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 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 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.

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。

[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。

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：探讨同源重组修复（HRR）基因突变对晚期非小细胞肺癌（NSCLC）患者免疫治疗疗效和预后的影响。方法：收集2018年3月至2023年4月间在郑州大学第一附属医院接受PD-1抑制剂治疗的124例晚期NSCLC患者的临床资料。根据有无HRR基因突变将患者分为突变组（n=57例）和野生组（n=67例），采用卡方检验或Fisher’s精确检验比较两组患者的临床特征及免疫治疗疗效差异，采用Kaplan-Meier方法比较两组患者的PFS，采用单因素和多因素Cox回归分析PFS的影响因素。结果：HRR基因突变组中鳞癌及肿瘤突变负荷（TMB）≥10 mut/Mb的占比显著多于野生组（54.4% vs 32.8%，61.4% vs 29.9%，均P<0.05）。HRR基因突变组与野生组患者的ORR分别为17.5%和10.4%（P=0.252），DCR分别为86.0%和73.1%（P=0.080）。HRR基因突变组与野生组的PFS比较差异具有统计学意义（6.8个月 vs 3.9个月，P<0.001）。多因素分析结果显示，有无HRR基因突变[HR=0.550，95%CI（0.352, 0.860）, P=0.009]与免疫治疗线数[HR=0.468，95%CI（0.312, 0.702）, P<0.001]和PFS显著相关。结论：HRR基因突变组患者的免疫治疗疗效优于野生组患者，HRR基因突变是晚期NSCLC患者免疫治疗预后的独立保护因素。

[摘 要] 目的：探讨甲基转移酶样因子3（METTL3）在食管鳞状细胞癌（ESCC）组织和细胞中的表达水平及其对ESCC细胞糖酵解和增殖能力的影响和潜在的分子机制。方法：基于TCGA数据库分析METTL3在ESCC细胞中的表达及可能的富集通路。收集2021年1月至2021年6月间在北川医学院附属医院外科手术切除的34例ESCC组织及相应癌旁组织，采用免疫组化法验证ESCC组织中METTL3的表达。采用CCK-8法和平板克隆形成实验检测干扰METTL3后ESCC细胞增殖能力的变化，利用比色法检测干扰METTL3后ESCC细胞总RNA中m6A的表达水平，采用甲基化RNA免疫沉淀定量PCR（MeRIP-qPCR）检测METTL3对葡萄糖转运蛋白4（GLUT4）基因mRNA的m6A修饰水平的影响，采用WB和qPCR等技术探索METTL3参与ESCC细胞糖酵解的生物学机制。结果：METTL3在ESCC组织以及细胞中均呈高表达（均P<0.001）。干扰METTL3表达后，ESCC细胞的增殖能力明显减弱、细胞内总RNA的m6A修饰水平显著降低（均P<0.001）。此外，干扰METTL3可显著抑制KYSE150和TE-1细胞中GLUT4基因mRNA的m6A修饰水平（均P<0.01），并通过下调GLUT4的表达抑制葡萄糖的摄取以及乳酸的释放（均P<0.01），最终下调mTORC1通路活性并抑制ESCC细胞的增殖；在干扰METTL3的ESCC细胞同时联合运用mTORC1通路抑制剂显示有协同的抗癌作用。结论：METTL3介导的m6A修饰通过调控GLUT4-mTORC1信号轴影响ESCC细胞的糖酵解及增殖。

In the present study, serum samples from 402 sheep and 216 goats were collected from 5 counties in Jinzhou from August to October 2012 and antibodies to Toxoplasma gondii were detected by modified agglutination test (MAT). Overall, 104 (16.8%) had antibodies to T. gondii with antibody titres of 1:25 to 1:800. Seropositive samples were distributed in all the 5 counties and seroprevalences of T. gondii varied significantly with flock size, age and rearing system, but not with breed, gender and farm location. The seroprevalences in small farms (18.3%, 95/518, 95% confidence interval [CI], 15.0-21.7%) were statistically higher than that in large farms (9%, 9/100, 95% CI, 3.4-14.6%) (P < 0.05), older animals were statistically higher than that in younger animals (P < 0.01). The prevalence in extensively and semiintensively raised samples was statistically higher than that in intensively raised animals (P < 0.01). Small flock size and extensive rearing system are the potential risk factors for the prevalence of Toxoplasma infection in sheep and goats in Jinzhou. This is the first report of T. gondii infection in sheep and goats in Jinzhou, northeastern China, and of an association of seropositivity to T. gondii and the risk factors.