Psoriasis, a chronic, immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes, is difficult to cure and prone to relapse, often leading to systemic damage. Triptolide (TPL) can modulate cutaneous immune responses and inflammation, yet its therapeutic window is narrow with significant toxicity. To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity, a TPL/hyaluronic acid/phospholipid polymeric micelle (TPL/HA-DOPE) was constructed via HA's targeting of the CD44 receptor on skin cells. The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of (130.4±1.23) nm, drug loading capacity of (19.74±0.084) %, and encapsulation efficiency of (85.53±1.34) %. Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention. In a murine model of psoriasis, the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d) showed the most significant improvement in erythema, scaling, and epidermal thickening. Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness, epidermal hyperplasia, and inflammatory cell infiltration. Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α. The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.

AlM: The Chinese medicinal herb Hanfangji is dried roots of Stephania tetrandra S. Moore (Family, Menispermaceae). Tetrandrine and fangchinoline are two major constituents of Hanfangji and these bisbenzyltetrahydroisoquinoline alkaloids possess anti - cancer and other pharmacological activities. To facilitate further pharmacodynamic investigation of these compounds, a pharmacokinetic investigation was performed in rats and in vitro. METHODS: Pharmacokinetics of tetrandrine and fangchinoline were characterized in rats p.o. or i.v. dosing an aqueous extract of Hanfangji or the individual compound. Unbound levels of systemic exposure to these two alkaloids were assessed using in vitro studies of plasma protein binding, blood-plasma partition, and lysosomal trapping. All the study samples were analyzed by liquid chromatography/mass spectrometry.RESULTS: We found two pharmacokinetic features of tetrandrine and fangchinoline. First, the two compounds had blood levels of systemic exposure substantially higher than the respective plasma levels of systemic exposure. Second, the two compounds exhibited significantly higher systemic exposure levels after p.o. dosing an aqueous extract of Hanfangji than the respective exposure levels after p.o. dosing the individual compound, at the same compound dose levels and under the same conditions for analytical measurement and the same conditions for animal study. Unbound fractions of tetrandrine and fangchinoline in rat plasma were 2%-5% and the concentrations of the alkaloids in rat erythrocytes were 5-times higher than those in rat plasma. Lysosomal inhibitor could block their trapping in lysosomes and significantly reduce their concentrations in HEK-293 cells. CONCLUSlON: The following pharmacokinetic aspects should be noted in pharmacodynamic investigation of tetrandrine and fangchinoline: extensive binding with plasma proteins, extensive binding with erythrocytes, and trapping by lysosomes of tissue cells substantially reduce the levels of unbound tetrandrine and fangchinoline in the systemic circulation.

The influence of circadian rhythm disorder on nonalcoholic fatty liver disease (NAFLD) has attracted more and more attention in recent years, and studies in China and globally have shown that individuals who work in shifts at night or often stay up late have a higher incidence rate of NAFLD-related hepatocellular carcinoma (NAFLD-HCC) than those with regular work and rest. This article summarizes the research advances in the effect of circadian rhythm system on the pathogenesis of NAFLD-HCC by regulating lipid metabolism, glucose metabolism, and intestinal flora, and it is pointed out that restoration of normal circadian rhythm has potential clinical significance in delaying the development and progression of disease.

Objective To explore the three ultrasonic technologies of two -dimensional ultrasound(2D -US),ultrasonic elastography(UE) and contrast -enhanced ultrasound(CEUS) for the measurement error in breast cancer and the correlation with the expression of ER,PR,VEGF.Methods 50 patients with breast cancer were meas-ured by 2D -US,UE,CEUS preoperatively,and the pathological specimen were measured postoperatively.Then used the immunohistochemistry to detect the expression of ER,PR,VEGF in tumor,and analyzed the correlation with the measurement errors.Results The results of differences between 2D -US,UE,CEUS and pathology were respectively as follows:( -0.59 ±-0.34)cm,( -0.20 ±-0.14)cm,( -0.40 ±-0.31)cm,and the differences were statistically significant(F =20.497,P <0.001).The positive expression rate of ER and PR was high if the difference between UE and 2D -US was less than or equal to 0.44cm.And the positive expression rate of VEGF was low if the difference between CEUS and 2D -US was less than or equal to 0.19cm.Three ultrasonic technologies in the measurement of breast cancer were different,the trend of difference between UE and 2D -US was smaller if the ER and PR were positively expression,and the trend of difference between CEUS and 2D -US was bigger if the VEGF was positively expression.Conclusion There is correlation between different immunohistochemical expression of breast cancer with measurement error in three different ultrasonic imaging technologies.The results suggest that the molecular pathology difference of breast cancer can impact on ultrasonic imaging,which contributes to know the reason and regulation of measurement error in different ultrasonic imaging technology.