Objective:To prepare a polyvinyl butyral(PVB)nanofiber membrane loaded with propolis,and to clarify its physicochemical properties,drug release behavior,antibacterial activity,and biocompatibility.Methods:Propolis with a mass fraction of 0.12％was dissolved in 18％(mass fraction)PVB methanol solution.PVB and PVB-propolis(PVB-P)nanofiber membranes were prepared using electrospinning from PVB and PVB-P solutions,respectively.Scanning electron microscope(SEM)was used to observe the microscopic morphology of PVB-P nanofibers,and the Nano Measurer software was used to analyze the fiber diameter distribution.Fourier transform infrared spectroscopy(FTIR)was used to analyze the chemical composition of PVB-P.Water contact angle measurements were used to evaluate the hydrophilicity of PVB-P.UV spectrophotometer was used to detect the cumulative release of propolis at different time points.PVB and PVB-P nanofiber membranes were co-cultured with Staphylococcus aureus(S.aureus),Escherichia coli(E.coli),Candida albicans(C.albicans),Salmonella,and Pseudomonas aeruginosa(P.aeruginosa)and divided into PVB group and PVB-P group.The absorbance method was used to calculate the antibacterial values of PVB and PVB-P against the five types of bacteria.The NIH-3T3 cells were seeded on PVB and PVB-P nanofiber membranes and divided into PVB group and PVB-P group.The CCK-8 method was used to detect the survival rates of NIH-3T3 cells on the nanofiber membranes in PVB group and PVB-P group at 1,3,and 7 d.Results:The SEM results showed that PVB and PVB-P nanofibers were interconnected in a mesh-like porous structure,with uniform thickness and no beads.The Nano Measurer software measurement results showed that the diameter of PVB nanofibers was(0.50±0.10)μm,and the diameter of PVB-P nanofibers was(0.54±0.16)μm.FTIR analysis showed that PVB-P nanofiber membranes exhibited characteristic peaks of PVB(1 140 and 1 002 cm-1)and propolis(1 161 cm-1).The water contact angle measurement results showed that the contact angle of PVB membrane was(144.26°±2.90°)and that of PVB-P membrane was(128.13°±1.36°).The UV spectrophotometer results showed that the cumulative release of propolis was 0.04 mg at 1d,0.07 mg at 3 d,and reached a steady state of 0.79 mg at 7 d.The absorbance method results showed that the antibacterial values of PVB-P nanofiber membranes against S.aureus,E.coli,C.albicans,Salmonella,and P.aeruginosa were 4.39,1.27,5.68,3.16,and 1.87,respectively.The CCK-8 method results showed that the survival rates of NIH-3T3 cells on PVB and PVB-P nanofiber membranes was＞90％at 1,3,and 7 d,and there were no significant differences between various groups(P＞0.05).Conclusion:The diameter of PVB nanofiber membranes loaded with propolis is increased,and these membranes exhibit antibacterial effects against S.aureus and C.albicans,while also achieving sustained release of propolis.

Objective:To verify the performance of the immunoturbidimetric assay(ITMA)kit of detecting oxidized low-density lipoprotein(ox-LDL).Methods:In accordance with the requirements of China National Accreditation Service for Conformity Assessment[(CNAS)-GL037:2019]and the National Health Industry Standards,the precision,trueness,linear range and reportable range of ITMA test kit for ox-LDL were verified on AU5800 fully automatic biochemical analyzer,which were compared with enzyme linked immunosorbent assay(ELISA)of Mercodia comparison reagents for ox-LDL through experiment of methodological comparison.Results:The coefficients of variation(CV)values of within-run and between-run precisions of the two concentration levels of quality control materials in the ITMA reagent kit for ox-LDL were respectively(3.74%,3.36%)and(4.75%,5.49%).The trueness bias of the two concentration levels of standards were respectively 0.46%and 1.78%,and the linear range was(15-120 U/L),which verification regression coefficient was R2=0.999 5 with a slope of 0.989.The maximum dilution multiple was 4 times,and the upper limitation of the clinically reportable range was 240.00 U/L.The manufacturer-provided biological reference interval was 0-64.49 U/L,and the coincidence rate was 100%.The results of hemoglobin,bilirubin,triglycerides,high density lipoprotein(HDL),low density lipoprotein(LDL)and rheumatoid factor were respectively 10 mg/ml,342 μmol/L,10.0 mg/ml,100 mg/dl,200 mg/dl,<200 IU/ml.The stationary duration was there was not influence within 30 h after opened the kit.The correlation between ITMA and ELISA detection methods was excellent(R2=0.9766).The positive and negative coincidence rates of clinical identification were respectively 92.3%and 96.5%.Conclusion:The performances of ox-LDL ITMA test kit based on fully automatic biochemical analyzer can all meet the requirement of clinical application,which shows excellent consistency with the results of ELISA method.

Objective:To establish a practical patient-based internal quality control method for valproic acid drug concentration monitoring.Methods:Observational Study. A PBRTQC model based on the exponentially weighted moving average (EWMA) method was established using Python. All results of a total of 28, 757 valproic acid concentration data from February 1, 2023 to January 31, 2024 were collected and split into training set and validation set at a ratio of 80% and 20% respectively. The truncation limit (TL) was optimized by using the winsorized mean method and the trimmed mean method. Different weighting coefficients λ were set. Different TL and different λ were combined with the EWMA algorithm into different patient-based real-time quality control (PBRTQC) models. The optimized models were verified by introducing simulated constant errors (CE) and proportional errors (PE) respectively. The false positive alarm rate (FAR) was used to evaluate specificity, and the average number of patients before error detection (ANPed) was used to evaluate sensitivity. According to the daily test volume and quality target requirements, we comprehensively judged whether the performance evaluation indicators of FAR and ANPed meet the laboratory requirements. Bias detection curve was used for determination of the best model.Results:The parameters of the best PBRTQC model for valproic acid drug concentration monitoring are: trimmed mean method with 1.5 standard deviations (i.e., truncating data outside 1.5 standard deviations of the data mean), λ=0.01. The performance verification result shows that ANPed of CE and PE of this model are both less than 100. The comparison between the EQA results and the EWMA results show that the EWMA method results are comparable to the EQA results.Conclusion:A PBRTQC model for the valproic acid drug concentration monitoring project based on the EWMA method has been successfully established. It is comparable with both IQC and EQA results, which means PBRTQC may be used as a supplement to the quality control of daily quality control products.

Objective:To evaluate alterations in dopaminergic neurons, cortical metabolism, and functional connectivity networks in patients with early-onset Parkinson′s disease (EOPD) using multimodal neuroimaging.Methods:In this prospective cross-sectional study, 26 patients with EOPD and 16 healthy controls (HC group) were recruited from the PLA General Hospital between April and November 2023. All participants underwent integrated 11C-β-CFT PET/MR, 18F-FDG PET/CT brain imaging and resting-state functional MRI. Clinical assessments were conducted using the Unified Parkinson′s Disease Rating Scale and Hoehn-Yahr staging. Cognitive status was evaluated using the Mini-Mental State Examination and Montreal Cognitive Assessment. Standardized uptake value ratios for both 11C-β-CFT and 18F-FDG PET images were calculated using cerebellar gray matter as the reference region. Voxel-wise two-sample t-tests were performed to identify regions with significant group differences in tracer uptake. Seed regions showing altered 11C-β-CFT or 18F-FDG uptake were used to compute seed-based functional connectivity (FC) with all other brain voxels, and group differences in FC were assessed. Correlations between imaging metrics and clinical scales were evaluated using Pearson or Spearman analyses as appropriate. Results:Compared with HC group, EOPD group showed significantly reduced 11C-β-CFT uptake in the bilateral putamen, globus pallidus, and left temporal pole ( P<0.05), and decreased 18F-FDG uptake in the right superior frontal gyrus and anterior cingulate cortex ( P<0.05). Relative to HC group, EOPD group exhibited markedly lower FC between the right putamen and the left gyrus rectus as well as the right parahippocampal gyrus; the right superior frontal gyrus and the left gyrus rectus; the anterior cingulate cortex and the olfactory area of the frontal lobe, the left gyrus rectus, and the right superior parietal gyrus; the left temporal pole and the left orbitofrontal cortex as well as the left olfactory area ( P<0.05). Correlation analyses revealed no statistically significant associations between altered FC values and clinical scale scores in the EOPD group. Conclusions:Patients with EOPD demonstrate impaired nigrostriatal dopaminergic function, regional cortical hypometabolism, and aberrant functional connectivity across multiple brain networks.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To establish a practical patient-based internal quality control method for valproic acid drug concentration monitoring.Methods:Observational Study. A PBRTQC model based on the exponentially weighted moving average (EWMA) method was established using Python. All results of a total of 28, 757 valproic acid concentration data from February 1, 2023 to January 31, 2024 were collected and split into training set and validation set at a ratio of 80% and 20% respectively. The truncation limit (TL) was optimized by using the winsorized mean method and the trimmed mean method. Different weighting coefficients λ were set. Different TL and different λ were combined with the EWMA algorithm into different patient-based real-time quality control (PBRTQC) models. The optimized models were verified by introducing simulated constant errors (CE) and proportional errors (PE) respectively. The false positive alarm rate (FAR) was used to evaluate specificity, and the average number of patients before error detection (ANPed) was used to evaluate sensitivity. According to the daily test volume and quality target requirements, we comprehensively judged whether the performance evaluation indicators of FAR and ANPed meet the laboratory requirements. Bias detection curve was used for determination of the best model.Results:The parameters of the best PBRTQC model for valproic acid drug concentration monitoring are: trimmed mean method with 1.5 standard deviations (i.e., truncating data outside 1.5 standard deviations of the data mean), λ=0.01. The performance verification result shows that ANPed of CE and PE of this model are both less than 100. The comparison between the EQA results and the EWMA results show that the EWMA method results are comparable to the EQA results.Conclusion:A PBRTQC model for the valproic acid drug concentration monitoring project based on the EWMA method has been successfully established. It is comparable with both IQC and EQA results, which means PBRTQC may be used as a supplement to the quality control of daily quality control products.

Objective:To evaluate alterations in dopaminergic neurons, cortical metabolism, and functional connectivity networks in patients with early-onset Parkinson′s disease (EOPD) using multimodal neuroimaging.Methods:In this prospective cross-sectional study, 26 patients with EOPD and 16 healthy controls (HC group) were recruited from the PLA General Hospital between April and November 2023. All participants underwent integrated 11C-β-CFT PET/MR, 18F-FDG PET/CT brain imaging and resting-state functional MRI. Clinical assessments were conducted using the Unified Parkinson′s Disease Rating Scale and Hoehn-Yahr staging. Cognitive status was evaluated using the Mini-Mental State Examination and Montreal Cognitive Assessment. Standardized uptake value ratios for both 11C-β-CFT and 18F-FDG PET images were calculated using cerebellar gray matter as the reference region. Voxel-wise two-sample t-tests were performed to identify regions with significant group differences in tracer uptake. Seed regions showing altered 11C-β-CFT or 18F-FDG uptake were used to compute seed-based functional connectivity (FC) with all other brain voxels, and group differences in FC were assessed. Correlations between imaging metrics and clinical scales were evaluated using Pearson or Spearman analyses as appropriate. Results:Compared with HC group, EOPD group showed significantly reduced 11C-β-CFT uptake in the bilateral putamen, globus pallidus, and left temporal pole ( P<0.05), and decreased 18F-FDG uptake in the right superior frontal gyrus and anterior cingulate cortex ( P<0.05). Relative to HC group, EOPD group exhibited markedly lower FC between the right putamen and the left gyrus rectus as well as the right parahippocampal gyrus; the right superior frontal gyrus and the left gyrus rectus; the anterior cingulate cortex and the olfactory area of the frontal lobe, the left gyrus rectus, and the right superior parietal gyrus; the left temporal pole and the left orbitofrontal cortex as well as the left olfactory area ( P<0.05). Correlation analyses revealed no statistically significant associations between altered FC values and clinical scale scores in the EOPD group. Conclusions:Patients with EOPD demonstrate impaired nigrostriatal dopaminergic function, regional cortical hypometabolism, and aberrant functional connectivity across multiple brain networks.

Objective:To verify the performance of the immunoturbidimetric assay(ITMA)kit of detecting oxidized low-density lipoprotein(ox-LDL).Methods:In accordance with the requirements of China National Accreditation Service for Conformity Assessment[(CNAS)-GL037:2019]and the National Health Industry Standards,the precision,trueness,linear range and reportable range of ITMA test kit for ox-LDL were verified on AU5800 fully automatic biochemical analyzer,which were compared with enzyme linked immunosorbent assay(ELISA)of Mercodia comparison reagents for ox-LDL through experiment of methodological comparison.Results:The coefficients of variation(CV)values of within-run and between-run precisions of the two concentration levels of quality control materials in the ITMA reagent kit for ox-LDL were respectively(3.74%,3.36%)and(4.75%,5.49%).The trueness bias of the two concentration levels of standards were respectively 0.46%and 1.78%,and the linear range was(15-120 U/L),which verification regression coefficient was R2=0.999 5 with a slope of 0.989.The maximum dilution multiple was 4 times,and the upper limitation of the clinically reportable range was 240.00 U/L.The manufacturer-provided biological reference interval was 0-64.49 U/L,and the coincidence rate was 100%.The results of hemoglobin,bilirubin,triglycerides,high density lipoprotein(HDL),low density lipoprotein(LDL)and rheumatoid factor were respectively 10 mg/ml,342 μmol/L,10.0 mg/ml,100 mg/dl,200 mg/dl,<200 IU/ml.The stationary duration was there was not influence within 30 h after opened the kit.The correlation between ITMA and ELISA detection methods was excellent(R2=0.9766).The positive and negative coincidence rates of clinical identification were respectively 92.3%and 96.5%.Conclusion:The performances of ox-LDL ITMA test kit based on fully automatic biochemical analyzer can all meet the requirement of clinical application,which shows excellent consistency with the results of ELISA method.

objective:To prepare a composite photocrosslinked hydrogel containing zeolite imidazole framework-8(ZIF-8),and to evaluate its in vitro cytotoxicity,drug release capability,and antimicrobial propertie.Methods:The ZIF-8 particles were synthesized by hydrothermal method,and the microstructure characteristic was observed under scanning electron microscope(SEM).The particles were mixed with the gelatin methacryloyl(GelMA)with the mass fraction of 0.2%to obtain the composite hydrogel GelMA-Z.The atomic absorption spectroscope was used to detect the cumulative zinc ion(Zn2+)release amounts in GelMA-Z at different time points.The NIH-3T3 cells were co-cultured with GelMA-Z for 1,3,and 7 d;the viabilities of the cells in various groups were detected by CCK-8 assay;the GelMA-Z was co-cultured with Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)for 6,12,and 24 h and divided into control group,GelMA group,and GelMA-Z group.The bacterial activities of the cells in various groups at different time points were detected by microplate reader;the bacterial formation and the presence of live/dead becterial staining condition were detected by plate antibacterial experiment and live/dead bacterial staining method.Results:The SEM observation results showed that the hydrothermally synthesized ZIF-8 particles had the uniform particle sizes.The atomic absorption spectroscope results showed that Zn2+ in GelMA-Z showed an initial burst phase within 1 d,followed by a slow release,and reached the equilibrium around 7 d.Compared with control group,the viabilities the cells in GelMA group and GelMA-Z group were above 90%on the 1st,3rd,and 7th days,but there was no significant difference(P>0.05).The bacterial activity detection results showed that when co-cultured with bacteria for 6,12,and 24 h,compared with control group and GelMA group,the bacterial activities of the E.coli and S.aureus in GelMA-Z group were decreased(P<0.05).The plate antibacterial experiment results showed that the number of bacterial formation in GelMA-Z group was fewer than those in control group and GelMA group.The live/dead bacterial staining results showed that in GelMA-Z group,there was a large number of red fluorescence stained dead bacteria;in control group and GelMA group,there was a large number of green fluorescence stained live bacteria.Conclusion:The GelMA hydrogel loaded with ZIF-8 particles can achieve the in situ photocrosslinking and possesses good Zn2+ release capability and antimicrobial activity,and it is a novel hydrogel dressing for treatment of the infected wounds.