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

OBJECTIVES: To investigate the clinical characteristics and prognosis of chronic disseminated candidiasis (CDC) in children with acute leukemia (AL) following chemotherapy. METHODS: A retrospective analysis was conducted on children diagnosed with CDC (including confirmed, clinically diagnosed, and suspected cases) after AL chemotherapy from January 2015 to December 2023 at Fujian Medical University Union Hospital, Zhangzhou Municipal Hospital, and Quanzhou First Hospital Affiliated to Fujian Medical University. Clinical characteristics and prognosis were analyzed. RESULTS: The incidence of CDC in children with AL following chemotherapy was 1.92% (32/1 668). Among the children with acute lymphoblastic leukemia, the incidence of CDC in the high-risk group was significantly higher than in the low-risk group (P=0.002). All patients presented with fever unresponsive to antibiotics during the neutropenic period, with 81% (26/32) involving the liver. C-reactive protein (CRP) levels were significantly elevated (≥50 mg/L) in 97% (31/32) of the patients. The efficacy of combined therapy with liposomal amphotericin B and caspofungin or posaconazole for CDC was 66% (19/29), higher than with caspofungin (9%, 2/22) or liposomal amphotericin B (18%, 2/11) monotherapy. The overall cure rate was 72% (23/32). The proportion of patients with CRP ≥50 mg/L and/or a positive β-D-glucan test for more than 2 weeks and breakthrough infections during caspofungin treatment was significantly higher in the treatment failure group compared to the successful treatment group (P<0.05). CONCLUSIONS CDC in children with AL after chemotherapy may be associated with prolonged neutropenia due to intensive chemotherapy. Combination antifungal regimens based on liposomal amphotericin B have a higher cure rate, while persistently high CRP levels and positive β-D-glucan tests may indicate poor prognosis.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Antifungal Agents/therapeutic use* ; Candidiasis/diagnosis* ; Chronic Disease ; Leukemia/complications* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications* ; Prognosis ; Retrospective Studies

OBJECTIVES: To investigate the incidence of small for gestational age (SGA) infants among singleton live births and identify risk factors. METHODS: Clinical data for 1 020 singleton live-born infants and their mothers at People's Hospital Affiliated to Shandong First Medical University from January 2019 to January 2024 were retrospectively collected. The incidence of SGA was calculated, and univariate and multivariable logistic regression analyses were performed to determine independent risk factors. RESULTS: Among 1 020 singleton live births, the incidence of SGA was 9.90%. SGA was more frequent in female neonates and in cases with lower placental weight or umbilical cord abnormalities (all P<0.05). Both preterm and post-term birth showed significant linear trends with SGA incidence (P<0.05). Maternal factors associated with higher SGA incidence included age <20 years or ≥35 years, primary-school education or below, low pre-pregnancy body mass index (BMI), insufficient gestational weight gain, gestational hypertension, diabetes, anemia, hyperthyroidism, hypothyroidism, amniotic fluid/placental abnormalities, and smoking history (all P<0.05). Multivariable logistic regression identified preterm birth, post-term birth, low placental weight, umbilical cord abnormalities, low pre-pregnancy BMI, insufficient gestational weight gain, gestational hypertension, anemia during pregnancy, and maternal smoking as independent risk factors for SGA (all P<0.05). CONCLUSIONS The occurrence of SGA among singleton live births is associated with preterm or post-term delivery, low placental weight, umbilical cord abnormalities, low pre-pregnancy BMI, inadequate gestational weight gain, gestational hypertension, anemia during pregnancy, and maternal smoking. Targeted strengthening of perinatal management is warranted to reduce the risk of SGA.
Humans ; Female ; Infant, Small for Gestational Age ; Risk Factors ; Infant, Newborn ; Retrospective Studies ; Pregnancy ; Male ; Incidence ; Adult ; Logistic Models ; Live Birth ; Young Adult

Objective:To investigate the expression and role of DEAD-box RNA helicases 5(DDX5 helicases)in head and neck squamous carcinoma(HNSCC).Methods:Tissue microarray microarray was used to assess relevant mRNA expression profile data,and R software was used to screen differential mRNAs(DEGs).The expression level of DDX5 was predicted using GEPIA 2,TCGA databases,and detected by immunohistochemistry,western blot and RT-qPCR in the HNSCC tissue and cell lines.Based on high-throughput sequencing data of DECs,differentially expressed miRNAs(DEMIs)relevant DDX5 competitive endogenous RNA network(ceRNA)was constructed.The software cytoscape was used to visualize the ceRNA network map and further screen the regulatory ax-is.Results:The results of microarray screening revealed that DDX5 expression in HNSCC was upregulated.Immunohistochemistry ver-ified that DDX5 was stronger expressed in the nuclei of squamous carcinoma cells.qPCR results suggested that significant expression of DDX5 mRNA at the tissue and cellular levels(P＜0.05).Western blot results showed high expression of DDX5 protein in the tissues.The ceRNA network was constructed,from which the relevant HNSCC axis circRNA-039626-miR-222-5p-DDX5 was identified.Con-clusion:DDX5 is highly expressed in HNSCC,and the circRNA-039626-miR-222-5p-DDX5 axis may be a potential regulatory axis for the development of HNSCC.

This study investigates whether compounds in Salvia miltiorrhiza Bunge can bind to the Toll like receptor 4/myeloid differentiation protein 2 (TLR4/MD2) protein complex and exhibit anti-inflammatory activity. Virtual screening of reported chemical components of Salvia miltiorrhiza Bunge against TLR4/MD2 was conducted in this study. The selected compound, neoprzewaquinone A (Neo A), was tested for its impact on the binding of lipopolysaccharide (LPS) to receptors on the cell membrane, its affinity for the protein, its influence on the dimerization of TLR4 and MD2 in LPS-induced cells, and its effects on the phosphorylation of nuclear factor-κB (NF-κB) p65 protein and the secretion of inflammatory cytokines in cells. Results indicate that Neo A in Salvia miltiorrhiza Bunge exhibited the highest virtual binding affinity with TLR4/MD2, with a value of -12.8 kcal·mol^-1. Neo A significantly inhibited the binding of LPS to receptors on the cell membrane (P < 0.01). Moreover, Neo A demonstrated affinity for rhTLR4/MD2, rhTLR4, and rhMD2, with K_D values of 267, 534, and 228 nmol·L^-1, respectively. Amino acid residues like TYR131 and PHE121 in TLR4/MD2 might play a role in the alkyl and π-alkyl hydrophobic interactions with Neo A. Neo A also significantly inhibited the dimerization of TLR4 and MD2 in LPS-mediated cells (P < 0.01) and markedly suppressed the phosphorylation of NF-κBp65 protein (P < 0.05). Furthermore, Neo A significantly or markedly inhibited the secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in LPS-induced cells (P < 0.05, P < 0.01). In conclusion, Neo A exerts its anti-inflammatory effects by binding TLR4/MD2 then disrupting the binding of LPS to TLR4/MD2. It may serve as a TLR4/MD2 inhibitor with the potential to treat inflammation-related diseases targeting TLR4/MD2.

Aim To examine the neuroprotective im-pacts of total saponins from Trillium tschonoskii maxim(TST)on cerebral ischemia-reperfusion injury(CIRI)in rats and delve into the mechanisms of ferroptosis.Methods The CIRI model was prepared by dividing male SD rats into the model group,TST(0.1 g·kg-1)group,Donepezil hydrochloride(0.45 mg·kg-1)group,and sham group.The cognitive functions of rats in each group were assessed through the Morris water maze test,the changes in neurological function were evaluated using the Zea-Longa method,the infarct area was observed via TTC staining,and the pathologi-cal alterations in brain tissue were analysed using HE and Nissl staining.To further investigate the underly-ing mechanism,the mitochondrial structural changes were examined using transmission electron microscopy,and the levels of GSH-PX,MDA,and SOD were ana-lyzed.Additionally,the expressions of GPX4 and Nrf2 proteins were evaluated through immunohistochemistry and immunofluorescence.Furthermore,the protein lev-els of Keap1/Nrf2/HO-1 and Nrf2/SLC7A11/GPX4 pathways in rats were examined using Western blot-ting.Results The rats in the model group displayed diminished learning and memory capabilities in com-parison to those in the sham group,as well as a signifi-cantly increased cerebral infarction area and higher neurological function scores(P＜0.01),significantly increased cerebral infarct area,disordered and loosely arranged neurons,and reduced Nissl bodies.Addition-ally,mitochondria showed typical signs of ferroptosis.Changes related to ferroptosis included decreased activ-ities of SOD and GSH-PX(P＜0.01)and increased MDA levels(P＜0.01).The expression of GPX4 and Nrf2-positive cells was significantly reduced,along with decreased fluorescence intensity of GPX4.Further-more,the protein expression of Keap1,Nrf2,HO-1,GPX4,SLC7A11 in the hippocampus decreased(P＜0.05,P＜0.01).Following the administration of TST,these effects showed improvement.Conclusions TST has neuroprotective effects,enhancing learning and memory abilities while reducing oxidative stress levels.The mechanism may involve the inhibition of ferroptosis through the Keap-1/Nrf2/HO-1 and Nrf2/SLC7 A11/GPX4 pathways.

Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) μmol/L(range:8.0 to 344.2 μmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

OBJECTIVES: To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis. METHODS: Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed. RESULTS: A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P<0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P>0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×10⁹/L at diagnosis was an influencing factor for 5-year OS rate in children with JMML (P<0.05). CONCLUSIONS The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.
Child ; Humans ; Male ; Female ; Child, Preschool ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Prognosis ; Genetic Testing ; Mutation ; Hematopoietic Stem Cell Transplantation