Based on the research situation of the regulatory scientific research project of combination products technical evaluation in recent years, this study introduces the relevant research on how to optimize the supervision of combination products, summarizes the research progress and research results of the project, in order to promote the development of related industries.

This article combines the joint review of combination products in recent years, sorts out the links and common problems in the joint review process, introduces the work carried out to optimize the joint review process of combination products, and puts forward relevant suggestions for improvement, aim to improving the work of joint review and providing reference for relevant product declaration.

Based on observing the cytological characteristics of the flower buds of the functional male sterile line (S13) and the fertile line (F142) in eggplant, it was found that the disintegration period of the annular cell clusters in S13 anther was 2 days later than that of F142, and the cells of stomiun tissue and tapetum in F142 disintegrated on the blooming day, while it did not happen in S13. The comparative transcriptomic analysis showed that there were 1 436 differential expression genes (DEGs) (651 up-regulated and 785 down-regulated) in anthers of F142 and S13 at 8, 5 days before flowering and flowering day. The significance analysis of GO enrichment indicated that there were more unigene clusters involved in single cell biological process, metabolism process and cell process, and more catalytic activity and binding function were involved in molecular functions. Through KEGG annotation we found that the common DEGs were mainly enriched in the biosynthesis of secondary metabolites, metabolic pathway, protein processing in endoplasmic reticulum, biosynthesis of amino acids, carbon metabolism and plant hormone signal transduction. The fifteen genes co-expression modules were identified from 16 465 selected genes by weighted gene co-expression network analysis (WGCNA), three of which (Plum2, Royalblue and Bisque4 modules) were highly related to S13 during flower development. KEGG enrichment showed that the specific modules could be enriched in phenylpropanoid biosynthesis, photosynthesis, porphyrin and chlorophyll metabolism, α-linolenic acid metabolism, polysaccharide biosynthesis and metabolism, fatty acid degradation and the mutual transformation of pentose and glucuronic acid. These genes might play important roles during flower development of S13. It provided a reference for further study on the mechanism of anther dehiscence in eggplant.
Flowers/genetics* ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Humans ; Infertility, Male ; Male ; Metabolic Networks and Pathways/genetics* ; Solanum melongena/genetics* ; Transcriptome/genetics*

The number of combination products is increasing, and the cutting-edge and innovative technologies are constantly being used. How to evaluate combination products become difficult points. This study team summarizes the supervision conditions of the combination products and analyzes the common problems of these products application from the perspective of technical review, in order to provide reference for Chinese manufacturers and investigators in these products registration.
Biomedical Technology

This paper briefly introduces the recent regulatory regulations issued by the European Union and the United States on the drug-device combinations. The contents include the definition of drug-device combinations, the attribute definition process, the registration requirements, the review and approval procedures, the management of production systems, and the post-marketing safety supervision. Some inspirations have been obtained from them for reference by the regulatory authorities.
European Union ; Marketing ; United States

This article summarizes the attribute conditions to the combination products designation from 2009 to 2018 in China,analyzes the common problems of combination products attribution definition.It is hoped to be helpful for researchers and manufacturers of combination products.
China ; Equipment and Supplies ; Terminology as Topic

Objective: To understand the fruit consumption of adults of Qingdao and examine the association between fruit consumption and stroke. Methods: We analyzed baseline data and stroke incidence of the participants who were aged 30-79 years and had been enrolled into the China Kadoorie Biobank (CKB) study from Qingdao city. Cox proportional hazards regression model was conducted to estimate the association of fruit consumption with risk of stroke. Results: A total of 35 509 participants were investgated in the baseline survey. Ratio of male to female was 1∶1.27, and the average age was (50.3±10.2) years. Respondents with higher frequency of fruit consumption were younger, more women, with higher education level and higher income (P<0.05). A total of 1 011 new cases of stroke were observed, with a stroke incidence of 387.63/100 000 person-years. Multivariate Cox regression analysis showed that fruit consumption had a protective effect on stroke incidence. Compared to the respondents who never consumed fruit, respondents who consumed fruit more than 4 days per week had a 44% lower risk of stroke incidence (HR=0.56, 95%CI: 0.50-0.62, P<0.05), and the risk reduced by 46% (HR=0.54, 95%CI: 0.46-0.64, P<0.05) and 42% (HR=0.58, 95%CI: 0.52-0.69, P<0.05) in male and female, respectively. Further adjustment for WC, BMI, SBP and random blood glucose did not change the association. Conclusion Increasing fruit consumption can effectively decrease the risk of stroke. People should increase fruit consumption advisably to set up reasonable and healthy dietary habits.

Lactic acid bacteria and cellulose degrading bacteria play an important role in fermentation process of silage, because they can prevent the rancidity and increase the nutritive value of silage. But the propagation of lactic acid bacteria will inhibit the activity of cellulose degrading bacteria in the silage fermentation system. This problem can be solved by releasing lactic acid bacteria and cellulose degrading bacteria in different time. Therefore, we immobilized lactic acid bacteria as a microbial agent for sustained release. Firstly, the optimal balling concentration of the composite immobilized carrier and composite immobilized carrier were obtained by immobilization of blank balls and corncob adsorbed Lactobacillus plantarum S1 respectively. The best immobilization condition of L. plantarum S1 was obtained by comparing the immobilized rate and balling effect of two kinds of balls, which were embedded by sodium alginate (SA), CMC-Na and embedded-crosslinked by SA, CMC-Na, polyvinyl alcohol (PVA). The results showed that the best balling concentration was achieved by using 6% PVA+0.4% SA+0.3% CMC-Na for embedding-crosslinking and 1.2% SA+0.5% CMC-Na for direct embedding respectively. In addition, comparing with the mechanical strength and embedding rate of five kinds of immobilization process, the best immobilized process was obtained by adding of the mixture of immobilized carriers (1.2%SA+ 0.5%CMC-Na) and corncob adsorbed L. plantarum S1 slowly into 4% CaCl₂ for 24 hours. The corncob adsorption and SA embedding methodology can effectively increase the embedding efficiency of Lactobacillus plantarum S1.

Objective: To evaluate the effects of endothelial cell-targeted soluble Notch ligand hD1R protein on the proliferation of acute myeloid leukemia (AML) cells. Methods: The expression levels of Notch1, Notch2, Notch3, Notch4, Hes1 in bone marrow CD34⁺ cells from 24 cases of untreated AML (AML group) and 9 healthy controls (control group) were determined by real time quantitative polymerase chain reaction (PCR) . Recombinant hD1R protein was first induced and purified. Bone marrow CD34⁺ cells were co-cultured on human umbilical vein endothelial cells (HUVEC) supplemented with a cocktail containing 5 types of human cytokines (5GF) and soluble hD1R. The cultured cells were tested under different culture conditions including PBS group (PBS replaces HUVEC) , hD1R group, 5GF group, GSI group (hD1R plus GSI) . Proliferation and apoptosis of cultured cells were also analyzed. Real time quantitative PCR was used to test the expression levels of Hes1 and Bcl-2 in cultured cells. Results: The expression levels of Notch1 and Hes1 in primary AML patients were significantly lower, and Notch4 expression was higher compared to the control group (P<0.05) . Cell counting showed a remarkable decrease of AML cells number in the culture with hD1R compared with that in the PBS group[ (0.74±0.13) ×10⁵ vs (2.16±0.21) ×10⁵, P<0.01]. FACS analysis showed that the percentage of AML cells was (18.48±2.51) % in apoptosis, which was higher than that of control cells (3.19±0.58) % after co-culture with hD1R. AML cells in the hD1R group underwent significantly increased apoptosis compared with those in the PBS one (P<0.05) . Moreover, apoptosis of AML cells in the GSI group was lower than that in the hD1R one (P<0.05) . Apoptosis in the PBS group also decreased compared with that in the 5GF one (P<0.05) . Finally, hD1R up-regulated Hes1 expression and inhibited Bcl-2 one in the AML cells. Conclusion hD1R effectively activated Notch signaling and down-regulated Bcl-2 mRNA in AML cells, which lead to cell apoptosis.

Objective To investigate the regularity of intrapulnonary lobar and segmental lymph nodes metastasis in patients with cT1N0M0 stage lung adenocarcinoma.To provide a basis for more accurate determination of N stage and indication for pulmonary segmental resection.Methods A prospective study was performed from March 2014 to December 2015.103 cases of cT1 N0M0 stage lung adenocarcinoma received lobectomy and mediastinal lymph node dissection in the thoracic surgery department of China-Japan Friendship Hospital.Intrapulmonary lobar and segmental lymph nodes were dissected and sorted carefully then sent to the pathological department with the corresponding lung specimen and other lymph nodes.Statistical analysis was carried out considering size of the lesion,imaging features,serum CEA levels,pathological subtypes and so on.Results In total 103 cases,pN0 was confirmed in 82 cases,pN1 in 15 cases,pN1 + N2 in 5 cases,and skipping-pN2 in 1 case.14 cases(93.3％) in pN1 group were detected with station 12-14 lymph node metastasis,while only 5 cases (33.3％) were detected with station 12-14 LSNs metastasis.4 cases(66.7％) in pN2 group were detected with station 12-14 lymph node metastasis,while only 1 case(16.7％) with station 13 and station 7 lymph node metastasis.If LSNs were not detected,the false negative rate of N staging could be as high as 6.1％ (5/82),The rate of missed diagnosis of lymph node metastasis might be 30％ (6/20) to N1 stations alone.41.2％ (7/17)cases with metastasis to the adjacent LSNs had been proved with metastasis to the isolated LSNs.The metastasis rate of the isolated LSNs was significantly lower(P =0.049) in pure GGNs compared with those part-solid/solid nodules.Invasive adenocarcinoma had higher metastasis rate of isolated LSNs,compared with preinvasive lesions or minimally invasive adenocarcinomas,with no statistical difference between groups (P =0.055).No significant difference in isolated LSNs metastasis rate was found between groups with different serum CEA levels(P =0.251) or tumor size(P =0.197).Conclusion Dissection of intrapulmonary lobar and segmental lymph nodes might facilitate a more accurate N stage,reduce the false negative rate of lymph node metastasis,and provide basis for more accurate assessment of prognosis and postoperative adjuvant treatment.The sampling area of lymph nodes during segmental resection should include the adjacent LSNs of the target segment.The isolated LSNs metastasis rate of cT1N0M0 stage lung adenocarcinoma with pureGGN as imaging feature is relative low,which might be suitable for segmentectomy when meeting other criteria.