Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system, primarily affecting the optic nerve and spinal cord.In addition to aquaporin 4 antibody, more and more studies have shown that interleukins (IL) also play an important role in the progression of NMOSD.For example, among the most common CD4 + T cells, Th17 cells can destroy the blood-brain barrier to invade the central nervous system and then affect autoimmunity; Th2-mediated IL-4 and IL-10 regulate immune activities by activating macrophages; Tregs can suppress the immune response by restricting various immune cell functions.The levels of related IL in the cerebrospinal fluid and blood of NMOSD patients vary at different stages of the disease course.This article mainly reviews the role and a change characteristics of interleukins related to NMOSD, which helps us to understand its pathogenic mechanism in-depth, and discusses whether IL can be used as immunophysiological markers to diagnose NMOSD.

The holding of the national college students' clinical skills competition reflects the importance of medical education for clinical practice training . Although through intensive itemized skills drills, the competitors can complete each individual operation with satisfaction, due to the lack of clinical experience, in the integrated circuit training, they will easily stray into question stemtrap. The concrete analysis of the national college students' clinical skills contest competition reflects the medical students' insufficient recognition of clinical skills, lack of the overall concept of the intensive medical treatment, not flexible and insufficient mastery of the connotation of the clinical skills, which seriously restricts the improvement of clinical education. Therefore this article raises special sugges-tions, referring to training focusing on “Airway and Circulation”, developing the critical care thinking based on the relationship of multi-organ and improving the first-aid capability of the team work, so as to provide reference for the improvement of training effect.

Objective:To detect the expression of tumor necrosis factor alpha in (TNF alpha) breast cacner and its relationship with imaging features.Methods:Using immunofluorescence and flow cytometry to detect the expression of TNF-α in MDA-MB-231 and MCF-7.Collect 82 patients with mammary gland disease,which was confirmed by pathological tissue,its pathological data,imaging data,and by immunohistochemistry to detect the expression of TNF-α in breast tissues,and analyze and the relationship between its expression and the pathological features and imaging characteristics.Results:TNF-α high expression in MDA-MB-231,the expression of TNF-oα in malignant breast tumor tissue significantly higher than that in benign tumor,the expression quantity associated with lymph node metastasis,TNM stages,strengthen uniform in MRI,the boundary and the shape of the X-ray Mammography (P=0.01),and color flow signal strength in ultrasound (P＜0.05).Conclusions:TNF alpha in breast tumor tissue was unusually high expression,and is closely related to some of the imaging features of breast tumor.

Objective To observe the blood perfusion of optic nerve and macular areas and investigate its relationship with visual field defect in nonarteritic anterior ischemic optic neuropathy (NAION). Methods Twelve consecutive unilateral NAION patients (course of disease <3 months) and 12 healthy Chinese adults were enrolled in the study. The affected eyes and fellow eyes from 12 NAION patients were defined as group A and group B; 12 eyes from 12 healthy adults were defined as group C. Best corrected visual acuity (BCVA), intraocular pressure (IOP), indirect ophthalmoscope and computer optometry were performed on all of the three groups of patients. Visual field (VF) and optical coherence tomography (OCT) were performed on NAION patients. Logarithm of the minimum angle of resolution (logMAR) was used to calculate visual acuity. Compared to group B, logMAR BCVA, mean deviation (MD) and pattern standard deviation (PSD) in group A were significant decreased (t=3.278, -4.909, 4.130, P<0.05). There was no significant difference in spherical equivalent, IOP, peripapillary retinal nerve fibre layer (pRNFL) between group A and group B (t=0.000, 0.890, 1.215; P>0.05). OCT angiography (OCTA) was used to measure the flow area (FA) at optic disc, flow area at radial peripapillary capillaries (RCFA) and FA, non-perfusion area (NFA), parafoveal vessel density (PVD) and parafoveal vascular index (PVI) in macular area. Pearson correlations between the deficiency of optic blood flow and visual field were analyzed. Results The differences of FA at optic disc and peripapillary RCFA among 3 groups were significant (F=4.162, 3.357; P<0.050). Compared to group B (t=-5.822, -7.467; P<0.001) and C (t=9.435, 4.615, P<0.05), FA at optic disc and peripapillary RCFA in group A was significantly reduced. There is several NAION showed quadrantal FA decreased in optic nerve. However, there was no significant difference in optic disc FA and peripapillar RCFA between group B and C (F=0.004, 0.030; P>0.050). There was no differences of FA, NFA, PVD and PVI among 3 groups (F=0.488, 1.107, 0.493, 1.086, 1.098, 0.093, 1.093, 1.221; P>0.05). Positive correlation between optic disc FA, peripapillary RCFA and MD (r=0.542, 0.585;P<0.05) were observed. However, there was no significant correlation between optic disc FA, peripapillary RCFA and PSD (r=-0.404, -0.430; P>0.05), and negatively correlated to BCVA (r=-0.617, -0.596; P<0.05). PRNFL was negatively correlated to optic disc FA (r=-0.643, P<0.05), but not correlated to peripapillary RCFA (r=-0.377, P>0.05). Conclusions The optic disc blood flow reduced in affected eyes of unilateral NAION whose disease course was less than 3 months, while the macular perfusion was normal. There was a positive correlation between optic disc flow and visual field.

Plasma exchange (PE) is a therapeutic blood component replacement method. The blood of patients is first separated into plasma and blood cell components using a blood cell separator in vitro, the plasma containing harmful pathogenic substances is then discarded and replaced with the same volume of exchange solution. Finally the separated blood cells together with the exchange solution are returned back to the blood circulation of patients. By reducing the circulating antibodies, abnormal plasma proteins or cytokines and other pathogenic molecules, PE can block the disease process. PE has a good therapeutic effect on neuromyelitis optica-related optic neuritis (NMO-ON), which shows resistant to glucocorticoid therapy for the first onset. The American Society for Apheresis guideline evaluates PE for acute optic neuritis as a recommended grade 1B, type II indication. In the implementation of PE treatment for NMO-ON and other diseases, indications and contraindications should be strictly adhered to the guideline, treatment procedures and protocols should be optimized, common adverse events and its prevention and management should be known and alerted. It is important to conduct multi-center clinical cooperation and a high standard clinical randomized controlled study, to find out the optimal time window, the best protocol, and the associated factors for the efficacy and prognosis of PE in NMO-ON.

Teaching of Critical Care Medicine faces several challenging issues includingcomprehensive intensive or specialist intensive, approach of curriculum, tralning of team working ability, building of teaching platform and teaching staff. Critical care medical education requires the concept of viewing the discipline as a whole. Under its guidance and with the opportunity of critical care medical subspecialties building, critical care medical education should focus on bothcompre-hensive critical care and specialist critical care, and have rational planning of Critical Care Medicine course. Through the construction and integration of ICU, we should create a comprehen-sive clinical practice platform of critical care medicine to carry out clinical practice and team work tralning. Meanwhile, construction of quality critical care medicine faculty should be based on its pro-fessional features.

To study the effects of rCBF and brain function in the patients with cerebral infarction byearly rehabilitation training. 89 cases were randomized into rehabilitation and control groups and were ex-amined rCBF by 133Xe inhalation method and BEAM. Total effect rate was 93.9%in rehabilitationgroup,to the control 77.5%(X2=3. 95,P<0.05). The rCBF rised up in two groups,but it was higher inthe foriner,to the contro1,t=4. 99,P<0. 01. BEAM improve rate was 95.9%,to the control,77.5%(X2=5. 30,P<0. 05). So we confirmed that early rehabilitation training may promote rCBF and improve brainfunction of patients with cerebral infarction.

Objective To observe the clinical characteristics of demyelinating optic neuritis (DON) in Chinese children under the age of 16. Methods A retrospective review of the medical charts of 42 pediatric patients with DON was conducted in this study. Twenty-two patients (52.4%) were male, and 20 patients (47.6%) were female. The patients aged from 3 to 15 years, with the mean age of (9.5±2.3) years. There were 35 bilateral patients and 7 unilateral patients. Twenty-seven patients (64.3%) had prodromal symptoms before onset. All patients underwent visual function and imaging tests, such as best corrected visual acuity (BCVA), fundus photography, visual evoked potential (VEP), visual field, MRI. The patients were tested for serum levels of antibodies for aquaporin 4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) with a cell-based assay. All patients were received corticosteroid therapy. The mean follow-up was (1.17±0.42) years. The children who had coordination ability and with BCVA≥0.3 were received examination of Humphery automatic perimeter. Data were collected on the age, gender, clinical features, neuroimaging, serological specific antibodies, treatment and vision prognosis. Results 23.8% of the children were bilateral optic neuritis in onset stages. 64.2% were recurrent optic neuritis and 83.3% exhibited bilateral diseases eventually. BCVA had decreased to ≤0.1 in 87.0%% eyes and disc swelling was observed in 77.9% eyes during the onset stages. All eyes had visual field defects and abnormal VEP exam results, with delayed latency of P100 and P2, and varying degrees of amplitude reduction. Serum AQP4 antibody and MOG antibody were tested by cell-based assay, 2/42 children (4.7%) were positive for AQP4 antibody and 5/24 children (20.8%) were positive for MOG antibody. All of anti-AQP4+ and anti- MOG+ cases relapsed. All children underwent orbital magnetic resonance imaging (MRI), 40 cases (95.2%) showed demyelination features of optic nerve, and 5 cases (11.9%) showed long segments lesion (more than 1/2 length of the optic nerve). There were 2 anti-AQP4+ cases and 3 anti- MOG+ cases from the 5 cases with long segments lesion. MRI also showed brain demyelinating lesions in 4 children (3 of them were anti- MOG+) or spinal cord demyelinating lesions in 3 children (2 of them were anti- MOG+). After treatment with glucocorticoid, visual acuity improved in all eyes, of which 84.4% with BCVA≥0.5. Forty-eight eyes of 26 children accept dynamic visual field during the course of treatment, showed the vision abnormalities associated with optic nerve damage. Conclusions Children under the age of 16 with DON can experience severe visual impairment, higher recurrence tendencies, and higher rate of disc involvement, but good response to glucocorticoid therapy. AQP4 or MOG antibodies positive might be concurrent with brain and (or) spinal cord demyelinating lesions and indicated a poorer prognosis.

Objective:To analyze the clinical features and prognosis factors of aquaporin 4 (AQP4) antibody-positive neuromyelitis optica spectrum disorders related optic neuritis (NMOSD-ON).Methods:An ambidirectional cohort study. From June 1, 2015 to June 1, 2019, 103 patients with AQP4 antibody-positive NMOSD-ON in Department of Neuro-ophthalmology, The First Medical Center of PLA General Hospital were included. All patients of followed-up period were ≥24 months. According to the best corrected visual acuity (BCVA) at the last follow-up, the affected eyes were divided into the low vision group [log of minimum resolution angle (logMAR) BCVA≥1.0] and the non-low vision group (logMAR BCVA<1.0), 66 and 37 cases, respectively. The two groups of patients were compared the genernal clinical characteristics, and the logistic regression model and COX proportional hazard model were used to analyze the relevant factors affecting the patient's visual prognosis and recurrence.Results:Among the 103 cases, 96 cases (93.2%, 96/103) were female; 94 cases (91.3%, 94/103) had unilateral disease; 48 cases (46.6%, 48/103) were the first onset; 85 cases (82.5%, 85/103) were effected by eye pain or orbital pain; 21 cases (20.4%, 21/103) had optic disc edema; 51 cases (49.5%, 51/103) serologically autoimmune antibody test were positive. Orbital magnetic resonance imaging (MRI) was performed in 101 cases. There was no obvious abnormal signal in visual pathways except for 5 cases (5.0%, 5/101); 96 cases (95.0%, 96/101) had abnormal signal in the visual path, and the optic nerve was found in the orbit; 52 cases had abnormal optic nerve in orbital segment (51.5%, 52/101); 37 cases (35.9%, 37/103) recurred within 24 months. The recovery of logMAR BCVA after the first onset and the logMAR BCVA at the first onset, at 6 months of follow-up in two groups were 1.4±1.0, 0.3±0.4, 1.9±0.7 and 0.4±0.5, 2.1±0.6, 0.3±0.4, respectively; and there were statistically significant differences between the two groups of patients at different times ( Z=-4.967,-7.603,-8.027; P<0.001). Logistic regression multivariate analysis showed that recovery of BCVA≥1.0 logMAR after the first onset [odds ratio ( OR)=226.276, P<0.001 ] and the number of attacks ( OR=8.554, P=0.003) were independent risk factors for low vision. Multivariate analysis of the Cox proportional hazards model showed the higher the MRI score [hazard ratio ( HR)=0.588, P=0.007] and plasma exchange ( HR=0.124, P=0.049) in the acute phase were protective factors for recurrence. Conclusions:Vision loss accompanied by eye pain or orbital pain is the main symptom of onset AQP4 antibody-positive NMOSD-ON, a small number of patients have disc edema, 49.5% patients serologically autoimmune antibody test are positive. Abnormal optic nerve signals can be seen in 95.0% of patients in orbital MRI, and 51.5% patients have abnormalities in the orbital optic nerve. The worse the recovery of BCVA after the first onset and the greater the number of attacks are unfavorable factors affecting the prognosis of vision. High MRI scores and plasma exchange in the acute phase are favorable factors to prevent the recurrence of the disease.

Ranpirnase (onconase, ONC) is a new drug, with weak RNase activity and strong cytotoxicity to various tumor cells in vitro and in vivo. This study is to obtain recombination onconase (rONC) with high bioactivity. Based on the codon preference of Pichia pastoris, we designed and synthesized the gene according to cDNA sequences of ONC and the α mating factor's prepeptide. We screened positive clones after transforming the recombination plasmids into P. pastoris X-33, GSS115 and SMD1168. We screened the best combination of seven different vectors and host strains. Moreover, we optimized culture condition in shake flasks and 10 L bioreactor, and purified rONC from the supernatant after inducing it with 0.25% methanol by aqueous two-phase extraction coupling G50 molecular exclusion method. The highest rONC production was 13 mg/L in pPICZα-A/X-33/ONC combination under the condition of pH 5.5 and 23 degrees C in shake flasks for 7 d; and that the highest rONC production was 180 mg/L when the induction is performed in the lower basic salt medium with pH 5.5 in the 10 L bioreactor for 7 d. The yield of rONC is more than 90% at a purity of above 95%. rONC can kill various tumor cells in vitro. The expression and purification of rONC would be useful for further investigation of this new drug.
Antineoplastic Agents ; metabolism ; Bioreactors ; Cell Line, Tumor ; Codon ; DNA, Complementary ; Genetic Vectors ; Humans ; Pichia ; metabolism ; Recombinant Proteins ; biosynthesis ; Ribonucleases ; biosynthesis