BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Objective To investigate biological markers associated with psychotic symptoms in patients with bipolar disorder(BD)based on electronic medical records of patients,and to develop an interpretable risk prediction model that supports the identification of high-risk individuals and that facilitates decision-making for providing clinical intervention in a timely manner.Methods A total of 2 352 patients diagnosed with BD and admitted to West China Hospital,Sichuan University were enrolled using the electronic medical records system of the hospital.The participants were divided into two subgroups,the bipolar disorder depression(BDD)group and the bipolar disorder mania(BDM)group.The logistic regression algorithm was used to train and validate the prediction model,and interpretability methods were used to analyze the contribution of each feature to individuals and the effect of the features on specific target prediction decisions.Results The logistic regression model demonstrated robust predictive performance across the BD,BDD,and BDM cohorts,with areas under the curve(AUC)of the receiver operating characteristic curves always exceeding 81.6%.The core predictive features included platelet distribution width(PDW),fibrinogen(FIB),platelet large cell ratio(P-LCR),activated partial thromboplastin time(APTT),prothrombin time(PT),and triglyceride(TG).The logistic regression model exhibited strong interpretability and was combined with nomograms for intuitive risk quantification and individualized prediction.Conclusion The logistic regression model enables rapid and simple screening of BD patients with psychotic symptoms.Distinct patterns of changes observed in blood biomarkers of BDD and BDM subgroups enrich the understanding of the underlying pathophysiological mechanisms and highlight the importance of considering subtypes in the intervention and management of patients.

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.

Cardiac cephalalgia is a rare disease caused by underlying coronary artery disease that presents as headache with or without chest symptoms.Headache symptoms are often caused by referred pain,increased intracranial pressure and release of large amounts of pain-causing neurochemicals due to myocardial ischemia,and cortical hypoperfusion.Due to the low overall prevalence of the disease,the lack of chest pain typical of coronary heart disease,and the fact that it may be difficult to distinguish from headaches caused by neurological diseases,accurate diagnosis and treatment of the disease are often delayed.We report a case of acute coronary syndrome with headache only.Revascularization was achieved through percutaneous coronary intervention therapy,followed by standard secondary prevention pharmacotherapy.Follow-up six months postoperatively showed a significant improvement in exercise tolerance,with no further headache episodes.The purpose is to improve the understanding of patients with cardiac cephalalgia,with a view to early identification and timely intervention,and ultimately improve the symptoms and prognosis.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Objective To analyze the safety and efficacy of neuroendoscopic minimally invasive surgery and traditional extraventricular drainage in the treatment of severe hypertensive intraventricular hemorrhage.Methods The clinical data of 50 cases with neuroendoscopic ventricular hematoma evacuation(endoscopy group)and 44 cases with traditional ventricles external puncture drainage(drainage group)from July 2020 to July 2023 were retrospectively analyzed,and the hematoma clearance rates,classification of activities of daily living(ADL)scale,incidence of hydrocephalus,secondary bleeding,intracranial infection,and pulmonary infection were observed between the two groups of patients.Results After surgery,the proportion of patients with hematoma clearance rate>60％and ADL grades Ⅰ,Ⅱ,and Ⅲ in the endoscopy group were significantly higher than those in the drainage group[the proportion of patients with hematoma clearance rate>60％:88.0％(44/50)vs.47.7％(21/44),χ2=17.794,P<0.001;the proportion of individuals with ADL grades Ⅰ,Ⅱ,and Ⅲ:94.0％(47/50)vs.77.3％(33/44),respectively,χ2=5.459,P=0.019],the incidence of complications in endoscopy group was significantly lower in the drainage group[8.0％(4/50)vs.34.1％(15/44),χ2=9.879,P=0.002].Conclusion Compared with traditional ventricular puncture drainage surgery,neuroendoscopic minimally invasive surgery for the treatment of severe hypertensive intracerebral hemorrhage with ventricular casting can achieve better treatment outcomes,a higher hematoma clearance rate,and fewer postoperative complications.

Gambogic acid, a caged xanthone compound derived from Garcinia, has been proven to be an important substance basis for the pharmacological effects of the plant. In recent years, it has received continuous attention due to its broad and significant pharmacological activities. Modern pharmacological investigations have demonstrated that gambogic acid endows various therapeutic effects such as anti-inflammatory, antioxidant, and anti-tumor activities, as well as benefits in retinopathy, organ protection, anti-microbial infection, bone protection, and neuropathic pain relief. Nevertheless, there is currently a lack of systematic summary and integration of the pharmacological effects and mechanisms of gambogic acid, which is critical for advancing the clinical application of this natural product. In addition, current research has raised concerns about potential safety risks associated with gambogic acid, such as organ toxicity, developmental toxicity, and hemolysis. Given this, this paper systematically reviewed and summarized the pharmacological effects, mechanisms, and toxicological profiles of gambogic acid, aiming to provide reference and data support for its clinical translation.
Xanthones/toxicity* ; Humans ; Animals ; Drugs, Chinese Herbal/toxicity* ; Garcinia/chemistry*

Aim To investigate the effects of angelica sinensis polysaccharide (ASP) antagonizing 5-fluorou-raeil (5-FU) on spleen stress erythropoiesis in mice and its related mechanism. Methods C57BL/6J mice aged 6-8 weeks were randomly divided into control group, ASP group, 5-FU group and ASP + 5-FU group. The mouse body weight during the modeling pe-riod was recorded, and peripheral blood routine and the number of mononuclear cells in the bone marrow of femur were measured. Histopathology of spleen was de-tected, also the index and cellularity of spleen were analyzed. BFU-E of spleen mononuclear cells was counted. The number of F4/80

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).