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 understand the prevalence of school bullying and the comorbidity of anxiety and depressive symptoms among middle school students and their association, so as to provide a basis for developing related intervention strategies. Methods: From September to December 2023, a multistage random cluster sampling was employed to select 107 851 middle school students across 104 counties in Anhui Province. The Center for Epidemiological Studies Depression Scale (CES-D) and the Generalized Anxiety Disorder-7 (GAD-7) Scale were used to assess depressive and anxiety symptoms. Logistic regression analysis was utilized to examine the correlations between experiences of school bullying and the comorbidity of anxiety and depressive symptoms. Results: The findings revealed that 2.80% of middle school students had experienced school bullying in the past 30 days. Additionally, 27.03% exhibited potential symptoms of depression, 8.94% showed signs of anxiety symptom, and the comorbidity rate of anxiety and depressive symptoms was 8.04%. Logistic regression analysis showed that statistically significant correlations were identified between experiences of school bullying and increased risks of depressive symptoms (OR=6.42, 95%CI=5.93-6.94, P<0.01), anxiety symptoms (OR=5.94, 95%CI=5.47-6.44, P<0.01), and their comorbidity (OR=6.38, 95%CI=5.88-6.93, P<0.01). Compared with those who did not suffer from school bullying, junior high school students, ordinary senior high school students, vocational senior high school students, boys and girls who suffered from school bullying all had increased risks of comorbidity of anxiety and depressive symptoms (OR=7.25, 5.55, 4.80, 6.42, 6.27, P＜0.01). Conclusions The study underscores the significant impact of school bullying on increasing the risk of comorbidity of anxiety and depressive symptoms among middle school students. It is important to pay attention to the psychological health of bullied students and implement timely psychological intervention measures.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

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 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.

Temporomandibular disorders (TMD) are a heterogeneous group of diseases that affect the temporomandibular joint, chewing muscle system, dental occlusion, and even various structures throughout the body, with significant characteristics of biological-psychological-social pattern. TMD related chronic pain, as the most important clinical symptom, can result in negative emotions seriously affecting patients′ quality of life and physical and mental health. Although a variety of therapies have been previously reported to treat TMD related chronic pain, there is a lack of widely recognized therapies. Professor Jason W Busse (from Michael G DeGroote National Pain Centre, McMaster University, Hamilton ON, Canada) took the lead and collaborated with multiple internationally renowned schools/hospitals of stomatology to develop an international consensus on the management of chronic pain associated with TMD, a clinical practice guideline, which took two years and was published in December 15th, 2023 in a global top journal of clinical research The British Medical Journal. This clinical practice guideline explored the comparative effectiveness of available therapies for chronic pain associated with TMD, conditionally recommended the specific intervention for different treatment or pain relief, proposed a comprehensive, agreed, and standardized clinical practice guideline. This present article describes the methodology and key elements of the clinical practice guideline to help clinicians fully understand and appropriately apply this guidance, which could provide the references for clinical practice of TMD associated chronic pain in China.