Quxie Capsule Alleviates Colitis-associated Colorectal Cancer Through Modulating the Gut Microbiota and Suppressing A. fumigatus-induced Aerobic Glycolysis.

AIM: Quxie capsule (QX), a compound of 21 kinds of Traditional Chinese Medicine (TCM) herbs, has been used to treat patients with metastatic colorectal cancer (mCRC) and could suppress the growth of colon cancer. However, the mechanisms of QX inhibiting colorectal cancer remain unclear. In current study, we attempted to determine the anti-colorectal cancer (CRC) effects of QX and the mechanisms of QX in alleviating colorectal cancer. METHODS: A colitis-associated colon cancer (CAC) model was established by intraperitoneally injecting mice with AOM followed by 3 cycles of 2% DSS in water. During establishment of CAC model, we orally gavaged mice with QX. Hematoxylin and eosin (H&E) and immunohistochemistry were performed to assess lesion of the colonic tumors. The expression of pro-inflammatory cytokines in colonic tumors was measured by qPCR. The proportion of immune cells in colonic tumors was analyzed by flow cytometry. Internal transcribed spacer (ITS) sequencing and 16S rRNA gene sequencing were performed to detect intestinal microbiota. The expression of glycolytic related enzymes, lactate production, and extracellular acidification rate (ECAR) were used to assess the level of aerobic glycolysis. RESULTS: QX markedly inhibited intestinal tumorigenesis by decreasing the expression of pro-inflammatory cytokines and the proportion of myeloid-derived suppressor cells (MDSCs), and increasing the proportion of CD8+ T cells in colon tumors. Fecal microbiota sequencing revealed that QX increased the relative abundances of intestinal symbiotic probiotics, such as, Lactobacillus, Bifidobacterium and Faecalibacterium genera. What's more, opportunistic pathogens, Bacteroides genera and Aspergillus-Aspergillus fumigatus, exhibited remarkably reduced abundances in mice treated with QX compared with untreated CAC mice. Further experiments showed that QX significantly reduced glycolysis of colon tumor and suppressed A. fumigatus-induced glycolytic metabolism of colon cancer cells. CONCLUSIONS: QX alleviates the development of CRC at least in part through modulating intestinal microbiota and reducing A. fumigatus-induced aerobic glycolysis of colon cancer cells.

Basic Characteristics, Status, and Challenges of Integrative Oncology in China.

Integrative oncology has developed for about 20 years in some countries; however, integrative oncology is still a relative new term for most China's oncologists. Thus, it is essential to summarize the experience and expertise, share details of differing existing models and discuss future perspectives to help define and guide practice in integrative oncology in China. This study presents a summary of the basic characteristics, status, and challenges of integrative oncology in China, and also reports on China's integrative physicians' service delivery, clinical practice and research patterns of integrative oncology by an online national survey, including 405 oncologists. It is easy for cancer patients to access to integrative therapies in China. Public funding is sufficient for integrative oncology in China, and services are often provided through general hospitals and academic hospitals. Most (95.3%) of oncologists showed a positive attitude toward the development of integrative oncology. More than half (55.6%) of the oncologists worried about the influence on integrative oncology of COVID-19, especially for routine treatment, follow-up and holding seminars. We found that integrative oncology in China has swiftly developed in recent years. However, we suggest that standard diagnosis and treatment patterns and national professional guidelines should be set up as soon as possible.

Determination of Endogenous Bufalin in Serum of Patients With Hepatocellular Carcinoma Based on HPLC-MS/MS.

Bufalin is a cardiotonic steroid and a key active ingredient of the Chinese medicine ChanSu. It has significant anti-tumor activity against many malignancies, including hepatocellular carcinoma (HCC). Previous studies have shown that human bodies contain an endogenous bufalin-like substance. This study aimed to confirm whether the endogenous bufalin-like substances is bufalin and further detect the differences between HCC and control groups of endogenous bufalin concentration by the high-performance liquid chromatography coupled tandem mass spectrometry (HPLC-MS/MS). The results confirmed the endogenous bufalin-like substance is bufalin. Totally, 227 serum samples were collected: 54 from HCC patients and 173 from healthy volunteers constituting a control group. Both the test group and the control group contained bufalin in serum, revealing that bufalin is indeed an endogenous substance. The bufalin concentration was 1.3 nM in HCC patients and 5.7 nM in normal people (P < 0.0001). These results indicate that human bodies contain endogenous bufalin, and it may be negatively correlated with the incidence of HCC.

How does the social environment during life course embody in and influence the development of cancer?

OBJECTIVES: This review assessed the complex longitudinal processes involved in cancer etiology during life course to understand how the social inequality may be embodied in and influence cancer risk. METHODS: A narrative literature review was performed with a keyword search conducted using PubMed, Scientific Electronic Library Online and Google. Three aspects of literatures were mainly included: social environmental mechanisms of cancer, life course of cancer development and social inequality of cancer risk. This review was complemented with manual searches of relevant journals and reference lists of primary articles. RESULTS: Social inequality is mostly embodied in genetic susceptibility and early childhood development, the duration and intensity of exposures and the access to medical resources, which influence the timing and accumulation of cancer risk during life course. CONCLUSIONS: The individuals with lower socioeconomic status are more likely to have higher cancer risk because of more frequency of timing and quantity of accumulation of adverse exposures and greater impact on epigenetic mechanisms. Primary prevention is the best prevention strategy to reduce cancer risk.

Quality of Reporting in Oncology Randomized Controlled Trials: From 2011 to 2015.

Randomized controlled trials (RCTs) are important for evidence-based medicine; however, their quality of reporting remains to be evaluated. The aim of this study was to assess the quality of the report concerning solid tumor medication. Articles were searched in PubMed to identify all oncology phase III RCTs published from 2011 to 2015, and the results were classified manually through Endnote X7.0 software. Registration rate, primary end point (PEP) consistency, positive result rate, enrollment time point, outcome feedback in the registry, and publish time zone were extracted and assessed. The overall registration rate was higher than years before; nevertheless, a portion of trials showed PEP discrepancies and enrolled patients before registration in either journal formats. Trials published in top 5 general medical journals paid more attention to results feedback on registration websites and were more prompt with publication after study accomplishment. Our data suggested general medical journals may be more rigorous compared to oncology journals but identified a preference for positive results. On the whole, RCTs published between 2011 and 2015 seemed fairly standardized. Surveillance in registry and outcome feedback still needs to be strengthened for the stringency and reliability of clinical trials in solid tumor medication territory.

Discrepant Views of Oncologists and Cancer Patients on Complementary and Alternative Medicine in a Chinese General Hospital.

PURPOSE: Complementary and alternative medicine (CAM) has been widely used by cancer patients but rarely discussed by oncologists. This study was designed to evaluate the communication gap between China's oncologists and cancer patients on CAM. METHODS: Two parallel cross-sectional studies assessed 83 oncologists and 402 cancer patients on CAM communication between patients and oncologists, and attitudes toward CAM use and clinical decisions about CAM. RESULTS: A majority (75.1%) of the cancer patients (302/402) were identified as CAM users within the most recent three months while 77.6% of the cancer patients (312/402) were identified as CAM users since diagnosis of cancer. Oncologists and patients responded differently ( P < .001) on CAM communications. Both oncologists and patients expected that CAM could improve the immune system. They both agreed that oncologists usually discouraged their patients from using CAM. Regarding the effectiveness of CAM, cancer patients were more likely to believe that CAM was effective while oncologists had more concerns about adverse effects of CAM use. CAM use by patients was predicted by disease duration (≥9 months) in the multivariable logistic regression model. CONCLUSION: China's oncologists and cancer patients may hold discrepant views on CAM. China's oncologists are encouraged to improve their knowledge on CAM and to initiate more discussions with their patients regarding effective and the safe use of CAM.

Characteristic Analysis of Complementary and Alternative Medicine in Randomized Controlled Trials of Oncology: A Comparison of Published Studies.

BACKGROUND: Complementary and alternative medicine (CAM) has been widely used by cancer patients and oncologists in the past decades. The present study aimed to examine and compare the characteristics and registration status of published studies in a sample of recently published CAM randomized controlled trial (RCT) reports of oncology in leading journals of 3 categories: general and internal medicine (GIM), clinical oncology (CO), and CAM. METHODS: Articles published in the top 5 journals of the 3 categories from 2006 to 2015 were searched in PubMed. Basic characteristics, registration information, impact factor, and citations were identified and extracted from the included RCTs. Data were summarized by frequency, mean, and median and compared using χ2 test and Kruskal-Wallis H test. RESULTS: A total of 59 RCTs were included; among them, 34 (58%) could be identified with a registration number. GIM journals (15) enjoyed the highest average number of citations per article, followed by CO (12) and CAM (3) journals ( P < .0001). ClinicalTrials.gov was the most popular registry for these RCTs. Of the RCTs registered in ClinicalTrials.gov , 24% (4/17) of the published studies in CO journals put their results in the registry; however, no study in GIM and CAM journals put the result in the registry ( P = .372). CONCLUSION: The top GIM, CO, and CAM journals rarely published CAM RCTs of oncology from 2006 to 2015, and the CAM articles of oncology were less cited. However, there was a clear improvement in the trial registration rate over the past decades.

Bufalin-loaded bovine serum albumin nanoparticles demonstrated improved anti-tumor activity against hepatocellular carcinoma: preparation, characterization, pharmacokinetics and tissue distribution.

OBJECTIVE: To prepare and evaluate the liver-targeted drug delivery system of Bufalin with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma. METHODS: Bufalin-loaded bovine serum albumin nanoparticle was prepared by desolvation method, to investigate the in vitro release performance and to evaluate the pharmacokinetic and tissue distribution. The antitumor activity against hepatocellular carcinoma was evaluated in vitro and in vivo, respectively. RESULTS: The Bufalin-loaded bovine serum albumin nanoparticle with an average particle size of 125.1 nm exhibited a sustained release behavior in vitro. The half-life, blood plasma area under the curve and apparent volume of distribution of Bufalin-loaded bovine serum albumin nanoparticle were significantly higher than that of Bufalin, whereas the clearance rate was lower than Bufalin group. The uptake of liver for Bufalin-loaded bovine serum albumin nanoparticle was 352.045 ± 35.665 ng/g while for Bufalin was 164.465 ± 48.080 ng/g (P < 0.01) at 5 min. The uptake of tumor for Bufalin-loaded bovine serum albumin nanoparticle was significantly higher than that of Bufalin both at 5 min (50.169 ± 11.708 ng/g, 93.415±13.828 ng/g, P < 0.01) and 15 min (43.683 ± 11.499 ng/g, 64.219 ± 17.684 ng/g, P > 0.05). Bufalin-loaded bovine serum albumin nanoparticle and Bufalin have similar antitumor activity in vitro. The tumor inhibition effect of Bufalin-loaded bovine serum albumin nanoparticle was stronger than that of Bufalin alone in vivo. CONCLUSION: Bufalin-loaded bovine serum albumin nanoparticle is a promising liver-targeted drug delivery system with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma.

National survey of China's oncologists' knowledge, attitudes, and clinical practice patterns on complementary and alternative medicine.

It is common for cancer patients to use complementary and alternative medicine (CAM). This study was designed to explore China's oncologists' knowledge, attitudes and clinical practices regarding CAM use by their patients. An online survey was conducted of China's oncologists. Among 11,270 participants who completed the online survey, 6,007 (53.3%) were identified as oncologists. Most were men (75.2%), with a mean age of 33.4 (standard deviation: 6.5) years. The 6,007 oncologists discussed with 36.5% of their patients about CAM. Most of them (75.6%) did not want to initiate discussions due to lack of knowledge on CAM. Oncologists estimated that 40.0% of their patients used CAM treatments. Oncologists reported that 28.7% of their patients underwent anticancer therapy with the concurrent use of CAM. Four out of five of the responding oncologists self-reported inadequate knowledge and only 22.0% reported receiving professional education on CAM. Nearly half (44.9%) of the oncologists believed CAM treatment was effective for symptoms and treatment of cancer. Physician factors associated with initiating discussions with patients about CAM use included sex, age (≥ 33 years), medical license for traditional Chinese medicine, enough knowledge and professional education experience. China's oncologists infrequently discussed with their patients about CAM due to lack of knowledge. Most of the oncologists did not encourage CAM use.

China's growing contribution to military Chinese medicine (2005-2014): a ten-year literature survey.

OBJECTIVE: In China, people have relied on traditional Chinese medicine (TCM) for thousands of years to keep healthy and treat diseases. TCM also plays an important role in military health services and now forms a new discipline called military Chinese medicine (MCM). However, the type, quality and focus of research articles about MCM have not been reported. The present study was performed to analyze the growing trends of MCM and investigate China's contribution to military health services. METHODS: China's MCM publications were retrieved from the PubMed database, as well as China National Knowledge Infrastructure, Wanfang Data and Chongqing VIP database from 2005 to 2014. RESULTS: The study found that the number of published articles increased markedly from 2005 to 2014. Basic research studies comprised a small percentage of the literature. Among these studies, military training injury and special military environmental medicine were the most common research subjects in MCM. Military hospitals were the main institutions generating MCM literature. CONCLUSION: The quality of MCM research is generally low, as indicated by the proportion of publications in core journals. Studies on MCM still lack high-quality publications and international cooperation.

HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review.

As there are millions of cancer deaths every year, it is of great value to identify applicable prognostic biomarkers. As an important alarm, the prognostic role of high mobility group box 1 (HMGB1) in cancer remains controversial. We aim to assess the association of HMGB1 expression with prognosis in cancer patients. Systematic literature searches of PubMed, Embase and Web of Science databases were performed for eligible studies of HMGB1 as prognostic factor in cancer. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the influence of HMGB1 expression on overall survival (OS) and progression-free survival (PFS) in cancer patients. 18 studies involving 11 different tumor types were included in meta-analysis. HMGB1 overexpression was significantly associated with poorer OS (HR: 1.99; 95% CI, 1.71-2.31) and PFS (HR: 2.26; 95% CI, 1.65-3.10) irrespective of cancer types including gastric cancer, colorectal cancer, hepatocellular carcinoma, pancreatic cancer, nasopharyngeal carcinoma, head and neck squamous-cell carcinoma, esophageal cancer, malignant pleural mesothelioma, bladder cancer, prostate cancer, and cervical carcinoma. Subgroup analyses indicated geographical area and size of studies did not affect the prognostic effects of HMGB1 for OS. Morever, HMGB1 overexpression had a consistent correlation with poorer OS when detected by immunohistochemistry in tissues and enzyme-linked immunosorbent assay in serum, whereas the correlation did not exist by quantitative real-time reverse-transcription polymerase chain reaction in tissues. HMGB1 overexpression is associated with poorer prognosis in patients with various types of cancer, suggesting that it is a prognostic factor and potential biomarker for survival in cancer.

A case report of gastric cancer with brain metastasis: Rare peripheral nervous system symptoms.

Gastric cancer with brain metastasis is rare. The present study reports a case of gastric cancer with isolated brain metastasis 1 year after gastrectomy. To the best of our knowledge, there have been no prior reports of solitary brain metastasis from gastric cancer with peripheral nervous system symptoms. A distal gastrectomy was performed on a 60-year-old male patient with gastric cancer in November 2012. Postoperative pathological analysis revealed a moderately differentiated adenocarcinoma with tumor invasion into the serosa and metastasis to one dissected lymph node. No abnormalities were found at follow-up examination. However, a tumor representing metastasis to the brain was recognized by a cranial enhanced magnetic resonance imaging examination 1 year after gastrectomy, which was performed when the patient exhibited numbness and thigmesthesia. The patient was administered 30 Gy of stereotactic radiotherapy, delivered in 5 fractions. The patient succumbed to disease 10 months subsequent to undergoing radiotherapy. This case report suggests that gastric cancer may re-present as brain metastasis with peripheral nervous system symptoms.

Corosolic acid analogue, a natural triterpenoid saponin, induces apoptosis on human hepatocarcinoma cells through mitochondrial pathway in vitro.

Context 2a,-3a,-24-Trihydroxyurs-12-en-28-oic acid (TEO, a corosolic acid analogue) is a triterpenoid saponin isolated from Actinidia valvata Dunn (Actinidiaceae), a well-known traditional Chinese medicine. Objective This study investigated the anti-proliferation and inducing apoptosis effects of TEO in three human hepatocellular carcinoma (HCC) cell lines. Materials and methods Cytotoxic activity of TEO was determined by the MTT assay at various concentrations from 2.5 to 40 µg/mL in BEL-7402, BEL-7404 and SMMC-7721 cell lines. Cell morphology was assessed by acridine orange/ethidium bromide and 4'-6-diamidino-2-phenylindole dihydrochloride staining and fluorescence microscopy. Cell-cycle distribution and DNA damage were determined by flow cytometry and comet assay. Mitochondrial dysfunction was assessed by JC-1 staining and transmission electron microscopy. Apoptosis changes were explored by Western blot, TNF-α and caspase-3, -8, -9 assays. Results TEO exhibited inhibition effects on BEL-7402, BEL-7404 and SMMC-7721 cells treated for 24 h, the IC50 values were 34.6, 30.8 and 30.5 µg/mL, respectively. TEO (40 µg/mL)-treated three cell lines increased by more than 21% in the G1 phase and presented the morphological change and DNA damage. TEO also declined the mitochondrial membrane potential and altered mitochondrial ultra-structure. Furthermore, caspase-3, caspase-8, caspase-9 and TNF-α were also activated. Mechanism investigation showed that TEO could decrease anti-apoptotic Bcl-2 protein expression, increase proapoptotic Bax and Bid proteins expressions and increase Bax/Bcl-2 ratio. Conclusion Our results demonstrate for the first time that TEO inhibited growth of HCC cell lines and induced G1 phase arrest. Moreover, proapoptotic effects of TEO were mediated through the activation of TNF-α, caspases and mitochondrial pathway.

How do systematic reviews of acupuncture for pain relief incorporate risk of bias assessments into the synthesis? A methodological study.

OBJECTIVE: By reviewing the assessment of internal validity in relevant systematic reviews (SRs), the aim of this study was to identify how critical appraisals of risk of bias (RoB) inform the synthesis of evidence in SRs of acupuncture for pain relief. METHODS: SRs were searched in Medline, EMBASE, and the Cochrane Database of SRs from their inception to 30 December 2014. Only SRs of acupuncture for pain relief were included. Basic information, types of RoB appraisal tool, whether or not there was domain-level assessment of RoB, whether or not the reviews ranked studies by RoB, plus whether or not (and, if so, how) RoB appraisal was incorporated into the synthesis were determined. RESULTS: A total of 91 SRs met the inclusion criteria and were included in the final analysis. Over half of the SRs (85, 64.8%) used standard tools, such as the Jadad quality score and the Cochrane RoB tool, followed by adapted tools (n=23, 25.3%). Of the 85 SRs that assessed RoB, 29 (34.1%) presented domain-level assessment and 71 SRs (83.5%) included ranking of the studies based on RoB assessment. Of these 71, 35 (49.4%) used a cut-off threshold score and 26 (36.6%) required all criteria sum-up. Of the 85 SRs that assessed RoB, 48 (56.5%) incorporated RoB appraisal into the data synthesis. CONCLUSIONS: Although most SRs of acupuncture for pain relief conducted some form of RoB assessment, nearly half of them failed to incorporate the RoB assessment into the synthesis.

The application status of Chinese herbal medicine in military health service in China.

Military medicine has had a long history in China since the emergence of the war. Chinese medicine, especially Chinese herbs, was widely used in China as well as other Asian countries for the prevention and treatment of diseases in the military for hundreds of years. However, the use of Chinese medicine in military health service has never been well studied. In this article, we briefly summarize the application status of Chinese herbal medicine in military health service in China, putting particular emphasis on special military environment, in an attempt to build a bridge between Chinese medicine and military health service and promote the quality of health service for the military and maintain world peace.

Comparison of registered and published primary outcomes in randomized controlled trials of gastroenterology and hepatology.

OBJECTIVES. The need for trial registration as well as the benefits it has brought for the transparency of medical research has been recognized for years. Trial registration has turned from an exception to a mandatory guideline in recent years. The present study aimed to examine the characteristics of registered randomized controlled trials (RCTs) in a sample of recently published gastroenterology RCTs, and to assess the consistency of registered and published primary outcome (PO) in RCTs. METHODS. Articles published in the top five "general and internal journals" and top five "gastroenterology and hepatology journals" categories between 2009 and 2012 were searched in PubMed. Basic characteristics and the registration information were identified and extracted from the included RCTs. PO consistency analysis was conducted to compare between the registered and published format. RESULTS. A total of 305 RCTs were included; among them 252 could be identified with a registration number. Nearly half of these RCTs were funded solely by industry (141/305, 46.3%). ClinicalTrials.gov was the most popular registry for these RCTs (214/252, 84.9%). A total of 155 RCTs were included in the PO consistency analysis. Among them, 22 (14.2%) RCTs had discrepancies between POs registered in the trial registry compared to the published article. CONCLUSIONS. Based on the results of the present study, selective outcome reporting of gastroenterology RCTs published in leading medical journals has been much improved over the past years. However, there might be a sampling bias to say that consistency of registered and published POs of gastroenterology RCTs has been better than before.