TCM clinical research covers different design types on basis of objective of the study. For exploratory research of TCM, cross-sectional study and descriptive research (e.g. case report and case analysis) is suitable. For hypothesis-testing research, RCT design is commonly adopted. RCT is most commonly used in activity or prevention therapy research, when using randomized cross-over design, the influence of sequence effects should be considered, and double-blind method is the best choice. Cohort study includes various intervention measures, as it doesn’t involve randomized allocation and blinding. Case-control study is widely applicable, but it may bring about bias. Cross-sectional study is much used in syndrome investigation of TCM clinical research. Descriptive research is available for summarization of TCM clinical experience and TCM exploratory research. Third party-central randomization system is recommended, as the randomization is not easy to be damaged. Randomization concealment should also be attached importance to. When blinding is impossible, blindness testing could reduce measurement bias, positive control should be supported high-level evidence. Placebo application could improve the level of evidence-based medicine.

OBJECTIVE:To observe therapeutic efficacy and safety of tobramycin dexamethasone in the treatment of meibo-mian gland dysfunction(MGD). METHODS:108 MGD patients were randomly divided into control group(53 cases)and observa-tion group(55 cases). Control group was given eyelid cleaning with conventional physical cleaning method,at the same time,giv-en Doxycycline hydrochloride tablets 0.1 g orally after meal,twice a day. Based on control group,observation group was addition-ally given Tobramycin and dexamethasone eye ointment with length of 1.0-1.5 cm,smearing into conjunctival sac,4 times a day. Treatment courses of 2 groups lasted for 4 weeks. Clinical efficacies of 2 groups were observed as well as eyelid observation score, symptom score,the levels of IL-6 and TNF-α,the occurrence of ADR before and after treatment. RESULTS:The total response rate of observation group was significantly higher than that of control group(89.1% vs. 77.4%),with statistical significance(P<0.05). Before treatment,there was no statistical significance in eyelid observation score,symptom score,the levels of IL-6 and TNF-α between 2 groups(P>0.05). After treatment,eyelid observation score of 2 groups were significantly higher than before treatment,and the observation group was significantly higher than the control group;symptom score and the levels of IL-6 and TNF-α in 2 groups were significantly lower than before treatment,and the observation group was significantly lower than the con-trol group,with statistical significance(P<0.05).There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Based on routine treatment,tobramycin dexamethasone shows significant therapeutic efficacy for MGD,and can improve clinical symptoms significantly but does not increase the occurrence of ADR.

Sample size design is to determine the minimum number of observed cases in the case of ensuring the reliability of research conclusions.The reliability of sample size estimation mainly related to the reliability of the basis of sample size calculation.Some things are essential,such as the emphasis on pre-test quality,extensive collection of relevant literature and research materials and accurate analysis.Estimation of sample size is first to determine the value of ?,?,or 1-? and effect indicators and their types,the effect indicators predictive value of each comparison group,the emphasis on sources and requirements of the effect indicators predictive value(the basis of calculation),besides,should pay close attention to study design and comparison of types,each group allocation ratio,the expected rate of lost to follow,the level of expected treatment compliance,the choice of some main effect indicators in outcome evaluation.An introduction and explaining with examples to estimation method and estimation of sample size formula,such as design of randomized controlled trials,cohort studies and case-control study commonly used in the clinical validation study of TCM,and study design commonly used in the clinical exploratory study of TCM,case analysis and so on.

Statistical analysis plan (SAP) is an important guidance document in clinical research which is intended to be a comprehensive and detailed description of the methods and presentation of data analyses proposed for a clinical research. The analysis plan will be completed after finalising the protocol and should be finalised before treatment unblinding, to provide full details, even to the extent of including templates of tables, listings and figures to be presented in the statistical report. Any changes between the methods in the protocol and analysis plan will be explained in the analysis plan. In order to improve the quality of TCM clinical research, it is need to optimize the SAP. Considerations in optimizing the SAP include: determine the analysis sets and analysis variables, select analysis methods and statistical software.

Abstract: Beginning with 4-level quality control measures of clinical research in traditional Chinese medicine (TCM), we elaborated the implementation process and demands of quality control measures of each level, including quality control, monitoring, auditing, and inspection. On the basis of joint inspection experience of 41 projects of the "Prevention and Treatment of Difficult and Complicated Diseases of TCM" plan of the "11th Five-year National Key Technology R&D Program", we analyzed the ensuring effect of 4-level quality control system and joint inspection model, and then pointed out the existing problems in the executing process of quality control system at different levels and joint inspection model. Finally we investigated what should be revised in the quality control system and joint inspection model, thus providing the theoretical support for quality inspection improvement of TCM clinical research.

TCM clinical research should attach importance on ethical issues,as it takes the human for the research subjects and the clinical research activities definitely involve the benefits and risks to the subjects.Ethics optimization on the basis of safety and scientificity is necessary.This study explores the optimization of some key links of ethics of TCM clinical research,i.e.optimization of ethics committee membership,optimization of ethical review of study protocol,optimization of informed consent process,and optimization of protection and compensation of the subject,thus providing the theoretical support for ethics improvement of TCM clinical research.

Objective To investigate the clinical application value of fluorescence laparoscopy in radical resection of hepatocellular carcinoma (HCC).Methods Data of totally 113 patients with HCC in Henan Provincial People's Hospital between June 2016 to June 2018 were retrospectively analyzed.Among the 113 patients,46 patients underwent laparoscopic hepatectomy (LLR),and 67 patients underwent fluorescence guided laparoscopic hepatectomy (FLLR).Results No significant differences were observed between LLR group and FLLR group in terms of age,male proportion,liver function classification,surgical resection methods,and operation time (P＞0.05).The positive ratio of specimen surgical margin in LLR group was significantly higher than that in FLLR group,13.0％ vs.3.0％,and the difference was statistically significant (P＜0.05).In the FLLR group,22 patients received fluorescence guided anatomic hepatectomy with indocyanine green (ICG),10 with positive staining and 12 with negative staining,and fluorescence imaging was observed 2 minutes after ICG injection.There was no significant difference in operation time,hospitalization cost and length of stay between positive and negative staining (P＞ 0.05).Conclusion Fluorescence laparoscopy has certain advantages in hepatectomy,and can display the boundary of hepatocellular carcinoma in real time to ensure the safe margin of tumor resection.

Objective:To investigate the value of tumor budding in the clinicopathology and prognosis of pancreatic neuroendocrine tumors.Methods:The Cliniccal data of 105 pancreatic neuroendocrine tumor patients underwent resection in Henan Provincial People's Hospital from Jan 2010 to Dec 2016 were retrospectively analyzed. Tumor budding was calculated through hematoxylin-eosin (HE) and immunohistochemical stained slides. Based on the receiver operating characteristic curve (ROC), the number of tumor budding ≥10 was defined as the high-grade budding group, and <10 as the low-grade budding group. Multiple analysis was performed to determine the relationship between tumor budding and clinicopathology as well as prognosis.Results:High-grade budding group was observed in 35 cases and low-grade group in 70. High-grade budding were more common in tumors with advanced T stage, high risk of lymphatic metastasis, preoperative liver metastasis, vascular invasion and postoperative recurrence (respectively χ 2=9.043, 4.286, 10.130, 12.090, 9.260, all P<0.05). Multivariate COX regression analysis showed that tumor budding ( P=0.018), tumor grade ( P=0.026), preoperative liver metastasis ( P=0.042), vascular invasion( P=0.048) was independent risk factors predicting poor prognosis. Conclusion:Tumor budding is highly correlated with clinicopathological parameters which reflect the aggressiveness of pancreatic neuroendocrine tumor, it is also an important prognostic factor.

Objective: To investigate the clinical significance of high definition (HD) MRI rectal lymph node aided diagnostic system based on deep neural network. Methods: The research selected 301 patients with rectal cancer who underwent pelvic HD MRI and reported pelvic lymph node metastasis from July 2016 to December 2017 in Affiliated Hospital of Qingdao University. According to the chronological order, the first 201 cases were used as learning group. The remaining 100 cases were used as verification group. There were 149 males (74.1%) and 52 females in the study group, with an average age of 58.8 years. There were 76 males (76.0%) and 24 females in the validation group, with an average age of 60.2 years. Firstly, Using deep learning technique, researchers trained the 12 060 HD MRI lymph nodes images data of learning group with convolution neural network to simulate the judgment process of radiologists, and established an artificial intelligence automatic recognition system for metastatic lymph nodes of rectal cancer. Then, 6 030 images of the validation group were clinically validated. Artificial intelligence and radiologists simultaneously diagnosed all cases of HD MRI images and made the diagnosis results of metastatic lymph node. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to compare the diagnostic level of them. Results: After continuous iteration training of the learning group data, the loss function value of artificial intelligence decreased continuously, and the diagnostic error decreased continuously. Among the 6 030 images of verification group, 912 images were considered to exist metastatic lymph nodes in radiologists′ diagnosis and 987 in artificial intelligence diagnosis. There were 772 images having identical diagnostic results of lymph node location and number of metastases with the two methods. Compared with manual diagnosis, the AUC of the intelligent platform was 0.886 2, the diagnostic time of a single case was 10 s, but the average diagnostic time of doctors was 600 s. Conclusion The HD MRI lymph node automatic recognition system based on deep neural network has high accuracy and high efficiency, and has the clinical significance of auxiliary diagnosis.