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.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Despite of the widespread use of hydrogen and methane breath test, the variability in testing protocols, gas measurement techniques, and interpretation criteria continues to challenge the reproducibility and comparability across centers, especially in the Asia-Pacific region. The Asian Neurogastroenterology and Motility Association hence presents the first Asian monograph guiding application and interpretation of breath test. The monograph was formulated according to the framework of indications, preparatory process, performance, and interpretation of results, as well as future direction for research.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

This study investigated the therapeutic effects of a low-dose phage cocktail combined with antibiotics on burn wounds in-fected with multidrug resistant Pseudomonas aeruginosa.Given the risk of sepsis caused by drug-resistant bacteria infection after burns and the limitations of antibiotic monotherapy,we constructed a mouse model of burns combined with Pseudomonas aeruginosa infection.A saline control group,phage cocktail monotherapy group,antibiotic monotherapy group,and combined treatment group were examined.The combined treatment group showed a synergistic effect on the 7th day after infection:this group of mice had a sig-nificantly lower pathogenic bacterial load in the skin and liver tissues than observed in the single drug treatment group,and showed the strongest bacterial clearance effect.Histopathological analysis indicated improved structural integrity of the skin tissue,as well as decreased infiltration of inflammatory cells,and no obvious tissue damage,in the combined treatment group.Detection of serum in-flammatory factors indicated that the levels of the pro-inflammatory factors IL-6 and TNF-α significantly decreased,whereas the level of anti-inflammatory factor IL-10 significantly increased.The combination of low-dose phage cocktail and antibiotics synergistically en-hanced antibacterial activity and ameliorated infection through a dual mechanism of direct removal of pathogens and regulation of the host immune response.Our findings provide an experimental basis for the optimal treatment of wounds infected with multidrug-resistant bacteria.

Objectives:To analyze and summarize the clinical experience of the Y-incision technique in aortic root enlargement surgery.Methods:A retrospective analysis was conducted based on the data of 53 patients who underwent aortic root enlargement using the Y-shaped incision technique by the same surgical team from January to December 2024.The primary endpoint of the study was the efficacy of the technique,as measured by the enlargement size of the valve annulus.The secondary endpoint focused on the safety of the procedure,specifically the incidence of major complications,including re-sternotomy due to bleeding,third-degree atrioventricular block,and major adverse cardiovascular events(MACE).MACE included cardiovascular death,myocardial infarction,stroke,and re-aortic valve intervention.Echocardiography was performed at 3 months after discharge.Root blood flow compliance was analyzed by computer fluid dynamics.Results:Among the 53 patients,30 were male(56.6%),with a mean age of(59.3±13.3)years(range:13-81 years).Five cases(9.4%)were reoperations.Biological valves were replaced in 36 cases(67.9%),and mechanical valves in 17 cases(32.1%).The intraoperatively measured mean native annulus diameter was(20.5±2.2)mm,the post-root enlargement implanted valve size was(25.4±2.5)mm,with a mean enlargement of(4.9±1.5)mm.The mean cardiopulmonary bypass time was(159.9±46.1)minutes,aortic cross-clamp time was(123.3±35.6)minutes,postoperative intensive care unit stay was(2.6±3.0)days,and invasive mechanical ventilation duration was(18.3±29.7)hours.One case(1.9%)required re-exploration for postoperative bleeding.One case(1.9%)developed transient postoperative elevation of cardiac troponin I,and coronary computed tomography angiography(CTA)confirmed asymptomatic compression of the coronary ostium.Follow-up at 1 month showed normal coronary blood flow.No third-degree atrioventricular block or MACE occurred in the entire cohort.Postoperative computer fluid dynamics analysis showed that the high-speed blood flow at the root disappeared after the operation,the blood flow compliance was improved,and no signs of tilt of the prosthetic valve were found.The mean follow-up was(6.2±2.7)months.The follow-up completion rate was 100%,and no death occurred during the follow-up.Both the aortic prosthetic valve and mitral valve functioned well,there was no dysfunction caused by mitral curtain injury.One case of moderate patient-prosthesis mismatch(PPM)occurred in a reoperation patient,there was no severe PPM post surgery.Compared with the preoperative values,left ventricular ejection fraction,peak transaortic valve flow velocity,and the degree of mitral regurgitation all significantly improved at 3 months after discharge(all P<0.001).Conclusions:The Y incision technique is safe and effective for aortic root enlargement,enabling the implantation of larger-diameter prosthetic valves and providing better hemodynamic outcomes.Further follow-up is required to assess its long-term efficacy.

Objective:To analyze policy differences in general outpatient fund pooling of employee basic medical insurance in Yangtze River Delta Region and raise suggestions from the perspective of coordinated development.Methods:The study analyzed policy documents on general outpatients financing,outpatient chronic and special diseases,and inclusion of retail pharmacies into risk pooling at provincial level and in some economically developed cities before August,2024.Typical cases were selected for detailed introduction.Results:General outpatient coverage of employee medical insurance in Yangtze River Delta Region is high,with individual account payment scenarios expanding to commercial health insurance,Long Term Care Insurance and family physician contracted service fees.Number of outpatient chronic and special diseases ranges from 3 to 83.Retail pharmacy policies differ less in access conditions and treatment and e-prescription is advancing rapidly.Suzhou is actively exploring total budget management of retail pharmacies.Conclusions:Outpatient fund pooling policies should be gradually promoted under the principle of"differentiated coordination".It is necessary to transform outpatient chronic and special diseases from"disease coverage"to"cost coverage";strengthen the management of retail pharmacies under the outpatient fund pooling scheme,and improve the coordinated regulatory mechanism for direct settlement of outpatient and medication expenses incurred in other places in the Yangtze River Delta.

Objective To explore the mechanism of the intervention effect of Qizhu Xiaozheng Fang(QZXZF),a representative prescription of Yiqi Jianpi Jiedu(replenishing qi,strengthening spleen,and removing toxicity),in treating HBx-mediated liver cancer stem cells(LCSCs).Methods The Kaplan-Meier survival analysis was used to investigate the effects of Yiqi Jianpi Jiedu on the prognosis of patients with HBV-HCC.The network pharmacology method was utilized to predict the targets and pathways of QZXZF in treating HBx-related LCSCs(HBx-LCSCs).HBx-LCSCs cells were screened by stably transfecting HBx and serum-free culture.The therapeutic effect of QZXZF on HBx-LCSCs was tested in vitro,and its effect on stemness markers and PI3K/Akt pathway was verified by qRT-PCR and Western blot.Results Yiqi Jianpi Jiedu could improve the overall survival time of HBV-HCC patients.Combined with the results of network pharmacology,the mechanism of action of QZXZF against HBx-LCSCs was explored from the PI3K/Akt pathway.Compared with the blank vector group,HBx can promote the expression of stemness markers in HBx-LCSCs cells;compared with the HBx-LCSCs control group,QZXZF could significantly inhibit the proliferation and colony formation of HBx-LCSCs cells(in a concentration-dependent manner),and could reduce the expression of stemness markers(EpCAM,NANOG,SOX2,and OCT4),phosphorylated PI3K(p-PI3K)and phosphorylated AKT(p-AKT)proteins.Conclusion QZXZF may regulate HBx-mediated LCSCs through PI3K/AKT pathways,providing a reference for the mechanism of TCM intervention in LCSCs.

Objectives:To analyze and summarize the clinical experience of the Y-incision technique in aortic root enlargement surgery.Methods:A retrospective analysis was conducted based on the data of 53 patients who underwent aortic root enlargement using the Y-shaped incision technique by the same surgical team from January to December 2024.The primary endpoint of the study was the efficacy of the technique,as measured by the enlargement size of the valve annulus.The secondary endpoint focused on the safety of the procedure,specifically the incidence of major complications,including re-sternotomy due to bleeding,third-degree atrioventricular block,and major adverse cardiovascular events(MACE).MACE included cardiovascular death,myocardial infarction,stroke,and re-aortic valve intervention.Echocardiography was performed at 3 months after discharge.Root blood flow compliance was analyzed by computer fluid dynamics.Results:Among the 53 patients,30 were male(56.6%),with a mean age of(59.3±13.3)years(range:13-81 years).Five cases(9.4%)were reoperations.Biological valves were replaced in 36 cases(67.9%),and mechanical valves in 17 cases(32.1%).The intraoperatively measured mean native annulus diameter was(20.5±2.2)mm,the post-root enlargement implanted valve size was(25.4±2.5)mm,with a mean enlargement of(4.9±1.5)mm.The mean cardiopulmonary bypass time was(159.9±46.1)minutes,aortic cross-clamp time was(123.3±35.6)minutes,postoperative intensive care unit stay was(2.6±3.0)days,and invasive mechanical ventilation duration was(18.3±29.7)hours.One case(1.9%)required re-exploration for postoperative bleeding.One case(1.9%)developed transient postoperative elevation of cardiac troponin I,and coronary computed tomography angiography(CTA)confirmed asymptomatic compression of the coronary ostium.Follow-up at 1 month showed normal coronary blood flow.No third-degree atrioventricular block or MACE occurred in the entire cohort.Postoperative computer fluid dynamics analysis showed that the high-speed blood flow at the root disappeared after the operation,the blood flow compliance was improved,and no signs of tilt of the prosthetic valve were found.The mean follow-up was(6.2±2.7)months.The follow-up completion rate was 100%,and no death occurred during the follow-up.Both the aortic prosthetic valve and mitral valve functioned well,there was no dysfunction caused by mitral curtain injury.One case of moderate patient-prosthesis mismatch(PPM)occurred in a reoperation patient,there was no severe PPM post surgery.Compared with the preoperative values,left ventricular ejection fraction,peak transaortic valve flow velocity,and the degree of mitral regurgitation all significantly improved at 3 months after discharge(all P<0.001).Conclusions:The Y incision technique is safe and effective for aortic root enlargement,enabling the implantation of larger-diameter prosthetic valves and providing better hemodynamic outcomes.Further follow-up is required to assess its long-term efficacy.