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BACKGROUND@#Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.@*RESULTS@#At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310.@*CONCLUSION@#CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.
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Adulto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inyecciones Subcutáneas , Método Doble CiegoRESUMEN
Objective:To determine the expression of glucose transporter 3 (GLUT3) in cutaneous squamous cell carcinoma (cSCC), and to evaluate its effect on the cSCC cell line A431.Methods:From June 2016 to December 2020, 22 paraffin-embedded tissue specimens were collected from patients with pathologically confirmed cSCC in the Department of Dermatology, Peking University Third Hospital, and 20 discarded normal skin tissues after dermatological surgeries served as controls. Immunohistochemical assay was performed to determine the GLUT3 expression in cSCC tissues and normal skin tissues. Cultured A431 cells were divided into two groups: GLUT3 overexpression group transfected with a lentiviral vector carrying the SLC2A3 gene, and negative control group transfected with an empty lentiviral vector. Real-time fluorescence-based quantitative PCR and Western blot analysis were conducted to determine the mRNA and protein expression of GLUT3 in A431 cells in different groups, the cell proliferation assay (MTS assay) was performed to estimate the cell proliferative activity, and the live-cell analysis system Incucyte S3 was used for real-time evaluation of the migratory and invasive abilities of A431 cells in different groups. The relative glucose consumption and lactic acid production in A431 cells at 48 hours were measured by using glucose and lactic acid assay kits, retrospectively. Two independent samples t-test was used for comparisons between two groups, and one-way analysis of variance was used for comparisons among multiple groups. Results:The GLUT3 expression was significantly higher in the cSCC tissues than in the normal skin tissues (immunohistochemical assay score: 9.39 ± 2.56 points vs. 2.30 ± 2.60 points; t = 8.91, P < 0.05). Compared with the negative control group, the mRNA and protein expression of GLUT3 markedly increased in the GLUT3 overexpression group. MTS assay showed significantly increased proliferative activity of A431 cells in the GLUT3 overexpression group compared with the negative control group after 24- and 96-hour treatment ( t = 2.49, 3.54, P = 0.048, 0.012, respectively); cell fusion rates in the scratched area were significantly higher in the GLUT3 overexpression group than in the negative control group in the cell migration assay at 6, 12 18, and 24 hours and cell invasion assay at 12, 18, and 24 hours (all P < 0.05). At 48 hours, the relative glucose consumption and lactic acid production in A431 cells were significantly higher in the GLUT3 overexpression group than in the negative control group ( t = 2.98, 2.20, P = 0.011, 0.038, respectively) . Conclusion:GLUT3 was highly expressed in the cSCC tissues, and may participate in the occurrence and development of cSCC by providing energy to cSCC cells via promoting glucose uptake in cells to enhance their proliferative, migratory and invasive abilities.
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Strengthening medical ethics education for medical students is the need for the healthy development of human medical health, the cultivation of medical students’ professional ethics and the integration of medical ethics spirit and medical ethics practice. Through in-depth discussion of the new mode of the integration of medical ethics education and medical ethics practice, stimulating the new impetus of the integration of medical students’ self-cultivation into practice, and the new ways to cultivate the growth of medical students in the new era, this paper put forward specific measures to create an education suitable for each student’s development by selecting the medical ethics education team, learning ethics and humanistic education, taking medical students as the center, and creating a suitable learning environment for students, with a view to cultivating medical students to grow into guardians who can cope with the challenges of public health emergencies.
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【Objective】 To investigate the psychological status of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and to analyze the effects of anxiety on the total National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) in patients in Ngari Prefecture of Tibet. 【Methods】 CP/CPPS patients treated during Oct.2019 and Oct.2021 were involved and divided into anxiety group and non-anxiety group. The non-anxiety group received routine drug treatment, while the anxiety group received drugs and psychological intervention. 【Results】 A total of 117 patients were involved, including 68 in the anxiety group and 49 in the non-anxiety group. There were no statistical differences between the two groups in terms of age, body mass index (BMI), marital status, smoking history, and education level (P>0.05). The total NIH-CPSI score in the anxiety group (18.53±3.47) was higher than that in non-anxiety group (15.67±3.33), which was mainly manifested by the increase of pain and decrease of quality of life scores. Further stratification of anxiety level revealed that quality of life score and total NIH-CPSI score increased as anxiety symptoms worsened. After drug treatment, pain and urination symptoms were improved in the non-anxiety group, but the quality of life score and total NIH-CPSI score did not change significantly. After psychological intervention, the anxiety group had lower total NIH-CPSI score and other scores. 【Conclusion】 It is not uncommon for CP/CPPS patients to have a comorbidity of anxiety. The increase in the total NIH-CPSI score is caused by the increase of pain score and decrease of quality of life score. Active psychological intervention can improve anxiety, urinary symptoms, pain symptoms and quality of life.
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Objective:To analyze clinical and pathological features of 6 cases of papular acantholytic dyskeratosis of the anogenital area.Methods:Clinical and histopathological data were collected from 6 patients with papular acantholytic dyskeratosis of the anogenital area in the Department of Dermatology, Peking University Third Hospital from January 2013 to December 2022, and retrospectively analyzed.Results:Among the 6 patients, 3 were males and 3 were females. Their ages at onset ranged from 22 to 58 years. The time from the onset to diagnosis ranged from 1 to 18 months. All patients had no family history of similar skin lesions. The 6 patients all clinically presented with multiple clustered millet-sized flesh-colored or gray-whitish papules in the perianal and genital areas, with erosions and crusts on the surface of some lesions, sometimes accompanied by pruritus. Histopathological findings of skin lesions were similar, including hyperkeratosis with focal parakeratosis, as well as acantholytic and dyskeratotic cells scattered in the epidermis. The 6 patients were treated with topical glucocorticoids or tacrolimus ointment, etc., which exhibited varying efficacy, and some skin lesions persisted with repeated attacks.Conclusions:Papular acantholytic dyskeratosis was a rare skin disease, and mostly occurred in the anogenital area. Its diagnosis should rely on both clinical manifestations and histopathological findings.
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With the advances in research on cutaneous T-cell lymphomas (CTCL), some new strategies, such as traditional targeted drugs, immune checkpoint inhibitors, histone deacetylase inhibitors and allogeneic hematopoietic stem cell transplantation, have emerged and shown favorable efficacy and safety in clinical trials. This review summarizes recent research progress in non-chemotherapeutic drugs for relapsed/refractory cutaneous T-cell lymphomas.
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Objective:To identify factors influencing the recurrence of psoriasis, and to explore the association between the recurrence of psoriasis and metabolism-related markers.Methods:A retrospective investigation was conducted on the recurrence status of patients with psoriasis vulgaris, who visited the Department of Dermatology, Peking University Third Hospital from January 2016 to April 2023. Patients with recurrence intervals > 3 months were included in the non-rapid recurrence group (non-persistent psoriasis group), while patients with recurrence intervals ≤ 3 months were included in the rapid recurrence group (persistent psoriasis group). General conditions and relapse triggers were analyzed between the two groups. Metabolism-related laboratory data, as well as detection results of serum fatty acid-binding protein 4 (FABP4) and FABP5 in some patients, were collected, and relationships between these indicators and psoriasis recurrence were analyzed. Comparisons between groups were performed using t test, non-parametric test or chi-square test; linear regression analysis was performed to identify possible factors influencing the FABP levels, and multivariate logistic regression analysis to identify relapse triggers. Results:A total of 255 patients were collected, including 194 with non-persistent psoriasis and 61 with persistent psoriasis. There were no significant differences in gender, age (stratified every 30 years), course of psoriasis (stratified every 10 years), family history of psoriasis, and main therapies between the two groups (all P > 0.05). The patients in the non-persistent psoriasis group were more prone to recurrence due to seasonal effects ( χ2 = 18.98, P < 0.001). The proportion of patients with dyslipidemia was significantly higher in the persistent psoriasis group than in the non-persistent psoriasis group ( χ2 = 54.44, P < 0.001). Compared with the non-persistent psoriasis group, the persistent psoriasis group showed significantly increased body mass index and levels of triglycerides, uric acid, and C-reactive protein (all P < 0.05), but significantly decreased high-density lipoprotein cholesterol levels ( U = 3 348.00, P < 0.001). The levels of FABP4 and FABP5 were significantly higher in the persistent psoriasis group than in the non-persistent psoriasis group (both P < 0.05). In the linear regression model adjusted for body mass index and dyslipidemia, FABP4 levels were associated with recurrence status of psoriasis ( P < 0.001). Multivariate logistic regression analysis revealed a significant correlation between dyslipidemia and persistent psoriasis ( P < 0.001) . Conclusion:The psoriasis patients with recurrence intervals ≤ 3 months may be more prone to develop metabolic diseases such as dyslipidemia, and dyslipidemia and elevated FABP4 levels may be associated with the recurrence of psoriasis.
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@#The petroleum ether fraction of ethanol extracts from Boenninghausenia sessilicarpawas isolated by combination of several chromatographic methods including silica gel, ODS, and Sephadex LH-20 column chromatography, and finally purified by preparative HPLC. The structures of the isolated compounds were identified based on the spectral data. As a result, 15 coumarin compounds were isolated and identified from the petroleum ether extraction. Their structures were determined as osthenon (1), murrangatin (2), 3-(1,1-dimethylallyl)-8-hydroxy-7-methoxycoumarin (3), xanthotoxin (4), isopimpinellin (5), chalepensin (6), isodemethylfuropinarine (7), imperatorin (8), phellopterin (9), heraclenol (10), byakangelicin (11), neobyakangelicol (12), chalepin (13), luvangetin (14), 3-(1, 1-dimethylallyl)-xanthyletin (15). Among them, compounds 1 - 3, 6 - 10 and 14 -15 were firstly isolated from B. sessilicarpa.
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Sulforaphane is a phytochemical with a variety of biological activities that exists widely in Cruciferae plants. This article summarizes the recent experimental studies of sulforaphane in the treatment of various types of liver injury in China and globally and reviews the role and mechanism of sulforaphane in protecting against liver injury. Based on the experimental animal models of liver injury, this article summarizes the therapeutic effect of sulforaphane on the models of chemical liver injury, drug-induced liver injury, alcoholic liver injury, immunological liver injury, and ischemia/reperfusion liver injury and analyzes the mechanism of action of sulforaphane in improving experimental liver injury, so as to provide a reference for in-depth research on sulforaphane in protecting against liver injury.
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Objective:To investigate the application effects of a one-time filling root canal in root canal therapy in plateau areas and evaluate its feasibility in oral clinic in plateau areas.Methods:Sixty-eight patients who received root canal therapy for anterior teeth and premolars (75 teeth) from August to December 2018 in Shannan People's Hospital were included in this study. They were divided into control group ( n = 33; 36 teeth) and observation group ( n = 35; 39 teeth) according to odd and even numbers of admission date. Patients in the control group received conventional root canal therapy and those in the observation group underwent one-time root canal filling therapy. Efficacy was compared between the two groups. Results:After 1 week, 2 weeks and 1 month of treatment, the success rate in the control group was 88.9%, 94.4%, 100.0%, respectively, and it was 87.2%, 94.9% and 100.0%, respectively in the observation group. There was no significant difference in success rate between the two groups at three time points studied (all P > 0.05). Conclusion:One-time filling root canal therapy can achieve ideal therapeutic effects under strict control of surgical indications. This method is worthy of clinical promotion especially in plateau areas.
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OBJECTIVE To investigat e the effects of water extract (WCS)and ethanol extract (ECS)from the root of Caragana sinica on hyperuricemia (HUA)in mice. METHODS Kunming mice were randomly divided into normal control group , model group ,allopurinol group (positive control ,5 mg/kg),benzbromarone group (positive control ,7.8 mg/kg),WCS low-dose , medium-dose and high-dose groups (38,75,150 mg/kg),ECS low-dose ,medium-dose and high-dose groups (50,100,200 mg/kg), with 10 mice in each group. Except for the normal control group ,the other mice were given potassium oxazinate intraperitoneally and hypoxanthine intragastrically for consecutive 7 d to establish HUA model. On the third day of modeling ,mice in each administration group were given corresponding drugs intragastrically ,and normal control group and model group were given equal volume of normal saline once a day for 5 consecutive days.The body weight of mice were weighted during administration ;one hour after the last administration ,the organ indexes of liver ,kidney and spleen were calculated ;the contents of serum uric acid (SUA), blood urea nitrogen (BUN)and serum creatinine (SCR);the activity of xanthine oxidase (XOD)in serum and liver tissue were determined. Relative mRNA and protein expressions of XOD in liver tissue ,relative expre ssions of GLUT9,URAT1 and OAT 1 in renal tissue were all detected ;and the pathological changes of renal tissue were observed. RESULTS There were no significant differences in liver index and spleen index in each group (P>0.05). Compared with normal control group , except for allopurinol group , there were no significant differences in the body weight and the contents of BUN and SCR in mice of other administration groups (P>0.05);the renal index and SUA content of mice in the m odel group and allopurinol group were significantly increased (P<0.05);in the model group ,the XOD activity in serum and liver tissue ,the relative mRNA and protein expression of XOD in liver tissue ,the relative expressions of GLUT 9 and URAT 1 protein in renal tissue were significantly increased (P<0.05),and the relative expression of OAT 1 protein in renal tissue was significantly decreased (P< 0.05). Compared with model group ,renal indexes of mice were decreased significantly in WCS and ECS groups (P<0.05),and the pathological damage of renal tissue was significantly improved ;SUA content ,XOD activity in serum and liver tissue ,the relative mRNA and protein expression of XOD in liver tissue ,and the relative expression of URAT 1 protein in renal tissue were decreased significantly in administration groups (P<0.05). The relative expression of GLUT 9 protein in renal tissue of mice in benzbromarone group and ECS high-dose group decreased significantly (P<0.05);relative expression of OAT 1 protein in renal tissue of mice in benzbromarone group ,WCS low-dose and high-dose groups ,ECS low-dose group were increased significantly (P<0.05). CONCLUSIONS WCS and ECS can significantly decrease the contents of SUA in HUA model mice ,and improve pathological state of renal tissue ,the mechanism of which may be associated with inhibiting XOD activity and uric acid reabsorption,and down-regulating protein and mRNA expression of XOD.
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OBJECTIVE:To investigate the improvement effect of Tiarella polyphylla ethanol extract (TPME)on CCl 4-induced hepatic fibrosis in mice ,and to explore its possible mechanism preliminarily. METHODS :Totally 60 male Kunming mice were randomly divided into normal group ,model group ,positive control group (colchicine 0.1 mg/kg),TPME low-dose ,medium-dose and high-dose groups (250,500,1 000 mg/kg)according to body weight ,with 10 mice in each group. Except for normal group , other groups were given 20% CCl4 olive oil solution intraperitoneally to induce hepatic fibrosis ,twice a week ,for consecutive 8 weeks. From the fifth week after modeling ,administration groups were given relevant medicine intragastrically ,normal group and model group were given constant volume of normal saline intragastrically ,once a day ,for consecutive 4 weeks. Twelve hours after last administration ,the liver weight of mice in each group was measured and the liver index was calculated. The serum contents of ALT,AST,SOD,MDA,PC-Ⅲ,C-Ⅳ,LN,TNF-α and IL- 6 were determined. Western blot assay was used to detect the protein expression of α-SMA,TGF-β1 and Smad 3 in liver tissue. HE and Masson staining were used to observe the pathological changes of hepatic tissue. RESULTS :Compared with normal group ,the liver index ,the activities of ALT and AST and the contents of MDA , LN,PC- Ⅲ ,C- Ⅳ ,LN,TNF-α and IL- 6 in serum were increased significantly , while the activity of SOD was 6011) decreased significantly in model group (P<0.01);the protein expression of α-SMA,TGF-β1 and Smad 3 in liver tissues were hfjsznd8@126.com increased significantly (P<0.01). Obvious fibrosis lesions was observed in liver tissue. Compared with model group ,the live indexes ,the activities of ALT and AST ,the contents of MDA,PC-Ⅲ,C-Ⅳ,LN,TNF-α and IL-6 in serum were decreased significantly in positive control group and TPME groups , while the activities of SOD were increased significantly (P<0.05 or P<0.01). The protein expression of α-SMA,TGF-β1 and Smad3 in liver tissue were decreased significantly (P<0.05 or P<0.01),and liver fibrosis was improved to different extent. Compared with TPME low-dose group ,the contents of PC- Ⅲ,LN and IL- 6 in serum ,protein expression of TGF-β1 and Smad 3 in liver tissue were decreased significantly in TPME high-dose group (P<0.05). CONCLUSIONS :TPME can improve hepatic fibrosis induced by CCl 4 in mice ,the mechanism of which may be associated with the inhibition of collagen synthesis and oxidative stress,the reduction of inflammatory factors ,and the down-regulation of the expression α-SMA and relative proteins of TGF-β1/ Smad signal pathway.
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Objective:To investigate the therapeutic effect of human umbilical cord mesenchymal stem cells (MSCs) on psoriasis-like mouse models induced by imiquimod and the underlying mechanisms.Methods:Eighteen C57BL/6 mice were randomly and equally divided into vaseline group, model group and treatment group according to a random number table. The mice in the model group and treatment group received topical treatment with 5% imiquimod cream at a dose of 62.5 mg once a day for 6 consecutive days on the shaved back, and those in the vaseline group received the treatment with the same amount of vaseline ointment; the mice in the treatment group were injected with 1.5×10 6 human umbilical cord MSCs via the caudal vein on days 1 and 4. The severity of skin lesions on the back of the mice was assessed everyday according to the psoriasis area and severity index (PASI) . Twenty-four hours after the last treatment, that is, on day 7, blood samples were taken, and the mice were sacrificed. The dorsal skin tissues were resected and subjected to hematoxylin and eosin (HE) staining. A single cell suspension of the resected spleen was prepared, and flow cytometry was performed to detect the Th1 and Th17 cell subsets in the spleen cells. Enzyme-linked immunosorbent assay was conducted to detect serum levels of cytokines interleukin (IL) -17A and tumor necrosis factor (TNF) -α. One-way analysis of variance was used for comparisons among groups, Tukey test for multiple comparisons, and repeated measures analysis of variance for the analysis of changes in the PASI score over time. Results:On day 7, there was obvious scaly erythema on the back of the mice in the model group, and the skin thickness and number of infiltrating inflammatory cells were significantly higher in the model group (78.73 ± 23.11 μm, 36.16 ± 2.95 cells/mm 2) than in the vaseline group (13.28 ± 4.57 μm, 13.33 ± 1.15 cells/mm 2, q=19.25, 7.21, respectively, both P < 0.001) . The treatment group showed significantly decreased PASI score, epidermal thickness and number of infiltrating inflammatory cells compared with the model group (all P < 0.001) . The percentage of Th17 cell subsets in the spleen cells and serum level of TNF-α were significantly lower in the treatment group than in the model group (both P < 0.05) . There were no significant differences in the spleen weight, spleen index, spleen cell count, Th1 cell percentage or serum IL-17A level between the treatment group and the model group (all P>0.05) . Conclusion:Human umbilical cord MSCs can effectively alleviate skin inflammation induced by imiquimod in the psoriasis-like mouse models, likely by inhibiting Th17 cell formation and TNF-α expression.
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Mesenchymal stem cells are an important member of the stem cell family, characterized by self-renewal ability, multipotent differentiation potential, immunomodulatory effects, low immunogenicity, etc. Studies have demonstrated varying degrees of clinical efficacy of mesenchymal stem cells in the treatment of psoriasis, with long remission periods. This review summarizes the application of mesenchymal stem cells in psoriasis and related research progress.
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The diagnosis of bone metastasis of prostate cancer (PC) is of great significance to the treatment and prognosis of patients with PC.Bone scan is the most commonly used in the early diagnosis of bone metastasis, but its specificity is low and there is a high false positive.In recent years, with the in-depth study of the application of CT, MRI, emission computed tomography (ECT), positron emission computed tomography/computed tomography (PET/CT) and deep learning algorithm-convolutional neural networks (CNN) in the diagnosis of bone metastasis, the combined application of various auxiliary parameters in the diagnosis of bone metastasis has significantly been improved. The therapeutic effect of PC patients with bone metastasis can also be evaluated, which is expected to achieve the treatment of bone metastasis as well as diagnosis. By systematically expounding the research progress of the above-mentioned techniques in the diagnosis of bone metastasis, it can provide clinicians with new methods for the diagnosis of bone metastasis and improve the diagnostic efficiency for bone metastasis.
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Humanos , Masculino , Enfermedades de la Médula Ósea , Neoplasias Óseas/diagnóstico por imagen , Imagen por Resonancia Magnética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagenRESUMEN
Objective:To investigate the effects and the mechanism of renal protection of curcumin on oxidative stress and lipid metabolism in diabetic rats.Methods:60 Wistar rats were randomly divided into normal control group ( n=20) and diabetic model preparation group ( n=40). Rats in the normal control group were fed with normal diet, while rats in the diabetes model group were fed with high sugar and high fat diet. After 4 weeks of feeding, rats in the diabetic model preparation group were injected with streptozotocin (60 mg/kg) intraperitoneally once. A total of 35 rats were successfully modeled and then randomly divided into diabetic model group ( n=17) and curcumin group ( n=18). The diabetic model group continued to be fed with high sugar and high fat diet, and the curcumin group was given high sugar and high fat diet and 200 mg/(kg·d) curcumin (1% carboxymethyl fiber sodium prepared into suspension) intervention every day; while the normal control group and the diabetic model group were given 1% carboxymethyl fiber sodium of the same volume. The body weight, kidney index, blood glucose , serum creatinine, urea nitrogen, blood lipid and 24-hour urinary microalbumin excretion rate (24 h UAER) of rats in each group were measured. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and m-alondialdehyde (MDA) in serum and kidney tissues were measured. Results:Compared with the control group, the levels of the body weight, kidney index, blood glucose, serum creatinine, urea nitrogen, triglyceride, total cholesterol and 24 h UAER in the diabetic model group increased significantly. The level of MDA in serum and kidney tissues increased significantly ( P<0.05), while the levels of SOD, CAT and GSH-Px activities in serum and kidney tissues decreased significantly ( P<0.05). Compared with diabetic model group, the levels of the body weight increased, while the kidney index, blood glucose, serum creatinine, urea nitrogen , triglyceride, total cholesterol and 24 h UAER in the curcumin group decreased significantly, the level of MDA in serum and kidney tissues decreased significantly ( P<0.05); the levels of SOD, CAT and GSH-Px in serum and kidney tissues increased significantly ( P<0.05) in the curcumin group. Conclusions:Curcumin may play a renal protective role in diabetic rats by inhibiting oxidative stress in serum and kidney and reducing blood lipid.
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Objective To evaluate the effect of chidamide combined with matrine on proliferation and apoptosis of cutaneous T-cell lymphoma (CTCL) cell lines HH and Hut78,and to explore their apoptotic mechanisms.Methods Both HH and Hut78 cells were treated with 0.4 μmol/L chidamide and 0.6 g/L matrine alone or in combination for 24,48 and 72 hours,with those treated with dimethyl sulfoxide (DMSO) serving as control groups.MTS assay was performed to deteet cellular proliferation rates of HH and Hut78 cells at each time point.After 48-hour treatment,flow cytometry was conducted to detect cell apoptosis,and Western blot analysis to determine expression of apoptosis-related proteins in these cells.Statistical analysis was carried out by using repeated measures analysis of variance,one-way analysis of variance,and least significant difference (LSD)-t test for multiple comparisons.Results Compared with DMSO,chidamide and matrine alone or in combination could inhibit the proliferation of HH and Hut78cells to different extents (F =15.88,558.26,P < 0.05,< 0.001,respectively).At 48 hours,the apoptosis rate in Hut78 cells was significantly higher in the matrine group (20.98% ± 1.53%),chidamide group (22.44% ± 7.74%) and combination group (44.53% ± 1.85%) than in the control group (8.42% ± 4.23%;LSD-t =4.76,5.31,13.69 respectively,all P < 0.05),as well as in the combination group than in the matrine group and chidamide group (LSD-t =8.93,8.37 respectively,both P < 0.01);no significant differences were observed in the apoptosis rate of HH cells between the matrine group (13.98% ± 3.86%)or chidamide group (13.61% ± 1.62%) and control group (11.44% ± 1.43%,both P > 0.05),while the combination group (20.94% ± 0.64%) showed a significantly higher apoptosis rate compared with the control group,matrine group and chidamide group (LSD-t =7.37,5.40,5.69 respectively,all P < 0.05).In the case of HH cells,the combination group showed significantly higher cleaved caspase-3 expression (all P < 0.05),but significantly lower protein expression of E-cadherin,nuclear factor (NF)-κB,phosphorylated-Bad (p-Bad) and Bcl-2 compared with the other 3 groups (all P < 0.05).In the case of Hut78 cells,the expression of E-cadherin,NF-κB,p-Bad and Bcl-2 was significantly lower in the matrine group,chidamide group and combination group than in the control group (all P < 0.05),while cleaved caspase-3 expression was significantly higher in the chidamide group and combination group than in the control group (both P <0.05).No matter in HH cells or in Hut78 cells,there were no significant differences in Bad protein expression between the 4 groups (all P > 0.05).Conclusion Chidamide in combination with matrine can inhibit proliferation and induce apoptosis of HH and Hut78 cells,likely by regulating the expression of apoptosis-related proteins E-cadherin,NF-κB,p-Bad,Bcl-2 and cleaved caspase-3.
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OBJECTIVE:To study in vi tro inhibitory act ivities of 9 kinds of TCM for dredging collaterals and dispelling wind on xanthine oxidase (XO),and to screen TCM with outstanding activity. METHODS :Using xanthine as substrate and xanthinase as reaction enzyme ,allopurinol as positive control ,with water extract and methanol extract (hereinafter referred to as “ethanol extract”)from the stem and leaves of Hedera nepalensis ,the whole plant of Piper wallichii ,the fruits of Rubus corchorifolius ,the root of Caragana sinica ,the root of Wisteria sinensis ,the root of Rubus crataegifolius ,the bark of Catalpa ovata ,the root of Campsis grandiflora ,the stem of P. hancei (hereinafter referred to by plant name )and petroleum ether ,dichloromethane,ethyl acetate,n-butanol and water fraction of active extract as the objects ,inhibition rate of each sample to XO was detected by spectrophotometry;IC50values were calculated with Graphpad prism 6.0 software to screen active extract/fraction. Double reciprocal method was used to determine the type of enzyme inhibition. RESULTS :Among 9 kinds of TCM and 18 kinds of the extracts ,the inhibitory rates to XO of 500 μg/mL extracts from each TCM(except for ethanol extract of P. wallichii ),250 μg/mL water extract and ethanol extract of H. nepalensis ,P. wallichii ,R. corchorifolius and P. hancei ,250 μg/mL water extract of C. ovata ,250 μ g/mL ethanol extract of C. sinica ,R. crataegifolius and C. grandiflora ,125 μ g/mL ethanol extract of C. sinica and R. crataegifolius,62.5 μg/mL ethanol extract of C. sinica were more than 50%. The IC 50 value of the ethanol extract from C. sinica was 43.43 μg/mL,which was lower than the extracts of other TCM ,and which was the active extract. The IC 50 values of petroleum ether,dichloromethane,ethyl acetate ,n-butanol and water fracti on of ethanol extract from C. sinica were >200,193.35,7.67, 14.80 and >200 μg/mL,respectively. The IC 50 value of ethyl XO was competitive-noncompetitive inhibition , which was different from competi tive inhibition of positive control. CONCLUSIONS:The ethanol extracts of C. sinica ,R. crataegifolius ,P. wallichii ,R. corchorifolius ,P. hancei ,H. nepalensis and the water extracts of H. nepalensis ,P. wallichii ,C. ovata show certain inhibitory activity in vitro to XO ,especially ethanol extract of C. sinica . The ethyl acetate fraction of the ethanol extract of C. sinica has similar inhibitory activity to allopurinol but their inhibition types are different.
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Objective To evaluate the efficacy of long-term treatment with infliximab in patients with moderate to severe psoriasis vulgaris.Methods Patients with moderate to severe psoriasis vulgaris,who started infliximab therapy in Department of Dermatology,Peking University Third Hospital between March 2016 and May 2018,were followed up.The patients treated with infliximab for more than 54 weeks were enrolled into this study.The patients were treated with infliximab at a weight-based dosage of 5 mg/kg,and the total dosage used per session was 200,300 and 400 mg for patients with the body weight of 40-59 kg,60-79 kg,and > 80 kg respectively.The patients were treated at week 0,2,6,14,22,30,38,46 and 54,and the psoriasis area and severity index (PASI) score was determined before each treatment.Mauchly's test of sphericity,randomized block analysis of variance and Bonferroni method were used to analyze changes of PASI scores after 2-,6-,14-,22-,30-,38-,46-and 54-week treatment.Sequelae and adverse reactions were also recorded.Results Twelve patients received the treatment with infliximab,and 9 patients were treated for more than 54 weeks,whose clinical data were analyzed.Before the treatment,the PASI score (M[P25,P75]) of the 9 patients was 26.3 (23.4,27.7).There were significant differences in the PASI score among different time points (F =7.12,P =0.0004),and the PASI score of the patients showed a generally decreasing trend over time.After 30-week treatment,the PASI score was 4 (2.5,5.2),and the PASI improvement rate was 86.38% ± 6.98%;of the 9 patients,8 achieved PASI50,7 achieved PASI75,and 2 achieved PASI90.After 54-week treatment,the PASI score was 8 (3.5,8.9),the PASI improvement rate was 64.23% ± 17.32%,and the number of patients achieving PASI50,PASI75 and PASI90 was 8,4 and 1 respectively.Bonferroni method showed that the PASI score significantly increased at week 54 compared with that at week 30 (t =3.269,P =0.0048),but significantly decreased at weeks 30 and 54 compared with that before the treatment(week 30:t =18.49,P < 0.0001;week 54:t =5.81,P =0.0004).Conclusion Infliximab is remarkably effective for moderate and severe psoriasis vulgaris in the 54-week treatment.
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Objective To explore and establish a method for quantitative evaluation of facial skin pores based on dermoscopy,and to evaluate the scientificity and practicability of this method.Methods Totally,30 patients with enlarged facial skin pores were enrolled from Department of Dermatology,Peking University Third Hospital between June 2017 and December 2017,and treated with 2 940 nm Er pixel laser.Photographs were taken,and dermoscopic images were collected before and after treatment.According to the standard photographs of facial pores,the improvement of enlarged facial pores was evaluated by comparing the photos before and after the treatment.A dermoscope-based pore detection system was established,and quantified indices for pore area and color difference before and after the treatment were evaluated by using this system.A pre-post self-contrast study was conducted,and statistical analysis was carried out by using paired t test for the comparison of measurement data and paired non-parametric test (Wilcoxon signed-rank test) for the comparison of ranked data.Results After the treatment,the standard photograph method for the assessment of facial pores showed score reduction by 3 grades in 1 of the 30 patients (3.3%),by 2 grades in 7(23.3%),by 1 grade in 21(70%),and no changes of grades in 1 (3.3%).Additionally,the differences between pre-and post-treatment grades were significant (Z =-4.94,P < 0.01).The detection rate of skin pores by using the detection system was (70.59 ± 3)%.After the treatment,the quantified values of pore area and color difference both significantly decreased compared with those before the treatment (pore area:712.95 ± 87.45 vs.831.45 ± 88.92,t =5.70,P < 0.05;color difference:23.82 ± 9.43 vs.28.92 ± 9.91,t =2.76,P < 0.05).Conclusion The dermoscopy-based method for quantitative evaluation of skin pores after the treatment with 2 940 nm Er pixel laser showed highly consistent results with the standard photograph method,which can be further verified and popularized in the evaluation of enlarged skin pores.