肝硬化原发性肝癌直径<1 cm超声造影表现及其与血清AFU、AFP-L3、GPC3、TSGF、GP73水平相关性研究

摘要 目的：探讨肝硬化原发性肝癌（PHC）直径<1cm超声造影（CEUS）表现及其与血清α-L-岩藻糖苷酶（AFU）、甲胎蛋白异质体-L3（AFP-L3）、磷脂酰肌醇蛋白聚糖-3（GPC3）、肿瘤特异生长因子（TSGF）、高尔基体糖蛋白（GP73）水平相关性。方法：选取2018年1月-2022年8月于湖北省襄阳市中医院收治的肝硬化PHC直径<1 cm患者44例,根据术后病理结果分为高分化组、中分化组和低分化组。所有患者术前均完善CEUS和血清AFU、AFP-L3、GPC3、TSGF、GP73水平检查。比较三组CEUS表现、定量时间-强度曲线（TIC）分析、血清AFU、AFP-L3、GPC3、TSGF、GP73水平。采用Spearman相关性分析肝硬化PHC直径<1 cm患者的CEUS表现与血清AFU、AFP-L3、GPC3、TSGF、GP73水平的相关性。结果：44例肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶,呈圆形或类圆形,病灶边界清晰,周围可见声晕。不同分化程度肝硬化PHC直径<1 cm患者在动脉期、门脉期和延迟期的CEUS表现上差异均无统计学意义（P＞0.05）。高分化组、中分化组和低分化组的达峰时间、廓清时间和峰值加速时间逐渐减少,差异有统计学意义（P＜0.05）。而高分化组、中分化组和低分化组的峰值强度增加率逐渐增加,差异有统计学意义（P＜0.05）。高分化组、中分化组和低分化组的增强时间对比差异无统计学意义（P＞0.05）。高分化组、中分化组和低分化组血清AFU、AFP-L3、GPC3、TSGF、GP73水平逐渐升高,差异有统计学意义（P＜0.05）。Spearman相关性分析显示,达峰时间、廓清时间和峰值加速时间与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈负相关（P＜0.05）;峰值强度增加率与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈正相关（P＜0.05）。结论：肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶,呈圆形或类圆形,病灶边界清晰,周围可见声晕。CEUS表现和血清AFU、AFP-L3、GPC3、TSGF、GP73水平具有相关性,两者可辅助鉴别肝硬化PHC直径<1 cm的不同分化程度。     

铜蓝蛋白、鳞状细胞癌相关抗原与慢性肾功能衰竭的关系及对病情进展的预测价值研究

摘要 目的：分析铜蓝蛋白（CER）、鳞状细胞癌相关抗原（SCCA）与慢性肾功能衰竭的关系及对病情进展的预测价值。方法：选择我院自2019年4月至2021年4月接诊的169例慢性肾功能衰竭患者作为研究对象,根据24 h尿白蛋白定量分为微量白蛋白尿组（＜200 mg/24 h,102例）和大量白蛋白尿组（＞200 mg/24 h,67例）。比较两组各项实验室指标及血清CER、SCCA水平,分析CER、SCCA与慢性肾功能衰竭患者肾功能指标的关系。随访12个月,观察病情进展,使用受试者工作特征曲线（ROC）评价血清CER联合SCCA对病情进展的预测效能。结果：大量白蛋白尿组血清肌酐（Scr）、血尿素氮（BUN）水平均明显高于微量白蛋白尿组,肾小球滤过率（GFR）低于微量白蛋白尿组（P＜0.05）;大量白蛋白尿组血清CER、SCCA水平均高于微量白蛋白尿组（P＜0.05）;经Pearson相关性分析,慢性肾功能衰竭患者血清CER、SCCA水平均与Scr、BUN呈正相关,与GFR呈负相关（P＜0.05）;经多因素Logistic回归分析,GFR、CER、SCCA均是慢性肾功能衰竭患者病情进展的独立预测因素（P＜0.05）;经ROC曲线分析,血清CER联合SCCA预测慢性肾功能衰竭患者病情进展的AUC为0.925,明显大于GFR的0.620（P＜0.05）。结论：血清CER、SCCA水平与慢性肾功能衰竭患者肾功能呈负相关,联合预测病情进展效能较好,值得临床予以重视应用。     

肝细胞癌组织miR-124-3p、miR-212-5p表达与PI3K/Akt信号通路和预后的关系研究

摘要 目的：探讨肝细胞癌组织中微小核糖核酸（miR）-124-3p、miR-212-5p表达与磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路和预后的关系。方法：选择2017年9月至2019年9月徐州医科大学附属医院肝胆外科收治的93例肝细胞癌患者,采用实时荧光定量聚合酶链反应（qRT-PCR）检测肝细胞癌组织中miR-124-3p、miR-212-5p、PI3K 信使RNA（mRNA）、Akt mRNA的表达。Pearson相关性分析miR-124-3p、miR-212-5p表达与PI3K/Akt信号通路相关mRNA表达的相关性。绘制Kaplan-Meier生存曲线,Log-Rank检验不同miR-124-3p、miR-212-5p表达肝细胞癌患者3年总生存率（OS）的差异。结果：肝细胞癌组织中miR-124-3p表达低于癌旁组织（P＜0.05）,miR-212-5p、PI3K mRNA、Akt mRNA表达高于癌旁组织（P＜0.05）。肝细胞癌组织中miR-124-3p表达与PI3K mRNA、Akt mRNA表达呈负相关（P＜0.05）,miR-212-5p表达与PI3K mRNA、Akt mRNA表达呈正相关（P＜0.05）。Ⅱa期、低分化患者肝细胞癌组织中miR-124-3p表达低于Ⅰa-Ⅰb期、中高分化患者（P＜0.05）,miR-212-5p表达高于Ⅰa-Ⅰb期、中高分化患者（P＜0.05）。随访期间死亡37例, miR-124-3p低表达组3年OS为42.55%,低于miR-124-3p高表达组的78.26%（P＜0.05）,miR-212-5p高表达组3年OS为50.00%,低于miR-212-5p低表达组的71.11%（P＜0.05）。结论：肝细胞癌组织中miR-124-3p表达下调,miR-212-5p表达上调,且与肝细胞癌PI3K/Akt信号通路激活,PI3K mRNA和Akt mRNA高表达,低分化,CNLC分期Ⅱa期以及低OS有关。     

Planar cell polarity regulators in asymmetric organogenesis during development and disease

The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules. Six “core” proteins, including Frizzled, Flamingo (Celsr), Van Gogh (Vangl), Dishevelled, Prickle, and Diego (Ankrd6), are major components of the Wnt/planar cell polarity pathway. The Fat/Dchs protocadherins and the Scrib polarity complex also function to instruct cellular polarization. In vertebrates, all these pathways are essential for tissue and organ morphogenesis, such as neural tube closure, left–right symmetry breaking, heart and gut morphogenesis, lung and kidney branching, stereociliary bundle orientation, and proximal–distal limb elongation. Mutations in planar polarity genes are closely linked to various congenital diseases. Striking advances have been made in deciphering their contribution to the establishment of spatially oriented pattern in developing organs and the maintenance of tissue homeostasis. The challenge remains to clarify the complex interplay of different polarity pathways in organogenesis and the link of cell polarity to cell fate specification. Interdisciplinary approaches are also important to understand the roles of mechanical forces in coupling cellular polarization and differentiation. This review outlines current advances on planar polarity regulators in asymmetric organ formation, with the aim to identify questions that deserve further investigation.     

Calcineurin—immunosuppressor complexes

Crystal structures of the Ser/Thr phosphatase calcineurin (protein phosphatase 2B) have recently been solved by X-ray crystallography, both in the free-protein state, and complexed with the immunophilin/immunosuppressant FKBP12/FK506. Core elements of the calcineurin phosphatase have been found to be similar to the corresponding elements of Ser/Thr phosphatase 1 and purple acid phosphatase. The structures provide a basis for understanding calcineurin inhibition by a ternary complex of immunophilin and immunosuppressant proteins.     

结直肠癌P53蛋白定量分析及其与肿瘤生物学行为的关系

应用MD-20显微图象分析仪对30例结直肠癌的P53蛋白免疫组织化学反应产物进行定量测定,以观察P53蛋白相对含量与肿瘤生物学行为的关系.结果显示:结直肠癌P53蛋白MOD值与PCNA增殖指数呈正相关(P<0.05).P53蛋白MOD值大的肿瘤多里浸润性生长方式,且浸润至浆膜外者多(PM<0.01,P<0.05).淋巴结转移与MOD值无明显关系(P>0.05).结果提示:结直肠癌P53蛋白相对含量对肿瘤的生物学行为有重要影响.     

放射治疗对鼻咽癌患者细胞免疫功能的影响

应用抗人淋巴细胞单克隆抗体检测３２例鼻咽癌患者放疗前、后外周血Ｔ淋巴细胞亚群,并与１２例非癌人群（对照组）进行对比。结果：鼻咽癌患者ＯＫＴ３、ＯＫＴ４及ＯＫＴ４／ＯＫＴ８值与对照组相比明显降低,ＯＫＴ８显著上升（Ｐ＜０．０５）;放疗后ＯＫＴ３、ＯＫＴ４及ＯＫＴ４／ＯＫＴ８值进一步下降,ＯＫＴ８进一步升高（Ｐ＜０．０１）。提示鼻咽癌患者细胞免疫功能低下,放射治疗可进一步抑制鼻咽癌患者的细胞免疫功能。     

金黄色葡萄球菌L型和人乳头瘤病毒与宫颈癌关系的研究

应用改良革兰氏染色和免疫组化染色（ＡＢＣ法）,对２７０例宫颈癌和３３例慢性宫颈炎进行了研究。结果发现,宫颈癌革兰氏染色切片中细菌Ｌ型感染率（７５．１％）明显高于慢性宫颈炎（４５．５％）（Ｐ＜０．０５）,金黄色葡萄球菌Ｌ型抗原阳性率（７６．２％）明显高于人乳头瘤病毒（ＨＰＶ）抗原阳性率（５７．１％）。Ｌ型、ＨＰＶ混合感染率为４２．８％。上述结果表明宫颈癌中金葡菌Ｌ型与ＨＰＶ感染均常见,尤其金葡菌Ｌ型感染更为多见;金葡菌Ｌ型与ＨＰＶ感染的致病特征相似,两者均有不同程度的空泡细胞出现。提示金葡菌Ｌ型感染可能也是宫颈癌的致癌重要因素之一。     

Inhibition of the NADH oxidase activity of plasma membranes isolated from xenografts and cell lines by the antitumor sulfonylurea,N-(4-methylphenylsulfonyl)-N′-(4-chlorophenyl)urea (LY 181984) correlates with drug susceptibility of growth

Summary Inhibition of NADH oxidase activity of plasma membranes isolated from a series of human xenografts and cell lines by the antitumor sulfonylurea, N-(4-methylphenylsulfonyl)-N-(4-chlorophenyl) urea (LY 181984), correlated with the ability of the sulfonylurea to inhibit cell growth. Growth of rat kidney cells either untransformed or transformed with Kirsten-ras (K-ras) were unaffected by the sulfonylurea. Similarly, the NADH oxidase activity of isolated plasma membranes from K-ras transformed cells was unaffected by LY 181984. In contrast, when transformed with Harvey-ras (H-ras), both growth and NADH oxidase activity were inhibited. With the inactive but structurally related LY 181985 (N-4-methylphenyl-sulfonyl)-N-(phenyl)urea), neither growth nor plasma membrane NADH oxidase activity of either sulfonylurea-susceptible or -resistant tissues or cell lines was inhibited. Both sulfonylureas were inactive with rat liver plasma membranes but NADH oxidase activity of plasma membranes and growth with HeLa cells was inhibited by the active (LY 181984) but not by the inactive (LY 181985) sulfonylurea. The findings suggest a possible correlation between inhibition of plasma membrane NADH oxidase activity by the antitumor sulfonylureas and their oncolytic action.