Objective To investigate the effect of blood pressure control for early enlargement of hypertensive intracerebral hemorrhage.Methods A total of 96 patients were divided randomly into intensive blood pressure lowering group (n = 48 )and standard antihypertensive group(n=48).Patients were checked head CT and was evaluated defect of nerve function score immedi-ately when they arrive at hospital and after 24 hours.Then the clinical curative effect was evaluated.Results The defect of nerve function score in intensive blood pressure lowering group was lower than that of the standard antihypertensive group(P <0.05 ). The hematomas volume within 24 hours of admission and the rate of hematoma enlargement of intensive blood pressure lowering group were sharply smaller than those of standard antihypertensive group(P <0.05).Conclusion Controlling blood pressure ac-tively could decrease ratio early enlargement of hematoma and defect of nerve function score in patients with hypertensive cerebral hemorrhage.

Objective To evaluate the changes in the expression of hippocampal long non-coding RNAs ( lncRNAs) and bioinformatics analysis in mice with perioperative neurocognitive disorders ( PND) . Methods Thirty clean-grade male C57BL∕6 mice, aged 12-14 weeks, weighing 25-30 g, were divided into 2 groups (n=15 each) according to the random number table method: control group (group C) and PND group. The model of PND was established by performing open tibial fracture with intramedullary fixa-tion under isoflurane anesthesia in anesthetized mice. The Morris water maze test, open field test and fear conditioning test were performed at 1, 3 and 7 days postoperatively. The animals were sacrificed after the end of behavioral testing on 3 days after operation, the hippocampus was obtained, the high-throughput gene sequencing was performed to identify the differentially expressed lncRNAs, and Gene Ontology func-tional analysis and Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis were used to ana-lyze the results. Results Compared with group C, the escape latency was significantly prolonged, and the percentage of time spend in the target quadrant and percentage of freezing time in the fear conditioning test were decreased at different time points after operation in group PND ( P<0. 05) . A total of 121 differential-ly expressed lncRNAs were identified, of which 69 were up-regulated and 52 were down-regulated. The Gene Ontology functional analysis showed that there were differences in various biological processes, such as synaptic transmission, cholinergic neurotransmitters, or adiponectin secretion and regulation. The KEGG signaling pathway analysis showed that there were also differences in cholinergic synapses, MAPK signaling pathway, glucagon signaling pathway, TNF signaling pathway, NOD-like receptors, Toll-like re-ceptors, chemokine signaling pathway and etc. Conclusion There are 121 differentially expressed lncR-NAs in the hippocampus of PND mice, and lncRNAs- and the target gene-related inflammatory responses, synaptic transmission, energy metabolism and etc. may be related to the pathogenesis of PND.

BACKGROUND AND PURPOSE: This study investigated the contribution of white-matter hyperintensities (WMH) and lacunar infarcts (LI) to the risk of Alzheimer's disease (AD) in an elderly cohort in China. METHODS: Older adults who were initially cognitively normal were examined with MRI at baseline, and followed for 5 years. WMH were classified as mild, moderate, or severe, and LI were classified into a few LI (1 to 3) or many LI (≥4). Cognitive function was assessed using the Mini Mental State Examination and the Activities of Daily Living scale. RESULTS: Among the 2,626 subjects, 357 developed AD by the end of the 5-year follow-up period. After adjusting for age and other potential confounders, having only WMH, having only LI, and having both WMH and LI were associated with an increased risk of developing AD compared with having neither WMH nor LI. Moderate and severe WMH were associated with an increased risk of developing AD compared with no WMH. Furthermore, patients with many LI had an increased risk of developing AD compared with no LI. CONCLUSIONS: Having moderate or severe WMH and many LI were associated with an increased risk of developing AD, with this being particularly striking when both WMH and LI were present.
Activities of Daily Living ; Adult ; Aged* ; Alzheimer Disease* ; China* ; Cognition ; Cohort Studies ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Strikes, Employee ; Stroke, Lacunar*

Objective:To investigate the relationship between inherited dysplasminogenemia and cerebral infarction (CI) by phenotype and gene mutation analysis of 2 inherited dysplasminogenemia pedigrees.Methods:Retrospective analysis was carried out on clinical data of 2 patients diagnosed with CI who were treated in the Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University in January and March 2021, and peripheral venous blood samples were collected from proband 1 and his family members (8 subjects, 4 generations in total) and proband 2 and her family members (5 subjects of 3 generations in total), and their plasminogen (PLG) activity (PLG:A), protein C activity, protein S activity, antithrombin activity and the content of PLG antigen (PLG: Ag), fibrinogen, D-dimer and fibrinogen degradation products were measured for definite diagnosis. All 19 exons,5′ and 3′ untranslated regions of PLG were amplified with polymerase chain reaction, and the amplification products were analyzed by direct DNA sequencing. The results were compared with human PLG reference sequences published in the National Center for Biotechnology Information database using Chromas software to find the mutation sites, and confirmed by reverse sequencing.Results:Both of the 2 patients with confirmed CI had a young onset, and PLG: A was reduced to 21% in the proband 1 and to about 50% in 4 family members; PLG: A was reduced to about 50% in the proband 2 and 2 family members; PLG:Ag and the above tests were essentially normal in both probands and family members. Gene analysis showed that the proband 1 had the homozygous mutation of c.1858G>A in exon 15, the 4 family members of the proband 1, proband 2 and her 2 family members had the heterozygous mutation of c.1858G>A in exon 15, which resulted in a mutation of alanine at position 620 in PLG to threonine (p.Ala620Thr).Conclusions:The decrease of PLG:A was caused by the p.Ala620Thr missense mutation of PLG gene. Proband having CI may be related to the inhibition of fibrinolytic function in the organism due to the p.Ala620Thr missense mutation.

Objective:To study the clinical characteristics and gene mutations in a family with combined inherited antithrombin (AT) and factor Ⅶ (FⅦ) deficiency, and explore the relationship between AT gene, F7 gene mutations and diseases. Methods:Pedigree investigation. Blood samplesand clinical dataswere collected fromthe proband and her family members (a total of 16 people in 3 generations) who admitted to the First Affiliated Hospital of Wenzhou Medical University in November 2018. The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), antithrombin activity (AT: A), antithrombin antigen (AT: Ag), protein C activity (PC: A), protein S activity (PS: A), FⅦ activity (FⅦ: C), FⅦ antigen (FⅦ: Ag) and other indicators were detectedto confirm the diagnosis. DNA direct sequencing analysis of all exons, flanking sequences, 5′ and 3′ untranslated regions of AT genes and F7 genes, and the mutation sites were confirmed by clone sequencingor reverse sequencing. Results:The AT: A and AT: Ag of the proband were 46% and 135 mg/L, respectively (reference range: 250-360 mg/L), some of her family members′ s (father, aunt, two cousins, younger brother and nephew) AT: A and AT: Ag were reduced to 50% of normal range. Her father (Ⅰ 2), aunt (Ⅰ 4), elder brother (Ⅱ 7), younger brother (Ⅱ 8), and nephew (Ⅲ 3)′s FⅦ: C were 45%, 50%, 48%, 47% and 48%, respectively; and their FⅦ:Ag was within the normal range. Genetic analysis revealed that the proband(Ⅱ 6) and some of her family members (father, aunt, two cousins, younger brother and nephew) took rs3138521 polymorphism in the 5′ untranslated region of AT gene. Her father (Ⅰ 2), aunt (Ⅰ 4), elder brother (Ⅱ 7), younger brother (Ⅱ 8), nephew (Ⅲ 3) took c.1091G>A heterozygous missense mutationin exon 8 of F7 gene, resulting in p.Arg304Gln. Conclusion:The rs3138521 in AT gene and c.1091G>A in F7 gene, which may be the molecular mechanism leading to combined inherited AT and FⅦ deficiency in this family.

OBJECTIVE: To analyze the phenotype and genetic variants of a pedigree affected with hereditary protein C (PC) deficiency. METHODS: The protein C activity (PC:A) of the proband and her family members (a four-generation pedigree including 11 individuals) were tested by chromogenic substrate method, and the protein C antigen (PC:Ag) was detected with an enzyme-linked immunosorbent assay(ELISA). The 9 exons and flanking sequences of the protein C (PROC) gene were amplified by PCR and directly sequenced. Suspected mutation was validated by clone sequencing and in other members of the family. MutationTaster and ClustalX-2.1-win was used to analyze the pathogenicity and conservation of the mutation site,respectively. Three-dimentional protein model and amino acids interaction were analyzed with Swiss-PdbViewer software. RESULTS: The PC: A and PC: Ag of the proband were decreased to 46% (reference range: 70%-130%) and 50% (referencerange:70%-140%), respectively. Her grandmother,aunt, cousin and younger brother also showed declined PC:A and PC:Ag by approximately 50%. Genetic analysis revealed that the above individuals have all carried a deletional mutation c.1212-1212delG (p.Met364TrpfsX15) in exon 9 of the PROC gene which can cause replacement of Methionine at position 364 by Tryptophan and alteration of 15 downstream amino acids, and produce a premature stop codon at position 378. The score of MutationTaster was 1.000, indicating that the variant is pathogenic. Conservative analysis showed that the 15 altered amino acids are located in a conserved region across nine homologous species. Protein model analysis showed that the mutation has disrupted a catalytic domain of protein C thereby affected its function. CONCLUSION The heterozygous c.1212-1212delG deletional mutation in exon 9 of the PROC gene, which was unreported previously,probably accounts for the decrease of PC:A and PC:Ag in this pedigree.

Objective:To analyze 12 antithrombins (AT) gene mutations that cause AT deficiency and discuss the relationship between the SERPINC1 gene. mutations and venous thrombotic events.Methods:This study belongs to case series of observational studies. Collected the clinical data of 12 AT deficiency cases in the First Affiliated Hospital of Wenzhou Medical University from April 2014 to April 2021 and collected the blood samples before treatment. The AT activity (AT: A) and AT antigen (AT: Ag) was detected by chromogenic substrate and immunoturbidimetry, respectively. The 7 exons and flanking sequences of the SERPINC1 gene were sequenced directly by PCR, the suspected mutations were validated by reverse sequencing. Analyzed the correlation between the SERPINC1 gene. mutations and venous thrombotic events and figured out the proportion.Results:The AT: A of the 12 patients all decreased significantly, ranging from 30% to 66%, and the AT: Ag of the 7 patients decreased accordingly, showing type Ⅰ AT deficiency, and the AT: Ag of the other 5 patients were normal, presented type Ⅱ AT deficiency. 12 mutations were found including 6 heterozygous mutations which were discovered for the first time: c.456_458delCTT(p.phe121del), c.318_319insT(p.Asn75stop), c.922G>T(p.Gly276Cys), c.938T>C (p.Met281Thr), c.1346T>A(p.Leu417Gln)and c.851T>C(p.Met252Thr). All 12 patients had venous thrombosis, and 3 cases including 2 compound heterozygotes and 1 single heterozygote all suffered from deep venous thrombosis (DVT) when they were younger without obvious triggers. The other 9 patients all combined with the other thrombotic factors including old age, hypertensive, smoking, pregnancy, and prolonged immobilization.Conclusion:Patients with AT deficiency caused by SERPINC1 gene defects are prone to venous thrombosis, especially combined with other thrombotic factors.

Mechanistic target of rapamycin (mTOR) signaling governs important physiological and pathological processes key to cellular life. Loss of mTOR negative regulators and subsequent over-activation of mTOR signaling are major causes underlying epileptic encephalopathy. Our previous studies showed that UBTOR/KIAA1024/MINAR1 acts as a negative regulator of mTOR signaling, but whether UBTOR plays a role in neurological diseases remains largely unknown. We therefore examined a zebrafish model and found that ubtor disruption caused increased spontaneous embryonic movement and neuronal activity in spinal interneurons, as well as the expected hyperactivation of mTOR signaling in early zebrafish embryos. In addition, mutant ubtor larvae showed increased sensitivity to the convulsant pentylenetetrazol, and both the motor activity and the neuronal activity were up-regulated. These phenotypic abnormalities in zebrafish embryos and larvae were rescued by treatment with the mTORC1 inhibitor rapamycin. Taken together, our findings show that ubtor regulates motor hyperactivity and epilepsy-like behaviors by elevating neuronal activity and activating mTOR signaling.
Animals ; Hyperkinesis/genetics* ; Mutation/genetics* ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Zebrafish/metabolism*

Mechanistic target of rapamycin (mTOR) signaling governs important physiological and pathological processes key to cellular life. Loss of mTOR negative regulators and subsequent over-activation of mTOR signaling are major causes underlying epileptic encephalopathy. Our previous studies showed that UBTOR/KIAA1024/MINAR1 acts as a negative regulator of mTOR signaling, but whether UBTOR plays a role in neurological diseases remains largely unknown. We therefore examined a zebrafish model and found that ubtor disruption caused increased spontaneous embryonic movement and neuronal activity in spinal interneurons, as well as the expected hyperactivation of mTOR signaling in early zebrafish embryos. In addition, mutant ubtor larvae showed increased sensitivity to the convulsant pentylenetetrazol, and both the motor activity and the neuronal activity were up-regulated. These phenotypic abnormalities in zebrafish embryos and larvae were rescued by treatment with the mTORC1 inhibitor rapamycin. Taken together, our findings show that ubtor regulates motor hyperactivity and epilepsy-like behaviors by elevating neuronal activity and activating mTOR signaling.