Objective To explore the efficacy of mycophenolate mofetil (MMF), which is a kind of immuno-suppressant drugs, on the treatment of Connective tissue diseases-pulmonary arterial hypertension (CTD-PAH). Methods Medical charts of eleven cases of hospitalized patients who were diagnosed as CTD-PAH and treated by MMF in Beijing Chaoyang Hospital affiliated to the Capital Medical University, from January 2014 to June 2016 were collected and analyzed. Results In the 11 cases of CTD-PAH, the systemic lupus erythematosus (SLE) related pulmonary hypertension (SLE-PAH) were 7, while the systemic sclero-derma associated pulmonary hypertension (SSc-PAH) were 2, and rheumatoid arthritis related pulmonary hy-pertension (RA-PAH) was 1, and the mixed connective tissue disease related pulmonary hypertension (MCTD-PAH) was 1. All patients were women, and the average age was (40 ±14) years, and the average duration of PAH was (34 ±35) months. The combination therapy of corticosteriods and MMF was applied to 7 cases, meanwhile the therapy of corticosteriods, MMF and bosentan was used in 1 case, corticosteriods, MMF and sildenafil was prescribed for 3 cases, and symptoms of the patients alleviated. Except for one case having been followed up for 7 months and one for 6 months, 9 patients completed the 1-year follow-up, and the survival rate was 100%(9/9). Notably, one patient, who had been alleviated for 111 months with therapy of corticosteriods and MMF, adopted the combination therapy of corticosteriods, MMF and bosentan for aggravated chest distress, and became stable eventually. Conclusion MMF may have therapeutic effects on inducing and even maintaining the stabilization of CTD-PAH.

Objective To evaluate the clinical value of 18floro-deoxyglucose positron emission tomography-CY(~(18)FDG PET-CT)in the diagnosis of lymph node metastasis from advanced esophageal carcinoma. Methods A prospective study is perfonued here to assess whether ~(18)FDG PET-CT can improve the diagnostic accuracy in lymph node metastasis for patients with advanced esophageal carcinoma.Thirty patients had undergone esophagectomy with extensive lymph node dissection.PET-CT findings were compared with that d CT with pathological finding as the final say.Results All patients were operated successfully without peri-operative complications.The pathological examination conformed metastasis in 22 patients and 49 out of 243 excised lymph nodes.In CT analysis,the sensitivity was 40.8%,specificity was 96.9%,with a diagnostic accuracy of 85.6%, The positive and negative predictive value was 76.9%,86.4% respectively;PET-CT resulted in a sensitivity of 93.9%,specificity of 91.2%,accuracy of 91.8%.The positive predictive value was 73.0% and negative predictive value was 98.3%,The difference of sensitivity(P＜0.001),accuracy(P＜0.05)and negative predictive value between the two radiological modalities was statistically significant(P＜0.001).Conclusions With a high sensitivity and accuracy in the diagnosis of lymph node metastasis,PET-CT appears necessary in preoperative examination for advanced esophageal carcinoma in the hope that surgical treatment be guided by the results of PET-CT,especially for the elder patients with poor pulmonary function or heart or brain complications. Moreover,it could be used as the basis of the conformal radiation therapy planning for inoperable patients.

OBJECTIVETo investigate the frequency of EML4-ALK fusion gene in non-small-cell lung cancer (NSCLC) patients, and its correlation with clinicopathologic features.

METHODSReal-time PCR was used to detect the presence of EML4-ALK fusion gene in 268 cases of NSCLCs using paraffin-embedded tissue samples(among which 164 samples were re-validated by Sanger sequencing). Related clinicopathological correlation was analyzed.

RESULTSEML4-ALK fusion gene was found in 4.1% (11/268) of the cases. One hundred and sixty four samples were verified by Sanger sequencing, and the overall coincidence of the results of two methods (Sanger sequencing and Real-time PCR) was 100%. Female patients (5.9%, 5/85), ≤ 60 years of age (4.3%, 6/140), non-smokers (6.8%, 8/118) and adenocarcinomas (7.6%, 10/132) had a higher mutation rate than that in male patients (3.3%, 6/183), > 60 years of age (4.0%, 5/124), smokers (1.6%, 2/132) and squamous cell carcinomas (1.3%, 1/79), although no statistical significance in age (P = 0.918), gender (P = 0.503), smoking history (P = 0.092) and histological type (P = 0.094).

CONCLUSIONSChinese NSCLC patients have a 4.1% detection rate of EML4-ALK fusion gene in the tumor tissues. Female, non-smoker and adenocarcinoma histological subtype tend to be associated with a higher rate of EML4-ALK gene fusion.

Adenocarcinoma ; genetics ; metabolism ; pathology ; surgery ; Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; pathology ; surgery ; Female ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; metabolism ; Sex Factors ; Smoking ; Young Adult

BACKGROUNDPrevention is presently the only available method to limit radiation-induced lung morbidity. A good predictor is the key point of prevention. This study aimed to investigate if [(18)F]2-fluoro-2-deoxyglucose (FDG) uptake changes in the lung after radiotherapy could be used as a new predictor for acute radiation pneumonitis (RP).

METHODSForty-one patients with lung cancer underwent FDG positron emission tomography/computed tomography (FDG-PET/CT) imaging before and after radiotherapy. The mean standardized uptake value (SUV) was measured for the isodose regions of 0 - 9 Gy, 10 - 19 Gy, 20 - 29 Gy, 30 - 39 Gy, 40 - 49 Gy. The mean SUV of these regions after radiotherapy was compared with baseline. The mean SUV in patients who developed RP was also compared with that in those who did not. The statistical difference was determined by matched pair t test. The Radiation Therapy Oncology Group (RTOG) criteria were used for diagnosis and grading of RP.

RESULTSWith a median follow-up of 12 months, 11 (26.8%) of the 41 patients developed grade 2 and above acute RP. The mean SUV of regions (10 - 19 Gy, 20 - 29 Gy, 30 - 39 Gy, 40 - 49 Gy) increased after radiation therapy in all 41 patients. The mean SUVs after radiation therapy were 0.54, 0.68, 1.31, 1.74 and 2.27 for 0 - 9 Gy, 10 - 19 Gy, 20 - 29 Gy, 30 - 39 Gy and 40 - 49 Gy, respectively. Before the radiation therapy, the mean SUV in each region was 0.53, 0.52, 0.52, 0.53 and 0.54, respectively. These patients had significantly higher FDG activities in regions receiving 10 Gy or more (P < 0.001). Compared with their counterparts, the elevation of SUV was significantly greater in those patients who developed acute RP subsequently.

CONCLUSIONThe mean SUV of the lung tissue may be a useful predictor for the acute RP. FDG-PET/CT may play a new role in the study of the radiation damage of the lung.

Aged ; Aged, 80 and over ; Female ; Fluorodeoxyglucose F18 ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; methods ; Radiation Pneumonitis ; diagnosis ; etiology ; Tomography, X-Ray Computed ; methods

Hemangioendothelioma, Epithelioid ; Humans ; Liver Neoplasms ; Male ; Middle Aged

5-Flucytosine (5-FC) could be changed to 5-fluorouracil (5-FU) by cytosine deaminase (CD), the latter is able to kill cancer cells. However, there is no efficient method to deliver the CD gene into the tumor cells, which hampers the application of the suicide gene system. In this experiment, for the first time, the NDV has been utilized as a vector to deliver the CD gene into the cancer cells, the virus can infect the cancer cells specifically, replicate and assemble, while the cytosine deaminase is expressed. Then the CD converts the prodrug 5-FC into 5-FU to achieve the purpose of inhibiting tumor. Firstly, the whole genome of E. coli JM109 was extracted, and the CD gene was obtained by cloning method. Then the CD and IRES-EGFP were ligated into the pEE12.4 expression vector to become a recombinant pEE12.4IE-CD eukaryotic expression plasmid. The human liver cancer cells were transfected with the plasmid. The cells were treated with different concentrations of 5-FC, MTT method was used to determine the killing effect of CD/5-FC system on the human liver cancer cells. The cell deaths were 18.07%, 42.98% and 62.20% respectively when the concentrations of prodrug were at 10, 20 and 30 mmol x L(-1). In 5-FC acute toxicity experiment, Kunming mice were injected with different concentrations of 5-FC at intervals of 1:0.5. The LD50 of 5-FC through iv injection was determined by improved Karber's method, the LD50 was 507 mg x kg(-1) and the 95% confidence limit was 374-695 mg x kg(-1). According to the maximum LD0 dose of the LD50, the maximum safe dose was 200 mg x kg(-1). Body weight and clinic symptoms of the experimental animals were observed. These results laid the foundation to verify the antitumor effect and safety of CD/5-FC system in animal models. The CD gene was ligated into the NDV (rClone30) carrier, then the tumor-bearing animal was established to perform the tumor inhibiting experiment. The result showed that the recombinant rClone30-CD/5-FC system has a high antitumor activity in vivo. To summarize, CD gene has been cloned and its bioactivity has been confirmed in the mammalian cells. It is the first time in this study to utilize the recombinant NDV to deliver the CD gene into the tumor cells; our result proves the rClone30-CD/5-FC system is a potential method for cancer therapy.
Animals ; Antimetabolites, Antineoplastic ; metabolism ; pharmacology ; Cell Death ; drug effects ; Chick Embryo ; Cytosine Deaminase ; genetics ; metabolism ; Escherichia coli ; genetics ; metabolism ; Flucytosine ; metabolism ; pharmacology ; Fluorouracil ; metabolism ; pharmacology ; Genetic Vectors ; Hep G2 Cells ; Humans ; Lethal Dose 50 ; Liver Neoplasms, Experimental ; pathology ; Mice ; Newcastle disease virus ; genetics ; Plasmids ; Recombinant Proteins ; genetics ; metabolism ; Transfection ; Tumor Burden ; drug effects

Biomarkers, Tumor ; analysis ; Fatty Acid-Binding Proteins ; analysis ; Humans ; Receptors, Retinoic Acid ; analysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Two-Dimensional Difference Gel Electrophoresis ; methods ; Up-Regulation ; Urinary Bladder Neoplasms ; chemistry

OBJECTIVETo investigate the effect of the different immunosuppression therapy on CD4(+)Foxp3(+)regulatory T cells (CD4(+)Foxp3(+)Treg cells) in the peripheral blood monocytes of kidney transplantation recipients.

METHODSA Closed Cohort study was conducted in 50 primary living kidney transplant recipients between January 2006 and January 2008, who had been followed up for 1 year. The recipients divided into calcineurin inhibitors group (CNI + MMF + Pred) (19 recipients, including cyclosporin group 10 recipients and tacrolimus group 9 recipients), rapamycin group (RAPA + MMF + Pred) (31 recipients). Twenty end-stage renal disease patients were in control group. The frequency of CD4(+)Foxp3(+)Treg cells in total CD4(+)T cells was analyzed by flow cytometry in peripheral blood from three groups, results were compared.

RESULTSThe clinical variables of recipients such as age, sex, cold ischemia time, human leucocyte antigen mismatch, panel reaction antibody, rejection episode were no significant difference. The percentage of CD4(+)Foxp3(+)Treg cells in total CD4(+) cells was significantly higher in rapamycin group and end-stage renal disease group than calcineurin inhibitors group (P < 0.01). The level of CD4(+)Foxp3(+)Treg cells between cyclosporin group and tacrolimus group was no significant difference (P > 0.05).

CONCLUSIONThe level of CD4(+)Foxp3(+)Treg was significantly higher in patients receiving RAPA + MMF + Pred than the patients receiving CNI + MMF + Pred, which suggested that RAPA may be play a more important role in immune tolerance induction.

Adult ; Female ; Follow-Up Studies ; Forkhead Transcription Factors ; Humans ; Immunosuppression ; methods ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Sirolimus ; therapeutic use ; T-Lymphocytes, Regulatory ; drug effects ; immunology

Objective To compare the diagnostic value 18F-fluorothymidine (FLT) and 18F-fluorodeoxyglucose (FDG) PET/CT in detecting lymph node metastases of untreated thoracic esophageal carcinoma. Methods Twenty-two patients with thoracic esophageal squamous cell carcinoma underwent both 18F-FLT and 18F-FDG PET/CT before surgery. The imaging results of the two modalities in detecting regional lymph node metastases were compared prospectively with the pathologic findings. The X2-test was used with SPS S 13.0. Results All patients underwent esophagectomy and lymphadenectomy. The metastatic lymph nodes were found in 16 patients, from which 47 of 424 excised nodes were positive by pathologic examination. False positive results were 14 while false negative 8 on 18F-FDG PET/CT. In contrast, false positive results were only 3 but false negative were 12 on 18 F-FLT PET/CT. The sensitivity, specificity, accuracy,negative predictive value, and positive predictive value were 74.47% ( 35/47 ), 99.20% ( 374/377 ),96.46% (409/424), 96.89% ( 374/386 ) and 92.11% ( 35/38 ) respectively for 18 F-FLT PET/CT, whereas the corresponding values were 82.98% (39/47), 96.29% (363/377), 94.81% (402/424), 97.84%(363/371 ) and 73.58% (39/53) respectively for 18 F-FDG PET/CT (X2 = 0.572, 6.018, 1.017, 0.348,3.852, P＞0. 05, ＜0.05, ＞0.05, ＞0.05 and ＞0.05). Conclusions Compared with 18F-FDG PET/CT, 18F-FLT PET/CT may be less sensitive but more specific for the detection of lymph node metastases of thoracic esophageal carcinoma.

OBJECTIVETo report a patient with congenital plasminogen activator inhibitor-1 (PAI-1) deficiency and explore its molecular mechanism.

METHODSThe activities of tissue plasminogen activator (tPA), alpha(2) antiplasmin (alpha(2)AP) and PAI-1 were measured by the methods of chromogenic substrate, the antigens of tPA and PAI-1 were measured by ELISA. PAI-1 gene was studied by PCR product sequencing and restriction endonuclease ana-lysing.

RESULTSIn the present patient, the euglobulin clot lysis time was 70 minutes and was corrected to normal range after added 50 ng/ml PAI-1 to his plasma. The activities of t-PA, alpha(2)AP, and factor were normal; the activity and antigen of PAI-1 in plasma were both significantly decreased. Nucleotide sequence analysis revealed that the patient had a heterozygous missense mutation in exon 2, a G to A transition at nucleotide 43. The possibility of gene polymorphism was excluded by restriction endonuclease analysing.

CONCLUSIONSIt is the first patient with congenital PAI-1 deficiency reported in China. The PAI-1 deficiency in the patient may be caused by compound heterozygosity, one of which is the G to A transition at nt43, a new mutation in congenital PAI-1 deficiency.

Adult ; Base Sequence ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Plasminogen Activator Inhibitor 1 ; blood ; deficiency ; genetics