Methionine enkephalin inhibits colorectal cancer by remodeling the immune status of the tumor microenvironment.

There is evidence that methionine enkephalin (MENK), an opioid peptide, promotes anti-tumor immune responses. In this study, the effect of MENK on colorectal cancer (CRC) and its mechanisms of action were examined in vivo. The intraperitoneal administration of 20 mg/kg MENK effectively inhibited MC38 subcutaneous colorectal tumor growth in mice. MENK inhibited tumor progression by increasing the immunogenicity and recognition of MC38 cells. MENK down-regulated the oncogene Kras and anti-apoptotic Bclxl and Bcl2, suppressed Il1b, Il6, iNOS, and Arg1 (encoding inflammatory cytokines), and increased Il17a and Il10 levels. MENK promoted a tumor suppressive state by decreasing the immune checkpoints Pd-1, Pd-l1, Lag3, Flgl1, and 2b4 in CRC. MENK also altered the immune status of the tumor immune microenvironment (TIME). It increased the infiltration of M1-type macrophages, CD8+T cells, and CD4+T cells and decreased the proportions of G-MDSCs, M-MDSCs, and M2-type macrophages. MENK accelerated CD4+TEM and CD8+TEM cell activation in the TIME and up-regulated IFN-γ, TNF-α, and IL-17A in CD4+T cells and Granzyme B in CD8+T cells. In addition, analyses of PD-1 and PD-L1 expression indicated that MENK promoted the anti-tumor immune response mediated by effector T cells. Finally, OGFr was up-regulated at the protein and mRNA levels by MENK, and the inhibitory effects of MENK on tumor growth were blocked by NTX, a specific blocker of OGFr. These finding indicate that MENK remodels the TIME in CRC to inhibit tumor progression by binding to OGFr. MENK is a potential therapeutic agent for CRC, especially for improving the efficacy of immunotherapy.

Oral S2-Ag85 DNA Vaccine Activated Intestinal Cell dsDNA and RNA Sensors to Promote the Presentation of Intestinal Antigen.

Objective: To explore the molecular mechanism by which oral S2-Ag85DNA vaccines present intestinal antigens. The oral S2-Ag85 vaccine has been shown to protect the human body and effectively improve the titration of the vaccine by acting on intestinal mucosa cells and enhancing their immunogenicity. Method: Mice were immunized with the recombinant S2-Ag85 vaccine, and antibody secretion was then detected in the intestinal tissue. The molecular mechanisms of in vitro detection sensor molecules RIG-1, Pol III, and related conductor transductor molecules DAI, STING, AIM2, IRF3, and IRF7 were determined by separating intestinal IEC, DC, and IELC cells. Results: The S2-Ag85A vaccine was effective in activating dsDNA and RNA transduction pathways in intestinal cells and improving intestinal antigen presentation in mice.

Combined nucleic acid assays for diagnosis of A19 vaccine-caused human brucellosis.

Brucellosis is a common zoonotic disease caused by Brucella and is an epidemic worldwide. Currently, the most effective way to prevent and control the disease in animals is to use live, attenuated vaccines A19 strain. In China, the live attenuated Brucella abortus vaccine is widely used in animal immunization. To detect and confirm which vaccine strain caused the infection, we developed a new method to distinguish A19 strain from non-A19 strains. By comparing the genomic sequences of A19 and wild strain 2,308, we identified signature sequences that are unique to A19. A PCR assay for specific A19 identification was developed based on the genetic marker ABC transporter permease gene. Samples from the outbreak patients were then analysed using the universal quantitative PCR and A19-specific PCR assay, and the A19 strain was successfully identified in them, providing pathogenic evidence of the vaccine-derived infection outbreak. This combined A19-specific differential diagnosis method can provide a means to distinguish between animal vaccine immunization, natural infection and human infection by the vaccine strain. This strategy also has applications in diagnosis, epidemiology and surveillance of A19-related immunizations or infections.

Clinical observationoncure of 1 case of chronic brucellosis by improving immunity / 中华地方病学杂志

Objective To investigate the effect of improving immunity in the treatment of chronic brucellosis,and to analyze and evaluate its clinical curative effect.Methods A patient with chronic brucellosis was treated with Mongolian medicine combined with chemical drugs to enhance immunity.The clinical symptoms,serological antibodies,Brucella DNA and immune function were compared before and after treatment.The specific antibody against Brucella in serum was detected by tube agglutination test (SAT) and tiger red plate agglutination test (RBPT).Brucella DNA in serum and blood cells was detected by PCR,and the peripheral blood lymphocyte subsets were detected by flow cytometry.Immuno-luminescence technique was used to detect serum immunoglobulin and complement components.Results After treatment,the clinical symptoms such as cold back,fatigue,and joint pain disappeared completely,and the results of serum specific antibodies against Brucella were SAT 1 ∶ 50 (++)and RBPT (+) with no changes before and after treatment,and the results of cells and serum were both negative after treatment though the results of DNA detection of Brucella were cell positive and seronegative before treatment.The results of immunological function test showed that γδT cells decreased to 9.50％ after treatment compared to 14.00％ before treatment,and the percentage of monocytes and Treg cells were 5.59％ and 7.33％ after treatment,which were higher than 3.35％ and 4.72％ of before treatment,and the level of complement C3 was 0.79 g/L before treatment and 0.91 g/L after treatment that was returned to normal reference range (0.88 ～ 2.01 g/L).Conclusion The patients with chronic brucellosis can improve their clinical treatment by improving immunity.

Quality assessment of reporting items in randomized controlled trials of Chinese herbal medicine as an adjunctive therapy for advanced non-small cell lung cancer / 国际生物医学工程杂志

Objective To evaluate the reporting item quality of randomized controlled trials of Chinese herbal medicine as an adjunctive therapy for advanced non-small cell lung cancer. Methods The terms including Chinese medicine, Chinese herbal medicine, randomized controlled trials, and non-small cell lung cancer were searched in Chinese and English databases by computer systems to collect relevant literatures. Based on the CONSORT 2010 (consolidated standards of reporting trials 2010), the reporting item quality of the abstracts and main text in eligible papers was evaluated. Results Ninety-five eligible studies were identified from 692 potential eligible articles. None reported all of abstract and main text items in CONSORT 2010. Only 4.12％could be identified as the randomized trial in the title. More than 40％of reports showed the scientific background or rationale in the abstract but not in the main text. Three (3.16％) eligible reports defined the primary or secondary outcome measures. None reported complete information of subjects throughout the clinical trial process. Results A total of 95 eligible papers were collected, of which 0 papers reported complete abstracts and text entries according to the CONSORT. The titles of 4.12％papers were identified as randomized trials. More than 40％of the papers only reported the study purpose or hypothesis in the abstract. 3.16％of the papers reported primary and secondary efficacy index entries, and 0 papers reported complete information of subjects from enrollment to included data analysis sets. Conclusion There is a serious problem of items shortage in the literatures of randomized controlled clinical trials on Chinese herbal medicine as an adjunctive therapy for advanced non-small cell lung cancer. The randomized controlled clinical trials of Chinese herbal medicine as an adjunctive therapy for advanced non-small cell lung cancer should be reported based on the CONSORT to improve the quality of trials.

Ethical Issues on Hospital Centralized Monitoring for the Safety of Traditional Chinese Medical (TCM) Injections / 世界科学技术-中医药现代化

The safety of TCM injection triggered attentions and hotspots in recent years in China.The centralized monitoring of TCM injection provided important evidence for analyzing the safety risk of TCM injections,recognizing adverse reactions and contraindications and perfecting the instructions.This study aimed at exploring the ethical problems on centralized monitoring.In this paper,we retrieved and screened the ethical issues of TCM injections over hospital centralized monitoring in China National Knowledge Infrastructure (CNKI,1979-Ju1.,2016).Issues over it were put forward and addressed.It is found that the current ethical issues related to hospital centralized monitoring lacks sufficient attentions,corresponding norms and requirements.Based on the ethical issues reflected from the literatures,suggestions should be pressed ahead with the ethical review of centralized surveillance,signing of informed consents,registration of research programs,data statistics and reporting stages,for the better protection of the rights and interests of subjects and improvement of research quality.

Problems and Solutions of Statistical Analysis for Hospital Centralized Safety Monitoring of Traditional Chinese Medical (TCM) Injections / 世界科学技术-中医药现代化

Safety hospital centralized monitoring is one of the important methods for evaluating the medication safety of TCM injections in clinic.It is critical to warrant research quality by reasonable statistical analysis.However,universally accepted standards and guidelines for the statistical analysis of hospital centralized monitoring of TCM injections have not been issued so far,which would probably reduce the research quality of safety hospital centralized monitoring of TCM injections since the unreasonable use of statistical analysis methods.Combined with previous practical experience and understanding,we put forward the problems of statistical analysis of hospital centralized monitoring of TCM injections with the provision of some advice in this paper based on the analysis of the preceding studies,laying a foundation for the same kind of researches.

The Process Quality Control and Key Technology of Post-Marketing Clinical Safety Evaluation of Chinese Medical Injection (Draft Report for Comment) / 世界科学技术-中医药现代化

At present,the various levels of safety evaluations of traditional Chinese medical (TCM) injections were in force in post-marketing clinical researches,while the process quality is guaranteed with difficulty.Therefore,it is requisite to call for technical guidance.By drawing lessons from the international experience of drug marketing safety evaluation and the related methods,we proposed the key techniques of quality control for clinical safety evaluation of TCM injections from the three aspects:preparation,implementation and summarization of researches,combining with the characteristics of TCM injections.The key techniques contained some scientific problems,ethics,publicity,data management,statistical analysis,specification report,etc.This paper comprehensively introduced the requisite technologies and methods over research quality,laying a foundation for the studies of post-marketing clinical safety evaluation of TCM injections.

Consideration on Hospital Related Issues for Centralized Safety Monitoring of Post-Marketing Chinese Medical Injections / 世界科学技术-中医药现代化

The implementation process management plays a important role for the quality of centralized safety monitoring study of post-marketing Chinese medical injections.One of the critical link is hospital.Currently,there is no principle or specification for hospital choosing,number of monitoring points,data collection responsible part and forms of data collection as well.These issues caused uneven quality,huge differences in results and questioned conclusion.Based on the previous research experience,this paper focused on discussing the link of hospital where research data may be influenced,and proposed some suggestions.

Standardized Construction in Hospital Centralized Monitoring for the Safety of Traditional Chinese Medical (TCM) Injections / 世界科学技术-中医药现代化

Safety is a critical link restricting the development of TCM injections.Hospital centralized monitoring is of importance in the safety evaluation of TCM injections.However,the results of centralized monitoring studies usually deviated from the actual situation because of problems in design and process quality.Our research team have completed several projects over centralized monitoring in recent years.Based on the previous research experience,this paper mainly discussed the current statuation,the significance and methods for standard process of hospital centralized monitoring in regard to TCM injections,in order to improve the quality of centralized monitoring studies and provide technique support for recognizing the safety of TCM injections.

Contents and Key Points of Data Management During Hospital Centralized Monitoring of the Safety of Traditional Chinese Medical (TCM) Injections / 世界科学技术-中医药现代化

According to the related requirements of safety reevaluation of TCM injections,hospital centralized monitoring of the safety of TCM injection was consecutively pressed ahead.Centralized security monitoring was a large-scale real world research involving numerous data acquisition,transmission,verification and analysis.The quality of data acquisition and data verification directly affected the authenticity and reliability of research data and results.Therefore,data management played a significant role in the safety monitoring of TCM injections.Based on the analysis of previous researches,this paper discussed the implementation content,links and the frequent problems and corresponding solutions of data management during the safety monitoring of TCM injections,combining with the experience in the implementation of projects.

Establishment of the Clinical Safety Research Registration Platform of Chinese Medicine / 世界科学技术-中医药现代化

The launch of the clinical trial registry is a milestone event in the field of clinical research in the 21st century that has played an important role in safeguarding the openness,transparency,ethics,data sharing and process control of clinical research.The current clinical research registry is mainly aimed at clinical trial research with lack of professional registration system for security and other real events of observational study.In order to improve the level of clinical safety research,promote transparency and process quality control,we proactively proposed and established a registration platform for clinical safety research of traditional Chinese medicine.This paper made a brief introduction hereof.

Incidence and mortality of cancers appeared in the Hebei provincial cancer registry system in 2011 / 中华流行病学杂志

Objective To analyze the cancer incidence and mortality in Hebei cancer registry available areas in 2011.Methods Data were collected from 8 population-based cancer registries systems in Hebei province.Incidence and mortality rates stratified by areas (urban/rural),sex,age group and cancer site were analyzed.10 common cancers in different groups,proportions and cumulative rates were calculated.The Chinese population census in the year 2000 and Segi's populations were used for age-standardized incidence/mortality rates.Results In all the 8 cancer registries that covering a total of 4 573 293 population (2 139 779 in urban and 2 433 514 in rural areas),data was used for the analysis.The total new cancer incidence cases and deaths were 11 269 and 7 477,respectively.All the morphologically verified cancer cases (MV％) accounted for 75.26％ while 3.85％ of the incident cases were identified only through death certification records (DCO％).The mortality to incidence ratio appeared as 0.66.The crude incidence appeared in the Hebei cancer registration areas was 246.41/105 (264.55/105 in males and 227.75/105 in females).The age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) appeared as 207.13/105 and 206.61/105 respectively,with the cumulative incidence rates as (0-74 age years old) 23.57％.The cancer incidence and ASIRC were 242.64/105 and 200.19/105 in urban areas,whereas 249.72/105 and 214.11/105,respectively in rural areas.The crude mortality in Hebei cancer registration areas was 163.49/105(196.54/105 in male,129.51/105 in female),with age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) as 144.48/105 and 147.69/105.The cumulative mortality rate (0-74 age years old) was 14.71％.The cancer mortality (167.91/105) in rural areas seemed higher than the mortality (158.47/105) in urban areas.The most common sites of cancers were:stomach,lung,esophagus,breast,liver and colorectal,which accounted for 71.66％ of all the cancer cases.Lung cancer,stomach cancer,esophagus cancer,liver cancer and colorectal cancer were the major causes responsible for the cancer deaths in the areas with data of cancer registration,which accounted for 74.79％ of all the cancer deaths.Conclusion The coverage of Hebei cancer registration population could reflect the cancer burden in various areas and populations.The most commonly seen cancers were stomach,lung,esophagus,breast,liver,and colorectal,in Hebei province.In order to reduce the burden of cancers,prevention and control measures should be strengthened.

Survey of Prevalence and Need of Visual Disability in Shanxi Province / 中国康复理论与实践

@#ObjectiveTo investigate the situation characteristic, cause and needs of visual disability in Shanxi Province and to provide prevention measures corresponding to different causes.MethodsBy cluster random sampling, 88 townships were selected and 75016 persons received the eye examination in 22 countries in Shanxi from July 1 to May 31 in 2006. Visual acuity and eye examination were performed by ophthalmologist and judged the causes.ResultsThe total prevalence rate of visual impairment in Shanxi was estimated to be 6.21‰.The was a significant increase in the prevalence rate of visual impairment as the age grew older(χ2＝415.54, P<0.05), those in women was higher than that in men(χ2＝40.62, P<0.05). The prevalence rate of visual impairment in countryside was significantly higher than that in city(χ2＝25.37, P<0.05).The chief causes of visual impairment were cataract(39.34%), there are 43.91% of visual impairment who had not received any rehabilitation services, and most of those were medical services (35.26%).ConclusionVisual impairment prevention should establish a social security system and security system. Increase the investment of medical services and relief. To take different preventive measures corresponding to different ages. The preventive of visual impairment of shanxi should be focus on senile eye diseases. The major work should be put in remote rural area.