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

BACKGROUND: High temperatures are known to be associated with an increased risk of self-harm, but the influence of demographic changes and country-level indicators on the burden of heat-related self-harm remains unclear. This study examined the key factors driving changes in self-harm mortality linked to high temperatures and explored their impact at the country level. METHODS: This is an ecological study that analyzes data from the 2021 Global Burden of Disease (GBD) study, the World Bank, and the Climate Research Unit (CRU) were analyzed. Decomposition analyses were used to identify key factors driving changes in high temperature-related self-harm mortality between 1990 and 2021. A panel data model assessed the impact of national indicators on heat-related self-harm mortality. RESULTS: In 2021, 14,885 deaths globally were attributed to heat-related self-harm, a 41.94% increase from 1990, with low-middle SDI regions accounting for 47.84% of these deaths. While the global death rate from heat-related self-harm declined slightly over this period, South Asia and low-middle SDI regions contributed most to the decline. However, population aging exacerbated mortality rates. Demographic and meteorological factors were also linked to heat-related self-harm. CONCLUSION The global decline in heat-related self-harm mortality is largely driven by reductions in females, low-middle SDI regions, and South Asia. However, population aging and growth in these regions have added to the mortality burden, slowing the overall decline. Factors such as population density are also associated with heat-related self-harm. Targeted measures are needed to mitigate heat-induced self-harm more effectively in future.
Humans ; Self-Injurious Behavior/etiology* ; Hot Temperature/adverse effects* ; Global Health/statistics & numerical data* ; Female ; Male ; Adult ; Middle Aged ; Aged ; Young Adult ; Adolescent

OBJECTIVES: To explore the active components that mediate the therapeutic effect of Centella asiatica on psoriasis and their therapeutic mechanisms. METHODS: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in Centella asiatica and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis. In a RAW264.7 macrophage model of LPS-induced inflammation, the anti-inflammatory effect of 7.5, 15, 30, and 60 μmol/L quercetin, asiaticoside, and asiatic acid, which were identified as the main active components in Centella asiatica, were tested by measuring cellular production of NO, TNF‑α and IL-6 using Griess method and ELISA and by detecting mRNA expressions of IL-23, IL-17A, TNF-α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727) with RT-qPCR and Western blotting. RESULTS: A total of 139 targets of Centella asiatica and 4604 targets of psoriasis were obtained, and among them CASP3, EGFR, PTGS2, and ESR1 were identified as the core targets. KEGG analysis suggested that quercetin, asiaticoside, and asiatic acid in Centella asiatica were involved in cancer and IL-17 and MAPK signaling pathways. In the RAW264.7 macrophage model of inflammation, treatment with quercetin significantly reduced cellular production of NO, TNF‑α and IL-6, and lowered mRNA expressions of IL-23, IL-17A, TNF‑α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727). CONCLUSIONS Quercetin, asiaticoside and asiatic acid are the main active components in Centella asiatica to mediate the therapeutic effect against psoriasis, and quercetin in particular is capable of suppressing cellular production of NO, TNF‑α and IL-6 and regulating the IL-23/IL-17A inflammatory axis by mediating STAT3 phosphorylation to inhibit inflammatory response.
Quercetin/pharmacology* ; Psoriasis/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice ; Animals ; Centella/chemistry* ; Triterpenes/pharmacology* ; Phosphorylation ; Interleukin-17/metabolism* ; Interleukin-23/metabolism* ; RAW 264.7 Cells ; Pentacyclic Triterpenes/pharmacology* ; Macrophages/drug effects* ; Signal Transduction ; Plant Extracts

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Objective:To analyze the status of anemia at the beginning of dialysis in maintenance hemodialysis (MHD) adult patients, and to explore the relationship between early dialysis anemia and early survival and long-term survival.Methods:It was a retrospective cohort study. The baseline demographic and clinical data of newly admitted MHD patients from January 1, 2013 to December 31, 2020 were retrospectively analyzed. According to the hemoglobin (Hb) level at the beginning of dialysis, the patients were divided into high Hb group (Hb≥110 g/L), middle Hb group (80 g/L≤Hb<110 g/L) and low Hb group (Hb<80 g/L). The baseline data among the three groups were compared, and the changing trend of Hb level in MHD patients during the 8 years was analyzed. The follow-up ended at peritoneal dialysis, kidney transplantation, death or on December 31, 2021. All-cause death event within 6 months after the initiation of dialysis was defined as early death, while all-cause death event more than 6 months after the initiation of dialysis was defined as long-term death. Kaplan-Meier survival curve was used to analyze the survival rate, and log-rank test was used to compare the survival rates among the three groups. Multivariate Cox regression analysis model was used to analyze the association between anemia (Hb<110 g/L) at the beginning of dialysis and both early and long-term mortality.Results:A total of 36 216 MHD patients were included in this study, with age of (61.3±15.5) years old and 22 163 males (61.20%). The Hb at the beginning of dialysis was (89.33±20.89) g/L. The compliance rate of Hb (≥110 g/L) was 16.43% (5 952/36 216). There were 12 232 patients (33.78%), 18 032 patients (49.79%), and 5 952 patients (16.43%) in low Hb group, middle Hb group, and high Hb group, respectively. There were statistically significant differences in gender distribution, age, serum creatinine, blood phosphorus, blood calcium, C-reactive protein, intact parathyroid hormone, blood leukocytes, platelets, serum albumin, triglyceride, total cholesterol, and proportions of chronic glomerulonephritis, diabetic nephropathy, diabetes mellitus, cardiovascular and cerebrovascular diseases, tumors, emporary catheter, long-term catheter and autologous arteriovenous fistula among the three groups (all P<0.05). During the 8-year period, the Hb level had an increased trend steadily each year, and Hb was (88.48±22.07) g/L, (88.52±21.43) g/L, (87.86±21.29) g/L, (88.93±20.69) g/L, (88.87±20.69) g/L, (90.03±20.47) g/L, (90.74±20.31) g/L and (90.31±20.54) g/L year by year. There were 2 176 early deaths (6.01%), and 6 557 long-term deaths (18.10%) by the end of follow-up. Kaplan-Meier survival curve showed that early survival rate of low Hb group was significantly lower than those of high Hb group (log-rank test, χ2=57.115, P<0.001) and middle Hb group (log-rank test, χ2=49.918, P<0.001), and long-term survival rates of low Hb group (log-rank test, χ2=107.097, P<0.001) and middle Hb group (log-rank test, χ2=47.430, P<0.001) were significantly lower than that of high Hb group. Multivariate Cox regression analysis showed that Hb<80 g/L at the beginning of dialysis was an independent influencing factor of early death (Hb ≥110 g/L as a reference, HR=1.307, 95% CI 1.096-1.559), and 80 g/L≤Hb<110 g/L and Hb<80 g/L at the beginning of dialysis were the independent influencing factors of long-term death (Hb≥110 g/L as a reference, HR=1.108, 95% CI 1.021-1.203; HR=1.228, 95% CI 1.127-1.339, respectively) in MHD patients. Conclusions:The compliance rate of Hb at the beginning of dialysis in MHD patients is low. Hb <80 g/L at the beginning of dialysis is an independent risk factor of early death, and Hb <110 g/L at the beginning of dialysis is an independent risk factor of long-term death in MHD patients.

Objective:To explore the changes of iron metabolism in patients with hepatitis B cirrhosis and esophageal and gastric varices complicated with portal vein thrombosis.Methods:This study was a cross-sectional study. 253 patients with hepatitis B cirrhosis with esophageal and gastric varices who were hospitalized in the Zhongshan Hospital, Fudan University from January 1, 2020 to December 31, 2021 were included in this study. They were divided into portal vein thrombosis group ( n=57) and non portal vein thrombosis group ( n=196) according to the presence or absence of portal vein thrombosis. The iron metabolism characteristics of the two groups were compared, and subgroups were analyzed according to the presence or absence of ascites, platelet count level, D-dimer level, and Child grade. The factors related to portal vein thrombosis were screened through multivariate logistic regression analysis. Results:The ratio of Child pugh B/C, ascites, D-dimer and platelet count in patients with hepatitis B cirrhosis and esophageal and gastric varices complicated with portal vein thrombosis was higher (all P<0.05). Patients with portal vein thrombosis had higher levels of soluble transferrin receptor [2.4(1.8, 3.6)mg/L vs 1.8(1.3, 2.7)mg/L, P=0.006], and lower levels of ferritin [33.1(18.9, 63.3)ng/ml vs 57.7(19.4, 142.5)ng/ml, P=0.038]. Layered analysis showed that ascites, platelet count levels, D-dimer levels, and Child-pugh grade did not affect the negative correlation trend between ferritin and portal vein thrombosis, and the positive correlation trend between soluble transferrin receptors and portal vein thrombosis. Moreover, soluble transferrin receptors showed a statistically significant positive correlation with portal vein thrombosis in the absence of ascites, low D-dimer levels, and Child-pugh grade A. Multivariate analysis suggested that after weighing Child-pugh grading, platelet count, and D-dimer levels, ferritin ( OR=0.943, 95% CI: 0.904-0.983, P=0.006) and soluble transferrin receptor ( OR=1.034, 95% CI: 0.001-1.067, P=0.044) were independently associated with portal vein thrombosis. Conclusions:In patients with hepatitis B cirrhosis with esophageal and gastric varices, the characteristics of iron metabolism in patients with portal vein thrombosis are different from those in patients without thrombosis, with higher levels of soluble transferrin receptor and lower levels of ferritin.

Objective:To investigate whether discontinuation of previous targeted immunotherapy increases the risk of rebleeding in patients with advanced liver cancer complicated with esophageal and gastric variceal bleeding after endoscopic treatment.Methods:A retrospective cohort study was conducted to include advanced liver cancer patients who were diagnosed with esophageal and gastric variceal bleeding through endoscopic examination and treated under endoscopy at Zhongshan Hospital, Fudan University from March 1, 2020 to March 1, 2022, due to upper gastrointestinal bleeding. We collected clinical data from patients and divided them into targeted immunotherapy group and non targeted immunotherapy group based on whether they received targeted immunotherapy before bleeding; Follow up observation was conducted for 6 months to evaluate the patient′s re bleeding and survival status.Results:A total of 55 patients were included, of which 24 had previously received targeted immunotherapy and 31 had not received targeted immunotherapy. There was no significant difference between the two groups in gender distribution, etiology, hypertension and diabetes (all P>0.05). The age of the target immunotherapy group was younger than that of the non target immunotherapy group, and the level of fibrinogen was higher than that of the non target immunotherapy group, with statistical significance ( P=0.002, 0.017). There was no statistically significant difference in the 6-month re bleeding rate (20.83% vs 22.58%, P=0.269) and 6-month mortality rate (45.83% vs 29.03%, P=0.199) between the targeted and non targeted groups of patients. Further Cox regression multivariate analysis revealed that Child-pugh grading was an independent risk factor for 6-month survival in patients with advanced liver cancer with esophageal and gastric varices ( HR=2.64, P=0.009). Conclusions:Targeted immunotherapy does not increase the rate of rebleeding in patients with advanced unresectable liver cancer after endoscopic treatment of esophageal and gastric varices. Child-pugh grading is a factor that affects the 6-month survival of advanced liver cancer patients after bleeding, and the poorer the liver function, the shorter the survival period.

OBJECTIVE: To explore the mechanisms that mediate the anti-inflammatory activity of Eurycoma longifolia. METHODS: Kunming mouse models of xylene-induced ear swelling and lipopolysaccharide (LPS)-induced acute pneumonia were used to compare the anti- inflammatory activities of aqueous and ethanol extracts of Eurycoma longifolia. UPLC-Q-TOF-MS/MS was used to identify the chemical composition in the ethanol extract of Eurycoma longifolia, based on which the potential antiinflammatory targets of Eurycoma longifolia were screened using the databases including SwissADME, SwissTargetPrediction, and Genecards. The String database was used to generate the protein-protein interaction (PPI) network, and Cytoscape was used for network topology analysis and screening the core targets. The enrichment of the core targets was analyzed using Metascape database, the core components and targets were docked with Autodock software, and the docking results were visualized using Pymol software. In a RAW264.7 cell model of LPS-induced inflammation, the Griess reagent was used to measure NO level, and Western blotting was performed to detect the expression levels of MAPK1, JAK2, and STAT3 proteins to verify the anti- inflammatory mechanism of Eurycoma longifolia. RESULTS: The ethanol extract (75%) of Eurycoma longifolia (ELE) was the active site, which contained a total of 37 chemical components. These chemical compounds and diseases had 541 targets, involving the JAK/STAT3, cAMP and other signaling pathways. Twelve indicator components were identified, which all showed good results of molecular docking with two core targets involved in the signaling pathways. In the cell validation experiment, treatment of the cells with low-, medium-, and high-dose ELE significantly reduced NO release in the cells, and ELE at the medium dose significantly decreased the cellular expressions of JAK2 and STAT3. CONCLUSION The anti-inflammatory activity of Eurycoma longifolia is attributed primarily to its active ingredients bitter lignin and alkaloids, which may regulate the JAK/STAT3 signaling pathway by targeting JAK2 and STAT3.
Animals ; Mice ; Network Pharmacology ; Eurycoma ; Lipopolysaccharides ; Molecular Docking Simulation ; Tandem Mass Spectrometry ; Anti-Inflammatory Agents/pharmacology* ; Ethanol ; Plant Extracts/pharmacology*