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.

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.

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.

OBJECTIVELysosomal storage diseases are a group of inherited disorders caused by deficiency of lysosomal enzymes or structural components. The manifestations of lysosomal storage diseases are complicated due to different enzyme deficiency. It has been reported that a range of metabolic diseases resulting in abnormal accumulation of metabolic byproducts may exhibit abnormal cytoplasmic vacuolation of lymphocytes. The aim of this study was to elicit the usefulness of vacuolated peripheral lymphocytes detection in screening and diagnosis of lysosomal storage diseases.

METHODClinical data of 42 patients who underwent microscopic and electron microscopic examination of peripheral blood specimens in our department were retrospectively evaluated between January 2008 and December 2009.

RESULTForty-two patients with the suspected lysosomal storage diseases were included, these patients presented with motor and developmental retardation and/or regression. Seizure occurred in 32 patients. Hepatosplenomegaly were found in 4 patients. Three patients presented with declined visual acuity. Atrophy and/or abnormal signals were detected on cranial CT/MRI images in 24 patients. Blood biochemical tests were normal. Serum levels of ammonia, lactic acid and pyruvate were normal. Serum amino acid profiles and urinary organic acid profiles were normal. Serum fatty acid profiles were normal. Vacuolated lymphocytes were detected on microscopic examination of blood film in 14 patients, and 8 of these patients were confirmed to have lysosomal storage disease. Curvilinear body was found on electronic microscopic examination of peripheral lymphocytes specimens in 4 patients, confirming the diagnosis of neuronal ceroid lipofuscinosis. In 3 of these 4 patients, curvilinear body were also found on electronic microscopic examination of skin and/or muscle specimens. Enzyme analysis confirmed the diagnosis of metachromatic leukodystrophy in one patient and Pompe's disease in another patient. Typical pathological changes were found on the examination of bone marrow in 2 patients with normal acid sphingomyelinase activity. So the patients were diagnosed with Niemann-Pick disease type C. The diagnosis of other 6 patients with vacuolated lymphocytes was unknown.

CONCLUSIONBecause of its usefulness and minimal invasiveness, vacuolated peripheral lymphocytes examination should be a screening test for lysosomal storage disease. As for patients with suspected neuronal ceroid lipofuscinosis, electron microscopic examination of peripheral lymphocyte specimens may provide specific clues to the final diagnosis.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lymphocytes ; pathology ; Lysosomal Storage Diseases ; blood ; diagnosis ; pathology ; Male ; Microscopy, Electron ; Retrospective Studies ; Vacuoles

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

Objective: To explore the injury pattern and features of peripheral nerve in congenital muscular dystrophy patients caused by LAMA2 gene mutation. Method: Seventeen patients genetically or molecular pathologically diagnosed as LAMA2-related congenital muscular dystrophy were recruited in Peking University First Hospital between 2002 and 2015. All the patients received nerve conduction velocity (NCV) and needle electromyography tests. Clinical and laboratory examination data of the patients was retrospectively analyzed. The correlation between the NCV and disease course was determined by Pearson correlation analysis. Additionally, one patient underwent a sural nerve biopsy. Result: Among these 17 identified patients (13 male and 4 female), all of them were diagnosed as congenital muscular dystrophy, and all of them underwent electrophysiological examination at ages between 1 month to 6 years. Electromyogram indicated seventeen patients of myogenic damage, of whom 10 cases were complicated with reduced NCV. Twenty-six of 95 analyzed nerves showed NCV slower than the normal average of contemporary in 17%-47%. Correlation analysis between NCV and the disease course indicated that NCV of median nerves, ulnar nerves, tibial nerves and common peroneal nerves were negatively associated with the disease course (r=-0.737, -0.771, -0.540 and -0.682, respectively; all P<0.05). Sural nerve biopsy revealed peripheral neuropathy changes of myelin. Conclusion There is peripheral nerve injury in LAMA2-related muscular dystrophy patients. It mainly manifests as demyelinating lesions. Moreover, the NCV of peripheral nerve will decrease with the increase of the course of the disease.

OBJECTIVETo construct the recombinant plasmid containing human microdystrophin cDNA, and study the microdystrophin expression in vivo and in vitro.

METHODSMicrodystrophin cDNA was obtained from recombinant plasmid pBSK-MICRO digested with restrictive endonuclease Not I, the product was inserted into plasmid pVAX1, resulting in pAMICDYS. And then 3T3 cells were transfected with pAMICDYS. Forty-eight hours after transfection, the expression of the microdystrophin was detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. Finally, TA muscles of mdx mice were injected with the recombinant plasmid pAMICDYS through i.m. and the pathological change of TA was evaluated by histology, and the expression of microdystrophin in mdx TA was detected by immunohistochemical analysis.

RESULTSThe recombinant plasmid containing human microdystrophin cDNA was constructed successfully. The recombinant plasmid was proved to be able to express microdystrophin protein both in vivo and in vitro. Moreover, treatment of the TA of mdx mice with the recombinant plasmid could decrease the number of centrally nucleated myofibers.

CONCLUSIONRecombinant plasmid containing the microdystrophin gene was constructed successfully, and it could express microdystrophin protein both in vivo and in vitro. It provides basis for further study on microdystrophin as a target gene to treat Duchenne muscular dystrophy (DMD) by electrotransfer, i.v, arterial injection and combining with other exogenous gene to enhance microdystrophin expression.

Animals ; Cloning, Molecular ; DNA Restriction Enzymes ; metabolism ; DNA, Complementary ; genetics ; metabolism ; DNA, Recombinant ; genetics ; metabolism ; Dystrophin ; genetics ; Gene Expression ; Genetic Engineering ; Genetic Therapy ; Genetic Vectors ; metabolism ; Humans ; Immunohistochemistry ; Mice ; Muscular Dystrophy, Duchenne ; genetics ; metabolism ; therapy ; NIH 3T3 Cells ; Plasmids ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection

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.