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.

OBJECTIVE To establish a high-risk medication list and preventive and therapeutic measures for drug-induced hypofibrinogenemia， and to provide a reference for the prevention and treatment of this condition. METHODS By integrating domestic and international case reports， retrospective case-control studies， and spontaneous adverse drug reaction reporting databases， 19 domestically marketed high-risk drugs for drug-induced hypofibrinogenemia were identified. Based on the clinical characteristics and mechanisms of these drugs， relevant risk factors were systematically reviewed， and existing treatment options were summarized， leading to the preliminary development of recommended preventive and therapeutic measures. A two-round Delphi consultation was conducted to evaluate， revise， and ultimately reach consensus on the preliminary findings， using a mean importance score of ≥3.5 points for indicators and a coefficient of variation ＜0.3 as screening criteria. RESULTS The coefficient of expert authority for both rounds of expert consultation was 0.904. In the first round， the Kendall coordination coefficients （Kendall’s W ） for the high-risk medication list and the proposed preventive and therapeutic measures were 0.390 and 0.223 （ P ＜0.05）， respectively. In the second round， the Kendall’s W were 0.227 and 0.200 （ P ＜0.05）， respectively. After two rounds of expert consultation and discussion， 11 high-risk drugs for drug-induced hypofibrinogenemia， represented by hemocoagulase and certain anti-infective agents， were ultimately identified， along with 5 preventive and therapeutic measures spanning the entire process of “pre-medication assessment， intra-medication monitoring， and bleeding event management”. CONCLUSIONS This study has established a scientific and reliable high-risk medication list， and corresponding preventive and therapeutic measures for drug-induced hypofibrinogenemia， providing a theoretical basis and practical support for the early identification， stratified management， and precise intervention of this condition.

ObjectiveThis study aims to explore the potential of different orders of magnitude single-nucleotide polymorphism (SNP) locus combinations for predicting distant kinship relationships. A high-density SNP locus set was constructed, and a comprehensive assessment of its inference capability was conducted. MethodsFirstly, we selected three commercial chip panels, CGA (Chinese genotyping array, Illumina), GSA (Global screening array, Illumina), Affy (23MF_V2 high-density SNP array, Affymetrix) and merged them after quality control, forming a high-density SNP locus panel(1 180 k). Secondly, we selected 161 samples and collected their peripheral blood samples by using whole-genome sequencing technology. Within this sample population, the levels of kinship relationships fully covered the range from level 1 to level 9, and the number of kinship pairs at each level was consistently maintained at over 50 pairs. From 161 samples data of whole-genome sequencing, the 1 180 k locus set was extracted, which is referred to as the high-density SNP locus set in the following text. The kinship inference was conducted using the identity-by-descent (IBD) algorithm with the selected optimal parameters. To comprehensively evaluate the performance of the high-density SNP locus set in kinship inference, we compared it with the three commercial chip panels, the intersection of these three chip loci, and the control sets constructed by randomly reducing the number of the high-density SNP locus set. Based on the changes in the IBD lengths, as well as the dynamic trends in prediction accuracy, we conducted a scientific assessment of the kinship inference capability of the high-density SNP locus set. ResultsAfter screening, a set of 1 184 334 autosomal SNPs was obtained. During the process of screening the optimal IBD length threshold, the result revealed that 0 cM, 1 cM, and 2 cM all demonstrated good applicability. However, to avoid the issue of a large amount of redundant information caused by setting a too low IBD length threshold, this study ultimately selected 2 cM as the optimal threshold. Compared with the average results of three chip panels, the high-density SNP locus set increased the total IBD length and the average IBD length across levels 1-9; the accuracy of the confidence interval for level 8 was 70.97%, which represented a 3.50% improvement; the average confidence interval accuracy for levels 1-8 was 91.39%, representing a 1.00% increase; and the false negative rates at levels 8 and 9 were reduced by 2.42% and 6.76%, respectively. The system efficacy of the high-density SNP locus set for kinship inference of first to eighth degree relationships reached 98.91%. Through random reduction of the high-density SNP locus set results, it is found that increasing the number of SNPs with the panel, the detection efficiency of IBD length showed a significant upward trend. At the same time, the overall trend in the accuracy of kinship relationship prediction as well as the confidence interval accuracy also indicated that both metrics steadily increased with the addition of more loci. ConclusionThe results show that the high-density SNPs panel significantly enhances the efficacy of distant kinship inference, accurately covering kinship degrees, with the average confidence interval accuracy for first to eighth degree relationships stably above 90%. The study finds that increasing the number of SNPs panel can improve the ability to predict distant kinship.

ObjectiveTo observe the prognosis effect of soluble programmed death ligand-1（sPD-L1） in treating patients with advanced lung adenocarcinoma treated with epidermal growth factor receptor-tyrosine kinase inhibitors（EGFR-TKIs） and the influence of Yiqi Yangyin Jiedu prescription. MethodA prospective cohort-controlled study was conducted to enroll patients treated with EGFR-TKIs in the first line of treatment，who were admitted to the Oncology Department of Longhua Hospital and Shanghai Chest Hospital from May 1^st， 2021 to June 30^th， 2023， and they were evaluated as non-progressive and identified with deficiency of Qi and Yin after one month of treatment. The patients were divided into an exposed group （EGFR-TKIs combined with Yiqi Yangyin Jiedu prescription） and a non-exposed group （EGFR-TKIs alone）according to whether or not they were treated with Yiqi Yangyin Jiedu prescription and were treated until disease progression， or death and intolerable adverse reactions occurred. The enzyme-linked immunosorbent assay （ELISA） was applied to detect the level of sPD-L1 in patients at the time of enrollment and disease progression，and Cox risk proportionality model was used to analyze the independent prognostic factors affecting disease progression of patients treated with EGFR-TKIs. ResultA total of 90 patients （39 in the exposed group and 51 in the non-exposed group） undergoing disease progression after EGFR-TKI treatment were enrolled. At the time of enrolment and after disease progression，the levels of serum sPD-L1 in the 90 patients were 12.06 （27.54） ng·L^-1 and 41.99 （62.93） ng·L^-1，respectively. Compared with that at the time of enrollment， the serum sPD-L1 level in the 90 patients was significantly increased after disease progression （P<0.01）. The serum sPD-L1 level in patients in the exposed group was 12.27 （24.78） ng·L^-1 and 29.57 （61.12）ng·L^-1 respectively at the time of enrolment and after disease progression. In the non-exposed group， patients had serum sPD-L1 levels of 11.81 （28.46） ng·L^-1 and 49.54 （74.12） ng·L^-1 respectively at the time of enrolment and after disease progression. Compared with that at the time of enrollment， the serum sPD-L1 level in the two groups of patients was significantly increased after disease progression （P<0.01）. In addition， compared with that in the non-exposed group， the sPD-L1 level in the exposed group was greatly reduced after disease progression（P<0.01）. Cox multifactorial analysis showed that sPD-L1 level and age at the time of enrolment were associated with patients' progression-free survival（PFS），and that low levels of sPD-L1 （<12.06 ng·L^-1） prolonged the PFS and reduced the risk of disease progression in patients treated with EGFR-TKIs compared with high levels of sPD-L1. ConclusionElevated sPD-L1 level is a poor prognostic factor for the long-term efficacy of EGFR-TKIs，and treatment with Yiqi Yangiin Jiedu prescription can down-regulate sPD-L1 level of patients treated with EGFR-TKIs.

Objective To develop an automatic segmentation network for thyroid nodules by integrating wavelet transform and CNN-Transformer in order to improve the efficiency and accuracy of ultrasound image segmentation.Methods A total of 1 371 sets of ultrasound images of thyroid nodules were collected from Department of Ultrasonography of Second Affiliated Hospital of Army Medical University between May 2023 and February 2024.After preprocessing and normalization,the data were divided into training,validation,and testing sets in a ratio of 8∶1∶1.Based on UNet,CNN and Swin-Transformer were used in parallel as the encoder,with a wavelet transform module inserted between the encoder and decoder to construct a thyroid nodule segmentation network.The performance of the segmentation model was evaluated on the collected internal dataset using accuracy,IoU,and Dice coefficient metrics.Results The finally verified 1 371 sets of ultrasonic thyroid nodules had an average Dice coefficient of 79.63%and an IoU of 67.30%.Compared with UNet,the segmentation accuracy was improved by 1.02%.The segmentation model obtained accurate location and smooth edges of thyroid nodules,and the segmentation was more consistent in thyroid nodule edge and morphology with those marked by doctors manually when compared with other segmentations.Compared with UNet,this segmentation method can learn the texture of nodules more fully and avoid the situation that nodules had been incorrectly divided into surrounding tissues.Conclusion Our developed segmentation model based on wavelet transform and CNN-Transformer demonstrates better segmentation accuracy in comparison to conventional UNet variants,such as UNet,Attention-UNet,and UNetv2,and medical segment anything models like SAM Med2D.This segmentation method enables accurate segmentation of ultrasound thyroid nodules,thereby enhancing clinical workflow efficiency through automated precise delineation.

Objective To investigate the effects and potential mechanisms of polystyrene micro/nanoplastics(PS-MNPs)on testicular Sertoli cells.Methods Sixty male C57BL/6N mice(8 weeks old)were randomly divided into a control group(deionized water),a PS-NPs group[particle size of 20 nm,2.5 mg/(kg·d)],and a PS-MPs group[particle size of 5 μm,2.5 mg/(kg·d)],with 20 mice in each group.The corresponding agents were gavaged once daily for 6 months.HE staining was used to observe the histopathological and morphological changes in the testicular tissues.Immunohistochemistry of marker proteins was employed to evaluate the changes in the number of Sertoli cells.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to identify functions and signaling pathways enriched in the testicular transcriptome.Mouse testicular Sertoli cell line TM4 was divided into a control group(deionized water),a 2.5NPs group(2.5 μg/mL),and a 2.5MPs group(2.5 μg/mL).All groups received continuous exposure through 130 cell passages.Cell viability and proliferative capacity were evaluated using CCK-8 assay and EdU incorporation,while cell migration was assessed using transwell and cell scratch assays.RT-qPCR and Western blotting were used to detect the changes in the expression of key molecules regulating mesenchymal phenotypic transformation(MPT)at mRNA and protein levels.Results Pathological analysis revealed that,when compared to the control group,PS-NPs and PS-MPs treatment resulted in extended spaces between testicular seminiferous tubules,loosely arranged spermatogenic cells,and enhanced vacuolization.Immunohistochemical analysis of marker proteins indicated a decreasing trend in the number of testicular Sertoli cells in the PS-NPs and PS-MPs groups than the control group,with the PS-NPs group having statistical significance(P<0.01).GO and KEGG enrichment analyses revealed that PS-MNPs exposure-related altered genes were significantly enriched in cell adhesion signaling pathways(P<0.05).PS-MPs exposure significantly inhibited the growth and migration ability of TM4 cells(P<0.05),but PS-NPs exposure had no such effect on cell growth but notably enhanced cell migration ability.PS-NPs exposure inhibited the expression levels of E-cadherin and ZO-1(P<0.01)and up-regulated the expression of N-cadherin and vimentin(P<0.01),and PS-MPs exposure led to significant up-regulation of vimentin(P<0.01)and down-regulation of E-cadherin,N-cadherin,and ZO-1(P<0.05).Both PS-MPs and PS-NPs exposure up-regulated the mRNA levels of Snail2,Twist1,and Zeb2(P<0.01).Conclusion Exposure of PS-MNPs leads to abnormal proliferation and migration of TM4 cells,induces decreases in cell-cell contacts among Sertoli cells and spermatogenic cells at all levels possibly through MPT,and thus results in testicular damage.

Objective To investigate whether long-term low-dose exposure to polystyrene microplastics(PS-MPs)induces ferroptosis in testicular Sertoli cells and then leads to testicular injury.Methods Forty 8-week-old male C57BL/6 mice were randomly divided into a control group(deionized water group)and a PS-MPs group[2.5 mg/(kg·d)],with 20 mice in each group.Corresponding agents were gavaged once a day for 12 consecutive months.HE staining and Prussian blue staining were used to detect histopathological damage and accumulation of ferrous ions in the testes.Electron transmission microscopy was employed to observe the mitochondrial morphology of testicular Sertoli cells.Mouse Sertoli cell line TM4 was divided into a Con group(standard culture)and an MPs group(2.5 μg/mL PS-MPs).After both groups underwent continuous exposure and passed up to the 100th generation,morphological changes were observed under the microscope;cell viability was detected with CCK8 assay,and production of reactive oxygen species(ROS)and mitochondrial membrane potential(MMP)were detected with a ROS probe and a mitochondrial membrane potential probe(JC-1),respectively.Flow cytometry,ferrous ion(Fe2+)kit and Western blotting were applied to detect cell apoptosis,intracellular iron ion content,and protein levels of key molecules of ferroptosis in tissues and cells.Results Long-term exposure to PS-MPs resulted in significantly reduced diameter and thickness of mouse varicocele(P<0.01),fewer testicular Sertoli cells(P<0.05),with characteristic ferroptosis alterations in the mitochondria,and increased accumulation of ferrous ions in testicular tissue.Exposure to PS-MPs down-regulated the key molecules of ferroptosis,glutathione peroxidase 4(GPX4)and ferritin light chain(FTL)when compared with the control group(P<0.05).In the cell model,long-term PS-MPs exposure led to morphological changes and decreased cell viability(P<0.05),more production of ROS(P<0.01),and decrease in MMP(P<0.05)of TM4 cells.The exposure had no effect on cell apoptosis,but elevated the intracellular content of ferric ions(P<0.01),and down-regulated GPX4 and FTL protein levels(P<0.05).Conclusion Long-term low-dose exposure to PS-MPs induces mitochondrial damage and oxidative stress in testicular Sertoli cells,activates the ferroptosis pathway,and ultimately leads to testicular injury in mice.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.

Objective To observe the therapeutic effects of Fourteen-Needle Awakening Acupuncture combined with repetitive transcranial magnetic stimulation(rTMS)on post-stroke patients with minimally conscious state(MCS).Methods Sixty MCS patients admitted to the Rehabilitation Department of Guangdong Second Traditional Chinese Medicine Hospital between December 2023 and December 2024 were randomly divided into an observation group and a control group,with 30 cases in each group.Both groups received conventional awakening therapy.The control group received additional sham rTMS,while the observation group received Fourteen-Needle Awakening Acupuncture combined with rTMS.The treatment duration was 14 days for both groups.After two weeks,awakening status was evaluated.Changes in Coma Recovery Scale-Revised(CRS-R)scores,Glasgow Coma Scale(GCS)scores,Full Outline of Unresponsiveness(FOUR)scores,as well as serum levels of vascular endothelial growth factor(VEGF)and neuron-specific enolase(NSE)were compared between groups before and after treatment.Results(1)After treatment,17 patients in the observation group regained consciousness,with a recovery rate of 56.67％(17/30);9 patients in the control group regained consciousness,with a recovery rate of 30.00％(9/30).The recovery rate in the observation group was significantly higher than that in the control group(P＜0.05).(2)After treatment,the CRS-R scores in both groups were significantly improved(P＜0.05),with the observation group showing a greater degree of improvement(P＜0.05).(3)After treatment,the FOUR scores and GCS scores of both groups were significantly improved(P＜0.05),with the observation group showing a greater degree of improvement(P＜0.05).(4)After treatment,the serum VEGF and NSE levels of both groups were significantly improved(P＜0.05),with the observation group showing a greater degree of improvement(P＜0.05).Conclusion Fourteen-Needle Awakening Acupuncture combined with rTMS effectively enhances cortical excitability and modulates electrophysiological activity of cerebral neurons in post-stroke MCS patients.This combined therapy demonstrates positive therapeutic effects in improving MCS and significantly accelerates consciousness recovery.