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

Lactate dehydrogenase A(LDHA)is an important enzyme involved in the anaerobic glycolysis of cells,catalyzing the conversion of pyruvate to lactate and participating in processes such as tumor proliferation,mi-gration,invasion,and the regulation of the tumor microenvironment.High expression levels of LDHA are often in-dicative of disease progression and poor prognosis in malignant hematological diseases.The expression of LDHA in malignant hematological diseases is closely associated with various molecules,including HIF-1,microRNAs and c-Myc,as well as signaling pathways like PI3K/AKT/GSK3,USP1/PLK1/LDHA and Fbw7/LDHA/lactate/miR-223.Meanwhile,the progression of malignant hematological conditions facilitated by LDHA primarily occurs through the regulation of energy metabolism via glycolytic pathways.

Purpose To investigate the expression and prog-nostic value of programmed death-ligand 1(PD-L1),CD 163 and CD8 in lymphocyte-predominant breast cancer(LPBC),and to analyze the expression of PD-L1,CD 163 and CD8 in primary cancer and corresponding lymph node metastatic cancer.Meth-ods LPBC with complete pathological data were selected.Im-munohistochemical EnVision method was used to detect the ex-pression of PD-L1,CD163 and CD8 in 82 cases of primary cancer and 23 cases of corresponding lymph node metastatic cancer.Their relationships with clinicopathological features and prognosis were analyzed,and the difference of expression be-tween primary cancer and lymph node metastatic cancer.Results The positive rates of PD-L1 in tumor cell(TC)and immune cell(IC)in primary cancer were 25.61％(21/82)and 79.27％(65/82),respectively.The positive rates of TC-PD-L1 in grade Ⅱ and grade Ⅲ were 18.00％(9/50)and 37.50％(12/32),respectively.The expression of TC-PD-L1 was corre-lated with the histological grade(P＜0.05).The positive rates of IC-PD-L1 in tumor maximum diameter ≤2 cm and＞2 cm were 66.67％(18/27)and 85.45％(47/55),respectively.The positive rates of IC-PD-L1 in Ki67≤20％and＞20％were 60.00％(12/20)and 85.48％(53/62),respectively.The ex-pression of IC-PD-L1 was related to tumor maximum diameter and Ki67(P＜0.05).TC-PD-L1 expression was positively correlated with CD8+intratumoral tumor-infiltrating lymphocytes(iTILs)density(r=0.277,P＜0.05),and IC-PD-L1 expression was positively correlated with CD163(r=0.259,P＜0.05).High expression of CD163 was significantly correlated with shorter DFS(P＜0.05).Between primary cancer and lymph node metastatic cancer,the co-expression rates of TC-PD-L1 and IC-PD-L1 were 82.61％(19/23)and 47.82％(11/23),respectively,and the difference was not statistically significant(P＞0.05).There were statistically differences of CD163 expression and CD8+iTILs be-tween primary cancer and lymph node metastatic cancer(P＜0.05).Conclusion PD-L1 expression in primary cancer is as-sociated with poor clinicopathologic features,and high expression of CD163 suggests poor prognosis.There are differences in tumor immune microenvironment between LPBC primary cancer and lymph node metastatic cancer,and re-evaluation of PD-L1 of lymph node metastatic cancer may provide valuable guidance for clinical immunotherapy.

Objective To explore the role and mechanism of the exosomes derived from bronchoalveolar lavage fluid(BALF)of patients with chronic obstructive pulmonary disease(COPD-Exo)in regulating osteoblast differentiation.Methods A total of 6 COPD patients and 6 non-COPD patients admitted in our hospital in June 2023 were recruited,and their BALF samples were collected during the process.COPD-Exo and exosomes from the non-COPD patients(Ctrl-Exo)were extracted and identified by electron microscopy and Western blotting.Alizarin red staining and qRT-PCR were used to detect the differences in osteoblast differentiation after COPD-Exo and Ctrl-Exo intervention.Bioinformatics analysis was performed on the microRNA(miRNA)expression profiles of COPD-Exo and Ctrl-Exo in the GEO database(GSE218571)to obtain differentially expressed miRNAs.Antagomir was used to block mircoRNA function,and the miRNAs with osteogenic differentiation regulatory function were identified.Targetscan software was used to predict the downstream target genes of the miRNAs,and then these miRNAs were verified.Results Exo could be extracted from BALF of both COPD and non-COPD patients.Alizarin red staining and qRT-PCR results showed that COPD-Exo inhibited the osteogenic differentiation of human hFOB 1.19 osteoblasts(P＜0.05).Bioinformatics analysis indicated that the expression level of miR-223-3p was significantly up-regulated in COPD-Exo.Blocking miR-223-3p with Antagomir could alleviate the osteogenic differentiation of human hFOB 1.19 osteoblasts inhibited by COPD-Exo(P＜0.05).Targetscan prediction revealed that miR-223-3p may target and inhibit the expression of osteogenic differentiation-related factor FOXO3(P＜0.05).Conclusion COPD-Exo can inhibit the osteogenic differentiation of human hFOB 1.19 osteoblasts through miR-223-3p,which may be related to the inhibition of FOXO3 expression by miR-223-3p.

Objective:To investigate the drug resistance status and genomic characterization of Proteus mirabilis (PM) isolated from outpatient cases with diarrhea in Tai′an City and Laizhou City, Shandong Province. Methods:A total of 510 fecal samples were collected from 510 patients with acute diarrhea admitted to 43 sentinel hospitals in Tai′an City and Laizhou City, Shandong Province, between January 2021 and December 2022. The samples were cultured and isolated to identify Proteus spp. by direct inoculation, the drug susceptibility testing was performed by microbroth dilution method, and resistance genes and virulence genes were obtained by whole genome sequencing and bioinformatic analysis, thereby revealing the genetic environment surrounding the blaOXA-1 and blaCTX-M-65 genes. Single nucleotide polymorphism (SNP) analysis and core genome multilocus sequence typing (cgMLST) were conducted on the current strains and 100 PM isolates downloaded from the National Center for Biotechnology Information (NCBI) database via customizable methods utilizing RidomSeqSphere+ software, with the objective of exploring the phylogenetic relationships among the strains. Results:A total of 35 strains of Proteus were isolated from 510 fecal samples, including 31 strains of PM with a detection rate of 6.08% (31/510) and four strains of Proteus vulgaris.The multidrug resistance rate of PM was 100.00% (31/31).The 35 isolates carried a total of 43 resistance genotypes.Thirteen strains of PM carried blaOXA-1, six strains carried both blaOXA-1 and blaCTX-M-65, and 15 PM strains carried at least 15 antibiotic resistance genes (ARGs). The virulence genes included ureA, mrpA, ZapA, hpmA and so on. blaOXA-1 and blaCTX-M-65 genes were surrounded by mobile elements such as Tn3, ISL3 and IS6. cgMLST showed consistency with the SNP clustering results. Isolate 2022LZ41 from Laizhou City clustered with isolates 2022TA018, 2022TA017 and 2022TA019 from Tai′an City, with the number of allelic differences ranging from zero to two, and the Laizhou City isolate 2022LZ40 was highly genetically related to strain CRK0056 (human, USA, 2015). Conclusions:PM isolated from patients with diarrhea is multidrug-resistant, carrying many resistance and virulence genes.The presence of mobile genetic elements can lead to horizontal transfer of resistance genes.

Objective To mine the adverse drug event(ADE)signals of galcanezumab based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)to provide reference for clinical drug safety.Methods The data from the FAERS database from the third quarter of 2018 to the fourth quarter of 2023 were extracted.After data cleaning and standardization,the duplicate data was removed using structured query language,ADE reports with galcanezumab as the main suspected drug were screened.ADE reports were standardized and categorized using the Medical Dictionary for Drug Regulatory Activities.The reporting odds ratio(ROR)method and information component(IC)method were applied for signal detection.Results A total of 60 ADE signals were detected after screening,11 system organ classes were involved,mainly general disorders and administration site conditions.The ADE signals that occurred most frequently were a variety of discomfort reactions at the injection site,consistent with the most common ADEs documented in the drug insert.The top 3 new ADE signals in order of occurrence frequency were alopecia,weight increased and constipation,and in order of ROR and IC values were injection site pustule,vertebral artery dissection and Raynaud's phenomenon.Conclusion ADE related to galcanezumab mainly involve systemic diseases and various reactions at the site of administration,among which vertebral artery dissection and Raynaud's phenomenon are stronger signals and newer ADEs.The patient's disease progression should be closely monitored during the treatment period to avoid serious consequences.

Objective To systematically evaluate the effect and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy for resectable non-small cell lung cancer (NSCLC). Methods The PubMed, EMbase, The Cochrane Library, CNKI, and Wanfang data were searched by computer to identify relevant studies on anti PD-1 /PD-L1 combined with chemotherapy for resectable NSCLC from inception to March 2023. Two authors independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. The single-arm study was evaluated for quality using the methodological index for non-randomized studies (MINORS). Meta-analysis was conducted by RevMan 5.4 software. Results Twenty-six studies with 965 patients were included in this meta-analysis. MINORS scores of single-arm studies were ≥12 points. The meta-analysis results showed that the pooled pathologic complete response, major pathologic response, and objective response rates as well as partial response, surgical rate and R0 surgical resection rate of neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy were 39% [RD=0.39, 95%CI (0.31, 0.47) ], 59% [RD=0.59, 95%CI (0.53, 0.65) ], 72% [RD=0.72, 95%CI (0.65, 0.80) ], 62% [RD=0.62, 95%CI (0.56, 0.69) ], 86% [RD=0.86, 95%CI (0.81, 0.92) ], and 94% [RD=0.94, 95%CI (0.92, 0.97) ], respectively. In terms of safety, the rate of adverse events (AEs) was 65% [RD=0.65, 95%CI (0.52, 0.78) ], and the rate of grade 3 to 5 AEs was 16% [RD=0.16, 95%CI (0.10, 0.23) ]. Conclusion The combination of neoadjuvant PD-1/PD-L1 inhibitors with chemotherapy has good efficacy and safety in the treatment of patients with resectable NSCLC.

Objective:To investigate the drug-resistant gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae (CR-ECL) in rural residents of Weifang City, Shandong Province. Methods:Fecal samples were collected from rural community residents in Weifang City, Shandong Province in 2017. Drug-resistant strains were screened using a carbapenem-resistant enterobacter chromogenic medium. CR-ECL positive strains were acquired via Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry(MALDI-TOFMS) analysis. The antibiotic resistance phenotype of CR-ECL was determined using a microbroth dilution assay. Whole genome sequencing (WGS) and analysis were conducted, along with an examination of the immediate vicinity of the blaNDM gene and phylogenetic analysis of the strains. Results:A total of 628 fecal samples were collected and tested, of which 6 were CR-ECL positive (detection rate 0.96%), all exhibiting multiple drug resistance (MDR) phenotypes. Six CR-ECL strains had four MLST genotypes (ST), all of which carried multiple drug resistance genes ( blaNDM-1, blaNDM-5, etc.) and virulence genes ( acrA, acrB, entB, fepC, etc.). There were mobile genetic elements ISAba125, TN3-IS3000, TN3 and IS5 in the genetic environment surrounding the blaNDM gene. The phylogenetic tree showed that the multi-locus sequence typing of the core genome (cgMLST) was consistent with the single nucleotide polymorphism (SNPs) results. The cgMLST results showed that the allele differences between strains 2BC0101B and 2BC0251B, 2BG0561B and 2BI0221B were 2 and 1, respectively. The SNPs results showed that the above two pairs of bacteria also clustered together. It was found that the strains of chicken fecal samples in the National Center for Biotechnology Information (NCBI) database were located in the center of the evolutionary tree, and the local sequences could be traced back to American human sequences. Conclusion:Multidrug-resistant CR-ECL is detected in rural community residents in Weifang City, Shandong Province.

[Objective]To explore the regulatory mechanism of hypoxia exposure on carbon metabolism pathway in spleen of mice.[Methods]C57BL/6 mice were raised at altitudes of 400 m and 4 200 m,with 5 mice in each group.After 30 days,spleen tissues were aseptically removed for analysis of differentially expressed genes,proteins,and metabolites using transcriptome sequencing,proteomics,and non-targeted metabolomics.GO and KEGG enrichment analysis were conducted to explore key pathways.The key genes and protein in the pathway were validated by RT-qPCR and Western blot.[Results]Transcriptome sequencing revealed a significant difference in the expression of 4 213 genes in hypoxic exposure,of which 1 947 were up-regulated and 2 266 were down-regulated.The analysis of differentially expressed proteins showed that 166 proteins were up-regulated and 39 proteins were down-regulated.The results of non-targeted metabolomics showed that 133 different metabolites were screened under high altitude hypoxia condition,of which 95 were up-regulated and 38 were down-regulated.KEGG enrichment analysis showed that differentially expressed genes,differentially expressed proteins and differentially expressed metabolites were enriched into the carbon metabolic pathway.Therefore,the key genes and proteins in the carbon metabolic pathway were verified.The mRNA and protein expressions of PGAM2、ENO3、PRPS2、PGLS、RPE、IDH3A、SUCLA2 and MDH2 were significantly down-regulated in the carbon metabolism pathway.[Conclusion]Low oxygen environment at high altitude weakens glycolysis,tricarboxylic acid cycle and pentose phosphate pathway by inhibiting the carbon metabolism pathway of the body,resulting in oxidative stress and energy metabolism imbalance.

ObjectiveTo investigate the correlation between the color， odor and volatile components of Paeoniae Radix Alba（PRA） and its processed products， and to examine the effects of different processing methods on the odor and color formation of PRA. MethodThe odor and chromaticity information of PRA， honey chaff-fried PRA and honey bran-fried PRA were identified by electronic nose and colorimeter， and the volatile components in the different processed products of PRA were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and analyzed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， then the differential key flavor components among the three were screened according to the principles of variable importance in the projection（VIP） value>1 and relative odor activity value（ROAV）≥1. Pearson correlation analysis was used to investigate the association between the differential flavor components and the colorimetric values and electronic nose sensors， respectively. ResultAfter being fried with honey chaff and honey bran， the lightness value（L^*） of PRA decreased， and red-green value（a^*） and yellow-blue value（b^*） increased significantly（P<0.05， P<0.01）. The odor differences were mainly reflected in the S1， S2， S4， S5， S6， S8 and S11 sensors， and the results of PCA of the electronic nose indicated that the odor differences among PRA， honey chaff-fried PRA and honey bran-fried PRA were obvious， among which the overall odor intensity of honey bran-fried PRA was higher than that of honey chaff-fried PRA. A total of 47 volatile components were identified from PRA and its processed products， including 21 for PRA， 36 for honey chaff-fried PRA， and 37 for honey bran-fried PRA. Odor analysis revealed that 12， 24 and 22 volatile components may be the key flavor components in PRA， honey chaff-fried PRA and honey bran-fried PRA， respectively. Correlation analysis showed that the L^* of the decoction pieces was negatively correlated with the content of the Maillard reaction products， the a^* and b^* were positively correlated with the content of the Maillard reaction products， the S1 and S8 sensors were negatively correlated with the content of the Maillard reaction products， and the S2， S4， S5， S6 and S11 sensors were positively correlated with the Maillard reaction products. ConclusionThe color of PRA is deepened after being stir-fried with honey chaff and honey bran， and 5-hydroxymethylfurfural， furfural and other components are generated at the same time， which is in line with the theory of burning aroma strengthens the spleen of stir-fried with honey chaff and honey bran. Honey bran-fried PRA has a stronger Maillard reaction than honey chaff-fried PRA， which makes honey bran-fried PRA with a burnt flavor and a dark yellow color， while honey chaff-fried PRA has a sweet flavor and a bright yellow color.