Objective To study the clinical characteristics,muscle pathological features,diagnosis and prognosis of TK2-related mitochondrial DNA depletion syndrome(MDS).Methods Clinical and laboratory data of 2 cases of TK2-related myopathic MDS were reported.And data of previously reported 58 TK2-related MDS cases were reviewed.Results Total 60 patients consisted of 35 male and 25 female.The age of onset ranged from the birth to the age of 74 years old,and 54 of the patients were attacked at the age younger than 3 years old.Muscle weakness and hypotonia were detected in all patients,with 40 patients(including the newly diagnosed 2 cases) manifested as pure myopathic form,and 20 patients with other multiple organs involvement.Serum creatine kinase was mildly increased (211-6 500 IU/L) in 53 patients.Elevated serum lactic acid level (2.3-12.0 mmol/L)was observed in 24 patients.Muscle biopsy was available from 55 patients,and ragged red fibers and/or cytochrome C oxidase (COX)-negative fibers were detected in 48 out of them.Nine out of 11 patients received electronic microscope study showed proliferation of abnormal mitochondria.Respiratory chain enzymatic activities in skeletal muscle were reduced in 31 out of 33 patients.Marked mtDNA content reduction was observed in 36 out of 41 patients (4％-25％ of age-and tissue-matched controls).A total of 42 TK2 mutations were found in 60 patients,including 2 novel mutations c.923A ＞ G and c.619-2A ＞ T in this study.Conclusions The most common clinical manifestations of TK2-related MDS are severely,rapidly progressing myopathy with infantile or early childhood onset.As the detection rate of characteristic pathologic features in muscle is high,muscle biopsy is important for the diagnosis of TK2-related MDS.

Objective To assess the proficiency of water monitoring laboratory at rural, county, and provincial levels in Guangdong province, to ensure the province's drinking water monitoring results accurate and reliable. Methods State quality of certified reference materials as water arsenic, fluoride and chloride of 90 copies each were numbered and distributed to 90 monitoring laboratories in the province for testing, The measurement results of the participatory labs were evaluated through normative values and expanded uncertainty, and were compared with those of robust statistics method. Results All participatory labs had timely feedback of their measurement results. The qualified rate was higher when arsenic was tested by hydride generation atomic fluorescence spectrometry and zinc-new silver salt of sulfuric acid spectrophotometric system, while fluoride and chloride by ion chromatography. The average qualified rates of water arsenic, fluoride and chloride of the province's rural drinking water quality monitoring laboratory were 66% (59/90), 72% (65/90) and 72% (65/90), respectively.Seven participatory labs failed the proficiency testing of all three analytes and unqualified rate was 7.8% (7/90)among the ninety participated monitoring labs. The qualified rates of robust statistics method for arsenic fluoride and chloride were greater than those evaluated by the expanded uncertainty, and large deviations with small sample sizes. Conclusions The testing ability of drink-water monitoring labs in Guangdong province has improved.However, by comparison with the requirements of national quality control and testing skills, there is still a gap. It is suggested that internal quality control be included in routine inspeetion to improve laboratory testing technology.

Objective To investigate the value of the Wells score and D-dimer assay in assisting pulmonary perfusion imaging (PPI) for the diagnosis of acute pulmonary embolism (APE). Methods One hundred twenty-one patients with suspected APE were studied from January, 2006 to December, 2008. All patients underwent the Wells score, the quantitative D-dimer assay, chest X-ray photography, and PPI. The diagnostic sensitivity, specificity, positive predictive value and negative predictive value of PPI with the assistance of Wells score and D-dimer assay were calculated. Results Fifty (41.3%) patients were diagnosed with APE. PPI combined with chest X-ray photography (Q/X scan) showed positive results in 49 patients. The sensitivity, specificity, positive predictive value and negative predictive value of the Q/X scan were 86.0% (43/50), 91.5% (65/71), 87.8% (43/49) and 90.3% (65/72), respectively. With assistance of Wells score >4 and D-dimer≥0. 5 mg/L, Q/X scan had a positive predictive value of 100.0% (29/29), for patients with Wells score ≤4 and D-dimer<0.5 mg/L, the negative predictive value for Q/X scan was 100.0% (41/41). Conclusion Combined with Wells score and D-dimer assay, PPI can make accurate diagnosis of APE.

BACKGROUND: Few studies have reported the effects of early tracheotomy in acute severe asthmatic patients. We report two patients with acute severe asthma who were successfully treated with early tracheotomy. METHODS: The two patients with acute severe asthma were retrospectively reviewed. They had been treated at the Department of Emergency and Critical Care, Renji Hospital, Shanghai Jiaotong University School of Medicine. RESULTS: They developed progressively hypercapnia and severe acidosis, and were not improved after conventional therapies. Early tracheotomy after mechanical ventilation decreased airway resistance and work of breathing, and corrected hypercapnia and acidosis. Adequate gas exchange was maintained after tracheotomy. The two patients were subsequently weaned from mechanical ventilation and discharged. CONCLUSION: Early tracheotomy could be a valuable approach in certain patients with severe asthma.

ObjectiveTo investigate the value of 18F-FDG SPECT myocardial imaging in evaluating haemodynamic change,treatment outcome and prognosis for idiopathic pulmonary arterial hypertension (IPAH).MethodsAll 24 patients with IPAH underwent 18 F-FDG SPECT myocardial imaging.Right ventricle/left ventricle (RV/LV)-FDG uptake was calculated by ROI method drawing over the central areas of left and right ventricular free walls.All patients underwent right heart catheterization within 3 days after imaging studies.Mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were recorded.After six month pharmaceutical treatment,15 IPAH patients were re-examined with 18F-FDG SPECT myocardial imaging followed by repeated right heart catheterization within 3 days.Plasma N-terminal pro-brain naturetic peptide (NT-proBNP) and endothelin-1 ( ET-1 ) were measured in 17 patients using electrochemiluminescent immunoassay and enzyme immunoassay respectively.All patients were followed up for 12 months at least.Correlations between RV/LV-FDG uptake and mPAP and PVR were determined by simple linear regression analysis.Change of RV/LV-FDG before and after treatment was calculated using Student's t-test.Survival in groups with RV/LV FDG uptake ≥ 1.15 and RV/LV-FDG uptake ＜ 1.15 were compared using Log-rank test.ResultsSignificant correlations were found between RV/LV-FDG uptake and mPAP (r =0.562,P ＜ 0.01 ),and between RV/LV-FDG uptake and PVR ( r =0.574,P ＜ 0.01 ).There were no significant correlation between RV/LV-FDG uptake and NT-proBNP( r =0.18 1,P ＞ 0.05 ),but a significant correlation between RV/LV-FDG and ET-1 was observed (r =0.669,P ＜ 0.01 ).The RV/LV-FDG uptake in patients with positive treatment outcome ( n =6) decreased from 1.38 ± 0.52 to 0.92 ±0.26 (t =4.018,P ＜ 0.05) after 6 months treatment.In contrast,no significant change of RV/LV-FDG uptake was seen in those patients (n =9) with negative treatment outcome ( t =1.861,P ＞ 0.05 ).The mean follow-up time was (21 ±8) months.Mean survival time for the patients with RV/LV- FDG uptake ≥ 1.15was 28 months (95％ confidence interval:24-32 months),which was significantly lower than 34 months survival (95％ confidence interval:33-35 months) for the patients with RV/LV-FDG ＜ 1.15 (x2 =3.956,P ＜0.05 ).Conclusions Detection of right ventricle myocardial glucose metabolism level with 18F-FDG SPECT may be a practical method for evaluating haemodynamic change,treatment outcome and prognosis of IPAH.

Objective To analyze the clinical characteristics,muscle pathological features and pathogenic gene mutation in 4 cases with LMNA-related congenital muscular dystrophy (L-CMD).Methods Clinical data of the probands and the parents were collected.Skeletal muscle specimens were biopsied from the probands for pathological analysis.Genomic DNA and RNA were extracted from peripheral blood leukocytes,and PCR,reverse transcription(RT)-PCR and DNA direct sequencing were employed to analyze the LMNA gene to determine the gene mutation and confirm the pathogenicity.Results Four patients had symptoms from fetal period to several months after birth.They presented with motor retardation,muscle weakness with prominent the proximal upper limbs,distal lower limbs and neck extensor,hypotonia,contractures,with mild to moderate elevation of CK level.The muscle biopsies showed muscular dystrophic and with inflammatory changes,and the abnormal nuclear morphology was observed with transmission electron microscopy.Genetic analysis of them detected 4 dominant de novo mutations.Three of them had unreported pathogenic mutations.The same sites of the LMNA gene were wild type in their parents.Conclusions Four cases of L-CMD are genetically identified.Genetic counseling of the family can be possible.The patients should be considered LMNA gene mutation of they present themselves with muscle weakness with the proximal upper limbs,distal lower limbs and neck extensor,hypotonia,contractures,mild to moderate elevation of CK level,and if the biopsies show muscular dystrophic changes but also with inflammatory changes should be considered LMNA gene mutation.Genetic analysis is the most reliable method for diagnosing L-CMD.

OBJECTIVETo summarize the clinical features of those Duchenne and Becker muscular dystrophy (DMD and BMD) patients who are complicated with epilepsy, and try to analyze the genotype- phenotype correlation.

METHODBy a retrospective analysis of 307 patients with DMD and BMD who attended Peking University First Hospital from February 2006 to September 2014,7 patients complicated with epilepsy were identified and their clinical data were collected. The possible mechanism of epilepsy in DMD and BMD patients was proposed after analyzing the genotype-phenotype correlation.

RESULT(1) Among 307 DMD and BMD patients, 7 cases had epilepsy, the prevalence was 2. 28%. (2) The age of onset of epilepsy ranged from 8 months to 11 years. Focal seizure was the most common seizure type (6 cases) , while other seizure types were also involved, such as generalized tonic-clonic seizure. As to epilepsy syndromes, 1 boy was diagnosed as benign childhood epilepsy with centrotemporal spikes (BECT). Six patients were treated with 1 or 2 types of antiepileptic drugs and seizures were controlled well. On follow-up, 6 of the 7 children had normal mental development, while the remaining 1 patient was diagnosed as mild mental retardation. (3) DMD gene mutations of all 7 patients were analyzed. Exons deletions were found in 6 cases while point mutation was found in 1 case.

CONCLUSIONThe prevalence of epilepsy in DMD and BMD patients was higher than the prevalence in normal population. The age of onset of epilepsy varies, and focal seizure may be the most common seizure type. Some patients may also present as some kind of epilepsy syndrome, such as BECT. In most patients, seizures can be controlled well by 1 or 2 types of antiepiletic drugs. No clear correlation was found between genotype and phenotype in DMD and BMD patients who were complicated with epilepsy, probably due to limited number of cases.

Anticonvulsants ; therapeutic use ; Child ; Epilepsy ; complications ; drug therapy ; epidemiology ; Exons ; Genotype ; Humans ; Intellectual Disability ; etiology ; Male ; Muscular Dystrophy, Duchenne ; complications ; genetics ; Mutation ; Phenotype ; Prevalence ; Retrospective Studies ; Seizures ; Sequence Deletion

OBJECTIVETo explore the efficacy, time to disease progression (TTP), overall survival (OS) and toxicity of paclitaxel liposome versus paclitaxel combined with 5-fluorouracil (5-Fu) for patients with advanced gastric cancer.

METHODSThe therapeutic efficacy of chemotherapy with either of the two regimens for 67 cases of naïve advanced gastric cancer was analyzed. Among them, 31 patients in the paclitaxel liposome-5-Fu group received paclitaxel liposome 175 mg/m(2) d1, CF 200 mg/m(2) d1, 5-Fu 2.6 g/m(2) civ. 46 hours, 21 days as one cycle, and 34 patients in the paclitaxel-5-Fu group received paclitaxel 175 mg/m(2) d1, CF 200 mg/m(2) d1, 5-Fu 2.6 g/m(2) civ. 46 hours, 21 days as one cycle.

RESULTSThe objective response rate was 54.8% in the paclitaxel liposome group and 44.1% in the paclitaxel group (P = 0.388). The median time to progression was 5.10 months vs. 5.20 months (P = 0.266) and the median survival time was 10.07 months vs. 8.97 months (P = 0.186). The most frequent side-effects were nausea, vomit and hematological toxicities. The rates of grade III-IV nausea and vomit were 16.1% and 50.0% (P = 0.038), muscle and joint pain were 9.7% and 29.4% (P = 0.047).

CONCLUSIONBoth regimens are effective in the treatment of advanced gastric cancer. However, less adverse effects occur in the paclitaxel liposome group.

Adult ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Disease Progression ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Humans ; Liposomes ; Male ; Nausea ; chemically induced ; Paclitaxel ; administration & dosage ; adverse effects ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; Survival Rate ; Vomiting ; chemically induced

OBJECTIVETo investigate the effect of adenovirus-mediated endostatin gene transfer on transplanted lung cancer in mice and its mechanism of action.

METHODSTransplant tumor model was induced by subcutaneous inoculation of 2 x 10(6) Lewis lung cancer (LLC) cells into the back of C57BL/6 mice. The mice were treated by intratumoral injection of 2 x 10(9) pfu Ad-mEndostatin. The expression of endostatin in situ and its maintaining time were detected by immunohistochemistry and Western Blot, respectively. The endostatin level in serum was determined by ELISA . The inhibition of tumor growth and changes of survival were recorded and the microvessel density (MVD) was determined by histochemical stainingwith CD31 and CD105 antibodies. The tumor apoptosis was observed by electron microscopy.

RESULTSIn comparison with controls, intratumoral injection of Ad-mEndostatin significantly inhibited the tumor growth and metastasis, and prolonged the survival rate of mice (P < 0.05). Strong positive expression of mEndostatin was seen in the tumor tissue after injection of Ad-mEndostatin, immunhistochemically ostained by mouse endostatin monoclonal antibody, while the control groups showed only very low expression or absence. Serum endostatin concentration was 1540 +/- 560 ng/ml at the second week of administration, the expression of endostatin diminished a month later. The microvessel density (MVD)) decreased from 42.4 +/- 4.8 to 10.5 +/- 3.2 per x 200 magnificetion microscopic field by CD10 staining and from 68.5 +/- 4.5 to 37.5 +/- 4.6 by CD31 staining, respectively (P < 0.05). More apoptotic tumor cells were seen under the transmission electron microscope.

CONCLUSIONEndostatin gene therapy mediated by adenoviral vector efficiently induces expression of endostatin in vivo, and inhibits the growth and metastasis of tumor. It is concluded that its action is targeted to tumor neovasculature and the mechanism is inhibition of tumor angiogenesis.

Adenoviridae ; genetics ; Angiogenesis Inhibitors ; genetics ; metabolism ; therapeutic use ; Animals ; Carcinoma, Lewis Lung ; metabolism ; pathology ; therapy ; Cell Line, Tumor ; Endostatins ; genetics ; metabolism ; therapeutic use ; Genetic Therapy ; Genetic Vectors ; Male ; Mice ; Mice, Inbred C57BL ; Microvessels ; pathology ; Neoplasm Transplantation ; Neovascularization, Pathologic ; pathology ; Random Allocation ; Transfection ; Tumor Burden

OBJECTIVETo analyze and characterize the clinical, molecular pathological and genetic features of a Chinese family with congenital muscular dystrophy type 1A (MDC1A).

METHODSClinical data of the proband and her family members were collected. Immunohistochemistry staining was performed on muscular biopsy tissues with anti-merosin, alpha-dystroglycan, beta-dystroglycan and dystrophin antibodies. Genomic DNAs from the patient and her parents were extracted using standard procedures from the peripheral blood leukocytes. PCR and DNA direct sequencing were employed to analyze all of the 65 exons of the LAMA2 gene to determine the gene mutation, and the relationships between genotype and phenotype were analyzed.

RESULTSThe proband presented with delayed motor development and a myopathic face. Her midrange elevated serum creatine kinase (CK) levels and white matter signal intensity changes are consistent with MDC1A, and was clinically diagnosed as MDC1A. The immunohistochemistry analysis for the proband exhibited complete loss of merosin staining. Further test with PCR detected a homozygous mutation of c.817A>T in exon 5, while her parents were heterozygotes for the mutation.

CONCLUSIONThe authors have defined the clinical manifestation of the Chinese family with MDC1A. The proband carried a homozygous nonsense mutation c.817A>T, and her parents were heterozygous carriers, consistent with autosomal recessive inheritance.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child, Preschool ; Creatine Kinase ; blood ; Female ; Humans ; Laminin ; genetics ; Male ; Molecular Sequence Data ; Motor Activity ; Muscular Dystrophies ; congenital ; genetics ; pathology ; physiopathology ; Pedigree ; Point Mutation