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

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Background and objective Bone is a common site for metastasis in lung adenocarcinoma,but the mechanism behind lung adenocarcinoma bone metastasis is still unclear.And currently,there is a lack of easily traceable and stable lung adenocarcinoma bone metastasis cell models,which limits the research on the mechanism of lung adenocarcinoma bone metastasis.The establishment of human lung adenocarcinoma cell line that are highly metastatic to bone,labeled with green fluorescent proteins(GFP)and fireflies luciferase(LUC),along with transcriptomic characterization,would be beneficial for research on lung adenocarcinoma bone metastasis and provide new experimental methods.Methods The human lung ad-enocarcinoma cell line A549-GFP-LUC was injected into nude mice via the left ventricle to construct a bone metastasis model,and was domesticated in vivo for three consecutive times to obtain the human high bone metastasis lung adenocarcinoma cell line A549-GFP-LUC-BM3;cell counting kit-8(CCK-8),colony formation assay,scratch wound assays,Transwell assay and Western blot were used to compare the proliferation and invasion abilities of A549-GFP-LUC-BM3 with the parental cells.A549-GFP-LUC-BM3 cells and parental cells were further analyzed by transcriptomic sequencing.Results Human high-bone metastatic lung adenocarcinoma cells A549-GFP-LUC-BM3 was successfully established.Compared to parental cells,this cells exhibited a significantly higher incidence of bone metastasis and enhanced in vitro proliferation,migration,and invasion abilities.Transcriptomic sequencing results revealed that the A549-GFP-LUC-BM3 cell line had 2954 differentially expressed genes compared to the parental cells,with 1021 genes up-regulated and 1933 genes down-regulated.Gene Ontology(GO)functional enrichment analysis indicated that the differentially expressed genes were primarily localized in cellular components such as the cell periphery.The molecular functions identified as significantly enriched included signaling receptor activity,cal-cium ion binding,and extracellular matrix structural constituent.Additionally,the biological processes found to be enriched were cell adhesion and biological adhesion.The enrichment analysis conducted using the Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed that the differentially expressed genes were primarily involved in the metabolism of xenobiot-ics by cytochrome P450,retinol metabolism,drug metabolism-cytochrome P450,cell adhesion molecules,steroid hormone biosynthesis,and the nuclear factor kappa B(NF-κB)signaling pathway.Conclusion The highly bone-metastatic human lung adenocarcinoma cell line with GFP and luciferase double labeling was successfully established.The biological behavior and transcriptome sequencing of the cell line suggest that it has a high bone-metastatic potential.

Objective To observe the effect of Danshen injection (DSI) on pulmonary fibrosis in silicosis mice, and to analyze the differential metabolic pathway on pulmonary fibrosis in silicosis using DSI by urine metabolomics. Methods The specific pathogen free C57BL/6J mice were randomly divided into control group, silicosis model group, DSI prevention group and DSI treatment group. The mice in the last three groups were given 1 mL silica suspension with a mass concentration of 50 g/L by the one-time non-exposed tracheal method, and the mice in the control group were not given any treatment. Subsequently, mice in the DSI prevention group and the DSI treatment group were given intraperitoneal injection of DSI with a dose of 5 mL/kg body weight from 24 hours after exposure to dust and from the 29th day after exposure to dust, respectively, once per day until the 56th day after exposure. Mice in the other two groups were not treated. After DSI intervention, the lung histopathological changes of mice in all groups were evaluated. The components of mouse urine metabolites were analyzed using ultra-high performance liquid chromatography-quadrupole-time-of-fight mass spectrometry method. Human Metabolome Database was used to screen the potential differential metabolites (DMs). The related metabolic pathways were analyzed using MetaboAnanlyst 5.0 Web analytics platform. Results The result of hematoxylin-eosin staining and Van Gieson staining of mouse lung tissues showed that the pulmonary alveolar structure destroyed, typical fibrotic nodules appeared, collagen fiber deposition increased, and clumpy accumulation in the silicosis model group, compared with the control group. Compared with the silicosis model group, the degree of pulmonary alveolar inflammation and fibrosis in the lung tissues of mice in the DSI prevention group was obviously reduced to close to the control group, while pulmonary alveolar inflammation and fibrosis in the lung tissues of mice in the DSI treatment group were also reduced, although the outcome was not as good as that in the DSI prevention group. The result of urine metabolomics analysis identified four DMs in the model group and control group, seven DMs were identified in the DSI prevention group and silicosis model group, seven DMs were identified in the DSI treatment group and silicosis model group. A total of three DMs pathways related to pulmonary fibrosis in silicosis model group and the protective effect of DSI prevention group were identified, including D-arginine and D-ornithine metabolism, folic acid biosynthesis and metabolism, pantothenate and succinyl coenzyme A biosynthesis pathways (all P<0.01). Conclusion DSI treatment in any time point can interfere the process of pulmonary fibrosis in the silicosis mice, while the interference is more effective in the DSI group treated right after dust-exposure. DSI interferes with the urinary metabolism pathway of silicosis mice, and the D-arginine and D-ornithine metabolism, folic acid biosynthesis and metabolism, pantothenate and succinyl coenzyme A biosynthesis pathways may participate in the inhibiting process of early pulmonary fibrosis in silicosis mice by DSI.

BACKGROUND: The early stages of tumor bone metastasis are closely associated with changes in the vascular niche of the bone microenvironment, and abnormal angiogenesis accelerates tumor metastasis and progression. However, the effects of lung adenocarcinoma (LUAD) cells reprogrammed by the bone microenvironment on the vascular niche within the bone microenvironment and the underlying mechanisms remain unclear. This study investigates the effects and mechanisms of LUAD cells reprogrammed by the bone microenvironment on endothelial cells and angiogenesis, providing insights into the influence of tumor cells on the vascular niche within the bone microenvironment. METHODS: The culture media from bone-metastatic LUAD cell A549-GFP-LUC-BM3 (BM3-CM) and A549-GFP-LUC (A549-CM) were separately applied to human umbilical vein endothelial cell (HUVEC). A colony formation assay, scratch assay, and tube formation assay were conducted to evaluate the proliferation, migration, and angiogenesis of HUVEC. Gene set enrichment analysis (GSEA) was conducted to identify enriched pathways, while reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme linked immunosorbent assay (ELISA) were performed to quantify hepatocyte growth factor (HGF), a protein that plays a crucial role in angiogenesis. Furthermore, the pivotal function of HGF and its underlying molecular mechanisms have been substantiated through the utilisation of recombinant proteins, neutralising antibodies, pathway inhibitors, immunofluorescence staining, and Western blot. RESULTS: BM3-CM demonstrated a more pronounced impact on the proliferation, migration, and angiogenesis of HUVEC compared to A549-CM. Bioinformatics analysis, combined with in vitro experiment, demonstrated that the secretory protein HGF was significantly elevated in BM3 cells and BM3-CM (P<0.05). The addition of HGF neutralizing antibodies to BM3-CM inhibited the promoting effect of BM3-CM on HUVEC (P<0.05), while the addition of recombinant HGF to A549-CM reproduced that promoting effect of BM3-CM on HUVEC (P<0.05). HGF can enhance the activation of YAP (Yes-associated protein) in HUVEC, and this promotion effect may be achieved by activating Src and activating YAP into the nucleus (P<0.05), but this effect can be inhibited by HGF neutralizing antibodies (P<0.05). Furthermore, the addition of recombinant HGF to A549-CM can recapitulate the YAP activation effect of BM3-CM in HUVEC (P<0.05). CONCLUSIONS Bone microenvironment reprogrammed bone-metastatic LUAD cells BM3 promote the proliferation, migration, and angiogenesis of HUVEC through the HGF/YAP axis, potentially playing a significant role in the modifications of the vascular niche.
Humans ; Hepatocyte Growth Factor/genetics* ; Signal Transduction ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells ; Bone Neoplasms/blood supply* ; Adenocarcinoma of Lung/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Lung Neoplasms/genetics* ; Cell Movement ; Cell Proliferation ; YAP-Signaling Proteins ; Transcription Factors/genetics* ; Cell Line, Tumor ; Tumor Microenvironment ; Angiogenesis

Polymer nanoparticles generally refer to hydrophobic polymers-based nanoparticles, which have been extensively studied in the nanomedicine field due to their good biocompatibility, efficient long-circulation characteristics, and superior metabolic discharge patterns over other nanoparticles. Existing studies have proved that polymer nanoparticles possess unique advantages in the diagnosis and treatment of cardiovascular diseases, and have been transformed from basic researches to clinical applications, especially in the diagnosis and treatment of atherosclerosis (AS). However, the inflammatory reaction induced by polymer nanoparticles would induce the formation of foam cells and autophagy of macrophages. In addition, the variations in the mechanical microenvironment of cardiovascular diseases may cause the enrichment of polymer nanoparticles. These could possibly promote the occurrence and development of AS. Herein, this review summarized the recent application of polymer nanoparticles in the diagnosis and treatment of AS, as well as the relationship between polymer nanoparticles and AS and the associated mechanism, with the aim to facilitate the development of novel nanodrugs for the treatment of AS.
Humans ; Polymers/chemistry* ; Cardiovascular Diseases ; Nanoparticles/chemistry* ; Drug Delivery Systems ; Atherosclerosis/pathology*

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 long-term efficacy of two-level cervical artificial disc replacement (CADR) and anterior cervical decompression and fusion (ACDF) in the treatment of cervical degenerative diseases.Methods:A retrospective analysis was performed on patients who had received two-level anterior cervical surgery for cervical degenerative diseases for more than 15 years from December 2003 to December 2007. The patients were divided into two groups: CADR and ACDF according to surgical methods. There were 15 patients in the CADR group, including 7 males and 8 females, with an average age of 49.73±10.26 (range, 32-70) years. Three cases of mixed cervical spondylosis, 5 cases of cervical spondylotic radiculopathy, 7 cases of cervical spondylotic myelopathy, including C 3, 4 and C 4, 5 level 1 case, C 3, 4 and C 5, 6 level 2 cases, C 4, 5 and C 5, 6 level 7 cases, C 5, 6 and C 6, 7 level 5 cases, operative segment range of motion (ROM) was 9.10°±4.00°. The follow-up time in the CADR group was 189.07±13.51 (range, 162-210) months. There were 20 patients in the ACDF group, including 12 males and 8 females, with an average age of 52.60±8.83 (range, 32-68) years. Two cases of mixed cervical spondylosis, 3 cases of cervical spondylotic radiculopathy, 15 cases of cervical spondylotic myelopathy, including C 3, 4 and C 4, 5 level 1 case, C 4, 5 and C 5, 6 level 15 cases, C 5, 6 and C 6, 7 level 4 cases, the ROM of the surgical segment was 8.31±5.23°. The mean follow-up time of ACDF group was 184.20±21.39 (range, 156-222) months. The Japanese Orthopaedic Association (JOA) score and neck disability index (NDI) were evaluated preoperatively and at the last follow-up. The overall ROM of the cervical spine, ROM of the surgical segment, and Miyazaki grading of the adjacent intervertebral disc, Odom score and complications of the two groups were evaluated at the last follow-up. Results:In the CADR group, the JOA score improved from 13.20±2.64 preoperatively to 15.93±1.22 at last follow-up, and NDI improved from 27.60%±6.44% preoperatively to 15.07%±9.71% at last follow-up, JOA improvement rate was 59.44%±60.86%, and NDI decreased by 12.53%±9.64%. In the ACDF group, JOA score improved from 12.93±2.46 preoperatively to 15.65±1.25 at last follow-up, NDI improved from 30.80%±8.11% preoperatively to 12.80%±6.31% at last follow-up, JOA improvement rate was 60.51%±43.17%, NDI decreased by 18.00%±8.34%. There was no significant difference in JOA and NDI between the two groups before surgery and at the last follow-up. At the last follow-up, the overall ROM of the cervical spine in the CADR group was 38.33°±12.31°, the ROM of the surgical segment was 6.51°±4.61°, and the overall ROM of the cervical spine in the ACDF group was 31.11°±8.65°, the ROM of the surgical segment was 0°. There was a significant difference in the overall ROM of the cervical spine between the two groups at the last follow-up ( t=7.22, P=0.049). The incidence of increased Miyazaki grading of the upper and lower adjacent segment of the cervical intervertebral disc in the CADR group were 40% and 47%, and the rate of new intervertebral disc herniation were 20% and 13%. The incidence of increased Miyazaki grading of the upper and lower adjacent segment of the cervical intervertebral disc in the ACDF group were 45% and 50%, and the incidence of new herniated disc were 25% and 40%, there is a significant difference in the degeneration rate of the lower adjacent segments between the two groups (χ 2=4.38, P=0.036). At the last follow-up, the excellent and good rate of Odom in the CADR group was 80%, and 1 case was revised; the excellent and good rate of Odom in the ACDF group was 85%, and 1 case was revised. There was no significant difference in the overall efficacy between the two groups. Conclusion:The long-term clinical efficacy of two-level CADR is comparable to that of traditional ACDF, and it preserved the ROM of the surgical segment, and is superior to ACDF in terms of the overall cervical spine ROM, and the incidence of adjacent segment degeneration.

Objective:To analyze the differences of peripheral blood transcriptome between mild and severe influenza A (H1N1) patients, and to find indicators for the assessment of disease severity.Methods:A total of ten patients (five patients with mild disease and five patients with severe disease) diagnosed with H1N1 infection from January to May 2018 at Huashan Hospital, Fudan University in Shanghai were enrolled, and five healthy people were also enrolled as controls. The peripheral blood of patients was collected for transcriptome sequencing at the time when they were first diagnosed. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using Fisher exact test when appropriate. Data analysis of transcriptome predictions was performed using bioinformatics methods. Results:The platelet counts were significantly different between mild and severe groups ((163.4±21.5 )×10 9/L vs (255.6±52.5)×10 9/L, t=3.636, P=0.007). There were no differences between the two groups in gender, age, white blood cell counts, neutrophil percentage, lymphocyte percentage and hemoglobin levels (all P>0.05). However, the average expression levels of matrix metalloproteinase (MMP) 8 and MMP9 in severe group (18.41 and 174.00, respectively) were both higher than those in mild group (2.33 and 22.91, respectively) and healthy control (1.43 and 34.65, respectively; all P<0.01). Conclusion:MMP8 and MMP9 could be expected to serve as the molecular biological markers for predicting the disease severity in patients with influenza A (H1N1) infection.

Objective:To investigate the diagnostic values of interleukin-22 (IL-22), interferon-γ(IFN-γ)and macrophage migration inhibition factor (MIF) in pleural effusion for tuberculosis pleurisy.Methods:From April 2018 to May 2019, a total of 77 patients including 45 cases of tuberculous pleurisy, 19 cases of malignant pleurisy, 13 cases of parapneumonia and 13 cases of healthy control in Wuxi Fifth People′s Hospital were enrolled. The levels of IL-22, IFN-γ and MIF in plasma and pleural effusion were detected by enzyme linked immunosorbent assay (ELISA). Mann-Whitney U test was used for statistical analysis.The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic values of IL-22, IFN-γ and MIF for tuberculous pleurisy. Results:The median levels of IL-22, IFN-γ, MIF and adenosine deaminase in 45 cases with pleural effusion in tuberculosis pleurisy group were 396.8 ng/L, 2 200.0 ng/L, 241.3 μg/L and 70.8 U/L, respectively, which were all significantly higher than 32 cases with non-tuberculosis pleurisy group, including 19 cases with malignant pleurisy and 13 cases with parapneumonia (52.8 ng/L, 232.3 ng/L, 179.6 μg/L and 17.0 U/L, respectively). The differences were all statistically significant ( U=179.000, 118.500, 287.000, 162.000, respectively, all P<0.05). The median levels of IL-22 and IFN-γ in plasma of tuberculosis pleurisy group were 20.0 ng/L and 45.9 ng/L, respectively, which were both higher than healthy control group (14.3 ng/L and 33.4 ng/L, respectively). The level of MIF was 96.2 μg/L, which was lower than healthy control (159.5 μg/L). The differences were all statistically significant ( U=74.000, 13.000 and 73.000, respectively, all P<0.05). The areas under ROC curve (AUC) of IL-22, IFN-γ and MIF in pleural effusion for the diagnosis of tuberculosis pleurisy were 0.876, 0.917 and 0.682, respectively.The sensitivities were 93.75%, 100.00% and 63.64%, respectively; the specificities were 82.22%, 91.11% and 65.85%, respectively. The median levels of IL-22 and IFN-γ in plasma in tuberculosis pleurisy group at two months of follow-up after anti-tuberculosis therapy were 16.0 ng/L and 33.9 ng/L, respectively, which were both lower than baseline (20.0 ng/L and 44.7 ng/L, respectively). The differences were both statistically significant ( U=2.156 and 2.221, respectively, both P<0.05). Conclusion:IFN-γ and IL-22 in pleural effusion could be used as effective indicators to identify tuberculous pleurisy, and the dynamic monitoring of IL-22 in patients′plasma could be an important biomarker in evaluating the efficacy of anti-tuberculosis treatment.