ObjectiveDiscriminating atypical hepatocellular carcinoma (HCC) from other malignancies in liver nodules classified as Liver Imaging Reporting and Data System category M (LR-M) remains a significant diagnostic challenge on conventional ultrasound examination. The LR-M category, originally intended to capture non-HCC malignancies, paradoxically contains up to 63% of atypical HCCs that deviate from classic enhancement patterns, leading to potential misdiagnosis and suboptimal treatment planning. While deep learning has shown promise in HCC diagnosis, most existing models rely exclusively on single-modality ultrasound, overlooking the diagnostic benefits of integrating complementary information from multiple imaging sources. To address this gap, we propose a novel attention-weighted tri-modal ultrasound network (TUS-Net) that integrates contrast-enhanced ultrasound (CEUS), B-mode ultrasound (BUS), and time-intensity curves (TICs) to improve diagnostic accuracy for these clinically challenging lesions. MethodsOur framework incorporates a three-dimensional convolutional neural network (C3D) backbone to extract spatiotemporal features from CEUS videos, capturing dynamic vascular patterns critical for lesion characterization. To effectively fuse complementary modalities, we introduce a dual-channel feature fusion module (DCFFM) that adaptively combines features from CEUS and BUS through channel-wise attention mechanisms, allowing the model to dynamically weigh the contribution of each modality based on diagnostic relevance. Additionally, we propose a temporal intensity feature fusion module (TIFFM) that leverages quantitative hemodynamic information from TICs to guide the model’s attention toward diagnostically critical temporal phases, such as arterial wash-in and portal venous washout. The model is further enhanced by automated lesion localization using YOLOX and class activation mapping for interpretability, ensuring that predictions align with clinically meaningful imaging features. ResultsEvaluated on a tri-modal ultrasound dataset comprising 161 patients with pathologically confirmed LR-M nodules (131 atypical HCC and 30 non-HCC malignancies), our model achieved an accuracy of 86.83%, a sensitivity of 92.50%, a specificity of 75.50%, and an AUC of 89.32% in screening atypical HCC. Compared to single-modality baselines, TUS-Net demonstrated superior specificity, a clinically critical metric given the higher risk associated with misclassifying non-HCC malignancies. Ablation studies confirmed the contribution of each module, with the full model outperforming both standard C3D and 3D ResNet backbones integrated with attention mechanisms. A reader study involving junior and senior radiologists further validated the clinical utility of AI assistance, showing consistent improvements in specificity and inter-reader consistency, particularly for less experienced clinicians. ConclusionThese results surpass existing benchmark models and demonstrate the potential of our approach to enhance diagnostic precision in clinically specific cases. By intelligently fusing multi-modal ultrasound data with attention-guided mechanisms, TUS-Net offers a reliable and interpretable tool that holds promise for improving the non-invasive diagnosis of atypical HCC in challenging LR-M liver nodules.

ObjectiveDiscriminating atypical hepatocellular carcinoma (HCC) from other malignancies in liver nodules classified as Liver Imaging Reporting and Data System category M (LR-M) remains a significant diagnostic challenge on conventional ultrasound examination. The LR-M category, originally intended to capture non-HCC malignancies, paradoxically contains up to 63% of atypical HCCs that deviate from classic enhancement patterns, leading to potential misdiagnosis and suboptimal treatment planning. While deep learning has shown promise in HCC diagnosis, most existing models rely exclusively on single-modality ultrasound, overlooking the diagnostic benefits of integrating complementary information from multiple imaging sources. To address this gap, we propose a novel attention-weighted tri-modal ultrasound network (TUS-Net) that integrates contrast-enhanced ultrasound (CEUS), B-mode ultrasound (BUS), and time-intensity curves (TICs) to improve diagnostic accuracy for these clinically challenging lesions. MethodsOur framework incorporates a three-dimensional convolutional neural network (C3D) backbone to extract spatiotemporal features from CEUS videos, capturing dynamic vascular patterns critical for lesion characterization. To effectively fuse complementary modalities, we introduce a dual-channel feature fusion module (DCFFM) that adaptively combines features from CEUS and BUS through channel-wise attention mechanisms, allowing the model to dynamically weigh the contribution of each modality based on diagnostic relevance. Additionally, we propose a temporal intensity feature fusion module (TIFFM) that leverages quantitative hemodynamic information from TICs to guide the model’s attention toward diagnostically critical temporal phases, such as arterial wash-in and portal venous washout. The model is further enhanced by automated lesion localization using YOLOX and class activation mapping for interpretability, ensuring that predictions align with clinically meaningful imaging features. ResultsEvaluated on a tri-modal ultrasound dataset comprising 161 patients with pathologically confirmed LR-M nodules (131 atypical HCC and 30 non-HCC malignancies), our model achieved an accuracy of 86.83%, a sensitivity of 92.50%, a specificity of 75.50%, and an AUC of 89.32% in screening atypical HCC. Compared to single-modality baselines, TUS-Net demonstrated superior specificity, a clinically critical metric given the higher risk associated with misclassifying non-HCC malignancies. Ablation studies confirmed the contribution of each module, with the full model outperforming both standard C3D and 3D ResNet backbones integrated with attention mechanisms. A reader study involving junior and senior radiologists further validated the clinical utility of AI assistance, showing consistent improvements in specificity and inter-reader consistency, particularly for less experienced clinicians. ConclusionThese results surpass existing benchmark models and demonstrate the potential of our approach to enhance diagnostic precision in clinically specific cases. By intelligently fusing multi-modal ultrasound data with attention-guided mechanisms, TUS-Net offers a reliable and interpretable tool that holds promise for improving the non-invasive diagnosis of atypical HCC in challenging LR-M liver nodules.

BACKGROUND:Erythropoietin/erythropoietin receptor signaling pathway not only participates in bone marrow hematopoiesis,but also regulates the metabolic response of non-hematopoietic tissues,such as brain,heart,skeletal muscle,and adipose tissue.Simultaneously,it can accelerate the mineralization process of periodontal ligament stem cells and reduce oxidative stress damage.However,the mechanism of action on osteogenic differentiation of periodontal ligament stem cells is still unclear.OBJECTIVE:To investigate the effect and action mechanism of erythropoietin/erythropoietin receptor signaling pathway on osteogenic differentiation of periodontal ligament stem cells.METHODS:Enzyme digestion method was used to isolate and culture periodontal ligament stem cells from periodontal disease patients and healthy people.The mRNA and protein levels of erythropoietin receptor in two kinds of periodontal ligament stem cells were detected by qRT-PCR and western blot assay.Erythropoietin receptor expression was silenced by small interfering RNA(siRNA)or activated by erythropoietin.qRT-PCR and western blot assay were used to detect the expression of erythropoietin receptor,levels of osteogenic marker genes Runt-related transcription factor 2(Runx2),osteocalcin,osteopontin,and bone sialoprotein.Alkaline phosphatase staining and alizarin red staining were applied to measure osteogenic differentiation ability of periodontal ligament stem cells.The phosphorylation of signal transducer and activator of transcription 5(STAT5)was detected by western blot assay.RESULTS AND CONCLUSION:(1)The results of qRT-PCR and western blot assay showed that the mRNA and protein levels of erythropoietin receptor in periodontal ligament stem cells in the disease group were significantly lower than those in periodontal ligament stem cells in the healthy group.(2)Alkaline phosphatase staining and alizarin red staining showed that knocking down the erythropoietin receptor can inhibit the osteogenic differentiation ability of periodontal ligament stem cells.qRT-PCR results showed that compared with the control group,knockdown of the erythropoietin receptor group significantly reduced expression levels of Runt-related transcription factor 2,osteocalcin,osteopontin,and bone sialoprotein(P＜0.05).(3)qRT-PCR results showed that after erythropoietin treatment,the expression of erythropoietin receptor in periodontal ligament stem cells recovered.Silencing erythropoietin receptor and then administration of erythropoietin treatment reversed the expression level of erythropoietin receptor.Erythropoietin treatment increased the osteogenic differentiation ability of periodontal ligament stem cells in the disease group and the expression level of the osteogenic marker gene Runt-related transcription factor 2(P＜0.05).Silencing the expression of STAT5 inhibited this effect of erythropoietin.(4)Western blot assay results showed that with the extension of erythropoietin treatment time,the phosphorylation level of STAT5 increased in periodontal ligament stem cells in the disease group(P＜0.05).The above results indicate that erythropoietin restores the osteogenic differentiation ability of pathological periodontal ligament stem cells by inducing the phosphorylation of STAT5.

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

BACKGROUND:Erythropoietin/erythropoietin receptor signaling pathway not only participates in bone marrow hematopoiesis,but also regulates the metabolic response of non-hematopoietic tissues,such as brain,heart,skeletal muscle,and adipose tissue.Simultaneously,it can accelerate the mineralization process of periodontal ligament stem cells and reduce oxidative stress damage.However,the mechanism of action on osteogenic differentiation of periodontal ligament stem cells is still unclear.OBJECTIVE:To investigate the effect and action mechanism of erythropoietin/erythropoietin receptor signaling pathway on osteogenic differentiation of periodontal ligament stem cells.METHODS:Enzyme digestion method was used to isolate and culture periodontal ligament stem cells from periodontal disease patients and healthy people.The mRNA and protein levels of erythropoietin receptor in two kinds of periodontal ligament stem cells were detected by qRT-PCR and western blot assay.Erythropoietin receptor expression was silenced by small interfering RNA(siRNA)or activated by erythropoietin.qRT-PCR and western blot assay were used to detect the expression of erythropoietin receptor,levels of osteogenic marker genes Runt-related transcription factor 2(Runx2),osteocalcin,osteopontin,and bone sialoprotein.Alkaline phosphatase staining and alizarin red staining were applied to measure osteogenic differentiation ability of periodontal ligament stem cells.The phosphorylation of signal transducer and activator of transcription 5(STAT5)was detected by western blot assay.RESULTS AND CONCLUSION:(1)The results of qRT-PCR and western blot assay showed that the mRNA and protein levels of erythropoietin receptor in periodontal ligament stem cells in the disease group were significantly lower than those in periodontal ligament stem cells in the healthy group.(2)Alkaline phosphatase staining and alizarin red staining showed that knocking down the erythropoietin receptor can inhibit the osteogenic differentiation ability of periodontal ligament stem cells.qRT-PCR results showed that compared with the control group,knockdown of the erythropoietin receptor group significantly reduced expression levels of Runt-related transcription factor 2,osteocalcin,osteopontin,and bone sialoprotein(P＜0.05).(3)qRT-PCR results showed that after erythropoietin treatment,the expression of erythropoietin receptor in periodontal ligament stem cells recovered.Silencing erythropoietin receptor and then administration of erythropoietin treatment reversed the expression level of erythropoietin receptor.Erythropoietin treatment increased the osteogenic differentiation ability of periodontal ligament stem cells in the disease group and the expression level of the osteogenic marker gene Runt-related transcription factor 2(P＜0.05).Silencing the expression of STAT5 inhibited this effect of erythropoietin.(4)Western blot assay results showed that with the extension of erythropoietin treatment time,the phosphorylation level of STAT5 increased in periodontal ligament stem cells in the disease group(P＜0.05).The above results indicate that erythropoietin restores the osteogenic differentiation ability of pathological periodontal ligament stem cells by inducing the phosphorylation of STAT5.

Objective:To explore the clinical characteristics of biliary system diseases complicated by severe acute pancreatitis(SAP) and the risk factors.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on the clinical data of 159 SAP patients admitted to the Department of Pancreatic and Biliary Surgery,the First Affiliated Hospital of Harbin Medical University from January 2019 to October 2024. There were 105 male cases, 54 female cases;aged (42.3±10.8)years (range:20 to 71 years). Grouping was performed according to the presence or absence of concurrent acute acalculous cholecystitis (AAC) and biliary stricture. There were 58 cases in the AAC group,including 40 males and 18 females;aged (43.8±10.6) years (range:28 to 71 years);101 cases in the non-AAC group,including 64 males and 37 females;aged (41.5±10.8) years (range:20 to 64 years);there were statistically significant differences between the two groups in terms of admission total bilirubin,Balthazar-CTSI score,fasting time,and the proportions of concurrent shock and sepsis (all P<0.05);the time from onset of SAP to diagnosis of AAC( M (IQR)) was 10.5 (13.3) days (range: 3 to 34 days). There were 15 cases in the biliary stricture group,including 13 males and 2 females;age (46.5±10.0) years (range:33 to 63 years);141 cases in the non-biliary stricture group,including 89 males and 52 females;age (41.9±10.8) years (range: 20 to 71 years); there were statistically significant differences between the two groups in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis (all P<0.05);the time from the onset of SAP to the diagnosis of biliary stenosis in patients with biliary stenosis was 2.0 (3.0) months (range: 1 to 19 months). Univariate analysis was performed using independent sample t-test, Mann-Whitney U test, χ 2 test,or Fisher′s exact probability method,and variables with P<0.05 in univariate analysis were included in multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic and predictive value of the multivariate logistic regression model for AAC and biliary stricture. Results:There were statistically significant differences in fasting time,Balthazar-CTSI score,admission total bilirubin,and the proportions of concurrent shock and sepsis between the AAC group and non-AAC group ( P<0.05). Multivariate logistic analysis showed that admission total bilirubin ( OR=1.033,95% CI: 1.010 to 1.058, P=0.004),Balthazar-CTSI score ( OR=1.276,95% CI: 1.036 to 1.572, P=0.022),fasting time ( OR=1.127,95% CI: 1.044 to 1.216, P=0.002), and sepsis ( OR=4.033, 95% CI: 1.419 to 11.462, P=0.009) were independent risk factors for AAC complicated by SAP. The area under the curve (AUC) of the ROC curve was 0.820 (95% CI: 0.752 to 0.888). There were statistically significant differences in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis between the biliary stricture group and non-biliary stricture group ( P<0.05). Multivariate logistic analysis showed that infected pancreatic necrosis ( OR=7.376,95% CI:1.566 to 37.750, P=0.012) and pancreatic head necrosis ( OR=3.898,95% CI:1.180 to 12.877, P=0.026) were independent risk factors for biliary stricture complicated by SAP. The AUC of the ROC curve was 0.806 (95% CI:0.715 to 0.898). Conclusions:AAC typically occurs in the early stage of SAP,and biliary stricture usually occurs in the late stage of SAP. Admission total bilirubin,Balthazar-CTSI score,fasting duration,and concurrent sepsis are independent risk factors for AAC complicating SAP. Infected pancreatic necrosis and pancreatic head necrosis are independent risk factors for biliary stricture complicating SAP.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.