• <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 ?

    Transjugular intrahepatic portosystemic shunt for pyrrolizidine alkaloid-related hepatic sinusoidal obstruction syndrome

    2020-07-18 02:49:12ChunZeZhouRuiFengWangWeiFuLvYuQinFuDeLeiChengYiJiangZhuChangLongHouXianJunYe
    World Journal of Gastroenterology 2020年24期

    Chun-Ze Zhou, Rui-Feng Wang, Wei-Fu Lv, Yu-Qin Fu, De-Lei Cheng, Yi-Jiang Zhu, Chang-Long Hou,Xian-Jun Ye

    Abstract

    Key words: Transjugular intrahepatic portosystemic shunt; Sinusoidal obstruction syndrome; Pyrrolizidine alkaloids; Survival; Ascites

    INTRODUCTION

    Hepatic sinusoidal obstruction syndrome (HSOS) is a hepatic vascular disease in which edema, necrosis, and shedding of endothelial cells and formation of microthrombi occur in the hepatic sinusoids, hepatic venules, and interlobular vein,leading to intrahepatic congestion, liver dysfunction and portal hypertension[1,2]. In China, the predominant cause of HSOS is the administration of plants containing pyrrolizidine alkaloids (PAs), particularlyGynura segetum[3-5].

    The clinical manifestations of hematopoietic stem cell transplantation-induced HSOS (HSCT-HSOS) and PA-induced HSOS (PA-HSOS) differ in several aspects.First, HSCT-HSOS typically presents with hepatomegaly, hepatalgia, ascites, and jaundice[6]. By contrast, PA-HSOS mainly manifests as abdominal distension and ascites[7], with only around half of all patients exhibiting hepatomegaly or jaundice and few having hepatalgia[8]. Furthermore, the serum levels of alanine transaminase,aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase and total bilirubin are not severely elevated in most patients with PA-HSOS. Second, the speed of onset differs, with HSCT-HSOS usually occurring within 21 d after bone marrow transplantation[9]but PA-HSOS developing after a variable latent period that is generally around 30 d after drug ingestion but can be as long as several years. Third,the proportion of patients with severe disease is higher for HSCT-HSOS than for PAHSOS[9-12]. Fourth, HSCT-HSOS is associated with higher mortality than PA-HSOS.The mortality rate can exceed 80% in patients with severe HSCT-HSOS[13], with most dying from multiple organ dysfunction syndrome and pyemia. However, the mortality rate is generally around 40% in patients with PA-HSOS[4,7], with most deaths due to progressive liver failure and infection.

    Currently, there are no standardized management protocols for HSOS, and the available therapeutic options are limited. Symptomatic and supportive treatments for HSOS include strategies for liver protection, diuresis, and improvement of the microcirculation[14]. Glucocorticoids and anticoagulant therapy may be effective in some patients, but this remains controversial[7,15], while defibrotide has shown promise[16,17]. During the past two decades, attempts have been made to use transjugular intrahepatic portosystemic shunting (TIPS) for the management of HSCT-HSOS[18,19]. However, TIPS is not a recommended treatment in current guidelines because the overall efficacy is not satisfactory and the postoperative survival rate is only about 20%[20-22], but those European guidelines are based mostly on HSCT-HSOS, which is more common in Europe, while PA-HSOS is more common in China and there might be some differences between the two conditions.Postoperative death in these patients is predominantly associated with multiple organ failure, sepsis and hemorrhage largely caused by underlying hematologic disease.However, patients with PA-HSOS generally have no major underlying hematologic disease, less severe disease, and a slower rate of progression than those with HSCTHSOS.

    The aim of this retrospective analysis was to evaluate whether TIPS might have clinical benefit in the management of PA-HSOS.

    MATERIALS AND METHODS

    Study design and participants

    This was a retrospective analysis of patients with PA-HSOS who were admitted to the Department of Interventional Radiology, Gastroenterology, and Infectious Diseases of the First Affiliated Hospital of USTC (Hefei, Anhui Province, China) between June 2015 and January 2019. The inclusion criteria were: (1) Diagnosis of PA-HSOS[23]; (2)Age 18-80 years; (3) < 60 d since symptom onset; and (4) Failure of conservative therapy (including medications for liver protection, diuresis, and anticoagulation)given for at least 2 wk. The exclusion criteria were: (1) Multiple organ failure at admission; (2) Other liver diseases; and (3) Incomplete clinical and follow-up data at the required time points (such as the results of liver and renal function tests and radiological examinations). The patients included in the final analysis were assigned to a TIPS group and conservative treatment group according to the treatment method.The study was approved by the Medical Research Ethics Committee of the First Affiliated Hospital of USTC. The study was exempted from informed consent because it was retrospective and anonymized.

    Initial treatment during the first 2 wk

    After admission, all patients received reduced glutathione (1.8 ivgtt qd) and ademetionine (1.0 ivgtt qd) for liver protection and treatment of cholestasis, low molecular weight heparin (LMWH 4000-5000 U q12h ih) for anticoagulation and diuretic drugs (20-120 mg/d furosemide and 40-240 mg/d spironolactone). The initial treatment was considered effective if there was a decrease in ascitic fluid, improved liver function and discontinuation of diuretic drugs after 2 wk; the initial therapy was considered ineffective if there was no improvement or even progression of abdominal distension, ascites and/or liver dysfunction or if diuretics were still needed to maintain treatment after 2 wk. All patients included in this study experienced failure of initial therapy.

    Subsequent treatment for patients in the conservative treatment group

    Although TIPS was recommended after clinical assessment for all patients who failed the initial 2 wk of therapy, some patients refused TIPS given the controversy regarding the long-term efficacy of this technique in the treatment of HSOS. The patients who declined TIPS (conservative treatment group) were given symptomatic and supportive treatments, including reduced glutathione (1.8 ivgtt qd), ademetionine(1.0 ivgtt qd), LMWH (4000-5000 U ih Q12h) and diuretic drugs (20-120 mg/d furosemide and 40-240 mg/d spironolactone). The use of antibacterial drugs was determined according to the presence or absence of infection.

    Typical TIPS

    Patients in the TIPS group underwent TIPS under local anesthesia. After successful puncture of the internal jugular vein, the guidewire was maneuvered into the right hepatic vein, and a RUPS-100 puncture needle was introduced. Then a balloon catheter (generally 6-7 mm in diameter) was delivered along the guidewire to dilate the puncture channel, and a double stent was implanted for shunting (8 mm in diameter; a bare stent measuring 8-10 cm in length and a covered stent measuring 6-8 cm in length). The distal end of the covered stent was at the junction of the portal vein and liver parenchyma, and the proximal end reached the entrance of the inferior vena cava of the hepatic vein. The pressures of the portal vein, splenic vein, and inferior vena cava were measured separately before and after placement of the shunt. The target portal pressure gradient after shunting was ≤ 12 mmHg. The main differences between the present technique and conventional TIPS were a smaller balloon diameter and no requirement for combined embolization of the esophageal and gastric varicose vessels. Anticoagulation with warfarin or rivaroxaban was administered for at least 3 mo postoperatively.

    Follow-up and data collection

    Baseline clinical characteristics and follow-up data were extracted from the medical records. Data were recorded at 7 d, 14 d, 30 d, 90 d, 6 mo, 1 year, and 2 years after surgery (TIPS group) or at the same time points after completion of the initial 2-wk conservative therapy (conservative treatment group).

    Statistical analysis

    Statistical analyses were performed using SPSS 17.0 (SPPS Inc., Chicago, IL, United States). All measurement data were tested for normality using the Kolmogorov-Smirnov method. Data conforming to a normal distribution are presented as the mean± SD and were compared between groups using the independent-samplest-test or one-way analysis of variance (ANOVA) and the least significant difference post hoc test. Data not conforming to a normal distribution are presented as the median(interquartile range) and were compared between groups using the Kruskal-Wallis test and Mann-WhitneyUtest. Count data were compared using the chi-squared test,and ranked data were compared using the rank-sum test. Survival time was compared between the two groups using Kaplan-Meier survival analysis and the logrank test.P< 0.05 was considered significant.

    RESULTS

    Baseline clinical characteristics of the patients in the two groups

    A total of 54 patients with PA-HSOS were included, with 37 in the TIPS group and 17 in the conservative treatment group. The baseline clinical characteristics of the patients in the two groups are shown in Table 1. Portal pressure gradient in the TIPS group was 29 (18-39) mmHg before shunting and reduced to 7 (2-17) mmHg after shunting.

    Survival

    The follow-up period was 18 (0-52) mo. A total of 9 patients died by the end of followup, including 2 in the TIPS group and 7 in the conservative treatment group. The 3-, 6-, 12- and 24-month survival rates were 94.6%, 94.6%, 94.6% and 94.6%, respectively, in the TIPS group and 70.6%, 57.8%, 57.8% and 57.8%, respectively, in the conservative treatment group. Kaplan-Meier survival analysis (Figure 1) revealed that patients in the TIPS group had a significantly longer survival time than those in the conservative treatment group (P= 0.001, log-rank test).

    Liver function

    The differences in liver function at the same time point between the two groups were compared. There was no statistically significant difference in changes in liver function between the two groups at each time point, and the box plot was shown in Supplementary Figure 1. The results showed that there were significant differences (allP<0.05) in total bilirubin, direct bilirubin, alanine transaminase, and aspartate transaminase before and after treatment in the TIPS group, but there were no significant changes in these indicators in the conservative treatment group, as shown in Table 2.

    Depth of ascites

    The maximum depth of ascitic fluid in the TIPS group was significantly smaller at all post-treatment time points than before treatment (P< 0.001; Table 3,Supplementary Figure 2). Indeed, the majority of patients in the TIPS group showed complete resolution of ascites by 2 wk after treatment, and the effect was maintained at 1 month and 2 mo after treatment (Table 3, Supplementary Figure 2). By contrast,there were no changes in maximal ascites depth in the conservative treatment group(Table 3, Supplementary Figure 2). Furthermore, the maximum depth of ascitic fluid was significantly smaller in the TIPS group than in the conservative treatment groupat all post-treatment time points (allP< 0.05). Ascites drainage was only considered if the patient has obvious symptoms of abdominal distension. In the TIPS group, after the operation, the ascites subsided, and no patients were treated with ascites drainage.In the conservative treatment group, even if ascites drainage were performed, it is only for symptom relief without managing the cause of ascites.

    Table 1 Baseline clinical characteristics of the patients in the two groups

    Imaging

    Preoperative imaging in both groups suggested a diffuse enlargement of the liver, and plain scans showed an uneven decrease in the density of the liver parenchyma and a large amount of ascites. Enhanced computed tomography scanning demonstrated that the liver parenchyma exhibited characteristic confluent patchy enhancement during the venous and equilibrium phases as well as a high degree of enhancement around the hepatic vein with the characteristic "clover sign"[24]; the lumen of the hepatic vein was stenosed or unclear, and the hepatic segment of the inferior vena cava was compressed and thinned (Figure 2). Imaging investigations performed after TIPS revealed a smaller liver volume than that before surgery, a reduction in ascites, and the disappearance of signs of uneven enhancement (Figure 2). In addition, atrophy of the liver lobe was present on the shunt side, and compensatory enlargement of the liver was noted on the non-shunt side.

    Figure 1 Kaplan-Meier survival curves for patients in the transjugular intrahepatic portosystemic shunting and conservative treatment groups. Survival was significantly longer in the transjugular intrahepatic portosystemic shunting group than in the conservative treatment group (P < 0.001, log-rank test). TIPS: Transjugular intrahepatic portosystemic shunting.

    Pathological investigations

    Eight patients in the TIPS group underwent percutaneous transhepatic biopsy (n= 5)or transjugular liver biopsy (n= 3) before surgery. Of these eight patients, 6 underwent biopsy again at 1 month after surgery, five underwent repeat biopsy at 6 months after surgery, and two underwent biopsy at 2 years after surgery.Hematoxylin/eosin-stained sections taken before surgery (Supplementary Figure 3)demonstrated hepatocyte swelling with focal degeneration and necrosis, localized abnormalities in the arrangement of hepatic cells, mild vacuolar degeneration, hepatic sinusoidal dilatation, congestion, focal hemorrhage, and a prominent central vein.Scattered and small focal lymphatic infiltration was present in the portal area, and mild proliferation of the small bile duct was seen. Liver congestion and hepatocyte swelling notably improved with time after surgery (Supplementary Figure 3).

    Comparison of treatment outcomes between groups

    Two patients in the conservative treatment group received remedial TIPS 2 wk and 3 wk after ineffective conservative treatment. Table 4 compares the treatment outcomes between the two groups. The TIPS group had a significantly lower incidence of spontaneous peritonitis (P< 0.001), pyemia (P= 0.014), liver failure (P= 0.013),multiple organ failure (P= 0.033) and death (P= 0.001). Two patients in the TIPS group died, and none of them had any complications like iatrogenic hemorrhage or hepatic encephalopathy. One patient with preoperative bilirubin of 380 μmol/L died of liver failure 1 wk after surgery. Another patient with bilirubin at 84 μmol/L before surgery developed a severe pulmonary infection on the third day after surgery and died of respiratory failure.

    DISCUSSION

    Our data provide evidence that TIPS may result in better outcomes than conventional symptomatic therapies in patients with PA-HSOS. However, prospective randomized controlled trials will be needed to verify our findings.

    In this study, patients with PA-HSOS who were treated conservatively had a 1-year and 2-year mortality rate of 42.2%, which is similar to the value of approximately 40%reported in the literature for patients receiving conventional symptomatic therapy[7].By contrast, patients in the TIPS group had a significantly higher survival rate and a significantly longer survival time than those in the conservative treatment group. The preoperative baseline characteristics of the two groups were similar, and theconservative group at baseline did not show more severe conditions. In addition,most of the patients in the conservative group died by 1-6 mo after the conservative treatment, and the main causes of death were infection, liver failure, and multiple organ failure. We consider that this was due to the aggravation of the disease rather than the severity of the underlying disease. Limited evidence is available regarding the use of TIPS in the treatment of HSCT-HSOS, and it might not be appropriate to compare the mortality of PA-HSOS to that of HSCT-HSOS. Nevertheless, a small series of case reports, which mainly included patients with severe disease, described a 1-mo mortality rate of 33.3%-83.3% and a 6-mo mortality rate of 90%-100% after TIPS[18,25,26]. The clinical cure rate reached 64.3%-95.2% in patients with PA-HSOS[7,27].Although two patients in the present study died within 2 wk after surgery, the remaining patients showed clinical improvement and survived for at least 2 years.Therefore, we believe that patients with PA-HSOS can benefit from decompression of the portal vein. However, it should be noted that the timing of surgery is critical.Careful monitoring of ascites and jaundice should be performed for patients during the conservative treatment stage, and a gradual worsening of ascites and jaundice should prompt timely intervention with TIPS to avoid progression to severe SOS since severe disease is associated with a significant increase in the risk of death (one patient with severe SOS in the TIPS group died of acute liver failure 1 d after surgery). Two of 37 patients in the TIPS group died within 2 wk after surgery (due to liver failure and pyemia, respectively), but all the other patients achieved long-term survival (i.e., at least 2 years). By contrast, 7 of 17 patients in the conservative treatment group died within 6 months after initiation of therapy, and the main causes of death were pyemia and chronic liver failure. Therefore, it is clear that TIPS is beneficial in terms of patient survival. Nevertheless, attention should be given to reducing the risks during the 2-wk postoperative period to further improve patient survival after TIPS.

    Table 2 Results of liver function tests for patients in the two groups

    Figure 2 Representative enhanced computed tomography images from a 76-year-old male patient in the transjugular intrahepatic portosystemic shunting group. A: Enhanced computed tomography (CT) findings(delayed phase) before transjugular intrahepatic portosystemic shunting (TIPS). At the level of the opening of the hepatic vein, the liver parenchyma showed patchy confluent enhancement as well as a high degree of enhancement around the hepatic vein, resulting in a characteristic "clover sign". The lumen of the hepatic vein showed stenosis or was unclear, and the hepatic segment of the inferior vena cava was compressed and thinned; B: Enhanced CT findings (delayed phase) before TIPS. At the level of the left branch of the portal vein, the liver parenchyma exhibited patchy confluent enhancement, and the left lateral lobe and the caudate lobe of the liver were slightly involved. Lowdensity edema was present around the portal vein, and there was a large amount of perihepatic effusion; C:Enhanced CT findings (delayed phase, at the level of the opening of the hepatic vein) for the same patient 2 years after TIPS. The ascites had subsided, and the signs of uneven enhancement had disappeared; D: Enhanced CT findings (delayed phase, at the level of the portal vein left branch) for the same patient 2 years after TIPS. Atrophy of the liver was present on the shunt side (i.e., right lobe), and compensatory enlargement of the liver was noted on the non-shunt side (i.e., left lobe).

    The effect of TIPS on liver function in patients with PA-HSOS remains unclear.According to previous experience, TIPS can exacerbate liver dysfunction in patients with cirrhotic portal hypertension[28,29]. Therefore, many clinicians are concerned that shunting will further damage the hepatic function of patients with PA-HSOS.However, the results of this study suggest that there was a short-term exacerbation of liver dysfunction at 7-14 d after TIPS, followed by a gradual improvement. Indeed,liver function was better at 1 month after surgery than before TIPS, although the bilirubin level did not decrease to within the normal range. The reasons for these biphasic alterations in liver function remain unclear, but there are several possibilities.During the initial stage (7-14 d after surgery), portal vein blood flow would have been rapidly reduced after shunting. Given that the portal vein would have been the main nutrient vessel of the liver, short-term compensation by the hepatic artery may not have been sufficient to prevent a reduction in blood supply that worsened liver function after TIPS. The trauma of surgery may also have impacted negatively on hepatic function in the short term. During the next stage, three mechanisms may have contributed to a gradual improvement in liver function. First, patients with PA-HSOS have hepatic veno-occlusive disease and hepatic sinusoidal obstruction that lead to obstruction of hepatic arterial flow and reversal of portal vein flow, and this results in hypoxia and dysfunction of hepatocytes. The reduction of hepatic sinusoidal resistance after TIPS would improve hepatic arterial flow and perfusion (which has been demonstrated by ultrasonography) and thereby relieve hepatocyte hypoxia.Second, portal hypertension damages the intestinal mucosal barrier, leading to endotoxemia and aggravation of liver damage[30,31]. The TIPS-induced decrease in portal hypertension would help to restore the normal intestinal microecology, reduce endotoxin levels in the portal vein, and protect liver function. Third, TIPS increases glomerular filtration rate[32]and the clearance of metabolic products; this would reduce the damaging effects of toxic substances on hepatic cells, thus promoting recovery of liver function.

    The changes in liver pathology observed after TIPS were consistent with those detected by imaging studies. Preoperative pathological characteristics included remarkable dilatation and congestion of hepatic sinusoids with hepatic acinar zone IIIpredominating, various degrees of hepatocyte swelling and focal hemorrhage,localized disordering of hepatic cell arrangement, focal degeneration and necrosis with a prominent central vein, scattered and small focal lymphatic infiltration of the portal area, and proliferation of the small bile ducts[3,21]. After TIPS, there were improvements in hepatic swelling and congestion over time. However, although TIPS reduced the extent of the liver damage, it did not completely reverse it. In our study,biopsy after 2 years of follow-up suggested that the histopathological structure of the liver had not completely returned to normal, and the imaging findings concurred with the pathology results. Although the characteristic signs of SOS, such as hepatomegaly, perfusion disorder, and uneven enhancement, disappeared after shunting[24], manifestations similar to those after portal vein embolization appeared over time, including a reduction in liver volume on the shunt side and compensatory liver enlargement on the non-shunt side.

    Table 3 Results of ascites depth for patients in the two groups

    This study may have some limitations. First, the study may have been prone to selection bias and information bias. Second, the sample size is small, so the generalizability of the findings is not known. Third, since the methods of takingGynura segetumvaried between patients, the effects of dosage on prognosis could not be accurately evaluated. Fourth, in this study, conservative treatment was undertaken in patients who had failed conservative treatment for 2 wk or who had refused TIPS treatment for ascites and jaundice during treatment. Since the patients with effective conservative treatment were not included in this study, the sample size of the conservative treatment group was small, and there was indeed a bias. Nevertheless,the preoperative baseline level of the two groups was basically the same, which reduced the bias to some extent. Finally, although this study attempted to conduct a complete follow-up, the reexamination times were not completely consistent for all patients, and this may have influenced the results.

    In conclusion, this study suggests that TIPS may have advantages over conventional symptomatic therapy in the treatment of PA-HSOS, including better resolution of ascites and longer survival time. Large-scale, multicenter, randomized controlled trials are needed to confirm the findings.

    Table 4 Comparison of treatment outcomes between the two groups during follow up

    ARTICLE HIGHLIGHTS

    久久精品国产综合久久久| 亚洲 国产 在线| 18禁黄网站禁片午夜丰满| 国产真人三级小视频在线观看| 欧美性长视频在线观看| xxxwww97欧美| 国产一区二区激情短视频| 999久久久国产精品视频| 欧美乱色亚洲激情| 一进一出抽搐动态| 日日干狠狠操夜夜爽| 午夜福利欧美成人| 亚洲欧美日韩东京热| 一卡2卡三卡四卡精品乱码亚洲| av超薄肉色丝袜交足视频| 宅男免费午夜| 午夜福利在线在线| 成人一区二区视频在线观看| 亚洲五月婷婷丁香| 国产亚洲欧美在线一区二区| 亚洲真实伦在线观看| 在线观看舔阴道视频| 国产成人aa在线观看| 亚洲av日韩精品久久久久久密| 欧美+亚洲+日韩+国产| 看黄色毛片网站| 久久久久性生活片| 欧美日韩乱码在线| 十八禁网站免费在线| 免费看a级黄色片| 欧美成人午夜精品| 成人18禁高潮啪啪吃奶动态图| 国产精品av久久久久免费| 黄色女人牲交| 中文亚洲av片在线观看爽| 精品高清国产在线一区| 欧美极品一区二区三区四区| 最近最新免费中文字幕在线| 精品国产美女av久久久久小说| 久久精品91蜜桃| 成人一区二区视频在线观看| 成人av在线播放网站| 色综合站精品国产| 国产真人三级小视频在线观看| 一边摸一边做爽爽视频免费| 在线播放国产精品三级| 欧美人与性动交α欧美精品济南到| 在线免费观看的www视频| 婷婷精品国产亚洲av| 女人爽到高潮嗷嗷叫在线视频| 欧美日韩一级在线毛片| 极品教师在线免费播放| 国产一区二区在线观看日韩 | 免费在线观看成人毛片| 久久中文字幕人妻熟女| 国产亚洲精品第一综合不卡| 国产伦一二天堂av在线观看| 可以免费在线观看a视频的电影网站| 69av精品久久久久久| 免费在线观看完整版高清| 黄色 视频免费看| 国产精品亚洲av一区麻豆| 亚洲一码二码三码区别大吗| 国产精品免费一区二区三区在线| 老熟妇仑乱视频hdxx| 国产伦在线观看视频一区| 美女扒开内裤让男人捅视频| 午夜免费激情av| 亚洲无线在线观看| 亚洲国产看品久久| 久久香蕉精品热| 成人欧美大片| 色尼玛亚洲综合影院| 久久性视频一级片| 中文字幕熟女人妻在线| 色综合亚洲欧美另类图片| 久久婷婷成人综合色麻豆| 国产伦在线观看视频一区| 精品久久久久久成人av| 国产激情久久老熟女| 99久久精品国产亚洲精品| 中国美女看黄片| 男人舔女人下体高潮全视频| 手机成人av网站| 黄色a级毛片大全视频| 国产精品美女特级片免费视频播放器 | 久久婷婷人人爽人人干人人爱| 国产精品亚洲一级av第二区| 国产av麻豆久久久久久久| 国产成人欧美在线观看| 成熟少妇高潮喷水视频| 一个人免费在线观看电影 | 亚洲成av人片免费观看| 久久精品成人免费网站| 免费电影在线观看免费观看| 精品人妻1区二区| 久久久久久久久中文| 午夜精品一区二区三区免费看| 黄色丝袜av网址大全| 狂野欧美激情性xxxx| 日本一区二区免费在线视频| 一个人观看的视频www高清免费观看 | 日韩成人在线观看一区二区三区| av免费在线观看网站| 真人做人爱边吃奶动态| 成人国语在线视频| 午夜福利视频1000在线观看| 欧美日韩中文字幕国产精品一区二区三区| 国产精品久久久av美女十八| 99热这里只有精品一区 | 麻豆av在线久日| 18禁黄网站禁片免费观看直播| 午夜激情av网站| 亚洲av中文字字幕乱码综合| 国产久久久一区二区三区| 在线看三级毛片| 亚洲人与动物交配视频| 日韩av在线大香蕉| 国产蜜桃级精品一区二区三区| 亚洲一区二区三区色噜噜| 亚洲国产欧美网| 高清在线国产一区| 欧美成狂野欧美在线观看| 久久久久久久精品吃奶| 亚洲18禁久久av| 国产av在哪里看| 国产三级在线视频| 亚洲欧美精品综合一区二区三区| 国产亚洲精品av在线| 久久热在线av| 老司机福利观看| av片东京热男人的天堂| 亚洲国产精品成人综合色| 悠悠久久av| 日韩欧美在线乱码| 91老司机精品| 午夜久久久久精精品| 久久久久国产一级毛片高清牌| 欧美日韩一级在线毛片| 一级片免费观看大全| 欧美zozozo另类| 色精品久久人妻99蜜桃| 国产精品 国内视频| 国产伦人伦偷精品视频| 成在线人永久免费视频| 欧美黑人欧美精品刺激| 午夜福利欧美成人| av天堂在线播放| 精品国产超薄肉色丝袜足j| 老司机深夜福利视频在线观看| 免费在线观看日本一区| 91麻豆av在线| 精品无人区乱码1区二区| 又大又爽又粗| 欧美色视频一区免费| 这个男人来自地球电影免费观看| 视频区欧美日本亚洲| 1024香蕉在线观看| 亚洲自拍偷在线| 老汉色∧v一级毛片| 亚洲午夜理论影院| 脱女人内裤的视频| 正在播放国产对白刺激| 亚洲第一欧美日韩一区二区三区| 狂野欧美白嫩少妇大欣赏| 俺也久久电影网| 人成视频在线观看免费观看| 欧美性猛交黑人性爽| 宅男免费午夜| 午夜a级毛片| 亚洲专区中文字幕在线| 99精品在免费线老司机午夜| 久久久久精品国产欧美久久久| 中出人妻视频一区二区| 国产亚洲欧美98| 久99久视频精品免费| 俺也久久电影网| 久久精品91无色码中文字幕| 老鸭窝网址在线观看| 久久精品成人免费网站| 久久精品国产亚洲av高清一级| 欧美黄色片欧美黄色片| 男人舔奶头视频| 999精品在线视频| 熟女电影av网| 国产乱人伦免费视频| 老熟妇乱子伦视频在线观看| 成人精品一区二区免费| 国产av麻豆久久久久久久| 精品国产乱子伦一区二区三区| 正在播放国产对白刺激| 日韩欧美在线二视频| 桃色一区二区三区在线观看| 成人av在线播放网站| 两性夫妻黄色片| 久久精品91无色码中文字幕| 日韩欧美免费精品| 国产三级黄色录像| 午夜福利欧美成人| 久久国产乱子伦精品免费另类| 日韩欧美 国产精品| 在线观看舔阴道视频| 成人欧美大片| 高潮久久久久久久久久久不卡| 亚洲欧洲精品一区二区精品久久久| 精品日产1卡2卡| 国产区一区二久久| 国产高清videossex| 国产1区2区3区精品| 亚洲成av人片在线播放无| 岛国在线观看网站| 手机成人av网站| 国产精品1区2区在线观看.| 国产精品99久久99久久久不卡| 亚洲一区中文字幕在线| 日韩国内少妇激情av| 国产99白浆流出| 成人av一区二区三区在线看| 亚洲美女黄片视频| 午夜免费成人在线视频| 五月伊人婷婷丁香| av国产免费在线观看| 久久精品aⅴ一区二区三区四区| 国产一区二区在线观看日韩 | 日韩精品中文字幕看吧| 两个人看的免费小视频| 日本黄色视频三级网站网址| 两个人的视频大全免费| 三级国产精品欧美在线观看 | 久久久国产成人精品二区| 国产69精品久久久久777片 | 亚洲人成77777在线视频| 最近视频中文字幕2019在线8| 亚洲av日韩精品久久久久久密| 亚洲av成人av| 国内毛片毛片毛片毛片毛片| 欧美zozozo另类| 最近最新免费中文字幕在线| 中国美女看黄片| 麻豆成人午夜福利视频| 成人国语在线视频| 成人欧美大片| 欧美精品啪啪一区二区三区| 999精品在线视频| 黄色女人牲交| 国产精品自产拍在线观看55亚洲| 两性夫妻黄色片| 黑人欧美特级aaaaaa片| 曰老女人黄片| 97碰自拍视频| 亚洲国产精品999在线| 精品国产美女av久久久久小说| 男女床上黄色一级片免费看| 国产精品自产拍在线观看55亚洲| 国模一区二区三区四区视频 | 在线观看一区二区三区| 男女床上黄色一级片免费看| 国产黄色小视频在线观看| 日韩高清综合在线| 18禁黄网站禁片午夜丰满| www.精华液| 亚洲av成人精品一区久久| 色综合婷婷激情| 日韩精品中文字幕看吧| 亚洲国产日韩欧美精品在线观看 | 老司机靠b影院| 亚洲专区中文字幕在线| 巨乳人妻的诱惑在线观看| 国产免费av片在线观看野外av| av国产免费在线观看| 国产三级在线视频| 两个人免费观看高清视频| 久久中文看片网| 国产一区在线观看成人免费| av在线播放免费不卡| 人人妻人人澡欧美一区二区| 男女下面进入的视频免费午夜| 在线免费观看的www视频| 欧美日韩乱码在线| 久久午夜亚洲精品久久| 国产日本99.免费观看| 国产精品久久电影中文字幕| 欧美最黄视频在线播放免费| 特级一级黄色大片| 妹子高潮喷水视频| 久9热在线精品视频| 久久这里只有精品19| 国产精品 欧美亚洲| 久久 成人 亚洲| 国产1区2区3区精品| 亚洲av五月六月丁香网| 一进一出抽搐gif免费好疼| 午夜免费成人在线视频| 丁香欧美五月| 久久中文字幕一级| 免费看十八禁软件| 在线观看日韩欧美| 久久久久国产一级毛片高清牌| 国产精品永久免费网站| 亚洲在线自拍视频| 搡老熟女国产l中国老女人| 日韩精品中文字幕看吧| 人妻夜夜爽99麻豆av| 亚洲精品色激情综合| 日韩欧美免费精品| 一本一本综合久久| 欧美黄色淫秽网站| 国产成人av激情在线播放| 久久久久免费精品人妻一区二区| 老司机深夜福利视频在线观看| 97碰自拍视频| 婷婷六月久久综合丁香| 淫秽高清视频在线观看| 免费搜索国产男女视频| 一级作爱视频免费观看| 夜夜夜夜夜久久久久| 在线播放国产精品三级| 中文资源天堂在线| 亚洲成人久久性| 宅男免费午夜| 亚洲欧美一区二区三区黑人| 欧美日韩一级在线毛片| 男女视频在线观看网站免费 | 首页视频小说图片口味搜索| 久久久久国产精品人妻aⅴ院| 亚洲精品一卡2卡三卡4卡5卡| 亚洲真实伦在线观看| 国产精品久久久久久精品电影| 一个人免费在线观看的高清视频| 久久久国产成人免费| 免费看日本二区| 成人一区二区视频在线观看| 777久久人妻少妇嫩草av网站| 欧美一区二区精品小视频在线| 一a级毛片在线观看| 99在线人妻在线中文字幕| 18禁美女被吸乳视频| 国产精品美女特级片免费视频播放器 | 精品第一国产精品| 中文资源天堂在线| 亚洲中文字幕一区二区三区有码在线看 | 亚洲狠狠婷婷综合久久图片| 免费搜索国产男女视频| 麻豆成人午夜福利视频| 国产激情久久老熟女| 黄色毛片三级朝国网站| 黑人巨大精品欧美一区二区mp4| 国产av一区二区精品久久| 免费搜索国产男女视频| 麻豆国产av国片精品| 老司机午夜福利在线观看视频| 成人精品一区二区免费| 亚洲av成人不卡在线观看播放网| 亚洲熟妇中文字幕五十中出| 男女之事视频高清在线观看| 精品无人区乱码1区二区| 50天的宝宝边吃奶边哭怎么回事| 曰老女人黄片| 五月伊人婷婷丁香| 淫秽高清视频在线观看| 国产精华一区二区三区| 性欧美人与动物交配| 99久久99久久久精品蜜桃| 老汉色∧v一级毛片| 久久中文看片网| 日韩av在线大香蕉| 成人三级做爰电影| 老熟妇乱子伦视频在线观看| 精品久久蜜臀av无| av片东京热男人的天堂| 无限看片的www在线观看| 欧美又色又爽又黄视频| 琪琪午夜伦伦电影理论片6080| 国产成人av教育| 黑人操中国人逼视频| 2021天堂中文幕一二区在线观| 俄罗斯特黄特色一大片| 国产高清videossex| 国产精品免费视频内射| 亚洲av成人av| 国内久久婷婷六月综合欲色啪| 久久精品人妻少妇| 欧美成人性av电影在线观看| 国产高清videossex| 亚洲电影在线观看av| 久久香蕉国产精品| 午夜老司机福利片| 99国产精品一区二区三区| 国产真人三级小视频在线观看| 中亚洲国语对白在线视频| 91老司机精品| 日韩欧美国产一区二区入口| 大型av网站在线播放| 两个人看的免费小视频| 精品电影一区二区在线| 日本免费a在线| 日本三级黄在线观看| 夜夜看夜夜爽夜夜摸| 天堂动漫精品| 两人在一起打扑克的视频| 亚洲午夜精品一区,二区,三区| 久久精品国产清高在天天线| 久久香蕉激情| 99久久99久久久精品蜜桃| 美女大奶头视频| 男人的好看免费观看在线视频 | 人人妻,人人澡人人爽秒播| a级毛片在线看网站| 免费一级毛片在线播放高清视频| 久久久国产欧美日韩av| 俺也久久电影网| 天堂av国产一区二区熟女人妻 | 亚洲精品美女久久av网站| 久久久久久亚洲精品国产蜜桃av| 精品少妇一区二区三区视频日本电影| 十八禁网站免费在线| 日韩有码中文字幕| 国产成+人综合+亚洲专区| 久久精品aⅴ一区二区三区四区| 高清毛片免费观看视频网站| 伦理电影免费视频| 日韩欧美 国产精品| 叶爱在线成人免费视频播放| 校园春色视频在线观看| 又紧又爽又黄一区二区| 国产精品一区二区三区四区久久| 国产成人aa在线观看| 成人永久免费在线观看视频| 他把我摸到了高潮在线观看| 久99久视频精品免费| 激情在线观看视频在线高清| 宅男免费午夜| 欧美丝袜亚洲另类 | 人成视频在线观看免费观看| 国产又黄又爽又无遮挡在线| 国内少妇人妻偷人精品xxx网站 | 九九热线精品视视频播放| 狂野欧美激情性xxxx| 婷婷精品国产亚洲av| av有码第一页| 色尼玛亚洲综合影院| 婷婷亚洲欧美| 日韩免费av在线播放| 国产精品自产拍在线观看55亚洲| 搞女人的毛片| 日韩免费av在线播放| 亚洲av熟女| 丁香六月欧美| 午夜福利欧美成人| 久久午夜亚洲精品久久| 女人爽到高潮嗷嗷叫在线视频| 一区福利在线观看| 一本一本综合久久| 好看av亚洲va欧美ⅴa在| 国产高清激情床上av| 久久香蕉激情| 不卡av一区二区三区| 欧美午夜高清在线| 国产成人一区二区三区免费视频网站| 超碰成人久久| 免费电影在线观看免费观看| 国产精品美女特级片免费视频播放器 | 啪啪无遮挡十八禁网站| 亚洲成av人片在线播放无| 婷婷六月久久综合丁香| 国产成人aa在线观看| 欧美日韩瑟瑟在线播放| 99精品欧美一区二区三区四区| 老司机午夜十八禁免费视频| 成人高潮视频无遮挡免费网站| 美女高潮喷水抽搐中文字幕| 成年女人毛片免费观看观看9| 男人舔女人的私密视频| 欧美黑人巨大hd| 日日摸夜夜添夜夜添小说| www日本黄色视频网| 国产熟女午夜一区二区三区| 白带黄色成豆腐渣| 午夜亚洲福利在线播放| 亚洲午夜理论影院| 一个人免费在线观看的高清视频| 国产激情偷乱视频一区二区| 色综合亚洲欧美另类图片| 18禁黄网站禁片午夜丰满| 国内精品一区二区在线观看| 色综合站精品国产| 两个人看的免费小视频| 一区福利在线观看| 成年免费大片在线观看| 国产亚洲精品久久久久久毛片| 久久久久久大精品| 欧美日韩亚洲国产一区二区在线观看| 一区二区三区激情视频| 国产成人精品久久二区二区91| 在线国产一区二区在线| 中文字幕人成人乱码亚洲影| 国产精品精品国产色婷婷| 国产日本99.免费观看| 亚洲一区二区三区不卡视频| 女人高潮潮喷娇喘18禁视频| 极品教师在线免费播放| 国产成人欧美在线观看| 在线十欧美十亚洲十日本专区| 美女免费视频网站| av视频在线观看入口| 亚洲精品国产一区二区精华液| 少妇熟女aⅴ在线视频| 国产蜜桃级精品一区二区三区| 18禁裸乳无遮挡免费网站照片| 精品久久久久久久久久久久久| 人妻夜夜爽99麻豆av| 国产精品九九99| x7x7x7水蜜桃| 亚洲欧美日韩东京热| 日韩精品免费视频一区二区三区| a级毛片在线看网站| 观看免费一级毛片| 精品一区二区三区视频在线观看免费| 长腿黑丝高跟| 国产成人一区二区三区免费视频网站| 久久精品亚洲精品国产色婷小说| 精品久久久久久,| 一边摸一边抽搐一进一小说| 黑人欧美特级aaaaaa片| 国产高清视频在线播放一区| 国产黄a三级三级三级人| 热99re8久久精品国产| 欧美乱码精品一区二区三区| 久久人人精品亚洲av| 嫁个100分男人电影在线观看| 不卡av一区二区三区| a级毛片a级免费在线| 夜夜躁狠狠躁天天躁| 久久亚洲精品不卡| 欧美丝袜亚洲另类 | 国产午夜精品久久久久久| 欧洲精品卡2卡3卡4卡5卡区| 亚洲成人精品中文字幕电影| 操出白浆在线播放| 国产精品久久久久久久电影 | 国产99久久九九免费精品| 国产精品香港三级国产av潘金莲| 精品无人区乱码1区二区| 亚洲一区二区三区色噜噜| 男女视频在线观看网站免费 | 99在线人妻在线中文字幕| 国产精品 欧美亚洲| 村上凉子中文字幕在线| 别揉我奶头~嗯~啊~动态视频| 又紧又爽又黄一区二区| 亚洲av第一区精品v没综合| 99久久99久久久精品蜜桃| 日韩三级视频一区二区三区| 国产高清videossex| 99久久精品热视频| www.熟女人妻精品国产| 国产精品香港三级国产av潘金莲| 首页视频小说图片口味搜索| 久久精品人妻少妇| 黄色片一级片一级黄色片| 亚洲真实伦在线观看| 美女 人体艺术 gogo| 亚洲精品中文字幕在线视频| 国产精华一区二区三区| 999久久久精品免费观看国产| 黄片大片在线免费观看| 亚洲av五月六月丁香网| а√天堂www在线а√下载| 欧美绝顶高潮抽搐喷水| 欧美日韩乱码在线| 超碰成人久久| 一个人免费在线观看电影 | 黑人欧美特级aaaaaa片| 狠狠狠狠99中文字幕| 91大片在线观看| 1024香蕉在线观看| 久久人妻av系列| 久久精品国产清高在天天线| 亚洲第一电影网av| av在线播放免费不卡| 老司机午夜福利在线观看视频| 18禁黄网站禁片免费观看直播| 少妇的丰满在线观看| 精品久久久久久,| 国产69精品久久久久777片 | 国产视频一区二区在线看| 男女视频在线观看网站免费 | 亚洲性夜色夜夜综合| 亚洲成av人片在线播放无| 90打野战视频偷拍视频| 看黄色毛片网站| 99国产综合亚洲精品| 老司机深夜福利视频在线观看| 日韩欧美免费精品| 亚洲欧美日韩东京热| a级毛片在线看网站| 麻豆成人av在线观看| 最近在线观看免费完整版| 老汉色∧v一级毛片| 国产成人aa在线观看| 伊人久久大香线蕉亚洲五| 久久这里只有精品19| 无遮挡黄片免费观看| 日本一区二区免费在线视频| 久久欧美精品欧美久久欧美| 国产97色在线日韩免费| 亚洲欧美日韩无卡精品| 可以免费在线观看a视频的电影网站| 欧美在线黄色| 国产av一区在线观看免费| 久久久久久久久久黄片| 国产1区2区3区精品| 叶爱在线成人免费视频播放| 欧美绝顶高潮抽搐喷水| 欧美在线一区亚洲|