• <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 ?

    Effect of Xingnao-Jianshen granules in treating AIS patients: study protocol for a non-randomized controlled intervention trial

    2022-12-03 02:09:32ChunYuMaMiaoLiuHaoYuZhangMinYangXinNaWangDeXiZhao
    Clinical Research Communications 2022年4期

    Chun-Yu Ma ,Miao Liu ,Hao-Yu Zhang ,Min Yang ,Xin-Na Wang ,De-Xi Zhao

    1Department of Traditional Chinese Medicine,Changchun University of Chinese Medicine,Changchun 130117,China.2Department of Geriatrics,The Fifth Affiliated Hospital Sun Yat-Sen University,Zhuhai 528406,China.3Central Hospital in Panyu District,Guangzhou University of Chinese Medicine,Guangzhou 511486,China.4School of Traditional Chinese Materia Medica,Jilin Agricultural Science and Technology University,Jilin 130118,China.5Department of Neurology,Jilin Province Hospital of Chinese Medicine:First Affiliated Hospital to Changchun University of Chinese Medicine,Changchun 130021,China.

    Abstract Objective:Acute ischemic stroke (AIS) is characterized by high morbidity and high mortality.In recent years,complementary and alternative medicine has gradually been widely accepted and applied.At present,traditional Chinese medicine therapy and standard treatments are used for the treatment of AIS.Xingnao-Jianshen prescriptions (XNJS) is an effective prescription for the clinical treatment of AIS,but there is a lack of large-scale clinical evidence to confirm its clinical efficacy.Therefore,our team designed this protocol to evaluate the initial therapeutic effect of XNJS.Methods:The protocol for a non-randomized controlled trial is designed in which 72 eligible patients will be allocated to one of two groups.The control group (n=36) will receive standard treatment for AIS,the test group (n=36) will receive XNJS and standard treatment.Patients will be recruited after stroke onset and will receive the intervention continuously over 10±1 days,with a follow-up period of 90 days.The primary outcome will be the change in the NIHSS,BI,mRS scores.All outcome measures will be assessed at inception,after the intervention (10±1 days),and at the follow-up(90 days).The results will be disseminated to the public through peerreviewed journals and academic conferences.Discussion: The study will provide evidence of the preliminary effects.

    Keywords: Xingnao-Jianshen prescriptions;AIS;non-randomized controlled intervention trials;study protocol

    Introduction

    Acute stroke manifests as interruption of blood flow or bleeding in the central nervous system [1],including ischemic stroke,hemorrhagic stroke and subarachnoid hemorrhage.Ischemic stroke (cerebral infarction) is the most common type,accounting for approximately 70% of all strokes,and it is also one of the main causes of death and disability for adults over 60 years old[2,3].It occurs after thrombosis of a blood vessel in the brain or neck and is a devastating disease with complex pathophysiology [4].From 1990 to 2010,in low-and middle-income countries,the number of first-time IS patients increased by 37%,and mortality increased by 21% [5].

    A European paper on the epidemiology of stroke and trends in the 21st century predicts that the absolute number of strokes is expected to increase dramatically in the coming years due to an aging population: By 2025,1.5 million Europeans will have a stroke each year.In addition to primary outcomes,stroke patients are at increased risk of poor outcomes in the first year after the event [6].In addition,due to factors such as accelerated population aging,changes in dietary structure,and increased work pressure,there is an increasing prevalence of stroke among younger individuals.This finding coincides with an increase in the prevalence of vascular risk factors and substance abuse among young adults [7].Strategies to improve preventive measures are therefore needed.Intravenous thrombolysis with recombinant tissue plasminogen activator is currently an effective method for the treatment of AIS [8].However,due to the narrow time window for thrombolysis and the presence of bleeding complications,only a minority of patients can receive thrombolysis[9].

    Traditional Chinese medicine (TCM) is widely used in Asia as a complementary therapy to modern medicine for AIS [10,11].For example,in China,TCM that activates blood circulation is widely used in the treatment of ischemic stroke.XNJS was created by Professor Ren Jixue,a master of traditional Chinese medicine,and is an effective prescription for the treatment of stroke.Phlegm-heat and fu-organism syndrome is one of the common types of AIS.It is a combination of "internal wind","internal fire" and "phlegm dampness"and "blood stasis" syndrome elements (the smallest unit of the syndrome).XNJS can give a way out to abnormal products (including"internal wind","internal fire","phlegm dampness"and "blood stasis").The application of XNJS in the treatment of AIS conforms to the principle of TCM syndrome differentiation and treatment ent.Therefore,it can be used for the treatment of AIS,especially with"phlegm-heat and fu-organism syndrome".For other syndromes,herbs can be added or subtracted or the dosage can be adjusted.However,there is a lack of large-scale clinical evidence to confirm the clinical efficacy of XNJS.Therefore,we designed the trial to assess preliminary effects (the control group received standard treatment for AIS,and the test group received XNJS and standard treatment.)and to inform sample size calculations for future studies on the treatment of AIS.Our hypothesis is that the effect of this method is not lower than that of the standard treatment recommended by the guidelines.

    Materials and methods

    Study design

    This trial will be a non-randomized,controlled,intervention study of AIS with phlegm-heat and fu-organism syndrome.The patients will be allocated to two parallel treatment groups using a 1:1 ratio.To compare the clinical efficacy of XNJS and routine treatment (test group) and routine treatment (control group) by observing the effects of XNJS on the recovery of neurological function,ability of daily life,improvement of syndrome elements and time of first defecation in patients with AIS.We will recruit patients who have sustained AIS and present with constipation,according to predefined inclusion and exclusion criteria,between April 2021 and October 2022.

    To reduce potential bias caused by non-randomization,we held large expert seminars,a unified standard of diagnosis and treatment plan was formulated for the two participating hospitals.Strict inclusion and exclusion criteria were established.Strict training was given to the participants,and a system of review scale was developed for superior physicians to minimize the degree of bias.(See Figure 1 for the research flow chart and Table 1 for the research plan.)

    Table 1 Flow chart of Clinical trial study of Xingnao-Jianshen prescriptions for ischemic stroke (experimental phlegm-heat and fu-organism)

    Figure 1 Flow diagram of the study selection process

    Ethics and registration

    The trial was registered in the China Clinical Trial Registration Center(No.ChiCTR2100045760) and fully complies with the principles of the Helsinki Declaration and Good Clinical Practice (GCP) guidelines.The clinical trial will recruit 72 participants after the participants provide informed consent,including a 10 ± 1 day treatment period and a 90 day follow-up period.They can stop or withdraw from the trial at any time during the study.All information collected will be kept strictly confidential.Ethical approval of this trial has been granted by the Research Ethics Committee of the Affiliated Hospital of Changchun University of Traditional Chinese Medicine (No.CCZYFYLL2021zhunzi-019).All the participants signed informed consent form.

    Patients

    Diagnostic basis.The Western medicine diagnostic criteria of IS will refer to the ‘Guidelines for the diagnosis and treatment of AIS in China’ (2018 edition) [12].The Chinese medicine diagnostic criteria of IS will refer to the ‘Guiding Principles for Clinical Study of New Chinese Medicines’[13].

    The diagnostic criteria of phlegm-heat and fu-organism syndrome in TCM will refer to the ‘Guiding Principles for Clinical Study of New Chinese Medicines’.

    Inclusion criteria.Patients will be recruited for this study if they meet all of the following criteria: (1) 40 ≤age ≤80 years;(2)consistent with the Western and Chinese medicine diagnostic criteria of AIS;(3) meet the diagnostic criteria of TCM symptom differentiation(phlegm-heat and fu-organism syndrome);(4)course of disease of 1-14 days;(5) 4 ≤National Institute of Health Stroke Scale(NIHSS) score ≤15;and (6) the patient or the entrusted immediate family signed the informed consent.

    Exclusion criteria.The exclusion criteria will be as follows: (1)patients diagnosed with other brain diseases based on head CT or MRI,such as cerebral hemorrhage,brain tumor,brain trauma,transient ischemic attack (TIA);(2) comatose patients;(3) those who need or have undergone thrombolysis or endovascular treatment;(4) allergic constitution,allergic to the test drug or its related components;(5)after treatment,the blood pressure is still <90/60 mmHg or ≥220 mmHg/120 mmHg;(6) combined with severe liver and kidney damage,the levels of ALT,AST,Cr and BUN are 1.5 times higher than normal values;(7) those with other comorbidities and complications that affect drug evaluation,such as severe cardiac insufficiency,severe mental illness,depression and dementia after stroke,and cerebral hemorrhage after cerebral infarction;(8) previous ischemic stroke mRS score ≥ 2;(9) disabled patients specified by law(blindness,deafness,muteness,intellectual disability,mental disorder,etc.),physical disabilities caused by other diseases that affect the evaluation of neurological deficits;(10) those with bleeding tendency or severe bleeding within 90 days;(11) suspected or actual history of alcohol,drug abuse,or other conditions that,in the investigator's judgment,reduce the likelihood of enrollment or complicate enrollment;(12) menstruating women,pregnant and breastfeeding women,those with a positive pregnancy test or those who plan to have children recently;(13) those who are participating in other clinical trials or who have participated in other drug clinical trials for less than 90 days.

    Sample size

    Since no randomized controlled trials (RCTs) have previously investigated the topic,the study will provide effect size data for sample size calculations for subsequent large RCTs.For practical reasons,a sample size of 36 per group for a total of 72 participants will be recruited based on the hospital's outpatient and inpatient censuses throughout the study period.

    Interventions

    All the participants will receive standard treatment in accordance with the “Guidelines for diagnosis and treatment of ischemic stroke in China”.All these treatments will be well documented in the CRF.During the study period,the CRF will also keep detailed records of the patients' medications for other underlying medical conditions.However,during the entire study period,any traditional Chinese medicine with similar effects to XNJS will not be allowed.

    The treatment group is the standard treatment recommended in the guidelines plus XNJS (Jiangyin Tianjiang Pharmaceutical Co.,Ltd.,Jiangyin,China).Including Niuhuang (Bos taurus domesticus),Shexiang (Moschus berezovskii),Honghua (Carthamus tinctorius),Lingyangjiao (Saiga tatarica),Shuizhi (Hirudo nipponica),Puhuang(Typha angustifolia),Chuanxiong (Ligusticum chuanxiong,Dahuang(Rheum palmatum),Shichangpu (Acorus tatarinowii),Jianghuang(Curcuma Longa),Dannanxing (Arisaema cumBile),Difuzi (Kochia scoparia).Take 100 mL with water,orally twice a day.All medicines were provided by the prescription pharmacy and Western medicine pharmacy in the treatment area of the Affiliated Hospital of Changchun University of Traditional Chinese Medicine.

    Recruitment and baseline assessment

    Patients with AIS will be recruited from the Encephalopathy Center of the Affiliated Hospital of Changchun University of Traditional Chinese Medicine in Changchun,four wards of the Department of Neurology,China-Japan Union Hospital of Jilin University.Recruitment strategies will include publishing recruitment advertisements on social media,online publications,and at community centers.Following written informed consent,eligible patients will be asked to complete a general information form,including personal information,medical history,treatment history and allergy history,past medical history and treatment history of other diseases.A neurologist will determine the NIHSS,BI,mRS scores and TCM syndrome elements scale scores.

    Outcomes

    Primary outcome.The primary outcomes will be NIHSS,BI,and mRS scores.These scores will be measured at the end of the 10 ± 1 day treatment period with a follow-up period of 90 days and compared with baseline,and changes will be compared between groups.

    Secondary outcomes.The time of the patient's first defecation should be recorded,and the effective rate of the treatment of constipation symptoms should be determined with reference to the ‘Guiding Principles for Clinical Study of New Chinese Medicines’.

    Safety reporting

    Adverse events (AEs) were defined as any adverse or unexpected signs,symptoms,or illnesses related to the trial treatment during the study period between the two groups.Investigators should take appropriate steps to ensure patient safety and follow up all AEs until disease returns to normal or stable.Serious adverse events (SAEs) are events that may lead to permanent or severe disability or may even be life-threatening.In the event of SAEs,the principal investigator should be notified by telephone the first time(within 24 hours).The Principal Investigator reports to the Safety Monitoring Board and consults with relevant experts to develop a treatment plan.During the study,all reported or observed AEs or SAEs will be recorded in the CRF,including the nature of the event,time of onset,duration,intensity,severity (symptoms and signs),assessment of its cause,treatment options (how the event resolved or did not resolve during treatment),and outcomes.

    Follow-up

    A follow-up phone call will be conducted 90 days after leaving the group.During this time,they will receive the usual health care and secondary prevention provided to all other ischemic stroke patients.During the follow-up period,laxatives will be permitted as emergency medication.

    Data management and quality control

    To ensure the quality of this trial,the trial coordination committee and the general director will be responsible for solving related problems.To ensure data reliability,all patient personal information will be collected and stored in a separate storage room and regularly monitored by a good data management and monitoring committee(Quality Control Department of Clinical Trials,Affiliated Hospital of Changchun University of Traditional Chinese Medicine).

    Statistical analysis

    The collected data were statistically analyzed using SPSS 26.0 software.Chi-square test was used for counting data.Mean ±standard deviation () was used for measurement data,independent sample t test would be used for normal distribution,and Mann-WhitneyUtest would be used for skewness distribution.Differences were considered statistically significant whenP<0.05.

    Discussion

    Stroke is an acute cerebrovascular disease characterized by sudden coma,unconsciousness,hemiplegia,slanted tongue and speech difficulties without coma.Stroke has high morbidity,mortality and morbidity in the world,and it is the third most common cause of death in Western countries [14,15].On the one hand,the damage to the brain and body caused by stroke is multi-link,multi-path and multi-factor.Current studies have found that cerebrovascular disease can be attributed to a small proportion of single-gene genetic diseases[16].The occurrence and development of stroke may be related to the toxic effects of excitatory amino[17,18],glutamate [19] and other metabolites,activation of apoptotic genes,and inflammatory responses [20].On the other hand,stroke is a complex disease that is often accompanied by a series of neuropsychological symptoms in addition to neurological symptoms and signs[21].Therefore,stroke is not a single neurological disorder but a manifestation of an underlying systemic problem.Treatment for a single link is not enough to deal with stroke itself and the series of problems it produces.

    As a supplementary and complementary medicine,traditional Chinese medicine has attracted increasing attention and has gradually been widely accepted and applied.At present,many proprietary Chinese medicines are used in combination with conventional Western medicine for the treatment of AIS.Compound Chinese medicine has been used in China and some Asian countries for thousands of years,and research in recent years has revealed its significant advantages in the treatment of complex diseases.Studies have shown that the treatment of cerebrovascular disease by traditional Chinese medicine compounds may be related to various effects,such as anti-oxidative free radical damage,inhibiting the release of excitatory amino AISds,maintaining intracellular calcium balance,inhibiting the activation of apoptotic genes,and promoting vascular endothelial growth and nerve regeneration [22].Promoting the recovery of neurological function is the key to improving the prognosis of stroke patients.Integrative medicine therapy has become an optimized method to improve neurological function in patients with AIS.Relevant Chinese treatment guidelines note that Chinese patent medicines can play an important role in the treatment of AIS [23].A number of clinical systematic reviews have reported that Chinese patent medicine adjuvant therapy for AIS can improve clinical efficacy.For example,an RCT showed that the total effective rate of adding the Chinese patent medicine Naoxintong Capsule for AIS was higher than that of routine treatment.A study that included 58 meta-analyses showed that the clinical efficacy of Naoxintong capsule combined with conventional Western medicine in the treatment of cerebral infarction was 22% higher than that of Western medicine alone,and it could significantly reduce the neurological deficit score and hemorheological indexes of patients,making it more secure [24].Danhong injection has remarkable curative effect and is a representative traditional Chinese medicine injection for the treatment of AIS.In addition,Danhong injection and other drugs have also been approved by the China Food and Drug Administration for the treatment of AIS [25-27].

    XNJS is an effective prescription for the clinical treatment of stroke.Among them,the active ingredient of the most important drug Puhuang,Puhuang flavonoid,can improve the activity of human umbilical vein endothelial cells under hypoxia,increase the content of nitric oxide (NO) and prostaglandin (PGI2) in cells,and reduce the content of ET-1.It has a protective effect on vascular endothelial cells damaged by hypoxia.Moreover,total flavonoids of Puhuang may inhibit Akt/mTOR to activate autophagy and achieve anti-inflammatory protective effects [28,29].Ligustrazine has a variety of cardiovascular and cerebrovascular pharmacological effects,such as protecting the vascular endothelium,resisting platelets,resisting ischemia-reperfusion injury,and resisting oxidative stress.Importantly,it can pass through the blood-brain or blood-eye barrier[30].In the study of Guan D et al.,it was found that the bioactive component tetramethylpyrazine in ligustrazine can reverse the hypoxic injury of PC12 cells in vitro,which may be related to the activation of the Nrf2/GCLc/GSH pathway and the inhibition of the expression of HIF1-αNOX2/ROS [31].Rhein is the main active ingredient in Chinese herbal decoction pieces of rhubarb [32].Rhein can reduce the degree of cerebral edema caused by cerebral ischemia injury,and its mechanism may be related to its inhibition of neuroinflammation mediated by microglia and downregulation of aquaporin 4(AQP4)protein expression[33].Modern pharmacological studies have found that crocin can inhibit the transport of G protein-coupled receptor kinase 2 (GRK-2) and prevent the phosphorylation of ERK1/2,thereby reducing secondary injury after ischemia[34].

    The classic evidence-based scale results suggest that RCTs have become the gold standard available for evaluating the effects of medical interventions and are designed as unbiased experimental practices that greatly reduce the risk of systematic error [35].Of course,RCTs also have research limitations and deficiencies,especially in the field of disease research on this topic.AIS is dangerous and progresses rapidly,and complications and sequelae are also important considerations that cannot be ignored.In addition,the therapeutic effect of the combination of traditional Chinese medicine and Western medicine is being explored,so it is difficult to carry out a randomized,double-blind,multi-center clinical controlled trial in an ideal state.For example,the disadvantages mentioned in an article introducing "the advantages and limitations of randomized clinical trials of each type of stroke" are that RCTs require a lot of time and energy and increase the pressure of communication between doctors and patients [36].To carry out TCM clinical trials of stroke more effectively and make it feasible and authentic,non-randomized interventional trials can be designed.Many scholars at home and abroad also believe that it is indispensable.Non-randomized controlled trials are as important as RCTs,and in some specific cases,they can make up for the shortcomings of RCTs [37].Theoretically,RCTs have good internal validity but may have poor external validity,whereas non-randomized designs may do the opposite.Judging from the feasibility and authenticity of clinical trials,this clinical research method is gradually enriching the evidence-based basis for medical research.

    We will combine the evaluation scale of modern medicine with the evaluation standard of traditional Chinese medicine,which can comprehensively evaluate the clinical efficacy from the perspective of traditional Chinese and Western medicine,which not only reflects the advantages and characteristics of traditional Chinese medicine but also reflects the evaluation of the efficacy of Western medicine.In addition,the use of non-randomized controlled studies can better ensure the external validity,feasibility and authenticity of this trial.

    However,this study has some limitations,such as the lack of long-term effect assessment of the primary outcome measure of XNJS and the relatively short follow-up time.Due to limited time,the potential role of prescribing in reducing overall mortality and major vascular events remains uncertain.Therefore,future clinical trials should include longer follow-up.We took the patient's blood samples for further biochemical testing to discuss the possible mechanism and safety evaluation of XNJS's effectiveness in the treatment of AIS.Since the evaluation index of cerebral infarction recovery does not depend on radiation/pathology,it may be more meaningful to improve sequelae,restore neurological function,and relieve the painful symptoms of the patient.Later,randomized controlled trials with larger sample sizes will be considered.The pharmacological mechanism of XNJS components and the determination of some active compounds also need to be further studied.In addition,this pilot study also has shortcomings such as insufficient sample size,which will lead to biased results and reduce the reliability of clinical evidence.Finally,since this study is based on the standard treatment to observe the preliminary efficacy of XNJS,we are still unable to determine whether XNJS can be used as a complete replacement therapy for AIS.

    免费搜索国产男女视频| 韩国av在线不卡| 精品一区二区三区av网在线观看| 看十八女毛片水多多多| 3wmmmm亚洲av在线观看| 国内毛片毛片毛片毛片毛片| 精品无人区乱码1区二区| 日韩大尺度精品在线看网址| 99久久久亚洲精品蜜臀av| 久久这里只有精品中国| 狠狠狠狠99中文字幕| 美女 人体艺术 gogo| 欧美最黄视频在线播放免费| 国内少妇人妻偷人精品xxx网站| 高清日韩中文字幕在线| 俺也久久电影网| 欧洲精品卡2卡3卡4卡5卡区| 精品不卡国产一区二区三区| 亚洲精品色激情综合| videossex国产| 特大巨黑吊av在线直播| 婷婷精品国产亚洲av| 91av网一区二区| 精品久久久久久久久av| 熟女人妻精品中文字幕| 欧美最黄视频在线播放免费| 国产精品久久久久久亚洲av鲁大| 欧美性猛交╳xxx乱大交人| 午夜激情欧美在线| 亚洲国产日韩欧美精品在线观看| 国产午夜精品久久久久久一区二区三区 | 少妇丰满av| 国产精品日韩av在线免费观看| 一本久久中文字幕| 联通29元200g的流量卡| 国产乱人视频| 亚洲性夜色夜夜综合| 少妇人妻精品综合一区二区 | av女优亚洲男人天堂| 又黄又爽又刺激的免费视频.| 黄色日韩在线| 久久这里只有精品中国| 国产精华一区二区三区| 成人一区二区视频在线观看| 国产精品久久久久久亚洲av鲁大| 国产精品女同一区二区软件 | 嫩草影视91久久| 香蕉av资源在线| 99国产精品一区二区蜜桃av| 亚洲avbb在线观看| 国内精品一区二区在线观看| 3wmmmm亚洲av在线观看| 国产精品女同一区二区软件 | 国产av在哪里看| 麻豆国产97在线/欧美| 久久久久九九精品影院| 国内久久婷婷六月综合欲色啪| 亚洲,欧美,日韩| 成人毛片a级毛片在线播放| 国产精品一区二区三区四区久久| 最近在线观看免费完整版| 老女人水多毛片| 亚洲av二区三区四区| eeuss影院久久| 午夜亚洲福利在线播放| 如何舔出高潮| 国产乱人伦免费视频| 精品久久久久久久久亚洲 | 少妇熟女aⅴ在线视频| 日本五十路高清| 成年女人永久免费观看视频| 99在线视频只有这里精品首页| 又黄又爽又刺激的免费视频.| av福利片在线观看| 久久久久久伊人网av| 久久亚洲真实| 观看免费一级毛片| 1000部很黄的大片| 国国产精品蜜臀av免费| 色视频www国产| 亚洲,欧美,日韩| 国产精品无大码| 午夜亚洲福利在线播放| 尤物成人国产欧美一区二区三区| 成人毛片a级毛片在线播放| 琪琪午夜伦伦电影理论片6080| 国产精品美女特级片免费视频播放器| 在线国产一区二区在线| 国产av在哪里看| 制服丝袜大香蕉在线| 欧美丝袜亚洲另类 | 欧美激情在线99| 蜜桃久久精品国产亚洲av| 在线观看66精品国产| 99热只有精品国产| 51国产日韩欧美| netflix在线观看网站| 97碰自拍视频| 91久久精品国产一区二区三区| 中文字幕精品亚洲无线码一区| 看黄色毛片网站| 免费在线观看影片大全网站| 久久久久久久久久黄片| 日韩 亚洲 欧美在线| 看片在线看免费视频| 男人舔奶头视频| 亚洲内射少妇av| 久久午夜亚洲精品久久| 午夜视频国产福利| 大型黄色视频在线免费观看| 国产一区二区三区在线臀色熟女| 麻豆精品久久久久久蜜桃| 国产伦一二天堂av在线观看| 99热网站在线观看| 美女cb高潮喷水在线观看| 国产探花在线观看一区二区| 日韩人妻高清精品专区| 听说在线观看完整版免费高清| 欧美丝袜亚洲另类 | 高清毛片免费观看视频网站| 精品一区二区三区av网在线观看| 一区二区三区高清视频在线| 最近视频中文字幕2019在线8| 在线免费观看不下载黄p国产 | 久久午夜福利片| 中文字幕人妻熟人妻熟丝袜美| 夜夜看夜夜爽夜夜摸| 亚洲国产欧洲综合997久久,| 国产美女午夜福利| 免费无遮挡裸体视频| 久久精品国产清高在天天线| 非洲黑人性xxxx精品又粗又长| 国产精品99久久久久久久久| 亚洲av.av天堂| 毛片女人毛片| 日日摸夜夜添夜夜添小说| 久久久午夜欧美精品| 午夜亚洲福利在线播放| 成人美女网站在线观看视频| 大型黄色视频在线免费观看| 最近中文字幕高清免费大全6 | 亚洲国产精品sss在线观看| 岛国在线免费视频观看| 人妻丰满熟妇av一区二区三区| 欧美+亚洲+日韩+国产| 在线观看美女被高潮喷水网站| 久久精品国产亚洲av天美| 国产午夜福利久久久久久| 亚洲国产欧美人成| 国产久久久一区二区三区| 人妻夜夜爽99麻豆av| 久久久精品欧美日韩精品| 亚洲av不卡在线观看| 日韩中文字幕欧美一区二区| or卡值多少钱| 一本精品99久久精品77| 国产爱豆传媒在线观看| 欧美在线一区亚洲| 日本一本二区三区精品| 中文字幕av成人在线电影| 观看美女的网站| 亚洲第一电影网av| 高清毛片免费观看视频网站| 国产探花在线观看一区二区| 97人妻精品一区二区三区麻豆| 狠狠狠狠99中文字幕| av黄色大香蕉| 不卡一级毛片| 天美传媒精品一区二区| 人妻丰满熟妇av一区二区三区| av在线观看视频网站免费| 亚洲五月天丁香| 窝窝影院91人妻| 国产真实伦视频高清在线观看 | 色哟哟哟哟哟哟| 我要看日韩黄色一级片| 又爽又黄a免费视频| 悠悠久久av| 亚洲七黄色美女视频| 久久国产精品人妻蜜桃| 亚洲精品日韩av片在线观看| 可以在线观看的亚洲视频| 特级一级黄色大片| 在线免费观看的www视频| 人妻少妇偷人精品九色| 婷婷精品国产亚洲av| 女生性感内裤真人,穿戴方法视频| 国产精品伦人一区二区| 三级男女做爰猛烈吃奶摸视频| 99在线人妻在线中文字幕| 最新在线观看一区二区三区| 99视频精品全部免费 在线| 女生性感内裤真人,穿戴方法视频| 特大巨黑吊av在线直播| 国产精品一区二区性色av| 观看美女的网站| 又黄又爽又刺激的免费视频.| 欧美日本亚洲视频在线播放| 在线免费十八禁| 欧美日韩瑟瑟在线播放| 欧美日韩中文字幕国产精品一区二区三区| 直男gayav资源| 午夜福利高清视频| 在线观看午夜福利视频| 国产精品人妻久久久久久| 国产高清激情床上av| 国产精品美女特级片免费视频播放器| 国产精品98久久久久久宅男小说| 琪琪午夜伦伦电影理论片6080| 亚洲男人的天堂狠狠| 12—13女人毛片做爰片一| 极品教师在线免费播放| 成人欧美大片| 91麻豆精品激情在线观看国产| 中文字幕精品亚洲无线码一区| 婷婷精品国产亚洲av| 日韩强制内射视频| 精品一区二区三区av网在线观看| 黄片wwwwww| 国产人妻一区二区三区在| 日本熟妇午夜| 久久久久久国产a免费观看| 精品99又大又爽又粗少妇毛片 | 91精品国产九色| 国产熟女欧美一区二区| 校园人妻丝袜中文字幕| 亚洲av中文字字幕乱码综合| 久久精品国产清高在天天线| 精品久久久久久成人av| 深夜a级毛片| 禁无遮挡网站| 亚洲色图av天堂| 国产一区二区激情短视频| 国产单亲对白刺激| 神马国产精品三级电影在线观看| 毛片女人毛片| 国产白丝娇喘喷水9色精品| 色哟哟·www| 欧美高清性xxxxhd video| 在线观看av片永久免费下载| 91久久精品国产一区二区成人| 99热精品在线国产| 久久精品国产清高在天天线| 欧美成人免费av一区二区三区| 亚洲成人久久性| 女人十人毛片免费观看3o分钟| 日韩大尺度精品在线看网址| 久久婷婷人人爽人人干人人爱| 国内精品久久久久久久电影| 午夜福利在线观看免费完整高清在 | 大型黄色视频在线免费观看| 精品欧美国产一区二区三| 日韩,欧美,国产一区二区三区 | 美女黄网站色视频| 十八禁网站免费在线| 精品久久久噜噜| 午夜视频国产福利| 国产91精品成人一区二区三区| 97超级碰碰碰精品色视频在线观看| 九九在线视频观看精品| 99九九线精品视频在线观看视频| 日日摸夜夜添夜夜添小说| 丰满的人妻完整版| 内地一区二区视频在线| 亚洲欧美日韩无卡精品| 热99re8久久精品国产| 夜夜看夜夜爽夜夜摸| 日本爱情动作片www.在线观看 | 人妻制服诱惑在线中文字幕| 欧美一区二区国产精品久久精品| 大又大粗又爽又黄少妇毛片口| 精品国产三级普通话版| 99久国产av精品| 亚洲 国产 在线| 国产亚洲av嫩草精品影院| 黄色一级大片看看| 日日干狠狠操夜夜爽| 成人精品一区二区免费| 女生性感内裤真人,穿戴方法视频| 日韩欧美国产在线观看| 人人妻人人澡欧美一区二区| 一进一出抽搐动态| 人妻夜夜爽99麻豆av| 午夜福利在线观看吧| 欧美+日韩+精品| 国产黄a三级三级三级人| 亚洲天堂国产精品一区在线| 欧美三级亚洲精品| 日韩高清综合在线| 黄色日韩在线| 亚洲五月天丁香| 不卡视频在线观看欧美| 国产黄色小视频在线观看| 日日摸夜夜添夜夜添小说| 亚洲一级一片aⅴ在线观看| 特大巨黑吊av在线直播| 日本色播在线视频| 国产69精品久久久久777片| 精品人妻偷拍中文字幕| 久久久国产成人免费| 欧美日韩综合久久久久久 | 午夜免费男女啪啪视频观看 | 国产欧美日韩一区二区精品| 国产极品精品免费视频能看的| 少妇猛男粗大的猛烈进出视频 | 亚洲无线观看免费| 99九九线精品视频在线观看视频| 91在线观看av| 国产一区二区在线av高清观看| 国产高清三级在线| 97超视频在线观看视频| 中文字幕人妻熟人妻熟丝袜美| 老熟妇乱子伦视频在线观看| 亚洲av第一区精品v没综合| 成人精品一区二区免费| 国产精品三级大全| 国产精品电影一区二区三区| 有码 亚洲区| 亚洲不卡免费看| 欧美日韩精品成人综合77777| 亚洲人成伊人成综合网2020| 日韩欧美国产一区二区入口| 国产人妻一区二区三区在| 国产一级毛片七仙女欲春2| 日韩欧美精品免费久久| 九九在线视频观看精品| 嫁个100分男人电影在线观看| 国产精品国产高清国产av| 国产黄色小视频在线观看| 中文资源天堂在线| 国产精品自产拍在线观看55亚洲| 尾随美女入室| 我要搜黄色片| 色5月婷婷丁香| a级毛片免费高清观看在线播放| 精品久久久噜噜| 久久久久久久久久黄片| 黄色欧美视频在线观看| 国产男人的电影天堂91| 最近最新中文字幕大全电影3| 久久99热这里只有精品18| 欧美极品一区二区三区四区| 在线观看一区二区三区| 亚洲人成网站在线播| 最好的美女福利视频网| 女生性感内裤真人,穿戴方法视频| 亚洲一区高清亚洲精品| 欧美精品啪啪一区二区三区| 他把我摸到了高潮在线观看| 中亚洲国语对白在线视频| 亚州av有码| 久久久久久久精品吃奶| 麻豆一二三区av精品| 婷婷六月久久综合丁香| 精品无人区乱码1区二区| 亚洲人成网站在线播放欧美日韩| 久久婷婷人人爽人人干人人爱| 偷拍熟女少妇极品色| 免费人成在线观看视频色| 久久精品国产亚洲av香蕉五月| 性插视频无遮挡在线免费观看| 18+在线观看网站| 在线免费观看的www视频| 国产淫片久久久久久久久| 网址你懂的国产日韩在线| 国产一区二区在线av高清观看| 老女人水多毛片| 男女下面进入的视频免费午夜| 春色校园在线视频观看| 成人欧美大片| 草草在线视频免费看| bbb黄色大片| 伦理电影大哥的女人| 色哟哟·www| 亚洲av电影不卡..在线观看| 悠悠久久av| 岛国在线免费视频观看| 欧美一级a爱片免费观看看| 99国产极品粉嫩在线观看| 18禁裸乳无遮挡免费网站照片| 午夜精品一区二区三区免费看| 欧美+亚洲+日韩+国产| 淫秽高清视频在线观看| aaaaa片日本免费| 免费av观看视频| 午夜福利欧美成人| 成人性生交大片免费视频hd| 看片在线看免费视频| 亚洲精品一区av在线观看| 极品教师在线免费播放| 99热6这里只有精品| 夜夜看夜夜爽夜夜摸| 国产三级中文精品| a级毛片a级免费在线| 久久草成人影院| 国产精品1区2区在线观看.| 免费电影在线观看免费观看| 亚洲人与动物交配视频| 91狼人影院| 久久久久久久久久黄片| 国产欧美日韩一区二区精品| 欧美绝顶高潮抽搐喷水| 国产不卡一卡二| 亚洲性夜色夜夜综合| 老师上课跳d突然被开到最大视频| 亚洲电影在线观看av| 久久人人爽人人爽人人片va| 精品欧美国产一区二区三| netflix在线观看网站| 久久精品人妻少妇| 久久精品国产亚洲av香蕉五月| 嫩草影院入口| 尤物成人国产欧美一区二区三区| 国产精品亚洲一级av第二区| 免费电影在线观看免费观看| 国产淫片久久久久久久久| 两性午夜刺激爽爽歪歪视频在线观看| 深夜a级毛片| 一级毛片久久久久久久久女| 国产亚洲欧美98| 亚洲电影在线观看av| 亚洲av熟女| 国产精品野战在线观看| 中文亚洲av片在线观看爽| 日本精品一区二区三区蜜桃| 韩国av在线不卡| 国产午夜福利久久久久久| 搡老妇女老女人老熟妇| 日本一本二区三区精品| 亚洲欧美日韩无卡精品| 欧美成人一区二区免费高清观看| 欧洲精品卡2卡3卡4卡5卡区| av.在线天堂| 99在线人妻在线中文字幕| 午夜福利成人在线免费观看| 中文字幕免费在线视频6| 99国产极品粉嫩在线观看| 最新在线观看一区二区三区| 亚洲美女视频黄频| 国产在线精品亚洲第一网站| 色哟哟·www| 精品国内亚洲2022精品成人| 国内毛片毛片毛片毛片毛片| 人妻制服诱惑在线中文字幕| 桃红色精品国产亚洲av| 一区二区三区高清视频在线| 色视频www国产| 欧美日韩精品成人综合77777| 尤物成人国产欧美一区二区三区| 亚洲熟妇中文字幕五十中出| 中文资源天堂在线| 91在线精品国自产拍蜜月| 亚洲经典国产精华液单| 禁无遮挡网站| 午夜福利高清视频| 国产v大片淫在线免费观看| 一区福利在线观看| 国产色婷婷99| 乱人视频在线观看| 亚洲精品一卡2卡三卡4卡5卡| 日韩欧美精品免费久久| 成人av一区二区三区在线看| 久久久久性生活片| 精华霜和精华液先用哪个| 精品久久久久久久久久久久久| 亚洲一级一片aⅴ在线观看| 99热精品在线国产| 国产黄色小视频在线观看| 久久久久国产精品人妻aⅴ院| 久久久久九九精品影院| 免费看美女性在线毛片视频| 老熟妇乱子伦视频在线观看| 一本久久中文字幕| 日韩一本色道免费dvd| 美女高潮的动态| 成人三级黄色视频| 直男gayav资源| 国产精品一区二区三区四区久久| 看片在线看免费视频| 日本爱情动作片www.在线观看 | 婷婷精品国产亚洲av| 久久久久九九精品影院| 久久精品人妻少妇| 91精品国产九色| 久久亚洲精品不卡| 国内精品久久久久精免费| 欧美一区二区国产精品久久精品| 又黄又爽又免费观看的视频| 免费观看的影片在线观看| 男女啪啪激烈高潮av片| 人妻久久中文字幕网| 九九久久精品国产亚洲av麻豆| 亚洲欧美日韩高清在线视频| 久久久久久大精品| 成人高潮视频无遮挡免费网站| 在线观看午夜福利视频| 身体一侧抽搐| 啦啦啦啦在线视频资源| eeuss影院久久| 中文字幕人妻熟人妻熟丝袜美| 亚洲av日韩精品久久久久久密| 国产精品亚洲美女久久久| 日本 欧美在线| 国产极品精品免费视频能看的| 午夜激情福利司机影院| www日本黄色视频网| 精品一区二区三区av网在线观看| 亚洲精品国产成人久久av| 免费无遮挡裸体视频| 99久久精品国产国产毛片| 亚洲av中文av极速乱 | 亚洲av美国av| 午夜免费男女啪啪视频观看 | 亚洲欧美精品综合久久99| 国产精品,欧美在线| 看片在线看免费视频| 一区二区三区四区激情视频 | 欧美最新免费一区二区三区| av女优亚洲男人天堂| 久久国产乱子免费精品| 十八禁国产超污无遮挡网站| 黄色视频,在线免费观看| 精品不卡国产一区二区三区| 18禁黄网站禁片午夜丰满| 3wmmmm亚洲av在线观看| 窝窝影院91人妻| 91在线精品国自产拍蜜月| 国内精品美女久久久久久| 少妇人妻精品综合一区二区 | 麻豆成人av在线观看| 一进一出抽搐动态| 久久亚洲精品不卡| 大又大粗又爽又黄少妇毛片口| 嫩草影院新地址| 中文亚洲av片在线观看爽| 亚洲成a人片在线一区二区| 久久亚洲精品不卡| 中文字幕av在线有码专区| 国产伦人伦偷精品视频| 欧美日韩综合久久久久久 | 国产女主播在线喷水免费视频网站 | 麻豆av噜噜一区二区三区| 日本 av在线| 窝窝影院91人妻| 少妇猛男粗大的猛烈进出视频 | 亚洲中文字幕一区二区三区有码在线看| 国产视频内射| 色综合亚洲欧美另类图片| 亚洲成av人片在线播放无| 一区二区三区免费毛片| 午夜福利在线在线| 观看免费一级毛片| 免费大片18禁| 午夜福利在线观看免费完整高清在 | 久久久久久大精品| .国产精品久久| 麻豆成人午夜福利视频| av在线观看视频网站免费| 亚洲avbb在线观看| 亚洲精品国产成人久久av| 亚洲精品一卡2卡三卡4卡5卡| 能在线免费观看的黄片| 少妇人妻一区二区三区视频| 亚洲欧美日韩高清在线视频| 丝袜美腿在线中文| 日本免费一区二区三区高清不卡| 亚洲久久久久久中文字幕| 少妇的逼好多水| 国产乱人伦免费视频| 人妻少妇偷人精品九色| 久久久成人免费电影| 小蜜桃在线观看免费完整版高清| 18禁裸乳无遮挡免费网站照片| 亚洲av中文av极速乱 | 黄色视频,在线免费观看| 国产熟女欧美一区二区| xxxwww97欧美| 亚洲熟妇中文字幕五十中出| 老司机深夜福利视频在线观看| 99精品久久久久人妻精品| 日本 av在线| 久久久久久久久中文| 日本一二三区视频观看| 最好的美女福利视频网| 人妻丰满熟妇av一区二区三区| 午夜亚洲福利在线播放| 日韩欧美 国产精品| 色av中文字幕| 亚洲最大成人av| 欧美日韩综合久久久久久 | 国产乱人视频| 色av中文字幕| or卡值多少钱| 在线观看免费视频日本深夜| 一级av片app| 久久久久久久久久黄片| 国产精品一区二区三区四区免费观看 | 最新在线观看一区二区三区| 精品午夜福利在线看| 看十八女毛片水多多多| 国产亚洲欧美98| 国产精品一区二区三区四区久久| 亚洲av五月六月丁香网| 在线免费观看不下载黄p国产 | 亚洲午夜理论影院| 日本一二三区视频观看| 久久精品久久久久久噜噜老黄 | 一区二区三区免费毛片| 最好的美女福利视频网| 欧美一级a爱片免费观看看| 亚洲精品影视一区二区三区av| 亚洲av中文av极速乱 | 欧美日韩乱码在线| 国产高清视频在线播放一区| 亚洲天堂国产精品一区在线|