脑胶质瘤组织长链非编码RNA FTX、RHPN1-AS1表达与预后的关系

摘要 目的：探讨脑胶质瘤组织长链非编码核糖核酸(LncRNA) FTX、RHPN1-AS1表达与预后的关系。方法：选取我院105例脑胶质瘤患者手术切除的癌组织和癌旁组织（距离肿瘤边缘3~5 cm）。采用实时荧光定量PCR（qRT-PCR）检测组织中LncRNA FTX、RHPN1-AS1表达。分析LncRNA FTX、RHPN1-AS1表达与脑胶质瘤患者临床病理特征的关系。K-M法绘制不同LncRNA FTX、RHPN1-AS1表达脑胶质瘤患者术后5年无进展生存期和总生存期曲线。Cox回归分析脑胶质瘤患者预后不良的影响因素。结果：脑胶质瘤组织中LncRNA FTX、RHPN1-AS1表达水平高于癌旁组织(P＜0.05)。LncRNA FTX、RHPN1-AS1表达与脑胶质瘤患者卡氏体力状态(KPS)评分和世界卫生组织(WHO)分级相关(P＜0.05)。LncRNA FTX、RHPN1-AS1高表达组无进展生存期和总生存期均短于低表达组(P＜0.05)。KPS评分(HR=2.621,95%CI：1.284～5.348)、WHO分级(HR=2.264,95%CI：1.152～4.449)、LncRNA FTX(HR=1.997,95%CI：1.017～3.922)、LncRNA RHPN1-AS1(HR=2.431,95%CI：1.257～4.701)均是脑胶质瘤患者预后不良的影响因素(P＜0.05)。结论：脑胶质瘤组织中LncRNA FTX、RHPN1-AS1表达水平升高,且二者与KPS评分、WHO分级均是患者预后不良的影响因素,可用于脑胶质瘤患者预后评估。     

脑胶质瘤组织miR-211、miR-374、miR-510表达水平与临床病理特征及预后的关系研究

摘要 目的：探讨脑胶质瘤组织微小RNA（miR）-211、miR-374、miR-510表达水平与临床病理特征及预后的关系。方法：选择2013年8月至2015年8月我院诊治的83例脑胶质瘤患者作为研究对象,选择同期由于脑外伤在我院行内减压术切除的正常脑组织样本31份作为对照样本。采用荧光定量PCR检测miR-211、miR-374、miR-510表达水平,生存分析采用Kaplan-Meier法,应用Cox比例风险回归模型分析预后的影响因素。结果：与正常脑组织相比,脑胶质瘤组织中miR-211、miR-374表达水平明显下降,miR-510表达水平明显升高（P<0.05）。脑胶质瘤组织miR-211、miR-374、miR-510表达均与WHO分级和卡氏功能状态量表(KPS)评分有关（P<0.05）。miR-211、miR-374低表达患者的5年总生存率明显低于高表达患者,miR-510低表达患者的5年总生存率明显高于高表达患者（P<0.05）。WHO分级、KPS评分、miR-211、miR-374和miR-510表达是脑胶质瘤患者预后的影响因素（P<0.05）。结论：脑胶质瘤组织中miR-211和miR-374表达下调,而miR-510表达上调,miR-211、miR-374和miR-510表达均与WHO分级、KPS评分和预后相关,检测miR-211、miR-374和miR-51在脑胶质瘤患者的诊断和治疗中具有一定临床意义。     

miR-324-5p、miR-605-3p在脑胶质瘤组织的表达及与临床病理参数和预后的关系

摘要 目的：探讨微小核糖核酸（miRNA）-324-5p、miR-605-3p在脑胶质瘤组织的表达及与临床病理参数和预后的关系。方法：选取2018年1月～2019年12月徐州医科大学附属医院收治的90例脑胶质瘤患者。收集术中部分瘤组织和瘤旁组织,采用实时荧光定量聚合酶链式反应（qRT-PCR）检测miR-324-5p、miR-605-3p表达。根据脑胶质瘤组织中miR-324-5p、miR-605-3p表达的平均值分为高表达组和低表达组,采用Kaplan-Meier法分析不同miR-324-5p、miR-605-3p表达脑胶质瘤患者生存情况,采用多因素Cox回归分析脑胶质瘤患者预后的影响因素。结果：与瘤旁组织比较,脑胶质瘤组织中miR-324-5p、miR-605-3p表达降低（P＜0.05）。不同分化程度、淋巴结转移、世界卫生组织（WHO）中枢神经系统肿瘤分类的脑胶质瘤患者miR-324-5p、miR-605-3p表达比较有差异（P＜0.05）。90例脑胶质瘤患者3年总生存率为36.67%（33/90）。Kaplan-Meier生存曲线分析显示,miR-324-5p高表达组、miR-605-3p高表达组总生存率高于miR-324-5p低表达组、miR-605-3p低表达组（P＜0.05）。多因素Cox回归分析显示,低分化、淋巴结转移和WHO中枢神经系统肿瘤分类Ⅲ～Ⅳ级为脑胶质瘤患者死亡的独立危险因素,miR-324-5p和miR-605-3p升高为独立保护因素（P＜0.05）。结论：脑胶质瘤组织中miR-324-5p、miR-605-3p呈低表达,与分化程度、淋巴结转移、WHO中枢神经系统肿瘤分类有关,miR-324-5p、miR-605-3p低表达还可导致不良预后。     

脑胶质瘤组织CMTM1、ME2表达与临床病理特征和复发的关系研究

摘要 目的：探讨脑胶质瘤组织含CKLF样MARVEL跨膜结构域的蛋白1（CMTM1）、苹果酸酶2（ME2）表达与临床病理特征和复发的关系。方法：选取2018年1月～2021年1月徐州医科大学附属医院接受切除手术的92例脑胶质瘤患者，根据术后是否复发分为复发组和未复发组。采用免疫组化法检测脑胶质瘤组织和瘤旁组织CMTM1、ME2表达，分析二者与临床病理特征的关系，采用多因素Logistic回归分析脑胶质瘤患者术后复发的影响因素。结果：与瘤旁组织比较，脑胶质瘤组织中CMTM1、ME2阳性表达率升高（P＜0.05）。不同分化程度、世界卫生组织（WHO）中枢神经系统肿瘤分类脑胶质瘤组织中CMTM1、ME2阳性表达率比较，差异有统计学意义（P＜0.05）。随访2年，92例脑胶质瘤患者术后复发率为47.83%（44/92）。多因素Logistic回归分析显示，低分化、WHO中枢神经系统肿瘤分类Ⅲ～Ⅳ级、部分切除和CMTM1、ME2阳性表达为脑胶质瘤患者术后复发的独立危险因素（P＜0.05）。结论：脑胶质瘤组织中CMTM1、ME2阳性表达率升高，与分化程度、WHO中枢神经系统肿瘤分类等级和术后复发有关，可能成为脑胶质瘤患者术后复发的辅助评估指标。     

术前预后营养指数、中性粒细胞与淋巴细胞比值及血小板与淋巴细胞比值对脑胶质瘤患者术后预后的评估价值研究

摘要 目的：探讨术前预后营养指数（PNI）、中性粒细胞与淋巴细胞比值（NLR）及血小板与淋巴细胞比值（PLR）对脑胶质瘤患者术后预后的评估价值。方法：回顾性分析2016年2月至2019年2月我院收治的131例脑胶质瘤患者（脑胶质瘤组）的临床资料,另选择同期86例于门诊健康体检的志愿者为对照组,收集相关资料计算PNI、NLR、PLR。比较脑胶质瘤患者不同临床病理特征PNI、NLR、PLR的差异,Kaplan-Meier法绘制不同PNI、NLR、PLR水平脑胶质瘤患者的生存曲线,单因素和多因素COX回归分析影响脑胶质瘤患者预后的相关因素,受试者工作特征曲线（ROC）分析术前PNI、NLR、PLR预测脑胶质瘤患者预后的价值。结果：脑胶质瘤组NLR、PLR高于对照组（P＜0.05）,PNI低于对照组（P＜0.05）。世界卫生组织（WHO）分级Ⅲ 级患者NLR、PLR高于WHO分级Ⅰ～Ⅱ级患者（P＜0.05）,PNI低于WHO分级Ⅰ～Ⅱ级患者（P＜0.05）。高NLR组、高PLR组3年生存率低于低NLR组、低PLR组（P＜0.05）,低PNI组3年生存率低于高PNI组（P＜0.05）。WHOⅢ级、NLR（较高）、PLR（较高）是脑胶质瘤患者预后不良的危险因素（P＜0.05）,PNI（较高）是保护因素（P＜0.05）。术前PNI、NLR、PLR联合预测脑胶质瘤患者预后的曲线下面积为0.849,高于单独指标预测的0.703、0.706、0.704。结论：脑胶质瘤患者术前PNI降低,NLR、PLR均升高,且与预后不良有关,术前PNI、NLR、PLR可作为脑胶质瘤患者预后评估的参考指标。     

脑胶质瘤患者血清VTN、IGFBP、UBE2C水平与临床病理特征和预后的关系研究

摘要 目的：研究脑胶质瘤患者血清玻连蛋白（VTN）、类胰岛素样生长因子结合蛋白（IGFBP）、泛素耦联酶2C（UBE2C）水平与临床病理特征和预后的关系。方法：将新疆医科大学第一附属医院从2019年1月～2020年1月收治的97例脑胶质瘤患者纳入研究,记作研究组,另取同期于本院进行体检的健康志愿者90例作为对照组。此外,对所有研究组人员均进行为期1年的随访,将其按照随访结局的差异分作死亡组40例和存活组57例。检测并比较各组血清VTN、IGFBP、UBE2C水平,分析血清VTN、IGFBP、UBE2C水平与脑胶质瘤患者临床病理特征和预后的关系,并以受试者工作特征（ROC）曲线分析血清VTN、IGFBP、UBE2C水平预测脑胶质瘤患者死亡的效能。结果：研究组血清VTN、IGFBP及UBE2C水平均高于对照组（均P＜0.05）。肿瘤大小≥5 cm、世界卫生组织（WHO）分级为Ⅲ～Ⅳ级、Karnofsky功能状态（KPS）＜70分脑胶质瘤患者的血清VTN、IGFBP水平均高于肿瘤大小＜5 cm、WHO分级为Ⅰ～Ⅱ级、KPS评分≥70分的脑胶质瘤患者（均P＜0.05）;WHO分级为Ⅲ～Ⅳ级、KPS评分＜70分脑胶质瘤患者的血清UBE2C水平高于WHO分级为Ⅰ～Ⅱ级、KPS评分≥70分的脑胶质瘤患者（均P＜0.05）。死亡组血清VTN、IGFBP、UBE2C水平均高于存活组（均P＜0.05）。经ROC曲线分析发现：血清VTN、IGFBP、UBE2C水平联合检测预测脑胶质瘤患者死亡的曲线下面积、灵敏度、特异度及约登指数均高于上述三项指标单独检测。结论：脑胶质瘤患者血清VTN、IGFBP、UBE2C水平均存在异常高表达,且与肿瘤恶性进展相关,联合检测可能有利于预测患者的预后。     

调强放疗联合替莫唑胺对高级别脑胶质瘤术后患者免疫功能和生活质量的影响

摘要 目的：观察调强放疗联合替莫唑胺对高级别脑胶质瘤术后患者免疫功能和生活质量的影响。方法：选择我院2015年7月~2017年9月收治的有完整临床资料的高级别脑胶质瘤患者107例,根据双色球随机分组法将患者分为对照组和观察组,分别为53例和54例,对照组给予调强放疗,观察组给予调强放疗联合替莫唑胺治疗,均治疗6周。对比两组疗效、免疫功能、生活质量、无进展生存时间、总生存时间和不良反应发生情况。结果：治疗6周后,观察组的客观缓解率55.56%、疾病控制率77.78%高于对照组的35.85%、56.60%（P<0.05）。观察组的无进展生存时间、总生存时间长于对照组（P<0.05）。治疗6周后,观察组的CD8⁺水平低于对照组,CD3⁺、CD4⁺水平高于对照组（P<0.05）。治疗6周后,观察组的躯体功能、机体疼痛、健康状况、生命力、心理职能、躯体角色、情感角色、社会功能维度评分高于对照组（P<0.05）。两组不良反应总发生率对比无显著性差异（P>0.05）。结论：调强放疗联合替莫唑胺应用于高级别脑胶质瘤术后患者,可减轻调强放疗导致的免疫抑制,提高患者生活质量,延长其无进展生存时间、总生存时间。     

脑胶质瘤患者术后睡眠障碍的影响因素分析及对认知功能、心理状态和康复进程的影响

摘要 目的：分析脑胶质瘤患者术后睡眠障碍的影响因素,并探讨术后睡眠障碍对机体认知功能、心理状态和康复进程的影响。方法：选择2019年4月~2021年12月期间中国医科大学附属第一医院收治的260例脑胶质瘤患者。根据病例资料收集并记录患者基本信息,采用单因素和多因素Logistic回归分析脑胶质瘤患者术后睡眠障碍的影响因素。以匹茨堡睡眠质量指数量表（PSQI）评估所有患者的睡眠质量;以简易智力状态检查量表（MMSE）、蒙特利尔认知评估量表（MoCA）评估所有患者的认知功能;以焦虑自评量表（SAS）评分和抑郁自评量表（SDS）评估所有患者的心理状态。观察睡眠障碍对机体认知功能、心理状态和康复进程的影响。结果：260例脑胶质瘤患者中,出现睡眠障碍的有98例,睡眠障碍发生率为37.69%。根据是否发生睡眠障碍将患者分为睡眠障碍组（n=98）和无睡眠障碍组（n=162）。单因素分析结果显示：脑胶质瘤患者术后睡眠障碍与性别、肿瘤部位、脑胶质瘤病理分级、肿瘤直径、合并疾病数量、术后疼痛评分有关（P<0.05）,而与年龄、体质量指数、文化程度、家庭人均月收入、手术时间、术中出血量、肿瘤占位症状、吸烟史、饮酒史、术前卡式功能状态（KPS）评分无关（P>0.05）。多因素Logistic回归分析结果显示：性别为女、合并疾病数量2种及其以上、术后疼痛评分偏高、肿瘤部位为多个脑叶、脑胶质瘤病理分级为Ⅲ级是脑胶质瘤患者术后睡眠障碍的危险因素（P<0.05）。睡眠障碍组的MoCA、MMSE评分均低于无睡眠障碍组（P<0.05）。睡眠障碍组的SAS、SDS评分均高于无睡眠障碍组（P<0.05）。睡眠障碍组的术后恢复进食时间、首次下床活动时间、尿管拔除时间、术后住院时间均长于无睡眠障碍组（P<0.05）。结论：脑胶质瘤患者术后睡眠障碍的发生率较高,性别、术后疼痛评分、合并疾病数量、脑胶质瘤病理分级、肿瘤部位均是睡眠障碍的影响因素,睡眠障碍会影响患者的认知功能,增加抑郁焦虑程度,影响康复进程。     

调强适形放疗联合替莫唑胺对脑胶质瘤患者生命质量及血清VEGF、EGF水平的影响

摘要 目的：探讨调强适形放疗联合替莫唑胺对脑胶质瘤患者生命质量及血清表皮生长因子（EGF）、血管内皮生长因子（VEGF）水平的影响。方法：选取我院于2015年3月到2017年2月期间收治的脑胶质瘤患者86例,分为对照组（n=43,调强适形放疗治疗）和研究组（n=43,对照组的基础上联合替莫唑胺治疗）,比较两组患者疗效、生命质量、生存率血清VEGF、EGF水平以及不良反应。结果：治疗6个疗程后,研究组的总有效率为69.77%（30/43）,高于对照组的48.84%（21/43）（P<0.05）。治疗6个疗程后,两组血清VEGF、EGF水平均较治疗前降低,且研究组低于对照组（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。治疗6个疗程后,两组生活质量量表（QOL）、卡劳夫斯基（KPS）评分升高,且研究组高于对照组（P<0.05）。研究组治疗后1年、2年、3年生存率均高于对照组（P<0.05）。结论：调强适形放疗联合替莫唑胺治疗胶质瘤患者疗效较好,可有效降低患者血清VEGF、EGF水平,且不增加不良反应发生率,同时还可有效改善患者生命质量。     

胶质瘤中CT联合MR动态扫描的诊断价值及其表观弥散系数的定量研究

摘要 目的：探讨胶质瘤中电子计算机断层扫描（CT）联合核磁共振（MR）动态扫描的诊断价值及其表观弥散系数（ADC）定量价值,以促进胶质瘤的有效早期诊断。方法：2017年4月到2021年3月选择在本院进行诊治的颅内肿瘤患者68例作为研究对象,所有患者均给予CT联合MR动态扫描,记录ADC值并判断诊断价值。结果：在68例患者中,病理诊断为胶质瘤38例（胶质瘤组）,非胶质瘤30例（非胶质瘤组）。胶质瘤组的CT出血、水肿、跨中线、界限不清等特征与非胶质瘤组对比差异有统计学意义（P<0.05）。胶质瘤组多表现为T1WI低信号、T2WI高信号,非胶质瘤组多表现为T1WI等信号或低信号、T2WI高信号,对比差异有统计学意义（P<0.05）。胶质瘤组的MR ADCmax、ADCmedian、ADCmin都低于非胶质瘤组（P<0.05）。胶质瘤中CT联合MR动态扫描诊断为胶质瘤37例,非胶质瘤31例,CT联合MR动态扫描诊断胶质瘤的敏感性与特异性为97.4 %（37/38）和100.0 %（30/30）。结论：CT联合MR动态扫描诊断胶质瘤具有很好的敏感性与特异性,ADC值能有效反映病灶组织的病理特征,为临床上提供了一种较为安全、有效的胶质瘤影像检查方法。     

白蚁与动物及微生物的共生类型及其机制

综述了白蚁螱客的主要种类、共生关系及相关机制的研究进展。白蚁螱客中,已报道的动物种类达170种。在与动物的共生关系中存在偏利共生（宾主共栖和异种共栖）、互利共生和无关共生三种;在与微生物的共生关系中,存在与内生菌（原生动物、细菌、真菌和放线菌）和外生菌（蚁巢伞菌等）间的互利关系。指出了白蚁与螱客研究中存在的问题,给出了解决方案,并提出了今后可能的研究热点或方向,为白蚁的综合利用（如纤维素酶）及今后研究物种间的协同进化提供了基础资料。     

Relative and combined effects of ethanol and protein deficiency on strontium and barium bone content and fecal and urinary excretion

To elucidate accumulation of minerals in human iliac arteries with aging, the content of minerals was analyzed by inductively coupled plasma atomic emission spectrometry. Bilateral common, internal, and external iliac arteries of 16 men and 8 women, ranging ages from 65 to 93 yr, were examined. It was found that an extremely high accumulation of calcium and phosphorus occurred in the common iliac artery at old age, being higher than that of the internal and external iliac arteries. It should be noted that the accumulation of calcium and phosphorus is the highest in the common iliac artery among the human arteries examined to date. Regarding sexual differences, the content of calcium and phosphorus in the common and internal iliac arteries was higher in women than in men, whereas their content in the external iliac artery was lower in women than in men.     

New amino-dithiaphospholanes and phosphoramidodithioites and their rhodium and iridium complexes

New sulfur derivatives of phosphoramidite ligands were synthesized and the impact of the sulfur unit on the spectroscopic properties of their rhodium and iridium complexes was investigated. The new ligands Bn₂NPSCH₂CH₂S^a(P-S^a) (Bn = benzyl, 4), Bn₂NPSCHCHS^a(CH₂)₃C^aH₂(P-S^a)(C^a-S^a) (6) and Bn₂NP(4-XC₆H₄OMe)₂ (X = S, 7a; X = O, 7b) were converted to the rhodium and iridium complexes trans-[Rh(CO)Cl(L)₂] (L = 4, 6, 7), [RhCl(COD)(L)] (L = 4, 6, 7), [IrCl(COD)(7a)] and [IrCl₂Cp∗(6)]. For comparison, some phosphoramidite complexes of these formulations also were synthesized. The new metal complexes were spectroscopically analyzed. For the carbonyl complexes, the ν_CO IR stretching frequencies were lower than for the corresponding phosphite and phosphoramidite ligands. The ¹J_PRh coupling constants for the rhodium complexes with the new ligands were also smaller than for the respective phosphoramidite and phosphite complexes. Finally, the ¹J_PSe coupling constants of the selenides of the new ligands were lower than those of the phosphoramidite ligands but higher than for PPh₃. The spectroscopic data reveal that the new thio ligands 4, 6 and 7a are more electron donating than phosphites and phosphoramidites but less electron donating than PPh₃.     

Astrocytes and Synaptosomes Transport and Metabolize Lactate and Acetate Differently

Astrocytes transport the monocarboxylate acetate, but synaptosomes do not. The reason for this is unknown, because both preparations express monocarboxylate transporters (MCT). The transport and metabolism of lactate, another monocarboxylate, was examined in these two preparations, and the results were compared to those for acetate. Lactate transport is more rapid in astrocytes than in synaptosomes, but of lower affinity (Kms of 17 and 4 mM, respectively). Lactate (0.2 mM) is metabolized to CO2 more rapidly in synaptosomes than in astrocytes (rates of 0.37 and 0.07 nmol x mg protein(-1) x min(-1), respectively). The reason for this is unclear, but cellular differences in lactate dehydrogenase isotype expression may be involved. Acetate is metabolized to CO2 more rapidly in astrocytes than in synaptosomes (rates of 0.43 and 0.02 nmol x mg protein(-1) x min(-1), respectively). This is likely due to cellular differences in the expression of monocarboxylate transporter subtypes.     

Rapporteur report: Basics and technology and metrology and standards

The first and second sessions of the Workshop focussed on the basics of ultrasound and infrasound, their applications in both industry and medicine, and metrology and protection standards for ultrasound applications.     

Prostaglandin and thromboxane production by human and guinea-pig macrophages and leucocytes

The ability of partially purified human and guinea-pig haematogenous cell populations, when cultured in vitro, to metabolise arachidonic acid (AA) has been studied. Supernatants from 24 hour cell culture have been subjected to analysis for products of AA metabolism by gas chromatography with electron-capture detection.The cell types studied were human peripheral blood monocytes (both glass adherent and non-adherent), neutrophils, eosinophils and leukemic leucocytes; thoracic duct lymphocytes and lung alveolar macrophages. From the guinea-pig, induced and non-induced macrophage or neutrophil enriched peritoneal exudate populations, lymph node cells, peritoneal eosinophils and peripheral blood platelets were examined. Supernatants were assayed for the presence of PGE₂, PGD₂, PGF_2α, TXB₂ and 6-keto-PGF_1α. In all types studied PGE₂ and TXB₂ were the major products formed. The identification of PGE₂ and TXB₂ was confirmed by GC/MS with multiple ion monitoring.The results have been compared with other reports and their possible significance discussed in relation to the proposed role of prostaglandins as mediators and modulators in immunopathology.     

Cytoskeleton and mitochondrial morphology and function

It has been well established that the cytoskeleton is an essential modulator of cell morphology and motility, intracytoplasmic transport and mitosis, however cytoskeletal linkage to the organelles has not been unequivocally demonstrated. Indeed, cytoskeleton appears to be essential in determining and modulating gene phenotype as a function of cellular environment. According to recent studies, the organization of the cytoskeleton network together with associated protein(s) could be essential in regulating mitochondrial function and particularly the permeability of the mitochondrial outer membrane to ADP. The aim of this chapter is to summarize the main properties of the cytoskeletal environment of mitochondria and the possible role(s) of this network in mitochondrial function in myocytes.     

Cross-reactivity between storage and dust mites and between mites and shrimp

Many patients have sensitivities to multiple species of storage and house dust mites. It is not clear if this is because patients have multiple sensitivities to species-specific mite allergens or if these mites share many cross-reacting allergens. Our objective was to further define the cross-allergenicity between several species of storage and house dust mites using crossed-immunoelectrophoresis (CIE), crossed-radioimmunoelectrophoresis (CRIE), immunoblotting, and ELISA. CIE and CRIE reactions revealed that storage mites shared two cross-antigenic molecules and one of these bound IgE in a serum pool from mite allergic patients. Antibody in anti-sera built to each species of mite recognized many SDS–PAGE resolved proteins of other mite species and this suggested the potential for other cross-reactive allergens. Among patient sera, IgE bound to many different proteins but few had IgE that bound to a protein with common molecular weights across the mite species and this suggested mostly species-specific allergens. Antiserum built to each mite species precipitated one protein in shrimp extracts that bound anti-Der p 10 (tropomyosin) and IgE in the serum pool. Anti-Der p 10 showed strong binding to shrimp tropomyosin but very little to any of the mite proteins. ELISA showed the mite extracts contained very little tropomyosin. The storage and dust mites investigated contain mostly species-specific allergens and very small amounts of the pan-allergen tropomyosin compared to shrimp and snail.