人乳头瘤病毒与食管鳞状上皮细胞不典型增生及癌变相关性的研究

人乳头瘤病毒 (ＨＰＶ)易侵犯人鳞状上皮细胞 ,近年来有研究报道 ,食管鳞状细胞癌组织存在ＨＰＶ(尤其是ＨＰＶ16 )的感染 ,推测ＨＰＶ可能在食管鳞状细胞癌的发生过程中起一定的作用[1 3 ] ,而另一些研究未发现ＨＰＶ的感染 ,故否定上述观点[4 ,5] 。本研究应用ＰＣＲ结合核酸分子杂交放射性自显影检测方法 ,对食管良恶性病变组织中ＨＰＶ 16和ＨＰＶ18的感染进行检测 ,探讨ＨＰＶ在食管黏膜不典型增生及食管癌发生中的作用及其相互之间的关系。一、材料与方法1.标本 :收集本院 34 8例经甲醛固定、石蜡包埋的食管组织标本 ,均经病理学证实 …     

HPV E6/E7 mRNA检测用于绝经后未明确诊断意义的不典型鳞状上皮细胞分流筛查的价值

目的 评估人乳头瘤病毒(HPV)E6/E7 mRNA检测在绝经后未明确诊断意义的不典型鳞状上皮细胞(ASCUS)分流筛查中的诊断效能.方法 收集液基细胞学结果为ASCUS的绝经后患者196例,收集子宫颈管、子宫颈移行带及子宫颈表面的细胞,分别行子宫颈高危人乳头状瘤病毒(HR-HPV)DNA、HPV E6/E7 mRNA...     

宫颈非典型鳞状上皮细胞、人乳头状瘤病毒联合宫颈多点活检及宫颈管搔刮诊断老年宫颈疾病的价值

目的通过对宫颈细胞学检查结果为非典型鳞状上皮细胞(ASU-US)的中老年患者进行人乳头状瘤病毒(HPV)联合宫颈多点活检及宫颈管搔刮(ECC)检查的诊断价值。方法系统性回顾分析≥55岁的262例宫颈ASCUS患者的液基细胞学、高危型HPV定量检测(HC2-HPV DNA)、阴道镜检查和组织病理学检查资料。结果组织病理学确诊情况,良性病变177例(67.56%)、宫颈上皮内瘤变(CIN)Ⅰ38例(14.5%)、CINⅡ18例(6.87%)、CINⅢ23例(8.78%)和浸润性癌6例(2.29%)。相应的HC2-HPV DNA阳性率分别为9.6%(17/177),55.26%(21/38),88.89%(16/18),95.45%(21/23)和100%(6/6)。ECC所得的组织病理学为高级别鳞状上皮内病变(HSIL)6例,而对应患者活检完整组织块病理学结果分别为低级别鳞状上皮内病变(LSIL)和良性病变。HPV阳性组≥CINⅡ的检出率53.09%(44/81),阴性组为0(0/181),二者差异有统计学意义(P<0.05)。结论宫颈细胞学检查为ASC-US的患者中存在不小比例的HSIL(CINⅡ和CINⅢ),甚至浸润性癌。阴道镜下宫颈活检+宫颈管搔术有助于诊断,防止漏诊。对ASC-US患者及时进行HC2-HPV DNA检测,可作为ASC-US患者的分流手段,并采取规范诊疗措施能有效地发现潜在的HSIL或浸润性癌病变。     

人食管鳞状细胞癌标本中乳头状瘤病毒DNA的检测

目的食管鳞状细胞癌有明显的地域性差异,它的发生与遗传、环境、饮食和某些微生物的感染有密切的关系,本研究通过检测食管鳞状细胞癌和相应正常食管组织中HPV-11型和HPV-16型的DNA,阐明HPV与食管鳞状细胞癌的关系.方法用PCR的方法检测22位食管鳞状细胞癌患者手术切除的癌组织和相应癌旁正常食管粘膜(共44例标本)中的HPV-11型和HPV-16型DNA的存在情况,并对其中一例HPV阳性肿瘤标本的HPV序列进行测定. 结果在本组所涉及的22位患者共计44例标本中,对于HPV-11型,12例癌组织为阳性;有7例癌旁组织为阳性;癌组织和癌旁组织均为阳性的有6例.对于HPV-16型,6例癌组织为阳性;6例癌旁组织为阳性;癌组织和癌旁组织均为阳性的有3例.序列分析结果表明所测定的序列与GeneBank登录的NC001525.1(HPV-11)、M14119.1(HPV-11)和AF217526.1(HPV-11)的同源性极高,均为99%.结论通过实验结果分析,我们认为食管鳞状细胞癌与HPV-11型和HPV-16型主要衣壳蛋白L1基因密切相关,HPV可能在一定的地域环境中与食管鳞状细胞癌的发生具有相关性.马群风,男,1961-01-04生,贵州省贵阳市人,汉族.1983年遵义医学院医疗系本科毕业,1993年第四军医大学普胸外科专业硕士毕业.主要从事普胸外科疾病的临床和研究工作.发表论文4篇项目负责人马群风,710038,陕西省西安市,中国人民解放军第四军医大学唐都医院胸外科.     

广西地区宫颈意义未明的非典型鳞状细胞患者临床病理特点研究

［摘要］　目的　比较广西地区宫颈液基细胞学诊断为意义未明的非典型鳞状细胞（ASCUS）的组织学诊断结果,寻找合理的ASCUS患者管理方法。方法　复习237例有组织病理学诊断的ASCUS患者临床病理资料。结果　237例患者年龄19～67岁,中位年龄41岁,48例为绝经后妇女。223例患者无临床症状。专科检查,108例宫颈光滑,105例宫颈糜烂,23例宫颈肥大。组织学诊断为宫颈黏膜慢性炎伴鳞状上皮单纯性增生及宫颈黏膜慢性炎伴腺上皮鳞化、宫颈尖锐湿疣、宫颈上皮内病变（CIN）Ⅰ级、CINⅡ及Ⅲ级、癌分别为121例（51.05%）、31例（13.08%）、54例（22.78%）、28例（11.80%）、3例（1.30%）。结论　广西地区ASCUS患者大部分无临床症状,对ASCUS患者建议做阴道镜检查,疑为CIN或肿瘤者同时取活检,及时发现高级别CIN和癌。     

食管鳞状细胞癌及不典型增生组织中 hMLH1基因蛋白表达的研究

目的 探讨在食管鳞状细胞癌及不典型增生组织中hMLH1基因的蛋白表达情况及其与食管鳞状细胞癌发生发展的关系。方法 40例食管鳞状细胞癌，相应40例正常组织及26例不典型增生组织，采用免疫组织化学方法，检测了hMLHI蛋白的表达情况。结果 在正常组织、小典跫增生组织、肿瘤组织中的阳性率分别为90％、57．6％和45％，不典型增生组织及肿瘤组织均低于正常组织（P〈0．05）。肿瘤组织中hMLH1蛋白表达阳性者年龄较阴性者大（P〈0．05）。结论 错配修复缺陷早期参与了食管鳞状细胞癌的发生过程；hMLH1蛋白可能抑制和延缓食管鳞状细胞癌的发生和浸润。     

人乳头瘤病毒基因型在宫颈细胞病变中的分布

目的探讨人乳头瘤病毒(HPV)感染在宫颈病变中的分布及其与宫颈病变之间的关系。方法用刷拭子法对1591例门诊就诊妇女采集宫颈细胞,用PCR-膜斑点杂交法进行HPV分型,薄层液基细胞学检查(TCT)观察宫颈细胞病理变化。结果在338例TCT检出宫颈病变的女性中,HPV和HR-HPV感染率分别高达68.64%和63.02%,HPV和HR-HPV感染率均随着宫颈病变级别递增而升高,差异有统计学意义(P<0.05)。除HPV51外,其它HR-HPV基因型和HPVCP8304在不同宫颈疾病组中具有极显著差异(P<0.01)。年龄≤40岁妇女HR-HPV和LR-HPV感染的机率显著高于年龄>40岁妇女(P<0.05);年龄>40岁妇女HPV感染罹患宫颈相关疾病的机会显著高于年龄≤40岁妇女(P<0.01)。结论 HR-HPV与宫颈病变关系密切,适龄妇女作HPV筛查对预防宫颈癌具有重要意义。     

扁桃体鳞状细胞癌中CK7 CK19和p16的表达关系研究

目的 分析细胞角蛋白7(CK7)、细胞角蛋白19(CK19)和p16INK4a蛋白(p16)在扁桃体鳞状细胞癌(TSCC)组织及癌周隐窝上皮和表面上皮中的表达关系,探讨其在人乳头状瘤病毒(HPV)感染相关扁桃体癌变机制中的作用.方法 选择2015-07～2018-01广西医科大学第一附属医院耳鼻喉头颈外科收治的17例T...     

维吾尔族妇女子宫颈癌及宫颈上皮内瘤变组织中micRNA-21表达及与人乳头瘤病毒的关系

目的探讨维吾尔族妇女宫颈上皮内瘤变(CIN)Ⅰ～Ⅲ级和子宫颈癌组织中miRNA-21的表达情况,并分析子宫颈癌中miRNA-21与人乳头瘤病毒(HPV)感染的关系。方法应用荧光定量RT-PCR技术和原位杂交技术检测维吾尔族妇女子宫颈鳞状细胞癌、CINⅠ～Ⅲ级病变组织中miRNA-21的表达情况,并对子宫颈鳞状细胞癌中miRNA-21与HPV感染情况进行相关性分析。结果 miRNA-21在宫颈鳞状细胞癌组织、CINⅢ级、Ⅰ和Ⅱ级病变组织中的相对表达量分别是8.19±1.96,5.19±1.75,3.78±0.81。在HPV16阳性和阴性病变中miRNA-21表达存在明显的统计学差异(4.62±0.74 vs 3.57±0.70,P=0.014)。结论 miRNA-21在子宫颈癌前病变以及维吾尔族妇女子宫颈鳞状细胞癌的发生、发展中起重要作用,并且与高危型HPV16感染相关联,因此,miRNA-21可被作为子宫颈鳞状细胞癌的早期筛查及早期诊断的分子指标之一。     

十堰地区妇女宫颈人乳头瘤病毒感染及基因亚型分布情况调查分析

目的:对十堰地区妇女宫颈(HPV)亚型进行筛查,以探讨其分布规律。方法:采用核酸分子快速导流杂交基因芯片技术,对1 116例妇科就诊患者的宫颈刷片标本进行了21种HPV基因分型检测。结果:1 116例样本中,HPV感染者283例,总感染率25.36%,高危型HPV感染率14.52%,低危型HPV感染率2.96%,高危型及低危型混合感染阳性率7.89%;单一基因型别195例,占阳性患者的68.91%;双重混合感染59例,占阳性患者的20.85%;三重以上混合感染者29例,占阳性患者的10.25%。HPV感染阳性率居前5位的高危亚型依次是HPV16型50例(4.48%)、HPV52型47例(4.21%)、HPV53型28例(2.51%)、HPV58型17例(1.52%)及HPV39型15例(1.34%),常见的低危型是HPV6(1.26%)和HPV42(1.26%)。结论:十堰地区妇女HPV感染率较高,且以高危型HPV感染为主,感染型别既符合亚洲及中国地区人群的分布规律,又有独特的区域分布特点,并且多重感染率高,值得重视。     

人乳头瘤病毒致宫颈癌细胞免疫逃逸机制探讨

目的探讨人乳头瘤病毒（HPV）感染与宫颈癌细胞免疫逃逸之间的关系,揭示HPV在宫颈癌发生、发展中的作用。方法以宫颈癌细胞系,宫颈癌组织及其相应的正常宫颈组织为材料,采用实时聚合酶链反应（PCR）检测HPV mRNA表达水平,采用流式细胞仪进行宫颈癌细胞表面C3b沉积检测。结果在30对配对组织中有26对肿瘤组织HPV表达高于配对的癌旁正常组织,C3b的沉积在HPV感染宫颈癌细胞组明显低于无感染组,尤以老年组变化更为明显,同时宫颈癌细胞的迁徙和侵袭能力在HPV感染组明显升高。结论HPV感染的宫颈癌组织通过抑制C3b的沉积而引发免疫逃逸,在宫颈癌的发生、发展中发挥重要作用。     

宫颈上皮内瘤变组织中高危型HPV DNA的检测及意义

目的探讨宫颈上皮内瘤变（CIN）患者高危型人乳头瘤病毒（HPV）的感染情况。方法采用PCR技术检测CIN患者病变组织中高危型HPVDNA。结果Ⅰ、Ⅱ、Ⅲ级CIN组织中HPVDNA检出率分别为53．85％、72．73％、96．97％,χ^2=25．762,P〈0．01。CIN患者存在多重HPV感染的情况,Ⅰ、Ⅱ、Ⅲ级CIN多重HPVDNA感染率不同。结论不同级别CIN的高危型HPV感染率不同,同时存在多重感染的情况。     

贵州地区宫颈上皮内瘤变和宫颈浸润癌患者HPV感染状态及其亚型分布

目的观察贵州地区宫颈上皮内瘤变（CIN）和宫颈浸润癌患者人乳头状瘤病毒（HPV）的感染状态及其亚型分布。方法采用导流杂交技术对30例CIN（CIN组）、33例宫颈浸润癌患者（宫颈癌组）、60例自愿接受宫颈HPV感染筛查的妇女（对照组）进行HPV分型检测,所有受检者均来自贵州地区。结果 CIN组HPV阳性13例（43.33%）,宫颈癌组19例（57.58%）,对照组5例（8.33%）。CIN组、宫颈癌组与对照组比较,P均〈0.01。CIN组共检出7种亚型HPV,均为高危型（HR-HPV）,无多型HPV感染（M-HPV）。其中HPV16 7例,HPV31、52各2例,HPV18、33、53、58各1例。宫颈癌组检出5种亚型,亦均为HR-HPV,M-HPV3例。其中HPV16 11例,HPV534例,HPV58 3例,HPV18、59各1例。对照组检出7种亚型,HR-HPV中的HPV16、18、31、39、53、58和低危型HPV的HPV6各1例;M-HPV 1例。CIN组、宫颈癌组HPV16感染率明显高于对照组,P均〈0.05。HR-HPV感染与CIN（OR=8.412,95%CI为2.62~26.99）和宫颈浸润癌（OR=14.929,95%CI为4.74~46.98）紧密相关,且主要与HPV16感染有关（CIN：OR=17.957,95%CI为2.09~154.15;宫颈浸润癌：OR=29.500,95%CI为3.60~242.07）,P均〈0.05。结论贵州地区CIN和宫颈浸润癌与HR-HPV感染密切相关,HPV16为主要感染亚型。     

Acute effect of oestrogen replacement therapy on treadmill performance in postmenopausal women with coronary artery disease

The significant reduction in cardiovascular morbidity and mortalityfollowing oestrogen replacement therapy in postmenopausal womenis only partly explained by an improved lipid profile. Givenacutely, oestradiol causes vasodilatation and increases coronaryblood flow and, in large doses, improves treadmill performancein postmenopausal women with coronary artery disease. However,the significance of oestrogen-mediated vasodilatation is unknownsince the acute effects of oestradiol in doses and preparationscommonly used clinically have not been tested. The aim of thisstudy was to evaluate the acute effects of conventional replacementtherapy with 17 ß-oestradiol on treadmill performancein 16 postmenopausal women with angina in a randomized, double-blind,placebo-controlled cross-over trial. Following baseline treadmill testing a transdermal oestrogenpatch releasing 50 µg oestradiol. 24 h^–1 or matchingplacebo was applied and the exercise test repeated 24 h later.The patch was then removed. Seven to 14 days later the sequencewas repeated using the alternative patch. The changes in timeto angina, time to 1 mm ST segment depression and total exercisetime for each treatment compared with the corresponding baselinetest were calculated. Plasma 17 ß-oestradiol increased with active therapyfrom 56±30pmol. l^–1 to 204±90pmol. l^–1,indicating adequate replacement. Compared with their respectivebaseline exercise tests there were no differences between activeand placebo patches for time to angina (active: 13±55s vs placebo: 10±47 s), time to 1 mm ST segment depression(active: –30 ±52 s vs placebo: 24±71 s)or total exercise time (active: 14±45 s vs placebo: 13±35s). Despite the recognized acute vasodilator action of larger dosesof oestrogen, doses conventionally used in hormone replacementtherapy had no acute effect on treadmill performance in thisgroup of postmenopausal women with coronary artery disease.     

Significance of human papillomavirus 16/18 infection in association with p53 mutation in lung carcinomas

Introduction: The role of high‐risk human papillomavius (HPV) 16/18 in the development of lung cancer has recently been explored, and p53 mutation is a finding in lung cancer; however, its association with HPV infection is not well studied. Objectives: To investigate HPV 16/18 infection and p53 mutation in lung carcinomas and their association with tumor behavior. Methods and Results: We expanded our prior study to include 107 squamous cell carcinoma (SCC), 63 adenocarcinoma (AC) and 91 non‐cancer control cases of lung from a population of Western China. The results confirmed that HPV infection is more prevalent in SCC (59.8%) comparing with that of AC (17.5%) and the control cases (23.1%) (P < 0.001), and genotyping demonstrated predominant HPV 16/18 infection in the carcinomas and HPV 6 in the control cases. By immunohistochemistry, p53 mutation was detected in 67.3% of SCC and 60.3% of AC, in comparison with 9.9% in the control (P < 0.001). Within the group of SCC, the p53 mutation rate is significantly higher in those with HPV infection (78.1%) than that of the non‐infected carcinomas (51.2%, P = 0.004). However, this difference is not proven to be significant in the groups of AC and the controls. Clinicopathological analysis demonstrated that the coexistence of p53 mutation and HPV infection was associated with lymph node metastasis (P = 0.001) and high‐clinical TNM stage of SCC (P = 0.001). As there was no sequencing data, the evidence for HPV 16/18 E₆ induced p53 mutation is still indirect. Conclusion: This study indicates that p53 mutation and HPV 16/18 infection might coordinate in the development of lung squamous cell carcinomas, and their coexistence is associated with poor prognosis. Please cite this paper as: Yu Y, Yang A, Hu S, Zhang J and Yan H. Significance of human papillomavirus 16/18 infection in association with p53 mutation in lung carcinomas. Clin Respir J 2013; 7: 27–33.     

The prevalence and genotype distribution of human papilloma virus in cervical squamous intraepithelial lesion and squamous cell carcinoma in Taizhou,China

Human papillomavirus (HPV) infection is a common sexually transmitted disease worldwide and the leading cause of cervical cancer. Current vaccines do not cover all HPV genotypes whereas the distribution of HPV genotypes varies in different geographic regions. The study aimed to investigate the distribution of HPV genotypes in patients with cervical squamous intraepithelial lesion (SIL) and cervical squamous cell carcinoma (SCC) in Taizhou City of Jiangsu Province, China. A total of 940 patients including 489 cases with cervical low-grade squamous intraepithelial lesions (LSIL), 356 cases with cervical high-grade squamous intraepithelial lesions (HSIL), and 95 cases with cervical SCC, underwent a biopsy or surgery in Taizhou People''s Hospital between January 2019 and December 2019. The HPV testing results were retrospectively analyzed. The overall prevalence of any, high-risk, and low-risk HPV was 83.83%, 81.91%, and 12.13%, respectively. The 5 most common HPV genotypes were HPV16 (35.64%), HPV52 (16.91%), HPV58 (13.94%), HPV33 (8.94%), and HPV18 (7.98%). The prevalence of any and HR-HPV in SCC was significantly higher than those in LSIL and HSIL, while the prevalence of LR-HPV in SCC was significantly lower than those in LSIL and HSIL (P < .01). Single and dual HPV infections were prevalent in SCC, LSIL, and HSIL. Furthermore, the prevalence of dual HPV infection in SCC was significantly higher than those in LSIL and HSIL (P = .002). The HPV prevalence varied by age, being highest among women with SCC, LSIL, and HSIL aged 40 to 49 years, 40 to 49 years, and 50 to 59 years, respectively. In conclusion, the findings revealed a very high prevalence of HPV in women with cervical lesions in Taizhou. Routine HPV tests must cover all common HPV genotypes in clinical practice.     

Differential effects of raloxifene and estrogen on insulin sensitivity in postmenopausal women

OBJECTIVES: To test the hypothesis that both raloxifene and estrogen would improve insulin sensitivity in postmenopausal women and that the magnitude of the effect would be similar for both drugs. DESIGN: Placebo-controlled, double-blind, randomized study. SETTING: The General Clinical Research Center of the University of Michigan Medical Center, a university hospital. PARTICIPANTS: Forty-four healthy postmenopausal women 73 +/- 7 years old (mean age +/- standard deviation) who were not receiving hormone replacement therapy. INTERVENTION: Eight weeks of drug therapy with randomization to raloxifene (n = 16), estrogen (n = 14), or placebo (n = 14). MEASUREMENTS: These subjects underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity (SI) and total and regional (central) body composition measurements by dual-energy x-ray absorptiometry at baseline and after 8 weeks of drug therapy. RESULTS: There were no statistically significant differences in age, body mass index, total or central fat mass, or SI between the three groups at baseline. The major outcome variable was SI. After 8 weeks of drug therapy, there was no significant change in SI in the placebo group or in the estrogen group and a significant decrease in SI in the raloxifene group, P =.003. CONCLUSION: In contrast to estrogen's ability to maintain insulin sensitivity, raloxifene decreases insulin sensitivity in healthy nondiabetic postmenopausal women. The clinical significance of this effect of raloxifene to impair insulin sensitivity in postmenopausal women warrants further evaluation in future studies.     

米索前列醇配伍利多卡因在绝经妇女取环术中的临床效果观察

目的探讨米索前列醇配伍利多卡因在绝经妇女取环术中的临床效果。方法对绝经半年以上宫内带无尾丝节育环要求取环的95例妇女随机分为2组：A组为试验组,B组为对照组。A组52例,在取环术前2 h给予阴道放置米索前列醇0.4 mg,术中予2%利多卡因5 ml宫颈注射;B组43例,术前2 h给予阴道放置安慰剂甲硝唑片400 mg,术中予2%利多卡因5 ml宫颈注射,术后应用数字模拟疼痛评分法（VAS）对疼痛程度（无痛0分,疼痛难忍10分）进行评估,且对2组手术效果进行比较观察。结果A组妇女取环成功率（98.1%）显著高于B组（83.7%）（P〈0.05）,手术时需扩张宫颈者显著少于B组（P〈0.05）,以及手术时疼痛程度也低于B组（P〈0.01）。结论绝经妇女取环术前给予阴道放置米索前列醇配伍2%利多卡因5 ml宫颈注射效果满意,值得临床推广使用。     

Identification of translocation products but not K-RAS mutations in memory B cells from patients with multiple myeloma

Background

Several laboratories have shown that cells with a memory B-cell phenotype can have the same clonotype as multiple myeloma tumor cells.

Design and Methods

The aim of this study was to determine whether some memory B cells have the same genetic alterations as their corresponding multiple myeloma malignant plasma cells. The methodology included sorting multiple myeloma or memory B cells into RNA stabilizing medium for generation of subset-specific polymerase chain reaction complementary DNA libraries from one or 100 cells.

Results

Cells with the phenotype of tumor plasma cells (CD38⁺⁺CD19⁻CD45^−/+CD56^−/+/++) or memory B cells (CD38⁻/CD19⁺/CD27⁺) were isolated by flow activated cell sorting. In samples from all four patients with multiple myeloma and from two of the three with monoclonal gammopathy of undetermined significance, we identified memory B cells expressing multiple myeloma-specific oncogenes (FGFR3; IGH-MMSET; CCND1 high) dysregulated by an IGH translocation in the respective tumor plasma cells. By contrast, in seven patients with multiple myeloma, each of whom had tumor plasma cells with a K-RAS61 mutation, a total of 32,400 memory B cells were analyzed using a sensitive allele-specific, competitive blocker polymerase chain reaction assay, but no K-RAS mutations were identified.

Conclusions

The increased expression of a specific “early” oncogene of multiple myeloma (monoclonal gammopathy of undetermined significance) in some memory B cells suggests that dysregulation of the oncogene occurs in a precursor B-cell that can generate memory B cells and transformed plasma cells. However, if memory B cells lack “late” oncogene (K-RAS) mutations but express the “early” oncogene, they cannot be involved in maintaining the multiple myeloma tumor, but presumably represent a clonotypic remnant that is only partially transformed.