Basaloid squamous cell carcinoma (BSCC) of the uterine cervix is a rare malignancy of the female genital tract with a poorer clinical outcome than SCC of the uterine cervix. We report a case of BSCC of the uterine cervix developing rapidly in a young adult Taiwanese. A 35-year-old woman, Para 2, visited the emergency room with severe dizziness, palpitations and sudden excessive vaginal bleeding with hemoglobin of 3.6 g/dl. She had been well and healthy but intermittent vaginal spotting developed for around 6 months previously and was treated as abnormal uterine bleeding by ob-gyn practitioners. She had a repeat cesarean operation 16 months prior to this episode and the last Pap smear showed reactive change 12 months ago at our hospital. On examination, she had an ulcerated, necrotic, and punched-out lesion of 5 cm of the cervix. A cervical biopsy revealed poorly differentiated typical BSCC. Abdominal/pelvic computerized tomography and whole body positron emission tomography confirmed FIGO staging IB2. She responded well to concurrent chemoradiotherapy. Follow-up for the patient is ongoing. This is a rapid developing BSCC of the uterine cervix, although we cannot actually ascertain when it started and how rapidly it progressed.

ObjectiveTo study the proper treatment of the patient with positive margins after cervical conization. MethodsA total of 220 cervical conizations were performed in the department of obstetrics and gynecology in Conception Hospital in Marseille in France from January 1, 1996 to June 30, 1998. Among them, we studied 73 patients, who had positive margins, by using cervical cytology examination and colposcopy in 3,6,12,18 and 24 months after cervical conization. Results7 cases of cancer invasive were treated with radiotherapy; 17 underwent a second conization or hysterectomy, among whom 8 had residual disease of positive margins near internal orifice of uterus (residual rate, 47. 06 ％ ); 40 remained follow- up; but 9 were lost.ConclusionCytology and colposcopy are effec- tive in the surveillance of patients with positive margins after cervical conization, and can give the indica- tion of the second conization.

OBJECTIVE：To develop a method for the determination of eperisone hydrochloride by high performance liquid chromatography(HPLC).METHOD:C18 column as the stationary phase and methanol-water-triethylamine(80∶19.5∶0.5,V/V,adjusted to pH 7.5 with glacial acetic acid) as the mobile phase were adopted.The detection was performed at 254nm.Eperisone hydrochloride tablets were disssolved in methanol,supersonic-vibrated and filtered.Tolperisone was used as internal standard.RESULTS:The standard curve was linear in the range of 0.4～1.6mg/ml with the excellent correlation coefficient of 0.9999.The average recovery was 98.4%(RSD=1.2%,n=15).Three batches of eperison hydrochloride tablets were analyzed and the labelled contents were 97.8%,98.3% and 98.9% respectively.CONCLUSION:The method was simple,sensitive,rapid and suitable for the quantitative anylysis of the preparation.

Objective: To investigate the effect of sulforaphane (SFN) on CD8+ T cells differentiation, phenotype and the secretion of intracellular cytokines, as well as to study the underlying molecular mechanism. Methods: In the in vitro culture experiment, the cells were categorized into control group, SNF 10 mmol/L group and SNF 20 mmol/L group according to the SNF concentration. The effect of SFN treatment on CD8+ T cells differentiation, phenotype and cytokine secretion were detected by flow cytometry, and the effect of mTOR siRNA on the expression of CD127 and LKRG1 in CD8+T cells was also detected by flow cytometry. Expression of Bcl-2 and Bcl-6 were analyzed by qRT-PCR. The effect of SFN on apoptosis of CD8+T cells was examined byAnnexin-V/PI staining. The protein expressions of p-mTOR, p-S6 and b-actin were detected by western blotting. Results: SFN significantly promoted the formation of memory precursor CD8+ T cells and decreased the expression level of PD-1 and Tim-3 in CD8+T cells(P<0.01); meanwhile, after the treatment of SFN, the expressions of anti-apoptosis genes Bcl-2 and Bcl-6 were significantly increased while the apoptosis of CD8+ T cells was significantly inhibited and the protein expressions of p-mTOR and p-S6 were also significantly inhibited(P<0.05 or P<0.01). Moreover, mTOR siRNA could significantly increasethe expression of CD127 and decrease the expression of LKRG1 (all P<0.01). Conclusion: Sulforaphone promotes the formation of memory precursor CD8+T cells possibly by inhibiting the p-mTOR signaling pathway, and this could obtain more T cells to provide new thoughts for clinical immunotherapy.

Objective To investigate the kinetics and the magnitude of intragraft gene expression of interleukin-2 (IL-2), interferon-gamma (IFN-y), perforin and granzyme B, and intragraft expression of interieukin-2 receptor (IL-2R) and intercellular adhesion molecule-1 ( ICAM-1 ) during acute rejection episodes, and to analyze the changes in apoptosis in small intestinal allograft rejection. Methods Heterotopic small intestine transplantation was performed with inbred rats F344/N (RT11) and Wistar/A (RT1-Ak, RT1-Ed). All recipients were divided into four groups: group 1 : Wistar, native control; group 2: Wistar→Wistar; group 3: F344→Wistar and group 4: F344→Wistar + cyclosporine A (6 mg·kg-1 ·d-1 I.M. ). The grafts were harvested on postoperative days (PODs) 3, 5 and 7. All samples were examined pathologically. Intragraft mRNA expression of IL-2, IFN-γ, perforin and granzyme B were detected with reverse transcriptase polymerase chain reaction (RT-PCR) and intragraft expression of IL-2R and ICAM-1 were stained using immunohistochemistry. We also analyzed the change in apoptosis rejection with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Results Mild acute rejection occurred on POD 3 in the ailograft group, moderate acute rejection on POD 5, and severe acute rejection on POD 7, while none of the isografts had histological evidence of acute rejection. Cyclosporine A could effectively control rejection. Gene expression was virtually negative in the native control. Only on POD 5 was IL-2 mRNA expression of ailografts significantly higher than that of isografts ( P ＜ 0.05). IFN-γ mRNA expression was significantly higher than that of the control groups ( P ＜ 0.01 ) on PODs 3, 5 and 7, and the level of perforin and granzyme B mRNA expression reached significantly higher levels than in the other two control groups on POD 5 and POD 7. Intragraft IL-2R expression of the allograft was significantly higher than that of the other three control groups. Only on POD 3 was intragraft ICAM-1 expression of allografts significantly higher than isografts. The number of apoptotic cells per crypt of allografts was significantly higher than that of the other three control groups on POD 3 and POD 5 ( P ＜ 0.01 ). Conclusion Transcription of IL-2, IFN-γ, perforin and granzyme B, and expression of IL-2R and ICAM-1 as well as apoptosis of epithelial cells of the grafts play an important role in small intestine allograft rejection. Intragraft gene expression of IFN-γ and intragraft expression of IL-2R as well as apoptotic epithelial cells may become a specific and sensitive diagnostic method of clinical value. Furthermore, therapeutic strategies to alter these molecules in small intestine transplantation may improve the outcome of current antirejection therapy.

Objective: To explore the molecular mechanism of miR-195-5p targeting FGF2 to inhibit the proliferation, apoptosis, invasion and migration of endometrial cancer HEC-1B cells. Methods: After culture and transfection, HEC-1B cells were divided into 4 groups: HEC-1B group, miR-195-5p mimic group, pLV-FGF2 group and miR-195-5p+FGF2 group. The expressions of miR-195-5p and mRNA levels of FGF2 were detected by qRT-PCR. The targeted relationship of miR-195-5p and FGF2 was verified by luciferase assay. The protein expression of FGF2 was examined by Western blotting; Proliferation of HEC-1B cells was measured by CCK-8; Apoptosis was tested by flow cytometry; HEC-1B cell invasion was detected by transwell, and migration was measured by scratch assay. Results: Compared with HEC-1B group, the expression of miR-195-5p in miR-195-5p mimic group was elevated while FGF2 mRNA level was declined (all P<0.01). Luciferase assay indicated that FGF2 was a target of miR-195-5p. Compared with HEC-1B group, the protein level of FGF2 in miR-195-5p mimic group was decreased, and the protein levels of FGF2 in pLV-FGF2 group were enhanced (P<0.01). The protein levels of FGF2 in miR-195-5p+FGF2 group were lower than that in pLV-FGF2 group (all P<0.01). The proliferation in miR-195-5p mimic group was lower than HEC-1B group (P<0.01), while the proliferation in pLV-FGF2 group was higher than that in HEC-1B group (all P<0.01). Compared with HEC-1B group, apoptosis in miR-195-5p mimic group was increased, and apoptosis in pLV-FGF2 group was decreased (P<0.01); moreover, apoptosis in miR-195-5p+FGF2 group was higher than that in pLV-FGF2 group (P<0.01). Compared with HEC-1B group, the number of invasive cells per field and the rate of wound healing in miR195-5p mimic group were decreased, while those in pLV-FGF2 group was enhanced (P<0.01); moreover, the number of invasive cells per field and the rate of wound healing in miR-195-5p+FGF2 group was lower than those in pLV-FGF2 group (all P<0.01). Conclusion: miR-195-5p inhibits proliferation, invasion and migration and promotes apoptosis of endometrial cancer HEC-1B cells by targeting FGF2, and could be used as a treatment target of endometrial cancer.

[摘 要] 免疫细胞介导的药物递送系统是以免疫细胞为载体，利用细胞固有的趋化作用将治疗药物靶向递送至特定病灶部位，因其具有优异的生物相容性、低免疫原性、组织特异性归巢及易穿过生物屏障等多重优势，已成为药物递送和疾病治疗的重要手段。本文系统论述免疫细胞的载药策略和单核细胞、中性粒细胞、间充质干细胞和树突状细胞等作为载体细胞的生物学特性、主要优缺点，以及应用于肿瘤治疗的最新研究进展，为深入研究免疫细胞介导的药物递送系统和临床转化提供重要参考。

间变性淋巴瘤激酶（anaplastic lymphoma kinase，ALK）是一种受体型酪氨酸激酶，被认为是肿瘤的驱动基因，它的变异会 改变自身激酶活性，进而激活下游信号分子，使细胞增殖调控出现紊乱，从而导致肿瘤的发生。ALK的体细胞变异主要有融合和 突变两类，ALK融合在肺癌中已有较多研究，并已研发出相关小分子靶向药物， 而ALK突变则在神经胶质瘤中研究相对较多。本 文将阐述ALK融合及突变的研究现状及其与肿瘤发生发展的关系，为个性化医疗及靶向药物的研发提供一定的理论线索。

Objective: To discuss the changes in the tight junction protein of intestinal epithelium and permeability of colonic mucosa and its possible mechanism by building the rat mode of inflammatory bowel disease at the chronic recovery stage. Methods: A total of 36 SD rats were divided into the model group and control one according to the random number table, with 18 rats in each group. Rats in the model group were given the 3% dextran sulfate sodium solution by the way of drinking for 7 d to build the rat model of inflammatory bowel disease, while rats in the control group were given free drinking of water. Six rats were executed at day 7, 14 and 21 respectively. The colonic tissues were collected from rats to observe the pathological changes of colonic mucosa. The activity of myeloperoxidase was detected and the white blood count was performed for rats in each group. The Ussing chamber technique was employed to detect the transepithelial electrical resistance (TER) and short-circuit current (SC) of colonic mucosa of rats in different time intervals; the quantum dots labeling technique was employed to detect the expression level of claudin-1 and claudin-2 in the colonic tissues. Results: After the successful modeling, the weight of rats in the model group was significantly reduced, while the disease activity index score was increased. The weight was at the lowest level at day 14 and then it began to increase afterwards. The disease activity index score was at the highest level at day 12 and then it began to decrease gradually. The activity of myeloperoxidase and WBC for rats in the model group all reached the peak value at day 14 and then decreased gradually. There was no significant difference in the changes of TER and SC in different time intervals for rats in the control group (P > 0.05). TER of model group was at the lowest level at day 14 and then increased gradually; SC was at the highest level at day 14 and then decreased gradually. TER of model group at day 7, 14 and 21 was significantly lower than that of control group, while SC of model group was significantly higher than that of control group (P < 0.05). There was no significant difference in the change of mean fluorescence intensity of claudin-1 and claudin-2 in different time intervals for rats in the control group (P > 0.05). The claudin-1 and claudin-2 for rats in the model group reached the highest level at day 14 and then decreased gradually. The claudin-1 and claudin-2 of model group at day 7, 14 and 21 was significantly higher than that of control group (P < 0.05). Conclusions: After the acute stage, the inflammatory bowel disease is then in the chronic recovery stage; the increased permeability of colonic mucosa and increased expression of tight junction protein of intestinal epithelium are closely related to the pathogenesis and development of disease. The tight junction protein plays a key role in the pathogenesis of injured colonic barrier of inflammatory bowel disease.

[摘 要] 目的：探讨干扰四个半LIM结构域蛋白2（FHL2）的表达对胶质母细胞瘤U87细胞中O6-甲基鸟嘌呤DNA甲基转移酶(MGMT) 表达的影响，以及对U87细胞替莫唑胺（TMZ）耐药性的影响。方法：利用慢病毒感染技术分别将携带不同FHL2干扰序列的慢病毒（shFHL2-1#、shFHL2-4#）及其阴性对照（shN）感染U87细胞，分别命名为shFHL2-1#、shFHL2-4#和shN组；采用siRNA转染技术将siMGMT-1#、siMGMT-4#和siN转染至U87细胞，为siMGMT-1#、siMGMT-4#和siN组，qPCR和WB法验证FHL2或MGMT的敲低效果。用TMZ处理上述各组细胞（以DMSO处理组为对照），随后以CCK-8法和细胞克隆形成实验检测TMZ处理前后FHL2或MGMT敲低组细胞的增殖情况，FCM检测TMZ处理前后FHL2敲低组细胞的凋亡情况，WB法和免疫荧光法检测敲低FHL2对U87细胞中MGMT表达的影响，WB法检测TMZ处理对各组细胞中FHL2和MGMT表达水平的影响。结果：成功构建敲低FHL2或MGMT表达的U87细胞。与shN组相比，shFHL2-1#、shFHL2-4#组U87细胞的增殖能力减弱、凋亡水平升高（均P<0.01），MGMT表达水平明显降低（均P<0.01）。经TMZ处理后，与相应的DMSO处理组相比，shN组细胞中FHL2和MGMT的表达水平显著升高（均P<0.05），而细胞的增殖和凋亡均无显著变化（均P>0.05）；shFHL2-1#、shFHL2-4#组细胞中FHL2和MGMT的表达水平无显著改变（均P>0.05），但细胞增殖能力进一步显著降低、凋亡水平进一步显著升高（均P<0.01）。敲低MGMT使U87细胞增殖减慢（P<0.01），而siMGMT-1#、siMGMT-4#组细胞经TMZ处理后增殖能力进一步降低（均P<0.01）。结论：干扰FHL2表达使得U87细胞增殖减慢而凋亡加剧、MGMT表达下调，提示FHL2可能通过影响MGMT的表达调控U87细胞对TMZ的耐药性。