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.

Objective To evaluate the practical application of the Media Fill Test(MFT)in assessing aseptic compounding competency of personnel in Pharmacy Intravenous Admixture Services(PIVAS).Methods A multicenter controlled study was conducted across six tertiary hospitals(center ①-⑥)in China.Participants were divided into an inexperienced group(Group A,n=118)and an experienced group(Group B,n=118),each performing five MFT operations.Positive controls validated medium efficacy.Contamination rates and pass rates were analyzed using chi-square and Fisher's exact tests.Results Valid samples included 584 for Group A and 588 for Group B.The sample pass rate was 66.78%(390/584)in Group A and 91.67%(539/588)in Group B,while personnel pass rates were 46.15%(54/117)and 80.51%(95/118),respectively,with significant intergroup differences(both P<0.01).All centers except Center ⑥ showed significantly higher pass rates in Group B(all P<0.05).Conclusion MFT effectively differentiates technical proficiency levels and is suitable for training evaluation of novice PIVAS staff.

BACKGROUND:D1-3-n-butylphthalide has antioxidant and anti-inflammatory effects and has been explored to have protective role in Parkinson's disease,but the underlying mechanisms are unknown.OBJECTIVE:To investigate the protective effect of D1-3-n-butylphthalide by the approach of network pharmacology,molecular docking,and cellular experimental validation.METHODS:(1)Network pharmacology and molecular docking:The database was used to screen the targets of D1-3-n-butylphthalide and Parkinson's disease.The intersection was taken from the construction of the target protein interaction network,and then screen the core targets.The GO and KEGG pathway enrichment was used to further analyze the core targets.The interaction between the target proteins and D1-3-n-butylphthalide was verified by molecular docking.(2)Cell validation:The passage 6 PC12 cells were divided into six groups for culture.The control group was cultured with conventional culture medium.The model group was cultured with N-methyl-4-phenylpyridinium iodide to induce Parkinson's disease model.The ML385 inhibitor group was added with nuclear factor E2-related factor 2 inhibitor ML385 on the basis of inducing Parkinson's disease model.The D1-3-n-butylphthalide treatment group was added with butylphthalide on the basis of inducing Parkinson's disease model.The D1-3-n-butylphthalide combined with ML385 treatment group was added with D1-3-n-butylphthalide and ML385 on the basis of inducing Parkinson's disease model.The D1-3-n-butylphthalide group was cultured with conventional culture medium containing butylphthalide alone.Cell proliferation,intracellular reduced glutathione and malondialdehyde levels,and protein expression of protein kinase B/glycogen synthase kinase 3β/nuclear factor E2-related factor 2(AKT/GSK-3β/Nrf2)signaling pathway were detected.RESULTS AND CONCLUSION:(1)A total of 52 targets were screened for the intersection of drugs and disease targets,and the core targets including the matrix metalloproteinase 9 and GSK-3β were involved the phosphatidylinositol 3-kinase(PI3K)/AKT and oxidative stress-related signaling pathways.The molecular docking binding energy of D1-3-n-butylphthalide and GSK-3β was-18.27 kJ/mol,which indicated that D1-3-n-butylphthalide had a good binding ability with GSK-3β.(2)Compared with the model group,the PC12 cell activity and reduced glutathione level in the D1-3-n-butylphthalide treatment group were increased(P＜0.05),the malondialdehyde level was decreased(P＜0.05),and the expression of p-AKT,p-GSK-3β,Nu-Nrf2,and T-Nrf2 proteins was increased(P＜0.05).Compared with the D1-3-n-butylphthalide group,the PC12 cell activity and reduced glutathione level in the D1-3-n-butylphthalide combined with ML385 treatment group were decreased(P＜0.05),the malondialdehyde level was increased(P＜0.05),and the expression of Nu-Nrf2 and T-Nrf2 proteins was decreased(P＜0.05).(3)These results demonstrate that D1-3-n-butylphthalide can inhibit oxidative stress and improve cell activity through the AKT/GSK-3β/Nrf2 signaling pathway,and has a protective effect on the Parkinson's cell model induced by N-methyl-4-phenylpyridinium iodide.

Objective To evaluate the practical application of the Media Fill Test(MFT)in assessing aseptic compounding competency of personnel in Pharmacy Intravenous Admixture Services(PIVAS).Methods A multicenter controlled study was conducted across six tertiary hospitals(center ①-⑥)in China.Participants were divided into an inexperienced group(Group A,n=118)and an experienced group(Group B,n=118),each performing five MFT operations.Positive controls validated medium efficacy.Contamination rates and pass rates were analyzed using chi-square and Fisher's exact tests.Results Valid samples included 584 for Group A and 588 for Group B.The sample pass rate was 66.78%(390/584)in Group A and 91.67%(539/588)in Group B,while personnel pass rates were 46.15%(54/117)and 80.51%(95/118),respectively,with significant intergroup differences(both P<0.01).All centers except Center ⑥ showed significantly higher pass rates in Group B(all P<0.05).Conclusion MFT effectively differentiates technical proficiency levels and is suitable for training evaluation of novice PIVAS staff.

Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

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 the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

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

BACKGROUND:D1-3-n-butylphthalide has antioxidant and anti-inflammatory effects and has been explored to have protective role in Parkinson's disease,but the underlying mechanisms are unknown.OBJECTIVE:To investigate the protective effect of D1-3-n-butylphthalide by the approach of network pharmacology,molecular docking,and cellular experimental validation.METHODS:(1)Network pharmacology and molecular docking:The database was used to screen the targets of D1-3-n-butylphthalide and Parkinson's disease.The intersection was taken from the construction of the target protein interaction network,and then screen the core targets.The GO and KEGG pathway enrichment was used to further analyze the core targets.The interaction between the target proteins and D1-3-n-butylphthalide was verified by molecular docking.(2)Cell validation:The passage 6 PC12 cells were divided into six groups for culture.The control group was cultured with conventional culture medium.The model group was cultured with N-methyl-4-phenylpyridinium iodide to induce Parkinson's disease model.The ML385 inhibitor group was added with nuclear factor E2-related factor 2 inhibitor ML385 on the basis of inducing Parkinson's disease model.The D1-3-n-butylphthalide treatment group was added with butylphthalide on the basis of inducing Parkinson's disease model.The D1-3-n-butylphthalide combined with ML385 treatment group was added with D1-3-n-butylphthalide and ML385 on the basis of inducing Parkinson's disease model.The D1-3-n-butylphthalide group was cultured with conventional culture medium containing butylphthalide alone.Cell proliferation,intracellular reduced glutathione and malondialdehyde levels,and protein expression of protein kinase B/glycogen synthase kinase 3β/nuclear factor E2-related factor 2(AKT/GSK-3β/Nrf2)signaling pathway were detected.RESULTS AND CONCLUSION:(1)A total of 52 targets were screened for the intersection of drugs and disease targets,and the core targets including the matrix metalloproteinase 9 and GSK-3β were involved the phosphatidylinositol 3-kinase(PI3K)/AKT and oxidative stress-related signaling pathways.The molecular docking binding energy of D1-3-n-butylphthalide and GSK-3β was-18.27 kJ/mol,which indicated that D1-3-n-butylphthalide had a good binding ability with GSK-3β.(2)Compared with the model group,the PC12 cell activity and reduced glutathione level in the D1-3-n-butylphthalide treatment group were increased(P＜0.05),the malondialdehyde level was decreased(P＜0.05),and the expression of p-AKT,p-GSK-3β,Nu-Nrf2,and T-Nrf2 proteins was increased(P＜0.05).Compared with the D1-3-n-butylphthalide group,the PC12 cell activity and reduced glutathione level in the D1-3-n-butylphthalide combined with ML385 treatment group were decreased(P＜0.05),the malondialdehyde level was increased(P＜0.05),and the expression of Nu-Nrf2 and T-Nrf2 proteins was decreased(P＜0.05).(3)These results demonstrate that D1-3-n-butylphthalide can inhibit oxidative stress and improve cell activity through the AKT/GSK-3β/Nrf2 signaling pathway,and has a protective effect on the Parkinson's cell model induced by N-methyl-4-phenylpyridinium iodide.

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.