前列腺健康指数在PI-RADS 评分3分前列腺癌患者中的应用价值

目的:探讨前列腺健康指数(PHI)和前列腺健康指数密度(PHID)在PI-RADS评分3分前列腺癌诊断中的应用价值。方法:收集我院在2018年11月—2022年9月行前列腺穿刺术的112例PI-RADS v2评分为3分的患者病例资料。并将患者分为前列腺癌组(47例)和前列腺良性病变组(65例)。术前检测血清tPSA和PSA同源异构体2(p2PSA),并计算前列腺特异抗原密度(PSAD)、PHI和PHID。采用ROC曲线评估各参数在PI-RADS评分3分前列腺癌诊断中效能。结果:前列腺癌组p2PSA、PHI、PSAD、PHID相较于良性病变组均明显增高(P均<0.05)。ROC曲线分析结果显示,PHID、PHI、PSAD和p2PSA诊断前列腺癌的AUC分别为0.808、0.781、0.731、0.725,相较于tPSA(AUC=0.605)均有统计学差异(P均<0.05)。PHID、PHI、PSAD和p2PSA诊断临床有意义前列腺癌(csPCa)的AUC分别是:0.812、0.792、0.756、0.715,但只有PHID、PHI相较于tPSA有统计学上差异(P<0.001)。结论:与其他PSA衍生物相比,PHID和PHI在PI-RADS评分3分人群中诊断前列腺癌或csPCa的准确性上更具优势。

基于Caspase-3/Bcl-2/Bax信号通路探究加味旋覆代赭汤治疗食管癌前病变的作用机制

目的:探究加味旋覆代赭汤对食管癌前病变大鼠Caspase-3/Bcl-2/Bax信号通路的调控作用机制。方法:将48只雄性SD大鼠随机分为4组,空白组、模型组、中药组、西药组,每组各12只。除空白组外均采用复合造模法制作食管癌前病变大鼠模型,造模成功后,分别进行药物灌胃干预,空白组、模型组用生理盐水灌胃,中药组和西药组分别给予加味旋覆代赭汤、西药(雷贝拉唑+莫沙必利)灌胃,给药8周取材。利用光学显微镜观察食管上皮组织的形态学变化;分别应用蛋白质印迹法(Western-blot)及聚合酶链式反应(PCR)检测食管上皮组织Caspase-3、Bcl-2及Bax的表达水平。结果:与空白组比较,模型组大鼠食管上皮病理积分升高(P<0.01);与模型组比较,中药组、西药组大鼠食管上皮病理积分均降低(P<0.01)。PCR及Western-blot检测结果显示,与空白组比较,模型组大鼠Caspase-3、Bax mRNA、蛋白表达均降低(P<0.01);与模型组比较,中药、西药组大鼠Caspase-3、Bax mRNA、蛋白表达均增高(P<0.05)。与空白组比较,模型组大鼠食管组织中Bcl-2 m RNA及蛋白表达水平均升高(P<0.05);与模型组比较,中药组和西药组Bcl-2 mRNA及蛋白表达水平均降低(P<0.05)。结论:加味旋覆代赭汤可能通过下调Bcl-2/Bax比值,增加线粒体外膜通透性,释放凋亡因子,激活Caspase-3,使病变组织发生凋亡,扭转食管上皮异型增生,从而起到治疗食管癌前病变的作用。

Expression of p-STAT3 and vascular endothelial growth factor in MNNG-induced precancerous lesions and gastric tumors in rats

AIM: To investigate the dynamic expression of p-signal transducer and activator of transcription 3(STAT3) and vascular endothelial growth factor(VEGF) in the formation of gastric tumors induced by drinking water containing N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) in Wistar rats.METHODS: One hundred and twenty Wistar rats were randomly divided into two groups(60 in each group): Control group and Model group. The rats in each group were then randomly divided into three groups(20 in each group): C/M15, C/M25 and C/M40(15, 25 and 40 represent the number of feeding weeks from termination). Rats in the control group received normal drinking water and rats in the model group received drinking water containing 100 μg/m L MNNG. Stomach tissues were collected at the end of the 15 th, 25 th and 40 th week, respectively, for microscopic measurement using hematoxylin and eosin staining. The expression of p-STAT3 and VEGF in different pathological types of gastric tissue, including normal, inflammation, atrophy, hyperplasia and gastric stromal tumor, was observed by immunohistochemistry and Western blot, and the corelation between p-STAT3 and VEGF was analyzed. RESULTS:(1) The expression of p-STAT3 in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor were significantly increased in the model group compared with the control group(2.5 ± 1.0, 2.75 ±0.36, 6.2 ± 0.45, 5.67 ± 0.55 vs 0.75 ± 0.36, P = 0.026, 0.035, 0.001, 0.002, respectively); the expression of p-STAT3 in tissue with dysplasia was higher than that in samples with gastritis or atrophy(6.2 ± 0.45 vs 2.5 ± 1.0, P = 0.006; 6.2 ± 0.45 vs 2.75 ± 0.36, P = 0.005, respectively); however, the expression of p-STAT3 in gastritis and atrophy was not significantly different(P > 0.05);(2) the expression of VEGF in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor was significantly increased in the model group compared with normal gastric mucosa; and the expression of VEGF in tissue with dysplasia was higher than that in tissue with inflammation and atrophy(10.8 ± 1.96 vs 7.62 ± 0.25, P = 0.029; 10.8 ± 1.96 vs 6.26 ± 0.76, P = 0.033, respectively); similarly, the expression of VEGF in tissue with gastritis and atrophy was not significantly different(P > 0.05); and(3) the expression of VEGF was positively correlated with p-STAT3. CONCLUSION: p-STAT3 plays an important role in gastric cancer formation by regulating the expression of VEGF to promote the progression of gastric tumor from gastritis.

Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions

BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.

Significance and relationship between Cripto-1 and p-STAT3 expression in gastric cancer and precancerous lesions

AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal meta-plasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were signifi cantly higher in GC with lymphnode metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relation-ship between CR-1 and p-STAT3 expressions in GC (rk = 0.189, P = 0.002).CONCLUSION: The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.

Relatively Increased Number of Liver Foxp3^+ Regulatory T Cells against Hepatic Lesions in Murine Lupus

Systemic lupus erythematosus（SLE） is a multiple organ autoimmune disorder,including the liver,but the possible reason in impairment in the liver is still unclear.Our present study assessed alterations of transcription factor Foxp3＋ regulatory T cells（Tregs） and several other immune molecules [programmed cell death 1 and its ligand（PD1 and PD-L1）,and interleukin 10（IL-10） and transform growth factor β（TGF-β）] in the liver and other major organs of lupus-prone BXSB mice by flow cytometry,real-time quantitative reverse transcription PCR,and enzyme-linked immunosorbent assay.Results showed that both frequency and number of Foxp3＋ Tregs were dramatically reduced in the thymus,spleen and kidney of the BXSB mice（P0.05）,but those in the liver were kept in nearly normal range,when compared to negative control C57BL/6 mice.In comparison to control mice,the mRNA levels of Foxp3,PD1 and PD-L1 were significantly decreased in the kidneys of BXSB mice（P0.05）,but there was no significant difference in the livers of the BXSB mice（P0.05）.Protein levels of IL-10 and TGF-β in serum showed no significant difference between BXSB and C57BL/6 mice,but were significantly increased in the kidneys and livers of BXSB mice as compared with those in C57BL/6 mice（P0.05）.These results suggest that reduced Foxp3＋ Tregs are involved in the pathogenesis of SLE in BXSB mice,and relatively higher number of these cells in the livers than in the other target organs could constitute a protective mechanism against hepatic lesions in lupus-prone mice,which may provide insights into development of new therapeutic approaches in SLE patients.

PillCam~ SB3 capsule: Does the increased frame rate eliminate the risk of missing lesions?

Since its emergence in 2000, small bowel capsule endoscopy(SBCE) has assumed a pivotal role as an investigation method for small bowel diseases. The PillCam SB2-ex offers 12 h of battery time, 4 more than the previous version(SB2). Rahman et al recently found that the PillCam SB2-ex has a significantly increased completion rate, although without higher diagnostic yield, compared with the SB2. We would like to discuss these somewhat surprising results and the new potentialities of the PillCam SB3 regarding the diagnostic yield of small bowel studies. PillCam SB3 offers improved image resolution and faster adaptable frame rate over previous versions of SBCE. We recently compared the major duodenal papilla detection rate obtained with PillCam SB3 and SB2 as a surrogate indicator of diagnostic yield in the proximal small bowel. The PillCam SB3 had a significantly higher major duodenal papilla detection rate than the PillCam SB2(42.7% vs 24%, P = 0.015). Thus, the most recent version of the PillCam capsule, SB3, may increase diagnostic yield, particularly in the proximal segments of the small bowel.

PSADR、DPC及TSRP在PI-RADS评分3分前列腺穿刺患者中的应用价值

目的研究前列腺特异性抗原(PSA)周下降速率(PSADR)、前列腺塌陷程度(DPC)及前列腺组织信号比(TSRP)与前列腺影像报告和数据系统(PI-RADS)评分相结合在前列腺癌(PCa)与前列腺炎性疾病鉴别诊断中的价值。方法回顾性分析74例PSA>10 ng/mL的前列腺穿刺患者的临床资料,根据病理结果分为PCa组与前列腺炎性疾病组。以最新PI-RADS V2.1评分为基础,采用双参数MRI(bp MRI)评分方案对研究对象的MRI图像进行评分。选出PI-RADS评分为3分的患者,收集其PSADR、DPC及TSRP协助诊断。最后,将诊断结果与最终的病理结果相对比,寻求PSADR、DPC及TSRP与PI-RADS评分相结合在PCa与前列腺炎性疾病鉴别诊断中的价值。结果在所有患者中,PI-RADS评分为3分者共有25例,其中11例为PCa,14例为前列腺炎性疾病。对于PI-RADS评分为3分的患者,当结合PSADR、DPC及TSRP时,PCa的诊断敏感性为81.82%,诊断特异性为92.86%。结论PSADR、DPC和TSRP相结合可被用于PI-RADS评分3分患者前列腺穿刺前的炎性疾病与癌的鉴别,减少不必要的前列腺穿刺。

高危型人乳头瘤病毒感染患者宫颈脱落细胞JAM3/PAX1高甲基化诊断宫颈高级别病变

目的:传统的宫颈癌筛查手段——高危型人乳头瘤病毒(high-risk human papillomavirus,hrHPV)和宫颈脱落细胞学检测存在局限性。本研究通过检测宫颈脱落细胞中连接黏附分子3(junctional adhesion molecule 3,JAM3)/配对盒基因1(paired box gene 1,PAX1)高甲基化水平,并将其与液基薄层细胞学(liquid based cytology,LBC)进行比较,评价JAM3/PAX1甲基化对于宫颈高级别病变的诊断能力,以探索新的宫颈高级别病变的诊断模式,实现宫颈高级别病变“精准筛查”的目的。方法:回顾性收集2021年6月至2022年6月在中南大学湘雅三医院妇科阴道镜门诊接受检查的患者共136例,包括宫颈非高级别病变122例,高级别病变14例。研究的变量包括:基本临床信息(年龄、体重指数、是否绝经)、LBC、hrHPV、宫颈组织病理、阴道微生态结果、阴道镜结果(宫颈转化区类型)、JAM3(ΔCtJ)和PAX1(ΔCtP)基因甲基化的ΔCt值。首先通过logistic回归分析筛选影响宫颈高级别病变的影响因素,并进行相关性分析,然后用差异有统计学意义的变量构建条件推断树模型。结果:Logistic回归分析提示高级别宫颈病变组与非高级别宫颈病变组的PAX1与JAM3基因甲基化ΔCt值以及LBC检测结果差异均有统计学意义(均P<0.05)。相关性分析发现,宫颈病理结果与ΔCtP(r=-0.360,P<0.001)、ΔCtJ(r=-0.448,P<0.001)、LBC(r=-0.305,P<0.001)、菌群多样性(r=-0.183,P=0.037)呈负相关。条件推断树显示:当ΔCtJ>10.13时,全部为宫颈非高级别病变的患者;当ΔCtP>6.22时,非高级别病变的患者有117例,占97.5%,高级别病变者仅3例,占2.5%。ΔCtJ>8.61且LBC为不明确的非鳞状上皮细胞(atypical squamous cell of undetermined significance,ASC-US)或未见上皮内病变细胞时,105例(99.1%)为宫颈非高级别病变的患者,仅1例(0.9%)检出为高级别病变;当LBC结果为高级别病变时,仅9例患者检出高级别病变,3例检出非高级别病变;而当LBC提示低级别病变、ASC-US、未见上皮内病变细胞,且ΔCtP>6.22时,有117例(97.5%)的患者检出非高级别病变。结论:在人乳头瘤病毒感染妇女中,JAM3/PAX1双基因甲基化检测可独立应用于宫颈高级别病变/非高级别病变的分层诊断,且不依赖于宫颈脱落细胞学检测结果;亦可与LBC联合使用以弥补LBC敏感度低的缺点。此外,未来将甲基化试剂盒应用于大规模宫颈癌筛查,有利于发现更多宫颈高级别病变患者,并达到早筛、早治宫颈病变/癌的目的。

黄芪莪术药对调控Akt/FoxO3a信号通路对胃癌前病变的影响研究

目的 基于蛋白激酶B(Akt)/叉头状转录因子O亚族3(FoxO3a)通路探究黄芪-莪术药对逆转胃癌前病变的机制。方法 取48只雄性Wistar大鼠,随机选择12只作为正常组,其余大鼠采用甲基硝基亚硝胍(MNNG)复合造模法建立胃癌前病变模型。将造模成功的大鼠随机分为模型组、黄芪-莪术组、叶酸组,每组10只。正常组和模型组给予蒸馏水灌胃,黄芪-莪术组给予黄芪-莪术水煎浓缩液3.6 g/kg灌胃,叶酸组给予叶酸1.8 mg/kg灌胃,均1次/d,连续灌胃10周。观察大鼠日常生活情况、体重、精神状态,HE染色观察胃黏膜组织病理形态,RT-PCR法检测胃组织中Akt1、FoxO3a、Beclin1、LC3-Ⅱ、p62 mRNA表达情况,Western blot法检测胃组织中Akt1、FoxO3a、LC3-Ⅰ/Ⅱ蛋白表达情况。结果 与正常组比较,模型组大鼠体重、食量、活力下降,精神变差;胃黏膜见腺体增大,腺体间细胞增生,少量炎症细胞浸润;胃组织中Akt1、p62 mRNA相对表达量和Akt1、LC3-Ⅰ/Ⅱ蛋白相对表达量均明显升高(P均<0.05),Beclin1、FoxO3a、LC3-ⅡmRNA相对表达量和FoxO3a蛋白相对表达量均明显降低(P均<0.05)。与模型组比较,黄芪-莪术组和叶酸组大鼠精神、食量及活力均有好转;胃黏膜腺体细胞排列较为整齐紧密,未见出血、炎症细胞浸润;胃组织中Akt1、p62 mRNA相对表达量和Akt1、LC3-Ⅰ/Ⅱ蛋白相对表达量均明显降低(P均<0.05),Beclin1、FoxO3a、LC3-ⅡmRNA相对表达量和FoxO3a蛋白相对表达量均明显升高(P均<0.05)。结论 黄芪-莪术药对可一定程度逆转大鼠胃癌前病变,其可能是通过影响Akt/FoxO3a信号通路,激活增强体内自噬系统从而清除胃癌前病变细胞实现的。

CHI3L1在川崎病样血管炎小鼠模型冠状动脉损伤中的作用及机制研究

目的探究壳多糖酶3样蛋白1(chitinase-3-like protein 1,CHI3L1)在川崎病(Kawasaki disease,KD)样血管炎小鼠模型冠状动脉损伤中的作用及其潜在机制。方法将4周龄雄性SPF级C57BL/6小鼠随机分为正常对照组和模型组,每组10只。模型组小鼠通过腹腔注射干酪乳杆菌细胞壁提取物(lactobacilluscaseicell wall extract,LCWE)0.5 mL构建KD样血管炎小鼠模型,对照组腹腔注射等量的生理盐水。注射后第3天、第7天和第14天观察小鼠的一般情况。采用苏木精-伊红染色法观察冠状动脉组织病理学变化。采用酶联免疫吸附法检测小鼠血清中CHI3L1水平。采用免疫荧光染色法检测CHI3L1、血管性血友病因子(von Willebrand factor,vWF)、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)在冠状动脉组织中的表达及定位。采用Western blot法检测冠状动脉组织中CHI3L1、vWF、血管内皮钙黏蛋白(vascular endothelial cadherin,VE cadherin)、半胱天冬酶-3(Caspase-3)、B细胞淋巴瘤-2(B cell lymphoma-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)、核转录因子κB(nuclear factor-κB,NF-κB)及磷酸化NF-κB(p-NF-κB)表达情况。结果模型组小鼠血清中CHI3L1含量较对照组明显升高(P<0.05)。与对照组相比,模型组小鼠冠状动脉组织中CHI3L1表达高于对照组,vWF表达低于对照组。模型组小鼠CHI3L1、Bax、Caspase-3、NF-κB及p-NF-κB蛋白相对表达量明显高于对照组(P<0.05)。模型组vWF、VE cadherin和Bcl-2蛋白相对表达量低于对照组(P<0.05)。结论LCWE诱导的KD样血管炎小鼠模型中,血清及冠状动脉CHI3L1的表达水平升高,可能通过炎性反应介导血管内皮细胞凋亡在冠状动脉损伤中发挥作用。

宫颈癌组织中BAG3蛋白表达水平及意义

目的分析Bcl-2相关抗凋亡基因3(BAG3)在宫颈癌组织中的表达水平及意义。方法选取2016年10月至2018年10月该院收治的201例研究对象的宫颈组织标本为研究对象,其中宫颈癌组织标本70例(宫颈癌组)、低级别鳞状上皮内瘤变(LSIL)组织标本46例(LSIL组)、高级别鳞状上皮内瘤变(HSIL)组织标本50例(HSIL组)和宫颈正常组织标本35例(正常组)。采用免疫组织化学染色法检测所有标本组织中BAG3蛋白表达水平,分析不同临床病理特征宫颈癌患者BAG3蛋白表达差异,采用多因素Cox回归分析影响宫颈癌患者预后的因素。结果BAG3蛋白在宫颈癌组中的高表达率>HSIL组>LSIL组>正常组(P<0.05);低分化、淋巴结转移宫颈癌患者的BAG3蛋白高表达率分别高于高/中分化、无淋巴结转移患者(P<0.05);70例宫颈癌患者3年生存率为60.00%,K-M生存曲线显示BAG3高表达患者3年生存率低于BAG3低表达患者,差异有统计学意义(Log-rankχ^(2)=4.821,P=0.023)。不同分化程度、有无淋巴结转移、不同BAG3蛋白表达水平的宫颈癌患者3年生存率差异有统计学意义(P<0.05)。多因素Cox分析结果显示,低分化、有淋巴结转移、BAG3蛋白高表达均是影响宫颈癌患者预后的独立危险因素(P<0.05)。结论BAG3蛋白在宫颈癌组织中呈高表达,其表达水平与宫颈癌分化程度、淋巴结转移有关,BAG3蛋白高表达是宫颈癌预后的危险因素,有望作为诊治宫颈癌的有效生物标志物。

CXCL11和CXCR3在宫颈癌患者中的表达及其与高危型人乳头状瘤病毒感染的关系

目的探讨宫颈癌患者CXC趋化因子配体11(CXCL11)、CXC趋化因子受体-3(CXCR3)表达及其与高危型人乳头状瘤病毒(HR-HPV)感染的关系。方法选取2019年5月至2022年5月该院诊治的宫颈癌患者75例为宫颈癌组,宫颈上皮内瘤变(CIN)患者78例为CIN组,宫颈炎患者52例为宫颈炎组。采用免疫组化法测定宫颈病变组织CXCL11、CXCR3表达,检测患者HR-HPV感染情况,分析CXCL11、CXCR3表达与HR-HPV感染的关系。结果宫颈癌组宫颈病变组织CXCL11、CXCR3阳性表达率及HR-HPV阳性感染率分别为85.33%、80.00%、90.67%,高于宫颈炎组的15.38%、11.54%、13.46%及CIN组的52.56%、50.00%、62.82%,差异均有统计学意义(P<0.05);CIN组CXCL11、CXCR3阳性表达率及HR-HPV阳性感染率高于宫颈炎组(P<0.05)。宫颈癌患者宫颈病变组织CXCL11、CXCR3表达及HR-HPV感染与淋巴结转移、分化程度有关(P<0.05)。宫颈癌患者中HR-HPV感染共68例,其中单一感染率为38.24%,多重感染率为61.76%;多重感染HR-HPV类型患者宫颈病变组织CXCL11、CXCR3阳性表达率高于单一感染HR-HPV类型患者(P<0.05)。宫颈癌患者宫颈病变组织CXCL11、CXCR3表达与HR-HPV感染有关(P<0.05);宫颈癌患者宫颈病变组织CXCL11表达与CXCR3有关(P<0.05)。结论CXCL11、CXCR3在CIN及宫颈癌患者的宫颈病变组织中表达较高,二者在宫颈癌患者中表达最高,CXCL11、CXCR3与HR-HPV感染相关,其可能是宫颈癌的治疗靶标。

Effect of hTERC and FOXP3 gene magnification in condyloma acuminate lesion on the immune response and cell apoptosis

Objective:To study the effect of hTERC and FOXP3 gene amplification in condyloma acuminate lesions on the immune response and cell apoptosis.Methods:The condyloma acuminate lesions diagnosed between May 2014 and October 2016 and the normal skin tissue from circumcision during the same period were collected to extract RNA and then determine hTERC, FOXP3 and apoptosis-related gene mRNA amplification, and after protein extraction, the protein levels of immune response-related cytokines were determined.Results:hTERC, FOXP3, Livin and Survivin gene mRNA amplification as well as IL-4 and IL-10 protein levels in condyloma acuminatum lesions were significantly higher than those in normal skin tissue while TRAIL, Caspase-3 and PDCD4 mRNA amplification as well as IL-2 and TNF-α protein levels were significantly lower than those in normal skin tissue;IL-2 and TNF-α protein levels in condyloma acuminatum lesions with high FOXP3 mRNA expression were significantly lower than those in condyloma acuminatum lesions with low FOXP3 mRNA expression while IL-4 and IL-10 protein levels were significantly higher than those in condyloma acuminatum lesions with low FOXP3 mRNA expression;Livin and Survivin mRNA amplification in condyloma acuminatum lesions with high hTERC mRNA expression were significantly higher than those in condyloma acuminatum lesions with low hTERC mRNA expression while TRAIL, Caspase-3 and PDCD4 mRNA amplification were significantly lower than those in condyloma acuminatum lesions with low hTERC mRNA expression.Conclusion:Highly expressed hTERC and FOXP3 genes in condyloma acuminatum lesions can inhibit apoptosis and inhibit antiviral immune response respectively.

B淋巴细胞瘤-2关联永生基因3蛋白、多重肿瘤抑制基因1在宫颈癌癌前病变中表达及联合液基细胞学检查的临床意义

目的研究B淋巴细胞瘤-2关联永生基因3(BAG3)蛋白、多重肿瘤抑制基因1(P16)在宫颈癌癌前病变中表达及联合液基细胞学检查的临床意义。方法选择绵阳市中心医院2015年6月至2017年6月在妇科门诊筛查并确诊的120例宫颈病变病人为研究对象,根据其病变情况分为两组,其中癌前病变组病人69例,宫颈癌组病人51例。对比两组病人的BAG3、P16水平,将不同严重程度宫颈癌癌前病变病人的BAG3、P16水平进行比较,分析联合检测效能。结果宫颈癌组病人的BAG3(2.74±0.37)水平、P16(1.45±0.38)水平显著高于癌前病变组BAG3(1.70±0.51)、P16(0.53±0.16),差异有统计学意义(P<0.05)。不同严重程度宫颈癌癌前病变病人的BAG3和P16水平差异有统计学意义(P<0.05),其中宫颈上皮内瘤变Ⅰ级(CINⅠ)组的BAG3(1.01±0.24)水平低于CINⅡ组BAG3(1.78±0.79)和CINⅢ组的BAG3(2.33±0.88),且CINⅡ组低于CINⅢ组,差异有统计学意义(P<0.05);CINⅠ组的P16(0.21±0.06)水平低于CINⅡ组P16(0.45±0.10)和CINⅢ组的P16(0.72±0.17)水平,且CINⅡ组低于CINⅢ组,差异有统计学意义(P<0.05)。联合诊断对于宫颈癌的诊断特异度显著高于单独检测,差异有统计学意义(P<0.05)。通过ROC曲线分析结果发现联合检测对于宫颈癌癌前病变的诊断ROC曲线下面积显著高于单独检测(P<0.05)。结论随着宫颈癌前病变的进展,P16、BAG3表达增加,BAG3蛋白、P16联合液基细胞学检查对于病人的诊断具有积极的意义。

增强多层螺旋CT与3.0T MRI检查在肝脏占位性病变临床诊断中的应用价值

目的:分析增强多层螺旋CT与3.0T MRI检查在肝脏占位性病变临床诊断中的应用价值.方法:选取2020年3月至2022年3月河南科技大学第一附属医院收治的89例肝脏占位性病变患者为研究对象.根据不同的诊断方法,将其分为观察组(n=46,3.0T MRI检查)和对照组(n=43,增强CT检查).分析两组影像学图像表现及诊断价值,比较两组的不良反应及受检者耐受情况.结果:以术后切除组织的病理学检查结果为金标准,两组漏诊率比较,差异无统计学意义(P>0.05);观察组的诊断符合率高于对照组,误诊率低于对照组,差异均有统计学意义(P<0.05).观察组不良反应发生率及视觉模拟评分(VAS),均低于对照组,差异均有统计学意义(P<0.05).结论:增强多层螺旋CT与3.0T MRI检查,在肝脏占位性病变诊断中的应用效果均较为显著,但3.0T MRI检查的诊断符合率及安全性更高.

A network lightweighting method for difficult segmentation of 3D medical images

Currently,deep learning is widely used in medical image segmentation and has achieved good results.However,3D medical image segmentation tasks with diverse lesion characters,blurred edges,and unstable positions require complex networks with a large number of parameters.It is computationally expensive and results in high requirements on equipment,making it hard to deploy the network in hospitals.In this work,we propose a method for network lightweighting and applied it to a 3D CNN based network.We experimented on a COVID-19 lesion segmentation dataset.Specifically,we use three cascaded one-dimensional convolutions to replace a 3D convolution,and integrate instance normalization with the previous layer of one-dimensional convolutions to accelerate network inference.In addition,we simplify test-time augmentation and deep supervision of the network.Experiments show that the lightweight network can reduce the prediction time of each sample and the memory usage by 50%and reduce the number of parameters by 60%compared with the original network.The training time of one epoch is also reduced by 50%with the segmentation accuracy dropped within the acceptable range.

胃癌前病变及胃癌组织中survivin和caspase-3蛋白表达的意义

目的:检测survivin和caspase-3蛋白在胃癌前病变及胃癌组织中的表达情况,探讨其与胃黏膜癌变的关系及作用机制.方法:采用Envision免疫组化学二步法检测不同胃黏膜病变组织131例(包括慢性炎症44例、单纯肠化生31例,异型增生40例和胃癌16例)中survivin和caspase-3蛋白的表达情况.结果:慢性炎症,单纯肠化生,异型增生和胃癌中的survivin蛋白阳性表达率分别为4.5%(2/44),51.6%(15/31),100.0%(40/40)和93.8%(15/16).胃癌组织和异型增生组survivin蛋白表达显著高于单纯肠化生组(P<0.05).胃癌survivin蛋白表达阳性组caspase-3蛋白表达(3/13,23.1%)显著低于survivin蛋白表达阴性组(2/3,66.7%,P<0.05).结论:胃癌survivin蛋白表达水平与异型增生相当,高于单纯肠化生,survivin可能通过阻抑caspase-3促进胃癌的演进.

冠心病患者冠状动脉病变程度与半乳糖凝集素-3水平的相关性分析

目的:探讨冠心病患者冠状动脉病变程度与血清半乳糖凝集素-3水平的关系。方法:选取于烟台毓璜顶医院就诊并行冠状动脉造影(CAG)的患者158例,根据冠状动脉狭窄程度分为冠心病组(至少有一支冠状动脉狭窄≥50%,n=120)和对照组(冠状动脉造影正常,n=38)。冠心病组根据病变血管数又分为单支病变患者(n=42),双支病变(包括左主干病变)患者(n=40),三支病变患者(n=38)。冠心病组根据Gensini积分的四分位数又分为第一四分位数亚组(积分≤18.5,n=30)、第二四分位数亚组(18.5<积分≤45.0,n=30)、第三四分位数亚组(45<积分≤71.5,n=30)、第四四分位数亚组(积分>71.5,n=30)。通过病变血管数及Gensini积分评估冠状动脉病变程度。结果:冠心病组血清半乳糖凝集素-3水平显著高于对照组[中位数(四分位数)为10.66 ng/ml(5.81 ng/ml,16.17 ng/ml)vs 1.83 ng/ml(1.14 ng/ml,2.52 ng/ml),P<0.01]。随着病变血管数增加,血清半乳糖凝集素-3水平增加,不同病变血管数间差异均有统计学意义(P均<0.01)。根据Gensini积分四分位数分组,随着Gensini积分升高,血清半乳糖凝集素-3水平升高,除三、四四分位数亚组间差异无统计学意义外,其余各亚组间差异均有统计学意义(P均<0.01)。校正混杂因素后,偏相关分析表明,血清半乳糖凝集素-3水平与Gensini积分(R=0.17,P=0.04)和病变血管数(R=0.52,P<0.01)呈正相关。结论:血清半乳糖凝集素-3水平与冠状动脉病变严重程度呈正相关,提示半乳糖凝集素-3可能对冠状动脉粥样硬化的发生、发展存在潜在的不利影响。

TFF3在胃癌、癌前病变及胃腺瘤中的表达及其与血管生成的关系

目的:分析三叶因子3(TFF3)在不同胃黏膜病变中的表达及其与间质微血管密度(MVD)值的关系,探讨其在胃癌、癌前病变及胃腺瘤发生、发展中的作用.方法:应用免疫组织化学PV6000法检测20例正常胃黏膜、20例胃腺瘤、20例萎缩性胃炎伴肠化生、20例不典型增生、40例胃癌组织中TFF3的表达,同时检测MVD值,以抗CD34标记.结果:TFF3在胃腺瘤、萎缩性胃炎伴肠化生、不典型增生和胃癌各组表达均高于正常组(50.0%,65.0%,70.0%,57.5% vs 5.0%,均P<0.01).胃癌MVD值高于正常胃黏膜、胃腺瘤、萎缩性胃炎伴肠化生和不典型增生(30.65±6.04 vs 14.87±3.06,22.33±3.78,23.16±3.20,25.22±4.66,均P<0.01),各组MVD值均高于正常胃黏膜组(均P<0.01).TFF3表达和MVD值与胃癌淋巴结转移和分期有关(均P<0.05),MVD值还与胃癌浸润深度有关(P<0.05).TFF3阳性表达组的MVD值明显高于TFF3阴性组(34.53±4.45 vs 25.39±3.25,P<0.01).结论:TFF3可能是胃黏膜癌变过程中的早期分子事件,在胃黏膜癌变和癌变后的恶性演进过程中起作用,对胃癌早期诊断和预测胃癌发生转移可能具有重要的提示作用.