1.Construction of a prognostic model for breast cancer based on lipid metabolism-related genes and functional verification of ALDH2.
Zirong LU ; Yufeng LU ; Ji ZHOU ; Yichao ZHU
Journal of Zhejiang University. Medical sciences 2025;():1-10
OBJECTIVES:
To investigate the expression patterns and prognostic value of lipid metabolism-related genes in breast cancer.
METHODS:
RNA sequencing data and clinical information were obtained from The Cancer Genome Atlas breast cancer (TCGA-BRCA) dataset, including 1100 breast cancer tissue samples (18 paired with adjacent tissues) and 112 normal breast tissue samples. Differentially expressed lipid metabolism-related genes were screened from a predefined set of 2043 genes using Bioconductor in R, with a false discovery rate <0.05 and |log2(fold change)|>2. Eligible samples were randomly divided into a training cohort (n=651) and a validation cohort (n=431) at a 6∶4 ratio. Prognostic lipid metabolism-related genes were identified using univariate Cox regression (P<0.005) and further refined via LASSO regression. A risk score model was constructed using multivariate Cox regression, and patients were stratified into high- and low-risk groups based on the median risk score. The model's performance was evaluated using Kaplan-Meier survival analysis with the log-rank test and time-dependent receiver operating characteristic (ROC) curves. A nomogram integrating age, TNM stage, clinical grade, and risk score was developed and validated using calibration curves and the concordance index. Immune cell infiltration was quantified using an immune scoring algorithm, and weighted gene co-expression network analysis (WGCNA) was applied to identify key modules associated with immune cell infiltration. Finally, to validate the function of the key gene ALDH2, small interfering RNA targeting ALDH2 was transfected into breast cancer cells, and its effects on invasion and migration were assessed using Transwell invasion and wound healing assays.
RESULTS:
A total of 185 differentially expressed lipid metabolism-related genes were identified. Univariate Cox and LASSO regression analyses identified three genes-ALDH2, CYP21A2, and IL24-which were incorporated into the multivariate Cox model. The prognostic model based on these genes demonstrated good predictive performance in both cohorts: patients in the high-risk group had significantly shorter overall survival (P<0.01), and the area under the ROC curve for predicting 1-, 3-, and 5-year survival rates was above 0.64. Analysis of the tumor microenvironment revealed an immunosuppressive phenotype in the high-risk group, characterized by reduced infiltration of several anti-tumor immune cells and downregulation of key immune checkpoint molecules such as PDCD1 and CTLA4. WGCNA suggested an association between ALDH2 and immune cell infiltration. Functional experi-ments confirmed that ALDH2 knockdown significantly enhanced the migration and invasion abilities of breast cancer cells.
CONCLUSIONS
This study established and validated a pro-gnostic model for breast cancer based on lipid metabolism-related genes. It revealed that low ALDH2 expression is closely associated with poor prognosis and immunosuppression, suggesting its potential as a prognostic biomarker and therapeutic target in breast cancer.
2.Research progress of traditional Chinese and Western medicine non-pharmacological prevention strategies for acute high altitude disease
Li LI ; Peipei LU ; Zhiwen CAO ; Bo WEN ; Shanshan SHEN ; Zirong WANG ; Yong TAN ; Cheng LYU
Chinese Critical Care Medicine 2024;36(6):669-672
Acute high altitude disease (AHAD) is a general term for a series of clinical reactions that occur when the body fails to adapt to the low-pressure hypoxic environment of high altitudes. Mild cases can cause symptoms such as headache, nausea and vomiting, while more severe cases can lead to life-threatening conditions such as pulmonary edema, cerebral edema and other critical conditions that can be fatal. With the increasing demand for high altitudes deployment, understanding the common preventive measures of AHAD can reduce its morbidity or mortality to a certain extent, which is of great benefit to those who reside temporarily at high altitudes. In recent years, as people's health awareness has improved, there has been a growing attention towards non-pharmacological methods of disease prevention. At the same time, non-pharmacological therapy has significant therapeutic effects in preventing and treating high-altitude diseases, which has attracted the attention of researchers in this field. This review summarizes the major non-pharmacological preventive components of modern medicine and outlines the current non-pharmacological approaches to AHAD from the perspective of traditional Chinese medicine, intending to serve clinical purposes and improve the onset and prognosis of AHAD.
3.Comparison of domestic and international elderly care needs assessment system and the implication
Jiayun WANG ; Yingjia WANG ; Zirong LIU ; Hao QIN ; Wei LU ; Chengyue LI
Shanghai Journal of Preventive Medicine 2022;34(4):388-393
The construction of elderly care needs assessment system is conducive to realize the reasonable matching between care services and needs of the elderly, and to promote the effective allocation of pension resources. It is the basis and premise of the development of long-term care insurance system. Questions such as "Who is responsible for the assessment? Who can apply for the assessment? What is the assess tool? How to pay the assessment fee?" are the core issues that need to be addressed in the construction of the evaluation system. This study compared the current situation of the elderly care needs assessment systems in China, the Netherlands, Germany, Japan and the United States from four aspects: assessment subject, assessment object, assessment cost source, and assessment tools’ dimensions. It has been a trend to entrust a third party for the evaluation work in pilot cities in China. Compared with foreign countries, domestic appraisers’ discipline and professional background are simpler. In foreign countries, the evaluation objects of elderly care needs are more extensive; the legal and financial support system of needs evaluation is more mature; and the evaluation dimensions are more objective and comprehensive. Based on this study, we suggest China to establish a national unified elderly care needs assessment system, cultivate professional assessment teams, expand the coverage of care needs assessment objects, improve the standards of assessment objects and assessment dimensions, and improve the law and financial support regulations related to needs assessment.
4.Curcumin attenuates renal ischemia reperfusion injury via JNK pathway with the involvement of p300/CBP-mediated histone acetylation
Lu YANG ; Xiaoxiang CHEN ; Zirong BI ; Jun LIAO ; Weian ZHAO ; Wenqi HUANG
The Korean Journal of Physiology and Pharmacology 2021;25(5):413-423
Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague–Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.
5.Curcumin attenuates renal ischemia reperfusion injury via JNK pathway with the involvement of p300/CBP-mediated histone acetylation
Lu YANG ; Xiaoxiang CHEN ; Zirong BI ; Jun LIAO ; Weian ZHAO ; Wenqi HUANG
The Korean Journal of Physiology and Pharmacology 2021;25(5):413-423
Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague–Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.
6.Effect of comprehensive nursing intervention on coping style and self-efficacy in chronic hepatitis B patients
Xiding CHEN ; Xinhong ZHANG ; Yongxiu LU ; Junlan YU ; Zirong YU
Chinese Journal of Modern Nursing 2014;20(20):2529-2531
Objective To explore the comprehensive nursing intervention on coping style and self -efficacy in chronic hepatitis B patients .Methods Eighty chronic hepatitis B patients were chosen and randomly divided into the control group and the observation group , each with 40 cases.The control group received the routine nursing , and the observation group received the nursing intervention on the basis of routine nursing .The coping style and self-efficacy were compared through the Medical Coping Modes Questionnaire ( MCMQ ) and General Self-efficacy Scale (GSES) between two groups after 3 weeks.Results The subscale scores of MCMQ including face, avoid and abandon were respectively (27.93 ±5.84), (10.91 ±5.90), (4.94 ±1.09) in the observation group after the intervention , and were better than those of the control group , and the differences were statistically significant (t=4.65,2.24,9.73, respectively;P<0.05).The differences were found in the scores of face, avoid and abandon in the observation group before and after the intervention ( P <0.01 ).The differences were found in the scores of avoid and abandon in the control group before and after the intervention (P<0.05).The total scores of GSES was (20.50 ±5.50) in the control group after the intervention , and was lower than (30.35 ±5.0) in the observation group, and the difference was statistically significant (t=8.38, P<0.05).Conclusions Nursing intervention can change the coping style and improve their self-efficacy in chronic hepatitis B patients .
7.Diffusion tensor imaging of the bilateral uncinate fasciculus in patients with temporal lobe epilepsy.
Limei DIAO ; Zirong CHEN ; Donghong HUANG ; Lu YU ; Liping LI ; Jinou ZHENG
Journal of Southern Medical University 2012;32(11):1639-1642
OBJECTIVETo study the structural integrity and continuity of the bilateral uncinate fasciculus (UF) in patients with temporal lobe epilepsy (TLE) using magnetic resonance diffusion tensor imaging (DTI) and evaluate the impact of structural damage of the UF on the executive function of the patients.
METHODSThirty patients with TLE (14 left, 16 right) and 15 healthy control subjects underwent DTI scanning between January, 2007 and July, 2011, and the left and right UF were analyzed for fractional anisotropy (FA) and fiber mean length.
RESULTSIn the control subjects, the average FA was significantly higher in the left than in the right UF (P<0.01). In patients with left TLE, the average FA of the left UF was significantly lower than that of the control subjects (P<0.01), but the FA of the right UF was comparable with that of the control group (P>0.05). In patients with right TLE, the average FA of the left and right UF was significantly lower than that of the control group (P<0.05 and P<0.01). In patients with unilateral TLE, the FA of their bilateral UF was similar. No significant difference was found in the mean length of UF fiber between these 3 groups.
CONCLUSIONSFA is normally higher in the left UF than in the right UF, but inpatients with TLE, the left FA tends to have a lowered UF regardless of which hemisphere is involved, suggesting an early pathology in the microstructure of the left UF. This finding may help in the investigation of possible reasons for executive function damage in TLE patients.
Case-Control Studies ; Diffusion Tensor Imaging ; Epilepsy, Temporal Lobe ; pathology ; Female ; Humans ; Male

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