1.Clinical value of transcriptome mRNA sequencing-derived SLC12A1 gene in heart failure patients with mildly reduced or preserved ejection fraction
Mengwei WANG ; Hongfei LIU ; Yunqiang ZHANG ; Ze HOU ; Xinyi WANG ; Yingnan YE ; Zifan WANG ; Yuxin ZHANG ; Kegang JIA
Chinese Journal of Laboratory Medicine 2025;48(8):1071-1079
Objective:To explore the relationship between the differential genes derived from transcriptome mRNA sequencing and prognosis among heart failure patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).Methods:This was a case-control study. Ten patients with HFmrEF and 10 patients with HFpEF treated at TEDA International Cardiovascular Disease Hospital from November 2021 to January 2022 were selected and differentially expressed genes were screened by transcriptome mRNA sequencing. Ten healthy people served as control group. In addition, 50 patients with HFmrEF, 62 patients with HFpEF, who were treated at TEDA International Cardiovascular Disease Hospital at the same period, were selected as validation groups, 57 healthy people served as control validation group. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of differential genes in each group. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to assess the differential diagnosis and prognostic value of differential genes in these patients. Patients were followed up regularly to document adverse events within 1 year after discharge including cardiac death and readmission for heart failure. Survival analysis was performed using Kaplan-Meier curves and tested by log rank test. Cox regression analysis was used to explore whether differential mRNA was risk factors for poor prognosis in HFmrEF and HFpEF patients.Results:A total of four genes were differentially expressed (three upregulated and one downregulated gene) between the HFmrEF group and HFpEF group (adjust P<0.05). SLC12A1, C15orf48 and SPP1 were associated with the progress of cardiovascular disease, and selected for validation in the clinical cohort. RT-qPCR results showed that the gene expression of SLC12A1 in the HFmrEF group was significantly higher than that in the HFpEF group ( P<0.001). The AUC for the adjunctive differential diagnostic value of SLC12A1 for HFmrEF and HFpEF was 0.802 ( P<0.001) and the AUC of SLC12A1 with a cut-off value of 6.634 was 0.737 ( P=0.003) in determining poor prognosis in patients with HFpEF. Kaplan-Meier survival analysis showed that patients with SLC12A1≤6.634 had a higher incidence of adverse cardiac events than patients with SLC12A1 >6.634 ( P=0.001). Cox regression analysis showed that the risk of adverse cardiac events in the SLC12A1 ≤6.634 group was 6.787 times higher than in the SLC12A1 >6.634 group ( HR=6.787, P=0.011). Conclusions:Transcriptome mRNA sequencing analysis is valuable for detecting clinical relevant differentially expressed genes in HFmrEF and HFpEF patients, among which SLC12A1 can be used as a novel molecular biomarker to aid the differential diagnosis of HFmrEF and HFpEF. In addition, SLC12A1 may be used as an adjunctive biomarker for the prognosis evaluation in patients with HFpEF.
2.Comparison of the Windowing and Open Book techniques in the treatment of tibial plateau fractures of Schatzker type Ⅱ
Tianming YU ; Jichong YING ; Jianlei LIU ; Yunqiang ZHUANG
Chinese Journal of Orthopaedic Trauma 2025;27(8):658-664
Objective:To compare the treatment efficacy between the Windowing and Open Book techniques in the treatment of tibial plateau fractures of Schatzker type Ⅱ.Methods:A retrospective study was performed to analyze the clinical data of the 211 patients with tibial plateau fracture of Schatzker type Ⅱ who had been treated by open reduction and internal fixation via the anterolateral knee incision at Department of Traumatic Orthopaedics, The Sixth Hospital of Ningbo from January 2014 to June 2022. There were 142 males and 69 females, with an age of (57.7±14.3) years. Based on the intraoperative reduction techniques, the patients were divided into 2 groups: a Windowing group ( n=107) in which reduction of the split bone fragments was followed by reduction of the depressed articular surface, and an Open Book group ( n=104) in which reduction of the depressed articular surface was followed by reduction of the split bone fragments. The following data were collected and compared between the 2 groups: preoperative general data, operative time, quality of fracture reduction, loss of fracture reduction, fracture healing rate at postoperative 6 months, visual analogue scale (VAS) pain score at postoperative 24 months, post-traumatic arthritis grading at the final follow-up (based on the Resnick-Niwoyam criteria), and Rasmussen classifications of knee function at postoperative 3 and 24 months. Results:There were no significant differences in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The follow-up period for all patients was (34.0±10.6) months. The operative time was (65.0±8.3) minutes for the Windowing group and (64.2±10.2) minutes for the Open Book group, showing no significant difference ( P>0.05). Postoperative CT scans revealed residual articular depression in 10 cases in the Windowing group and in 25 cases in the Open Book group, showing a significant difference ( P<0.05). However, there was no significant difference in plateau widening or varus/valgus alignment between the 2 groups ( P>0.05). There were no statistically significant differences between the 2 groups in loss of fracture reduction, fracture healing rate at postoperative 6 months, VAS score at postoperative 24 months, post-traumatic arthritis grading at the final follow-up, or Rasmussen classifications of the knee function at postoperative 3 or 24 months ( P>0.05). Conclusions:In the treatment of Schatzker type Ⅱ tibial plateau fractures, the Windowing technique demonstrates superior radiographic outcomes compared to the Open Book technique, but the 2 techniques show similar efficacy in functional evaluation and medium-term prognosis.
3.Recent advance in role of metabolism reprogramming of microglia in Alzheimer's disease
Jie WANG ; Xiaoting ZHU ; Yunqiang LI ; Xinyue ZHANG ; Fan LI ; Mingquan LI
Chinese Journal of Neuromedicine 2025;24(4):401-406
Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment, memory decline and emotional loss, which is more common in middle-aged and elderly people. In recent years, studies have shown that chronic neuroinflammation is an important factor leading to AD development. As the core participant in neuroinflammation, microglia play a dual role in the pathological process of AD: on one hand, through M1 polarization, they exert a pro-inflammatory effect and exacerbate the neurotoxic response; on the other hand, through M2 polarization, they enhance the phagocytic ability of amyloid β-protein and exert a neuroprotective effect. Metabolic reprogramming is the key in determining the polarization of microglia M1/M2 type and exerting neurotoxicity/protection. Therefore, this article reviews the recent advance in role of metabolism reprogramming of microglia in AD, in order to provide new idea and direction for studing AD pathogenesis and treatment in the future.
4.Effects of di(2-ethylhexyl) phthalate on glucose homeostasis in rats due to impaired autophagy flux of islet β cells mediated by oxidative stress
Hongyang ZHOU ; Yuting HU ; Xue CHEN ; Yunqiang ZHOU ; Liping LI ; Ling LI ; Herong LIU
Journal of Environmental and Occupational Medicine 2025;42(6):674-683
Background Di(2-ethylhexyl) phthalate (DEHP) is the most prevalent environmental endocrine disruptor among phthalate acid esters (PAEs) worldwide. Previous studies have indicated that exposure to DEHP may disrupt glucose metabolism. Objective To investigate the impact of DEHP on glucose homeostasis in rats, focusing on oxidative stress-induced impairment of autophagy in islet β cells. Methods Forty male SD rats were randomly assigned to four groups, receiving DEHP doses of 0, 187, 375, and 750 mg·kg−1 for 12 weeks. Oral glucose tolerance (OGTT) and insulin tolerance tests (ITT) were conducted 24 h after the final exposure. Pancreatic microstructural alterations were assessed using hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM). Commercial ELISA kits were employed to quantify the levels of insulin, adenosine triphosphate (ATP), and adenosine monophosphate (AMP) in rat serum, as well as the protein expression level of activated caspase-3 in pancreatic tissue. Additionally, commercial microplate kits were utilized to measure the concentration of reduced glutathione (GSH) in serum, the activity of superoxide dismutase (SOD) using water-soluble tetrazolium salt-1, the content of malondialdehyde (MDA) by thiobarbituric acid method, and the level of reactive oxygen species (ROS) in pancreatic tissue by chemical fluorescence method. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure sequestosome1 (SQSTM1/p62), Beclin1, microtubule-associated protein 1 light chain 3 (LC3), and cysteinyl aspartate specific proteinase-8 (Caspase-8) mRNA levels. Western blot analysis was applied to detect the protein relative expression levels of p62, Beclin-1, LC3-I, LC3 II, AMPK, p-AMPK, mTOR, p-mTOR, ULK1, and Caspase-8. Results Compared to the 0 mg·kg−1 DEHP group, the 750 mg·kg−1 DEHP group exhibited a significant increase in fasting blood glucose levels at 2, 4, 6, and 12 weeks (P<0.05). The OGTT showed that, following high-glucose gavage, the 187 mg·kg−1 DEHP group had elevated blood glucose at 30 min (P<0.05), the 375 mg·kg−1 DEHP group showed increased glucose levels at 15, 30, and 180 min (P<0.05), and the 750 mg·kg−1 DEHP group exhibited elevated levels at 15, 30, 60, and 180 min (P<0.05). The 375 and 750 mg·kg−1 DEHP groups demonstrated significantly increased OGTT area under the curve (AUC) values (P<0.05). In contrast, ITT results indicated no significant differences in blood glucose levels or AUC among the DEHP exposure groups at all time points (P>0.05). Compared to the 0 mg·kg−1 DEHP group, the 750 mg·kg−1 DEHP group exhibited significantly higher HOMA-IR levels and markedly lower HOMA-ISI values (P<0.05). HE and TEM showed that in each DEHP exposure group, the number of islet cells decreased, the islet area reduced, and chromatin condensation occurred. The endocrine granules in the cytoplasm of islet β cells decreased, and there were varying degrees of widening of the nuclear membrane gap, flattening and expansion of the Golgi complex, and expansion of the endoplasmic reticulum. Ribosome separation was observed, and autophagosomes were visible. In the 375 and 750 mg·kg−1 DEHP groups, the mitochondria were deformed to varying degrees, and some cristae structures disappeared, presenting vacuolization. Moreover, the chromatin condensation in the nuclei was more severe in the 750 mg·kg−1 DEHP group. The serum SOD activity was significantly elevated in the 750 mg·kg−1 DEHP group (P<0.05). Both the 375 mg·kg−1 and 750 mg·kg−1 DEHP groups exhibited a significant increase in the relative ROS content in pancreatic tissue (P<0.05). In DEHP-treated groups, the MDA content increased (P<0.05), while the GSH content decreased (P<0.05). Additionally, in the 750 mg·kg−1 DEHP group, the AMP/ATP ratio in serum was significantly raised (P<0.05), and the expression of cleaved Caspase-3 protein in pancreatic tissue was also significantly increased (P<0.05). The relative mRNA levels of p62, Beclin-1, LC3, and Caspase-8 in the pancreatic tissue of rats exposed to DEHP were significantly elevated (P<0.05). The relative expression levels of p-AMPK/AMPK, p-ULK1/ULK1, and Beclin-1 proteins in the DEHP-treated groups were significantly increased (P<0.05). In the 375 mg·kg−1 and 750 mg·kg−1 DEHP treatment groups, the relative expression levels of p62, LC3 II/LC1, and Caspase-8 proteins were significantly increased (P<0.05), while the relative expression level of p-mTOR/mTOR was significantly decreased (P<0.05). Conclusion DEHP can disrupt glucose homeostasis by inducing oxidative stress, which subsequently activates autophagy via the ROS/AMPK/ULK1 pathway, impairing autophagic flux and promoting apoptosis of islet β cells, ultimately decreasing their function and number.
5.Sorafenib promotes the E3 ubiquitin ligase FBXW7 to increase tau degradation and ameliorate tauopathies.
Yunqiang ZHOU ; Yong WANG ; Huiying YANG ; Chi ZHANG ; Jian MENG ; Lingliang ZHANG ; Kun LI ; Ling-Ling HUANG ; Xian ZHANG ; Hong LUO ; Yunwu ZHANG
Acta Pharmaceutica Sinica B 2025;15(11):5817-5831
Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.
6.Genetic analysis of a child with Oculo-facio-cardio-dental syndrome due to a deletional variant of BCOR gene.
Rui TANG ; Yuan YANG ; Yunqiang LIU
Chinese Journal of Medical Genetics 2025;42(11):1364-1368
OBJECTIVE:
To explore the genetic etiology of a Chinese boy affected with Oculo-facio-cardio-dental syndrome (OFCD).
METHODS:
A child diagnosed with OFCD at West China Hospital of Sichuan University on September 21, 2024 was selected as the study subject. Clinical phenotype of the child was collected through ophthalmologic examination, cardiac ultrasonography, and X-ray imaging. Potential pathogenic variants were detected by trio-whole exome sequencing (Trio-WES). Candidate variant was validated with TA-cloning followed by Sanger sequencing. Mosaic variant was analyzed by ultra-deep sequencing (10,000-fold) and quantitative PCR. This study was approved by the Medical Ethics Committee of the West China Hospital of Sichuan University (Ethics No.: 2019-772 ).
RESULTS:
The proband had presented with congenital cataracts, mitosis, atrial and ventricular septal defects, dental abnormalities, and right radioulnar synostosis. His mother also exhibited congenital cataracts and dental anomalies, suggesting a diagnosis of OFCD. Trio-WES revealed an novel heterozygous 14-bp deletion (c.4724_4737del) in exon 12 of the BCOR gene in the proband. Deep sequencing identified a mosaic BCOR c.4724_4737del mutation in approximately 3.4% of peripheral leukocytes from his mother. Quantitative PCR analysis also confirmed the presence of this low-level mosaicism. The 14-bp deletion was predicted to cause a frame shift and premature termination (p.Met1575AsnfsTer6). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PM2+PP1).
CONCLUSION
Above findings have expanded the spectrum of BCOR mutations associated with OFCD, which highlighted the role of low-level mosaicism with maternal transmission and provided a basis for genetic counseling and reproductive guidance for the family.
Humans
;
Male
;
Repressor Proteins/genetics*
;
Proto-Oncogene Proteins/genetics*
;
Tooth Abnormalities/genetics*
;
Eye Abnormalities/genetics*
;
Microphthalmos/genetics*
;
Child
;
Sequence Deletion
;
Female
;
Cataract/congenital*
;
Heart Septal Defects
7.Effect of measurement site on diagnostic performance of CT-derived fractional flow reserve
Yutao ZHOU ; Na ZHAO ; Yunqiang AN ; Lei SONG ; Chaowei MU ; Jingang CUI ; Tao JIANG ; Li XU ; Hongjie HU ; Lin LI ; Dumin LI ; Wenqiang CHEN ; Lijuan FAN ; Feng ZHANG ; Yang GAO ; Bin LYU
Chinese Journal of Radiology 2025;59(6):704-711
Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.
8.Effect of measurement site on diagnostic performance of CT-derived fractional flow reserve
Yutao ZHOU ; Na ZHAO ; Yunqiang AN ; Lei SONG ; Chaowei MU ; Jingang CUI ; Tao JIANG ; Li XU ; Hongjie HU ; Lin LI ; Dumin LI ; Wenqiang CHEN ; Lijuan FAN ; Feng ZHANG ; Yang GAO ; Bin LYU
Chinese Journal of Radiology 2025;59(6):704-711
Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.
9.Clinical value of transcriptome mRNA sequencing-derived SLC12A1 gene in heart failure patients with mildly reduced or preserved ejection fraction
Mengwei WANG ; Hongfei LIU ; Yunqiang ZHANG ; Ze HOU ; Xinyi WANG ; Yingnan YE ; Zifan WANG ; Yuxin ZHANG ; Kegang JIA
Chinese Journal of Laboratory Medicine 2025;48(8):1071-1079
Objective:To explore the relationship between the differential genes derived from transcriptome mRNA sequencing and prognosis among heart failure patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).Methods:This was a case-control study. Ten patients with HFmrEF and 10 patients with HFpEF treated at TEDA International Cardiovascular Disease Hospital from November 2021 to January 2022 were selected and differentially expressed genes were screened by transcriptome mRNA sequencing. Ten healthy people served as control group. In addition, 50 patients with HFmrEF, 62 patients with HFpEF, who were treated at TEDA International Cardiovascular Disease Hospital at the same period, were selected as validation groups, 57 healthy people served as control validation group. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of differential genes in each group. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to assess the differential diagnosis and prognostic value of differential genes in these patients. Patients were followed up regularly to document adverse events within 1 year after discharge including cardiac death and readmission for heart failure. Survival analysis was performed using Kaplan-Meier curves and tested by log rank test. Cox regression analysis was used to explore whether differential mRNA was risk factors for poor prognosis in HFmrEF and HFpEF patients.Results:A total of four genes were differentially expressed (three upregulated and one downregulated gene) between the HFmrEF group and HFpEF group (adjust P<0.05). SLC12A1, C15orf48 and SPP1 were associated with the progress of cardiovascular disease, and selected for validation in the clinical cohort. RT-qPCR results showed that the gene expression of SLC12A1 in the HFmrEF group was significantly higher than that in the HFpEF group ( P<0.001). The AUC for the adjunctive differential diagnostic value of SLC12A1 for HFmrEF and HFpEF was 0.802 ( P<0.001) and the AUC of SLC12A1 with a cut-off value of 6.634 was 0.737 ( P=0.003) in determining poor prognosis in patients with HFpEF. Kaplan-Meier survival analysis showed that patients with SLC12A1≤6.634 had a higher incidence of adverse cardiac events than patients with SLC12A1 >6.634 ( P=0.001). Cox regression analysis showed that the risk of adverse cardiac events in the SLC12A1 ≤6.634 group was 6.787 times higher than in the SLC12A1 >6.634 group ( HR=6.787, P=0.011). Conclusions:Transcriptome mRNA sequencing analysis is valuable for detecting clinical relevant differentially expressed genes in HFmrEF and HFpEF patients, among which SLC12A1 can be used as a novel molecular biomarker to aid the differential diagnosis of HFmrEF and HFpEF. In addition, SLC12A1 may be used as an adjunctive biomarker for the prognosis evaluation in patients with HFpEF.
10.Comparison of the Windowing and Open Book techniques in the treatment of tibial plateau fractures of Schatzker type Ⅱ
Tianming YU ; Jichong YING ; Jianlei LIU ; Yunqiang ZHUANG
Chinese Journal of Orthopaedic Trauma 2025;27(8):658-664
Objective:To compare the treatment efficacy between the Windowing and Open Book techniques in the treatment of tibial plateau fractures of Schatzker type Ⅱ.Methods:A retrospective study was performed to analyze the clinical data of the 211 patients with tibial plateau fracture of Schatzker type Ⅱ who had been treated by open reduction and internal fixation via the anterolateral knee incision at Department of Traumatic Orthopaedics, The Sixth Hospital of Ningbo from January 2014 to June 2022. There were 142 males and 69 females, with an age of (57.7±14.3) years. Based on the intraoperative reduction techniques, the patients were divided into 2 groups: a Windowing group ( n=107) in which reduction of the split bone fragments was followed by reduction of the depressed articular surface, and an Open Book group ( n=104) in which reduction of the depressed articular surface was followed by reduction of the split bone fragments. The following data were collected and compared between the 2 groups: preoperative general data, operative time, quality of fracture reduction, loss of fracture reduction, fracture healing rate at postoperative 6 months, visual analogue scale (VAS) pain score at postoperative 24 months, post-traumatic arthritis grading at the final follow-up (based on the Resnick-Niwoyam criteria), and Rasmussen classifications of knee function at postoperative 3 and 24 months. Results:There were no significant differences in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The follow-up period for all patients was (34.0±10.6) months. The operative time was (65.0±8.3) minutes for the Windowing group and (64.2±10.2) minutes for the Open Book group, showing no significant difference ( P>0.05). Postoperative CT scans revealed residual articular depression in 10 cases in the Windowing group and in 25 cases in the Open Book group, showing a significant difference ( P<0.05). However, there was no significant difference in plateau widening or varus/valgus alignment between the 2 groups ( P>0.05). There were no statistically significant differences between the 2 groups in loss of fracture reduction, fracture healing rate at postoperative 6 months, VAS score at postoperative 24 months, post-traumatic arthritis grading at the final follow-up, or Rasmussen classifications of the knee function at postoperative 3 or 24 months ( P>0.05). Conclusions:In the treatment of Schatzker type Ⅱ tibial plateau fractures, the Windowing technique demonstrates superior radiographic outcomes compared to the Open Book technique, but the 2 techniques show similar efficacy in functional evaluation and medium-term prognosis.

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