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 explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS).Methods:A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome ( SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by Medical Ethics Committee of the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070). Results:The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46, XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c. 1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister′s first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+ PM4+ PP3_Moderate+ PP4). Conclusion:The c. 1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians′ thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction

Objectives:To observe the incidence of residual shunt post patent foramen ovale(PFO)closure and the effect of PFO closure in these migraine patients at one year after PFO. Methods:This retrospective study included patients who underwent PFO closure for migraine in the Second Affiliated Hospital Zhejiang University School of Medicine from January 2019 to June 2022,patients were divided into the grade 0 shunt group(n=67),the grade Ⅰ shunt group(n=10),the grade Ⅱ shunt group(n=13)and the grade Ⅲ shunt group(n=16)according to the results of contrast transthoracic echocardiography(cTTE)at 1 year after PFO closure.The incidence of postoperative migraine attacks among different groups of patients were compared.The risk factors of residual shunt after PFO closure were explored. Results:The mean age of enrolled 106 patients with migraine was(35.80±11.70)years,of which 83 patients(78.30%)were female.One year after PFO closure,the migraine attack and rating scale were significantly decreased compared to baseline in the grade 0 shunt group,in the grade Ⅰ shunt group and in the grade Ⅱ shunt group(all P<0.05),but not in the grade Ⅲ shunt group(P>0.05).The rate of significant and complete migraine was significantly higher in the grade 0 shunt group(58.21%),in the gradeⅠ shunt group(60.00%),in the grade Ⅱ shunt group(69.23%)as compared to the grade Ⅲ shunt group(18.75%,P=0.02)at one year after PFO.The rate of grade 0 shunt after PFO closure in patients with the microvesicles appearing in≥6 cardiac cycles in resting state before operation was significantly lower than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles in resting state(24.00%vs.83.87%vs.70.00%,P=0.04).Logistic multivariate regression analysis showed that patients with microvesicles appearing beyond 6 cardiac cycles in resting state were more likely to have residual shunts in postoperative cTTE compared to the patients with negative cTTE and microvesicles appearing within 6 cardiac cycles in the cTTE in resting state before operation(OR=0.06,95%CI:0.02-0.23,P<0.01;OR=0.014,95%CI:0.05-0.41,P<0.01). Conclusions:Migraine patients who underwent PFO closure and with grade 0 to grade Ⅱ residual shunt at one year after PFO are most likely to have significant remission of migraine,while the incidence of migraine remission is low in patients with grade Ⅲresidual shunt.The incidence of residual shunt after PFO closure is higher in patients with the microvesicles appearing in 6 cardiac cycles in resting state in the cTTE before operation than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles.

Objective To explore the effect and possible mechanism of berberine on the macro-phage polarization of human myeloid leukemia monocytic cell line THP-1 induced by oxidized low-density lipoprotein(ox-LDL).Methods THP-1 cells were induced into macrophages by PMA,and then according to different concentrations of berberine,the cells were divided into con-trol group,and 5,10,20,40 and 50 μmol/L berberine groups.After intervention for 24 or 48 h,CCK8 assay was used to detect cell viability for optimal concentration and time of berberine treat-ment.PMA-induced THP-1 macrophages were assigned into blank group,model group(ox-LDL),berberine group,inhibitor group(phosphatidyl inositol 3-kinase(PI3K)inhibitor LY294002)and berberine+inhibitor group(berberine+LY294002).The contents of inducible nitric oxide syn-thase(iNOS)and TGF-β1 were detected by ELISA.qPCR was employed to measure the mRNA expression of TNF-α,arginase 1(Arg1),PI3K and protein kinase B Akt1,and Western blotting was applied to detect the protein levels of Akt1 and phosphorylated protein kinase B antibody(p-Akt1).Results In 24 h after intervention,the macrophage activity was significantly lower in the 40 and 50 μmol/L berberine groups than the control group(P＜0.05),and after 48 h,the ac-tivity in all the 5 doses of berberine groups was obviously lower than that in the control group[(0.89±0.02)％,(0.82±0.03)％,(0.71±0.02)％,(0.62±0.03)％and(0.53±0.02)％vs(1.01±0.01)％,P＜0.05].Berberine treatment of 20 μmol/L for 24 h had little effect on cell viability,and the dose and the time were regarded as the best concentration and time.Compared with the blank group,iNOS content and TNF-α mRNA level were increased in the model group,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1,and p-Akt1/Akt1 protein levels were de-creased(P＜0.05).iNOS content and TNF-α mRNA level were decreased,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1s were increased in the berberine group than the model group(P＜0.05).Compared with the berberine group,iNOS con-tent and TNF-α mRNA level were increased,while mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1 were decreased in the berberine+inhibitor group(P＜0.05).Con-clusion Berberine can inhibit the inflammatory response of THP-1 macrophages induced by ox-LDL by activating PI3K/Akt1 pathway,and inhibit the M1 polarization and promote the M2 polarization of macrophages.

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.

Background: To date, consistent data have not been reported on the association between serum amyloid A (SAA) levels and type 2 diabetes mellitus (T2DM). The purpose of this study was to systematically summarize their relationship. Methods: Databases including PubMed, Cochrane Library, Embase, Web of Science, and MEDLINE were searched until August 2021. Cross-sectional and case-control studies were included. Results: Twenty-one studies with 1,780 cases and 2,070 controls were identified. SAA levels were significantly higher in T2DM patients than in healthy groups (standardized mean difference [SMD], 0.68; 95% confidence interval [CI], 0.39 to 0.98). A subgroup analysis showed that the mean age of participants and the continent that participants were from were related to differences in SAA levels between cases and controls. Furthermore, in T2DM patients, SAA levels were positively associated with body mass index (r=0.34; 95% CI, 0.03 to 0.66), triglycerides (r=0.12; 95% CI, 0.01 to 0.24), fasting plasma glucose (r=0.26; 95% CI, 0.07 to 0.45), hemoglobin A1c (r=0.24; 95% CI, 0.16 to 0.33), homeostasis model assessment for insulin resistance (r=0.22; 95% CI, 0.10 to 0.34), C-reactive protein (r=0.77; 95% CI, 0.62 to 0.91), and interleukin-6 (r=0.42; 95% CI, 0.31 to 0.54), but negatively linked with highdensity lipoprotein cholesterol (r=–0.23; 95% CI, –0.44 to –0.03). Conclusion The meta-analysis suggests that high SAA levels may be associated with the presence of T2DM, as well as lipid metabolism homeostasis and the inflammatory response.

Objective To construct an professional quality training management system for in-service nurses and to evaluate its effect in clinical practice.Methods From June 2014 to October 2016, a total of 1233 nurses in a classⅢ grade A hospital were selected. Through the establishment and improvement of the organizational structure of the professional quality management of the in-service nurses, the various training content combining theory and practice were adopted, including case study, role playing and simulation scenario training to implement the professional training.Results The average score of nursing professional quality was (91.78±3.82) before training and (94.53±4.33) after training. The difference between before and after training was statistically significant (t=-3.156,P=0.006). The patient satisfaction rate was 90.57％ before training and 97.42％ after training, and the difference was statistically significant (Z=-2.516,P=0.006). The doctor satisfaction rate was 90.57％ before training and 94.88％ after training, and the difference was statistically significant (Z=-2.233,P<0.01).Conclusions The construction of nurses' professional quality training strengthens the importance of nurses' professional quality, improves the evaluation of professional quality, and has guiding significance for the training of in-service nurses' professional quality.

Objective To investigate self-management behaviors of kidney transplantation recipients after discharge.Methods A total of 97 kidney transplantation recipients were recruited from a teaching hospital of Peking University From September 2009 to June 2012,and all eligible subjects were then assigned to 3 groups:post-transplantation less than 6 months group (group A),post-transplantation 6-12 months group (group B),and post-transplantation more than 12 months group (group C).The subjects were required to complete self-management scale for renal transplant recipients.ANOVA was used for data analysis.Results There were 32 patients in group A,31 in group B,and 34 in group C.Self-management behavior score of the participants of the three groups was 100.1 ± 7.0,99.0 ± 7.3 and 91.3 ± 5.8,respectively (F =3.53,P =0.03).In terms of diet,group B got the highest score (F =16.41,P =0.00).However,group A showed excellence in physical activities (F =11.50,P =0.00).For three groups,score of drug effect and side effect was 2.00 ±0.00,2.03 ±0.18,and 2.41 ±0.50; score of routine laboratory values was 2.00 ±0.00,2.05 ± 0.16 and 2.82 ±0.39; and score of skin protection was 3.09 ±0.30,3.03 ± 0.91,and 2.85 ±0.36,respectively.Conclusions Post-transplantive self-management behavior of patients who completed the surgery for more than 12 months may not be better than others.Healthcare professionals need to improve patients' self-management through health education.

Objective To investigate human papilloma virus(HPV) infection in normal endometrium, atypi-cal hyperplasia of endometrium and endometrial carcinoma. Methods By the nucleic acid hybridization,we detected 28 pairs of endometrial carcinomas, 21 pairs of atypical hyperplasia of endometrium. Normal endometrium from 16 pa-tients with uterine myomas were as control. Results HPV16/18 DNA was detected in 25 endometrial carcinoma and 2 atypical hyperplasia of endometrium and 1 normal endometrium. Conclusions Endometrial carcinoma HPV16/18 DNA were significantly higher than those infected with atypical endometrial hyperplasia and normal endometrium. Note the occurrence of endometrial cancer,the development may be associated with HPV infection.