Objective·To identify and evaluate novel and reliable non-invasive serological biomarkers for detecting pancreatic ductal adenocarcinoma(PDAC).Methods·Sixty-seven PDAC patients(Ruijin cohort Ⅰ)were recruited at Pancreatic Center,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from May 2018 to December 2019.Global proteome profiling of 67 PDAC tumor tissues and 67 matched adjacent normal tissues was performed using mass spectrum.Bioinformatics analysis on the proteomics data was conducted to identify new biomarkers,and receiver operating characteristic(ROC)curves and the area under the curve(AUC)were used to evaluate their value of detecting PDAC.The proteomic and mRNA sequencing data were further downloaded and analysed from the Clinical Proteomic Tumor Analysis Consortium(CPTAC)cohort for validation.In addition,the Ruijin Cohort Ⅱ,consisting of 47 PDAC patients and 75 healthy individuals,was recruited for a case-control study from June 2021 to June 2022.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression level of new biomarkers in the serum of patients and healthy individuals to evaluate the serological diagnostic values of them.Results·Collagen type Ⅻ α1 chain(COL12A1)was identified as a candidate biomarker for PDAC diagnosis based on differential expression analysis on the proteomic data and was validated to be higher in tumor tissues than in adjacent normal tissues in the CPTAC cohort.In addition,COL12A1 protein levels were significantly higher in the sera of PDAC patients than in those of healthy controls,showing good diagnostic performance with an AUC of 0.82,a sensitivity of 81%,and a specificity of 83%.ROC analysis revealed that COL12A1 improved the performance of carbohydrate antigen 199(CA199)in distinguishing PDAC patients from healthy individuals(AUCCA199=0.91 vs AUCCA199+COL12A1=0.95,P<0.05).Furthermore,COL12A1 also showed excellent ability to distinguish early-stage PDAC patients(stage Ⅰ?Ⅱ)from healthy individuals(AUCCOL12A1=0.83),and significantly improved the AUC of CA199 in early-stage PDAC patients(AUCCA199=0.92 vs AUCCA199+COL12A1=0.97,P<0.05).Conclusion·COL12A1 is a potential serological diagnostic marker that complements CA199 in detecting early-stage PDAC.

Objective:To construct a quality evaluation index system for perianal infection care in patients with hematologic neoplasms, aiming to establish a standardized approach for care.Methods:A quality evaluation index system for perianal infection management in patients with hematologic neoplasms was developed from January to June 2023 using Donabedian′s "Structure- Process- Outcome" approach, based on evidence- based literature study and expert conference discussions. An index system for evaluating the quality of perianal infection care in patients with hematologic neoplasms was established through expert consultation, and the weights for each indicator were derived using the analytic hierarchy process.Results:Two rounds of expert consultations were conducted, involving 27 experts aged 30 to 53 (38.85 ± 6.13) years, in which of them there were 1 male and 26 females. The positive coefficients of the experts in the two rounds of consultations were 100.00% (27/27) and 96.30% (26/27), respectively. The expert authority coefficients were 0.874 and 0.881, respectively, and the Kendall coordination coefficients were 0.234 and 0.219 (both P<0.05). The quality evaluation index system for perianal infection management in patients with hematologic neoplasms consisted of 3 main indicators (structural quality, process quality, outcome quality), 12 secondary indicators, and 48 tertiary indicators. Conclusions:The process of developing the quality assessment criteria for perianal infection care in patients with hematologic neoplasms is systematic and yields dependable results. The criteria cover a wide range of aspects and are specific, offering a valuable framework for assessing the quality of perianal infection care in patients with hematologic neoplasms.

Milk-derived exosomes are nanoscale extracellular vesicles naturally present in mammalian milk and are rich in proteins,lipids,nucleic acids,and bioactive metabolites.They exhibit biological activities such as anti-inflammatory,antioxidant,and immunomodulatory effects.Owing to their unique advantages of low immunogenicity,excellent biocompatibility,stability,and natural targeting ability,milk-derived exosomes have emerged as promising natural nanocarriers,garnering significant attention in disease treatment and nutritional interventions.Sarcopenia,characterized by reduced skeletal muscle mass and diminished strength,is closely associated with aging,chronic inflammation,and oxidative stress.Recent studies have highlighted the potential role of milk-derived exosomes in combating sarcopenia.These exosomes can increase myotube diameter,enhance muscle mass and fiber cross-sectional area,and improve exercise performance metrics such as grip strength.Potential mechanisms may include promoting muscle anabolism,improving mitochondrial function through antioxidant mechanisms,and modulating the inflammatory microenvironments.However,challenges remain in their application for sarcopenia at present,such as the unclear mechanisms of key bioactive components[e.g.,microRNAs(miRNAs),L-ornithine,and milk fat globule-epidermal growth factor 8(MFG-E8)],and the targeting and stability of delivery systems need to be optimized.Future research should focus on the functional analysis of components in exosomes,optimization of delivery systems,and preclinical validation to promote their practical application in managing age-related muscle health.

Objective·To identify and evaluate novel and reliable non-invasive serological biomarkers for detecting pancreatic ductal adenocarcinoma(PDAC).Methods·Sixty-seven PDAC patients(Ruijin cohort Ⅰ)were recruited at Pancreatic Center,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from May 2018 to December 2019.Global proteome profiling of 67 PDAC tumor tissues and 67 matched adjacent normal tissues was performed using mass spectrum.Bioinformatics analysis on the proteomics data was conducted to identify new biomarkers,and receiver operating characteristic(ROC)curves and the area under the curve(AUC)were used to evaluate their value of detecting PDAC.The proteomic and mRNA sequencing data were further downloaded and analysed from the Clinical Proteomic Tumor Analysis Consortium(CPTAC)cohort for validation.In addition,the Ruijin Cohort Ⅱ,consisting of 47 PDAC patients and 75 healthy individuals,was recruited for a case-control study from June 2021 to June 2022.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression level of new biomarkers in the serum of patients and healthy individuals to evaluate the serological diagnostic values of them.Results·Collagen type Ⅻ α1 chain(COL12A1)was identified as a candidate biomarker for PDAC diagnosis based on differential expression analysis on the proteomic data and was validated to be higher in tumor tissues than in adjacent normal tissues in the CPTAC cohort.In addition,COL12A1 protein levels were significantly higher in the sera of PDAC patients than in those of healthy controls,showing good diagnostic performance with an AUC of 0.82,a sensitivity of 81%,and a specificity of 83%.ROC analysis revealed that COL12A1 improved the performance of carbohydrate antigen 199(CA199)in distinguishing PDAC patients from healthy individuals(AUCCA199=0.91 vs AUCCA199+COL12A1=0.95,P<0.05).Furthermore,COL12A1 also showed excellent ability to distinguish early-stage PDAC patients(stage Ⅰ?Ⅱ)from healthy individuals(AUCCOL12A1=0.83),and significantly improved the AUC of CA199 in early-stage PDAC patients(AUCCA199=0.92 vs AUCCA199+COL12A1=0.97,P<0.05).Conclusion·COL12A1 is a potential serological diagnostic marker that complements CA199 in detecting early-stage PDAC.

Objective:New HIV infections serve as a crucial indicator for assessing the dynamic changes in the HIV epidemic. This study aims to estimate the number of new HIV infections in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan Province (Dehong), using a back-calculation method that integrates diagnosis delay approaches and Bayesian theory. Additionally, it compares the differences between these two estimation methods.Methods:Data were obtained from the Chinese Information System for Disease Control and Prevention. Based on CD4 + T lymphocytes (CD4) counts depletion model, the first CD4 count prior to antiretroviral therapy of HIV-infected individuals diagnosed in Dehong from 2010 to 2023 was utilized to retroactively determine the infection date of HIV-infected individuals and ascertain the annual number of new HIV infections who had been diagnosed. Subsequently, the diagnosis delay distribution method and Bayesian theory were leveraged to assess the diagnosis probability of newly infected individuals, thereby projecting the number of new HIV infections in the region over the specified period. Results:During 2010-2023, a total of 5 693 individuals aged 15 and above, excluding mother-to-child transmission, were diagnosed with HIV in Dehong. After excluding 364 cases due to missing CD4 count results or abnormal first CD4 counts (≥2 000 cells/μl), 5 329 HIV-infected individuals were included in the final analysis. Through CD4 counts back-calculation from 2010 to 2023, the annual number of new infections diagnosed was 479, 427, 337, 305, 256, 219, 194, 193, 131, 166, 120, 71, 42 and 47. When using the diagnosis delay distribution method and life table analysis, the cumulative diagnosis probability rose from 0.301 within one year to 0.913 within 14 years, leading to a reduction in the number of estimated new infections from 577 in 2010 to 168 in 2023, with a total estimate of 4 412 (95% CI:4 350-4 480). Alternatively, based on Bayesian theory, the diagnosis probability increased from 0.413 within one year to 0.946 within 14 years, leading to a reduction in the number of estimated new infections from 557 in 2010 to 122 in 2023, with a total of 3 814 (95% CI: 3 787-3 837). Conclusions:Both methods yielded consistent results in estimating new HIV infections in Dehong from 2010 to 2023. Given the region's ongoing expansion of HIV testing, the estimates derived from Bayesian theory may more accurately reflect the actual situation. These findings provide a reference basis for formulating and optimizing HIV/AIDS prevention and control strategies in Dehong, facilitating progress toward the goal of eliminating AIDS by 2030 in the region.

Since the 1980 s, AIDS has been a significant global public health threat. With the "95-95-95" targets for HIV/AIDS prevention and control, the HIV/AIDS "prevention, testing, and treatment" care cascade covering the entire process has become a core strategy. The present study examines combs the connotation and development of the HIV/AIDS care cascade, exploring application throughout the entire process and at each linkage. It analyzes extension value in key populations and HIV co-infected other infectious diseases, identifies obstacles in practice, and proposes strategies to help optimize, innovate, and precisely target HIV/AIDS prevention and control in China.

Milk-derived exosomes are nanoscale extracellular vesicles naturally present in mammalian milk and are rich in proteins,lipids,nucleic acids,and bioactive metabolites.They exhibit biological activities such as anti-inflammatory,antioxidant,and immunomodulatory effects.Owing to their unique advantages of low immunogenicity,excellent biocompatibility,stability,and natural targeting ability,milk-derived exosomes have emerged as promising natural nanocarriers,garnering significant attention in disease treatment and nutritional interventions.Sarcopenia,characterized by reduced skeletal muscle mass and diminished strength,is closely associated with aging,chronic inflammation,and oxidative stress.Recent studies have highlighted the potential role of milk-derived exosomes in combating sarcopenia.These exosomes can increase myotube diameter,enhance muscle mass and fiber cross-sectional area,and improve exercise performance metrics such as grip strength.Potential mechanisms may include promoting muscle anabolism,improving mitochondrial function through antioxidant mechanisms,and modulating the inflammatory microenvironments.However,challenges remain in their application for sarcopenia at present,such as the unclear mechanisms of key bioactive components[e.g.,microRNAs(miRNAs),L-ornithine,and milk fat globule-epidermal growth factor 8(MFG-E8)],and the targeting and stability of delivery systems need to be optimized.Future research should focus on the functional analysis of components in exosomes,optimization of delivery systems,and preclinical validation to promote their practical application in managing age-related muscle health.

ObjectiveTo improve the accuracy of discrete element method in simulating the processing of traditional Chinese medicine（TCM） powder system under low shear conditions. MethodsIn this study， extract powders of Tongsaimai tablets and Qige granules were used as the research objects， the angle of repose（AOR） and effective angle of internal friction of the two materials were determined by AOR test method and shear cell test method. Based on the Hertz-Mindlin with JKR V2 contact model and particle scaling theory， taking the particle-particle restitution coefficient（A）， particle-particle static friction coefficient（B）， particle-particle rolling friction coefficient（C）， particle-steel restitution coefficient（D）， particle-steel static friction coefficient（E）， particle-steel rolling friction coefficient（F） and Johnson-Kendall-Roberts（JKR） surface energy（G） as test factors， the simulated contact parameters of Tongsaimai tablets extract powder were first calibrated with a single reference value using AOR as the reference value， and then the simulated contact parameters of Tongsaimai tablets extract powder as well as Qige granules extract powder were co-calibrated with AOR and effective angle of internal friction as the joint reference value， respectively. Then， Plackett-Burman design was used to screen the critical contact parameters that have a significant effect on the simulated reference value， and the steepest ascent design was used to determine the optimal range of the critical contact parameters， finally， the regression model between the critical contact parameters and the simulated reference values was established through the design of the response surface test， and the critical contact parameters were calibrated based on the regression model and the desirability function approach. ResultsThe optimal combination of discrete elemental contact parameters A-G for Tongsaimai tablets extract powder under a single reference value was 0.100， 0.718， 0.616， 0.100， 0.400， 0.250 and 0.075 J·m^-2， which was validated to have relative errors of 0.10% and -8.64% for the simulated AOR and the simulated effective angle of internal friction， respectively. And the optimal combination of discrete elemental contact parameters A-G for Tongsaimai tablets extract powder at the joint reference values was 0.100， 0.682， 0.598， 0.100， 0.521， 0.294 and 0.075 J·m^-2， which was verified to have relative errors of 0.10% and -0.18% for the simulated AOR and the simulated effective angle of internal friction， respectively. The optimal combination of discrete elemental contact parameters A-G for Qige granules extract powder at the joint reference values was 0.150， 0.370， 0.330， 0.150， 0.500， 0.500 and 0.100 J·m^-2， which was verified to have relative errors of 2.70% and -1.30% for the simulated AOR and the simulated effective angle of internal friction， respectively. Compared with the single reference value method， the joint calibration method not only increased the number of the critical contact parameters for characterizing particle-device interactions， but also was more accurate and reliable. ConclusionCompared with the results of single reference value calibration， the results obtained by the method of joint calibration of discrete element simulation contact parameters with AOR and effective angle of internal friction as the reference values are more accurate， which can provide more accurate and reliable simulation physical property data for the simulation experiments of TCM extract powder under low shear process conditions.

Objective:New HIV infections serve as a crucial indicator for assessing the dynamic changes in the HIV epidemic. This study aims to estimate the number of new HIV infections in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan Province (Dehong), using a back-calculation method that integrates diagnosis delay approaches and Bayesian theory. Additionally, it compares the differences between these two estimation methods.Methods:Data were obtained from the Chinese Information System for Disease Control and Prevention. Based on CD4 + T lymphocytes (CD4) counts depletion model, the first CD4 count prior to antiretroviral therapy of HIV-infected individuals diagnosed in Dehong from 2010 to 2023 was utilized to retroactively determine the infection date of HIV-infected individuals and ascertain the annual number of new HIV infections who had been diagnosed. Subsequently, the diagnosis delay distribution method and Bayesian theory were leveraged to assess the diagnosis probability of newly infected individuals, thereby projecting the number of new HIV infections in the region over the specified period. Results:During 2010-2023, a total of 5 693 individuals aged 15 and above, excluding mother-to-child transmission, were diagnosed with HIV in Dehong. After excluding 364 cases due to missing CD4 count results or abnormal first CD4 counts (≥2 000 cells/μl), 5 329 HIV-infected individuals were included in the final analysis. Through CD4 counts back-calculation from 2010 to 2023, the annual number of new infections diagnosed was 479, 427, 337, 305, 256, 219, 194, 193, 131, 166, 120, 71, 42 and 47. When using the diagnosis delay distribution method and life table analysis, the cumulative diagnosis probability rose from 0.301 within one year to 0.913 within 14 years, leading to a reduction in the number of estimated new infections from 577 in 2010 to 168 in 2023, with a total estimate of 4 412 (95% CI:4 350-4 480). Alternatively, based on Bayesian theory, the diagnosis probability increased from 0.413 within one year to 0.946 within 14 years, leading to a reduction in the number of estimated new infections from 557 in 2010 to 122 in 2023, with a total of 3 814 (95% CI: 3 787-3 837). Conclusions:Both methods yielded consistent results in estimating new HIV infections in Dehong from 2010 to 2023. Given the region's ongoing expansion of HIV testing, the estimates derived from Bayesian theory may more accurately reflect the actual situation. These findings provide a reference basis for formulating and optimizing HIV/AIDS prevention and control strategies in Dehong, facilitating progress toward the goal of eliminating AIDS by 2030 in the region.

Since the 1980 s, AIDS has been a significant global public health threat. With the "95-95-95" targets for HIV/AIDS prevention and control, the HIV/AIDS "prevention, testing, and treatment" care cascade covering the entire process has become a core strategy. The present study examines combs the connotation and development of the HIV/AIDS care cascade, exploring application throughout the entire process and at each linkage. It analyzes extension value in key populations and HIV co-infected other infectious diseases, identifies obstacles in practice, and proposes strategies to help optimize, innovate, and precisely target HIV/AIDS prevention and control in China.