Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective To evaluate the safety and efficacy of transcatheter arterial chemoembolization(TACE)combined with lenvatinib and camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 63 patients with advanced HCC,who received TACE combined with lenvatinib and camrelizumab(triple therapy)or TACE combined with lenvatinib(dual therapy)at the Jingmen Municipal People's Hospital of China between April 2020 and December 2021,were retrospectively analyzed.Triple therapy group had 30 patients,and dual therapy group had 33 patients.The post-treatment tumor response,disease progression-free survival(PFS),overall survival(OS),and the incidence of adverse drug reactions were recorded.Results The median follow-up period of the two groups was 14 months(range of 4-26 months).Compared with the dual therapy group,in the triple therapy group the objective response rate(ORR)was remarkably higher(83.3%vs.57.6%,P=0.026),the disease control rate(DCR)was obviously higher(93.3%vs.69.7%,P=0.039),the median PFS was significantly longer(8.0 months vs.5.0 months,P＜0.01),and the median OS was strikingly longer(24.0 months vs.12.0 months,P=0.004).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P＞0.05).Conclusion For the treatment of advanced HCC,TACE combined with lenvatinib and camrelizumab is clinically safe and effective.(J Intervent Radiol,2024,32:57-62)

Skin color is regulated by the change of melanin. Previous studies have shown that there are 4 modes of melanin transfer, including exocytosis-endocytosis, shedding-phagocytosis, cell phagocytosis and membrane fusion, and melanosomes are the main carrier for melanin transfer. Recent studies have shown that melanocores depending on the exocytosis-endocytosis pathway play an important role in melanin transfer. This review summarizes the melanocyte exocytosis and keratinocyte endocytosis processes in melanocore transfer, as well as the melanocore degradation process in keratinocytes after melanocore transfer, providing a new therapeutic direction for refractory pigmentory diseases.

Objective To analyze the clinocopathological characteristics of infectious granulomas.Methods The clinical features,histopathological manifestations of 39 patients with infectious granulomas were analyzed retrospectively.Results Among 39 cases of infectious granulomas,there were 15 males and 24 females,and 17 cases of fungal granuloma and 22 cases of tuberculous granuloma.There was no statistically significant difference in gender and age between fungal granulomas and tuberculous granulomas.The mean course of tuberculous granuloma aud tuberculous granuloma was (0.88 ± 0.67) years and (5.54 ± 3.49) years,respectively (t =4.51,P =0.00);there was no significant difference in mean age of onset in fungal granuloma patients and tuberculous granuloma patients [(54.6 ± 19.6) vs.(47.6 ± 18.1) years,P ＞0.05)].There were 4 and 18 cases of fungal and tuberculous granulomatosis at the face,and 13 and 3 cases at the extremities (all P =0.00);the lesions occurred in the trunk in one case of tuberculous granuloma.The clinical manifestations of fungal and tuberculous granulomas as plaques/nodules were in 14 cases aud 22 cases (P =0.08);as ulcers and pus exudates were in 10 and 2 cases,respectively (P =0.00).The histopathological features showed epidermal hyperplasia in 12 and 4 cases,infiltrative patterns in 4 and 21 cases,infiltration of neutrophils in 14 and 3 cases,infiltration of plasma cells in 15 and 5 cases,infiltration of eosinophils in 10 and 0 cases,necrosis in 1 and 10 cases in fungal granulomas and tuberculous granulomas,respectively (P =0.00,0.00,0.00,0.00,0.00,0.01).Conclusion Fungal granuloma and tuberculous granuloma are different in the lesion sites,clinical manifestations and histopathological features.

Objective To investigate risk factors for and clinical features of steroid-induced diabetes mellitus due to glucocorticoid treatment.Methods Clinical data were collected from 798 patients who received systemic glucocorticoid treatment in Department of Dermatology of Hangzhou Third People's Hospital from 2013 to 2016,and analyzed retrospectively.Logistic regression analysis was performed to analyze the factors influencing the occurrence of steroid-induced diabetes mellitus (SDM),repeatedmeasures analysis of variance to compare peripheral blood glucose levels of patients with SDM after breakfast,lunch and dinner,and t test to compare the levels of fasting blood glucose and glycosylated hemoglobin (HbA1 c) between patients with SDM and those with type 2 diabetes mellitus.Results Of the 798 patients,38 developed SDM due to glucocorticoid treatment.The average age was significantly older in the patients with SDM ([66.86 ± 13.30] years,n =38) than in those without SDM ([39.95 ± 17.01] years,n =760;t =8.86,P ＜ 0.01),but there was no significant difference in the gender ratio between the patients with and thhose without SDM (x2 =1.61,P =0.20).The prevalence of fatty liver,hyperlipidemia,hypertension,abnormal liver function and family history of diabetes mellitus was significantly higher in the patients with SDM than in those without SDM (x2 =12.25,19.25,32.69,21.47,16.70 respectively,all P ＜0.01).Logistic regression analysis showed that age,fatty liver,hyperlipidemia,hypertension,abnormal liver function,dosage of glucocorticoids,duration of glucocorticoid therapy,use of immunosuppressive agents and family history of diabetes mellitus were risk factors for SDM (all P ＜ 0.05).There were no significant differences in fasting blood glucose levels or postprandial peripheral blood glucose levels among the SDM patients receiving glucocorticoid therapy at different dosages of 0.50-0.74,0.75-0.99,1.00-1.25 mg·kg-1· d-1 (P ＞ 0.05).The peripheral blood glucose levels after breakfast,lunch and dinner were (11.50 ± 2.90),(16.02 ± 5.81) and (16.81 ± 4.52) mmol/L respectively in the patients with SDM.The levels of fasting blood glucose and glycosylated HbA 1 c were both significantly lower in the patients with SDM than in those with type 2 diabetes mellitus (t =3.74,9.92 respectively,both P ＜ 0.001).Conclusions The risk factors for SDM are age,dosage of glucocorticoids,duration of glucocorticoid therapy,fatty liver,hyperlipidemia,hypertension,abnormal liver function,use of immunosuppressive agents and family history of diabetes mellitus.The patients with SDM showed obviously elevated blood glucose levels mostly after lunch and dinner,but slightly increased levels of fasting blood glucose and glycosylated HbA 1c,which can be used to distinguish between SDM and type 2 diabetes mellitus.

Objective To investigate clinical and histopathological features of cutaneous epithelioid hemangioma (EH).Methods Clinical and histological data were collected from 22 patients with EH and analyzed.Results Of the 22 EH patients,10 were male,and 12 were female.The age at onset ranged from 16 to 62 years,with an average age of 45.91 years.The duration of disease varied from 1 month to 20 years,with an average disease duration of 37 months.Skin lesions most frequently occurred on the scalp in 14 cases (63.6％),followed by the ear in 6 cases (27.3％),the forehead in 2 cases (9.1％),and the thigh in 1 case (4.5％).Lesions affected both the scalp and forehead in 1 case.Histopathological examination of the 22 cases revealed vascular proliferation.The blood vessels were lined with epithelioid endothelial cells,and a large number of lymphocytes and eosinophils infiltrated around the vessels.The dermis were involved in all cases,and subcutaneous tissues were involved in 8 cases (36.4％).Immunohistochemical examination of 6 cases showed positive staining for CD31,CD34 and factor Ⅷ in blood vessel walls.Conclusion EH is an uncommon disease characterized by vascular proliferation and inflammatory infiltration,and clinical manifestations in combination with histopathological examination facilitate its diagnosis.

Objective To evaluate the effect of narrow-band ultraviolet (NB-UVB) radiation on the autophagy of cultured human melanocytes in vitro,and to explore possible mechanisms underlying the treatment of vitiligo by NB-UVB.Methods In vitro cultured human melanocytes were divided into 4 groups to be irradiated with NB-UVB at different irradiation doses of 0 (control group),50,100 and 200 mJ/cm2 (50-,100-and 200-mJ/cm2 NB-UVB groups) respectively.After 24-hour treatment,the cells were collected,and monodansylcadaverin (MDC) staining was conducted to detect changes of autophagosomes in melanocytes.Western blot analysis was performed to determine the protein expression of autophagy signals including phosphorylated AMP-activated protein kinase (p-AMPK),phosphorylated mammalian target of rapamycin (p-mTOR),microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ (LC3 Ⅱ/Ⅰ) and P62,and transmission electron microscopy to observe ultrastructural changes of autophagosomes and melanosomes in the melanocytes.Statistical analysis was done by using one-way analysis of variance (ANOVA) for the comparison of Western blot results,and by Kruskal-Wallis H test for the comparison of the number of melanosomes,autophagosomes and autolysosomes.Results MDC staining showed that the percentages of autophagosome-positive melanocytes were significantly higher in the 100-,200-mJ/cm2 NB-UVB groups (38.08％ ± 4.10％,40.23％ ± 1.45％,respectively) than in the control group (21.83％ ± 3.50％,both P ＜ 0.05) and 50 mJ/cm2 NB-UVB group (23.66％ ± 4.12％,both P ＜ 0.05).As Western blot analysis revealed,the 100-,200-mJ/cm2 NB-UVB groups showed significantly increased expression of p-AMPK and LC3 Ⅱ/Ⅰ,but significantly decreased expression of p-mTOR and P62 compared with the control group (all P ＜ 0.05).Transmission electron microscopy showed that the number of autophagosomes and autolysosomes was significantly higher in the 100-,200-mJ/cm2 NB-UVB groups (5.12 ± 1.13,5.25 ± 1.04) than in the control group (1.88 ± 1.18,both P ＜ 0.05).Meanwhile,the number of melanosomes was significantly higher in the 50-,100-and 200-mJ/cm2 NB-UVB groups (39.12 ± 9.42,57.38 ± 7.11,59.75 ± 15.15,all P ＜ 0.05) than in the control group (18.50 ± 4.18,all P ＜ 0.05).Conclusion NB-UVB radiation can not only promote the formation of melanosomes,but also activate the autophagy signal pathways in the melanocytes and promote the formation of autophagosomes and autolysosomes,which may be one of the mechanisms underlying the treatment of vitiligo by NB-UVB.

Objective To evaluate the effect of tea polyphenol epigallocatechin gallate (EGCG)on ultraviolet B (UVB)-induced skin pigmentation,transfer and degradation of melanosomes in mice,and to explore the role of autophagy in the mechanism of melanosome degradation.Methods A total of 32 ears from 16 female C57/BL6 mice were randomly and equally divided into 4 groups:acetone control group topically treated with acetone solution daily,EGCG group topically treated with 10 g/L EGCG acetone solution daily,UVB irradiation group irradiated with 500 mJ/cm2 UVB once a day and 2 hours later topically treated with acetone solution,UVB + EGCG group irradiated with 500 mJ/cm2 UVB once a day and 2 hours later topically treated with EGCG acetone solution.Ten days later,all the mice were sacrificed,and skin tissue samples were collected from the ears.Transmission electron microscopy was performed to observe ultrastructural changes of melanosomes and autophagosomes,immunohistochemical study to measure expression of protease-activated receptor 2 (PAR2) and microtubule-associated protein light chain 3 (LC3) in the epidermis,and Western blot analysis to determine the protein expression of PAR2,Rasrelated protein Rab27a and LC3 in the epidermis.Results There was a significant difference in the number of melanosomes and autophagosomes among the acetone control group,EGCG group,UVB irradiation group and UVB + EGCG group (H =12.249,13.888,respectively,both P ＜ 0.05).Compared with the acetone control group,the UVB irradiation group showed significantly increased number of melanosomes (1.85 ± 0.32 vs.1.00 ± 0.41,P ＜ 0.05)and autophagosomes (1.94 ± 0.64 vs.1.00 ± 0.46,P ＜ 0.05) in epidermal keratinocytes in mouse skin.Compared with the UVB irradiation group,the UVB + EGCG group showed significantly decreased number of melanosomes (1.30 ± 0.44,P ＜ 0.05),but significantly increased number of autophagosomes (3.03 ± 0.75,P ＜ 0.05).Immunohistochemical study showed a significant difference in the level of PAR2 in the epidermis among the 4 groups (H =18.700,P ＜ 0.05),and the expression of PAR2 was significantly lower in the UVB + EGCG group than in the UVB irradiation group (7.94 ± 4.57 vs.12.54 ± 3.07,Z =2.143,P ＜ 0.05).However,the 4 groups all showed a low level of LC3,and there was no significant difference among the 4 groups (H =5.051,P ＞ 0.05).Western blot analysis revealed significant differences in the protein expression of PAR2 and Rab27a,as well as in the LC3-Ⅱ/LC3-Ⅰ ratio,among the 4 groups (F =18.739,25.967,24.022,respectively,all P ＜ 0.05).Compared with the UVB irradiation group,the UVB + EGCG group showed significantly decreased expression of PAR2 (0.91 ± 0.54 vs.3.12 ± 0.61,P ＜ 0.05) and Rab27a (0.99 ± 0.16 vs.1.42 ± 0.07,P ＜ 0.05),but significantly increased LC3-Ⅱ/LC3-Ⅰ ratio (1.67 ± 0.08 vs.1.24 ± 0.07,P ＜ 0.05).Conclusion Topical EGCG treatment can effectively suppress UVB-induced skin pigmentation,which may be related to the inhibition of melanosome transfer and promotion of melanosome autophagy.