目的 构建吉西他滨耐药乳腺癌细胞4T1耐药株并建立裸鼠乳腺癌肝转移模型。方法 采用低浓度加量持续诱导法,诱导吉西他滨耐药乳腺癌细胞4T1耐药株,命名为4T1/Gem;CCK-8法测定4T1与4T1/Gem细胞的增殖抑制率,计算耐药指数; Western blot法检测细胞P-gp蛋白表达;B超引导下注射4T1/Gem细胞悬液诱导裸鼠肝脏成瘤;HE染色观察肿瘤组织病理情况,免疫组化法检测瘤组织ER、PR、HER2、Ki-67和P-gp蛋白的表达。结果 经过14个月的诱导成功建立4T1/Gem细胞株,可在含40 μg/mL的Gem培养液中稳定生长。4T1/Gem细胞耐药指数为4T1细胞的788.547倍。与亲代相比,4T1/Gem处于G1期和G2期的细胞增加,S期细胞减少;上调P-gp蛋白的表达。4T1/Gem细胞成功建立裸鼠乳腺癌肝转移模型,瘤组织中ER、PR、HER2蛋白阴性表达,Ki-67阳性10％和P-gp蛋白阳性表达。结论 成功构建吉西他滨耐药乳腺癌细胞4T1耐药株并建立裸鼠乳腺癌肝转移模型,为开发治疗乳腺癌肝转移化疗耐药的药物提供实验基础。

Objective To construct a gemcitabine-resistant variant of the breast cancer cell line (4T1/Gem) and establish a nude mouse model of breast cancer with hepatic metastatic. Methods A gemcitabine-resistant variant of the breast cancer 4T1 cell line was induced by gradually increasing the concentration of gemcitabine; this variant is referred to in this study as 4T1/Gem. The proliferation suppression rates of 4T1 and 4T1/Gem cells were determined by using the CCK-8 essay to evaluate the drug resistance indices of the cell lines. Western blot analysis was used to detect P-gp protein expression. Under ultrasonography, a 4T1/Gem cell suspension was injected into nude mice to induce liver tumors. H&E staining was used to observe tumor pathology, and immunohistochemistry was used to detect the expression of ER, PR, HER-2, Ki-67, and P-gp. Results After 14 months of induction, a 4T1/Gem cell line is established successfully. The cell line can grow stably in culture liquid containing 40 μg/ml gemcitabine. The drug resistance index of 4T1/Gem is 788.547. Compared with the 4T1 cell line, the 4T1/Gem cell line can upregulate P-gp protein expression and successfully establish a nude mouse model of breast cancer with hepatic metastatic. ER, PR, and HER-2 proteins exhibit negative expression in the tumor tissue. The positive expression of P-gp and 10% of Ki-67 proteins is also observed. Conclusion This study successfully constructs a gemcitabine-resistant variant of the breast cancer cell line (4T1/Gem)and establishes a nude mouse model of breast cancer with hepatic metastatic, thereby providing an experimental basis for developing and treating a drug-resistant variant of breast cancer.

目的 探讨血清胃蛋白酶原在胃癌筛查中的价值。方法 用ELISA方法对1102名患者血清PG水平进行检测,并行内镜病理组织学检查,采用ROC曲线确定PG筛查胃癌的最佳界定值。结果 与对照组、萎缩性胃炎组、胃良性溃疡组相比,早期胃癌组、进展期胃癌组PGI、PGR下降(P＜0.05),进展期胃癌组PGI、PGR较早期胃癌组下降(P＜0.05)。与对照组相比,早期胃癌组、进展期胃癌组、胃良性溃疡组PGII升高(P＜0.05)。PGI及PGR在ROC曲线下面积为0.920和0.831,对胃癌的诊断价值较高。PGI≤71.50 μg/L或PGR≤4.50作为筛查标准时,对胃癌高危人群筛查的灵敏度为83.33%,特异度为82.25%。结论 血清PGI、PGR在不同胃部病变中的表达水平不一致,对胃癌的早期筛查和早期诊断具有重要价值。PGI≤71.50 μg/L或PGR≤4.50是东莞地区筛查胃癌较合适的界定值。

Objective To investigate the value of serum pepsinogen PG detection for screening of gastric cancer. Methods PG was detected by ELISA of 1102 people, gastrointestinal endoscopy and biopsy pathology were also carried on. Using ROC curve to establish the PG screening standard, and verified its' value at high risk population of gastric cancer. Results Compared with control group, atrophic gastritis group and benign gastric ulcer group, serum PGI and PGR in early gastric cancer group and advanced gastric cancer group decreased significantly(P＜0.05). Serum PGI and PGR in advanced gastric cancer group were lower than early gastric cancer group(P＜0.05). Serum PGII in early gastric cancer group, advanced gastric cancer group and benign gastric ulcer group were higher than control group(P＜0.05). The area under ROC curve of PGI and PGII was 0.920 and 0.831 respectively, both of them showed high value for the diagnosis of gastric cancer. Took PGI≤71.50μg/L or PGR≤4.50 as the diagnosis criteria, the sensitivity was 83.33% and specificity was 82.25% at high risk population of gastric cancer. Conclusion Serum PGI and PGR were inconsistent in different gastric disease, which showed high sensitivity and specificity in the screening of gastric cancer,and have important value in early screening and early diagnosis of gastric cancer. PGI≤71.50μg/L or PGR≤4.50 were established as the appropriate standard for PG screening.

支气管哮喘是由多种细胞和和细胞因子参与的气道慢性炎症性疾病,白细胞介素、干扰素、集落刺激因子、肿瘤坏死因子、趋化因子等细胞因子在哮喘发生发展过程中发挥着重要作用。

目的 通过观察隔姜灸神厥穴并同时口服黄芪汤治疗脓毒症急性肾损伤患者的效果分析,初步探讨该方法能否改善患者的APACHEⅡ评分,入住重症监护病房的时间有没有缩短,14天内死亡率有否差异。方法 以2014年1月—2015年8月于我院确诊的脓毒症急性肾损伤患者为研究对象,观察常规治疗(对照组)及常规治疗基础上给予隔姜灸神厥穴同时口服黄芪汤治疗(治疗组)对脓毒症急性肾损伤患者危重情况的影响。结果 治疗组患者的危重指标(APACHEⅡ评分)明显改善,患者治疗5天后组间比较差异有统计学意义(P<0.05);两组患者入住重症监护病房的时间比较,患者治疗第四周χ²=4.5241,P=0.0334,差异有统计学意义(P<0.05);14天死亡率差异无统计学意义(P>0.05)。结论 隔姜灸神厥穴同时口服黄芪汤治疗能有效改善脓毒症急性肾损伤患者的APACHEⅡ评分,入住重症监护病房的时间减少。

目的 探讨ε-3多不饱和脂肪酸在胃肠道肿瘤患者化疗后的胃肠道毒性及生活质量的作用。方法 在研究前经过化疗筛选,按照WHO化疗副反应在2级或者以上的50名住院的胃癌或者直结肠癌患者,随机分为对照组(单纯化疗)(n=25)和研究组(化疗加ε-3多不饱和脂肪酸)(n=25),两组的化疗方案均为化疗筛选的方案。预防性每天静脉使用ε-3多不饱和脂肪酸 200 mg,连续5天,记录评估胃肠道并发症,如恶心、呕吐和腹泻,以及KPS评分、血清白蛋白、IL-2、IFN-γ和CRP。结果 与对照组比较,恶心、呕吐和腹泻评分、IL-2、IFN-γ和CRP低于于对照组,相反,生活质量评分研究组高于对照组,差异有统计学意义(P<0.05)。结论 预防性使用ε-3多不饱和脂肪酸能够减轻胃肠道肿瘤患者化疗后的胃肠道毒性症状、降低全身炎症因子反应并改善生活质量。

Objective To explore the effect omega-3polyunsaturated fatty acid omega-3 FA on clinical manifestations of gastrointestinal toxicity and quality of life (QOL) induced by chemotherapy for patients with gastric or colorectal cancer. Methods After screening chemotherapy, Fifty patients with gastric or colorectal cancer, according to developing WHO side-effect grading system of grade 2 or higher were randomly divided into either control group (n=25) or omega-3 FAs group (n=25) during next cycle of chemotherapy. In the control group, the patients received the same chemotherapy regimens as screening cycle and in the omega-3 FA group, received chemotherapy and omega-3 FAs. Prophylactic intravenous 200 mL /d was given for 5 days. The gastrointestinal complications such as nausea,vomiting or diarrhoea and Karnofsky performance status(KPS ),IL-2,IFN-γandCRP,ect, were evaluated respectively. Results Compared with the control group, the scores of nausea vomiting and diarrhea and IL-2,IFN-γor CRP levels decreased , significantly,on the contrary, the score of QOL increased. There was significantly statistical difference (P<0.05). Conclusion Prophylactic intravenous omega-3 FA can ameliorate clinical manifestations of gastrointestinal toxicity and systemic inflammatory response syndrome(SIRS) induced by chemotherapy and improve QOL for patients with gastric or colorectal cancer.

目的 探讨微泡增强的超声空化对荷瘤兔乳腺癌的治疗效果。方法 建立兔VX2乳腺癌模型,肿瘤兔随机分成两组,超声微泡组及单纯超声组,各组于治疗前及治疗后分别行超声造影,分析造影前后肿瘤灌注情况。结果 超声微泡组治疗前后造影灰阶值改变明显,造影灰阶值从治疗前的(20.26±2.59)降至(3.71±1.61)(P<0.01);而单纯超声组肿瘤造影灰阶值无明显统计学差异(P>0.05)。结论 微泡增强的超声空化对荷瘤兔乳腺癌有一定的治疗效果。

Objective To investigate the treatment effect of microbubbles-enhanced ultrasound cavitation on VX2 breast tumor in rabbits. Methods The rabbit model of VX2 breast tumor were established. The rabbits were randomly divided into two groups, microbubbles-enhanced ultrasound (US+MBs) group and standard ultrasound (US) group. The VX2 breast tumor perfusion were imaged and assessed using contrast enhanced ultrasonography (CUES) before and after treatment. Results The contrast enhanced grayscale value (GSV) of VX2 breast tumors decreased significantly in the US+MBs group, from 20.26±0.59(before treatment) to 3.71±.761 (after treatment)(P<0.01). While there was no significance of GSV before and after treatment (P>0.05) in the US group. Conclusion Microbubble-enhancement ultrasound cavitation has a certain therapeutic effect on the VX2 breast tumor in rabbits.

目的 探讨糖尿病胃轻瘫大鼠不同血糖水平对Cajal间质细胞(ICC)的影响及其机制。方法 选择雌性Wista大鼠60只进行随机分组,实验组40只,对照组20只。实验组糖尿病Wista大鼠模型以单次腹腔注射链脲佐菌素法诱导。免疫组织化学荧光染色检测不同血糖浓度大鼠胃ICC数量及网络结构。结果 实验组大鼠血糖浓度高于对照组,ICC数量,低于对照组,且比较差异有统计学意义(P<0.05)。实验组大鼠中血糖浓度越高,ICC数量越低,说明血糖浓度升高可能与平滑肌及神经末梢之间缝隙连接的减少及其ICC网络的超微结构损伤及异常有关。结论 DM小鼠胃组织中血糖水平的升高,可能是DM胃中ICC数量减少的原因;外源性降低血糖能改善DM相关的胃肠道ICC病变。

Objective To observe the effects of glucose fluctuations on Cajal interstitial cells (ICC) of rats with diabetic gastroparesis(DGP) and its mechanistic. Methods 60 Wistar rats were selected and randomly divided into two groups. 20 rats in experimental group and 40 rats in control group. Used immunofluorescence staining to detect the amount of gastric ICC and network structure in DGP rats with different glucose levels. Results The blood glucose concentration in the experimental group was significantly higher than that in the control group, the amount of ICC in the experimental group was significantly lower than that in the control group(P<0.05). The amount of ICC decreased with the increase of glucose levels. In the experimental group, The gap junctions between smooth muscle and nerve endings, ultrastructural damage and abnormalities of the ICC network were probably related to glucose level. Conclusion The increase of glucose level was probably the cause of the decrease of the amount in ICC. Exogenousy decrease glucose levels probably can help to improve the lesion of ICC with DGP.

目的 观察氟伐他汀联合环磷腺苷葡胺治疗慢性肺心病急性加重期的临床疗效。方法 将我院收治的74例慢性肺心病急性加重期病人,使用随机数字表法分为联合用药组与对照组,每组各37例。对照组单独使用环磷腺苷葡胺,联合用药组在对照组的基础上加服氟伐他汀。两组疗程均为7周。观察比较两组患者治疗前后的NO,ET-1,CRP,PaO₂水平以及治疗效果。结果 经7周疗程治疗后,对照组有效率为64.86%,联合用药组94.59%。两组间比较,差异有统计学意义(P<0.05)。两组NO,ET-1,CRP,PaO₂水平比较,联合用药组均优于对照组,差异有统计学意义(P<0.05)。结论 氟伐他汀联合环磷腺苷葡胺治疗慢性肺心病急性加重期的临床疗效更为显著,值得临床推广。

Objective To observe the clinical efficacy of combined treatment of Fluvastatin combined with Meglumine Adenosine Cyclophosphate on acute exacerbation of chronic pulmonary heart disease. Methods 74 patients with acute exacerbation of chronic pulmonary heart disease were randomly divided into combined treatment group and control group. The control group was treated by Meglumine Adenosine Cyclophosphate for 7 weeks.The combined treatment group was treated by Meglumine Adenosine Cyclophosphate and Fluvastatin for 7 weeks. The clinical efficacy and the score of NO,CRP,ET-1,PaO₂ were assessed before and after the treatment. Results After 7 weeks treatment, the total clinical efficacy rate was 64.86% in the control group and 94.59% in the combined treatment group. The differences between them has statistically significant(P<0.05). The score of NO,ET-1,CRP,PaO₂ in combined treatment group were significantly improved compared to control group (P<0.05). Conclusion The clinical efficacy of Fluvastatin combined with Meglumine Adenosine Cyclophosphate on acute exacerbation of chronic pulmonary heart disease is more efficient. It is worth to develop clinically.

目的 分析总结异丙酚静脉麻醉复合利多卡因乳腺后间隙局部浸润麻醉在乳腺多发性肿块真空辅助微创旋切术的临床应用体会。方法 通过对我院2012年3月—2015年3月380例乳腺多发性肿物在异丙酚静脉麻醉复合利多卡因乳腺后间隙局部浸润麻醉下行真空辅助微创旋切术的病例,进行回顾性综合分析。结果 手术前、中和手术后血氧饱和度无明显变化;手术中平均动脉压、心率与术前比较,差异有统计学意义(P<0.05);麻醉效果好,术后并发症少。结论 乳腺多发性肿物真空辅助微创旋切术采用异丙酚静脉麻醉复合利多卡因乳腺后间隙局部浸润麻醉,安全可行,患者依从性好、满意度和耐受度较高,临床效果满意。

Objective To investigate the applicative value of Propofol intravenous anesthesia combining with local infiltration anesthesia in vacuum assisted biopsy minimal invasive system for multiple breast lumps excision. Methods Encor minimally invasive surgery was performed under Propofol intravenous anesthesia together with local infiltration anesthesia in 380 cases with multiple breast lumps admitted to our department from March 2012 to March 2015. Anesthesia effect, SpO₂, MAP and HR were analyzed retrospectively. Results All 380 patients achieved good anesthetic effect for completing multiple breast lumps excision. The postoperative complications were less. There was no obvious change of oxyhemoglobin saturation (SpO₂) before, during and after the surgery period (P>0.05). The mean arterial pressure (MAP) and heart rate (HR) had statistical significance compared the surgery period with the pre-operative time (P<0.05). Conclusion Vacuum assisted biopsy minimal invasive system under Propofol intravenous anesthesia combining with local infiltration anesthesia is a safety and feasible method for multiple breast lumps excision. It has more advantages including perfect anesthetic effect, good patient compliance, higher satisfaction and higher tolerance level.

目的 探讨单倍体亲缘异基因造血干细胞移植治疗重型再生障碍性贫血(SAA)的可行性。方法 对1例诊断SAA 4年余,先后经CsA治疗、脐血移植治疗均无效并反复输注红细胞、血小板的12岁男性患者进行单倍体亲缘异基因造血干细胞移植,供者为其胞兄,高分辨HLA基因型5/10相合,预处理方案为BU+CTX+ATG:BU 3.2 mg/kg×2 d,CTX 50 mg/kg×4 d,ATG 2.5 mg/kg×4 d。干细胞来源为G-CSF动员的骨髓+外周造血干细胞,共计输注单个核细胞(MNC)4.055×10⁸/kg(受者体重),CD 34 2.331×10⁶/kg。GVHD预防:-1 d采用与受者HLA部分相合的第三方脐带血细胞,术后联合应用环孢素A、短程氨甲碟呤、霉酚酸酯。结果 造血缓慢重建,术后22天(+22 d)ANC>0.5×10⁹/L,术后3月血小板脱离输注。+26天DNA指纹图全部表现为供者基因型。+40天血型转为供者型“O”型。+29 d出现急性移植物抗宿主病aGVHD(胃肠型,Ⅲ度),+31 d、+34 d及+42 d予巴利昔单抗20 mg静滴,+40 d、+44 d、+63 d输注间充质干细胞,患者急性GVHD逐渐控制。期间曾出现肺部感染、口腔黏膜炎及巨细胞病毒血症,经抗感染后可控制。现随访3年,血象正常稳定,Kamofsky评分100分。结论 单倍体亲缘异基因造血干细胞移植治疗SAA,对无相合供者(包括亲缘或非亲缘)且强效免疫抑制治疗失败的患者,可考虑进行,GVHD和感染为主要并发症,需根据患者病情采用相应措施。

Objective To investigate the feasibility of haploid genetic allogeneic hematopoietic stem cell transplantation in the treatment of severe aplastic anemia(SAA) in our hospital. Methods A 12-year-old patient with acquired SAA for 4 years showed no response to CsA and cord blood transplant treatment and was transfusion-dependent. Lacking an HLA-identical sibling donor, the patient was treated with HSCT from his brother 5/10 matched at the generic level. Theconditioning regimen was BU+CTX+ATG:BU 3.2 mg/kg×2 d,CTX 50 mg/kg×4 d,ATG 2.5 mg/kg×4 d. Stem cells were the source of G-CSF mobilization of bone marrow and peripheral blood stem cells, dose of stem cells infused: mononuclear cells (MNC) 4.055×10⁸/kg (body weight of subject), CD34 2.331×10⁶/kg. Prevention of GVHD: -1 d Third-party umbilical cord blood cells which were HLA partially matched were used. Postoperative joint use included cyclosporine A, short-course methotrexate, mycophenolate mofetil. Results Hematopoiesis was slowly rebuilding, 22 d after surgery (+22 d) ANC> 0.5×10⁹/L, after three months departing from transfusion of platelets. +26 d suggesting that the DNA fingerprints showed donor genotypes. +40 d into donor blood type “O” type. + 29 d occurred acute GVHD (GI type, Ⅲ degrees), + 31 d, + 34 d + 42 d infusion of basiliximab 20mg, + 40 d, + 44 d, + 63 d infusion of mesenchymal stem cells. Gradually acute GVHD was controlled in the patient, who had lung infections, oral mucositis and cytomegalovirus viremia, could be controlled with anti-infective. Now followed up for 3 years, hemogram change has been normal and stable. Kamofsky score was 100 points. Conclusion It may be considered to have haploid genetic allogeneic hematopoietic stem cell transplantation for treatment of SAA, for those patients who have non-matched donor (including relatives and non-relatives) and potent immunosuppressive therapy failure. GVHD and infection are major complications. Need to adopt appropriate measures in accordance with the patient's condition.