Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

With the change of infectious disease incidence pattern and the development of related technologies, progresses have been made in the research of infectious disease epidemiology. In recent years, due to the change in the requirements of infectious disease prevention and control, the research focus has expanded from common infectious diseases to diseases which have been eliminated or might be eliminated, as well as emerging and re-emerging infectious diseases. Infectious disease data has been characterized by multiple sources and modalities. Along with the rapid development of pathogen detection methods, infectious disease surveillance has shifted from a single disease-targted one to a comprehensive one. Moreover, novel technologies such as multi-omics and artificial intelligence have been applied in infectious disease epidemiology research. The international cooperation in this field has become increasingly crucial, and the revision of the International Health Regulations and the negotiation of pandemic agreement will have a profound impact. In the future, infectious disease epidemiology research will develop with more powerful tools to improve its capabilities.

Virtual avatar possesses unique advantages such as high degree of realism,immersion and visualization,and the research on applying it to the assessment and treatment of anorexia nervosa is increasing year by year.In terms of assessment,there are mainly avatar versions of the figure rating scales,yes-no tasks and its variations,method of adjustment,and the use of virtual cylinder technique.In terms of treatment,there are mainly intervention methods based on virtual avatar exposure therapy,body swapping illusions,perceptual/attention training and self-empowerment,as well as some new potential interventions.Overall,the current research around anorexia nervosa using virtual avatar techniques is still in its early stages and there is still a lot of room for further exploration.

Objective To investigate the clinical effect of shoulder arthroscopic rotator cuff repair combined with shoulder three needles in treatment of rotator cuff injury.Methods 86 patients with rotator cuff injury from June 2021 to May 2023 were divided into two groups using a random number table method.The research group received 43 cases of rotator cuff repair under arthroscopy combined with shoulder three needles rotator cuff repair,while the control group received 43 cases of rotator cuff repair under arthroscopy combined with placebo needling.Then compare the pain level,shoulder joint function,and shoulder joint range of motion between the two groups before and 6 months after surgery,and calculate the excellent and good shoulder joint function rates between the two groups at 6 months after surgery,and compare the changes in inflammatory factors between the two groups at before and 4 weeks after surgery.Results 6 months after surgery,the visual analogue scale(VAS)score of both groups was lower than that before surgery,and the VAS score in research group(including the moderate tearing subgroup and the major tearing subgroup)was lower than that of the control group(including the moderate tearing subgroup and the major tearing subgroup),while the American Shoulder and Elbow Surgeons(ASES)score and shoulder joint range of motion were higher than those before surgery,and the ASES score and shoulder joint range of motion in research group(including the moderate tearing subgroup and the major tearing subgroup)were higher than those of the control group(including the moderate tearing subgroup and the major tearing subgroup),the differences were statistically significant(P＜0.05).6 months after surgery,the excellent and good rate of shoulder joint function in the research group was higher than that in the control group,the difference was statistically significant(P＜0.05).At 4 weeks after surgery,the levels of tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),interleukin-6(IL-6),and interleukin-8(IL-8)in both groups were lower than those before surgery,and the research group(including the moderate tearing subgroup and the major tearing subgroup)were lower than those of control group(including the moderate tearing subgroup and the major tearing subgroup),the differences were statistically significant(P＜0.05).Conclusion Arthroscopic rotator cuff repair combined with shoulder three needles can alleviate the pain level of patients with rotator cuff injury,improve shoulder joint function and range of motion,increase the excellent and good rate of shoulder joint function,and reduce inflammatory reaction.It is worthy of clinical application.

With the change of infectious disease incidence pattern and the development of related technologies, progresses have been made in the research of infectious disease epidemiology. In recent years, due to the change in the requirements of infectious disease prevention and control, the research focus has expanded from common infectious diseases to diseases which have been eliminated or might be eliminated, as well as emerging and re-emerging infectious diseases. Infectious disease data has been characterized by multiple sources and modalities. Along with the rapid development of pathogen detection methods, infectious disease surveillance has shifted from a single disease-targted one to a comprehensive one. Moreover, novel technologies such as multi-omics and artificial intelligence have been applied in infectious disease epidemiology research. The international cooperation in this field has become increasingly crucial, and the revision of the International Health Regulations and the negotiation of pandemic agreement will have a profound impact. In the future, infectious disease epidemiology research will develop with more powerful tools to improve its capabilities.

Objective To investigate the clinical effect of shoulder arthroscopic rotator cuff repair combined with shoulder three needles in treatment of rotator cuff injury.Methods 86 patients with rotator cuff injury from June 2021 to May 2023 were divided into two groups using a random number table method.The research group received 43 cases of rotator cuff repair under arthroscopy combined with shoulder three needles rotator cuff repair,while the control group received 43 cases of rotator cuff repair under arthroscopy combined with placebo needling.Then compare the pain level,shoulder joint function,and shoulder joint range of motion between the two groups before and 6 months after surgery,and calculate the excellent and good shoulder joint function rates between the two groups at 6 months after surgery,and compare the changes in inflammatory factors between the two groups at before and 4 weeks after surgery.Results 6 months after surgery,the visual analogue scale(VAS)score of both groups was lower than that before surgery,and the VAS score in research group(including the moderate tearing subgroup and the major tearing subgroup)was lower than that of the control group(including the moderate tearing subgroup and the major tearing subgroup),while the American Shoulder and Elbow Surgeons(ASES)score and shoulder joint range of motion were higher than those before surgery,and the ASES score and shoulder joint range of motion in research group(including the moderate tearing subgroup and the major tearing subgroup)were higher than those of the control group(including the moderate tearing subgroup and the major tearing subgroup),the differences were statistically significant(P＜0.05).6 months after surgery,the excellent and good rate of shoulder joint function in the research group was higher than that in the control group,the difference was statistically significant(P＜0.05).At 4 weeks after surgery,the levels of tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),interleukin-6(IL-6),and interleukin-8(IL-8)in both groups were lower than those before surgery,and the research group(including the moderate tearing subgroup and the major tearing subgroup)were lower than those of control group(including the moderate tearing subgroup and the major tearing subgroup),the differences were statistically significant(P＜0.05).Conclusion Arthroscopic rotator cuff repair combined with shoulder three needles can alleviate the pain level of patients with rotator cuff injury,improve shoulder joint function and range of motion,increase the excellent and good rate of shoulder joint function,and reduce inflammatory reaction.It is worthy of clinical application.

Objective:To explore the diagnostic value of blood flow parameters of carotid ultrasound combined with serum Sortilin and paraoxonase-1 (PON-1) for stability of carotid atherosclerotic plaque (CAP). Methods:A total of 100 CAP patients who admitted to Rugao Hospital of Traditional Chinese Medicine from January 2021 to December 2023 were selected,and they were divided into a stable plaque group (n=54) and a unstable plaque group (n=46). Enzyme linked immunosorbent assay (ELISA) was adopted to determine the expression levels of serum Sortilin and PON-1 of patients in two groups. Multi factor logistic regression was implemented to analyze the influencing factors on CAP stability. The receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic efficiency of blood flow parameters of carotid ultrasound combined with Sortilin and PON-1 on CAP stability. Results:Compared with the end diastolic blood flow velocity (EDV) and intima-media thickness (IMT) of stable plaque group,unstable plaque group showed increased EDV and IMT,and decreased PSV,and the differences were significant (t=7.536,4.680,5.487,P<0.05),respectively. Compared with stable plaque group,the serum Sortilin level in unstable plaque group significantly increased,while the PON-1 level significantly decreased,and the differences of them were significant (t=8.362,5.581,P<0.05),respectively. Multivariate logistic analysis found that Sortilin was a risk factor that affected CAP stability (OR=3.165,P<0.05),while PON-1 was a protective factor that affected CAP stability (OR=0.765,P<0.05). ROC curve analysis indicated that the area under curve (AUC) values of single Sortilin,PON-1,EDV,IMT,PSV,and the combination of them were respectively 0.788 (95％CI:0.695-0.864),0.814 (95％CI:0.724-0.885),0.847 (95％ CI:0.761-0.911),0.767 (95％ CI:0.672-0.846),0.707 (95％ CI:0.607-0.793) and 0.963 (95％ CI:0.839-0.907). The AUC value of the combination of above 5 indicators was highest,which was better than that of each single indicator,and its sensitivity and specificity were respectively 95.65％ and 83.33％. Conclusion:The EDV,IMT and PSV of blood flow parameters of ultrasound can provide CAP information of morphology and hemodynamics,and serum Sortilin level and PON-1 level can reflect the biological processes of formation and development of CAP. The combined detection of the five indicators can better diagnose CAP stability.

Virtual avatar possesses unique advantages such as high degree of realism,immersion and visualization,and the research on applying it to the assessment and treatment of anorexia nervosa is increasing year by year.In terms of assessment,there are mainly avatar versions of the figure rating scales,yes-no tasks and its variations,method of adjustment,and the use of virtual cylinder technique.In terms of treatment,there are mainly intervention methods based on virtual avatar exposure therapy,body swapping illusions,perceptual/attention training and self-empowerment,as well as some new potential interventions.Overall,the current research around anorexia nervosa using virtual avatar techniques is still in its early stages and there is still a lot of room for further exploration.

Objective:To explore the diagnostic value of blood flow parameters of carotid ultrasound combined with serum Sortilin and paraoxonase-1 (PON-1) for stability of carotid atherosclerotic plaque (CAP). Methods:A total of 100 CAP patients who admitted to Rugao Hospital of Traditional Chinese Medicine from January 2021 to December 2023 were selected,and they were divided into a stable plaque group (n=54) and a unstable plaque group (n=46). Enzyme linked immunosorbent assay (ELISA) was adopted to determine the expression levels of serum Sortilin and PON-1 of patients in two groups. Multi factor logistic regression was implemented to analyze the influencing factors on CAP stability. The receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic efficiency of blood flow parameters of carotid ultrasound combined with Sortilin and PON-1 on CAP stability. Results:Compared with the end diastolic blood flow velocity (EDV) and intima-media thickness (IMT) of stable plaque group,unstable plaque group showed increased EDV and IMT,and decreased PSV,and the differences were significant (t=7.536,4.680,5.487,P<0.05),respectively. Compared with stable plaque group,the serum Sortilin level in unstable plaque group significantly increased,while the PON-1 level significantly decreased,and the differences of them were significant (t=8.362,5.581,P<0.05),respectively. Multivariate logistic analysis found that Sortilin was a risk factor that affected CAP stability (OR=3.165,P<0.05),while PON-1 was a protective factor that affected CAP stability (OR=0.765,P<0.05). ROC curve analysis indicated that the area under curve (AUC) values of single Sortilin,PON-1,EDV,IMT,PSV,and the combination of them were respectively 0.788 (95％CI:0.695-0.864),0.814 (95％CI:0.724-0.885),0.847 (95％ CI:0.761-0.911),0.767 (95％ CI:0.672-0.846),0.707 (95％ CI:0.607-0.793) and 0.963 (95％ CI:0.839-0.907). The AUC value of the combination of above 5 indicators was highest,which was better than that of each single indicator,and its sensitivity and specificity were respectively 95.65％ and 83.33％. Conclusion:The EDV,IMT and PSV of blood flow parameters of ultrasound can provide CAP information of morphology and hemodynamics,and serum Sortilin level and PON-1 level can reflect the biological processes of formation and development of CAP. The combined detection of the five indicators can better diagnose CAP stability.

Objective:To investigate the diagnostic performance of continuous-time random-walk (CTRW) diffusion model combined with vesical imaging-reporting and data system (VI-RADS) in the diagnosis of muscle invasion of bladder cancer.Methods:In this case-control study, 64 patients with pathologically confirmed bladder urothelial carcinoma in Peking University First Hospital were retrospectively enrolled from August 2022 to March 2023. The patients were divided into the muscle invasive bladder cancer (MIBC) group and the nonmuscle invasive bladder cancer (NMIBC) group (29 cases and 35 cases, respectively) according to the pathological results. All patients underwent bladder MRI within 4 weeks before surgery, including T 2WI, conventional diffusion weighted imaging (DWI), and multi-b-value DWI. The CTRW model was used to obtain three quantitative diffusion parameters, including D m (an anomalous diffusion coefficient), α (related to temporal diffusion heterogeneity), and β (related to spatial diffusion heterogeneity). The apparent diffusion coefficient (ADC) was calculated using a mono-exponential model. The VI-RADS scores were evaluated based on T 2WI and conventional DWI. The Mann-Whitney U test was used to compare the diffusion parameters between the MIBC group and the NMIBC group. The combination of the parameters was investigated with logistic regression analysis. The diagnostic performance for muscle invasion of bladder cancer was evaluated by receiver operating characteristic analysis and the area under the curve (AUC). The difference between AUC was compared using the DeLong test. Results:There were statistically significant differences in ADC, D m, and α between the MIBC group and the NMIBC group ( Z=-2.31, -2.91, -3.97, P=0.021, 0.004,<0.001). No significant difference was found in β between the two groups ( Z=1.69, P=0.091). The AUC (95% CI) of D m and α for diagnosing MIBC were 0.712 (0.587-0.838) and 0.790 (0.676-0.904) respectively, both of which were higher than that of ADC (AUC 0.669, 95% CI 0.537-0.801) with statistically significant differences ( Z=2.86, 2.27, P=0.004, 0.023). The AUC (95% CI) of CTRW (D m+α) was 0.782 (0.661-0.876), which was significantly higher than that of ADC ( Z=2.35, P=0.019). The AUC (95% CI) of VI-RADS score and VI-RADS combined with CTRW parameter (VI-RADS+D m+α) were 0.823 (0.716-0.930) and 0.900 (0.799-0.961) respectively, with a statistically significant difference between them ( Z=2.16, P=0.031). Conclusion:The D m and α parameters in the CTRW diffusion model show better performance than the ADC in the mono-exponential model for muscle-invasive evaluation of bladder cancer, and the CTRW diffusion model can enhance the diagnostic performance of VI-RADS.