Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.

Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.

Objective:To describe the clinical manifestations, genetic mutation site, diagnosis, and treatment of a patient with multisystem proteinopathy type 1 (MSP1) caused by valosin-containing protein ( VCP) gene mutation, and to improve clinicians′ understanding of this disease. Methods:A retrospective analysis was performed on clinical and genetic data from a confirmed VCP gene missense mutation-associated MSP1 case diagnosed at the Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Southeast University in January 2024. A 12-month follow-up and systematic literature review were performed for comprehensive analysis. Results:The 53-year-old male patient presented with progressive limb weakness over 7 months. Neurological examination demonstrated tongue fasciculations, asymmetric proximal muscle weakness in all four limbs, left patellar hyperreflexia, positive right Chaddock sign, and bilateral Hoffmann signs. Electrophysiological studies demonstrated extensive neurogenic damage. Lower-limb muscle magnetic resonance imaging (MRI) showed selective fatty infiltration in specific muscle groups. Biceps brachii biopsy pathology revealed rimmed vacuoles and grouped atrophy of typeⅡfibers. Immunofluorescence confirmed aberrant aggregation of VCP within atrophic myofibers, showing co-localization with p62 and transactive response DNA binding protein 43 (TDP-43). Whole-genome sequencing identified a heterozygous c.463C>T (p.Arg155Cys) missense mutation in exon 5 of the VCP gene, classified as a likely pathogenic mutation according to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The patient was diagnosed with MSP1 with amyotrophic lateral sclerosis and inclusion body myopathy as the main clinical manifestation based on clinical manifestations, electrophysiology, imaging, histopathology, and genetic findings. After 12 months of riluzole therapy, disease progression remained relatively slow. Literature review identified 67 relevant articles, revealing 87 VCP mutation genotypes and 19 clinical phenotypes. Conclusions:MSP1 is a genetically and phenotypically heterogeneous spectrum of multisystem degenerative disorders. This case represents the first reported VCP-related MSP1 in China, characterized by amyotrophic lateral sclerosis combined with inclusion body myopathy. Riluzole treatment demonstrates slowed disease progression over 1 year.

Objective:To describe the clinical manifestations, genetic mutation site, diagnosis, and treatment of a patient with multisystem proteinopathy type 1 (MSP1) caused by valosin-containing protein ( VCP) gene mutation, and to improve clinicians′ understanding of this disease. Methods:A retrospective analysis was performed on clinical and genetic data from a confirmed VCP gene missense mutation-associated MSP1 case diagnosed at the Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Southeast University in January 2024. A 12-month follow-up and systematic literature review were performed for comprehensive analysis. Results:The 53-year-old male patient presented with progressive limb weakness over 7 months. Neurological examination demonstrated tongue fasciculations, asymmetric proximal muscle weakness in all four limbs, left patellar hyperreflexia, positive right Chaddock sign, and bilateral Hoffmann signs. Electrophysiological studies demonstrated extensive neurogenic damage. Lower-limb muscle magnetic resonance imaging (MRI) showed selective fatty infiltration in specific muscle groups. Biceps brachii biopsy pathology revealed rimmed vacuoles and grouped atrophy of typeⅡfibers. Immunofluorescence confirmed aberrant aggregation of VCP within atrophic myofibers, showing co-localization with p62 and transactive response DNA binding protein 43 (TDP-43). Whole-genome sequencing identified a heterozygous c.463C>T (p.Arg155Cys) missense mutation in exon 5 of the VCP gene, classified as a likely pathogenic mutation according to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The patient was diagnosed with MSP1 with amyotrophic lateral sclerosis and inclusion body myopathy as the main clinical manifestation based on clinical manifestations, electrophysiology, imaging, histopathology, and genetic findings. After 12 months of riluzole therapy, disease progression remained relatively slow. Literature review identified 67 relevant articles, revealing 87 VCP mutation genotypes and 19 clinical phenotypes. Conclusions:MSP1 is a genetically and phenotypically heterogeneous spectrum of multisystem degenerative disorders. This case represents the first reported VCP-related MSP1 in China, characterized by amyotrophic lateral sclerosis combined with inclusion body myopathy. Riluzole treatment demonstrates slowed disease progression over 1 year.

[Objective] To analyze factors influencing the postoperative progression-free survival (PFS) in patients with renal cell carcinoma (RCC), construct a nomogram model for predicting PFS, and compare it with other predictive models. [Methods] A retrospective analysis was conducted on the general and clinical data of 263 RCC patients who underwent surgery at the Department of Urology, the Second Affiliated Hospital of Xi'an Jiaotong University, during Apr.2014 and Nov.2021.Patients were divided into the progression group (n=34) and non-progression group (n=229). The data of the two groups were analyzed to identify prognostic variables associated with PFS, and a nomogram model was constructed.The performance of this model was compared with that of the University of California, Los Angeles Integrated Staging System (UISS) score, tumor staging, tumor size, tumor pathological grade, and tumor necrosis scoring system (SSIGN score), and Leibovich score by plotting receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Calibration curve of the nomogram was used to validate the model's performance, and K-fold cross-validation was employed to assess its external validity. [Results] Multivariate Cox regression analysis revealed that age (HR=2.255, 95%CI: 1.032-4.926), T stage (HR=5.766, 95%CI: 2.351-14.142), pathological grade (HR=3.100, 95%CI: 1.445-6.651), and pathological necrosis (HR=2.656, 95%CI: 1.253-5.629) were independent risk factors of PFS (P<0.05). The nomogram model based on these four independent variables had AUCs (95%CI) of 0.750 (0.630-0.870), 0.803 (0.705-0.902), and 0.847 (0.757-0.937) for 1, 3, and 5 years, respectively, which were higher than those of UISS score, SSIGN score, and Leibovich score.The calibration curve of the nomogram showed good consistency between predicted and actual probabilities.In K-fold cross-validation, the average AUCs of the nomogram at 1, 3, and 5 years were 0.761, 0.808, and 0.842, indicating good external validity of the nomogram. [Conclusion] The nomogram based on age, T stage, pathological grade and pathological necrosis can accurately predict the risk of postoperative PFS in RCC patients at 1, 3, and 5 years, which can aid clinicians in the early identification of high-risk progression.

Objective To analyze the fluorescence quantitative detection results of hepatitis B virus(HBV)DNA and distribution characteristics of serological markers in children aged 16 and below in Wuxi area,and provide evidence for improving the prevention and control measures of HBV in children.Methods The HBV DNA load in the serum of pediatric patients was detected by fluores-cence quantitative PCR,and the serological markers and liver function indexes of HBV were detected by the chemiluminescence and automatic biochemical analyzer methods,respectively.The data were analyzed using SPSS 13.0 statistical software.Results Among the 86 children who underwent fluorescence quantitative detection of HBV DNA,45 were detected for HBV DNA,with a positive rate of 52.3％,of which 34 had high viral load.Among the children with positive HBV DNA,35 were boys and 10 were girls.There was no statistical significance in the positive rate of HBV DNA between boys and girls(x2=3.688,P=0.055).There was a statistically signif-icant difference in the positive rate of HBV DNA among different age groups(x2=5.540,P=0.019),and the highest positive rate was found in children aged 15.A total of 64 pediatric patients were tested for the serological antigen and antibody markers of HBV,and 9 antigen-antibody combination patterns were found.A total of 80 pediatric patients were tested for liver function indexes,and 33 of them were found to have at least one abnormal index.Conclusion The detection of HBV DNA by fluorescence quantitative PCR comple-ments the detection of serological markers and biochemical indexes,and their combination can improve the accuracy of clinical diagno-sis of hepatitis B in children,which may provide effective reference for clinical judgment of the degree and infectivity of HBV infection.

Objective To analyze the fluorescence quantitative detection results of hepatitis B virus(HBV)DNA and distribution characteristics of serological markers in children aged 16 and below in Wuxi area,and provide evidence for improving the prevention and control measures of HBV in children.Methods The HBV DNA load in the serum of pediatric patients was detected by fluores-cence quantitative PCR,and the serological markers and liver function indexes of HBV were detected by the chemiluminescence and automatic biochemical analyzer methods,respectively.The data were analyzed using SPSS 13.0 statistical software.Results Among the 86 children who underwent fluorescence quantitative detection of HBV DNA,45 were detected for HBV DNA,with a positive rate of 52.3％,of which 34 had high viral load.Among the children with positive HBV DNA,35 were boys and 10 were girls.There was no statistical significance in the positive rate of HBV DNA between boys and girls(x2=3.688,P=0.055).There was a statistically signif-icant difference in the positive rate of HBV DNA among different age groups(x2=5.540,P=0.019),and the highest positive rate was found in children aged 15.A total of 64 pediatric patients were tested for the serological antigen and antibody markers of HBV,and 9 antigen-antibody combination patterns were found.A total of 80 pediatric patients were tested for liver function indexes,and 33 of them were found to have at least one abnormal index.Conclusion The detection of HBV DNA by fluorescence quantitative PCR comple-ments the detection of serological markers and biochemical indexes,and their combination can improve the accuracy of clinical diagno-sis of hepatitis B in children,which may provide effective reference for clinical judgment of the degree and infectivity of HBV infection.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg^-1·d^-1） or AAⅠ（5 mg·kg^-1·d^-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L^-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min^-1. Positive ion mode of electrospray ionization（ESI⁺） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MS^E was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.

Objective:To explore the barrier factors perceived by community nurses in evidence-based nursing practice.Methods:A cross-sectional survey of perceived barriers in 769 community nurses of China was conducted by using the Barriers to Research Utilization Scale from October 2017 to April 2018. In a semi-structured interview, a total of 15 community nurses were selected by purpose sampling for deeply exploring details of perceived barriers, the influencing of barriers and the needed supports for overcoming the barriers in evidence-based practice. The interview data were transcribed to text and analyzed by using thematic analysis in Nvivo 11.0.Results:Community nurses faced barriers including insufficient resources, support and ability of evidence-based practice of community nurses. The results of interview provided the details of these barriers which had negative impacts on community nurses. To overcome these barriers, evidence-based related training, enhanced supporting resources were needed.Conclusions:Community nurses are facing multiple barriers in evidence-based practice. To promote the ability of evidence-based practice of community nurses, it is necessary to strengthen the support from organization, personnel, resources, and improve the ability of community nurses in evidence-based practice.

【Objective】 To explore the safety of RhD-positive red blood cells (RBCs) immunization schedules in RhD-negative volunteers, so as to facilitate the development of domestic anti-D immunoglobulin. 【Methods】 From January 2018 to April 2020, 23 RhD negative volunteers with informed consent were enrolled and divided into initial immunization group and booster immunization group. The initial immunization included first immunization, second immunization and third immunization. Four groups, i. e. 3 cases of 20 mL, 8 of 30 mL, 6 of 40 mL, and 6 of 50 mL, were involved in initial immunization. After the initial immunization response, booster immunizations were performed every 3 months. According to the anti-D titer before each immunization, the booster immunization doses were set to 0.5, 1 and 2 mL. Whole blood samples of 5mL/ person (time) were collected 24 h and 1 week after each infusion, and the blood routine, liver, kidney and blood coagulation function and anti-D titer were detected. The differences of detection (index) values at 24 h and 1 week after the first immunization and booster immunization in each (dose) group were compared. 【Results】 No statistically significant differences were observed in hemolysis index values (all within the range of medical reference values) 24 h or 1 week after initial immunization among RhD positive RBCs of 20, 30, 40 and 50mL(P>0.05). The differences between the hemolysis index values and the basic values before the immune response (all within the range of medical reference values) after 0.5 or 1 mL booster immunizations were also not statistically different (P>0.05). However, the differences (μmol/L)between total bilirubin levels and the basic values before the immune response (1.55±1.87, 6.29±2.66) were significantly different after 2 mL booster immunization (P<0.05). 【Conclusion】 No risks affecting the safety of RhD negative volunteers was found in the immunization schedule proposed in this study.