1.Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients: A 12-week randomized placebo-controlled phase III trial with long-term extension
Chen YU ; Songmei GENG ; Bin YANG ; Yunhua DENG ; Fuqiu LI ; Xiaojing KANG ; Mingye BI ; Furen ZHANG ; Yi ZHAO ; Weili PAN ; Zhongwei TIAN ; Jinhua XU ; Zhenghua ZHANG ; Nan YU ; Xinsuo DUAN ; Shuping GUO ; Qing SUN ; Weiquan LI ; Juan TAO ; Zhijun LIU ; Yuanyuan YIN ; Gang WANG
Chinese Medical Journal 2024;137(10):1190-1198
Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.
2.Clinical characteristics and outcomes of psoriasis patients with COVID-19: A retrospective, multicenter cohort study in China
Yanhua LIU ; Zhongrui XU ; Jian ZHOU ; Aijun CHEN ; Junling ZHANG ; Xiaojing KANG ; Xian JIANG ; Chengzhi LYU ; Chunrui SHI ; Yuling SHI ; Xiaoming LIU ; Fuqiu LI ; Bin YANG ; Yongmei HUANG ; Chen YU ; Gang WANG
Chinese Medical Journal 2024;137(14):1736-1743
Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.
3.Research progress of targeted therapy in vitiligo
Manhui CHEN ; Wen HU ; Xiaojing KANG
Chinese Journal of Immunology 2024;40(12):2676-2679
Vitiligo is a common acquired depigmentation disorder characterized by the loss of melanocytes in the skin,hair,and mucous membranes.Its characteristics of difficulty in re-pigmentation and easy recurrence are great challenges for vitiligo treat-ment.At present,vitiligo has been clearly classified as an autoimmune disease with a complex pathogenesis involving genetic and envi-ronmental factors,oxidative stress and autoimmune responses that synergistically promote the loss of melanocytes.With the in-depth understanding of the pathogenesis of vitiligo,a large number of clinical trials have been carried out for targeted therapy of key small molecules,cell subsets,and immune-related signaling pathways in vitiligo.Targeted therapy will become the mainstream in the treat-ment of vitiligo in the future.Research progress of targeted therapy for tissue resident memory T cells(TRM)pathway,JAK-STAT pathway,and WNT/β-catenin pathway in vitiligo.
4.Correlation between 1, 5-anhydroglucitol and mild cognitive impairment in elderly patients with type 2 diabetes mellitus
Lina WANG ; Xinju JIA ; Yuqing GUO ; Yan KANG ; Fan LIU ; Xiaojing LYU ; Huimin ZHOU
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(7):618-623
Objective:To explore the correlation between serum 1, 5-anhydroglucitol (1, 5-AG) and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes mellitus (T2DM).Methods:A total of 160 patients with T2DM aged 60-75 years old who visited the First Hospital of Hebei Medical University from May 2021 to July 2022 were selected. According to the Montreal cognitive assessment (MoCA), all patients were divided into T2DM with MCI group (T2DM+ MCI group, n=81) and T2DM without MCI group (T2DM group, n=79). All research subjects were tested for glycated hemoglobin A1c (HbA1c), serum 1, 5-AG, serum β-amyloid peptide 42 (Aβ42), and blood biochemical indicators.SPSS 25.0 statistical software was used for data analysis. The t test, Mann-Whitney U test and χ2 test were used to compare the two groups. Binary Logistic regression analysis was used to examine the relevant influencing factors. Results:(1) Compared with T2DM group, patients in T2DM+ MCI group had significantly higher age, systolic pressure and HbA1c(all P<0.05).The level of 1, 5-AG in T2DM+ MCI group was significantly lower than that in T2DM group( (15.65±2.56 )μg/mL, (18.17±3.72 )μg/mL, P<0.01), and the level of Aβ42 was higher than that of T2DM group (2.95 (3.36) pg/mL, 1.91 (2.48) pg/mL, P<0.05). (2) Binary Logistic regression analysis results showed that HbA1c( β=0.230, OR=1.259, 95% CI=1.010-1.568, P=0.040) and Aβ42( β=0.188, OR=1.206, 95% CI=1.033-1.409, P=0.018) were the independent risk factors for MCI in elderly patients with T2DM, while 1, 5-AG ( β=-0.240, OR=0.786, 95% CI=0.698-0.886, P<0.001) was the protective factor for MCI. Conclusion:There is a positive correlation between serum 1, 5-AG and cognitive function, and the decrease of 1, 5-AG level was associated with the increased risk of MCI in elderly patients with T2DM.
5.Role of circRNA 0001400/RELL1 in regulating the activation of mitogen-activated protein kinase signaling pathway during the development of Kaposi′s sarcoma
Yuanyuan QU ; Peng WANG ; Jingzhan ZHANG ; Tingting LI ; Xiaojing KANG
Chinese Journal of Dermatology 2024;57(8):685-692
Objective:To explore the role and mechanisms of action of human circular RNA 0001400 (hsa_circ_0001400) and its linear transcript RELL1 in the development of Kaposi's sarcoma (KS) .Methods:KS-associated herpesvirus (KSHV) was induced and extracted from BCBL-1 cells by phorbol ester. Human umbilical vein endothelial cells (HUVECs) were then infected with KSHV, inverted microscopy and real-time fluorescence-based quantitative PCR (qRT-PCR) were performed to observe cellular morphology and determine the expression of KSHV lytic gene ORF50 and latent gene LANA, respectively, so as to verify whether the infection was successful. HUVECs in the logarithmic growth phase were divided into 3 groups: HUVEC group (uninfected HUVECs), KSHV + HUVEC group (HUVECs infected with KSHV at a multiplicity of infection [MOI] of 0.5), and mitogen-activated protein kinase (MAPK) inhibitor group (HUVECs infected with KSHV at a MOI of 0.5 for 6 hours, followed by the treatment with 1 μmol/L MAPK inhibitor). Cell counting kit (CCK8) assay and flow cytometry were performed to assess the cellular proliferative ability and detect apoptosis in the above 3 groups, respectively. qRT-PCR and Western blot analysis were conducted to determine the transcription and protein expression levels of hsa_circ_0001400, its linear transcript RELL1, and rat sarcoma viral oncogene homolog (RAS) /MAPK signaling pathway-related genes in the HUVEC group and KSHV + HUVEC group. Five pairs of KS tissues and paraneoplastic tissues were collected, and mRNA expression of the above genes was verified by qRT-PCR in the KS tissue samples. Statistical analyses were performed using two-way analysis of variance, one-way analysis of variance, and t test. Results:Compared with the uninfected HUVECs, the infected HUVECs became rounder and grew more densely at 48 hours after the infection with KSHV. The mRNA expression of ORF50 and LANA genes could be detected in the KSHV-infected HUVECs, and their mRNA expression levels were significantly higher than those in the uninfected HUVECs (both P < 0.001), indicating successful infection of HUVEC by KSHV. The cellular proliferative rate in the KSHV + HUVEC group gradually increased over time during 24 to 72 hours after the infection, while that in the MAPK inhibitor group was markedly inhibited. The total apoptosis rate at 48 hours significantly differed among the 3 groups ( F = 673.98, P < 0.001), and was significantly higher in the MAPK inhibitor group than in the KSHV + HUVEC group and the HUVEC group (both P < 0.001), while there was no significant difference between the KSHV + HUVEC group and the HUVEC group ( P > 0.05). qRT-PCR showed that the mRNA expression of hsa_circ_0001400, RELL1, Kirsten rat sarcoma viral oncogene homologue (KRAS), MAPK11, and extracellular signal-regulated kinase (ERK) -2 was significantly higher in the KSHV + HUVEC group than in the HUVEC group (all P < 0.05), while ERK1 mRNA expression did not significantly differ between the 2 groups ( t = 0.92, P = 0.410). Western blot assay showed that the protein expression of RELL1, KRAS, MAPK11, ERK1, and ERK2 was significantly higher in the KSHV + HUVEC group than in the HUVEC group (all P < 0.01). The mRNA expression of RELL1, ERK1, and ERK2 was significantly higher in the KS tissues than in the paraneoplastic tissues (all P < 0.05) . Conclusion:KSHV infection may regulate the occurrence and development of KS by inducing the expression of hsa_circ_0001400 and its linear transcript RELL1, as well as activating the MAPK signaling pathway.
6.Relationship between zinc finger protein A20, CTGF and FibroScan and fibrosis in chronic hepatitis B patients
Song ZHANG ; Zilong ZHAO ; Qian HU ; Jian LI ; Xiaojing WANG ; Huijie GENG ; Haiyan KANG ; Dianxing SUN ; Zhengrong GUO
Journal of Public Health and Preventive Medicine 2024;35(3):133-136
Objective Studies on the expression and location of zinc finger protein A20 (A20) and connective tissue growth factor (CTGF) in liver tissues of patients with chronic hepatitis B were conducted, and the relationship between them and liver fibrosis was determined by FibroScan. Methods Studies on A20 and CTGF in liver tissues of 160 patients with chronic hepatitis B were conducted in accordance with the stage of pathological fibrosis and inflammation of the liver, and quantitative immunohistochemistry test was conducted, and statistical analysis was conducted by FibroScan. Results The expressions of A20 and CTGF in liver tissues increased with the aggravation of liver pathological fibrosis and inflammation, and there were significant differences between each stage and the control group (P<0.05), and there were significant differences between adjacent groups (P<0.05). Studies have shown that FibroScan increases along with pathological fibrosis and inflammation in the liver. There are significant differences between the stage and the control group (P<0.05), and no significant differences between the adjacent groups (P>0.05). There was positive correlation between liver A20 and CTGF, r=0.796 (P<0.05). Conclusions In patients with chronic hepatitis B, A20, CTGF and FibroScan are positively correlated with the degree of liver fibrosis, and A20 and CTGF are also positively correlated with the degree of liver inflammation, which can be used as indicators to evaluate the degree of liver inflammation and fibrosis, and further guide the anti-inflammatory and anti-fibrosis treatment of patients.
7.Treatment of Kaposi′s sarcoma
Yan GAO ; Peng WANG ; Xiaojing KANG
Chinese Journal of Dermatology 2024;57(1):85-89
The occurrence of Kaposi′s sarcoma (KS) is closely related to Kaposi′s sarcoma-associated herpesvirus (KSHV) infection of endothelial cells. KSHV infection can present as various types of KS, and clinical features, severity and prognosis differ among different types of KS. Classic KS is characterized by localized lesions and slow progression, AIDS-related KS and endemic KS are highly aggressive, and iatrogenic KS needs control of the primary disease during treatment. Therefore, individualized therapies should be developed according to the clinical classifications and characteristics of KS. This review summarizes treatment modalities of and research progress in KS.
8.Clinical analysis of 12 cases of Kaposi′s sarcoma with a single skin lesion as the initial manifestation
Xiaowen CHEN ; Tingting LI ; Wenjing CHEN ; Xiaojing KANG
Chinese Journal of Dermatology 2024;57(1):39-42
Objective:To summarize clinical features of Kaposi′s sarcoma with a single skin lesion as the initial manifestation, and to analyze causes of its misdiagnosis.Methods:Data were retrospectively collected from 12 patients with Kaposi′s sarcoma with a single skin lesion as the initial manifestation in the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2020 to January 2022. Clinical and histopathological features and causes of misdiagnosis were analyzed.Results:Among the 12 patients, 10 were males and 2 were females; 9 were of Uyghur nationality, and 3 were of Kazakh nationality; their ages ranged from 20 to 76 years, and 10 patients were aged ≥ 60 years. Skin lesions were mostly located on the feet (8 cases), including the lateral edge of the foot (3 cases), the sole of the foot (2 cases), the ankle (1 case), the dorsal side of the third toe (1 case), and the interdigital regions between the third and fourth toes (1 case) ; skin lesions were also observed on the fibular side of the right lower limb (2 cases), on the right side of the dorsal tongue (1 case), and on the dorsal side of the right little finger (1 case). The skin lesions manifested as purple-red nodules in 9 cases, dark-red nodules in 2 cases, and purple-red plaques in 1 case, with maximum diameters of 0.5 - 3.0 (1.9 ± 0.83) cm. Skin lesions were accompanied by pain in 6 cases and by pruritus in 1 case. Histopathologically, skin lesions manifested as the proliferation of vascular endothelial cells, which could form obvious vascular cavity, or presented as a large number of proliferative spindle cells depending on the degree of tumor differentiation; immunohistochemical study showed that all the 12 patients were positive for human herpes virus 8; immunohistochemical staining of CD34 and CD31 was performed in 11 and 4 patients respectively, all the 11 patients were positive for CD34, and all the 4 patients were positive for CD31. Among the 11 patients presenting with nodules, 6 were initially misdiagnosed with skin infection, 2 with hemangioma, 2 with cutaneous squamous cell carcinoma, and 1 with dermatofibroma; the 1 patient presenting with plaques was initially misdiagnosed with psoriasis; 8 patients were first diagnosed in the department of dermatology, 3 in the department of burns, and 1 was first diagnosed in the department of maxillofacial surgery.Conclusion:The Kaposi′s sarcoma initially manifesting as a single skin lesion was more common in males aged over 60 years, usually occurred on the feet, especially on the lateral edge of the foot, and mainly manifested as purple-red nodules; half of the patients were accompanied by pain; it was frequently misdiagnosed as skin infection in clinical practice, but histopathological examination could be helpful for its differential diagnosis.
9.Advances in cell transplantation combined with other therapeutic strategies in the treatment for vitiligo
Shangkun LIU ; Hongjuan WANG ; Xiaojing KANG
Basic & Clinical Medicine 2024;44(11):1584-1588
Vitiligo is an acquired depigmentation skin disease characterized by a decrease or loss of function of mel-anocytes.The conventional treatment for vitiligo include drug therapy,phototherapy and surgical treatment.As an important surgical treatment for vitiligo,cell transplantation is effective especially for the case which is stable,lim-ited or fail to respond to other methods,but the recoloration rate varies greatly.The combination therapy is a better choice to maximize the recoloration of skin lesions in patients with refractory vitiligo.In recent years,reports on the combined strategy of cell transplantation have gradually increased,bringing new hope to improve the rate of discolo-ration of vitiligo patients.This paper reviews the progress of the application of cell transplantation combination strat-egy aiming for providing more options for the clinical treatment of refractory vitiligo.
10.The clinical characteristics of nail involvement in pemphigus patients and the correlation between nail involvement and the severity of pemphigus
Fengxia HU ; Junqin LIANG ; Xiaojing KANG
Journal of Chinese Physician 2023;25(1):11-15
Objective:To analyze the clinical characteristics of nail involvement in patients with pemphigus and the correlation between nail damage and the severity of pemphigus.Methods:The clinical data of 23 patients with pemphigus combined with nail damage admitted to the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2011 to August 2019 were retrospectively analyzed, the manifestations of pemphigus combined with nail damage were summarized. The nail damage number of patients with pemphigus complicated with nail damage of different genders were analyzed, as well as the distribution of nail damage in nail and toenail. The titer of anti-desmocoglycoprotein(dsg) antibody was detected in all patients. The relationship between nail damage and disease severity and course in pemphigus patients was analyzed.Results:A total of 132 damage nails were found in 23 patients (14 males and 9 females) with pemphigus, including 66 nails in male, 66 nails in female, 82 nails and 50 toenails. There were 10 forms of nail damage, of which chronic paronychia was the most common. The number of damage nails between different genders in pemphigus patients was statistically significant (χ 2=9.183, P<0.001). The distribution of nail and toenail damage in pemphigus patients was statistically significant (χ 2=10.880, P<0.001). Of the 23 patients, only 3 were positive for dsg1 and 1 was positive for dsg3. There were 19 patients with both positive for dsg1 and dsg3. The titers of dsg1 and dsg3 were compared in 14 patients before and after nail damage. The results showed that the titers of anti-dsg antibody in pemphigus patients after nail damage were significantly higher than before. Thirteen of the 23 patients had nail damage at the time of the initial onset of pemphigus. The nail damage occurred from 6 weeks before the onset to 4 weeks after the onset. The nail damage occurred in 10 patients when the disease recurred. The nail damage occurred within 4 weeks before or at the same time with the blister. Conclusions:The number of damage nails per capita in female patients with pemphigus and nail damage was significantly higher than that in male patients, and nail damage was more common. The titers of anti-dsg antibody will be at a high level when pemphigus patients with nail damage, and the condition gets worse. Nail involvement is positive to the severity of the disease, and it can prolong the time of disease.


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