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Open Access Clinical Medicine Issue
Predictive value of peripheral blood SNORD55 for prognosis of atrial fibrillation patients
Journal of Army Medical University 2025, 47(2): 151-160
Published: 30 January 2025
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Objective

To explore the association between the relative expression level of SNORD55 in peripheral blood and the outcomes of all-cause mortality and stroke in patients with atrial fibrillation (AF), and to evaluate the predictive value of SNORD55 for prognosis.

Methods

A total of 133 patients with non-valvular AF admitted in Department of Cardiology of the First Affiliated Hospital of Army Medical University from January 2014 to December 2017 were enrolled in this study. Their baseline information was collected, and the relative expression level of plasma SNORD55 was detected. Cox proportional hazards model was used to explore the association between the relative expression level of SNORD55 in peripheral blood and all-cause mortality as well as stroke in the patients. The predictive performance of CHA2DS2-VASc score for all-cause mortality and stroke was compared with the score combined with the relative expression level of SNORD55 in the AF patients. The area under the receiver operating characteristic curve (AUC) was utilized to evaluate the discrimination, and the net reclassification index (NRI) and comprehensive discriminant improvement index (IDI) were calculated to evaluate the improvement of reclassification ability. Decision curve analysis (DCA) was applied to analyze the change in clinical net benefit.

Results

The results of multivariate Cox regression showed that high expression of SNORD55 in peripheral blood was an independent risk factor for all-cause mortality and stroke in the AF patients. In predicting the outcomes of all-cause mortality and stroke, the addition of relative expression SNORD55 level with the CHA2DS2-VASc score obtained higher AUC value [0.80 (95%CI: 0.67~0.93) vs 0.67 (95%CI: 0.53~0.81), P<0.05]. In predicting the outcome of all-cause death and stroke, combination of the relative expression level of SNORD55 with CHA2DS2-VASc score increased both NRI [54.3 (95%CI: 10.6~61.9) vs 31.9 (95%CI: 2.8~47.5), P<0.05] and IDI [16.1 (95%CI: 2.4~27.0) vs 7.9 (95%CI: 0.5~14.8), P<0.05]. The results of DCA showed that our combination of CHA2DS2-VASc score relative expression level of SNORD55 had higher clinical net benefits than the foreign ABC score in the prediction of the outcomes.

Conclusion

Peripheral blood SNORD55 level is an independent risk factor for all-cause mortality and stroke in AF patients, and has good predictive performance for all-cause mortality and stroke in the patients.

Open Access Basic Medicine Issue
Screening and validation of tsRNAs associated with lung adenocarcinoma
Journal of Army Medical University 2025, 47(2): 122-131
Published: 30 January 2025
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Objective

To explore the roles of transfer RNA-derived small RNAs (tsRNAs) in the oncogenesis and progression of lung adenocarcinoma by analyzing the differential expression of tsRNAs in lung adenocarcinoma and the relationship between the expression levels of tsRNAs in lung adenocarcinoma and the prognosis of patients in order to further screen and validate the tsRNAs associated with lung adenocarcinoma.

Methods

The differential expression of tsRNAs between lung adenocarcinoma tissues and normal tissues was analyzed based on the database of the Computational Medicine Center. The effects of tsRNAs expression levels on the prognosis of lung adenocarcinoma patients were analyzed based on the Cancer Genome Atlas (TCGA) database (TCGA-LUAD). The target genes were predicted based on TRFtarget2.0 and tRFTar databases. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed based on DAVID and KOBA KEGG online websites.The expression levels of target genes in lung adenocarcinoma tissues and normal tissues were analyzed based on the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) database. In vitro cell proliferation, migration, and invasion assays were performed to investigate the biological functions of tRF-19-69M8LOJX in lung adenocarcinoma cells.

Results

Compared with the normal tissues, tRF-19-69M8LOJX was up-regulated in lung adenocarcinoma tissues (log2FC=4.28, FDR<0.05). High expression level of tRF-19-69M8LOJX was associated with shorter progression-free survival (HR=1.565, 95%CI=1.142-2.145, P=0.005). And its overexpression promoted cell proliferation and migration (P<0.001), and invasion (P=0.009) of A549 cells, and up-regulated COL1A1 (P=0.002) and VCAN (P=0.022) significantly in the tRF-19-69M8LOJX overexpression cell model.

Conclusion

tRF-19-69M8LOJX is up-regulated in lung adenocarcinoma tissues. And its high expression is closely associated with poor prognosis. The tsRNA may play an important role in the pathogenesis and development of lung adenocarcinoma.

Open Access Clinical Medicine Issue
Predictive value of peripheral blood piR-hsa-2700592 for prognosis of atrial fibrillation patients
Journal of Army Medical University 2025, 47(6): 551-560
Published: 30 March 2025
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Objectives

To explore the association of peripheral blood PIWI-interacting RNA, piR-hsa-2700592, with all-cause mortality and stroke outcomes in patients with atrial fibrillation (AF), and to determine whether piR-hsa-2700592 has the potential to be an AF biomarker.

Methods

A total of 127 patients with non-valvular AF were enrolled, and the relative expression level of plasma piR-hsa-2700592 was detected. Cox proportional hazard regression was used to analyze the correlation between the expression of piR-hsa-2700592 and all-cause death as well as stroke outcome in the patients. Then the molecule expression level was combined with CHA2DS2-VASc score and ABC stroke (or death) score to establish 2 new prediction models, the improvement of the predictive performance was compared and analyzed. Receiver operating characteristic (ROC) curve analysis (area under the curve, AUC), net reclassification index (NRI), and comprehensive discriminant improvement index (IDI) were used to evaluate the predictive performance, and decision curve analysis (DCA) was employed to assess the clinical benefit.

Results

Multivariate Cox regression analysis showed that the patients with higher expression level of piR-hsa-2700592 in peripheral blood had a higher risk of stroke (HR: 2.203, 95%CI: 1.120~4.332; P=0.022). In the stroke outcome, combination of plasma piR-hsa-2700592 expression level with CHA2DS2-VASc score and ABC stroke score obtained an AUC of 0.70 (95%CI: 0.55~0.85, P<0.001) and 0.84 (95%CI: 0.73~0.96, P=0.02), respectively. But, no significant association was observed between high plasma piR-hsa-2700592 level and all-cause mortality in the AF patients (HR: 1.997; 95%CI: 0.884~4.509; P=0.096). Combination of plasma piR-hsa-2700592 level improved the discriminative capability than the single CHA2DS2-VASc score and ABC stroke score models, with an NRI and IDI value of 44.20% (95%CI: 3.40~59.90, P<0.001) and 8.20% (95%CI: 0.60~15.40, P<0.001), respectively for the new CHA2DS2-VASc score model, and an NRI and IDI value of 44.20% (95%CI: 9.80~58.90, P<0.001) and 10.40% (95%CI: 0.70~21.40, P<0.001), respectively for the new ABC stroke score model. The DCA curve showed that both new prediction models obtained better net clinical benefits.

Conclusion

High peripheral blood expression of piR-hsa-2700592 is an independent risk factor for stroke in the AF patients, and the indicator has a good predictive value for prognosis of the patients. piR-hsa-2700592 might be used as a potential biomarker in the diagnosis and prevention of cardiovascular diseases.

Issue
Trajectory of systolic blood pressure fluctuation and its influencing factors in community-dwelling patients with hypertension
Journal of Army Medical University 2024, 46(12): 1457-1466,F3
Published: 30 June 2024
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Objective

To analyze and construct systolic blood pressure (SBP) fluctuation trajectory in a community population with hypertension and to analyze the factors influencing different trajectories.

Methods

This is a community-based retrospective cohort study. A latent class trajectory model was used to identify and construct longitudinal trajectories of blood pressure change. Multinomial logistic regression analysis was performed to identify the associated factors of blood pressure trajectories by adjusting for different confounders. Potential confounding factors were identified using a directed acyclic graph based on a priori knowledge.

Results

A total of 793 patients with hypertension were enrolled in the analysis. They were divided into 3 groups by LCTM-fitted systolic blood pressure trajectories, namely stable low-level group (n=561, 70.74%), declining group (n=170, 21.44%) and rising group (n=62, 7.82%). Significant differences were observed among the 3 trajectories groups in terms of age, frequency of exercise, ways of follow-up, salt intake, compliance behavior, and referral (P<0.05). Compared to the stable low-level group and adjusting for corresponding confounding factors, the male patients and the patients with "outpatient follow-up" were more likely to be classified into "declining group", with OR and 95% CI of 1.436 (1.016~2.030) and 1.702 (1.202~2.410), respectively. The participants aged ≥65 years, who did not exercise or occasionally exercised, and had moderate and severe salt intake, were more likely to be classified into the "rising group" (OR=1.949, 2.284, 2.433, 4.540, 95%CI: 1.145~3.317, 1.305~3.998, 1.272~4.654, 1.291~15.963).

Conclusion

SBP trajectories in community-dwelling hypertensive population can be divided into stable low-level, declining and rising groups. Gender, age, salt intake, exercise frequency, and follow-up methods may be influencing factors for SBP blood pressure trajectory.

Issue
Expression of long non-coding RNA SFTA1P and its effect on biological functions in lung squamous cell carcinoma
Journal of Army Medical University 2024, 46(11): 1226-1234
Published: 15 June 2024
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Objective

To investigate the expression of long non-coding RNA (lncRNA), surfactant associated 1 pseudogene (SFTA1P) in lung squamous carcinoma and its effect on the biological functions of SFTA1P in lung squamous carcinoma cell lines.

Methods

Based on the cancer genome atlas (TCGA) database, the differential expression of SFTA1P in tumor and normal tissues were compared in patients diagnosed with lung squamous cell carcinoma. Then, the expression of SFTA1P was detected in human normal lung epithelial cell line BEAS-2B and lung squamous cell lines SK-MES-1 and H520 with real-time quantitative polymerase chain reaction (RT-qPCR). SK-MES-1 and H520 cells with overexpression and/or knockdown of SFTA1P were constructed by transfecting the overexpression plasmids (pcDNA3.1-SFTA1P) and small interfering RNAs (si-SFTA1P-1 and si-SFTA1P-2). CCK-8 assay and Transwell assay were used to investigate the effect of SFTA1P on biological functions in lung squamous carcinoma cells. Differential gene expression analysis, correlation analysis and functional enrichment analysis were employed to explore the potential mechanism that SFTA1P may affect biological functions of lung squamous cells.

Results

Analysis of TCGA showed that the expression of SFTA1P was significantly lower in lung squamous cell carcinoma tissue than adjacent normal tissue (P<0.05). RT-PCR results showed that the expression of SFTA1P was obviously lower in lung squamous carcinoma cells than the human normal lung epithelial cells (P<0.05). And the expression level of SFTA1P was relatively lower in the SK-MES-1 cells than the H520 cells (P<0.05). Overexpression of SFTA1P suppressed the proliferation, migration and invasion of lung squamous carcinoma cells (P<0.05), while its knockdown promoted these abilities (P<0.05). Differential gene expression analysis, correlation analysis and functional enrichment analysis indicated that SFTA1P may inhibit MYC, G2m checkpoints and E2f signaling pathways in lung squamous cell carcinoma.

Conclusion

SFTA1P shows anti-cancer function in lung squamous cell carcinoma, and it may affect the biological functions of lung squamous cell carcinoma cells through down-regulating MYC, G2m checkpoints and E2f signaling pathways.

Issue
Monitoring of wearable long-range ambulatory electrocardiographic monitor for a community-based homebound elderly population
Journal of Army Medical University 2024, 46(11): 1316-1322
Published: 15 June 2024
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Objective

To investigate the results of ambulatory electrocardiographic (ECG) monitoring in a community-based homebound elderly population and to explore the applicability of wearable long-range ambulatory ECG monitor for them.

Methods

Elderly volunteers were recruited in Shuangbei Community, Shapingba District, Chongqing, from November 2021 to June 2023. A single-lead wearable ambulatory ECG recorder was applied to them to obtain ECG for 7 consecutive days. The adverse reactions, acceptability, monitoring duration, and arrhythmia detection rate during the wearing were described and recorded. Serious arrhythmic events included frequent atrial premature, atrial flutter, atrial fibrillation (AF), frequent ventricular premature, and RR intervals ≥5 s.

Results

There were 416 individuals enrolled, with a mean age of 71.2±6.6 years, and a male percentage of 36.1% (150 men). Finally, 384 (92.3%) participants completed the wearing of the ECG monitor for 7 d, with an average time of 159.2±29.4 h. There were 179 participants (48.5%) reporting no discomfort during wearing, and 175 ones (47.4%) feeling itchy at the wearing site. The monitoring results showed that the common arrhythmias were atrial premature contractions (97.1%), premature ventricular contractions (93.3%), atrial tachycardia (84.6%), bradycardia (46.6%), frequent atrial premature contractions (15.1%), ventricular tachycardia (13.2%), and long RR interval (11.8%). Among them, 29.1% of the participants experienced serious arrhythmic events, and the detection rate of certain serious arrhythmic events was comparatively higher in the individuals ≥70 years of age and those with history of previous cardiac disease.

Conclusion

The detection rate of common arrhythmias is quite high in the community-based homebound elderly population. A 7-day long-range ambulatory ECG monitoring may be appropriate.

Issue
Circular RNA mmu_circ_0005019 regulates small conductance calcium-activated potassium current and action potential duration in mouse cardiomyocytes
Journal of Army Medical University 2024, 46(2): 100-109
Published: 30 January 2024
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Objective

To investigate the effect of mmu_circ_0005019 on regulating Kcnn3 expression, small conductance calcium-activated potassium current (IK,Ca) which is generated by the small conductance calcium-activated potassium (SK) channel that is partly coded by Kcnn3, and action potential duration (APD).

Methods

We transfected pcDNA3.1-mmu_circ_0005019 expressing vectors and 2 independent small interfering RNAs into HL-1 cells to establish gain- and loss-of-expression cell models, respectively. The transfected cells were divided into overexpression group(n=3), empty vector group(n=3), interference 1 group(n=3), interference 2 group(n=3), and blank control group(n=3). RT-qPCR and Western blotting were used to determine the expression of Kcnn3. Whole-cell patch clamp technology was performed to record the IK, Ca and APD. The effects of mmu_circ_0005019 on Kcnn3 expression, IK, Ca and APD were observed.

Results

Gain- and loss-of-expression cell models were established successfully. The expression of Kcnn3 and IK,Ca current density significantly increased, and the APD was shortened in overexpression group compared with empty vector group(P < 0.05). The expression of Kcnn3 and IK,Ca current density were significantly decreased, and the APD was prolonged in interference groups compared with blank control group(P < 0.05).

Conclusion

Mmu_circ_0005019 promotes the expression of Kcnn3 and its coding channel protein, which regulates IK,Ca and APD in mouse cardiomyocytes, and may play a promoting role in the occurrence of atrial fibrillation.

Issue
Dihydromyricetin induces mitophagy by regulating Prohibitin 2 pathway in vascular endothelial cells
Journal of Army Medical University 2022, 44(4): 356-362
Published: 28 February 2022
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Objective

To observe the effects of dihydromyricetin on mitophagy in vascular endothelial cells, and to clarify the underlying role of Prohibitin 2 in the process.

Methods

After human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of dihydromyricetin (0, 0.1, 1, 10, 100 μmol/L) for 12 h, intensity of MitoTracker® Deep Red (MTDR, a widely used mitochondria-selective probe) was determined for mitochondrial staining by fluorescence microscopy and flow cytometry, and the expression of Prohibitin 2 at mRNA and protein levels as determined by qRT-PCR and Western blotting, respectively. Furthermore, after treatment with of without control/Prohibitin 2 siRNA, HUVECs were incubated with dihydromyricetin for 12 h or carbonyl cyanide 3-chlorophenyl hydrazone (CCCP) for 6 h in the presence of the lysosomal blocker chloroquine, and then subjected to flow cytometry analysis to determine mitophagy.

Results

As compared with the non-dihydromyricetin group, dihydromyricetin (≥0.1 μmol/L) treatment markedly decreased MTDR fluorescence levels (P<0.05), and meanwhile, the treatment significantly increased the mRNA and protein levels of Prohibitin 2 (P<0.05). After pretreated with chloroquine, dihydromyricetin (≥10 μmol/L) significantly enhanced mitophagy in HUVECs, which was consistent with the effect of CCCP (P<0.05). After Prohibitin 2 siRNA transfection, mitophagy induced by dihydromyricetin was significantly suppressed when compared with the control siRNA treatment group (P<0.05).

Conclusion

Dihydromyricetin enhances mitophagy in vascular endothelial cells by regulating Prohibitin 2.

Issue
Association of ADAP2 gene with prognosis and immune infiltration in tumor microenvironment in patients with lung squamous cell carcinoma
Journal of Army Medical University 2022, 44(4): 337-345
Published: 28 February 2022
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Objective

To investigate the correlation between ADAP2 gene and immune infiltration in tumor microenvironment in lung squamous cell carcinoma (LUSC), and to explore the prognostic values of ADAP2 in patients with LUSC.

Methods

The clinical information of patients with LUSC as well as the data of ADAP2 mRNA levels in cancer tissues were downloaded from The Cancer Genome Atlas (TCGA) database. The association between ADAP2 gene and prognosis of patients was subsequently analyzed using Kaplan-Meier survival curve and Cox risk model analyses. xCell database was adopted to analyze the correlation of ADAP2 expression with immune infiltration in tumor microenvironment. Immunofluorescence double-staining test was employed to observe the co-localization of ADAP2 protein and CD163 (a specific biomarker of M2 macrophage).

Results

Multivariate Cox analysis showed that the expression of ADAP2 was an independent prognostic factor for LUSC patients, and its high expression was closely associated with the poor prognosis of patients (HR=1.533, 95%CI: 1.139~2.064, P=0.005). xCell analysis indicated that ADAP2 gene was positively correlated with both the tumor microenvironment score (r=0.609, 95%CI: 0.550~0.661, P<0.001), and the immune infiltration score (r=0.596, 95%CI: 0.536~0.650, P<0.001), and the expression of ADAP2 also showed a high positive association with mononuclear phagocyte system (macrophage, macrophage M1, macrophage M2 and monocyte) in LUSC (r=0.737, 0.718, 0.603 and 0.631, respectively, P<0.001). Moreover, ADAP2 presented co-localization with CD163 and was mainly expressed in the cell membrane.

Conclusion

ADAP2 can act as a potential biomarker for predicting prognosis and evaluating the efficacy of immunotherapy in LUSC.

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