Background Coal workers' pneumoconiosis is a serious occupational disease in China. Exhaled volatile organic compounds (VOCs) can serve as the "breath fingerprint" of internal pathological processes, which provides a theoretical basis for exhaled VOCs to be used as potential non-invasive biomarkers for early diagnosis of coal workers' pneumoconiosis. Objective To screen out the characteristic VOCs and important characteristic VOCs of exhaled air in patients with coal workers' pneumoconiosis, and to explore the potential of these VOCs as biomarkers for early non-invasive diagnosis of the disease. Methods In this study, 27 VOCs in the exhaled breath of 22 patients with stage I coal workers' pneumoconiosis, 77 workers exposed to dust, and 92 healthy controls were quantitatively detected by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Substances with P<0.05 in univariate analysis and variable importance projection (VIP) >1 in supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model were selected as the characteristic VOCs for early diagnosis of coal workers' pneumoconiosis. Age was included in the LASSO regression model as a covariate to screen out important characteristic VOCs, and the diagnostic performance was evaluated by receiver operating characteristic (ROC) curve. Spearman correlation was further used to explore the correlation between important characteristic VOCs and clinical lung function indicators. Results Through univariate analysis and OPLS-DA modeling, 8 VOCs were selected, including 2-methylpentane, 3-methylpentane, n-hexane, methylcyclopentane, n-heptane, methylcyclohexane, 4-methyl-2-pentanone, and 2-hexanone, in exhaled breath of patients with coal workers' pneumoconiosis. The concentrations of 4 VOCs, including 3-methylpentane, n-hexane, 4-methyl-2-pentanone, and 2-hexanone, showed a decreasing trend with the increase of dust exposure years. By LASSO regression, the important characteristic VOCs of the coal workers' pneumoconiosis group and the dust exposure group were n-hexane, methylcyclohexane and 4-methyl-2-pentanone, and the important characteristic VOCs of the coal workers' pneumoconiosis group and the healthy group were 2-methyl-pentane and 4-methyl-2-pentanone. The ROC analysis showed that the area under the curve (AUC) of n-hexane, methylcyclohexane, and 4-methyl-2-pentanone were 0.969, 0.909, and 0.956, respectively, and the AUC of combined diagnosis was 0.988 and its Youden index was 0.961, suggesting that these results can serve as a valuable reference for further research on early diagnosis. The Correlation analysis found that there was a positive correlation between n-hexane and lung function indicators in the important characteristic VOCs, indicating that it could indirectly reflect the obstruction of lung function ventilation, further proving that important characteristic VOCs have the potential to monitor lung function decline. Conclusion Three important characteristic VOCs selected in this study have the potential to be used as non-invasive biomarkers for early diagnosis and disease monitoring of coal workers' pneumoconiosis, and are worthy of further study and verification.

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 effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression. METHODS: ESCC cell lines with lentivirus-mediated ACC1 knockdown or transfected with a negative control sequence (shNC) were treated with DMSO, JQ1 (a BRD4 inhibitor), co-transfection with shNC-siBRD4 or siNC with additional DMSO or C646 (an ahistone acetyltransferase inhibitor) treatment, or JQ1combined with 3-MA (an autophagy inhibitor). BRD4 mRNA expression in the cells was detected using RT-qPCR. The changes in cell proliferation, migration, autophagy, and epithelial-mesenchymal transition (EMT) were examined with CCK8 assay, Transwell migration assay, and Western blotting. RESULTS: ACC1 knockdown did not significantly affect BRD4 expression in the cells but obviously increased their sensitivity to JQ1. JQ1 treatment at 1 and 2 μmol/L significantly inhibited ESCC cell proliferation, while JQ1 at 0.2 and 2 μmol/L promoted cell migration. The cells with ACC1 knockdown and JQ1 treatment showed increased expresisons of vimentin and Slug and decreased expression of E-cadherin. BRD4 knockdown promoted migration of ESCC cells, and co-transfection with shACC1 and siBRD4 resulted in increased vimentin and Slug expressions and decreased E-cadherin expression in the cells. C646 treatment of the co-transfected cells reduced acetylation levels, decreased vimentin and Slug expressions, and increased E-cadherin expression. Treatment with JQ1 alone obviously increased LC3A/B-II levels in the cells either with or without ACC1 knockdown. In the cells with ACC1 knockdown and JQ1 treatment, additional 3-MA treatment significantly decreased the expressions of vimentin, Slug and LC3A/B-II and increased the expression of E-cadherin. CONCLUSIONS BRD4 inhibition promotes autophagy of ESCC cells via a histone acetylation-dependent mechanism, thereby enhancing EMT and ultimately increasing cell migration driven by ACC1 deficiency.
Humans ; Cell Movement ; Transcription Factors/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Line, Tumor ; Cell Cycle Proteins ; Azepines/pharmacology* ; Epithelial-Mesenchymal Transition ; Carcinoma, Squamous Cell/metabolism* ; Esophageal Squamous Cell Carcinoma ; Triazoles/pharmacology* ; Nuclear Proteins/genetics* ; Cell Proliferation ; Acetyl-CoA Carboxylase/genetics* ; Transfection ; Autophagy ; Bromodomain Containing Proteins

Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.

Objective To investigate the changes of macular microcirculation and aqueous humor cytokine expression in patients with diabetic macular edema(DME)after anti-vascular endothelial growth factor(VEGF)treatment,and analyze the relationship with efficacy.Methods A total of 62 patients(91 eyes)with DME who were treated in the First Hospital of Nanchang from October 2021 to August 2023 were selected and treated with intravitreal injection of conbercept.According to the reduction of central macular thickness(CMT),they were divided into efficacy significant group(CMT reduction≥100μm,59 eyes)and non-efficacy significant group(CMT reduction＜100μm or increase,32 eyes).The changes of CMT,vessel density(VD)of superficial capillary plexus(SCP),fovea avascular area(FAZ),VEGF,interleuki(IL)-6,IL-8,and IL-10 after anti-VEGF treatment were analyzed.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each index.Results Before treatment,the levels of VEGF and IL-10 in aqueous humor in efficacy significant group were significantly higher than those in non-efficacy significant group,and the level of IL-8 was significantly lower than that in non-efficacy significant group(P＜0.05).After treatment,levels of VEGF,IL-6,IL-8 and IL-10 in aqueous humor in both groups were significantly lower than before treatment(P＜0.05).The levels of VEGF,IL-6 and IL-8 in aqueous humor in efficacy significant group were significantly lower than those in non-efficacy significant group,and the level of IL-10 was significantly higher than that in non-efficacy significant group(P＜0.05).Before and after anti-VEGF treatment,there were no significant changes in FAZ area and SCP-VD in both groups(P＞0.05).Correlation analysis showed that VEGF(r=0.571,P＜0.001)and IL-10(r=0.382,P=0.008)in aqueous humor at baseline were positively correlated with CMT reduction,IL-8 was negatively correlated with CMT reduction(r=-0.689,P＜0.001).IL-6,FAZ area and SCP-VD were not correlated with CMT reduction(P＞0.05).Cytokine levels were not correlated with FAZ area and SCP-VD(P＞0.05).ROC curve results showed that area under the curve of IL-8,VEGF and IL-10 at baseline predicting anti-VEGF efficacy were 0.825,0.813 and 0.676,respectively.Conclusion The levels of VEGF,IL-8,and IL-10 in aqueous humor at baseline in DME patients were correlated with anti-VEGF efficacy and could predict the efficacy of anti-VEGF.

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.

Objective To explore the effect and the possible mechanism of knockdown acetyl CoA carboxylase 1(ACC1)on the migration of KYSE450 cells.Methods KYSE450 cells during the logarithmic phase were randomly divided into the shNC group,shACC1 group,shNC+AEB071 group,and shACC1+AEB071 group.The KYSE450 cells in the shNC group were transfected with empty plasmid;the KYSE450 cells in the shACC1 group were transfected with lentiviral plasmid;the KYSE450 cells in the shNC+AEB071 group were transfected with empty plasmid and then added with 5 μL of 2 mmoL·L-1 protein kinase C(PKC)inhibitor AEB071(final concentration 5 μmoL·L-1);The KYSE450 cells in the shACC1+AEB071 group were transfected with lentiviral plasmid and then added with 5 μL of 2 mmoL·L-1 PKC inhibitor AEB071(final concentration 5 μmoL·L-1).The migration of KYSE450 cells was detected by Transwell assay.The morpho-logical changes of KYSE450 cells were observed under the microscope.The expression levels of ACC1,histone H3(H3),histone H3 lysine 9 acetylation(H3K9Ac),and epithelial-mesenchymal transition(EMT)markers such as β-catenin,Vimentin and Snail were measured by Western blot.Results The migration of KYSE450 cells in the shACC1 group was significantly higher than that in the shNC group(P＜0.05);there was no significant difference in the migration ability of KYSE450 cells between the shNC+AEB071 group and the shNC group(P＞0.05);the migration of KYSE450 cells in the shACC1+AEB071 group was significantly lower than that in the shACC1 group(P＜0.05).The KYSE450 cells in the shNC group revealed an elliptical epithelial-like cell morphology;the KYSE450 cells in the shACC1 group exhibited a spindle-like interstitialcell morphology;the KYSE450 cells in the shNC+AEB071 and shACC1+AEB071 groups showed an elliptical epithelial-like cell morphology.The relative expression level of ACC1 in KYSE450 cells in the shACC1 group was significantly lower than that in the shNC group(P＜0.05),while the relative expression levels of β-catenin,Vimentin and Snail as well as the ratio of H3K9Ac/H3 were significantly higher than those in the shNC group(P＜0.05);the relative expression levels of ACC1,β-catenin,Vimentin and Snail as well as the ratio of H3K9Ac/H3 showed no significant difference between the shNC+AEB071 group and the shNC group(P＞0.05);the relative expression levels of β-catenin,Vimentin and Snail as well as the ratio of H3K9Ac/H3 in the shACC1+AEB071 group were significantly lower than those in the shACC1 group(P＜0.05);there was no significant difference in the relative expression level of ACC1 in KYSE450 cells between the shACC1+AEB071 group and the shACC1 group(P＞0.05).Conclusion Knockdown of ACC1 promotes migration of KYSE450 cells and thus aggravates the tumor,which may be mediated by PKC-related signaling pathways.

Objective To investigate the efficacy of methylprednisolone in preventing postoperative pulmonary infections in locally advanced esophageal cancer patients undergoing neoadjuvant chemotherapy combined with immunotherapy.Methods A total of 89 patients with locally advanced esophageal cancer treated at the First Affiliated Hospital of Xinxiang Medical University from January 2022 to December 2023 were selected as the research subjects.All patients underwent thoracolaparoscopic radical esophagectomy for esophageal cancer.The patients were randomly divided into an observation group(n=45)and a control group(n=44)using a random number table method.In the observation group,one patient with intraoperative thoracotomy,two patients with extensive pleural adhesion,and one patient with preoperative upper respiratory tract infection were excluded.In the control group,one patient with extensive pleural adhesion and one patient with preoperative upper respiratory tract infection were excluded.As a result,a total of 83 patients were included in the study,with 41 in the observation group and 42 in the control group.Preoperatively,a neoadjuvant treatment regimen of paclitaxel(albumin-bound)+nedaplatin in combination with camrelizumab was given to patients in both groups for 2 cycles.Patients in the control group received conven-tional anti-infection treatment after surgery,while patients in the observation group were intravenously injected with methylpred-nisolone at a dose of 1 mg·kg-1 daily from the first to the third day after surgery.Postoperative inflammatory markers,incidence of postoperative pulmonary infections,incidence of anastomotic fistula,postoperative hospital stay,and total hospitalization costs were compared between the two groups.Results There were no statistically significant differences in leukocyte count,neutrophil ratio,procalcitonin(PCT),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6)levels of patients between the two groups before treatment(P＞0.05).On day 1 and 4 after treatment,patients in the observation group had significantly higher leu-kocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels compared to those before treatment(P＜0.05).On postoperative day 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels were significantly lower than those on day 1 postopera-tively(P＜0.05).On postoperative days 1 and 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP and IL-6 levels of patients in the control group were significantly higher than those in the preoperative period(P＜0.05),and the leukocyte count,neutro-phil ratio and hs-CRP level were significantly lower on day 4 after surgery than on day 1 after surgery(P＜0.05);the differe-nces in PCT and IL-6 level of patients between day 4 after surgery and day 1 after surgery were not statistically significant(P＞0.05).On postoperative day 1,there were no statistically significant differences in leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels between patients in the observation group and the control group(P＞0.05).On postoperative day 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels of patients in the observation group were significantly lower than those in the control group(P＜0.05).The incidence of pulmonary infections in patients in the control group and the ob-servation group was 30.9％(13/42)and 12.2％(5/41),respectively;the incidence of pulmonary infections in patients in the observation group was significantly lower than that in the control group(x2=4.298,P＜0.05).The incidence of anasto-motic fistula in patients in the observation group and the control group was 9.76％(4/42)and 21.43％(9/42),respectively;there was no statistically significant difference between the two groups(x2=2.140,P＞0.05).The postoperative hospital stay was significantly longer in the control group than in the observation group(P＜0.05),and the total hospitalization costs were significantly higher in the control group than in the observation group(P＜0.05).Conclusion Methylprednisolone can effec-tively reduce the levels of inflammatory markers and the incidence of postoperative pulmonary infections in esophageal cancer patients undergoing neoadjuvant chemotherapy combined with immunotherapy before surgery.It is a highly safe treatment thera-py without increasing the incidence of anastomotic fistula.

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 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.