Uremic pruritus is one of the skin complications that perplex patients with end-stage renal disease undergoing hemodialysis or peritoneal dialysis. Because the specific pathogenesis is not clear, there is no unified treatment plan in the world. In August 2021, the US Food and Drug Administration approved the use of difelikefalin (under the trade name Korsuva) for the treatment of moderate to severe pruritus associated with chronic kidney disease in adult patients undergoing hemodialysis. Studies have shown that difelikefalin can remarkably reduce the intensity of pruritus and improve sleep and pruritus-related quality of life. The recommended dose of difelikefalin is 0.5 μg/kg, and difelikefalin is well tolerated and has high safety. This paper reviews the pharmacological effects, pharmacokinetics, clinical efficacy and safety of difelikefalin.

Objective: In this study,we examined the effects of Shizhenqing granule(SZQG)on hypothalamic-pituitary-adrenal(HPA)axis and serum inflammatory factors in a rat model of chronic eczema,in or-der to explore the mechanism of action of SZQG in treatment of this disease.Methods: Sixty Sprague—Dawley male rats were randomly divided into six groups(with 10 rats per group): blank group; model group; positive control group(prednisone); and the low-,medium-,and high-dose SZQG groups.Except for the blank group,rats in all other groups were treated with 2,4-dinitrochlorobenzene to induce chronic eczema.These rats were administered prednisone or SZQG for 7 consecutive days after successful establishment of the chronic eczema model,and samples were collected 12 h after the last administration.The degree of skin lesions and the changes in serum levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),cortisol(CORT),inter-leukin(IL)-4,interferon(IFN)-γ,IL-25,and IL-31 among the groups were compared.Results: SZQG effectively increased the levels of CRH,ACTH,and CORT,which decreased in the serum of rats with chronic eczema,stimulated the function of the HPA axis,and promoted the expression of glucocorticoids.SZQG reduced the serum levels of inflammatory factors including IL-4,IL-25 and IL-31,which were overexpressed in rats with chronic eczema,and increased those of anti-inflammatory factor IFN-γ,thereby alleviating the inflammatory symptoms and itching,and ameliorating the clinical symptoms of chronic eczema.Conclusion: SZQG effectively alleviates skin lesions in the chronic eczema rat model by stimulating the function of the HPA axis.

Objective:To explore the value of synthetic MRI and dynamic contrast-enhanced MRI (DCE-MRI) in differentiating benign and malignant breast lesions.Methods:Totally 116 patients (female, aged 22-80 years) with suspicious breast lesions found by clinical examination in General Hospital of Ningxia Medical University from September 2020 to March 2021 were retrospectively analyzed. All patients received synthetic MRI and DCE-MRI scans, and the quantitative parameters of synthetic MRI [T 1, T 2, proton density (PD) value before enhancement of breast lesions (T 1pre, T 2pre, PD pre) and T 1, T 2, PD value after enhancement of breast lesions (T 1Gd, T 2Gd, PD Gd)] were measured. The difference before and after enhancement (?T 1, ?T 2, ?PD) and the ratio before and after enhancement(T 1ratio, T 2ratio, PD ratio) were calculated. All lesions were confirmed by biopsy or surgery. Independent sample t test was used to compare the differences of parameters between benign and malignant lesions, and parameters with statistically significant differences were analyzed by multivariate logistic regression to screen out independent predictors for the diagnosis of breast malignant lesions. The efficacy of quantitative parameters alone and in combination with DCE-MRI, was evaluated by the receiver operating characteristic (ROC) curve. Results:Of 116 patients, 27 patients were benign and 89 patients were malignant. T 2pre, PD pre, T 2Gd, PD Gd, ?T 2, T 1ratio and T 2ratio values of malignant patients were lower than those of benign lesions ( P<0.05). Multivariate logistic regression analysis showed that T 2pre (OR=0.961,95%CI 0.926-0.993, P=0.022)and PD pre(OR=0.945, 95%CI 0.908-0.979, P=0.003) were independent predictors of breast malignant lesions. The area under ROC curve (AUC) of T 2pre+PD pre in differentiating benign and malignant breast lesions was 0.77, and the accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 0.84, 0.87, 0.68, 0.92 and 0.56, respectively. The AUC of T 2pre+PD pre combined with DCE-MRI in differentiating benign and malignant breast lesions was 0.95, indicating the best diagnostic efficiency, and higher than that of DCE-MRI alone (0.92)( Z=2.20, P<0.05). Conclusions:T 2pre and PD pre values of synthetic MRI can be used as reference parameters for differentiating benign and malignant breast lesions. Synthetic MRI combined with DCE-MRI can effectively improve the diagnostic efficiency of breast malignant lesions.

This study aims to investigate the function of lmo2363 gene in stress resistance of Liste-ria monocytogenes strain LM83-1.In this study,the lmo2363 gene deletion strain and complement-ation strain of Listeria monocytogenes were constructed using overlapping extended PCR and ho-mologous recombination techniques,and the growth ability,stress survival rate and biofilm forma-tion ability of wild,deletion strain and complementation strain were compared under different stress environments.lmo2363 gene deletion strain and complementation strain of Listeria monocy-togenes were successfully constructed in this experiment.The growth curves showed that the growth capacity of the deletion strain was weaker than the wild strain LM83-1 under 4 ℃,7％NaCl,10％NaCl,3.5％ethanol,4.0％ethanol and pH5 stress(P＜0.001).The results of stress survival test showed that the survival rate of the deletion strain was significantly lower than the wild strain after 1 h treatment with pH3 and 10 mmol/L H2 O2 stress(P＜0.010).The biofilm forming ability of the deletion strain was decreased compared with that of the wild strain(P＜0.050).This study confirmed that lmo2363 gene mediated the adaptation of LM to low temperature,high osmotic pressure,ethanol and acid stress environment and affected the formation of LM bio-film.This study laid a foundation for further exploring the function of lmo2363 gene in the stress resistance process of Listeria monocytogenes.

Objective:To compare the effects of different test meals on postprandial triglycerides and to optimize the standard meal composition and the blood sampling protocol for the oral fat tolerance test.Methods:This study is a prospective, open-label, randomized, cross-over trial. In March 2023, 36 volunteers were recruited in Hebei General Hospital. They underwent a health examination and oral glucose tolerance test. Twenty-six healthy volunteers(11 males and 15 females) were included in this study, with an average age of(39.08±4.56) years. Each volunteer received 75 g protein meal, 75 g fat meal, 700 kcal fixed-calorie high-fat mixed meal, and a high-fat mixed meal with energy adjusted based on 10 kcal/kg body weight. A one-week washout period of regular diet was applied before each trial. Blood was collected at fasting status and 1, 2, 3, 4, 5, and 6 hours after a meal to detect serum triglycerides, total cholesterol, low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), glucose, and insulin. The variations of postprandial metabolic indicators over time following the consumption of different test meals were analyzed. The disparities in postprandial metabolic responses between the two types of mixed meals were compared.Results:The protein meal, fat meal, fixed-calorie high-fat mixed meal, and adjusted-calorie high-fat mixed meal resulted in postprandial triglyceride increases of 22.45%, 115.40%, 77.14%, and 63.63%, and insulin increase of 560.43%, 85.69%, 554.18%, and 598.97%, respectively, and with reductions in total cholesterol, LDL-C, and HDL-C ranging from 5.64%-21.81%, respectively. The blood glucose changed slightly. Changes in metabolic indicators mainly occured within 4 hours. The comparison of the characteristics of postprandial triglycerides between the two high-fat mixed meals showed no statistically significant differences( P>0.05). Conclusion:A standardize protocol with a 700 kcal fixed-calorie high-fat mixed meal as test meal, and blood lipid levels measured at fasting and at 1, 2, 3, and 4 hours after consumption, can serve as an optimized approach for oral fat tolerance test.