ObjectiveTo explore the molecular characteristics of partial epilepsy with febrile seizures plus(PEFS+). MethodsWe systematically reviewed all SCN1A mutation-related publications that published between Jan.2000 and Dec.2014 on Pubmed and established a database of SCN1A mutations (http://www.gzneurosci.com/SCN1Adatabase/). The characteristics of mutations that cause PEFS+ were analyzed and compared with that of severe myoclonic epilepsy in infancy (SMEI). ResultsThe database included 1, 257 SCN1A mutations, which identified from 1, 727 unrelated cases. In which there were 30 mutations, from 32 unrelated cases, were associated with PEFS+. 76.7% (23/30) mutations were missense, of which 47.8% (11/23) were located on pore region. Significant difference in the percentage of truncation mutation was observed between PEFS+ and SMEI (P < 0.05). There was no significant difference in the percentage of missense mutation that located on the pore region between PEFS+ and SMEI; but the differ significantly in D-value of the missense mutations, which quantified the alteration of amino acid(P=0.042, rank sum test). ConclusionsPEFS+, which distinguishes from GEFS+ and SMEI in clinical and molecular characteristics, is a special phenotype of epilepsy that is associated with SCN1A mutations.
ObjectiveTo investigate the clinical research development of dementia in the UK Biobank database in SCIE and PubMed. MethodsThe literatures of dementia in the UK Biobank database published in SCIE and PubMed from January 1, 2018 to November 30, 2022 were searched, and the number of articles, publishing institutions, journals, citations, authors and keywords were statistically analyzed. ResultsA total of 279 papers were included, and the number of papers presented an annual growth trend. The United Kingdom has the largest number of publications, the United States journals have the greatest influence, and China has the third largest number of publications. Springer Nature from Germany published the most papers, with the largest number of 47 papers. Among the authors, Yu JT from China published the most, with 11 articles, and the most major keyword in the research content is Alzheimer. ConclusionThe literatures of dementia in the UK Biobank-related field included in SCIE and PubMed databases show an increasing trend year by year, mainly in English, and the core author group has not yet formed. The papers published by Chinese scholars are concentrated in 2020-2022, and there are few transnational cooperative papers.
ObjectiveBenign familial epilepsies that present themselves in the first year of life include benign familial neonatal epilepsy (BFNE), benign familial neonatal-infantile epilepsy (BFNIE) and benign familial infantile epilepsy (BFIE). We aim to investigate gene mutations and the relationship between genotypes and clinical phenotypes in benign familial epilepsies in the first year of life.MethodsWe recruited families with benign familial epilepsies in the first year of life at Peking University First Hospital from September 2006 to January 2018. Clinical information and blood samples were obtained from probands and their family members. For BFIE families, mutation screening of PRRT2 was performed by using the polymerase chain reaction (PCR) and Sanger sequencing at first. The PRRT2 mutation negative probands of BFIE families were further screened for pathogenic mutations by targeted next-generation sequencing. The probands of BFNE and BFNIE families were screened for pathogenic mutations by targeted next-generation sequencing.ResultsA total of 89 families with benign familial epilepsies in the first year of life were collected. Of the 89 families, 4 were classified as BFNE, 7 as BFNIE, and 78 as BFIE. Genetic testing led to the identification of gene mutations in 68 families (76.4%), including 50 families had PRRT2 mutations (hotspot mutation c.649dupC was detected in 32 families; c.649delC was detected in 6 families), 9 families had KCNQ2 mutations, 8 families had SCN2A mutations, and one family had GABRA6 mutation. In the 4 BFNE families, causative mutations were only found in KCNQ2, which was identified as the causative gene in 3 families. The remaining one BFNE family was not detected with any pathogenic mutation. All 7 BFNIE families had identifiable gene mutations, KCNQ2 was found in 3 families, SCN2A in 3 families, and PRRT2 in one family. In the 78 BFIE families, gene mutations were identified in 58 families (74.4%), with PRRT2 mutations found in 49 families (62.8%), SCN2A mutations found in 5 families, KCNQ2 mutations found in 3 families, and a novol GABRA6 mutation found in one family. Twenty BFIE families were not identified with any gene mutations. In 78 BFIE families, 18 were subclassified as infantile convulsions with paroxysmal choreoathetosis syndrome(ICCA). 17 of 18 ICCA families were detected with PRRT2 mutations (17/18, 94.4%). The remaining ICCA family was not detected with any pathogenic mutation.ConclusionsOur results confirmed that mutations in KCNQ2, SCN2A, and PRRT2 are major genetic causes of benign familial epilepsy in the first year of life in the Chinese population. KCNQ2 is the major gene related to BFNE. PRRT2 is the main gene responsible for BFIE. KCNQ2 and SCN2A mutations are common in BFNIE families. GABRA6 mutation might be a new cause of BFIE. Identification of underlying gene mutation can be helpful for clinical diagnosis and judgement of the prognosis.
Objective To study the growth characteristics of umbil ical cord MSCs (UCMSCs) in vitro and its effect on the nerve regeneration after spinal cord injury (SCI). Methods UCMSCs isolated from pregnant rats umbil ical cord were cultured and purified in vitro. Sixty female Wistar rats weighing (300 ± 10) g were randomized into three groups (n=20per group). UCMSCs group (group A) in which UCMSCs suspension injection was conducted; DMEM control group (groupB) in which 10% DMEM injection was conducted; sham group (group C) in which the animal received laminectomy only.Establ ish acute SCI model (T10) by Impactor model-II device in group A and group B. The recovery of the lower extremity was observed using BBB locomotor scoring system, neurofilament 200 (NF-200) immunofluorescence staining was performed to detect the neural regeneration, and then the corticospinal tract (CST) was observed using the biotinylated dextran amine (BDA) tracing. Results Cultured UCMSCs were spindle-shaped fibrocyte-l ike adherent growth, swirl ing or parallelly. The USMSCs expressed CD29, but not CD31, CD45, and HLA-DR. The BBB score was higher in group A than group B 4, 5, and 6 weeks after operation, and there was a significant difference between two groups (P lt; 0.05). The BBB scores at different time points were significantly lower in groups A and B than that in group C (P lt; 0.05). UCMSCs was proved to survive and assemble around the injured place by frozen section of the cords 6 weeks after injury. NF-200 positive response area in groups A, B, and C was (11 943 ± 856), (7 986 ± 627), and (13 117 ± 945) pixels, respectively, suggesting there was a significant difference between groups A, C and group B (P lt; 0.05), and no significant difference was evident between group A and group C (P gt; 0.05). BDA anterograde tracing 10 weeks after operation demonstrated that more regenerated nerve fibers went through injured area in group A, but just quite few nerve fibers in group B went through the injuried cavity. The ratios of regenerative axons amount to T5 axons in group A and group B were smaller than that of group C (P lt; 0.05). Conclusion UCMSCs can prol iferate rapidly in vitro, survive and differentiate to neurons after being grafted into injured spinal cord. The transplantation of UCMSCs is effective in promoting functional recovery and axonal regeneration after SCI.
【Abstract】 Objective To review the recent progress of BMSCs acting as seeding cell for tissue engineeredcartilage. Methods The recent ten years l iterature about BMSCs acting as seeding cell for tissue engineered cartilage was extensively reviewed. Results Scaffold provided an optimal environment for the growth of BMSCs. Cytokine and gene del ivery could promote BMSCs to differentiate toward chondrocytes. All of them played important roles in the field of cartilage tissue engineering. Conclusion The improvement of three-dimensional scaffolds, the rational use of cytokine, and the enhancement of gene del ivery will promote the development of cl inical cartilage reconstruction.
Objective To introduce the research of cell transplantation for treating intervertebral disc degeneration. Methods The original articles in recent years about cell transplantation for treating intervertebral disc degeneration were extensively reviewed, and retrospective and comprehensive analysis was performed. Results Transplantation of intevertebraldisc-derived cells or BMSCs by pure cell transplantation or combined with collagen scaffold into intervertebral disc couldexpress nucleus pulposus-l ike phenotype. All the cells transplanted into intervertebral disc could increase extracellular matrix synthesis and rel ieve or even inhibit further intervertebral disc degeneration. Conclusion Cell transplantation for treating intervertebral disc degeneration may be a promising approach.
Objective To investigate the adhesiveness of osteoblasts and vascular endothel ial cells from rat BMSCs co-cultured on allogeneic freeze-dried partially bone in vitro. Methods The BMSCs were isolated from 4-week-old SD rats (weighing 100-110 g) and cultured in vitro. The third generation of BMSCs were induced into osteoblasts and vascular endothel ial cells. The osteoblasts and vascular endothel ial cells after being induced for 7 days in a ratio of 1 to 1 were directlyco-cultured (experimental group), while the second generation of uninduced BMSCs was used as a control (control group). The growth and prol iferation abil ity were analyzed by MTT examination and the growth curve was drawn at 1-8 days. The osteoblasts and vascular endothel ial cells after being induced for 14 days were implanted in the allogeneic freeze-dried partially bone coated by 20% Col I or not at different densities (0.25 × 106/mL、0.50 × 106/mL、1.00 × 106/mL、2.00 × 106/mL、4.00 × 106/mL), as modified group and unmodified group, the cell adherence rate was calculated after 24 hours. These two kinds of cells were implanted in the pre-disposal treated allogeneic freeze-dried partially bone and observed by scanning electron microscope. Results ALP staining of osteoblasts showed that there were blue grains in cytoplasm at 7 days. CD31 and CD34 immunocytochemical staining of vascular endothelial cell showed that there were positive signals in the cytoplasm at 14 days. The MTT test showed that the prol iferation level of the experimental group was lower than those of the control group. There were significant differences in absorbance value between two group from 3 days to 8 days (P lt; 0.05). The cell adherence rate increased with increasing seeding density when the seeding density was (0.25-1.00) × 106/mL. The cell adherence rate reached the peak when the seeding density was 1.00 × 106/mL. The cell adherence rate decreased when the seeding density was more than 2.00 × 106/mL. There were significant differences in cell adherence rate between modified group and unmodified group at different seeding densities (P lt; 0.05). The prol iferation of the osteoblasts and endothel ial cells presented better growth and histocompatibil ity under scanning electron microscope. Conclusion The growing behavior of two kinds of cells is good in the allogeneic freezedried partially bone coated by 20% Col I , which can be used in reconstrction of vascularized tissue engineered bone.
Objective To investigate a new composite matrix (BMSCs seeded on the denuded human amniotic membrane, BMSCs-DHAM) bridging the both stumps of spinal cord injury in rats to promote axon regeneration and improve motor function of hind l imbs. Methods The human amniotic membrane (HAM) was voluntarily donated by the healthy pregnant women after a caesarean section. The cells on the HAM were completely removed with a tryptic and mechanical approach to prepare DHAM. The BMSCs were separated and cultured from 4-week-old female rats (n=4), then the forth passage of BMSCs were labeled by PKH26 and seeded on DHAM (BMSCs-DHAM). The growing state of BMSCs was observed under themicroscopy. Moreover, 40 female rats (8-week-old, weighting 200-220 g) were made spinal cord injury models by transecting at T9 level, and were randomly divided into 4 groups (each group, n=10). The both stumps were respectively wrapped by BMSCs- DHAM or simple DHAM in groups A and C, and the same dose of BMSCs or physiological sal ine were also respectively injected the central lesion in groups B and D. At 12 weeks after surgery, the functional recovery of the hindl imbs was evaluated by the BBB locomotor rating score, and other indexes were tested including cortical motion evoked potential (MEP), anterograde biopinylated dextan amine (BDA) tracing, and immunofluorescence of neurofilament protein 200 (NF-200). Results HE staining proved that the DHAM was devoid of cellular components by this way, and BMSCs grew well on the substrate under the microscopy. At 12 weeks after operation, the BBB score (12.50 ± 1.26) in group A was significantly higher than those of other groups (P lt; 0.05), and the recovery in latency (3.52 ± 2.45) ms and ampl itude (480.68 ± 18.41) μV of MEP was also obviously improved in group A (P lt; 0.05) when compared with other groups. In addition, anterograde BDA tracing revealed that the rate of the positive BDA axons 54.12% ± 3.30% under the lesion level in group A was higher than those of other groups (P lt; 0.05), and lots of the regeneration axons (positive NF-200) were found to grow into the spinal cord under the composite matrix in group A. Conclusion The BMSCs-DHAM composite matrix can improve hindl imb motor function to some extent after spinal cord injury. It will be widely appl ied as the matrix material in the future.
With significantly increasing proportion of high-risk patients undergoing cardiovascular surgery, a quantitative risk stratification system of perioperative patients is needed for cardiovascular surgeons. European system for cardiac operative risk evaluation (EuroSCORE) is a widely-used risk prediction model for adult patients undergoing cardiovascular surgery in the world. Research data from Chinese Cardiac Surgery Registry show that the performance of EuroSCORE in the prediction of postoperative risk of Chinese cardiovascular surgical patients is not satisfactory. Thus, the first Chinese coronary operative risk evaluation model (Sino system for coronary operative risk evaluation,SinoSCORE) is established with latest cardiovascular surgery data by Collaboration Association of Cardiovascular Surgeon in China, and has been widely used in clinical practice. This review focuses on the application and prospect of EuroSCORE and SinoSCORE for the prediction of mortality after cardiovascular surgery in adults.
Objective To explore the label ing efficiency and cellular viabil ity of rabbit BMSCs labeled with different concentrations of superparamagnetic iron oxide (SPIO) particles, and to determine the feasibil ity of magnetically labeled stem cells with MR imaging. Methods The BMSCs were collected from il iac marrow of 10 adult rabbits (weighing 2.5-3.0 kg) and cultured. The SPIO-poly-L-lysine compound by different ratios mixed with medium, therefore, the final concentration of Fe2+ was 150 (group A), 100 (group B), 50 (group C) and 25 μg (group D) per mL, respectively, the 3rd generation BMSCs culture edium was added to lable; non-labeled cells served as a control (group E). MR imaging of cell suspensions was performed by using T1WI and T2WI sequences at a cl inical 1.5 T MRI system. Results BMSCs were efficiently labeled with SPIO, labeled SPIO particles were stained in all cytoplasms of groups A, B, C and D. With the increasing of Fe2+ concentration, blue dye particles increased. The staining result was negative in group E. The cell viabil ity in groups A, B, C, D and E was 69.20% ± 6.11%, 80.41% ± 2.42%, 94.32% ± 0.67%, 96.24% ± 0.34% and 97.43% ± 0.33%, respectively. There were statistically significant differences between groups A, B and groups C, D and E (P lt; 0.05), and between group A and group B (P lt; 0.05). T1WI images had no specific difference among 5 groups, T2WI images decreased significantly in groups A, B, C, decreased sl ightly in group D, and had l ittle change in group E. The T2WI signal intensities of groups A, B, C, D and E were 23.37 ± 6.21, 26.73 ± 3.60, 29.63 ± 2.82, 45.03 ± 6.76 and 783.15 ± 7.38, respectively, showing significant difference between groups A, B, C, D and group E (P lt; 0.05), and between groups A, B, C and group D (Plt; 0.05). Conclusion BMSCs can be easily and efficiently labeled by SPIO without interference on the cell viabil ity in labled concentration of 20-50 μg Fe2+ per mL. MRI visual ization of SPIO labeled BMSCs is feasible, which may be critical for future experimental studies.