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

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Objective To investigate the role of Dicentrine in regulating lipopolysaccharide(LPS)-induced inflammatory responses in RAW264.7 macrophages and its underlying mechanisms.Methods RAW264.7 macropha-ges were cultured and pretreated with different concentrations of Dicentrine(250,500,1 000 μmol/L).An inflam-matory response model was established using LPS stimulation(model group),with a control group receiving no treatment.Cytotoxicity of Dicentrine was evaluated by MTT assay.Nitric oxide(NO)levels in cell culture supernatants were measured using the Griess method.Fluorescence microscopy was employed to observe in-tracellular reactive oxygen species(ROS)accumulation and apoptosis.Finally,mRNA expression levels of in-flammatory cytokines including IL-1β,IL-6,inducible nitric oxide synthase(iNOS),and tumor necrosis factor-α(TNF-α)were analyzed by qPCR.Results MTT assay results indicated that Dicentrine exhibited no cyto-toxic effects at concentrations below 1 000 μmol/L.Griess method and fluorescence microscopy showed signif-icantly elevated NO and ROS levels in the model group compared to the control group(P<0.05).Compared with the model group,the 250,500,and 1 000 μmol/L Dicentrine groups demonstrated significantly reduced NO and ROS levels(P<0.05).qPCR analysis revealed significantly increased mRNA expression of IL-1β,IL-6,iNOS,and TNF-α in the model group versus the control group(P<0.05).Compared with the model group,the 250,500,and 1 000 μmol/L Dicentrine groups showed significantly decreased mRNA expression of IL-1β,IL-6,iNOS,and TNF-α(P<0.05).Conclusion Dicentrine regulates macrophage apoptosis,thereby ef-fectively inhibiting LPS-induced inflammatory responses in macrophages.

With the increasing abuse of antibiotics,the development of rapid,accurate and sensitive methods for antibiotic detection has become critical.Nucleic acid sensors as new biosensors have shown great potential in the field of antibiotic detection due to their high selectivity,high sensitivity and real-time monitoring ability.This paper reviews the research progress in antibiotic detection based on nucleic acid sensors,including colorimetric,optical and electrochemical nucleic acid sensors,in the hope of providing a reference for the research and development of new types of antibiotic detection technologies based on nucleic acid sensors.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Objective To explore the value of plaque-to-aorta CT value ratio(standardized CT value)in differentiating coronary lipid and fibrous plaques,and to preliminarily analyze the stability of the cutoff.Methods Patients who underwent coronary computed tomography angiography(CCTA)and intravascular ultrasound(IVUS)within 1 week were included.The plaque CT value was obtained by measuring the all,four and two short-axis planes,respectively.The CT value of the ascending aorta was measured and standardized(plaque-to-aorta CT value ratio).The receiver operating characteristic(ROC)curves of the standardized and the traditional CT values were drawn.Results A total of 60 patients with 74 plaques were included,35 lipid and 39 fibrous plaques were diagnosed by IVUS.The aorta CT value was significantly correlated with the plaque(r=0.420,P<0.01);the cutoffs for the CT value of all,four and two plaque slices were 55 HU,48 HU and 52 HU,respectively,and all there of the cutoffs of standardized CT value were 0.149;the sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of four-slice traditional and standardized CT values to differentiate lipid and fibrous plaques were 69%,87%,83%,76%and 91%,82%,82%,91%,respectively.Conclusion Compared with traditional CT value,the standardized CT value can greatly improve the sensitivity and NPV in differentiating coronary lipid and fibrous plaques,while maintaining modest to high specificity and PPV.Furthermore,the cutoff is stable.

Objective:To evaluate the prognostic significance of inflammatory biomarkers,prognostic nutritional index and clinicopathological characteristics in tongue squamous cell carcinoma(TSCC)patients who underwent cervical dissection.Methods:The retrospective cohort study consisted of 297 patients undergoing tumor resection for TSCC between January 2017 and July 2018.The study population was divided into the training set and validation set by 7:3 randomly.The peripheral blood indices of interest were preoperative neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),platelet-to-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),systemic inflammation score(SIS)and prognostic nutritional index(PNI).Kaplan-Meier survival analysis and multivariable Cox regression analysis were used to evaluate independent prognostic factors for overall survival(OS)and disease-specific survival(DSS).The nomogram's accuracy was internally validated using concordance index,receiver operating characteristic(ROC)curve,area under the curve(AUC),calibration plot and decision curve analysis.Results:According to the univariate Cox regression analysis,clinical TNM stage,clinical T category,clinical N category,differentiation grade,depth of invasion(DOI),tumor size and pre-treatment PNI were the prognostic factors of TSCC.Multivariate Cox regression analysis revealed that pre-treatment PNI,clinical N category,DOI and tumor size were independent prognostic factors for OS or DSS(P＜0.05).Positive neck nodal status(N≥1),PNI≤50.65 and DOI＞2.4 cm were associated with the poorer 5-year OS,while a positive neck nodal status(N≥1),PNI≤50.65 and tumor size＞3.4 cm were associated with poorer 5-year DSS.The concordance index of the nomograms based on independent prognostic factors was 0.708(95％CI,0.625-0.791)for OS and 0.717(95％CI,0.600-0.834)for DSS.The C-indexes for external validation of OS and DSS were 0.659(95％CI,0.550-0.767)and 0.780(95％CI,0.669-0.890),respectively.The 1-,3-and 5-year time-dependent ROC analyses(AUC=0.66,0.71 and 0.72,and AUC=0.68,0.77 and 0.79,respec-tively)of the nomogram for the OS and DSS pronounced robust discriminative ability of the model.The calibration curves showed good agreement between the predicted and actual observations of OS and DSS,while the decision curve confirmed its pronounced application value.Conclusion:Pre-treatment PNI,clinical N category,DOI and tumor size can potentially be used to predict OS and DSS of patients with TSCC.The prognostic nomogram based on these variables exhibited good accurary in predicting OS and DSS in patients with TSCC who underwent cervical dissection.They are effective tools for predicting sur-vival and helps to choose appropriate treatment strategies to improve the prognosis.

Objective:To analyze the disease characteristics, diagnosis and treatment methods of venous pulsatile tinnitus treated by intervention of sigmoid sinus.Methods:Fifty patients (from Shandong Provincial ENT Hospital, Shandong University between February 2014 and July 2020) with venous pulsatile tinnitus treated by sigmoid sinus surgery were analyzed retrospectively. The tinnitus characteristics, imaging findings, surgical methods, intraoperative findings and postoperative tinnitus changes were recorded. The patients were followed up for 6-12 months. The sign rank sum test was used to analyze the difference in tinnitus grading before and after surgery. There were 50 patients with unilateral venous pulsatile tinnitus, including 49 females and 1 male. The age ranged from 17 to 67 years, with a median age of 44 years. There were 45 cases of right tinnitus and 5 cases of left tinnitus. The degree of tinnitus before operation was grade Ⅱ or above, including 4 cases of gradeⅡ, 11 cases of grade Ⅲ, 22 cases of grade Ⅳ and 13 cases of grade Ⅴ.Results:Thirty-seven cases were cured, 8 cases were ineffective (no change in tinnitus), 3 cases were markedly effective (tinnitus grade decreased by 3 in 2 cases, 4 in 1 case), and 2 cases were effective (tinnitus grade decreased by 1). The difference of tinnitus grade before and after operation was statistically significant ( Z=-5.70, P<0.05). Temporal bone CT showed 36 cases of sigmoid diverticulum (including 17 cases with sigmoid sinus dehiscence), 12 cases of sigmoid sinus dehiscence and 2 cases of absence of the temporal bone cortex abutting to sigmoid sinus. Thirty-five cases were performed with closure of sigmoid sinus diverticulum, 4 cases were performed with resurfacing of the sigmoid plate, 5 cases were performed with narrowing of sigmoid sinus, 4 cases were performed with simple opening of pre sigmoid mastoid air chamber, 1 case of opening was performed with pre sigmoid mastoid air chamber combined with narrowing of sigmoid sinus, and 1 case was performed with opening of pre sigmoid mastoid air chamber combined with closure of sigmoid sinus diverticulum. Conclusions:Venous pulsatile tinnitus is common in women. The common causes may be sigmoid sinus wall abnormalities such as sigmoid sinus diverticulum and perisigmoid bone defect. Imaging examinations are helpful for diagnosis. Venous pulsatile tinnitus can be treated with surgery.