Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

The introduction of anti-amyloid therapies for Alzheimer’s disease (AD), such as lecanemab (Lequembi®), which was recently approved in Korea, necessitates careful monitoring for amyloid-related imaging abnormalities (ARIA) using brain MRI. To optimize ARIA monitoring in Korean clinical settings, the Korean Society of Neuroradiology (KSNR) and the Age and Neurodegeneration Imaging (ANDI) Study Group proposed MRI protocol recommendations on essential MR sequences, MRI acquisition parameters, timing and condition of MRI examinations, and essential details to provide a scientific basis for maximizing the safety and efficacy of AD treatment. A customized, standardized MRI protocol focusing on Korea’s healthcare environment can improve ARIA management and ensure patient safety through early detection of potential anti-amyloid therapy side effects, thereby enhancing treatment quality.

The introduction of anti-amyloid therapies for Alzheimer’s disease (AD), such as lecanemab (Lequembi®), which was recently approved in Korea, necessitates careful monitoring for amyloid-related imaging abnormalities (ARIA) using brain MRI. To optimize ARIA monitoring in Korean clinical settings, the Korean Society of Neuroradiology (KSNR) and the Age and Neurodegeneration Imaging (ANDI) Study Group proposed MRI protocol recommendations on essential MR sequences, MRI acquisition parameters, timing and condition of MRI examinations, and essential details to provide a scientific basis for maximizing the safety and efficacy of AD treatment. A customized, standardized MRI protocol focusing on Korea’s healthcare environment can improve ARIA management and ensure patient safety through early detection of potential anti-amyloid therapy side effects, thereby enhancing treatment quality.

The introduction of anti-amyloid therapies for Alzheimer’s disease (AD), such as lecanemab (Lequembi®), which was recently approved in Korea, necessitates careful monitoring for amyloid-related imaging abnormalities (ARIA) using brain MRI. To optimize ARIA monitoring in Korean clinical settings, the Korean Society of Neuroradiology (KSNR) and the Age and Neurodegeneration Imaging (ANDI) Study Group proposed MRI protocol recommendations on essential MR sequences, MRI acquisition parameters, timing and condition of MRI examinations, and essential details to provide a scientific basis for maximizing the safety and efficacy of AD treatment. A customized, standardized MRI protocol focusing on Korea’s healthcare environment can improve ARIA management and ensure patient safety through early detection of potential anti-amyloid therapy side effects, thereby enhancing treatment quality.

Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0％in patients without synovitis and 28.5％in those with moderate synovitis,whereas it was significantly higher(60.4％)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95％CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.

Objective:To investigate the association of serum/body fluid heparin-binding protein (HBP) and blood lactate levels with disease severity and their impact on prognosis in intensive care unit (ICU) patients with sepsis.Methods:Clinical data from 100 sepsis patients admitted to Ma'anshan Shiqiye Hospital ICU (January 2023-September 2024) were retrospectively analyzed. According to Sepsis-3.0 criteria, patients were divided into: uncomplicated sepsis (general group, n=28), sepsis with organ failure/hypotension (severe group, n=61), and septic shock (shock group, n=11). Comparisons included serum/body fluid HBP, lactate, APACHE Ⅱ scores, and mortality across severity groups and laboratory parameters between survivors and non-survivors. Logistic regression was used to identify prognostic predictors. Non-normally distributed data were presented as M(Q1,Q3), comparison between groups were completed by Kruskal-Wallis H test and Mann-Whitney U tests. Spearman correlation was used to analyze relationships between biomarkers and APACHE Ⅱ scores. Categorical data were presented as n(%), and comparison between groups were completed by χ2 test or Fisher's exact tests. ROC curves was used to evaluate predictive value. Results:Shock group demonstrated significantly higher serum HBP [13.3 (12.6-16.4) μg/L], infection-site HBP [230.3 (226.3-241.1) μg/L], lactate [5.4 (4.9-5.6) mmol/L], and APACHE Ⅱ[22.0 (21.0-24.0)] than severe group [9.6 (8.9-10.5) μg/L; 208.9 (200.5-216.1) μg/L; 2.7 (2.6-2.8) mmol/L; 18.0 (17.0-19.0)] and general group [7.4 (6.3-8.1) μg/L; 190.6 (180.5-202.1) μg/L; 1.5 (1.4-1.7) mmol/L; 13.0 (12.0-14.0)] (all P<0.001). There was statistically significant difference in the mortality rate during hospita lization among three groups of patients ( χ2=30.49, P<0.001). Mortality was higher in shock group than severe group than general group [72.7% (8/11) vs. 11.5% (7/61) vs. 3.6% (1/28), all P<0.001]. Non-survivors exhibited elevated lactate [4.8 (2.7-5.5) vs. 2.6 (1.7-2.8) mmol/L, Z=-4.13, P=0.001], serum HBP [12.2 (9.2-13.3) vs. 9.3 (7.8-10.4) μg/L, Z=-3.12, P=0.002], and infection-site HBP [226.8 (209.9-237.6) vs. 203.6 (194.0-212.8) μg/L, Z=-4.32, P<0.001] vs. survivors. Serum HBP ( r=0.74), infection-site HBP ( r=0.64), and lactate ( r=0.86) were all positively correlated with APACHE Ⅱ (all P<0.001). After adjusting for age and APACHE Ⅱ, elevated serum HBP ( OR=3.743, 95% CI:1.834-7.640), infection-site HBP ( OR=3.540, 95% CI:1.932-6.486), and lactate ( OR=5.155, 95% CI:1.868-14.229) independently predicted mortality (all P<0.001). Combined biomarker detection showed superior predictive value (AUC=0.909) versus individual markers (serum HBP:0.747, infection-site HBP:0.842, lactate:0.827, all P<0.001). Conclusion:Elevated blood lactate and serum/infection-site HBP levels correlate with sepsis severity and independently predict mortality. The biomarker combination provides optimal prognostic stratification.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective:To investigate the association of serum/body fluid heparin-binding protein (HBP) and blood lactate levels with disease severity and their impact on prognosis in intensive care unit (ICU) patients with sepsis.Methods:Clinical data from 100 sepsis patients admitted to Ma'anshan Shiqiye Hospital ICU (January 2023-September 2024) were retrospectively analyzed. According to Sepsis-3.0 criteria, patients were divided into: uncomplicated sepsis (general group, n=28), sepsis with organ failure/hypotension (severe group, n=61), and septic shock (shock group, n=11). Comparisons included serum/body fluid HBP, lactate, APACHE Ⅱ scores, and mortality across severity groups and laboratory parameters between survivors and non-survivors. Logistic regression was used to identify prognostic predictors. Non-normally distributed data were presented as M(Q1,Q3), comparison between groups were completed by Kruskal-Wallis H test and Mann-Whitney U tests. Spearman correlation was used to analyze relationships between biomarkers and APACHE Ⅱ scores. Categorical data were presented as n(%), and comparison between groups were completed by χ2 test or Fisher's exact tests. ROC curves was used to evaluate predictive value. Results:Shock group demonstrated significantly higher serum HBP [13.3 (12.6-16.4) μg/L], infection-site HBP [230.3 (226.3-241.1) μg/L], lactate [5.4 (4.9-5.6) mmol/L], and APACHE Ⅱ[22.0 (21.0-24.0)] than severe group [9.6 (8.9-10.5) μg/L; 208.9 (200.5-216.1) μg/L; 2.7 (2.6-2.8) mmol/L; 18.0 (17.0-19.0)] and general group [7.4 (6.3-8.1) μg/L; 190.6 (180.5-202.1) μg/L; 1.5 (1.4-1.7) mmol/L; 13.0 (12.0-14.0)] (all P<0.001). There was statistically significant difference in the mortality rate during hospita lization among three groups of patients ( χ2=30.49, P<0.001). Mortality was higher in shock group than severe group than general group [72.7% (8/11) vs. 11.5% (7/61) vs. 3.6% (1/28), all P<0.001]. Non-survivors exhibited elevated lactate [4.8 (2.7-5.5) vs. 2.6 (1.7-2.8) mmol/L, Z=-4.13, P=0.001], serum HBP [12.2 (9.2-13.3) vs. 9.3 (7.8-10.4) μg/L, Z=-3.12, P=0.002], and infection-site HBP [226.8 (209.9-237.6) vs. 203.6 (194.0-212.8) μg/L, Z=-4.32, P<0.001] vs. survivors. Serum HBP ( r=0.74), infection-site HBP ( r=0.64), and lactate ( r=0.86) were all positively correlated with APACHE Ⅱ (all P<0.001). After adjusting for age and APACHE Ⅱ, elevated serum HBP ( OR=3.743, 95% CI:1.834-7.640), infection-site HBP ( OR=3.540, 95% CI:1.932-6.486), and lactate ( OR=5.155, 95% CI:1.868-14.229) independently predicted mortality (all P<0.001). Combined biomarker detection showed superior predictive value (AUC=0.909) versus individual markers (serum HBP:0.747, infection-site HBP:0.842, lactate:0.827, all P<0.001). Conclusion:Elevated blood lactate and serum/infection-site HBP levels correlate with sepsis severity and independently predict mortality. The biomarker combination provides optimal prognostic stratification.

Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0％in patients without synovitis and 28.5％in those with moderate synovitis,whereas it was significantly higher(60.4％)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95％CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.