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

OBJECTIVE: To investigate the effects of liriodendrin on the intestinal flora and the ferroptosis signaling pathway in renal tissue of rats with sepsis-induced acute kidney injury (AKI). METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into sham operation group (Sham group), sepsis model induced by cecal ligation and puncture group (CLP group), and liriodendrin intervention group (CLP+LIR group), with 10 rats in each group. The CLP+LIR group was given 0.2 mL of 100 mg/kg liriodendrin by gavage 2 hours before modeling; Sham group and CLP group were given the same volume of normal saline by gavage. The samples were collected after anesthesia 24 hours after modeling. The pathological changes of renal tissue were observed by hematoxylin-eosin (HE) staining. The levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukins (IL-1β, IL-6) were detected by enzyme linked immunosorbent assay (ELISA). The levels of renal function indicators such as creatinine (Cr), and urea nitrogen (UREA) in peripheral blood, and the content of malondialdehyde (MDA) and Fe²⁺ in renal tissue were detected. Western blotting was used to detect the expressions of nuclear factor E2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) in renal tissues. The changes of intestinal flora were detected by 16S rDNA high-throughput sequencing. RESULTS: Compared with the Sham group, the CLP group showed significantly enlarged glomeruli, noticeable renal interstitial edema, disorganized kidney tissue, and significantly increased pathological scores. The contents of TNF-α, IL-1β, IL-6, Cr, and UREA in peripheral blood and the levels of MDA and Fe²⁺ in renal tissue were significantly increased. The protein expressions of Nrf2, GPX4, and HO-1 in renal tissue were significantly down-regulated. The species richness of intestinal flora decreased significantly, and the relative abundances of pathogenic bacteria such as Morganella, Citrobacter, Proteus, Klebsiella, Shigella, Aggregatibacter, and Enterococcus increased significantly, while the relative abundances of beneficial bacteria such as Butyricimonas, Veillonella, Prevotella, Lactobacillus, Bifidobacterium, and Ruminococcus decreased significantly. Compared with the CLP group, CLP+LIR group could significantly reduce the pathological damage of renal tissue, the pathological score significantly decreased (1.80±0.84 vs. 4.20±1.30, P < 0.05), and improve the composition of intestinal flora, reduce the relative abundances of pathogenic bacteria such as Proteus, Klebsiella, Shigella, Aggregatibacter, and Enterococcus, and significantly increase the relative abundances of Lactobacillus, Bifidobacterium, and Ruminococcus, significantly reduce the contents of TNF-α, IL-1β, IL-6, Cr, and UREA in peripheral blood and the levels of MDA and Fe²⁺ in renal tissue [blood TNF-α (ng/L): 191.31±7.23 vs. 254.90±47.89, blood IL-1β (ng/L): 11.15±4.04 vs. 23.06±1.67, blood IL-6 (ng/L): 163.20±17.83 vs. 267.69±20.92, blood Cr (μmol/L): 24.14±4.25 vs. 41.17±5.43, blood UREA (mmol/L): 4.59±0.90 vs. 8.01±1.07, renal MDA (μmol/g): 9.67±0.46 vs. 16.05±0.88, renal Fe²⁺ (mg/g): 0.71±0.07 vs. 0.93±0.04, all P < 0.05], and increase the protein expressions of Nrf2, GPX4, and HO-1 (Nrf2/GAPDH: 1.21±0.01 vs. 0.39±0.01, GPX4/GAPDH: 0.74±0.04 vs. 0.48±0.04, HO-1/GAPDH: 0.91±0.01 vs. 0.41±0.02, all P < 0.05). CONCLUSIONS Liriodendrin has an obvious protective effect on sepsis-induced AKI. The mechanism may involve regulating the intestinal flora, increasing the activation of the Nrf2/HO-1/GPX4 signaling pathway in renal tissue, and reducing ferroptosis.
Animals ; Acute Kidney Injury/microbiology* ; Rats, Sprague-Dawley ; Sepsis/complications* ; Male ; Ferroptosis/drug effects* ; Gastrointestinal Microbiome/drug effects* ; Rats ; Signal Transduction ; Kidney/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Objective To investigate effects of calycosin(CA)on cigarette smoke(CS)induced airway epithelial cell damage in mice and the sirtuin 3/superoxide dismutase 2(SIRT3/SOD2)signaling pathway in mice.Methods A total of 90 mice were randomly separated into the control group,the cigarette smoke(CS)group,the CA low-dose treatment group(CA-L group),the CA high-dose treatment group(CA-H group)and the CA high-dose treatment plus SIRT3 inhibitor 3-TYP group(CA-H+3-TYP group),with 18 mice in each group.Tidal volume(TV)and peak expiratory flow rate(PEF)of lung function were detected by whole body plethysmography system.Serum levels of inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α]and oxidative stress indicators[reactive oxygen species(ROS),SOD]were detected by enzyme-linked immunosorbent assay(ELISA).The injury of airway epithelial cells in lung tissue was observed by HE staining.The expression levels of barrier related proteins(OCLN and ZO-1)in airway epithelial cells were detected by immunohistochemistry.Immunoblotting was applied to detect the expression of SIRT3/SOD2 signaling pathway related proteins.Results Compared with the control group,levels of TV,PEF,MAN and SOD and the expression levels of OCLN,ZO-1,SIRT3 and SOD2 were decreased in the CS group,while the levels of MLI,IL-6,TNF-α and ROS were increased(P＜0.05).Compared with the control group,the lung tissue structure was significantly damaged,the alveolar enlargement was obvious,the surrounding alveolar was accompanied by inflammatory cell infiltration,and the airway epithelial cells were obviously shed in the CS group.Different doses of CA alleviated lung tissue destruction,improved alveolar structure,reduced inflammatory cell infiltration,reduced airway epithelial cell shedding,increased levels of TV,PEF,MAN,SOD and OCLN,ZO-1,SIRT3 and SOD2,and decreased levels of MLI,IL-6,TNF-α and ROS.The effect of high dose CA was more significant than that of low dose CA(P＜0.05).SIRT3/SOD2 signaling pathway inhibitor 3-TYP partially reversed the ameliorative effect of CA on CS induced airway epithelial cell injury in mice.Conclusion CA can ameliorate CS induced airway epithelial cell damage in mice,and its mechanism is related to the activation of the SIRT3/SOD2 signaling pathway.

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 explore the mechanism of spleen tissue inflammatory response induced by altitude hypoxia in mice.Methods C57BL/6 mice were randomly assigned to a plain,i.e.,low-altitude,normoxia group and an altitude hypoxia group,with 5 mice in each group.In the plain normoxia group,the mice were kept in a normoxic environment at the altitude of 400 m above sea level(with an oxygen concentration of 19.88%).The mice in the altitude hypoxia group were kept in an environment at the altitude of 4200 m above sea level(with an oxygen concentration of 14.23%)to establish the animal model of altitude hypoxia.On day 30,spleen tissues were collected to determine the splenic index.HE staining was performed to observe the histopathological changes in the spleen tissues of the mice.Real time fluorogenic quantitative PCR(RT-qPCR)and Western blot were conducted to determine the mRNA and protein expressions of interleukin(IL)-6,IL-12,and IL-1β in the spleen tissue of the mice.High-throughput transcriptome sequencing was performed with RNA sequencing(RNA-seq).KEGG enrichment analysis was performed for the differentially expressed genes(DEGs).The DEGs in the key pathways were verified by RT-qPCR.Results Compared with the plain normoxia group,the mice exposed to high-altitude hypoxic environment had decreased spleen index(P<0.05)and exhibited such pathological changes as decreased white pulp,enlarged germinal center,blurred edge,and venous congestion.The mRNA and protein expression levels of IL-6,IL-12,and IL-1β in the spleen tissue of mice in the altitude hypoxia group were up-regulated(P<0.05).According to the results of transcriptome sequencing and KEGG pathway enrichment analysis,4218 DEGs were enriched in 178 enrichment pathways(P<0.05).DEGs were significantly enriched in multiple pathways associated with immunity and inflammation,such as T cell receptor signaling pathway,TNF signaling pathway,and IL-17 signaling pathway(P<0.05)in the spleen of mice exposed to high-altitude hypoxic environment.Among them,IL-17 signaling pathway and the downstream inflammatory factors were highly up-regulated(P<0.05).Compared with the plain normoxia group,the mRNA expression levels of key genes in the IL-17 signaling pathway,including IL-17,IL-17R,and mitogen-activated protein kinase genes(MAPKs),and the downstream inflammatory factors,including matrix metallopeptidase 9(MMP9),S100 calcium binding protein A8 gene(S100A8),S100 calcium binding protein A9 gene(S100A9),and tumor necrosis factor α(TNF-α),were up-regulated or down-regulated(P<0.05)in the altitude hypoxia group.According to the validation of RT-qPCR results,the mRNA expression levels of DEGs were consistent with the RNA-seq results.Conclusion Altitude hypoxia can induce inflammatory response in the mouse spleen tissue by activating IL-17 signaling pathway and promoting the release of downstream inflammatory factors.

Objective:To investigate the correlation of the expression of Ephrin A receptor 2(EphA2)and its promoter region DNA hypomethylation with the occurrence of pyroptosis in invasive breast cancer. Methods:The expression level of pyroptosis-related protein EphA2 in normal breast tissue,paracancerous tissues and cancer tissues from 42 breast cancer patients was examined by Immunofluorescence staining and Western blotting.The expression level of pyroptosis related protein nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)was analyzed by immunofluorescence staining and Western blotting.The expression levels of apoptosis related proteins Caspase 1 and inflammatory cytokine interleukin-1β(IL-1 β)were studied by Western blotting.The DNA methylation level in the promoter region of EphA2 was investigated by nested methylation-specific PCR(nMS-PCR).The expression levels of DNA methyltransferase 1(DNMT1)and DNA methyltransferase 3a(DNMT3a)were examined by Western blotting.The correlation of the protein expression and methylation level of EphA2 in cancer tissues with the expression NLRP3,Caspase 1,IL-1 β,DNMT1 and DNMT3a was analyzed by Pearson correlation coefficient. Results:Compared with normal breast tissues and paracancerous tissues,the expression level of EphA2 protein was significantly increased(P＜0.01),while that of NLRP3,Caspasel and IL-1 βwas significantly decreased(P＜0.05)in breast cancer tissues.Meanwhile,compared with normal breast tissues and paracancerous tissues,the DNA methylation level of EphA2 promoter in breast cancer tissues was significantly decreased(P＜0.05),the expression level DNMT3a protein was significantly decreased(P＜0.01,P＜0.05),and the difference in the expression level of DNMT1 protein was not statistically significant.Pearson correlation analysis showed that the expression level of EphA2 protein is negatively correlated with that of NLRP3(r=-0.651 2,P＜0.05),Caspasel(r=-0.571 2,P＜0.05),IL-1β(r=-0.654 6,P＜0.05)or DNMT3a(r=-0.537 4,P＜0.05),while the methylation level of EphA2 was positively correlated with the protein expression level of NLRP3(r=0.634 1,P=0.026 8),Caspase1(r=0.672 8,P=0.01 6 5),IL-1 β(r=0.694 0,P=0.01 2 3)and DNMT3a(r=0.687 1,P=0.01 3 6). Conclusion:The expression of EphA2 protein is upregulated in breast cancer tissues is negatively correlated with pyroptosis.DNMT3a may be involved in the process of DNA hypomethylation in the promoter region of EphA2.

Jianwei Xiaoshi tablets， as a common variety of Chinese patent medicine with "one product with many manufacturers"， have many manufacturers and huge market sales. However， the phenomenon about uneven quality and discrepant price is prominent. Based on this， this study was carried out for the quality evaluation of Jianwei Xiaoshi tablets by applying the high-quality evaluation criteria with the quality as core for Chinese patent medicine， which was based on the full production cycle， from the multi-dimension including raw material selection， production process， quality control， post-marketing research and so on. The evaluation results showed that the quality evaluation scores of Jianwei Xiaoshi tablets from different manufacturers varied greatly （ranging from 35 to 66）， indicating that the quality was significantly different. In the actual production， generally inadequate attention was paid to the quality of raw materials， and the quality of raw materials was insufficient with the score ratio of 43%， especially the poor consistency control of them. The role of good manufacturing practice was obvious， and the scores of production process were generally high with the average score ratio of 62%， and the maximum up to 80%. The technological advancement of the manufacturer was outstanding. The score ratio of quality control was only 31% that the internal quality standard of each manufacture almost stayed at the qualified line， which was equal to the national standard， and the consistency of products was insufficient. The post-marketing research was lacking with the score ratio of 37%. Manufacturers with high brand awareness and market share were upper scores， while the others lagged far behind. The results of this evaluation are in line with the overall prediction， which can provide a reference for the high-quality evaluation of Chinese patent medicine， and supply the scientific data for high-quality and high-price application.

Objective:To compare the efficacy of standardized incision and conventional incision for reduction and internal fixation of multiple rib fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 192 patients with multiple rib fracture treated in 909th Hospital of Joint Logistics Support Force (Affiliated Dongnan Hospital of Xianmen University Medical College) from January 2020 to January 2022. There were 101 males and 91 females; aged 32-94 years [(51.5±16.6)years]. The patients underwent open reduction and internal fixation with nickel-titanium shape memory alloy embracer via standard incision such as anterior axillary longitudinal incision (standard incision group, n=96) or conventional incision such as posterolateral incision (conventional incision group, n=96). The incision length, operation time, intraoperative blood loss, number of fixed fractures, indwelling time of closed thoracic drainage tube, postoperative thoracic drainage volume, postoperative spontaneous ambulation time and length of hospital stay were compared in the two groups. The visual analogue scale (VAS) was used to evaluate pain at 1 month after operation. Postoperative complications were recorded. Results:All patients were followed up for 1-16 months [4.0(3.0, 10.5)months]. The operation time, intraoperative blood loss, indwelling time of closed thoracic drainage tube, postoperative thoracic drainage volume, postoperative spontaneous ambulation time, length of hospital stay and VAS at postoperative 1 month in standard incision group [(12.1±1.6)cm, (51.4±13.0)minutes, (191.5±16.8)ml, (2.8±0.6)days, (568.9±109.0)ml, (4.1±0.7)days, (11.4±1.7)days, (2.5±0.7)points] were better than those in conventional incision group [(13.7±1.9)cm, (62.0±8.8)minutes, (248.9±65.4)ml, (4.8±1.1)days, (655.9±121.9)ml, (5.2±0.9)days, (15.3± 1.7)days, (3.5±0.7)points] ( P<0.05 or 0.01). There was no statistical difference in the number of fixed fractures between standard incision group and conventional incision group (5.1±0.8 vs. 5.4±0.9) ( P>0.05). In standard incision group, there were 3 patients with poor wound healing, 5 with pulmonary infection, 3 with atelectasis and 3 with small pleural effusion. In conventional incision group, there were 11 patients with poor wound healing, 9 with pulmonary infection, 7 with atelectasis and 7 with small pleural effusion. The incidence of postoperative complications was 14.6% (14/96) in standard incision group and 35.4% (34/96) in conventional incision group ( P<0.01). Conclusion:For multiple rib fracture, standard incision is superior to conventional incision reduction in shortening the incision length, operation time, indwelling time of drainage tube, postoperative spontaneous ambulation time and length of hospital stay, reducing the intraoperative blood loss and postoperative thoracic drainage volume, alleviating the pain and reducing the postoperative complications.

Objective:To analyze the molecular epidemiological characteristics of the Corona virus disease 2019 (COVID-19) cases in Shijiazhuang, which can reveal the origin of the outbreak and provide a scientific basis for COVID-19 prevention and control.Methods:From January 2 to January 8, 2021, a total of 404 samples from 170 COVID-19 cases were collected from the Shijiazhuang Fifth Hospital. The consensus sequence of 2019 novel Coronavirus(2019-nCoV) was obtained through multiplex polymerase chain reaction-based sequencing. The sequences of 170 COVID-19 cases were analyzed by the PANGOLIN, and the data were statistically analyzed by T-test.Results:Among the 404 COVID-19 samples, a total of 356 samples obtained high quality genome sequences (>95%,100×sequencing depth). The whole genome sequences of 170 COVID-19 cases were obtained by eliminating repeated samples. All 170 sequences were recognized as lineage B1.1 using PANGOLIN. The number of single nucleotide polymorphism arrange from 18-22 and most of the single nucleotide polymorphism were synonymous variants. All of 170 genomes could be classified into 48 sub-groups and most of the genomes were classified into 2 sub-groups (66 and 31, respectively).Conclusions:All cases in this study are likely originated from one imported case. The viruses have spread in the community for a long time and have mutated during the community transmission.

The blood donation, component preparation and manufacturing, laboratory, issuing and quality control were studied and compared between the UK and China, in order to learn British experience in the clinical practice and blood services. The age limits of blood donors, blood collection units, donation times per year, laboratory items, and the types(volumes) of component preparation and manufacturing in the UK are more superior than those in China. In addition, the blood quality monitoring and regarding indicators are more scientific and reasonable in the UK. The full reimbursement of clinical blood expenses for patients has been realized in the UK. The British experience in continuous safeguard of the blood safety and balance of requirement and availability contributes to the constant and scientific development of British blood services over the years, and is worthy of references.