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Abstract Macrophages play a pivotal role in the healing of diabetic ulcers. The sustained elevation of glucose levels damages the insulin signaling pathway in macrophages, leading to dysfunctional macrophages that struggle to transition from pro-inflammatory (M1) to reparative (M2) states. Therefore, modulating macrophage inflammatory responses via the insulin pathway holds promise for diabetic ulcer treatment. Additionally, the presence of biofilm impedes drug penetration, and the resulting immunosuppressive microenvironment exacerbates the persistent infiltration of pro-inflammatory M1 macrophages. Therefore, we designed an array of dissolvable microneedle (denoted as NPF@MN) loaded with self-assembled nanoparticles that could deliver NPF nanoparticles, acid-sensitive NPF-releasing Protocatechualdehyde (PA) with hypoglycemic and insulin-like effects, regulating macrophage polarization to an anti-inflammatory M2 phenotype. Additionally, this study extensively examined the mechanism by which NPF@MN accelerates the healing of diabetic ulcers through the activation of the insulin signaling pathway. Through RNA-seq and GSEA analysis, we identified a reduction in the expression of pathway-related factors such as IR, IRS-1, IRS-2, and SHC. Our work presents an innovative therapeutic approach targeting the insulin pathway in diabetic ulcers and underscores its translational potential for clinical management.

Introduction Smoking is an independent and modifiable risk factor for the onset and development of psoriasis; however, evidence on the association between tobacco smoking and psoriasis treatment efficacy is limited. This study aimed to explore the influence of smoking on treatment efficacy in a cohort of patients with psoriasis in Shanghai, China. Methods Patients with psoriasis were recruited from the Shanghai Skin Disease Hospital between 2021 and 2022. The treatment for patients with psoriasis includes acitretin, methotrexate, narrow-band ultraviolet/benvitimod, and biologics. Data were collected using a structured questionnaire, physical examination, and disease severity estimation at baseline, week four, and week eight. The achievement of a ≥75% reduction in psoriasis area and severity index (PASI 75 ) score from baseline to week 8 was set as the primary outcome for treatment efficacy estimation. Data were analyzed using SAS 9.4. Results A total of 560 patients with psoriasis were enrolled in this study, who were predominantly males (72.9%). The average age of patients was 48.4 years, and 38.8% of them were current smokers, 5.0% of them were former smokers. The median score of PASI among patients changed from 11.1 (interquartile range, IQR: 7.9–16.6) at baseline to 6.2 at week 4 and 3.1 at week 8, and 13.8% and 47.3% of patients with psoriasis achieved PASI 75 at weeks 4 and 8, respectively. Logistic regression indicated that patients without tobacco smoking had a higher proportion of PASI 75 achievement at week 8. The adjusted odds ratio (AOR) was 11.43 (95% CI: 6.91–18.89), 14.14 (95% CI: 8.27–24.20), and 3.05 (95% CI: 1.20–7.76) for non-smokers compared with smokers, current smokers, and former smokers, respectively. Moreover, former smokers had higher PASI 75 achievement than current smokers (AOR=3.37), and patients with younger smoking initiation age, longer smoking duration, and higher smoking intensity had lower PASI 75 achievement. Conclusions Tobacco smoking was negatively associated with PASI 75 achievement both in current and former smokers, and former smokers had higher PASI 75 achievement than current smokers. The implementation of tobacco control measures is beneficial for improving treatment responses.

Abstract Psoriasis is a common inflammatory disease of especially high recurrence rate (90%) which is suffered by approximately 3% of the world population. The overexpression of reactive oxygen species (ROS) plays a critical role in psoriasis progress. Here we show that biomimetic iron single-atom catalysts (FeN4O2-SACs) with broad-spectrum ROS scavenging capability can be used for psoriasis treatment and relapse prevention via related gene restoration. FeN4O2-SACs demonstrate attractive multiple enzyme-mimicking activities based on atomically dispersed Fe active structures, which are analogous to those of natural antioxidant enzymes, iron superoxide dismutase, human erythrocyte catalase, and ascorbate peroxidase. Further, in vitro and in vivo experiments show that FeN4O2-SACs can effectively ameliorate psoriasis-like symptoms and prevent the relapse with augmented efficacy compared with the clinical drug calcipotriol. Mechanistically, estrogen receptor 1 (ESR1) is identified as the core protein upregulated in psoriasis treatment through RNA sequencing and bioinformatic analysis. Together, this study provides a proof of concept of psoriasis catalytic therapy (PCT) and multienzyme-inspired bionics (MIB).

Abstract Histologically, melanoma tissues had fewer positive cells percentage of pyroptosis-related genes (PRGs), GZMA, GSDMB, NLRP1, IL18, and CHMP4A in epidermal than in normal skin. Pyroptosis, a new frontier in cancer, affects the tumor microenvironment and tumor immunotherapy. Nevertheless, the role of pyroptosis remains controversial, which reason is partly due to the heterogeneity of the cellular composition in melanoma. In this study, we present a comprehensive analysis of the single-cell transcriptome landscape of pyroptosis in melanoma specimens. Our findings reveal dysregulation in the expression of PRGs, particularly in immune cells, such as CD8+ cells (representing CD8+ T cells) and CD57+ cells (representing NK cells). Additionally, the immunohistochemical and multiplex immunofluorescence staining experiments results further confirmed GZMA+ cells and GSDMB+ cells were predominantly expressed in immune cells, especially in CD8 + T cells and NK cells. Melanoma specimens secreted a minimal presence of GZMA+ merged CD8+ T cells (0.11%) and GSDMB+ merged CD57+ cells (0.08%), compared to the control groups exhibiting proportions of 4.02% and 0.62%, respectively. The aforementioned findings indicate that a reduced presence of immune cells within tumors may play a role in diminishing the ability of pyroptosis, consequently posing a potential risk to the anti-melanoma properties. To quantify clinical relevance, we constructed a prognostic risk model and an individualized nomogram (C-index=0.58, P = 0.002), suggesting a potential role of PRGs in malignant melanoma prevention. In conclusion, our integrated single-cell and bulk RNA-seq analysis identified immune cell clusters and immune gene modules with experiment validation, contributing to our better understanding of pyroptosis in melanoma.

Accumulating evidence has highlighted a strong association between gut microbiota and the occurrence, development, prevention, and treatment of atopic dermatitis (AD). The regulation of gut microbial dysbiosis by oral traditional Chinese medicine (TCM) has garnered significant attention. In the treatment of AD, the TCM formula Qingre-Qushi Recipe (QRQS) has demonstrated clinical efficacy. However, both the therapeutic mechanisms of QRQS and its impact on gut microbiota remain unclear. Thus, our study aimed to assess the efficacy of QRQS and evaluate its influence on the composition and diversity of gut microbiota in AD animal models. First, we investigated the therapeutic effect of QRQS on AD using two animal models: filaggrin-deficient mice (Flaky tail, ft/ft) and MC903-induced AD-like mice. Subsequently, we explored its influence on the composition and diversity of gut microbiota. Our results demonstrated that QRQS treatment ameliorated the symptoms in both ft/ft mice and MC903-induced AD-like mice. It also reduced the levels of serum IgE and pro-inflammatory cytokines, including IL-1β, IL-4, IL-5, IL-9, IL-13, IL-17A, and TNF-α. Furthermore, QRQS remarkably regulated gut microbiota diversity by increasing Lactobacillaceae and decreasing Bacteroidales. The inflammatory factors in peripheral serum of ft/ft mice showed a close correlation with gut microbiota, as determined using the Spearman correlation coefficient. Additionally, PICRUSt analysis revealed an enrichment in ascorbate and aldarate metabolism, fatty acid metabolism and biosynthesis, and propanoate metabolism in the QRQS group compared to the ft/ft group. Finally, we identified liquiritin as the primary active ingredient of QRQS using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Our findings revealed that QRQS improved AD-like symptoms and alleviated skin inflammation in ft/ft and MC903-induced mice. This suggests that modulating the gut microbiota may help elucidate its anti-inflammation activation mechanism, highlighting a new therapeutic strategy that targets the intestinal flora to prevent and treat AD.

Introduction Quitting smoking can lead to substantial health gains, even later in life. Many smokers who attempt to quit experience several relapses before achieving sustainable cessation. This study aims to ascertain the differences between quitters with short and long abstinence time and to explore relapse reasons among smokers with cessation experience in Shanghai. Methods From January to December 2022, 1745 current smokers were recruited in Minhang, Jiading, Qingpu and Songjiang districts of Shanghai. We used an electronic questionnaire to collect data. We implemented logistic regression for odds ratio (OR) and 95% confidence interval (CI) calculation to explore factors associated with long cessation time among smokers with cessation experience of ≥3 months, ≥6 months, and ≥12 months. Results Of the 1745 smokers included, 1452 (83.2%) were males, with an average age of 44.2 years, and 48.0% (838/1745) had cessation experience but relapsed. Logistic regression indicated that smokers aged ≥45 years had a longer cessation duration (adjusted odds ratio, AOR=3.10; 95% CI: 1.97– 4.88). Moreover, longer cessation duration among smokers was positively associated with low education level of junior high or lower (AOR=2.30; 95% CI: 1.42–3.72) and senior high (AOR=2.19; 95% CI: 1.53–3.15), older age at first tobacco smoking (AOR=1.62; 95% CI: 1.1.16–2.25), but was negatively associated with longer smoking duration (AOR=0.67; 95% CI: 0.43–0.00) and higher smoking burden (AOR=0.44; 95% CI: 0.28–0.72). The main reasons for cessation relapse were social interaction needs (34.5%) and discomfort due to abstinence (29.1%). Conclusions The relapse rate was high among smokers even after 12 months of abstinence. Smokers with older age, lower education level, shorter smoking duration and lower tobacco burden had longer cessation duration. Social interaction needs and withdrawal symptoms were the main relapse reasons. It is highly recommended that health bureaux consistently conduct tobacco control initiatives to spread awareness about the detrimental effects of tobacco smoke and the advantages of quitting smoking, even after achieving cessation.

AbstractBackground Psoriasis critically influences the psychosocial well-being of patients and reduces their quality of life and work efficiency beyond skin symptoms. However, evidence on the association between life quality based on the Dermatology Life Quality Index (DLQI) and psoriasis severity is limited, particularly in China. This study aimed to explore the association between life quality based on the DLQI evaluation and disease severity among psoriasis patients in China.Methods Four thousand two hundred and thirty psoriasis patients were recruited from the Chinese National Clinical Research Center for Skin and Immune Diseases from 2020 to 2021. Information was collected by applying a structured questionnaire and onsite physical examination. Data analysis was performed by using SAS software (version 9.4; SAS Inc., Cary, NC), and statistical significance was set at p

Our research investigates two questions: Who is leading the metaverse? Who should lead? The questions are important because metaverse will have significant consequences for individuals, businesses, and society. We examined the current leaders of metaverse on two evolutionary paths, namely Web 2 and Web 3. Based on regulatory reports, corporate press releases, and patents, we found that only a handful of Web 2 companies are “all-in” on metaverse, and at least one of these enterprises, Meta, is on track to end up as a dominant platform provider. Based on market capitalization, user activity, and patents, only a handful of Web 3 communities are emerging. Despite the hype, we are still in the early days for metaverse on both evolutionary paths. As far as who should lead, we advocate for Web 3 because it benefits more users, content creators, and businesses. However, the future of metaverse is not deterministic and it will emerge from the choices we make today. We offer recommendations on how scholars and companies can support the Web 3 path to the metaverse.

Background: Gout is one of the most prevailing inflammatory arthritis, in which joint pain and dysfunction may drastically reduce patients' quality of life, work efficiency, and increase the burden of medical treatment. The Huzhang Tongfeng granule (HZTFG) has been utilized clinically for more than 30 years with satisfactory effects and no significant adverse reactions. However, the mechanisms that underlie HZTFG's effect remain indeterminate. Methods: Firstly, the Liquid Chromatography-Mass Spectrometry (LC-MS) analyses were applied to clarify the multi-components of HZTFG to establish the quality control parameters. After the monosodium urate (MSU) crystals induced Acute gouty arthritis (AGA) model was established, behavioral testing, joint swelling, hematoxylin, and eosin (H&E) staining were applied to assess the effect of HZTFG on improving joint pain, swelling, synovial inflammation of the MSU crystals-injected mice. Moreover, to further understand the underlying mechanism of the action of HZTFG on AGA, RNA Sequencing (RNA-seq) analysis was performed to detect differentially expressed genes (DEGs) after HZTFG treatment. Thereafter, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched via gene set enrichment analysis (GSEA) to assess the functions and pathways of DEGs. Furthermore, Reverse Transcription Polymerase Chain Reaction (RT-qPCR) analysis and enzyme-linked immunosorbent assay (ELISA) were applied for validation in vivo. Results: After treatment with HZTFG, RNA-seq results revealed 44 DEGs, of which 20 genes were remarkably down-regulated and 24 genes were up-regulated. Besides, the expression of these assayed genes were noticeably decreased, including Cxcl1, Cxcl2, Cebpb, Lcn2, Ptgs2, Mmp13, Fos, Socs3, Sele, and Junb. Moreover, animal experiments also demonstrated that TNF signaling pathway and IL-17 signaling pathway are key pathways in HZTFG treated MSU-induced AGA mouse model. Conclusion: HZTFG attenuated MSU crystals-induced inflammatory response through TNF and IL-17 signaling pathways by inhibiting the activation of related chemokines, inflammatory proteins, transcription factors, suppressor of cytokine signaling, and adhesion molecule in AGA. This study further provides the potential therapeutic targets for AGA treatment.

Abstract Mid‐tropospheric Carbonyl sulfide (OCS) retrievals from the Tropospheric Emission Spectrometer (TES) are utilized to study OCS distributions during the dry/wet seasons over the Amazon rainforest. TES OCS retrievals reveal positive OCS anomalies (∼16 ppt) over the central and southern parts of the Amazon during August–October (dry season) compared to January–March (wet season). There is less OCS taken up by vegetation and soil and more OCS released from biomass burning during the dry season, which causes an increase in OCS concentrations. Strong sinking air during the dry season also helps to trap OCS and this contributes to positive OCS anomalies. MOZART‐4 model captures positive OCS anomalies over the central and southern regions of the Amazon and negative OCS anomalies over the northern part of the Amazon, which are similar to those from TES mid‐tropospheric OCS retrievals. Our studies can help us better understand OCS variations and photosynthetic activities.

Introduction A number of studies have reported a high correlation between psoriasis and metabolic syndrome (MetS), and tobacco smoking is one independent risk factor accounting for the increased prevalence both for psoriasis and MetS. However, few studies have been conducted to assess the effects of tobacco smoking on co-morbidities of psoriasis and MetS. Methods We conducted a cross-sectional study with 1014 psoriasis patients recruited from January to May 2021. Patients were recruited with a cluster survey method in Yueyang Hospital (affiliated with Shanghai University of Traditional Chinese Medicine) and Shanghai Skin Diseases Hospital (affiliated with Tongji University). Data were collected by face-to-face questionnaire interviews which included basic information, personal life habits, medical history, and clinical examinations. SPSS 24.0 was used for data analysis and a p

Objective: To identify the potential mechanism of Huzhang Tongfeng Granules (HTG) for the treatment of acute gouty arthritis (AGA). Methods: First of all, we used network pharmacology to build a network of components-targets of HTG. Secondly, the ClusterONE algorithm was applied to construct a modular network as well as discover hub genes and kernel pathways. Lastly, the MSU crystals-induced AGA mice model was used to verify the hub genes and kernel pathways of HTG. Results: HTG down-regulated the expressions of ADRB3, PIK3CA, FYN, PIK3R1, CASR, PLCG1, SYK, EGFR, and up-regulated MC1R, MC5R. Moreover, according to the kernel clusters enrichment analysis, HTG down-regulated NF-κB and P13K-Akt signaling pathways to ameliorate the AGA mice model. Conclusion: In summary, the potential targets and kernel pathways were proved in this study, supporting the clinical application of HTG for the treatment of AGA.

Background: Psoriasis is a chronic and immune-mediated skin disorder that currently has no cure. Pyroptosis has been proved to be involved in the pathogenesis and progression of psoriasis. However, the role pyroptosis plays in psoriasis remains elusive.Methods: RNA-sequencing data of psoriasis patients were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed pyroptosis-related genes (PRGs) between psoriasis patients and normal individuals were obtained. A principal component analysis (PCA) was conducted to determine whether PRGs could be used to distinguish the samples. PRG and immune cell correlation was also investigated. Subsequently, a novel diagnostic model comprising PRGs for psoriasis was constructed using a random forest algorithm (ntree = 400). A receiver operating characteristic (ROC) analysis was used to evaluate the classification performance through both internal and external validation. Consensus clustering analysis was used to investigate whether there was a difference in biological functions within PRG-based subtypes. Finally, the expression of the kernel PRGs were validated in vivo by qRT-PCR.Results: We identified a total of 39 PRGs, which could distinguish psoriasis samples from normal samples. The process of T cell CD4 memory activated and mast cells resting were correlated with PRGs. Ten PRGs, IL-1β, AIM2, CASP5, DHX9, CASP4, CYCS, CASP1, GZMB, CHMP2B, and CASP8, were subsequently screened using a random forest diagnostic model. ROC analysis revealed that our model has good diagnostic performance in both internal validation (area under the curve [AUC] = 0.930 [95% CI 0.877–0.984]) and external validation (mean AUC = 0.852). PRG subtypes indicated differences in metabolic processes and the MAPK signaling pathway. Finally, the qRT-PCR results demonstrated the apparent dysregulation of PRGs in psoriasis, especially AIM2 and GZMB.Conclusion: Pyroptosis may play a crucial role in psoriasis and could provide new insights into the diagnosis and underlying mechanisms of psoriasis.

Abstract. Increasing evidence suggests that long non-coding RNAs (lncRNAs) are of vital importance for various biological processes, and dysregulation of lncRNAs is frequently associated with various diseases such as psoriasis. LncRNAs modulate gene expression at the transcriptional, post-transcriptional, and translational levels; however, the specific regulatory mechanisms of lncRNAs in psoriasis remain largely unexplored. This review provides an overview of recent studies investigating mechanisms and functions of lncRNAs in psoriasis, especially focusing on the role of lncRNAs in keratinocytes, T cells, and dendritic cells.

Atopic dermatitis (AD) is a chronic and relapsing cutaneous disorder characterized by compromised immune system, excessive inflammation, and skin barrier disruption. Post-translational modifications (PTMs) are covalent and enzymatic modifications of proteins after their translation, which have been reported to play roles in inflammatory and allergic diseases. However, less attention has been paid to the effect of PTMs on AD. This review summarized the knowledge of six major classes (including phosphorylation, acetylation, ubiquitination, SUMOylation, glycosylation, o-glycosylation, and glycation) of PTMs in AD pathogenesis and discussed the opportunities for disease management.

IntroductionTobacco smoking is associated with the onset and severity of psoriasis, and understanding the prevalence of tobacco smoking among patients with psoriasis is critical due to its high physical and mental influence and heavy disease burden. However, evidence on the association between tobacco smoking and psoriasis severity is still limited in China.ObjectivesThe objective of this study was to examine the prevalence of tobacco smoking and explore the association between tobacco smoking and diseases severity among patients with psoriasis.MethodsA total of 4,529 patients with psoriasis in 200 selected hospitals were recruited in China between January 2020 and September 2021. Detailed information covering demographic feature, tobacco smoking, and psoriasis history were collected through an electronic questionnaire, and clinical data were extracted from the health information system (HIS). SAS 9.4 was used for data analysis, and a p-value of 13, when compared with patients with PASI score < 3.0. Similarly, the OR of current tobacco smoking prevalence was 1.8 [95% CI: (1.5–2.2)] for PASI score (3.0–7.0), 1.9 for PASI score (7.1–13.0), and 3.1 for PASI score >13, when compared with patients with PASI score

Ever since the deployment of the first-generation of mobile telecommunications, wireless communication technology has evolved at a dramatically fast pace over the past four decades. The upcoming fifth-generation (5G) holds a great promise in providing an ultra-fast data rate, a very low latency, and a significantly improved spectral efficiency by exploiting the millimeter-wave spectrum for the first time in mobile communication infrastructures. In the years beyond 2030, newly emerged data-hungry applications and the greatly expanded wireless network will call for the sixth-generation (6G) communication that represents a significant upgrade from the 5G network - covering almost the entire surface of the earth and the near outer space. In both the 5G and future 6G networks, millimeter-wave technologies will play an important role in accomplishing the envisioned network performance and communication tasks. In this paper, the relevant millimeter-wave enabling technologies are reviewed: they include the recent developments on the system architectures of active beamforming arrays, beamforming integrated circuits, antennas for base stations and user terminals, system measurement and calibration, and channel characterization. The requirements of each part for future 6G communications are also briefly discussed.

BackgroundPostoperative ileus (POI) is an important complication of gastrointestinal (GI) surgery. Acupuncture has been increasingly used in treating POI. This study aimed to assess the effectiveness and safety of acupuncture for POI following GI surgery.MethodsSeven databases (PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wan fang Data, VIP Database for Chinese Technical Periodicals, and Chinese Biomedical Literature Database) and related resources were searched from inception to May 30, 2021. Randomized controlled trials (RCTs) reporting the acupuncture for POI in GI were included. The quality of RCTs was assessed by the Cochrane Collaboration Risk of Bias tool, and the certainty of the evidence was evaluated by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. A meta-analysis was performed by using RevMan 5.4 software.ResultsEighteen RCTs involving 1413 participants were included. The meta-analysis showed that acupuncture could reduce the time to first flatus (TFF) (standardized mean difference [SMD] = -1.14, 95% confidence interval [CI]: -1.54 to -0.73, P < 0.00001), time to first defecation (TFD) (SMD = -1.31, 95% CI: -1.88 to -0.74, P < 0.00001), time to bowel sounds recovery (TBSR) (SMD = -1.57, 95% CI: -2.14 to -1.01, P < 0.00001), and length of hospital stay (LOS) (mean difference [MD] = -1.68, 95% CI: -2.55 to -0.80, P = 0.0002) compared with usual care. A subgroup analysis found that acupuncture at distal acupoints once daily after surgery had superior effects on reducing TFF and TFD. A sensitivity analysis supported the validity of the finding. Acupuncture also manifested an effect of reducing TFF, TFD and TBSR compared with sham acupuncture but the result was not stable. Relatively few trials have reported whether adverse events have occurred.ConclusionsAcupuncture showed a certain effect in reducing POI following GI surgery with very low-to-moderate quality of evidence. The overall safety of acupuncture should be further validated. More high-quality, large-scale, and multicenter original trials are needed in the future.

Sheng-Ji Hua-Yu (SJHY) formula has been proved to reduce the severity of diabetic wound healing without significant adverse events in our previous clinical trials. However, based on multi-target characteristics, the regulatory network among herbs, ingredients, and hub genes remains to be elucidated. The current study aims to identify the biomarkers of the SJHY formula for the treatment of diabetic wound healing. First, a network of components and targets for the SJHY formula was constructed using network pharmacology. Second, the ClusterONE algorithm was used to build a modular network and identify hub genes along with kernel pathways. Third, we verified the kernel targets by molecular docking to select hub genes. In addition, the biomarkers of the SJHY formula were validated by animal experiments in a diabetic wound healing mice model. The results revealed that the SJHY formula downregulated the mRNA expression of Cxcr4, Oprd1, and Htr2a, while upregulated Adrb2, Drd, Drd4, and Hrh1. Besides, the SJHY formula upregulated the kernel pathways, neuroactive ligand–receptor interaction, and cAMP signaling pathway in the skin tissue homogenate of the diabetic wound healing mice model. In summary, this study identified the potential targets and kernel pathways, providing additional evidence for the clinical application of the SJHY formula for the treatment of diabetic wound healing.

Pigment production is a unique character of melanocytes. Numerous factors are linked with melanin production, including genetics, ultraviolet radiation (UVR) and inflammation. Understanding the mechanism of melanogenesis is crucial to identify new preventive and therapeutic strategies in the treatment of melanoma. Here, we reviewed the current available literatures on the mechanisms of melanogenesis, including the signaling pathways of UVR-induced pigment production, MC1R’s central determinant roles and MITF as a master transcriptional regulator in melanogenesis. Moreover, we further highlighted the role of targeting BRAF, NRAS and MC1R in melanoma prevention and treatment. The combination therapeutics of immunotherapy and targeted kinase inhibitors are becoming the newest therapeutic option in advanced melanoma.

ObjectiveA proportional hazard model was applied to develop a large-scale prognostic model and nomogram incorporating clinicopathological characteristics, histological type, tumor differentiation grade, and tumor deposit count to provide clinicians and patients diagnosed with colon cancer liver metastases (CLM) a more comprehensive and practical outcome measure.MethodsUsing the Transparent Reporting of multivariable prediction models for individual Prognosis or Diagnosis (TRIPOD) guidelines, this study identified 14,697 patients diagnosed with CLM from 1975 to 2017 in the Surveillance, Epidemiology, and End Results (SEER) 21 registry database. Patients were divided into a modeling group (n=9800), an internal validation group (n=4897) using computerized randomization. An independent external validation cohort (n=60) was obtained. Univariable and multivariate Cox analyses were performed to identify prognostic predictors for overall survival (OS). Subsequently, the nomogram was constructed, and the verification was undertaken by receiver operating curves (AUC) and calibration curves.ResultsHistological type, tumor differentiation grade, and tumor deposit count were independent prognostic predictors for CLM. The nomogram consisted of age, sex, primary site, T category, N category, metastasis of bone, brain or lung, surgery, and chemotherapy. The model achieved excellent prediction power on both internal (mean AUC=0.811) and external validation (mean AUC=0.727), respectively, which were significantly higher than the American Joint Committee on Cancer (AJCC) TNM system.ConclusionThis study proposes a prognostic nomogram for predicting 1- and 2-year survival based on histopathological and population-based data of CLM patients developed using TRIPOD guidelines. Compared with the TNM stage, our nomogram has better consistency and calibration for predicting the OS of CLM patients.

In this paper, a 37-42.5GHz (N260 Band) 64 channel full-digital multi-beam array for 5G massive multiple input multiple output (MIMO) applications is developed. The multi-beam array is built on a time division duplexing (TDD) architecture in which the transmitter and receivers are independent and working separately to enable more flexible channel configuration and hardware distribution. The 64 antenna elements of the array are aligned in a way that 16 elements lie in the horizontal and 4 in the vertical direction to deliver higher beam resolution in the horizontal plane. By using cables of unequal lengths, the 16 × 4 antenna elements are connected to a cluster of 8 × 8 transmitters/receivers. The hardware design of the transmitters, receivers, antennas and other circuits is demonstrated, with excellent measured RF performance achieved. Furthermore, the calibration of the massive MIMO array is presented, and the influence of inequality of array feedlines on calibration accuracy in a wide bandwidth is analyzed and experimentally verified. Finally, experimental studies on single beam scanning, multiple concurrent beam generation and over-the-air (OTA) performance of the transmitting and receiving array have been done. Simulation and measurement results suggest that the array has an excellent beam-forming capability that supports beam steering and generation of multiple concurrent beams. The OTA test reveals that the array can provide high modulation and demodulation accuracy for communication.

BackgroundAnti-interleukin (IL)-23 agents are widely used for autoimmune disease treatment; however, the safety and risks of specific symptoms have not been systematically assessed.ObjectivesThe aim of this study was to summarize the characteristics and mechanisms of occurrence of five immunological and non-immunological adverse events caused by different anti-IL-23 agents.MethodsThe Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched for eligible randomized clinical trials published from inception through May 1, 2020. Randomized clinical trials that reported at least one type of adverse event after treatment were included, regardless of sex, age, ethnicity, and diagnosis. Two investigators independently screened and extracted the characteristics of the studies, participants, drugs, and adverse event types. The Cochrane Handbook was used to assess the methodological quality of the included randomized clinical trials. Heterogeneity was assessed using the I2 statistic. Meta-regression was applied to determine the sources of heterogeneity, and subgroup analysis was used to identify the factors contributing to adverse events.ResultsForty-eight studies were included in the meta-analysis, comprising 25,624 patients treated with anti-IL-23 agents. Serious immunological or non-immunological adverse events were rare. Anti-IL-12/23-p40 agents appeared to cause adverse events more easily than anti-IL-23-p19 agents. The incidence of cancer did not appear to be related to anti-IL-23 agent treatment, and long-term medication could lead to mental diseases. The prevention of complications should be carefully monitored when administered for over approximately 40 weeks to avoid further adverse reactions, and the incidence of infection was the highest among general immunological adverse events.ConclusionsThe application of anti-IL-23 agents induced a series of immunological and non-immunological adverse events, but these agents tend to be well-tolerated with good safety profiles.

Taodan granules (TDGs) are clinically efficacious for treating psoriasis, buttheir specific mechanisms of action are unclear. In this study, we determined the concentrations of tanshinone IIA and curcumol using high-performance liquid chromatography (HPLC) to establish quality control parameters for assessing the mechanism of TDGs in treating psoriasis. Thereafter, a mouse model of psoriasis was treated with TDGs. TDGs attenuated imiquimod-induced typical erythema, scales, and thickening of the back and ear lesions in the psoriatic mouse model. Furthermore, PCNA and Ki67-positive cells were reduced in the epidermis of psoriatic lesions following TDG treatment. Finally, the sequencing results were verified using a multitude of methods, and the mechanism of action of TDGs against psoriasis was found to be via the upregulation of metabolic signaling pathways such as the Gly-Ser-Thr axis, the downregulation of immune and inflammatory pathways, and the decrease in Rac2 and Arhgdib concentrations. Overall, this study clarified the mechanism of TDG treatment for psoriasis and provided evidence for its clinical application.

Background: Chinese herbal medicine (CHM) provides a theoretical basis for the treatment of psoriasis with considerable benefits and a low toxicity. The purpose of this quantitative study was to show high-quality evidence of the efficacy and safety of CHM for the treatment of psoriasis to promote its clinical application.Methods: Several databases were systematically searched including PubMed, Embase, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure, Chinese Scientific Journals Database, and Wan Fang Database. High-quality randomized controlled trials that compared CHM with non-CHM interventions were included. The RevMan5.3 software was used to calculate risk ratios (RR) at 95% confidence intervals (CI) and conduct the meta-analysis.Results: Altogether, 1,215 patients participated in this study, including 711 in the experimental group and 504 in the control group. The psoriasis area severity index (PASI) score of the CHM group was significantly lower than that of the placebo group (MD, −4.02; 95% CI, −6.71 to −1.34; p = 0.003). To achieve PASI-60 and PASI-75, the arrival rate of the CHM group was higher than that of the placebo group (PASI-60: RR, 3.52; 95% CI, 1.17 to 10.61; p = 0.03; PASI-75: RR, 9.87; 95% CI, 3.11 to 31.31; p = 0.0001). Furthermore, the efficacy rate was higher in patients receiving CHM than in those receiving placebo (RR, 1.72; 95% CI, 1.01 to 2.93; p = 0.04). The results suggested a greater impact of CHM in improving the dermatology life quality index (DLQI) of patients (MD, −2.12; 95% CI, −3.75 to −0.49; p = 0.01). Regarding pruritus severity, there was no significant difference between the two groups (MD, −1.90; 95% CI, −3.79 to −0.01; p = 0.05). The meta-analysis revealed that the recurrence rate (RR, 0.74; 95% CI, 0.32 to 1.71; p = 0.48) and proportion of adverse events (RR, 1.36; 95% CI, 0.95 to 1.93; p = 0.09) associated with using CHM were similar to those associated with using a placebo.Conclusion: CHM appears safe and effective in the treatment of psoriasis and has a great positive impact on the DQLI of patients; however, CHM could not completely eliminate skin lesions, improve pruritus severity, and reduce the recurrence rate.

Background: Psoriasis and dementia are both inflammatory diseases. The association between psoriasis and dementia has rarely been investigated, and the existing results are conflicting. Thus, we conducted this study to evaluate whether an association exists between psoriasis and dementia.Methods: We searched for studies from six databases from inception to July 30, 2020, using subject and free words. RevMan 5.4 was used to calculate the risk ratio (RR) of dementia in the subjects with psoriasis. When heterogeneity was present, a random-effects model was used. Subgroup, sensitivity, and meta-regression analyses were performed using Stata 15.1.Results: Nine studies were identified and included in the study, of which seven that involved a total of 3,638,487 participants were included in the meta-analysis. We found that among the patients with psoriasis (RR: 1.14, 95% confidence interval [CI]: 1.06–1.24, p = 0.0009) and psoriatic arthritis (RR: 2.20, 95% CI: 1.29–3.78, p = 0.004), the proportions of those with non-vascular dementia (RR: 1.13, 95% CI: 1.11–1.15, p < 0.00001) and vascular dementia (RR: 1.41, 95% CI: 1.09–1.82, p = 0.009) were higher than that among the patients without psoriasis. Those with dementia were also more likely to develop psoriasis, and those with severe psoriasis were less likely to die from dementia (RR: 1.88, 95% CI: 0.72–4.90, p = 0.020). The meta-regression analysis did not show any significant sources of heterogeneity.Conclusions: The patients with psoriasis and psoriatic arthritis show high prevalence of different types of dementia. Based on the findings of this study, dementia may not be considered a high-risk factor of death from severe psoriasis. However, identification of this potential risk allows for early intervention, thereby reducing comorbidities and deaths.

Abstract Background Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro−/anti-inflammatory factors on transforming growth factor-β(TGF-β) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. Methods SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. Results Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula accelerated re-epithelialization of diabetic wound healing. Conclusion The present study found that diabetic delayed wound healing time is closely related to the high expression level of activin/follistatin, which leads to excessive inflammation in the process of re-epithelization. SJHY Formula accelerates re-epithelialization and healing time of diabetic wounds through decreasing the high expression of activin/follistatin. Graphical abstract

Background. Cyr61 is considered a novel proinflammatory factor. Gouty arthritis (GA) is a self-limited inflammatory reaction caused by monosodium urate (MSU) crystals. In this study, we assessed the role of Cyr61 in the inflammatory process of GA. Methods. We investigated the expression of Cyr61 in MSU-induced rat gout models and MSU-stimulated rat fibroblast-like synovial (FLS) cells. After inhibiting the expression of Cyr61, levels of IL-1β, TNF-α, and IL-6 were detected by ELISA, qPCR, western blot, and immunohistochemical methods. We probed the downstream NF-κB signaling pathway using the NF-κB inhibitor PDTC, and levels of NF-κB and p-NF-κB were detected by western blot and qPCR. Results. Our results demonstrate that Cyr61 plays a potent role in the formation of local inflammation in vitro and in vivo. Cyr61 was highly expressed in synovial tissues of gout models, and the expression of Cyr61 protein was also significantly increased in MSU-stimulated FLS cells. Cyr61 promoted MSU-induced acute inflammation via the NF-κB signaling pathway. Conclusions. Our study has revealed that Cyr61 is an important regulatory factor for the initiation of inflammation in GA. The high expression of Cyr61 protein can induce synovial cells to produce many inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, partly in an NF-κB-dependent manner. Thus, inhibition of Cyr61 could be a new target and strategy for the prevention and treatment of GA.

Summary: Autophagy plays a critical role in the maintenance of immunological memory. However, the molecular mechanisms involved in autophagy-regulated effector memory formation in CD8+ T cells remain unclear. Here we show that deficiency in NIX-dependent mitophagy leads to metabolic defects in effector memory T cells. Deletion of NIX caused HIF1α accumulation and altered cellular metabolism from long-chain fatty acid to short/branched-chain fatty acid oxidation, thereby compromising ATP synthesis during effector memory formation. Preventing HIF1α accumulation restored long-chain fatty acid metabolism and effector memory formation in antigen-specific CD8+ T cells. Our study suggests that NIX-mediated mitophagy is critical for effector memory formation in T cells. : Gupta et al. demonstrate that mitophagy mediated by NIX, a mitochondrial outer membrane protein, plays a critical role in CD8+ T cell effector memory formation by regulating mitochondrial superoxide-dependent HIF1α protein accumulation and fatty acid metabolism. These findings elucidate the molecular mechanisms regulating T cell effector memory formation against viruses. Keywords: NIX, mitophagy, autophagy, CD8+ T cells, effector memory cells, HIF1α, fatty acid metabolism, long-chain fatty acid oxidation, short/branched-chain fatty acid oxidation, mitochondrial superoxide

Background:Tripterygium wilfordii Hook F can cause adverse effects (AEs) in clinical application and may be harmful to human health. This study aim to summarize the AEs caused by T. wilfordii tgpolyglycoside (TWP), the most common preparation of T. wilfordii Hook F for clinical use.Methods: The Cochrane Library, EMBASE, PubMed, and Web of Science were searched to identify potential articles on this topic. All single-arm trials, controlled clinical trials, and randomized controlled trials were selected and summarized. Meta-regression was used to determine the sources of heterogeneity, and subgroups were used to identify factors leading to AEs.Results: Forty-six studies, comprising 25 randomized controlled trials, 13 controlled clinical trials, and 8 single-arm trials, were included in this meta-analysis, representing 2437 enrolled TWP-treated participants. Combined intervention, drug dosage, medication treatment, pharmaceutical manufacturers, and specific organ toxicity were identified as potential factors leading to TWP-induced AEs in this meta-analysis. In patients treated with TWP, the global incidence of AEs was 30.75% (95% confidence interval [21.18–40.33], I2 = 97%), and that of severe grade AEs was 4.68% (95% confidence interval [0.00–12.72], I2 = 53%). Organ-specific analyses indicated that TWP treatment elicited intestinal toxicity, reproductive toxicity, hepatotoxicity, nephrotoxicity, hematotoxicity, cutaneous toxicity, and other damages. The AEs analyzed in the subgroups of combined intervention, drug dosage, medication treatment, and pharmaceutical manufacturers were considered as primary outcomes, and organic-specific AEs were considered as secondary outcomes.Conclusions: The occurrence of TWP-induced AEs was systemic, organ-specific, and related to medication course, combined intervention, and drug dosage.

The influence of the hydrological cycle in the greenhouse gas (GHG) effect of tropospheric ozone (O3) is quantified in terms of the O3longwave radiative effect (LWRE), which is defined as the net reduction of top-of-atmosphere flux due to total tropospheric O3absorption. The O3LWRE derived from the infrared spectral measurements by Aura’s Tropospheric Emission Spectrometer (TES) show that the spatiotemporal variation of LWRE is relevant to relative humidity, surface temperature, and tropospheric O3column. The zonally averaged subtropical LWRE is ~0.2 W m-2higher than the zonally averaged tropical LWRE, generally due to lower water vapor concentrations and less cloud coverage at the downward branch of the Hadley cell in the subtropics. The largest values of O3LWRE over the Middle East (>1 W/m2) are further due to large thermal contrasts and tropospheric ozone enhancements from atmospheric circulation and pollution. Conversely, the low O3LWRE over the Inter-Tropical Convergence Zone (on average 0.4 W m-2) is due to strong water vapor absorption and cloudiness, both of which reduce the tropospheric O3absorption in the longwave radiation. These results show that changes in the hydrological cycle due to climate change could affect the magnitude and distribution of ozone radiative forcing.