Nowadays,aging is the general trend of population development in the world.Type 2 diabetes is one of the most common chronic diseases in the elderly.Because of the atypical symptoms and signs,accompaniment of chronic cardiovascular disease and vulnerability to low blood glucose in the elder patients with diabetes,we should to make safe,effective,and individualized therapeutic programs for them.This paper will review the current prevalence,characteristics,and oral drug selection among elderly individuals with T2DM.

Autoimmune disease is a condition arisen from an abnormal immune response to the tissue cells itself, its precise mechanism remains unknown, and the failure to distinguish self from non-self is often termed a breach of tolerance and is the basis for autoimmune illness. The tumor necrosis factor-α (TNF-α) induced protein 8 like-2 (TIPE2) is a newly discovered member of TNF-α induced protein 8 (TNFAIP8) family which is an essential negative controller of both innate and adaptive immunity. It has been documented that marked expressions of TIPE2 are evident in various autoimmune diseases, including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), myasthenia gravis (MG) and systemic lupus erythematosus (SLE), which appear to be closely related to the severity, progression as well as prognosis of the illness, thereby contribute to the pathogenesis of autoimmune diseases. Deficient expression of TIPE2 might contribute to the hyper-reactivity of auto-reactive lymphocytes and macrophages, or aggregate inflammatory reaction by prompting high concentration of pro-inflammatory cytokines in peripheral blood, thus, trigger the development and progression of autoimmune diseases. In addition, dysregulation of immune homeostasis could be another latent target involved into the mechanism of autoimmune diseases. The present paper summarized the potential role and its mechanism of TIPE2 in the development of autoimmune diseases.

hydroxysteroid dehydrogenase (11? HSD) catalyzes the interconversion of cortisol with its inactive metabolite cortisone. The congenital deficiency of 11? HSD2 induce hypertension and hypokalemia. This disorder is called "Apparent Mineralocorticoid Excess(AME)". Glycyrrhizic acid and other endo and xenobiotics have been found to inhibit the activity of 11? HSD and cause excess mineralocorticoid effects that is similar to AME. The decrease in 11? HSD activity is related with the acquired and congenital hypertention.

Peroxiredoxins(Prxs) are a family of antioxidant protein that have been identified in prokaryotes and eukaryotes. As antioxidants, Prxs protein contains an active site cysteine that is sensitive to oxidation by H 2 O2, eliminate active oxygen that exist in normal tissues and cells, protect cells from oxidative damage induced by reactive oxygen species ( ROS). Prxs protein is a known free radical scavenger, and has been shown to play a role in several diseases. In this review, recent advances on the study of Prxs protein family and tumor related diseases are reviewed, which is expected to provide new ideas for the diagnosis and treatment of the related clinical diseases.

11? Hydroxysterold dehydrogenases (11?-HSDs )catalyse the interconversion of active glucocorticoids(cortisol,corticosterone )and their inert 11?-keto derivatives(cortisone,11-dehydrocorticosterone)They play an important role in regulating the local glucocorticoids activities.Glucoeorticoids can induce insulin resistance.The alteration of 11?-HSD activities in tissues such as liver ,adipose tissue, is closely relevant to some common disorders,including obesity and type 2diabetes mellitus.

Infectious diseases are resulted from the invasion of an organism's body tissues by multiple disease-causing agents. It has been demonstrated that the occurrence and development of infectious diseases are closely associated with the functional status of immune system. Cytokines play significant roles in modulating the host immune response to the clearance of pathogenic microorganisms and maintaining immune homeostasis. Interleukin-35 (IL-35), as a newly identified member of IL-12 family, exerts suppressive effect on immune response by means of a specific pattern. With the progress of research in recent years, IL-35 might serve as an essential contributor in the immunopathogensis of vast infectious diseases, including hepatitis B, sepsis, tuberculosis and parasite infection, which simultaneously appear to be closely related to the severity, progression as well as prognosis of the illness. Apparently, IL-35 is regarded as a potent and promising anti-inflammatory cytokine in clinical application; its potential value may shed light on the therapeutic strategies for infectious diseases. Herein, we mainly review the potential role and its mechanism of IL-35 in the pathogenesis of infectious diseases.

Objective To evaluate the efficacy of telbivudine in HBeAg-positive chronic hepatitis B (CHB) patients by comparing the efficacy of initial telbivudine therapy in treatment-naive patients with sequential telbivudine therapy in patients with poor response to adefovir.Methods A total of 90 HBeAg-positive CHB patients were assigned to receive sequential telbivudine therapy following poor response to adefovir dipivoxil (n=45),or initial telbivudine therapy in antiviral treatment-naive patients (n=45).All patients were treated with telbivudine 600 mg daily for 104 weeks.The efficacy was evaluated in terms of liver function tests,serum HBV markers,HBV DNA and antiviral drug resistance.Results Telbivudine showed good overall efficacy after treatment for 104 weeks in terms of alanine aminotransferase normalization rate (91.1％),HBV DNA negative conversion rate (80.0％),HBeAg loss rate (57.8％),and HBeAg/HBeAb seroconversion rate (30.0％).The HBV DNA negative conversion rate in initial treatment group was significantly higher than that in sequential treatment group (P＜0.05).However,among the patients with early response,the efficacy did not show significant difference between groups (P＞0.05).The patients with early response showed significantly better efficacy than those without early response,in terms of higher HBV DNA negative conversion rate,higher HBeAg loss rate and HBeAg/ HBeAb seroconversion rate (P＜0.000 1 or P＜0.05),but lower virological breakthrough rate (P＜0.05).Conclusions Telbivudine has shown reliable efficacy in CHB patients.Initial telbivudine therapy is better than sequential therapy in CHB patients with poor response to adefovir.However,for patients with early response to telbivudine,no statistical difference is found between initial and sequential therapy in long-term treatment efficacy (104 weeks).The patients receiving sequential telbivudine therapy should be monitored closely for early antiviral response to optimize treatment.

Background The pathogenesis of allergic conjunctivitis has not been clearly established.Current researchers indicate that interleukin-4 (IL-4), IL-5 and IL-13 may play an important role in allergic conjunctivitis.But whether the roles of these inflammatory factors are same in different types of allergic conjunctivitis remains unclear.Objective This study was to investigate the expressions of IL-4, IL-5 and IL-13 in ocular surface with different types of allergic conjunctivitis.Methods A prospective cohort study was designed.Eighty individuals were recruited in Shanxi Eye Hospital from April 2013 to September 2014, including 20 patients with vernal keratoconjunctivitis (VKC), 20 patients with seasonal allergic conjunctivitis (SAC), 20 patients with perennial allergic conjunctivitis (PAC) and 20 normal healthy subjects.Surficial tissues were binocularly scraped using disinfected scraper from upper eyelid conjunctiva, and 4 μl of tear fluid was obtained with capillary tube.The expressions of IL-4, IL-5 and IL-13 protein and mRNA in the conjunctival epithelial cells were detected by immunohistochemistry and real-time fluorescence quantitative PCR.The IL-4, IL-5 and IL-13 concentrations in tear fluid were assayed by Luminex method.This study complied with Declaration of Helsinki and the research protocol was approved by the Shanxi Eye Hospital Ethics Committee.Written informed consent was obtained from each subject prior to entering the cohort.Results IL-4, IL-5 and IL-13 were positively expressed in cytoplasm of conjunctival epithelial cells in the VKC group,SAC group and PAC group,but the expressions of IL-4,IL-5 and IL-13 were absent in the normal control group.The relative expression levels of IL-4 mRNA were 4.11±1.24,2.71±0.71 and 2.00±0.80;the relative expression levels of IL-5 mRNA were 4.02±0.43,2.07±0.45 and 1.47±0.50;and the relative expression levels of IL-13 mRNA expression levels were 6.44±0.66,4.35±1.26 and 2.39±0.86 in the VKC group,SAC group and PAC group, showing significant differences among the 4 groups (F =51.32,220.18,162.49, all at P＜0.01).The relative expression levels of IL-4,IL-5 and IL-13 mRNA were significantly higher in the VKC group than those in the SAC group and PAC group;and those in the SAC group were significantly elevated in comparison with the PAC group (all at P＜0.05).No IL-4, IL-5 and IL-13 were detected in the tear fluid in the normal control group;while the concentrations of IL-4,IL-5 and IL-13 in the tear fluid were (14.06±3.50), (10.88±1.82) and (34.28±8.42) pg/ml in the VKC group,and (7.71 ±0.65), (5.10± 1.33), (23.77±6.29) pg/ml in the SAC group as well as (3.30± 1.50) pg/ml, (2.43± 1.28) pg/ml and (17.67 ± 4.28) pg/ml in the PAC group, showing significant differences among the 3 groups (F =200.29,260.49,128.23, all at P＜0.01).IL-4, IL-5 and IL-13 concentrations in the tear fluid were significantly higher in the VKC group than those in the SAC group and PAC group,and those in the SAC group were significantly raised in comparison with the PAC group (all at P＜0.01).Conclusions IL-4,IL-5 and IL-13 participate in the pathogenesis of multiple allergic conjunctivitis,but their expressions in the ocular surficial tissue are discriminatory in different types of allergic conjunctivitis.

Objective Up to now, the role of Brucea in early embryonic development of mice and its mechanism is still unclear.This paper aims to explore the role of Brusatol in mouse early embryonic development and its possible mechanism.Methods 100 kunming rats of clean grade(80 female rats and 20 male rats) were divided into 6 group: negative control group(no DMSO)、blank control group(culture in fresh CM with equal DMSO)、20nmol/L brusatol treated group、50nmol/L brusatol treated group、100nmol/L brusatol treated group、200nmol/L brusatol treated group(A solution of Brusatol was diluted in CM to concentrations of 20, 50, 100 or 200nmol/L.).Each group used an average of 20 embryos each time, repeated 4 times.Fertilized eggs after cultured 24h, 48h,72h, 96h were respectively 2-cell stage, 4-cell stage,morula and blastocyst stage..The embryo development rate was observed in the culture medium and the optimal concentration was selected, the embryos were collected to analysis the subcellular localization of the Nrf2 by immunofluorescence.The mRNA expression level of Cyclin B, CDK1 and the protein expression of Nrf2 were detected by Q-PCR and western blot respectively.Results In 4-cell stage, the embryo development rates of 20、50、100nmol/L brusatol treated groups[(75.0±2.8)%、(30.4±7.5)%、(4.2±5.9)%] significantly reduced compared with the negative control group[(93.0±2.8)%]、blank control group[(90.9±1.2)%].In morula stage, compared with blastocyst rates of negative control group、blank control group [(83.5±2.1)%、(84.2±1.2)%], 50nmol/L brusatol treated group[(19.3±13.1)%] decreased obviously [(79.00±0.06)% vs 100%, P<0.05].In the cellular immunofluorescence assay, the expression of Nrf2 protein in 50nmol/L brusatol treated group was lower than blank control group(P<0.05).We further found that 50nmol/L brusatol treated group decreased more mRNA levels of Cyclin B[(59.5±9.2)%] and CDK1[(56.0±1.4)%] than blank control group(100%) in G2/M phase(P<0.05).Conclusion In this study, Brusatol mainly affects the cell cycle transformation from G2 to M phase dependent on Cyclin B-CDK1, further inhibiting the development of the embryo through down-regulating Nrf2.

Objective To retrospectively evaluate effects of early dynamization of interlocking intramedullary nail on union of tibial shaft fractures.Methods From January 2002 to Septemher 2004,75 patients with tibial shaft fractures were treated in our department with internal fixation using static interlocking iutramedullary nails.Early dy- namization(6 to 10 weeks postoperative)was adopted in 32 patients (the dynamic group) according to the fracture con- ditions,while the other 43 patients were treated without early dynamization (the non-dynamic group).The healing time of fractures and the rate of delayed union in both groups were documented.Results All the cases were followed up for a mean duration of 6.5 months (range,4 to 13 months).The mean healing time was 115.6 days (range,105 to 126 days) in the dynamic group and 124.5 days (range,119 to 133 days) in the non-dynamic group.The difference was statistically significant between the two groups (P＜0.05).There were two cases (6.2%) of delayed union in the dynamic group and four (9.4%) in the non-dynamic group.The difference was not significant (P＞0.05). Conclusion Early dynamization of interlocking intramedullary nail can promote union of tibial shaft fractures.