Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective:To investigate the anti-heart failure mechanism of N-acetylcysteine(NAC)in diabetic cardiomyop-athy independent from coronary artery factors.Methods:A total of 40 diabetic mice after heart failure model construction were randomly divided into two groups,NAC group(n=20,NAC 100mg·kg-1·d-1)and control group(n=20,Saline 100 mg·kg-1·d-1).Echocardiography was performed to detect left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),mitral left ventricular early-dias-tolic peak flow velocity/left ventricular late-diastolic peak flow velocity(E/A),isovolumic relaxation time(IVRT)and cardiac output(CO)after 4 weeks.Terminal uridine nick-end labeling(TUNEL)was performed to detect apoptosis in-dex,and Western Blot was performed to detect the expression of extracellular regulated protein kinases(ERK)1/2 after 6 weeks in two groups.Results:Compared to those in control group,mice in NAC group had significant higher LVEF[(40.5±3.4)％vs.(36.9±3.2)％],E/A[(1.5±0.1)vs.(1.4±0.1)]and CO[(10.3±0.6)ml/min vs.(9.9±0.5)ml/min](P＜0.05 or＜0.01);and significant lower LVESV[(23.1±1.3)μl vs.(24.7±1.5)μl],apoptosis index[(31.2±0.5)％vs.(45.1±0.9)％]and the expression of ERK1/2[(2.2±0.2)vs.(3.9±0.1)](P＜0.001 all).Conclusion:NAC exerts anti-heart failure effect by attenuating apoptosis of cardiomyocytes via regulating ERK1/2 pathway.

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

[Purpose]To analyze the compliance and its influencing factors of lung cancer screening using low-dose computed tomography(LDCT)among high-risk population in urban districts of Chongqing from 2013 to 2021.[Methods]The lung cancer screeing of Cancer Early Diagnosis and Treatment Project was conducted among permanent residents aged 40～69 years old from 14 urban districts of Chongqing selected by cluster sampling method from 2013 to 2021.The questionnaire survey was performed to assess the risk level of lung cancer,and individuals with high risk were advised to have LDCT examination.The compliance rate of LDCT examination among high-risk populations was calculated and compared using Chi-square test among residents with different de-mographic features;the influencing factors of compliance was analyzed with generalized linear mixed models.[Results]A total of 316 066 residents completed the risk assessment questionnaire survey,52 858 people were assessed as high-risk(17.17％).Among the high-risk population,20 398 completed LDCT screening,with an overall compliance rate of 38.59％.The generalized linear mixed model showed that male participants(OR=0.871,95％CI:0.823～0.922)and smokers(light smokers:OR=0.829,95％CI:0.775～0.886;heavy smokers:OR=0.842,95％CI:0.792～0.896)had lower compliance rates;while people with higher education level(OR=1.347,95％CI:1.265～1.435),occupational exposure to harmful substances(OR=1.400,95％CI:1.340～1.463),passive smoking for 20 years or more(OR=1.472,95％CI:1.376～1.576),infrequent physical exercise(OR=1.203,95％CI:1.152～1.256),family history of lung cancer(OR=2.312,95％CI:2.201～2.429),and those having media promotion by community staff(OR=1.365,95％CI:1.223～1.524),and trained community staff(OR=1.343,95％CI:1.227～1.470)had higher compliance rates.Comorbidities were also factors influencing compliance,and there was an increasing trend of compliance rate with the increase of comorbidity numbers(P＜0.001).[Conclusion]The compli-ance rate of LDCT examination for lung cancer screening in Chongqing needs to be improved,and more precise health education should be implemented for groups with different characteristics to improve the compliance among high-risk population.

Aim To investigate the effect of cordycepin(COR)on gentamicin(GEN)-induced nephrotoxicity and the molecular mechanism of inhibiting oxidative stress and ferroptosis induced by GEN.Methods The oral SD rats were divided into a control group,GEN group,and GEN+COR group.Following the success-ful setting up of the animal model,the serum creatinine(CR)and urea nitrogen(BUN)levels of rats were measured,and renal tissue injury was assessed using HE staining.In addition,the contents of malondialde-hyde and glutathione in kidney tissues of SD rats in each group were detected,and the expressions of fer-roptosis markers GPX4 and SLC7A11 were analyzed by Western blot.Results Compared with the control group,CR and BUN in GEN-stimulated group signifi-cantly increased(P＜0.01),and the level of CR and BUN was effectively reduced after 50 mg·kg-1 COR oral administration.HE results also showed that COR could alleviate the kidney tissue damage caused by GEN.COR could reverse the increase of malondialde-hyde level and the decrease of glutathione level caused by GEN in rat kidney tissue,and COR could restore the decrease of GPX4 and SLC7A11 protein levels induced by GEN.Conclusion COR can reduce GEN-induced kidney injury by inhibiting oxidative stress and ferrop-tosis.

Objective:To investigate the anti-heart failure mechanism of N-acetylcysteine(NAC)in diabetic cardiomyop-athy independent from coronary artery factors.Methods:A total of 40 diabetic mice after heart failure model construction were randomly divided into two groups,NAC group(n=20,NAC 100mg·kg-1·d-1)and control group(n=20,Saline 100 mg·kg-1·d-1).Echocardiography was performed to detect left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),mitral left ventricular early-dias-tolic peak flow velocity/left ventricular late-diastolic peak flow velocity(E/A),isovolumic relaxation time(IVRT)and cardiac output(CO)after 4 weeks.Terminal uridine nick-end labeling(TUNEL)was performed to detect apoptosis in-dex,and Western Blot was performed to detect the expression of extracellular regulated protein kinases(ERK)1/2 after 6 weeks in two groups.Results:Compared to those in control group,mice in NAC group had significant higher LVEF[(40.5±3.4)％vs.(36.9±3.2)％],E/A[(1.5±0.1)vs.(1.4±0.1)]and CO[(10.3±0.6)ml/min vs.(9.9±0.5)ml/min](P＜0.05 or＜0.01);and significant lower LVESV[(23.1±1.3)μl vs.(24.7±1.5)μl],apoptosis index[(31.2±0.5)％vs.(45.1±0.9)％]and the expression of ERK1/2[(2.2±0.2)vs.(3.9±0.1)](P＜0.001 all).Conclusion:NAC exerts anti-heart failure effect by attenuating apoptosis of cardiomyocytes via regulating ERK1/2 pathway.

[Purpose]To analyze the compliance and its influencing factors of lung cancer screening using low-dose computed tomography(LDCT)among high-risk population in urban districts of Chongqing from 2013 to 2021.[Methods]The lung cancer screeing of Cancer Early Diagnosis and Treatment Project was conducted among permanent residents aged 40～69 years old from 14 urban districts of Chongqing selected by cluster sampling method from 2013 to 2021.The questionnaire survey was performed to assess the risk level of lung cancer,and individuals with high risk were advised to have LDCT examination.The compliance rate of LDCT examination among high-risk populations was calculated and compared using Chi-square test among residents with different de-mographic features;the influencing factors of compliance was analyzed with generalized linear mixed models.[Results]A total of 316 066 residents completed the risk assessment questionnaire survey,52 858 people were assessed as high-risk(17.17％).Among the high-risk population,20 398 completed LDCT screening,with an overall compliance rate of 38.59％.The generalized linear mixed model showed that male participants(OR=0.871,95％CI:0.823～0.922)and smokers(light smokers:OR=0.829,95％CI:0.775～0.886;heavy smokers:OR=0.842,95％CI:0.792～0.896)had lower compliance rates;while people with higher education level(OR=1.347,95％CI:1.265～1.435),occupational exposure to harmful substances(OR=1.400,95％CI:1.340～1.463),passive smoking for 20 years or more(OR=1.472,95％CI:1.376～1.576),infrequent physical exercise(OR=1.203,95％CI:1.152～1.256),family history of lung cancer(OR=2.312,95％CI:2.201～2.429),and those having media promotion by community staff(OR=1.365,95％CI:1.223～1.524),and trained community staff(OR=1.343,95％CI:1.227～1.470)had higher compliance rates.Comorbidities were also factors influencing compliance,and there was an increasing trend of compliance rate with the increase of comorbidity numbers(P＜0.001).[Conclusion]The compli-ance rate of LDCT examination for lung cancer screening in Chongqing needs to be improved,and more precise health education should be implemented for groups with different characteristics to improve the compliance among high-risk population.

Objective:To analyze the genetic characteristics of the VWF gene c.7332G＞A nonsense mutation and explore its molecular pathogenesis.Methods:Phenotypic diagnosis of the proband was performed using VWF:Ag,VWF:RCo,FⅧ:C and multimeric analysis.The probands were genotyped by NGS whole-exome sequencing,and the sequencing results were validated by sanger sequencing.The family members were genotyped by Sanger sequencing.The VWF gene c.7332G＞A nonsense mutant plasmid was constructed.After transfection,the function of VWF gene c.7332G＞A mutant plasmid was verified at cell level in vitro.The mRNA level was detected by qRT-PCR,and the expression level of protein was detected by Western blot,the function of multimerization was verified by the multimeric analysis.Results:VWF:Ag and VWF:RCo were all less than 3％in the proband,and the multimeric analysis showed multimer deficiency.The proband was diagnosed as type 3 VWD.The homozygous nonsense mutation of VWF gene c.7332G＞A was detected by gene sequencing.The VWF mRNA level of the mutant plasmid was decreased,and the VWF protein expression in the cell supernatant was decreased,the mutant protein was truncated and the function of VWF multimerization was impaired.Conclusion:A homozygous mutation in exon 43 of VWF gene,c.7332G＞A,was responsible for the probands type 3 VWD in the proband.The mutation caused a decrease in the relative level of VWF mRNA and protein,and impaired the function of VWF multimerization.

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide