Effectiveness of Ixekizumab in Chinese Patients with Moderate-Severe Plaque Psoriasis with Special Area Involvement: Subanalysis of a Prospective, Multicenter, Observational Real-World Study.

INTRODUCTION: Ixekizumab, a monoclonal antibody against interleukin-17A, demonstrated effectiveness in the treatment of psoriasis in a Chinese real-world study that was consistent with previous randomized controlled trials. Here, we report further analyses from this study to explore the effectiveness of ixekizumab for treating patients with psoriasis and the involvement of special body areas (scalp, nail, joint, palmoplantar, or genital areas). METHODS: A multicenter, prospective, observational, single-arm, post-marketing surveillance study was conducted in patients aged ≥ 18 years with moderate-to-severe plaque psoriasis and prescribed with ixekizumab in 26 Chinese hospitals. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were compared between patients with versus without psoriasis in special body areas in the overall study population and across subgroups by body area. RESULTS: In total, 612 patients were included. At baseline, most patients (93.6%) had psoriasis involvement in at least one special body area. Overall, patients with psoriasis in special body areas reported a worse quality of life (QoL) than those without. Patients with versus without psoriasis in special body areas achieved a comparable mean reduction from baseline in PASI score (10.9 vs. 9.2 at week 2, and 16.9 vs. 14.7 at week 12, respectively) and DLQI score (6.0 vs. 4.4 at week 2, and 9.9 vs. 7.5 at week 12, respectively); a similar proportion of patients also achieved PASI 50 at week 2, and PASI 75 and PASI 90 at week 12, and a DLQI (0/1) at weeks 2 and 12. Several significantly different results were reported between subgroups, the majority of which favored patients with special body area involvement. CONCLUSION: Most patients had psoriasis involvement in a special body area which was associated with worse QoL. Ixekizumab is similarly effective in reducing disease severity and improving QoL in patients with plaque psoriasis across different special body areas.

Transcriptome Analysis of Compensatory Growth and Meat Quality Alteration after Varied Restricted Feeding Conditions in Beef Cattle.

Compensatory growth (CG) is a physiological response that accelerates growth following a period of nutrient limitation, with the potential to improve growth efficiency and meat quality in cattle. However, the underlying molecular mechanisms remain poorly understood. In this study, 60 Huaxi cattle were divided into one ad libitum feeding (ALF) group and two restricted feeding groups (75% restricted, RF75; 50% restricted, RF50) undergoing a short-term restriction period followed by evaluation of CG. Detailed comparisons of growth performance during the experimental period, as well as carcass and meat quality traits, were conducted, complemented by a comprehensive transcriptome analysis of the longissimus dorsi muscle using differential expression analysis, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and weighted correlation network analysis (WGCNA). The results showed that irrespective of the restriction degree, the restricted animals exhibited CG, achieving final body weights comparable to the ALF group. Compensating animals showed differences in meat quality traits, such as pH, cooking loss, and fat content, compared to the ALF group. Transcriptomic analysis revealed 57 genes and 31 pathways differentially regulated during CG, covering immune response, acid-lipid metabolism, and protein synthesis. Notably, complement-coagulation-fibrinolytic system synergy was identified as potentially responsible for meat quality optimization in RF75. This study provides novel and valuable genetic insights into the regulatory mechanisms of CG in beef cattle.

A model for risk factors harms and of smartphone addiction among nursing students: A scoping review.

AIM: To delineate the prevalence of smartphone addiction among nursing students. Further, to identify associated harms and underlying risk factors based on established theoretical models. BACKGROUND: Smartphones have become indispensable tools for students. However, excessive use can lead to smartphone addiction, causing physiological, psychological and social harm. Nursing students represent a unique population whose smartphone use may differ from other disciplines due to clinical training demands. METHODS: A scoping review was conducted following the Arksey and O'Malley framework. Seven databases were systematically searched from inception to August 2023. Inclusion criteria encompassed original research on smartphone addiction, harms and risks among nursing students. Data were extracted and thematically synthesized. RESULTS: Studies (n=39) met inclusion criteria, representing 15 countries. Rates of smartphone addiction among nursing students ranged from 19% to 72%, averaging 40-50%. Incorporated into Engel's biopsychosocial models, the harm is emphasized across individual inclinations, emotional aspects, cognitive processes and executive functions. Physiological harms include sleep disruption, vision concerns,other physiological concerns. psychologically, addiction correlated with increased anxiety and depression,decline in self-esteem, learning and attention and other psychological concerns. socially, it encompasses harms such as interpersonal relationships challenges, career development and decline in social abilities. The I-PACE model identifies various risk factors for smartphone addiction among nursing students, including personal factors such as interpersonal relationship anxiety and perceived academic pressure, affective factors like high stress and learning burnout, cognitive factors such as the need for online social interaction and low perception of social support, as well as executive factors like extended usage duration, poor self-control and usage before sleep. CONCLUSION: Smartphone addiction among nursing students presents tangible harms. A proposed theoretical model integrating established frameworks provides avenues to better comprehend addiction genesis and potential intervention strategies. Given addiction's multi-factorial nature, future research investigating harm mitigation through optimizing predisposing, precipitating and perpetuating factors is warranted.

MiR-199a-3p Regulates the PTPRF/ß-Catenin Axis in Hair Follicle Development: Insights into the Pathogenic Mechanism of Alopecia Areata.

Alopecia areata is an autoimmune disease characterized by the immune system attacking self hair follicles, mainly in the scalp. There is no complete cure, and the pathogenesis is still not fully understood. Here, sequencing of skin tissues collected from 1-month-old coarse- and fine-wool lambs identified miR-199a-3p as the only small RNA significantly overexpressed in the fine-wool group, suggesting a role in hair follicle development. MiR-199a-3p expression was concentrated in the dermal papillae cells of sheep hair follicles, along with enhanced ß-catenin expression and the inhibition of PTPRF protein expression. We also successfully constructed a mouse model of alopecia areata by intracutaneous injection with an miR-199a-3p antagomir. Injection of the miR-199a-3p agomir resulted in hair growth and earlier anagen entry. Conversely, local injection with the miR-199a-3p antagomir resulted in suppressed hair growth at the injection site, upregulation of immune system-related genes, and downregulation of hair follicle development-related genes. In vivo and in vitro analyses demonstrated that miR-199a-3p regulates hair follicle development through the PTPRF/ß-catenin axis. In conclusion, a mouse model of alopecia areata was successfully established by downregulation of a small RNA, suggesting the potential value of miR-199a-3p in the study of alopecia diseases. The regulatory role of miR-199a-3p in the PTPRF/ß-catenin axis was confirmed, further demonstrating the link between alopecia areata and the Wnt-signaling pathway.

Epigenetic mechanism of Gtl2-miRNAs causes the primitive sheep characteristics found in purebred Merino sheep.

BACKGROUND: It is not uncommon for some individuals to retain certain primitive characteristics even after domestication or long-term intensive selection. Wild ancestors or original varieties of animals typically possess strong adaptability to environmental preservation, a trait that is often lacking in highly artificially selected populations. In the case of the Merino population, a world-renowned fine wool sheep breed, a phenotype with primitive coarse wool characteristic has re-emerged. It is currently unclear whether this characteristic is detrimental to the production of fine wool or whether it is linked to the adaptability of sheep. The underlying genetic/epigenetic mechanisms behind this trait are also poorly understood. RESULTS: This study identified lambs with an ancestral-like coarse (ALC) wool type that emerged during the purebred breeding of Merino fine wool sheep. The presence of this primitive sheep characteristic resulted in better environmental adaptability in lambs, as well as improved fine wool yield in adulthood. Reciprocal cross experiments revealed that the ALC phenotype exhibited maternal genetic characteristics. Transcriptomic SNP analysis indicated that the ALC phenotype was localized to the imprinted Gtl2-miRNAs locus, and a significant correlation was found between the ALC wool type and a newly identified short Interstitial Telomeric Sequences (s-ITSs) at this locus. We further confirmed that a novel 38-nt small RNA transcribed from these s-ITSs, in combination with the previously reported 22-nt small RNAs cluster from the Gtl2-miRNAs locus, synergistically inhibited PI3K/AKT/Metabolic/Oxidative stress and subsequent apoptotic pathways in wool follicle stem cells, resulting in the ALC wool type. The necessity of Gtl2-miRNAs in controlling primary hair follicle morphogenesis, as well as the wool follicle type for ALC wool lambs, was verified using intergenic differentially methylated region-knockout mice. CONCLUSION: The ALC wool type of Merino sheep, which does not reduce wool quality but increases yield and adaptability, is regulated by epigenetic mechanisms in the imprinted Gtl2-miRNAs region on sheep chromosome 18, with the maternally expressed imprinted gene responsible for the ALC phenotype. This study highlights the significance of epigenetic regulation during embryonic and juvenile stages and emphasizes the advantages of early adaptation breeding for maternal parents in enhancing the overall performance of their offspring.

Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis.

Substance use disorder remains a major challenge, with an enduring need to identify and evaluate new, translational targets for effective treatment. Here, we report the upregulation of Hypoxia-inducible factor-1α (HIF-1α) expression by roxadustat (Rox), a drug developed for renal anemia that inhibits HIF prolyl hydroxylase to prevent degradation of HIF-1α, administered either systemically or locally into selected brain regions, suppressed morphine (Mor)-induced conditioned place preference (CPP). A similar effect was observed with methamphetamine (METH). Moreover, Rox also inhibited the expression of both established and reinstated Mor-CPP and promoted the extinction of Mor-CPP. Additionally, the elevation of HIF-1α enhanced hepcidin/ferroportin 1 (FPN1)-mediated iron efflux and resulted in cellular iron deficiency, which led to the functional accumulation of the dopamine transporter (DAT) in plasma membranes due to iron deficiency-impaired ubiquitin degradation. Notably, iron-deficient mice generated via a low iron diet mimicked the effect of Rox on the prevention of Mor- or METH-CPP formation, without affecting other types of memory. These data reveal a novel mechanism for HIF-1α and iron involvement in substance use disorder, which may represent a potential novel therapeutic strategy for the treatment of drug abuse. The findings also repurpose Rox by suggesting a potential new indication for the treatment of substance use disorder.

An optimal medicinal and edible Chinese herbal formula attenuates particulate matter-induced lung injury through its anti-oxidative, anti-inflammatory and anti-apoptosis activities.

Objective: Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury. Methods: PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments. Results: Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1ß and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3. Conclusion: Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.

Comprehensive assessment of detoxification mechanisms of hydrolysis fish peptides in largemouth bass (Micropterus salmoides) under copper exposure: Tracing from bioaccumulation, oxidative stress, lipid deposition to metabolomics.

As a heavy metal, copper is toxic to aquatic organisms in water, causing oxidative stress and lipid deposition. However, there is currently no effective dietary strategy to prevent damage caused by copper exposure. Here, copper bioaccumulation, antioxidant enzymes, lipogenic enzymes, lipid metabolism-related gene expression levels and metabolic pathways were synthesized and evaluated in copper-exposed largemouth bass (Micropterus salmoides) after hydrolysis fish peptides (HFP) pretreatment. The results showed that supplementation with 1% (P < 0.05), 3% (P < 0.01) and 5% (P < 0.05) HFP significantly reduced the copper bioaccumulation in largemouth bass. Hydrolysis fish peptides supplementation significantly reduced the activities of total antioxidant capacity (P < 0.01) and catalase (P < 0.01) and the contents of glutathione (P < 0.01) and malondialdehyde (P < 0.05). Fatty acid synthetase concentration was significantly reduced in fish supplemented with 3% (P < 0.05) and 5% HFP (P < 0.05). Similarly, fish fed 3% (P < 0.05) and 5% (P < 0.01) HFP significantly reduced the glucose-6-phosphate dehydrogenase concentration. Serum metabolomics revealed that 85, 144 and 207 differential metabolites were obtained in fish supplemented with 1%, 3% and 5% HFP, respectively. The differential metabolites were mainly lipids and lipid-like molecules, which were associated with the lipid metabolism pathways. The expression levels of fatty acid synthase (P < 0.01), sterol regulatory element binding protein-1c (P < 0.05), liver X receptor (P < 0.001), peroxisome proliferator activated γ (P < 0.01), apolipoprotein B (P < 0.001) and fatty acid-binding protein 1 (P < 0.01) were significantly down-regulated and the expression levels of carnitine palmitoyltransferase 1α (P < 0.01), hormone-sensitive lipase (P < 0.001), apolipoprotein A 1 (P < 0.05) were significantly up-regulated in fish fed with 3% HFP. Additionally, supplementation with 3% (P < 0.01) and 5% (P < 0.001) HFP significantly up-regulated the expression level of B-cell lymphoma-2 with a dose-dependent effect. In conclusion, our study confirmed that HFP supplementation was closely associated with oxidative stress, enzymatic activities and related pathways of lipid metabolism, and apoptosis, and in general alleviated lipid deposition caused by copper exposure in largemouth bass.

Momordica charantia saponins administration in low-protein-high-carbohydrate diet improves growth, blood biochemical, intestinal health and microflora composition of juvenile common carp (Cyprinus carpio).

An 8-week feeding trial was conducted to explore the feasibility of Momordica charantia saponins (MCS) administration to facilitate the protein-sparing action of high carbohydrate in diets for juvenile common carp (Cyprinus carpio) with initial mass of 5.41 ± 0.02 g. Based on our previous study, four diets with different the ratio of protein and carbohydrate (P/C ratio) were designed: 32%P/40%C, 30%P/43%C, 28%P/46%C, 28%P/46%C supplemented with 0.16% MCS (28%P/46%C + MCS). Each diet treatment was divided into 3 replicates. Results revealed that 30%P/43%C group increased growth performance and intestinal digestion, decreased intestinal inflammation, and optimized the intestinal microbiota compared to 32%P/40%C group, which presented the stronger protein-sparing action of high carbohydrate. But if the P/C ratio reduced to 28%P/46%C or less, the saving action would be restrained. However, compared to the 30%P/43%C and 28%P/46%C groups, 28%P/46%C + MCS group significantly elevated growth performance and activities of digestive enzymes and antioxidative enzymes, whilst the opposite trend occurred in the contents of glucose, triglyceride, total cholesterol, low density lipoprotein cholesterol, blood urea nitrogen, glutamic oxalacetic transaminase, glutamic-pyruvic transaminase and malondialdehyde. In addition, 28%P/46%C + MCS group markedly upregulated the expressions of GH/IGF axis genes, genes involved in protein synthesis, antioxidant genes and anti-inflammatory cytokine, whilst the opposite trend occurred in the expressions of pro-inflammatory cytokines. Moreover, 28%P/46%C + MCS group obtained the remarkably higher Enterococcus proportion and lower Lactococcus proportion compared to the 30%P/43%C and 28%P/46%C groups, whereas the opposite occurred in 30%P/43%C group, which indicated that there existed differences in the improvement mechanism on intestinal microflora composition between MCS and appropriate P/C ratio. Combined with the above mentioned changes in our research, we concluded that 0.16% MCS administration in a 28%P/46%C diet could facilitate the protein-sparing action of high carbohydrate in diets for common carp, which could decrease the 5% dosage of soybean meal and synchronously reduce the 4% crude protein of diets without affecting the growth and immune ability for common carp.

Integration of microRNA and mRNA analyses depicts the potential roles of Momordica charantia saponin administration in insulin resistance of juvenile common carp (Cyprinus carpio) fed with a high-starch diet.

Background: The regulation of target gene mRNA mediated by microRNA may play an important role in glucose metabolism in fish. Previous research findings of our research group revealed that Momordica charantia saponin (MS) administration in a high-starch diet could improve insulin resistance of common carp through renovating insulin signaling pathways, whose fundamental mechanisms have remained unknown by far. To reveal this potential mechanism, we aimed to investigate the difference in miRNA and mRNA expression profiles between common carp fed with high-starch diets containing MS (HS_MS1 and HS_MS2) and common carp fed with high-starch (HS) diets. Results: Through miRNA deep-sequencing, 10 significantly differentially expressed miRNAs in HC and HS_MS1, including one upregulated and nine downregulated miRNAs, were identified, whereas 10 significantly differentially expressed miRNAs in HC and HS_MS2, including four upregulated and six downregulated miRNAs, were identified. These miRNAs may not only be involved in the regulation of insulin signaling pathways and insulin resistance in common carp but also be the markers for liver insulin resistance in MS therapy for the remission of insulin resistance. This study identified 10 potential known miRNAs, namely, ccr-miR-10b, ccr-miR-122, ccr-miR-143, ccr-miR-146a, ccr-miR-155, ccr-miR-16c, ccr-miR-200a, ccr-miR-29a, ccr-miR-34, and ccr-miR-375, as candidates participating in modulating the liver insulin resistance. According to the biopathway enrichment analysis of the 252 target genes using the KEGG classical biopathway database, the relative expression levels of gsk3bb, pik3r1, and pik3r3b were analyzed using RNA-seq. Compared to the HC group, a significant decrease in the relative expression levels of pik3r1 and pik3r3b was observed in HS_MS1 and HS_MS2 groups (p < 0.05). This study raised a presumption of the presence of ccr-miR-29a targeting pik3r1 or ccr-miR-143 targeting pik3r3 playing likely roles in Momordica charantia saponins remitting the liver insulin resistance. Conclusion: The findings will further deepen the understanding of the carbohydrate metabolism of common carp and provide an important scientific basis for the application of Momordica saponins as functional nutrients to alleviate insulin resistance of fish in fish culture.

Real-World Analysis of Clinical Characteristics, Treatment Patterns, and Patient-Reported Outcomes of Insufficient Responders and Responders to Prescribed Acute Migraine Treatment in China.

INTRODUCTION: Migraine is a common disabling primary headache disorder characterized by attacks of severe pain, sometimes accompanied by symptoms including nausea and photo-/phono-phobia. Real-world data of patients with migraine who sufficiently (responders) and insufficiently (insufficient responders) respond to acute treatment (AT) are limited in China. This analysis explored whether responders to AT differ from insufficient responders in terms of clinical characteristics, treatment patterns, and patient-reported outcomes in China. METHODS: Data were drawn from the Adelphi Migraine Disease Specific Programme™, a point-in-time survey of internists/neurologists and their consulting patients with migraine, conducted in a real-world setting in China, January-June 2014. Responders and insufficient responders to prescribed AT were patients who typically achieved headache pain freedom within 2 h of AT in ≥ 4 and ≤ 3 of five migraine attacks, respectively. Responders were compared with insufficient responders; logistic regression was used to identify factors associated with insufficient response. RESULTS: Of 777 patients currently receiving AT, 44.0% were insufficient responders. Significantly fewer responders than insufficient responders had migraine with aura (13.1 vs. 23.8%; p = 0.0001). Responders reported a significantly lower mean Migraine Disability Assessment (MIDAS) total score (5.5 vs. 6.6; p = 0.0325). Responders reported a lower mean impairment while working (50.0 vs. 63.9%; p < 0.0001), overall work impairment (52.6 vs. 66.0%; p < 0.0001), and activity impairment (48.9 vs. 59.0%; p < 0.0001). Statistically significant factors associated with insufficient response to AT included diabetes, unilateral pain, vomiting, sensitivity to smell, visual aura/sight disturbance, and an increase in MIDAS total score. However, there were no statistically significant differences in ATs received by responders and insufficient responders at any regimen of therapy. CONCLUSIONS: Many patients with migraine in China are insufficient responders to AT, experiencing worse symptoms that lead to overall poorer quality of life than responders. This unmet need suggests that new effective treatment options are required for migraine.

Angioimmunoblastic T-Cell Lymphoma Diagnosed From Serous Effusion by Integration of Cytologic Features and Ancillary Studies.

OBJECTIVES: To explore the approach to the diagnosis of malignant serous effusion (SE) caused by angioimmunoblastic T-cell lymphoma (AITL). METHODS: The clinical, cytomorphologic, immunophenotypic, and molecular features of 6 patients were summarized. RESULTS: Clinically, SE caused by AITL was predominant in middle-aged and older male patients with multiple SEs and lymphadenopathy. Cytomorphology showed small to medium-sized, irregular lymphocytes with clear cytoplasm and mixed with various inflammatory cells and apoptosis. Hodgkin/Reed-Sternberg-like cells were detected in 2 of 6 cases. Furthermore, 2 patterns of cytomorphology were described for the first time. Flow cytometry revealed abnormal T-cell populations with loss of surface CD3 (3/4 cases) and CD7 (3/4 cases). In addition, B-cell populations lacking surface immunoglobulin (Ig) were identified in 2 of 4 cases. Immunocytochemical staining revealed expression of at least 2 T follicular helper markers. Epstein-Barr virus-encoded RNA (EBER)-positive cells were demonstrated in 4 of 5 cases. Clonal T-cell receptor γ chain rearrangement was detected in 6 cases, and 3 of them had concomitant clonal immunoglobulin gene rearrangement. Moreover, 2 cases revealed discrepant findings regarding IgH/Igκ rearrangements in cytohistologic correlation. CONCLUSIONS: This study broadens the morphologic spectrum of malignant SE caused by AITL and provides diagnostic criteria in routine practice.

Real-World Treatment Patterns and Outcomes Among Patients with Episodic Migraine in China: Results from the Adelphi Migraine Disease Specific Programme™.

Objective: This study assessed treatment patterns, disease burden, outcomes, and unmet needs among patients with episodic migraine (EM) in China using Adelphi Migraine Disease Specific Programme™ (DSP) real-world data. Background: Migraine is a prevalent and debilitating neurological disorder which presents a major public health burden globally. Research on characteristics, disease burden, and treatment patterns in EM patients in China is limited. Methods: Data were drawn from an existing data set Adelphi Migraine DSP, a point-in-time survey conducted in China (January-June 2014). Internists/neurologists completed patient record forms for the next 9 patients who consulted them in clinical practice; these same patients completed the 'patient self-completion questionnaires'. Descriptive analyses were used to assess key variables: patient demographics, treatment patterns (current acute and preventive medication [AM/PM]), effectiveness, issues with existing treatment, Migraine Disability Assessment (MIDAS) scores, and Work Productivity and Activity Impairment scores. Results: Total of 125 internists/neurologists provided data on 1113 patients with EM (headache days/month <15). Mean (standard deviation [SD]) age was 43.8 (13.1) years; mean (SD) number of migraine days/month was 3.2 (1.7). AM was prescribed in 86.1% of patients (non-steroid anti-inflammatory drugs [NSAIDs]: 62.7%; triptans: 7.7%), PM in 38.5%, and both in 24.9% of patients. Approximately 55% of patients experienced ≥1 issue with their current AM or PM. Migraine-related symptoms (including nausea, photophobia, and phonophobia) were fully controlled in <50% of patients receiving NSAIDs (21.7-38.4%) or triptans (32.4-43.5%). Insufficient response to current AM (migraine headache fully resolved within 2 hours in ≤3/5 attacks) was reported by 42.5% of patients. Mild-to-severe disability was reported by 36.8% of patients with a mean (SD) MIDAS score of 5.8 (7.3). Overall, 58.0% of work time was impaired (including time missed and impairment while working). Conclusion: This analysis suggests, despite existing treatment options, disease burden and unmet medical needs remain substantial in Chinese patients with EM.

Outcomes of Biologic Use in Asian Compared with Non-Hispanic White Adult Psoriasis Patients from the CorEvitas Psoriasis Registry.

INTRODUCTION: Real-world data are limited comparing Asian and White patients with psoriasis using biologic therapy. This study compared the 6-month effectiveness of biologic therapy between Asian and White plaque patients with psoriasis in the CorEvitas Psoriasis Registry. METHODS: Analyses included biologic initiations and 6-month follow-up visits from self-identified Asian (n = 293) and White (n = 2314) patients in the USA/Canada (4/2015-4/2020). Outcomes included: Psoriasis Area Severity Index (PASI) 75, disease activity measures [body surface area (BSA) ≤ 1, BSA ≤ 3, PASI90, PASI100, Investigator's Global Assessment (IGA) 0/1], and patient-reported outcomes [Dermatology Life Quality Index (DLQI) 0/1, itch, fatigue, skin pain, EuroQoL visual analog scale (EQ-VAS), patient global assessment, Work Productivity Activity and Impairment (WPAI) domains]. Unadjusted regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for achievement of binary outcomes and difference in mean change in continuous outcomes (ß, 95% CI) at 6 months, followed by adjustment for age, sex, body mass index, alcohol, smoking, health insurance, education, comorbidities, scalp psoriasis morphology, psoriatic arthritis, biologic class, previous biologics, and baseline outcome value. RESULTS: Asians had lower proportions of women (32.8% versus 49.1%) and obesity (27.3% versus 54.5%), and higher proportions on Medicaid (19.9% versus 8.8%), graduated college (50.9% versus 40.1%) and never smoked (67.1% versus 44.1%). In unadjusted analyses, Asians had 52% higher odds of achieving PASI75 versus White patients (OR 1.52; 95% CI 1.15, 2.02). After adjustment, the association was attenuated (OR 1.11; 0.81, 1.52). Secondary outcomes experienced similar patterns except for DLQI: Asians had 33% lower odds of achieving DLQI 0/1 in both the unadjusted (OR 0.67; 0.50, 0.90) and adjusted (OR 0.67; 0.49, 0.92) models. CONCLUSION: Unadjusted differences in biologic therapy effectiveness between Asians compared with White patients were likely explained by differences in demographic, lifestyle, and psoriatic disease characteristics between groups. However, Asians still experienced lesser improvements in skin-related quality of life, even after adjustment.

A multi-center effectiveness comparison study of fruquintinib with constructed external control cohort of other targeted kinase inhibitors using real-world data in third-line treatment of metastatic colorectal cancer.

Objective: The objective of this study was to assess the comparative efficacy in third-line setting for metastatic CRC (mCRC) patients using matched population of FRESCO trial with fruquintinib and real-world data with other TKIs. Materials and methods: The arm of fruquintinib from the FRESCO phase III trial (NCT02314819) included the data of patients with metastatic CRC that progressed after at least two lines of chemotherapy and received fruquintinib treatment. An external control arm was constructed using real-world data (RWD) of patients who received other TKIs based on key eligibility criteria of FRESCO. The baseline characteristics of two arms was balanced by propensity score matching (PSM). The Kaplan-Meier method and Cox proportional hazard model was used to evaluate progression free survival (PFS) and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), respectively. Results: Overall, 128 patients were successfully matched by PSM in each, fruquintinib and other TKIs group. The patients in fruquintinib group showed significant increase in median PFS than other TKIs (3.71 vs. 2.49 months, HR = 0.67, 95%CI, 0.48-0.94, p = 0.019). In the subgroup analysis, fruquintinib showed a significant benefit in PFS compared with other TKIs among patients undergoing two or three previous chemotherapy regimens (HR 0.58, 95%CI 0.40-0.84; p=0.004), with rectum as primary disease site (HR 0.52, 95%CI 0.31-0.87; p=0.013), with left sided primary tumor location (HR 0.62, 95%CI 0.42-0.90; p=0.011), with multiple metastasis sites (HR 0.68, 95%CI 0.48-0.97; p=0.034) and with lung metastasis (HR 0.65, 95%CI 0.43-0.98; p=0.042). Conclusion: With the approach of establishing the external control arm from RWD, this study has demonstrated that treatment with fruquintinib significantly prolonged PFS as compared to other TKIs in patients as third-line mCRC treatment.

Resveratrol ameliorates oxidative stress, inflammatory response and lipid metabolism in common carp (Cyprinus carpio) fed with high-fat diet.

High-fat diet is regarded as crucial inducers of oxidative stress, inflammation, and metabolic imbalance. In order to investigate the ameliorative potential of resveratrol against the progression of liver injury towards steatohepatitis, common carp (Cyprinus carpio) were distributed into six experimental groups and were fed with a normal-fat diet, a high-fat diet, and supplemented with resveratrol (0.8, 1.6, 2.4, and 3.2 g/kg diet) for 8 weeks. The high-fat diet decreased the antioxidant capacities, as well as causing the inflammatory response and lipid deposition of common carp. Resveratrol induced a marked elevation in the final body weight, weight gain rate, condition factor and significant decrease in the feed conversion ratio. Moreover, dietary resveratrol showed a significant decrease in the alanine aminotransferase, aspartate aminotransferase, triglyceride and low-density lipoprotein levels, which was accompanied by an increase in high-density lipoprotein concentration in serum. A significant elevation in total superoxide dismutase, catalase, glutathione peroxidase and a decreased malondialdehyde content were observed, along with a substantial elevation in antioxidant activities were found. Additionally, fish fed with resveratrol had an up-regulation of hepatic catalase, copper, zinc superoxide dismutase, glutathione peroxidase 1a, and glutathione peroxidase 1b gene expression via Nrf2 signaling pathway. Expectedly, our results also demonstrated that resveratrol regulates hepatic lipid metabolism in fish by inhibiting the expression of hepatic lipogenesis genes (acetyl-CoA carboxylase 1, fatty acid synthase, and sterol regulatory element binding protein 1), fatty acid uptake-related genes of lipoprotein lipase, and ß-oxidation-related genes via PPAR-γ signaling pathway. Furthermore, dietary resveratrol reduced inflammation, as evident by down-regulating the interleukin-1ß, interleukin-6, interleukin-8, and tumor necrosis factor-α expression levels and upregulating the interleukin-10 and transforming growth factor-ß2 expression levels via NF-κB signaling pathway. As a whole, our results demonstrated that resveratrol defensed the impacts against high-fat diet on the serum biochemical, hepatic antioxidants, inflammation, and lipid metabolism.

Phosphorus Nutrition in Songpu Mirror Carp (Cyprinus carpio Songpu) During Chronic Carbonate Alkalinity Stress: Effects on Growth, Intestinal Immunity, Physical Barrier Function, and Intestinal Microflora.

Carbonate alkalinity is a major environmental stress factor affecting aquatic feed configuration, which easily causes oxidative stress and hypoimmunity for fish. Hence, the purpose of the study is to assess the potential effect of phosphorus on growth, intestinal oxidation resistance, physical barrier function, and microflora for Songpu mirror carp (Cyprinus carpio Songpu) (initial average weight of 2.95 ± 0.21 g) reared at the high-concentration carbonate alkalinity environment. A two-factor, three-level (2 × 3) design was applied, in which diets with three different phosphorus levels (3.6, 7.0, and 10.5 g/kg dry matter) were randomly assigned to 0 and 15 mmol/L carbonate alkalinity groups with three replicate aquariums. After the 8-week trial, we found that weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER), and lipase and amylase activities in the intestine significantly (p < 0.05) declined with increasing carbonate alkalinity. Carbonate alkalinity of 15 mmol/L significantly reduced glutathione peroxidase (GSHPx) activities in the intestine (p < 0.05). The relative expressions of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), glutathione peroxidase 1a (GPX1a), Clautin3, Clautin11, and tumor necrosis factor ß (TNF-ß) in the intestine were markedly downregulated by increasing carbonate alkalinity levels (p < 0.05), whilst the relative expressions of interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α) in the intestine were markedly upregulated (p < 0.05). At the 15 mmol/L carbonate alkalinity treatment, Songpu mirror carp suffer from hypoimmunity status with failed digestion, antioxidant, inflammation, and immune response, thereby inducing impaired growth. Additionally, significant increments in the abundance of Proteobacteria and a significant decrease in the abundance of Fusobacteria and the Firmicutes/Bacteroidetes ratio were caused due to excessively high carbonate alkalinity (15 mmol/L) and excessively low dietary phosphorus supply (3.6 g/kg). Collectively, 7.0 g/kg dietary phosphorus supplementation was effective in promoting intestinal antioxidant enzyme activities and the corresponding gene expression via the Keap1-Nrf2 signaling pathway and in enhancing intestinal immunity by upregulating anti-inflammatory and downregulating pro-inflammatory genes. Appropriate dietary phosphorus supply could promote the formation of beneficial microflora in freshwater, and it has the potential ability to transfer the adverse effect of carbonate alkalinity stress to the structural composition of intestinal microflora. Hence, consideration should be given to suitable phosphorus supply for fish under the chronic carbonate alkalinity stress.

Low Protein Diets Supplemented With Alpha-Ketoglutarate Enhance the Growth Performance, Immune Response, and Intestinal Health in Common Carp (Cyprinus carpio).

To investigate the effects of alpha-ketoglutarate (AKG) supplementation in a low protein (LP) diet on the growth performance, immune response, and intestinal health of common carp (Cyprinus carpio), 600 carp were randomly divided into five dietary groups: a normal protein (NP) diet containing 32% crude protein, an LP diet formulated with 28% crude protein, and LP with AKG at 0.4%, 0.8%, and 1.2% (dry matter). After an 8-week trial period, the results demonstrated that an LP diet led to a decrease in performance, immune response, and intestinal barrier function. Compared with the LP group, the final body weight and weight gain rate in the LP+0.4% AKG group were significantly higher, the feed conversion ratio was significantly decreased with the addition of 0.4% and 0.8% AKG. The supplementation with 0.4% and 0.8% AKG markedly increased the activities of T-SOD and GSH-Px, as well as the expression levels of GPX1a and GPX1b relative to the LP group, whereas the MDA content was significantly decreased in the LP+0.4% AKG group. In addition, the expression levels of tight junctions including claudin-3, claudin-7, ZO-1, and MLCK were significantly up-regulated in the LP+0.4% AKG group, and the relative expression levels of the pro-inflammatory factors IL-1ß and IL-6α were significantly lower with the addition of 0.4%, 0.8%, and 1.2% AKG. Moreover, the abundance of Proteobacteria in the LP+0.4% AKG group was lower than that in the LP group, and the abundance of Firmicutes and Fusobacteria was higher at the phylum level. The abundance of Citrobacter in the LP+0.4% AKG group was decreased compared to the LP group, while the abundance of Aeromonas was increased at the genus level. In short, the effects of AKG on the intestinal health of the common carp were systematically and comprehensively evaluated from the perspectives of intestinal physical barrier, chemical barrier, biological barrier, and immune barrier. We found that an LP diet supplemented with 0.4% AKG was beneficial to the growth performance and intestinal health of common carp.

Assessment of Fish Protein Hydrolysates in Juvenile Largemouth Bass (Micropterus salmoides) Diets: Effect on Growth, Intestinal Antioxidant Status, Immunity, and Microflora.

Varying dietary inclusion levels of fish protein hydrolysates (FPH) were applied in a feeding experiment with juvenile largemouth bass (Micropterus salmoides) to assess their effects on growth, intestinal antioxidant status, immunity, and microflora. FPH were added in 4 dietary levels: 0 g/kg (control group, FPH-0), 10 g/kg (FPH-10), 30 g/kg (FPH-30), and 50 g/kg (FPH-50) dry matter, respectively substituting 0, 5.3, 16.3, and 27.3% of fish meal with dietary fish meal. Quadruplicate groups of 25 juvenile largemouth bass with initial body weight 9.51 ± 0.03 g were fed during the 56-day feeding experiment. Experimental results showed that fish fed FPH-30 obtained a significantly higher weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER), and significant feed conversion rate (FCR) compared to the other three groups (P < 0.05). FPH-30 group also promoted protein synthesis and deposition, as evidenced by the higher whole-body crude protein contents, the higher expressions of GH1, IGF-1, TOR, and S6K in the liver, and SLC7A5, SLC7A8, SLC38A2, and SLC15A2 in the intestine than the other three groups. FPH-30 group could also enhance intestinal health status by increasing the activities of SOD, POD, CAT, GSH-Px, and T-AOC activities by upregulating the expressions of SOD, GSH-Px, IL1ß, and TNFß, and by reducing the MDA contents and the expressions of IL15, Caspase 3, Caspase 9, and Caspase 10 than other groups. Compared to the control group, the Actinobacteriota abundance markedly decreased in FPH treatments, while the variation tendency of the phylum Proteobacteria was opposite. The peak value of Firmicutes:Bacteroidetes ratio and the lowest of Bacteroidetes abundance were seen in largemouth bass fed FPH-30 (P < 0.05). Fish in three FPH treatments had lower abundances of opportunistic pathogens Staphylococcus and Plesiomonas than fish in the control group. In conclusion, FPH is a nutritious feed ingredient for juvenile largemouth bass, and can be added to a dietary level of 30 g/kg dry matter replacing fish meal without any negative effect on growth and feed utilization. FPH supplements could also strengthen the intestinal immune mechanisms of largemouth bass to tackle the immunodeficiency produced by fish meal replacement.

Assessment of chicken intestinal hydrolysates as a new protein source to replace fishmeal on the growth performance, antioxidant capacity and intestinal health of common carp (Cyprinus carpio).

Promoting circular economy by transforming food residues into alternative high-value protein sources for aquaculture feed is a new way to develop alternative raw materials for fishmeal. This study systematically evaluated the effects of chicken intestinal hydrolysates (CIH) on the intestinal immune health of common carp through growth performance, antioxidant capacity, and intestinal immunity analysis in order to replace fishmeal. Five iso-nitrogenous and iso-lipidic experimental feeds were formulated to replace 0% (CIH-0), 25% (CIH-25), 50% (CIH-50), 75% (CIH-75) and 100% (CIH-100) of the fishmeal with CIH. Each experimental diet was fed to triplicate groups of 30 carp for 8 weeks. The results revealed that no significant differences in the final body weight, weight gain rate, feed coefficient radio, feed intake and protein efficiency ratio were found among the CIH-0, CIH-25, and CIH-50 groups, while the final body weight and weight gain rate in the CIH-75 and CIH-100 groups were significantly decreased and the feed coefficient radio was significantly increased. The aspartate aminotransferase of all CIH groups were significantly decrease, and the total protein, albumin did not differ among the CIH-0, CIH-25, CIH-50, and CIH-75 groups. The trypsin content was significantly increased in the CIH-75 and CIH-100 groups. No significant differences in the antioxidant index (catalase, glutathione peroxidase and malonaldehyde) were found among all CIH groups compared with the CIH-0 group. The expression levels of pro-inflammatory cytokines IL-1ß and TNF-α were significantly down-regulated in the CIH-50 group and anti-inflammatory cytokines IL-10 and TGF-ß2 were significantly up-regulated in the CIH-50 and CIH-75 groups. No significant differences in the expression levels of claudin-1, claudin-7 and claudin-11 were observed between the CIH-0 and CIH-50 groups, while the expression levels of ZO-1, occludin and MLCK were significantly up-regulated in the CIH-50 group compared with the CIH-0 group. The expression level of claudin-1 was down-regulated in the CIH-75 and CIH-100 groups. Hence, the study demonstrated the potential of CIH as a novel protein source for replacing fishmeal, and replacing 50% of fishmeal with CIH did not significantly influence the growth performance, immune responses, and intestinal barrier of common carp (Cyprinus carpio).