula Tian Xian Liquid (TXL) has been used clinically for cancer therapy in China for more than 25 years. However, the comprehensive and holistic effects of its bioactive fractions for various antitumor therapeutic effects have not been unraveled. This is the first study to scientifically elucidate the holistic effect of Chinese medicine formula for treating colon cancer, hence allowing a better understanding of the essence of Chinese medicine formula, through the comparison of the actions of TXL and its functional constituent fractions, including ethyl acetate (EA), butanol (BU), and aqueous (WA) fractions. Tissue-specific proliferative/antiproliferative effects of these fractions on human colorectal carcinoma HT-29 cells and splenocytes were studied by using the MTT assay. Their modulations on the expression of markers of antiproliferation, antimetastasis, reversion of multidrug resistance in treated HT-29 cells were examined with real-time polymerase chain reaction and Western blot analysis, and their modulations in a xenografted nude mouse model were examined by Western blot analysis. Results revealed that EA fraction slightly inhibited the proliferation of HT-29 cells, but tissue-specifically exerted the most potent antiproliferative effect on splenocytes. On the contrary, only TXL and BU fraction tissue-specifically contributed to the proliferation of splenocytes, but inhibited the proliferation of HT-29 cells. WA fraction exerted the most potent antiproliferative effect on HT-29 cells and also the strongest inhibitory action on tumor size in the nude mouse model in our previous study. In the HT-29 model, TXL and WA fraction exerted the most pronounced effect on upregulation of p21 mRNA and protein; TXL, and EA and WA fractions exerted the effect on downregulation of G1 phase cell cycle protein, cyclin D1 mRNA and protein; EA and BU fractions exerted the most prominent anti-invasive effect on anti-invasion via downregulation of MMP-1 mRNA; TXL potently reversed most multidrug resistance via downregulation of MDR-1 protein. In conclusion, the comprehensive and holistic effects of TXL were demonstrated with ( a) mutual accentuation and mutual enhancement, ( b) mutual counteraction and mutual suppression, and ( c) mutual antagonism among the 3 constituent fractions. Moreover, the design of the present study may lead to further development of more tissue-specific effective drugs with minimal side effects for clinical use in combating carcinoma.

Objective To observe the therapeutic effect of intensive and deep needling method of fire-needle for chronic gluteus medius impairment. Methods The tenderness of anterior superior iliac spine which was the starting point of gluteus medius was taken as the center, 1 cm around it, 4–8 needle insertion points were fixed. Fire-needle with intensive and deep needling method was applied deeply on the surface of the bone then immediately taken out. The treatment was given once every 3 days, 3 times as a course. Results After 2 courses, 21 cases were fully recovered, 22 cases with remarkable effect, 4 cases without effect, and the total effective rate was 91.5%. Conclusion Fire-needle with intensive and deep needling method has remarkable therapeutic effect.

To observe the effect of Modified Yiqi Chutan Recipe (MYCR) on blood flow perfusion in treating mid-late stage non-small cell lung cancer (NSCLC) patients by using multislice CT perfusion (CTP) , and to assess the relationship between each CTP parameter and the prognosis as well.Totally 87 mid-late stage NSCLC patients were randomly assigned to the treatment group (44 cases, Shenyi Capsule + MYCR +chemotherapy) and the control group (43 cases, chemotherapy alone) in the ratio of 1:1. And 21 days consisted of 1 therapeutic course, 4 courses in total. All of them underwent CTP of primary tumor and routine thoracic CT examination (plain CT and enhancement CT) 3 times (before therapy, after 2 and 4 cycles). CT findings were analyzed for tumor size and perfusion parameters [blood flow (BF), blood volume (BV), permeability surface (PS), mean transit time (MTT), and time to peak (TP) before and after treatment, and relationship between perfusion parameters and prognosis was also assessed.In 87 cases, 7 dropped out and 80 cases were available, 40 in the treatment group and 40 in the control group. (1) The relief rate was 47.5% (19/40) and the total stable rate was 77.5% (31/40) in the treatment group, and they were 40.0% (16/40) and 65.0% (26/40) in the control group, with no statistical difference between the two groups (χ² = 0.672, 1.227; P0.05). (2) Compared with before treatment group in the same group, BF and PS decreased, and MTT increased in the two groups after 2 and 4 courses (P0.05); BE and PS decreased, and MTT increased in the control group after 2 courses (P0.05). Compared with the control group after 4 courses, BE decreased more significantly in the treatment group (P0.05). (3) After 4 courses, all patients were assigned to the remission group (35 cases) and the non-remission group (45 cases) according to the RECIST standard. Compared with before treatment in the same group, BF, BF, and PS all decreased, and MTT increased in the remission group after treatment (all P0.05); BF increased in the non-remission group after treatment (P0.05). (4) All patients were assigned to the BE increase group (34 cases) and the BE decrease group (46 cases) according to changed BE values after treatment. Results showed the mean survival rate was 246 days in the BF increase group (the 1-year accumulative survival rate being 13.0%) and 387 days in the BE decrease group (the 1-year accumulative survival rate being 53.1%). The life span was prolonged and the 1-year accumulative survival rate was elevated in the BE increase group, with statistical difference as compared with the BE decrease group (χ² = 19.057, P0.01).Shenyi Capsule plus MYCR could reduce BE in mid-late stage NSCLC patients , improve vascular permeability, showing better synergistic effect with chemotherapy. CTP could not only reflect the change of tumor size, but also reflect vascular function of the tumor. Meanwhile, changes of CTP parameters were closely associated with prognosis. Patients with post-treatment decreased BE value had better prognosis and longer life span.

To study the predicting effect of proly 4-hydroxylase beta polypeptide (P4HB) in treating non-small cell lung cancer (NSCLC) patients by Yiqi Chutan Recipe (YCR).Totally 46 stage III and IV NSCLC patients were treated by YCR for 4 therapeutic courses. Effect was assessed by RECIST of solid tumor. P4HB expression was detected in the lung cancer tissue by immunohistochemical assay. Factors affecting disease control rates (DCR) of YCR were analyzed by Logistic regression analysis. The correlation between P4HB expression and the effect of YCR was analyzed.The DCR of advanced NSCLC treated by YCR was 36.96% (17/46 cases). P4HB was high expressed in advanced lung cancer tissue (6/15 cases). Gender, initial treatment, and retreatment are independent factors for affecting DCR of treating lung cancer by YCR.P4HB might be taken as a factor for predicting the effect of YCR in treating NSCLC.