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Summary: Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18–65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin −10% (2.69%; 95% CI −4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (−3.25; 95% CI −5.56, −0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP

BackgroundCryoballoon ablation (CBA) and laser balloon ablation (LBA) are two innovative ways for the treatment of atrial fibrillation (AF). This study aimed to evaluate the efficacy and safety of cryoballoon ablation and laser balloon ablation in patients with AF.MethodsWe searched Pubmed, Embase, Ovid, Web of Science and other databases for comparative trials comparing CB and LB ablation in the treatment of AF, from establishment of database to August, 2023.ResultsA total of 13 studies and 3,582 patients were included (CBA, n = 2,308; LBA, n = 1,274). There was no difference between CBA and LBA in acute PVI rate per vein, 12-months recurrence rate of AF, 12-months recurrence rate of atrial arrhythmia, occurrence rate of pericardial tamponade, occurrence rate of inguinal complications. LBA presented a lower acute PVI rate per patients (CBA 97.0% vs. LBA 93.4%, RR = 1.04, 95%CI: 1.01–1.07). Transient nerve palsy was more likely to occur after CBA (CBA 2.7% vs. LBA 0.7%, RR = 4.25, 95%CI: 2.06–8.76). However, the occurrence of persistent nerve palsy between CBA and LBA groups were similar (CB 1.4% vs. LB 1.0%, RR = 1.09, 95%CI: 0.55–2.14). In terms of procedural duration, the procedural time of CBA was shorter than that of LBA (WMD = −26.58, 95%CI: −36.71–16.46).ConclusionsCompared with LBA, CBA had a shorter procedural duration. There was a higher incidence of transient but not persistent phrenic nerve palsy after CBA.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=272607 Identifier (CRD42021272607).

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczema-like skin lesions, dry skin, severe itching, and recurrent recurrence. The whey acidic protein four-disulfide core domain gene WFDC12 is highly expressed in skin tissue and up-regulated in the skin lesions of AD patients, but its role and relevant mechanism in AD pathogenesis have not been studied yet. In this study, we found that the expression of WFDC12 was closely related to clinical symptoms of AD and the severity of AD-like lesions induced by DNFB in transgenic mice. WFDC12-overexpressing in the epidermis might promote the migration of skin-presenting cells to lymph nodes and increase Th cell infiltration. Meanwhile, the number and ratio of immune cells and mRNA levels of cytokines were significantly upregulated in transgenic mice. In addition, we found that ALOX12/15 gene expression was upregulated in the arachidonic acid metabolism pathway, and the corresponding metabolite accumulation was increased. The activity of epidermal serine hydrolase decreased and the accumulation of platelet-activating factor (PAF) increased in the epidermis of transgenic mice. Collectively, our data demonstrate that WFDC12 may contribute to the exacerbation of AD-like symptoms in DNFB-induced mouse model by enhancing arachidonic acid metabolism and PAF accumulation and that WFDC12 may be a potential therapeutic target for human atopic dermatitis.

Abstract Defective execution of proteases and protease inhibitors that mediate abnormal signaling cascades is emerging as a key contributor to skin diseases, such as psoriasis. SerpinB7 is identified as a skin-specific endogenous protease inhibitor, but the role and underlying mechanism in psoriasis are poorly understood. Here we found that SerpinB7 is highly expressed in psoriatic keratinocytes of patients and imiquimod-induced psoriatic lesions in mice. SerpinB7-/- mice showed abnormal epidermal barrier integrity and skin architecture in homeostasis, and aggravated psoriatic lesion with inhibiting terminal differentiation and increasing inflammatory cells infiltration compared to SerpinB7+/+ mice after Imiquimod treatment. Mechanistically, SerpinB7 deficiency results in excessive proliferation and impaired differentiation, as well as increased chemokines and antimicrobial peptide expression in normal human epidermal keratinocyte and mouse primary keratinocyte. Transcriptomics and proteomics results showed that the SeprinB7 deficiency affected keratinocyte differentiation and proinflammatory cytokines, possibly by affecting the calcium ion channel-related proteins. Notably, we demonstrated that SerpinB7 deficiency prevented the increase in intracellular Ca2+ influx, which was partly eliminated by the intracellular Ca2+ chelator BAPTA-AM. Our findings first described the critical role of SerpinB7 in the regulation of keratinocyte differentiation and psoriatic microenvironment mediated via keratinocytes' intracellular calcium flux, proposing a new candidate for therapeutic targets in psoriasis.

Abstract Interleukin 37 (IL‐37), a member of the IL‐1 family, is considered a suppressor of innate and adaptive immunity and, hence is a regulator of tumor immunity. However, the specific molecular mechanism and role of IL‐37 in skin cancer remain unclear. Here, we report that IL‐37b‐transgenic mice (IL‐37tg) treated with the carcinogenic 7,12‐dimethylbenzoanthracene (DMBA)/12‐o‐tetradecylphorbol‐13‐acetate (TPA) exhibited enhanced skin cancer and increased tumor burden in the skin by inhibiting the function of CD103+ dendritic cells (DCs). Notably, IL‐37 induced rapid phosphorylation of adenosine 5‘‐monophosphate (AMP)‐activated protein kinase (AMPK), and via single immunoglobulin IL‐1‐related receptor (SIGIRR), inhibited the long‐term Akt activation. Specifically, by affecting the SIGIRR‐AMPK‐Akt signaling axis, which is related to the regulation of glycolysis in CD103+DCs, IL‐37 inhibited their anti‐tumor function. Our results show that a marked correlation between the CD103+DC signature (IRF8, FMS‐like tyrosine kinase 3 ligand, CLEC9A, CLNK, XCR1, BATF3, and ZBTB46) and chemokines C‐X‐C motif chemokine ligand 9, CXCL10, and CD8A in a mouse model with DMBA/TPA‐induced skin cancer. In a word, our results highlight that IL‐37 as an inhibitor of tumor immune surveillance through modulating CD103+DCs and establishing an important link between metabolism and immunity as a therapeutic target for skin cancer.

ObjectiveIt has long been debated whether rhythm control vs. rate control strategies have differing effects on mortality and morbidity for atrial fibrillation (AF). Recently, several randomized controlled studies (RCTs) and observational trials described that an early rhythm management method was linked to a lower likelihood of negative clinical outcomes in individuals with AF. We wanted to see if an early rhythm management method may help patients with AF.MethodsWe performed a systematic search to retrieve studies assessing the outcomes of early rhythm control vs. rate control in AF by using PubMed, Web of Science, Cochrane Library, and Embase published between 01/01/2000 and 15/04/2022.ResultsFinally, two RCTs, one retrospective analysis of RCTs, and four observational studies were identified. Compared with rate control, early rhythm control has been linked to lower all-cause mortality. [risk ratio (RR), 0.76; 95% CI 0.69–0.83; P < 0.00001; I2 = 77%]. The early rhythm control group was also associated with a lower risk of cardiovascular mortality (RR, 0.68; 95% CI 0.63–0.74; P < 0.00001; I2 = 33), stroke (RR, 0.77; 95% CI 0.67–0.87; P < 0.001; I2 = 64), and heart failure hospitalization (RR, 0.74; 95% CI 0.59–0.93; P = 0.0009; I2 = 93%). We found no significant difference in nights spent in hospital per year, acute coronary syndrome, major bleeding, and cardiac arrest/ventricular arrhythmia between the groups.ConclusionIn this meta-analysis, early rhythm therapy was linked to a lower risk of all-cause mortality, cardiovascular mortality, stroke, and heart failure hospitalization compared with the rate control group.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022333592.

PurposeThis meta-analysis aimed to explore the comparative short-term efficacy and safety of drug-coated balloon (DCB) vs. drug-eluting stent (DES) for treating small-vessel coronary artery lesions in diabetic patients.MethodsWe searched PubMed, EMBASE, the Cochrane Library, and China National Knowledgement Infrastructure (CNKI) for retrieving relevant studies regarding the comparison of DCB with DES in treating small-vessel coronary artery lesions in diabetic patients until May 31, 2022. Two independent authors screened study, extracted data, and assessed methodological quality. Then, the meta-analysis was conducted using RevMan software, version 5.4.ResultsWe included 6 studies with 847 patients in this meta-analysis. Pooled results showed that DCB was associated with fewer major adverse cardiac events (MACE) [RR, 0.60; 95% confidence interval (CI), 0.39–0.93; p = 0.02], myocardial infarction (MI) (RR, 0.42; 95% CI, 0.19–0.94; p = 0.03), target lesion revascularization (TLR) (RR, 0.24; 95% CI, 0.08–0.69; p < 0.001), target vessel revascularization (TVR) (RR, 0.33; 95% CI, 0.18–0.63; p < 0.001), binary restenosis (RR, 0.27; 95% CI, 0.11–0.68; p = 0.005), and late lumen loss (LLL) [mean difference (MD), −0.31; 95% CI, −0.36 to −0.27; p < 0.001], but was comparable technique success rate, death, minimal lumen diameter (MLD), and net lumen gain (NLG) to DES. There was no difference in long-term outcomes between these two techniques.ConclusionsThis meta-analysis shows that DCB is better than DES in the short-term therapeutic efficacy and safety of small-vessel coronary artery lesions in diabetic patients. However, more studies are required to validate our findings and investigate the long-term effects and safety of DCB.

BackgroundThe results of studies evaluating the left atrial appendage (LAA) function and structure as predictors of atrial fibrillation (AF) recurrence after catheter ablation (CA) are contradictory. Therefore, we performed a meta-analysis to assess whether the LAA function and structure can predict the recurrence of AF after CA.MethodsThe PubMed, EMBASE, Web of Science, and Cochrane library databases were used to conduct a comprehensive literature search. Finally, 37 studies encompassing 11 LAA parameters were included in this meta-analysis.ResultsCompared with those in the non-recurrence group, the recurrence group had increased LAA volume (SMD 0.53, 95% CI [0.36, 0.71] p < 0.00001), LAA volume index, LAA orifice area, and LAA orifice short/long axis and decreased LAA emptying flow velocity (SMD -0.54, 95% CI [-0.68, -0.40], P < 0.00001), LAA filling flow velocity, and LAA ejection fraction, while there was no significant difference in LAA morphology or LAA depth.ConclusionLarge LAA structure of pre-ablation (LAA volume, orifice area, orifice long/short axis, and volume index) and decreased LAA function of pre-ablation (LAA emptying flow velocity, filling flow velocity, ejection fraction, and LASEC) increase the odds of AF recurrence after CA.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022324533].

Whey acidic protein four-disulfide core domain protein 12 (WFDC12) has been implicated in the pathogenesis of psoriasis but the specific molecular mechanism is not clearly defined. In this study, we found the expression of WFDC12 protein closely correlated with psoriasis. WFDC12 in keratinocyte might increase infiltration of Langerhans cells (LCs) and monocyte-derived dendritic cells (moDDCs), up-regulating the co-stimulation molecular CD40/CD86. Th1 cells in lymph nodes were higher in K14-WFDC12 transgenic psoiasis-like mice. Meanwhile, the mRNA of IL-12 and IFN-γ in the lesion skin was significantly increased in transgenic mice. Moreover, we found that the expression of the proteins that participated in the retinoic acid–related pathway and immune signaling pathway was more changed in the lesion skin of K14-WFDC12 transgenic psoriasis-like mice. Collectively, the results implied that WFDC12 might affect the activation of the retinoic acid signaling pathway and regulate the infiltration of DC cells in the skin lesions and lymph nodes, thereby inducing Th1 cells differentiation and increasing the secretion of IFN-γ to exacerbate psoriasis in mice.

Background: Left atrial appendage closure (LAAC) is an established therapy for patients with atrial fibrillation (AF); however, there is a limited understanding of LAAC in elderly patients (≥75 years old). We conducted a meta-analysis to investigate the procedural complications and long-term outcomes after LAAC in the elderly versus the non-elderly. Methods: We screened PubMed, EMBASE, Cochrane Library, and Web of Science. Procedural endpoints of interest included successful implantation LAAC rates, in-hospital mortality, major bleeding events, pericardial effusion/tamponade, stroke, and vascular access complications related to LAAC. Long-term outcomes included all-cause mortality, major bleeding events, and stroke/transient ischemic attack (TIA) during follow-up. Results: Finally, 12 studies were included in the analysis; these included a total of 25,094 people in the elderly group and 36,035 people in the non-elderly group. The successful implantation LAAC rates did not differ between the groups, while the elderly patients experienced more periprocedural mortality (OR 2.62; 95% CI 1.79–3.83, p < 0.01; I2 = 0%), pericardial effusion/tamponade (OR 1.39; 95% CI: 1.06–1.82, p < 0.01; I2 = 0%), major bleeding events (OR 1.32; 95% CI 1.17–1.48, p < 0.01; I2 = 0%), and vascular access complications (OR 1.34; 95% CI 1.16–1.55, p < 0.01; I2 = 0%) than the non-elderly patients. The long-term stroke/TIA rates did not differ between the elderly and the non-elderly at least one year after follow-up. Conclusions: Even though successful implantation LAAC rates are similar, elderly patients have a significantly higher incidence of periprocedural mortality, major bleeding events, vascular access complications, and pericardial effusion/tamponade after LAAC than non-elderly patients. The stroke/TIA rates did not differ between both groups after at least one-year follow-up.

Abstract Background The anticoagulation of atrial fibrillation catheter ablation during the perioperative stage does matter and should be treated with discretion. We aimed to assess impact of three important genes participating in vitamin K cycle (i.e. VKORC1 rs9923231, CYP4F2 rs2108622 and NQO1 rs1800566) on the daily stable warfarin dose requirement in Sichuan Han Chinese patients with catheter ablation of atrial fibrillation. Methods A total of 222 atrial fibrillation patients taking stable warfarin therapy after catheter ablation operation were enrolled in this study. The study population included had high (≥2) risk according to the CHA2DS2-VASc risk score. Genotypes of VKORC1 rs9923231, CYP4F2 rs2108622 and NQO1 rs1800566 were analyzed by using the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). Multiple linear regression analysis was applied to depict the impact of VKORC1 rs9923231, CYP4F2 rs2108622 and NQO1 rs1800566 on the daily stable warfarin dose requirement. Results Carriers of VKORC1 rs9923231 AG/GG genotypes required significantly higher warfarin dose (3.03 ± 0.28 mg/day, 7.19 mg/day, respectively) than AA carriers (2.52 ± 0.07 mg/day; P

Abstract Background Interleukin-1β (IL-1β) is a pivotal proinflammatory cytokine that is strongly associated with the inflammation of gout. However, the underlying mechanism through which the production of IL-1β is regulated has not been fully elucidated. Our previous work identified that miR-302b had an important immune regulatory role in bacterial lung infections. This study was conducted to evaluate the function of miR-302b on monosodium urate (MSU) crystal-induced inflammation and its mechanism. Methods The expression pattern and the immune-regulatory role of miR-302b were evaluated both in vitro and in vivo. The functional targets of miR-302b were predicted by bioinformatics, and then validated by genetic approaches. In addition, the clinical feature of miR-302b was analyzed using serum samples of patients with gouty arthritis. Results The extremely high expression of miR-302b was observed in both macrophages and mouse air membranes treated with MSU. Intriguingly, overexpression of miR-302b regulated NF-κB and caspase-1 signaling, leading to significantly attenuate MSU-induced IL-1β. By genetic analysis, miR-302b exhibited inhibitory function on IRAK4 and EphA2 by binding to their 3′-UTR regions. Corporately silencing IRAK4 and EphA2 largely impaired MSU-induced IL-1β protein production. Moreover, it was also found that miR-302b and EphA2 suppressed the migration of macrophages. Finally, it was observed that high expression of miR-302b was a general feature in patients with gouty arthritis. Conclusions These results suggest that miR-302b can regulate IL-1β production in MSU-induced inflammation by targeting NF-κB and caspase-1 signaling, and may be a potential therapeutic target for gouty arthritis.

Abstract Background Patient initiated aggression is common among Chinese health-care workers, reaching over 10,000 incidents annually (Jinyang web. http://6d.dxy.cn/article/55497 . 2013), and the tense doctor-patient relationship generates stress among medical students. Because of the paucity of data (few surveys pay attention to the effects of violence perpetrated by patients on medical students), this study aimed to characterize patient initiated aggression against medical students. Methods In this cross-sectional survey conducted at a medical school in West China in 2015, 157 medical students completed a self-administered questionnaire and the Short Form-36, which assesses quality of life. The associations between patient initiated aggression exposure and medical students’ career planning or quality of life were assessed using a chi-square test. Results Of the 157 medical students, 48 (30.6%) reported having suffered patient initiated aggression at least once during the previous year in the form of mental abuse (20.4%), offensive threat (14.6%), physical violence (8.3%), sexual harassment (verbal: 8.3% or physical: 1.6%), and extreme violence (physical violence leading to surgical treatment or hospitalization) (0.6%). Insufficient communication was the primary reason cited (27.2%). Emotional attack (mental abuse and offensive threat) occurrence differed among age groups (χ2 = 9.786, P = 0.020) and was ubiquitous among those aged >30 years old. Women were more likely than men to suffer physical violence (χ2 = 6.796, P = 0.009). Patient initiated aggression was not significantly associated with medical students’ career planning or quality of life. Conclusions In this study, patient initiated aggression, albeit common, as in the rest of China, did not appear to be associated with medical students’ career planning or quality of life. However, the characteristics described can inform policymaking and the design of programs to minimize patient initiated aggression occurrence.

Epidermal growth factor receptor (EGFR) is overexpressed in a variety of human malignancies, including pancreatic cancer, breast cancer, colon cancer, and non-small cell lung cancer. Overexpression of EGFR is a predictive marker of therapeutic response and several lines of evidence suggest that EGFR is an excellent target for tumor therapy. However, the effective antitumor capacity of EGFR-specific T cells against EGFR-overexpressing tumor cells has not been fully elucidated. In our previous study, we identified an anti-EGFR single-chain variable fragment (scFv) with specific and high affinity after screening by ribosome display. In this study, the anticancer potential of anti-EGFR scFv was investigated on the basis of cell-targeted therapy. A chimeric antigen receptor (CAR) targeting EGFR was constructed and expressed on the cell membrane of T lymphocytes. These CAR-modified T cells demonstrated antitumor efficacy both in vitro and in vivo. In addition, the safety evaluation showed that CAR-modified lymphocytes have no or very minimal acute systemic toxicity. Taken together, our study provided the experimental basis for clinical application of genetically engineered lymphocytes; moreover, we also evaluate a new and interesting cell therapy protocol.

Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been shown to be involved in a spectrum of cellular processes. In a previous study, we constructed a novel multigenic vector that contained two separate transcription units, each consisting of a strong promoter and an efficient polyadenylation signal. The two promoters were chosen for their ability to work simultaneously. Dual gene transfer of bFGF and PDGF in a single plasmid resulted in a significant increase in collateral blood vessel formation in a rabbit model of hind limb ischemia. The aim of the present study was to investigate the effect of this dual gene transfer strategy in a rat model of acute myocardial infarction (AMI). AMI was induced in rats by ligation of the left anterior descending coronary artery. The animals were randomly divided into four groups and treated with the following therapeutic strategies: Empty plasmid (control), plasmid encoding bFGF (PL-bFGF), plasmid encoding PDGF (PL-PDGF) or plasmid encoding bFGF and PDGF (PL-F-P). Echocardiography and histological examinations were performed 28 days subsequent to gene transfer. Dual gene therapy with bFGF and PDGF resulted in a significant angiogenic effect accompanied by vessel maturation, along with a significant reduction in infarct size and improvement in cardiac function. In a rat model of AMI, single plasmid-mediated dual gene therapy with bFGF and PDGF decreased infarct size and improved cardiac function due to the formation of functionally and morphologically mature vasculature. These results are relevant to the ongoing clinical trials involving the use of single plasmid-mediated angiogenic factors for the treatment of myocardial ischemic disease. [ABSTRACT FROM AUTHOR]

In numerous patients with multiple primary malignant neoplasms, it is difficult to determine whether the mass is benign or malignant, and the method to treat these lesions is controversial. For patients with a history of cancer, a point of high-risk for the development of a second primary tumor occurs following a 10-year gap. To the best of our knowledge, to date, there has been no large clinical trial to observe the appropriate method to manage the lesions in patients with multiple primary malignant neoplasms. The present study reports the case of a patient who was initially diagnosed with rectal cancer, treated with Dixon's rectectomy and post-operative chemotherapy. The patient's disease was evaluated as complete response following these treatments. However, the patient then presented with bladder cancer and underwent transurethral resection of the bladder tumor, again achieving a complete response. The patient more recently presented with hepatocellular carcinoma, which developed from an unexplained mass in the liver. The patient underwent partial liver resection and to date, has achieved a complete response. The management of masses of unknown malignancy is also discussed. The current case provides useful insight for future research in this field. [ABSTRACT FROM AUTHOR]

IL-37 is a potent inhibitor of innate immunity by shifting the cytokine equilibrium away from excessive inflammation. Psoriasis is thought to be initiated by abnormal interactions between the cutaneous keratinocytes and systemic immune cells, triggering keratinocyte hyperproliferation. In the current study, we assessed IL-37 in two well-known psoriasis models: a human keratinocyte cell line (HaCaT) and the keratin 14 VEGF-A-transgenic mouse model. First, we used the HaCaT cell line, which was transiently transfected with an overexpressing IL-37 vector, and tested the effect of IL-37 on these cells using a mixture of five proinflammatory cytokines. IL-37 was effective in suppressing the production of CXCL8, IL-6, and S100A7, which were highly upregulated by the mixture of five proinflammatory cytokines. Keratin 14 VEGF-A-transgenic mice were treated with plasmid coding human IL-37 sequence-formulated cationic liposomes, and we observed potent immunosuppressive effects over the 18-d period. In this model, we observed reduced systemic IL-10 levels, local IFN-γ gene transcripts, as well as mild mast cell infiltration into the psoriatic lesions of the mice. Immunohistochemical analysis indicated that IL-37 was expressed by effector memory T cells, as well as macrophages, in human psoriatic plaques. In conclusion, our studies strongly indicate that IL-37 plays a potent immunosuppressive role in the pathogenesis of both experimental psoriasis models in vitro and in vivo by downregulating proinflammatory cytokines. Importantly, our findings highlight new therapeutic strategies that can be designed to use this immunosuppressive antiinflammatory cytokine in psoriasis and other inflammatory cutaneous diseases. [ABSTRACT FROM AUTHOR]