Objective To investigate the clinical features and LRRK2 gene mutation in patients with autosomal dominant familial Parkinson's disease (PD). Methods The clinical features of 16 autosomal dominant familial PD probands were analyzed in terms of age at onset, onset symptoms, UPDRS scores, response to the levodopa treatment and drug-induced dyskinesia. The LRRK2 gene exons 5,13,31,32,35,37,41 and 48 of 16 probands were sequenced after polymerase chain reaction. The novel mutation was further screened in 24D sporadic PD patients and 214 controls using PCR-RFLP for the genotypo frequency analysis. Results Clinically, most of 16 probands had late-onset age. Resting tremor (9patients, 56. 25%,t=0.558,P=0.679)and bradykinesia (9 patients,56.25%,t=0.369,P=0.454)were common onset symptoms followed by rigidity(6 patients,37.50%,t=1.324,P=0.735)and postural instability(5 patients,31.25%,t=2.369,P=0.956).Majority of them had good response to levedopa treatment and rare occurrence of drug-induced dyskinesia. Among the 16 autosomal dominant familial PD probands,6 variants were identified:c.457 T＞C(Leu153Leu),c.1432 G＞T(Asp478Tyr),c.5457 T＞C(Gly1819Gly),c.7153 G＞A(Gly2385Arg),IVS31+28 T＞G and IVS37+162 T＞C. The c.1432G＞T(Asp478Tyr)variant was a novel mutation and it was not detected in 240 sporadic PD patients and 214 controls. The reported mutations associated with the PD, such as Arg1441 Cys/Gly/His, Arg1514Gln, Tyr1699Cys, Ile2012Thr, Gly2019Ser and Ile2020Thr,were not found in our study. Conclusions The autosomal dominant familial PD patients present with classical symptoms of PD and bear the LRRK2 variantsAsp478Tyr and Gly2385Arg.

In order to evaluate the effect of omega-3 fish oil supplement by gavage (0.4 mL/100 g body weight) on the chronic lead-induced (0.2% lead acetate) impairments of long-term potentiation (LTP) in rat dentate gyrus (DG) in vivo, we designed the experiments which were carried out in four groups of newborn Wistar rats (the control, the lead-exposed, the control with fish oil treatment and the lead-exposed with fish oil treatment, respectively). The excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in the DG of rats with above different treatments at the age of 80-90 d in response to stimulation applied to the lateral perforant path. The results showed (1) postnatal chronic lead-exposure impaired LTP measured on both EPSP slope and PS amplitude in DG area of the hippocampus; (2) in the control rats, omega-3 fish oil had no effect on LTP while in the lead-exposed rats, omega-3 fish oil had a protective effect on LTP. These results suggest that omega-3 fish oil supplement could protect rats from the lead-induced impairment of LTP. Omega-3 fish oil might be a preventive substance in reducing LTP deficits induced by lead.
Animals ; Animals, Newborn ; Dentate Gyrus ; drug effects ; Excitatory Postsynaptic Potentials ; Fatty Acids, Omega-3 ; pharmacology ; Fish Oils ; chemistry ; Lead Poisoning ; physiopathology ; Long-Term Potentiation ; drug effects ; Perforant Pathway ; Rats ; Rats, Wistar

OBJECTIVETo observe the pathological changes in ovary or testis of the SD rats after n-hexane inhalation, and to investigate the effects of n-hexane to sexual glands.

METHODSForty-eight adult healthy rats were selected and randomizedly divided into four groups control group and three n-hexane groups (1, 3 and 7 d) six rats for each group. After inhalation, SD rats were killed and n-hexane concentration of blood from celiac artery were detected. Super-oxide dismutase (SOD) glutathione peroxidase (GSH-Px) malondialdehyde (MDA) glutathione (GSH) were measured by photometry, and organ coefficients were calculated. The ovary or testis were embedded with paraffin, sliced, stained by HE method and observed using microscope.

RESULTSAs the time of n-Hexane effect increased, the activities of SOD, GSH-Px and GSH were decreased, but the content of MDA was increased, especially in the 7 d group (P < 0.01).

CONCLUSIONSn-hexane can induce a series of damages in ovary or testis of SD rats, and lipid-pre-oxidation may be one of the effect process.

Administration, Inhalation ; Animals ; Female ; Hexanes ; toxicity ; Male ; Ovary ; drug effects ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Testis ; drug effects ; metabolism ; pathology

Objective To conduct a computer simulation to evaluate the discrepancy between the cumulative doses calculated by four-dimensional computed tomography (4DCT) images and 4DCT scans (for real-time respiratory motions) due to the patient's irregular breathing.Methods A series of digital phantoms were generated from a patient's 4DCT images to simulate 4DCT images and 4DCT scans (for real-time respiratory motions) resulting from various irregular breathing curves.A six-field intensity-modulated radiotherapy plan was generated.Two cumulative doses in the target were calculated.The first one, named Dall, was calculated by tracking the point displacements in the target manifested on the 4DCT images;the second one, named D4D, was calculated based on the point displacements along the whole breathing motion during 4DCT scanning.Dose discrepancy between D4D and Dall was calculated to evaluate the correlation between breathing pattern and dose discrepancy in the target.Results The dose discrepancy in the target was correlated with mean motion excursion and the standard deviation of motion excursion.ΔDmin(ΔD99) in the target increased from 2.39%(2.04%) to 11.91%(5.24%) as the mean motion excursion increased from 5 mm to 15 mm, and increased from 5.93%(2.15%) to 14.65%(5.01%) as the standard deviation of motion excursion increased from 15% to 45% of the mean motion excursion.When the mean period increased from 3 s to 5 s or the standard deviation of period increased from 10% to 40% of the mean period,ΔDmin(ΔD99) in the target was greater than 6.0%(2.0%), but less than 9.0%(3.0%).When the target diameter was 2 cm, 3 cm, and 4 cm,ΔDminΔD99) in the target was 11.88%(5.50%), 6.91%(2.42%), and 7.53%(3.62%), respectively.Conclusions There is a large discrepancy between the cumulative doses calculated using 4DCT images and 4DCT scans (for real-time respiratory motions) when the patient has irregular breathing.This dose discrepancy depends on mean motion excursion and the standard deviation of motion excursion, but has little relationship with mean period, the standard deviation of period, and tumor volume.

To prepare and evaluate dry powder inhalation (DPI) of extraction of Trollius chinensis Bunge (TCB). Orthodox design was employed to optimize the parameters of spray drying to prepare micronized TCB powder, the DPI was prepared by mixing micronized TCB powder and lactose. The results showed that the fine particle fraction (FPF) and emitted dose (ED) of micronized TCB powder was (21.07 +/- 1.74)%, (75.31 +/- 21.05)%, respectively, and for DPI was (56.4 +/- 2.2)%, (95.9 +/- 3.0)%, respectively. Therefore, the prepared DPI meeted requirements in the Chinese Pharmacopeia, indicating a good application prospect.
Administration, Inhalation ; Dry Powder Inhalers ; Excipients ; Plant Extracts ; administration & dosage ; isolation & purification ; Powders ; Ranunculaceae

OBJECTIVETo study the clinical value and operation skills of nasal endoscopy-assisted bulboprostatic anastomosis in the treatment of posterior urethral stricture.

METHODSBetween January 2012 and November 2014, we performed nasal endoscopy-assisted bulboprostatic anastomosis for 12 male patients with posterior urethral stricture. We recorded the operation time, blood loss, exposure of operation visual field, and success rate of anastomosis and summarized the operation skills.

RESULTSEight of the patients experienced first-stage recovery. Two underwent a urethral dilation at 3 months postoperatively, 1 received 10 urethral dilations within 5 months after surgery, and 1 underwent internal urethrotomy after failure in urethral dilation, but all the 4 cases were cured.

CONCLUSIONNasal endoscopy can significantly improve the operation field exposure, elevate the precision, reduce the difficulty, and enhance the efficiency of bulboprostatic anastomosis in the treatment of posterior urethral stricture.

Anastomosis, Surgical ; Endoscopy ; Humans ; Male ; Operative Time ; Postoperative Period ; Urethra ; pathology ; surgery ; Urethral Stricture ; surgery

The aim of this study was to investigate the clinical characteristics and prognosis of acute erythroleukemia (AEL, AML-M6). The clinical features and results of morphologic, immunophenotypic, cytogenetic and molecular biologic detections were retrospectively analyzed in 13 cases of AEL from 305 acute leukemia patients hospitalized between October 2007 and October 2012. The results showed that the expression of erythroid and non-erythroid cells increased at the same time. The myeloid antigens mainly expressed CD13/CD33/CD117/CD34, while the erythroid antigens expressed Gly and CD71. The karyotypic detection indicated that there were 1 case with normal karyotype, 3 cases with simple karyotypic abnormality and 2 cases with complex karyotypic abnormality, the other cases were not detected. The molecular biological detection found that the poor prognosis gene existed in 5 cases [38.5% (5/13)], including 3 cases with MLL-MLL fusion gene, 1 case with MLL mutation, and 1 cases with NRAS gene mutation, the abnormal genes were not detected in remainder 8 cases. After chemotherapy with decitabine, the complete remission (CR) rate achieved 53.5% (7/13), partial remission (DR) rate achieved 15.4% (2/13). Finally, 8 patients received allo-HSCT, the median overall survival (OS) was 20.7 months, 3 year survival rate was 79%, 3 year disease-free survival rate was 78%. It is concluded that the acute erythroleukemia is a rare subtype of AML, which is transformed from MDS and has harmful genes and poor prognosis. Allo-HSCT and treatment with decitabine may enhance the survival rate of AEL.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Karyotyping ; Leukemia, Erythroblastic, Acute ; diagnosis ; genetics ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; Young Adult

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin's lymphoma (NHL), characterized by great heterogeneity in clinical manifestations and molecular genetics. This study was aimed to explore the clinical significance of applying multiplex PCR to detect BCL2/IGH and BCL6/IGH fusion genes in DLBCL. Multiplex PCR was used to detect bone marrow samples from 80 cases of DLBCL. The results showed that 12 patients (15%) carried BCL2/IGH or BCL6/IGH fusion genes, BCL2/IGH was found in 6 patients (7.5%), and BCL6/IGH in another 6 patients (7.5%). The patients with different molecular markers displayed different clinical features and outcomes. It is concluded that multiple PCR is rapid and accurate method to identify gene abnormalities in DLBCL, but further studying a quantitative or semi-quantitative assay for the expression of fusion genes is needed.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; pathology ; Female ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Lymphoma, Large B-Cell, Diffuse ; genetics ; pathology ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction ; Oncogene Proteins, Fusion ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; Proto-Oncogene Proteins c-bcl-6 ; genetics ; Young Adult

The study was aimed to investigate the clinical characteristics of acute myeloid leukemia (AML) with CBFB-MYH11 gene. The clinical data of 12 cases were analyzed retrospectively, including age, clinical characteristics, immunophenotype, treatment protocols and efficacy as well as the prognosis. The results indicated that 12 patients with CBFB-MYH11 were detected in 293 AML patients. The median age of the 12 patients was 32.5 (21 - 57) years old. According to French-American-British (FAB) classification, 66.7% (8/12) patients was diagnosed as M4Eo and 33.3% patients was diagnosed as M4. At new diagnosis, the median WBC count was 19.8×10(9)/L (2.46 - 164.30×10(9)/L). The WBC count > 100×10(9) was found in 16.7% patients (2/12). The complete remission (CR) rate after 1 and 2 cycles of induction chemotherapy were 83.3% and 16.7% respectively, so the total CR rate was 100%. Estimated 5-year relapse-free survival (RFS) and overall survival (OS) were 80% and 83%, respectively. It is concluded that patients with CBFB-MYH11 are usually M4Eo and M4. Patients with this fusion gene are often associated with high frequency of CD33, CD34, CD117, HLA-DR, CD15, CD64 and CD14 expression. Patients with CBFB-MYH11 have a tendency of higher CR rate, longer RFS and OS.
Adult ; Female ; Humans ; Immunophenotyping ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Prognosis ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the association between the single nucleotide polymorphisms (SNPs) of paraoxonase-2 (PON2) gene and the susceptibility to occupational noise-induced deafness among Chinese Han population exposed to high noise levels [>85 dB (A)].

METHODSA case-control study was conducted in Chinese Han population exposed to high noise levels. The subjects were divided into case group (n = 127) and control group (n = 136) according to the Diagnostic criteria of occupational noise-induced deafness (GBZ 49-2007). The case group was composed of 127 workers with a mean binaural high-frequency hearing threshold not less than 40 dB, as measured using an electro-audiometer, while the control group was composed of 136 workers with a mean binaural high-frequency hearing threshold less than 40 dB, as measured using the electro-audiometer, who were on shift in the same position as the cases and matched with them for age, sex, and years of noise exposure. Peripheral venous blood (2 ml) was collected from each subject during physical examination to extract genomic DNA, and genotypes were identified using a TaqMan probe.

RESULTSPON2 genotypes rs7493 CG+GG, rs7785846 CT+TT, rs12026 CG+GG, and rs7786401 GT+TT were the risk factors for occupational noise-induced deafness, and the adjusted odds ratios (95%confidence intervals) were 5.87 (3.11∼11.07), 5.92 (3.10∼11.32), 5.53 (2.93∼10.45), and 5.93 (3.10∼11.34), respectively. In addition, the higher the noise exposure levels, the higher the risk of developing occupational noise-induced deafness among the individuals carrying mutant genotypes.

CONCLUSIONPON2 genotypes rs7493 CG+GG, rs7785846 CT+TT, rs12026 CG+GG, and rs7786401 GT +TT may be associated with the susceptibility to occupational noise-induced deafness among Chinese Han population exposed to high noise levels, and the effects of mutant genotypes and noise exposure levels may be mutually enhanced.

Adult ; Aryldialkylphosphatase ; genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; Hearing Loss, Noise-Induced ; etiology ; genetics ; Humans ; Male ; Middle Aged ; Noise, Occupational ; adverse effects ; Polymorphism, Single Nucleotide ; Risk Factors