Journal of Shandong University (Health Sciences)

Therapeutic effect of nifedipine and metoprolol on heart disease

LYU Mingyue, SUN Hanchen, LUO Qingxin, XU Zhaoke, XU Ruize, ZHANG Shuo, YAN Luning, HU Xifeng, ZHAO Qingbo, ZHU Gaopei, XUE Fuzhong

Journal of Shandong University (Health Sciences). 2025, 63(9): 1-10. doi:10.6040/j.issn.1671-7554.0.2024.1469

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Objective To investigate the effects of nifedipine and metoprolol on major cardiovascular events, all-cause mortality, and drug-induced liver injury in patients with heart disease using real-world data. Methods Based on Cheeloo Lifespan Electronic Health Research Data-library(Cheeloo LEAD), a real-world study was conducted through a new user cohort design matched by a propensity score, including patients who were first diagnosed with heart disease between January 1, 2012 and December 31, 2022. A large-scale L1 regularized propensity score was used to match covariates and achieve quasi-randomization. The Cox proportional hazards regression model was then employed to assess the average causal effects of nifedipine(exposure group)and metoprolol(control group)on major cardiovascular events, all-cause mortality, and drug-induced liver injury, respectively. Results Men with heart disease were more likely to have major cardiovascular events, all-cause mortality, and drug-induced liver injury. Following the implementation of L1 regularized propensity score matching, the standardized differences of covariates were found to be less than 0.2, with the majority falling below 0.1, and the Kaplan-Meier survival curve revealed no discernible crossover between the exposed group and the control group. The log-rank tests for both drug-induced liver injury and all-cause mortality revealed statistically significant differences between groups(both P<0.05). Furthermore, the cumulative survival rate of patients who received nifedipine during the follow-up period was higher than that of patients who received metoprolol. The Cox proportional hazard regression model showed that nifedipine had a lower risk of drug-induced liver injury(HR=0.39, 95%CI: 0.16-0.93, P=0.025)and all-cause mortality(HR=0.53, 95%CI: 0.28-0.98, P=0.034)than metoprolol, no significant difference was observed between nifedipine and metoprolol in the prevention of major cardiovascular events(HR=1.30, 95%CI: 0.97-1.90, P=0.061). Conclusion Nifedipine may reduce the risk of all-cause mortality in patients with heart disease compared to metoprolol and is associated with a lower risk of drug-induced liver injury. These results provide supplementary evidence to support the safe usage of medications in patients with heart disease, particularly a reference for assessing the risk of pharmacogenetic liver injury.

Association between modifiable cardiovascular risk factors clustering patterns and stroke in the elderly population

PANG Jinhong, SU Ping, QIAO Junpeng, CHEN Qiaoqiao, CHEN Xueyu, ZHAO Yingying, SHI Jie, SUN Xiaoru, LI Qiuchun, HE Ruiyan, FAN Yiou, CHI Weiwei

Journal of Shandong University (Health Sciences). 2025, 63(9): 11-19. doi:10.6040/j.issn.1671-7554.0.2024.1421

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Objective To explore the gender-specific clustering patterns of modifiable cardiovascular risk factors(MCVRFS)and assess their associations with stroke incidence among the elderly population in Shandong Province. Methods Based on the Cheeloo Lifespan Electronic Health Research Data-library(Cheeloo LEAD)database, 58,633 participants aged ≥60 years old with complete health examination records, electronic medical records, and public health archives from June 1 to December 31, 2015 were included. A seven-year follow-up cohort was constructed, with occurence of stroke as the study endpoint. Latent class analysis(LCA)was used to identify MCVRFS clustering patterns, and Cox proportional hazards regression models were applied to evaluate associations between clusters and stroke risk. Results LCA identified four MCVRFS clusters in both genders. Males comprised the low-risk(39.02%), smoking and alcohol consumption(16.41%), overweight/obesity(36.34%), and metabolic syndrome(8.22%)groups. Females comprised the low-risk(41.00%), smoking and alcohol consumption(0.44%), overweight and dyslipidemia(46.76%), and metabolic syndrome(11.80%)groups. During follow-up, 6,764 new stroke cases occurred in males(incidence density: 4,947/100,000 person-years)and 8,141 in females(incidence density: 4,273/100,000 person-years). Adjusted Cox regression showed that males in smoking and alcohol consumption group(HR=1.13, 95%CI=1.05-1.21), overweight obesity group(HR=1.16, 95%CI=1.09-1.23), and metabolic syndrome group(HR=2.20, 95%CI=2.04-2.38)had elevated stroke risks compared to the low-risk group. In females, overweight and dyslipidemia group(HR=1.16, 95%CI=1.10-1.21)and metabolic syndrome group(HR=2.39, 95%CI=2.25-2.54)showed higher stroke risks compared to the low-risk group. Conclusion Four kinds of gender-specific MCVRFS clustering patterns are identified in Shandongs elderly population. Overweight-obesity, smoking-alcohol, and metabolic syndrome clusters increase stroke risk in males, while weight-dyslipidemia and metabolic syndrome clusters elevate risks in females. Targeted intervention strategies tailored to these clusters may reduce stroke incidence and disease burden in the elderly.

Associations between frailty and the risk of epilepsy: a prospective cohort study and Mendelian randomization analysis

WANG Le, LUO Qingxin, WU Sijia, WU Yutong, GE Yilei, YU Yifan, WEI Yun, JI Hanbing, LIU Tiemei, ZHANG Ziyan, XIU Jiawei, XUE Fuzhong, LI Hongkai

Journal of Shandong University (Health Sciences). 2025, 63(9): 20-30. doi:10.6040/j.issn.1671-7554.0.2024.1463

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Objective To evaluate the associations between physical frailty and the risk of epilepsy based on the UK Biobank(UKB)database. Methods A total of 368,857 target participants were selected from the UKB database. Five exposures from the baseline data were collected from 2006 to 2020, which included weight loss, exhaustion frequency, weakness, physical inactivity and slow walking speed. New epilepsy incidents during the follow-up period were further obtained. COX proportional hazards regression models were applied to evaluate the hazard ratio(HR)and 95% confidence interval(CI)of frailty phenotype with the risk of epilepsy after adjusting for age, gender, race, education level, family income, smoking status, alcohol status, cerebrovascular diseases, dementia, head injuries, brain infections and alcohol-related disorders at baseline. Propensity score matching was applied as supplementary analysis. Mendelian randomization(MR)analysis was conducted using genetic instrumental variables(IVs)selected from genome-wide association study(GWAS)data, including inverse variance-weighting(IVW)method, MR-Egger method, weighted median(WME)method, simple mode(SM)method and weighted mode(WM)method. Sensitivity analysis was performed to verify the robustness of results. Results The cohort analysis revealed a significant association between physical frailty and the risk of epilepsy after adjustment for potential confounding, with an HR(95%CI)of 1.72(1.44-2.05), P<0.001. Results after matching were consistent with the main analysis. IVW method(OR=1.99, 95%CI: 1.21-3.28, P=0.007)and WME method(OR=2.24, 95%CI: 1.12-4.46, P=0.022)indicated a positive correction between genetically determined frailty index and epilepsy risk. Sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy. Conclusion Physical frailty may contribute to the development of epilepsy. These results help to explore the etiology and pathogenesis of epilepsy, and provide evidence for clinical epilepsy treatment and prevention strategies.

Pan-cancer cell type-specific gene-gene co-expression pattern

LI Jing, JU Weihang, LIU Ke

Journal of Shandong University (Health Sciences). 2025, 63(9): 31-39. doi:10.6040/j.issn.1671-7554.0.2024.1401

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Objective To investigate the gene co-expression patterns across diverse cell types within multiple cancer tissues using single-cell omics data. Methods Utilizing large-scale public single-cell transcriptomics data and the CS-CORE method, cell type-specific gene co-expression profiles were generated for six common cell types across five distinct cancers. Results A total of 30 high-quality gene co-expression maps were obtained. Among the analyzed cell types, malignant cells exhibited the highest number of co-expressed gene pairs, suggesting a relatively complex gene regulatory mechanism. Hierarchical clustering across cancer types revealed that the regulatory breadth of transcription factors tended to be conserved within the same cell type. Additionally, macrophages displayed the most differentially co-expressed gene pairs, suggesting that the gene regulatory network of macrophages might be susceptible to the influence of the tumor microenvironment. Conclusion This study systematically constructs a cell type-specific gene co-expression map in cancer tissues, uncovering several gene co-expression patterns from a pan-cancer perspective.

Influencing factors of acute ischemic stroke in population during 18-50 years old: a real-world study analysis

SUN Shuangshuang, ZHANG Shuaijie, ZHANG Botao, YUAN Ying, YU Yuanyuan, XUE Fuzhong

Journal of Shandong University (Health Sciences). 2025, 63(9): 40-46. doi:10.6040/j.issn.1671-7554.0.2024.0634

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Objective To investigate the factors that contribute to the occurrence of acute ischemic stroke(AIS)in individuals aged 18 to 50 years in real-world settings. Methods This study employed data from the Cheeloo Lifespan Electronic Health Research Data-library(Cheeloo LEAD), housed within the National Health and Medical Big Data Research Institute of Shandong Province. The AIS group comprised individuals aged between 18 and 50 years who had been newly diagnosed with AIS during 2012-2022 and who had complete physical examination data. The non AIS group consisted of individuals without AIS, matched at a ratio of 1∶2 by age and sex. Multivariate Logistic regression analyses were conducted to identify factors associated with the occurrence of AIS. A nomogram was constructed to illustrate the contribution of each factor, and the models performance was evaluated using the area under the receiver operating characteristic curve(AUC). Results A total of 17 independent risk factors for AIS were identified, including female sex, smoking, elevated body mass index(BMI), hypertension, diabetes mellitus, coronary atherosclerotic heart disease, hyperlipidemia, sleep disorders, anxiety, chronic obstructive pulmonary disease, asthma, hyperhomocysteinemia, patent foramen ovale, valvular heart disease, migraine, rheumatic diseases, and intracerebral hemorrhage. A nomogram model was developed based on these risk factors, achieving an AUC of 0.803. Conclusion Among people aged 18 to 50, the occurrence of AIS is significantly associated with multi-system diseases and lifestyle factors, including metabolic diseases(such as hypertension and diabetes), cardiovascular diseases, mental and neurological disorders(such as sleep disorders and anxiety), and chronic inflammatory diseases, and so on.

Quantitative analysis of Chinas public hospital salary policy texts based on the two-dimensional framework of policy tools and stakeholders

LI Xinyao, LI Min, CHAO Jianqian, JIN Shengxuan, CHEN Jianli, HAO Zeming

Journal of Shandong University (Health Sciences). 2025, 63(9): 47-56. doi:10.6040/j.issn.1671-7554.0.2025.0113

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Objective To provide basis and reference for policy optimization by analyzing the text of compensation policy of public hospitals in China and exploring the distribution characteristics of policy tools and stakeholder dimensions. Methods Using the content analysis, the two-dimensional analysis framework of "policy tools-stakeholders" was constructed to conduct a coding analysis of the salary policies of public hospitals at the national level from 2015 to 2024. Results A total of 49 policy texts was included. A total of 258 policy text codes were extracted for the policy tool dimension, of which command and regulation type tools were used the most with 59.30%(153/258); followed by information and horticulture type tools with 18.22%(47/258); and capacity building type tools were used the least with 6.20%(16/258). A total of 261 policy text codes were extracted for the stakeholder dimension, with the highest percentage of government-related departments at 70.11%(183/261); followed by hospitals at 12.64%(33/261); and patients and social health insurance organizations at the lowest percentage, both at 1.53%(4/261). Conclusion The current remuneration policy of public hospitals needs improvement. It is recommended to optimize the proportion of the use of policy tools and to build a mechanism of synergistic participation by multiple subjects.

Health-related quality of life and its influencing factors of the elderly in Shandong Province based on multilevel models

FU Yu, JIANG Wei, ZHU Gaopei, XUE Fuzhong

Journal of Shandong University (Health Sciences). 2025, 63(9): 57-64. doi:10.6040/j.issn.1671-7554.0.2024.0780

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Objective To examine the health-related quality of life of the elderly in Shandong Province, and to analyze its influencing factors on the basis of controlling for regional heterogeneity. Methods A total of 5,447 elderly people over 65 years old in 10 demonstration counties in Shandong Province were selected by Multicenter cluster random sampling. Face-to-face questionnaires were used to collect information. The European Five Dimensions of Health(EQ-5D-5L)scale was used to investigate the health-related quality of life of the subjects. The Mann-Whitney U test and Kruskal-Wallis test were used to compare health-related quality of life. Because of the nested structure of the data in this study, a multilevel Logistic regression model was used to analyze the factors influencing health-related quality of life and a comparison was made with a single-level Logistic regression model. Results Health utility value ［M(P25, P75)］ of elderly people over 65 years old in Shandong Province was 0.942(0.861, 1.000), and the EQ-VAS ［M(P25, P75)］ was 80(80, 90). Among the five dimensions of the EQ-5D-5L scale, the highest proportion of people without difficulties was "self-care"(91.33%), while the highest proportion of people with difficulties was "pain or discomfort"(45.4%). The results of univariate analysis showed that county, age, gender, smoking, alcohol consumption, physical exercise and accidental injury affect the health utility values, while age, alcohol consumption, physical exercise and accidental injury were also influential factors of the EQ-VAS scores(P<0.05). The results of multilevel Logistic regression analyses showed that age, gender, alcohol consumption, physical exercise, and accidental injury affected the health utility value, while alcohol consumption, physical exercise and accidental injury were also the influencing factors of EQ-VAS score(P<0.05). Conclusion The health-related quality of life of the elderly in Shandong Province is relatively high; Geographical differences affect health-related quality of life; On the basis of considering regional heterogeneity, attention should be given to proactive interventions in the areas of smoking, alcohol consumption, physical activity and accident prevention.

Research progress on the function and mechanism of lactylation in the process of tumor inflammation and cancer

LI Xuekai, SUN Linhan, LIU Duanrui, NI Yang

Journal of Shandong University (Health Sciences). 2025, 63(9): 65-76. doi:10.6040/j.issn.1671-7554.0.2025.0310

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Lactylation modification, as a novel post-translational modification(PTM)of proteins, is one of the main mechanisms of epigenetic regulation. It can affect the structure, function, activity and stability of proteins. Lactylation modification provides a new perspective for better understanding the connection between cellular metabolic reprogramming and epigenetic regulation. Recently, studies have increasingly found that lactylation modification regulates tumor proliferation and drug resistance by participating in the inflammatory-cancer process. It promotes inflammatory-cancer transformation and immunosuppression and is closely related to poor tumor prognosis. Understanding the molecular mechanism of lactylation modification provides new perspectives and strategies for tumor treatment, and promotes the transformation of lactate research from basic research to clinical applications. This article reviews the roles of lactylation metabolism and modification in the inflammatory-cancer process, highlighting their key roles in multiple tumors such as gastrointestinal and liver tumors. These findings are important for exploring the mechanism of tumor occurrence and development, as well as for identifying new therapeutic targets.

Research progress on the mechanism of berberines anti-atherosclerosis effects based on the synergistic effect of lipid deposition inhibition and metabolic clearance

LI Xiping, QIU Mei, HUANG Ruifeng, LIN Huihui, LIU Sisi, LUO Hongying, WANG Yuyue, WANG Min, YANG Xiaotong

Journal of Shandong University (Health Sciences). 2025, 63(9): 77-83. doi:10.6040/j.issn.1671-7554.0.2025.0019

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Atherosclerosis(AS), the primary pathological basis of cardiovascular diseases, poses a growing global public health challenge. Current therapies face limitations in synergistically addressing lipid metabolism disorders and inflammatory dysregulation, prompting exploration of multi-target natural agents. Berberine, a natural compound, combats AS through dual mechanisms: suppressing cholesterol biosynthesis, enhancing reverse cholesterol transport, and inhibiting macrophage foam cell formation to reduce arterial lipid deposition; while improving lipoprotein homeostasis and activating fatty acid β-oxidation to diminish visceral fat accumulation. These actions collectively prevent AS progression, ameliorate metabolic syndrome, and alleviate hepatic lipotoxicity. This review elucidates berberines molecular mechanisms in rebalancing lipid-inflammatory networks during AS pathogenesis and evaluates its clinical potential, offering novel strategies to overcome single-target drug limitations.

Outcomes of a Y-composite arterial graft using free right internal mammary artery and radial artery for patients undergoing total arterialization myocardial revascularization in multi-center in China

GUO Ke, CHEN Xujun, SHI Chao, LUO Junhui, YANG Min, WANG Xiaowu, WANG Zhendong, LI Youjin, MENG Chunying, CHEN Wensheng

Journal of Shandong University (Health Sciences). 2025, 63(9): 84-91. doi:10.6040/j.issn.1671-7554.0.2024.1063

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Objective To evaluate the safety and efficacy of a composite Y arterial graft(fRIMA-RA-Y graft)using free right internal mammary artery(fRIMA)and radial artery(RA)for patients undergoing total arterial myocardial revascularization(TAR). Methods From January 2020 to May 2024, 112 patients who underwent TAR in 10 hospitals in China and used fRIMA and RA to construct fRIMA-RA-Y bridges were included, including 91 males and 21 females, aged 55.5±11.7 years. Perioperative data and follow-up data after surgery, including survival, echocardiography, and CT angiography(CTA), were collected and analyzed. Results Coronary lesions in all patients were multiple-vessel disease, with 40 cases of severe left main disease. There were 72 patients with diabetes mellitus. All patient underwent TAR by on pump technique. The duration of aorta cross-clamping was 61-100(57.5±11.4)mins and cardiopulmonary bypass time was 79-127(113.4±19.2)mins. Among 112 TAR patients, 112 pedicled LIMA, 112 left RA, 100 right RA and 112 fRIMA conduits were harvested. A total of 112 fRIMA-RA-Y grafts were constructed in in left coronary territory. The number of distal anastomoses was 3-5(4.2±0.7). The duration of mechanical ventilation and ICU stay was 1-18(10.5±7.7)hours and 12-117(23.5±12.9)hours respectively. There was one surgical death. A percent of 7.69%(7/112)of patients were implanted with intraoperative aortic balloon bump. There were 22 patients of new set postoperative atrial fibrillation, 7 of forearm hematoma, 5 of postoperative left chest hemorrhage and 5 of acute renal insufficiency. No chest bone infection occurred. The follow-up duration was 2-49(34.3±5.5)months, with a follow-up rate of 75.89%. There was a significant improvement in left ventricular ejection fraction compared to that of before surgery ［(53.3±5.3)% vs.(62.0±4.5)%, t=17.16, P<0.001］). All patients survived without major adverse cardiovascular or cerebrovascular events during follow-up. It was showed in CTA examination that graft patency of fRIMA-RA-Y graft was 94.12%. Conclusion This multi-center study indicates that fRIMA-RA-Y composite arterial grafts in left coronary territory appears to be safe and effective in TAR patients.

Whole genome characterization analysis of Coxsackievirus A6 in Jining in 2021

WANG Shan, LIU Wei, FENG Qiang, FAN Yingying, LIU Haixia, DUAN Yanhua, WEN Hongling, JIAO Boyan

Journal of Shandong University (Health Sciences). 2025, 63(9): 92-101. doi:10.6040/j.issn.1671-7554.0.2024.1149

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Objective To analyze the epidemiological characteristics and whole-genome features of Coxsackievirus A6(CVA6)in Jining City in 2021, providing a basis for the prevention and control of hand, foot, and mouth disease(HFMD). Methods Reverse transcription quantitative real-time PCR(RT-qPCR)was used to detect CVA6 nucleic acid in HFMD case samples collected from 11 counties and districts in Jining City in 2021. CVA6-positive samples were inoculated into human rhabdomyosarcoma cells for viral culture, and viral nucleic acid was extracted for whole-genome sequencing using next-generation sequencing technology. Bioinformatics analyses, including sequence similarity analysis, internal ribosome entry site(IRES)secondary structure modeling, phosphorylation site analysis, glycosylation site analysis, and lipidation site analysis, were conducted using MEGA 7.0.14, RNAfold, NetPhos 3.1, NetNGlyc 1.0, and GPS Lipid software. Results Nucleic acid testing showed that the positive rate of CVA6 among the confirmed HFMD cases in Jining City in 2021 was 35.79%(97/271). Whole-genome sequencing results revealed that three CVA6 strains exhibited nucleotide homology of 80.69%-80.95% and polyprotein amino acid homology of 94.83%-94.92% with the prototype strain Gdula. Bioinformatics analysis showed that all three CVA6 strains belonged to the D3a evolutionary branch but were located in different evolutionary clusters. Compared to the Gdula prototype strain, seven nucleotide mutations were observed in the 5'UTR IRES region, Q98L and G160S mutations occurred in the VP1 antigenic epitope, an S194T mutation was found in the VP1 receptor-binding site, and T308S, L342S, and K346R mutations were identified in the 3D polymerase active site. Additionally, multiple variations were observed in phosphorylation, glycosylation, and lipidation sites of the encoded proteins. Conclusion CVA6 was the predominant pathogen in HFMD cases in Jining City in 2021. It was evolving in the direction of adapting to the host. The monitoring and prevention efforts against CVA6 should be strengthened.

Correlation between the levels of serum Isthmin1, Gremlin2 and retinopathy in type 2 diabetic patients

MENG Xiaomei, HAO Yaping, WANG Liang, YU Xiao, TANG Yuxiao

Journal of Shandong University (Health Sciences). 2025, 63(9): 102-107. doi:10.6040/j.issn.1671-7554.0.2025.0087

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Objective To investigate the correlation between the levels of serum Isthmin1(ISM1), Gremlin2(GREM2)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM). Methods A total of 148 patients with T2DM who were treated in the Affiliated Yantai Yuhuangding Hospital of Qingdao University from January 1,2023 to December 31,2023 were included in the study and divided into a non-DR(NDR)group(n=81)and a DR group(n=67)based on the absence or presence of DR. Serum ISM1 and GREM2 levels were measured by enzyme-linked immunosorbent assay. Results Significant differences in diabetic duration, the presence of hypertension, systolic blood pressure(SBP), interleukin 6, urinary albumin-to-creatinine ratio(UACR)and carotid intima-media thickness(cIMT)were observed between the NDR and DR groups(all P<0.05). Compared with the NDR group, DR group had higher levels of ISM1 ［2.63±0.99 vs. 1.24±0.72 ng/mL］ and GREM2 ［1 001.01(920.00,1 149.71), vs. 896.51(771.02,997.45)pg/mL］(all P<0.001). After adjustments for age and gender, partial correlation analysis revealed that the presence of DR was positively correlated with SBP, triglycerides, UACR, cIMT, ISM1 and GREM2(all P<0.05). Multivariate Logistic regression analysis showed that ISM1, GREM2, SBP and UACR were independent influencing factors of DR in patients with T2DM(all P<0.05). Conclusion The risk of DR in T2DM patients increases with the elevation of ISM1 and GREM2, and early screening for DR may be facilitated by detecting their levels in serum.

The functional role and clinical significance of lncRNA HEATR3-AS1 in colorectal cancer tumorigenesis and progression

LI Ziqi, WEI Yanruoxue, LIU Xiaohan, LIU Chuncheng, ZHAO Ran, LIU Yukun

Journal of Shandong University (Health Sciences). 2025, 63(9): 108-115. doi:10.6040/j.issn.1671-7554.0.2025.0357

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Objective To investigate the expression characteristics, subcellular localization, molecular functions, clinicopathological significance, and prognostic evaluation value of long non-coding RNA HEATR3-AS1 in colorectal cancer(CRC). Methods Quantitative real-time polymerase chain reaction(RT-qPCR)was used to detecte the expression level of HEATR3-AS1 in CRC tissues, and fluorescence in situ hybridization(FISH)was used to clarify its subcellular localization. The correlation between the expression of HEATR3-AS1 and HEATR3 mRNA was analyzed. The eukaryotic expression vector containing HEATR3-AS1 was constructed using molecular cloning techniques and the HEATR3-AS1-overexpressed cell model was constructed to elucidate the effect of its overexpression on HEATR3 mRNA expression. In situ hybridization(ISH)was employed to analyze the correlation of its expression in CRC tissues with clinicopathological features and poor prognosis in CRC patients. Results The expression of HEATR3-AS1 in CRC tissues demonstrated a marked upregulation compared with paracancerous normal tissues(P=0.019 2)and was explicitly localized in the nucleus of CRC cells. A significant positive correlation was observed between HEATR3-AS1 and HEATR3 mRNA expression levels(P=0.020 2), and its overexpression promoted the expression of HEATR3 mRNA(P=0.007 7). High expression of HEATR3-AS1 was significantly associated with advanced TNM stage(P=0.029)and lymph node metastasis(P=0.036). Survival curve analysis revealed that colorectal cancer patients with elevated HEATR3-AS1 expression experienced a marked reduction in overall survival(OS)compared to those with low expression(P=0.001 1). Multivariate Cox analysis confirmed that high expression of HEATR3-AS1 could serve as an independent poor prognostic factor in CRC patients(HR=3.355, 95%CI=1.632-7.193, P=0.001 3). Conclusion HEATR3-AS1 is overexpressed and specifically localized in the nucleus of CRC cells. Its overexpression may regulate the transcription of HEATR3, and its aberrantly high expression serves as an independent prognostic factor for colorectal cancer, highlighting its potential as a novel biomarker for molecular classification and survival prediction in CRC.

Effect of nighttime heat on mortality risk of cardiovascular disease during warm seasons in Zibo City

YUE Fang, QIAO Yingyi, SHI Xinglong, XU Xinying, LYU Jing, CHENG Chuanlong, ZUO Hui, CUI Feng, LI Xiujun

Journal of Shandong University (Health Sciences). 2025, 63(9): 116-124. doi:10.6040/j.issn.1671-7554.0.2025.0238

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Objective To investigate the impact of nighttime heat on cardiovascular disease mortality during warm seasons in Zibo City, and to identify patients with cardiovascular disease who are sensitive to nighttime heat. Methods The daily cardiovascular disease death data, meteorological and air pollution data in Zibo City were collected from December 31 2015 to January 1 2019. The intensity of nighttime heat was assessed using the hot night excess(HNE)index, which was calculated by determining the excess sum of high temperatures during the night. The distributed lag nonlinear model was used to analyse the impact and lag effects of nighttime heat on cardiovascular disease mortality. Subgroup analyses were performed by age and gender. Results During the study period, there were 28,079 deaths due to cardiovascular disease in warm seasons(May to September). The exposure-response relationship curve showed that HNE was associated with cardiovascular disease mortality, with a lag effect. The relative risk of extreme HNE peaked at days 0 after exposure, with RR of 1.09(95%CI: 1.03-1.15); the cumulative effect peaked at the 7th day, with RR of 1.40(95%CI: 1.27-1.54). Mortality risk was higher for ischemic heart disease and myocardial infarction than for cardiovascular disease and cerebrovascular disease. Furthermore, females and the elderly(aged ≥65 years)had a higher attributable risk. Conclusions Nighttime heat was associated with an increased risk of mortality from cardiovascular disease. Patients with ischemic heart disease, females and people aged ≥65 years were more susceptible to extreme nighttime heat. It is necessary to consider nighttime heat in heatwave warning systems and to focus on vulnerable populations. Targeted public intervention strategies should be implemented based on the hazards of nighttime heat.

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