Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R² = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users.     

卵巢子宫内膜异位症相关不孕年轻女性患者术后应用GnRH-a对自然受孕率的影响

目的观察腹腔镜手术后应用促性腺激素释放激素激动剂(Gn RH-a)对卵巢子宫内膜异位症(OEM)相关不孕的治疗效果,为临床应用提供依据。方法回顾性分析2013年1月-2017年12月于盘锦市中心医院接受保守性腹腔镜手术治疗的83例OEM伴不孕患者的临床资料。其中,37例患者单纯接受手术治疗,记为对照组;46例患者术后接受Gn RH-a治疗,记为观察组。对比两组月经周期与月经量恢复正常的时间、盆腔痛与痛经的视觉模拟评分法(VAS)评分、性激素[黄体生成素(LH)、雌二醇(E2)、卵泡刺激素(FSH)]水平、自然受孕率,并分析观察组给药期间的不良反应发生率。结果观察组月经周期与月经量的恢复时间均短于对照组,差异有统计学意义(P<0.05);治疗后,观察组盆腔痛、痛经的VAS评分低于对照组,差异有统计学意义(P<0.05);治疗后,观察组LH、E2、FSH水平低于对照组,差异有统计学意义(P<0.05);给药期间,观察组不良反应发生率为8.70%;随访期间,观察组自然受孕率高于对照组,差异有统计学意义(P<0.05)。结论腹腔镜手术后应用Gn RH-a对OEM相关不孕的治疗效果确切,可促进患者月经恢复正常,改善盆腔痛、痛经症状与性激素水平,提高患者自然受孕率,且安全性较高。     

经旋股内侧动脉深支和旋股外侧动脉升支介入治疗股骨头缺血性坏死的应用解剖

对 50例成人下肢标本的旋股内侧动脉深支和旋股外侧动脉升支的起源、起点、外径、走行、分布以及经这二支血管介入有关的结构进行观测 ,为介入治疗股骨头缺血性坏死提供更接近病变部位及可进行插管的血管。结果表明 ,旋股外侧动脉升支与横支共干起自旋股外侧动脉者占 68% ,升支单独起自旋股外侧动脉占 2 6 % ;旋股内侧动脉深支由旋股内侧动脉主干延续而来。旋股内、外侧动脉深支或升支起点外径分别为 3 0± 0 8mm、 2 8± 0 7mm。从股动脉的起点 ,经股深动脉、旋股外侧动脉至其升支长度为 7 1± 1 1cm ;经股深动脉、旋股内侧动脉至其深支长度为 5 6± 1 4cm。旋股内侧动脉与其深支间约呈 90 。 角 ;旋股外侧动脉与其升支间约呈 1 33。 角。旋股内、外侧动脉深支 (升支 )为营养股骨头和颈的血管 ,这二支血管符合导管插入要求     

Anatomic study of femoral vein occlusion during simulated hip arthroplasty

Summary An anatomic study was undertaken to establish whether positioning of the leg and surgical approaches for total hip replacement (THR) cause changes in the femoral v. which may contribute to the development of deep vein thrombosis (DVT). The patency of 32 femoral vv. of 18 cadavers was inspected at different levels during simulated THR. Before and after removal of the femoral head through a transgluteal or posterior approach, a wide-angle endoscope was inserted into the femoral v. via the external iliac v. Blood flow was simulated by proximal irrigation with saline through the popliteal v. After removal of the femoral head distinct changes were observed in both approaches. In the transgluteal approach the changes were dependent on the degree of adduction and the body build of the cadaver. Initially, an oval form was seen in a constricted lumen with an increasingly oblique oval deformation and a final facet-like closure, usually at about 5 to 7.5 cm below the inguinal ligament. In total adduction this stenosis occured regardless of build. Using a posterior approach, the necessary internal rotation caused a closure of the vein in 50% of cases. In combination with flexion and adduction there was stenosis in all cadavers regardless of body build. Our results indicate that the duration of the adducted position of the thigh during THR via a transgluteal approach should be minimised, as there is a reduction in blood flow with even minor degrees of adduction. In the posterior approach the stenosis occurs earlier, and is independent of the build of the cadaver.

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Étude anatomique de la sténose de la veine fémorale au cours des arthroplasties totales de hanche

Résumé L'étude anatomique a été réalisée pour établir la relation entre les différentes positions du membre inférieur au cours des arthroplasties totales de hanche et la survenue d'une thrombose veineuse profonde. Cette étude a été réalisée sur 18 cadavres, dont 32 vv. fémorales ont pu être examinées à différents temps de l'arthroplastie totale de hanche, avant et après ablation de la tête fémorale, par voie trans-glutéale ou par voie postérieure. Un endoscope (grand angle) a été introduit dans la v. fémorale par la v. iliaque externe. Le flux sanguin a été simulé par irrigation antérograde avec du sérum salé à travers la v. poplitée. Après l'ablation de la tête fémorale, il a été noté des différences significatives entre la voie d'abord trans-glutéale et la voie d'abord postérieure pour ce qui concerne l'aspect de la lumière de la v. fémorale et le flux sanguin. En ce qui concerne la voie trans-glutéale, ces modifications dépendaient du degré d'adduction et de la corpulence du cadavre. L'aspect de la lumière de la v. fémorale était initialement ovale, puis évoluait progressivement vers la sténose complète qui se situait à peu près entre 5 et 7,5 cm audessous du ligament inguinal. En adduction complète de la cuisse, la sténose se produisait, quelle que soit la corpulence du cadavre. En ce qui concerne la voie d'abord postérieure, la rotation médiale, indispensable à l'accès pour la mise en place de l'élément prothétique fémoral, causait une sténose de la v. fémorale dans 50% des cas. En ce qui concerne la combinaison des mouvements d'adduction et de flexion de la hanche, elle était responsable d'une sténose de la v. fémorale dans tous les cas, et ceci quelle que soit la corpulence du cadavre. Nos résultats indiquent que le durée de la position d'adduction de la cuisse durant l'arthroplastie totale de hanche par voie transglutéale devrait être diminuée car la réduction du flux sanguin dans la v. fémorale survient, même pour des petits degrés d'adduction. Dans la voie d'abord postérieure, la sténose survient plus tôt, elle ne dépend pas de la corpulence du cadavre.

     

Functional characterization of somatic point mutations of the human estrogen receptor alpha (hERalpha) in adenomyosis uteri

Endometriosis and adenomyosis uteri are chronic, benign diseases caused by the presence of endometrial tissue in ectopic locations, e.g. peritoneal or deep inside the myometrial wall of the uterus and/or in the rectovaginal septum. Although adenomyosis might be considered as a special form of endometriosis, both conditions differ with respect to clinical symptoms and treatment. Induction of a hypo-estrogenic state alone or in combination with surgical removal of the extra-uterine lesion is mostly sufficient for treatment of peritoneal endometriosis. By contrast, adenomyosis uteri rarely responds to hormonal therapy and usually requires a hysterectomy for cure. Consequently, the role of steroid hormone receptors with respect to the aetiology of either condition is still a matter of discussion. Using PCR/single strand conformation polymorphism analysis, we identified somatic estrogen receptor (ER) alpha gene mutations in three out of 55 samples from adenomyosis uteri. Functional characterization revealed that two of the mutant ERalpha proteins display severely impaired DNA-binding and transactivation properties secondary to an altered response to estrogens or changes in epidermal growth factor-mediated ligand-independent activation. Although the exact mechanism remains unknown, we suggest that mutation-related silencing of estrogen responsiveness might render endometriotic cells resistant to hypo-estrogenic conditions thereby accounting for failure of estrogen-ablative therapy in adenomyosis.     

益气通阳化痰方联合迈之灵治疗下肢深静脉血栓形成的临床研究

目的:研究益气通阳化痰方联合迈之灵治疗下肢深静脉血栓形成的临床疗效。方法:将60例下肢深静脉血栓形成患者随机分为单药治疗组和联合治疗组,两组均予迈之灵口服治疗,联合治疗组加用益气通阳化痰方,10天为1个疗程,两个疗程后分析临床疗效,肢体阻抗血流图和血液流变学变化。结果:联合治疗组在疼痛缓解、下肢肿胀消退、血粘度及肢体血流的改善方面明显优于迈之灵单药治疗组;两组总有效率比较差异具有显著性。结论:益气通阳化痰方联合迈之灵治疗下肢深静脉血栓形成具有较好疗效。     

血清抗原125、子宫内膜异位抗体测定在子宫内膜异位症诊断中的价值

[目的]探讨联合检查在诊断子宫内膜异位症中的临床价值.[方法]研究对象为子宫内膜异位症病人45例和非子宫内膜异位症病人30例.术前用放射免疫法测定血清糖抗原125,并用酶联免疫吸附法测定子宫内膜异位抗体水平.[结果]子宫内膜异位症组血清糖抗原125水平为(79±40)U/mL,高于对照组(22 U/mL±11 U/mL).子宫内膜异位症组子宫内膜异位抗体阳性率为55%,对照组为10%.单项测定糖抗原125诊断子宫内膜异位症的敏感性为75%,特异性为83%;单项测定子宫内膜异位抗 体诊断子宫内膜异位症的敏感性为55%,特异性为90%;如以两者均阳性为诊断标准,则敏感性为48%,特异性为100%;如以其中之一阳性为诊断标准,则敏感性为82%,特异性为73%.[结论]测定血清中糖抗原125、子宫内膜异位抗体水平对子宫内膜异位症有较好的辅助诊断价值,联合测定更能提高诊断的正确性.     

胸腺因子D/重组白细胞介素2高效诱导人脑胶质瘤浸润淋巴细胞的增殖及杀伤活性

探讨建立胸腺因子Ｄ（ＴＦＤ）／重组白细胞介素２高效诱导人脑胶质瘤浸润淋巴细胞的可行性 。方法按ＴＦＤ与ｒＩＬ－２的不同组合,分组在体外对ＧＩＬ进行培养,分别用ＭＴＴ法,４ｈ＾５１Ｃｒ释放法和间接免疫荧光法检测其增殖,杀伤活性及ｒＩＬ－２受体的表达情况。结果ＴＦＤ与ｒＩＬ－２共同诱导ＧＩＬ,与对照组相比,其增殖活性及对自体瘤细胞的杀伤活性显著增强且持续时间更长。结论应用ＨＦＤ／ｒＩＬ－２体外诱导方法     

腹腔镜剥离卵巢子宫内膜异位囊肿92例分析

目的探讨腹腔镜下卵巢子宫内膜异位囊肿剥出术的可行性及技术要点。方法回顾性分析1995年5月～1999年5月施行的92例腹腔镜下卵巢巧克力囊肿剥出术的手术情况。结果92例患者按RAFS分期,Ⅲ期61％、Ⅳ期39％。手术均顺利完成,无中转开腹手术,平均手术时间62min,平均术中出血50ml,术后平均住院2．6d。病理均证实为卵巢子宫内膜异位囊肿。无术时术后并发症。结论对属于中、重度(Ⅲ、Ⅳ期)的卵巢子宫内膜异位囊肿进行腹腔镜下囊肿剥出术是安全可行的,应作为治疗的首选术式。在进行囊肿剥出前必须先分离卵巢与周围脏器的粘连,游离卵巢,为减少术后复发,应完全剥除囊壁,不缝合卵巢有利于减少术后粘连。     

子宫内膜异位症癌抗原(CA125)检测及其临床意义

目的：探讨子宫内膜异位症与ＣＡ１２５有无相关性、提高临床子宫内膜异位症诊断雍诊断最佳途径。方法：用放射免疫测定法（ＲＩＡ）检测７９例子宫内膜异位症、７０例子宫肌瘤、６４例子宫颈癌、８０名正常育龄女性为对照。结果：子宫内膜异位症、子宫肌瘤、子宫颈癌、正常对照组阳性率分别是７９．７５％、８．５７％、１７．１９％、０．００％。前者显著高于后三者（Ｐ〈０．０１）。结论：ＣＡ１２５检测为临床诊断子宫内膜异位