Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium. Currently, treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia. However, these modalities are unsatisfactory in achieving the desired therapeutic outcomes. Halofuginone hydrobromide (HF), an herbal active ingredient, has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation. However, HF's medical efficacy is limited due to its poor water solubility, short half-life (t _1/2), and non-target toxicity. In the current study, by using the advantages of nanotechnology, we presented a novel dual-targeted nanocomplex, termed HA-M@P@HF NPs, which consisted of a hyaluronic acid (HA)-modified hybrid membrane (M)-camouflaged poly lactic-co-glycolic acid (PLGA) nanosystem for HF delivery. These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA (HFLS-RA). In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia, safeguarding against bone destruction in rats with adjuvant-induced arthritis (AIA). Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA, thereby offering a promising therapeutic strategy for RA.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective To study the effects of angiotensin Ⅱ (AngⅡ) on insulin signal transduction pathway in skeletal myoblast of L6 rats,and further to explore the possible mechanism of AngⅡ on glucose utilization.Methods Myoblast cells of L6 rats were cultured and induced to differentiate.They were divided into 4 groups according to different treatment by AngⅡ or JAK2-PKA inhibitor H89:normal control group ( NC group),insulin group,insulin + AngⅡ group and insulin + AngⅡ + H89 group.Expression of IRS1 and GLUT4 mRNA was detected by RT-PCR.Expression of IRS1,Ptyr-IRS1 and GLUT4 (total and membrane protein) were detected by Western blot.Results The difference of GLUT4 mRNA expression in the 4 groups detected by RT-PCR had no statistical significance(P ＞ 0.05).The difference of IRS1 mRNA expression among the latter 3 groups had no statistical significance(P ＞ 0.05),however,IRS1 expression in the latter 3 groups was higher than that in NC group(P ＜ 0.05).Western blot results showed expression of IRS1,Ptyr-IRS1 and GLUT4 (membrane protein)was higher in the latter 3 groups than in NC group(P ＜0.05).The difference of IRS1 expression among the latter 3 groups(P ＞ 0.05 ) and GLUT4 (total protein) expression among the 4 groups had no statistical significance (P ＞ 0.05).The expression of of ptyr-IRS1 and GLUT4 membrane protein in Ins + AngⅡ + H89 group was much higher than that in Ins + AngⅡ group,and lower than that in insulin group(P ＜0.05).Conclusion AngⅡ inhibits IRS1's tyrosine phosphorylation and GLUT4's transfer from cytoplasm to plasma membrane in skeletal muscle cells through JAK2-PKA signaling pathway,and therefore induces insulin resistance.

Objective To evaluate the clinical efficacy of radical cystectomy with orthotopic ileal neobled-der. Methods 28 cases of bladder tumor treated with radical cystectomy with ileal orthotopic neobladder were studiedretrospectively. Results All patients achieved excellent continence,whereas possessory patients needed time-lapse e-mietion at nighttime. The mean bladder capacity for the entire group was 330 ml. Residual urine was less than 70 ml.All of these patients have been followed up for 4～58 months with a mean of 18 months. They were survival with no re-currences except 1 case. Good urinary stream was reported. A little operative complications occurred. ConclusionThe operation of radical cystectomy with orthotopic ileal neobladder might be an ideal way of bladder replacement,characterized by large capacity,low pressure, orthotopie continent urination.