A multicenter, randomized, double-blinded, placebo-controlled, phase â ¢ study evaluating the efficacy and safety of Xeligekimab (GR1501) in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Xeligekimab is a fully human monoclonal antibody that selectively neutralizes IL-17A and had shown potential efficacy in preliminary trials. OBJECTIVE: To evaluate the efficacy and safety of Xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg Xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by extending the treatment schedule to GR1501 every 4 weeks for further 40 weeks. Efficacy was assessed by evaluating the Physician's Global Assessment (PGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75/90/100 improvement. The safety profile was also evaluated. RESULTS: At week 12, The PASI 75/90/100 were achieved in 90.7%/74.4%/30.2%% patients in GR1501 group compared with 8.6%/1.4%/0% patients in placebo group, respectively. The PGA 0/1 were achieved in 74.4% patients of GR1501 group and 3.6% patients in placebo group, respectively. The PASI 75 and PGA 0/1 maintained until week 52. No unexpected adverse events were observed. CONCLUSION: Xeligekimab showed high efficacy and is well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

Peripheral atherosclerosis in acute coronary syndrome patients with plaque rupture vs plaque erosion: A prospective coronary optical coherence tomography and peripheral ultrasound study.

BACKGROUND: Plaque rupture (PR) and plaque erosion (PE) are 2 distinct, different, and most common culprit lesion morphologies responsible for acute coronary syndrome (ACS). However, the prevalence, distribution, and characteristics of peripheral atherosclerosis in ACS patients with PR vs PE has never been studied. The aim of this study was to assess peripheral atherosclerosis burden and vulnerability evaluated by vascular ultrasound in ACS patients with coronary PR vs PE identified by optical coherence tomography (OCT). METHODS: Between October 2018 and December 2019, 297 ACS patients who underwent preintervention OCT examination of the culprit coronary artery were enrolled. Peripheral ultrasound examinations of carotid, femoral, and popliteal arteries were performed before discharge. RESULTS: Overall, 265 of 297 (89.2%) patients had at least one atherosclerotic plaque in a peripheral arterial bed. Compared with coronary PE, patients with coronary PR had a higher prevalence of peripheral atherosclerotic plaques (93.4% vs 79.1%, P < .001), regardless of location: carotid, femoral, or popliteal arteries. The number of peripheral plaques per patient was significantly larger in the coronary PR group than coronary PE (4 [2-7] vs 2 [1-5], P < .001). Additionally, there was a greater prevalence of peripheral vulnerable characteristics including plaque surface irregularity, heterogeneous plaque, and calcification in patients with coronary PR vs PE. CONCLUSIONS: Peripheral atherosclerosis exists commonly in patients presenting with ACS. Patients with coronary PR had greater peripheral atherosclerosis burden and more peripheral vulnerability compared to those with coronary PE, suggesting that comprehensive evaluation of peripheral atherosclerosis and multidisciplinary cooperative management maybe necessary, especially in patients with PR. TRIAL REGISTRATION: clinicaltrials.gov (NCT03971864).

Triglyceride glucose index is associated with obstructive coronary artery disease in hypertensive patients.

BACKGROUND: Hypertension is a leading risk of coronary artery disease (CAD). Triglyceride glucose index (TyG) is a surrogate of insulin resistance (IR). Few studies explore the association between TyG and the incidence of obstructive CAD (OCAD) in hypertensive patients. METHODS: We retrospectively screened 1841 hypertensive subjects who were free of a history of CAD and underwent coronary computed tomography angiography (CCTA) because of chest pain. TyG index was calculated as ln (fasting TG [mg/dL] * fasting glucose [mg/dL]/2). The outcome of this research was OCAD, which was defined as the presence of diameter stenosis ≥ 50% in any of the four major epicardial coronary arteries detected on CCTA. RESULTS: A total of 310 (16.8%) patients developed obstructive CAD. The restricted cubic spline (RCS) analysis showed a J-shaped relationship between TyG and OCAD and the OR for OCAD increased as the TyG rose over 8.61 (OR perSD) 1.64, 95% CI 1.13-2.54, p = 0.008). After full adjustments for confounding covariates, patients with TyG index in tertile 3 (T3) had 2.12 times (95% CI 1.80 to 3.81) and in T2 had 2.01 times (95% CI 1.40 to 2.88) as high as the risk of OCAD compared with patients in T1 (p for trend = 0.001). When regarding TyG as a continuous variable, 1-SD increase elevated 49% (OR (95%CI), 1.49 (1.30-1.74)) risk of obstructive CAD (p = 0.007). This positive effect was still consistent across the subgroups (p for interaction > 0.05). CONCLUSION: TyG index was associated with the incidence of obstructive CAD in hypertensive patients.

Predictive value of CAC score combined with clinical features for obstructive coronary heart disease on coronary computed tomography angiography: a machine learning method.

OBJECTIVE: We investigated the predictive value of clinical factors combined with coronary artery calcium (CAC) score based on a machine learning method for obstructive coronary heart disease (CAD) on coronary computed tomography angiography (CCTA) in individuals with atypical chest pain. METHODS: The study included data from 1,906 individuals undergoing CCTA and CAC scanning because of atypical chest pain and without evidence for the previous CAD. A total of 63 variables including traditional cardiovascular risk factors, CAC score, laboratory results, and imaging parameters were used to build the Random forests (RF) model. Among all the participants, 70% were randomly selected to train the models on which fivefold cross-validation was done and the remaining 30% were regarded as a validation set. The prediction performance of the RF model was compared with two traditional logistic regression (LR) models. RESULTS: The incidence of obstructive CAD was 16.4%. The area under the receiver operator characteristic (ROC) for obstructive CAD of the RF model was 0.841 (95% CI 0.820-0.860), the CACS model was 0.746 (95% CI 0.722-0.769), and the clinical model was 0.810 (95% CI 0.788-0.831). The RF model was significantly superior to the other two models (p < 0.05). Furthermore, the calibration curve and Hosmer-Lemeshow test showed that the RF model had good classification performance (p = 0.556). CAC score, age, glucose, homocysteine, and neutrophil were the top five important variables in the RF model. CONCLUSION: RF model was superior to the traditional models in the prediction of obstructive CAD. In clinical practice, the RF model may improve risk stratification and optimize individual management.

Serum alkaline phosphatase levels are associated with coronary artery calcification patterns and plaque vulnerability.

OBJECTIVES: This study aimed to investigate the association of serum alkaline phosphatase (ALP) with calcification patterns and plaque morphology detected by intravascular ultrasound (IVUS) in acute coronary syndrome (ACS) patients. BACKGROUND: ALP has been shown to predict vascular calcification and long-term cardiovascular events. However, the relationship between ALP and vascular calcification patterns or plaque morphology remains unclear. METHODS: In total, 328 ACS patients who underwent IVUS examinations were screened from January 2017 to December 2018; among them, 234 eligible participants were grouped according to the tertiles of ALP levels (<68, 68-80, and >80 IU/L). Demographic data and IVUS parameters were documented and analyzed. RESULTS: After adjusting for potential confounders, independent associations were observed between ALP and the presence of coronary calcification, spotty calcification, minimum lumen area (MLA) ≤ 4.0 mm2 , and plaque burden (PB) > 70%. Compared with the lowest ALP tertile group, the highest ALP group had higher risks of calcification (odds ratio [OR], 2.85; 95% confidence interval [95%CI], 1.38-5.90; p = .005), spotty calcification (OR, 1.86; 95%CI, 1.09-3.84; p = .012), MLA≤4.0 mm2 (OR, 3.32; 95%CI, 1.51-7.28; p = .003), and PB > 70% (OR, 4.59; 95%CI, 1.83-11.50; p = .001). Similar results were found when ALP was analyzed as a continuous variable or a category variate according to the cut-off value determined by the receiver operating characteristic curve analysis. Furthermore, the model including clinical factors and ALP significantly improved the predictive power for coronary calcification, spotty calcification, MLA≤4.0 mm2 , and PB > 70%. CONCLUSION: Our findings suggest that ALP may be a potential predictive biomarker for calcification and plaque vulnerability.

The association between glucose-related variables and plaque morphology in patients with ST-segment elevated myocardial infarction.

BACKGROUND: Plaque rupture (PR) and plaque erosion (PE) are main causes of acute myocardial infarction with different demographic and histology characteristics and need different treatment strategy. PR and PE can be identified with optical coherence tomography (OCT) accurately, but convenient and effective noninvasive markers for them are rarely found. History of diabetes mellitus (DM) was reported to be a potential predictor of PR in ST-segment elevated myocardial infarction (STEMI) patients, but the predictive value of other glucose-related variables for it is still uncertain. Present study aimed to clear the relationship between some glucose-related variables and plaque morphology in patients with STEMI. METHODS: We consecutively enrolled 872 STEMI patients and divided them into PR group (n = 616) and PE group (n = 256) based on OCT diagnostic criteria. The relationship of glucose-related variables, including random plasma glucose on admission (ARPG), glycosylated hemoglobin (HbA1c), post-PCI fasting plasma glucose (PFPG), DM history, glucose variable tendency (GVT) and the acute-to-chronic glycemic ratio (A/C), to the PR risk of STEMI patients was analyzed. The correlation between the glucose-related variables and plaque morphology was analyzed meanwhile. RESULTS: Among the glucose-related variables, ARPG and GVT were confirmed to be independent predictors for PR after adjusting for other traditional risk factors in nondiabetic patients. The higher the ARPG level, the more PR risk the STEMI patients had. And high HbA1c and APPG were demonstrated to have a weak and positive correlation with lipid constituents and stenosis degree of culprit vessel. CONCLUSIONS: Compared to HbA1c, DM history, and some other glucose-related variables, ARPG and GVT were risk factors for PR in STEMI patients, especially those without DM. And high HbA1c and ARPG were positively correlated with the development of vulnerable plaque in culprit vessels. Trial registration Present study is a retrospective one and the population came from the EROSION study of our center previously. It was approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (Approval reference number, KY2017-249), and all patients provided written informed consent prior to the inclusion in the study and the investigation conformed to the principles outlined in the Declaration of Helsinki.

Proteomics Profiling Reveals Insulin-Like Growth Factor 1, Collagen Type VI α-2 Chain, and Fermitin Family Homolog 3 as Potential Biomarkers of Plaque Erosion in ST-Segment Elevated Myocardial Infarction.

BACKGROUND: Plaque erosion (PE) has been considered a secondary pathogenesis of ST-segment elevated myocardial infarction (STEMI) following plaque rupture (PR). Previous studies demonstrated that they had different demographic and histology characteristics and need different treatment strategy. But there are few non-invasive plasma biomarkers for distinguishing them. The present study aimed to identify non-invasive predictive biomarkers for PE and PR in patients with STEMI.Methods and Results:A total 108 patients were recruited and grouped into a PE group (n=36), a PR group (n=36), and an unstable angina pectoris (UAP) (n=36) group for analysis. A 9-plex tandem mass tag (TMT)-based proteomics was used to compare plasma protein profiles of PE, PR, and UAP. In total, 36 significant differential proteins (DPs) were identified among groups, 10 of which were screened out using bio-information analysis and validated with enzyme-linked immunosorbent assay (ELISA). The relationship of angiography and optical coherence tomography (OCT) imaging data and the 10 target DPs was analyzed statistically. Logistic regression showed elevated collagen type VI α-2 chain (COL6A2) and insulin-like growth factor 1 (IGF1), and decreased fermitin family homolog 3 (FERMT3), were positively associated with PE. Multivariate analysis indicated IGF1, FERMT3, and COL6A2 had independent predictive ability for PE. IGF1 was inversely correlated with lumen stenosis and the lipid arc of the plaque. CONCLUSIONS: IGF1, COL6A2, and FERMT3 are potential predictive biomarkers of PE in STEMI patients. And IGF1 was negatively correlated with the developing of culprit plaque.

High Levels of Circulating MicroRNA-3667-3p Are Associated with Coronary Plaque Erosion in Patients with ST-Segment Elevation Myocardial Infarction.

Plaque erosion (PE) is a significant substrate of acute coronary thrombosis. An improved ability to distinguish plaque phenotype in vivo among patients with ST-segment elevation myocardial infarction (STEMI) is of considerable interest because of the potential to formulate tailored treatment. This study assessed the plaque features and screened the circulating microRNAs (miRNAs) characteristically expressed in patients with PE compared with those with plaque rupture (PR). An miRNA microarray profile was generated in an initial cohort of eight STEMI patients with PE and eight clinically matched subjects with PR to select the circulating miRNAs with significant differences. miRNAs of interest were validated in a prospective cohort, and the plaque characteristics of enrolled patients were assessed by optical coherence tomography (OCT). Thirty culprit lesions were classified as PE (32.6%) and 46 as PR (50%). The main component of PE was fibrotic tissue, whereas the chief component of PR was lipids (P < 0.001). Thirty-four miRNAs were differentially expressed between the two groups; we validated five candidates and found that only the level of circulating miR-3667-3p exhibited significant discriminatory power in predicting the presence of PE (AUC = 0.767; P < 0.001). Our results show that high levels of circulating miR-3667-3p are closely related to PE in STEMI patients, which provides further evidence for PE pathophysiology and potential tailor treatment strategies.

Isolated Cutaneous Granuloma Caused by Candida glabrata: A Rare Case Report and Literature Review.

The incidence of candidiasis due to non-albicans Candida species (especially Candida glabrata) has significantly increased in recent decades. Candida glabrata often invades immunocompromised hosts and causes systemic or mucosal infections, whereas cutaneous infections are rarely reported. We present a rare case of cutaneous infection caused by C. glabrata and review all similar cases available in the PubMed database. A patient was admitted to the hospital with a 2-month history of a plaque on the face. Histopathological examination displayed typical infectious granulomas in the deep dermis, and the pathogen was finally confirmed as C. glabrata using a series of microbial examinations (fungal culture, biochemical test, and PCR-directed sequencing). The patient was completely cured after 4 months of treatment with oral itraconazole combined with topical terbinafine. We reviewed similar reports of cutaneous infection caused by C. glabrata. All the data suggested that an accurate diagnosis of cutaneous candidiasis depends mainly on histological and fungal examinations, especially molecular biological assays. Antifungal agents based on microbial susceptibility tests are the first-line treatment choice for C. glabrata infection, but the prognosis might be more dependent on the basic condition of the host.

CSN1201, a subunit of the COP9 signalosome, regulates the virulence in Cryptococcus neoformans infection.

The COP9 signalosome (CSN) is a multisubunit protein complex, and it now has been found to participate in diverse cellular and developmental processes in various eukaryotic organisms. Cryptococcus neoformans (C. neoformans) is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily in the immune compromised population. Here, we generated CSN deletion mutants to investigate the role in Cryptococcus infection. Compared to other CSN mutants, we identified a CSN1201 mutant exhibited severely attenuated virulence. Deletion of CSN1201 made cryptococcal cells more susceptible to nearly all in vitro stresses. Furthermore, deletion of CSN1201 obviously impaired survival of C. neoformans. At the same time, in vivo virulence assay of mouse infection models demonstrated that CSN1201 significantly enhanced the virulence of C. neoformans compared with the other CSN subunit strains, while ELISA analysis of C. neoformans infection in innate or adaptive immune response showed that deletion of CSN1201 significantly impaired cytokines and interferon expression. In vitro model of the blood-brain barrier (BBB) analysis indicated that deletion of CSN1201 reduced the invasion efficacy of Cryptococcusto cross BBB. Taken together, our findings reveal a novel mechanism of CSN1201, which plays a critical role for the virulence composite of C. neoformans, and also provides an additional yeast survival and propagation advantage in the host.

miR­576­3p/M­phase phosphoprotein 8 axis regulates the malignant progression of hepatocellular carcinoma cells via the PI3K/Akt signaling pathway.

Hepatocellular carcinoma (HCC) is a fatal digestive system cancer with unclear pathogenesis. M-phase phosphoprotein 8 (MPP8) has been shown to play a vital role in several cancer types, such as non-small cell lung cancer, gastric cancer and melanoma; however, there have been no studies into its role in HCC. The present study aimed to evaluate the role of MPP8 in regulating malignant phenotypes of liver cancer cells, and to further investigate the underlying mechanism. Bioinformatics analysis was performed to analyze related data from a public database, and to predict the potential microRNAs (miRNAs) that might target MPP8 mRNA; reverse transcription-quantitative PCR was used to measure the levels of mRNA and miRNA; western blotting was employed to detect protein levels; Cell Counting Kit-8 (CCK-8) and plate colony formation assays, wound healing assay and Transwell invasion assay were performed to evaluate the ability of cell proliferation, migration and invasion, respectively; dual-luciferase reporter gene assay was performed to identify the target association. The results showed that MPP8 was a risk factor for the survival of patients with HCC, and was up-regulated in HCC tissue samples and cell lines; MPP8 knockdown inhibited the proliferation, migration and invasion of liver cancer cells; MPP8 knockdown suppressed the PI3K/Akt pathway, and activation of this pathway reversed the inhibited liver cancer cell phenotypes by down-regulating MPP8; miR-576-3p, which was low in liver cancer cells, negatively regulated MPP8 expression by directly targeting its mRNA; up-regulating MPP8 expression reversed the inhibited signaling pathway and malignant phenotypes of liver cancer cells by miR-576-3p overexpression. In conclusion, the miR-576-3p/MPP8 axis regulates the proliferation, migration, and invasion of liver cancer cells through the PI3K/Akt signaling pathway. These findings lead novel insights into HCC progression, and propose MPP8 as a potential therapeutic target for HCC.

Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients: A 12-week randomized placebo-controlled phase III trial with long-term extension.

BACKGROUND: There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients. METHODS: In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12. RESULTS: At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician's Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs . 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs . 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. CONCLUSION: Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05108766.

Association of triglyceride glucose index levels ​​with calcification patterns and vulnerability of plaques: an intravascular ultrasound study.

PURPOSE: High triglyceride glucose (TyG) index level is one of the risks for cardiovascular events. The purpose of this research was to examine the correlation of the triglyceride glucose (TyG) index levels with plaque characteristics and calcification types determined by intravascular ultrasound (IVUS) in acute coronary syndrome (ACS) patients. METHODS: A total of 234 acute coronary syndromes (ACS) participants who completed intravascular ultrasound (IVUS) and coronary angiography (CAG) were finally enrolled. RESULTS: Logistic regression analysis manifested that the TyG index was independently correlated with the occurrence of coronary calcification, minimum lumen area (MLA) ≤ 4.0 mm², plaque burden (PB) > 70%, and spotty calcification. Taking the lowest group as a reference, the risk of coronary calcification (OR, 2.57; 95%CI, 1.04-6.35; p = 0.040), MLA ≤ 4.0 mm² (OR, 7.32; 95%CI, 2.67-20.01; p < 0.001), PB > 70% (OR, 2.68; 95%CI, 1.04-6.91; p = 0.041), and spotty calcification (OR, 1.48; 95%CI, 0.59-3.71; p = 0.407) was higher in the highest TyG index group. TyG index was converted into a dichotomous variable or a continuous variable for analysis, and we found that a similar result was observed. In addition, optimal predictive models consisting of clinical variables and the TyG index distinctly improved the ability to predict the prevalence of coronary calcification and MLA ≤ 4.0 mm² (p < 0.05). CONCLUSION: The TyG index may serve as a potential predictor for calcification patterns and plaque vulnerability.

Diagnostic accuracy of a novel optical coherence tomography-based fractional flow reserve algorithm for assessment of coronary stenosis significance.

BACKGROUND: This study aimed to introduce a novel optical coherence tomography-derived fractional flow reserve (FFR) computational approach and assess the diagnostic performance of the algorithm for assessing physiological function. METHODS: The fusion of coronary optical coherence tomography and angiography was used to generate a novel FFR algorithm (AccuFFRoct) to evaluate functional ischemia of coronary stenosis. In the current study, a total of 34 consecutive patients were included, and AccuFFRoct was used to calculate the FFR for these patients. With the wire-measured FFR as the reference standard, we evaluated the performance of our approach by accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Per vessel accuracy, sensitivity, specificity, PPV, and NPV for AccuFFRoct in identifying hemodynamically significant coronary stenosis were 93.8%, 94.7%, 92.3%, 94.7%, and 92.3%, respectively, were found. Good correlation (Pearson's correlation coefficient r = 0.80, p < 0.001) between AccuFFRoct and FFR was observed. The Bland-Altman analysis showed a mean difference value of -0.037 (limits of agreement: -0.189 to 0.115). The area under the receiver-operating characteristic curve (AUC) of AccuFFRoct in identifying physiologically significant stenosis was 0.94, which was higher than the minimum lumen area (MLA, AUC = 0.91) and significantly higher than the diameter stenosis (%DS, AUC = 0.78). CONCLUSIONS: This clinical study shows the efficiency and accuracy of AccuFFRoct for clinical implementation when using invasive FFR measurement as a reference. It could provide important insights into coronary imaging superior to current methods based on the degree of coronary artery stenosis.

The Predictive Value of Lp(a) for Adverse Cardiovascular Event in ACS Patients With an Achieved LDL-C Target at Follow Up After PCI.

Low-density lipoprotein cholesterol (LDL-C) is a traditional and important risk factor for atherosclerotic cardiovascular disease (CVD). Recently, lipoprotein (a) (lp(a)) attracts considerable attention as a residual risk factor for CVD. However, the roles of lp(a) in acute coronary syndrome (ACS) patients with well-controlled LDL-C (≤1.8mmol/L) after percutaneous coronary intervention (PCI) remain unclear. Current study results demonstrated that occurrence of major adverse cardiovascular events (MACE) and recurrent myocardial infarction (MI) increased with the Lp(a) increasing in patients with LDL-C≤1.8mmol/L at 1-month follow-up. In relatively low-risk patients presented with ACS and underwent PCI (LDL-C ≤1.8mmol/L at 1-month follow-up), lp(a) is still independently related to adverse prognosis. Further researches of targeted therapy against lp(a) are warranted.

A randomized, double-blind phase III study to demonstrate the clinical similarity of biosimilar SCT630 to reference adalimumab in Chinese patients with moderate to severe plaque psoriasis.

INTRODUCTION: This phase III study aimed to compare the efficacy, safety, and immunogenicity of SCT630 with the reference adalimumab. METHODS: A total of 367 Chinese patients with moderate-to-severe plaque psoriasis were randomly assigned to receive 80 mg of SCT630 or adalimumab subcutaneously at week 1, 40 mg at week 2, then 40 mg biweekly. At week 16, those with 50 % or more improvement in psoriasis area and severity index (PASI) were eligible to enter an extension period up to week 52. Patients on SCT630 continued the same treatment, whereas patients receiving adalimumab were re-randomized at a ratio of 1:1 to adalimumab or SCT630 group. The primary endpoint was percentage improvement in PASI at week 16. Other endpoints included PASI 50/75/90/100, Physician's Global Assessment, Dermatology Life Quality Index, safety, and immunogenicity. RESULTS: PASI improvement at week 16 was 85.07 % for SCT630 and 84.82 % for adalimumab. The mean difference (3.10 %, 95 % CI: -1.875 %, 8.066 %) was within the equivalence interval. Other efficacy endpoints, safety and immunogenicity profiles were similar across the two groups. There were no safety or immunogenicity difference between switched/continued groups. CONCLUSION: This phase III study demonstrated the equivalences in efficacy, safety and immunogenicity of SCT630 to adalimumab in patients with moderate to severe psoriasis.

Plasma Ceramides in Relation to Coronary Plaque Characterization Determined by Optical Coherence Tomography.

Plasma ceramides (Cer), a subset of bioactive lipids, have mechanistic links to development of atherosclerosis and are related to major adverse cardiovascular events (MACEs). Previous researches have demonstrated vulnerable plaques contribute to acute cardiovascular events and poor prognosis. This study aimed to explore the associations between Cer and culprit plaque characterizations evaluated by optical coherence tomography (OCT). It was found that plasma Cer are associated with culprit plaque vulnerability evaluated by OCT, providing evidence supporting proatherogenic roles and potential to act as markers for plaque vulnerability of Cer. Graphical Abstract With increasing plasma ceramide levels, the prevalence of thin-cap fibroatheroma (TCFA) and plaque rupture (PR) is higher, that is, culprit plaques are more vulnerable.

The PI3K/Akt Pathway: Emerging Roles in Skin Homeostasis and a Group of Non-Malignant Skin Disorders.

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway regulates cell proliferation, differentiation, and migration, along with angiogenesis and metabolism. Additionally, it could mediate skin development and homeostasis. There is much evidence to suggest that dysregulation of PI3K/Akt pathway is frequently associated with several human cutaneous malignancies like malignant melanoma (MM), basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (SCC), as well as their poor outcomes. Nevertheless, emerging roles of PI3K/Akt pathway cascade in a group of common non-malignant skin disorders including acne and psoriasis, among others, have been recognized. The enhanced understanding of dysfunction of PI3K/Akt pathway in patients with these non-malignant disorders has offered a solid foundation for the progress of updated therapeutic targets. This article reviews the latest advances in the roles of PI3K/Akt pathway and their targets in the skin homeostasis and progression of a wide range of non-malignant skin disorders and describes the current progress in preclinical and clinical researches on the involvement of PI3K/Akt pathway targeted therapies.

Melatonin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-related Diseases.

Cartilage is a relatively simple connective tissue that plays a variety of roles in the human body, including joint support and protection, load bearing of the intervertebral discs, joint lubrication, formation of the external structure of the ears and nose and support of the trachea. The maintenance of cartilage homeostasis is therefore crucial. Cartilage-related diseases are difficult to diagnose and treat because their molecular and pathological mechanisms are not fully understood. Melatonin, which has a wide range of physiological effects, is an endocrine hormone mainly secreted by the pineal gland. Its biological effects include its antioxidant, antiaging, analgesic, and hypnotic effects and its ability to stabilize the circadian rhythm. In recent years, research on cartilage homeostasis and melatonin has been increasing, and melatonin has gradually been used in the treatment of cartilage-related diseases. Therefore, this article will briefly review the role of melatonin in cartilage homeostasis, including its anti-inflammatory effects and effects in protecting cartilage from damage by other factors and promoting chondrocyte growth and the expression of cartilage-related genes. Based on the above, the current status and future developmental direction of melatonin in the treatment of cartilage-related diseases are also discussed, demonstrating the broad prospects of melatonin in maintaining cartilage homeostasis and treating cartilage injury-related diseases.

Mitochondrial Quality Control in Sarcopenia: Updated Overview of Mechanisms and Interventions.

Sarcopenia is a common geriatric disorder characterized by decreased muscle strength, low muscle mass and poor physical performance. This aging-related skeletal muscle deterioration leads to adverse outcomes and severely impairs the quality of life of patients. The accumulation of dysfunctional mitochondria with aging is an important factor in the occurrence and progression of sarcopenia. Mitochondrial quality control (MQC) fundamentally ensures the normal mitochondrial functions and is comprised of four main parts: proteostasis, biogenesis, dynamics and autophagy. Therefore, any pathophysiologic factors compromising the quality control of homeostasis in the skeletal muscle may lead to sarcopenia. However, the specific theoretical aspects of these processes have not been fully elucidated. Current therapeutic interventions using nutritional and pharmaceutical treatments show a modest therapeutic efficacy; however, only physical exercise is recommended as the first-line therapy for sarcopenia, which can ameliorate skeletal muscle deficiency by maintaining the homeostatic MQC. In this review, we summarized the known mechanisms that contribute to the pathogenesis of sarcopenia by impairing normal mitochondrial functions and described potential interventions that mitigate sarcopenia through improving MQC.