Analysis of difficult-to-treat sites in patients with psoriasis who received biological therapy / 中华皮肤科杂志

Objective:To investigate difficult-to-treat sites in patients with psoriasis receiving biological therapy.Methods:Clinical data were retrospectively collected from 73 adult patients with psoriasis in the database of Psoriasis Center, National Clinical Research Center for Skin and Immune Diseases from June 2020 to September 2021, who had received sufficient and standardized treatment with biological agents for ≥ 24 weeks, and were still treated with biological agents at the time of enrolment into this study with the psoriasis area and severity index (PASI) score being 1 - 5 at the time of enrolment into the database of Psoriasis Center. Distribution of psoriatic lesions resistant to biological therapy were analyzed, and differences in refractory sites were compared between different biologics. Chi-square test or Fisher′s exact test was used to analyze differences in the anatomical distribution of residual skin lesions after treatment with different biologics, McNemar test to compare the anatomical distribution of skin lesions before and after biological therapy, and Kruskal-Wallis H test to analyze the association between PASI scores for residual skin lesions and dermatology life quality index (DLQI) scores. Results:After ≥ 24 weeks of sufficient and standardized biological therapy in the 73 patients, refractory skin lesions mostly involved the lower limbs (46 cases, 63.01%) , followed by the scalp (36 cases, 49.32%) and upper limbs (27 cases, 36.99%) ; proportions of patients with residual skin lesions on the face and neck, trunk, upper limbs, lower limbs, hands and feet significantly decreased after biological therapy compared with those before treatment (paired χ2 = 5.14, 7.69, 9.90, 4.17 and 6.13, P = 0.016, 0.003, 0.001, 0.031 and 0.008, respectively) , while there was no significant difference in the proportions of patients with skin lesions on the scalp and genital areas before and after treatment (both P > 0.05) . No significant difference in the anatomical distribution of residual skin lesions was observed between the 13 patients receiving treatment with tumor necrosis factor inhibitors (adalimumab, infliximab, or tumor necrosis factor receptor-antibody fusion protein) and 59 receiving treatment with interleukin-17 (IL-17) inhibitors (secukinumab or ixekizumab) (all P > 0.05) . There was no significant difference in the anatomical distribution of residual skin lesions in the 13 patients before and after the treatment with tumor necrosis factor inhibitors (all P > 0.05) ; in the 59 patients treated with IL-17 inhibitors, the proportions of patients with residual skin lesions on the trunk, upper limbs, hands and feet significantly decreased after treatment (paired χ2 = 4.90, 9.09 and 7.11, P = 0.021, 0.001 and 0.004, respectively) , while there was no significant difference in the distribution of skin lesions on the scalp, face and neck, lower limbs and genital area before and after treatment (all P > 0.05) . Among the 73 patients, the PASI scores for lesions on the upper and lower limbs and the total PASI scores were all associated with the DLQI scores ( H = 7.52, 12.61, 6.75, respectively, all P < 0.05) , and were significantly higher in the patients with DLQI scores of > 10 points than in those with DLQI scores of ≤ 5 points (all P < 0.05) . Conclusions:Biological therapy-resistant psoriatic lesions were mostly located on the scalp, and refractory skin lesions mostly involved the lower limbs, scalp and upper limbs. No significant difference in the anatomical distribution of residual skin lesions was observed between patients treated with tumor necrosis factor inhibitors and IL-17 inhibitors, but IL-17 inhibitors may result in lesion clearance at more anatomical sites compared with tumor necrosis factor inhibitors.

The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy

Macrophages have a leading position in the tumor microenvironment (TME) which paves the way to carcinogenesis. Initially, monocytes and macrophages are recruited to the sites where the tumor develops. Under the guidance of different microenvironmental signals, macrophages would polarize into two functional phenotypes, named as classically activated macrophages (M1) and alternatively activated macrophages (M2). Contrary to the anti-tumor effect of M1, M2 exerts anti-inflammatory and tumorigenic characters. In progressive tumor, M2 tumor-associated macrophages (TAMs) are in the majority, being vital regulators reacting upon TME. This review elaborates on the role of TAMs in tumor progression. Furthermore, prospective macrophage-focused therapeutic strategies, including drugs not only in clinical trials but also at primary research stages, are summarized followed by a discussion about their clinical application values. Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.

Expression of nucleobindin 2-encoded satiety and fat-influencing protein-1 and interleukin-26 in the serum of patients with vitiligo and its significance / 中华皮肤科杂志

Objective To determine the expression of nucleobindin 2-encoded satiety and fatinfluencing protein-1 (nesfatin-1) and interleukin (IL)-26 in the serum of patients with vitiligo,and to explore the relationship of nesfatin-1 and IL-26 with anxiety status,disease stage and distribution pattern of vitiligo lesions.Methods From March 2017 to September 2018,123 outpatients with vitiligo,as well as 30 healthy controls (control group),were enrolled from Department of Dermatology,Affiliated Hospital of Jiangsu University.Of these patients,93 rated as anxious (vitiligo with anxiety group),and 30 as nonanxious (vitiligo without anxiety group).Another 30 anxious patients with other autoimmune diseases and background diseases like hypertension and diabetes mellitus but not vitiligo (anxiety group) were enrolled from Zhenjiang Fifth People's Hospital.Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of nesfatin-1 and IL-26 in the above groups,and state-trait anxiety inventory (STAI) was used to evaluate the anxiety status.According to the vitiligo disease activity (VIDA) score,the vitiligo patients with anxiety were divided into 3 subgroups:stable stage group,active stage group and rapid progressive stage group.According to the distribution pattern of skin lesions,the vitiligo patients with anxiety were divided into 5 subgroups:localized vitiligo group,segmental vitiligo group,generalized vitiligo group,sporadic vitiligo group and acral vitiligo group.The levels of nesfatin-1 and IL-26 were compared among different stage groups and type groups.Statistical analysis was carried out using one-way analysis of variance for comparison among several groups,multi-way analysis of variance and stratification analysis for multifactor data,paired t-test for comparison before and after treatment,and Pearson correlation analysis for analyzing correlations.Results The serum level of nesfatin-1 significantly differed among the vitiligo with anxiety group,vitiligo without anxiety group,anxiety group and control group (F =10.78,P ＜ 0.001),and was significantly higher in the vitiligo with anxiety group than in the other 3 groups (P ＜ 0.001).No significant difference in the serum level of IL-26 was found among the 4 above groups (F =1.34,P =0.26).As pearson correlation analysis showed,the serum level of nesfatin-1 was positively correlated with the STAI score in the 93 vitiligo patients with anxiety (r =0.55,P ＜ 0.001).The serum level of nesfatin-1 was significantly higher in the rapid progressive stage group than in the stable stage group (P ＜ 0.05),while there was no significant difference in the IL-26 level among different stage groups (P ＞ 0.05).The generalized vitiligo patients with anxiety showed significantly increased serum level of nesfatin-1 compared with the localized vitiligo patients with anxiety (P ＜ 0.001).After 3-month treatment,the nesfatin-1 level in the 10 vitiligo patients with anxiety significantly decreased compared with that before the treatment (paired t =4.40,P =0.02),but the STAI score did not change (P ＞ 0.05).Conclusion Nesfatin-1 as an emotioninfluencing factor may participate in the occurrence of vitiligo,especially affect patients with rapid progressive vitiligo or generalized vitiligo,while IL-26 may be irrelevant to vitiligo.

Effect of latanoprost on cell proliferation of and melanogenesis in human epidermal melanocytes and its mechanism / 中华皮肤科杂志

Objective To evaluate the effect of latanoprost on cell proliferation of and melanogenesis in human epidermal melanocytes,and to explore its mechanism.Methods Latanoprost was added into the 254 medium to prepare latanoprost solutions at different concentrations of 10-5,10-6 and 10-7 mol/L.In vitro cultured human epidermal melanocytes were divided into 4 groups to be cultured with media containing no latanoprost (control group) or 10-5,10-6 and 10-7 mol/L latanoprost for 48 hours.Cell counting kit-8 (CCK8) assay was performed to evaluate the proliferative activity of melanocytes,dopa oxidation assay to estimate the activity of tyrosinase.Sodium hydroxide (NaOH)-lysis method was used to determine the content of melanin,and Masson-Fontana staining to observe the number and distribution of melanin granules.Westernblot analysis and real-time fluorescence-based quantitative PCR were performed to determine the protein and mRNA expression of melanogenesis-related genes including microphthalmia-associated transcription factor (MITF),tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1).Comparison among the 4 groups and multiple comparisons were done by using one-way analysis of variance and least significant difference (LSD)-t test.Results Compared with the control group,the 10-6-,10-5-mol/L latanoprost groups showed significantly increased proliferative activity of melanocytes (1.064 ± 0.172 and 1.078 ± 0.080 vs.0.784 ± 0.015;t =3.289,3.454 respectively,both P ＜ 0.05),increased activity of tyrosinase (0.510 ± 0.017 and 0.454 ± 0.009 vs.0.355 ± 0.041;t =6.139,3.939 respectively,P ＜ 0.01 or 0.05),and increased content of melanin (t =7.232,5.967,both P ＜ 0.01).However,there were no significant differences in the proliferative activity of melanocytes,activity of tyrosinase or content of melanin between the 10-7-mol/L latanoprost group and control group (all P ＞ 0.05).Masson-Fontana staining showed more and darker melanin granules on melanocyte dendrites in the 10-5-,10-6-,10-7-mol/L latanoprost groups than in the control group,and the color of melanin granules changed from light brown to black brown along with the increase in the concentration of latanoprost.The mRNA expression of MITF increased along with the increase in the concentration of latanoprost (P ＜ 0.01),and the protein expression of MITF wassignificantly higher in the 10-6,10-5-mol/L latanoprost groups than in the control group and 10-7-mol/L latanoprost group (all P ＜ 0.01).The 10-6-mol/L latanoprost group showed significantly increased mRNA and protein expression of TYR and TYRP1 compared with the control group,10-7-,10-5-mol/L latanoprost groups (all P ＜ 0.01).Conclusion Latanoprost can increase the proliferation of human epidermal melanocytes,and promote tyrosinase activity and melanogenesis likely by enhancing the mRNA and protein expression of MITF,TYR,TYRP1.

Metabolic characteristics and risk factors for newly diagnosed type 2 diabetes mellitus combined with non-alcoholic fatty liver disease / 中国综合临床

Objective To explore metabolic characteristics of and risk factors for newly diagnosed type 2 diabetes mellitus(T2DM) combined with non-alcoholic fatty liver disease (NAFLD).Methods One hundred and forty-two cases of newly diagnosed T2DM were divided into two groups according to whether they have comorbid NAFLD:group A (without NAFLD,n =79) and group B (combined with NAFLD,n =63).Data collected included body height,body weight,blood pressure,fasting plasma glucose (FPG),blood lipid,serum uric acid (UA),HbA1c and fasting insulin,body mass index and insulin resistance index with homeostasis model(HOMA-IR) were calculated to compare the clinical and biochemical parameters between groups A and B.Results (1) The difference of age and blood pressure between groups A and B were not statistical different (P ＞ 0.05).Compared with group A,BMI ((26.79 ± 1.93) kg/m2 vs (24.61 ± 2.46) kg/m2,t =5.76),FINS((15.49±2.44) mU/L vs (13.20±2.17) mU/L),t =5.91),HOMA-IR((6.74± 1.32) vs (5.65 ±1.10),t =5.37),glycerin trimyristate (TG) ((2.94 ± 0.65) mmol/L vs (1.74 ± 0.46) mmol/L),t =12.86),low density lipoprotein cholesterin (LDL-C) ((3.46 ±0.73) mmol/L vs (2.78 ±0.86) mmol/L,t =5.07) and UA((342.41 ±71.49) mmol/L vs (312.98 ±66.24) mmol/L,t =2.54) were significantly higherand hight density lipoprotein cholesterin (HDL-C) ((0.99 ± 0.17) mmol/L vs (1.21 ± 0.29) mmol/L,t =5.33) was significantly lower in group B (P ＜ 0.05).(2) Using whether to combined with NAFLD as dependent variable,and BMI,FINS,HOMA-IR,TG,LDL-C,HDL-C and UA as independent variable,logistics regression analysis showed that BMI,HOMA-IR and TG were risk factors for NAFLD(OR =2.838,19.241,and 2.019 respectively,P ＜ 0.05).Conclusion Newly diagnosed type 2 diabetes mellitus combined with NAFLD have more obvious dyslipidemia and insulin resistance.Obesity,insulin resistance,hyper-triglyceridemia are risk factors for newly diagnosed type 2 diabetes mellitus combined with NAFLD.

The expression and significance of p-IRE-1α in rat liver with insulin resistance / 中华内分泌代谢杂志

Fed with high-fat diet and assessed by hyperinsulinemia-euglycemia clamp technique, rat models with insulin resistance were successfully induced. Compared with normal chow group ( NC ), serum concentrations of free-fatty acids(FFAs) and baseline insulin in high-fat diet group(HF) was higher( P＜0.05 ), the average glucose infusion rate from 60 to 120 min( GIR60-120 ) was lower( P＜0.01 ), and the expression of p-IRE-lα in the liver was higher( P＜0.05 ). Furthermore, the expression of p-IRE-1α in the liver was positvely correlated with the serum concentration of FFAs. All these data indicate that high-fat diet may induce endoplasmic reticulum stress in the liver by elevating serum concentration of FFAs, and may participate in the genesis of insulin resistance via p-IRE-1α.