Laparoscopic spleen-preserving total pancreatectomy for the treatment of low-grade malignant pancreatic tumors:Two case reports and review of literature

BACKGROUND Function-preserving pancreatectomy can improve the long-term quality of life of patients with benign or low-grade malignant tumors,such as intraductal papillary mucinous neoplasms(IPMNs)and mucinous cystic neoplasms.However,there is limited literature on laparoscopic spleen-preserving total pancreatectomy(LSpTP)due to technical difficulties.CASE SUMMARY Patient 1 was a 51-year-old male diagnosed with IPMN based on preoperative imaging,showing solid nodules in the pancreatic head and diffuse dilation of the main pancreatic duct with atrophy of the distal pancreas.We performed L-SpTP with preservation of the splenic vessels,and the postoperative pathology report revealed IPMN with invasive carcinoma.Patient 2 was a 60-year-old male with multiple cystic lesions in the pancreatic head and body.L-SpTP was performed,and intraoperatively,the splenic vein was injured and required ligation.Postoperative pathology revealed a mucinous cystic tumor of the pancreas with low-grade dysplasia.Both patients were discharged on postoperative day 7,and there were no major complications during the perioperative period.CONCLUSION We believe that L-SpTP is a safe and feasible treatment for low-grade malignant pancreatic tumors,but more case studies are needed to evaluate its safety,efficacy,and long-term outcomes.

Clinical analysis of malignant pancreatic endocrine tumors:reports of 27 cases

To investigate clinicopathological features,diagnosis and treatment of malignant pancreatic tumors.Methods A retrospective clinical analysis was made in 27 cases of malignant pancreatic tumors admitted from 1989 to 2003.Results Tumors were surgically resected in 22 patients.Tumor infiltration into surrounding organs was found in 13 cases.Four patients had lymph nodes metastasis and 5 had liver metastasis.Two cases were found tumor embolus in vascular or lymph tube.Neural invasion was found in 3.Conclusion Malignant pancreatic tumors has good prognosis.Aggressive attempts of surgical management should be performed.6 refs,1 tab.

Obstructive jaundice caused by secondary pancreatic tumor from malignant solitary fibrous tumor of pleura:A case report

对胸膜的恶意的独居的含纤维的肿瘤的手术后的双边的多重肺转移的全身的化疗上的一个 77 岁的人受不了瘙痒和黄疸。血检查显示出肝胆管酶的提高的层次。腹的计算断层摄影术在胰腺的头与外部改进显示出一个肿瘤，与 intra 肝、额外肝的胆汁管的膨胀伴随了。他作为把妨碍的黄疸被一个胰腺的头肿瘤引起了被诊断。胰腺的头肿瘤大概作为胸膜的恶意的独居的含纤维的肿瘤的转移被诊断，因为腹的 CT 上的胰腺的头肿瘤上的调查结果类似于胸膜的恶意的独居的含纤维的肿瘤的主要的肺损害上的那些。胰腺的肿瘤在胆总管的劣等的部分在金属性的斯滕特氏印模膏的培植以后很快成长了。病人死于肺的癌性淋巴管炎。尸体揭示了从胰腺的头传播了到肝的核的一个肿瘤。用显微镜，和骨胶原免职展出原子 atypicality 或分割的塑造锭子的房间被观察。Immunohistochemically 胰腺的头肿瘤房间为 alpha 光滑的肌肉肌动朊(alpha-SMA ) 或 CD117 染色是否定的，但是为 vimentin， CD34 和 CD99 积极。这些调查结果与胸膜的恶意的独居的含纤维的肿瘤上的那些一致。我们报导一个第二等的胰腺的肿瘤从胸膜的恶意的独居的含纤维的肿瘤引起的妨碍的黄疸的第一个案例。

A case of primary malignant fibrous histiocytoma of the pancreas: CT and MRI findings

Primary malignant fibrous histiocytoma (MFH) of the pancreas is rare and a distinct clinical entity. We report a case of recurrence of pancreatic MFH with computed tomography (CT) and magnetic resonance imaging (MRI) findings. A 67-year-old man presented with a history of decreased body weight over the past 6 mo. Abdominal CT revealed a large, multilocular cystic mass in the head of the pancreas with obvious atrophy in the body and tail of the pancreas. After 6 mo postoperatively, MRI demonstrated a recurrent large mass in the primary area of the head of the pancreas. The lesion was heterogeneous, hypointense to the liver on T1-weighted imaging, and heterogeneously hyperintense to the liver with a hypointense area in the central part of the tumor on fat-saturated T2-weighted imaging. Contrast- enhanced T1-weighted imaging demonstrated a large multilocular cystic mass with a cystic wall, fibrous septa and enhancement of solid components. To the best of our knowledge, this is the first report on recurrence of primary MFH of the pancreas, and the first with MRI findings.

Central pancreatectomy:a new technique for resection of selected pancreatic tumors

BACKGROUND:Pancreatic tumors located in the neck region usually require pancreaticoduodenectomy or splenopancreatectomy.For small benign tumors enucleation is not usually feasible due to their size and localization;then pancreatectomy is often needed.Central pancreatectomy consists of a limited resection of the midportion of the pancreas and can be offered in benign and low-grade malignant tumors of the neck of the pancreas.The study aimed to evaluate whether central pancreatectomy has a place in pancreatic surgery. METHODS:In this study,which covered a period of 14 months,we performed central pancreatectomy in four selected patients.Preoperative evaluation and operative frozen section biopsy in indicated cases allowed proper selection for the procedure.Operative details,complications and follow-up were recorded. RESULTS:Four patients,two with serous cystadenoma,and one with an islet cell tumor,and one with a hydatid cyst, were identified for the procedure.The mean tumor size was 3 cm,the mean operative time was 217.5 minutes,and the mean blood loss was 382.5 ml.There was no morbidity or mortality in this series.No endocrine or exocrine deficiency was observed in any patient during a mean follow-up of 22.7 months. CONCLUSIONS:Central pancreatectomy is a procedure that offers excellent results in benign and low-grade malignant tumors.It preserves functional elements(endocrine and exocrine)of the pancreas and also eliminates the infective and hematological effects of splenectomy.Thus,central pancreatectomy should be included in the armamentarium of pancreatic surgery,and in order to obtain good results,proper indications and adequate experience are recommended.

胰腺腺泡细胞癌伴脾脏侵犯肿瘤破裂出血1例

胰腺腺泡细胞癌(PACC)是一种临床上罕见的胰腺恶性肿瘤,缺乏特异性临床表现及肿瘤标志物,检查发现胰腺占位应考虑到PACC的可能性,临床确诊需术后活组织病理学检查明确,早期积极手术并辅以术后综合性治疗可明显改善患者预后。现报道怒江州人民医院收治的1例术后病理学检查明确PACC伴脾脏侵犯肿瘤破裂出血行开放胰腺体尾部切除+全脾脏切除+淋巴结清扫术的患者临床病例资料并结合相关文献对本病的发病机制、临床表现、诊断、治疗、预后等进行讨论分析,以提高对该疾病的认识。

Current surgical management of pancreatic endocrine tumor liver metastases

BACKGROUND: The management of metastatic disease in pancreatic endocrine tumors (PETs) demands a multidisciplinary approach and the cooperation of several medical specialties. The role of surgery is critical, even when a radical excision cannot always be achieved. DATA SOURCES: A PubMed search of relevant articles published up to February 2011 was performed to identify current information about PET liver metastases regarding diagnosis and management, with an emphasis on surgery. RESULTS: The early diagnosis of metastases and their accurate localization, most commonly in the liver, is very important. Surgical options include radical excision, and palliative excision to relieve symptoms in case of failure of medical treatment. The goal of the radical excision is to remove the primary tumor bulk and all liver metastases at the same time, but unfortunately it is not feasible in most cases. Palliative excisions include aggressive tumor debulking surgeries in well-differentiated carcinomas, trying to remove at least 90% of the tumor mass, combined with other additional destructive techniques such as hepatic artery embolization or chemoembolization to treat metastases or chemoembolization to relieve symptoms in cases of rapidly growing tumors. The combination of chemoembolization and systemic chemotherapy results in better response and survival rates. Other local destructive techniques include ethanol injection, cryotherapy and radiofrequency ablation. CONCLUSION: It seems that the current management of PETs can achieve important improvements, even in advanced cases.

Primary pancreatic lymphoma: Report of six cases

瞄准：在临床的实践提高主要胰腺的淋巴瘤(PPL ) 的识别。方法：临床的演讲，成像特征和 PPL 病人的病理学的特征的回顾的评论被介绍，以及他们的诊断和治疗，在有文学评论的联合。结果：组织学的诊断被 EUS-FNA 被外科并且在二个病人在四个病人做。六个 PPL 病人(5 男性和 1 女性；年龄变化， 16-65 年；吝啬的年龄， 46 年) 有症状的持续时间二个星期到三个月。主要主要症状不特征，是腹的疼痛，腹的群众，重量损失，黄疸，恶心并且呕吐。病人之一开发了尖锐胰腺炎。在一个病人，浆液 CA19-9 的水平是 76.3 microg/L。腹的 CT 扫描证明六个肿瘤中的三个位于胰的头，二在里面身体和尾巴，和在整个胰的身体。在在四种情况中的胰的肿瘤的直径是超过 6 厘米，与同类的密度和不清楚的边阶。提高的 CT 扫描证明仅仅肿瘤边稍微被提高。胰腺的管不规则地在其肿瘤位于胰腺的头和身体的二种情况中被缩小，在哪个内视镜后退 cholangiopancreatography (ERCP ) 证明近似片断稍微被扩大。二个病人经历了惠普尔操作，一个病人经历了胰切除术，并且另一个病人经历了起作用的胆汁的解压缩。PPL 在舞台我在 2 个病人并且在在 4 个病人的阶段 II E 的 E 根据安乔木分类系统。B 房间 non-Hodgkin 的淋巴瘤的诊断在所有病人被成为组织病理学说的联盟者。所有六个病人经历了全身的化疗，其中一也与鲸鱼群妈辐射线测定被对待。一个病人二个星期在诊断以后死了，二个病人失去了后续，收到的化疗熬过 49 和 37 瞬间的二个病人，和留下的病人仍然是活着的 21 瞬间，在诊断和治疗以后。结论：PPL 是从胰腺的实质发源的额外的节的淋巴瘤的一种稀罕形式。临床并且成像调查结果另外不在胰腺的淋巴瘤和胰腺的癌症的区别是特定的，它值得注意。胰的指导 EUS 的好针的渴望(EUS-FNA ) 象先进免疫一样要求富有经验的 cytopathologists 在组织的小数量上获得最后的诊断的组织化学的试金。外科和辅助化疗或放射疗法能生产相当好的结果。

Analysis of invasiveness and tumor-associated macrophages infiltration in solid pseudopapillary tumors of pancreas

BACKGROUND Solid pseudopapillary tumor(SPT)is a rare pancreatic tumor.Considering its malignant behaviors,SPT has been classified as a low-grade malignant tumor.Indeed,only 9.2%of all SPT patients are initially diagnosed as malignant with invasion or metastasis.Thus,one of the challenges in managing SPT patients is predicting malignant behavior.AIM To investigate the malignant behavior and tumor-associated macrophage(TAM)infiltration between different histopathologic features of SPT patients.METHODS Twenty-five formalin-fixed paraffin-embedded tissue samples from 22 patients pathologically diagnosed with an SPT between 2009 and 2019 at West China Hospital were included in this retrospective study.Integrity of the capsule and growth pattern of the tumor cells was assessed microscopically in hematoxylineosin(HE)-stained sections.Based on the histopathological features,the SPT patients were divided into two groups:capsule or invasion.Clinical features,malignant behavior,and TAM infiltration were compared between the two groups.RESULTS Among the 22 SPT patients,11 were identified for each group,having either a capsule or invasion histopathologic feature.Malignant behavior was more frequent in the invasion group,including 2 patients who had peripheral organ invasion,3 with liver metastasis,and 1 with both lymph node and spleen metastases(P=0.045).Ki-67 index of more than 3%was also more frequent in the invasion group(P=0.045).Immunohistochemical analysis showed that the invasion group had a significant increase of CD68-positive TAMs in intratumor and peritumor sites in comparison with the capsule group(all P<0.0001).Similarly,CD163-positive M2-like macrophages were also markedly increased in the intratumor and peritumor sites in the invasion group(all P<0.0001).At the liver metastasis site,both intratumor and peritumor tissues showed relatively high-level CD68-positive TAMs and CD163-positive M2-like macrophages infiltration.However,the differences between the intratumor,peritumor and normal hepatic tissues did not reach statistical significance(all P>0.05).CONCLUSION SPT patients with invasion evident under microscope were more likely to exhibit malignant behavior and TAM infiltration,especially M2-like macrophages.This finding can help in future investigations of the underlying mechanism of TAM-mediated SPT malignant behavior.

Castleman disease of the pancreas mimicking pancreatic malignancy on^(68)Ga-DOTATATE and 18F-fluorodeoxyglucose positron emission tomography/computed tomography:A case report

BACKGROUND Castleman disease is an uncommon nonclonal lymphoproliferative disorder,which frequently mimics both benign and malignant abnormalities in several regions.Depending on the number of lymph nodes or regions involved,Castleman disease(CD)varies in diagnosis,treatment and prognosis.It rarely occurs in the pancreas alone without any distinct clinical feature and tends to be confused with pancreatic paraganglioma(PGL),neuroendocrine tumors(NETs),and primary tumors,thus impeding proper diagnosis and treatment.CASE SUMMARY A 28-year-old woman presented with a lesion on the neck of the pancreas,detected by ultrasound during a health examination.Physical examination and laboratory findings were normal.The mass showed hypervascularity on enhanced computed tomography(CT),significantly increased 18F-fluorodeoxyglucose uptake on positron emission tomography(PET)/CT,and slightly increased somatostatin receptor(SSTR)expression on^(68)Ga-DOTATATE PET/CT,suggesting no distant metastases and subdiagnoses such as pancreatic PGL,NET,or primary tumor.Intraoperative pathology suggested lymphatic hyperplasia,and only simple tumor resection was performed.The patient was diagnosed with the hyaline vascular variant of CD,which was confirmed by postoperative immunohistochemistry.The patient was discharged successfully,and no recurrence was observed on regular review.CONCLUSION High glucose uptake and slightly elevated SSTR expression are potentially new diagnostic features of CD of the pancreas.

Pathologic pancreatic endocrine cell hyperplasia

Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known.β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy,which is commonly caused by mutations in the islet ATP-sensitive potassium channel,and to noninsulinoma pancreatogenous hypoglycemia in adults,which may or may not be associated with bariatric surgery.α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors.An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia.Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge. Based on morphological evidence,the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium.Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia,elevated islet hormone levels,and pancreatic neuroendocrine tumors.Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors.

Malignant insulinoma:Can we predict the long-term outcomes?

Insulinomas are the most frequent type of functional pancreatic neuroendocrine tumors with a variety of neuroglycopenic and autonomic symptoms and welldefined diagnostic criteria;however,prediction of their clinical behavior and early differentiation between benign and malignant lesions remain a challenge.The comparative studies between benign and malignant cases are limited,suggesting that short clinical history,early hypoglycemia during fasting,high proinsulin,insulin,and C-peptide concentrations raise suspicion of malignancy.Indeed,malignant tumors are larger with higher mitotic count and Ki-67 proliferative activity,but there are no accurate histological criteria to distinguish benign from malignant forms.Several signaling pathways have been suggested to affect the pathophysiology and behavior of insulinomas;however,our knowledge is limited,urging a further understanding of molecular genetics.Therefore,there is a need for the identification of reliable markers of metastatic disease that could also serve as therapeutic targets in patients with malignant insulinoma.This opinion review reflects on current gaps in diagnostic and clinical aspects related to the malignant behavior of insulinoma.

MRI在胰腺癌新辅助治疗疗效评估中的研究进展

新辅助治疗(neoadjuvant treatment, NAT)提高了胰腺癌根治性切除的可能性,有助于改善患者预后。但患者个体间差异导致NAT疗效差别较大,故而早期、准确评价NAT疗效成为胰腺癌研究热点之一。MRI可以从解剖学和功能学角度间接反映肿瘤细胞和微环境的变化,无创评估治疗效果,弥补了其他影像检查技术的不足。本文就常规MRI和功能MRI技术包括扩散加权成像、体素内不相干运动、动态对比增强MRI、T1 mapping、T2 mapping,以及PET/MRI等技术在胰腺癌NAT疗效评估方面的研究现状展开综述,旨在协助临床制订有效的诊治策略;便于临床医生及科研人员更系统全面地理解胰腺癌NAT引起肿瘤微环境变化及其治疗相关反应影像学表现的差异。随着MRI功能序列的发展及多参数MRI研究的推进,未来有望构建一个基于MRI的胰腺癌综合序列评估体系。

碘125粒子植入治疗胰腺癌的现状

胰腺癌作为一种临床上常见的恶性程度极高的恶性肿瘤,通常有着起病隐匿,早期诊断困难,病情发展迅速等特点,预后较差。正是由于胰腺癌的这些特点,患者常常出现因确诊较晚而失去根治手术的机会,因此需要寻找其他替代治疗方案。放疗是治疗晚期癌症的常用方法,在胰腺癌的临床治疗中应用广泛,但其对病灶周围组织容易造成不同程度的损害而产生相应并发症,伴随着医疗技术的发展,临床上出现了粒子植入近距离组织内放射治疗的方案,而其中碘125粒子植入近距离放疗因其安全性和有效性颇受欢迎,本文综述了碘125粒子植入治疗的作用,碘125粒子植入治疗的应用,碘125粒子植入的不足与优势。

CT增强薄层靶扫描与MRCP在IPMN良恶性鉴别诊断中的对比研究

目的 比较CT增强薄层靶扫描和MRCP在胰腺导管内乳头状粘液性肿瘤(IPMN)良恶性鉴别诊断中应用价值的差异。方法 收集45例经手术切除病理证实、同时行CT增强薄层靶扫描和MRCP检查的IPMN患者影像资料,按2017福冈指南专家共识标准,分别分析并计算CT增强薄层靶扫描和MRCP检查病灶出现的征象中,肿瘤强化壁结节≥5mm、主胰管扩张≥10mm、胆管扩张、厚分隔、胰腺萎缩、分支胰管型最大囊肿≥3cm在鉴别诊断IPMN良恶性的准确性、曲线下面积(AUC)、敏感性及特异性,统计比较两组间的差异。结果 各影像征象诊断恶性IPMN两种检查方法间差异均无统计学意义(P>0.05)。综合以上四个影像征象,CT增强薄层靶扫描诊断恶性IPMN中的总准确性、敏感性、特异性及分别为:86.67%、87.10%、85.71%,阳性预测值及阴性预测值为93.10%、75.00%;而MRCP在诊断恶性IPMN的总准确性、敏感性、特异性及分别为80.00%、80.64%、78.50%,阳性预测值及阴性预测值为89.28%、64.70%,且各征象总的诊断效能,两种检查方法组间差异均无统计学意义(P>0.05)。结论 CT增强薄层靶扫描,可以作为缺乏MRCP设备的基层医院诊断恶性IPMN的一种有效的替代检查方法。

医护一体化护理+随访护理模式对肝胆胰恶性肿瘤患者心理健康和生活质量的影响

目的探讨医护一体化护理+随访护理模式对肝胆胰恶性肿瘤患者心理健康和生活质量的影响。方法选取2020年10月1日至2022年4月30日我院肝胆外科收治的89例肝胆胰恶性肿瘤患者为研究对象,以2020年10月1日至2021年7月31日收治的44例为对照组(常规临床护理),2021年8月1日至2022年4月30日收治的45例为试验组(医护一体化护理+随访护理模式)。比较两组的护理效果。结果护理后,试验组的焦虑自评量表(SAS)、抑郁自评量表(SDS)评分均低于对照组(P<0.05)。护理后,两组的躯体功能、角色功能、情绪功能、认知功能及社会功能评分均升高,且试验组高于对照组(P<0.05)。结论医护一体化护理+随访护理模式有助于改善肝胆胰恶性肿瘤患者的心理健康和生活质量。

CT灌注成像在胰腺肿瘤诊断中的应用价值

目的:探讨胰腺肿瘤的CT灌注成像(CTPI)特征,评价CTPI在胰腺肿瘤诊断中的价值。方法:对50例胰腺肿瘤患者和45例非胰腺疾病患者行CTPI,选择获得良好灌注图像者共76例,其中胰腺肿瘤患者44例和非胰腺病变患者32例。测量ROI的血流量(BF)、血容量(BV)、达峰时间(TTP)和表面通透性(PS)的值,并进行统计学分析。结果:胰腺癌组织的BF、BV、PS较正常胰腺组织明显减低,TTP较正常胰腺组织升高,差异均有统计学意义。实性假乳头状肿瘤组织的BF、BV、PS较正常胰腺组织明显减低,差异有统计学意义。胰岛细胞瘤的BF、BV较正常胰腺组织明显增高,差异有统计学意义。结论:CTPI可反映胰腺肿瘤的血流动力学特征,对胰腺肿瘤的临床诊断及鉴别诊断有重要的作用。

恶性胰岛细胞瘤23例诊治分析

目的探讨恶性胰岛细胞瘤的临床特点及诊治方法。方法回顾性分析我院1993-2012年收治的经手术或穿刺病理证实的恶性胰岛细胞瘤23例。结果其中恶性胰岛素瘤6例,平均直径2.1 cm,首发症状为Whipple三联征或低血糖昏迷,肿瘤均单发,位于胰体尾部,5例伴有肝脏转移,3例行手术治疗,术后低血糖症状均改善。恶性无功能胰岛细胞瘤17例,平均直径6.2 cm,首发症状为腹部包块、腹痛或无痛性黄疸,15例肿瘤单发,11例位于胰腺体尾部,10例有肝脏转移,12例手术,术后梗阻症状均有显著改善。23例术前均应用多种影像学方法定位。结论恶性胰岛细胞瘤主要包括恶性胰岛素瘤和恶性无功能胰岛细胞瘤,大多单发,位于胰腺体尾部,肝转移最常见;以手术为主的综合治疗可有效缓解低血糖及梗阻症状。

薄层增强MRI多期扫描技术诊断功能性胰岛细胞瘤(附3例报告)

目的探讨薄层增强MRI多期扫描技术即探讨梯度回波MRI三维容积插入法屏气检查(volumetric interpolatedbreath holdexamination,3D VIBE)序列对功能性胰岛细胞瘤的诊断价值。方法对3例临床以及实验室检查怀疑为功能性胰岛细胞瘤的患者,按以下顺序分别进行MRI常规轴位的T2W和T1W平扫、冠状位的真实稳态旋进快速成像(truefastimagingwithsteadystateprocession,True FISP)、磁共振胆胰管成像(magnetic resonancecholangiopancreatography,MRCP)、轴位钆剂增强的3D VIBE三期动态扫描和2DGRET1W增强扫描。3D VIBE三期扫描数据采集分别于注射对比剂后15、40及65s进行。将影像资料与手术和病理发现作对比分析。结果3D VIBE序列的动脉早期、动脉晚期和门静脉期图像能准确显示功能性胰岛细胞瘤的微小病灶,并能反映病灶的血供特征,而其它常规MRI序列可能漏诊该病灶。结论薄层动态增强的MRI序列在功能性胰岛细胞瘤的显示和定性诊断中具有重要作用。

薏苡仁甘油三酯(康莱特)治疗晚期恶性肿瘤患者机制研究进展

薏苡仁甘油三酯是薏苡仁中主要的抗肿瘤活性成份,其制剂康莱特注射液为双相广谱抗肿瘤、可供静脉直接输注的新型脂肪乳剂。研究表明,康莱特注射液在肺、肝、脑、乳腺等多种癌症治疗中均有较好疗效,特别在原发性肝癌和晚期非小细胞癌的治疗中有显著疗效,且副作用较少。在控制癌变的同时还能增加患者的机体免疫力,延长疾病的进展时间,很大程度上提高了临床疗效。本文主要阐述近些年薏苡仁甘油三酯在晚期恶性肿瘤中的疗效和作用机制的研究进展。