Objectives:To explore the relationship between carboxymethyl lysine (CML) and type 2 diabetes (T2DM) with myopenia, so as to provide some clinical reference for clinical prevention and early intervention of myopenia.Methods:A case-control study was conducted, selecting 142 T2DM patients admitted to the Endocrinology Department of the Affiliated Hospital of North China University of Science and Technology from November 2022 to November 2023. According to the diagnostic criteria of the 2019 consensus of experts on the diagnosis and treatment of sarcopenia, the patients were divided into a case group (T2DM with sarcopenia, 58 cases) and a control group (T2DM without sarcopenia, 84 cases). Collect and compare general information, serological data, and body composition data of two groups of patients. Two independent sample t-test is used for inter group comparison of metric data that conforms to normal distribution; Non parametric tests are used for inter group comparisons of non normally distributed quantitative data; The comparison of count data between groups is conducted using χ2 test. Multivariate logistic regression analysis was used to analyze the relationship between carboxymethyl lysine and type 2 diabetes with myopenia. Draw receiver operating characteristic (ROC) curves and analyze the efficacy of carboxymethyllysine in diagnosing T2DM with muscle atrophy. Results:Univariate analysis showed the BMI ((21.59±3.04) kg/m 2), FINS (4.49 (1.85,9.03) U/L), and FCP ((1.45±0.96) mg/L) levels of the patients in the case group were lower than those in the control group(27.32±3.74) kg/m 2, 6.91 (3.74, 11.99) U/L, (2.64±1.23) mg/L), while age, ((64.67±6.75) years old) of disease duration(12.16±6.69) years, and CML (5.70±2.14 μg/L) were higher than those in the control group ((62.23±7.33) years old, (8.70±8.01) years, (2.38±0.73) μg/L), and the differences were statistically significant (Statistical values were t=9.66, Z=2.86, t=6.46, t=2.02, t=2.70, t=13.17; P values were <0.001, 0.004, <0.001, 0.046, 0.008, <0.001). Multifactorial binary logistic regression analysis showed that CML ( OR(95%CI):3.242 (1.933-5.437)) and BMI ( OR(95%CI):0.636 (0.505-0.801)) were associated with T2DM combined with sarcopenia (all P<0.001). The results of the ROC curve showed that the area under the curve (AUC) of CML was 0.934, and the corresponding optimal cut-off value was 3.038 μg/L. The diagnostic efficacy of CML for the diagnosis of T2DM combined with myasthenia gravis was high, and the diagnostic results were in good agreement with the actual results. Conclusions:Carboxymethyl lysine is associated with T2DM combined with muscle atrophy. CML has a high diagnostic efficacy in diagnosing T2DM combined with muscle atrophy, and it has certain practical value in diagnosing T2DM combined with muscle atrophy.

AIM:To investigate the potential mechanisms by which cell division cycle protein 42(Cdc42)regulates endothelial-mesenchymal transition(EndMT)in pulmonary hypertension(PH).METHODS:The pulmonary hypertension(PH)model was established using Sugen-5416 combined with hypoxia.Twenty-four C57BL/6 mice were ran-domly divided into four groups:normoxia control(CON)group,normoxia+ML141(CON+ML141)group,Sugen-5416+hypoxia(SuHx)group,and SuHx+ML141 group,with 6 mice in each group.After 4 weeks,right ventricular systolic pressure(RVSP)and cardiac ultrasound parameters were measured,and lung tissues were collected for immunofluores-cence staining.Pulmonary microvascular endothelial cells(PMVECs)were isolated using magnetic bead sorting.Calcium imaging was performed to assess Ca2+signaling,and Western blot was used to detect EndMT-related proteins as well as stromal interaction molecule 1(STIM1)and Orai1 expression.RESULTS:In the SuHx group,mice exhibited signifi-cantly increased RVSP,Fulton index(right ventricle/left ventricle+septum),end-diastolic right ventricular free wall thick-ness(RVEDWT),and end-systolic right ventricular free wall thickness(RVESWT)(P<0.01).Conversely,pulmonary artery acceleration time/pulmonary artery ejection time(PAT/PET)and tricuspid annulus plane systolic excursion(TAPSE)were significantly reduced(P<0.01).The Cdc42 inhibitor ML141 ameliorated these changes.The SuHx group exhibited a significant decrease in CD31 fluorescence intensity in pulmonary vascular endothelial cells(P<0.01),a marked increase in α-smooth muscle actin(α-SMA)fluorescence intensity in smooth muscle cells(P<0.01),and the emergence of CD31/α-SMA co-localization.These alterations were reversed by ML141.Hypoxia induced EndMT in PM-VECs,characterized by decreased CD31 and vascular endothelial cadherin(VE-cadherin)along with increased α-SMA and vimentin(P<0.01),which was suppressed by ML141(P<0.01).Hypoxia activated store-operated calcium entry(SOCE),enhancing intracellular Ca2? release,extracellular Ca2? influx,and basal Ca2? levels(P<0.01),while upregulat-ing STIM1 and Orai1 expression(P<0.01).These changes were reversed by ML141.Furthermore,both ML141 and STIM1 knockdown inhibited the upregulation of EndMT-related transcription factors Snail and Twist(P<0.05).CON-CLUSION:Cdc42 may participate in EndMT in PH by regulating store-operated calcium channels in pulmonary microvas-cular endothelial cells.

Objective:To investigate the effect of atosiban on hemodynamic parameters of uterine arteries and clinical effect evaluation in patients with previous implantation failure undergoing frozen-thawed embryo transfer.Methods:A retrospective cohort study was conducted to analyze 298 cycles of FET in the Department of Reproductive Medicine of the Second Affiliated Hospital of Zhengzhou University from January 2021 to June 2023. Patients were categorized into atosiban group ( n=149) and control group ( n=149) according to whether administered atosiban or not. The related indicators and clinical outcomes were compared between the two groups. Hemodynamic parameters of the uterine arteries, including bilateral uterine artery peak systolic velocity/diastolic velocity (S/D), pulsatility index (PI), resistance index (RI), and serum levels of prostaglandin F2α (PGF2α) and oxytocin were compared before and after atosiban treatment. Univariate and multivariate logistic regression analysis were applied to assess the effect of atosiban on pregnancy outcomes. The effect of atosiban on live birth rate was analyzed by age stratification. Results:The implantation rate [51.92% (135/260)], the clinical pregnancy rate [67.11% (100/149)] and the live birth rate [59.06% (88/149)] in atosiban group were significantly higher than those in control group [41.13% (102/248), P=0.015; 51.01% (76/149), P=0.005; 40.27% (60/149), P=0.001]; and the early miscarriage rate [9.00% (9/100)] was lower than that of control group [19.74% (15/76), P=0.040]. Multivariate logistic regression analysis showed that atosiban was an independent influencing factor of live birth rate ( OR=2.236, 95% CI: 1.371-3.646, P=0.001). The post-treatment right uterine artery blood flow S/D [4.61 (4.00, 5.36)], PI [1.81 (1.58, 2.05)], RI [0.79 (0.75, 0.82)], and left uterine artery blood flow S/D [4.62 (3.83, 5.61)], PI (1.84±0.38), RI [0.79 (0.74, 0.82)] were all lower than those before treatment [right S/D 4.93 (4.06, 6.04), P<0.001; PI 1.93 (1.60, 2.17), P=0.001; RI 0.80 (0.76, 0.83), P<0.001; left S/D 5.05 (4.20, 6.32), P<0.001; PI 1.95±0.43, P<0.001; RI 0.81 (0.76, 0.84), P<0.001]. Besides, the levels of PGF2α [97.01 (85.15, 109.93) ng/L] and oxytocin [41.18 (37.16, 46.78) ng/L] after treatment in atosiban group were significantly lower than those before treatment [119.71 (108.85, 129.99) ng/L, P<0.001; 51.87 (46.44, 55.54) ng/L, P<0.001). Moreover, the endometrial peristalsis waves in atosiban group were significantly less after treatment [1.00 (0.00, 2.00) times/min] than before treatment [2.00 (1.00, 3.00) times/min], and the difference was statistically significant ( P<0.001). Conclusion:Atosiban can improve uterine artery blood flow and reduce endometrial peristalsis waves in women with previous implantation failure, which increases endometrial blood perfusion. Additionally, it can also reduce the levels of PGF2α and oxytocin, and optimize the pregnancy outcome of the frozen-thawed embryo transfer.

Objective:To explore the relationship between life events, anxiety, depression, and behavior problems in adolescents.Methods:From September to October 2022, the cluster sampling method was used to select 5 341 adolescents from 4 middle schools in Xinxiang urban area.The subjects and their parents were investigated by the adolescent self-rating life events check list (ASLEC), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and child behavior checklist (CBCL). SPSS 27.0 software was used for Spearman correlation analysis, and AMOS 28.0 software was used to construct the structural equation model.Results:The scores of anxiety, depression, and behavioral problems were 1 (0, 4), 1 (0, 4), and 3 (0, 10). The total score of life events was 5 (1, 13), and the dimensions scored as follows: interpersonal conflict 1 (0, 4), academic pressure 2 (0, 5), punishment 0 (0, 2), loss 0 (0, 0), health and adaptation problem 0 (0, 1), and others 0 (0, 2). There were positive correlations between life events and its dimensions, depression, anxiety and behavioral problems ( r=0.28-0.69, all P<0.01). In the overall population, anxiety and depression played parallel mediating roles in the impact of life events on behavior problems. Life events could positively predict anxiety ( β=0.68, P<0.01), and anxiety could positively predict behavior problems ( β=0.04, P=0.02). Life events could positively predict depression ( β=0.77, P<0.01), and depression could positively predict behavior problems ( β=0.18, P<0.01). The standardized total effect size of the impact of life events on behavioral problems was 0.622 (95% CI=0.564-0.675). The standardized direct effect size and indirect effect size were 0.460 (95% CI=0.374-0.539) and 0.162 (95% CI=0.108-0.218), accounting for 74.0% and 26.0%of the total effect, respectively. After stratification by gender, the results for male adolescents were consistent with the overall population, while the mediating effect of anxiety was not significant in the female adolescents. Conclusion:Life events can lead to anxiety and depression in adolescents, thereby increasing the risk of behavior problems.

AIM:To investigate the potential mechanisms by which cell division cycle protein 42(Cdc42)regulates endothelial-mesenchymal transition(EndMT)in pulmonary hypertension(PH).METHODS:The pulmonary hypertension(PH)model was established using Sugen-5416 combined with hypoxia.Twenty-four C57BL/6 mice were ran-domly divided into four groups:normoxia control(CON)group,normoxia+ML141(CON+ML141)group,Sugen-5416+hypoxia(SuHx)group,and SuHx+ML141 group,with 6 mice in each group.After 4 weeks,right ventricular systolic pressure(RVSP)and cardiac ultrasound parameters were measured,and lung tissues were collected for immunofluores-cence staining.Pulmonary microvascular endothelial cells(PMVECs)were isolated using magnetic bead sorting.Calcium imaging was performed to assess Ca2+signaling,and Western blot was used to detect EndMT-related proteins as well as stromal interaction molecule 1(STIM1)and Orai1 expression.RESULTS:In the SuHx group,mice exhibited signifi-cantly increased RVSP,Fulton index(right ventricle/left ventricle+septum),end-diastolic right ventricular free wall thick-ness(RVEDWT),and end-systolic right ventricular free wall thickness(RVESWT)(P<0.01).Conversely,pulmonary artery acceleration time/pulmonary artery ejection time(PAT/PET)and tricuspid annulus plane systolic excursion(TAPSE)were significantly reduced(P<0.01).The Cdc42 inhibitor ML141 ameliorated these changes.The SuHx group exhibited a significant decrease in CD31 fluorescence intensity in pulmonary vascular endothelial cells(P<0.01),a marked increase in α-smooth muscle actin(α-SMA)fluorescence intensity in smooth muscle cells(P<0.01),and the emergence of CD31/α-SMA co-localization.These alterations were reversed by ML141.Hypoxia induced EndMT in PM-VECs,characterized by decreased CD31 and vascular endothelial cadherin(VE-cadherin)along with increased α-SMA and vimentin(P<0.01),which was suppressed by ML141(P<0.01).Hypoxia activated store-operated calcium entry(SOCE),enhancing intracellular Ca2? release,extracellular Ca2? influx,and basal Ca2? levels(P<0.01),while upregulat-ing STIM1 and Orai1 expression(P<0.01).These changes were reversed by ML141.Furthermore,both ML141 and STIM1 knockdown inhibited the upregulation of EndMT-related transcription factors Snail and Twist(P<0.05).CON-CLUSION:Cdc42 may participate in EndMT in PH by regulating store-operated calcium channels in pulmonary microvas-cular endothelial cells.

Objective:To investigate the effect of atosiban on hemodynamic parameters of uterine arteries and clinical effect evaluation in patients with previous implantation failure undergoing frozen-thawed embryo transfer.Methods:A retrospective cohort study was conducted to analyze 298 cycles of FET in the Department of Reproductive Medicine of the Second Affiliated Hospital of Zhengzhou University from January 2021 to June 2023. Patients were categorized into atosiban group ( n=149) and control group ( n=149) according to whether administered atosiban or not. The related indicators and clinical outcomes were compared between the two groups. Hemodynamic parameters of the uterine arteries, including bilateral uterine artery peak systolic velocity/diastolic velocity (S/D), pulsatility index (PI), resistance index (RI), and serum levels of prostaglandin F2α (PGF2α) and oxytocin were compared before and after atosiban treatment. Univariate and multivariate logistic regression analysis were applied to assess the effect of atosiban on pregnancy outcomes. The effect of atosiban on live birth rate was analyzed by age stratification. Results:The implantation rate [51.92% (135/260)], the clinical pregnancy rate [67.11% (100/149)] and the live birth rate [59.06% (88/149)] in atosiban group were significantly higher than those in control group [41.13% (102/248), P=0.015; 51.01% (76/149), P=0.005; 40.27% (60/149), P=0.001]; and the early miscarriage rate [9.00% (9/100)] was lower than that of control group [19.74% (15/76), P=0.040]. Multivariate logistic regression analysis showed that atosiban was an independent influencing factor of live birth rate ( OR=2.236, 95% CI: 1.371-3.646, P=0.001). The post-treatment right uterine artery blood flow S/D [4.61 (4.00, 5.36)], PI [1.81 (1.58, 2.05)], RI [0.79 (0.75, 0.82)], and left uterine artery blood flow S/D [4.62 (3.83, 5.61)], PI (1.84±0.38), RI [0.79 (0.74, 0.82)] were all lower than those before treatment [right S/D 4.93 (4.06, 6.04), P<0.001; PI 1.93 (1.60, 2.17), P=0.001; RI 0.80 (0.76, 0.83), P<0.001; left S/D 5.05 (4.20, 6.32), P<0.001; PI 1.95±0.43, P<0.001; RI 0.81 (0.76, 0.84), P<0.001]. Besides, the levels of PGF2α [97.01 (85.15, 109.93) ng/L] and oxytocin [41.18 (37.16, 46.78) ng/L] after treatment in atosiban group were significantly lower than those before treatment [119.71 (108.85, 129.99) ng/L, P<0.001; 51.87 (46.44, 55.54) ng/L, P<0.001). Moreover, the endometrial peristalsis waves in atosiban group were significantly less after treatment [1.00 (0.00, 2.00) times/min] than before treatment [2.00 (1.00, 3.00) times/min], and the difference was statistically significant ( P<0.001). Conclusion:Atosiban can improve uterine artery blood flow and reduce endometrial peristalsis waves in women with previous implantation failure, which increases endometrial blood perfusion. Additionally, it can also reduce the levels of PGF2α and oxytocin, and optimize the pregnancy outcome of the frozen-thawed embryo transfer.

Objective:To explore the relationship between life events, anxiety, depression, and behavior problems in adolescents.Methods:From September to October 2022, the cluster sampling method was used to select 5 341 adolescents from 4 middle schools in Xinxiang urban area.The subjects and their parents were investigated by the adolescent self-rating life events check list (ASLEC), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and child behavior checklist (CBCL). SPSS 27.0 software was used for Spearman correlation analysis, and AMOS 28.0 software was used to construct the structural equation model.Results:The scores of anxiety, depression, and behavioral problems were 1 (0, 4), 1 (0, 4), and 3 (0, 10). The total score of life events was 5 (1, 13), and the dimensions scored as follows: interpersonal conflict 1 (0, 4), academic pressure 2 (0, 5), punishment 0 (0, 2), loss 0 (0, 0), health and adaptation problem 0 (0, 1), and others 0 (0, 2). There were positive correlations between life events and its dimensions, depression, anxiety and behavioral problems ( r=0.28-0.69, all P<0.01). In the overall population, anxiety and depression played parallel mediating roles in the impact of life events on behavior problems. Life events could positively predict anxiety ( β=0.68, P<0.01), and anxiety could positively predict behavior problems ( β=0.04, P=0.02). Life events could positively predict depression ( β=0.77, P<0.01), and depression could positively predict behavior problems ( β=0.18, P<0.01). The standardized total effect size of the impact of life events on behavioral problems was 0.622 (95% CI=0.564-0.675). The standardized direct effect size and indirect effect size were 0.460 (95% CI=0.374-0.539) and 0.162 (95% CI=0.108-0.218), accounting for 74.0% and 26.0%of the total effect, respectively. After stratification by gender, the results for male adolescents were consistent with the overall population, while the mediating effect of anxiety was not significant in the female adolescents. Conclusion:Life events can lead to anxiety and depression in adolescents, thereby increasing the risk of behavior problems.

Objectives:To explore the relationship between carboxymethyl lysine (CML) and type 2 diabetes (T2DM) with myopenia, so as to provide some clinical reference for clinical prevention and early intervention of myopenia.Methods:A case-control study was conducted, selecting 142 T2DM patients admitted to the Endocrinology Department of the Affiliated Hospital of North China University of Science and Technology from November 2022 to November 2023. According to the diagnostic criteria of the 2019 consensus of experts on the diagnosis and treatment of sarcopenia, the patients were divided into a case group (T2DM with sarcopenia, 58 cases) and a control group (T2DM without sarcopenia, 84 cases). Collect and compare general information, serological data, and body composition data of two groups of patients. Two independent sample t-test is used for inter group comparison of metric data that conforms to normal distribution; Non parametric tests are used for inter group comparisons of non normally distributed quantitative data; The comparison of count data between groups is conducted using χ2 test. Multivariate logistic regression analysis was used to analyze the relationship between carboxymethyl lysine and type 2 diabetes with myopenia. Draw receiver operating characteristic (ROC) curves and analyze the efficacy of carboxymethyllysine in diagnosing T2DM with muscle atrophy. Results:Univariate analysis showed the BMI ((21.59±3.04) kg/m 2), FINS (4.49 (1.85,9.03) U/L), and FCP ((1.45±0.96) mg/L) levels of the patients in the case group were lower than those in the control group(27.32±3.74) kg/m 2, 6.91 (3.74, 11.99) U/L, (2.64±1.23) mg/L), while age, ((64.67±6.75) years old) of disease duration(12.16±6.69) years, and CML (5.70±2.14 μg/L) were higher than those in the control group ((62.23±7.33) years old, (8.70±8.01) years, (2.38±0.73) μg/L), and the differences were statistically significant (Statistical values were t=9.66, Z=2.86, t=6.46, t=2.02, t=2.70, t=13.17; P values were <0.001, 0.004, <0.001, 0.046, 0.008, <0.001). Multifactorial binary logistic regression analysis showed that CML ( OR(95%CI):3.242 (1.933-5.437)) and BMI ( OR(95%CI):0.636 (0.505-0.801)) were associated with T2DM combined with sarcopenia (all P<0.001). The results of the ROC curve showed that the area under the curve (AUC) of CML was 0.934, and the corresponding optimal cut-off value was 3.038 μg/L. The diagnostic efficacy of CML for the diagnosis of T2DM combined with myasthenia gravis was high, and the diagnostic results were in good agreement with the actual results. Conclusions:Carboxymethyl lysine is associated with T2DM combined with muscle atrophy. CML has a high diagnostic efficacy in diagnosing T2DM combined with muscle atrophy, and it has certain practical value in diagnosing T2DM combined with muscle atrophy.

Objective To explore the factors influencing enteral nutrition intolerance in critically ill patients and to develop a risk prediction model to provide medical staff with a tool for early identification of patient intolerance.Methods Domestic and international databases such as CNKI,PubMed and Web of Science were searched and supplemented by searching references and grey literature.The search period was from inception to November 2022.Data were independently screened and extracted by 2 systematically trained researchers,and the quality of the literature was evaluated.Meta-analysis was performed using Review Manager 5.4 software.The OR value of the comprehensive effect of the factors was taken as the coefficient of each factor in the formula,and the natural logarithm of the ratio of intolerance incidence and non-incidence was the constant term of the formula.From December 2022 to June 2023,360 patients who met the inclusion and exclusion criteria in the ICU of a tertiary hospital were collected as a model verification group by convenient sampling method,and the collected clinical data were substituted into the formula to evaluate the discrimination and calibration of the model.Results A total of 13 articles were included.7 influencing factors with more than 3 times of reports and statistically significant results were obtained.For age[OR=0.97,95％CI(0.94,0.99),P=0.010],Acute Physiology and Chronic Health Evaluation scoreⅡ[OR=1.17,95％CI(1.01,1.36),P=0.040],comorbidity with diabetes[OR=1.21,95％CI(1.05,1.40),P=0.008],comor-bidity with neurological diseases[OR=0.85,95％CI(0.74,0.98),P=0.020],mechanical ventilation[OR=3.21,95％CI(1.82,5.66),P＜0.001],using sedative analgesics[OR=2.27,95％CI(1.66,3.10),P＜0.001],using gastric motility drugs[OR=0.23,95％CI(0.15,0.36),P＜0.001].The incidence of enteral nutrition intolerance was 35.00％.The risk prediction model for enteral nutrition intolerance in critically ill patients was logit(P)=-0.619-0.031×age+0.157 × APACHE Ⅱ+0.191 ×comorbidity with diabetes-0.163 ×comorbidity with neurosurgery+0.820 ×using sedatives and analgesics+1.166×mechanical ventilation-1.470×using gastric dynamic drugs.The area under the receiver operating characteristic curve of the model was 0.864.The maximum Youden index was 0.589.The sensitivity was 0.922.The specificity was 0.667.The corresponding clinical diagnostic threshold was 0.536.Hosmer-Leme-show test x2=13.410,P=0.098.Brier score was 0.195.Conclusion The risk prediction model of enteral nutrition intolerance in critically ill patients based on large sample evidence-based medicine is universal,scientific and practical.It provides a tool for medical staff to identify patients with enteral nutrition feeding intolerance in ICU.

Based on the isolation and identification of Nosema ceranae(N.ceranae)in honeybees,this study optimized the synthesis method of nano-FeS derived from albumen and explored in vitro and in vivo antifungal effects against N.ceranae.Pathogens were isolated from infected honeybee colonies and identified as N.ceranae using morphological and molecular biology techniques.In vitro experiments were conducted to confirm the antifungal effects of nano-FeS against N.ceranae and elucidate the mechanism.In vivo experiments were carried out to validate the therapeutic effects of nano-FeS against N.ceranae infection.Nano-FeS was synthesized using the solvothermal method with an optimal scheme determined through orthogonal experiments,with an average par-ticle size of 75 nm.Flow cytometry and fluorescence staining experiments confirmed that nano-FeS induced apoptosis and necrosis in N.ceranae.After N.ceranae was exposed to nano-FeS,intracellu-lar iron accumulation,disruption of the glutathione and glutathione peroxidase antioxidant system,and subsequent ROS accumulation were observed,ultimately leading to lipid peroxidation of cell membranes.In vivo experiments demonstrated reduced mortality and decreased spore counts in the midgut of honeybees fed with nano-FeS.Transcriptome analysis and qPCR revealed the impact of nano-FeS on gene expression in the N.ceranae infected honeybee midgut.This study presented a promising alternative antifungal agent for N.ceranae infection in honeybees and elucidated the an-tifungal mechanism of nano-FeS related to ferroptosis.Additionally,the study found a positive cor-relation between the mass concentration of nano-FeS and its antifungal effectiveness against N.ceranae.