本文選題：內(nèi)鏡粘膜下剝離術(shù) + 粘膜下注射　； 參考：《第二軍醫(yī)大學(xué)》2014年博士論文

【摘要】：第一部分 目的：內(nèi)鏡粘膜下剝離術(shù)（endoscopic submucosal dissection，ESD）是消化道早期腫瘤病變的首選治療方法，它普及的重要障礙在于手術(shù)的操作難度較大和穿孔的發(fā)生率較高。通過消化道粘膜下注射形成一個(gè)粘膜下液體墊層（submucosal fluid cushion,SFC）是避免穿孔的最好方法，因此合適的注射材料成為改進(jìn)這種微創(chuàng)內(nèi)鏡技術(shù)的重要環(huán)節(jié)。在本研究中，我們將一種可注射的熱致水凝膠的生物材料作為新型的粘膜下注射材料嘗試用于ESD術(shù)中，以觀察可行性、安全性、持久性和組織相容性。 方法：這種水凝膠成分是聚乳酸羥基乙酸-聚乙二醇-聚乳酸羥基乙酸三嵌段共聚物Poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolicacid)(PLGA-PEG-PLGA)，這種高分子水凝膠溶液在室溫下是一種粘性液體，因此可以注射，在注射到體內(nèi)之后接觸體溫，變成一種不能流動(dòng)的凝膠。我們在活體外和活體內(nèi)分別將這種熱致水凝膠進(jìn)行粘膜下注射，來評估它的生物安全性、注射可行性、粘膜隆起的高度和時(shí)間以及對ESD手術(shù)的幫助。具體來說，合成該水凝膠溶液之后，將該溶液經(jīng)皮下注射到小型豬的后腿內(nèi)側(cè)，觀察皮下隆起灶形成情況；購買新鮮的離體豬胃，分別抽取水凝膠溶液和甘油果糖、透明質(zhì)酸注射到胃的粘膜下層，在不同時(shí)間點(diǎn)評價(jià)不同的注射劑形成的粘膜隆起，相機(jī)拍照記錄；將活體小型豬麻醉后，通過內(nèi)鏡腔道，采用內(nèi)鏡注射針，將三種注射劑注射（水凝膠溶液、甘油果糖和透明質(zhì)酸）到粘膜下層，形成的粘膜隆起在0，15，30min和1周時(shí)通過內(nèi)鏡觀察，留取相應(yīng)內(nèi)鏡圖片，1周后處死取材做HE染色評價(jià)，光學(xué)顯微鏡觀察；將活體小型豬麻醉后，使用該水凝膠溶液進(jìn)行粘膜下注射并進(jìn)行ESD手術(shù)，3只立即處死以檢查組織急性損傷，另2只1周后處死以觀察遲發(fā)性組織損害。粘膜下注射和ESD手術(shù)部位的胃黏膜組織用福爾馬林固定，石蠟包埋后HE染色，光鏡觀察。 結(jié)果：在將熱致水凝膠溶液皮下注射到豬的大腿內(nèi)側(cè)之后，注射部位因?yàn)樯眢w溫所致的快速凝膠化（約30s）在注射后形成明顯的橢圓形隆起，它的形狀保持時(shí)間超過了1月，高度和大小因?yàn)槟z體的活體內(nèi)降解逐漸減小，沒有觀察到紅腫熱痛、壞死等副作用；在離體豬胃的粘膜下注射實(shí)驗(yàn)中，雖然3種注射液注射之后都產(chǎn)生了明顯的粘膜隆起，但水凝膠形成的SFC明顯更為持久，觀察60分鐘之后沒有見到水凝膠的粘膜隆起灶的大小、外形和硬度有明顯變化，相反，其他兩者的隆起在15min之后逐漸塌陷；在活體豬的粘膜下注射實(shí)驗(yàn)中，三種溶液都造成了明顯的粘膜隆起灶，在剛注射完畢時(shí)，三者形成的粘膜隆起外形明顯，高度上沒有明顯的差異，但透明質(zhì)酸和甘油果糖注射完畢15min之后粘膜隆起逐漸塌陷，到了30min時(shí)候，內(nèi)鏡下已經(jīng)觀察不到粘膜隆起灶，相反，水凝膠形成的粘膜隆起的外形和清晰邊界在30min時(shí)都沒有改變，1周之后水凝膠形成的粘膜隆起仍然清楚存在且邊界清晰，局部沒有缺血征象或者潰瘍，病理顯示沒有明顯的上皮損傷，也沒有觀察到炎癥細(xì)胞；在活體豬的ESD實(shí)驗(yàn)中，所有的ESD手術(shù)都成功完成，當(dāng)用電刀切開粘膜隆起灶時(shí)，隆起灶的環(huán)周切除能夠很方便地完成，接下來，粘膜下形成的膠體很容易地就通過內(nèi)鏡吸取孔道被吸走，粘膜下形成一個(gè)干凈的空腔，最終病變用圈套器被完整的整塊切除下來，整個(gè)過程中無需任何重復(fù)注射，沒有發(fā)生大量出血和穿孔等嚴(yán)重并發(fā)癥，病理沒有觀察到除手術(shù)切緣以外其他部位粘膜和固有肌層的損傷，炎癥僅停留在淺層。 結(jié)論：在該凝膠的協(xié)助下，ESD手術(shù)能夠精確地施行病變的整塊切除，并且顯著縮短了手術(shù)時(shí)間。同時(shí)，沒有發(fā)生大出血、穿孔和組織損傷等并發(fā)癥。該凝膠的使用不僅使得ESD程序變得簡便，也增加了ESD的有效性和安全性。PLGA-PEG-PLGA熱致水凝膠適合作為一個(gè)理想的粘膜下注射材料來形成更高的粘膜抬舉和維持更長抬舉時(shí)間，從而減少了并發(fā)癥。它的獨(dú)特的粘膜下剝離功能簡化了ESD的操作步驟，避免了傳統(tǒng)方法中繁瑣冗長的剝離過程，因此有利于ESD手術(shù)的普及和應(yīng)用。 第二部分 目的：隧道內(nèi)鏡是一種創(chuàng)新的內(nèi)鏡技術(shù)，在包括經(jīng)口內(nèi)鏡食管括約肌切開術(shù)(peroral endoscopic myotomy, POEM)在內(nèi)的多種內(nèi)鏡手術(shù)中起到核心作用。但目前的隧道內(nèi)鏡技術(shù)仍然復(fù)雜而費(fèi)時(shí)，而且在某些解剖部位和病理情況下無法成功建立粘膜下隧道(submucosal tunnel, SMT)，這大大限制了它的臨床應(yīng)用，，亟待開發(fā)能夠解決這些局限性的新方法。PLGA-PEG-PLGA熱致水凝膠溶液在我們的前期研究中已經(jīng)證實(shí)了在ESD手術(shù)中，它是一種很好的粘膜下注射材料，因此本研究進(jìn)一步評價(jià)它在消化道粘膜下隧道建立過程中的作用。 方法：小型豬禁食麻醉后，經(jīng)豬的肛門將1個(gè)三腔二囊管插入結(jié)腸，生理鹽水沖洗以建立清潔的腸段。在3頭小型豬的食管、胃、結(jié)腸依次采用PLGA-PEG-PLGA水凝膠溶液作為粘膜下注射液來建立粘膜下隧道，將內(nèi)鏡通過口部或肛門插入消化道并到達(dá)手術(shù)部位，選擇合適的位置通過一個(gè)注射針進(jìn)行水凝膠溶液的粘膜下注射，然后在墊層的一側(cè)用內(nèi)鏡電刀做一個(gè)1.5cm左右的橫行切口，然后內(nèi)鏡進(jìn)入粘膜下空間并通過吸引孔道吸引凝膠逐漸前進(jìn)，視頻記錄整個(gè)操作過程，評價(jià)可行性和并發(fā)癥。手術(shù)完成之后，處死所有的豬并進(jìn)行病理解剖，同時(shí)，在進(jìn)行粘膜下注射之后盡快取消化道粘膜組織，10%中性福爾馬林固定，石蠟包埋，HE染色，光鏡觀察。 結(jié)果：所有3只豬的食管、胃和結(jié)腸均成功建立隧道，沒有并發(fā)癥發(fā)生。食管隧道的位置位于距門齒約20-25cm處，胃隧道的位置位于胃體，結(jié)腸隧道的位置位于距肛門15-20cm左右的腸段。在食管、胃、結(jié)腸建立每個(gè)隧道所需要的注射膠的體積約為20ml，每次粘膜下注射都形成了一個(gè)厚的粘膜下墊層，在切開粘膜隆起灶之后，帶帽的內(nèi)鏡順利的進(jìn)入粘膜下空間并吸取膠體，凝膠基本吸取干凈后隧道自然形成，無需使用電刀剝離或者鈍性分離。在三個(gè)部位建立隧道的中位操作時(shí)間分別是13.6,11.5和9.4分鐘。形成的隧道長度約5cm。解剖沒有發(fā)現(xiàn)明顯的粘膜層和固有肌層的撕裂傷，也沒有鄰近器官的損傷。 結(jié)論：我們的初步實(shí)驗(yàn)證實(shí)了PLGA-PEG-PLGA熱致水凝膠溶液作為一種新的粘膜下注射來建立胃腸道SMT是安全可行的，未來需要進(jìn)行一系列的對照研究來比較它與目前臨床上常用的粘膜下注射物質(zhì)對手術(shù)療效的影響。 第三部分 目的：經(jīng)自然腔道內(nèi)鏡手術(shù)(natural orifice transluminal endoscopic surgery，NOTES)是近年興起的一類新型手術(shù)類型，它使微創(chuàng)手術(shù)從腹壁無可見瘢痕變?yōu)檎嬲臒o瘢痕，徹底消除了腹壁切口以及相關(guān)的切口感染、疼痛、切口疝等問題，患者術(shù)后恢復(fù)快，心理應(yīng)激程度低，費(fèi)用也低。但是內(nèi)鏡在進(jìn)行NOTES手術(shù)時(shí)有一些固有的缺陷：內(nèi)鏡鏡身柔軟，軸向力不足，在進(jìn)行腹腔內(nèi)分離時(shí)操作起來很困難，分離過程成為內(nèi)鏡進(jìn)行NOTES手術(shù)中最耗時(shí)和風(fēng)險(xiǎn)最大的步驟，開發(fā)能夠幫助內(nèi)鏡在腹腔內(nèi)分離過程的方法，有利于NOTES的發(fā)展和應(yīng)用。我們的前期研究用PLGA-PEG-PLGA熱致水凝膠溶液作為粘膜下注射液，可以極大地方便ESD手術(shù)和消化道隧道的建立，受此啟發(fā)，我們提出設(shè)想：如果在NOTES手術(shù)進(jìn)入腹腔之前，用EUS的定位優(yōu)勢將此類凝膠直接注射到手術(shù)的目標(biāo)區(qū)域附近，溶液固化后因其本身的占位效應(yīng)，形成一個(gè)直達(dá)手術(shù)目標(biāo)的膠體通路，然后NOTES進(jìn)入腹腔后通過吸走固化的凝膠，從而形成一個(gè)直達(dá)手術(shù)目標(biāo)的“隧道”，從而省去了費(fèi)時(shí)和復(fù)雜繁瑣的腹腔內(nèi)剝離過程，簡化了手術(shù)過程。因此，我們利用熱致水凝膠溶液嘗試在動(dòng)物身上進(jìn)行這種基于腹腔內(nèi)生物材料注射的NOTES-腹腔神經(jīng)叢松解術(shù)(celiac plexus neurolysis, CPN)，研究其可行性和安全性。 方法：活體小型豬禁食麻醉后，將超聲內(nèi)鏡通過豬口插入，在EUS實(shí)時(shí)監(jiān)測下將穿刺針刺入，注射膠約30ml。接著沿食道下方用常規(guī)隧道技術(shù)打一隧道，切開后進(jìn)入腹腔，發(fā)現(xiàn)凝膠位置后在藍(lán)色凝膠塊的一側(cè)用內(nèi)鏡電刀切開，內(nèi)鏡鏡頭進(jìn)入膠塊內(nèi)空間，通過吸引孔道吸走凝膠，邊吸引邊前進(jìn)，直到看到腹腔干和腹主動(dòng)脈匯合處，前進(jìn)過程中避免暴力分離，以防出血影響視野，少量出血采用電活檢鉗進(jìn)行電凝處理。腹腔干和腹主動(dòng)脈匯合處附近即為腹腔神經(jīng)節(jié)的位置。采用電活檢鉗電凝周圍組織。視頻記錄整個(gè)操作過程，評價(jià)可行性和并發(fā)癥。手術(shù)完成之后，處死所有的豬并進(jìn)行病理解剖，仔細(xì)檢查手術(shù)部位和附近的器官有無損傷。 結(jié)果：所有三頭豬均成功完成這種方式的NOTES-CPN手術(shù)，沒有明顯的并發(fā)癥（穿孔或者大出血）。注射所用的水凝膠溶液平均體積為36ml (range25-28ml)。每次粘膜下注射都形成了一個(gè)半球狀的藍(lán)色凝膠團(tuán)塊。帶帽的內(nèi)鏡進(jìn)入團(tuán)塊內(nèi)空間之后，凝膠很容易就被吸走，從而形成一個(gè)內(nèi)鏡前進(jìn)的隧道。無需電刀剝離或者其他形式的鈍性分離即可到達(dá)手術(shù)部位。在病理解剖時(shí)沒有看到粘膜層或者固有肌層的撕裂傷，鄰近器官組織也沒有任何損傷。操作的平均時(shí)間是35mins (range28-41mins)。 結(jié)論：本研究中我們成功地將一種對溫度敏感可逆的PLGA-PEG-PLGA水凝膠溶液作為一種腹腔內(nèi)注射材料來引導(dǎo)NOTES手術(shù)中內(nèi)鏡快速到達(dá)目標(biāo)區(qū)域。因此，PLGA-PEG-PLGA熱致水凝膠除了可作為內(nèi)鏡粘膜下注射液之外，它的膠化特性和生物相容性使得它可以作為體內(nèi)手術(shù)的標(biāo)志物和引導(dǎo)物，在NOTES等新興手術(shù)中可能也有更大的應(yīng)用范圍。
[Abstract]:Part one
Objective: endoscopic submucous dissection (endoscopic submucosal dissection, ESD) is the first choice for the early digestive tract lesions of the digestive tract. Its important obstacle is the difficulty of operation and the high incidence of perforation. A submucosal liquid cushion (submucosal fluid cushion, SF) is formed by Submucous injection of the digestive tract. C) is the best way to avoid perforation, so appropriate injection material is an important part of improving this minimally invasive endoscopic technique. In this study, we tried to use an injectable thermo hydrogel biomaterial as a new submucosal injection material in ESD to observe the feasibility, safety, persistence and histocompatibility.
Method: this hydrogel is a three block copolymer Poly (lactic acid-co-glycolic acid) -poly (ethylene glycol) -poly (lactic acid-co-glycolicacid) (lactic acid-co-glycolicacid) (lactic acid-co-glycolicacid) (PLGA-PEG-PLGA). The polymer hydrogel solution is a viscous liquid at room temperature, so it can be injected. After being injected into the body, the body is exposed to body temperature and becomes an inflow gel. We have submucous injection of this thermohydrogel in both living and living bodies to assess its biological safety, the feasibility of the injection, the height and time of the protruding of the mucous membrane, and the help of the ESD operation. Specifically, after the synthesis of the hydrogel solution, The solution was injected subcutaneously into the inside of the hind leg of a small pig to observe the formation of the subcutaneous eminence, and the fresh isolated pig stomach was purchased and the hydrogel and glycerol fructose were extracted respectively. Hyaluronic acid was injected into the submucous layer of the stomach, and the mucosal protruding of different injections was evaluated at different time points and the camera was photographed; the living body was recorded and the living body was small. After anaesthesia, the three kinds of injections (hydrogel, fructose and hyaluronic acid) were injected into the submucosa by endoscopic injection, and the mucosal bulge formed by endoscopy was observed by endoscopy at 0,15,30min and 1 weeks. After 1 weeks, HE staining was performed and the optical microscope observation was used. After anaesthesia, submucous injection of the hydrogel solution and ESD operation were performed with the hydrogel solution. 3 rats were killed immediately to examine the acute tissue injury. The other 2 were executed 1 weeks later to observe the tardive tissue damage. The submucous injection and the ESD surgical site of the gastric mucosa were fixed with Faure Marin, paraffin embedded HE staining, and light microscopy.
Results: after subcutaneous injection of the thermohydrogel solution into the inner thigh of the pig, the rapid gelation (about 30s) caused by the physiological body temperature of the injection site formed an obvious elliptical uplift after the injection. Its shape retention time exceeded January. The height and size of the injection site decreased gradually and the swelling of the body was gradually reduced and the swelling was not observed. Heat pain, necrosis and other side effects; in the submucosal injection experiment of the isolated pig stomach, although 3 kinds of injection produced obvious mucosal protruding after injection, but the SFC formed by hydrogel was obviously more lasting. After 60 minutes, the size of the mucosa of the mucous membrane of the hydrogel was not seen, the shape and hardness of the gel were obviously changed, on the contrary, the other two. The protuberances were gradually collapsed after 15min; in the submucosal injection experiment of living pigs, the three solutions all caused obvious mucosal protuberances. At the end of the injection, the mucosal protuberances formed in the three groups were obvious, and there was no obvious difference in height. However, after the hyaluronic acid and glycerin fructose were injected, the mucosal bulge gradually collapsed after the injection of hyaluronic acid and glycerol. By the time of 30min, the mucosal protrusion was not observed under endoscopy. On the contrary, the morphology and clear boundary of the mucous membrane formed by the hydrogel did not change at 30min. After 1 weeks, the mucous protruding of the hydrogel was still clear and the boundary was clear. There were no ischemic signs or ulcers in the local area. Pathology showed no obvious epithelial injury. No inflammatory cells were observed. In the ESD experiment of living pigs, all the ESD operations were successfully completed. The circumferential resection of the bulge can be easily completed when an electric knife is cut into the mucosal bulge. Then the colloids formed under the mucous membrane are easily sucked away through the endoscope and form a clean space under the mucous membrane. In the cavity, the final lesion was removed with a complete block. No repeated injections were needed during the whole process. No massive bleeding and perforation occurred. The pathology did not observe the damage of the mucosa and the inherent muscularis in other parts except the cutting edge of the operation. The inflammation only stayed in the shallow layer.
Conclusion: with the help of the gel, the ESD operation can accurately perform an integral resection of the lesion and significantly shorten the operation time. At the same time, there are no complications such as massive hemorrhage, perforation and tissue damage. The use of the gel not only makes the ESD program easier, but also increases the effectiveness and safety of ESD heat induced water. The gel is suitable as an ideal submucosal injection material to form higher mucosal lifts and maintain longer lifts, thus reducing complications. Its unique submucosal dissection simplifies the procedure of ESD operation and avoids the tedious and lengthy stripping process in traditional methods, which is conducive to the popularization and application of ESD surgery.
The second part
Objective: tunnel endoscopy is an innovative endoscopic technique that plays a core role in a variety of endoscopic surgery including peroral endoscopic myotomy (POEM), but the current tunnel endoscopy is still complex and time-consuming and can not be successfully established under some anatomical and pathological conditions. Submucosal tunnel (SMT), which greatly restricts its clinical application, is urgent to develop a new method to solve these limitations,.PLGA-PEG-PLGA thermo hydrogel solution. In our previous study, it has been proved that it is a very good sub mucous injection material in ESD operation. Therefore, this study further evaluated it in this study. The role of the submucosal tunnel of the digestive tract during the establishment of the tunnel.
Methods: after a small pig's anaesthesia, 1 three cavities and two cystic tubes were inserted into the colon through the pig's anus, and the normal saline was washed to establish a clean intestinal segment. The esophagus, stomach and colon of 3 miniature pigs were used as submucous submucous tunnel by PLGA-PEG-PLGA hydrogel solution in order to insert the endoscope through the mouth or anus into the digestive tract. At the site of the operation, an injection needle is selected for the submucous injection of the hydrogel solution, and an endoscopic scalpel is used to make a 1.5cm transverse incision on one side of the cushion, then the endoscope enters the submucosal space and draws the gel by attracting the channel to advance gradually. The video records the entire operation process, and the evaluation can be made. After the operation was completed, all pigs were killed and pathologically dissected. At the same time, the mucosal tissue was removed as soon as submucous injection. 10% neutral formalin fixation, paraffin embedding, HE staining, and light microscopy were observed.
Results: the esophagus, stomach and colon were successfully established in all 3 pigs, without complications. The location of the tunnel was located about 20-25cm from the teeth, the position of the stomach tunnel was located in the body of the stomach and the location of the tunnel in the colon was located around the 15-20cm of the anus. In the esophagus, stomach and colon, the volume of injection needed for each tunnel was established. For 20ml, each submucosal injection formed a thick submucous cushion. After opening the mucosal bulge, the endoscopy with the cap entered the submucosal space and absorbed the colloid. The tunnel was naturally formed after the gel was basically clean. The middle operation time of the tunnel was established in three parts without the need of electric knife stripping or blunt separation. It was 13.6,11.5 and 9.4 minutes respectively. The length of the tunnel was about 5cm., and there was no obvious tear in the mucous layer and the inherent muscularis, and there was no injury to the adjacent organs.
Conclusion: our preliminary experiments confirm that the PLGA-PEG-PLGA thermal hydrogel solution is safe and feasible as a new submucous injection to establish the gastrointestinal tract SMT. In the future, a series of controlled studies are needed to compare the effect of the submucosal injections that are commonly used in clinic on the surgical effect.
The third part
Objective: natural orifice transluminal endoscopic surgery (NOTES) is a new type of surgery in recent years. It makes minimally invasive surgery from the invisible scar of the abdominal wall to a real no scar. It completely eliminates the abdominal wall incision and related incision infection, pain, incisional hernia, and so on. It is fast, low psychological stress and low cost. But endoscopy has some inherent defects in NOTES operation: the endoscopy is soft, the axial force is insufficient and it is difficult to operate in the abdominal cavity. The separation process becomes the most time-consuming and most risky step in the endoscopy for NOTES operation, and the development can help the endoscope in abdominal cavity. The method of internal separation is beneficial to the development and application of NOTES. Our previous study using PLGA-PEG-PLGA thermal hydrogel solution as submucosal injection can greatly facilitate the establishment of ESD surgery and the tunnel of the digestive tract. Inspired by this, we suggest that if the NOTES operation enters the abdominal cavity, the EUS positioning advantage will be used. The gel is injected directly near the target area of the operation. After the solution is solidified, a colloid pathway is formed because of its own occupying effect. Then NOTES enters the abdominal cavity and absorbs the solidified gel through the intraperitoneal cavity to form a "tunnel" that reaches the objective of the operation, thereby saving the time-consuming and complicated intricate intraperitoneal stripping. The procedure simplifies the procedure. Therefore, we try to use a thermohydrogel solution to try the NOTES- plexus neurolysis (CPN) based on intraperitoneal biological materials (celiac neurolysis, CPN) to study the feasibility and safety of the intraperitoneal injection of the intraperitoneal (CPN).
Methods: after the living miniature pig was fasting anaesthesia, the ultrasound endoscopy was inserted through the porcine mouth. The puncture was punctured under the EUS real-time monitoring. The injection glue was inserted into the tunnel under the conventional tunnel technique under the esophagus, and then entered the abdominal cavity after the incision. After the gel position was found on one side of the blue gel block, the endoscopic scalpel was cut and the endoscope lens entered the glue. The intraperitoneal space takes away the gel by attracting the passage and draws the edge to attract the edge, until the abdominal trunk and abdominal aorta converge to avoid violent separation in order to prevent the hemorrhage to affect the field of vision. A small amount of bleeding is electrocoagulated by electrobiopsy forceps. The abdominal trunk and abdominal aorta are the location of the celiac ganglion near the confluence of the abdominal and abdominal aorta. The whole operation was recorded by video. The whole operation was recorded to evaluate the feasibility and complications. After the operation was completed, all pigs were executed and the pathological anatomy was carried out. The surgical site and the adjacent organs were carefully examined.
Results: all three pigs successfully completed this NOTES-CPN operation without obvious complications (perforation or massive bleeding). The average volume of the hydrogel solution used for injection was 36ml (range25-28ml). Each submucosal injection formed a hemispherical blue gelation group. The glue is easily sucked away to form an endoscope tunnel. The surgical site is reached without an electric knife or other form of blunt separation. There is no tear in the mucous layer or the inherent muscularis in the pathological anatomy, and there is no damage to the adjacent organs. The average time of operation is 35mins (range28-41mins).
Conclusion: in this study, we successfully used a temperature sensitive and reversible PLGA-PEG-PLGA hydrogel solution as an intraperitoneal injection material to guide the rapid arrival of endoscopy in the target area in the NOTES operation. Therefore, the PLGA-PEG-PLGA thermo induced hydrogel, in addition to the injection of the endoscopic mucosal injection, its gelation properties and biocompatibility. Sex enables it to be used as a biomarker and guide in vivo. It may also have a wider application in new operations such as NOTES.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R735

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 林浩;田華雨;孫敬茹;莊秀麗;陳學(xué)思;李悅生;景遐斌;;溫度敏感的PLGA-PEG-PLGA水凝膠的合成、表征和藥物釋放[J];高等學(xué)校化學(xué)學(xué)報(bào);2006年07期

2 Kwang Bum Cho;Won Joong Jeon;Jae J Kim;;Worldwide experiences of endoscopic submucosal dissection:Not just Eastern acrobatics[J];World Journal of Gastroenterology;2011年21期

本文編號：1961134