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.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

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.

Objective To study the age-dependent relationship between body mass index(BMI)and cognitive impairment in rural population aged 40 years and above.Methods From October 2014 to March 2015,people aged 40 years and above,who lived in two natural villages in Huyi District of Xi'an,were selected as the research subjects.Their general demographic information,lifestyle,medical history,family history,physical examination,and biochemical examination were collected.Mini-Mental State Examination(MMSE)was used to evaluate global cognitive function.Cognitive impairment was defined as an MMSE score lower than the cutoff value,specifically,scores ≤17 for subjects who were illiterate,scores ≤20 for subjects with primary school education,and scores ≤24 for subjects with junior high school education or above.The age-dependent relationship between BMI and cognitive impairment was discussed using stratified analysis,restricted cubic spline(RCS),and multivariate Logistic regression.Results We included a total of 1 792 subjects in the analysis,of whom 230(12.8％)were diagnosed with cognitive impairment.There were 726 males(40.5％);the average age was(55.53±9.92)years,ranging from 40 to 85 years,1 193 subjects aged 40-59 years(66.6％),and 599 subjects aged ≥60 years(33.4％).The average BMI was(25.29±3.14)kg/m2.In the total population,BMI index was fitted as restricted cubic splines in the Logistic regression model,and other confounding factors were corrected.The results showed that BMI index was significantly correlated with cognitive impairment(Poverall=0.023),and there was a trend of nonlinear relationship(P nonlinear=0.097).The specific relationship was that with BMI=25 kg/m2 as the reference(OR=1),when BMI index was＜25 kg/m2,the OR value increased as BMI index decreased.However,when BMI index was ≥25 kg/m2,the OR value did not change significantly as BMI index increased.The population was divided into two subgroups according to age(40-59 years vs.≥60 years).Stratified analysis showed that in the ≥60 years old subgroup,cognitive impairment had significant correlation with BMI index(Poverall=0.038,Pnonlinear=0.097),and the changing trend of the correlation was similar to that of the overall population.By contrast,in the 40-59 years old subgroup,BMI index was not significantly associated with cognitive impairment(Poverall=0.722,Pnonlinear=0.738).Conclusion The relationship between BMI and cognitive impairment is affected by age.No significant association is found in the middle-aged population of 40-59 years old,but there may be a nonlinear association in the elderly population over 60 years old.Specifically,with BMI=25 kg/m2 as the boundary,as BMI decreases,the risk of cognitive impairment gradually increases.As BMI further increases,the risk of cognitive impairment does not change significantly even though it reaches the obesity level.

Objective:To investigate the expression of transcription factor Zinc finger and BTB domain-containing 4 (ZBTB4) in papillary thyroid carcinoma and its relationship with the clinicopathological features of the tumor.Methods:Immunohistochemistry (IHC) was used to assess ZBTB4 protein of cancerous tissues and paired-normal tissues extracted from surgical samples of 60 patients with papillary thyroid carcinoma (30 classical and 30 with Hashimoto’s thyroiditis) . Fresh tissue samples were collected from above patients, and the expression of ZBTB4 gene mRNA and ZBTB4 protein in cancerous tissues was detected by qRT-PCR and Western blot methods. SPSS statistical software was used to analyze the relationship between the expression level of this gene in tumor tissues, clinicopathological features and tumor prognosis.Results:Immunohistochemical results showed that the expression of ZBTB4 protein in papillary thyroid carcinoma tissues was significantly higher than that in normal thyroid tissues (25.0% vs. 3.3%, P=0.001) . The results of qRT-PCR showed that the expression of ZBTB4 gene mRNA in tumor tissues was significantly higher than that in normal thyroid tissues ( P<0.001) . There was no significant difference in the expression level of ZBTB4 between patients with classical papillary carcinoma and those with Hashimoto’s thyroiditis. Multivariate analysis showed that the patients with higher expression of ZBTB4 had relatively smaller tumor diameter ( t=2.31, P=0.025) and less lateral cervical lymph node metastasis ( t=4.13, P=0.042) . Conclusions:Patients with higher ZBTB4 expression level have better outcome, as reflected in smaller tumor diameter and lower rates of lateral cervical lymph node metastasis. The molecular mechanism of ZBTB4 gene in papillary thyroid carcinoma needs further study.

Objective:To retrieve, evaluate and summarize the best evidence on the use of bedside ultrasound by ICU nurses to assess the lungs of adult critically ill patients, and to provide a reference for clinical practice and the construction of related processes and protocols.Methods:Based on the "6S" pyramid model, a computer-based search was conducted on relevant computer decision support system, guideline networks, professional associations, and domestic and international databases, the search time limit was from the establishment of the database to June 5, 2024. The panel members who had been trained in the evidence-based course evaluated the included literature with corresponding tools, extracted evidence according to the theme.Results:Twenty-five papers were finally included, including 6 guidelines, 8 expert consensus, 2 expert opinion, 3 clinical decision-making, 3 systematic evaluation, and 3 randomized controlled trials. A total of 35 pieces of evidence were formed from 4 aspects, including personnel training, operation specifications, clinical application (including dyspnea screening, intervention implementation, efficacy evaluation, diaphragm function evaluation) and precautions.Conclusions:The best evidence for lung assessment and intervention in adult critically ill patients based on bedside ultrasound can provide a reference for the adjustment and decision-making of nursing measures for adult critically ill patients. In the subsequent process of evidence transformation, attention should be paid to combining clinical practice and the joint cooperation of medical staff.

Objective To develop a risk management system for complications associated with peripheral venous indwelling needles and to evaluate its application effect in order to reduce the risk of related complications.Methods We designed a comprehensive risk management system for peripheral intravenous indwelling needle complications,integrating specialized evidence-based guidelines with clinical practice insights,including 5 modules:intelligent assessment and decision support,intelligent inspection reminders,educational modules,collaborative case management procedures,and a knowledge base.Patients admitted to the neurology and internal classification metabolism departments of a tertiary hospital in Jilin Province were conveniently selected as the research subjects.Patients were assigned to a control group(from May to July 2022,before the implementation of the system)and an experimental group(from September to December 2022,after the implementation of the system).The incidence of complications,duration of indwelling needle,compliance rate of core indicators for nursing quality and number of nursing consultations were compared between the groups.Additionally,a self-administered questionnaire was used to assess clinical nurses'evaluations of the system.Results A total of 189 patients were included in the experimental group and 177 patients in the control group.The incidence of complications associated with peripheral intravenous indwelling needles was lower than that in the control group.The duration of indwelling peripheral intravenous needles was longer than that in the control group.The quality compliance rate of peripheral venous indwelling needle care in the experimental group was higher than that in the control group,and the number of consultation cases in the experimental group was higher than that in the control group.Comparisons between the 2 groups showed statistically significant differences for all indicators(P＜0.05).The nurses'recognition rates for the system's user-friendliness,professional guidance,and patient benefit were 77.78％,81.74％,and 82.13％,respectively.Conclusion The application of a peripheral vein indwelling needle complication risk management system can reduce the incidence of complications,prolong the duration of indwelling,and improve nursing quality.Nurses have a high recognition of this system.

Objective To analyze the effects of different traction sites and directions on the maxilla and upper dentition when using clear aligners combined with protraction for the treatment of maxillary deficiency.Methods A three-dimensional(3D)finite element model including the zygomaticomaxillary complex,maxillary dentition,and clear aligners was constructed.The models were divided into Group 1(traction hook at the distal of the lateral incisor)and Group 2(traction hook at the distal of the canine).Each group was analyzed under four loading conditions with protraction angles of 0°,10°,20°,and 30° relative to the occlusal plane.A unilateral protraction force of 500 g was applied.The differences in stress distribution and displacement of the maxillary bone and dentition under different loading conditions were analyzed.Results When the protraction angle was 30°,both groups showed forward and downward displacement of the maxilla,while other angles resulted in counterclockwise rotation.Under the same protraction direction,the total displacement of the maxilla and displacements in all directions in Group 2 were greater than those in Group 1.The upper central incisors in Group 1 showed lingual displacement,which increased with the protraction angle.The maxillary dentition in Group 2 showed forward displacement,with the minimum total and sagittal displacements at a protraction angle of 30°.Stress concentration was mainly observed in the zygomaticomaxillary suture and anterior alveolar bone regions in both groups,decreasing as the protraction angle increased.Conclusions Clear aligners combined with protraction can be applied to skeletal Class Ⅲ patients with mild maxillary deficiency.When the protraction site is located at the distal of the canine with a 30° downward and forward angle to the occlusal plane,the maxilla can achieve ideal forward and downward displacement with the minimum labial movement of the upper anterior teeth.