Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice

AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.METHODS: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors, and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice. Seventy-five animals were randomized divided into five groups (n = 15). Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg (BF1), 1 mg/kg (BF2) and 0.5 mg/kg (BF3) for d 15-24, respectively. The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15. Ten mice in each group were killed at d 25 and the survival time in each group was calculated. We also observed the morphologic alterations in the myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscopy, measured the apoptotic rate by TUNEL staining method, and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues. RESULTS: The tumor volumes in each group of bufalin were reduced significantly (35.21 ± 12.51 vs 170.39 ± 25.29; 49.83 ± 11.46 vs 170.39 ± 25.29; 83.99 ± 24.63 vs 170.39 ± 25.29, P < 0.01, respectively), and the survival times were prolonged in group BF1-2 (31.8 ± 4.2 vs 23.4 ± 2.1 and 29.4 ± 3.4 vs 23.4 ± 2.1, P < 0.05, respectively), and necrosis was mainly in severe or moderate degree in group BF1-2. No morphologicalchanges were detected in the myocardium, brain, liver and kidney tissues. Apoptotic characteristics could be seen in group BF1-2. The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0%, 10.0%, 20.0%, 10.0% and 20.0%; 90.0%, 80.0%, 80.0%, 40.0% and 30.0%, respectively. Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR. CONCLUSION: Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax, which may be involved in its anti-tumor mechanism of bufalin.

Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: a multicenter randomized controlled trial

BACKGROUND： Disease recurrence is a main challenge in treatment of hepatocellular carcinoma （HCC）. There is no generally accepted method for preventing recurrence of HCC after resection. OBJECTIVE： To compare the efficacy of a traditional herbal medicine （THM） regimen and transarterial chemoembolization （TACE） in preventing recurrence in post-resection patients with small HCC. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This is a multicenter, open- label, randomized, controlled study, which was undertaken in five centers of China. A total of 379 patients who met the eligibility criteria and underwent randomization were enrolled in this trial. One hundred and eighty-eight patients were assigned to the THM group and received Cinobufacini injection and Jiedu Granule, and the other 191 patients were assigned to the TACE group and received one single course of TACE. MAIN OUTCOME MEASURES： Primary outcome measures were the annual recurrence rate and the time to recurrence. Incidence of adverse events was regarded as the secondary outcome measure. RESULTS： Among the 364 patients who were included in the intention-to-treat analysis, 67 patients of the THM group and 87 of the TACE group had recurrence, with a hazard ratio of 0.695 （P = 0.048）. Median recurrence-free survival of the patients in the THM and TACE groups was 46.89 and 34.49 months, respectively. Recurrence rates at 1, 2 and 3 years were 17.7%, 33.0% and 43.5% for the THM group, and 28.8%, 42.5% and 54.0% for the TACE group, respectively （P = 0.026）. Multivariate analysis indicated that the THM regimen had a big advantage for prolonging the recurrence-free survival. Adverse events were mild and abnormality of laboratory indices of the two groups were similar. CONCLUSION： In comparison with TACE therapy, the THM regimen was associated with diminished risk of recurrence of small-sized HCC after resection, with comparable adverse events. TRIAL REGISTRTION IDENTIFIER： This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-07000033.

Psychosocial and spiritual needs of patients with chronic diseases: validation of the Chinese version of the Spiritual Needs Questionnaire

OBJECTIVE： Even in secular societies, a small portion of patients find their spirituality to help cope with illness. But for the majority of patients, psychosocial and spiritual needs are neither addressed nor even considered a relevant factor by health care professionals. To measure such specific needs, the Spiritual Needs Questionnaire （SpNQ） was developed. The aim of this study was to validate the Chinese version of the SpNQ （SpNQ-Ch） and thus to measure psychosocial and spiritual needs of Chinese patients. METHODS： This was a cross-sectional study among 168 patients with chronic diseases who were recruited in the Changhai Hospital of Traditional Chinese Medicine, Shanghai, China using standardized questionnaires. We performed reliability and factor analyses, as well as analyses of variance, first order correlations and regression analyses. RESULTS： The 17-item SpNQ-Ch had a similar factorial structure as the original version with two main and three minor factors which accounted for 64% of variance, and internal consistency estimates （Cronbach＇s a） ranging from 0.51 to 0.81. Included were the 4-item scale Inner Peace Needs, the 5-item scale Giving/Generativity （with 2 sub-constructs, Praying and Sources）, and a Needs, the 5-item scale Religious Needs 3-item scale Reflection/Release Needs. In Chinese patients with cancer （63%）, pain affections （10%）, or other chronic conditions （23%）, the needs for Giving/Generativity （which refer to categories of Connectedness and Meaning） and Inner Peace Needs scored highest, while Religious Needs and the Reflection/Release Needs scored lower. CONCLUSION： The SpNQ-Ch is congruent with its primary version, and can be used in future studies with the mostly nonreligious patients from China. First findings indicate specific psychosocial and spiritual needs which should be addressed by health care professionals to support patients in their struggle with chronic illness in terms of psycho-emotional stabilization, finding hope and meaning, and thus achieving peaceful states of mind despite chronic illness.

Health-related quality of life evaluated by tumor node metastasis staging system in patients with hepatocellular carcinoma

AIM: To investigate and evaluate the change in healthrelated quality of life (HRQoL) by tumor node metastasis (TNM) staging system in patients with hepatocellular carcinoma (HCC). METHODS: A total of 140 patients diagnosed with HCC between June 2008 and April 2009 in our department were enrolled to this study. One hundred and thirty-five (96.5%) patients had liver cirrhosis secondary to hepatitis B virus (HBV) infection, 73 (54.07%) of them being HBV DNA positive; the other etiologies of liver cirrhosis were alcoholic liver disease (1.4%), hepatitis C (1.4%) or cryptogenic (0.7%). All subjects were fully aware of their diagnosis and provided informed consent. HRQoL was assessed before treatment using the functional assessment of cancer therapy-hepatobiliary (FACT-Hep) questionnaire. Descriptive statistics were used to evaluate demographics and disease-specific characteristics of the patients. One-way analysis of variance and independent samples t tests were used to compare the overall FACT-Hep scores and clinically distinct TNM stages. Scores for all FACT-Hep items were analyzed by frequency analyses. The mean scores obtained from the FACT-Hep in different Child-Pugh classes were also evaluated. RESULTS: The mean FACT-Hep scores were reduced significantly from TNM StageⅠto Stage Ⅱ, Stage ⅢA, Stage ⅢB group (687 ± 39.69 vs 547 ± 42.57 vs 387 ± 51.24 vs 177 ± 71.44, P = 0.001). Regarding the physical and emotional well-being subscales, scores decreased gradually from Stage Ⅰ to Stage ⅢB (P = 0.002 vs Stage Ⅰ; P = 0.032 vs Stage Ⅱ; P = 0.033 vs Stage ⅢA). Mean FACT-Hep scores varied by Child-Pugh class, especially in the subscales of physical well-being, functional well-being and the hepatobiliary cancer (P = 0.001 vs Stage I; P = 0.036 vs Stage Ⅱ; P = 0.032 vs Stage ⅢA). For the social and family well-being subscale, only Stage ⅢB scores were significantly lower as compared with Stage Ⅰ scores (P = 0.035). For the subscales of functional well-being and hepatobiliary cancer, there were significant differences for Stages ⅡΙ, ⅢA and ⅢB (P = 0.002vs StageⅠ). CONCLUSION: HRQoL of patients with HCC worsens gradually with progression of TNM stages. The most impaired subscales of HRQoL, as measured by FACT-Hep, were physical and emotional well-being.

Treatment of cholecystitis with Chinese herbal medicines:A systematic review of the literature

AIM:To analyze the literature on the use of Chinese herbal medicines for the treatment of cholecystitis.METHODS:The literature on treatment of cholecystitis with traditional Chinese medicines(TCM) was analyzed based on the principles and methods described by evidence-based medicine(EBM).Eight databases including MEDLINE,EMbase,Cochrane Central(CCTR),four Chinese databases(China Biological MedicineDatabase,Chinese National Knowledge Infrastructure Database,Database of Chinese Science and Technology Periodicals,Database of Chinese Ministry of Science and Technology) and Chinese Clinical Registry Center,were searched.Full text articles or abstracts concerning TCM treatment of cholecystitis were selected,categorized according to study design,the strength of evidence,the first author's hospital type,and analyzed statistically.RESULTS:A search of the literature published from 1977 through 2009 yielded 1468 articles in Chinese and 9 in other languages;and 93.92% of the articles focused on clinical studies.No article was of levelⅠevidence,and 9.26% were of level Ⅱ evidence.The literature cited by Science Citation Index(SCI),MEDLINE and core Chinese medical journals accounted for 0.41%,0.68% and 7.29%,respectively.Typically,the articles featured in case reports of illness,examined from the perspective of EBM,were weak in both quality and evidence level,which inconsistently conflicted with the fact that most of the papers were by authors from Level-3 hospitals,the highest possible level evaluated based on their comprehensive quality and academic authenticity in China.CONCLUSION:The published literature on TCM treatment of cholecystitis is of low quality and based on low evidence,and cognitive medicine may functions as a useful supplementary framework for the evaluation.

Introducing the Journal of Integrative Medicine

At the beginning of this New Year of 2013, we are very pleased to present the English edition of the Journal of Integrative Medicine （JIM）, a PubMed-indexed, peer-reviewed, open-access journal on integrative medicine. The JIM is a continuation of the former Chinese-language journal, the Journal of Chinese Integrative Medicine （JCIM）, established in 2003 and published in Shanghai. Integrative medicine, grounded in patient-centered, evidence-based practice, incorporates the broad spectrum of complementary and alternative medicine （CAM） and includes acupuncture and traditional Chinese medicine, Ayurveda medicine, herbal medicine, homeopathy, nutrition, chiropractic, mind-body medicine, taichi, qigong, and meditation, among other professions. In the past two decades, CAM has become one of the fastest growing branches of health care. CAM now commands attention worldwide and is rapidly being integrated into conventional medicine. China is the country in the world that has great number of scientists doing clinical and research work on integrative medicine. With this new, English-language publication, we are committed to make JIM an international platform for high-quality CAM papers and an open forum in which the different professions and international scholarly communities can exchange views, share research and their clinical experience, discuss CAM education, and confer about issues and problems in our various disciplines and in CAM as a whole in order to promote integrative medicine.

Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency

Objective Melittin and its derivatives have been characterized to establish effective gene delivery systems.Their capability of facilitating endosomal release enhances the nanoparticles-based gene delivery.Nevertheless,little investigation has been conducted to explore its potential application in the context of viral vectors.Methods Various melittin-derived peptides were inserted into the loop VIII of the capsid proteins of recombinant adeno-associated virus vectors.These vectors carrying either gfp or fluc genes were subjected to qPCR assays and transduction assays of HEK293T cells to investigate the efficiency of vector production and gene delivery.In addition,the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 mice.Finally,the intricate details of the vector-mediated transduction mechanisms were revealed by specific pharmacological inhibitors of every stage of the rAAV2 intracellular life cycle.Results A total of 76 melittin-related peptides were compiled from existing literature.Among them,cMA2,Melt13,p5RHH and aAR3 were found to significantly enhance the gene delivery efficiency of rAAV2 vectors.The p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to rAAV.Mechanistically,bafilomycin A1,a vacuolar endosome acidification inhibitor,completely inhibited the transgene expression mediated by the p5RHH-rAAV2 vectors.Most importantly,p5RHH-rAAV8 vectors also demonstrated increased hepatic transduction in vivo in C57BL/6 mice.Conclusion The incorporation of melittin analogues into the rAAV capsids results in a significant improvement in rAAV-mediated transgene expression.While further modifications remain an area of interest,our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery.

Jiedu recipe,a compound Chinese herbal medicine,suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment

Objective:Tumor-derived exosomes(TDEs)play crucial roles in intercellular communication.Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis.Jiedu recipe(JR),a traditional Chinese medicinal formula,has demonstrated efficacy in preventing the metastasis of hepatocellular carcinoma(HCC).However,the underlying mechanism remains largely unknown.Methods:Animal experiments were performed to investigate the metastasis-preventing effects of JR.Bioinformatics analysis and in vitro assays were conducted to explore the potential targets and active components of JR.TDEs were assessed using nanoparticle tracking analysis(NTA)and Western blotting(WB).Exosomes derived from normoxic or hypoxic HCC cells(H-TDEs)were collected to establish premetastatic mouse models.JR was intragastrically administered to evaluate its metastasis-preventive effects.WB and lysosomal staining were performed to investigate the effects of JR on lysosomal function and autophagy.Bioinformatics analysis,WB,NTA,and immunofluorescence staining were used to identify the active components and potential targets of JR.Results:JR effectively inhibited subcutaneous-tumor-promoted lung premetastatic niche development and tumor metastasis.It inhibited the release of exosomes from tumor cells under hypoxic condition.JR treatment promoted both lysosomal acidification and suppressed secretory autophagy,which were dysregulated in hypoxic tumor cells.Quercetin was identified as the active component in JR,and the epidermal growth factor receptor(EGFR)was identified as a potential target.Quercetin inhibited EGFR phosphorylation and promoted the nuclear translocation of transcription factor EB(TFEB).Hypoxia-impaired lysosomal function was restored,and secretory autophagy was alleviated by quercetin treatment.Conclusion:JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release,restoring lysosomal function,and suppressing secretory autophagy.Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling.Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion.

Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor

Objective:Ginsenoside Rh1(G-Rh1)has been confirmed to inhibit the growth of breast cancer and colon cancer,but its therapeutic effect on hepatocellular carcinoma(HCC)is unclear.This study investigates the therapeutic effect of G-Rh1 on HCC as well as the underlying mechanism.Methods:Bioinformatics methods were used to analyze glucocorticoid receptor(GR)expression and the tumor microenvironment in HCC tissues from HCC patients.The effect of G-Rh1 on HCC cells was investigated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.The therapeutic effect of G-Rh1 was investigated in vivo using subcutaneous transplantation models in C57BL/6J and nude mice.Additionally,the proportion of infiltrating immune cells in tumors was analyzed using flow cytometry,the GR and major histocompatibility complex class-I(MHC-I)expression of HCC cells after G-Rh1 treatment was analyzed using Western blotting,and G-Rh1-treated Hepa1-6 cells were cocultured with bone marrow-derived dendritic cells and B3Z T cells to further analyze the ability of G-Rh1 to induce dendritic cell(DC)maturation and CD8+T cell activation.Results:GR expression was upregulated in HCC tissues,and high GR expression was associated with a worsened immune microenvironment.In vitro studies showed that G-Rh1 had no significant effect on the proliferation of HCC cells,while in vivo studies showed that G-Rh1 exerted antitumor effects in C57BL/6J mice but not in nude mice.Further research revealed that G-Rh1 ameliorated the immunosuppressive tumor microenvironment,thereby enhancing the antitumor effects of lenvatinib by increasing the infiltration of CD8+T cells,mature DCs,and MHC-I-positive cells.MHC-I was upregulated by G-Rh1 via GR suppression.Moreover,overexpression of GR abolished the G-Rh1-mediated promotion of MHC-I expression in Huh7 cells,as well as the maturation of DCs and the activation of CD8+T cells.Conclusion:G-Rh1 can regulate the immune microenvironment of HCC by targeting GR,thus increasing the antitumor effect of lenvatinib.

Three advantages of using traditional Chinese medicine to prevent and treat tumor

Traditional Chinese medicine （TCM）, an important component of complementary and alternative medicine, has evolved over thousands of years with its own unique system of theories, diagnostics and therapies. TCM has been increasingly used in the last decades and become well known for its significant role in preventing and treating cancer. We believe that TCM possesses advantages over Western medicine in specific aspects at a certain stage of cancer treatment. Here we summarize the advantages of TCM from three aspects： preventing tumorigenesis; attenuating toxicity and enhancing the treatment effect; and reducing tumor recurrence and metastasis.

Progress in research on the effects of traditional Chinese medicine on the tumor microenvironment

Tumor microenvironment （TME） has received more and more attention as modern medical research has begun to understand its importance in tumorigenesis. The occurrence, development, metastasis and drug resistance of tumors are closely related to TME. TME is a complicated system, including nontumor cells, their secreted cytokines, extracellular matrix, among other components. The concepts of wholism and multitarget regulation in traditional Chinese medicine （TCM） make it well suited to the regulation of TME. in this paper, the authors reviewed the progress of TME research and the effect of TCM on TME, providing some views of Chinese medicine in antitumor research.

Traditional Chinese medicine is a resource for drug discovery against 2019 novel coronavirus(SARS-CoV-2)

Novel coronavirus pneumonia,named as COVID-19 by the World Health Organization,has spread widely since December 2019[1–3],with more than 40,000 confirmed cases in China and exportations to over 20 countries[4].On January 30,2020,the World Health Organization declared the epidemic to be a public health emergency of international concern in the second meeting of the Emergency Committee[5].It was recommended that potential vaccines and antiviral medicines should be developed.However,the development of these therapeutics will take months,even years.For this specific indication,rapid performance of traditional Chinese medicine(TCM)can contribute as an alternative measure.

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 prac-tice 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 method- ological 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.

The roles of traditional Chinese medicine in gene therapy

The field of gene therapy has been increasingly studied in the last four decades, and its clinical application has become a reality in the last 15 years. Traditional Chinese medicine （TCM）, an important component of complementary and alternative medicine, has evolved over thousands of years with its own unique system of theories, diagnostics and therapies. TCM is well-known for its various roles in preventing and treating infectious and chronic diseases, and its usage in other modern clinical practice. However, whether TCM can be applied alongside gene therapy is a topic that has not been systematically examined. Here we provide an overview of TCM theories in relation to gene therapy. We believe that TCM theories are congruent with some principles of gene therapy. TCM-derived drugs may also act as gene therapy vehicles, therapeutic genes, synergistic therapeutic treatments, and as co-administrated drugs to reduce side effects. We also discuss in this review some possible approaches to combine TCM and gene therapy.

Pristimerin enhances recombinant adeno-associated virus vector-mediated transgene expression in human cell lines in vitro and murine hepatocytes in vivo

OBJECTIVE： In the present study, we systemically evaluated the ability of two bioactive compounds from traditional Chinese medicine, celastrol and pristimerin, to enhance recombinant adeno-associated virus （rAAV） serotype vector-mediated transgene expression both in human cell lines in vitro, and in murine hepatocytes in vivo. METHODS： Human cell lines were infected with rAAV vectors with either mock treatment or treatment with celastrol or pristimerin. The transgene expression, percentage of nuclear translocated viral genomes and the ubiquitination of intracellular proteins were investigated post-treatment. In addition, nonobese diabetic/severe combined immunodeficient gamma （NSG） mice were tail vain-injected with rAAV vectors and co-administered with either dimethyl sulfoxide, celastrol, pristimerin or a positive control, bortezomib. The transgene expression in liver was detected and compared over time. RESULTS： We observed that treatment with pristimerin, at as low as 1 IJmol/L concentration, significantly enhanced rAAV2 vector-mediated transgene expression in vitro, and intraperitoneal co- administration with pristimerin at 4 mg/（kg.d） for 3 d dramatically facilitated viral transduction in murine hepatocytes in vivo. The transduction efficiency of the tyrosine-mutant rAAV2 vectors as well as that of rAAV8 vectors carrying oversized transgene cassette was also augmented significantly by pristimerin. The underlying molecular mechanisms by which pristimerin mediated the observed increase in the transduction efficiency of rAAV vectors include both inhibition of proteasomal degradation of the intracellular proteins and enhanced nuclear translocation of the vector genomes. CONCLUSION： These studies suggest the potential beneficial use of pristimerin and pristimerincontaining herb extract in future liver-targeted gene therapy with rAAV vectors.

Comparable effects of Jiedu Granule, a compound Chinese herbal medicine, and sorafenib for advanced hepatocellular carcinoma: A prospective multicenter cohort study

Objective:Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma(HCC),and Chinese herbal medicine has also been used to manage advanced HCC.The present work evaluates the effectiveness and safety of Jiedu(JD)Granule,a compound of traditional Chinese herbal medicine,side-by-side with sorafenib for the treatment of advance HCC.Methods:Patients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March 2018.The primary endpoint was overall survival(OS).The secondary endpoints were progression-free survival(PFS)and safety.Propensity score matching(PSM)analysis was used to control for possible selection bias from the study group allocation process.Results:Of the 325 patients included,161 received JD Granule and 164 received sorafenib.No significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib(P>0.05).Median OS of the two study groups was 6.83 months(95%confidence interval[CI]:5.83–9.47)in the group receiving JD Granule and 8 months(95%CI:6.67–9.80)in the group receiving sorafenib,with half-,1-and 2-year survival rates of 53.6%,31.2%and 13.2%vs 60.1%,35.5%and 14.2%,respectively.Even after PSM,the median survival time did not differ between the JD Granule group(9.03 months;95%CI:6.37–14.2)and the sorafenib group(7.93 months;95%CI:6.5–9.97),with comparable half-,1-and 2-year survival rates.The most common adverse events(AEs)were diarrhea(13.7%)and fatigue(5.6%)in the JD Granule group,and hand-foot skin reaction(46.3%)and diarrhea(36.6%)in the sorafenib group.The JD Granule was more cost-effective than sorafenib treatment for advanced HCC.Conclusion:Compared to sorafenib,JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.

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 Nationa~ 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 internationa cooperation.

Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo

OBJECTIVE： Little effort has been made to study the protein-encoding genes isolated from traditional Chinese medicine（TCM） drugs, and the delivery of these genes into malignant cells through recombinant adeno-associated virus（r AAV） vectors has not been attempted. METHODS： We synthesized the c DNAs of five known cytotoxic proteins isolated from TCM drugs and the FLAG epitope-tagged c DNAs were subcloned into a r AAV plasmid vector. The protein expression was confi rmed by Western blot assay. Various cancer cell lines were transfected with the above plasmids and cell growth was monitored both in vitro and in vivo. The best cytotoxic gene was further packaged into r AAV vectors, under the control of a liver cancer-specifi c promoter. The liver tumor growth was then monitored following intratumor administration of the r AAV vectors.RESULTS： The expression plasmids, encoding individual potential cytotoxic genes tagged with FLAG epitope, were successfully generated and sequenced. Among these genes, trichosanthin（TCS） gene yielded the most promising results for the inhibition of cancer cell growth in vitro. The over-expressed TCS functioned as a type I ribosome-inactivating protein, followed by inducing apoptosis that is associated with the Bcl-PARP signaling pathway. Furthermore, intratumor injection of r AAV vectors containing the TCS gene signifi cantly inhibited the growth of human hepatocellular carcinoma tumors in a murine xenograft model.CONCLUSION： Our studies suggest that the use of TCM cytotoxic genes is a useful therapeutic strategy for treating human cancers in general, and liver tumors in particular.

Interpretation of illness in patients with chronic diseases from Shanghai and their associations with life satisfaction, escape from illness, and ability to reflect the implications of illness

The aim of this study is to analyze how patients with chronic diseases from Shanghai interpret their disease, and how these interpretations influence patients＇ life satisfaction, intention to escape from their illness and their ability to reflect on the implications of their illness. METHODS： A cross-sectional study enrolling 142 patients （mean age （50 ±16） years; 63% men, 37% women） with chronic diseases （60% cancer） was recruited in the Changhai Hospital of Traditional Chinese Medicine, Shanghai, China and surveyed using standardized questionnaires. RESULTS： Patients with chronic diseases from Shanghai interpreted their illness mostly as an Adverse Interruption of Life （55%）, as a Threat/Enemy （50%）, but also as a Challenge （49%）, and only rarely as a Call for Help （18%） or as a Punishment （13%）. Particularly fatalistic negative （i.e., Threat/Enemy, Adverse Interruption of Life） and strategy-associated disease interpretations （i.e., Relieving Break, Call for Help） were moderately associated with patients＇ intention to escape from illness. In contrast, positive interpretations （i.e., something of Value, Challenge） and also the guilt-associated negative interpretation Failure were moderately related with patients＇ ability to reflect on their illness. However, life satisfaction was weakly associated only with the view that illness might be a Challenge. Interestingly, 58% of those who would see their illness as an Adverse Interruption （AI＋） could see it also as a Challenge （Ch＋）. Detailed analyses showed that AI＋Ch＋ patients differ from their AI＋Chcounterparts significantly with respect to their ability to reflect life and implications of illness （F=9.1 ; P=-0.004）.

Knowledge about, attitude and acceptance towards, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China: A cross-sectional survey

Objective: The coronavirus disease 2019(COVID-19) pandemic has had a serious impact on health all over the world. Cancer patient, whose immunity is often compromised, faces a huge challenge.Currently, some COVID-19 vaccines are being developed and applied on general population;however,whether cancer patients should take COVID-19 vaccine remains unknown. Our study aimed to explore the knowledge, attitude, acceptance, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China.Methods: A cross-sectional study was conducted in Eastern China from June 17 th to September 3 rd, 2021.Patients were selected using a convenience sampling method. A self-report questionnaire was developed to assess knowledge about the COVID-19 vaccine, attitude towards the vaccine and acceptance of the vaccine;following a review of similar studies previously published in the scientific literature, multivariate logistic regression analysis was used to determine the predictors associated with COVID-19 vaccine acceptance.Results: A total of 2158 cancer patients were enrolled in this study. The rate of vaccine hesitancy was 24.05%(519/2158);further, among the participants of vaccine acceptance, 767 had taken COVID-19 vaccine(35.54%), and 872 were willing to get vaccinated(40.01%). A total of 24 variables including demographic characteristics, clinical status of cancer, impact of COVID-19 pandemic on study participants,patients’ knowledge about the COVID-19 vaccine, and attitude towards the vaccine, had significant differences between the ‘‘vaccine hesitancy" population and ‘‘vaccine acceptance" population.Multivariate logistic regression analysis indicated that parameters including alcohol consumption(odds ratio [OR] = 1.849;95% confidence interval [CI]: 1.375–2.488;P-reference [P-Ref] < 0.001 vs nondrinkers), income impacted by COVID-19 pandemic(OR = 1.930, 2.037 and 2.688 for mild, moderate,and severe impact, respectively;all P-Ref < 0.01 vs no impact), knowledge of how the vaccine was developed(OR = 1.616;95% CI: 1.126–2.318;P-Ref = 0.009 vs unknown), believing in the safety of the vaccine(OR = 1.502;95% CI: 1.024–2.203;P-Ref = 0.038 vs denying the safety of vaccine), willingness to pay for the vaccine(OR = 3.042;95% CI: 2.376–3.894;P-Ref < 0.001 vs unwilling), and willingness to recommend families and friends to get vaccinated(OR = 2.744;95% CI: 1.759–4.280;P-Ref < 0.001 vs do not recommend) were contributors to vaccine acceptance. While such as being retired(OR = 0.586;95% CI: 0.438–0.784;P-Ref < 0.001 vs unemployed), undergoing multiple therapies of cancer(OR = 0.408;95% CI: 0.221–0.753;P-Ref = 0.004 vs no ongoing treatment), and worrying that the vaccine might deteriorate the prognosis of cancer(OR = 0.393;95% CI: 0.307–0.504;P-Ref < 0.001 vs might not) were contributors to vaccine hesitancy.Conclusion: This study provided preliminary estimates of the rates of vaccine acceptance and vaccine hesitancy among cancer patients in Eastern China. The intention to receive the COVID-19 vaccine was impacted by factors such as patient occupation, alcohol consumption, and some parts of knowledge about and attitude towards COVID-19 vaccine. It is recommended to develop individualized vaccination plans that meet the healthcare needs of cancer patients.