Objective To explore the changes and clinical significance of levels of serum vascular endothelial growth factor(VEGF)and endostatin in smokers. Methods In a case-control study,levels of serum VEGF and endostatin were determined in 82 smokers with lung cancer,82 pair-matched smokers without lung cancer and 20 healthy non-smokers by enzyme-linked immunoabsent assay(ELISA) or competitive enzyme immunoassay.Results The level of serum VEGF in smokers with lung anncer[(16.1±7.9)ng/ml]was markedly higher than that in the other two groups(both P＜0.01).The level of serum VEGF in smokers without lung cancer was significantly higher than that in healthy non-smokers(P＜0.05).The level of serum endostatin in smokers with lung cancer was significantly higher than that in healthy nonsmokers(P＜0.01),but was not significantly different from that in smokers without lung cancer(P＞0.05),and that in smokers without lung cancer was significantly higher than that in healthy non-smokers (P＜0.05).Notably,the ratio of endostatin to VEGF in smokers with lung cancer(1.3±0.5)was significantly lower than that in the other two groups(both P＜0.01).However.there was no significant difference in it between smokers without lung cancer and healthy non-smokers(P＞0.05).The level of serum VEGF correlated significantly to that of endostatin in smokers both with and without lung cancer(P＜0.01).Conclusions These findings suggest that smoking may result in imbalance of levels of serum endostatin and VEGF leading to tumorigenesis.The ratio of endostatin to VEGF can be used as an early diagnostic indicator for lung cancer in smokers.Periodic determination of levels of serum VEGF and endostatin as well as the ratio of endostatin to VEGF is of clinical importance.

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.

OBJECTIVETo investigate the effect of L-838,417 on the results of behavioral test in rats with experimentally induced trigeminal neuralgia.

METHODSMale SD rats were randomized into model group (n=34), sham-operated group (n=30) and control group (n=6). Thirty rats with trigeminal neuralgia induced by chronic constriction injury of the infraorbital nerve below the zygomatic bone were randomly divided into 5 equal groups for treatment with 1.0 mg/kg L-838,417 (L1 group), 10.0 mg/kg L-838,417 (L10 group), 5 mg/kg morphine (M group), 3 mg/kg diazepam (D group), or normal saline (NS group). The pain threshold of the tentacles pad to von-Frey filament stimulation was measured in the rats before and at 1, 2, 3, 4, 5 h after the treatments. The sedative effect of L-838,417 was evaluated by recording the position scores and righting reflex scores, and the drug tolerance was also evaluated.

RESULTSNine days after the operation, the pain threshold of the rats in the model group was significantly decreased compared with that before operation and that of the sham group (P<0.01). The threshold of L1 and L10 groups were both significantly increased 1 h after L-838,417 administration (P<0.01). The rats in the NS, L1, and L10 groups did not show unusual posture or righting reflex. In L1 and L10 groups, L838,417 did not show attenuated efficacy after prolonged use (10 days).

CONCLUSIONL-838,417 can effectively improve hyperalgesia in rats with trigeminal neuralgia without causing sedation, motor impairment, or drug tolerance.

Animals ; Fluorobenzenes ; pharmacology ; Hyperalgesia ; drug therapy ; Male ; Pain Measurement ; Pain Threshold ; drug effects ; Rats ; Rats, Sprague-Dawley ; Triazoles ; pharmacology ; Trigeminal Neuralgia ; drug therapy ; physiopathology

Objective:To examine the feasibility of using cerebral state index(CSI)for monitoring the sedation depth during target-controlled infusion(TCI)with propofol and remifentanil.Methods:Forty-four consenting ASAⅠorⅡpatients(aged 18-60 years)undergoing elective surgery under general anesthesia were randomly divided into 4 groups(n=11 each)according to the target effect-site concentrations of remifentanil administered by TCI during induction of anesthesia.The target effect-site concentrations of remifentanil of R_0,R_2,R_4,and R_6 groups were 0,2 ng?ml~(-1),4 ng?ml~(-1),and 6 ng?ml~(-1),respectively. Anesthesia was induced by TCI with remifentanil and propofol.CSI and bispectral index(BIS)were used to measure the sedation depth.The initial effect-site propofol concentration(PCe)was 1.5?g?ml~(-1),which was increased by 0.5?g?ml~(-1) every 4 min.The modified OAA/S score(5=alert,1=does not respond to prodding),loss of eyelash reflex(LOR eyelash)and loss of response to electric tetanie stimulation(LOR tetanic)were compared against CSI,BIS and PCe(calculated effect-site propofol concentration).Correlation coefficients were calculated between CSI and other parameters.Results:The 4 groups were comparable with respect to the ages and bodyweights.CSI and BIS values were higher but PCe value were lower at LOR eyelash and LOR tetanic in R_2,R_4,and R_6 than those in the R_0 group(P

The metabonomics method was used to study the intervention effect of Psoraleae Fructus and Myristicae Semen in "Ershen pill" on the changes in serum endogenous metabolites in spleen-kidney Yang deficiency diarrhea rats before and after processing, screen out differentiated metabolites related to spleen-kidney Yang deficiency diarrhea and explore the metabolic patterns related to spleen-kidney Yang deficiency diarrhea and the processing synergy mechanism of Psoraleae Fructus and Myristicae Semen in "Ershen pill". Efforts were made to detect SOD and MDA of each group, test rat serum metabolic fingerprints in different stages by using GC-MS, analyze by PCA and PLS-DA methods and screen out potential biomarks through VIP and t test. The results revealed that "Ershen pill" could enhance the level of SOD and decrease the level of MDA and identified 10 differentiated metabolites related to spleen-kidney Yang deficiency diarrhea. Compared with the model group, all of metabolites recovered to varying levels after being intervened with "Ershen pill", with the best effect shown in the "Ershen pill" IV group (salt-processed Psoraleae Fructus + bran-roasted Myristicae Semen). It is speculated that that Psoraleae Fructus and Semen Myristicae in "Ershen pill" show a synergistic effect by inhibiting peroxide, improving aglucolipid, amino acids and energy metabolism, with multiple target sites.
Animals ; Chemistry, Pharmaceutical ; Diarrhea ; drug therapy ; metabolism ; physiopathology ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Energy Metabolism ; drug effects ; Humans ; Kidney ; drug effects ; metabolism ; Male ; Metabolomics ; Myristicaceae ; chemistry ; Psoralea ; chemistry ; Rats ; Rats, Sprague-Dawley ; Spleen ; drug effects ; metabolism ; Yang Deficiency ; drug therapy ; metabolism

ObjectiveTo investigate the difference in protein expression between hepatocellular carcinoma (HCC) patients with recurrence and those with good prognosis, the differential expression and regulatory mechanism of miR-152-3p target proteins, and the role of miR-152-3p in the recurrence of HCC. MethodsTMT-labeled proteomic sequencing and RT-PCR were used to measure the expression of proteins and the expression of miR-152-3p in the HCC tissue of six patients with recurrence at 2 years after HCC resection and six patients with good prognosis at 5 years. Six databases were used to analyze the target genes of miR-152-3p, and Gene Ontology, DAVID, and REACTOME databases were used to perform target gene screening, enrichment annotation, and signal transduction pathway enrichment analysis. Gene mutation frequency and survival curve analysis were performed for the target genes of miR-152-3p to verify the role of miR-152-3p target genes in patients with HCC recurrence. The independent samples t-test was used for comparison of continuous data between two groups, and a Kaplan-Meier analysis was performed to investigate the survival rates of liver-related genes. ResultsCompared with the patients with HCC recurrence, the patients with good prognosis after HCC resection had a significantly higher transcriptional expression level of miR-152-3p in HCC tissue (P＜0.05). The results of protein sequencing showed that there were 365 differentially expressed proteins in HCC tissue between the patients with good prognosis and the patients with recurrence, and the analysis of HCC recurrence databases showed that 17 proteins were regulated by miR-152-3p. Further analysis of the signaling pathways showed that the function of the 17 target genes regulated by miR-152-3p was enriched in the translation and regulation of mitochondria and ribosome, and multiple enrichment revealed that six target genes were closely associated with mitochondrial respiratory chain complex, i.e., AKAP1, FOXRED1, MRPL28, MRPL50, SHC1, and STAU1. Gene mutation frequency and survival curve analysis showed that the loss or weakening of the function of mitochondrial respiratory chain-related target proteins seriously affected the prognosis and survival rate of patients. ConclusionThere is a significant difference in the expression of miR-152-3p in HCC tissue between patients with good prognosis and those with recurrence after HCC resection, and miR-152-3p may lead to the recurrence of HCC by regulating the target genes AKAP1, FOXRED1, MRPL28, MRPL50, SHC1, and STAU1, acting on the mitochondrial respiratory chain, and affecting the oxidative respiratory function of cells.

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 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

OBJECTIVETo study the changes of displacement and stress in the model of lumbar pelvic and proximal femur during lumbar rotatory manipulation.

METHODSThe date of lumbar pelvic and proximal femur CT scan by Mimics 10.01 software was established a lumbar pelvic and proximal femur geometric model, then the model was modified with Geomagic 9, at last the modified model was imported into hypermesh 10 and meshed with tetrahedron, at the same time,add disc and ligaments. According to the principle of lumbar rotatory manipulation,the lumbar rotatory manipulation were decomposed. The mechanical parameters assigned into the three-dimensional finite element model. The changes of displacement and stress in the model of lunbar pelvic and proximal femur under the four conditions were calculated with Abaqus model of Hypermesh 10.

RESULTS1) Under the same condition,the displacement order of lumbar was L1>L2>L3>L5 L5, anterior column > middle column > posterior column. 2) Under the different conditions, the displacement order of lumbar,case 3>case 1>case 4>case 2. 3) Under the same conditions, the displacement order of lumbar inter-vertebral disc from L1,2 to L5S1 was L1,2>L2,3>L3,4>L4,5>L5S1, as for the same inter-vertebral disc, the order was: second quadrant>third quadrant>first quadrant>fourth quadrant. 4) Under the different conditions,the displacement order of the inter-vertebral disc was L1,2>L2,3>L3,4>L4,5>L5S1, but to same inter-vertebral disc: case 3>case 4>case 1 >case 2. 5) There were apparent displacement and stress concentration in pelvis and hip during the manipulation.

CONCLUSION1) The principles of lumbar rotation manipulation closely related to the relative displacement caused by rotation of various parts of lumbar pelvic and proximal femur model; 2) During the process of lumbar rotatory manipulation, the angle of lateral bending and flexion can not be randomly increased; 3) During the process of lumbar rotatory manipulation, all the conditions of lumbar pelvic and proximal femur must be considered to determine indications and contraindications.

Femur ; Finite Element Analysis ; Humans ; Lumbar Vertebrae ; Musculoskeletal Manipulations ; Pelvis ; Rotation

Objective To observe the urodynamic change after spinal cord injury at different levels and the relationship with neurogenic dysfunction of bladder and urethra. Methods Eighty female rats were divided into a control group (20 rats) , a suprasacral spinal cord injury group (30 rats) and a sacral spinal cord injury (30 rats). The urodynamic exam was performed with all the rats before and 20 days after the spinal cord injury model was established by surgical operation. Results The maximum bladder volume and compliance in the su- prasacral injury group were significantly less than the sacral spinal cord injury group and the control, the maxi- mum volume and compliance in sacral spinal cord injury group were significantly less than the control. The DLPP in suprasacral injury group was significantly higher than that in the sacral spinal cord injury group and the con- trol, the DLPP in sacral spinal cord injury group was significantly less than that in the control group. Conclu- sion Urodynamic study is very useful for the early diagnosis and individualized treatment of the neurogenic bladder after spinal cord injury.