1.Mechanism of 1,25(OH)2D3 improving liver inflammation in a rat model of nonalcoholic steatohepatitis induced by choline-deficient L-amino acid-defined diet
Haiyang ZHU ; Jingshu CUI ; Liu YANG ; Mengting ZHOU ; Jian TONG ; Hongmei HAN
Journal of Clinical Hepatology 2025;41(2):254-262
ObjectiveTo investigate the effect of 1,25(OH)2D3 on the level of peroxisome proliferator-activated receptor-γ (PPAR-γ) in the liver, the phenotype of hepatic macrophages, and liver inflammation in a rat model of nonalcoholic steatohepatitis (NASH), as well as the mechanism of 1,25(OH)2D3 improving liver inflammation. MethodsAfter 1 week of adaptive feeding, 24 specific pathogen-free Wistar rats were randomly divided into normal group [choline-supplemented L-amino acid-defined (CSAA) diet], normal+1,25(OH)2D3 group [CSAA diet+1,25(OH)2D3], model group [choline-deficient L-amino acid-defined diet (CDAA) diet], and model+1,25(OH)2D3 group [CDAA diet+1,25(OH)2D3], with 6 rats in each group. The dose of 1,25(OH)2D3 was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured, liver histopathology was observed, and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages, and ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), and interleukin-10 (IL-10) in liver tissue, and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups, and the least significant difference t-test was used for further comparison; the Pearson method was used for correlation analysis. ResultsCompared with the normal group, the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT (P=0.019 and P<0.001), the SAF score of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), and the ratio of M1 and M2 hepatic macrophages (P<0.001), as well as a significant increase in the level of TNF-α (P<0.001) and a significant reduction in the level of IL-4 in liver tissue (P=0.025). The 1,25(OH)2D3 group had significant reductions in the serum levels of ALT (P<0.001), the SAF score of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), and the ratio of M1 and M2 hepatic macrophages (P=0.001), the level of IL-1β (P<0.001) and a significant increase in the level of M2 hepatic macrophages (P=0.017), the level of IL-10 (P=0.039), the level of IL-4 (P<0.001), the level of PPAR-γ (P=0.016). There were significant interactions between CDAA diet-induced NASH model and 1,25(OH)2D3 in serum the levels of AST and ALT (P=0.007 and P=0.008), the SAF scores of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), the level of M2 hepatic macrophages (P=0.008), the ratio of M1 and M2 of hepatic macrophages (P=0.005), the level of TNF-α (P<0.001), the level of IL-10 (P=0.038), the level of IL-4 (P<0.001) and the level of PPAR-γ (P=0.009). The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages (r=-0.415, P=0.044) and was positively correlated with M2 hepatic macrophages (r=0.435, P=0.033), IL-10 (r=0.433, P=0.035), and IL-4 (r=0.532, P=0.007). ConclusionThis study shows that 1,25(OH)2D3 improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.
2.Effect of laminin subunit α3 on epithelial-mesenchymal transition, invasion, and metastasis abilities of pancreatic cancer
Nenghong YANG ; Likun REN ; She TIAN ; Min HAN ; Zhu LI ; Yuxiang ZHAO ; Peng LIU
Journal of Clinical Hepatology 2025;41(2):322-332
ObjectiveTo investigate the effect of laminin subunit α3 (LAMA3) on the epithelial-mesenchymal transition (EMT), invasion, and metastasis abilities of pancreatic cancer (PC). MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC, especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines; immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells; Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC, i.e., LAMA3, AREG, and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC (risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG). The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC (hazard ratio=1.32, 95% confidence interval: 1.07 — 1.62, P<0.01). Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line, there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1, BxPC-3, PANC-1, MIA PaCa-2, and SW1990 cell lines, with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT, collagen metabolism, extracellular matrix degradation, the TGF-β pathway, and the PI3K pathway. After the knockdown of LAMA3, there were significant reductions in the expression levels of N-Cadherin, Vimentin, and Snail, while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT, invasion, and migration of PC cells, and therefore, LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.
3.Clinical practice guidelines for intraoperative cell salvage in patients with malignant tumors
Changtai ZHU ; Ling LI ; Zhiqiang LI ; Xinjian WAN ; Shiyao CHEN ; Jian PAN ; Yi ZHANG ; Xiang REN ; Kun HAN ; Feng ZOU ; Aiqing WEN ; Ruiming RONG ; Rong XIA ; Baohua QIAN ; Xin MA
Chinese Journal of Blood Transfusion 2025;38(2):149-167
Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.
4.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
5.Construction and Application Evaluation of an Integrated Traditional Chinese and Western Medicine Risk Prediction Model for Readmission in Patients with Stable Angina of Coronary Heart Disease:A Prospective Study Based on Real-World Clinical Data
Wenjie HAN ; Mingjun ZHU ; Xinlu WANG ; Rui YU ; Guangcao PENG ; Qifei ZHAO ; Jianru WANG ; Shanshan NIE ; Yongxia WANG ; Jingjing WEI
Journal of Traditional Chinese Medicine 2025;66(6):604-611
ObjectiveBy exploring the influencing factors of readmission in patients with stable angina of coronary heart disease (CHD) based on real-world clinical data, to establish a risk prediction model of integrated traditional Chinese and western medicine, in order to provide a basis for early identification of high-risk populations and reducing readmission rates. MethodsA prospective clinical study was conducted involving patients with stable angina pectoris of CHD, who were divided into a training set and a validation set at a 7∶3 ratio. General information, traditional Chinese medicine (TCM)-related data, and laboratory test results were uniformly collected. After a one-year follow-up, patients were classified into a readmission group and a non-readmission group based on whether they were readmitted. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for readmission. A risk prediction model of integrated traditional Chinese and western medicine was constructed and visualized using a nomogram. The model was validated and evaluated in terms of discrimination, calibration, and clinical decision curve analysis. ResultsA total of 682 patients were included, with 477 in the training set and 205 in the validation set, among whom 89 patients were readmitted. Multivariate logistic regression analysis identified heart failure history [OR = 6.93, 95% CI (1.58, 30.45)], wiry pulse [OR = 2.58, 95% CI (1.42, 4.72)], weak pulse [OR = 3.97, 95% CI (2.06, 7.67)], teeth-marked tongue [OR = 4.38, 95% CI (2.32, 8.27)], blood stasis constitution [OR = 2.17, 95% CI (1.06, 4.44)], phlegm-stasis mutual syndrome [OR = 3.64, 95% CI (1.87, 7.09)], and elevated non-high-density lipoprotein cholesterol [OR = 1.30, 95% CI (1.01, 1.69)] as influencing factors of readmission. These factors were used as predictors to construct a nomogram-based risk prediction model for readmission in patients with stable angina. The model demonstrated moderate predictive capability, with an area under the receiver operating characteristic curve (AUC) of 0.818 [95% CI (0.781, 0.852)] in the training set and 0.816 [95% CI (0.779, 0.850)] in the validation set. The Hosmer-Lemeshow test showed good calibration (χ² = 4.55, P = 0.80), and the model's predictive ability was stable. When the threshold probability exceeded 5%, the clinical net benefit of using the model to predict readmission risk was significantly higher than intervening in all patients. ConclusionHistory of heart failure, teeth-marked tongue, weak pulse, wiry pulse, phlegm-stasis mutual syndrome, blood stasis constitution, and non-high-density lipoprotein cholesterol are influencing factors for readmission in patients with stable angina of CHD. A clinical prediction model was developed based on these factors, which showed good discrimination, calibration, and clinical utility, providing a scientific basis for predicting readmission events in patients with stable angina.
6.Effect of fine particulate matter exposure in the air on dyslipidemia among primary school students in two privinces and cities of China
ZHU Yuanduo, HAN Yingying, LI Dandan, ZHANG Jingwei, XU Yanlong
Chinese Journal of School Health 2025;46(1):115-118
Objective:
To analyze the association between fine particulate matter (PM2.5) exposure in the air and dyslipidemia among primary school students, in order to provide the evidencebased support for the prevention and control of chronic diseases in children.
Methods:
The random sampling method was used to select 625 students from two primary schools in Anhui Province and Tianjin City from May to June 2024. Based on the home address, the annual average exposure levels of PM2.5 were obtained in 3 years before investigation, 2 years before investigation, and the past year before investigation. Fasting blood samples were collected for the detection of total cholesterol, triglycerides (TG), highdensity lipoprotein cholesterol and lowdensity lipoprotein cholesterol. Linear regression modeling was used to analyze the association between PM2.5 exposure and dyslipidemia among primary school students.
Results:
The rate of dyslipidemia among primary school students was 14.72% in the present study. The results of linear regression analysis showed that the TG increased by 0.019(95%CI=0.012-0.025),0.023(95%CI=0.016-0.030) and 0.021(95%CI=0.014-0.027) mmol/L for every 1 μg/m3 increase of PM2.5 in the past year before investigation, 2 years before investigation and 3 years before investigation respectively (P<0.05). The results of binary Logisitic analysis showed that the risks of dyslipidemia in primary school students were positively correlated with PM2.5 mass concentration in the past year before investigation, 2 years before investigation, and 3 years before investigation [OR(95%CI)=1.06(1.02-1.11), 1.06(1.01-1.12), 1.06(1.01-1.11), P<0.05].
Conclusions
PM2.5 exposure is associated with increased risk of dyslipidemia among primary school students. To protect the health of primary school students, effective measures should be taken to improve air quality.
7.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
8.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
10.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.


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