BACKGROUND:Psoriasis affects approximately 2% of the global population, with the IL-17A-STAT3 pathway mediating abnormal keratinocyte proliferation and inflammatory amplification. Solanum lyratum (Bai Ying) has long been used for skin disorders, and its steroidal alkaloids have anti-inflammatory potential, though the mechanisms remain unclear. OBJECTIVE:To elucidate the molecular basis and cytological efficacy of S. lyratum steroidal alkaloids in exerting anti-psoriatic effects via the IL-17A/STAT3 axis. METHODS:HPLC-MS-QTOF, network pharmacology, molecular simulation, and a HaCaT cell model with STAT3-siRNA assays were employed. RESULTS:Eighteen components were identified; steroidal alkaloids showed high affinity for STAT3 and IL17RA. S. lyratum (5-40 μg/mL) enhanced cell viability, inhibited p-STAT3 (IC50 = 14.30 μg/mL), and attenuated inflammatory responses and keratinocyte proliferation. CONCLUSION:S. lyratum steroidal alkaloids exert dual-targeted blocking effects on the IL-17A/STAT3 axis, supporting it as a potential therapeutic candidate for psoriasis.

Inspection is the first of the four diagnoses.Skin inspection is not only an important part of the four diagnoses of Chinese medicine,but also the characteristic and essence of Chinese dermatology.The development of artificial intelligence(AI)technology provides an opportunity for the intelligent research of skin inspection in traditional Chinese medicine(TCM).This study aims to review the application status of artificial intelligence in TCM skin inspection,and summarize the research progress of various artificial intelligence technologies in skin lesion differentiation,syndrome differentiation and location differentiation,and propose future directions for AI empowerment in TCM dermatology.Based on the basic theory of Chinese medicine and skin clinical thinking of Chinese medicine,this article puts forward the prospect of AI empowerment from the aspects of macro and micro combination,point and surface combination,mind-body combination and time-space combination.This study discusses the existing problems and challenges in the intersection of AI and TCM dermatology.The intersection of AI and TCM dermatological inspection is at the developmental stage.AI has broad application prospects within TCM dermatology,but it also faces numerous challenges.While AI offers opportunities to modernize TCM dermatology,challenges such as aligning AI with TCM's holistic principles and ensuring clinical relevance remain.Further research integrates AI with TCM skin inspection methods,the intricate connotations and applications of TCM dermatological Inspection will be fully realized,thereby providing reference for the development of artificial intelligence to help TCM dermatology diagnosis and treatment technology.

Ethnopharmacological relevance: The inflammatory skin condition psoriasis is immune-related. The decoction of Jianpi-Yangxue-Jiiedu (JPYX) is a useful medication for psoriasis. However, the underlying mechanics of JPYX have not yet been clarified. Aim of the study: The objective of this study was to investigate the mechanism underlying the efficacy of JPYX in the treatment of psoriasis in the context of a high-fat diet. Materials and methods: This work generated a high-fat feeding model of imiquimod (IMQ)-induced psoriasis-like lesion mice. The blood composition of JPYX was examined using ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS). The mechanism of JPYX decoction for treating psoriasis was predicted using methods of network pharmacology, metabolomics, and transcriptomics. Results: JPYX prevented the release of inflammatory cytokines, decreased keratinocyte proliferation, enhanced the percentage of Treg cells in the skin, lymph nodes, and thymus, and greatly alleviated psoriatic lesions. Network pharmacology predicted that IL-1 beta, TNF, STAT3, and EGFR may be potential targets, and KEGG results showed that PI3K-AKT-mTOR may be a potential mechanism of action. Verification of experimental data demonstrated that the JPYX decoction dramatically decreased mTOR and AKT phosphorylation. According to metabolomics analysis, amino acids and their metabolites, benzene and its substitutes, aldehyde ketone esters, heterocyclic compounds, etc. were the primary metabolites regulated by JPYX. KEGG enrichment analysis of differential metabolites was performed. Fatty acid biosynthesis, Type I polyketide structures, Steroid hormone biosynthesis, Biosynthesis of unsaturated fatty acid, etc. Transcriptomic results showed that JPYX significantly regulated skin development, keratinocyte differentiation, and oxidative phosphorylation. Further experimental data verification showed that JPYX decoction significantly reduced the mRNA levels of mt-Nd4, mt-Nd5, mt-Nd1, Ifi205, Ifi211, and mt-Atp8. Conclusions: JPYX may improve psoriasis by regulating the metabolic pathways of fatty acids and electron transport of oxidative phosphorylation.

目的 采用数据挖掘分析的方法,分析寻常型银屑病中医治疗有效处方的用药规律.方法 病历数据来自2019年7月—2021年12月就诊于12个中心并纳入"银屑病患者注册登记平台"进行统一管理的患者病历.建立数据库,采用频数统计及关联规则等数据挖掘方法对中医治疗银屑病用药进行统计分析.结果 达到银屑病面积与严重性指数(PASI)≥75的患者100例,涉及方剂603首,其中解毒类药物应用最多,土茯苓、甘草、紫草、白花蛇舌草、升麻等为应用频次最多的药物.对药物间关联规则进行挖掘,得到关联例数＞150药物的关联规则20条,进一步对高频中药系统聚类分析,得到3组核心药物组合和潜在新方组成.结论 临床治疗银屑病时解毒药物应用最多,在此基础上配伍解表、活血、养血等药物.

目的 探讨低强度聚焦超声联合耳穴压豆对剖宫产术后产妇泌乳的应用效果.方法 将100例剖宫产术后产妇随机分为对照组和观察组各50例,对照组行常规母乳喂养护理,观察组在对照组基础上增加低强度聚焦超声联合耳穴压豆干预.结果 观察组泌乳始动时间、泌乳素水平、乳汁分泌情况、乳房肿胀程度、乳房胀痛VAS评分及纯母乳喂养率显著优于对照组(均P＜0.05).结论 低强度聚焦超声联合耳穴压豆可有效促进产妇泌乳,改善乳房胀痛情况,提高纯母乳喂养率.

BACKGROUND Myristicin is a type of natural compound showing anti-proliferative, anti-microbial, and anti-inflammatory effects. However, its role in gastric cancer treatment remains unknown. Objective: In this study, the effect of myristicin on gastric cancer as well as its underlying mechanism was investigated. Methods: Human gastric cancer cells were exposed to various concentrations of myristicin (0, 7.8125, 15.625, and 31.25 μM) for 48 h. Then CCK-8, fluorescence-activated cell sorting, and Hoechst staining were performed to evaluate the cell proliferation and apoptosis. The levels of proteins associated with cell cycle, apoptosis, endoplasmic reticulum (ER) stress, and EGFR/ERK signaling pathway were detected by western blot. JC-1 staining was conducted to determine the mitochondrial membrane potential. On the other hand, the effect of myristicin on gastric cancer growth and apoptosis was also determined in vivo. Results: Myristicin retarded proliferation and induced ER stress and apoptosis in gastric cancer cells, with decreased expression of cyclins, increased Bax expression, activated caspases, and enhanced cytochrome C release and mitochondrial ROS. Furthermore, the EGFR/ERK signaling pathway was restrained by myristicin. In addition, EGFR over-expression abolished the inhibitory function of myristicin on proliferation, apoptosis, and ER stress. Also, myristicin inhibited the growth of gastric cancer cells as well as the EGFR/ERK signaling pathway in vivo. Conclusion: Myristicin exerts an anti-cancer effect on gastric cancer cells by restraining the EGFR/ ERK signaling pathway. It may have the potential to be applied as a novel drug in gastric cancer treatment.

皮肤科疾病是一类临床常见疾病,且病种繁多,影响患者工作、生活.现代医学治疗皮肤科疾病已取得一定进展,但存在容易耐受或依赖、不良反应多、易复发等问题.中医治疗皮肤病历史悠久,火针是传统中医特色疗法之一,有完善的理论体系,尤其在皮肤科领域具有疗效独特、适应证广泛、安全性好、操作简便等优势,逐渐成为研究热点.但目前关于火针操作及诊疗评估尚缺乏国际公认的规范,研究级别较低,因此未来应合理设置样本量、对照干预、疗效指标等,完善高质量的随机对照试验证据,促进火针在皮肤科疾病治疗中的临床应用.

Conventional cancer targeting methodology needs to be reformed to overcome the intrinsic barriers responsible for poor targeting efficiency. This study describes a concept of self-reinforced cancer targeting (SRCT) by correlating targeting with therapy in a reciprocally enhancing manner. SRCT is achieved on the basis of two prerequisites: (1) target molecules have to be expressed on cancer cell membranes but not on normal cells, and (2) notably, their expression on cancer cells must be actively upregulated in response to cellular attack by cancer treatments. As a proof-of-concept, a GRP78-targeting nanovehicle for chemotherapy was designed. Resultant data showed that chemotherapeutic drugs could effectively elevate GRP78 expression on the plasma membranes of cancer cells while having minimal influence on normal cells. DOX pretreatment of cancer cells and tumor tissues can greatly increase the targeting efficacy and therapeutic performance of the prepared GRP78-targeting nanomedicine while somewhat disfavoring the nontargeting counterpart. In vivo and in vitro results demonstrated that this GRP78-targeting nanomedicine could accurately target cancer cells to not only implement chemotherapy but also induce GRP78 upregulation on cancer cells, eventually benefiting continuous cancer-cell-targeted attack by the nanomedicines remaining in the blood circulation or administered in the next dose. The GRP78-targeting nanomedicine displays much better antitumor performance compared with the nontargeting counterpart. SRCT is expected to advance cancer-targeted therapy based on the positive dependency between targeting and therapeutic modalities.

Psoriasis is a common chronic inflammatory hypertrophic skin disease characterized by abnormal proliferation and differentiation of keratinocyte and immune T cell. The pathogenesis of psoriasis has not been fully elucidated and there is no effective therapy in clinic. As a traditional Chinese medicine formula, Yangxue Jiedu Soup (YJS) has been used to treat inflammatory diseases caused by Yin Deficiency and Blood Dryness. The purpose of present study was to investigate the therapeutic effect and molecular mechanism of YJS on psoriasis model mice. Results showed that YJS effectively inhibited the hypertrophy, erythema and scales of psoriasis-like lesions to alleviate the pathological changes of skin lesions, and further decreased the production of TNF-α, IL-6, IL-1β, IFN-γ, IL-17 and IL-23. Meanwhile, YJS also significantly reduced keratinocyte proliferation and maintained immune system balance by inhibiting the expression of PCNA, Ki-67, CD4 + and CD8 + in psoriasis mice. Moreover, the results further indicated that YJS could inhibit TLR4 activation and NF-κB p65 nuclear transfer by suppressing HSP70 secretion to attenuate the inflammatory response in IMQ-induced mice, which provided a theoretical basis for the clinical use of YJS in the treatment of psoriasis.

OBJECTIVE:To observe the effect of moxibustion on skin lesions and immune inflammatory response in psoriasis mice, and to explore the possible mechanism of moxibustion for psoriasis.METHODS:A total of 32 male BALB/c mice were randomly divided into a normal group, a model group, a moxibustion group and a medication group, 8 mice in each group. Psoriasis model was induced by applying 5% imiquimod cream on the back for 7 days in the model group, the moxibustion group and the medication group. At the same time of model establishment, the moxibustion group was treated with suspension moxibustion on skin lesions on the back, 20 min each time, once a day; the medication group was treated with 1 mg/kg methotrexate tablet solution by gavage, once a day. Both groups were intervened for 7 days. The daily changes of skin lesions were observed, and the psoriasis area and severity index (PASI) score was evaluated; the histopathological changes of skin lesions were observed by HE staining; the positive expression of proliferating cell nuclear antigen (PCNA) and T lymphocyte surface marker CD3 were detected by immunohistochemistry; the expression level of serum interleukin (IL) -17A was detected by ELISA, and the relative expressions of tumor necrosis factor-α (TNF-α), IL-1β and IL-6 mRNA in skin lesions were detected by real-time PCR.RESULTS:The increased and hypertrophy scale, dry skin, red and swollen epidermis and obvious infiltration were observed in the model group, and each score and total score of PASI were higher than those in the normal group (P<0.01). The scale score, infiltration score, and total score of PASI in the moxibustion group were lower than those in the model group (P<0.01); the infiltration score and total score of PASI in the medication group were lower than those in the model group (P<0.01, P<0.05). The inflammatory cell infiltration in the model group was obvious, and the thickness of epidermal layer was increased compared with that in the normal group (P<0.01); the inflammatory cell infiltration and Munro micro abscess were decreased in the moxibustion group and the medication group, and the thickness of epidermal layer was decreased compared with that in the model group (P<0.01). Compared with the normal group, the positive cell number of PCNA and T was increased (P<0.01), and the body mass was decreased, and the spleen index was increased (P<0.01), and the expression of serum IL-17A and the relative expression of TNF-α, IL-1β and IL-6 mRNA in the skin lesions was increased in the model group (P<0.01). Compared with the model group, the positive cell number of PCNA and T was reduced (P<0.01), and the spleen index and the relative expression of TNF-α, IL-1β and IL-6 mRNA were reduced (P<0.01) in the moxibustion group and the medication group; the body mass of mice in the moxibustion group was higher than that in the model group (P<0.01); the content of serum IL-17A in the medication group was lower than that in the model group (P<0.01); the relative expression of TNF-α, IL-1β mRNA in the moxibustion group was higher than that in the medication group (P<0.01).CONCLUSION:Moxibustion could effectively improve the scale and infiltration of skin lesions in psoriasis mice. Its mechanism may be related to inhibiting inflammatory response and regulating immunity.

目的:观察齐墩果酸对咪喹莫特诱导的银屑病样小鼠的皮损及STAT3通路的干预作用.方法:72只BALB/c雄性小鼠,按随机数字表法随机分为空白组、模型组、甲氨蝶吟组、齐墩果酸低、中、高剂量组,每组12只,于背部备皮.除空白组外,其余各组小鼠每日于背部备皮区域涂抹5％咪喹莫特乳膏诱导银屑病样皮损;甲氨蝶呤组及齐墩果酸各浓度组每日灌胃对应药物0.2 mL/只;每日观察皮损状态并拍照记录,每日对小鼠皮损面积及严重程度(Psoriasis Area and Severity Index,PASI)进行评分;造模第4、7天取小鼠皮损区域皮肤,免疫印迹法检测皮损中STAT3信号通路中STAT3磷酸化表达情况;第7天称量小鼠体重及脾重,计算脾指数,同时取小鼠皮损区域皮肤;苏木素-伊红(HE)染色观察皮损组织病理学改变,并测量表皮厚度;免疫组织化学法及免疫组织荧光法检测皮损中CD3+、CD4+、CD8+T细胞浸润情况及Ki67表达情况;实时荧光定量PCR法检测皮损中白介素-17(Interleukin-17,IL-17)mRNA相对表达情况.结果:与空白组相比,造模后模型组小鼠背部皮肤出现红斑、鳞屑、浸润性皮损,第4天及第7天PASI评分升高(P＜0.01);第7天模型组表皮厚度明显增加,体重下降,脾指数上升,皮损中Ki67、CD3+、CD4+、CD8+T细胞表达量升高,皮损中IL-17的mRNA相对表达量升高(均P＜0.01);第4及第7天,模型组小鼠皮损中p-STAT3的表达量均明显升高(P＜0.05,P＜0.01);与模型组相比,第4天各治疗组在PASI评分略降低(P＞0.05),第7天各治疗组PASI评分明显降低(均P＜0.01);第7天齐墩果酸各剂量组小鼠体重略有上升(P＞0.05);甲氨蝶吟组小鼠脾指数明显下降(P＜0.01),齐墩果酸低、中剂量组小鼠脾指数略下降(P＞0.05);各治疗组小鼠表皮厚度较模型组明显下降(P＜0.01或P＜0.05),小鼠皮肤中Ki-67表达量、CD4+、CD8+T细胞表达量均明显降低(均P＜0.01);甲氨蝶呤组、齐墩果酸低、中、高剂量组小鼠皮损中CD3+T细胞表达量均下降(P＜0.05,P＞0.05,P＜0.01,P＜0.01),其中在齐墩果酸各剂量组中,中剂量组在脾指数下降、表皮厚度变薄、CD3+、CD4+、CD8+T细胞减少方面均略优于低、高剂量组(P＞0.05);甲氨蝶呤组及齐墩果酸中剂量组小鼠皮损中IL-17的mRNA水平较模型组明显下降(P＜0.01,P＜0.05);造模给药第4天,甲氨蝶呤组小鼠皮损中p-STAT3水平较模型组明显下降(P＜0.05),齐墩果酸中剂量组略下降(P＞0.05);造模给药第7天,两个治疗组小鼠皮损中p-STAT3水平较模型组均明显下降(均P＜0.01).结论:齐墩果酸低、中、高剂量均可以改善咪喹莫特诱导的小鼠银屑病样皮损的严重程度,减轻炎性细胞浸润,中剂量组疗效较好,其机制可能通过抑制STAT3通路中p-STAT3的表达从而降低了 IL-17的含量,且药效随作用时间的延长而逐渐增加.

OBJECTIVE:To observe the effect of fire needling on psoriasis-like lesion and the signal transducer and activator of transcription 3 (STAT3) pathway in mice and compare the therapeutic effect between different interventions of fire needling therapy (surrounding technique of fire needling, fire needling at "Dazhui" [GV 14] and "Zusanli" [ST 36]).METHODS:Thirty male BALB/c mice were randomized into a blank group, a model group, a dexamthasone group, a surrounding technique group and an acupoint group, 6 mice in each one. Except the blank group, the mice in the rest groups were established as psoriasis-like lesion model by topical application with imiquimod cream, once daily, consecutively for 8 days. From day 4 to day 8, in the dexamthasone group, gastric infusion with 0.2 mL dexamthasone was administered, once daily. On day 4, 6 and 8, in the surrounding technique group, fire needling was exerted around the skin lesion; and fire needling was applied to "Dazhui" (GV 14) and "Zusanli" (ST 36) in the acupoint group, once a day. The changes in skin lesion on the dorsal parts of mice were observed in each group to score the psoriasis area and severity index (PASI). Using HE staining, the dermal morphological changes and epidermal thickness were observed in the mice of each group. The positive expression of proliferating cell-associated antigen Ki-67 was determined by immunofluorescence. Immunohistochemistry method was used to determine the expressions of , and T cells of skin tissue in each group. Using real-time PCR, the expressions of interleukin (IL)-17, IL-22, tumor necrosis factor α(TNF-α) mRNA were determined. Western blot method was adopted to determine the protein expressions of STAT3 and p-STAT3 in skin tissue in each group.RESULTS:Compared with the blank group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all increased in the mice of the model group (P<0.01). Except for the erythema scores of the dexamethasone group and the surrounding technique group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all decreased in each intervention group as compared with the model group (P<0.01). The infiltration scores and the total scores in the dexamethasone group and the acupoint group were lower than those in the surrounding technique group respectively (P<0.01, P<0.05). In comparison with the blank group, Ki-67 positive cell numbers and the numbers of , and T cells in skin tissue were increased in the mice of the model group (P<0.01). Ki-67 positive cell numbers and the numbers of , and T cells were reduced in each intervention group as compared with the model group (P<0.01), and the numbers of and T cells in the acupoint group were less than the surrounding technique group (P<0.01). Compared with the blank group, the mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all increased in the model group (P<0.01). The mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all decreased in each intervention group as compared with the model group (P<0.01, P<0.05). The mRNA expressions of IL-17, IL-22 and TNF-α in the acupoint group, as well as mRNA expression of IL-17 in the surrounding technique group were all lower than the dexamethasone group (P<0.01), while, the mRNA expression of IL-22 in the acupoint group was lower than the surrounding technique group (P<0.01).CONCLUSION:Fire needling therapy improves skin lesion severity in imiquimod induced psoriasis-like lesion of the mice, which is probably related to the inhibition of STAT3 pathway activation and the decrease of Th17 inflammatory factors expression. The systemic regulation of fire needling at "Dazhui" (GV 14) and "Zusanli" (ST 36) is superior to the local treatment.

Psoriatic skin inflammation is mainly driven by complex interactions of infiltrating immune cells and activated keratinocytes. Keratinocytes play an active role in initiating and maintenance of psoriatic skin inflammation by secreting chemokines and cytokines. IL-17A produced by T cells potently upregulates the production of chemokine CCL20 in the keratinocytes, which further chemoattracts IL-17A-producing CCR6+ immune cells to the site of inflammation. Indirubin, an active constituent of indigo naturalis, has been reported to possess anti-inflammatory activities, but whether it can suppress the production of chemokines in keratinocytes is largely unknown. To address this question, IL-17A stimulated HaCaT cells were used as cell model to explore the effects of indirubin on the expression and secretion of chemokines. Also, RNA-seq analysis was performed to extensively understand the entire gene expression changes after indirubin treatment and identify the differentially expressed genes further. Indirubin treatment strongly inhibited CCL20 expression and secretion in IL-17A stimulated HaCaT cells. The inhibitory action of indirubin on CCL20 expression was mainly mediated by TAK1 signaling pathway in a mouse psoriasis-like model and cultured HaCaT cells in vitro. Combining with our previous report, indirubin ameliorated psoriasiform dermatitis by breaking CCL20/CCR6 axis-mediated inflammatory loops. Our results provide novel insights into the mechanisms of indirubin in the treatment of psoriasis.

Gut microbiota is closely related to the tumorigenesis and progression of colorectal cancer (CRC), especially Fusobacterium nucleatum (Fn) could promote colorectal tumor growth and cause chemoresistance. Here, we developed a tumor-triggered release drug delivery gel to inhibit CRC cell growth in situ by intestinal perfusion. Antibiotic metronidazole (MTZ) and 5-fluorouracil (5-FU), the first-line chemotherapy drug of CRC, are individually incorporated into metal polyphenol network-coated mesoporous silica nanoparticle (MSN), and then blended with carboxymethyl cellulose (CMC) to obtain an anti-CRC gel, AB-Gel. In vivo studies showed that AB-Gel could efficiently inhibit the growth and metastasis of CRC in an orthotopic mouse model attributing to the MTZ-induced modulation in the CRC-related microbiota. Chemotherapy efficacy against orthotopic CRC was significantly enhanced by the elimination of Fn. This strategy based on the combination of gut microbiota modulation and chemotherapy would be considered as an enhanced strategy for CRC treatment with potential use in the clinic.

银屑病是一种复杂的慢性复发性炎症性疾病,不仅存在组织不可逆的损伤和免疫异常,还存在干细胞的严重异常.干细胞异常表达了表皮增生、血管生成和炎性反应等相关基因,还分泌了细胞生长因子(EGF)、血管内皮生长因子(VEGF)、炎性因子、免疫细胞趋化因子等,在银屑病的发病中有着重要的作用.本文对间充质干细胞(MSC)、表皮干细胞(ESC)、造血干细胞(HSC)在银屑病发病中的作用机制进行综述.

Clinical studies have demonstrated the anti-psoriatic effect of the LiangXueJieDu (LXJD) herbal formula. However, the systemic mechanism and the targets of the LXJD formula have not yet been elucidated. In the present study, a systems pharmacology approach, metabolomics, and experimental evaluation were employed. First, by systematic absorption-distribution-metabolism-excretion (ADME) analysis, 144 active compounds with satisfactory pharmacokinetic properties were identified from 12 herbs of LXJD formula using the TCMSP database. These active compounds could be linked to 125 target proteins involved in the pathological processes underlying psoriasis. Then, the networks constituting the active compounds, targets, and diseases were constructed to decipher the pharmacological actions of this formula, indicating its curative effects in psoriasis treatment and related complications. The psoriasis-related pathway comprising several regulatory modules demonstrated the synergistic mechanisms of LXJD formula. Furthermore, the therapeutic effect of LXJD formula was validated in a psoriasis-like mouse model. Consistent with the systems pharmacology analysis, LXJD formula ameliorated IMQ-induced psoriasis-like lesions in mice, inhibited keratinocyte proliferation, improved keratinocyte differentiation, and suppressed the infiltration of CD3+ T cells. Compared to the model group, LXJD formula treatment remarkably reduced the expression of inflammatory cytokines and factors, such as IL-1β, IL-6, TNF-α, Cox2, and inhibited the phosphorylation of p-P65, p-IқB, p-ERK, p-P38, p-PI3K, p-AKT, indicating that LXJD formula exerts its therapeutic effect by inhibiting the MAPK, PI3K/AKT, and NF-қB signaling pathways. The metabolic changes in the serum of psoriasis patients were evaluated by liquid chromatography coupled with orbitrap mass spectrometry (LC-MS). The LXJD formula improved two perturbed metabolic pathways of glycerophospholipid metabolism and steroid hormone biosynthesis. Overall, this study revealed the complicated anti-psoriatic mechanism of LXJD formula and also offered a reliable strategy to elucidate the complex therapeutic mechanism of this Chinese herbal formula in psoriasis from a holistic perspective.

BACKGROUND:psoriasis is a chronic inflammatory skin disease. The accumulation of IL-17 cytokines in the lesions leads to epidermis proliferation. Traditional Chinese medicine has a significant effect on psoriasis treatment. Among them, Tuhuaiyin is a representative prescription, which has an outstanding curative effect in acute and remission stage.METHODS:To reveal the target and molecular mechanism of Tuhuaiyin, systematic pharmacology platform and database screening were used to construct the Tuhuaiyin interaction network with compounds, targets and diseases. The intervention of Tuhuaiyin on keratinocyte proliferation and inflammation was verified in the model of psoriasis-like lesions induced by imiquimod. The effect on the number and function of IL-17-producing cells was detected, and the regulatory effect of Tuhuaiyin on gut microbial was explored.RESULTS:32 selected active molecules in Tuhuaiyin acted on psoriasis biological processes. Tuhuaiyin significantly alleviates erythema and scales in the psoriasis like mouse model induced by imiquimod. Excessive proliferation of keratinocytes and infiltration of inflammatory cells were restrained in the dermis by using Tuhuaiyin. The expression of IL-17 was down-regulated in skin and peripheral blood. The proportion of IL-17-producing cells was decreased in immune organs. And phosphorylation of JNK inhibited in skin lesions. At the same time, the change of gut microbial diversity in the psoriasis-like model was improved.CONCLUSION:our study predicted and verified the molecular immunological mechanism of Tuhuaiyin, alleviated the abnormal proliferation of keratinocytes by inhibiting the proportion of IL-17-producing cells and the expression of IL-17 cytokines. Taken together, our data identify the therapeutic potential of Tuhuaiyin for psoriasis.

慢性瘙痒病因复杂,易出现“搔抓-加重-搔抓”的恶性循环.全虫方是皮外科专家赵炳南先生的经验方,对于控制慢性瘙痒症状以及促进皮损消退疗效突出,临床常用于治疗结节性痒疹、慢性湿疹、慢性荨麻疹等疾病.在临床中“辨证”是全虫方遣方用药、加减化裁的关键.李萍教授运用“证同治亦同”的中医基础理论,根据临床患者疾病不同发展阶段以及不同临床表现,“辨证论治”和“辨症论治”相结合,灵活化裁,同时将全虫方应用慢性斑块型银屑病和皮肤淀粉样变,拓展了全虫方的应用范围.

目的 探讨脾虚在银屑病炎症反应相关发病环节中的作用机制.方法 采用苦寒泻下结合营养限制法建立脾虚小鼠模型,采用咪喹莫特诱导银屑病样皮损模型.小鼠随机分为正常对照组(Ctrl)、脾虚组(PD)、银屑病样模型组(IMQ)、脾虚复合银屑病样模型组(PD-IMQ),实时定量荧光PCR检测皮损和小肠中银屑病相关基因表达水平,液相蛋白芯片检测外周血中银屑病相关细胞因子和趋化因子的含量,肠道菌群16S测序分析各组菌群多样性.结果 PD-IMQ组皮损红斑、鳞屑等炎症浸润表现更加严重,皮损中白介素(IL)-17a、IL-23、IL-6、TGF-β、IL-10和IL-18 mRNA较IMQ组显著升高;PD-IMQ组外周血中IL-17A、巨噬细胞炎性蛋白(MIP)-1α、MIP-1β、MIP-2、单核细胞趋化蛋白(MCP)-1、MCP-3、RANTES、IP-10和Eotaxin的含量明显高于IMQ组,ST2含量显著低于IMQ组;PD-IMQ组小肠中IL-17a和RORγt mRNA显著高于IMQ组;PD-IMQ组肠道菌群的丰富度和均匀度降低,与IMQ组比较,AF12菌属的相对丰度显著升高,TM7菌门、TM7-3菌纲、CW040菌目和F16菌科的相对丰度显著减低.结论 脾虚可加重咪喹莫特诱导的小鼠银屑病样模型对促炎因素的响应程度,通过上调IL-17相关细胞因子和趋化因子的表达水平及脂代谢紊乱相关菌属AF12的丰度,导致严重的银屑病样皮损改变.

Psoriasis is a skin disease with autoimmune tendency, and taxifolin is an effective flavonoid with antiinflammatory activity. It has been reported that taxifolin alleviates psoriatic dermatitis, but the detailed regulatory mechanism of keratinocyte proliferation is unclear. In this study, we revealed the mechanism of taxifolin on imiquimod-induced inflammatory infiltration and keratinocyte over-proliferation. Our results show that taxifolin prevented proliferation cycle of keratinocyte in a concentration-dependent manner. Over-proliferation and abnormal apoptosis of epidermal cells were obvious in the mouse model of psoriasis induced by imiquimod. Taxifolin treatment improved erythema and scales of psoriatic lesions in mice, and reduced the proportion of CD3 + cells, especially gamma delta T cells, in lesions and thymus. Therefore, taxifolin decreased the expression level of IL17A-dominated inflammatory cytokines. Proteomic analysis showed that 30 up-regulated proteins and 23 downregulated proteins were compared with the lesions before and after the treatment with taxifolin. Among them, cytoplasmic phospholipase A2 (cPLA2), the key enzyme of the pro-inflammatory mediator, was the most significantly down-regulated protein. And enriched KEGG pathway shown that PPAR-gamma pathway was most involved. Taxifolin significantly reduced p-cPLA2 and increased PPAR-gamma protein level in keratinocytes and lesions induced by IL-17 and imiquimod respectively. Meanwhile, phosphorylation of ERK and P-38 were also inhibited. These results suggest that taxifolin prevented imiquimode-induced excessive immune activation and keratinocyte proliferation by decreasing p-cPLA2 and regulating the PPAR-gamma pathway. Our study provides new insights into the cellular regulatory mechanisms of taxifolin in psoriasis.