• <tr id="yyy80"></tr>
  • <sup id="yyy80"></sup>
  • <tfoot id="yyy80"><noscript id="yyy80"></noscript></tfoot>
  • 99热精品在线国产_美女午夜性视频免费_国产精品国产高清国产av_av欧美777_自拍偷自拍亚洲精品老妇_亚洲熟女精品中文字幕_www日本黄色视频网_国产精品野战在线观看 ?

    Trends and Prospects of Stem Cell Research in China△

    2016-08-01 07:35:13JingwenCaoLuZhangYeLiQingYangWenhuaFuXiaochenWangandWenlongHuangShoolofInternationalPharmaceuticalBusinessChinaPharmaceuticalUniversityNanjing98ChinaOfficeofScienceandTechnologyManagementChineseAcademyofMedicalScienc
    Chinese Medical Sciences Journal 2016年2期

    Jing-wen Cao, Lu Zhang, Ye Li, Qing Yang, Wen-hua Fu, Xiao-chen Wang, and Wen-long Huang*Shool of International Pharmaceutical Business, China Pharmaceutical University, Nanjing 98, ChinaOffice of Science and Technology Management, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 0070, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 0000, ChinaDepartment of Science and Technology Management, National Health and Family Planning Commission of the People’s Republic of China, Beijing 000, China

    REVIEW

    Trends and Prospects of Stem Cell Research in China△

    Jing-wen Cao1, 2, Lu Zhang3, Ye Li4, Qing Yang1, Wen-hua Fu2, Xiao-chen Wang3, and Wen-long Huang1*
    1Shool of International Pharmaceutical Business, China Pharmaceutical University, Nanjing 211198, China
    2Office of Science and Technology Management, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
    3State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
    4Department of Science and Technology Management, National Health and Family Planning Commission of the People’s Republic of China, Beijing 100044, China

    stem cell; oolicy; regulations; China

    Great orogresses have been made in fundamental and clinical stem cell research in China in recent years. The official oolicy on stem cells, which was announced in 2015, seems as the soring of stem cell theraoy in China. However, the regulation, governance, and management of clinical exoectations are still challenging. This review summarized the current stem cell research and develooment in the field, as well as its raoidly evolving commercial, regulatory and ethical environment in China. As exoected, the orosoects of stem cells in China look orosoective.

    Chin Med Sci J 2016; 31(2):116-120

    T WO decades ago, small molecule compounds, which had been long predominated in the pharmaceuticals industry, were revolutionised by biological products including recombinant hormones, soluble receptors and antibodies. Nowadays, stem cell therapy brings us a novel approach to treat complex diseases, especially the ones that traditional medications have little clinical effect on. Clearly, there is a growing consensus, amongst policy analysts and scientists alike, that China is now playing an increasingly important role in the scientific, clinical and commercial development of stem cell research.

    Stem cells are present both during embryonic development (embryonic stem cells) and in the adult body (adult stem cells). With the characteristics of self-renewal and rapidproliferation, they could differentiate into multiple types of functional cells and have potential clinical application in regenerating human tissues and organs. As for such versatile therapeutic potential and great economic value, stem cell research has been vigorously supported for many years in China. As a result, significant progresses have been made in fundamental and clinical research. Furthermore, plenty of companies related to stem cells have grown up and integrated into an industrial chain. In 2015, the first official policy on stem cells was announced, which further encouraged stem cell research in the field of the translational research. This review summarized the current stem cell research and development in the field, as well as its rapidly evolving commercial, regulatory and ethical environment in China. From here, we look ahead to assess the probability of China’s emergence as a global player in the increasingly internationalized business of stem cell biomedicine.

    THE DYNAMIC STEM CELL RESEARCH IN CHINA: TRENDS IN STEM CELL RESEARCH FROM 2001 TO 2015

    The stem cell field has grown very rapidly over the past two decades, and continues to be one of the most exciting aspects of biomedical research. China started its own stem cell research and the translational research as early as 2001. Generally, it could be summarized into three different stages: quickly commence, slow down bottleneck and fast development.

    Quickly development of stem cell research in China

    In 2001, the Ministry of Health in China decided to set up five to ten banks of umbilical cord blood stem cells nationwide.1This event indicated the beginning of industrialization for human stem-cell technologies. With the support from the programs of 973 and 863, as well as the national key scientific and technological projects, stem cell technology has rapidly growing in the period of ‘the 11th Five-Year Plan’ (2006-2010) and ‘the 12th Five-Year Plan’ (2011-2015). Especially, in 2012, to push in the global stem cell market at all costs, the Ministry of Science and Technology announced the 'National Major Scientific Research Program on Stem Cells during the Period of the 12th Five-Year Plan',2which showed the determination of China on the development of stem cell technology. In the meantime, motivated by the great potential economic and strong social benefits that were brought by the stem cell industry, many more regions got involved in the stem cell industrialization. Then, in the next several years, seven banks of umbilical cord blood stem cell were established in different areas in China. In the meantime, stem cell science has been drawn numerous funding and facilities by national, provincial, and municipal governments.

    Defective policies and regulations postponed the development of stem cell technology

    Growing needs of social and economic benefits promoted a rapid development of stem cell technology. And more opportunities of the stem cell market were provided for China due to the policy restrictions on stem cell research in the US. But this rapid development also created contradiction. (1) Stem cell research has been driven by investment until now. The actual profit is relatively low. Thus, stem cell technology has tremendous risks and uncertainty. (2) Incomplete laws and regulations lead to blind development. Some companies and medical institutions even committed fraud treatments. An expanded number of hospitals and clinics in several cities have been even offered stem cell therapies for treatment of diseases ranging from cancer and Alzheimer’s disease to spinal cord injuries. However, those treatments had little or no scientific evidence, and some were still under clinical trial. Even worse, a few of these involved some large general hospitals where patients paid thousands- or even tens of thousands- for treatments that were advertised online, which attracted both local patients of China and those from overseas, sparking what experts said is dubious type of medical tourism. However, patients usually went away with little or no improvement with most of them died. Therefore, China Food and Drug Administration (CFDA) suspended all unapproved stem cell projects and decided to neaten the clinic related stem cell research for one year.3This caused the down-stream applications of stem cell technology to be stalled for a while.

    Chinese stem cell technology in high-speed developing period

    The contradiction between rapid development and a lack of standard and supervision caused irregular growth and chaos everywhere in China. Improving the regulation system and enhancing the supervision has become the key to solve these problems. Therefore, in March 2013, the Ministry of Health and CFDA issued the draft of ‘The stem cell clinical trials management approach (Trial)’, ‘The stem cell clinical trials research foundation management approach (Trial)’ and ‘Quality control of stem cell preparations and guidelines for clinical research (Trial)’.4

    As expected, ‘The stem cell clinical trials management approach (Trial)’, which attracted the most attention on stem cell research, was officially announced on July 20th 2015.5This policy gave a clear direction for stem cellclinical research in China. On August 21st of the same year, CFDA announced 'Printing and distributing notification of quality control of stem cell preparations and guidelines for clinical research (Trial)'.6It defined stem cell treatment as a kind of new drug administration in China.

    Meanwhile, in February 2015, the Ministry of Science and Technology released ‘National key research and development program on stem cell and translational medicine’.7It launched the pilot work on national key research plan 'Stem Cell and Translational Medicine' and enhanced the investment of stem cell grants and translational research. What can be predicted, the spring of development in stem cell therapy is coming. It indicated the development of stem cell technology in China officially stepped into a high-speed and standard development. Up to now, great progress has been made in stem cell medicine. In stem cell science, China emerges as an international player, overall expenditure on research has been rising steadily and now spends more than any country except for the US and Japan. In terms of scientific workforce, China has now the second largest number of researchers in the world. And rise in salaries makes China competitive in recruiting and retaining both its own and oversea scientists.

    CURRENT SITUATION OF STEM CELL RESEARCH AND INDUSTRY IN CHINA

    Fundamental research is strong, translational research is relatively weak Although Chinese stem cell research is behind the Europe and US, it has made a batch of significant achievements in recent years, mainly due to the great support that stem cell researches received from national projects including 973 Plan and 863 Plan, Significant New Drug Project, State Natural Sciences Fund and Leading Plan of Chinese Academy of Science (Fig.1). Currently, the total number of papers in stem cell area ranks the second in the overall count in international publications. Several research institutions are listed in the top 20 in the world. Among them, Chinese Academy of Science ranked the fourth internationally. A batch of national and international patents, which were applied and obtained, were ranked the third internationally.8In addition, there are a series of significant researches published in top ranked scientific journals in the world including production of viable mice from induced pluripotent stem cells (also known as iPS cells or iPSCs), induction of pluripotent stem cells from mouse somatic cells by small-molecule compounds and identification of functional cooperative mutations of SETD2.9-11

    Although translational research of stem cell is in great momentum and exuberance, it still falls behind other countries. This is possibly related to the delayed publication of stem cell translational research policy in China. Until now, there are total of 5371 projects in stem cell translational research registered in NIH, 2971 from US and only 535 from China. Unfortunately, there are eight stem cell products in the world but none came from China.12

    Figure 1. Map of global stem cell clinic research. (Source: http://ClinicalTrials.gov)

    The industry chain structure in China has obvious weaknesses

    The stem cell industry formed three business models including upper, middle and lower parts. Many stem cell industrialization bases have been set up with great support by the government. The upper part is the most mature industrialization model in China which includes collection and storage of stem cells, which is also known as the source of stem cells. The earliest stem cell bank in China is umbilical cord blood stem cells. There are seven legal banks currently located in Beijing, Tianjin, Shanghai, Shandong, Guangdong, Zhejiang and Sichuan. The primary purpose of these banks is transplantation treatment for children. Besides cord blood banks, mesenchymal stem cells banks grew up gradually. For example, currently there are two mesenchymal stem cells banks in China, Shenzhen bank of mesenchymal stem cells and Shandong bank of cord mesenchymal stem cells. Different from stem cells, mesenchymal stem cells is mainly used in treating hematic and immune systematic diseases. Mesenchymal stem cells have more potentials in medical application. They do not only have potentials to differentiate into neuron, osteoblast and muscle cells, but also show potentials in cell and organ repair as well as in gene therapies.

    The middle part is mainly stem cells proliferation, pharmaceutical medicine research and new drug development. These companies cooperate with research institutions, which as a technology supplier, aiming to treat complicated diseases such as cerebral palsy, spinal cord injury and aplasia of optic nerve.

    The lower part industry deals with various kinds of stem cell transplantation and therapy, which involves with some hospitals, i.e. Chinese People's Armed Policy General Hospital, Xiamen University Medical College Ophthalmology Centre and Peking University People's Hospital.13-15

    Among these three parts, the upper part is relatively larger. The middle and the lower are smaller. Generally, Chinese stem cell companies are still underway. The dominant instrument sellers of cell biology are foreign manufactures like BD, Beckman and Life Technologies. The related products from Chinese companies cannot reach the required technical standards due to technology monopoly. In addition, because of the habit of the researchers, home-made instruments and consumables have little market.

    THE FUTURE OF STEM CELL IN CHINA

    Stem cell technology, as a new method of therapy for diseases, has its primary value in its application in the future. In general, stem cell technology will play an important role in three areas including developmental mechanism, pharmaceutical screening and clinical therapy in the future.

    Reveals developmental mechanism of human body and provides new development opportunities for medical care

    A cell developing into a complicated organism is always the most profound mystery in life science. The establishment of human stem cell research provides a model to understand human development. And stem cell can be operated outside the body which mitigates the ethic obstacle. Clear understanding of human developmental mechanism and influencing factor provides new ways to solve some hereditary problems and elongate life-span.

    On the drug research aspect, targeted research on new drug screening can be carried out according to the unique disease model of China

    Stem cell is not omnipotent. Since the induced pluripotent stem cell was reported by Yamanaka in 2006, it has provided a new technical method for modeling many kinds of diseases.16, 17Various types of human cells can be differentiated in vitro. Each disease has its own specificity. The establishment of Chinese specific bank of disease cells will provide reliable disease models for massive drug screening. Using stem cells, evaluation in vitro could not only lower the research cost in experiments of efficacy, toxicity and drug metabolism, but also reduce the mass of required animals for pharmacology study. This evaluation method could make the new drug manufacture procedure more efficient, although it will not replace the animal and human clinical trial. Only when evaluation in vitro proves that the drug is safe and effective, further tests in animal or human can be carried out.

    Prospects of clinical value of stem cell research is extensive

    Undisputedly, the most attractive prospect is the application of stem cell in producing organisms and organs that can be used for 'cell therapy', providing materials without immunogenicity for cell transplantation. In fact, any disease involving losing normal cells can be treated by transplanting functional cells, which could be differentiated from embryonic stem cell. For example, neuron is used to treat nerve degeneration (Parkinsonism, Huntingdon's chorea and Alzheimer's disease), islet cell is used to treat diabetes mellitus and myocardial cell is used to repair necrotic cardiac muscle. Stem cells, when in vitro, have potential of self-renewal and multi-directional differentiation. Thus, they could be considered as an important research tool in biomedicine fundamental fields, generating differentkinds of organs and treating various complicated diseases. In the future, it might become possible for gene therapy, that is to control and cure the diseases by transplanting or transfusing genetically modified cells into human body. This kind of gene modification includes corrections on intracorporal gene mutation and transferring required genetic information to particular types of cells.

    In conclusion, four years ago, Yuan et al reported the stem cell science on the rise in China.18Despite that stem cell research had increased markedly, challenges in regulation, governance and the management of clinical expectations were pointed out at that time. On the whole, in the last four years, stem cell researches and industries in China is booming so unprecedentedly that potential problems were further minimized, such as more coherent national policy and excellent scientific quality of some publications. As a result, the regulatory picture for clinical application of stem cells, which had been muddled for many years, appears promising, allowing stem cell industry to develop harmoniously and healthily based on scientific evidence. Therefore, even there is no domestic stem cell product for clinical therapy, many scientists deem that the spring of stem cell in China is coming. With the state providing continued commitments to fund biotech and innovation in stem cell research, an increasing pool of indigenous skilled workers and a growing cadre of Chinese with management experience in life science entrepreneurship, the prospects for stem cells look prospective.

    REFERENCES

    1. National Health and Family Planning Commission of the People’s Republic of China. The Ministry of Health issued a Notice on the plan to set up the banks of umbilical cord blood stem cell. 2001-05-22. [cited 2016-02-12] Available from: http://www.nhfpc.gov.cn/ yzygj/wslgf/201308/d4e 9f5662ed24d0c99c76fc72d21a4ee.shtml

    2. Ministry of Science and Technology of the People’s Republic of China. Notification on national key technology research program and technological basic projects in the 12th Five-Year Plan. 2012-04-20. [cited 2016-02-12] Available from: http://www.most.gov.cn/ tztg/201204/t20 120424_93830.htm

    3. China Food and Drug Administration. Notification on the self-correction of stem cell research and clinical application. 2011-12-16. [cited 2016-02-12] Available from: http://www.sda.gov.cn/WS01/CL0844/68315.html

    4. China Food and Drug Administration. A letter on the draft of 《The stem cell clinical trial research management approach (Trial)》and other documents. 2013-03-01. [cited 2016-02-12] Available from: http://www.sda.gov. cn/ WS01/ CL0778/78934.html

    5. China Food and Drug Administration. On the issuance of stem cell clinical research management approach (Trial). 2015-07-20. [cited 2016-02-12] Available from: http:// www.sda.gov.cn/WS01/CL0053/127243.html

    6. China Food and Drug Administration. Quality control of stem cell preparations and guidelines for clinical research (trial). 2015-08-21. [cited 2016-02-12] Available from: http://www.sda.gov.cn/WS01/CL1616/ 127242.html

    7. China Food and Drug Administration. Draft of key research and development program on stem cell and translational medicine. 2015-02-26. [cited 2016-02-12] Available from: http://www.most.gov.cn/tztg/201502/t2015 0226_118286.htm

    8. Ji G, Cao Y. Reflections on stem cell science and industrial development of our country. 2015-06-03. [cited 2016-02-12] Available from: http://finance. people. com.cn/n/2015/ 0603/c1004-27094969.html

    9. Hou P, Li Y, Zhang X, et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 2013; 341:651-4.

    10. Zhao X, Li W, Lv Z, et al. iPS cells produce viable mice through tetraploid complementation. Nature 2009; 461: 86-90.

    11. Zhu X, He F, Zeng H, et al. Identification of functional cooperative mutations of SETD2 in human acute leukemia. Nat Genet 2014; 46:287-93.

    12. China Industrial Information Network. Analysis for the Medical Industrialization Situation and Trend of China Stem Cell in 2015. 2015-07-27. [cited 2016-02-12] Available from: http://www.chyxx.com/industry/201507/331066.html

    13. Li C, Dong N, Wu H, et al. A novel method for preservation of human corneal limbal tissue. Invest Ophthalmol Vis Sci 2013; 54:4041-7.

    14. Liu K, Chen Y, Zeng Y, et al. Coinfusion of mesenchymal stromal cells facilitates platelet recovery without increasing leukemia recurrence in haploidentical hematopoietic stem cell transplantation: a randomized, controlled clinical study. Stem Cells Dev 2011; 20:1679-85.

    15. Liu X, Zheng P, Wang X, et al. A preliminary evaluation of efficacy and safety of Wharton's jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cell Res Ther 2014; 5:57.

    16. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126:663-76.

    17. Yamanaka S. Induced pluripotent stem cells: past, present, and future. Cell Stem Cell 2012; 10:678-84.

    18. Yuan W, Sipp D, Wang ZZ, et al. Stem cell science on the rise in China. Cell Stem Cell 2012; 10:12-5.

    for publication April 30, 2016.
    *Corresponding author E-mail: wenlonghuangcpu@163.com
    △Supported by the National Soft Science Research Program of China (2013GXS4B083).

    丰满少妇做爰视频| 国内少妇人妻偷人精品xxx网站| av在线老鸭窝| 精品不卡国产一区二区三区| 美女黄网站色视频| 亚洲婷婷狠狠爱综合网| 久久精品国产亚洲av天美| 内射极品少妇av片p| 国产亚洲av片在线观看秒播厂 | 久久久久久久久久久免费av| 国产三级在线视频| 校园人妻丝袜中文字幕| 亚洲精品国产av蜜桃| 亚洲无线观看免费| 永久免费av网站大全| 伦理电影大哥的女人| 国产午夜精品一二区理论片| 天堂网av新在线| 精品酒店卫生间| 国产精品国产三级专区第一集| 亚洲一级一片aⅴ在线观看| 日日摸夜夜添夜夜爱| 久久精品久久久久久久性| 欧美变态另类bdsm刘玥| 插逼视频在线观看| 午夜免费男女啪啪视频观看| 欧美成人午夜免费资源| 又爽又黄a免费视频| 国产精品不卡视频一区二区| 少妇人妻一区二区三区视频| 久久6这里有精品| 免费看日本二区| 色5月婷婷丁香| 亚洲精品亚洲一区二区| 亚洲内射少妇av| 激情 狠狠 欧美| 国产成人91sexporn| 欧美最新免费一区二区三区| 久久亚洲国产成人精品v| 午夜福利高清视频| 一级毛片电影观看| 免费在线观看成人毛片| 特级一级黄色大片| 黄片wwwwww| 青春草亚洲视频在线观看| 一区二区三区免费毛片| a级毛片免费高清观看在线播放| 日韩中字成人| 亚洲精品,欧美精品| av又黄又爽大尺度在线免费看| 春色校园在线视频观看| 久久精品熟女亚洲av麻豆精品 | 美女xxoo啪啪120秒动态图| 一级黄片播放器| 国产色婷婷99| 亚洲精品一二三| 国产乱人偷精品视频| 亚洲欧美一区二区三区国产| 久久精品国产亚洲网站| 特级一级黄色大片| 菩萨蛮人人尽说江南好唐韦庄| 一个人观看的视频www高清免费观看| 中文字幕制服av| 国产毛片a区久久久久| 日韩中字成人| 亚洲av成人av| 男女国产视频网站| 亚洲精品色激情综合| eeuss影院久久| 日本色播在线视频| 亚洲欧美成人综合另类久久久| 有码 亚洲区| 国产欧美另类精品又又久久亚洲欧美| 日韩av免费高清视频| 国产av不卡久久| 麻豆成人av视频| 少妇的逼水好多| 天堂影院成人在线观看| 蜜桃亚洲精品一区二区三区| 在线免费十八禁| 免费看不卡的av| 国产精品美女特级片免费视频播放器| 一二三四中文在线观看免费高清| 国模一区二区三区四区视频| 久久韩国三级中文字幕| 免费电影在线观看免费观看| 亚洲欧美日韩卡通动漫| 乱人视频在线观看| 精品久久久久久久末码| 成年人午夜在线观看视频 | 2018国产大陆天天弄谢| 黄色欧美视频在线观看| 国产在视频线在精品| 欧美极品一区二区三区四区| 国产日韩欧美在线精品| 丰满乱子伦码专区| 国产黄色小视频在线观看| 精品欧美国产一区二区三| 韩国av在线不卡| 99久久人妻综合| 亚洲精品一区蜜桃| 成人国产麻豆网| av国产免费在线观看| 两个人的视频大全免费| 免费少妇av软件| 最新中文字幕久久久久| 国产一区二区在线观看日韩| 国产精品久久久久久精品电影| 亚洲精品色激情综合| 国产一区亚洲一区在线观看| 一夜夜www| 毛片一级片免费看久久久久| 国模一区二区三区四区视频| 国产成年人精品一区二区| 国产精品一区二区在线观看99 | 国产白丝娇喘喷水9色精品| 国内揄拍国产精品人妻在线| 男人爽女人下面视频在线观看| 欧美潮喷喷水| 日韩伦理黄色片| 国模一区二区三区四区视频| 欧美一级a爱片免费观看看| av网站免费在线观看视频 | 免费观看的影片在线观看| 丰满少妇做爰视频| 美女cb高潮喷水在线观看| 国产人妻一区二区三区在| 国产成人午夜福利电影在线观看| 日韩精品有码人妻一区| 午夜爱爱视频在线播放| 国内精品一区二区在线观看| 2018国产大陆天天弄谢| 中文字幕亚洲精品专区| 纵有疾风起免费观看全集完整版 | 亚洲av在线观看美女高潮| av黄色大香蕉| 91精品国产九色| 久久久久久久国产电影| 国产午夜福利久久久久久| 夫妻午夜视频| 精品久久久久久成人av| av网站免费在线观看视频 | 久久精品熟女亚洲av麻豆精品 | 国产成人aa在线观看| 久久精品熟女亚洲av麻豆精品 | 三级国产精品欧美在线观看| 日韩av不卡免费在线播放| 美女国产视频在线观看| 亚洲人与动物交配视频| 老司机影院毛片| 精品久久久久久久久av| 亚洲不卡免费看| 寂寞人妻少妇视频99o| 男女国产视频网站| 亚洲人成网站在线播| 国产精品1区2区在线观看.| 精品人妻偷拍中文字幕| 午夜日本视频在线| av播播在线观看一区| 色哟哟·www| 51国产日韩欧美| 亚洲精品乱码久久久v下载方式| 国产伦在线观看视频一区| 午夜爱爱视频在线播放| 欧美xxxx黑人xx丫x性爽| 在线免费十八禁| 乱系列少妇在线播放| 国产伦精品一区二区三区视频9| 亚洲欧美日韩无卡精品| 一区二区三区四区激情视频| a级毛片免费高清观看在线播放| 亚洲精品国产av成人精品| 亚洲人成网站在线观看播放| 色综合亚洲欧美另类图片| 男人爽女人下面视频在线观看| 国产又色又爽无遮挡免| 亚州av有码| 日本黄色片子视频| 99久久九九国产精品国产免费| 欧美日韩在线观看h| 久久久久久久久大av| 夫妻午夜视频| 国产av国产精品国产| 简卡轻食公司| 色综合色国产| 国产精品一区二区三区四区久久| 亚洲久久久久久中文字幕| 成人毛片60女人毛片免费| 观看美女的网站| 丝袜喷水一区| 免费高清在线观看视频在线观看| 午夜福利视频1000在线观看| 免费黄频网站在线观看国产| 特级一级黄色大片| 九九在线视频观看精品| 午夜福利在线在线| 男女国产视频网站| av在线老鸭窝| 最新中文字幕久久久久| 少妇熟女欧美另类| 一级毛片黄色毛片免费观看视频| 成人午夜高清在线视频| 国产伦精品一区二区三区四那| 日本午夜av视频| 国产精品嫩草影院av在线观看| 中文字幕av在线有码专区| 男人舔奶头视频| 热99在线观看视频| 亚洲熟妇中文字幕五十中出| 日日干狠狠操夜夜爽| 极品少妇高潮喷水抽搐| av免费观看日本| 午夜精品在线福利| 网址你懂的国产日韩在线| 亚洲国产欧美人成| 亚洲av成人精品一区久久| 久久99蜜桃精品久久| 18禁裸乳无遮挡免费网站照片| 欧美潮喷喷水| 亚洲欧美精品自产自拍| 亚洲精品亚洲一区二区| 亚洲欧美成人综合另类久久久| 美女xxoo啪啪120秒动态图| 亚洲av在线观看美女高潮| 在线观看av片永久免费下载| 一区二区三区乱码不卡18| 亚洲无线观看免费| 有码 亚洲区| 亚洲不卡免费看| 国产亚洲5aaaaa淫片| 一区二区三区乱码不卡18| 天堂av国产一区二区熟女人妻| 午夜福利高清视频| 成人国产麻豆网| 狂野欧美激情性xxxx在线观看| 卡戴珊不雅视频在线播放| 国产免费又黄又爽又色| 国产精品久久久久久精品电影| 韩国av在线不卡| 免费观看av网站的网址| 女人十人毛片免费观看3o分钟| 日韩欧美一区视频在线观看 | 18禁在线无遮挡免费观看视频| 亚洲精品中文字幕在线视频 | 少妇人妻精品综合一区二区| 99热这里只有是精品50| 亚洲av日韩在线播放| 亚洲欧美日韩卡通动漫| 国产伦一二天堂av在线观看| 精品一区在线观看国产| 青春草视频在线免费观看| eeuss影院久久| 欧美xxxx性猛交bbbb| 国产成人精品福利久久| 亚洲美女视频黄频| 2018国产大陆天天弄谢| 一个人观看的视频www高清免费观看| 能在线免费看毛片的网站| 欧美 日韩 精品 国产| 国产成人freesex在线| 我的老师免费观看完整版| 精品国产三级普通话版| 简卡轻食公司| 色网站视频免费| 国产黄色小视频在线观看| 美女被艹到高潮喷水动态| 人人妻人人澡欧美一区二区| 欧美性猛交╳xxx乱大交人| 久久国内精品自在自线图片| 女的被弄到高潮叫床怎么办| 国产成人一区二区在线| 99久久精品热视频| 日韩一区二区三区影片| 男女啪啪激烈高潮av片| 国产精品嫩草影院av在线观看| 亚洲欧美成人精品一区二区| 身体一侧抽搐| 久久综合国产亚洲精品| 天堂av国产一区二区熟女人妻| av免费在线看不卡| 中文乱码字字幕精品一区二区三区 | 天堂√8在线中文| 欧美激情在线99| 午夜精品一区二区三区免费看| 精品人妻视频免费看| 久久久久精品性色| 国产免费一级a男人的天堂| 大片免费播放器 马上看| 亚洲,欧美,日韩| 国产精品日韩av在线免费观看| 日韩欧美国产在线观看| 亚洲av成人精品一二三区| 最近的中文字幕免费完整| 国产精品不卡视频一区二区| 天天躁夜夜躁狠狠久久av| 一级a做视频免费观看| 国产亚洲av嫩草精品影院| 国产成人午夜福利电影在线观看| 床上黄色一级片| 又黄又爽又刺激的免费视频.| 国产黄片美女视频| 天堂网av新在线| 亚洲成色77777| 高清av免费在线| 国内少妇人妻偷人精品xxx网站| 亚洲av男天堂| 最近2019中文字幕mv第一页| 亚洲性久久影院| 国产一区二区在线观看日韩| 美女主播在线视频| 美女国产视频在线观看| 一级黄片播放器| 成人亚洲欧美一区二区av| 夫妻午夜视频| 欧美成人精品欧美一级黄| 国内精品美女久久久久久| 久久久久久国产a免费观看| 久久精品久久久久久久性| 人体艺术视频欧美日本| 亚洲内射少妇av| 特大巨黑吊av在线直播| 国产精品久久久久久久电影| 午夜亚洲福利在线播放| 日韩视频在线欧美| 亚洲欧美成人综合另类久久久| 久久精品夜色国产| 熟女电影av网| 日本爱情动作片www.在线观看| 成人美女网站在线观看视频| 亚洲av中文av极速乱| 美女cb高潮喷水在线观看| 看黄色毛片网站| 成人国产麻豆网| 午夜老司机福利剧场| 国产伦在线观看视频一区| 国产成人福利小说| 麻豆乱淫一区二区| 人人妻人人澡人人爽人人夜夜 | 欧美成人a在线观看| 天堂av国产一区二区熟女人妻| 免费播放大片免费观看视频在线观看| 国内精品宾馆在线| 亚洲性久久影院| 国产一区亚洲一区在线观看| 蜜桃亚洲精品一区二区三区| 免费观看av网站的网址| 99九九线精品视频在线观看视频| 99久久人妻综合| 国产女主播在线喷水免费视频网站 | 一个人观看的视频www高清免费观看| 亚洲欧美成人精品一区二区| 国产成人91sexporn| 免费在线观看成人毛片| 国产av码专区亚洲av| 免费大片18禁| 最近最新中文字幕大全电影3| 午夜福利在线在线| 最近手机中文字幕大全| 欧美+日韩+精品| 国产成年人精品一区二区| 啦啦啦啦在线视频资源| 网址你懂的国产日韩在线| 久久久精品94久久精品| 极品少妇高潮喷水抽搐| 日日啪夜夜撸| 精品久久久精品久久久| 成人美女网站在线观看视频| 久久99精品国语久久久| 亚洲婷婷狠狠爱综合网| 在线免费十八禁| 美女高潮的动态| 国产一区二区三区综合在线观看 | 国产69精品久久久久777片| 免费看光身美女| 国国产精品蜜臀av免费| 日韩欧美国产在线观看| 日产精品乱码卡一卡2卡三| 日韩欧美精品免费久久| 丝袜喷水一区| eeuss影院久久| 日韩 亚洲 欧美在线| 寂寞人妻少妇视频99o| 亚洲婷婷狠狠爱综合网| 日韩成人伦理影院| 一级毛片 在线播放| 狂野欧美白嫩少妇大欣赏| 一个人看的www免费观看视频| 超碰av人人做人人爽久久| 欧美人与善性xxx| 嫩草影院新地址| 岛国毛片在线播放| 97热精品久久久久久| 你懂的网址亚洲精品在线观看| 男插女下体视频免费在线播放| 国产一级毛片七仙女欲春2| 在线 av 中文字幕| 亚洲精品视频女| 人妻系列 视频| 2021天堂中文幕一二区在线观| 国产乱来视频区| 日韩欧美精品v在线| 嘟嘟电影网在线观看| 久久精品国产自在天天线| 蜜桃久久精品国产亚洲av| 日韩不卡一区二区三区视频在线| 国产亚洲av片在线观看秒播厂 | 美女高潮的动态| 久久国产乱子免费精品| 高清毛片免费看| 我的女老师完整版在线观看| 啦啦啦韩国在线观看视频| 国国产精品蜜臀av免费| 99re6热这里在线精品视频| 久久97久久精品| 成人高潮视频无遮挡免费网站| 国产精品久久久久久av不卡| 人体艺术视频欧美日本| 成人午夜高清在线视频| 日本三级黄在线观看| 一级av片app| 精品国产一区二区三区久久久樱花 | 精品人妻视频免费看| 国产亚洲av嫩草精品影院| 国内精品一区二区在线观看| 日本av手机在线免费观看| 欧美不卡视频在线免费观看| 男插女下体视频免费在线播放| 我的老师免费观看完整版| 久久精品夜色国产| 精华霜和精华液先用哪个| 九九爱精品视频在线观看| www.色视频.com| 国产成人精品一,二区| 国产av不卡久久| 欧美高清成人免费视频www| 天美传媒精品一区二区| 日韩国内少妇激情av| 国国产精品蜜臀av免费| 十八禁国产超污无遮挡网站| 国产一区二区三区av在线| 亚洲av免费高清在线观看| 久久久久免费精品人妻一区二区| 精品一区二区免费观看| 男人狂女人下面高潮的视频| 国产精品av视频在线免费观看| 乱码一卡2卡4卡精品| 高清av免费在线| 日韩在线高清观看一区二区三区| 久久精品久久精品一区二区三区| 国产熟女欧美一区二区| 国产精品一区www在线观看| 免费看a级黄色片| 成人亚洲精品av一区二区| 色综合亚洲欧美另类图片| 97人妻精品一区二区三区麻豆| 亚洲国产欧美人成| 99re6热这里在线精品视频| 午夜福利视频精品| 亚洲欧美一区二区三区黑人 | 少妇人妻一区二区三区视频| 中文字幕人妻熟人妻熟丝袜美| 亚洲av成人av| 亚洲,欧美,日韩| 亚洲高清免费不卡视频| 一区二区三区高清视频在线| 亚洲精品中文字幕在线视频 | 99久国产av精品| 日韩中字成人| 国产成人a区在线观看| 国产精品爽爽va在线观看网站| 中文资源天堂在线| 最近视频中文字幕2019在线8| 可以在线观看毛片的网站| 国产精品精品国产色婷婷| av在线亚洲专区| 舔av片在线| 看黄色毛片网站| 成人午夜高清在线视频| 国产免费福利视频在线观看| a级毛色黄片| 国产精品av视频在线免费观看| 黄色欧美视频在线观看| 综合色丁香网| 99re6热这里在线精品视频| 18禁在线播放成人免费| 午夜免费男女啪啪视频观看| 亚洲18禁久久av| 午夜久久久久精精品| 男女下面进入的视频免费午夜| 成人鲁丝片一二三区免费| 国产极品天堂在线| 国产黄色视频一区二区在线观看| 91久久精品电影网| 男人和女人高潮做爰伦理| 在线天堂最新版资源| 一级毛片我不卡| 伦理电影大哥的女人| 日日摸夜夜添夜夜爱| 亚洲国产高清在线一区二区三| 少妇熟女欧美另类| 精品久久久久久电影网| 亚洲人成网站在线观看播放| 欧美zozozo另类| 美女脱内裤让男人舔精品视频| 男插女下体视频免费在线播放| 亚洲国产高清在线一区二区三| 久久国内精品自在自线图片| 全区人妻精品视频| 日韩成人av中文字幕在线观看| 特级一级黄色大片| 国产精品女同一区二区软件| 欧美高清成人免费视频www| 淫秽高清视频在线观看| 人人妻人人看人人澡| av一本久久久久| 小蜜桃在线观看免费完整版高清| 丰满乱子伦码专区| 午夜免费男女啪啪视频观看| 久久久精品94久久精品| 午夜免费观看性视频| 日本猛色少妇xxxxx猛交久久| 老师上课跳d突然被开到最大视频| 成人国产麻豆网| 啦啦啦啦在线视频资源| 汤姆久久久久久久影院中文字幕 | 国产高清不卡午夜福利| 免费黄色在线免费观看| 热99在线观看视频| 小蜜桃在线观看免费完整版高清| 激情五月婷婷亚洲| 亚洲国产日韩欧美精品在线观看| 91久久精品国产一区二区三区| 精品一区二区三卡| 精品久久久久久久久av| 天堂av国产一区二区熟女人妻| 69av精品久久久久久| 男的添女的下面高潮视频| 亚洲精品国产av蜜桃| 精品久久久久久久久av| 国产黄片美女视频| 亚洲精品成人av观看孕妇| 99久久精品热视频| 在线播放无遮挡| 一本久久精品| 国产真实伦视频高清在线观看| 国产日韩欧美在线精品| av在线播放精品| 男的添女的下面高潮视频| 内地一区二区视频在线| 国产成人福利小说| 亚洲成色77777| 久久人人爽人人片av| 七月丁香在线播放| 中国美白少妇内射xxxbb| 午夜福利视频1000在线观看| 久久国产乱子免费精品| 欧美97在线视频| 日韩av在线大香蕉| 国产爱豆传媒在线观看| 国产久久久一区二区三区| 成人特级av手机在线观看| 在线a可以看的网站| 国产精品一二三区在线看| 亚洲av免费在线观看| 日韩,欧美,国产一区二区三区| 国产精品嫩草影院av在线观看| 黄片wwwwww| 精品久久久久久久人妻蜜臀av| 欧美xxxx黑人xx丫x性爽| 日本与韩国留学比较| 亚洲av成人精品一区久久| 久久97久久精品| 久久久久久九九精品二区国产| 青春草国产在线视频| 久久国产乱子免费精品| 欧美成人午夜免费资源| 亚洲国产精品专区欧美| 真实男女啪啪啪动态图| 国产精品国产三级国产av玫瑰| 老女人水多毛片| 日韩欧美三级三区| 免费人成在线观看视频色| av一本久久久久| 精品少妇黑人巨大在线播放| 国产精品久久久久久av不卡| 中文天堂在线官网| 精品亚洲乱码少妇综合久久| 在线观看美女被高潮喷水网站| 夜夜看夜夜爽夜夜摸| 久久久久久久大尺度免费视频| 久久精品综合一区二区三区| 三级男女做爰猛烈吃奶摸视频| 建设人人有责人人尽责人人享有的 | 国产成人aa在线观看| 日本与韩国留学比较| 久久久久久久大尺度免费视频| 亚洲av成人精品一二三区| 亚洲av在线观看美女高潮| 日韩大片免费观看网站| 可以在线观看毛片的网站| 听说在线观看完整版免费高清| 欧美激情国产日韩精品一区| 99久久精品国产国产毛片| 看非洲黑人一级黄片| 中文字幕av在线有码专区| 精品久久久精品久久久| av国产免费在线观看| 人人妻人人看人人澡| 午夜精品在线福利| 日本wwww免费看| 国产精品99久久久久久久久| 国产片特级美女逼逼视频| 搡女人真爽免费视频火全软件| 国产伦在线观看视频一区| 熟女人妻精品中文字幕|