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.

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

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

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

BACKGROUNDEndogenous estrogen plays a very important role in the carcinogenesis and progression of breast cancer. The enzymes involved in the biosynthesis and metabolism of estrogen have been proposed to contribute to this effect. To examine this hypothesis, we conducted a case-control study to investigate the relationship between polymorphisms of genes responsible for estrogen biosynthesis (CYP17, cytochrome P450c17a and CYP19, aromatase cytochrome P450) and estrogen sulfation of inactivation (SULT1A1, sulfotransferase1A1) and the risk of breast cancer in Chinese women.

METHODSThis study involved 213 breast cancer patients and 430 matched controls. PCR-based restriction fragment length polymorphism (RFLP) and short tandem repeat polymorphism (STRP) assays were used to detect the mononucleotide transition of CYP17 and SULT1A1 and tandem repeat polymorphism of CYP19. Logistic regression analyses were used to determine OR and 95% CI of each and all three high-risk genotypes, of all three genotypes combined, and of estrogen exposure factors. The relationship between each high-risk genotype and clinicalpathological characteristics were also assessed.

RESULTSThe frequency of A2 allele of CYP17 was 49.8% in cases and 49.1% in controls (P = 0.82). The frequency of His allele of SULT1A1 was significantly higher in cases (13.6%) than in controls (9.5%) (P < 0.05). There was also significant difference of the (TTTA) 10 allele of CYP19 which was 12.4% in cases and 8.2% in controls (P < 0.05). When the CYP17 A2 allele, CYP19 (TTTA) 10 and SULT1A1 His allele were considered as the "putative high-risk" genotype, there was an increased risk of breast cancer with the number of high-risk genotypes in a dose-response effect (trend, P = 0.05). In multivariate analysis, the SULT1A1 genotype remained the most significant determinant for breast cancer, with OR = 2.37 (95% CI 1.23-4.74), followed by CYP19, with OR = 1.75 (95% CI 1.27-3.56). The (TTTA) 10 allele of CYP19 was associated with tumor size, and the His allele of SULT1A1 associated with status of lymph node metastasis.

CONCLUSIONSThis study supports the hypothesis that breast cancer can be initiated by estrogen exposure and that estrogen metabolizing genes are involved in this mechanism. This multigenic model is useful for identifying individuals who are at higher risks of breast cancer.

Adult ; Aged ; Aromatase ; genetics ; Arylsulfotransferase ; genetics ; Breast Neoplasms ; etiology ; genetics ; Case-Control Studies ; Estrogens ; metabolism ; Female ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; Polymorphism, Genetic ; Risk Factors ; Steroid 17-alpha-Hydroxylase ; genetics

OBJECTIVETo observe the contribution of Qingnao drop pilula to the alteration of myristoylated alanine-rich C kinase substrate (MARCKS) mRNA expression in acute multi-infarction hippocampus.

METHODRat models of acute multi-infarction were established by injecting the embolus of blood powder through the right external carotid arteryinto the internal carotid artery, rats were randomly divided into five groups (n = 12 in each): normal, sham operation, model, Chinese medicine treatment, and Western medicine treatment. Qingnao drop pilula (133.28 mg x kg(-1)), nimodipine (7.25 mg x kg(-1)) were administered respectively to Chinese medicine treatment group and Western medicine treatment group by gavage, equal volume of normal saline were given to three groups. Rats were treated with drugs starting at 3rd day before the operation, one time per day. Observing morphologic changes in hippocampus by optical microscope and electron microscope. Detecting expression level of MARCKS mRNA in hippocampus by semi-quantification PCR method.

RESULTHippocampus cells arrange tidy, administrative levels were compactness in normal group, which cells differentially impaired in model group, Chinese medicine treatment group and Western medicine treatment group. Hippocampus cells damage of Chinese medicine treatment group have more reckless than the model group in histopathology. The MARCKS mRNA were expressioned in model group vs medication treatment groups, in Chinese medicine treatment group vs the model group.

CONCLUSIONQingnao drop pilula can alleciate histomorphology lesion of hippocampus when occurring acute multi-infarction, to turn slower MARCKS mRNA expression, may play a neuroprotective effect role through accommodating PKC-MARCKS signal transduction system.

Acute Disease ; Animals ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Gene Expression Regulation ; drug effects ; Hippocampus ; drug effects ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Male ; Membrane Proteins ; genetics ; metabolism ; Myristoylated Alanine-Rich C Kinase Substrate ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo investigate the occupational health of the workers simultaneously exposed to acrylonitrile, epoxyethane, epoxypropane, and styrene.

METHODSA questionnaire survey was conducted in 70 front-line workers simultaneously exposed to acrylonitrile, epoxyethane, epoxypropane, and styrene (exposure group) and 50 managers (control group) in a polyether manufacturer; in addition, air monitoring at workplace and occupational health examination were also performed. The obtained data were analyzed.

RESULTSThe female workers in exposure group and the spouses of male workers in exposure group had significantly higher spontaneous abortion rates than their counterparts in control group (P < 0.01). The exposure group had a significantly higher abnormal rate of blood urea nitrogen than the control group (P < 0.01). The workers with different polyether-exposed working years had significantly higher mean levels of DNA damage than the control group (P < 0.01); the workers with not less than 5 and less than 20 polyether-exposed working years and those with not less than 20 polyether-exposed working years had significantly higher mean micronucleus rates than the control group (P < 0.01); there were no significant differences in overall chromosome aberration rate and mean level of DNA damage between each two groups of workers with different polyether-exposed working years (P > 0.05); the workers with not less than 5 and less than 20 polyether-exposed working years and workers with not less than 20 polyether-exposed working years had significantly higher mean micronucleus rates than those with less than 5 polyether-exposed working years (P < 0.01).

CONCLUSIONSimultaneous exposure to acrylonitrile, epoxyethane, epoxypropane, and styrene causes occupational hazards among the workers in polyether manufacturer.

Adult ; Air Pollutants, Occupational ; adverse effects ; Blood Urea Nitrogen ; DNA Damage ; Ethers ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Occupational Health ; Workplace

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

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