ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Objective: Traumatic brain injury (TBI) patients often experience massive bleeding and require blood transfusion. However, the storage duration of the transfused blood may affect the prognosis of these patients. This study explored the influence of exosomes derived from fresh and aged blood on the prognosis of rats with TBI, so as to provide theoretical support for the blood transfusion management of TBI patients. Methods: Exosomes were isolated from red blood cell (RBC) suspensions stored for 1 week and 5 weeks using ultracentrifugation method. The size, morphology and surface markers of the exosomes were identified by nanoparticle flow cytometry, transmission electron microscopy and Western blotting, respectively. A rat model of TBI was constructed using a mechanical impactor for brain injury. After the successful establishment of the model, exosomes from RBC suspensions stored for 1 week and 5 weeks were injected into the extracellular space of rat brain cells using a stereotactic syringe. Cerebral edema at day 1, 3, 7 and 14 were recorded through cranial magnetic resonance imaging (MRI) scans. Magnetic tracing technology (the tracer was Gd-DTPA solution) was used to evaluate the drug metabolism level in the extracellular space of brain cells of TBI rats. The cranial magnetic resonance imaging was scanned every 15 or 30 minutes, and the recording lasted for a total of 240 minutes. The magnetic images were imported into the 3D-Slicer software in Dicom data format for analysis. Mass spectrometry technology was used to analyze the differential proteins of exosomes from RBC suspensions stored for 1 week and 5 weeks, and functional prediction was carried out to explore the possible mechanisms by which exosomes affect the prognosis of TBI. Results: After injection of exosomes into TBI rats, the areas of cerebral edema on the day 1, 3, 7, and 14 were all significantly higher in the rats treated with exosomes from 5-week-stored RBC suspensions, with peak cerebral edema occurring at day 3. The diffusion volume of the tracer was significantly higher in TBI rats than in normal rats, which implied there was a disorder in the structure of the traumatic brain tissue in TBI rats. Compared with the rats injected with exosomes from 1-week-stored RBC suspensions, those treated with exosomes from 5-week-stored RBC suspensions showed increased tracer diffusion volume within 120 minutes. Mass spectrometry analysis identified 81 differentially expressed proteins between exosomes from RBC suspensions stored for 5 weeks vs 1 week. Among them, 93.83% (76/81) proteins had increased expression levels. The neurodegeneration-related pathways were among the most enriched pathways for upregulated proteins. Conclusion: The exosomes from aged RBC suspensions can lead to exacerbated cerebral edema, disrupted extracellular space, and suppressed metabolic rate in TBI rats, suggesting that transfusion of aged RBC suspensions may have adverse effects on TBI patients.

Objective: To explore the association between the joint association of screen time on weekdays and weekends with self rated sleep quality among adolescents, providing scientific basis for improving adolescent sleep health. Methods: Using data from "Huantai Children s Cardiovascular Health Follow up Cohort" survey conducted during November to December 2023, a total of 1 197 adolescents aged 12-17 years with complete demographic characteristics, physical measurements, and questionnaire data were included. The dose response relationship between screen time and sleep quality was evaluated by restrictive cubic splines (RCS). Based on screen time on weekdays and weekends (normal: < 2 h/d; excessive: ≥ 2 h/d), adolescents were categorized into 4 groups. Multivariate Logistic regression models were used to analyze the association between the combined effect of screen time on weekdays and weekends and sleep quality. Results: The RCS analysis results showed that there was a linear dose response relationship between average daily screen time and poor sleep quality in adolescents (non linear P >0.05). The results of multiple Logistic regression analysis showed that adjusting for potential covariates,compared with adolescents having normal screen time on both weekdays and weekends, those with excessive screen time on both weekdays and weekends had increased risk of poor sleep quality ( OR=2.51, 95%CI=1.33-4.62, P <0.01). Sex stratified analysis revealed that girls with excessive screen time on both weekdays and weekends had increased odds of poor sleep quality ( OR=3.03, 95%CI=1.23-7.14, P =0.01), compared to girls who had normal screen time on both weekdays and weekends. Conclusions A linear dose response relationship exists between daily screen time and poor sleep quality in adolescents. Excessive screen time on both weekdays and weekends is positively associated with poor sleep quality, particularly more pronounced among female adolescents.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To evaluate the role of hippocampal β4-Subunit-Containing Nicotinic Acetylcholine Receptors (Chrnb4) in postoperative delirium in aged mice.Methods:Forty-eight SPF male C57BL/6J mice, aged 18 months, weighing 29-35 g, were assigned into 6 groups using a random number table method: tibial fracture group (TF group, n=6), sham operation group (Sham group, n=6), tibial fracture + adipenine group (TA group, n=9), tibial fracture + control vehicle group (TV group, n=9), sham operation + adipenine group (SA group, n=9), and sham operation + control vehicle group (SV group, n=9). The postoperative delirium model was prepared by tibial fracture under sevoflurane anesthesia. Tibial fracture was simulated by implanting a steel pin into the tibia and then clamping it, while sham group only received a longitudinal incision and suture after anesthesia. A microinjection cannula was implanted into the mouse skull at 5 days before developing the model in TA group, TV group, SA group and SV group. Three mice from each group were randomly selected for microelectrode implantation in the hippocampal CA1 area. Starting from 30 min after surgery, adipenine (62.5 nmol/μl) 2 μl was infused into the cerebral ventricle for 7 consecutive days in TA and SA groups, and vehicle (2 μl) was administered instead at a 24-h interval for 7 consecutive days in TV and SV groups. The expression of Chrnb4 mRNA in the hippocampal tissues was detected by real-time quantitative polymerase chain reaction at 24 h after surgery. On the 7th and 8th days after surgery, the open-field test and O-maze experiment were conducted to assess the impulsive-like behavior in TA, TV, SA and SV groups. After the behavioral test, the expression of glial fibrillary acidic protein (GFAP) and vesicular glutamate transporter 1 (Vglut1) in the hippocampal CA1 region was detected by immunofluorescence staining. The local field potentials in the hippocampal CA1 region were recorded during the open field test. Results:The expression of Chrnb4 mRNA in the hippocampal tissues was significantly up-regulated in TF group compared to Sham group ( P<0.05). Compared with TV group, the percentage of central path distance in the open field test and percentage of time spent in the open arms of the O-maze were significantly decreased, the power of β-waves in the CA1 field potentials was decreased, the expression of GFAP and Vglut1 in the hippocampal CA1 region was down-regulated, and the co-staining area of GFAP + and Vglut1 + was decreased in TA group and SV group ( P<0.05). There was no significant difference in each parameter between SA group and SV group ( P>0.05). Conclusions:Hippocampal Chrnb4 may be involved in the mechanism of postoperative delirium in aged mice, and this process may be related to inhibition of neuron excitotoxicity.

Promoting the transformation and development of public hospitals into clinical research-oriented hospitals is the necessary way for China to deepen the reform of medicine and health system. In August 2019, Henan Cancer Hospital deeply combined the key elements of clinical research management with the concept of multidisciplinary collaborative governance, created an offline operating end of collaborative governance (including the front collaborative recruitment system, the middle collaborative quality management system, and the terminal collaborative transformation system), built a supporting internet plus intelligent auxiliary end (including the intelligent recruitment manager, the intelligent quality manager and the intelligent transformation manager), and built a clinical research intelligent management mode covering the trinity of subject recruitment, clinical research quality control, and innovation achievements transformation. The hospital focused on management elements such as " focusing on quality, improving efficiency, and increasing motivation" , and drove the front, middle, and terminal ends of the model to work together, to ensure the quality and efficiency of clinical research and achieve a comprehensive improvement in the hospital′s clinical research level. As of December 2023, the hospital had undertaken over 2 000 clinical research projects of various types, with a cumulative amount of clinical research conversion contracts exceeding 53 million yuan. This practice had achieved good results and could provided references for other tertiary public hospitals to promote high-quality development of clinical research.

Objective To investigate the mechanism of Ganmao Qingre Pills(GQP)against lung injury based on network pharmacology,molecular docking and in vivo experiments.Methods The potential targets of GQP in the treatment of lung injury were screened through traditional Chinese medicine systems pharmacology database and analysis platform(TCM-SP)and Genecards.A"Chinese medicine-active ingredients-targets"network was constructed using Cytoscape 3.9.0 software,then gene ontology(GO)function and Kyoto encyclopaedia of genes and genomes(KEGG)pathway enrichment analysis for potential targets were conducted using a bioinformatics cloud platform.We established a protein-protein interaction(PPI)network,which was intersected with"Chinese medicine-active ingredients-targets"network to obtain core targets.The molecular docking between key target proteins and active ingredients was performed.The effect of GQP on these key target proteins was verified by using a mouse model of lung injury.Results A total of 707 targets for the treatment of lung injury by GQP were identified,corresponding to 107 active ingredients in 11 Chinese medicines.It was found that GQP might regulate targets such as PTGS1,AR,and ACHE through active ingredients including stigmasterol,luteolin,and acacetin using the"Chinese medicine-active ingredients-targets"network analysis.Core targets such as SRC,EGFR,and STAT3 were discovered by using the PPI network.Key target proteins,including CDK1,CDK2,EGFR,ESR1 and SRC,were screened through the intersection analysis of the PPI network and"Chinese medicine-active ingredients-targets"network.Molecular docking study showed that stigmasterol,luteolin and acacetin had good binding effects with CDK1,CDK2,EGFR,ESR1,and SRC,respectively.In vivo experiments revealed that GQP dose-dependently attenuated lung injury and inflammatory infiltration,reduced the release of pro-inflammatory factors TNF-α,IL-1β and IL-6,increased the expression of CDK1 and CDK2,and decreased the expression of EGFR,ESR1 and SRC in lung injury mice.Conclusion The therapeutic effect of GQP against lung injury may be achieved through interaction of key active ingredients(stigmasterol,luteolin,and acacetin)and key target proteins(CDK1,CDK2,EGFR,ESR1,SRC),and regulation of key signaling pathways such as neuroactive ligand-receptor interactions,cancer pathways,and calcium signaling pathways.

Objective:To evaluate the morphological characteristics of the fetal heart and the contractile function of the left and right ventricles in fetuses with pulmonary stenosis (PS) and pulmonary atresia (PA) using fetal heart quantitative analysis technology (fetal HQ), and to assess the impact of different degrees of right ventricular outflow tract obstruction (RVOTO) on the contractile function of the fetal left and right ventricles. To accumulate early data and explore parameters for constructing a predictive model and clinical decision-making tool for the progression of fetal PS and PA.Methods:A retrospective analysis was conducted on 42 cases of mild to moderate PS and 23 cases of severe PS or PA detected through fetal echocardiography in the Department of Ultrasound, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, from July 2020 to December 2021. A control group of 195 normal fetal cases matching gestational weeks was selected. The fetal HQ technique was employed to measure the global sphericity index (GSI), left ventricular ejection fraction (EF), left/right ventricular area change percentage (LVFAC, RVFAC), and left/right ventricular longitudinal strain (LVGLS, RVGLS). Additionally, 24-segment sphericity index (SI) and fractional shortening (FS) for both left and right ventricles were measured. Comparative analyses were performed between the case and control groups, as well as within the case group.Results:In comparison with the control group, the case group exhibited significantly decreased GSI, LVGLS, LVEF, LVFAC, RVGLS, and RVFAC.The differences were statistically significant in the mild to moderate PS group (all P<0.05) and highly significant in the severe PS/PA group (all P<0.01). In the mild to moderate PS group, the left ventricle′s 2nd segment, right ventricle′s 24th segment SI, and the left ventricle′s 1st-13th segments, right ventricle′s 1st-16th and 20th-24th segments FS showed statistically significant differences compared to the control group (all P<0.05). In the severe PS/PA group, the right ventricle′s 1st-22nd segment SI, and the left ventricle′s 6th-13th, 21st-24th segments, and the right ventricle′s 1st-14th segments FS were reduced, showing statistically significant differences compared to the control group (all P<0.05). The severe PS/PA group showed lower RVGLS, RVFAC, and SI for the right ventricle′s 1st to 17th segments when compared to the mild to moderate PS group, with statistically significant differences (all P<0.05). Conclusions:Quantitative indices derived by fetal HQ is capable of evaluating the cardiac morphology and function of fetuses with PS/PA, which may provide for reference information for comprehensive understanding of cardiac morphological and functional changes in such fetuses.

Objective:To explore the potential application of two-dimensional speckle tracking echocardiography (2D-STE) in terms of quantification and evaluating left and right atrial function in normal fetuses, and to investigate the relevant factors affecting left and right atrial function in normal fetuses as well as differences between both atrial function.Methods:A total of 100 single fetuses underwent fetal echocardiography in the Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine from January 2019 to October 2022 were retrospectively enrolled. The standard basal or apical four-chamber view clips were obtained, and the left and right atrial function were quantitatively analyzed using TomTec-ARENA off-line cardiac analysis software for quantitative assessment of both atrial strain measurements including left atrial reservoir phase longitudinal strain (LASr), left atrial ductal phase longitudinal strain (LAScd), left atrial systolic phase longitudinal strain (LASct), right atrial reservoir phase longitudinal strain (RASr), right atrial ductal phase longitudinal strain (RAScd), right atrial systolic phase longitudinal strain (RASct), and the ratio of systolic longitudinal strain to conduit longitudinal strain in left and right atrial systolic display groups were calculated which was denoted as Sct/Scd.Routine fetal obstetric ultrasound measurements and fetal echocardiographic parameters in the two groups were obtained including fetal heart rate (FHR), left atrial end-systolic length (LAESL), left atrial end-systolic diameter (LAESD), left atrial end-systolic area (LAESA), left ventricular end-diastolic transverse diameter (LVEDD), right atrial end-systolic length (RAESL), right atrial end-systolic diameter (RAESD), right atrial end-systolic area (RAESA), right ventricular end-diastolic transverse diameter (RVEDD), peak blood flow velocity of mitral valve and tricuspid valve in early and late diastolic period (E, A), peak ratio of E and A: E/A (MV), E/A (TV), and the difference between the left and right atrial strain indices and the routine fetal obstetric ultrasound and fetal echocardiographic parameters, as well as the correlation between the above parameters and gestational age were analyzed. The repeatability tests were performed using the intra-class correlation coefficientt (ICC).Results:Significant differences were found in LASr and RASr, LAScd and RAScd, LASct and LAScd, Sct/Scd between the left atrium and right atrium, E/A (MV) and E/A (TV), LAESD and RAESD, LAESL and RAESL (all P<0.05), there was significant difference in FHR between the left atrial contraction display group and the no atrial contraction display group ( P=0.011), no significant difference in other parameters (all P>0.05). Correlation analysis showed that, LASr, LASct, RASr, and RASct showed moderate negative correlation with gestational age ( rs=-0.570, -0.601, -0.469, -0.568; all P<0.001). While LAScd, RAScd, E/A (MV), E/A (TV) were moderately positively related with gestational age ( rs=0.310, 0.350, 0.330, 0.343; all P<0.05). LAESL, LAESD, LAESA, RAESL, RAESD, RAESA, LVEDD and RVEDD were significantly positively related with gestational age ( rs=0.662, 0.768, 0.792, 0.728, 0.828, 0.822, 0.838, 0.802, all P<0.001). The inter-examiner ICC of fetal LASr and RASr were 0.89 and 0.84 (both P<0.05) and the intra-examiner ICC of fetal RASr and LASr both were 0.80 (both P<0.05), with good consistency. Conclusions:2D-STE is highly feasible and reproducible in assessing fetal atrial function. The corresponding variation values of fetal atria at different gestational weeks were obtained in this study, which provides a new reference index for us to further study normal fetal atria as well as comparative analysis of fetal cardiac function under prenatal pathological conditions.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.