OBJECTIVE To explore the effect and mechanism of Zhiqiao gancao decoction （ZQGCD） on pathological angiogenesis of degenerative intervertebral disc. METHODS The rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， hypoxia inducible factor-1α （HIF-1α） inhibitor （YC-1） group [2 mg/（kg·d）， tail vein injection]， and ZQGCD low-dose， medium-dose and high-dose groups [3.06， 6.12， 12.24 g/（kg·d）]， with 8 rats in each group. Except for sham operation group， lumbar disc degeneration model of rat was constructed in all other groups. After modeling， they were given relevant medicine once a day， for consecutive 3 weeks. After the last medication， pathological changes and angiogenesis of the intervertebral disc tissue in rats were observed； the levels of inflammatory factors [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] and the expressions of angiogenesis-related proteins [HIF-1α， vascular endothelial growth factor （VEGF）， VEGF receptor 2 （VEGFR2）， angiotensin 1（Ang 1）， Ang 2] in the com intervertebral disc tissue in rats were all determined. In cell experiment， the primary nucleus pulposus cells were isolated and cultured from rats， and cellular degeneration was induced using 50 ng/mL TNF-α. The cells were divided into blank control group （10% blank control serum）， TNF-α group （10% blank control serum）， YC-1 group （10% blank control serum+0.2 mmol/L YC-1）， and 5%， 10%， 15% drug-containing serum group （5%， 10%， 15% drug-containing serum）. After 24 hours of intervention， the nucleus pulposus cells were co-cultured with HUVEC. The expressions of Collagen Ⅱ， matrix metalloproteinase-3 （MMP-3） in nucleus pulposus cells were detected. HUVEC proliferation， migration and tube forming ability were detected， and the expression levels of the HIF-1α/VEGF/Ang signal axis and angiogenesis- related proteins （add MMP-2， MMP-9） in HUVEC were detected. RESULTS Animal experiments had shown that compared with model group， the positive expression of CD31 in the intervertebral disc tissues of rats in each drug group was down-regulated （P＜ 0.05）， the levels of inflammatory factors and angiogenesis-related proteins were decreased significantly （P＜0.05）， and the pathological changes in the intervertebral disc were alleviated. Cell experiments had shown that compared with TNF-α group， the expression of Collagen Ⅱ in nucleus pulposus cells of all drug groups was significantly up-regulated （P＜0.05）， and the expression of MMP-3 was significantly down-regulated （P＜0.05）； the proliferation， migration and tubulogenesis of HUVEC were significantly weakened （P＜0.05）. The mRNA and protein expressions of HIF-1α， VEGF， Ang 2 as well as the expression of angiogenesis-related proteins （except for the expression of Ang 2 mRNA and HIF-1α， VEGFR2， Ang 2 protein in 5% drug- containing serum group） were significantly down-regulated （P＜0.05）. CONCLUSIONS ZQGCD may inhibit the HIF-1α/VEGF/ Ang signal axis to weaken the angiogenic ability of vascular endothelial cells， improve pathological angiogenesis in the intervertebral disc， and delay the degeneration of the intervertebral disc.

Background Bromadiolone is the second-generation anticoagulant rodenticide widely used all over the world. Exposure to bromadiolone in early life stage can lead to neurodevelopmental toxicity, but its toxic mechanism of neurodevelopment is not clear so far. Objective To investigate the developmental neurotoxicity and mechanism of bromadiolone to zebrafish embryos. Methods Zebrafish embryos were randomly divided into four groups: a solvent control group (dimethylsulphoxide) and three bromadiolone exposure groups (0.39, 0.78, and 1.18 mg·L⁻¹). The exposure period was from 4 h to 120 h post-fertilization. The number of spontaneous movement per minute was recorded at 24 h post-treatment. The locomotor ability of zebrafish larvae and the activity of acetylcholinesterase (AChE) were tested at 120 h post-treatment. The relative expression levels of neurodevelopment-related genes (elavl3, gap43, mbp, and syn2a) were measured by fluorescence quantitative PCR. Results Compared with the control group, the number of spontaneous movement per minute at 24 h decreased significantly in the 1.18 mg·L⁻¹ bromadiolone exposure group (P<0.05). Compared with the control group, the total distance travelled of the zebrafish larvae in the 0.78 and 1.18 mg·L⁻¹ bromadiolone exposure groups decreased by 60% and 69% respectively (P<0.05, P<0.01), and the total movement time decreased by 34% and 65% respectively (P<0.05, P<0.01). The AChE activity in the 1.18 mg·L⁻¹ bromadiolone exposure group increased by 36% when compared with the control group (P<0.05). The fluorescence quantitative PCR results showed that compared with the control group, the expression levels of neurodevelopment-related genes elavl3, syn2a, and mbp were significantly down-regulated by 66%, 69%, and 65% in the 1.18 mg·L⁻¹ bromadiolone exposure group respectively (P<0.01), the expression level of gap43 was up-regulated by 56% in the 0.78 mg·L⁻¹ bromadiolone exposure group (P<0.01) and down-regulated by 34% in the 1.18 mg·L⁻¹ bromadiolone exposure group (P<0.05). Conclusion Bromadiolone exposure could inhibit spontaneous movement and locomotive behavior, down-regulate the expression levels of neurodevelopment-related genes, hinder the release of neurotransmitters, and result in neurodevelopmental toxicity in the early-staged zebrafish.

Pharmaceutical analysis is a discipline based on chemical, physical, biological, and information technologies. At present, biotechnological analysis is a short branch in pharmaceutical analysis; however, bioanalysis is the basis and an important part of medicine. Biotechnological approaches can provide information on biological activity and even clinical efficacy and safety, which are important characteristics of drug quality. Because of their advantages in reflecting the overall biological effects or functions of drugs and providing visual and intuitive results, some biotechnological analysis methods have been gradually applied to pharmaceutical analysis from raw material to manufacturing and final product analysis, including DNA super-barcoding, DNA-based rapid detection, multiplex ligation-dependent probe amplification, hyperspectral imaging combined with artificial intelligence, 3D biologically printed organoids, omics-based artificial intelligence, microfluidic chips, organ-on-a-chip, signal transduction pathway-related reporter gene assays, and the zebrafish thrombosis model. The applications of these emerging biotechniques in pharmaceutical analysis have been discussed in this review.

[Abstract] Objective: To develop a new type of CD7 chimeric antigen receptor modified T cell (CD7-CAR-T) for the treatment of CD7 positive acute myeloid leukemia (AML), and to observe its killing effect on CD7 positive AML cells. Methods: The CD7-CAR lentiviral vector was constructed based on the CD7 Nanobody sequence and costimulatory domain sequence of CD28 and 4-1BB. The lentiviral particles were packaged and used to co-transfect human T cells with protein expression blocker (PEBL), so as to prepare CD7- CAR-T cells. Real time cellular analysis (RTCA) was used to monitor the cytotoxicity of CD7-CAR-T cells on CD7 overexpressed 293T cells. Flow cytometry assay was used to detect the effect of CD7-CAR-T cells on proliferation and cytokine secretion of AML cells with high, medium and low CD7 expressions (KG-1, HEL and Kasumi-1 cells, respectively). Results: CD7-CAR-T cell was successfully constructed and its surface expression of CD7 was successfully blocked. Compared with T cells, CD7-CAR-T cells could significantly inhibit the proliferation of CD7-293T cells and promote the release of TNF, Granzyme B and INF-γ; in addition, CD7-CAR-T cells also significantly promoted the apoptosis (t=147.1, P<0.01; t=23.57, P<0.01) and cytokine release (P<0.05 or P<0.01) in CD7 positive KG-1 and HEL cells, but had little effect on Kasumi-1 cells that only expressed minimal CD7 antigen (t=0.7058, P>0.05). Conclusion: CD7-CAR-T cells can specifically kill CD7-positive AML cells in vitro.

Non-small cell lung cancer (NSCLC) accounts for 85% of total cases of lung cancer, which has the highest incidence and mor-tality in China. Most patients with lung cancer present with advanced stage disease at the time of diagnosis. With the limited develop-ment of cytotoxic chemotherapy for NSCLC therapy, median overall survival in patients receiving platinum-based doublet chemothera-py has been less than one year in several trials. To date, anti-angiogenesis agents combined with chemotherapy, small molecule tyro-sine kinase inhibitors (TKI) and immune checkpoint inhibitors were commonly applied in NSCLC instead of purely chemotherapy, which makes a great breakthrough in NSCLC therapy. This review summarizes and discusses the application of anti-angiogenic therapy in ad-vanced NSCLC.

Objective To examine the prevalence ofHelicobacter pylori in Shanghai and relevant risk factors, evaluate the resistance proifle ofH. pylori isolates to antibiotics used in ifrst-line therapy in two hospitals in Shanghai.MethodsH. pylori were isolated from the biopsy samples of gastric mucosa collected from September 2013 to January 2015. Antimicrobial susceptibility test was performed by E-test method for 131H. pylori strains to 4 antibiotics, clarithromycin, metronidazole, amoxicillin and tetracycline. Results A total of 955 patients receiving gastroscopy were enrolled. And 248 (26.0%)H. pylori strains were isolated from the biopsy samples of gastric mucosa. Overall, 14.5%, 64.1%, 0 and 0.8% of the strains were resistant to clarithromycin, metronidazole, amoxicillin and tetracycline, respectively. Resistance to two drugs was found in 10.7%(14/131) of the strains, and majority (92.8%, 13/14) of which were resistant to clarithromycin and metronidazole.Conclusions The prevalence ofH. pylori in gastric mucosa is rather lower compared with the data reported previously. It is associated with the sex, age and clinical outcome of patients, however, antibiotic resistance profile is not related to these factors.H. pylori eradication therapy should be individualized according to the results of susceptibility test in Shanghai.

Objective To investigate and analyze the data of continuing medical education in order to understand the real need of the learners.Methods Reviewing and making statistic analysis of the data of Renji hospital's continuing medical education courses from 2007 to 2012,including the amount,title,discipline,geographical distribution,training content and the questionnaire survey.Results It shows that the learners from coastal and developed areas have a higher demand for cuttingedge technology and the new progress in medicine(49.1％),while the learners from inland and western regions prefer to learn the basic medical theory and technology (41.9％).Senior doctors tend to study cutting-edge technology and new progress medical courses (51.7％) while the junior persons prefer the basic medical knowledge (46.6％).These mean that the needs of content of continuing medical education is associated with the regions and the level of the doctors (P＜0.05).Conclusion The conclusions prompt that medical development between different regions of China may be unbalanced.Chinese government should pay more attention in terms of allocation of health resources and personnel training.It also provides advice for future courses so that it may improve the efficiency of the medical education resources.

OBJECTIVETo improve the occupational health management levels in electroplating enterprises with quantitative classification measures and to provide a scientific basis for the prevention and control of occupational hazards in electroplating enterprises and the protection of workers' health.

METHODSA quantitative classification table was created for the occupational health management in electroplating enterprises. The evaluation indicators included 6 items and 27 sub-items, with a total score of 100 points. Forty electroplating enterprises were selected and scored according to the quantitative classification table. These electroplating enterprises were classified into grades A, B, and C based on the scores.

RESULTSAmong 40 electroplating enterprises, 11 (27.5%) had scores of >85 points (grade A), 23 (57.5%) had scores of 60∼85 points (grade B), and 6 (15.0%) had scores of <60 points (grade C).

CONCLUSIONQuantitative classification management for electroplating enterprises is a valuable attempt, which is helpful for the supervision and management by the health department and provides an effective method for the self-management of enterprises.

Objective To investigate the expression of stathmin and evaluate its influence to anti-microtubule adjuvant chemotherapy in non-small-cell lung cancer(NSCLC).Methods The clinical data and survival status of 78 NSCLC patients were collected,and their paraffin-embedded tissue were detected immunohistochemically with a rabbit anti-human stathmin polyclonal antibody.The clinical significance of stathmin expression and its influence to overall survival rate were analyzed statistically between patients who received paclitaxel or vinblastine adjuvant chemotherapy.Results The positive expression of stathmin could only be observed in the cytoplasm of cancer cells.Among 78 patients,40 (51.3 ％ ) patients were stained stathmin-positive.The positive rate of stathmin was significantly higher in male than female,in central type than peripheral type,in pleura-involved than non-involved,and in dead patients than survival patients ( P ＜ 0.05 ),but showed no significant differences in patients with different age,differentiated grade,pathological type,clinical stage,or lymph-node metastasis status.The expression of stathmin had a significant influence to overall survival rate(x2 =4.348,P ＜0.05 ),and those stathmin-negative patients showed a longer survival time.In stathmin-negative patients,those who received adjuvant chemotherapy with vinblastine exhibited a shorter survival time than those with paclitaxel,but the P =0.06.In stathmin-positive patients,the survival rate or time showed no difference between groups with paclitaxel and vinblastine.The differentiated grade,metastasis to lymph node and expression of stathmin were independent risk factors influencing survival rate.The positive expression of stathmin could only be observed in the cytoplasm of cancer cells.Among 78 patients,40 (51.3 ％ )patients were stained stathminpositive.The positive rate of stathmin was significantly higher in male than female,in central type than peripheral type,in pleura-involved than non-involved,and in dead patients than survival patients ( P ＜ 0.05 ),but showed no significant differences in patients with different age,differentiated grade,pathological type,clinical stage,or lymph-node metastasis status.The expression of stathmin had a significant influence to overall survival rate(x2 =4.348,P ＜ 0.05 ),and those stathmin-negative patients showed a longer survival time.In stathmin-negative patients,those who received adjuvant chemotherapy with vinblastine exhibited a shorter survival time than those with paclitaxel,but the P =0.06.In stathmin-positive patients,the survival rate or time showed no difference between groups with paclitaxel and vinblastine.The differentiated grade,metastasis to lymph node and expression of stathmin were independent risk factors influencing survival rate.Conclusion Our study suggested that the detection of stathmin in resected NSCLC tumor tissues may be helpful for prediction of prognosis,but helpless for making a choice between paclitaxel and vinblastine.NSCLC patients with stathmin-negative,no metastasis to lymph node or good-differentiated grade may have a better prognosis.

Background Researches have reported that arsenic trioxide (As_2O_3) is an effective method of treating solid tumor,and its mechanism is to inhibit the cellular proliferation and induce cellular apoptosis.However,the research on DNA damage caused by As_2O_3 is not clear.Objective This study is to investigate the roles of arsenic trioxide (As_2O_3) on DNA damage of retinal pigment epithelial cell in rabbit.Methods Retinal pigment epithelial cells were isolated from pigmented rabbits and cultured in vitro according to the method of Singh NP[2].Cultured cells were identified by cytokeratin.The third or fourth generation of cells were used to this study.50.00,5.00,2.00,1.00,0.50 and 0.25 μmol/L of As_2O_3 were added into medium respectively for 1 hour,and the same volume of PBS was added as negative control group.Cultured cells were exposed to ultraviolet (UV) rays with wave length of 254 nm for 10 minutes as positive control group.The cell vitality was detected by trypan-blue staining.The comet assay was applied to evaluate the DNA damage.SPSS 13.0 software was used for statistical analysis.Results The black granule were seen in cultured RPE cells.Cultured cells showed the positive brown-yellow particles in cytoplasm for cytokeratin with the positive rate over 90%.The morphology of the cells was similar among experimental group,UV irradiation group and PBS group under the inverted microscope.The normal cell activity was exhibited by trypan-blue staining in these three groups.Compared with PBS group,As_2O_3 caused obvious abnormality of DNA of RPE cell in a dose-dependent manner.Both the percentage of tail DNA and tail moment were gradually increased with the enhance of As_2O_3 concentration (F=88.548,P=0.000; F= 129.704,P=0.000).Significant differences also were found between different concentrations of As_2O_3 groups and UV irradiation group compared with PBS group (P＜0.05).As_2O_3 caused the obvious breaking up of DNA strands of RPE cells at the concentration of 50.00 μmol/L,but there was no statistical difference in spontaneous DNA damage of RPE cells between 0.50 and 0.25 μmol/L of As_2O_3 (P＞0.05).Conclusion As_2O_3 has a potential genotoxicity for rabbit retinal pigment epithelial cells in vitro.