Objective To explore the pro-inflammation resolution and protective effects of reactive oxygen species (ROS)-responsive liposomes modified with a cardiac-targeted peptide and loaded with resolvin D1 (RvD1, C-LP-RvD1) on myocardial ischemia-reperfusion (MI/R) injury. Methods The C-LP-RvD1 nanoliposomes were constructed, characterized physically and chemically, and evaluated for in vitro release. Non-targeting peptide-modified drug-loaded liposomes (LP-RvD1) were served as controls. Apoptotic adult mouse cardiomyocytes (AMCMs) were used to verify in vitro targeted binding capacity of C-LP-RvD1. In MI/R mice models, the in vivo distribution and cardiac enrichment of C-LP-RvD1 were assessed. Levels of specialized pro-resolving mediator (SPM) and inflammatory factors in cardiac tissue homogenates and cell culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Cardiac function and fibrosis remodeling were evaluated via echocardiography and Masson staining four weeks after treatment. Biosafety was evaluated in healthy mice injected by C-LP-RvD1. Results The C-LP-RvD1 exhibited good nanoscale uniformity and stability, with ROS-triggered accelerated release characteristics. In vitro experiments showed that C-LP-RvD1 had higher binding capacity to apoptotic AMCMs than LP-RvD1, with significantly higher SPM levels (P＜0.01) and lower inflammatory factor levels (P＜0.05). In vivo experiments indicated enhanced cardiac enrichment of C-LP-RvD1 in MI/R injured hearts, with higher local myocardial SPM levels and lower inflammatory factor levels compared to LP-RvD1 (P＜0.05). Four weeks after treatment, compared with LP-RvD1, the C-LP-RvD1 mice group showed improved cardiac function indicators and reduced ventricular fibrosis remodeling ratio (P＜0.05). Safety evaluation revealed no significant systemic inflammation, immunogenicity, or coagulation abnormalities in healthy mice, with liver and kidney function and major organ histology showing no notable damage. Conclusions C-LP-RvD1 improves effective delivery of RvD1 to MI/R injured hearts through injury-targeted enrichment and ROS-responsive release, promoting inflammation resolution and suppressing excessive inflammation, thereby improving cardiac function and reducing adverse remodeling, with favorable biosafety.

OBJECTIVE To formulate the Expert Consensus on the Implementation and Management of Drug Selection for Centralized Volume-Based Procurement in Medical Institutions of Guangxi （hereinafter referred to as the “ Consensus ”）， and to provide decision-making support and practical guidance for the drug selection and management of centralized volume-based procurement （hereinafter referred to as “centralized procurement”） drugs in medical institutions at all levels in Guangxi. METHODS A systematic review was conducted on the materials from previous batches of centralized procurement implemented in Guangxi. A comprehensive search was carried out for drug-related works and books， along with a systematic collation of guidelines on drug selection， expert consensus on centralized procurement， and policy documents. Through three rounds of specialized seminars， combined with existing evidence-based data and the practical drug selection experiences of medical institutions at various levels， this Consensus was formulated after thorough discussion and successive rounds of revision. RESULTS & CONCLUSIONS The Consensus systematically outlines the three key stages in the implementation of centralized procurement in medical institutions： procurement volume reporting， confirmation of agreed procurement volume， and procurement and usage implementation. It proposes drug selection strategies for centralized procurement bas ed on multiple dimensions， including specifications， dosage forms， packaging materials， fill volume， and manufacturing enterprises. In response to practical challenges encountered in the selection process， corresponding countermeasures are proposed， such as establishing a regularized information reserve mechanism， strengthening information technology support， and implementing categorized selection approaches. The Consensus advocates for medical institutions to construct an integrated “policy， data， and quality” decision-making system to promote full-cycle management of centralized procurement. This Consensus will provide scientific and practical guidance for medical institutions at all levels in Guangxi in the drug selection of centralized procurement， facilitating the smooth implementation and sustainable development of centralized procurement policies at the institutional level.

Objective:to investigate age-related changes in high-sensitivity cardiac troponin T(hs-cTnT)levels among middle-aged and elderly individuals, and to establish reference values for the 99th percentile upper reference limit(99th URL)of hs-cTnT within this demographic.Methods:This research is designed as a cross-sectional study.Hs-cTnT test results were collected from outpatients at Beijing Hospital between January 2018 and December 2023.The final sample included 5, 677 outpatients aged 45 to 85 years(65±10), all of whom were free from cardiovascular diseases and other chronic heart-related conditions.Multiple linear regression was utilized to assess the impact of gender and age group on hs-cTnT concentrations within the middle-aged and elderly populations.Furthermore, a generalized additive model for location, scale, and shape(GAMLSS)was employed to generate percentile curves of hs-cTnT by gender in this cohort, with the aim of determining the 99th URLs for both middle-aged and elderly individuals.Results:Multiple linear regression analyses indicated that both gender and age significantly influenced hs-cTnT levels in middle-aged and elderly populations( β60-69 years=1.399, β≥70 years=5.306, βgender=-2.650, all Pvalues<0.001).The hs-cTnT data for both males and females conformed to Box-Cox-Cole-Green(BCCG)distributions, with percentile curves fitted at the 25th, 50th, 75th, and 99th percentiles according to gender.The percentile values of hs-cTnT in both males and females demonstrated a progressive increase with advancing age.Notably, males exhibited higher 99th percentile values than females across all age groups. Conclusions:The GAMLSS approach is employed to establish continuous reference intervals for hs-cTnT in the middle-aged and elderly population.This effort aims to provide a theoretical foundation for reference values specific to this demographic in China and to offer guidance for clinical diagnosis and treatment.

From July 23, 2018, to December 31, 2019, a total of 299 219 children in Shandong Province received the fifth dose of the diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). Among these recipients, the distribution by age was as follows: 20 children under 2 years old (0.01%), 273 996 children aged 2 years (91.57%), 20 242 children aged 3 years (6.76%), 3 932 children aged 4 years (1.31%), 963 children aged 5 years (0.32%), and 66 children aged 6 years and above (0.02%). In total, 1 972 cases of adverse events following immunization (AEFI) were reported after the administration of the fifth dose of DTaP, resulting in an incidence rate of 659.05 per 100 000 doses. Among these, 1 718 cases were classified as common vaccine reactions, with an incidence rate of 574.16 per 100 000 doses, while 247 cases were identified as rare reactions, yielding an incidence rate of 82.55 per 100 000 doses. The incidence of AEFIs, as well as the rates of common and rare reactions, exhibited a significant increasing trend with the number of doses administered (all P<0.001). Among the rare reactions, there were 10 cases classified as severe, resulting in a reported incidence of 3.34 per 100 000 doses.

Objective:To investigate whether biochanin A(BCA)has a protective effect against dextran sodium sulfate(DSS)-in-duced ulcerative colitis(UC)in mice.Methods:Thirty C57BL/6N mice were randomly divided into normal control group,DSS model group,sulfasalazine(SASP)-positive drug control group,and low/medium/high-dose(5 mg/kg,10 mg/kg,and 20 mg/kg)BCA groups.The mouse model of UC was induced by administering 2.5%DSS aqueous solution for 7 days.During the experimental period,both the normal control and model groups were given 0.5%carboxymethyl cellulose sodium solution daily by gavage.The positive control group was given 100 mg/kg SASP,while the BCA groups were given BCA suspensions at doses of 5 mg/kg,10 mg/kg,and 20 mg/kg.The ad-ministration lasted for 10 days.Body weight changes and fecal status of the mice were recorded every day;the colon was dissected,col-lected,and measured for its length.The colon was stained with Hematoxylin-Eosin for pathomorphological study.Quantitative poly-merase chain reaction was used to determine the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)in the colon.Immunofluorescence was used to determine the expression of tight junction proteins,zonula occluden-1(ZO-1)and occludin,in the colon.Results:It showed that 5 mg/kg and 10 mg/kg BCA significantly alleviated weight loss in mice with UC,while 5 mg/kg,10 mg/kg,and 20 mg/kg BCA reduced the disease activity index scores.Additionally,BCA showed similar effects to SASP in improving the structure and reducing the shortening of the colon in mice with UC.Compared with the model group,all BCA groups had significantly decreased TNF-α(P=0.024、P=0.060、P=0.003)and IL-6(P=0.002、P<0.001、P<0.001)and significantly increased IL-10(P=0.006、P=0.003、P<0.001),with varying degrees of up-regulated expression of tight junction proteins.Conclusion:BCA can effectively alleviate DSS-induced symptoms,reduce intes-tinal damage,and protect the intestinal barrier in mice with UC.

Objective:To analyze the epidemiological patterns and temporal trends of gastric cancer incidence and mortality in China and globally, and to formulate evidence-based prevention strategies.Methods:Based on the GLOBOCAN 2022 database, we evaluated gastric cancer incidence and mortality patterns stratified by sex, age group, geographic region and human development index (HDI). Simple linear regression and Spearman's correlation analysis assessed associations between HDI and age-standardized incidence rate (ASIR) or age-standardized mortality rates (ASMR). Temporal trends from 2002 to 2020 were described in selected regions, and projections of global gastric cancer burden by 2050 were estimated.Results:In 2022, there were estimated 969 000 new gastric cases and 660 000 deaths worldwide. The burden was higher in men than in women, with incidence peaking at ages 65-69 and mortality at 70-74. ASIR was weakly correlated with HDI ( r=0.261, P＜0.001), while no significant association was found between HDI and ASMR ( r=-0.005, P=0.947). China accounted for 359 000 new cases and 260 000 deaths, representing 37.0% and 39.4% of the global totals, respectively. Both ASIR (13.7/10 5) and ASMR (9.4/10 5) in China exceeded the global averages (9.2/10 5 and 6.1/10 5, respectively). Although the overall global burden is decreasing, absolute case numbers are projected to increase by 84.1% (1.78 million cases) and deaths by 91.2% (1.26 million cases) by 2050. High-HDI regions will bear greater absolute burdens, whereas low-HDI regions face steeper relative increases. In China, new cases and deaths are projected to reach 607 000 and 504 000 by 2050, rising by 69.1% and 93.8%, respectively. Conclusions:Despite a declining global trend, the burden of gastric cancer remains substantial, with notable disparities across regions, sex and age groups. Targeted strategies are urgently needed, particularly in East Asia, among males, and older populations, to mitigate the future burden.

Objective:To investigate the differences in hippocampal subfield volumes and structural covariance network between participants with subjective cognitive decline (SCD) and healthy individuals, and to analyze the correlations of the volumes of the different subfields and altered covariance brain regions with memory function.Methods:A total of 57 SCD individuals(SCD group) and 44 normal controls(NC group) participants were assessed for memory function using composite scores from the auditory verbal learning test (AVLT) and the Wechsler memory scale visual reproduction (VR) test from June 2022 to October 2023.T1-weighted structural magnetic resonance imaging (MRI) data were collected from all participants, and hippocampal subfields, cortical regions, and subcortical nuclei were segmented using FreeSurfer to measure the gray matter volume of each structure. A structural covariance network was constructed based on the correlation of gray matter volumes across regions. Statistical analysis was performed using R 4.3.1 software. Inter-group differences in hippocampal subfield volumes were compared using multivariate analysis of covariance. Differences in structural covariance connectivity between groups were assessed using Z-test, while network topology differences were compared through permutation testing. Finally, partial correlation analysis was used to examine correlation of the volumes of the differential hippocampal subfields and covariance brain regions with memory function. Results:The SCD group exhibited significantly lower years of education, AVLT-immediate score, AVLT-delayed score, VR-immediate score, VR-delayed score, and memory function Z-score compared to the NC group ( t=2.064, 3.888, 2.622, 3.222, 4.761, 5.184, all P<0.05). The volumes of the right subiculum((387.75±55.20)mm 3, (352.70±70.25)mm 3), left presubiculum((263.12±38.52)mm 3, (239.79±46.02)mm 3), left subiculum((388.12±49.34)mm 3, (351.74±67.30)mm 3) and left CA1((571.01±80.01)mm 3, (526.51±98.80)mm 3) in the SCD group were smaller than the corresponding volumes in NC group ( F=9.139, 8.039, 11.207, 7.266, all P<0.05, FDR correction). Differences in structural covariance connectivity were found between the SCD and NC groups in the following pairs: right CA1-right subiculum, right CA1-left subiculum, right CA3-left parasubiculum and right hippocampus-amygdala transition area-left subiculum ( Z=-3.848, -3.896, -3.597, -3.895, all P<0.05, FDR correction).Partial correlation analysis revealed that in the SCD group, the volume of the left subiculum ( r=0.359, P=0.007), left CA1 ( r=0.430, P=0.001), right entorhinal cortex ( r=0.296, P=0.029), right middle temporal gyrus ( r=0.361, P=0.007), right parahippocampal gyrus ( r=0.313, P=0.021)were positively correlated with the total memory function score. Conclusion:Hippocampal subfields atrophy, as well as alterations in structural covariance network, have been found in SCD individuals. Furthermore, the decline in memory function may be closely associated with atrophy in hippocampal subfields and structurally covariant regions.

Objective To investigate the mechanism by which Yangmai Tongluo formula improves microcirculation disorders induced by high homocysteine(Hcy)levels via regulation of the acid sphingomyelinase(ASM)and endoplasmic reticulum(ER)stress pathways.Methods Fifty male C57BL/6J mice were divided randomly into a control group,Hcy model group,Yangmai Tongluo formula low-/high dose groups(5.3,10.4 g/kg,respectively),and a folic acid group(0.08 g/kg).Except for the control group,microcirculation disorders were induced in all mice using drinking water containing 1.8 g/L Hcy for 6 weeks.After modeling for 2 weeks,mice were administered the corresponding treatments by gavage for 4 weeks.Serum Hey concentrations and the blood perfusion volume of the lower extremity microvessels were measured.Protein expression levels of zonula occludens ZO-1,ZO-2,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),ASM,glucose-regulated protein 78(GRP78),and C/EBP homologous protein(CHOP)in the cardiac microvascular endothelium were analyzed using immunofluorescence.Results Serum Hcy levels were significantly increased in the Hcy model group compared with the control group(P＜0.05).Yangmai Tongluo formula did not significantly reduce Hey levels compared with the Hey model group,but blood perfusion in the lower extremities was significantly increased(P＜0.01)and expression levels of ZO-1 and ZO-2 in the cardiac microvascular endothelium were restored(P＜0.001)in the Yangmai Tongluo formula high dose group.It also inhibited the expression of ICAM-1,VCAM-1,ASM,GRP78,and CHOP(P＜0.05),with comparable effects to folic acid.Conclusions Yangmai Tongluo formula improves Hcy-induced microcirculation disorders and endothelial dysfunction by inhibiting ASM activity and alleviating ER stress,via a mechanism closely related to the regulation of endothelial inflammation and barrier stability.These result provide experimental evidence to support the use of traditional Chinese medicine to treat microvascular diseases.

Objective:To investigate the differences in hippocampal subfield volumes and structural covariance network between participants with subjective cognitive decline (SCD) and healthy individuals, and to analyze the correlations of the volumes of the different subfields and altered covariance brain regions with memory function.Methods:A total of 57 SCD individuals(SCD group) and 44 normal controls(NC group) participants were assessed for memory function using composite scores from the auditory verbal learning test (AVLT) and the Wechsler memory scale visual reproduction (VR) test from June 2022 to October 2023.T1-weighted structural magnetic resonance imaging (MRI) data were collected from all participants, and hippocampal subfields, cortical regions, and subcortical nuclei were segmented using FreeSurfer to measure the gray matter volume of each structure. A structural covariance network was constructed based on the correlation of gray matter volumes across regions. Statistical analysis was performed using R 4.3.1 software. Inter-group differences in hippocampal subfield volumes were compared using multivariate analysis of covariance. Differences in structural covariance connectivity between groups were assessed using Z-test, while network topology differences were compared through permutation testing. Finally, partial correlation analysis was used to examine correlation of the volumes of the differential hippocampal subfields and covariance brain regions with memory function. Results:The SCD group exhibited significantly lower years of education, AVLT-immediate score, AVLT-delayed score, VR-immediate score, VR-delayed score, and memory function Z-score compared to the NC group ( t=2.064, 3.888, 2.622, 3.222, 4.761, 5.184, all P<0.05). The volumes of the right subiculum((387.75±55.20)mm 3, (352.70±70.25)mm 3), left presubiculum((263.12±38.52)mm 3, (239.79±46.02)mm 3), left subiculum((388.12±49.34)mm 3, (351.74±67.30)mm 3) and left CA1((571.01±80.01)mm 3, (526.51±98.80)mm 3) in the SCD group were smaller than the corresponding volumes in NC group ( F=9.139, 8.039, 11.207, 7.266, all P<0.05, FDR correction). Differences in structural covariance connectivity were found between the SCD and NC groups in the following pairs: right CA1-right subiculum, right CA1-left subiculum, right CA3-left parasubiculum and right hippocampus-amygdala transition area-left subiculum ( Z=-3.848, -3.896, -3.597, -3.895, all P<0.05, FDR correction).Partial correlation analysis revealed that in the SCD group, the volume of the left subiculum ( r=0.359, P=0.007), left CA1 ( r=0.430, P=0.001), right entorhinal cortex ( r=0.296, P=0.029), right middle temporal gyrus ( r=0.361, P=0.007), right parahippocampal gyrus ( r=0.313, P=0.021)were positively correlated with the total memory function score. Conclusion:Hippocampal subfields atrophy, as well as alterations in structural covariance network, have been found in SCD individuals. Furthermore, the decline in memory function may be closely associated with atrophy in hippocampal subfields and structurally covariant regions.

From July 23, 2018, to December 31, 2019, a total of 299 219 children in Shandong Province received the fifth dose of the diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). Among these recipients, the distribution by age was as follows: 20 children under 2 years old (0.01%), 273 996 children aged 2 years (91.57%), 20 242 children aged 3 years (6.76%), 3 932 children aged 4 years (1.31%), 963 children aged 5 years (0.32%), and 66 children aged 6 years and above (0.02%). In total, 1 972 cases of adverse events following immunization (AEFI) were reported after the administration of the fifth dose of DTaP, resulting in an incidence rate of 659.05 per 100 000 doses. Among these, 1 718 cases were classified as common vaccine reactions, with an incidence rate of 574.16 per 100 000 doses, while 247 cases were identified as rare reactions, yielding an incidence rate of 82.55 per 100 000 doses. The incidence of AEFIs, as well as the rates of common and rare reactions, exhibited a significant increasing trend with the number of doses administered (all P<0.001). Among the rare reactions, there were 10 cases classified as severe, resulting in a reported incidence of 3.34 per 100 000 doses.