Molecular subtypes based on DNA sensors predict prognosis and tumor immunophenotype in hepatocellular carcinoma.

DNA sensors play crucial roles in inflammation and have been indicated to be involved in antitumor or tumorigenesis, while it is still unclear whether DNA sensors have potential roles in the prognosis and immunotherapy of hepatocellular carcinoma (HCC). Herein, The Cancer Genome Atlas and Gene Expression Omnibus databases were used to analyze RNA sequencing data and clinical information. A total of 14 DNA sensors were collected and performed consensus clustering to determine their molecular mechanisms in HCC. Two distinct molecular subtypes (Clusters C1 and C2) were identified and were associated with different overall survival (OS). Immune subtype analysis revealed that C1 was mainly characterized by inflammation, while C2 was characterized by lymphocyte depletion. Immune scoring and immunomodulatory function analysis confirmed the different immune microenvironment of C1 and C2. Notably, significant differences in "Hot Tumor" Immunophenotype were observed between the two subtypes. Moreover, the prognostic model based on DNA sensors is capable of effectively predicting the OS of HCC patients. Besides, the chemotherapeutic drug analysis showed the different sensitivity of two subtypes. Taken together, our study shows that the proposed DNA sensors were a reliable signature to predict the prognosis and immunotherapy response with potential application in the clinical decision and treatment of HCC.

Highly bioactive iridium metal-complex alleviates spinal cord injury via ROS scavenging and inflammation reduction.

Generation of a promising antioxidative reagent with superior biocompatibility is urgently needed to remedy spinal cord injuries (SCI), repair the damaged neurons and restrain the secondary injuries caused by inflammation-induced oxidative stress. Inhibitory elements in the injury sites and necessitous inherent neural regeneration ability were major challenges for functional recovery after spinal cord injuries. We here developed a highly bioactive iridium complex (IrFPHtz) with enhanced antioxidative activities and improved SCI therapeutic efficacy. Both in vivo and in vitro, IrFPHtz has exhibited neuroprotective and anti-inflammatory properties. Mechanically, IrFPHtz directly targets SOD1 and upregulates the expression of SOD1 to eliminate the excess Reactive Oxygen Species (ROS) production induced by SCI, and thus protecting neuron cells from further damage. As a result, IrFPHtz safeguarded the neurons and myelin sheaths against trauma, lessened glial scar conformations and facilitated the repair of neurons and long axon expansion in the glial scar. Furthermore, IrFPHtz significantly ameliorated the behavioral functions of SCI mice and promoted a satisfactory curative effect. Therefore, this study sheds light on a novel method for SCI treatment using IrFPHtz as a potential drug and implicates the clinical significance of metal complexes in diseases featuring with upregulated ROS species.

The effect of posterior lumbar dynamic fixation and intervertebral fusion on paraspinal muscles.

BACKGROUND: The aim of this study was to analyze the effect of unilateral K-rod dynamic internal fixation on paraspinal muscles for lumbar degenerative diseases. METHODS: This study retrospectively collected 52 patients who underwent lumbar surgery with the K-rod group or PLIF. The operation time, intraoperative blood loss, postoperative drainage volume, postoperative exercise time were compared in the two groups. The visual analog scale (VAS) score and the oswestry dysfunction index (ODI) were employed to evaluate the clinical outcomes. The functional cross-sectional area (FCSA) of the paraspinal muscles and paraspinal muscles fat infiltration were measured to assess on the paraspinal muscles. RESULTS: As compared with the PLIF group, the operation time, the postoperative time in the field, and the average postoperative hospital stay in the K-rod internal fixation group were significantly shortened. At the last follow-up, both the groups showed significant improvement in the VAS score and ODI. The FCSA atrophy of the upper and lower adjacent segments (UAS and LAS) of the K-rod internal group was significantly less than that of the PLIF group. The extent of increase in the fatty infiltration of the paraspinal muscles in the K-rod group was significantly lesser than that in the PLIF group. The postoperative low back pain of the two groups of patients was significantly positively correlated with the FCSA atrophy. CONCLUSIONS: As compared to PLIF, the posterior lumbar unilateral K-rod dynamic internal fixation showed significantly lesser paraspinal muscle atrophy and fatty infiltration, which were significantly positively correlated with postoperative low back pain.

Spastin interacts with collapsin response mediator protein 3 to regulate neurite growth and branching.

Cytoskeletal microtubule rearrangement and movement are crucial in the repair of spinal cord injury. Spastin plays an important role in the regulation of microtubule severing. Both spastin and collapsin response mediator proteins can regulate neurite growth and branching; however, whether spastin interacts with collapsin response mediator protein 3 (CRMP3) during this process remains unclear, as is the mechanism by which CRMP3 participates in the repair of spinal cord injury. In this study, we used a proteomics approach to identify key proteins associated with spinal cord injury repair. We then employed liquid chromatography-mass spectrometry to identify proteins that were able to interact with glutathione S-transferase-spastin. Then, co-immunoprecipitation and staining approaches were used to evaluate potential interactions between spastin and CRMP3. Finally, we co-transfected primary hippocampal neurons with CRMP3 and spastin to evaluate their role in neurite outgrowth. Mass spectrometry identified the role of CRMP3 in the spinal cord injury repair process. Liquid chromatography-mass spectrometry pulldown assays identified three CRMP3 peptides that were able to interact with spastin. CRMP3 and spastin were co-expressed in the spinal cord and were able to interact with one another in vitro and in vivo. Lastly, CRMP3 overexpression was able to enhance the ability of spastin to promote neurite growth and branching. Therefore, our results confirm that spastin and CRMP3 play roles in spinal cord injury repair by regulating neurite growth and branching. These proteins may therefore be novel targets for spinal cord injury repair. The Institutional Animal Care and Use Committee of Jinan University, China approved this study (approval No. IACUS-20181008-03) on October 8, 2018.

Application Status of Chinese Medicine on Cancer Rehabilitation: A Preliminary Questionnaire Survey.

OBJECTIVE: To investigate the application status of Chinese medicine (CM) in cancer rehabilitation, so as to provide references for improving the level of CM cancer rehabilitation. METHODS: A survey questionnaire regarding "application status of CM rehabilitation in cancer patients" for oncologists (doctor version) and cancer patients (patient version) were developed, respectively. From September 2014 to November 2016, a total of 1,000 doctors from oncology department in 48 hospitals and 2,000 cancer patients from CM oncology department from 8 hospitals in China were recruited in this survey. The psychological, nutrition and exercise rehabilitation guidance for cancer patients provided by doctors, their mastery conditions regarding cancer staging treatment and CM syndrome differentiation, and recommendation from doctors on CM rehabilitation were investigated. Cancer patients' awareness on the importance of psychological, nutrition and exercise rehabilitation, as well as their knowledge and needs for rehabilitation were also analyzed. The impact of gender, age, professional title, hospitals grades of physicians on their knowledge of cancer staging treatment and CM syndrome differentiation, and the relationship between gender, age, education level and economic conditions and patient's knowledge along with the needs of CM rehabilitation were further analyzed. RESULTS: Totally 1,000 questionnaires were issued to doctors and 963 questionnaires returned, among which 948 were valid representing a response rate of 94.80%. A total of 2,000 questionnaires were issued to patients and 1,705 valid data finally returned with a response rate of 85.25%. The survey showed that cancer patients generally paid much attention to psychological, nutritional and sports rehabilitation, and had a strong demand for CM rehabilitation. Knowledge of CM rehabilitation was not well provided by oncologists, and the rehabilitation guidance as well as CM rehabilitation measures were obviously insufficient in cancer patients. Educational and economic levels were positively correlated with cognition level of CM rehabilitation knowledge among cancer patients (Kendall-tau_b correlation coefficients=0.130, 0.057, respectively; P<0.05). Gender and education level were positively correlated with the patients' willingness for taking CM measures (Kendall-tau_b correlation coefficient=0.057, 0.105, respectively; P<0.05). Age was negatively correlated with intention of applying CM measures (kendall-taub correlation coefficient=-0.105, P<0.05). CONCLUSIONS: Health education and professional training for both cancer patients and oncologists should be strengthened and CM rehabilitation knowledge among cancer patients and oncologists should be improved, so as to give full play to CM in cancer rehabilitation.

SUMOylation of spastin promotes the internalization of GluA1 and regulates dendritic spine morphology by targeting microtubule dynamics.

Dendritic spines are specialized structures involved in neuronal processes on which excitatory synaptic contact occurs. The microtubule cytoskeleton is vital for maintaining spine morphology and mature synapses. Spastin is related to microtubule-severing proteases and is involved in synaptic bouton formation. However, it is not yet known if spastin can be modified by Small Ubiquitin-like Modifier (SUMO) or how this modification regulates dendritic spines. Spastin was shown to be SUMOylated at K427, and its deSUMOylation promoted microtubule stability. In addition, SUMOylation of spastin was shown to affect signalling pathways associated with long term synaptic depression. SUMOylated spastin promoted the development of dendrites and dendritic spines. Moreover, SUMOylated spastin regulated endocytosis and affected the transport of the AMPA receptor, GluA1. Our findings suggest that SUMOylation of spastin promotes GluA1 internalization and regulates dendritic spine morphology through targeting of microtubule dynamics.

Analysis of clinical effect and radiographic outcomes of Isobar TTL system for two-segment lumbar degenerative disease: a retrospective study.

BACKGROUND: Nonfusion fixation is an effective way to treat lumbar degeneration. In the present study, we analyzed the clinical effects and radiographic outcomes of the Isobar TTL system used to treat two-segment lumbar degenerative disease. METHOD: Forty-one patients diagnosed with two-segment lumbar degenerative disease underwent surgical implantation of the Isobar TTL dynamic stabilization system (n = 20) or a rigid system (n = 21) from January 2013 to June 2017. The mean follow-up time was 23.6 (range 15-37) months. Clinical results were evaluated with the Oswestry Disability Index (ODI), modified Macnab criteria, and the visual analog score (VAS). Radiographic evaluations included the height of the intervertebral space and the range of motion (ROM) of the treated and adjacent segments. The intervertebral disc signal was classified using the modified Pfirrmann grading system and the University of California at Los Angeles (UCLA) system. RESULTS: The clinical results, including the ODI and VAS, showed that there was significant improvement in the two groups after implantation and that the difference between the two groups was not significant. In addition, the clinical efficacy indicated by the modified Macnab criteria for the two groups was similar. Radiological outcomes included the height of the intervertebral space, lumbar mobility, and intervertebral disc signal. The height of the intervertebral space of the upper adjacent segment L2/3 in the rigid group was significantly lower than that in the Isobar TTL group at the last follow-up. Furthermore, the number of ROMs of the fixed-segment L3/4 in the Isobar TTL group was significantly less than that before implantation, suggesting that the fixed-segment ROMs in the Isobar TTL group were limited. In addition, the ROM of the upper adjacent segment L2/3 in the last follow-up of the rigid group increased significantly, while that of the Isobar TTL group did not change after implantation. Finally, the incidence of adjacent-segment degeneration (ASD) was significantly greater in the rigid group than in the Isobar TTL group according to the UCLA system. CONCLUSION: The Isobar TTL system can be clinically effective for treating two-segment lumbar degenerative disease. Compared with rigid fixation, the Isobar TTL system yielded better radiographic outcomes and maintained the mobility of the treated segments with less impact on the proximal adjacent segment.

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).

Investigation of miR-490-3p Expression in Hepatocellular Carcinoma Based on Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) and a Meta-Analysis of 749 Cases.

BACKGROUND miR-490-3p could play vital roles in multiple cancers. However, the role of miR-490-3p in hepatocellular carcinoma (HCC) remains uncertain. In this study, we sought to explore the underlying role of miR-490-3p in HCC. MATERIAL AND METHODS In this study, we explored the clinical role of miR-490-3p in HCC via quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and The Cancer Genome Atlas (TCGA) database. Then, a meta-analysis was performed to evaluate the expression trend and diagnostic value of miR-490-3p in HCC. Furthermore, 12 miRNA prediction algorithms were applied to predict the potential target genes of miR-490-3p. The differentially expressed genes in HCC in the Gene Expression Profiling Interactive Analysis (GEPIA) database were also selected. Additionally, bioinformatics analyses were utilized to investigate the possible functions and pathways of the target genes. RESULTS miR-490-3p was clearly down-regulated in HCC based on RT-qPCR (P=0.002). Consistent with the results of RT-qPCR, miR-490 was more highly expressed in normal liver tissue than in HCC (P<0.001). Additionally, the meta-analysis confirmed the results from RT-qPCR and TCGA. Furthermore, based on the prediction algorithms and GEPIA, a total of 113 genes were selected. According to the bioinformatics analyses, we found that the most remarkably enriched functional terms included protein transport, poly(A) RNA binding, and intracellular organelle part. Additionally, the miR-490-3p target genes were significantly related to the pathways in cancer. CONCLUSIONS We found that miR-490-3p is down-regulated in HCC and is related to genes that have potential tumoral functions. However, the exact mechanism should be confirmed by functional experiments.

Clinical practice guidelines for the treatment of primary liver cancer with integrative traditional Chinese and Western medicine.

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.

Gambogic Acid Induces Cell Apoptosis and Inhibits MAPK Pathway in PTEN-/-/p53-/- Prostate Cancer Cells In Vitro and Ex Vivo.

OBJECTIVE: To investigate the effect of gambogic acid (GA) on the growth and cell death of castrate resistant prostate cancer (PC) with phosphate and tension homology (PTEN) and p53 genes deleted in vitro and ex vivo, and elucidate the underlying possible molecular mechanisms. METHODS: PTEN-/-/p53-/- PC cells and Los Angeles prostate cancer-4 (LAPC-4) cells were treated with GA for 24 h and 48 h, then cell viability was determined by cell proliferation assay. PTEN-/-/p53-/- PC cells organoids number was calculated under GA treatment for 1 week. In addition, cell titer glo assay was performed to analyze 3 dimensional cell viability of patients derived xenografts (PDX) 170.2 organoids. Flow cytometry was used to detect apoptotic cells treated with GA. And confocal image was performed to detect the apoptotic mitochondrial morphological changes. Apoptotic cell death related protein levels were measured through Western blot (WB) in GA treated cells and organoids. The expression levels of mitogen-activated protein kinases (MAPKs) pathway related ribonucleic acid (RNAs) and proteins were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and WB, respectively. RESULTS: The treatment of GA significantly reduced cell viability of PTEN-/-/p53-/- PC cells and LAPC-4 in a time- and concentration-dependent manner. In organoids, GA showed strong inhibition towards organoids' numbers and diameters and continuously led to a complete organoids inhibition with GA 150 nmol/L. Ex vivo results validated that GA 1 µmol/L inhibited 44.6% PDX170.2 organoids growth. As for mechanism, flow cytometry detected continuously increased apoptotic portion under GA treatment from 1.98% to 11.78% (6 h) and 29.94% (8 h, P<0.05). In addition, mitochondrial fragmentation emerged in GA treated cells indicated the mitochondrial apoptotic pathway might be involved. Furthermore, WB detected caspases-3, -9 activation and light chain (LC)-3 conversion with GA treatment. WB revealed decreased activity of MAPK pathway and down-regulation of downstream c-fos oncogene RNA level was detected by RT-PCR before undergoing apoptosis (P<0.05). CONCLUSION: GA was a potent anti-tumor compound as for PTEN-/-/p53-/- PC, which contributed to cell apoptosis via inhibition of the MAPK pathway and c-fos.

Acupuncture for enhancing early recovery of bowel function in cancer: Protocol for a systematic review.

BACKGROUND: Cancer patients undergoing surgical procedure often suffer from bowel dysfunction and postoperative ileus (POI). Cancer management for early recovery of bowel function is still a challenging topic. Acupuncture has been commonly used in a variety of gastrointestinal diseases. The aim of this study is to evaluate the effects of acupuncture therapy to reduce the duration of POI and enhance bowel function in cancer patients. METHODS: We will systematically screen all randomized controlled trials (RCTs) published through electronically and hand searching. The following search engines including Medline, EMBASE, Cochrane CENTRAL, the Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, VIP Information, Wanfang Data, one Japanese database (Japan Science and Technology Information Aggregator, Electronic) and 2 Korean Medical Databases (Korean Studies Information, and Data Base Periodical Information Academic) will be retrieved. Supplementary sources will be searched including gray literature, conference proceedings, and potential identified publications. Two reviewers will independently conduct the trial inclusion, data extraction and assess the quality of studies. The time to first passing flatus and time to first bowel motion will be assessed as the primary outcomes. Adverse effects, time to first bowel sound, visual analog scale (VAS) pain score, hospital stay, and postoperative analgesic requirement will be measured as secondary outcomes. Methodological quality will be evaluated according to the Cochrane risk of bias. Details of interventions will be assessed by the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) checklist. All analyses will be applied by RevMan (version 5.3) and StataSE (version 12). ETHICS AND DISSEMINATION: This systematic review will provide up-to-date information on acupuncture therapy for early recovery of bowel function in cancer patients. This review does not require ethical approval and will be reported in a peer-reviewed journal and presented at a relevant conference. TRIAL REGISTRATION NUMBER: PROSPERO CRD42016049633.

Effects of Shugan Jianpi Formula () on myeloid-derived suppression cells-mediated depression breast cancer mice.

OBJECTIVE: To observe the intervention effect of Shugan Jianpi Formula (, SGJPF) on a breast cancer mouse model with depression and investigate the underlying mechanism of SGJPF in preventing the development of breast cancer. METHODS: The breast cancer model was induced by inoculation of breast cancer cells, the depression model was induced by chronic stress stimuli, and the depression cancer model was established by combining the two factors. The mice were divided into 7 groups: normal control, depression model, tumor model, depression tumor model, SGJPF, chemotherapy, and SGJPF+chemotherapy groups. The last 3 groups were depression breast cancer mice and treated respectively with SGJPF, chemotherapy drug gemcitabine (GEM), and SGJPF alongside GEM. The condition of the mice was evaluated by the expression of 5-hydroxytryptamine in hippocampus after the sucrose water test and open field test, weight change, and survival time. Tumor growth was monitored with in vivo imaging. Flow cytometry was used to analyze the level of myeloid-derived suppression cell (MDSC) in the mouse spleen, T cell subsets, and the early apoptosis of CD8+ T cells. RESULTS: The SGJPF+GEM group had the highest inhibition rate and the longest survival time (P<0.01). The MDSC level and the apoptosis rate of CD8+ T cells was the highest in the SGJPF+GEM group (P<0.05). CONCLUSIONS: Depressive disorders and tumor growth could suppress the immune function of mice to different degrees, and the microenvironment in late 4T1 inflammatory breast cancer may play an important role in the pathological process. SGJYF could regulate the immune microenvironment by reducing CD8+ T lymphocyte apoptosis and tumor cell activity, increasing immune surveillance capability, and inhibiting MDSC proliferation, thus prolonging the survival time of tumor-bearing mice.

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.

Effectiveness of Acupuncture for Early Recovery of Bowel Function in Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: The aim of this study was to evaluate the effects of acupuncture therapy to reduce the duration of postoperative ileus (POI) and to enhance bowel function in cancer patients. METHODS: A systematic search of electronic databases for studies published from inception until January 2017 was carried out from six databases. Randomized controlled trials (RCTs) involving the use of acupuncture and acupressure for POI and bowel function in cancer patients were identified. Outcomes were extracted from each study and pooled to determine the risk ratio and standardized mean difference. RESULTS: 10 RCTs involving 776 cancer patients were included. Compared with control groups (no acupuncture, sham acupuncture, and other active therapies), acupuncture was associated with shorter time to first flatus and time to first defecation. A subgroup analysis revealed that manual acupuncture was more effective on the time to first flatus and the time to first defecation; electroacupuncture was better in reducing the length of hospital stay. Compared with control groups (sham or no acupressure), acupressure was associated with shorter time to first flatus. However, GRADE approach indicated a low quality of evidence. CONCLUSIONS: Acupuncture and acupressure showed large effect size with significantly poor or inferior quality of included trials for enhancing bowel function in cancer patients after surgery. Further well-powered evidence is needed.

A multicenter randomized controlled open-label trial to assess the efficacy of compound kushen injection in combination with single-agent chemotherapy in treatment of elderly patients with advanced non-small cell lung cancer: study protocol for a randomized controlled trial.

BACKGROUND: With the aging of the global population, an increasing number of elderly are diagnosed with advanced non-small cell lung cancer. Although systematic chemotherapy has been one of the primary treatments for advanced non-small cell lung cancer worldwide, the elderly cannot always tolerate standard platinum-based doublet chemotherapy, thus resulting in treatment failure. To reduce toxicity, single-agent chemotherapy is often used to treat the elderly with non-small cell lung cancer; however, this may increase the risk of treatment failure due to an inadequate dose. It has been shown that compound kushen injection in combination with chemotherapy can enhance the efficacy and reduce the toxicity. The aim of this trial is to assess the clinical effectiveness and safety of compound kushen injection in combination with single-agent chemotherapy versus platinum-based doublet chemotherapy in the treatment of elderly patients with advanced non-small cell lung cancer. METHODS: This multicenter study will be an open-label, randomized controlled trial. Three hundred seventy elderly patients with advanced non-small cell lung cancer will be randomly divided into experimental (n = 185) and control groups (n = 185) to receive compound kushen injection in combination with single-agent chemotherapy or standard platinum-based doublet chemotherapy for two cycles. After two cycles, the disease control rate, objective response rate, clinical symptoms, quality of life, Karnofsky Performance Status, and side effects will be assessed. Follow-up evaluations will be performed every 8 weeks to evaluate the progression-free and overall survival. DISCUSSION: Before the trial was designed, compound kushen injection was shown to be effective for lung cancer through basic experiments and clinical trials. This study will determine whether or not the efficacy of compound kushen injection in combination with single-agent chemotherapy is comparable to that of platinum-based doublet chemotherapy, and whether or not the toxicity of compound kushen injection in combination with single-agent chemotherapy is lower than that of platinum-based doublet chemotherapy. TRIAL REGISTRATION: ChiCTR-IPR-14005484 (16 November 2014).

[Oxymatrine Diminished the Side Population and Inhibited Wnt/p-catenin Signaling Pathway in MCF- 7 Breast Cancer Cells].

Objective To observe the effects of oxymatrine (OM) in inhibiting the proliferation and percentage of cancer stem cell like cell of human breast cancer MCF-7 cells, and to study its molecular mechanism. Methods MCF-7 cells were taken as subject. Side population cells (SP) of cancer stem cell like cells rich in MCF-7 cells were isolated using side population (SP) method. The proliferation properties of SP cells and non-side population (non-SP) cells were detected by MTT assay. The proliferation and intervention of cisplatin (DDP) and OM at various concentrations were detected as well. The ex- pression levels of ß-catenin gene and protein were detected using flow cytometry and immunofluorescence technique. Results (1) OM in different concentrations had various inhibitions to the proliferation of subpopulations of MCF-7 cells. Of them, it had weakest inhibition on non-SP cells, weaker inhibition on unsorted cells, and strongest inhibition on SP cells. DDP in different concentrations had strongest inhibition on non-SP cells, weaker inhibition on unsorted cells, and weakest inhibition on SP cells. (2) SP cells accounted for 3. 1%, 1. 7%, and 0. 2% of the total cells after OM acted at 0. 25, 0. 50, 1. 00 mg/mL, respectively. The expression rate of phosphorylated ß-catenin was 42. 62% ±2. 62% after SP cells were ac- ted by OM, with statistical difference as compared with the blank control group [ (22. 8% ±1. 66%) ,P < 0. 01]. (3) Compared with SP cells without OM treatment, the expression of ß-catenin in OM treated SP cells was obviously reduced. Besides, they were specifically distributed under the cytomembrane, with nuclear translocation obviously reduced. Conclusion OM could intervene biological behaviors of cancer stem cell like cell of MCF-7 cells possibly through Inhibiting the activation of Wnt/ß-catenin signaling pathway.

Traditional Chinese medicine and cancer: History, present situation, and development.

Cancer treatment with traditional Chinese medicine (TCM) has a long history. Heritage provides general conditions for the innovation and development of TCM in oncology. This article reviews the development of TCM in oncology, interprets the position and function of TCM for cancer prevention and treatment, summarizes the innovations of TCM in oncology over nearly fifty years, and suggests the development direction.

[Effect of immune 2 with highly active antiretroviral treatment on immune function of HIV/AIDS patients with poor immune reconstitution].

OBJECTIVE: To observe the effection of immune reconstitution efficiency and the immune function on Immune 2 with HAART to HIV/AIDS patients which poor immune reconstitution after HAART. METHOD: Two hundred and sixty four patients failure to immune reconstitution after HAART were randomly divided into treatment group (131 cases) and control group (133 cases), respectively, using Immune 2 plus HAART and placebo combined with HAART for 6 months. the CD4, CD8, CD45RA, CD45RO, CD4CD28, CD8CD28, CD8CD38, HLA-DR and CD4CD25 were observed in order to evaluate the immune reconstitution efficiency. RESULT: After the intervention for 6 months, the effective rate of treatment group (34.48%) was significantly superior to the control group (21.37%) (P = 0.0217). Treated group could significantly increased the CD4, CD45RA, CD45RO cell counts compared with control group (P < 0.05); CD8, CD3, CD4CD28 absolute count comparison between the two groups had no significant difference; CD8CD28 relative counting the treatment group group significantly increased (P < 0.05) compared to the control; CD4CD28, CD8CD38, CD8DR, CD4CD25 relative counting groups showed no significant difference. CONCLUSION: Immune 2 can effectively improve the immune reconstitution efficiency, CD4 counts, CD45RA counts and CD45RO counts of patients after HAART, therefore promoting immune reconstitution.