Background and Aims: Type 2 diabetes (T2D) is common among patients with chronic hepatitis B infection (CHB) and has been associated with increased risk of carcinogenesis, including HCC. We investigated factors associated with HCC and fibrosis progression among patients with CHB with T2D (CHB+T2D). Approach and Results: Chinese patients with CHB were prospectively recruited for the incidence of HCC and fibrosis progression defined by transient elastography. Among patients with CHB+T2D, glycemic control was assessed by mean glycated hemoglobin (HbA1c) and HbA1c variability determined using HbA1c measurements in the 5 years preceding recruitment. A total of 2330 patients with CHB were recruited (mean age 54.6 ±11.8 years old, 55.5% male, 57.9% antiviral‐treated), with 671 (28.8%) having CHB+T2D (mean T2D duration 7.2 ± 4.6 years, mean HbA1c 7.2 ± 0.9%). T2D was independently associated with HCC (HR 2.080, 95% CI 1.343–3.222) and fibrosis progression (OR 4.305, 95% CI 3.416–5.424) in the overall cohort. In patients with CHB+T2D, factors reflecting glycemic burden (T2D duration [HR 1.107, 95% CI 1.023–1.198]), mean HbA1c (HR 1.851, 95% CI 1.026–3.339), time reaching target HbA1c (HbA1c‐TRT; HR 0.978, 95% CI 0.957–0.999), liver stiffness (HR 1.041–1.043), and smoking (HR 2.726–3.344) were independently associated with HCC (all p < 0.05), but not HbA1c variability or controlled attenuation parameter. The same glycemic burden–related factors (T2D duration, mean HbA1c, and HbA1c‐TRT), in addition to baseline fasting glucose, baseline HbA1c, AST and antiviral therapy, were independently associated with fibrosis progression at 3 years. Conclusions: High glycemic burden was associated with HCC development and fibrosis progression among patients with CHB+T2D, highlighting the importance of glycemic control in reducing liver‐related complications.

To establish the optimum conditions for improving the transdermal delivery of testosterone, we studied the relationship between the lipophilicity of testosterone ester derivatives and the rat skin permeation rate of testosterone. We performed a rat skin permeation study of testosterone and its commercially available ester derivatives, testosterone hemisuccinate, testosterone propionate and testosterone-17beta-cypionate, using an ethanol/water co-solvent system. The aqueous solubility and rat skin permeation rate of each drug, saturated in various compositions of an ethanol/water system, was determined at 37 degrees C. The aqueous solubility of testosterone and its ester derivatives increased exponentially as the volume fraction of ethanol increased up to 100% (v/v). The stability of testosterone propionate in both the skin homogenate and the extract was investigated to observe the enzymatic degradation during the skin permeation process. Testosterone propionate was found to be stable in the isotonic buffer solution and in the epidermis-side extract for 10h at 37 degrees C. However, in the skin homogenate and the dermis-side extract testosterone propionate rapidly degraded producing testosterone, implying that testosterone propionate rapidly degraded to testosterone during the skin permeation process. The steady-state permeation rates of testosterone in the ethanol/water systems increased exponentially as the volume fraction of ethanol increased, reaching the maximum value (2.69+/-0.69 microg cm(-2)h(-1)) at 70% (v/v) ethanol in water, and then decreasing with further increases in the ethanol volume fraction. However, in the skin permeation study with testosterone esters saturated in 70% (v/v) ethanol in water system, testosterone esters were hardly detected in the receptor solution, probably due to the rapid degradation to testosterone during the skin permeation process. Moreover, a parabolic relationship was observed between the permeation rate of testosterone and the log P values of ester derivatives. Maximum flux was achieved at a log P value of around 3 which corresponded to that of testosterone (log P = 3.4). The results showed that the skin permeation rate of testosterone and its ester derivatives was maximized when these compounds were saturated in a 70% ethanolic solution. It was also found that a log P value of around 3 is suitable for the skin permeation of testosterone related compounds.

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Photocopolymerizations of 3,5-dioxo-4,10-dioxatricyclo[5.2.02,6]dec-8-ene (DDTD) with methacrylic acid (MA) acrylamide (AAm) and vinyl pyrrolidone (VP) were carried out in 2-butanone using dimethoxy benzoin (DMB) as an initiator at 25¡C. The structures of the polymers obtained from photopolymerizations of corresponding monomer pairs were conÐrmed to be poly(DDTD-co-MA), poly(DDTD-co-AAm) and poly(DDTD-co-VP) by 1H NMR and 13C NMR spectroscopies, and the average molecular weights were determined by gel permeation chromatography (GPC). The weight average molecular weights of the polymers were in the range 9500È17 300. The poly-(M 1 w ) mers were soluble in water, dimethyl sulphoxide (DMSO) and dimethyl formamide (DMF). The contents of DDTD units in the copolymers were 19, 37 and 45%. The in vitro cytotoxicities of the polymers were evaluated using mouse mammary carcinoma (FM-3A), mouse leukaemia (P-388) and human histiocytic lymphoma (U-937) cell lines. The in vivo antitumour activities of the polymers were estimated by the survival time of sarcoma 180 tumour-bearing mice. The in vivo antitumour activities of the polymers were greater than those of 5-Ñuorouracil (5-FU) and monomeric DDTD at a dose of 0É8 mg kg~1. Poly(DDTD-co-AAm) and poly(DDTD-co-VP) showed higher antitumour activity than 5-FU and monomeric DDTD at all doses tested. 1998 SCI. ( Polym. Int. 45, 92È97 (1998)