OBJECTIVE To investigate the effects of ertugliflozin on pharmacokinetic of sorafenib and donafenib in rats and explore the mechanism. METHODS Twenty-four male SD rats were randomly divided into four groups， with 6 rats in each group. Groups A and B were respectively gavaged with 0.5% sodium carboxymethyl cellulose solution and ertugliflozin （1.5 mg/kg） for 7 consecutive days， and both were given sorafenib （100 mg/kg） on the 7th day. Groups C and D were administered intragastrically in the same way as those in Groups A and B， respectively， for the first 7 days； after the drug administration on the 7th day， all rats in Groups C and D were further gavaged with donafenib （40 mg/kg）. Blood samples were collected at different time points before and after administration of sorafenib or donafenib， the concentrations of sorafenib in plasma of rats in groups A and B and donafenib in groups C and D were determined by UPLC-MS/MS method. The pharmacokinetic parameters were calculated by DAS 2.1.1 software. Six additional rats were randomly divided into blank control group and ertugliflozin group， with three rats in each group. Blank control group was given 0.5% sodium carboxymethyl cellulose intragastrically， while rats in ertugliflozin group were given ertugliflozin （1.5 mg/kg） once a day for 7 consecutive days. After the last administration， the mRNA expression levels of uridine diphosphate glucuronosyl transferase 1A7 （UGT1A7）， breast cancer resistance protein （BCRP）， and P-glycoprotein （P-gp） in the liver and small intestine tissues of the rats were detected. RESULTS Compared with group A， the AUC0-t， AUC0-∞， cmax， tmax， MRT0-t and MRT0-∞ of sorafenib in group B were decreased significantly， while CL and V were increased significantly. Compared with group C， the AUC0-t， AUC0-∞ ， tmax， cmax and MRT0-t of Δ donafenib in group D were decreased significantly， while V and CL were increased significantly （P＜0.05）. mRNA expression of UGT1A7， P-gp and BCRP in the liver tissue and small intestine of rats were not significantly affected after intragastric administration of ertugliflozin for 7 consecutive days. CONCLUSIONS Ertugliflozin can affect the pharmacokinetics of sorafenib and donafenib in rats and decrease the plasma exposure of them significantly. However， its mechanism of action may not be through the regulation of related metabolic enzymes and transporters. When using drugs in combination clinically， one should be vigilant about the potential for disease progression due to poor therapeutic effects.

Objective: To design and establish a new method for flow cytometry-based detection of commonly observed highly expressed antigens on red blood cells, and to further evaluate the differences and distribution characteristics of antigen expression levels between ABO blood type homozygotes and heterozygotes in healthy individuals. Methods: Residual blood samples after donor blood type identification by Shanghai Blood Center in April 2024 were collected. Among them, samples of 19 homozygous and 19 heterozygous individuals of type A and type B were selected. Then the expression level of ABO antigen on red blood cells were detected using the new method established in this study and the traditional aldehyde fixed red blood cell method. Both methods were tested independently three times and the results were compared. Results: The mean values of the three detection results of the new method was (×10 /RBC): AA homozygous 3.3±0.5, AO heterozygous 2.8±0.3, BB homozygous 3.6±0.3, BO heterozygous 3.1±2.8. The mean values of the three detection results of the aldehyde fixation method were AA homozygous 5.9±0.9, AO heterozygous 5.0±1.4, BB homozygous 3.8±0.6, and BO heterozygous 3.3±0.4. The average antigen distribution of each genotype followed a normal distribution. Comparing the average antigen expression levels of homozygotes and heterozygotes, both methods showed that A/B homozygotes had higher antigen levels than heterozygotes, with AA being 1.17 to 1.18 times that of AO and BB being 1.15 to 1.16 times that of BO. Comparing the inter batch differences in the three test results of two methods, the new method showed no significant difference in the three test results for four genotypes (P>0.05). The aldehyde fixation method showed significant differences in the test results for all three genotypes (P<0.01) except for BB homozygotes (P>0.05). The reliability and reproducibility of the new method were better than those of the traditional aldehyde fixation method. Conclusion: The antigen expression level of ABO homozygotes is higher than that of heterozygotes, and the difference in antigen level between type A homozygotes and heterozygotes is slightly higher than that of type B. The new method is superior to traditional aldolization fixation methods.

ObjectiveTo investigate the effect of sorafenib and donafenib on the pharmacokinetics of ertugliflozin in rats， and to provide a theoretical basis for drug combination in clinical practice. MethodsA total of 24 male Sprague-Dawley rats were randomly divided into groups A， B， C， and D， with 6 rats in each group. The rats in groups A and B were given sorafenib control solvent and sorafenib （100 mg/kg）， respectively， by gavage for 7 consecutive days， followed by ertugliflozin （1.5 mg/kg） by gavage on day 7. Blood samples were collected from the angular vein plexus at different time points， and ultra-performance liquid chromatography-tandem mass spectrometry was used to determine the mass concentration of ertugliflozin and plot the plasma concentration-time curves， while the non-compartment model in DAS 2.1.1 software was used to calculate related pharmacokinetic parameters. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with group A， group B had significant increases in the AUC_0-t and AUC_0-∞ of the plasma concentration-time curve of ertugliflozin （both P<0.05）， significant prolongation of t_1/2， MRT_0-t， and MRT_0-∞ （all P<0.05）， and a significant reduction in CL_Z/F （P<0.05）. Compared with group C， group D had significant increases in the AUC_0-t and AUC_0-∞ of ertugliflozin （both P<0.05）， significant prolongation of T_max， t_1/2， MRT_0-t， and MRT_0-∞ （all P<0.01）， and significant reductions in V_Z/F and CL_Z/F （both P<0.05）. ConclusionBoth sorafenib and donafenib can affect the pharmacokinetics of ertugliflozin in rats and significantly increase the plasma exposure of ertugliflozin. The efficacy and adverse drug reactions of ertugliflozin should be closely monitored during combined use in clinical practice and the dose should be adjusted when necessary to avoid the potential risk of drug interaction.

Objective: To evaluate the efficacy of the left spermatic vein transposition to the great saphenous vein in treating left varicocele (VC) secondary to nutcracker syndrome (NCS). Methods: Clinical data of 8 patients treated during Feb.2020 and Feb.2023 in our hospital were retrospectively analyzed.A meticulous preoperative evaluation of the vascular status of the spermatic vein and the great saphenous vein was performed using color Doppler ultrasound.A spermatic vein-great saphenous vein shunt surgery was performed in patients who were strictly selected.The clinical symptoms and hemodynamics of renal vein were compared before and after operation. Results: The median age of patients was 23.5(18-33) years.There was a notable reduction in post-exercise scrotal and lower back pain in all patients，and the score of scrotal pain decreased to 0 in 7 patients. The median quantification of urinary protein was 352.8(54.4-687.3) mg prior to surgical intervention，which significantly diminished to 125.5(25.9-255.1) mg 6 months after operation.Notably，3 cases of preoperative positive urine occult blood tests were undetectable in the subsequent postoperative assessments.The median peak blood flow velocity at the site of stenosis in the left renal vein measured at 74.4(48.7-117.6) cm/s preoperatively，subsequently reduced to 45.1(25.5-61.2) cm/s postoperatively.During the 6-month follow-up，no recurrence of varicocele，vascular anastomotic stenosis or thrombosis were observed. Conclusion: Our research indicates that spermatic vein to great saphenous vein bypass is safe and feasible in the treatment of left varicocele secondary to nutcracker syndrome for strictly selected patients，which can effectively alleviate renal vein congestion without significant complications.

ObjectiveTo analyze the clinical characteristics and imaging features of effectively treated pediatric Mycoplasma pneumoniae pneumonia （MPP） with pulmonary consolidation， follow up the volume changes of pulmonary consolidation on lung CT scans of the affected children， and investigate the resolution patterns of pulmonary consolidation， and predict the time required for complete resolution. MethodsWe enrolled children with MPP and pulmonary consolidation hospitalized in the Department of General Pediatrics at Children's Hospital of Chongqing Medical University between January 2018 and May 2024. Data collected included demographics， clinical symptoms， laboratory indicators， treatment status， imaging data during hospitalization， as well as follow-up lung CT data and reexamination intervals after discharge. Consolidation volumes were measured before and after the treatment to calculate the resolution rate and resolution velocity. Descriptive statistical analysis was performed on clinical characteristics， imaging features and consolidation resolution. ResultsAmong 238 children with MPP and lung consolidation， females slightly outnumbered males （the male to female ratio is 109 vs.129）， with a mean age of approximately 5 years. At admission， the median cough and fever durations were 7 （5-9） days and 6 （ 4-7） days， respectively. No significant increase was found in white blood cells count or lactate dehydrogenase（LDH）， and hypersensitive high-sensitivity C-reactive protein （CRP） slightly increased. Azithromycin was the first line of treatment in most cases， though second-line drugs increased in the recent two years due to the rising resistance. Bronchoalveolar lavage was performed in 66.8% （159/238） of children， and 33.2% （79/238） did not receive lavage. Consolidation was predominantly unilateral （206 unilateral vs. 32 bilateral） and right-sided （117 right-sided vs. 89 left-sided）. The ratio of consolidation volume to total lung volume was 4.48 （2.61-7.35） %， the consolidation resolution rate at follow-up was 96.08 （ 88.02-98.95） %， the reexamination interval was 17 （ 15-21） days， the resolution velocity was 2.15 （1.23-4.01） cm³/d， and the time to complete resolution was 18.96 （16.14-23.33） days . ConclusionsPulmonary consolidation in pediatric MPP achieves substantial resolution on CT within 2-3 weeks after effective clinical treatment. Initial consolidation volume and resolution velocity can predict the time required for complete resolution， thereby clinically guiding optimal CT follow-up scheduling.

Background::Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods::We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.Results::In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5) and rural areas (123.0/10 5) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5), the western region had a slightly lower mortality (123.5/10 5), and the eastern region had the lowest mortality (97.3/10 5). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion::The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

Background::T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.Methods::Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.Results::The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4 + T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8 + T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8 + T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. Conclusions::Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

Objective:To analyze the current research status of ideological and political education content in domestic nursing courses and facilitate nursing education reform.Methods:Using purposeful sampling, 25 exemplary cases of ideological and political education in nursing courses from Xinhua Net were selected. NVivo 12 software was employed for content analysis, summarizing the ideological and political elements, carriers of these elements, and types of integration methods in nursing courses.Results:Nursing educators have thoroughly explored ideological and political elements, with the most attention given to professional ethics, though less focus was placed on personality development. A variety of carriers for ideological and political elements were utilized, with practical experience being the most common, but there was a lack of integration with policy and regulations. Various integration methods were applied, with interactive methods being the most frequently used, while practical approaches were less common.Conclusions:Future nursing education should emphasize fostering students' sense of national identity and focus more on personality development. It is important to promote a more balanced use of carriers for ideological and political elements, paying particular attention to policy-related content. The use of information technology in teaching should also be explored to flexibly apply various teaching methods, achieving the subtle integration of ideological and political education within nursing curricula.

Objectives:This study aims to investigate the association between cumulative fasting blood glucose(FBG)and presence of coronary artery calcification(CAC). Methods:A total of 1 113 participants were recruited from the Beijing Community-based Cohort of Atherosclerosis.Anthropometric measurements and laboratory examinations including FBG were performed in 1998,2008-2009 and 2013-2014 respectively,and coronary CT scan was performed in 2013-2014.Participants were classified into 4 groups according to the level of cumulative FBG(10-year weighted cumulative value of at least 2 FBGs):<50.0 mmol/L group(n=495),50.0-55.9 mmol/L group(n=345),56.0-69.9 mmol/L group(n=176),and≥70.0 mmol/L group(n=97).CAC score>0 was defined as presence of CAC.Multivariable logistic regression model was applied to analyze the impact of cumulative FBG exposure on the risk of CAC,and subgroup analyses were conducted according to factors such as sex and age. Results:The mean age of enrolled participants was(59.7±6.4)years,523(47.0%)were male and 478(42.9%)had CAC.The proportion of subjects with CAC increased with the increment of cumulative FBG.Compared with the<50.0 mmol/L group,the multivariable-adjusted OR(95%CI)for CAC in the 50.0-55.9 mmol/L group,56.0-69.9 mmol/L group,and≥70.0 mmol/L group were 1.43(1.04-1.98),1.92(1.24-2.99)and 2.79(1.35-5.77),respectively(Ptrend<0.05).The risk for CAC increased by 34%per 10 mmol/L increase in cumulative FBG,with OR(95%CI)of 1.34(1.12-1.59).There was no statistically significant difference in the risk of CAC presence for each 10 mmol/L increase in cumulative FBG level between the subgroups(all P≥0.05). Conclusions:Elevated cumulative FBG is a risk factor for the prevalence of CAC,indicating the importance of maintaining healthy FBG in preventing the occurrence of CAC.

Objective:To explore chromosomal copy number variations (CNVs) and pregnancy outcomes in fetuses with mild to moderate isolated ventriculomegaly (IVM), but without other indications for invasive prenatal diagnosis.Methods:A retrospective analysis was conducted on clinical data of 215 singleton pregnancies with mild to moderate IVM (lateral ventricular width≥10-<15 mm) who underwent chromosomal microarray analysis (CMA), not indicated by advanced age, high risk in serum screening or abnormal history of pregnancy, at the Fujian Maternity and Child Health Hospital between June 2016 and March 2023. The 215 fetuses were grouped into mild ( n=167) and moderate ( n=48) IVM;unilateral ( n=142) and bilateral ( n=73) IVM; first diagnosis of IVM before 28 weeks ( n=138) and thereafter ( n=77). Anomalies other than IVM were excluded via three-dimensional color Doppler ultrasound examination between 22 and 26 weeks of gestation. Out of these cases, 129 were confirmed by fetal cranial MRI, 191 underwent chromosomal karyotype analysis, and 202 cases received cytomegalovirus DNA quantification test for amniotic fluid. The detection rates of pathogenic CNVs in various groups were compared using Fisher's exact test. Results:Among the 215 fetuses, 11 cases (5.1%) of chromosomal abnormalities were detected through CMA, including one trisomy 21, five pathogenic CNVs, and five CNVs of uncertain clinical significance. Within the pathogenic CNVs, there were two de novo mutations with 16p11.2 microdeletion and one de novo mutation with 16p11.2 microduplication, while one 16p11.2 microduplication and one Xp22.31 microdeletion were inherited maternally. Of the CNVs of uncertain significance, there were two 16p13.11 microduplications, each inherited from a different parent, one paternally and one maternally; meanwhile, family validation was refused in the other three cases with 3p22.1 microdeletion, 3p26.3 microdeletion, and 9q21.33q22.31 microduplication. The detection rate of pathogenic CNVs in the moderate IVM group was higher than that in the mild IVM group [6.3% (3/48) vs. 1.2% (2/167)], but the difference was not statistically significant ( P=0.083). Similarly, no significant difference was found in the detection rate of pathogenic CNVs when comparing the unilateral IVM group [2.1% (3/142)] with the bilateral IVM group [2.7% (2/73)], nor between the group diagnosed with VM before 28 weeks gestation [2.2% (3/138)] and that diagnosed ≥28 weeks [2.6% (2/77)] (both P>0.05). After the exclusion of fetuses with chromosomal pathogenic abnormalities ( n=11), cytomegalovirus infection( n=1), and additional ultrasound anomalies ( n=7), and several cases with missing data intrauterine outcomes were followed up in 169 IVM fetuses, including 104 (61.5%) improved, 60 (35.5%) unchanged, and five (3.0%) progressed. Follow-ups were successful for 194 women, of which eight pregnancies were terminated (including one trisomy 21, four pathogenic CNVs, one fetal cytomegalovirus infection, and two progressed to severe IVM). Among the 186 newborns, one was diagnosed with X-linked ichthyosis, and one child who progressed to severe IVM before born was followed until 20 months of age without notable phenotypic abnormalities. The rest 184 babies, including those with CNVs of uncertain clinical significance, exhibited no developmental abnormalities during follow-up between the ages of three months and six years. Conclusions:For those fetuses with isolated mild to moderate IVM, but without indications for prenatal diagnosis such as advanced maternal age, high risk in serum screening or abnormal history of pregnancy, remain having the risk for chromosomal aberrations, and 16p11.2 microdeletion/microduplication might be a frequent CNV associated with this condition. Aside from those with pathogenic chromosomal aberrations, fetal cytomegalovirus infection, or progressive enlargement of the lateral ventricles, most fetuses with isolated mild to moderate IVM have a good prognosis.