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Objective To investigate the effect of dopaminergic neurons of midbrain ventral tegmental area(VTA) in general anesthesia.Methods Forty adult healthy male SD rats were randomly divided into lesion group (n=20) and control group (n=20).The lesion group was given the bilateral infusion of specific dopaminergic neuron injury agent 6-OHDA in midbrain lateral VTA,while the control group received the same volume of normal saline at the same areas.The time of loss of righting reflex (LORR)loss and recovery of righting reflex(RORR)at postoperative 2 week were observed in each group.Results Compared with the control group,the LORR time in the lesion group was shortened and the RORR time was significantly prolonged under propofol-induced anesthesia (P＜0.05).However,the LORR time under the isoflurane anesthesia had no statistically significant difference between the two groups(P＞0.05),while the RORR time in the lesion group was increased(P＜0.05).Conclusion Dopaminergic neurons in midbrain VTA might play different roles in the induction and recovery of different general anesthetics.
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Objective To investigate the effect of early cerebrospinal fluid replacement on nuclear factor-κB (NF-κB) level and clinical outcomes in patients with aneurismal subarachnoid hemorrhage (aSAH) after endovascular embolization.Methods Patients with aSAH received aneurysm embolization were enrolled.They were divided into a cerebrospinal fluid replacement group and a non-cerebrospinal fluid replacement group according to the treatment scheme.All patients were treated with cerebral aneurysm coil embolization within 3 days after admission.The cerebrospinal fluid replacement group performed lumbar puncture cerebrospinal fluid replacement within 24 h after coil embolization,once every other day,20-30 ml of cerebrospinal fluid was replaced each time and 3 mg dexamethasone was injected intrathecally.The NF-κB levels in cerebrospinal fluid were detected at day 1,7 and 14 after the coil embolization.The primary outcome measures were the clinical outcomes determined by the modified Rankin scale (mRS) and the Glasgow outcome scale (GOS) at 3 months after onset.Good outcome was defined as mRS score 0-2 or GOS ＞ 3.The secondary outcome measures included severe complications (hydrocephalus,cerebral vasospasm,cerebral infarction,and rebleeding) and death.Results A total of 81 patients with aSAH received aneurysm embolization were enrolled,including 42 in the cerebrospinal fluid replacement group and 39 in the non-cerebrospinal fluid replacement group.There was no significant differences in the baseline data between the cerebrospinal fluid replacement group and the non-cerebrospinal fluid replacement group (all P ＞0.05).The duration of neck stiffness in the cerebrospinal fluid replacement group was significantly shorter than that in the non-cerebrospinal fluid replacement group (11.3 ± 3.2 d vs.16.5 ± 3.5 d;t =6.985,P ＜ 0.001).The cerebrospinal fluid NF-κB levels were progressively reduced at day 1,7 and 14 after coil embolization in the cerebrospinal fluid rephcement group and non-cerebrospinal fluid rephcement group (all P ＜0.05),but the ccerebrospinal fluid levels of NF-κB in the cerebrospinal fluid replacement group at each time point were significantly lower than those in the non-cerebrospinal fluid replacement group (all P ＜ 0.01).The good outcome rates evaluated according to the mRS score (92.9％ vs.56.4％;x2 =14.446,P ＜ 0.001) and GOS score (97.6％ vs.76.9％;x2 =8.004,P=0.005) in the cerebrospinal fluid replacement group at 3 months were significantly higher than those in the non-cerebrospinal fluid replacement group,and the incidence of cerebral vasospasm was significantly lower than that in the non-cerebrospinal fluid replacement group (14.3％ vs.33.3％;x2 =4.086,P =0.043).Conelusiom Cerebrospinal fluid replacement therapy can reduce the incidence of cerebral vasospasm in patients with aSAH receiving aneurysm embolization and improve clinical outcomes.Its mechanism may be associated with the decrease of NF-κB level in cerebrospinal fluid.
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Objective To summarize the clinical features of 22 probands diagnosed with congenital muscular dystrophy (CMD),and to provide genetic counseling and prenatal diagnosis for 23 fetuses of these pedigrees.Methods Data of 22 CMD patients who were treated in the Pediatric Department of Peking University First Hospital during October 2006 to March 2016 were analyzed.Informed written consents for participation in this study were obtained from the parents or guardians.Prenatal diagnosis was performed using DNA samples extracted from fetal villus cells of 12 cases at 11-13 gestational weeks and amniotic fluid of 11 cases at 18-22 gestational weeks.Direct DNA sequencing by polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) were used to detect CMD-related gene mutations.Linkage analysis of short tandem repeats (STRs) was used to identify maternal blood contamination and biological parents.Results Thirteen out of the 22 probands with CMD were diagnosed with congenital muscular dystrophy type 1 A (MDC1A),and all of them carried compound heterozygous mutations in LAMA2 gene.Prenatal diagnosis of 13 fetuses from these pedigrees found that four fetuses were wild-type,seven were heterozygotes and two carried the same mutations as their proband.Three probands with LMNA-related congenital muscular dystrophy (L-CMD) carried de novo mutations in LMNA gene.In these pedigrees,two fetuses were wild-type and one whose mother was mosaicism carried the same mutations as the proband.One proband with Ullrich congenital muscular dystrophy carried compound heterozygous mutations in COL6A2 gene and the fetus of the same pedigree was wild-type.Five probands were diagnosed with α-dystroglycanopathies.And among them,two cases of muscle-eye-brain disease (MEB) carried compound heterozygous mutations in POMGnT1 gene and the fetuses of the two peidgrees were heterozygotes;one case of congenital muscular dystrophy type 1C (MDC1C) had compound heterozygous mutations in FKRP gene and the fetus carried the same mutations;one patient diagnosed with POMGnT1-related congenital muscular dystrophy with mental retardation (CMD-MR) carried compound heterozygous mutations in POMGnT1 gene,and the fetus was positive for the same mutations;one proband with POMT1-related CMD-MR was positive for compound heterozygous mutations in POMT1 gene and the results of prenatal diagnosis for two fetuses of this pedigree showed that the first fetus had the same mutations as the proband,while the second was heterozygote.Conclusions No effective therapeutic method is available for CMD.Therefore,accurate genetic counseling and prenatal diagnosis are necessary to prevent CMD child from birth.
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<p><b>OBJECTIVE</b>To analyze clinical features and genetic mutations in a Chinese family affected with autosomal dominant caveolinopathies.</p><p><b>METHODS</b>Clinical data of the proband and her family members were collected. Genomic DNA was extracted from peripheral blood samples with a standard procedure. Next generation sequencing was carried out for the proband, and direct sequencing was employed to detect potential mutation of the CAV gene.</p><p><b>RESULTS</b>The proband presented with slowly progressing distal muscle weakness and atrophy, especially distal upper limbs and muscular soreness during early childhood, with her CK level moderately elevated and EMG showing myogenic and neurogenic injuries. Her sisters presented mild symptoms with hand muscle atrophy and fasciculation after exercise. A heterozygous missense mutation c.80G>A (p.Arg27Gln), which was reported as being pathogenic, was identified in the CAV3 gene in the proband and her sisters.</p><p><b>CONCLUSION</b>A heterozygous c.80G>A (p.Arg27Gln) mutation in the CAV3 gene probably underlies the autosomal dominant caveolinopathies in this Chinese family.</p>
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Female , Humans , Middle Aged , Caveolin 3 , Genetics , High-Throughput Nucleotide Sequencing , Muscular Dystrophies , Genetics , MutationABSTRACT
Objective To investigate folic acid and vitamin B12 on the plasma homocysteine (Hcy) levels and neurological function in young and middle-aged acute ischemic stroke patients with hyperhomocysteinemia (HHcy).Methods Young and middle-aged acute ischemic stroke patients with HHcy were enrolled.They were randomly divided into either an intervention group or a control group.The patients with cerebral infarction in both groups were treated with conventional treatment.At the same time,the patients in the intervention group were treated with folic acid 5 mg and vitamin B12 25 μg,3 times a day for 4 weeks.Those in the control group were given placebo.The next day after admission and thereafter,the plasma Hcy levels were determined once every week.At the time of admission and after 4-week treatment,the National Institutes of Health Stroke Scale (NIHSS) was used to evaluate neurological deficits.Results A total of 78young and middle-aged acute lschemic stroke patients with HHcy were enrolled (n =39 in each group).The baseline plasma Hcy levels and the NIHSS scores in all patients had significant linear correlation (r =0.717;P＜0.01).Four weeks after treatment,the plasma Hcy levels of the intervention group were significantly lower than those of the control group (15.07 ± 2.01μmol/L vs.21.29 ± 2.48 μmol/L; t =4.539; P ＜0.05),but there was no significant difference in the NIHSS scores (4.87 ± 2.17 vs.5.13 ± 1.67; t =0.585,P =0.560).Conclusions The baseline plasma Hcy level was positively correlated with the severity of stroke.Folic acid in combination with vitamin B12 could effectively decrease the plasma Hey level in young and middle-aged acute ischemic stroke patients with HHcy,but it had no significant effect on the improvement of neurological function.