HMGB1下调的作用：通过抑制神经元细胞自噬和凋亡减轻大鼠脑出血后的神经元损伤

目的探讨高迁移率族蛋白1（HMGB1）在大鼠脑出血后对神经元细胞自噬和凋亡的作用机制。方法将20只Wistar大鼠随机分为4组（5只/组）：假手术组（Sham组）、脑出血组、HMGB1中和抗体治疗（anti-HMGB1）组、control IgG组。模型组选择颅内纹状体注射0.2 U/mL胶原酶Ⅳ建立脑出血大鼠模型。Sham组颅内注射2 μL生理盐水，术后尾静脉注射PBS，6 h后再次注入等量PBS；anti-HMGB1组术后尾静脉注射1 mg/kg anti-HMGB1单克隆抗体，6 h后再次注入等量抗体；control IgG组术后尾静脉1 mg/kg anti-IgG单克隆抗体，6 h后再次注入等量抗体。采用改良神经损害程度（mNSS）评分评估大鼠神经功能和损伤程度。TUNEL染色检测纹状体神经元凋亡。Western blot检测血肿周围脑组织神经元细胞HMGB1、自噬蛋白（Beclin-1、LC3-Ⅱ和LC3-Ⅰ）和凋亡相关蛋白（Bcl-2、Bax和cleaved caspase-3）的表达。免疫组化检测纹状体组织中HMGB1阳性表达。ELISA检测血清HMGB1含量变化。结果造模成功后，脑出血组中mNSS评分增加（P < 0.05），给予anti-HMGB1单克隆抗体后，mNSS评分减少（P < 0.05）。与Sham组相比，脑出血组大鼠纹状体神经元凋亡率增加（P < 0.001），Beclin-1、LC3-Ⅱ、Bax和cleaved caspase-3的表达增加（P < 0.05），而LC3-Ⅰ和Bcl-2的表达减少（P < 0.05），HMGB1含量增加（P < 0.05）。给予anti-HMGB1单克隆抗体后，大鼠纹状体神经元凋亡率减少（P < 0.05），Beclin-1、LC3-Ⅱ、Bax和cleaved caspase-3的表达减少（P < 0.05），而LC3-Ⅰ和Bcl-2的表达增加（P < 0.05），HMGB1含量减少（P < 0.05）。结论anti-HMGB1单克隆抗体下调HMGB1水平改善大鼠脑出血后的神经功能，其机制可能是抑制大鼠脑出血后的神经元细胞自噬和凋亡。     

肺癌脑膜转移癌诊疗的研究进展

脑膜转移癌（leptomeningeal metastases, LM）是晚期肺癌中进展迅速、预后差的常见并发症。脑膜转移癌临床诊断率低，治疗手段有限，疗效差，自然生存时间短。脑脊液细胞学作为诊断脑膜转移癌的金标准，但是目前临床症状及影像学阳性的患者脑脊液首次细胞病理学阳性诊断率一般不超过50%，导致脑膜转移癌患者的诊断延迟、治疗延误。随着驱动基因阳性肺癌靶向治疗、驱动基因阴性肺癌免疫治疗的进展，肺癌患者生存期延长，但是脑膜转移癌发病率逐年增加，如何提高诊断率、寻找有效的治疗手段是目前临床研究的热点。本文就肺癌脑膜转移癌诊断及治疗研究进展予以综述。     

Encuesta SEGO. Tratamiento de la amenaza de parto pretérmino en los hospitales españoles

Objective

To determine how threatened preterm labor is treated in Spanish hospitals.

Material and method

Under the aegis of the Spanish Society of Obstetrics and Gynecology, an Internet questionnaire on basic aspects of the treatment of threatened preterm labor was sent to 41 Spanish hospitals (37 public and four private hospitals).

Results

All hospitals use tocolysis in threatened preterm labor before 34th weeks. The most widely used tocolytic agent is atosiban (73,7%), followed by betamimetics (21.9%) and nifedipine (4.9%). Only 7.3% of the hospitals use tocolytics in threatened preterm labor after 34 weeks. All the hospitals use corticosteroids to accelerate lung maturation: 92.7% use betamethasone and 7.3% prefer dexamethasone. In 90% of the hospitals, steroid therapy is not repeated. In multiple pregnancies, the same steroid dose as that used in single pregnancies is administrated in all centers.

Conclusions

The most widely used tocolytic agent in Spanish hospitals is atosiban and the preferred corticosteroid is betamethasone.     

Tumores malignos ginecológicos sincrónicos. Casuística del Hospital de Manacor

Objective

To alert clinicians to the possibility of synchronous tumors in patients with gynecological cancer. An important tool in diagnosis is the family history. We describe several familial syndromes involving the development of synchronous gynecological tumors.

Subjects and methods

We studied all cases of synchronous gynecological tumors in the Manacor Hospital from 1997 to 2006.

Results

Synchronous gynecologic tumors represented 0.83% of all gynecological neoplasms treated in our center in the period studied.

Conclusions

This kind of tumor is uncommon but should be considered by clinicians, especially in women with a familial history of cancer or in those with certain genetic syndromes. Examination aimed at excluding the presence of synchronous tumors is recommended.     

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: clinical description and genetics

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part (two-third) of the vagina. It may be isolated (type I) or associated with other malformations (type II or MURCS association). These latter involve the upper urinary tract, the skeleton and, to a lesser extent, the otologic sphere or the heart. The incidence of MRKH syndrome has been estimated as 1 in 4500 women. The prime feature is a primary amenorrhea in women presenting otherwise with normal development of secondary sexual characteristics and normal external genitalia. However, the vagina is reduced to a vaginal dimple with variable depth. The ovaries are normal and functional as well as the endocrine status. Karyotype is 46,XX, with no visible chromosome modification. The phenotypic manifestations of MRKH syndrome overlap with various other syndromes or malformations and thus require accurate delineation as well as differential diagnosis. For a long time, the syndrome has been considered as a sporadic anomaly, but increasing familial cases now support the hypothesis of a genetic cause currently under investigation. The syndrome appears to be transmitted as an autosomal dominant trait with incomplete penetrance and variable expressivity.     

Valoración ecográfica del endometrio en pacientes tratadas con tamoxifeno

Objective

To measure endometrial thickness and characterize ultrasonographic endometrial images induced by tamoxifen, as well as to determine changes in ultrasonographic patterns throughout treatment.

Patients and methods

We analyzed 278 patients with breast cancer between 1995 and 2000 under adjuvant therapy with tamoxifen for 5 years. Annual ultrasonographic examination was performed. Endometrial thickness and the morphological endometrial patterns in stored ultrasonographic images were retrospectively analyzed.

Results

Endometrial thickness significantly increased during treatment from a mean of 7.84 mm in the first year to 16.67 mm in the fifth year. Five endometrial patterns were found on ultrasonography in patients receiving tamoxifen: linear, heterogeneous-hyperechoic, homogeneoushyperechoic, endometrial polyp, and suspicious for malignancy. The homogeneous-hyperechoic pattern predominated in the first year and the heterogeneous-hyperechoic pattern in the fifth year.

Conclusions

Tamoxifen increases endometrial thickness in the course of treatment and induces five ultrasonographic patterns which change year-by-year.     

Pregnancy and lung cancer: a case report and review of the literature

Lung cancer is a frequent pathology among women, as a result of tobacco increase. Lung cancer among pregnant women is especially rare when revealed by Pancoast-Tobias syndrome. Foetal injury is possible. The approach is multidisciplinary. Prognosis is bad.