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.     

Granulocyte colony-stimulating factor ameliorates coronary artery elastin breakdown in a mouse model of Kawasaki disease

Background Coronary artery damage from Kawasaki disease （KD） is closely linked to the dysfunction of the endothelial progenitor cells （EPCs）.The aim of the present study was to evaluate the modulatory effect of granulocyte colony stimulating factor （G-CSF） on EPCs and elastin breakdown of coronary arteries in a KD mouse model.Methods A Lactobacillus casei cell wall extract （LCWE）-induced KD model was established in C57BL/6 mice that were subsequently administrated with recombinant human G-CSF （rhG-CSF）.Nω-nitro-L-arginine methyl ester （L-NAME） was administrated for the negative intervention.Evaluations included coronary artery lesions,EPC number and functions,and the plasma concentration of nitric oxide （NO）.Results Elastin breakdown was found in the coronary arteries of model mice 56 days after injection of LCWE.The number of circulating EPCs,plasma concentration of NO,and functions of bone marrow EPCs,including proliferation,adhesion,and migration abilities,were all lower in the KD model group compared with those in the control group.After administration of rhG-CSF,the number of circulating EPCs and plasma concentration of NO were increased significantly compared with those in the KD model group.There were also increases in the functional indexes of EPCs.Furthermore,rhG-CSF administration improved the elastin breakdown effectively.However,these protective effects of rhG-CSF on coronary arteries were attenuated by L-NAME.Conclusion The present study indicated that the administration of G-CSF prevents elastin breakdown of the coronary arteries by enhancing the number and functions of EPCs via the NO system,and then accelerates the repair of coronary artery lesions in the KD.     

Autologous hematopoietic stem cell transplantation and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes: long term follow-up

Background It has been indicated that autologous hematopoietic stem cell transplantation （AHST） is a promising treatment to adults with type 1 diabetes, however, the application of AHST therapy to children with type 1 diabetes still needs more data. The aim of this study was to assess the clinical effect of immune intervention combined with AHST and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes. Methods This 1：2 matched case-control study was comprised of 42 children who were newly diagnosed with type 1 diabetes in the Department of Endocrinology, Beijing Children＇s Hospital from 2009-2010. The case group included 14 patients, who were treated with AHST within the first 3 months after being diagnosed with diabetes at request of their parents during 2009-2010. The control group included 28 patients with newly diagnosed type 1 diabetes at the same period of hospitalization. We compared the baseline and follow-up data of them, including ketoacidosis onset, clinical variables （glycosylated hemoglobin （HbAlc）, insulin dosage and serum C-peptide）. Results The clinical characteristics of the patients was comparable between the case group and the control group. At 6-12 months （（10.7±4.2） months） after AHST treatment, we found 11 patients in the case group did not stop the insulin therapy, three cases stopped insulin treatment for 2, 3 and 11 months, respectively. No diabetic ketoacidosis （DKA） occurred after transplantation in all the patients in the case group. HbAlc in the control group was significant lower than that in the case group （P 〈0.01）, while the insulin dosage and serum C-peptide were not significant different between the two groups （P 〉0.05）. In order to eliminate the honeymoon effect, we performed final follow-up at the 3-5 years （（4.2±1.8） years） after AHST treatment, and found that HbAlc in the control group was still lower than that in the case group （P 〈0.01）; however, the insulin dosage and serum C     

Immune-mediated neuromuscular complications after haploidendtical hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation （Allo-HSCT） is associated with neuromuscluar complications in fewer than 5% of patients.1 The most common causes are associated with the toxicity of the conditioning regimen,infections,bleeding,and malignant disease relapse.Allo-HSCT related neuromuscular complications can also be caused by immune-mediated mechanisms,which are usually present in the form of myositis/polymyositis or demyelinating polyneuropathy.Keywords：allogeneic hematopoietic stem cell transplantation; immune mediated; chronic demyelinating polyneuropathy;steroid myopathy     

Adipose-derived stem cells in stroke treatment: translational possibility and mechanism

Stroke has become one of the secondary worldwide mortal diseases that burdens the family and the society both emotionally and economically. The announcement of China＇s Ministry of Health in 2008 showed that stroke had been the first cause of death in urban and rural residents.1.2 Traditional therapies such as thrombolysis, anti-platelets, and rehabilitation showed limited effects. Replacement therapy with stem cells promises to be a good solution due to its possible thorough therapy for the damaged brain area, reconstruction of neuronal circuitry, and probable long-term efficacy. Previous studies demonstrated that stem ceils have played crucial roles in various kinds of tissue repair and immune disorders such as cardiovascular diseases, skeletal diseases, arthritis diseases, and lupus erythematodes.37 Evidence from lab experiments and clinical trials implies that adipose-derived stem cells （ADSCs） would be a feasible and ideal cell therapy source because of their multi-differentiation potentials, easy collection, low invasion to donor patients, rapid in vitro amplification, reliable biosafety, non-immunogenicity, privileged immune modulation, and escaping from ethical issues.8-12： Data on neurological disease treatment found that ADSCs transplantation protected against acute inflammatory injury, delayed neuron degeneration, and improved neurological behaviors.12-15 Previously, the detailed mechanisms by which transplanted ADSCs induce functional recovery for stroke treatment are far from being clearly demonstrated. Some proposed reasonable mechanisms just stayed at the level of explanation and hypothesis due to the absence of solid experimental evidence.13-14 In this article, we analyzed the previous data to figure out some new paths or ideas which may do favor to future translational clinical studies.     

Are Cancer Stem Cells the Sole Source of Tumor？

Tumors are believed to consist of a heterogeneous population of tumor ceils originating from rare cancer stem cells （CSCs）. However, emerging evidence suggests that tumor may also origi- nate from non-CSCs. To support this viewpoint, we are here to present definitive evidence indicating that the number of tumorigenic tumor cells is greater than that of CSCs in tumor, and tumor can also derive from non-CSCs. To achieve this, an idealized mathematical model was employed in the pre- sent study and theoretical calculation revealed that non-CSCs could initiate the occurrence of tumor if their proliferation potential was adequate. Further, experimental studies demonstrated that 17.7%, 38.6% and 5.2% of tumor cells in murine B16 solid melanoma, H22 hepatoma and Lewis lung carci2 noma, respectively, were potentially tumorigenic. Thus, based on the aforementioned findings, we propose that the scarce CSCs, if exist, are not the sole source of a tumor.     

Reinnervation of hair cells by neural stem cell-derived neurons

Background Replacement of spiral ganglion neurons would be one prioritized step in an attempt to restore sensory neuronal hearing loss.However,the possibility that transplanted neurons could regenerate new synaptic connections to hair cells has not been explored.The objective of this study was to test whether neural stem cell （NSC）-derived neurons can form synaptic connections with hair cells in vitro.Methods NSCs were mechanically separated from the hippocampus in SD rat embryos （E12-E14） and cultured in a serum-free medium containing basic fibroblast growth factor and epidermal growth factor.Rat NSCs were co-cultured with explants of cochlea sensory epithelia obtained from postnatal Day 3 rats under transway filter membrane.Results At Day 3,the NSCs began to show chemotactic differentiation and grew toward cochlea sensory epithelia.After 9-day co-culture,neurites of NSC-derived neurons predominantly elongated toward hair cells.Immunohistochemical analyses revealed the fibers overlapped with synapsin and hair cells,indicating the formation of new synaptic connections.After 14-day culture,triple staining revealed the fibers overlapped with PSD95 （postsynaptic density） which is juxtaposed with CtBP2 （presynaptic vesicle）,indicating the formation of new ribbon synapse.Conclusions NSC-derived neurons can make synaptic connections with hair cells and provide a model for studying synaptic plasticity and regeneration.Whether the newly forming synapse is functional merits further electrophysiological study.     

Interferon α: the salvage therapy for patients with unsatisfactory response to minimal residual disease-directed modified donor lymphocyte infusion

Background Minimal residual disease （MRD）-directedmodified donor lymphocyte infusion （mDLI） is used to treat relapse after hematopoietic stem cell transplantation （HSCT）. For patients who experience an unsatisfactory response tomDLI relapse is usually inevitable. Therefore we sought to evaluate the efficacy ofinterferon a therapy in these patients. Methods Regular MRD monitoring was carried out after the HSCT. The patients who were MRD-positive underwent mDLI. Patients with an unsatisfactory response to mDLI received interferon a therapy （3 million units, twice weekly） with regular monitoring of MRD. To ensure the immunomodulatory effects of interferon a, immunosuppressant treatment would be stopped before interferon a treatment. Results Five patients with an unsatisfactory response to mDLI treatment received interferon a （3 had t（8;21） chromosomal translocation acute myeloid leukemia, and 2 had common acute leukemia）. They had significantly reduced or resolved MRD. Four patients developed chronic graft-versus-host disease. Two of the 5 patients reported transient fevers, and no significant bone marrow suppression was observed. All of them were in continuous complete remission after interferon a treatment. The median survival time was 469 days （range 368-948 days）. Conclusions In patients with an unsatisfactory response to MRD-directed mDLI, interferon a may directly or indirectly induce the graft-versus-leukemia effect to improve mDLI efficacy and clear MRD. Chin Med J 2014;127 （14）： 2583-2587     

Astrocytes Facilitate the Growth and Differentiation of Co-cultured Mesenchymal Stem Cells

The effect of astrocytes on the growth and differentiation of co-cultured mesenchymal stem cells （MSCs） was studied. MSCs of Wistar rats were isolated, cultured and labeled with Hoechst33342. The labeled MSCs were co-cultured with astrocytes in DMEM/F12/10%FBS. The growth status and morphologic change of MSCs were observed. The expression of specific protein NeuN, GFAP and CNP was detected by using immunofluorescence staining. The results showed that the two kinds of co-cultured cells grew well. Some labeled MSCs stretched out long processes with spin, triangle and star shapes. Immunofluorescence stain showed that these cells expressed NeuN, GFAP or CNP. It was suggested that astrocytes could promote the prolifevation of co-cultured MSCs and induce them to differentiate into neural like cells.     

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.     

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.     

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.     

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.     

Effects of Bone Marrow-derived Mesenchymal Stem Cells on TGF-β and MCP-1 in Injured Lung of Rats

The primary objective of the present study is to investigate the therapeutic effect of bone marrow-derived mesenchymal stem cells （MSCs） on bleomycin （BLM）-induced lung injury of rats and the effect on transforming growth factor-β （TGF-β） and monocyte chemoattractant protein-1 （MCP-1）. MSCs were isolated from SD rats. The recipients rats were divided randomly into four groups： lung injury group, MSC treatment group, MSC control group and normal control group. Rats of lung injury group and MSC treatment group were perfused with BLM of 5mg/kg （0.2-0.3ml） intratracheally, others were perfused with normal saline. After twelve hours, rats of MSC treatment group and MSC control group were injected MSCs of 0.5×10^6per rat into tail vein. Haematoxylin-eosin staining was used to observe the morphology in lung tissue. ELISA was used to detect the contents of TGF-β and MCP-1 in serum and bronchoalveolar lavage fluid （BALF）. Collagen content of the lung tissue was assessed by hydroxyproline （HYP） concentration. It was found that the thickness of alveolar wall and lung interstitium were significantly reduced in the rats of MSC treatment group compared with the lung injury group. HYP content in lung interstitium, TGF-β and MCP-1 in serum and BALF were increased significantly in rats of lung injury group two weeks after BLM perfusion, but they were reduced significantly in the rats of MSC treatment group compared with the injured rats. These observations provide evidence that MSCs engraftment could alleviate bleomycin-induced lung injury and fibrosis in rats and the therapeutic effects might relate with the decrease of TGF-β and MCP-1.     

Prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer

Background The prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer （NSCLC） remains unclear.This study intends to identify the prognostic factors and to optimize treatments for these patients under update conditions.Methods The data of 124 NSCLC patients who underwent R1-resection at the bronchial stump was reviewed.There were 41 patients in the surgery group （S）,21 in the postoperative radiotherapy （PORT） group （S＋R）,30 in the postoperative chemotherapy （POCT） group （S＋C）,and 32 in the PORT plus POCT group （S＋R＋C）.The constitute proportion in different groups was tested using the X2 method,univariate analysis was performed using the Kaplan-Meier and log-rank method,and multivariate analysis was done using the Cox hazard regression with entry factors including age,sex,pathological type and stage,classification of the residual disease,and treatment procedure.The process was performed stepwise backward with a maximum iteration of 20 and an entry possibility of 0.05 as well as an excluded possibility of 0.10 at each step.Results In univariate analysis,survival was more favorable for patients with squamous cell carcinoma,early pathological T or N stage,and chemotherapy or radiotherapy.There was no significant difference in the survival for patients with different types of the residual disease,except for the difference between patients with carcinoma in situ and lymphangiosis carcinomatosa （P=0.030）.The survival for patients receiving chemoradiotherapy was superior to that for those undergoing surgery alone （P=0.016）.In multivariate analysis,the pathological type （HR 2.51,95% CI 1.59 to 3.96,P=0.000）,pathological T （HR 1.29,95% CI 1.04 to 1.60,P=-0.021） or N stage （HR 2.04,95% CI 1.40 to 2.98,P=0.000）,and chemotherapy （HR 0.24,95% CI 0.13 to 0.43,P=0.000） were independent prognostic factors.Conclusion Patients with squamous cell carcinoma,early pathological T or N stage,or receiving chemotherapy had a more favorable pro     

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.     

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.     

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.