Giant cell interstitial pneumonia: unusual lung disorder and an update

Background Giant cell interstitial pneumonia （GIP） was a rare form of pneumoconiosis,associated with exposure to hard metals,which had been reported mostly as isolated case reports.We described eight cases of GIP diagnosed in our hospital during the past seven years,with particular reference to new findings.Methods Eight patients with GIP confirmed by biopsy in the Nanjing Drum Tower Hospital affiliated to Medical School of Nanjing University from 2005 to 2011 were retrospectively analyzed.For each patient,the occupy histories and medical records were thoroughly reviewed and clinic data were extracted.Two radiologists,without knowledge of any of the clinical and functional findings,independently reviewed the HRCT scans of all patients.Follow-up data were collected.Results Among the eight patients,seven had a history of exposure to hard metal dusts,one denied an exposure history.The most common manifestations were cough and dyspnea.One patient initiated with pneumothorax and another pleural effusion,both of which were uncommon to GIP.The main pathologic appearances were the presence of macrophages and multinucleated giant cells in the alveolar space.The clinical symptoms and radiographic abnormalities were obviously improved after cessation of exposure and receiving corticosteroid treatments,recurrences were observed in two patients when they resumed work.In spite of exposure cessation and corticosteroid treatment,one patient developed pulmonary fibrosis at seven years follow-up.Conclusions Awareness of the patients＇ occupational history often provided clues to the diagnosis of GIP.Histopathologic examinations were necessary to establish the right diagnosis.Exposure cessation was of benefit to most patients; however,pulmonary fibrosis was possible in spite of exposure cessation and corticosteroid treatment.Better ways should be found out to improve the outcome and quality of life.     

非小细胞肺癌患者MET表达水平是MET单抗的预后预测因素

1文献来源 Koeppen H,Yu W,Zha JP,et al.Biomarker analyses from a placebo-controlled phaseⅡstudy evaluating Erlotinib±Onartuzumab in advanced non-small-cell lung cancer：MET expression levels are predictive of patient benefit[J].Clin Cancer Res,2014,Mar 31[Epub ahead of print].DOI：10.1158/1078-0432.CCR-13-1836.     

MET 激酶在非小细胞肺癌中的活化

1文献来源 研究一：Qiao H,Hung W,Tremblay E,et al.Constitutive activation of met kinase in non-small-cell lung carcinomas correlates with anchorageindependent cell survival[J].J Cell Biochem,2002,86（4）：665-677.     

艾迪注射液配合化疗治疗晚期非小细胞肺癌临床观察

目的观察艾迪注射液配合化疗治疗晚期非小细胞肺癌的临床疗效。方法将82例晚期非小细胞肺癌患者随机分成治疗组（艾迪注射液加化疗组）和对照组（单纯化疗组）,21d为1个疗程,共观察2个疗程,观察2组近期疗效、免疫学指标、体质量及生活质量的变化。结果治疗组近期总有效率为58．54％,对照组为36．59％,2组比较差异有统计学意义（p〈0．05）;治疗后治疗组CD^＋3、CD^＋4细胞百分率、CD^4/CD^＋8比值、NK细胞较治疗前明显增高,差异具有统计学意义（P〈0．05）,且优于对照组,差异具有统计学意义（P〈0．05）。结论艾迪注射液配合化疗治疗晚期非小细胞肺癌的近期疗效较好,能改善其免疫功能,提高生活质量。     

表皮生长因子受体酪氨酸激酶抑制剂在非小细胞肺癌应用的瓶颈——获得性耐药

以表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI）分子靶向治疗研究为肇始,转化性研究使基础实验和临床实践间的鸿沟迅速填平,改变着人们认识治疗肺癌的视角。无可否认,EGFR-TKI上市后极大地延伸了肿瘤学家治疗肺癌的手段,但不管从临床经验、临床研究数据、分子生物学层面还是文献计量学的角度,     

Inhibitory Effects of Roscovitine on Proliferation and Migration of Vascular Smooth Muscle Cells In Vitro

Abnormal proliferation and migration of vascular smooth muscle cells （VSMCs） are the major cause of in-stent restenosis （ISR）. Intervention proliferation and migration of VSMCs is an im- portant strategy for antirestenotic therapy. Roscovitine, a second-generation cyclin-dependent kinase in- hibitor, can inhibit cell cycle of multiple cell types. We studied the effects of roscovitine on cell cycle distribution, proliferation and migration of VSMCs in vitro by flow cytometry, BrdU incorporation and wound healing assay, respectively. Our results showed that roscovitine increased the proportion of Go/G1 phase cells after 12 h （69.57±3.65 vs. 92.50±1.68, P=0.000）, 24 h （80.87±2.24 vs. 90.25±0.79, P=0.000） and 48 h （88.08±3.86 vs. 88.87±2.43, P=-0.427） as compared with control group. Roscovifine inhibited proliferation and migration of VSMCs in a concentration-dependent way. With the increase of concen- tration, roscovitine showed increased capacity for growth and migration inhibition. Roscovitine （30 μmol/L） led to an almost complete VSMCs growth and migration arrest. Combined with its low toxicity and selective inhibition to ISR-VSMCs, roscovitine may be a potential drug in the treatment of vascular stenosis diseases and particularly useful in the prevention and treatment of ISR.     

Preliminary study on the evaluation of Langerhans cell histiocytosis using F-18-fluoro-deoxy-glucose PET/CT

Background Limited number of studies have been reported regarding the utilization of F-18-fluoro-deoxy-glucose （F-18-FDG） positron emission tomography/computed tomography （F-18-FDG PET/CT） in Langerhans cell histiocytosis （LCH）.The aim of this study was to assess the role of F-18-FDG PET/CT in the diagnosis and treatment of LCH.Methods Eight newly diagnosed and seven recurrent patients with LCH received F-18-FDG PET/CT scans.The diagnosis of LCH was established by pathology,multi-modality imaging,and clinical follow-up.Results F-18-FDG PET/CT was positive in 14 patients with 13 true positives and one false positive.All 45 LCH lesions were F-18-FDG avid including six small bone lesions ＜1.0 cm in diameter.The mean maximal standardized uptake value （SUVmax） was 7.13±4.91.F-18-FDG uptake showed no significant difference between newly diagnosed lesions vs recurrent lesions （SUVmax：6.50±2.97 vs.7.93±6.60,t=-0.901,P=0.376）.Among 45 LCH lesions,68.9％ （31/45） were found in bones and 31.1％ （14/45） in soft tissue.The most commonly involved bones were the pelvis and vertebrae.There was no significant difference in F-18-FDG uptake between bone lesions vs.non-bone lesions （SUVmax：6.30±2.87 vs.8.97±7.58,t=1.277,P=0.221）.In two patients,changes in F-18-FDG uptake on serial PET/CT scans reflected response of lesions to treatment.Conclusions The present study suggests that F-18-FDG PET/CT may be useful for diagnosis and assessing the treatment response of LCH.Because of the small sample size,further research is warranted to confirm our findings.     

Effects of substance P on growth of fibroblast-like cells derived from bile duct: an in vitro cell culture study

Background The possible role of substance P （SP） during wound healing has been the primary research focus in recent years,but its effect on the healing process after bile duct injury is little understood.This study aimed to investigate the effects of SP on growth of fibroblast-like cells derived from rabbit bile duct.Methods Fibroblast-like cells derived from rabbit bile duct were identified and divided randomly into control and experimental groups.SP-treated cells at different concentrations of 10^-9-10^-5 mol/L and control group were incubated,respectively,for 48 hours.After incubating,the effects of SP on cell proliferation were assessed by cell counts and MTT test.Apoptosis rate （AR） of cells was measured by flow cytometry.Results Cultured rabbit bile duct cells were fibroblast-like in morphology,and these cells were stained positively for vimentin and negatively for desmin.After SP was added to nonconfluent cells for 48 hours,cell numbers were significantly increased in experimental groups than in controls （P 〈0.05）.The maximum stimulation of cell proliferation was achieved at SP of 10^-5 mol/L.Bile duct fibroblast-like cells in the SP group showed a higher proliferating activity and lower AR than those in the control group or in the SP ＋ Spantide group （P 〈0.05）.Spantide partly inhibited the effects of SP on fibroblastlike cells.Examination under transmission electron microscopy revealed rough endoplasmic reticulum and prominent Golgi complexes after SP treatment.Conclusions SP has a growth regulatory property on cultivated bile duct fibroblast-like cells in vitro,suggesting that SP may involve in wound healing after bile duct injury by promoting wound fibroblast proliferation and inhibiting apoptosis and participate in pathological scar formation.     

Depressant effect and mechanism of atorvastatin on the chronic rejection of aortic allograft in rats

Objective To investigate the depressant effect and mechanism of atorvastatin on the chronic rejection of aortic allograft in rats. Methods： The models of abdominal aorta transplantation were made with micro-surgery in rats. The recipients were divided into three groups： allograft control group, atorvastatin-treated group and isograft control group. Vascular intimal thickness in all of the groups were observed by histological examination. The expression of PCNA and α-SMA were determined by immunohistochemistry. The content of nitric oxide was determined by nitrate reductase chromatometry. Results： The vascular intimal thickness in rats of atorvastatin-treated group （11.60% ± 2.40% ） were lower than those in allograft control group （34.60 % ± 6.40 % ; P 〈 0.05） and higher than those in isograft control group （1.15 % ± 0.65 %; P〈 0.05 ）. The expression level of PCNA was decreased in atorvastatin-treated group （4.80% ± 0.80% ） than allograft control group （18.40% ± 1.80% ; P〈0.05） and higher than isograft group （1.20% ± 0.40% ; P〈0.05）. Conclusion： The expression of PCNA in the transplant aorta could be suppressed by atorvastatin, which resalted in relief of chronic rejection of aortic allograft.     

Influence of blastocysts morphological score on pregnancy outcomes in frozen-thawed blastocyst transfers: a retrospective study of 741 cycles

The influence of inner cell mass （ICM） and trophectoderm （TE） score on pregnancy out- comes in frozen-thawed blastocyst transfer cycles was analyzed. A retrospective analysis of 741 cycles of frozen-thawed blastosysts transfer was performed. All cycles were divided into four groups based on the number and morphological score of blastocysts： S-ICM B/TE B group （n=91）, the single blastocyst transfer oflCM B and TE B; D-ICM B/TE B group （n=579）, double blastocysts transfer oflCM B/TE B; D-1CM B/TE C group （n=35）, double blastocysts transfer of ICM B/TE C; and D-ICM C/TE B group （n=36）, double blastocysts transfer ofTE B/ICM C. The pregnancy outcomes were compared among the four groups. As compared with D-ICM B/TE C group, the clinical pregnancy rate, implantation rate and multiple pregnancy rate were increased in D-ICM B/TE B group （74.96% vs. 57.14%, 57.43% vs. 37.14%, and .48.62% vs. 25%, respectively, P〈0.05 for all）. Clinical pregnancy rate and implantation rate in D-ICM B/TE B group were also higher than in D-ICM C/TE B group （74.96% vs. 50%, and 57.43% vs. 33.33%, both P〈0.05）. Multivariable Logistic regression analysis indicated that ICM score was a better predictive parameter for clinical pregnancy （OR=3.05, CI 1.70-5.46, P〈0.001）, while the trophectoderm score was a better one for early abortion （OR=0.074, CI 0.03-0.19, P〈0.001）. Clinical pregnancy rate and multiple pregnancy rate in S-ICM B/TE B group were significantly lower than those in D-ICM B/TE B group （46.15% vs. 74.96%, and 2.38% vs. 48.62%, both P〈0.05）, but there was no si~,,niflcant difference in the implantation rate between the two groups. It was suggested that the higher score of ICM and TE may be indicative of the better pregnancy outcomes. The ICM score is a better predictor of clinical pregnancy than TE, while TE score is a better one in predicting early abortion. Sin- gle ICM B/TE B blastocyst transfer in frozen-thawed cycles can also get satisfactory pregnancy out- comes.     

明智选择：常见的肺癌治疗决策

2014年3月6—7日。中国抗癌协会肺癌专业委员会和中国临床肿瘤学会（Chinese Society of Clinical Oneology,CSCO）联合主办了第十一届“中国肺癌高峰论坛”。本届高峰论坛讨论了常见肺癌治疗决策的几个问题。专家们认为,我们在临床实践中做出一项用于患者的医疗措施,必须符合以下四大原则：     

Immunosuppression for 6–8 weeks after modified donor lymphocyte infusion reduced acute graft-versus-host disease without influencing graft-versus-leukemia effect in haploidentical transplant

Background In haploidentical hematopoietic stem cell transplantation （HSCT）, the duration of graft-versus-host disease （GVHD） prophylaxis after modified donor lymphocyte infusion （DLI） was the only risk factor of DLI-associated grades 3-4 acute GVHD. However, the successful application of modified DLI depended not only on the reduction of severe GVHD, but also on the preservation of graft-versus-leukemia （GVL） effect. Therefore, this study was performed to compare the impact of prophylaxis for 6-8 weeks and prophylaxis for 〈6 weeks on GVL effect after modified DLI in haploidentical HSCT. Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease （MRD）-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively. Fifty-two patients received prophylaxis for 6-8 weeks after modified DLI; the remaining 51 patients received prophylaxis for 〈6 weeks. Results First, compared with prophylaxis for 〈6 weeks, prophylaxis for 6-8 weeks reduced incidence of relapse in total patients （26.6% vs. 69.0%, P 〈0.001）. Besides, prophylaxis for 6-8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant （P=0.018） and in 49 patients developing MRD-positive status post-transplant （P 〈0.001）. Second, prophylaxis for 6-8 weeks reduced incidence of acute GVHD （P 〈0.05）, reduced the therapeutic application of immunosuppressive agents （P=0.019）, but increased the incidence of chronic GVHD （P〈0.05）. Third, prophylaxis for 6-8 weeks improved overall survival and disease-free survival in total patients, as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant （P 〈0.05）. Conclusions In haploidentical HSCT, prophylaxis for 6-8 weeks after modified DLI does not reduce GVL effect, but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for 〈6 weeks.     

复合型肺癌的诊治策略

1病历摘要 患者女性,1956年11月出生。患者2012年初开始出现咳嗽．因病情持续未缓解至当地医院就诊,2012—12-24在江门市中心医院检查,胸部CT提示右肺上叶后段肿块,     

Immunophenotypic analysis of abnormal plasma cell clones in bone marrow of primary systemic light chain amyloidosis patients

Background Primary systemic light chain amyloidosis （AL） is a rare plasma cell disease,our purpose was to analyze the immunophenotypic characteristics of the plasma cells in bone marrow in AL patients,and explore whether the detection of abnormal plasma cell clones in bone marrow by flow cytometry （FCM） could be used as an important indicator of AL diagnosis.Methods Fresh bone marrow samples were collected from 51 AL,21 multiple myeloma （MM）,and 5 Waldenstr（o）m＇s macroglobulinemia （WM） patients.The immunophenotype of bone marrow cells were analyzed and compared by FCM using a panel of antibodies including CD45,CD38,CD138,CD117,CD56,and CD19.Results In AL,light chain restriction could be identified in 31 cases （60.9%）,in which the λ light chain restriction was found in 24 cases （77.4%）.In MM,κ light chain restriction was found in 13 cases （61.9%）,and λ light chain restriction in eight cases.CD45 on abnormal plasma cells was negative to weakly positive in both AL and MM,but was positive to strongly positive in WM.In the bone marrow plasma cells of the 51 AL,78.4% were CD56＋,68.6% were CD117＋,and 88.2% were CD19-.While in the 21 MM cases,66.7% were CD56＋,38.1% were CD117＋,and 90.4% were CD19-.The plasmacytoid lymphocytes in the five WM patients were CD19＋ and CD56-,CD117-.Conclusion Detection of abnormal plasma cell clones in bone marrow by FCM is valuable for the diagnosis of AL.     

Effects of Quercetin on Hedgehog Signaling in Chronic Myeloid Leukemia KBM7 Cells

Objective：To investigate the effects of quercetin on Hedgehog（Hh） signaling in chronic myeloid leukemia KBM7 cells.Methods：The KBM7 cells were treated with 50,100 and 200 μmol/L quercetin for48 h respectively.And then the trypan blue assay was used to examine the proliferative inhibition of quercetin.Apoptotic cells and cell cycle were measured by flow cytometry.The mRNA and protein expression were detected by quantitative real-time polymerase chain reaction（PCR） and Western blot,respectively.Results：Quercetin significantly inhibited KBM7 cell proliferation,induced cell apoptosis,and blocked cell cycle at G1 phase,which were in dose-dependent manners.The mRNA and protein expression of Smoothened and Gliomal（Gli1）,the members of Hh pathway decreased after treatment with quercetin.The Bcl-2 and Cyclin D1,targets of Hh signaling,also decreased after treatment with quercetin,respectively.Quercetin also could increase p53 and Caspase-3 expression.Bcr-abl mRNA copies decreased,but no changes of phosphorylated Bcr-abl and Bcr-abl proteins were observed,after treatment with quercetin.Conclusion：Quercetin could inhibit Hh signaling and its downstream targets in the KBM7 cells.And it might be one of mechanisms of inducing apoptosis and inhibiting cell cycle by quercetin.     

Younger age of onset and multiple primary lesions associated with esophageal squamous cell carcinoma cases with a positive family history of the cancer suggests genetic predisposition

Background Previous epidemiological studies have consistently found a positive family history of esophageal cancer is associated with a significantly increased risk of the cancer.However,whether the elevated risk could be attributed to common household exposure or inherited susceptibility is uncertain.This study aimed to highlight the effect of genetic predisposition by noting the significant differences in onset age and multiple primary cancers between esophageal squamous cell carcinoma （ESCC） cases with or without a positive family history of the cancer.Methods Age at onset and the percentage of multiple primary cancers were compared between ESCCs with （n=766） or without （n=1 776） a positive family history of the cancer in a consecutive surgery cohort at the Department of Thoracic Surgery of Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University.Results Overall,ESCCs with a positive family history of the cancer featured both a significantly younger age of onset and significantly more multiple primary cancers than those with a negative family history （onset age 51.83 vs.53.49 years old,P 〈0.01; percent of multiple primary cancers 5.50% vs.1.70%,x2=25.42,P 〈0.01）.Both the differences were evident in subgroup analyses,but did not correlate.While age at onset differed significantly by family history among the male,smoking,and drinking groups,the difference of multiple primary cancers was significant among the otherwise nonsmoking,nondrinking,and younger onset age groups.Conclusions Younger age of onset and multiple primary cancers associated with ESCCs with a positive,as opposed to a negative family history of the cancer,suggest a genetic predisposition.The results of subgroup analyses indicate a younger age of ESCC development results from the interaction of environmental and genetic risk factors,but multiple primary cancers may be related only to genetic predisposition.     

Negative association of donor age with CD34+ cell dose in mixture allografts of G-CSF-primed bone marrow and G-CSF-mobilized peripheral blood harvests

Background The effects of donor characteristics on CD34＋ cell dose remain controversial. Recently, we developed a novel haploidentical transplant protocol, in which mixture allografts of granulocyte colony-stimulating factor （G-CSF）- primed bone marrow （G-BM） and G-CSF-mobilized peripheral blood （G-PB） were used. The aim of this study was to investigate the effects of donor characteristics on CD34＋ cell dose in mixture allografts of G-BM and G-PB. Methods A total of 162 healthy adult donors, who underwent bone marrow harvest and peripheral blood collection between January 2009 and November 2010 in Peking University People＇s Hospital, were prospectively investigated. G-CSF was administered subcutaneously at a dose of 5 pg/kg once a day for 5-6 consecutive days. Bone marrow and peripheral blood stem cells were harvested on the fourth day and fifth day, respectively. A final total CD34＋ cell dose less than 2× 106 cells/kg recipient body weight was considered a poor mobilization. Results Of the 162 donors, 31 （19.1%） did not attain this threshold. The obtained median CD34＋ cell doses in bone marrow, peripheral blood, and mixture allografts were 0.83×106/kg, 2.40×106/kg, and 3.47×106/kg, respectively. Multiple regression analysis showed that donor age had a significant negative effect on CD34＋ cell dose in either G-BM, or G-PB, or mixture allografts of G-BM and G-PB. And a 1-year increase in age was associated with a 5.6% decrease in the odds of achieving mobilization cutoff. No significant correlation was found for donor gender, body mass index （BMI）, and weight. Conclusion Donor age is the only factor among the four parameters, including age, gender, weight, and BMI, that influence CD34＋ cell dose in mixture allografts of G-BM and G-PB, and younger donors should be chosen to obtain sufficient CD34＋ cells for transplantation.     

金长娟主任善用七叶灵方治疗晚期非小细胞肺癌学术经验

金长娟,上海交通大学附属胸科医院中西医结合科主任医师,胸科医院＂十二五＂国家中医药管理局重点专科学科带头人,上海市中医药学会肿瘤分会委员,上海市中西医结合学会肿瘤分会委员。从事中医和中西医结合肺部肿瘤的治疗、科研30余年,医术精湛,尤其对于晚期非小细胞肺癌的中西医治疗积累了丰富的临床经验,拥有独到的见解,并在长期临床实践的基础上,总结出验方＂七叶灵方＂。     

肺癌EGFR基因突变"Web of Science"溯源

2004年4—5月，美国的两个研究小组在《新英格兰医学杂志》和《Science》上几乎同时发表的两篇关于“表皮生长因子（epidermal growth factor receptor．EGFR）基因突变预测TKI（tyrosine kinase inhibitor）治疗肺癌敏感性”的文章．吸引了肺癌研究领域所有学者的眼球．无数临床医生、基础研究人员为此孜孜不倦。转化性研究迅速使肺癌治疗观念向个体化分子靶向治疗过渡。在随后的短短两年间．全球各个著名肺癌研究团队发表的大量论文重复和充实了相关知识领域，使人们对靶向治疗的认识不断深化。与此同时．引申出越来越多令人着迷、引人探索也使人困惑的论题。