A Single-center Retrospective Analysis of Clinical Epidemiology of Multiple Sclerosis / 中山大学学报(医学科学版)

@# 【Objective】To summarize current situation of multiple sclerosis in South China and provide reference for MS diagnosis and treatment.【Methods】We selected patients of whom the first diagnosis was MS from 2011 to March 2019，and divided them into Adults group and Pediatrics group according to onset age above or below 14. We analyzed them from epidemiology，symptomatology，accessory examinations and treatment situation.【Results】296 patients were admitted into this research. The ratio of male to female was 1∶1.67. Median onset age was 26. Relapsing-remitting MS accounted for 63.2% of all patients. For initial episode，130 patients had motor symptoms（43.9%），118 patients showed sensory symptoms（39.9%），and 55 patients were accompanied with visual symptoms（18.6%）. Statistical difference exists in sensory symptoms（114 vs. 4，Z = -2.155，P = 0.031）and paroxysmal symptoms（4 vs. 3，Z = -3.610，P = 0.000） of Adults group and Pediatrics group. For following episodes，the total relapsing time was 712，with motor symptoms relapsing 380 times（53.4%），sensory symptoms 265 times（37.2%）and visual symptoms 134 times（18.8%）. Statistical difference existed in motor，sensory，visual，other ocular symptoms and paroxysmal symptoms. Positive rate of Oligoclonal bond was 45.5%. Positive rate of MOG-Ab was 16.7%. For brain MRI，periventricular lesions ≥ 9 accounted for 57.4% of all patients，with cortical & juxtacortical lesions 28.1% and infratentorial lesions 0.3%. Patients who had optic nerve lesions accounted for 63.2%. No statistical difference existed in them. For treatment，drugs they had used previously were glucocorticoid（79.7%），beta Interferon（15.9%）and azathioprine（13.9%）.During the study，drugs they were using were glucocorticoid（15.5%），rituximab（9.1%），azathioprine（8.1%）and teriflunomide（8.1%）.【Conclusions】For gender， age，symptomatology and accessory examinations，results of this research are similar to previous papers about multiple sclerosis in Asian. For treatment，the trend indicates that usage of new disease-modifying drugs goes up.

Combined therapy with methylprednisolone and ulinastatin in experimental autoimmune encephalomyelitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Our previous study had demonstrated that ulinastatin (UTI) had a neuroprotective effect in experimental autoimmune encephalomyelitis (EAE). Methylprednisolone has been recommended to be a standard drug in multiple sclerosis (MS) therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE.</p><p><b>METHODS</b>Mice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)/ myelin basic protein (MBP)/ the precursor form of nerve growth factor (proNGF)/p75/ inducible nitric oxide synthase (iNOS) proteins in cerebral cortex of EAE were detected by Western blotting.</p><p><b>RESULTS</b>The combined treatment group had a lower clinical score (0.61 ± 0.06) and demyelinating score (1.33 ± 0.33) than the groups with normal saline (clinical score: 1.39 ± 0.08, P < 0.001; demyelinating score: 2.75 ± 0.49, P < 0.05) or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP (1.14 ± 0.06 vs. 0.65 ± 0.04, P < 0.001), MBP (1.28 ± 0.14 vs. 0.44 ± 0.17, P < 0.001), and decreased expressions of proNGF (1.08 ± 0.10 vs. 2.32 ± 0.12, P < 0.001), p75 (1.13 ± 0.13 vs. 2.33 ± 0.17, P < 0.001), and iNOS (1.05 ± 0.31 vs. 2.17 ± 0.13, P < 0.001) proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP (1.28 ± 0.14 vs. 1.01 ± 0.15, P < 0.05) expression and downregulate iNOS (1.05 ± 0.31 vs. 1.35 ± 0.14, P < 0.05) expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment (1.08 ± 0.10) than that in UTI (1.51 ± 0.24, P < 0.05) or methylprednisolone (1.31 ± 0.04, P < 0.05) treatment group.</p><p><b>CONCLUSION</b>Combination treatment of UTI with methylprednisolone was shown to protect EAE, suggesting that combination therapy is a potential novel treatment in MS.</p>

Level of β-amyloid peptide in cerebrospinal fluid of patients with multiple sclerosis and clinically isolated syndrome and its significance / 中华神经医学杂志

Objective To investigate the concentration of β-amyloid peptide 42 (Aβ42) in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and its first clinical event-clinically isolated syndrome (CIS), and explore its associations with duration, disability severity and total T2-hyperintense lesion numbers in MRI. Methods Thirty-three patients with MS, 23 patients with CIS and 13 controls were investigated in this study. The disability severity of patients with MS and CIS in attack period was assessed by Expanded Disability Status Scale (EDSS). MRI scanning of brain, spinal cord or optic nerve was performed. And Aβ42 concentration in CSF was assessed by liquid chip assay. Results No significant differences of Aβ42 concentrations in CSF from patients with MS and CIS in attack period were noted as compared with those from controls ([104.78±13.73]pg/mL, [134.13±25.06] pg/mL vs. [137.02±23.35]pg/mL, P>0.05). ButAβ42 concentration in CSF from patients with secondary progressive MS (SPMS, [167.99±36.39]pg/mL) was significantly higher than that from patients with relapsing-remitting MS (RRMS, [92.74±13.64] pg/mL, P=0.042). No correlations of Aβ42 concentration in CSF with the duration of MS and CIS and scores of EDSS were noted in patients with MS and CIS (P> 0.05). The concentration of Aβ42 in CSF from patients with MS with a duration for more than one year lower than the ones with a duration for less than one year, but the difference was not significant (P>0.05). Total T2-hyperintense lesion numbers in MRI of patients with MS and CIS were positively correlated with Aβ42 concentration in CSF (MS patients: r=0.507, P=0.038; CIS patients:r=0.485,P=0.049). Aβ42 concentration in CSF from patients with MS with total T2-hyperintense lesions ≥4 (129.34±19.96) was significantly higher than that from the ones with total T2-hyperintense lesions <4 (73.51±12.60, P=0.049). Conclusion Axonal damage in patients with SPMS is more severe than that in patients with RRMS.Increased CSF Aβ42-level in patients with MS is a feature of disease progression. There is a possible relation between T2-hyperintense lesion load and axonal damage in patients with MS.

Isolation and identification of reprogramming genes related to the development of the rabbit reconstructed embryos / 生物工程学报

By the method of single preimplantation embryos differential display polymerase chain reaction (SPEDDRT-PCR), 25 reprogramming cDNA fragments were obtained from single 2-cell, 8-cell embryos and blastula. After cloning and sequencing, five of them were identified by reverse-Northern and characterized with stage-specific expression during reconstructed embryo development. This results will help to isolate full length reprogramming genes and study their function during embryonic development.

Cloned goats produced from the somatic cells of an adult transgenic goat / 生物工程学报

This study was carried out to examine the effect of different donor cell type and micro-manipulation on the development of reconstituted embryos. Cultured mural cumulus cells or fibroblast cells from an adult transgenic goat expressing human erythropoietin(rhEPO) were used as the donor cells in nuclear transfer experiments. The reconstituted eggs were generated by transferring fibroblast cells or cumulus cells into the perivitelline space of enucleated M II oocytes and then followed by electrofusion and activation. After 6 days' incubation in vivo, the reconstructed embryos developed into morulae or blastocysts were transferred into 6 foster recipients. Two of the foster-mothers were pregnant and gave birth to two offspring, which were derived from the fibroblast cell and cumulus cell, respectively. Fingerprint analysis showed that the PCR-RFLP patterns of the two offspring were identical to that of donor goats. PCR results indicated that these cloned goats carried hEPO gene as same as their donor cells.