ObjectiveTo assess the differences of short- and long-term postintervention status on ocular and systemic symptoms for patients with ocular myasthenia gravis (OMG) after pyridostigmine bromide, corticosteroid, thymectomy, or thymectomy-corticosteroid combination therapy ( combination ).MethodsThis retrospective plus prospective study included 180 OMG patients, whose age of onset ≥ 15 years, treated non-randomly with above therapies separately: thymectomy group (60 cases ), corticosteroid group (39 cases), combination group ( 31 cases ), symptomatic group ( 50 cases ). Postintervention status complying with Myasthenia Gravis Foundation of America (MGFA)complete stable remission ,pharmacologic remission, or minimal manifestations was considered as desirable response, which was used as statistical indicator. Results ①Corticosteroid group showed higher desirable response rates on ptosis, ophthalmoplegia and general weakness at 3-6 months after treatment than other groups, and 42. 1％( 16/38 ) of them at 3 months achieved the desired state of ptosis, higher than the symptomatic group (7/48,14. 6％, ×2 = 8. 200, P = 0. 004 ). ② Ascending ideal rates had been presented in both combination and thymectomy groups since 1 year after treatments, while a little bit higher rate was presented in the former. At the end of observation, 21.7％ ( 13/60 )of patients in thymectomy group achieved complete stable remission.By paired longitudinal comparisons,thymectomy group showed higher ideal rates on ptosis (22/40,55.0％ ), ophthalmoplegia ( 16/27,59. 3％ ) and general weakness (20/40,50. 0％ ) at 2 years than that at 3 months( 11/59,18.6％ ;11/44,25.0％ ;9/60,15.0％ ;P =0. 002, 0. 031,0.000). ③For those patients by symptomatic treatment, the average age of onset was (51.9 ± 18.0) years, higher than that by other 3 therapies (F = 10. 563 ,P =0. 000). ④OMG patients with ophthalmoplegia more likely select corticosteroid or combined therapy. Ophthalmoplegia in combination group was higher than that in symptomatic and surgery groups( ×2 = 12. 939,14. 380, P =0. 000 in both). Ophthalmoplegia in corticosteroid group was higher than that in surgery group ( ×2 = 8. 017, P = 0. 005 ).Conclusions Corticosteroid appears to early overcome ptosis, ocular motor dysfunction and general weakness for patient with OMG in early-to-middle adulthood.Thymectomy andsurgery-corticosteroid combinationtherapies bothshowlong-term effectonthem.

ObjectiveTo demonstrate the project scope of the afferent nerves of the lumbar intervertebral disc,on which basis to explore the mechanism of the symptoms of discgenic low back pain.MethodsThirty Wistar rats were divided randomly into three groups of 10 rats each:the L4-5,L5-6,and L6 S1 group.Each group was further divided randomly into two subgroups,the experimental group and the control group,5 rats for each group.Intervertebral disc was exposed through the posterior approach under peritoneal cavity anesthesia,after the nerve roots were pull away,2 μl of 30％ cholera toxin-horseradish peroxidase (CT-HRP) was injected into the inner layer of the intervertebral disc in the experimental group,while 2 μl of 0.9％ Nacl was used in the control group.Forty-eight hours after the surgery,all rats were perfused and bilateral dorsal root ganglions(DRGs) of T10-L3 were resected and fixxied.Each DRG was sectioned at 30 μm thickness and processed by DAB method.The sections of DRGs were coverslipped and observed by optical microscopy for the neurons or axons labelled by CT-HRP.It was judged as positive that brownish-black particles were in the neurons or axons.ResultsNot in a single dorsal root ganglions,but in a scope of dorsal root ganglions axons labled by CT-HRP could be seen in the rats in the experimental groups.No CT-HRP labled neurons or axons were seen in dorsal root ganglions in the contral groups.ConclusionAfferent nerves of the lumbar intervertebral disc project to a scope of dorsal root ganglions,which is the anatomic basis of the mechanism of the symptoms of discgenic low back pain.

Objective To explore thc clinical manifestation of secondary generalized myasthenia gravis(GMG) and analyze the factors affecting the progression from ocular myasthenia gravis(OMG) to GMG.Methods This research constitutes a single-center,retrospectively-collected prospective cohort study.We comprehensively reviewed our self-managed myasthenia gravis (MG) database drawn from personal clinical experience from January 2000 to Junc 2013.Patients underwent series of examination including repetitive nerve stimulation (RNS) tests,measurement of serum acetylcholine receptors antibody and serum muscle-specific tyrosine kinase antibodies,thymus computer tomography scan etc.Patients were treated with pyridostigmine bromide,corticosteroid therapy and (or) thymectomy based on a nonrandomization pattern and they were documented for their respective symptoms of OMG and GMG and date of GMG conversion.Logistic regression analysis was adopted to determine the influencing factors correlated with the development of GMG during the follow-up.Results Totally 770 patients initially diagnosed with OMG were included,among whom 573 (74％) patients remained with OMG (R-OMG group) and 197(26％) patients developed into GMG (GMG group) during the follow-up.(1) In comparison with their R-OMG counterparts,patients with secondary GMG were older at onset; Displayed more frequent RNS abnormality of facial nerve,accessory nerve and ulnar nerve ; Showed higher incidence of thymoma and were less treated by early corticosteroids.(2) For GMG group,81％ (160/197) of them displayed bulbar MG; 67％ (132/197) of GMG conversion occurred within 2 years,and 84％ (166/197) within 5 years.In comparison with the patients with onset of≤ 14-year-old,both of patients with15-49-year-old and≥ 50-year-old displayed higher conversion rate and shorter conversion duration (median:10 years versus 1 year and 6.5 months).(3) RNS abnormality of accessory nerve(OR =6.650,95％ CI 3.547-12.471 ; P ＜ 0.05) and thymoma(OR =7.924,95％ CI 2.554-24.585 ; P ＜ 0.05) were prognostic factors for the development of GMG,while early corticosteroid(OR =0.232,95％ CI 0.119-0.452 ; P ＜ 0.05) predicted the reduction of the risk of generalization.Conclusions Multiple factors including abnormal RNS of proximal limb muscles,thymoma,early corticosteroids therapy and possibly even onset age of over 15-year-old may involve the generalization in patients with OMG at onset.

Objective To detect the expression of interleukin (IL)-18 of the peripheral blood cells and IL-18 receptor α chain(IL-18Rα) on the surface of CD_3~+ cells in patients newly diagnosed as immune thrombocytopenia (ITP) before medication and to explore the roles of IL-18 and IL-18Rα in the development of ITP. Methods Eighteen out-patients or inpatients with acute ITP accepting treatment in Qilu Hospital were enrolled in this study and 15 matching healthy subjects were taken as control. Plasma IL-18 level was detected with enzyme linked immunosorbent assay (ELISA), the expression of IL-18Rα on CD_3~+ lymphocytes and total lymphoeytes were measured with flow cytometry; T-bet and GATA-3 mRNA were measured with reverse transcriptase polymcrase chain reaction (RT-PCR). Results The expression of IL-18 in acute ITP plasma was (468. 57 ± 141.62) ng/L and IL-18Rα on the surface of CD_3~+ cells and lymphocytes were (8.50 ±3. 16)% and (9. 16±2.98)% respectively. The levels of IL-18 and IL-18Rα were increased in active ITP patients as compared with those in the controls (P <0. 05). The levels of IL-18 mRNA (0. 12 ±0. 02) and T-bet mRNA (0. 07 ±0. 02) were significantly increased in patients with active ITP as compared with those in the controls (P <0.05), while GATA-3 mRNA (0.0039±0.0014) were significantly decreased in patients with active ITP (P < 0. 05). The balance between T-bet and GATA-3 was significantly disturbed in ITP. Conclusions Through the variation of the levels of gene and protein, our study showed that IL-18 and IL-18Rα might upregulate the expression of Th1-cytokines in ITP patients. It is also suggested that IL-18 has potential association with the development of ITP. Especially, it may provide a new treatment method for ITP by regulating the ratio of T-bet and GATA-3 and resuming the balance of Th1/ Th2.

The new immune and targeted therapy medicines of multiple myeloma and recurrence of refractory multiple myeloma mainly include immunomodulatory drugs, proteasome inhibitors, monoclonal antibody, immune monitoring point inhibitors, histone deacetylase and chimeric antigen receptor. Although the emergence of new drugs and the application of autologous hematopoietic stem cell transplantation have significantly improved the prognosis of patients, more effective treatment methods and treatment strategies are still required to deal with the adverse reactions and the condition of recurrence during treatment.

Suppression of cellular O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) can repress prolifera-tion and migration of various cancer cells,which opens a new avenue for cancer therapy.Based on the regulation of insulin gene transcription,we designed a cell-based fluorescent reporter capable of sensing cellular O-GlcNAcylation in HEK293T cells.The fluorescent reporter mainly consists of a reporter (green fluorescent protein (GFP)),an internal reference (red fluorescent protein),and an operator (neuronal differentiation 1),which serves as a "sweet switch" to control GFP expression in response to cellular O-GlcNAcylation changes.The fluorescent reporter can efficiently sense reduced levels of cellular O-GlcNAcylation in several cell lines.Using the fluorescent reporter,we screened 120 natural products and obtained one compound,sesamin,which could markedly inhibit protein O-GlcNAcylation in HeLa and human colorectal carcinoma-116 cells and repress their migration in vitro.Altogether,the present study demonstrated the development of a novel strategy for anti-tumor drug screening,as well as for con-ducting gene transcription studies.

Liver fibrosis, a common pathological process of most types of chronic liver diseases, is caused by the excessive deposition of extracellular matrix proteins after chronic liver injury. An increasing number of evidence has shown that oxidative stress is closely associated with the development and progression of liver fibrosis and is involved in the pathological process of liver fibrosis caused by various factors. With natural constituents and a clear structure, Chinese herbal monomers herbs have achieved a marked clinical effect in the treatment of liver fibrosis. This article reviews the research advances in monomers of Chinese herbs in the treatment of liver fibrosis by regulating oxidative stress-related signaling pathways.

Liver fibrosis is a compensatory response in the process of tissue repair after chronic liver injury, and it is also a necessary pathological process in the progression of a variety of chronic liver diseases. In the pathological state, the imbalance between hepatic oxidative system and antioxidant system can lead to the excessive production or insufficient clearance of reactive oxygen species (ROS)/reactive nitrogen species (RNS), which may induce the injury of hepatocytes, expand inflammatory response, and promote the development and progression of liver fibrosis. As a master regulator of oxidative stress and inflammatory response, NF-κB plays a key role in the process of liver fibrosis. Therefore, the cascade interaction between ROS/RNS and the NF-κB signaling pathway plays a guiding role in further clarifying the pathogenesis of liver fibrosis and exploring effective prevention and treatment strategies. This article reviews and discusses the interaction between ROS/RNS and the NF-κB signaling pathway and its important role in the progression of liver fibrosis, so as to provide strategies and references for targeted therapy for liver fibrosis.

Humans ; Lymphoma, Non-Hodgkin ; Pemphigus