OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

Objective To explore the effects of physical activity(PA)on carotid intima-media thickness(CIMT)thickening in patients with type 2 diabetes mellitus(T2DM)with poor HbA1c control.Methods A total of 2505 T2DM inpatients with poor HbA1c control who visited the Endocrinology Department of the Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Traditional Chinese Medicine and Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2019 to February 2022 were enrolled in this study.The patients were categorized into the mild-intensity PA(1～599 MET-min/w,n=795),moderate-intensity PA(600～1499 MET-min/w,n=1107)and high-intensity PA(≥1500 MET-min/w,n=603)based on the metabolic equivalence level(MET).Logistic regression was performed to analyze the relationship between PA and CIMT thickening.Statified analysis was used to investigate the effects of blood pressure(BP)and low-density lipoprotein cholesterol(LDL-C)target status on CIMT thickness in different PA groups.Results Restricted cubic spline plots showed a nonlinear relationship between PA levels and the risk of CIMT thickening(P<0.05).Logistic regression showed that with moderate-intensity PA as the control,while high-intensity PA was the influence factor of CIMT thickening(OR 1.581,95%CI 1.244～2.010,P<0.05).Statified analyses showed that under mild-intensity PA,using neither BP nor LDL-C on target as reference,achievement of either index and both were the influence factor of CIMT thickening.Using BP on target as reference,achievements of both indexes,achievements of neither of both indexes,and achievement of LDL-C only were the influence factor of CIMT thickening.Using LDL-C on target as reference,achievement of neither of them and achievement of BP only were the influence factor of CIMT thickening.Under high-intensity PA,achievement of both indexes was negatively associated with CIMT thickening.Conclusions Moderate-intensity PA is the recommended scheme to prevent CIMT thickening in T2DM patients whose HbA1c is not up to standard.Mild-intensity PA is not related to the risk of CIMT thickening,while high-intensity PA is positively related to the risk of CIMT thickening,and focusing on LDL-C compliance is particularly important to avoid CIMT thickening.

Objective:To investigate the diagnostic value of umbilical cord blood lactic acid and base excess for multi-organ dysfunction following neonatal asphyxia.Methods:A retrospective analysis was conducted on the clinical data of 244 patients at high risk for perinatal asphyxia who received treatment at Dongyang People's Hospital from January 2021 to December 2023.Based on the presence of organ dysfunction, the infants were divided into three groups: a single organ dysfunction group (Group A, n = 55), a multi-organ dysfunction group (Group B, n = 16), and a no organ dysfunction group (Group C, n = 173). Lactic acid levels and base excess values were compared among the three groups. Receiver operating characteristic curves were used to validate the predictive value of lactic acid and base excess values for organ dysfunction. Results:There were no statistically significant differences in general data among the three groups ( P > 0.05). In Group B, the lactic acid level was 15.10 (13.85, 16.83) mmol/L, and the base excess value was 9.80 (6.65, 15.18) mmol/L. In Group A, the lactic acid level was 7.70 (6.25, 11.70) mmol/L, and the base excess value was 5.70 (3.85, 9.60) mmol/L. In Group C, the lactic acid level was 6.80 (4.30, 9.00) mmol/L, and the base excess value was 4.00 (3.00, 6.50) mmol/L. The lactic acid level and base excess value in Group B were significantly higher than those in both Group A and Group C. Additionally, the lactic acid level and base excess value in Group A were significantly greater than those in Group C ( t = 2.60, 20.19, 2.95, 1.92, all P < 0.05). Receiver operating characteristic curve analysis revealed that the combined assessment of base excess value and lactic acid level was more effective than evaluating each parameter individually in predicting the presence of organ damage and multiple organ dysfunction syndrome. Additionally, the detection of base excess value was found to be superior to the measurement of lactic acid level. The areas under the curve values for the combined assessment of base excess value and lactic acid level for the presence of organ damage and multiple organ dysfunction syndrome were 0.694 and 0.856, respectively. In comparison, the AUC values for base excess value detection were 0.678 and 0.846, while the AUC values for lactic acid level measurement were 0.633 and 0.797, respectively. Conclusions:Umbilical cord blood lactic acid and base excess are correlated with organ dysfunction following neonatal asphyxia, and both parameters have clinical value in assessing organ damage.

OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

Objective:To investigate the correlations among diabetes-related distress, self-management behavior, empowerment, and glycated hemoglobin (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM) .Methods:A convenience sampling method was used to recruit a total of 1 927 hospitalized patients with T2DM from the Endocrinology Departments of five tertiary general hospitals in Hainan, Jiangsu, and Henan Provinces between December 2022 and December 2023. General demographic and clinical data were collected. The Problem Areas in Diabetes 5 (PAID-5), the Summary of Diabetes Self Care Activities (SDSCA), and the Diabetes Empowerment Scale-Short Form (DES-SF) were used to evaluate patients' psychological distress, self-management behaviors, and empowerment levels. Pearson correlation analysis was performed to examine the relationships among diabetes-related distress, empowerment, self-management behaviors, and HbA1c levels.Results:Pearson correlation analysis showed that diabetes-related distress was negatively correlated with empowerment ( r=-0.119, P<0.001) and the total score of self-management behavior ( r=-0.106, P<0.001), and positively correlated with HbA1c levels ( r=0.103, P<0.001). Empowerment was positively correlated with self-management behavior ( r=0.538, P<0.001) and negatively correlated with HbA1c levels ( r=-0.170, P<0.001). Self-management behavior was negatively correlated with HbA1c levels ( r=-0.165, P<0.001) . Conclusions:Diabetes-related distress, empowerment, and self-management behavior are all associated with glycemic control. Future research and interventions should focus on enhancing patients' self-management abilities, strengthening empowerment, and providing psychological support in order to improve glycemic outcomes and offer a more comprehensive and effective management approach for patients with T2DM.

Objective:To analyze the clinical and genetic features of four children with pediatric acute liver failure (PALF) caused by neuroblastoma-amplified sequence ( NBAS) gene variant, as well as the correlation between clinical phenotype and genotype. Methods:The clinical data and genetic test results of four children with NBAS gene variants admitted to the Department of Gastroenterology, Children's Hospital Affiliated to Zhejiang University School of Medicine from August 2015 to June 2023 mainly presenting with pediatric acute liver failure (PALF) were retrospectively analyzed. The relevant literature from January 2015 to May 2024 was retrieved using the Chinese and English keywords " NBAS," "neuroblastoma amplified sequence," "SOPH," "short stature with optic nerve atrophy and Pelger Hu?t anomaly," "liver failure," and "neuroblastoma amplified sequence" indexed in the CNKI database, Wanfang Data Knowledge Service Platform, and PubMed database. The clinical features and gene mutation characteristics of domestic patients were summarized. Results:The age at which the initial PALF attack occurred in the four children varied from eight months to three years and seven months. All patients developed PALF within 1-2 days after the onset of fever, with symptoms such as vomiting, convulsions, and mental depression or confusion, accompanied by a sharp increase in transaminases, elevated bilirubin and blood ammonia, hyperlactatemia, and hepatomegaly. The PALF gradually improved, and three pediatric patients showed extrahepatic manifestations following antipyretic, fluid replacement, and other symptomatic supportive treatment. Long-term follow-up showed that active temperature control and symptomatic therapy reduced the recurrence of PALF. Genetic testing identified eight kinds of NBAS gene variants sites. Family testing validated compound heterozygous variants, which included four missense variants, one nonsense variants, and three frameshift mutations. A literature study revealed that out of 51 Chinese patients with NBAS gene variants, 98.0% (50/51) had liver involvement, and 37 cases showed PALF. A total of 61 mutation sites were identified, with c.3596G>A (45.1%, 23/51) as a hotspot variants. Conclusions:PALF caused by NBAS gene variant has obvious clinical and genetic characteristics, and there is a correlation between genotype and clinical phenotype. The c.3596G>A variant site is a hotspot mutation in China and is strongly correlated with the liver failure phenotype.

Objective:To evaluate the efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases.Methods:Relevant studies were retrieved from PubMed,EMBASE,Cochrane,Web of Science,Sinomed,CNKI and Wanfang data-bases.The Cochrane risk-of-bias assessment tool was used to evaluate the quality of included studies,and relevant data were extracted.meta-analysis was performed using RevMan 5.4 and RStudio software,and forest plots were generated.Results:Six randomized con-trolled trials(RCTs)were included.Compared with the control group,denosumab significantly reduced the risk of skeletal-related e-vents(HR=0.78,95％CI:0.62-0.93).In terms of safety,denosumab did not increase the risk of total adverse events,severe adverse events and the adverse events higher than CTC grade 3.Conclusion:Denosumab can delay the time to first skeletal-related event with good safety.However,due to the limitations of this study,further high-quality,large-sample,multicenter RCTs are needed to confirm these findings.

Objective:To investigate the correlations among diabetes-related distress, self-management behavior, empowerment, and glycated hemoglobin (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM) .Methods:A convenience sampling method was used to recruit a total of 1 927 hospitalized patients with T2DM from the Endocrinology Departments of five tertiary general hospitals in Hainan, Jiangsu, and Henan Provinces between December 2022 and December 2023. General demographic and clinical data were collected. The Problem Areas in Diabetes 5 (PAID-5), the Summary of Diabetes Self Care Activities (SDSCA), and the Diabetes Empowerment Scale-Short Form (DES-SF) were used to evaluate patients' psychological distress, self-management behaviors, and empowerment levels. Pearson correlation analysis was performed to examine the relationships among diabetes-related distress, empowerment, self-management behaviors, and HbA1c levels.Results:Pearson correlation analysis showed that diabetes-related distress was negatively correlated with empowerment ( r=-0.119, P<0.001) and the total score of self-management behavior ( r=-0.106, P<0.001), and positively correlated with HbA1c levels ( r=0.103, P<0.001). Empowerment was positively correlated with self-management behavior ( r=0.538, P<0.001) and negatively correlated with HbA1c levels ( r=-0.170, P<0.001). Self-management behavior was negatively correlated with HbA1c levels ( r=-0.165, P<0.001) . Conclusions:Diabetes-related distress, empowerment, and self-management behavior are all associated with glycemic control. Future research and interventions should focus on enhancing patients' self-management abilities, strengthening empowerment, and providing psychological support in order to improve glycemic outcomes and offer a more comprehensive and effective management approach for patients with T2DM.

The composition and working principle of MAQUET ROTAFLOW ECMO system were introduced.Four cases of common failures of ROTAFLOW ECMO systems were analyzed in terms of the cause and elimination method.The methods for the maintenance and quality control of ECMO system were put forward.References were provided for engineering technicians to treat similar faults.[Chinese Medical Equipment Journal,2025,46(5):116-120]

Objective: To explore the association between parent-child connectedness and romantic relationships of secondary vocational school students and the moderating effect of peers romantic behavior, providing scientific basis for family and school health education. Methods: From March to April 2021，2 426 students from six secondary vocational and technical schools in Shanghai and Shaanxi Province were selected to conduct the survey by combining convenience sampling and cluster sampling.Electronic questionnaires were used to collect data on students family characteristics,oneself and peer romantic behaviors, and parent-child bonding. The t-test was employed for inter group comparisons, and binary Logistic regression analysis was conducted to examine the relationship between parent-child bonding levels, peer romantic behavior, and the romantic behavior of secondary vocational students. Results: The mother-child connection (2.63±0.77) was higher than that of father-child connection (2.48±0.78), with statistically significant difference ( t =6.83, P <0.01). Multivariable Logistic regression showed that overall father-child connectedness was negatively associated with students romantic relationships( OR =0.86，95% CI =0.76-0.97， P =0.02)and was only associated to girls romantic relationships when stratified by gender( OR =0.79，95% CI =0.66-0.93， P =0.01). Peers romantic relationships were positively associated with students romantic relationships ( OR =3.19-5.12, all P <0.01), and there was a moderating effect of the association between maternal connectedness and boys romantic relationships ( OR =1.67, 95% CI =1.05-2.66, P =0.03). Among boys without romantic peers, mother-child connectedness was negatively associated with their romantic relationships ( OR = 0.60 , 95% CI =0.36-0.99, P <0.05). In the total sample of Shanghai and girls of Shaanxi, father-child connectedness was negatively correlated with the romantic relationships of secondary vocational school students ( OR =0.84,0.65,95% CI =0.71-1.00,0.50-0.85,both P <0.05). Peer romantic relationships exhibited a negative moderating effect on the influence of mother-child connectedness on the romantic relationships of males in Shanghai ( OR =1.91, 95% CI =1.03-3.57, P <0.05). Conclusions The father-daughter connectedness is negatively correlated with girls romantic behavior, and peer romantic behavior weakens the correlation between mother-child connectedness and boys romantic behavior. Efforts should be made to enhance the parent-child connectedness of secondary vocational students and their ability to cope with peer influence, providing proper guidance for adolescents heterosexual interactions.