AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcino...AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.展开更多
Objective: To investigate the distribution and recruitment of pulm onary dendritic cells (DCs) and the influence of low dosage arsenic trioxide (As 2O 3) on them in the airway of asthmatic mice. Methods: Thirty BAL...Objective: To investigate the distribution and recruitment of pulm onary dendritic cells (DCs) and the influence of low dosage arsenic trioxide (As 2O 3) on them in the airway of asthmatic mice. Methods: Thirty BALB/c mice were randomly divided into 3 groups: the control group, the asthmat ic group and the As 2O 3 treated group. The mice asthmatic model was induced v ia sensitizing with peritoneal injection of ovalbumin (OVA) for two times and th en provocated with aerosol inhalation of OVA for a week. The treated group was p eritoneally injected with 0.2 ml solution of As 2O 3 (4mg/kg) 0.5h after each provocation. The immunohistochemistry and computerised image analysis were appli ed to detect quantitatively the DCs in the lung and airway of mice. Resul ts: All intraepithelial nonlymphoid dendritic cells 145 (NLDC 145) throughout the respiratory tree in the mice of the control group formed a netwo rk with the density of DCs varying from (575±54) cells/mm 2 epithelial surface in the large airway, to (68±12) cells/mm 2 epithelial surface in the small ai rway. The distribution of airway NLDC 145 + in the asthmatic group was simil ar to that in the control group, but its density was significantly upregulated ( P <0.01). The distribution of airway NLDC 145 in the treated group was sim ilar to that in the asthmatic group, only its density was significantly downregu lated ( P <0.01). Conclusion: There is an integral network of N LDC 145 + throughout the respiratory tree. To downregulate the density but n ot change the distribution of pulmonary DCs could be an important therapeutic me chanism of low dosage As 2O 3 in treating asthma.展开更多
The stray crystals seriously affect the properties of metals which fabricated by directional solidification(DS). In order to observe the formation of the stray crystals, the growth behavior of Sn-10 wt.%Bi alloy was o...The stray crystals seriously affect the properties of metals which fabricated by directional solidification(DS). In order to observe the formation of the stray crystals, the growth behavior of Sn-10 wt.%Bi alloy was observed by synchrotron X-ray imaging technique using self-developed directional solidification(DS) apparatus. The experimental results show that Sn–10 wt.%Bi alloy is oriented with the form of dendrites to grow into the liquid phase during the DS process, and dendrites are arranged neatly to form columnar crystal microstructures. It is also found that parts of the dendrite arms begin to crack. These cracked dendrites drift upward to grow up in front of the solid-liquid interface and form stray crystals.展开更多
Osteoclasts are the bone resorbing cells essential for bone remodeling.Osteoclasts are formed from hematopoietic progenitors in the monocyte/macrophage lineage.Osteoclastogenesis is composed of several steps including...Osteoclasts are the bone resorbing cells essential for bone remodeling.Osteoclasts are formed from hematopoietic progenitors in the monocyte/macrophage lineage.Osteoclastogenesis is composed of several steps including progenitor survival,differentiation to mononuclear pre-osteoclasts,fusion to multi-nuclear mature osteoclasts,and activation to bone resorbing osteoclasts.The regulation of osteoclastogenesis has been extensively studied,in which the receptor activator of NF-κB ligand(RANKL)-mediated signaling pathway and downstream transcription factors play essential roles.However,less is known about osteoclast fusion,which is a property of mature osteoclasts and is required for osteoclasts to resorb bone.Several proteins that affect cell fusion have been identified.Among them,dritic cell-specific transmembrane protein(DC-STAMP)is directly associated to osteoclast fusion in vivo.Cytokines and factors influence osteoclast fusion through regula-tion of DC-STAMP.Here we review the recently discovered new factors that regulate osteoclast fusion with specific focus on DC-STAMP.A better understanding of the mechanistic basis of osteoclast fusion will lead to the development of a new therapeutic strategy for bone disorders due to elevated osteoclast bone resorption.Cell-cell fusion is essential for a variety of cellular biological processes.In mammals,there is a limited number of cell types that fuse to form multinucleated cells,such as the fusion of myoblasts for the formation of skeletal muscle and the fusion of cells of the monocyte/macrophage lineage for the formation of multinucleated osteoclasts and giant cells.In most cases,cellcell fusion is beneficial for cells by enhancing function.Myoblast fusion increases myofiber size and diameter and thereby increases contractile strength.Multinucleated osteoclasts have far more bone resorbing activity than their mono-nuclear counterparts.Multinucleated giant cells are much more efficient in the removal of implanted materials and bacteria due to chronic infection than macrophages.Therefore,they are also called foreign-body giant cells.Cell fusion is a complicated process involving cell migration,chemotaxis,cell-cell recognition and attachment,as well as changes into a fusion-competent status.All of these steps are regulated by multiple factors.In this review,we will discuss osteoclast fusion and regulation.展开更多
目的探讨血清涎液化糖链抗原⁃6(kreb von den lungen⁃6,KL⁃6)在非小细胞肺癌(non-small cell lung cancer,NSCLC)术后辅助治疗性肺损伤中的诊断价值。方法回顾性收集2017年11月-2020年7月中国医科大学附属盛京医院诊治的NSCLC患者(包括...目的探讨血清涎液化糖链抗原⁃6(kreb von den lungen⁃6,KL⁃6)在非小细胞肺癌(non-small cell lung cancer,NSCLC)术后辅助治疗性肺损伤中的诊断价值。方法回顾性收集2017年11月-2020年7月中国医科大学附属盛京医院诊治的NSCLC患者(包括术后采用辅助治疗者和仅手术者)资料,以药物诱导性肺损伤(drug induced lung injury,DILI)、放射性肺损伤(radiation induced lung injury,RILI)诊断共识为判断NSCLC术后辅助治疗性肺损伤的诊断标准,将NSCLC术后辅助治疗患者分为肺损伤组和无肺损伤组,仅手术者为NSCLC手术组;以年龄和性别匹配同期体检中心的健康成人为健康对照组。肺损伤组于肺损伤确诊当日,无肺损伤组于辅助治疗的第3~4个月,NSCLC手术组分别于术前、术后7~10 d,健康对照组于体检当日,空腹采集静脉血检测血清KL⁃6。比较各组血清KL⁃6差异,并以无肺损伤组为对照,采用受试者工作特征(receiver operating characteristic,ROC)曲线评估血清KL⁃6诊断NSCLC术后辅助治疗性肺损伤的效能。结果共206例符合纳入和排除标准的患者入选本研究,其中肺损伤组51例,无肺损伤组52例,NSCLC手术组103例;健康对照组103例,基线资料均衡可比。血清KL⁃6水平由高至低依次为肺损伤组[512.40(322.30,819.20)kU/L]、NSCLC手术组(术前)[204.40(162.70,283.20)kU/L]、健康对照组[177.70(154.20,206.40)kU/L]、无肺损伤组[147.80(114.25,229.80)kU/L]和NSCLC手术组(术后)[143.80(111.90,247.80)kU/L]。除无肺损伤组与NSCLC手术组术后血清KL⁃6无统计学差异(P=0.879)外,其余两两比较差异均有统计学意义(P均<0.05)。ROC曲线分析显示,血清KL⁃6诊断NSCLC术后辅助治疗性肺损伤的曲线下面积(area under the curve,AUC)为0.972(95%CI:0.948~0.997),灵敏度、特异度、阳性似然比、阴性似然比分别为86.3%(95%CI:73.0%~94.1%)、96.2%(95%CI:86.2%~98.7%)、22.43(95%CI:5.74~87.69)、0.14(95%CI:0.07~0.28),最佳诊断临界值为310.15 kU/L。结论NSCLC术后辅助治疗性肺损伤患者血清KL⁃6显著升高,其在NSCLC术后辅助治疗性肺损伤中具有较高的诊断价值,但仍需大样本前瞻性研究进一步验证。展开更多
基金Supported by Hong Kong Wang Kuan Cheng GrantInner Mongolia Stem Cell Grant, No. kjk10jhg
文摘AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.
基金This study was supported by a research foundation from Jian gsu Provincial Administration Bureau of TCM (No.9974)
文摘Objective: To investigate the distribution and recruitment of pulm onary dendritic cells (DCs) and the influence of low dosage arsenic trioxide (As 2O 3) on them in the airway of asthmatic mice. Methods: Thirty BALB/c mice were randomly divided into 3 groups: the control group, the asthmat ic group and the As 2O 3 treated group. The mice asthmatic model was induced v ia sensitizing with peritoneal injection of ovalbumin (OVA) for two times and th en provocated with aerosol inhalation of OVA for a week. The treated group was p eritoneally injected with 0.2 ml solution of As 2O 3 (4mg/kg) 0.5h after each provocation. The immunohistochemistry and computerised image analysis were appli ed to detect quantitatively the DCs in the lung and airway of mice. Resul ts: All intraepithelial nonlymphoid dendritic cells 145 (NLDC 145) throughout the respiratory tree in the mice of the control group formed a netwo rk with the density of DCs varying from (575±54) cells/mm 2 epithelial surface in the large airway, to (68±12) cells/mm 2 epithelial surface in the small ai rway. The distribution of airway NLDC 145 + in the asthmatic group was simil ar to that in the control group, but its density was significantly upregulated ( P <0.01). The distribution of airway NLDC 145 in the treated group was sim ilar to that in the asthmatic group, only its density was significantly downregu lated ( P <0.01). Conclusion: There is an integral network of N LDC 145 + throughout the respiratory tree. To downregulate the density but n ot change the distribution of pulmonary DCs could be an important therapeutic me chanism of low dosage As 2O 3 in treating asthma.
基金financially supported by the project of Yangtze Normal University under grant No.2017KYQD130 and No.2017XJQN08
文摘The stray crystals seriously affect the properties of metals which fabricated by directional solidification(DS). In order to observe the formation of the stray crystals, the growth behavior of Sn-10 wt.%Bi alloy was observed by synchrotron X-ray imaging technique using self-developed directional solidification(DS) apparatus. The experimental results show that Sn–10 wt.%Bi alloy is oriented with the form of dendrites to grow into the liquid phase during the DS process, and dendrites are arranged neatly to form columnar crystal microstructures. It is also found that parts of the dendrite arms begin to crack. These cracked dendrites drift upward to grow up in front of the solid-liquid interface and form stray crystals.
基金Supported by(in part)Grants R01-AR43510 to Boyce BF and R01-AR48697 to Xing L from the National Institute of Arthritis and Musculoskeletal and Skin Diseases,United States
文摘Osteoclasts are the bone resorbing cells essential for bone remodeling.Osteoclasts are formed from hematopoietic progenitors in the monocyte/macrophage lineage.Osteoclastogenesis is composed of several steps including progenitor survival,differentiation to mononuclear pre-osteoclasts,fusion to multi-nuclear mature osteoclasts,and activation to bone resorbing osteoclasts.The regulation of osteoclastogenesis has been extensively studied,in which the receptor activator of NF-κB ligand(RANKL)-mediated signaling pathway and downstream transcription factors play essential roles.However,less is known about osteoclast fusion,which is a property of mature osteoclasts and is required for osteoclasts to resorb bone.Several proteins that affect cell fusion have been identified.Among them,dritic cell-specific transmembrane protein(DC-STAMP)is directly associated to osteoclast fusion in vivo.Cytokines and factors influence osteoclast fusion through regula-tion of DC-STAMP.Here we review the recently discovered new factors that regulate osteoclast fusion with specific focus on DC-STAMP.A better understanding of the mechanistic basis of osteoclast fusion will lead to the development of a new therapeutic strategy for bone disorders due to elevated osteoclast bone resorption.Cell-cell fusion is essential for a variety of cellular biological processes.In mammals,there is a limited number of cell types that fuse to form multinucleated cells,such as the fusion of myoblasts for the formation of skeletal muscle and the fusion of cells of the monocyte/macrophage lineage for the formation of multinucleated osteoclasts and giant cells.In most cases,cellcell fusion is beneficial for cells by enhancing function.Myoblast fusion increases myofiber size and diameter and thereby increases contractile strength.Multinucleated osteoclasts have far more bone resorbing activity than their mono-nuclear counterparts.Multinucleated giant cells are much more efficient in the removal of implanted materials and bacteria due to chronic infection than macrophages.Therefore,they are also called foreign-body giant cells.Cell fusion is a complicated process involving cell migration,chemotaxis,cell-cell recognition and attachment,as well as changes into a fusion-competent status.All of these steps are regulated by multiple factors.In this review,we will discuss osteoclast fusion and regulation.
文摘目的探讨血清涎液化糖链抗原⁃6(kreb von den lungen⁃6,KL⁃6)在非小细胞肺癌(non-small cell lung cancer,NSCLC)术后辅助治疗性肺损伤中的诊断价值。方法回顾性收集2017年11月-2020年7月中国医科大学附属盛京医院诊治的NSCLC患者(包括术后采用辅助治疗者和仅手术者)资料,以药物诱导性肺损伤(drug induced lung injury,DILI)、放射性肺损伤(radiation induced lung injury,RILI)诊断共识为判断NSCLC术后辅助治疗性肺损伤的诊断标准,将NSCLC术后辅助治疗患者分为肺损伤组和无肺损伤组,仅手术者为NSCLC手术组;以年龄和性别匹配同期体检中心的健康成人为健康对照组。肺损伤组于肺损伤确诊当日,无肺损伤组于辅助治疗的第3~4个月,NSCLC手术组分别于术前、术后7~10 d,健康对照组于体检当日,空腹采集静脉血检测血清KL⁃6。比较各组血清KL⁃6差异,并以无肺损伤组为对照,采用受试者工作特征(receiver operating characteristic,ROC)曲线评估血清KL⁃6诊断NSCLC术后辅助治疗性肺损伤的效能。结果共206例符合纳入和排除标准的患者入选本研究,其中肺损伤组51例,无肺损伤组52例,NSCLC手术组103例;健康对照组103例,基线资料均衡可比。血清KL⁃6水平由高至低依次为肺损伤组[512.40(322.30,819.20)kU/L]、NSCLC手术组(术前)[204.40(162.70,283.20)kU/L]、健康对照组[177.70(154.20,206.40)kU/L]、无肺损伤组[147.80(114.25,229.80)kU/L]和NSCLC手术组(术后)[143.80(111.90,247.80)kU/L]。除无肺损伤组与NSCLC手术组术后血清KL⁃6无统计学差异(P=0.879)外,其余两两比较差异均有统计学意义(P均<0.05)。ROC曲线分析显示,血清KL⁃6诊断NSCLC术后辅助治疗性肺损伤的曲线下面积(area under the curve,AUC)为0.972(95%CI:0.948~0.997),灵敏度、特异度、阳性似然比、阴性似然比分别为86.3%(95%CI:73.0%~94.1%)、96.2%(95%CI:86.2%~98.7%)、22.43(95%CI:5.74~87.69)、0.14(95%CI:0.07~0.28),最佳诊断临界值为310.15 kU/L。结论NSCLC术后辅助治疗性肺损伤患者血清KL⁃6显著升高,其在NSCLC术后辅助治疗性肺损伤中具有较高的诊断价值,但仍需大样本前瞻性研究进一步验证。
