A-kinase anchor protein 12 (AKAP12) has been reported to be related to lung squamous cell carcinoma (LUSC) progression. However, its role and molecular mechanisms in LUSC have not been revealed. The mRNA and protein levels of AKAP12 and transcription factor 21 (TCF21) were tested by quantitative real-time PCR and western blot. Cell counting kit 8 assay, EdU assay, flow cytometry, wound healing assay, and transwell assay were used to evaluate cell proliferation, apoptosis, migration, and invasion. Cell glycolysis was measured by testing glucose consumption and lactate production. The interaction between AKAP12 and TCF21 was assessed by ChIP assay and dual-luciferase reporter assay. A mice xenograft model was constructed to explore AKAP12 and TCF21 roles in vivo. Our data showed that AKAP12 was underexpressed in LUSC tissues and cells, and its overexpression inhibited LUSC cell growth, metastasis, and glycolysis. TCF21 had decreased expression in LUSC, which facilitated AKAP12 expression through binding to its promoter region to enhance its transcription. Furthermore, TCF21 increased AKAP12 expression to repress LUSC cell growth, metastasis, and glycolysis. In vivo experiments showed that AKAP12 upregulation reduced LUSC tumorigenesis, and TCF21 knockdown reversed this effect. In conclusion, AKAP12 might be a tumor suppressor in LUSC, which was mediated by TCF21 and could inhibit cell growth, metastasis, and glycolysis to restrain LUSC malignant progression.

BACKGROUND:Advanced cancer (AC) patients experience serious physical and psychological problems with the disease progression. When approaching the end of life, these patients have to cope with not only the bodily illness, but also the spiritual crisis. Conventional psychological treatments reduce distress to a certain extent, but for patients with AC, especially when they face progressive illness and are approaching death, their psychological problems are complex, and no simple solutions are in sight. Therefore, we designed this study to evaluate the efficacy of the combined Naikan therapy (NT) and Morita therapy (MT) on psychological distress and posttraumatic growth in patients with AC. METHOD:One hundred thirty patients newly diagnosed with AC were allocated randomly into treatment (n = 65) and control (n = 65) groups. Patients in the treatment group received combined NT and MT for 7 consecutive weeks, while the control group received normal medical treatments without NT and MT. Patients were assessed before and after the therapies. The primary outcome measures include distress thermometer (DT) and posttraumatic growth, and the secondary outcome measure contains the list of distress problems. RESULTS:At the post-treatment stage, the treatment group displayed a decreased score of psychological distress as compared to that in the control group, which accompanied by a higher post-traumatic growth total score and subscale scores in relationship to others, new possibilities, personal strength, spiritual changes, and appreciation of life. A significant decrease in fear, sleeping difficulty/insomnia, nervousness/anxiety, and loss of appetite was also observed in the treatment group. CONCLUSION:The results proved that the combined Naikan and Morita therapies decreased the psychological distress and improved the posttraumatic growth of the patients with AC. TRIAL REGISTRATION:ChiCTR1900026691.

Zinc (Zn) has antioxidant effect in different types of organs and is closely associated with human health. Endometrial receptivity is one of the most important factors in the embryo implantation and development. However, the regulatory mechanism of Zn in endometrium tissue is still unclear. In the study, we found that plasma Zn level is significantly associated with female infertility, which severely affects female reproductive health. Primary endometrial stromal cells were isolated from female endometrium and cultured in the laboratory. Zn chelator TPEN treatment reduced the expression of stem cell markers CD73, CD90, and CD105 and generated reactive oxygen species in endometrial stromal cells. However, pretreatment of Zn (zinc sulfate) is able to prevent TPEN-induced oxidative stress in vitro. By transcriptional profiling and gene ontology analysis, we found that Zn increased the cellular pluripotency signaling and extracellular matrix-receptor interaction, but reduced autophagy, endocytosis, and the nitrogen metabolism pathway. We further discovered the antioxidant function of Zn through the peroxisome proliferator-activated receptor gamma coactivator 1α/nuclear factor erythroid-2-related factor signaling pathway in endometrial stromal cells. Zn supplementation may open up an effective therapeutic approach for patients with oxidative stress-related endometrial diseases.

本文探讨了非甾体抗炎药塞来昔布联合奥施康定与普瑞巴林治疗癌性阴部神经痛的临床疗效及安全性.选取合并癌性阴部神经痛的恶性肿瘤患者49例,采取随机数字表法,将其分成观察组26例和对照组23例.对照组给予奥施康定联合普瑞巴林治疗,观察组在对照组的用药基础上加用塞来昔布治疗.治疗后,观察组的临床有效率为92.3％,明显高于对照组的65.2％,差异有统计学意义(P<0.05).两组患者治疗后第7、14天的NRS评分均低于治疗前,且观察组患者的NRS评分下降更显著(P<0.05).同时,观察组患者的奥施康定日均使用量及不良反应发生率均低于对照组,差异均有统计学意义(P<0.05).在癌性阴部神经痛患者中使用塞来昔布联合奥施康定与普瑞巴林治疗效果显著,可有效改善患者疼痛情况,减少阿片类药物应用剂量及并发症的发生,特别是可以减少便秘及排尿困难的发生.

目的:探讨APS复发性流产患者血小板活化状态及其对内皮细胞活化的作用.方法:流式细胞术分别检测23例APS患者和31例正常早孕人群血小板CD62P和CD40L的表达水平.洗涤血小板悬液与人脐静脉内皮细胞(HUVECs)共培养6 h,ELISA法分析HUVECs培养上清IL-8的水平,荧光定量PCR法检测HUVECs细胞ICAM-1的mRNA水平.结果:APS组血小板CD62P和CD40L阳性表达百分率为(10.27±3.76)％和(13.26±5.21)％,较正常早孕组显著升高(P<0.05);APS组血小板悬液能显著促进HUVEC细胞ICAM-1基因表达水平和分泌IL-8水平.特异性CD40L单抗可以显著抑制HUVEC细胞表达ICAM-1水平和分泌IL-8水平.结论:APS流产患者外周血血小板活化程度增加,血小板-内皮细胞反应参与APS导致高凝、炎症和流产的病理过程.

Objective To analyze the expression of microRNA-126 (miR-126) and its relation with clinicopathological characteristics of colon carcinoma.Methods Resection specimens of 70 cases of colon carcinoma and 32 cases of adenomatous colon polyps were collected from January 2015 to September 2018 in Jilin Province People's Hospital.Expression of miR-126 in adenoma,carcinoma and adjacent tissue were tested by real-time fluorescence quantitative polymerase chain reaction.Patients with colon carcinoma were divided into miR-126 high expression group and low expression group according to the mean expression value.Relation between miR-126 expression and clinicopathological parameters of colon carcinoma was analyzed.Results Expression of miR-126 in colon adenoma(0.75 ± 0.09) was significantly lower than that in paracancerous tissue(1.00);the expression in high,medium and poor differentiated colon carcinoma [(0.47 ± 0.04),(0.36 ± 0.12),(0.29 ±0.07)] was significantly lower than that in adenoma(P ＜0.05 or P ＜0.01).The mean value of miR-126 expression was (0.37 ± 0.03) and the patients were divided into high expression group (19 cases) and low expression group (51 cases);tumor differentiation degree,TNM stage,lymphatic metastasis and distant metastasis showed significant differences between high expression group and low expression group (P ＜ 0.05 or P ＜ 0.01).Conclusion MiRNA-126 is low-expressed in colon carcinoma;it may play an important role in the occurrence and progression of colon carcinoma as an anti-oncogene.

阳光 在丘陵地带,祖先居住的地方多半就在山冈. 山冈和人一样,都是有名字的,根据不同的形态、地貌和住在当地的人的姓氏,叫夜红山、茅草冈、黄家岭、康家坡,总之是在田野和天空相接处,一条蜿蜒的山脉如同一堵墙,把眼前的世界分隔成了两个部分,人间和天上.山下的世界万物生长,一派生机,山上的世界白云飘浮,一派祥和;而连接这两个世界的隔墙,那条蜿蜒的山冈,灰黄裸露的山弯处浸染着一块深绿色,仿佛山冈的心脏,那是一片残存的树林,是大肆砍伐的人们提着刀具砍斧唯一踌躇的地方.在那片绿树掩映处,就是先人们居住的村庄.这个村庄,坐落在人间,行走在天堂.

目的 探讨普瑞巴林在老年晚期胰腺癌患者中的应用及安全性.方法 选取30例老年胰腺癌患者为观察组,接受普瑞巴林联合盐酸羟考酮(奥施康定)止痛治疗,同期临床特点相同的对照组26例,予单纯奥施康定止痛治疗,两组出现爆发痛,均应用盐酸吗啡片进行滴定,之后转为奥施康定治疗.比较两组疼痛数字分级法(NRS)评分,吗啡使用量,不良反应发生率及生活质量.结果 与对照组相比,观察组在治疗后14 d的NRS评分、日均吗啡用量、不良反应均显著下降(P<0.05).在生活质量及药物起效时间方面,与对照组无统计学差异(P>0.05).结论 普瑞巴林在老年晚期胰腺癌中应用安全,疼痛控制迅速有效,且可减少阿片类药物应用剂量.

Objective To explore the effect of combined Naikan therapy and modified Morita therapy on psychological distress and post traumatic growth in elderly patients with cancer pain.Methods Ninety elderly patients with cancer pain were randomly assigned into two groups;those in the study group(n =45)were given Naikan therapy and modified Morita therapy for 4 weeks and those in the control group (n =45) were given standardized aerodyne treatment and standardized nursing care.All subjects were assessed with the Distress Thermometer and Problem Listand the Post traumatic Growth Inventory before and after Naikan therapy and modified Morita therapy.Results Compared with the control group,the study group was associated with significantly decreased scores of psychological distress(1.8± 0.1 vs.3.9 ± 0.2,t =1.78,P＜0.05),emotional problems (1.2 ± 0.4,vs.2.4±0.4,t=1.41,P＜0.05)and family problems(1.1±0.1,vs.2.9±0.1,t=1.63,P＜0.05).The study group also showed markedly higher scores in posttraumatic growth(66.0± 19.9 vs.45.3± 27.6,t=2.58,P＜0.05),relationships to others(34.8±12.1 vs.23.8±12.2,t=1.91,P＜0.05),new possibilities(25.2 ± 10.1 vs.13.7± 4.4,t=1.94,P＜0.05),personal strength(20.7 ± 10.4 vs.7.6 ± 3.1,t =2.03,P ＜ 0.05),spiritual change (11.6 ± 5.6 vs.5.4 ± 2.7,t =1.26,P ＜ 0.05),and appreciation of life(18.9±6.2 vs.6.1±-2.1,t=1.88,P＜0.05) than the control group.Conclusions Naikan therapy and modified Morita therapy can decrease psychological distress and improve post traumatic growth in elderly patients with cancer pain.

High-dose ionizing radiation can cause harmful effects on the cardiovascular system. Notably, endothelial cells are critical targets in radiation-induced damage. γ radiation exerts its biological effects through the radiolysis of water, which further generates ROS and induces lipid peroxidation and DNA damage. The present study aimed to evaluate the potential protective effects of celastrol against γ radiation-induced oxidative stress in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to γ radiation at different doses with or without celastrol treatment. Cell viability and cytotoxicity, migratory ability, ROS production, lipid peroxidation, oxidative DNA damage and antioxidative enzyme levels were evaluated in HUVECs at 24 h post-irradiation. It was observed that HUVECs exhibited decreased cell viability, increased cytotoxicity and a decreased migratory ability after exposure to 20-Gy γ radiation. Celastrol treatment concentration-dependently reversed these effects. γ irradiation was also demonstrated to increase the production of ROS, enhance lipid peroxidation and oxidative DNA damage and decrease the levels of SOD, catalase, GST and GPx in HUVECs. These detrimental effects were blocked by treatment with celastrol for 24 h. These data suggested that celastrol not only attenuated γ radiation-induced cytotoxicity, but also effectively blocked oxidative stress in HUVECs. As an antioxidant agent, celastrol may have potential protective effects in HUVECs against γ irradiation-induced injury.

Objective Investigate the effect of miR-126 and miR-199 on the cell cycle in breast cancer cells.Methods The expression of miR-126 and miR-199 in breast cancer cells was detected by qRT-PCR assay;the effect of miR-126 and miR-199 expression on the cell cycle of breast cancer cells was detected after miRNA mimics were transfected into breast cancer cell line MDA-MB-231.Results The expression of miR-126 and miR-199 in breast cancer cell line MDA-MB-231 was significantly lower than that of MCF-7 cell line;after transfection of miRNA mimics 48h,the expression of miR-126 and miR-199 in breast cancer cell line MDA-MB-231 was up-regulated,which could promote cell apoptosis and block the cell cycle progression of breast cancer.Conclusion Increasing the expression of miR-126 and miR-199 in breast cancer cells can inhibit tumor cell cycle progression and exert anti-tumor effect.

Objective:To observe the specific killing effect on tumor cells of the spleen cells in mice immunized with three tandem repeats of CEA minigene DNA vaccine pcDNA-triCEA625-667 and to evaluate the safety of the vaccine. Methods: The BALB/c mice were randomly divided into blank vector group ( pcDNA3. 0 ) , haploid vaccine group ( pcDNA-CEA625-667 ) and tandem repeats vaccine group (pcDNA-triCEA625-667). The mice received a total of 4 intramuscular immunization every 10 days once. The changes of body weight,survival state were recorded and the levels of serum ALT and serum creatinine were detected. The specific CTL killing activity of spleen cells in accinated mice on mouse hepatoma cells(H22-CEA+),gastric cancer cells(MFC-CEA+),colorectal cancer cells ( CT26-CEA+) with high expression of CEA and mouse hepatoma cells ( H22-CEA-) without expression of CEA was detected. Results:The two vaccines had strong killing activity on CEA positive liver cancer,gastric cancer and colon cancer cells,and the difference was statistically significant ( P<0. 01 ) compared with the PcDNA3. 0 group. And they had almost no effect on CEA negative tumor cells (H22-CEA-). The killing activity on liver cancer cell(H22-CEA+) and gastric cancer cell(MFC-CEA+) induced by pcDNA-triCEA625-667 was stronger than that induced by pcDNA-triCEA625-667(P<0. 05). The survival status,change of body weight and function of liver and kidney of the mice were not affected by the vaccine. Conclusion:There was no adverse reaction in the course of vaccine immunization. The minigene DNA vaccine derived from CEA can induce tumor specific CTL effect and the immune response level elicited by three tandem repeats of minigene DNA vaccine was superior to that elicited by haploid vaccine.

一、 《冬天的梦》 的深远 高尔夫球场上的一个球童, 有一天迎来了一位特殊的顾客, 一个十一岁的少女琼士和她的保姆. 虽然球童和这少女都年纪轻轻 ,但是一种身份, 一种距离已经形成, 况且少女正像鲜花一样开放, 正萌发出 "美人坯子" 的青春活力, 长她两三岁的球童更是情窦初开, 但这初开的结果,却是一种身份悬殊的觉醒, 在一种朦胧的冬天的梦一般的驱使下 , 球童炒了大班的鱿鱼.

Objective To study the effect and mechanism of allogeneic CIK combined with plasmapheresis in the treatment of liver cancer.Methods Peripheral blood mononuclear cells (PBMC)were isolated from healthy volunteers and cultured in vitro by culturing the cells into cytokine-induced (CIK)cells.All cases were randomly assigned to allo-geneic CIK cell treatment group and allogeneic CIK+ plasma replacement therapy group.The levels of IFN-γ,IL-4,IL-10,TGF-βand VEGF in plasma were measured by ELISA.The percentage of CD3+ and CD4+ cells in the peripheral blood of the two groups before and after treatment were detected by flow cytometry.CD4+/CD8+ ratio and CD8+ cell ratio,and the quality of life and overall survival of the two groups were compared.Results The anti-tumor immunity effect of allogeneic CIK was up-regulated,and the up-regulation of IL-4,IL-10,TGF-βand VEGF was related to the up-regulation of CIK + plasma replacement therapy group (P<0.05);The percentage of CD3+,CD4+ and CD4+/CD8+ in peripheral blood in CIK+plasma replacement group were significantly higher than those in allogeneic CIK group(P<0.05),and the percentage of CD8+ cells decreased significantly after treatment(P<0.05),PFS has been prolonged(P<0.05)and no OS prolongation(P>0.05),and quality of life was significantly better than that of alloge-neic CIK cells treated group(P<0.01).Conclusion Adoptive CIK cell adoptive immunotherapy + plasma exchange program can inhibit and remove immunosuppressive cells and immunosuppressive factors,increase the immune effect and quantity of CIK cells,inhibit the progression of primary liver cancer and improve the quality of life of patients.

目的探讨二甲双胍对三阴乳腺癌细胞的抑制作用和可能的损伤机制。方法利用MTT、流式细胞仪检测二甲双胍对MDA-MB-231乳腺癌细胞周期的影响及诱导凋亡作用;应用Western blot技术检测加药后MDA-MB-231乳腺癌细胞外信号调节激酶1和2（ERK1/2）磷酸化表达水平变化。结果不同浓度二甲双胍作用MDA-MB-231乳腺癌细胞系24、48h后细胞增殖被不同程度抑制,并呈时间和浓度依赖性（P＜0.05）;可促进MDA-MB-231乳腺癌细胞系凋亡,并呈浓度依赖性（P＜0.05）;细胞周期检测,与对照组比较,G0/G1期比例增加（P＜0.05）,S期比例逐渐降低（P＜0.05）,G2/M期比例无明显变化（P＞0.05）;药物处理MDA-MB-231乳腺癌细胞系24h后,Western blot检测示随药物浓度的增加,细胞外信号调节激酶1和2（ERK1/2）磷酸化表达水平下降（P＜0.05）。结论二甲双胍对三阴性乳腺癌细胞MDA-MB-231增殖有抑制作用,下调P-ERK1/2的表达可能是其抗肿瘤机制之一,可能成为三阴乳腺癌潜在的维持治疗药物。

Objective:To investigate the expression of miR-126 in human colon cancer cell lines with different metastatic potential and its effect on the proliferation, invasion and metastasis of colon cancer cells, and to explore the possible mechanism.Methods:The expression of miR-126 in human colon cancer cell lines(SW480,SW620 and HCT116) was determined by Real-time fluorescence quantitative PCR.miR-126 mimics were transiently overexpressed in SW620 cells throuIgh liposome transfection and the negative control group was set up.The proliferation ability of cells was detected by CCK8 method and the mobility of cells was detected by wound healing assay and Transwell migration and invasion assay.The expression of E-cadherin,Vimentin was determined by Western blot.Results:The expression of miR-126 was decreased in SW620 and HCT116 cells with high metastatic potential compared SW480 cells with low metastatic potential.The overexpression of miR-126 significantly inhibited the proliferation,migration and invasion ability of SW620 cells and Western blot indicated that miR-126 overexpression increased the expression of E-cadherin and decreased the expression of Vimentin in SW620 cells,which was significantly different from that of negative control(P<0.05).Conclusion:Low expression of miR-126 is closely related to metastasis of colon cancer and the effect of miR-126 on the biological behavior of colon cancer cells may be mediated by the regulation of the EMT process.

Objective:To observe the inhibitory effect of haploid vaccine pcDNA-CEA625-667 and three tandem repeats of minigene DNA vaccine pcDNA-triCEA625-667 derived from CEA gene on tumor in mice bearing tumor and the changes of survival time. Methods:The experimental animal model of mouse liver cell carcinoma was established and the mice were immunized with pcDNA-CEA625-667 and three series of DNA vaccine. Some of the mice were treated with normal saline as control group. The growth curve of tumor growth curve was recorded and the effect of vaccine on the survival time of tumor bearing mice was observed. Results:Compared with the normal saline control group,the two vaccines were able to significantly inhibit the tumor size and growth rate ( P<0. 01 ) of CEA positive tumor bearing mice,the inhibition of pcDNA-triCEA625-667 vaccine group was significantly better than the pcDNA-CEA625-667 vaccine group (P<0. 01),while the two were not inhibited tumor growth in CEA negative tumor bearing mice. The average survival time of the pcDNA-CEA625-667 vaccine group was(48. 50±6. 73)d,and there was significant difference (P<0. 01) compared with the saline control group ( 39. 00 ± 6. 64 ) d. The survival time ( 48. 50 ± 6. 73 ) d of the pcDNA-triCEA625-667 vaccine group was significantly higher than that of the normal saline control group and the pcDNA-CEA625-667 vaccine group (P<0. 01). The survival time of CEA negative tumor bearing mice could not be prolonged in the two groups. Conclusion:Either the haploid or the three series of the DNA vaccine,were able to significantly inhibit tumor growth rate (P<0. 01) and significantly prolong the survival time (P<0. 01) of CEA positive tumor bearing mice,but they had no therapeutic effect on CEA negative tumor bearing mice.

目的 探讨疼痛护理在提高晚期乳腺癌患者生活质量中的临床效果.方法 在医院2015年4月至2016年2月诊治的晚期乳腺癌患者中抽取76例作研究对象并应用随机抽签法予以分组,对照组(n=38)应用常规护理,护理组(n=38)则在常规护理基础上加用疼痛护理,对比2组患者护理前后生活质量变化以及护理满意度.结果 护理组护理后的生活质量评分是(87.42±3.32)分,护理满意度是94.74%;对照组护理后的生活质量评分是(62.18±7.85)分,护理满意度是76.32%;2组患者在护理后生活质量评分和护理满意度上的对比均无统计学差异(P<0.05或P<0.01).结论 疼痛护理用于晚期乳腺癌患者临床护理中效果肯定,可显著提升其生活质量,从而提高其护理满意度,值得借鉴.

[Abstartc] Objetcive: To analyze the effect of p21 protein activated kinase 4( PAK4) on epithelial-mesenchymal transition of breast cancer cells.Met hods: The mRNA and protein expression of PAK4,E-Cadherin,N-Cadherin and Vimentin were detected by qRTP-CR and Western blot in breast cancer cells transfected with pcDNA -PAK4 or siRNA PAK4;The biology behaviors of MCF-7 cells and MDA-MB-231 cells transfected with pcDNA-PAK4 or siRNA PAK4 were analysed by cell migration assay ,invasion assay.Results:Overexpressing PAK4 could significant increase in the migration and invasion compared with vector-infected cells, decrease the expression of epithelial marker E-cadherin and upregulate the expression of mesenchymal markers N-cadherin and Vimentin in detached MCF7 cells.Silenced PAK4 gene in detached MDA-MB-231 cells could suppress the migration and invasion ,decrease the levels of the mesenchymal markers and increased the levels of the epithelial markers at both mRNA and protein levels .Conclusion:PAK4 plays a key role in EMT of breast cancer cells ,and its promoting EMT effect associated with upregulating the expression of Slug .

Objective:To observe the immunological activity of haploid vaccine and three tandem repeats of minigene DNA vac -cine derived from Carcinoembryonic Antigen (CEA) gene.Methods:The immunoreaction was induced by intramuscular injection with pc-DNA3.0,pcDNA-CEA625-667 and pcDNA-triCEA625-667 in BALB/c.Four weeks after injection,the spleen cells and serum were separa-ted respectively from the mice for the in vitro assessment .Changes of the T lymphocytes subset was analyzed by flow cytometry .Lymph proliferation responses were tested by 3 H-TdR incorporation ,IFN-γ,IL-4 and GM-CSF in their cultural supernatants were detected with ELISA and seral IgG antibody against CEA were detected with Western blot and ELISA .Results:The difference of the ratio of CD 4+/CD8+of the mice immuned by pc-DNA3.0,pcDNA-CEA625-667 or pcDNA-triCEA625-667 was not significant.Lymph proliferation responses were more significant in the mice immuned by pcDNA-CEA625-667 and pcDNA-triCEA625-667 in a shorter time by contrast with na ?ve mice.Low tilter IgG antibody against CEA was detected in the antiserum of the mice immuned by repeats of minigene DNA vaccine , which suggested the activation of helper T-cell.ELISA showed that the level of IFNγin the 3 days culture of the splenocytes was rela-tively higher in the groups of minigene DNA vaccination than in the control groups ,while IL-4 expression was absent in all groups .The immune response level elicited by three tandem repeats of minigene DNA vaccine pcDNA -triCEA625-667 was superior to that elicited by pcDNA-CEA625-667 ,which showed that any immunogenic inadequacies in minigene presentation can be rectified by linking itself in a string-of-beads vaccine.Conclusion:The haploid vaccine and three tandem repeats of minigene DNA vaccine derived from CEA geneboth can not change the ratio of CD 4+/CD8+but can induce the activation of helper T-cell and skew T -cells toward Th -1 response.The immune response level elicited by three tandem repeats of minigene DNA vaccine was superior to thatelicited by haploid vaccine .