Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Objective The aim of this study was to evaluate the long-term efficacy and safety of tocilizumab (TCZ) in Chinese patients with Takayasu's arteritis (TA).Methods We retrospectively studied the active TA patients treated with TCZ from January 2014 to April 2016 in our hospital.The demographic and clinical data,laboratory tests and vascular images were collected.Doppler ultrasonography was used to track vascular changes during TCZ treatment.The data were analyzed by t test and rank sum test.The data were analyzed by Fisher exact test or Chi square test.Results Eighteen patients with a median age of 25.5 (range 18,47) were analyzed.Seventeen patients had taken a median of 3 (range 1,5) immune suppressants before TCZ therapy.Three patients withdrew TCZ after receiving 1 infusion each due to unbearable neck pain.The other 15 patients were treated with TCZ for a median of 13 (range 6,26) months.After TCZ treatment,the median ESR level,hsCRP level,mural thickness of common carotid artery and subclavical artery decreased from 45.5 (range 7-101) mm/1 h (Z=6.731,P＜0.01),37.40 (range 7.6-163.12) mg/L,0.25 (range 0.06-0.59) cm,0.18 (range 0.07-0.47) cm to 7 (range 1-44) mm/l h (Z=6.731,P＜0.01),0.94 (range 0.08-93.21) mg/L (Z=3.212,P=0.016),0.18 (range 0.04-0.53) cm (Z=4.873,P=0.001),and 0.12 (range 0.07-0.18) cm (Z=5.568,P＜ 0.01) respectively,with median glucocorticoid dosage being successfully tapered.One patient discontinued TCZ for unsatisfactory response after 6 TCZ infusions.One episode of urinary infection was recorded and relieved after antibiotic therapy.Neither neutropenia nor abnormal liver enzyme was observed.Conclusion Our study suggests that tocilizumab is a safe and effective agent for long term use among Chinese TA patients,especially for those refractory cases.

Objective:To retrospectively summarize the clinicopathological features of epithelioid glioblastoma (Ep-GBM) and to explore new treatment for Ep-GBM.Methods:The clinical data of 13 patients with Ep-GBM,who were treated in our department from March 2016 to July 2017,were retrospectively analyzed.The clinicopathological features were summarized and the efficacy was evaluated.Results:The positive rate of BRAFV600E mutant and INI-1 was 76.9％ (10/13) and 80％ (8/10),respectively,while the median Ki-67 index was 30％.Meningeal metastases occurred in 9 cases (69.7％) during the course.The median follow-up time was 12 (6-25) months,and the median progression-free time was 8.6 (2.2-16.5) months.Three patients died and the 1-year overall survival rate was 54％.Conclusion:Ep-GBM has a high degree of malignancy and is prone to spread to leptomeninges.INI-1 expression and BRAFV600E mutation are common for Ep-GBM.BRAF inhibitor might be a potential therapeutic drug for it.

Objective To compare the rates and pathological features of diabetic keratopathy in mice induced by single high dose or multiple low dose streptozotocin (STZ) injections.Methods Eighty male C57BL/6 mice (6-8 weeks old) were randomly divided into 4 groups with each group contain 20 mice:normal control group,multiple low dose 1 month group and multiple low dose 3 months group (injected with 60 mg/kg STZ for 5 consecutive times),single high dose 1 month group (injected with 150 mg/kg STZ).The survival rate,model success rate,body weight,glycosylated hemoglobin (HbA1c) content were compared among different modeling group.The percentages of residual epithelial defect area were examined by fluorescein sodium staining after removal of central corneal epithelium.The expression of p-Akt,Sirt1 and Ki67 were evaluated by immunofluorescent staining.The corneal sensitivity were compared among different groups before corneal epithelial curettage,3,7,10 and 14 days after corneal epithelial curettage.The corneal subbasal nerve density at 14 days after corneal epithelial curettage were compared among different groups.This study complied with the declaration of ARVO Results The success rate of diabetic modeling in multiple low dose 1 month group,multiple low dose 3 months group and single high dose 1 month group was 90％,80％ and 70％,respectively.The HbA1c levels in the diabetic modeling groups were significantly higher than that in the normal control group (all at P＜0.05).The percentage of residual epithelial defect area 24 and 48 hours after corneal epithelial curettage in the multiple low dose 3 months group and single high dosc 1 month group were significantly higher than those in the normal control group (all at P＜0.05).The fluorescence intensity of p-Akt,Sirt1 and Ki67 in the multiple low dose 3 months group and single high dose 1 month group were stronger than those in the normal control group.There were no significant differences on corneal sensitivity and corneal nerve density between normal control and multiple low dose 3 months group before and 14 days after the corneal epithelial removal (all at P＞0.05).However,the corneal sensitivity and corneal nerve density were dramatically decreased in the multiple low dose 3 months group and single high dose 1 month group before and 14 days after the corneal epithelial removal,and there were significant differences compared with normal control group (all at P＜0.05).Conclusions The injection of 60 mg/kg STZ can not induce the features of diabetic keratopathy in mice within 1 month.However,the mice of both 1 month after 150 mg/kg STZ injection and 3 months after 60 mg/kg STZ injection appear the typical epithelial and nerve features of diabetic keratopathy,therefore can be the ideal animal models for research.

Based on an analysis of the compensation policy and its problems of the primary medical and health institutions, this paper put forward the corresponding reform framework in Zhejiang province. It proposed to change the compensation policy of " predefining revenue and expenditure, subsidizing its gap after performance appraisal" into " a mixed system of special subsidy and pay for performance". Related policies were also described including governmental functions, special subsidies for input-based payments, classified payments for output services, precautions against financial risks, etc. This paper also suggested that we focus on dealing with the six pairs of balance, such as that between subsidy for the supply and demand sides, and that between internal market and external market.

Objective To investigate the composition and pathological subtypes of thyroid cancer in patients with thyroid nodule surgery in Guiyang in recent 8 years, and to analyze their influencing factors. Methods A retrospective pathological analysis of 4 262 thyroid surgery cases in Affiliated Hospital of Guizhou Medical University during the 2009-2016 to investigate the proportion of thyroid cancer and pathological subtype. The iodine content of salt was reduced at the end of 2012 in Guiyang. 2009-2012 as the pre down-regulation group(n＝1 572), 2013-2016 as the after down-regulation group ( n＝2 690), then comparative analysis before and after the adjustment of the iodine content of salt composition of thyroid cancer and changes of pathological subtype was performed. Results From 2009 to 2016, the proportion of thyroid cancer were 17.08%, 17.52%,15.65%, 18.58%, 19.80%, 29.35%, 35.34%, and 48.33%, increased year by year (P＜0.05). Thyroid microcarcinoma were 2.14%, 4.74%, 3.40%, 3.65%, 3.80%, 7.03%, 9.10%, and 25.95%(P＜0.05). The constituent ratio of thyroid cancer after adjustment of salt iodine content was higher than before. Papillary thyroid carcinoma is the main pathological subtype before and after adjustment of salt iodine content. The proportion of female patients was higher than that of males. The age of patients with thyroid cancer after adjustmen was higher than before ( P＜0. 05). Conclusions In the past 8 years, the constituent ratio of thyroid cancer and thyroid microcarcinoma in Guiyang increased year by year. The reason may be related to the increase of radiation in the environment, the improvement of medical level and the higher detection rate of thyroid microcarcinoma. The relationship between iodine nutrition and thyroid cancer needs to be further studied.[Key words] Thyroid cancer; Thyroid microcarcinoma; Thyroid papillary carcinoma; Pathological type;Iodized salt; Iodine nutrition

Objective To assess the impact of additional cycles of temozolomide on the survival of glio-blastoma(GBM)patients after 6 months of maintenance temozolomide(TMZ)following concurrent TMZ chemo-therapy and radiation therapy. Methods Data of 51 GBM patients from 2009 to 2015 were retrospectively studied and the therapeutic effect was assessed according to whether receiving long-term treatment with TMZ. Results Sev-enteen of fifty-one GBM patients received 8 or more cycles and prolonged treatment improved progression-free sur-vival(P=0.011)and overall survival(P=0.004). Conclusions Extended use of TMZ is safe to GBM patients , which may improve response OS and PFS compared to conventional regimen. Prospective studies in larger popula-tions are needed to better-define the population to whom it can be proposed and its optimal duration.

Objective To evaluate the effect of hydrogen peroxide (H2O2) on a senescence marker protein-30 (SMP30) and an autophagy-related protein microtubule-associated protein 1 light chain 3 type Ⅱ (LC3-Ⅱ) in normal human skin fibroblasts (NHSFs).Methods NHSFs were isolated from the foreskin of children,and subjected to culture in vitro.The second-to fourth-passage NHSFs were treated with 150 μmol/L H2O2 for 2 hours to establish a model for cellular senescence,while un-treated NHSFs served as control group.Senescence-associated β-galactosidase (SA-β-gal) staining was performed to determine the percentage of senescent cells,indirect immunofluorescence assay to determine the expression of the autophagy-related protein LC3,reverse transcription PCR (RT-PCR) to measure the mRNA expression of SMP30,and Western blot analysis to measure the protein expression of SMP30 and LC3.Results The percentage of senescent (SA-β-gal-positive) cells was significantly higher in the H2O2 group than in the control group (41.70％ ± 2.95％ vs.3.03％ ± 0.25％,t =22.59,P ＜ 0.05).Indirect immunofluorescence assay showed that the percentage of LC3-positive cells was significantly lower in the H2O2 group than in the control group (12.60％ ± 1.57％ vs.23.67％ ± 3.04％,t =5.61,P ＜ 0.05).As Western blot analysis showed,no significant difference in the expression of LC3-Ⅰ (LC3-Ⅰ/glyceraldehyde-3-phosphate dehydrogenase [GAPDH] ratio) was observed between the H2O2 group and control group (0.40 ± 0.02 vs.0.41 ± 0.04,P ＞ 0.05),while the H2O2 group showed significantly lower expression of LC3-Ⅱ (LC3-Ⅱ/GAPDH ratio:0.20 ± 0.02 vs.0.80 ± 0.03,t =29.69,P ＜ 0.05) and lower LC3-Ⅱ/LC3-Ⅰ ratio (0.51 ± 0.03 vs.1.98 ± 0.23,t =10.967,P ＜ 0.05) compared with the control group.Moreover,the mRNA and protein expression of SMP30 (SMP30/GAPDH ratio) was significantly lower in the H2O2 group than in the control group (mRNA:0.16 ± 0.01 vs.0.35 ± 0.01;protein:0.27 ± 0.02 vs.0.63 ± 0.02,both P ＜ 0.05).Conclusion H2O2 can decrease the expression of SMP30 and LC3-Ⅱ in NHSFs,and accelerate the senescence of NHSFs.

OBJECTIVETo identify potential mutation of the PAX6 gene in a family affected with congenital aniridia from northeastern China.

METHODSTwo patients were collected from the family and underwent full ophthalmologic examinations. Genomic DNA was extracted from all family numbers and 100 healthy controls. The coding regions and flanking sequence of the PAX6 gene were amplified by PCR amplification and subjected to bidirectional DNA sequencing.

RESULTSA nonsense mutation (c.718 C>T) was identified in exon 9 in both patients but not in other unaffected families or the 100 healthy controls. However, obvious difference was noted in the phenotype between the two patients. One of the patient has presented irregular cornea, which was infrequently reported.

CONCLUSIONA c.718C>T transitional mutation has been found to underlie the aniridia, which showed an autosomal dominant inheritance pattern in this northeastern Chinese family.

Aniridia ; genetics ; Eye Proteins ; genetics ; Female ; Homeodomain Proteins ; genetics ; Humans ; Male ; Mutation ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; genetics ; Repressor Proteins ; genetics

Objective To investigate the relevance between relapse and course of treatment in genotype 1 chronic hepatitis C (CHC)pa-tients with slow virologic response.Methods Totally 157 genotype 1 CHC inpatients or outpatients were selected from the Third People′s Hospital of Jiaozuo and the People′s Hospital of Jiaozuo from April 2010 to March 2013.The patients were treated with interferon α-1b in conjunction with ribavirin.At 6 months of the initial treatment,5 1 patients with slow virologic response were randomly divided into groups A (24 cases)and B (27 cases),which received continued treatment for another 6 and 12 months,respectively.A 1 -year follow-up of pa-tients was performed after withdrawal of treatment.Adverse reactions in patients receiving the antiviral therapy were assessed.Furthermore, group comparisons were performed on the clearance rate of hepatitis C virus (HCV)RNA and normalization rate of alanine aminotransferase (ALT)at withdrawal of treatment,as well as the CHC relapse rate and ALT normalization rate at 6 months and 1 year after withdrawal of treatment.Continuous data were compared using t test,and categorical data were compared usingχ2 test.Results The rate of adverse reac-tions in patients receiving antiviral therapy had no significant difference between groups A and B (P>0.05 ).At withdrawal of treatment, there were no significant differences between groups in terms of HCV RNA clearance rate (95.65%vs 92.59%)and ALT normalization rate (95.65% vs 88.89%)(χ2 =0.02 and 0.13,respectively,both P>0.05).At 6 months and 1 year after withdrawal of treatment,the CHC relapse rate in group B was significantly lower than that in group A (20.00% vs 50.00%,χ2 =4.69,P <0.05;36.00% vs 68.18%,χ2 =4.85,P<0.05);the ALT normalization rate in group B was nonsignificantly higher than that in group A (84.00% vs 59.09%,χ2 =3.63,P>0.05;72.00% vs 50.00%,χ2 =2.40,P>0.05).Conclusion To extend the 6 -month course of treatment can significantly reduce the relapse following slow virologic response in patients with genotype 1 CHC.