A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

OBJECTIVE: To investigate lymph node metastasis (LNM) in the prostatic anterior fat pad (PAFP) of PCa patients after robot-assisted radical prostatectomy (RARP), and analyze the clinicopathological features and prognosis of LNM in the PAFP. METHODS: We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urology of PLA General Hospital from January 2017 to December 2022. All the patients underwent routine removal of the PAFP during RARP and pathological examination, with the results of all the specimens examined and reported by pathologists. Based on the presence and locations of LNM, we grouped the patients for statistical analysis, compared the clinicopathological features between different groups using the Student's t, Mann-Whitney U and Chi-square tests, and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio. RESULTS: Lymph nodes were detected in 77 (7.7%) of the 1 003 PAFP samples, and LNM in 11 (14.3%) of the 77 cases, with a positive rate of 1.1% (11/1 003). Of the 11 positive cases, 9 were found in the upgraded pathological N stage, and the other 2 complicated by pelvic LNM. The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group (81.8% ［9/11］ vs 36.2% ［359/992］, P = 0.005), and so did the cases with Gleason score ≥8 (87.5% ［7/8］ vs 35.5% ［279/786］, P = 0.009). No statistically significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the patients with PAFP LNM only and those with pelvic LNM only. CONCLUSION The PAFP is a potential route to LNM, and patients with LNM in the PAFP are characterized by poor pathological features. There is no statistically significant difference in biochemical recurrence-free survival between the patients with PAFP LNM only and those with pelvic LNM only. Routine removal of the PAFP and independent pathological examination of the specimen during RARP is of great clinical significance.
Humans ; Male ; Prostatectomy/methods* ; Robotic Surgical Procedures ; Lymphatic Metastasis ; Retrospective Studies ; Prognosis ; Prostatic Neoplasms/pathology* ; Adipose Tissue/pathology* ; Prostate/pathology* ; Lymph Nodes/pathology* ; Middle Aged ; Aged

OBJECTIVE: The aim of this study is to explore the correlation among serum hepcidin, ferritin, and q-Dioxn MRI with upgrading, upstaging and biochemical recurrence in prostate cancer (PCa) patients. METHODS: A total of 103 PCa patients diagnosed by biopsy were selected for this study. All patients underwent q-Dixon MRI prior to biopsy for T2* value measurement. Then serum hepcidin and ferritin were measured before receiving radical prostatectomy. Pathological grading and staging were conducted both preoperatively and postoperatively. The correlations among hepcidin, ferritin, T2* values, and postoperative upgrading, upstaging, biochemical recurrence were subsequently analyzed. RESULTS: The hepcidin level of PCa patients was measured at (123.51 ± 23.03) ng/mL, while the ferritin level was recorded at (239.80 ± 79.59) ng/mL, and the T2* value was (41.07 ± 6.37) ms. A total of 49 and 36 cases were observed with upgrading and upstaging in postoperative pathology, respectively. The median follow-up duration was 28.0 months (6.0－38.0 months), during which biochemical recurrence was observed in 12 cases. For upgrading, hepcidin and ferritin demonstrated the predictive efficacy, with areas under the ROC curve of 0.777 and 0.642, respectively, whereas T2* values did not show sufficient predictive power. For upstaging, hepcidin, ferritin, and T2* exhibited predictive efficacy, with areas under the ROC curve of 0.806, 0.696, and 0.655, respectively. Multivariate Logistic regression analysis indicated that hepcidin served as an independent risk factor for both upgrading (OR 1.055, 95%CI 1.027－1.085, P<0.001) and upstaging (OR 1.094, 95%CI 1.040－1.152, P<0.001). Cox regression analysis showed that hepcidin (95%CI 1.000－1.052, P = 0.049) was a significant risk factor for predicting biochemical recurrence. CONCLUSION Hepcidin could serve as a predictor for pathological upgrading, upstaging and biochemical recurrence after radical prostatectomy, which provides a novel potential index for risk stratification and prognostic evaluation of PCa patients.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Hepcidins/blood* ; Ferritins/blood* ; Middle Aged ; Magnetic Resonance Imaging/methods* ; Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging

OBJECTIVES: To explore the active components that mediate the therapeutic effect of Centella asiatica on psoriasis and their therapeutic mechanisms. METHODS: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in Centella asiatica and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis. In a RAW264.7 macrophage model of LPS-induced inflammation, the anti-inflammatory effect of 7.5, 15, 30, and 60 μmol/L quercetin, asiaticoside, and asiatic acid, which were identified as the main active components in Centella asiatica, were tested by measuring cellular production of NO, TNF‑α and IL-6 using Griess method and ELISA and by detecting mRNA expressions of IL-23, IL-17A, TNF-α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727) with RT-qPCR and Western blotting. RESULTS: A total of 139 targets of Centella asiatica and 4604 targets of psoriasis were obtained, and among them CASP3, EGFR, PTGS2, and ESR1 were identified as the core targets. KEGG analysis suggested that quercetin, asiaticoside, and asiatic acid in Centella asiatica were involved in cancer and IL-17 and MAPK signaling pathways. In the RAW264.7 macrophage model of inflammation, treatment with quercetin significantly reduced cellular production of NO, TNF‑α and IL-6, and lowered mRNA expressions of IL-23, IL-17A, TNF‑α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727). CONCLUSIONS Quercetin, asiaticoside and asiatic acid are the main active components in Centella asiatica to mediate the therapeutic effect against psoriasis, and quercetin in particular is capable of suppressing cellular production of NO, TNF‑α and IL-6 and regulating the IL-23/IL-17A inflammatory axis by mediating STAT3 phosphorylation to inhibit inflammatory response.
Quercetin/pharmacology* ; Psoriasis/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice ; Animals ; Centella/chemistry* ; Triterpenes/pharmacology* ; Phosphorylation ; Interleukin-17/metabolism* ; Interleukin-23/metabolism* ; RAW 264.7 Cells ; Pentacyclic Triterpenes/pharmacology* ; Macrophages/drug effects* ; Signal Transduction ; Plant Extracts

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:To assess the association between short-term ambient air pollution exposure and arterial stiffness and whether obesity modifies these associations.Methods:A cross-sectional study was conducted based on Fangshan family cohort in Beijing. The 24 hours average air pollutant levels on the day cohort participants took baseline survey were calculated as short-term air pollution. A generalized additive model (GAM) with Gaussian links was used to estimate changes in typical carotid artery intima-media thickness (CIMT), brachial-ankle pulse wave velocity (BAPWV), pulse pressure (PP) and ankle-branchial index (ABI) after short-term exposure to each air pollution (PM 2.5, PM 10, SO 2, NO 2, CO). The cross-product terms of each air pollution, body mass index (BMI), and waist-to-hip ratio were included in the GAM model to test the interaction. Further, they conducted a stratified analysis to test their effects on the relationship between short-term exposure to each air pollution and the arterial stiffness indicators. Results:A total of 4 211 individuals were included in the analysis. Individuals' age was (58.9±8.7) years, of which 2 268 (53.9%) were female. Several covariates, including sociodemographic factors, lifestyle behaviors, and history of drugs, were included in the analysis. The results of the GAM analysis showed that an increase in PM 2.5 ( β=2.912×10 -4, 95% CI: 1.424×10 -4-4.400×10 -4, P<0.001), CO ( β=0.027, 95% CI: 0.011-0.043, P<0.001), SO 2 ( β=2.070×10 -3, 95% CI: 7.060×10 -4-3.430×10 -3, P=0.003), and NO 2 ( β=3.650×10 -4, 95% CI: 2.340×10 -5-7.060×10 -4, P=0.036) were associated with an increase in CIMT, while an increase in PM 10 ( β=0.018, 95% CI: 0.002-0.033, P=0.028) was associated with an increase in PP in the study population. Besides, the waist-to-hip ratio had an effect-modification on the correlation of short-term exposure of PM 2.5 (interaction P=0.015), NO 2 (interaction P=0.008), and CO (interaction P=0.044) with CIMT, and the correlation between short-term exposure of PM 2.5 (interaction P=0.002), NO 2 (interaction P=0.010), CO (interaction P=0.029), PM 10 (interaction P<0.001) with PP. The significant association between CIMT, PP, and air pollution concentrations was more visible in people with lower waist-to-hip ratios. Conclusions:Short-term ambient air pollution exposure was associated with arterial stiffness indicators, and there was an effect modification of waist-to-hip ratio on these associations, and lower waist-to-hip ratios may enhance the association between air pollution exposure and indicators.

Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.