ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE₁), and the margin of exposure for carcinogenic toxicity (MOE₂). An MOE₁ greater than 200 and an MOE₂ greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP₅₀ values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)^-1, respectively. For pregnant women in Shanghai in 2023, the P₅₀ values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)^-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)^-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*

Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*