The number of new medical products based on chemistry launches at the lowest level for many years. The pharmaceutical industry puts emphasis on biotechnology-derived products. Both genomics and protemics are contributing to understanding and determining more targets which involved in human disease.This means that there will be more opportunities for biopharmaceutical breakthroughs,eventually,more and better biomedicines will be approved.Several trends in development for biopharmaceuticals were analyzed:(1) Biological medicine and Chinese traditional medicine have developed rapidly between 1998~2005, the number of the papers about biological medicine increases dramaticly. (2)The emphasis is on biological medicine in pharmaceutical industry and the biotech market is concentrating in United States and multinational. (3)The proportion of biotech products is becoming larger gradually. More concern is focused on biotech products.(4)In order to reduce the cost of R&D and increase the number of new drugs, more and more M&A occur between the biotech companies.(5)The governments all over the world attach importance to biotech products.(6)Tissue engineering, cell therapy and gene therapy have a good future, full of opportunities and challenges.

Objective:To develop a UV optical fiber in situ process monitoring method for the dissolution behavior of five cepha-lexin solid dosage forms and compare the drug dissolution behavior of different cephalexin preparations. Methods: The dissolution of five different cephalexin preparations was on-line monitored according to the dissolution method for cephalexin tablets in Chinese Phar-macopeia (2010 edition) combined with a six channel optical fiber chemical sensor in situ dissolution monitor. Results:The dissolu-tion curves could show the drug release characteristics of different cephalexin preparations, and the five different preparations exhibited various drug release features. Conclusion:An in-situ, real time, on-line and process analysis of dissolution can be obtained by optical fiber dissolution test system automatically. The release characteristics of different preparations can be presented through dissolution curves directly, which can provide reference for the overall assessment of drug internal quality and clinical medication.

To exploit the efficient application of the digital medical records information in the medical scientific research.The medical records department should improve the current management mode.To establish monitoring system concerning,and reduce the risk related to the safety of medical records,strictly regulate the authorization of user.

Objective:To evaluate the physiological roles of bmp3,bmp4 and bmp7 during the formation of permanent tooth roots in dog. Methods:The expression of bmp3,bmp4 and bmp7 mRNA at different stages of the development of permanent tooth roots was examined by in situ hybridization in 3 dogs aged 12-18 weeks. Results:bmp3 was found in dental sac surrounding the germs at the early stage of tooth root development, and in cementoblasts and periodontal cells at the later stage. bmp4 was found in odontoblasts, dental papilla and osteoblasts. bmp7 positive signals was found only in epithelial cells of root sheath around cervical circulus at early stage, then located in cementoblasts and odontoblasts at later stage. Conclusion:The spatiotemporal expressions of bmp3,bmp4 and bmp7 are widely diverse, indicating that they participate in the regulation of tooth root development.

BACKGROUND: The investigation of culturing, passaging and establishing human limbal stem cells can strengthen the recognition of the stem cells and provide the enough cellular reserve for the basic and clinical research of limbal stem cell transplantation.OBJECTIVE: To explore a method of pessaging and establishing cell line of human limbal stem cells cultured in vitro.DESIGN: Randomized controlled observation.SETTING: Gannan Medical College.MATERIALS: The experiment was performed at Scientific Center of Gannan Medical College and the National Key Laboratory of Ophthalmology Hospital Affiliated to Sun Yat-Sen University from June 2003 to April 2004. Fresh human limbus corneae were isolated from two healthy donors. Procedures were performed according to the informed consent of the donors. Main reagents contained RPMI-1640 (Sigma R8755, containing L-glutamine) and 200 g/L fetal calf serum (FCS) (Gibco 16140-071). DMEM medium, chondroitin sulfatase and human epidermal growth factor (hEGF) were purchased from Sigma Co. USA; HEPES and DMSO were bought from Gibco, USA; 100% glycerinum was purchased from Yunjia Huangpu Pharmaceutical Product Limited Company, PRC; glutaraldehyde was bought from E.Merk, Germany; Alcohol, chlorhydric acid, acetone and methyl aldehyde were purchased from Beijing Chemical Agent Company, PRC; 0.25% parenzyme was bought from Shanghai Xinhua Pharmaceutical Factory, PRC.Above-mentioned reagents were analytical pure grade.METHODS: After digestion, human limbal tissues in limbal basilar part with an abundant pigment were cultured in the culture flask containing RPMI-1640 and 200 g/L FCS and in culture dish containing amniotic extracellular matrix (AECM) as the cultural supporter. Primary and passage cells were observed under light microscope and scanning electron microscope (SEM). The revival ratio of stem cell refrigeration of every generation was calculated by the trypanblau exclusion experiment.MAIN OUTCOME MEASURES: ① Observational results of limbal stem cells during the primary culture and serial subcultivation in vitro, and ② revival ratio of stem cell refrigeration.RESULTS: ①Findings of primary culture: Most limbal stem cells in the culture flask had the adherence and were arrayed uniformly sparsely to form monolayer and adhered to the bottom of culture flask under the inverted phase contrast microscope after 1-day culture. ② Findings of serial subcultivation: After human epidermal growth factor (hEGF) was added into the second passage, cells were scattered into the monolayer and adhered to grow quickly.Morphological variability of all the cells increased obviously when passage the 30th generation. The cellular volume was obviously increasing, and the round or irregular round cells gathered together. The 33rd generation human limbal stem cells still could vigorously differentiate, proliferate and grow in ACEM. ③ The revival ratio of stem cell refrigeration was 82.2%.CONCLUSION: The human limbal stem cell lines were preliminarily established by culturing and freezing the cells of 33 generations in vitro. The human limbal stem cell lines preferred to grow in the culture dish containing AECM as the cultural supporter.

Objective To explore the nursing problems and application value of intrauterine instruments positioning in assistance of tubal interventional treatment. Methods Uterine probe or expanding-uterus stick was used in 66 cases who had abortde with routine methods for rectifying the position of uterus or adhesion re-lease, then the selected catheter was inserted to the targeted fallopian tube for interventional aim. Nurses paid at-tention to the nursing cooperation and summarized the nursing points during the whole processes. Results With this technique, the achievement ratio of selected insertion to fallopian tube was 100% and that of recanaliza-tion was 92.68%. The major adverse effects were hypogastralgia and little vaginal bleeding. Pneumogastric nervereactions were found in 3.03% cases. Conchusions The assistant-immanent could elevate the achievement ra-tio of selected insertion to the targeted fallopian tubes, but the nursing problems shouldn't be neglected.

Objective:To evaluate the predictive value of gait kinematic combined with total MRI burden for the risk of falls in patients with gait disorder in cerebral small vessel disease(CSVD)using logistic regression analysis and ROC curve. Method:Forty-three patients diagnosed with CSVD and presenting primarily with gait disorder at Rehabilitation Department of Gansu Province Hospital from March 1,2019 to March 30,2020 were selected.The statistical clinical data were collected,and according to the TUG test time,all patients were divided into a group with high risk of fall(high risk of falling,HRF,TUG≥15s)and a group of low risk of falls(low risk of falling,LRF,TUG＜15s).Logistic regression analysis and ROC curve were used to assess the predictive value of gait kinematic characteristic combined with total MRI burden for the risk of falls in CSVD patients. Result:A total of 43 patients were included with average age(71.07±8.17)years.Among them,there were 26 female(60.4％)and 30 hypertension patients(69.8％),After adjusting for age and TUG,the logistic regres-sion analysis showed that the step length(OR 0.821,95％CI 0.702-0.959,P=0.013)was an independent protec-tive factor against the risk of falls in CSVD patients,while the total MRI burden(OR 4.217,95％CI 1.444-12.317,P=0.009)was an independent risk factor for the falls in CSVD.The ROC curve analysis showed that the combination of step length and total MRI burden had a high predictive value for the risk of fall in CSVD patients with gait disorder(AUC=0.904),with a sensitivity of 82.6％and a specificity of 90％. Conclusion:Step length combined with total MRI burden has a high predictive value for the risk of falls in CSVD patients with gait disorder.

Purpose: Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. Materials and Methods: In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. Results: The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells. Conclusion Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

Objective To systematically evaluate the efficacy and safety of plum-blossom needle therapy for vitiligo by using the systematic review and meta analysis.Methods The randomized controlled trials(RCT)on plum-blossom needle for treating vitiligo were systematically retrieved from the databases of the PubMed,China Biological Medicine Database,CNKI,Wanfang Data and VIP database from the database estab-lishment to June 2,2022.The literatures were screened according to the inclusion and exclusion criteria.The finally included literatures conducted the data extraction.The RevMan 5.4 software was used for conducting the data analysis.The methodological quality evaluation on the included trials was performed by the ROB tool.The GRADE method was used to assess the evidence level.Results A total of 7 trials involving 469 pa-tients were finally included.The meta analysis results showed that the plum-blossom needle combined with other therapies(including laser or ultraviolet irradiation,tacrolimus ointment,compound Kaliziran tincture)was superior to the other therapies alone in the aspects of improving vitiligo skin lesion including reducing the of white spot skin lesion area(MD=-1.11,95％CI:-1.92 to-0.30,P=0.007),increasing the repigment-ation rate of vitiliginous lesions(MD=18.09,95％CI:1.55 to 34.63,P=0.030)and enhancing the pigment deposition in vitiligo lesions(MD=0.92,95％CI:0.32 to 1.52,P=0.003),and improving the patients'quali-ty of life(MD=-7.48,95％CI:-8.04 to-6.92,P＜0.001),and the differences were statistically signifi-cant.In terms of safety,there was no statistically significant difference in adverse events between plum blos-som acupuncture combined with other therapies and other therapies alone(RR=1.20,95％CI:0.77 to 1.84,P=0.420).Conclusion Low or very low evidence shows that plum-blossom needle combined with other therapies for treating vitiligo may enhance the effect in the aspects of improving the white spot skin lesions and quality of life in the patients with vitiligo,moreover which is relatively safe.

Objective:To explore the effects of estrogen receptor α (ERα) encoded by protein encoding gene ESR1 on the radiation resistance of breast cancer cells and their molecular mechanisms.Methods:The ESR1 overexpression plasmid was transfected into estrogen receptor (ER)-negative breast cancer cells. Then, the shRNA-ESR1 vector was introduced into ER-positive cell to establish models with different phenotype. The ATG5 mRNA level and protein expression levels of LC3B-I, LC3B-II, P62, FIP200, ATG5, ATG7, ATG12, Beclin1, ULK1 were detected using qPCR and Western blot techniques. Cell death was measured using flow cytometry. The radiation sensitivity was determined through the colony formation assay. The mortality of breast cancer cells under the autophagy gene knockdown and overexpression or treated with estrogen receptor inhibitor (TAM) combined with ionizing radiation were detected by trypan blue staining.Results:Under the condition of 8 Gy X-ray irradiation, the knockdown of ESR1 in ER-positive ZR75 breast cancer cells promoted cell death ( t = 3.49, 3.13, P < 0.05), while the overexpression of ESR1 in ER-negative MDA-MB-231 breast cancer cells inhibited cell death ( t = 4.16, 7.48, P < 0.05). Compared to the control group, the treatment with chloroquine increased the number of formed colonies of ESR1 knockdown ZR75 cells ( t = 8.49, P < 0.05), and inhibiting autophagy could reduce the death of ZR75 cells caused by ESR1 silencing. Under the treatment with ionizing radiation, the overexpression of ESR1 in MDA-MB-231 cells promoted protective autophagy, which, however, was reduced after ESR1 knockdown in ZR75 cells. Furthermore, it was observed that the knockdown of ATG5 in ZR75 cells was associated with reduced autophagy and an increase in cell death ( t = 4.19, 6.39, P < 0.05). In contrast, the overexpression of ATG5 in ZR75 cells reversed the increase in cell death caused by ESR1 knockdown ( t = 1.70, 4.65, P < 0.05). After the treatment of ER-positive ZR75 breast cancer cells with TAM, the expressions of ATG5 and ATG12 decreased, suggesting inhibited autophagy and an increase in cell death ( t = 18.70, P < 0.05). Furthermore, these processes were promoted by ionizing radiation ( t = 16.82, P < 0.05). Conclusions:The estrogen receptor encoded by ESR1 promotes protective autophagy of ER-positive breast cancer cells by increasing ATG5, further leading to radiation resistance in ER-positive breast cancer cells. Treatment with tamoxifen combined with ionizing radiation can increase the radiation sensitivity of ER-positive breast cancer cells.