OBJECTIVE To investigate the clinical characteristics and risk factors for batroxobin-related severe hypofibrinogenemia （HFIB） and construct a risk prediction model. METHODS A retrospective analysis was conducted on inpatients treated with batroxobin in the First Medical Center of a tertiary hospital from January 1， 2020， to December 31， 2024. Patients were categorized into non-severe HFIB group and severe HFIB group based on the severity of HFIB. Univariate and multivariate Logistic regression analyses were performed to identify the independent influencing factors for batroxobin-related severe HFIB. A nomogram was developed using the “rms” package in R 4.5 software. The predictive performance of the model was evaluated using the receiver operating characteristic curve. Calibration was assessed via the Bootstrap resampling method， and goodness-of-fit was evaluated with the Hosmer-Lemeshow test. RESULTS A total of 1 472 patients were included in this study. Of these， 1 445 developed HFIB， yi elding an incidence of 98.17%. Furthermore， 895 were classified as severe HFIB， accounting for 60.80% of the cohort. Multivariate Logistic regression analysis showed that increased age， high initial dose per 10 kg body weight， use of maintenance dose， and concomitant glucocorticoid use were independent risk factors for batroxobin-related severe HFIB， while high baseline fibrinogen （FIB） level was identified as a protective factor. The model demonstrated an area under the curve of 0.760 （95% CI： 0.735-0.785）. The mean absolute error of the calibration curve was 0.006. The P value of the Hosmer-Lemeshow test was 0.609. CONCLUSIONS Batroxobin can rapidly and significantly reduce FIB levels and carries a risk of inducing severe HFIB. Patients with advanced age， high initial dose per 10 kg body weight， use of maintenance dose and concomitant glucocorticoid use had a higher risk of batroxobin-related severe HFIB， while high baseline FIB level had a lower risk of batroxobin-related severe HFIB. The risk prediction model developed based on these factors can be used to predict the likelihood of batroxobin-related severe HFIB.

The development of tailor-made tumor vaccines targeting specific tumor antigens is crucial for improving treatment accuracy.Tumor mRNA,as an emerging and promising vaccine modality,holds dis-tinct technical edge in addressing this challenge,thus attracting considerable attention in cancer treat-ment.This article reviews the design and synthesis processes of tumor mRNA vaccines,highlighting the latest advances in antigen identification,optimization of RNA sequence and structure,and its delivery.Additionally,it discusses the challenges these vaccines face and outlines potential future directions for development.

Objective To explore the protective effects of genetically modified porcine erythrocyte suspension as a subnormothermic normoxic mechanical perfusate on hypoxic-ischemic brain injury in cynomolgus monkeys caused by traumatic hemorrhage.Methods Cynomolgus monkeys were randomly divided into positive and negative control groups(a total of 3 monkeys,with 3 left cerebral hemispheres as the positive control group and 3 right cerebral hemispheres as the negative control group)and the subnormothermic perfusion group(n=3).The positive control group was directly sampled 1 hour after circulatory arrest,while the negative control group was placed at subnormothermic conditions for 6 hours after circulatory arrest.The subnormothermic perfusion group underwent 6 hours of subnormothermic normoxic mechanical perfusion of the bilateral common carotid arteries of the cynomolgus monkey hypoxic-ischemic brain injury model using genetically modified porcine erythrocyte suspension 1 hour after circulatory arrest.Before perfusion,cross-matching experiments were conducted between the six genetically modified pig and the cynomolgus monkeys.After the start of perfusion,the levels of routine blood indicators in the perfusate were detected at 0,1,2,3,4,5 and 6 hours.Blood oxygen saturation was recorded,and the levels of Na+,K+,Ca2+,glucose and blood pH in the perfusate were measured,as well as the levels of IgG and IgM in the perfusate.After 6 hours of perfusion,the water content of the brain tissue was measured.Nissl staining was performed on the frontal cortex and hippocampal regions,and immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium-binding adapter molecule 1(Iba1)and neuronal nuclear antigen(NEUN).Results The cross-matching results between the six genetically modified pig and the cynomolgus monkeys were negative.The number of red blood cells in the perfusate decreased significantly at 3 hours of perfusion,and the hemoglobin level showed a downward trend at 1,3,5 and 6 hours.The number of white blood cells and platelets decreased at all time points.The blood oxygen saturation in the subnormothermic perfusion group remained stable at 95%-98%,and the levels of blood oxygen saturation,Na+,Ca2+,glucose and pH were stable,while the K+level first increased and then decreased.There was no significant difference in the levels of IgG and IgM before and after perfusion.The water content of brain tissue at the end of perfusion in the subnormothermic perfusion group was significantly higher than that in the positive control group(P<0.001).Nissl staining results showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex of the subnormothermic perfusion group maintained better morphological integrity,with no significant increase in enlarged and deformed cells.In the hippocampal CA1 region,there was a slight increase in enlarged and deformed cells,and a few cells with undamaged structures showed reduced cell size.In the hippocampal dentate gyrus,fewer granule neurons had compromised structural integrity,with increased cell edema.NEUN immunofluorescence staining showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex and hippocampal CA1 region of the subnormothermic perfusion group had better morphological states,with clear axons.The granule cells in the hippocampal dentate gyrus were well preserved,but the nuclei were less well protected.GFAP immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had sparser protrusions that were more tightly associated with neurons.Iba1 immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had thicker and fewer protrusions.Conclusions Compared with the positive control group,subnormothermic normoxic mechanical perfusion with genetically modified porcine erythrocyte perfusate increases brain tissue edema in cynomolgus monkeys,but better preserves the morphological integrity of neurons and glial cells.The protective effects may be related to the continuous oxygen and energy supply,maintenance of ion homeostasis and perfusate pH,reduced rejection,and low metabolic state of the whole brain.

Objective:To investigate the protective effect of achyranthes bidentata(AB)on sperm quality in mice with sper-matogenic disorder through the glycolytic metabolic pathway and its action mechanism.Methods:We equally randomized 40 Kun-ming mice into a normal control,a model control,a low-dose AB(3.5 g/kg)and a high-dose AB group(7.0 g/kg),and established the model of spermatogenic disorder in the latter three groups of mice by intraperitoneal injection of doxorubicin(30 mg/kg).Two days after modeling,we collected the testis and kidney tissues and blood samples from the mice for observation of the pathological changes in the testis tissue by HE staining,detection of perm motility with the sperm quality analyzer,examination of the apoptosis of testis cells by flow cytometry,measurement of the levels of testosterone(T),malondialdehyde(MDA),superoxide dismutase(SOD)and cata-lase(CAT)in the serum and testis tissue by ELISA,and determination of expressions of the key enzymes of glycolysis hexokinase Ⅱ(HK2),pyruvate kinase M2(PKM2),platelet phosphofructokinase(PFKP),lactate dehydrogenase A(LDHA)and the meiosis pro-teins REC8 and SCP3 by Western blot,and the mRNA expressions of glycolytic phosphofructokinase 1(PFK1),phosphoglycerate ki-nase 1(PGK1),tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1β)by fluorescence quantitative PCR(FQ-PCR).Results:Compared with the model controls,the mice in the AB groups showed significant increases in the testis coefficient,kidney in-dex,sperm concentration,sperm motility,spermatogonia,primary spermatocytes,spermatids,sperm count and the serum T level(P＜0.05 orP＜0.01),but dramatic decreases in the apoptosis of testis cells and percentage of morphologically abnormal sperm(P＜0.01).Achyranthes bidentata also significantly elevated the levels of SOD and CAT,and down-regulated the mRNA expressions of MDA,TNF-α and IL-1β(P＜0.05 or P＜0.01),and up-regulated the protein expressions of HK2,PKM2,PFKP,LDHA,REC8 and SCP3,and expressions of the glycolysis key genes Pfk1 and Pgk1(P＜0.05 orP＜0.01).Conclusion:Achyranthes bidentata ameliorates doxorubicin-induced spermatogenic disorder in mice by regulating the glycolytic pathway and reducing oxidative stress and the expressions of inflammatory factors.

Objective To identify high-risk factors for healthcare-associated infection(HAI)in patients in inten-sive care units(ICUs),and develop a quick response(QR)code-based APP prediction tool.Methods Information of inpatients in general ICUs of three hospitals in Guizhou Province from January to December 2024 were collected.Risk factors were analyzed with a logistic regression model.QR code-based APP was constructed and validated.Results A total of 1 782 patients in general ICUs of three hospitals in Guizhou Province in 2024 were included in the analysis,out of which 410 were HAI cases,and the incidence of HAI was 23.01％.Multivariate logistic regre-ssion analysis results of HAI in ICU inpatients showed that regional gross domestic product(GDP)≥58 685 Yuan,performing pathogen culture during this hospitalization,history of diabetes mellitus,history of cancer,length of hospital stay ≥7 days before infection,and duration of persistent fever＞5 days before infection were independent risk factors for HAI in ICU patients(all P＜0.05).The discrimination of the model(area under the receiver operating characteristic curve[AUC]of 0.841),calibration(Brier score of 0.129),and clinical effectiveness(net benefit of 11.4％when the risk threshold was 5％-74％)all performed well.Conclusion The QR code-based APP prediction tool is of great significance for scientific research transformation and precise HAI control.

Artificial intelligence(AI)has emerged as a cutting-edge technology leading the future and is a key engine for China's development.In the innovation and research of medical devices,AI has provided critical support in the areas of intelligent diagnostic assistance,intelligent therapeutic assis-tance,intelligent monitoring,life support,et al.Ma-chine learning-enabled device software functions(ML-DSFs)have become an essential component of many medical devices.Recently,the United States Food and Drug Administration(FDA)released a draft guidance titled"Marketing Submission Rec-ommendations for a Predetermined Change Con-trol Plan for Artificial Intelligence/Machine Learn-ing(AI/ML)-Enabled Device Software Functions(Draft)."that aimed to provide a forward-looking approach to foster the development of ML medical devices.By supporting iterative updates through modifications,this approach ensures the continu-ous safety and effectiveness of the devices.This guidance represents the latest in regulatory direc-tion and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI prod-ucts.Therefore,we plan to provide a detailed intro-duction and interpretation of the guidance,with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence.

Objective To investigate the value of synthetic MRI(syMRI)for evaluating structural changes of brain nuclei and white matter in patients with Parkinson disease(PD).Methods Forty-five PD patients(PD group)and 35 healthy controls(HC group)were prospectively enrolled.Head scanning with strategically acquired gradient echo sequence was performed,then syMRI was obtained with post-processing.The values of T1,proton density(PrD),R2* and magnetic sensitivity values(MSV)of nuclei and white matter were measured based on syMRI and compared between groups.The correlations of syMRI quantitative parameters of nuclei and white matter being significantly different between groups with neurological function scores of subject were analyzed,and a combined model was established using multivariate logistic regression analysis.Receiver operating characteristic(ROC)curve was drawn,the efficacy of single syMRI quantitative parameter and combined model for diagnosing PD was evaluated.Results Compared with HC group,T1 and PrD values of bilateral caudate nuclei decreased,while MSV of bilateral substatia nigra and right red nucleus increased(all FDR correction P＜0.05),while T1 and PrD values of bilateral splenium of corpus callosum,PrD values of left posterior limbs of the internal capsule(PLIC),R2* values of bilateral PLIC and right genu of the corpus callosum decreased in PD group(all FDR correction P＜0.05).syMRI quantitative parameters of the above brain regions were correlated with scores of Montreal cognitive assessment and Hamilton anxiety scale(r=-0.390-0.416,all P＜0.01).The area under the curve of single syMRI quantitative parameter for diagnosing PD was 0.664-0.788,lower than that of combined model(0.905,Z=2.653-4.096,all P＜0.05).Conclusion SyMRI could be used to quantitatively evaluate structural changes of brain nuclei and white matter in PD patients.

Objective To explore the optimisation path of medical resource allocation efficiency improvement in Traditional Chinese Medicine (TCM) hospitals under the synergistic effect of multiple factors,so as to provide powerful support for the balanced development of medical resources in TCM hospitals.Methods The comprehensive efficiency of resource allocation in TCM hospitals in 31 provinces (cities and districts) of China obtained by Data Envelopment Analysis was taken as the outcome variable,and with the help of Fuzzy-set Qualitative Comparative Analysis,it examined the configurations of efficient medical resource allocation,considering the following conditional variables:per capital Regional GDP,the proportion of fiscal allocation revenue to total income,the ratio of TCM practicing (assistant) physicians to all practicing (assistant) physicians,the average length of hospital stay for discharged patients,the number of total diagnosis and treatments per thousand population,and the number of hospital beds per thousand population.Results By analyzing the conditional patterns of efficient allocation of medical resources in TCM hospitals,three equivalent driving paths can be summarized,which are comprehensive service capacity,TCM advantage and hospitalization driving paths.Conclusion The overall level of medical resource allocation efficiency of TCM hospitals in China needs to be improved.In the future,efforts should be made to improve the comprehensive service capacity and operational efficiency of hospitals,give full play to the advantages of TCM,build a high-quality TCM talent team,reasonably shorten the average hospital stay,and improve the utilization efficiency of hospital beds.

Objective To observe the efficacy of self-guided attention network for detecting responsible lesions related to cerebral palsy(CP)in children with periventricular white matter injury(PVWMI).Methods Totally 383 children with PVWMI were retrospectively enrolled and divided into CP group(n=243)and non-CP group(n=140),while 214 children without obvious brain abnormality on brain MRI were taken as control group.ROI of 4 key anatomical structures related to CP,i.e.centrum semiovale,posterior limb of internal capsule,cerebral peduncle and thalamus were delineated on T1WI,while responsible lesions related to CP within the key anatomical structures were labeled on T2WI,and the images were then registrated and used as input of the networks.ResNet34 network was adopted combined with attention and self-guided networks to train the network for detecting responsible lesions related to CP in children with PVWMI,and their efficacies were evaluated.The optimal network was screened,and its efficacy for segmenting the key anatomical structures was evaluated.Results Self-guided attention network was the optimal network,its area under the curve(AUC)for detecting lesions was 0.794-0.914,and the Dice similarity coefficient for segmenting the key anatomical structures was 0.702-0.764.Conclusion Self-guided attention network could be used for preliminarily detecting responsible lesions related to CP in children with PVWMI.

Objective To analyze the dosimetric differences between Monaco Monte Carlo(MC)algorithm and Pinnacle collapse cone convolution(CCC)algorithm for the same machine model using the 6 MV flatten-filter free(FFF)mode,thus providing a reference for the clinical application of these two treatment planning systems.Methods According to the MPPG5 and TRS430 reports,the acceptance and commissioning of Monaco MC algorithm model and Pinnacle CCC algorithm model in Department of Radiation Oncology,Shenzhen Hospital,Cancer Hospital of Chinese Academy of Medical Sciences were performed.A retrospectively analysis was conducted on 30 cases,including 10 cases of nasopharyngeal cancer,6 cases of lung cancer,4 cases of esophageal cancer,and 10 cases of cervical cancer.For each case,a 6 MV FFF plan was designed in Pinnacle using CCC algorithm.A 2.5 mm dose grid was selected for plan optimization and dose calculation.The plan was then exported to Monaco,where dose to medium was calculated using MC algorithm and a 2.5 mm dose grid with a 1%uncertainty for each control point.Both calculations in Pinnacle and Monaco took into account the impact of the treatment couch and immobilization devices on dose attenuation.The dose differences to the target volumes and major organs at risk between Pinnacle and Monaco for 3 different body parts including the head,chest and abdomen were compared.Results(1)For nasopharyngeal cancer,compared with Pinnacle CCC algorithm,Monaco MC algorithm lowered the Vpd of PTVp,PTVn,PTVrpn,PTV1 and PTV2 by 9.98%,2.64%,15.0%,1.93%and 8.01%,elevated the Dmax of PTVp,PTVn and PTVrpn by 2.98%,5.62%and 2.39%,increased the Dmean of PTVn and PTV1 by 1.87%and 0.72%,respectively;and the Dmax of the brainstem,the Dmax of the optic chiasm,and the Dmean of the right parotid gland were 3.83%lower,7.03%higher and 1.32%higher in Monaco MC algorithm as compared with Pinnacle CCC algorithm,respectively.(2)For lung cancer and esophageal cancer,Monaco MC algorithm showed increases of 2.37%,4.18%,15.30%,6.36%and 1.04%in the Dmax of PGTV,the V20,V5 and Dmean of lungs,and the V30 of heart as compared with Pinnacle CCC algorithm,respectively.(3)For cervical cancer,the Vpd of PTV_LR,Dmax of PTV_LR,the V40 of the rectum,the Dmax of the small intestine,and the Dmean of humeral head were 7.70%lower,3.70%higher,4.31%lower,3.05%higher and 2.07%higher in Monaco MC algorithm than in Pinnacle CCC algorithm,respectively.These differences were statistically significant(P<0.05).Conclusion For the above 3 treatment sites,significant differences are found in dose calculations for target areas and organs at risk between Monaco MC algorithm and Pinnacle CCC algorithm for the same treatment plan.Attention should be paid to the differences in dose algorithms for different treatment planning systems in clinical applications,which may have impacts on patient survival rates and organ toxicity.