Ephedra can improve chronic obstructive pulmonary disease (COPD). Pseudoephedrine (PSE) is a main active ingredients of ephedra. It has anti-inflammatory pharmacological properties. Its effect on COPD and its possible mechanism have not been elucidated. The COPD rat model was constructed by systemic cigarette smoke exposure combined with lipopolysaccharide (LPS) tracheal instillation. BEAS-2B cells were treated using cigarette smoke extract; PSE was administered for treatment. The senescence level of rat lung tissue and bronchial epithelial cells was evaluated through staining, immunofluorescence and western blot.The mitochondrial damage of rats and BEAS-2B cells was detected by transmission electron microscopy, JC-1 probe, MitoSOX Red probe and kits. In addition, the lung function indexes of rats were detected by animal lung function analysis system. Hematoxylin and eosin (HE) staining analyzed the pathological damage. Enzyme-linked immunosorbent assay (ELISA), kit and immunohistochemistry were used to evaluate inflammation and oxidative stress. Western blot detected phosphoinositide 3-kinase/ protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) axis protein. PSE significantly reduced senescent cells, apoptosis rate and P21 level in rat lung tissue and BEAS-2B cells, significantly increased the levels of zonula occludens-1 (ZO-1) and adenosine triphosphate (ATP), restored mitochondrial structure, and visible mitochondrial cristae. It also inhibited reactive oxygen species (ROS) levels and mitochondrial excessive fission. PSE also significantly improved lung function in rats, increased mean alveolar number (MAN), reduced pro-inflammatory factors, and increased superoxide dismutase (SOD) levels. PSE markedly suppressed p-p85, p-AKT and p-mTOR protein expressions. In addition, the PI3K/AKT agonist 740Y-P weakened the effect of PSE on improving COPD. PSE inhibited PI3K/AKT/mTOR axis, improved lung tissue senescence, mitochondrial dysfunction and pathological damage, and reduced airway inflammation and oxidative stress damage, thereby alleviating COPD.

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

Objective:To detect the serum levels of 25(OH)D,miR-125b-5p,hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGFA)in patients with multiple myeloma(MM),and explore the role of miR-125b-5p/HIF-1α pathway in the involvement of vitamin D deficiency in the pathogenesis of MM.Methods:Fifty three newly diagnosed/relapsed MM patients admitted to the department of hematology of our hospital from October 2021 to December 2023 were included.Meanwhile,25 healthy individuals matched in gender and age from our hospital's Health Management Center were selected as controls.The serum level of 25(OH)D was monitored by mass spectrometry,the serum level of miR-125b-5p was detected by real-time fluorescence quantitative PCR,and serum levels of HIF-1α and VEGFA were measured by enzyme-linked immunosorbent assay.The levels of 25(OH)D,miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.According to the level of 25(OH)D,the MM patients were divided into vitamin D deficiency group(＜20 ng/ml)and vitamin D non-deficiency group(≥ 20 ng/ml),and the levels of miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.The correlations between 25(OH)D,miR-125b-5p,HIF-1α and VEGFA were analyzed.The receiver operating characteristic(ROC)curve analysis was used to determine the diagnostic value of25(OH)D combined with miR-125b-5p for newly diagnosed MM.Results:The level of 25(OH)D in MM patients was significantly lower than that in control group(P＜0.01).There was no significant difference in 25(OH)D level between newly diagnosed and relapsed MM patients(P＞0.05).Compared with the control group,the level of miR-125b-5p was significantly reduced in MM patients(P＜0.01),while the levels of HIF-1α and VEGFA were significantly increased(both P＜0.001).In MM patients,the miR-125b-5p level in the vitamin D deficiency group was significantly decreased than that in the non-deficiency group(P＜0.01),while the levels of HIF-1 α and VEGFA were significantly increased(both P＜0.05).In MM patients,25(OH)D was positively correlated with miR-125b-5p,while negatively correlated with HIF-1α and VEGFA(both P＜0.05).Moreover,miR-125b-5p was negatively correlated with HIF-1α and VEGFA(both P＜0.05).The area under the curve(AUC)for diagnosing MM with 25(OH)D,miR-125b-5p,and their combination were 0.699,0.751,and 0.791,respectively.Conclusion:The incidence of vitamin D deficiency is high in MM patients.Vitamin D deficiency may promote angiogenesis and participate in the occurrence and development of MM by downregulating miR-125b-5p and upregulating HIF-1α and VEGFA expression.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To detect the serum levels of 25(OH)D,miR-125b-5p,hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGFA)in patients with multiple myeloma(MM),and explore the role of miR-125b-5p/HIF-1α pathway in the involvement of vitamin D deficiency in the pathogenesis of MM.Methods:Fifty three newly diagnosed/relapsed MM patients admitted to the department of hematology of our hospital from October 2021 to December 2023 were included.Meanwhile,25 healthy individuals matched in gender and age from our hospital's Health Management Center were selected as controls.The serum level of 25(OH)D was monitored by mass spectrometry,the serum level of miR-125b-5p was detected by real-time fluorescence quantitative PCR,and serum levels of HIF-1α and VEGFA were measured by enzyme-linked immunosorbent assay.The levels of 25(OH)D,miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.According to the level of 25(OH)D,the MM patients were divided into vitamin D deficiency group(＜20 ng/ml)and vitamin D non-deficiency group(≥ 20 ng/ml),and the levels of miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.The correlations between 25(OH)D,miR-125b-5p,HIF-1α and VEGFA were analyzed.The receiver operating characteristic(ROC)curve analysis was used to determine the diagnostic value of25(OH)D combined with miR-125b-5p for newly diagnosed MM.Results:The level of 25(OH)D in MM patients was significantly lower than that in control group(P＜0.01).There was no significant difference in 25(OH)D level between newly diagnosed and relapsed MM patients(P＞0.05).Compared with the control group,the level of miR-125b-5p was significantly reduced in MM patients(P＜0.01),while the levels of HIF-1α and VEGFA were significantly increased(both P＜0.001).In MM patients,the miR-125b-5p level in the vitamin D deficiency group was significantly decreased than that in the non-deficiency group(P＜0.01),while the levels of HIF-1 α and VEGFA were significantly increased(both P＜0.05).In MM patients,25(OH)D was positively correlated with miR-125b-5p,while negatively correlated with HIF-1α and VEGFA(both P＜0.05).Moreover,miR-125b-5p was negatively correlated with HIF-1α and VEGFA(both P＜0.05).The area under the curve(AUC)for diagnosing MM with 25(OH)D,miR-125b-5p,and their combination were 0.699,0.751,and 0.791,respectively.Conclusion:The incidence of vitamin D deficiency is high in MM patients.Vitamin D deficiency may promote angiogenesis and participate in the occurrence and development of MM by downregulating miR-125b-5p and upregulating HIF-1α and VEGFA expression.

Objective:To explore the vigilant attention function and behavioral changes in sleep disordered breathing(SDB) children.Methods:Thirty SDB children (SDB group) and 30 normal children (control group) were selected from June 2022 to August 2023. All participants underwent continuous performance test(CPT-AX) (Go/Nogo) and behavioral test. The latency and amplitude of contingent negative variation(CNV) components under cue/uncue conditions in leads F3, Fz and F4 were measured. The t-test and Mann-Whitney U test were used to conduct statistical analysis by SPSS 25.0 software. Results:(1) There were no statistically significant differences in the number of correct responses, reaction time and number of false alarms between the SDB group and the control group (all P>0.05).(2) The latencies of cue-CNV in the SDB group(F3: 618.00(582.50, 644.50)ms, Fz: 603.00(579.50, 634.00)ms, F4: (606.87±25.07)ms) were longer than those in the control group(F3: (508.47±25.82)ms, Fz: 502.00(470.00, 520.50)ms, F4: 514.00(487.00, 536.50)ms) in leads F3, Fz and F4. The latency of cue-CNV of lead F4 in the SDB group was higher than that in the control group, and the difference was statistically significant ( P<0.05). The latencies of uncue-CNV in lead F3 and Fz in the SDB group were higher than those in the control group, and the differences were statistically significant (both P<0.05). Conclusion:SDB children have shown activation in the right brain area during attentional tasks, and the prolonged CNV latency may be a sensitive neuroelectrophysiological marker for early clinical assessment of vigilant attention dysfunction.

Aim To establish a quantitative immunofluorescent bioactivity assay(ICW)for insulin glargine based on CHO-IN-SRB 1284 transgenic cells,and to study its equivalence with in-sulin bioassay of Ch.P.Methods The cells were diluted 25 times with 1.5 × 108 L-1 cell density plates and 1 500 μmol·L-1 insulin glargine,and then diluted with a 3-fold gradient se-ries.The cells were stimulated in microporous plates for 20 min.After fixation,permeation and antibody incubation.Quantitative immunofluorescence biological activity was detected by odyssey two-color infrared fluorescence imaging system.Results There was a good dose-effect relationship between the concentration of insulin glargine in ICW and its relative potency.The method had good specificity,and the relative accuracy,intermediate preci-sion and linearity met the requirements.The relative deviation of biological activity results of 7 batches of insulin glargine samples measured by the two methods was less than 10％.The results were analyzed by SPSS and SAS software,which showed that the methods were correlated and equivalent.Conclusions The quantitative immunofluorescence assay for the biological activity of insulin glargine can be established.The method has good spe-cificity,high accuracy and precision,and has correlation and e-quivalent with biotiter assay,which can be applied to in vitro ef-ficacy evaluation and quality control of insulin glargine.

Objective To design a medical order pre-evaluation tool for perioperative prophylactic application of antibiotics,and to improve the efficiency of antibiotics management in hospitals during the perioperative period.Methods Using the open-source software R as the platform,a web application was built with tidy verse and shiny package based on related documents and guidelines.The discharge records of Affiliated Hospital of North Sichuan Medical College from April 1,2021,to December 31,2022,were retrospectively reviewed using the constructed pre-evaluation tool and compared with previous manual evaluation results using McNemar's Chi-squared test.Results This medical order pre-evaluation tool can quickly complete perioperative antibiotics order sampling,batch pre-evaluation,result statistics,visualization,and result output,and flexibly adjust the evaluation rules according to actual needs.The pre-evaluation tool is more efficient,with a review speed of 13.46 ms per medical record.Among the 2 642 discharge medical records of manual review,there was no significant difference between systematic pre-evaluation and manual evaluation results(ratio of prophylactic use:76.85%vs.78.21%)in terms of the type of use(preventive or curative)(P= 0.078).Among the 1 857 discharge records judged to be prophylactic for both manual and systematic reviews,the difference in unreasonable detection rate(39.90%vs.30.32%)was statistically significant(P＜0.001).Among the 63 typical ludicrous medical records confirmed by the review of clinical pharmacists with senior professional titles,60 were judged and limited by the pre-evaluation tool,and the detection rate of typical unreasonable was 95.24%.Conclusions The pre-evaluation tool based on R in this study can improve the efficiency of perioperative antibacterial drug evaluation.The evaluation conclusions and statistical results are reliable and are worthy of further development and application.

Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60％participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10％participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.