ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

Objective:To evaluate the efficacy and safety of blinatumomab in adult patients with relapsed/refractory(R/R)or measurable residual disease(MRD)positive B-cell acute lymphoblastic leukemia(B-ALL)in the real world.Methods:The clinical data of 30 B-ALL patients received at least 1 course of blinatumomab therapy in the Chinese PLA General Hospital from January 1st,2021 to December 31st,2023 were retrospectively analyzed,including pre-treatment baseline clinical feature,post-treatment complete response(CR),CR with partial hematologic recovery(CRh),CR with incomplete hematologic recovery(CRi),complete MRD response rate,MRD response rate(MRD＜10-4),overall survival(OS),and disease-free survival(DFS),as well as drug-related adverse reactions.Results:Among 5 patients who were not assessed 4 were MRD negative and 1 did not receive bone marrow biopsy.In the R/R B-ALL group(13 cases),11 patients achieved CR/CRh/CRi and 10 patients achieved complete MRD response.In MRD+group(12 cases),9 patients achieved overall MRD response and 7 patients achieved complete MRD response.The median follow-up time was 8.4(95％CI:6.3-10.4)months.The median OS was 15.5(95％CI:0.7-30.3)months in the R/R group,while not reached in the MRD+group.The median DFS of the two groups were not reached.Drug-related adverse reactions occurred in 22 patients,and pyrexia was the most common(13 cases).Grade ≥3 adverse reactions occurred in 15 patients,and neutropenia was the most common(9 cases).Cytokine release syndrome occurred in 6 patients,including 5 cases with grade 1 and 1 case with grade 3.No patients interrupted therapy or died due to drug-related adverse reactions.Conclusion:Blinatumomab is effective in the treatment of R/R or continuous MRD+B-ALL with acceptable adverse reactions.

Objective:To investigate the current status and challenges of pediatric life support training in China and provide references for improving training quality.Methods:A cross-sectional study was conducted to collect data from pediatric life support training centers across the country，covering basic institutional information，training capacity and training faculty，training program funding，as well as existing challenges and issues.The domestic registry of training centers in 2023 was obtained through the American Heart Association's online platform.After contacting and verifying each center，an online questionnaire was distributed，and the aggregated data were statistically analyzed.Results:A total of 42 institutions participated in the survey，including 19 children's hospitals，14 general hospitals，6 maternal and child health hospitals，2 women and children’s hospitals，and 1 training institution.The distribution of training centers showed a concentration in coastal areas，with the top three provinces/municipalities being Guangdong（7/42，16.7%），Zhejiang（6/42，14.3%），and Shanghai（4/42，9.5%）.As of December 31 2023，the 42 institutions had an annual basic life support（BLS）training volume of 8 587 individuals，the median was 120 (100,200)，and an annual pediatric advanced life support（PALS）training volume of 2 448 individuals，the median was 30 (20,50).Among the 42 institutions，there were 598 BLS instructors and 306 PALS instructors.Among the surveyed institutions，24（24/42，57.1%）reported BLS instructor teams comprising fewer than 10 members，and 33（33/42，78.6%）reported PALS instructor teams comprising fewer than 10.Only 7 centers(7/42,16.7%）reported having dedicated funding support.The top three challenges were：training sessions occupying instructors’personal time（27/42，64.3%），low instructor compensation（16/42，38.1%），and issues with the data submission system（16/42，38.1%）.Conclusion:Pediatric life support training centers in China are primarily children’s hospitals，with a geographical concentration in coastal areas，which is also reflected in the distribution of training scale and instructor resources.Most centers have relatively small training scales and limited instructor capacity，with many instructors conducting training during their personal time.These issues may hinder the implementation and effectiveness of training programs.

Objective To elucidate the mechanisms of trauma-induced coagulopathy(TIC),clarify the specific pathogenic factors and pathophysiological processes,and discover the effective diagnostic indicators and therapeutic targets.Methods Transcriptomic data of traumatic hemorrhagic shock patients were obtained from the Gene Expression Omnibus(GEO)to identify differentially expressed genes(DEGs).Coagulation-related genes(CRGs)from the Kyoto Encyclopedia of Genes and Genomes(KEGG)were intersected with DEGs.Machine learning algorithms,including least absolute shrinkage and selection operator(LASSO)and random forest(RF),were applied to identify key genes.The CIBERSORT algorithm was used to analyze the correlation between key genes and immune cell infiltration.Through consensus clustering,subtype analysis was conducted on trauma patients to compare the infiltration of immune cells.A rat model of traumatic hemorrhagic shock was established to validate coagulation function and the expression of key genes.Results The dataset included samples from 17 healthy controls and 478 patients with traumatic hemorrhagic shock.A total of 6 315 DEGs were identified under the screening criterion of corrected P<0.05.Gene set enrichment analysis(GSEA)showed that the up-regulated DEGs were significantly enriched in the glucose metabolism pathway,while the down-regulated DEGs were enriched in the immune reaction-related pathways.Through cross-analysis of DEGs and CRGs,a total of 65 differentially expressed coagulation-related genes(DE-CRGs)were screened out.GO functional enrichment showed that these genes were mainly located in secreting granular membranes and platelet α-granules,and were involved in physiological processes such as blood coagulation,regulation of body fluid levels,and wound healing.KEGG pathway analysis revealed that these genes were significantly enriched in pathways such as platelet activation,complement and coagulation cascade reactions,Rap1 signaling pathway,and human cytomegalovirus infection.Six key DE-CRGs were identified through machine learning.Receiver operating characteristic(ROC)curve analysis indicated that these genes had good diagnostic efficacy.CIBERSORT analysis revealed a significant correlation between key genes and immune cell infiltration.Patients were classified into two subtypes based on the six key genes:subtype A was rich in CD8+T cells and activated NK cells,presented an immune-active state;subtype B was mainly composed of monocytes and resting NK cells,with insufficient activation of immune pathways.Animal experiments on rats showed that hemorrhagic shock can lead to coagulation dysfunction.The results of qRT-PCR further confirmed that the expression trend of key genes was consistent with the results of bioinformatics analysis.Conclusion In this study,through transcriptomics and machine learning methods,six key genes closely related to TIC were systematically screened out,namely GNA13,PIK3R3,ITGAM,MAPK14,PPP1CC and LYN,and their close connections with coagulation function and immune infiltration were revealed.Animal experiments have further verified the value of these genes as potential diagnostic and therapeutic targets.

Objective To elucidate the regulatory effects of titanium surface modification on the immune function of immature dendritic cells(imDCs),different crystalline nanomorphologies were constructed on titanium surface to investigate the mechanobiological response of imDCs to nanomorphologies with different crystalline phases.Methods Nanomorphologies with different crystalline phases were constructed on the titanium surface by anodic oxidation and calcination.The changes of the cytoskeleton F-actin,cell adhesion and morphology of imDCs cultured on nanomorphologies with different crystalline phases were observed by fluorescence staining.The relative gene expression of adhesion molecules was detected by quantitative real-time PCR.The migration behaviors of imDCs were observed using real-time live-cell imaging,and the membrane fluidity was detected by fluorescence polarization.Results Nanomorphologies with different crystalline phases,namely amorphous phase,anatase and rutile,were obtained on the titanium surface by anodic oxidation and calcination.The cytoskeleton of imDCs on nanomorphologies with different crystalline phases was remodeled.The spreading area of cells on anatase crystalline phase was relatively small,which was(353.3±148.5)μm2.The number of adherent cells was the largest,which was 587±132.The expression of adhesion molecules such as CD11a,integrin β2,ICAM1,and VCAM1 were also increased in cells which cultured on anatase crystalline phase.The imDCs cultured on anatase crystalline phase were equipped with strong migration ability.The accumulative migration distance was(383.6±177.7)μm,and the Euclidean migration distance was(51.82±50.13)μm.The membrane fluidity was relatively weak,and the fluorescence polarization was 0.348 5±0.041 8.Conclusions imDCs can respond to nanomorphologies with different crystalline phases on the titanium surface and exhibit different biomechanical behaviors.The results might provide a theoretical basis for the design of titanium biomaterials with immunomodulatory functions.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.

Objective:To investigate the relationship between serum insulin-like growth factor-1 (IGF-1) levels and intracranial or extracranial atherosclerosis in patients with cerebral small vessel disease (CSVD).Methods:A total of 407 patients with CSVD admitted to Xiangya Hospital of Central South University between July 2021 and September 2023 were enrolled in the study. Carotid duplex ultrasound was used to measure the internal diameter, intima-media thickness (IMT), vascular wall thickness, plaque property score, stenosis index, and stenosis ratio of the bilateral common carotid arteries, internal carotid arteries, external carotid arteries, and vertebral arteries. Magnetic resonance angiography was used to assess the degree of stenosis in intracranial arteries. Patients were divided into 4 groups based on the serum IGF-1 levels (low level group:≤5.21 ng/ml, medium level group:>5.21 ng/ml and ≤10.73 ng/ml, high level group:>10.73 ng/ml and ≤24.26 ng/ml, extremely high level group:>24.26 ng/ml). The IMT of the common carotid artery, carotid plaques, diameters of various cervical vascular lumens, carotid artery diameter stenosis, and intracranial artery stenosis in 4 groups of the patients were compared. The relationship between IGF-1 and intracranial and extracranial atherosclerosis was analyzed by univariate Logistic regression analysis and multivariate Logistic regression analysis.Results:There were inter group differences among the 4 groups in internal carotid artery diameter [low level group 5.45 (0.50) mm vs medium level group 5.32 (0.55) mm vs high level group 5.30 (0.55) mm vs extremely high level group 5.30 (0.50) mm; H=8.210, P=0.042]. The carotid IMT [low level group 0.80 (0.05) mm vs medium level group 0.80 (0.05) mm vs high level group 0.83 (0.03) mm vs extremely high level group 0.83 (0.09) mm; H=8.107, P=0.044], the proportion of carotid artery vascular wall thickening [low level group 52.9%(54/102) vs medium level group 48.0%(49/102) vs high level group 68.3%(69/101) vs extremely high level group 60.8%(62/102); χ2=9.889, P=0.020], the carotid artery plaque property score [low level group 1 (2) vs medium level group 2 (2) vs high level group 2 (2) vs extremely high level group 2 (2); H=8.913, P=0.030] and the proportion of anterior cerebral artery stenosis [low level group 2.9%(3/102) vs medium level group 2.0%(2/102) vs high level group 4.0%(4/101) vs extremely high level group 10.8%(11/102); χ2=10.473, P=0.014] had inter group differences among the 4 groups, and the differences were statistically significant. Univariate Logistic regression analysis indicated that carotid artery vascular wall thickening ( OR=1.197, 95% CI 1.003-1.429, P=0.046), anterior cerebral artery stenosis ( OR=1.814, 95% CI 1.148-2.867, P=0.011), and basilar artery stenosis ( OR=1.530, 95% CI 1.084-2.159, P=0.015) were correlated with IGF-1 levels. Multivariate Logistic regression analysis revealed that after adjusting for age, gender, low-density lipoprotein cholesterol (LDL-C), and C-reactive protein, IGF-1 was positively correlated with the carotid artery vascular wall thickening ( OR=1.311, 95% CI 1.014-1.696, P=0.039); after adjusting for age, IGF-1 was positively correlated with the anterior cerebral artery stenosis ( OR=2.130, 95% CI 1.201-3.776, P=0.010); after adjusting for gender, low-density lipoprotein cholesterol, and cholesterol levels, IGF-1 was positively correlated with basilar artery stenosis ( OR=1.688, 95% CI 1.063-2.681, P=0.027). Conclusions:There is an association between IGF-1 levels and intracranial and extracranial atherosclerosis in patients with CSVD. IGF-1 may play a role in the development and progression of atherosclerosis in CSVD.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Chronic disease management is an important element in the strategy of"Healthy China",and the role of pharmacies in chronic disease prevention and treatment has been increasingly recognized.However,there are still differences in the understanding of the function of pharmacies in the chronic disease management system among various circles in China,and it is imperative to enhance the synergistic governance of multiple subjects such as the government,healthcare institutions and pharmacies in the management of chronic diseases.It is found that the theory and practice of chronic disease management system have made great progress in the international arena,and the representative theories include CCM,ICCC and other theoretical models,and the representative practices include community pharmacy management model,pharmacy service expansion model,and pharmacy health management model.The participation of pharmacies in chronic disease management in China has been continuously improved in terms of policy implementation and structural design,and the exploration of local models has been continuously innovated,but it still faces the challenges of insufficient synergy of the main body,insufficient safeguard of the object,insufficiently sound system,and insufficiently perfect mechanism.On the basis of the proposed"synergy-cooperation"chronic disease co-management system framework,we further propose an optimization path for the functional governance of pharmacies in the chronic disease management system,including the strengthening of the main body,the protection of the rights and interests of the object,the improvement of the management system,and the improvement of the supervision mechanism.