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Paradoxical psoriasis or psoriasiform lesions induced by anti-tumor necrosis factor (anti-TNF) therapies receive increasing attention worldwide. However, no comprehensive meta-analysis investigating the incidence estimates and risk factors for anti-TNF-induced psoriasis is currently available. We aimed to precisely quantify its incidence as well as risk factors in patients with inflammatory bowel disease (IBD). This study was registered on PROSPERO database under review registration number CRD42021233695. The electronic databases PubMed, EMBASE, and the Cochrane library were comprehensively searched for observational studies published as full-length papers in English and reporting the incidence and/or predictors for psoriasis or psoriasiform lesions in IBD patients. A random-effects meta-analysis was performed to calculate the pooled incidence. Pooled odds ratio (OR) and 95% confidence interval for potential predictors were combined using a fixed-effects or random-effects model. In total, 30 articles comprising 24,547 IBD patients treated by anti-TNF were finally included. The overall pooled incidence of psoriasis and/or psoriasiform lesions following anti-TNF therapy was 6.0% (5.0-7.0%; = 93.9%), with 6.9% (5.1-8.7%; = 92.4%) for psoriasiform lesions and 4.6% (3.6-5.6%; = 93.9%) for psoriasis. Multivariable meta-regression analysis indicated regions and populations that significantly contributed to the heterogeneity. A statistically higher risk for psoriasis or psoriasiform lesions during anti-TNF therapy was observed in female patients (OR 1.46, 1.23-1.73), those who are at a younger age at anti-TNF initiation (OR 1.03, 1.00-1.05), smokers (OR 1.97, 1.56-2.48), ileocolonic Crohn's disease patients (OR 1.48, 1.03-2.13), and those who are using adalimumab or certolizumab ( . infliximab) (OR: 1.48 and 2.87 respectively). The incidence of psoriasis or psoriasiform lesions was not uncommon in IBD patients following anti-TNF therapy. Female, younger age, smoker, ileocolonic Crohn's disease, and the types of anti-TNF were significantly associated with such risk. These findings may help gastroenterologists to make more individualized decisions and understand the mechanisms of this paradoxical phenomenon. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=233695, identifier CRD42021233695.

ObjectiveGlucocorticoids (GC) withdrawal is part of the targets in current recommendations for SLE, but relapse is the most worrying issue. We aimed to investigate the predictors for flare in patients with SLE after GC withdrawal.MethodsWe systematically searched PubMed, EMBASE and Cochrane Library as well as Scopus databases up to 9 July 2021 for studies concerning predictive factors of relapses in patients with SLE after GC cessation. Pooled OR and 95% CI were combined using a random-effects or fixed-effects model.Results635 patients with SLE with GC discontinuation in 9 publications were eligible for the final analysis. Of them, 99.5% patients were in clinical remission before GC withdrawal. Serologically active yet clinically quiescent (SACQ) was associated with an increased risk of flare after GC withdrawal (OR 1.78, 95% CI (1.00 to 3.15)). Older age and concomitant use of hydroxychloroquine (HCQ) trended towards decreased risk of flare (weighted mean difference (WMD) −2.04, 95% CI (−4.15 to 0.06) for age and OR 0.50, 95% CI (0.23 to 1.07) for HCQ), yet not statistically significant. No significant association was observed regarding gender (pooled OR 1.75; 95% CI (0.59 to 5.20)), disease duration (WMD −11.91, 95% CI (−27.73 to 3.91)), remission duration (WMD −8.55, 95% CI (−33.33 to 16.23)), GC treatment duration (WMD −10.10, 95% CI (−64.09 to 43.88)), concomitant use of immunosuppressant (OR 0.86, 95% CI (0.48 to 1.53)).ConclusionYounger age and SACQ were potential risk factors of SLE flare among patients who discontinued GC. HCQ, but not immunosuppressant might prevent flare. GC withdrawal should be done with caution in this subgroup of patients.

The debate persists regarding whether patients with psoriatic arthritis (PsA) face an increased risk of mortality. We aimed to ascertain the magnitude of all-cause mortality risk in patients with PsA compared to the general population through a systematic review and meta-analysis. We conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library for studies published from inception to June 2025. STATA meta-analysis software was used to calculate the pooled risk estimates for mortality, represented as the standardized mortality ratio (SMR). Among the 4,502 articles identified in our research, 20 studies were included in the analysis. Overall, our findings revealed a 1.12-fold increased risk of death among patients with PsA compared to the general population (meta-SMR: 1.12, 95% CI 1.09-1.15). Subgroup analyses showed that mortality risks were elevated in Asian countries (meta-SMR: 1.28, 95% CI 1.04-1.57), in population-based studies (meta-SMR: 1.13, 95% CI 1.02-1.25), and among studies including over 1,000 patients (meta-SMR: 1.12, 95% CI 1.01-1.25). Malignancy, cardiovascular and cerebrovascular diseases, and infection/respiratory diseases emerged as the most frequent causes of mortality. Our analysis suggested modestly elevated mortality in patients with PsA compared to the general population, though heterogeneity warrants cautious interpretation. Malignancy, cardiovascular and cerebrovascular diseases, and infection/respiratory disease were frequent causes of mortality and warrant further investigation. https://www.crd.york.ac.uk/prospero/, identifier CRD42021275209.

ObjectivesTo assess rates of early remission and investigate the concordance across different remission definitions, and to identify predictors of early remission in Chinese patients with rheumatoid arthritis (RA).MethodsFor this study, clinical records were retrospectively reviewed for RA patients at rheumatologic clinic in Peking University First Hospital from 2009 to 2018. Disease activity and remission were determined according to DAS28-ESR, CDAI, SDAI, and Boolean criteria. Early remission was defined as time to remission ≤ 6 months. A secondary definition evaluated early remission as ≤ 3 months. Logistic-regression analyses were performed to identify determinants of early remission.ResultsA total of 869 consecutive patients contributing 8640 clinic visits were studied. Early remission rates were respectively 42.0% (DAS28-ESR), 25.0% (CDAI), 29.4% (SDAI), and 26.1% (Boolean). Notably, patients achieving remission within 6 months more frequently attained sustained remission in contrast to those not achieving early remission (68.7–75.1% vs. 31.2–33.1%, p < 0.0001). Further logistic-regression analyses revealed male, early RA, as well as initial hydroxycloroquine treatment were independently associated higher probability of early remission, as demonstrated by nearly all definitions, while a higher baseline disease activity (DAS28-ESR, CDAI, and SDAI) lowered the possibility of early remission in corresponding remission indices. The significant associations of treatment-naïve, serological features with early remission were not confirmed.ConclusionsEarly remission was strongly associated with sustained remission, however. infrequently achievable in real-life practice. Male, early RA, a low baseline disease activity, and initial hydroxycloroquine treatment were stable independent predictors of early remission.Key Points• Early remission was infrequently achievable in real-life practice, especially measured by stringent indices.DAS28-based early remission appears to be the loosest criterion and the remaining three broadly agreed with each other.• Early remission was significantly associated with sustained remission.• Male, early RA, a low baseline disease activity, and initial hydroxycloroquine treatment were positively correlated with early remission.

Thrombocytopenia (TP) is considered as a warning sign of high-risk antiphospholipid syndrome (APS) and sometimes a paradoxical sign of anti-thrombosis treatment. Currently, there is an extreme paucity of effective and safe drugs for long-term management of TP in primary APS patients; therefore, we explored the efficacy and safety of sirolimus monotherapy. In this real-world study, we included 7 consecutive patients with primary APS who received sirolimus monotherapy for TP. Oral sirolimus was initiated at a dose of 1-2 mg once daily and then adjusted primarily based on clinical efficacy and tolerance, with consideration of the sirolimus trough concentration of ≤15 ng/ml. Of included patients, the median age was 58 years with a median disease course of 1.5 years and 4 patients were treatment-naïve. All patients completed 6 months of sirolimus therapy with a median follow-up of 6 months (range: 6-15). All patients received sirolimus monotherapy for TP during the entire follow-up, without any additional agents. Overall, the platelet count exhibited a substantially increasing trend after sirolimus administration during the first 6 months (p < 0.001) and stability later. Specifically, the median platelet count was significantly increased from 59 × 10 /l before sirolimus to 90 × 10 /l at month 1 (p = 0.028), 131 × 10 /l at 3 months (p = 0.028), and 178 × 10 /l at 6 months (p = 0.018). Overall and complete responses were respectively achieved in 6 (85.7%) and 5 (71.4%) patients at month 6. Importantly, overall response was achieved in all 4 treatment-naïve patients. Additionally, there were different extents of decline in the titers of antiphospholipid antibodies after sirolimus treatment. Regarding safety, only one patient experienced an elevated cholesterol level with recovery after atorvastatin treatment. Sirolimus monotherapy confers good efficacy and tolerance for TP in primary APS patients and therefore may be considered as a first-line therapy.

Agricultural non-point source (NPS) pollution directly affects the quality of soil and water, ecological balance and human health, and is a key challenge to achieve sustainable environmental development and efficient resource management. Taking the Nansi Lake Basin (NLB) as the study area, this study explores the main sources of agricultural NPS pollution and its influencing factors, aiming to provide scientific basis for the management of water resources in the basin. Current studies usually use the runoff pollution partitioning method to estimate agricultural NPS pollution loads in runoff, but the accuracy of the analyses is limited by the incompleteness of water quality monitoring data, especially the lack of complete runoff records in some years. To compensate for this deficiency, this study simulated the river runoff based on the Long-Term Hydrological Impact Assessment (L-THIA) model, and applied the simulation results to the quantitative calculation of agricultural NPS pollution loads after verifying the model reliability through accuracy calibration. Based on L-THIA model, the spatial and temporal distribution data of agricultural NPS pollution in the basin from 2010 to 2020 were obtained, the distribution characteristics of chemical oxygen demand (COD) and ammonia nitrogen (NH 3 -N) were quantitatively assessed, and the impacts of natural and socio-economic factors on them were analyzed. A regression model was developed to simulate future agricultural NPS pollution through multiple regression analysis. The results showed that the total agricultural NPS pollution in the NLB showed an increasing trend during the study period. In particular, among the socio-economic factors, COD and NH 3 -N were significantly correlated with fertilizer application, pesticide use, rural employment and total population. Among the natural factors, topographic index, watershed area and gully density were positively correlated with pollutants, while slope and soil organic matter were negatively correlated. The results of this study raise awareness of the contribution of influencing factors and allow researchers and planners to focus on the most important NPS pollution sources and influencing factors. The study provides an important reference for the prevention and control of agricultural NPS pollution in the NLB, which is of great practical importance.

Background Sepsis, a life-threatening syndrome with especially high incidence and mortality in older adults, imposes a major global health burden. Although the gut bacterial microbiota is known to influence sepsis pathogenesis, the role of the gut fungal community (mycobiota) and its functional metabolic output remains largely unknown. In this study, we characterized sepsis-associated alterations in the gut mycobiota and related plasma metabolic signatures, and explored their associations with age and survival outcomes. Methods We conducted an integrated multi-omics analysis of fecal samples from patients with sepsis and matched healthy controls. Using internal transcribed spacer 1 (ITS1) sequencing and untargeted plasma metabolomics at admission, we compared the gut mycobiota composition and metabolic profiles between groups across age strata (non-older vs. older adults) and survival outcomes. Results Patients with sepsis exhibited significant gut mycobiota dysbiosis, characterized by a loss of diversity and marked overgrowth of opportunistic Candida . Metabolomics revealed distinct perturbations, particularly in the bile acid and inflammatory pathways. These alterations were profoundly exacerbated in non-survivors and elderly patients and were strongly correlated with higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, organ failure, and mortality. Conclusion Our study identified a sepsis-specific gut mycobiota signature and associated plasma metabolomic disturbances that were associated with mortality and accentuated by aging. These findings reveal an association between the gut mycobiota, host metabolism, and clinical outcomes in sepsis, which merits further validation to assess its potential for prognostic or therapeutic applications. However, the causal relationship remains to be established, and future studies are needed to validate these associations and explore their translational potential. Graphical Abstract Summary of the study design and key findings. The integrated multi-omics analysis characterized alterations in the gut mycobiota and plasma metabolome in sepsis patients stratified by age and survival status, revealing associations of microbial and metabolic signatures with clinical outcomes.

Protein kinase B (AKT) hyperactivation and de novo lipogenesis are both common in tumor progression. Sterol regulatory element‐binding protein 1 (SREBP1) is the master regulator for tumor lipid metabolism, and protein arginine methyltransferase 5 (PRMT5) is an enzyme that can catalyze symmetric dimethyl arginine (SDMA) modification of the mature form of SREBP1 (mSREBP1) to induce its hyperactivation. Here, we report that SDMA‐modified mSREBP1 (mSREBP1‐SDMA) was overexpressed and correlated with Ser473‐phosphorylated AKT (AKT‐473P) expression and poor patient outcomes in human lung adenocarcinomas. Furthermore, patients with AKT‐473P and mSREBP1‐SDMA coexpression showed the worst prognosis. Mechanistic investigation revealed that AKT activation upregulated SREBP1 at both the transcriptional and post‐translational levels, whereas PRMT5 knockdown reversed AKT signaling‐mediated mSREBP1 ubiquitin‐proteasome pathway stabilization at the post‐translational level. Meanwhile, AKT activation promoted nuclear PRMT5 to the cytoplasm without changing total PRMT5 expression, and the transported cytoplasmic PRMT5 (cPRMT5) induced by AKT activation showed a strong mSREBP1‐binding ability. Immunohistochemical assay indicated that AKT‐473P and mSREBP1‐SDMA were positively correlated with cPRMT5 in lung adenocarcinomas, and high cPRMT5 levels in tumors were associated with poor patient outcomes. Additionally, PRMT5 knockdown reversed AKT activation‐induced lipid synthesis and growth advantage of lung adenocarcinoma cells both in vitro and in vivo. Finally, we defined an AKT/PRMT5/SREBP1 axis involved in de novo lipogenesis and the growth of lung cancer. Our data also support that cPRMT5 is a potential therapeutic target for hyperactive AKT‐driven lung adenocarcinoma. In this research, we defined an AKT/PRMT5/SREBP1 axis involved in de novo lipogenesis and growth of lung cancer. Our data also support that PRMT5 in the cytoplasm is a potential therapeutic target for hyperactive AKT‐driven lung adenocarcinoma.

Gibberellin 20-oxidases ( GA20oxs ) are multifunctional enzymes involved in regulating gibberellin (GA) biosynthesis and controlling plant growth. We identified and characterized the GA20ox1 gene in a plant height mutant of Sophora davidii , referred to as SdGA20ox1 . This gene was expressed in root, stem, and leaf tissues of the adult S. davidii plant height mutant, with the highest expression observed in the stem. The expression of SdGA20ox1 was regulated by various exogenous hormones. Overexpression of SdGA20ox1 in Arabidopsis resulted in significant elongation of hypocotyl and root length in seedlings, earlier flowering, smaller leaves, reduced leaf chlorophyll content, lighter leaf color, a significant increase in adult plant height, and other phenotypes. Additionally, transgenic plants exhibited a substantial increase in biologically active endogenous GAs (GA1, GA3, and GA4) content, indicating that overexpression of SdGA20ox1 accelerates plant growth and development. Using a yeast two-hybrid (Y2H) screen, we identified two SdGA20ox1-interacting proteins: the ethylene receptor EIN4 (11430582) and the rbcS (11416005) protein. These interactions suggest a potential regulatory mechanism for S. davidii growth. Our findings provide new insights into the role of SdGA20ox1 and its interacting proteins in regulating the growth and development of S. davidii .