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Background. Exosomes have been proven to play important diagnostic, regulatory, or communication roles in tumorigenesis, tumor progression, or metastasis; in recent studies, lots of molecules, including miRNAs, were found to be aberrantly expressed in tumor exosomes and were correlated with tumor development. However, studies about the expression, relationship, or control mechanisms of miRNAs in exosomes in pancreatic ductal adenocarcinoma (PDAC) are scarce and urgently needed. The aim of this article was to identify and investigate abnormally expressed miRNAs in PDAC exosomes in vivo and in vitro. Methods. Microarray studies were used to detect aberrantly expressed miRNAs in PDAC exosomes, and miR-210 expression in cells or exosomes was further analyzed by qRT-PCR. Bioinformatics analyses, dual-luciferase assays, WB, and other assays were utilized to explore the miRNA molecular mechanisms. The living cell coculture model and immunofluorescence analysis were employed to image the communication between PDAC cells and endothelial cells. Other biological experiments in the study include a real-time intravital imaging system, EdU, transwell, xenograft models, and so on. Results. miR-210 is significantly expressed in PDAC exosomes and malignant cells. High miR-210 significantly facilitated tumor angiogenesis, cell invasion, and proliferation in PDAC cells. Further mechanistic detection revealed that miR-210 negatively regulated EFNA3 expression and participated in the PI3K/AKT/VEGFA or Wnt/Β-catenin/RHOA pathways, thus promoting tumor angiogenesis and cellular permeability. PDAC cells promote endothelial angiogenesis or permeability via miR-210 transmission by tumor exosomes. Exosomal miR-210 promotes PDAC progression in vivo. Further detection of PDAC plasma exosomal miR-210 suggests that exosomal miR-210 expression was high and significantly associated with vascular invasion and TNM stage and was an independent risk factor for PDAC overall survival. Conclusions. PDAC cell-secreted exosomes could promote angiogenesis and cellular permeability of neighboring endothelial angiogenesis or permeability via miR-210 transmission. Exosomal miR-210 may play important roles in tumor biology and may be a useful prognostic marker in PDAC.

Objective. Traditional Chinese medicine (TCM) emphasizes treatment based on syndrome differentiation. This study aimed to clarify the characteristics of DNA methylation expression profiles in peripheral blood mononuclear cells (PBMCs) in patients with psoriasis and analyze the differences in these profiles among different TCM syndromes of psoriasis in order to provide a material basis for the diversity of these syndromes. Methods. Blood samples were collected from 32 participants, including 14 patients with psoriatic blood heat syndrome (BHS), 12 patients with psoriatic blood stasis syndrome (BSS), and 6 healthy controls. PBMCs were extracted and subjected to DNA quality inspection. An Illumina Human Methylation 850k chip was used to sequence each group of samples. According to gene annotation classification together with CpG island annotation classification, the differentially methylated regions between sample groups were screened, while Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were applied to perform functional analyses of DMGs. Finally, the DMGs closely correlating with psoriatic severity were screened using Spearman’s correlation analysis. Results. Compared with normal controls, patients with psoriasis showed an overall trend of hypermethylation. In psoriasis, the differential methylation probes were mainly distributed on gene body region on the genome, while those in CpG regions were mainly distributed in CpG islands. Compared with healthy controls, the overall trends in methylation were similar in psoriatic BHS and BSS patients compared to healthy controls. However, bioinformatic analysis revealed different functions of DMGs. We also found that the methylation levels of TRIM14 and PRDM16 were closely correlated with PASI scores and could serve as potential biomarkers to assess the severity of psoriasis. Conclusions. Our study, for the first time, indicated the possible involvement of DNA methylation in regulating the characteristics of TCM syndromes of psoriasis, providing a new direction for research into TCM psoriatic syndromes.

Xiaoying Sun,1,2 Liu Liu,1,2 Siting Chen,1,2 Jiao Wang,1,2 Xiaoce Cai,1,2 Jiankun Song,3 Mi Zhou,1,2 Dongjie Guo,1,2 Le Kuai,1,2 Xiaojie Ding,1,2 Bin Li,2,4 Xin Li1,2 1Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Dermatology of TCM, Shanghai Skin Diseases Hospital, Shanghai, People’s Republic of China; 4Department of Dermatology, Shanghai Skin Diseases Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Xin Li, Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437, People’s Republic of China, Tel +8613661956326, Email 13661956326@163.com Bin Li, Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437, People’s Republic of China, Tel +8618930568129, Email 18930568129@163.comBackground: Psoriasis is an immune-mediated chronic systemic inflammatory skin disease whose diagnosis and severity assessment pose challenges for clinicians worldwide. The use of serum biomarkers facilitates the early diagnosis and treatment of psoriasis.Methods: This case–control study compared tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-17, IL-10, and fibrinogen-like protein 1 (FGL1) levels of 139 untreated psoriasis patients and 140 healthy controls. Serum samples were collected, and enzyme-linked immunosorbent assays were performed to quantify their levels. Subgroups were analyzed according to abnormal lipid metabolism status.Results: Compared to controls, patients with psoriasis exhibited lower concentrations of serum TNF-α, IL-17, and FGL1 (P < 0.05). A correlation analysis showed that FGL1 was inversely correlated with high-density lipoprotein cholesterol and IL-17 in the psoriatic state. Stepwise multiple regression analysis revealed that FGL1 and total cholesterol were the independent determinants of Psoriasis Area and Severity Index (PASI) score in psoriasis patients. The area under the receiver operating characteristic curve of FGL1 assessing moderate-to-severe psoriasis and mild psoriasis was 0.70, while the area under the curve (AUC) assessing severe psoriasis and mild-to-moderate psoriasis was 0.67, better than that of IL-17. In addition, FGL1, but not IL-17, was able to identify psoriasis with abnormal lipid metabolism to a certain extent (AUC = 0.60).Conclusion: In conclusion, serum FGL1 may be a promising biomarker for diagnosing and staging psoriasis. It may also be involved in its progression and comorbid abnormal lipid metabolism.Keywords: psoriasis, disease severity, biomarker, fibrinogen-like protein 1, lipid metabolism

RationalePerifolliculitis capitis abscedens et suffodiens (PCAS), also known as dissecting cellulitis of the scalp (DCS), is a part of the “follicular occlusion tetrad” that also includes acne conglobate (AC), hidradenitis suppurativa (HS), and pilonidal sinus, which share the same pathogenic mechanism, such as follicular occlusions, follicular ruptures, and follicular infections.Patient concernsA 15-year-old boy had multiple rashes on the scalp accompanied by pain.DiagnosisThe patient was diagnosed with PCAS or DCS based on the clinical manifestations and laboratory examinations.InterventionsThe patient was initially administered adalimumab 40 mg biweekly and oral isotretinoin 30 mg daily for 5 months. Because the initial results were insufficient, the interval between adalimumab injections was extended to 4 weeks, and isotretinoin was changed to baricitinib 4 mg daily for 2 months. When the condition became more stable, adalimumab 40 mg and baricitinib 4 mg were administered every 20 and 3 days, respectively, for two more months until now.OutcomesAfter 9 months of treatment and follow-up, the original skin lesions of the patient were almost cured, and most inflammatory alopecia patches disappeared.ConclusionOur literature review did not find any previous reports on treating PCAS with TNF-α inhibitors and baricitinib. Accordingly, we presented the first successful treatment of PCAS with this regimen.

High resolution and wide-swath imaging always suffer channel errors of the multiple azimuth channels (MACs) SAR. This paper presents an image-domain channel error estimation algorithm based on image subspace least square (ISPLS) method, and a post-imaging reconstruction algorithm for MACs SAR. The proposed method mainly consists of three parts: firstly, preprocessing and SAR imaging; secondly, the ISP-LSbased channel error estimation and calibration algorithm; thirdly, post-imaging reconstruction and ambiguity suppression. The channel phase and baseline errors are joint-estimated based on image subspace after SAR imaging, providing advantages that the higher SNR regions SAR images and the subspace method can be used to achieve a more accurate estimate with a relatively low computational load. We also propose a post-imaging reconstruction method for ambiguity suppression, which can realize imaging each channel data and then combining the multichannel SAR images. Simulated and acquired airborne SAR data are processed to demonstrate the effectiveness of the proposed method.

Background As an immune regulator expressed on the surface of activated T cells, programmed cell death 1 (PDCD1) plays an important role in psoriasis. However, whether PDCD1 genetic polymorphism is associated with psoriasis has yet to be explored. Objective To study the association between polymorphisms of the immune‐related gene PDCD1 and psoriasis susceptibility in the Chinese population, to illustrate the genetic mechanism of psoriasis and provide new research ideas for the diagnosis and treatment of psoriasis (PS). Methods Overall, 128 psoriasis patients and 88 healthy controls were included in this study. Using polymerase chain reaction (PCR)‐Sanger sequencing analysis, six PDCD1 single nucleotide polymorphisms (SNPs) were sequenced: PD1.1, PD1.3, PD1.4, PD1.5, PD1.6, and PD1.9. Results Among the six tested SNPs, PD1.6 showed a significant association with psoriasis in genotype and allele frequency distribution. The G allele of PD1.6 increased the risk of psoriasis (P = 0.03). In contrast, the other five SNPs failed to show association with psoriasis. Further analysis within the patient group showed that the frequency of the PD1.6 G allele was relatively high in severe psoriasis, but the difference was nonsignificant. Conclusion PDCD1 gene polymorphism is associated with psoriasis. The population carrying PD1.6 allele G are at a higher risk of developing psoriasis, though the severity of psoriasis does not correlate with PD1.6 polymorphism.

In this paper, we study a type of stochastic McKean–Vlasov equations with non-Lipschitz coefficients. Firstly, by an Euler–Maruyama approximation the existence of its weak solutions is proved. Then we observe the pathwise uniqueness of its weak solutions. Finally, it is shown that the Euler–Maruyama approximation has an optimal strong convergence rate.

This study investigates the heterogeneous effects of online reviews on hotel revenue when online reviews and American Customer Satisfaction Index (ACSI) coexist. Using a sample of reviews for 303 H...

Glycosides from the roots of Tripterygium wilfordii Hook. f. are used for the treatment of oral lichen planus (OLP), a chronic inflammatory disease affecting the oral mucosa. To investigate the effectiveness and safety of Tripterygium glycosides (TGs) for OLP treatment, we conducted a systematic review of 18 randomized controlled trials, comprising 1,339 participants, from international and Chinese databases. We evaluated outcomes of TGs alone or in combination with conventional treatments. In combination with topical glucocorticoids (TGCs), including triamcinolone acetonide and prednisone, the total effectiveness rate (risk ratio [RR], 1.17; 95% confidence interval [CI], 1.09-1.25; p < .00001), symptom score reducing index (mean difference [MD], -2.44; 95% CI, -3.12 to -1.77; p < .0001), and visual analog scale score (MD, -1.61; 95% CI, -2.22 to -1.00; p < .0001) were significantly improved. Patients treated with TGs combined with TGCs experienced lower recurrence rates (RR, 0.37; 95% CI, 0.18-0.76; p = 0.007). The occurrence of adverse events was not significantly different between the TGs groups and controls. The combination of TG and TGCs improved clinical efficacy and reduced recurrence without increasing the risk of adverse events. A high-quality multicenter clinical study is needed to corroborate these findings.

BackgroundInherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology. The lung microbiome is getting rising attention in carcinogenesis. The present work sought to investigate the microbiome in lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution (IAP); and further, to compare host gene expression patterns with their microbiome for potential links.MethodsTissue sample pairs (cancer and adjacent nonmalignant tissue) were used for 16S rRNA (microbiome) and RNA-seq (host gene expression). Subgroup microbiome diversities and their matched gene expression patterns were analyzed. Significantly enriched taxa were screened out, based on different clinicopathologic characteristics.ResultsOur FLC microbiome seemed to be smaller, low-diversity, and inactive to change; we noted microbiome differences in gender, age, blood type, anatomy site, histology type, TNM stage as well as IAP and smoking conditions. We also found smoking and IAP dramatically decreased specific-OTU biodiversity, especially in normal lung tissue. Intriguingly, enriched microbes were in three categories: opportunistic pathogens, probiotics, and pollutant-detoxication microbes; this third category involved Sphingomonas, Sphingopyxis, etc. which help degrade pollutants, but may also cause epithelial damage and chronic inflammation. RNA-seq highlighted IL17, Ras, MAPK, and Notch pathways, which are associated with carcinogenesis and compromised immune system.ConclusionsThe lung microbiome can play vital roles in carcinogenesis. FLC and IAP subjects were affected by fragile lung epithelium, vulnerable host-microbes equilibrium, and dysregulated immune surveillance and response. Our findings provided useful information to study the triple interplay among environmental carcinogens, population genetic background, and diversified lung microbiome.

BACKGROUND: Inherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology, and both exhibit population heterogeneity. MUC16 is overexpressed in various cancers and often associated with poor prognosis. Present work was to investigate the clinical significance of MUC16 in non-small cell lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution caused by coal use. METHODS: Clinicopathologic characteristics and MUC16 expression were analyzed and evaluated in our subject population. Vectors were constructed for MUC16 gene knockout and overexpression, then we examined how MUC16 affected lung cancer cell behaviors, including proliferation, migration, invasion and chemoresistance. RESULTS: FLC showed significant association with early-onset (P

In this quantitative study, we evaluated the effectiveness and safety of fire needle therapy for nodular prurigo. We systematically searched several databases, including EMBASE, PubMed, the Cochrane Library, the Web of Science, the China Network Knowledge Infrastructure, the Wanfang Data Knowledge Service Platform, and the China Science and Technology Journal Database, and retrieved randomized controlled trials comparing conventional therapies (control group) with fire needle therapy alone or in combination with conventional therapies. Revman 5.2 software was used to calculate risk ratios (RR) with 95% confidence intervals (CI). In total, 14 trials with 1176 participants were included. Our quantitative study showed that the effectiveness rate of fire needle therapy combined with conventional therapies was significantly higher than that of conventional therapies alone (fire needle + traditional Chinese medicine [TCM] vs. TCM: RR, 1.11; 95% CI, 1.04 to 1.18; fire needle + oral thalidomide + topical glucocorticoid [TGC] vs. thalidomide + TGC: RR, 1.41; 95% CI, 1.17 to 1.70; fire needle + TGC vs. TGC only: RR, 1.18; 95% CI, 1.07 to 1.31). Similar results were obtained for the Symptom Score Reducing Index (fire needle + TCM vs. TCM: mean difference [MD], −3.39; 95% CI: −5.39 to −1.39), visual analog scale scores for itching severity (fire needle vs. halometasone cream: MD, −0.93; 95% CI, −1.29 to −0.58; fire needle + TCM vs. TCM: MD, −1.18; 95% CI, −1.78 to −0.58), and Dermatology Life Quality Index (fire needle vs. halometasone cream: MD, −3.03; 95% CI, −3.43 to −2.63; fire needle + TCM vs. TCM: MD, −2.53; 95% CI, −3.12 to −1.94). Adverse event and recurrence rates were comparable between groups. Thus, fire needle therapy alone or combined with conventional treatments may be effective for nodular prurigo, without any additional side effects.

Background: Taodan granules (TDGs), traditional Chinese herbals, are effective in treating psoriasis. However, mechanisms of TDGs remain indistinct. The current study aims to indicate the molecular mechanisms of TDGs in treating psoriasis.Methods: Primarily, transcriptional profiling was applied to identify differentially expression genes (DEGs). The following was that we used Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analysis for functional enrichment analysis. Eventually, RT-PCR was performed to validation. Results: The results revealed that TDGs could regulated the Wnt signaling pathway to ameliorate skin lesions of imiquimod (IMQ)-induced psoriatic mouse models. IPA core network associated with Wnt signaling pathways in TDGs for psoriasis was established. Thereinto zeste homolog (EZH) 2, CTNNB1, TP63, and WD repeat domain (WDR) 5 could be considered as upstream genes in the Wnt signaling pathway.Conclusions: The Wnt signaling pathway with these above upstream genes might be potential therapeutic targets of TDGs for psoriasis.

Myocardial infarction (MI) is a severe coronary artery disease resulted from substantial and sustained ischemia. Abnormal upregulation of calcium and integrin binding protein 1 (CIB1) has been found in several cardiovascular diseases. In this study, we established a mouse model of MI by permanent ligation of the left anterior descending coronary artery. CIB1 was upregulated in the heart of MI mice. Notably, CIB1 knockdown by intramuscular injection of lentivirus-mediated short hairpin RNA (shRNA) targeting Cib1 improved cardiac function and attenuated myocardial hypertrophy and infarct area in MI mice. MI-induced upregulation of α-SMA, vimentin, Collagen I, and Collagen III, which resulted in collagen production and myocardial fibrosis, were regressed by CIB1 silencing. In vitro, cardiac fibroblasts (CFs) isolated from mice were subjected to angiotensin II (Ang II) treatment. Inhibition of CIB1 downregulated the expression of α-SMA, vimentin, Collagen I, and Collagen III in Ang II-treated CFs. Moreover, CIB1 knockdown inhibited Ang II-induced phosphorylation of PI3K-p85 and Akt in CFs. The effect of CIB1 knockdown on Ang II-induced cellular injury was comparable to that of LY294002, a specific inhibitor of the PI3K/Akt pathway. We demonstrated that MI-induced cardiac hypertrophy, myocardial fibrosis, and cardiac dysfunction might be attributed to the upregulation of CIB1 in MI mice. Downregulation of CIB1 alleviated myocardial fibrosis and cardiac dysfunction by decreasing the expression of α-SMA, vimentin, Collagen I, and Collagen III via inhibiting the PI3K/Akt pathway. Therefore, CIB1 may be a potential target for MI treatment.

With the increase of the video Quality of Experience (QoE), the demand for effective video distribution increases sharply. As the wireless environment changes, it will significantly impact the user’s QoE in video streaming. The characteristics of Named Data Networking (NDN), such as multicast and Interest aggregation, which can improve the distribution efficiency of video streaming. However, the current video streaming transmission solution requires a large number of Interest request packets for video segments, which will increase the consumer channel competition in wireless NDN. In this paper, we propose an adaptive video streaming transmission mechanism for wireless NDN, which includes Data Batch Processing Scheme (DBPS) and Adaptive Transmission Scheme (ATS). To reduce the channel competition, we propose the DBPS to reduce the number of Interest sending. In addition, we propose the ATS to adaptively select the transmission mode under the different network conditions, which can improve the user’s QoE. Evaluation results show that the proposed scheme of the NDN video streaming transmission mechanism can effectively improve the user’s QoE.

Video streaming takes a dominant role for rapidly-increasing mobile Internet traffic in Wireless Local Area Networks (WLAN). As consumers often request the same contents, such as popular videos and live videos, using multicast transmissions under Named Data Networking (NDN) architecture can significantly reduce the network cost. However, to guarantee the transmission reliability for wireless multicast, the existing multicast schemes generally adopt the lowest data rate (e.g., 1 Mbps for IEEE 802.11b, and 6 Mbps for IEEE 802.11a) to transmit the multicast data, inevitably reducing the best quality of experience (QoE) for those high-speed consumers. In this paper, under the Scalable Video Coding (SVC) mechanism, we propose an adaptive video streaming scheme by using the NDN multicast (named NM-ABR), where NDN multicast groups are dynamically formed according to the network conditions and SVC characteristics. In NM-ABR, after detecting a multicast group, we first devise a multicast data rate selection algorithm in order to maximize the receiving throughput of consumers within the group. Then, we integrate the transmission data rate into the adaptive bit rate (ABR) algorithm to request for video segments with the most suitable bitrate. At last, for those low-speed consumers, we propose an SVC-based multiple-layer control approach to reduce the retransmission of video segments in enhancement layers. We implement the proposed NM-ABR in NS-3 via the ndnSIM module, and conduct extensive experiments to demonstrate its efficacy in terms of video bitrate, startup delay, and stalling time.

Ethnopharmacological relevance Our clinical practice demonstrated that Jueyin granules (JYG) benefit patients with mild to moderate psoriasis vulgaris without apparent adverse effects. JYG have been shown to inhibit epidermal proliferation in an imiquimod (IMQ)-induced psoriasis-like mouse model, as well as keratinocyte proliferation. Moreover, JYG causes no acute or chronic toxicity in animal models. However, its related molecular mechanism has still not been elucidated. Aim of the study To assess the mechanism of JYG against psoriasis. Materials and methods This study combined network pharmacology analysis with experiments to investigate the mechanism of JYG against psoriasis. First, the molecular docking technology was used to construct the network of medicinal materials-core active plant ingredients-core targets and identify possible drug targets. Next, high-performance liquid chromatography (HPLC) was used for quality control of JYG. Finally, a mice model of psoriasis was used to further verify the effects of JYG. Results (1) Molecular docking analysis of network pharmacology revealed that the therapeutic effects of JYG on psoriasis might be achieved through Vitamin D Receptor (VDR) effects. (2) The concentrations of chlorogenic acid and paeoniflorin were determined using HPLC to establish quality control of JYG. (3) JYG ameliorated pathological characteristics that included in vivo reductions in erythema, scale, and infiltration scores of back and ear lesions in IMQ-induced psoriasis-like mice. Moreover, a reduced number of PCNA-positive and Ki67-positive cells were observed in the epidermis of JYG-treated lesions. JYG also reduced inflammation (interleukin (IL)-17, IL-23) in the peripheral blood of IMQ-induced psoriasis-like mice. As expected, JYG was found to upregulate VDR expression and downregulate p-STAT3 expression in the IMQ group, which may contribute to its mechanism against psoriasis. Conclusion Overall, this study clarifies the mechanism of JYG against psoriasis and provides evidence to support its clinical use.

Dendritic cell (DC)-based vaccination is a promising approach for active-specific immunotherapy, but is currently of limited efficacy. The safety and effectiveness of a DC vaccine (DCV) loaded with glioblastoma stem cell-like (GSC) antigens was assessed in glioblastoma multiforme (GBM) patients. In this double-blind, placebo-controlled phase II clinical trial, 43 GBM patients were randomized after surgery at a 1:1 ratio to receive either DCV (n = 22) or normal saline placebo (n = 21). Overall survival (OS) and progression-free survival (PFS) were analysed. Participants were stratified into different molecular subgroups based on the mutation (MT) status of isocitrate dehydrogenase (IDH1/2) and telomerase reverse transcriptase (TERT). Plasma cytokine levels, tumor-infiltrating lymphocyte numbers and immune co-inhibitory molecules PD-L1 and B7-H4 were also assessed. Multivariate Cox regression analysis revealed that DCV treatment significantly prolonged OS (p = 0.02) after adjusting for IDH1 and TERT promoter MT and B7-H4 expression, primary vs recurrent GBM. Among IDH1wild type (WT) TERTMT patients, DCV treatment significantly prolonged OS (p

This study investigates the differential roles of negative and positive reviews on the growth of branded and independent hotels and their underlying interplays. We construct a dataset by combining the revenue data with TripAdvisor review data of hotels in four Texas cities. Based on the resource-based view of firm growth and signaling theory, we obtain several novel findings. Positive reviews exert greater positive effects on the growth of independent hotels than branded hotels, and high growth in turn brings them additional positive reviews. Such a positive feedback loop helps explain why independent hotels benefit more from positive reviews than branded hotels. Negative reviews negatively affect the growth of independent hotels. Although a high growth of branded hotels leads to more negative reviews, the latter does not jeopardize their growth significantly due to the protecting role of brands.

Taodan granules (TDG) have been observed to decrease interleukins, or psoriasis area and severity index (PASI) score for psoriasis vulgaris, without significant adverse events. However, the regulatory network remains elucidated.The objective is to identify critical genes and kernel pathways of TDG treated psoriasis.Firstly, construct a network of components-targets of TDG using network pharmacology. Secondly, the ClusterONE algorithm was used to build a modular network and identify critical genes and corresponding pathways. Thirdly, the critical genes and kernel pathways were verified in imiquimod (IMQ) induced psoriasis-like mice model.The results validated that TDG downregulated the mRNA expression of MMP2 (degree = 5, P 0.05), IL6 (degree = 9, P 0.05), TNF (degree = 14, P 0.05), CCL2 (degree = 8, P 0.05), CXCL2 (degree = 8, P 0.05), IL1B (degree = 9, P 0.05), and JUN (degree = 9, P 0.05), while upregulated IL10 (degree = 8) expression. Besides, TDG were observed to regulate IL17 signaling pathway and TNF signaling pathway (size = 18), via the skin tissue homogenate of psoriasis-like mice.In summary, this study identified the potential targets and pathways, providing additional evidence for the clinical application of TDG treated psoriasis.

Additional file 1. Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 checklist: recommended items to address in a clinical trial protocol and related documents.

Background Plaque psoriasis is a refractory inflammatory skin disease. Traditional Chinese medicine (TCM) and Western medicine (WM) therapies commonly used to treat plaque psoriasis have distinct characteristics and advantages. Although a combination of TCM and WM therapies adjusted to the clinical situation is widely used, there have been no systematic studies on the hierarchical selection of treatment combinations according to the severity of skin lesions. We therefore designed a randomized clinical trial to focus on the sequence of internal and external treatments in patients with mild-to-moderate plaque psoriasis and sought to optimize the integrated Chinese and Western medicine for treatment of patients with severe plaque psoriasis, so as to achieve high-level clinical evidence and establish treatment norms for the integrated use of Chinese and Western medicines. Methods In the proposed multi-center, single-blinded, randomized, controlled trial, 108 patients with mild-to-moderate plaque psoriasis will be randomly assigned to two groups in a 1:1 ratio to receive internal and external TCM treatments, respectively, and 270 patients with severe plaque psoriasis will be randomly assigned to three groups in a 1:1:1 ratio to receive treatment with TCM, WM, and integrated Chinese and Western medicine, respectively. All enrolled patients will receive 8 weeks of treatment and 8 weeks of follow-up. The primary outcome will be an evaluation of efficacy and relapse rate based on the Psoriasis Area and Severity Index . Secondary outcome measures will include a determination of affected body surface area, physician’s global assessment, pruritus scores determined using a visual analogue scale, TCM symptom score, dermatology life quality Index, patient-reported quality of life score, and incidence of serious adverse events. Discussion This study will provide a high level of clinical evidence for internal and external TCM treatment optimization and will contribute to establishing norms for the integration of Chinese and Western medicines.

Rationale Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. It appears as patches, plaques, and tumors depending on the stage of the disease, which presents a chronic progressive course. Compared to CD4/CD8 MF, CD4/CD8 dual-positive MF is an uncommon immune phenotype. Patient concerns A 36-year-old male patient presented with dryness and scales on his whole body. Diagnosis The patient was diagnosed with MF based on results of pathological examination, immunohistochemical staining, and T-cell receptor gene rearrangement test. Interventions The patient was advised to take an herbal medicine orally twice daily and apply a topical moisturizer after showering. Outcomes After treatment and follow-up, the patient's symptoms of dryness and scales improved and his condition stabilized. Conclusions While reviewing the literature, we found no previous reports on the treatment of dual-positive MF with Chinese medicine. In this report, we presented the first case of dual-positive MF successfully treated with Chinese medicine. The results suggest that oral ingestion of herbal medicine may be a feasible method for alleviating clinical symptoms of early stage MF. Therefore, the therapy should be explored for clinical use in the future.

BACKGROUND Clinical treatment of plaque psoriasis typically involves a comprehensive therapy, which is expensive and unsatisfactory, and some medications have serious side effects. Moving cupping therapy has shown good clinical efficacy in the treatment of plaque psoriasis; it can significantly relieve skin inflammation and excessive thickening of plaque psoriasis and has fewer side effects. However, a comprehensive evaluation of the current clinical evidence regarding its use is lacking. METHODS Several databases were systematically searched from inception to March 2, 2020, including PubMed, Embase, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure, and Wan Fang. This review included randomized controlled trials on plaque psoriasis treatment with the use of moving cupping and in combination with Chinese herbs or conventional Western medicine therapy. These trial findings were compared with the treatment results using placebo, pharmaceutical medications, or Chinese herbs. Moving cupping treatment frequency was also compared. RESULTS Sixteen trials with 1164 participants met the inclusion criteria. Meta-analysis showed that the intervention group (moving cupping therapy) had a significant effect compared with the no-moving cupping therapy group (weighted mean difference = -1.22, 95% confidence interval [CI] [-1.58, -0.85], P

Background Tripterygium wilfordii Hook. f. (TwHf) belonging to the Celastraceae family is widely used for psoriasis treatment, especially in topical therapy in Chinese traditional medicine. Purpose In this study, we investigated the anti-psoriatic effects of topical administration of Tripterygium wilfordii Hook. f. root decoction (TwHf-RD), as well as its safety and potential mechanisms of action in vivo and in vitro. Methods Psoriasis-like lesions were induced in mice using imiquimod (IMQ). The liver and kidney function and the pathological changes in the liver, kidney, and spleen were measured using ELISA and hematoxylin and eosin (H&E) staining after TwHf-RD treatment. H&E staining was used to determine the optimum concentration of TwHf-RD. The expression levels of ki67 and apoptosis related-factors in vivo and in vitro were measured by immunohistochemical staining, flow cytometry, and western blotting. Immunocyte differentiation and pro-inflammatory cytokine (IL-17A, IL-17F, IL-10, IL-22, IL-23, IFN-γ, and TNF-α) expression levels were determined by flow cytometry and RT-qPCR. Results TwHf-RD treatment attenuated skin inflammation, inhibited keratinocyte (KC) proliferation, increased the levels of apoptosis factors, and influenced the differentiation and inflammatory response of T lymphocytes and regulatory T cells in mice. In vitro experiments proved that Tripterygium wilfordii Hook. f. root extract (TwHf-RE) regulates the proliferation and apoptosis of PAM212 cells. Conclusion TwHf-RD alleviates IMQ-induced psoriasis lesions by regulating the proliferation and apoptosis of KC and immune cells and by inhibiting immunocyte differentiation and pro-inflammatory cytokine expression.

In this paper we consider the stability for a type of stochastic McKean-Vlasov equations with non-Lipschitz coefficients. First, sufficient conditions are given for the exponential stability of the second moments for their solutions in terms of a Lyapunov function. Then we weaken the conditions and furthermore obtain exponentially 2-ultimate boundedness of their solutions. After this, the almost surely asymptotic stability of their solutions is proved. Finally we give an example to motivate the choice of Lyapunov functions., Comment: 18 pages

Aims To investigate the effects and mechanisms of DLL3 in inflammation-mediated A2058 melanoma cell invasion and metastasis. Materials and methods Melanoma A2058 cells was stimulated with lipopolysaccharide (LPS), with or without transfection of DLL3 siRNA, or DLL3 overexpression vector, or Twist1 siRNA. Cell migration and invasion were detected by wound healing and transwell invasion assay. The production of inflammatory factors TNF-α and IL-6 was measured by ELISA. The expression of Notch signaling-related molecules was detected by PCR and western blot. The protein expression of MMP1, MMP9, VEGF, DLL3, and EMT-related molecules was tested by western blot. Key findings LPS treatment increased migration and invasion of A2058 cells, accompanied by increased expression of TNF-α and IL-6. DLL3 was both upregulated in the LPS- or TNF-α-stimulated A2058 cells, and DLL3 knockdown inhibited LPS-induced inflammation, migration and invasion of A2058 cells, accompanied by down-regulation of MMP1, MMP9 and VEGF. Besides, DLL3 knockdown inhibits the expression of Twist1, a key EMT regulating factor, as well as the EMT hallmarks slug, N-cadherin and vimentin. Moreover, Twist1 silence inhibited EMT, and limited LPS-induced migration and invasion of A2058 cells, with decreased expression of MMP1, MMP9 and VEGF and reduced production of TNF-α and IL-6 in LPS-stimulated A2058 cells. Significance Knockdown of DLL3 restricts LPS-induced inflammation, migration and invasion of A2058 melanoma cells via blocking Twist1-mediated EMT. Therefore, targeting DLL3 may be a promising therapeutic strategy against inflammation-aggravated melanoma progression.

Maximal surgical resection is associated with survival benefit in the majority of studies in adult diffuse glioma. This study aims to characterize the prognostic value of surgical resection in molecular subgroups of diffuse glioma. 1178 patients with diffuse glioma from our centers and 422 from TCGA dataset were collected. The Kaplan–Meier analysis and multivariable Cox regression models were conducted to identify the prognostic value of surgical resection through different histological and molecular stratifications. Firstly, we confirmed progression-free survival (PFS) benefit associated with gross total resection (GTR) over sub-total resection (STR) in lower-grade glioma (HR 1.49; 95% CI 1.17–1.90; P = 0.001). Intriguingly however, we were unable to detect a significant PFS or overall survival (OS) benefit in oligodendroglioma (N = 397; HR 1.36; 95% CI 0.86–2.14; P = 0.19 and HR 1.05; 95% CI 0.55–1.99; P = 0.89, respectively). Secondly, when analyzed in molecular subgroups, we were similarly unable to detect a significant PFS or OS benefit in IDH MT/codel subgroup (N = 269; HR 1.47; 95% CI 0.92–2.34; P = 0.11 and HR 1.54; 95% CI 0.78–3.05; P = 0.21, respectively), oligodendroglioma with IDH MT/codel subgroup (N = 233; HR 1.33; 95% CI 0.79–2.21; P = 0.28 and HR 1.16; 95% CI 0.53–2.54; P = 0.70, respectively) or other relevant subgroups. TCGA validation also showed a significant survival benefit in astrocytoma rather than oligodendroglioma. Exploratory RNAseq analysis displayed that fewer cell proliferation-related gene expression features were specific to oligodendroglioma. These results suggest that the benefit of maximal surgery may be attenuated in patients within oligodendroglioma relevant subgroups because of the chemosensitive and indolent nature. The aggressive surgery accompanying with risk of neurologic morbidity may be unnecessary for these patients given the lack of survival benefit with gross total resection.

In this work, a very sensitive electrochemical sensor for the determination of pentachlorophenol (PCP) was constructed based on the electrocatalytic activity of the composite of ZnSe quantum dots (ZnSe QDs) decorated multiwall carbon nanotubes (MWCNTs) (ZnSe QDs-MWCNTs). The behaviors of PCP on the surface of ZnSe QDs-MWCNT modified electrode showed that the composite of ZnSe QDs-MWCNTs introduced a favorable access for the electron transfer and make an obvious electrocatalytic activity toward the oxidation of PCP. Differential pulse voltammetry (DPV) was used for the quantitative determination of PCP. Under the optimum conditions, the peak current of PCP was proportional to its concentration at the range of 8.0 × 10−8 to 4.0 × 10−6 mol L−1 with a detection limit 2.0 × 10−9 mol L−1 (S/N = 3). Compared with the reported papers, the proposed method was more sensitive and simple. The developed method was successfully applied for the determination of PCP in fish meat with satisfactory recoveries.

Exposure to particulate matter (e.g., PM2.5) may result in DNA damage, a major culprit in mutagenesis and environmental toxicity. DNA damage levels may vary among individuals simultaneously exposed to PM2.5, however, the genetic determinants are still unclear. To explore whether PM2.5 exposure and genetic variants contribute to the alteration in DNA damage, we recruited 328 subjects from three independent cohorts (119 from Zhuhai, 123 from Wuhan and 86 from Tianjin) in southern, central and northern China with different PM2.5 exposure levels. Personal 24-h PM2.5 exposure levels and DNA damage levels of peripheral blood lymphocytes were evaluated. Genotyping were performed using Illumina Human Exome BeadChip with 241,305 single nucleotide variants (SNVs). The DNA damage levels are consistent with the PM2.5 exposure levels of each cohort. A total of 35 SNVs were consistently associated with DNA damage levels among the three cohorts with pooled P values less than 1.00 × 10 −3 after adjustment for age, gender, smoking status and PM2.5 exposure levels, of which, 18 SNVs together with gender and PM2.5 exposure levels were independent factors contributing to DNA damage. Gene-based test revealed 3 genes significantly associated with DNA damage levels ( P = 5.11 × 10 −3 for POLH , P = 2.88 × 10 −3 for RIT2 and P = 2.29 × 10 −2 for CNTN4 ). Gene ontology (GO) analyses indicated that the identified variants were significantly enriched in DNA damage response pathway. Our findings highlight the importance of genetic variation as well as personal PM2.5 exposure in modulating individual DNA damage levels.

Poly(diallyl dimethyl ammonium)chloride (PDDA) functionalized CdTe quantum dots (QDs) (PDDA–CdTe QDs) were synthesized through electrostatic self-assembly and used as fluorescence sensors. Mercury(II) ion (Hg2+) has a dramatic fluorescence quenching effect on the PDDA–CdTe QDs. Based on this quenching effect, a very sensitive fluorescence sensor for Hg2+ detection was established. Under the optimum conditions, the fluorescence quenching effect of PDDA–CdTe QDs was linear with the concentration of Hg2+ in the range from 0.006 μmol L−1 to 1.0 μmol L−1. The detection limit was calculated as 5.0 nmol L−1 according to the 3σ IUPAC criteria. This PDDA–CdTe QDs sensor system represents a new feasible method to improve the spectroscopic characterization of QDs used as Hg2+ sensors.

Cysteamine (CA)-capped CdTe quantum dots (QDs) (CA–CdTe QDs) were prepared by the reflux method and utilized as an efficient nano-sized fluorescent sensor to detect mercury (II) ions (Hg2+). Under optimum conditions, the fluorescence quenching effect of CA–CdTe QDs was linear at Hg2+ concentrations in the range of 6.0–450 nmol/L. The detection limit was calculated to be 4.0 nmol/L according to the 3σ IUPAC criteria. The influence of 10-fold Pb2+, Cu2+ and Ag+ on the determination of Hg2+ was

In this study, water-soluble ZnSe quantum-dots (QDs) capped with Glutathione(GSH) was synthesized. It was found that ZnSe QDs could enhance the chemiluminescence (CL) emission from the luminol-K 3 Fe(CN) 6 system in alkaline medium, and the enhancement mechanism of ZnSe QDs on luminol CL was discussed. What's more, we found that the CL from luminol-K 3 Fe(CN) 6 –ZnSe QDs system is strongly inhibited by the presence of phenols. Based on this inhibition, a novel CL method with a lower detection limit and wider linear range was developed for the determination of three kinds of phenols.

The transcription factor KLF2 has long been thought to play a critical role in controlling survival and quiescence of mature T cells, since KLF2-deficient T cells develop in the thymus but fail to populate peripheral lymph organs. A new study offers an alternative explanation for this phenotype, consistent with an entirely different function for KLF2 as a regulator of thymocyte and T-cell migration. Proteins of the KLF (Kruppel-like transcription factor) family are involved in many aspects of vertebrate development and are implicated in a number of disease states. This newly discovered role for KLF2 is similar to some other KLFs that are essential for terminal differentiation of various cell types. The transcription factor KLF2 has been thought to control survival of T lymphocytes, as KLF2-deficient T cells develop in the thymus, but fail to populate the peripheral lymphoid organs. But this report shows that the phenotype results from an unexpected role of KLF2 in regulating the expression of lymphocyte trafficking molecules. Mammalian Kruppel-like transcription factors are implicated in regulating terminal differentiation of several tissue types1,2,3. Deficiency in Kruppel-like factor (KLF) 2 (also known as LKLF) leads to a massive loss of the peripheral T-cell pool4, suggesting KLF2 regulates T-cell quiescence and survival4,5,6,7. Here we show, however, that KLF2 is essential for T-cell trafficking. KLF2-deficient (Klf2-/-) thymocytes show impaired expression of several receptors required for thymocyte emigration and peripheral trafficking, including the sphingosine-1-phosphate (S1P) receptor S1P1, CD62L and β7 integrin. Furthermore, KLF2 both binds and transactivates the promoter for S1P1—a receptor that is critical for thymocyte egress and recirculation through peripheral lymphoid organs. Our findings suggest that KLF2 serves to license mature T cells for trafficking from the thymus and recirculation through secondary lymphoid tissues.

Exposure to particulate matter 2.5 (PM2.5) may result in DNA damage. Histone variant H2AX phosphorylation plays a central role in the response to damaged chromatin. In the current study, we investigated whether H2AX gene polymorphisms account for PM2.5-modulated DNA damage levels. A total of 307 healthy urban residents were collected from three cities in southern, central, and northern China, Zhuhai, Wuhan, and Tianjin, respectively. The dust mass concentrations of PM2.5 were detected by Gilian 5000 pumps, and the DNA damage levels were measured using comet assay. Seven potentially functional single nucleotide polymorphisms (SNPs) of H2AX gene were selected and genotyped by Illumina Infinium(®) BeadChip. We found that three SNPs (rs10790283 G > A, rs604714 C > A and rs7759 A > G) were significantly associated with DNA damage levels (adjusted P = 0.002, 0.018 and 0.027, respectively). Significant interactions (P < 0.05) were observed between certain genetic polymorphisms and PM2.5-modulated DNA damage levels. These results suggested that genetic variations of H2AX might be associated with the DNA damage levels in urban residents with different exposure to PM2.5. Further studies with large sample size in independent populations merit validating these findings.

Cysteamine (CA)-capped CdTe quantum dots (QDs) (CA-CdTe QDs) were prepared by the reflux method and utilized as an efficient nano-sized fluorescent sensor to detect mercury (II) ions (Hg(2+) ). Under optimum conditions, the fluorescence quenching effect of CA-CdTe QDs was linear at Hg(2+) concentrations in the range of 6.0-450 nmol/L. The detection limit was calculated to be 4.0 nmol/L according to the 3σ IUPAC criteria. The influence of 10-fold Pb(2+) , Cu(2+) and Ag(+) on the determination of Hg(2+) was 7% (superior to other reports based on crude QDs). Furthermore, the detection sensitivity and selectivity were much improved relative to a sensor based on the CA-CdTe QDs probe, which was prepared using a one-pot synthetic method. This CA-CdTe QDs sensor system represents a new feasibility to improve the detection performance of a QDs sensor by changing the synthesis method.

The switching defective/sucrose nonfermenting (SWI/SNF) related, matrix associated, actin dependent regulators of chromatin (SMARC) are components of human SWI/SNF like chromatin remodeling protein complexes, which are essential in the process of DNA damage repair. In this study, we hypothesized that genetic variants in SMARC genes may modify the capacity of DNA repair to damage. To test this hypothesis, we genotyped a total of 20 polymorphisms in five key SMARC genes (SMARCA5, SMARCC2, SMARCD1, SMARCD2, SMARCD3) to evaluate their associations with DNA damage levels in 307 subjects. The DNA damage levels were measured with comet assay. The multiple linear regression was used to assess the relationship between each polymorphism and DNA damage levels in additive model. We found that the genotypes of rs6857360 (β=0.23, 95% CI=0.06-0.40, P=0.008) in SMARCA5, rs6919 (β=0.20, 95% CI=0.05-0.34, P=0.008) and rs2727280 (β=0.18, 95% CI=0.04-0.33, P=0.013) in SMARCD2, and rs17173769 (β=-0.27, 95% CI=-0.52 to -0.01, P=0.045) in SMARCD3 were significantly associated with DNA damage levels. After combining these four polymorphisms, we found that the more unfavorable alleles the subjects carried, the heavier DNA damage they suffered, suggesting a locus-dosage effect between combined genotypes and DNA damage levels (P for trend=0.006). These findings suggest that genetic variants in SMARC genes may contribute the individual variations of DNA damage levels in Chinese population. Further larger and functional studies are warranted to confirm our findings.

Background Many studies have linked ambient fine particulate matter (PM 2.5 ) air pollution to different cardiopulmonary diseases in the general population. However the complex mechanisms underlying PM 2.5 -induced adverse health effects are not yet to be fully elucidated. Method In this study, we aimed to identify genes and pathways that may contribute to PM 2.5 -induced lung toxicity in humans through genome-wide approaches. Human bronchial epithelial (HBE) cells, exposed to various concentrations of PM 2.5 collected from Wuhan, China, showed decreased cell viability in a dose-dependent manner. HBE cells were exposed to 200 μg/ml and 500 μg/ml PM 2.5 and microarrays were used to obtain a global view of the transcriptomic responses. Results A total of 970 and 492 genes were identified that significantly changed after 200 μg/ml and 500 μg/ml PM 2.5 exposures, respectively. PM 2.5 induced a large number of genes involved in inflammatory and immune response, response to oxidative stress, and response to DNA damage stimulus, which might contribute to PM 2.5 related cardiopulmonary diseases. Pathway analysis revealed that different dose of PM 2.5 triggered partially common disturbed pathways. Flow cytometry assay evidenced that there were statistically significant differences in the G1 phase of cell cycle after low or high-dose PM 2.5 exposure when compared to the unexposed controls. Only high-dose PM 2.5 significantly increased the proportion of cells in the S phase of cell cycle. Conclusion We identified many genes and pathways that altered significantly in HBE cells after PM 2.5 exposures. These findings are important in providing further understanding of the mechanisms underlying PM 2.5 -induced adverse health effects.

A recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese people has discovered a novel single nucleotide polymorphism (SNP) rs10484761 on 6p21.1 region. We hypothesized that SNP rs10484761 T/C is associated with survival of gastric cancer. We genotyped SNP rs10484761 in 940 gastric cancer patients treated with surgical resection. Kaplan–Meier survival analysis, log-rank test, and Cox proportional hazard models were used to evaluate the association between the SNP rs10484761 and gastric cancer survival. In the dominant model, those who carry TC/CC genotypes had a significant shorter survival time (log-rank P = 0.005), especially in the subgroups of aged male patients, cardia intestinal tumor (HR = 1.41, 95% CI = 1.08–1.84 for cardia cancer and HR = 1.64, 95% CI = 1.14–2.37 for intestinal-type), tumor size ≤ 5 cm (HR = 1.41, 95% CI = 0.56–0.99), T1 depth invasion (HR = 2.34, 95% CI = 1.20–4.56), lymph node metastasis (HR = 1.51, 95% CI = 1.19–1.96), no distant metastasis (HR = 1.33, 95% CI = 1.05–1.68), TNM stage III + IV (HR = 1.50, 95% CI = 1.13–1.98), and with chemotherapy (HR = 1.53, 95% CI = 1.17–1.99). The results indicated that SNP rs10484761 was associated with prognosis of gastric cancer, suggesting that this genetic variant may serve as a potential marker to predict the survival of gastric cancer in Chinese population.

This paper is a preliminary report on development of a screening method for carbohydrate-specific phage antibodies against recombinant human erythropoietin (rHuEPO), using a phage display antibody library. rHuEPO was oxidized with sodium periodate or treated with 1,4-dithiothreitol and guanidine hydrochloride for detecting the specificity of obtained phage antibodies. Of 100 phage clones, three initially showed higher carbohydrate-related specificity. One of them (No. 62) bound specifically to the carbohydrate chains of rHuEPO, while the other two (Nos. 63 and 83) might recognize the steric conformation related to both the carbohydrate and the polypeptide chain of rHuEPO. These phage antibodies may serve as useful capture ligands for future development of efficient analytical methods for rHuEPO.

In this paper, an efficient method is proposed for purification and preconcentration of erythropoietin (EPO) in human urine samples. The EPO-specific immunoaffinity column (IAC) was generated by covalent immobilization of anti-EPO polyclonal antibodies on Sepharose 4B support. The EPO-binding capacity of the IAC was found to be about 2.0 microg (6.6IU) per 1.5 mL of gel and the activity recoveries of EPO at low concentrations of 7.8, 10 and 120 m IU/mL by the IAC were between 78 and 86%. Substantial cleanup effect was observed when the IAC was applied to human urine samples.