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.

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.

Based on the"pivot movement"theory of distinguished physician Huang Yuanyu in the Qing Dynasty,it is believed that the core mechanism of abdominal flatulence disease is the unfavorable operation of the central axis pivot,and the ascent and descent disorder of qi movement in the central earth.The pathogenesis of abdominal flatulence disease was explained from the perspectives of mistakenly dropping the damage to yang,keeping the lung qi from falling,and declining central qi deficiency.The main concept of clinical practice was to promote the movement of the middle earth,promote the movement of the spleen and stomach,and restore position of yin and yang and clearing and turbidity.Examples were given of the five commonly used TCM prescriptions,including Xiaqi Decoction,Banxia Xiexin Decoction,Gancao Xiexin Decoction,Shengjiang Xiexin Decoction and Xuanfu Daizhe Decoction,to explain the treatment approach guided by the theory of"pivot movement",in order to provide reference for clinical diagnosis and treatment.

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 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.

Objective: To understand the trends of smoking and passive smoking exposure in adults in Shaanxi province from 2007 to 2015. Methods: Data was from China Chronic Disease and Risk Factor Surveillance in 2007, 2010, 2013 and 2015 to calculate the rates of smoking, smoking cessation and passive smoking exposure, as well as the amount of smoking of smokers indicated by each surveillance. Cochran-Armitage test was used to assess the trends across survey periods. The weighting rate was calculated by using sampling weight and data from the 6^th national census in 2010. Sensitivity analysis was done to test the trends as well. Results: The results of the surveillance indicated that the smoking rate in 2007 was 38.26%, highest in the results of four surveys, it decreased to 30.95% in 2013 and then increased to 34.11% in 2015 (Cochran-Armitage test: Z=2.46, P=0.014). The amount of smoking increased from 16.90 cigarettes per day in 2007 to 17.76 cigarettes per day in 2015. The overall rate of smoking cessation was 11.02% in 2007 and 16.95% in 2015 (Cochran- Armitage test: Z=-4.18, P<0.01). We observed the passive smoking exposure rate was 48.10% in 2010 and 63.88% in 2015 (Cochran-Armitage test: Z=-10.60, P<0.01). We found no difference in trends by sensitivity analysis. Conclusions The smoking rate and amount of cigarettes smoked in adults in Shaanxi remained stable and at a high level. The rate of smoking cessation increased gradually, while the passive smoking exposure rate increased rapidly.

Aim To investigate the effect of curcumin against high-fat-diet induced C57BL/6J mice bone changes and the correlation between the expression of cathepsin K and curcumin.Methods Curcumin treated C57BL/6J mice had been on high fat diet for 12 weeks.The HE, Alizarin red S staining and Safranin O/fast green staining of femur were employed to evaluate bone microstructure, bone metabolism and bone development.The expressions of cathepsin K were assessed by Western blot and immunohistochemical staining.Results Histopathological results showed that curcumin could improve the destruction of trabecular bone structure, cartilage development and bone calcification.Biomechanical results proved that curcumin could improve the bone strength of the type 2 diabetic mice induced by high fat.The results of immunohistochemistry and Western blot assay indicated that curcumin could significantly inhibit the expression of cathepsin K in bone tissues of mice.Conclusion Curcumin can increase bone strength, improve bone microstructure, and enhance the degree of bone calcification, which may be achieved by inhibiting the expression of cathepsin K.