Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

The Pharmacopeia of the People’s Republic of China 2025 Edition (referred to as the Chinese Pharmacopoeia 2025 Edition, ChP 2025) will be promulgated and implemented. This article introduces the process of development of ChP 2025 Edition (Volume Ⅱ), including the selection, the revision of general notices,the addition and revision of drug monographs, etc., and provides some analysis and examples to illustrate,which can facilitate the readers to understand and implement the ChP 2025 Edition (Volume Ⅱ).

Objective:To investigate the diagnostic efficacy of time-dependent diffusion MRI (t d-dMRI)-derived microstructural parameters for clinically significant prostate cancer (csPCa) and their associations with the pathological grade of prostate cancer(PCa) based on the International Society of Urological Pathology (ISUP) grades. Methods:This cross-sectional study prospectively enrolled 196 patients suspected of PCa from March 2023 to March 2024 at the First Affiliated Hospital, Sun Yat-Sen University. All patients underwent multiparametric MRI and t d-dMRI to obtain microstructural parameters, including cell diameter (d), intracellular volume fraction (f in), extracellular diffusion coefficient (D ex), cellularity, and apparent diffusion coefficient (ADC) value at oscillation frequencies of 33 Hz, 17 Hz, 0 Hz (ADC 33, ADC 17, and ADC 0). Pathologically, 95 cases were classified as csPCa (ISUP 2-5), and the rest 101 cases were classified as non-csPCa (benign or ISUP 1). Comparison of these microstructural metrics was made between csPCa and non-csPCa groups by independent t-tests or Mann-Whitney U tests, and multivariable logistic regression was used to identify independent predictors. A combined diagnostic model was then constructed based on the independent predictors. The receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. Finally, in PCa, the correlation between microstructural parameters and ISUP grades was investigated by Spearman correlation. Results:The t d-dMRI measurements, including d, f in, cellularity, ADC 33,ADC 17 and ADC 0, were significantly different between csPCa and non-csPCa groups (All P<0.05). But D ex was not significantly different between the two groups ( Z=-1.27, P=0.204). The area under the receiver operating characteristic curve (AUC) for diagnosing csPCa were 0.701 (95% CI 0.628-0.775) for d, 0.869 (95% CI 0.819-0.920) for f in, 0.884 (95% CI 0.835-0.932) for cellularity, 0.777 (95% CI 0.712-0.842) for ADC 33, 0.852 (95% CI 0.799-0.905) for ADC 17, and 0.840 (95% CI 0.786-0.894) for ADC 0. Cellularity ( OR=6.142, 95% CI 2.920-12.929, P<0.001) and ADC 17 ( OR=0.108, 95% CI 0.027-0.429, P=0.002) were identified as the independent predictors, and their combined model achieved an AUC of 0.896 (95% CI 0.852-0.941). In PCa f in and cellularity were positively correlated with ISUP grades ( r=0.490 and 0.397, P<0.001), while ADC 33, ADC 17, and ADC 0 were negatively correlated with ISUP grades ( r=-0.198, -0.345, -0.360; P=0.041,<0.001,<0.001). d and D ex were not correlated with ISUP grades ( P>0.05). Conclusion:t d-dMRI based microstructural mapping correlates with ISUP grades of PCa and may be useful for the differential diagnosis of csPCa.

The Pharmacopeia of the People's Republic of China 2025 Edition(referred to as the Chinese Pharmaco-poeia 2025 Edition,ChP 2025)will be promulgated and implemented.This article introduces the process of devel-opment of ChP 2025 Edition(Volume Ⅱ),including the selection,the revision of general notices,the addition and revision of drug monographs,etc.,and provides some analysis and examples to illustrate,which can facilitate the readers to understand and implement the ChP 2025 Edition(Volume Ⅱ).

Objective:To investigate the diagnostic efficacy of time-dependent diffusion MRI (t d-dMRI)-derived microstructural parameters for clinically significant prostate cancer (csPCa) and their associations with the pathological grade of prostate cancer(PCa) based on the International Society of Urological Pathology (ISUP) grades. Methods:This cross-sectional study prospectively enrolled 196 patients suspected of PCa from March 2023 to March 2024 at the First Affiliated Hospital, Sun Yat-Sen University. All patients underwent multiparametric MRI and t d-dMRI to obtain microstructural parameters, including cell diameter (d), intracellular volume fraction (f in), extracellular diffusion coefficient (D ex), cellularity, and apparent diffusion coefficient (ADC) value at oscillation frequencies of 33 Hz, 17 Hz, 0 Hz (ADC 33, ADC 17, and ADC 0). Pathologically, 95 cases were classified as csPCa (ISUP 2-5), and the rest 101 cases were classified as non-csPCa (benign or ISUP 1). Comparison of these microstructural metrics was made between csPCa and non-csPCa groups by independent t-tests or Mann-Whitney U tests, and multivariable logistic regression was used to identify independent predictors. A combined diagnostic model was then constructed based on the independent predictors. The receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. Finally, in PCa, the correlation between microstructural parameters and ISUP grades was investigated by Spearman correlation. Results:The t d-dMRI measurements, including d, f in, cellularity, ADC 33,ADC 17 and ADC 0, were significantly different between csPCa and non-csPCa groups (All P<0.05). But D ex was not significantly different between the two groups ( Z=-1.27, P=0.204). The area under the receiver operating characteristic curve (AUC) for diagnosing csPCa were 0.701 (95% CI 0.628-0.775) for d, 0.869 (95% CI 0.819-0.920) for f in, 0.884 (95% CI 0.835-0.932) for cellularity, 0.777 (95% CI 0.712-0.842) for ADC 33, 0.852 (95% CI 0.799-0.905) for ADC 17, and 0.840 (95% CI 0.786-0.894) for ADC 0. Cellularity ( OR=6.142, 95% CI 2.920-12.929, P<0.001) and ADC 17 ( OR=0.108, 95% CI 0.027-0.429, P=0.002) were identified as the independent predictors, and their combined model achieved an AUC of 0.896 (95% CI 0.852-0.941). In PCa f in and cellularity were positively correlated with ISUP grades ( r=0.490 and 0.397, P<0.001), while ADC 33, ADC 17, and ADC 0 were negatively correlated with ISUP grades ( r=-0.198, -0.345, -0.360; P=0.041,<0.001,<0.001). d and D ex were not correlated with ISUP grades ( P>0.05). Conclusion:t d-dMRI based microstructural mapping correlates with ISUP grades of PCa and may be useful for the differential diagnosis of csPCa.

Objectives:This study aims to explore the causal relationships between immune cells and serum metabolites in the development of coronary heart disease(CHD)using Mendelian randomization(MR)methods.Methods:We conducted a two-sample MR analysis utilizing data from the FinnGen Project's genome-wide association study(GWAS)on CHD,alongside data on metabolites and immune cells from the GWAS catalog.For the identified associated metabolites,we further employed mediation MR methods to evaluate their mediating roles in the influence of immune cells on CHD.Results:The MR analysis indicated that three immune cells(IgD-CD24-%B cell,CD11b on CD14+monocyte,HLA DR on DC)had stable causal relationship with CHD(under the premise of inverse variance weighted[IVW]method P<0.05,both MR-Egger and weighted median methods also showed P<0.05).Furthermore,these immune cells were associated with CHD through four metabolites(N-acetylneuraminic acid levels,the ratio of desmethyltaurine to taurine,X-24801 and X-18779).Conclusions:This study reveals the causal relationships between immune cells and serum metabolites in the pathogenesis of CHD,providing new biomarkers for early prediction and risk assessment of CHD.

Objective The aim of this study was to analyze the incidence,mortality,and epidemiological trends of malignant tumors in the cancer registration areas of Qinghai Province and provide a reference for the prevention and control strategies and meas-ures of malignant tumors.Methods According to the quality control standards for cancer registration,the data on malignant tumor in-cidence and mortality from 8 national cancer registration areas in Qinghai Province from 2014 to 2021 were collated.The crude inci-dence/mortality,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and World standard population(ASIRW/ASMRW),the cumulative rates(0-74 years old),and the age-specific incidence/mortality of malignant tumors were calculated for different sexes and regions.The Joinpoint 4.9.0.0 software was used to calculate the average annual percentage change(AAPC)and conduct trend analysis.Results The crude incidence of malignant tumors in the cancer registration areas of Qinghai Province from 2014 to 2021 was 221.25/100,000(243.31/100,000 for males and 198.68/100,000 for females),the ASIRC was 199.48/100,000(229.13/100,000 for males and 173.34/100,000 for females),the ASIRW was 196.38/100,000(228.32/100,000 for males and 167.97/100,000 for females).The cumulative rate for those aged 0-74 years was 21.57％;the crude mortali-ty of malignant tumors was 131.90/100,000(163.86/100,000 for males and 99.20/100,000 for females),the ASMRC was 121.07/100,000(157.33/100,000 for males and 87.45/100,000 for females),the ASMRW was 120.53/100,000(157.54/100,000 for males and 86.31/100,000 for females),and the cumulative rate for those aged 0-74 years was 12.79％.The crude incidence,ASIRC,ASIRW,crude mortality,ASMRC and ASMRW were all higher in males than those in females.Both the crude incidence and mortality of malignant tumors increased with age.The crude incidence rate increased rapidly after age 45,peaked in the 80-84 age group(2,352.29 per 100,000),and declined slightly in the 85+age group.The crude mortality increased rapidly after age 50,peaked in the 85+age group(2,305.44 per 100,000).The crude incidence(AAPC=5.68％,95％CI:3.48％-7.93％,P＜0.05)and erude mortality(AAPC=3.67％,95％CI:2.44％-4.91％,P＜0.05)of malignant tumors showed an overall upward trend from 2014 to 2021.The ASIRC(AAPC=-0.12％,95％CI:-3.70％-3.59％,P＞0.05)remained stable,while the ASMRC(AAPC=-2.81％,95％CI:-3.28％--2.03％,P＜0.05)showed a downward trend.The top five malignant tumors in terms of crude incidence were stom-ach cancer,lung cancer,liver cancer,female breast cancer,and cervical cancer,respectively;the top five malignant tumors in terms of crude mortality were stomach cancer,lung cancer,liver cancer,esophagus cancer,and colorectal cancer,respectively.Conclusion From 2014 to 2021,the incidence and mortality of malignant tumors in the Qinghai Province cancerregistration areas showed an in-creasing trend,with higher rates in males than those in females.It is recommended that targeted prevention and control measures should be implemented for people aged 45 and older,with stomach cancer,liver cancer,and cervical cancer as key cancers.

Objective The aim of this study was to analyze the incidence,mortality,and epidemiological trends of malignant tumors in the cancer registration areas of Qinghai Province and provide a reference for the prevention and control strategies and meas-ures of malignant tumors.Methods According to the quality control standards for cancer registration,the data on malignant tumor in-cidence and mortality from 8 national cancer registration areas in Qinghai Province from 2014 to 2021 were collated.The crude inci-dence/mortality,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and World standard population(ASIRW/ASMRW),the cumulative rates(0-74 years old),and the age-specific incidence/mortality of malignant tumors were calculated for different sexes and regions.The Joinpoint 4.9.0.0 software was used to calculate the average annual percentage change(AAPC)and conduct trend analysis.Results The crude incidence of malignant tumors in the cancer registration areas of Qinghai Province from 2014 to 2021 was 221.25/100,000(243.31/100,000 for males and 198.68/100,000 for females),the ASIRC was 199.48/100,000(229.13/100,000 for males and 173.34/100,000 for females),the ASIRW was 196.38/100,000(228.32/100,000 for males and 167.97/100,000 for females).The cumulative rate for those aged 0-74 years was 21.57％;the crude mortali-ty of malignant tumors was 131.90/100,000(163.86/100,000 for males and 99.20/100,000 for females),the ASMRC was 121.07/100,000(157.33/100,000 for males and 87.45/100,000 for females),the ASMRW was 120.53/100,000(157.54/100,000 for males and 86.31/100,000 for females),and the cumulative rate for those aged 0-74 years was 12.79％.The crude incidence,ASIRC,ASIRW,crude mortality,ASMRC and ASMRW were all higher in males than those in females.Both the crude incidence and mortality of malignant tumors increased with age.The crude incidence rate increased rapidly after age 45,peaked in the 80-84 age group(2,352.29 per 100,000),and declined slightly in the 85+age group.The crude mortality increased rapidly after age 50,peaked in the 85+age group(2,305.44 per 100,000).The crude incidence(AAPC=5.68％,95％CI:3.48％-7.93％,P＜0.05)and erude mortality(AAPC=3.67％,95％CI:2.44％-4.91％,P＜0.05)of malignant tumors showed an overall upward trend from 2014 to 2021.The ASIRC(AAPC=-0.12％,95％CI:-3.70％-3.59％,P＞0.05)remained stable,while the ASMRC(AAPC=-2.81％,95％CI:-3.28％--2.03％,P＜0.05)showed a downward trend.The top five malignant tumors in terms of crude incidence were stom-ach cancer,lung cancer,liver cancer,female breast cancer,and cervical cancer,respectively;the top five malignant tumors in terms of crude mortality were stomach cancer,lung cancer,liver cancer,esophagus cancer,and colorectal cancer,respectively.Conclusion From 2014 to 2021,the incidence and mortality of malignant tumors in the Qinghai Province cancerregistration areas showed an in-creasing trend,with higher rates in males than those in females.It is recommended that targeted prevention and control measures should be implemented for people aged 45 and older,with stomach cancer,liver cancer,and cervical cancer as key cancers.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.