1.Establishment and analysis of chronic rejection model of mouse heart transplantation
Wei ZHANG ; Qingrong ZHANG ; Maolin MA ; Qianghua LENG ; Fei HAN
Organ Transplantation 2025;16(1):99-105
Objective To establish a chronic rejection (CR) model of mouse heart transplantation and analyze its characteristics. Methods Allogeneic BALB/c and C57BL/6 mice were used as donor and recipient for heart transplantation, and intraperitoneal injection of cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig) was given 1 and 2 days after surgery. Graft survival time, donor specific antibody (DSA) level, graft pathology and inflammatory cell infiltration were observed. Results In allogeneic transplantation model, graft survival time was prolonged after CTLA4-Ig treatment [(28.2±4.1) d vs. (7.0±0.7) d, P < 0.01]. The level of serum DSA-IgG increased at 2, 3 and 4 weeks after surgery, while the level of DSA-IgM remained unchanged. Myocardial cell injury, inflammatory cell infiltration, interstitial fibrosis and C4d deposition in capillaries were aggravated 3 weeks after operation and worsened 4 weeks after operation. The infiltrated immune cells were mainly macrophages, T cells and plasma cells. Conclusions Mouse allogeneic heart transplantation combined with CTLA4-Ig successfully establishes a CR model, which provides a basis for subsequent studies on the pathogenesis and intervention of CR.
2.Visualization Analysis of Research Hotspots and Trends in Treatment of Radioactive Iodine Refractory Differentiated Thyroid Carcinoma
Cancer Research on Prevention and Treatment 2025;52(2):156-164
Objective To explore research hotspots and future development trends in radioactive iodine refractory differentiated thyroid carcinoma (RAIR-DTC) treatment from 2004 to 2024. Methods Literature on RAIR-DTC treatment published from January 2004 to May 2024 was retrieved from the Web of Science (WOS) database. CiteSpace, VOSviewer, and Microsoft Office Excel were used for visual analysis of publication volume, countries, institutions, authors, keywords, and co-citation networks. Results A total of 677 articles were included in the analysis. National and institutional co-occurrence analysis revealed that the United States, along with the MD Anderson Cancer Center at the University of Texas, was the most productive and influential in this field. Author and citation co-occurrence analysis highlighted the substantial contributions of Schlumberger M and Brose MS to the field. The exploration of high-frequency keywords and keyword clustering indicated tyrosine kinase inhibitors and disease prognostic factors were current research hotspots. Keyword burst analysis suggested that future research trends would focus on optimizing clinical benefits through reliable data provided from high-quality clinical trials and achieving personalized, precise treatment management. Conclusion Targeted drugs hold remarkable potential for RAIR-DTC treatment, and emphasizing predictive factors for disease prognosis offers valuable guidance for medical practice.
3.Research Progress in Single-cell Sequencing for Ischemia-reperfusion Injury
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):1-10
Ischemia reperfusion injury (IRI) is often accompanied by serious clinical manifestations, including myocardial hibernation, acute heart failure, brain dysfunction, kidney dysfunction, gastrointestinal dysfunction, liver transplant rejection, systemic inflammatory response syndrome, multiple organ dysfunction syndrome, and so on, which pose important treatment challenges for doctors in clinical practice. Single cell sequencing technology is high-throughput sequencing of the genome, transcriptome, or epigenome at the single-cell level, in order to reveal cellular heterogeneity, and to understand the developmental trajectory, type, state, and various interactions of cells. Since its first discovery, single-cell sequencing technology has been widely applied in various fields, especially in early diagnosis and personalized treatment of tumors. This article mainly reviews the application and progress of single-cell sequencing in various organ dysfunctions caused by IRI, so as to further understand the mechanisms and signaling pathways of IRI, and to provide new ideas for targeted therapy of organ IRI.
4.From Passive Health to Active Health: Research Progress on the Integration of Sports and Medicine
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):11-20
In the process of accelerating the construction of a strong country in health and sports in China, the mode of promoting health has shifted from passive health to active health. Guided by the concept of “active health”, there is a new understanding of the relationship between sports, health, and medical care. The integration of sports and medicine is a concrete manifestation and implementation of the concept of “active health”, and an important measure to implement the Healthy China strategy, which is regarded as an important strategy to promote public health reform. This article reviews the historical path of the integration of sports and medicine from its concept to practical implementation, and finds that China proposed the integration of sports and medicine relatively late, but it has become an intense focus of academic research; The sports and medical departments have launched guidelines for chronic disease exercise and standards related to exercise prescriptions, and local governments in China have explored diversified models of integrating sports and medicine; Under the institutional requirements of top-level design, the exploration of the “integration of sports and medicine” model is flourishing. There are currently problems in promoting the integration of sports and medicine, such as the lack of a “sports and medicine integration” system and a shortage of “sports and medicine integration” talents. Drawing on the international experience of integrating sports and medical services in other countries,We propose a development strategy of “concept first, government leading, and sports and medical cooperation”; We recommend institutional optimization such as improving medical insurance related systems, establishing certification, employment, and management systems for integrated sports and medical talents, and improving the training system for integrated sports and medical talents in universities; We also advocate propose a “dual wheel” promotion path of upgrading hospital rehabilitation centers and expanding community health centers, in order to provide reference for policy formulation and promote the integration of sports and medicine to play a greater role in China’s public health.
5.NAD+ Ameliorates Endothelial Dysfunction in Hypertension via Activation of SIRT3/IDH2 Signal Pathway
Yumin QIU ; Xi CHEN ; Jianning ZHANG ; Zhangchi LIU ; Qiuxia ZHU ; Meixin ZHANG ; Jun TAO ; Xing WU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):70-80
ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group (Saline) and hypertension group (Ang Ⅱ, which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps), and supplemented daily with nicotinamide mononucleotide (300 mg/kg), a precursor of NAD+. Blood pressure, endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA, SIRT3 and isocitrate dehydrogenase 2 (IDH2). 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS, eNOS, SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure (P<0.001) and improved endothelial function and arterial stiffness (P<0.001) in hypertensive mice. In vitro, NMN improved endothelial function in AngII-stimulated endothelial cells (P<0.05) and attenuated mitochondrial oxidative stress levels (P<0.001). Mechanistically, NMN elevated SIRT3 activity (P<0.001), which subsequently enhanced IDH activity (P<0.001) and reduced oxidative stress levels in endothelial cells. Conversely, knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function (P<0.001). ConclusionNAD+ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.
6.Association Between the Coexistence of Chronic Non-communicable Diseases and Quality of Life in Middle-aged and Elderly People Living with HIV/AIDS
Yao ZHANG ; Chi ZHANG ; Cong LIU ; Haidan ZHONG ; Peishan DU ; Quanmin LI ; Linghua LI ; Jing GU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):161-171
ObjectiveTo investigate the prevalence rate of chronic non-communicable diseases (NCDs) and the association with quality of life in middle-aged and elderly patients with HIV/AIDS. MethodsThis cross-sectional study surveyed 432 patients with HIV/AIDS (aged≥45 years) in the Infectious Disease Center in Guangzhou Eighth People’s Hospital of Guangzhou Medical University, and 366 participants were included in the analysis after quality control. A questionnaire and the EuroQol 5-Dimensional 3-level version (EQ-5D-3L) were used to investigate NCDs and quality of life and Tobit regression model was used to estimate the association between chronic diseases and quality of life. ResultsAmong the 366 participants, 29(7.9%) had cardiovascular disease, 45(12.3%) had hypertension, 122(33.3%) had hyperglycemia, 151(41.3%)had hyperlipidemia,7(1.9%) had cancer, 17 (4.6%) had chronic kidney disease, 38 (10.4%) had chronic liver disease, 21(5.7%) had musculoskeletal disorders, and 253(69.1%) suffered from at least one type of chronic diseases. The median (lower and upper quartiles) of EQ-5D utility index was 1.000(0.964~1.000). Multivariate Tobit regression results of the total population showed that cancer [ba=-0.08,95%CI (-0.15,-0.01),P=0.036], chronic kidney disease [ba=-0.07, 95%CI (-0.12,-0.02),P=0.006], musculoskeletal disease [ba=-0.09, 95%CI (-0.13, -0.05),P<0.001], and ≥3 types of chronic diseases[ba=-0.05, 95%CI(-0.08,-0.01),P=0.013] were negatively correlated with EQ-5D utility index. The stratified analysis results of different CD4+T cell levels showed that hypertension [ba=-0.07, 95%CI (-0.12, -0.02), P=0.007], chronic kidney disease [ba=-0.10,95%CI (-0.18,-0.03), P=0.006], musculoskeletal disease [ba=-0.15, 95%CI (-0.22,-0.07), P<0.001] and ≥3 types of chronic diseases [ba=-0.09, 95%CI (-0.09, -0.01), P<0.001] were negatively correlated with EQ-5D utility index in the group with CD4≤500 (cells/μL), whereas cancer[ba=-0.11, 95%CI (-0.20,-0.01), P=0.031] was negatively correlated with EQ-5D utility index in the group with CD4>500(cells/μL). ConclusionsThe prevalence rate of chronic non-communicable diseases in middle-aged and elderly patients with HIV/AIDS is relatively high. The classification of NCDs such as cancer or chronic kidney disease or other chronic diseases and the numbers of NCDs categories are negatively correlated with quality of life. However,this association varies among patients with HIV/AIDS of different CD4+T cell levels. It is suggested that we should try to prevent and identify NCDs at an early stage, strengthen linkages and integration of health services for AIDS and chronic NCDs, and jointly manage and control AIDS with chronic diseases to improve the quality of life among people living with HIV/AIDS.
7.Overlapping Reflux Symptoms in Functional Dyspepsia Are Mostly Unrelated to Gastroesophageal Reflux
Songfeng CHEN ; Xingyu JIA ; Qianjun ZHUANG ; Xun HOU ; Kewin T H SIAH ; Mengyu ZHANG ; Fangfei CHEN ; Niandi TAN ; Junnan HU ; Yinglian XIAO
Journal of Neurogastroenterology and Motility 2025;31(2):218-226
Background/Aims:
Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship.
Methods:
Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients.
Results:
The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences.
Conclusions
The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.
8.Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study
Yu Meng TIAN ; Wei Sen ZHANG ; Chao Qiang JIANG ; Feng ZHU ; Ya Li JIN ; Shiu Lun Au YEUNG ; Jiao WANG ; Kar Keung CHENG ; Tai Hing LAM ; Lin XU
Diabetes & Metabolism Journal 2025;49(1):60-79
Background:
The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods:
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results:
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.
9.Overlapping Reflux Symptoms in Functional Dyspepsia Are Mostly Unrelated to Gastroesophageal Reflux
Songfeng CHEN ; Xingyu JIA ; Qianjun ZHUANG ; Xun HOU ; Kewin T H SIAH ; Mengyu ZHANG ; Fangfei CHEN ; Niandi TAN ; Junnan HU ; Yinglian XIAO
Journal of Neurogastroenterology and Motility 2025;31(2):218-226
Background/Aims:
Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship.
Methods:
Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients.
Results:
The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences.
Conclusions
The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.
10.Study on the mechanism of hyperoside regulating hepatic lipid synthesis to ameliorate non-alcoholic fatty liver disease in mice
Changrui LONG ; Shijian XIANG ; Zhenhua ZHANG ; Huixing WU ; Benjie ZHOU ; Chengyu LU
China Pharmacy 2025;36(6):668-673
OBJECTIVE To investigate the improvement mechanism of hyperoside (HYP) on non-alcoholic fatty liver disease (NAFLD). METHODS Male C57BL/6 mice were randomly divided into normal (NFD) group, model (HFD) group and HYP group, with 8 mice in each group. Except for NFD group, the mice in other groups were fed with HF60 high-fat diet to establish NAFLD model; HYP group was simultaneously given HYP 100 mg/kg intragastrically every day, for 16 consecutive weeks. The body weight and liver weight of mice in each group were recorded 16 h after the last medication; the histopathological changes and lipid accumulation in the liver were observed, and the contents of triglyceride (TAG) in liver tissue and serum contents of TAG, aspartate transaminase (AST) and alanine transaminase (ALT) were measured; LC-MS/MS method was adopted to detect lipid changes in the liver tissue of mice for lipidomics analysis, and protein expressions of lipid synthesis-associated proteins peroxisome proliferator-activated receptor α (PPARα) were also tested. Human hepatocellular carcinoma cell line HepG2 was divided into normal control group, model group, HYP low-concentration group (50 μmol/L), HYP high-concentration group (100 μmol/L), HYP low-concentration+GW6471 (PPARαinhibitor) group, and HYP high-concentration+GW6471 group. Except for normal control group, the remaining cells were induced with oleic acid and palmitic acid to establish a high-fat cell model. The accumulation of lipid droplets in each group of cells was observed, and the TAG content was detected. RESULTS Compared with HFD group, HYP group exhibited significant reductions in liver fat vacuoles, lipid accumulation, liver weight, and TAG content in liver tissue, as well as serum contents of ALT, AST and TAG (P<0.05). Additionally, the expression of PPARα protein in liver tissue was significantly increased (P<0.05), and the pathological morphological changes associated with NAFLD were alleviated. Lipidomic analysis revealed that HYP significantly reduced the levels of TAG, diacylglycerol and other lipids in the liver. Compared with model group, cellular lipid droplet accumulation and TAG content decreased significantly in HYP low- and high-concentration groups (P<0.05); GW6471 could significantly reverse the improvement effect of HYP on above indicators (P<0.05). CONCLUSIONS HYP can effectively ameliorate NAFLD induced by a high-fat diet in mice, and the mechanism may be related to the activation of PPARα to regulate hepatic lipid synthesis.

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