1.Status of Clinical Practice Guideline Information Platforms
Xueqin ZHANG ; Yun ZHAO ; Jie LIU ; Long GE ; Ying XING ; Simeng REN ; Yifei WANG ; Wenzheng ZHANG ; Di ZHANG ; Shihua WANG ; Yao SUN ; Min WU ; Lin FENG ; Tiancai WEN
Medical Journal of Peking Union Medical College Hospital 2025;16(2):462-471
Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.
2.Mechanism of Ethoxysanguinarine in Regulating IRE1/RIDD Signaling Pathway to Inhibit Endoplasmic Reticulum Stress and Alleviate Cardiomyocyte Apoptosis
Zucheng SHANG ; Hongzheng LI ; Mengfan LI ; Wen SUN ; Guosheng LIN ; Aling SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):141-148
ObjectiveTo investigate the effects of ethoxysanguinarine (ETH) on angiotensin Ⅱ (Ang Ⅱ)-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 (IRE1)/regulated IRE1-dependent decay (RIDD) signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation, which was identified as a cardiomyocyte apoptosis model. Subsequently, the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 (CCK-8) to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group, a model group (Ang Ⅱ, 1 mmol·L-1), and low-, medium-, and high-dose ETH groups (1.25, 2.5, and 5 mmol·L-1). Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins, endoplasmic reticulum stress, and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip, p-IRE1, and Bid in H9c2 cells (P<0.05, P<0.01), indicating the induction of endoplasmic reticulum stress, activation of the IRE1/RIDD signaling pathway, and initiation of the apoptosis process. Compared with the blank group, the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes, as well as in both early and late apoptosis rates (P<0.01). The expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 proteins were significantly increased, while the expression level of Bcl-2 protein was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group (P<0.05). The expression levels of Bid, Bax, and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group (P<0.05, P<0.01). The high-dose ETH group significantly reduced the expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 (P<0.05, P<0.01) and significantly increased the expression level of Bcl-2 (P<0.05). The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins in the high-dose ETH group were significantly decreased (P<0.05, P<0.01). ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.
3.Mechanism of Ethoxysanguinarine in Regulating IRE1/RIDD Signaling Pathway to Inhibit Endoplasmic Reticulum Stress and Alleviate Cardiomyocyte Apoptosis
Zucheng SHANG ; Hongzheng LI ; Mengfan LI ; Wen SUN ; Guosheng LIN ; Aling SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):141-148
ObjectiveTo investigate the effects of ethoxysanguinarine (ETH) on angiotensin Ⅱ (Ang Ⅱ)-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 (IRE1)/regulated IRE1-dependent decay (RIDD) signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation, which was identified as a cardiomyocyte apoptosis model. Subsequently, the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 (CCK-8) to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group, a model group (Ang Ⅱ, 1 mmol·L-1), and low-, medium-, and high-dose ETH groups (1.25, 2.5, and 5 mmol·L-1). Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins, endoplasmic reticulum stress, and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip, p-IRE1, and Bid in H9c2 cells (P<0.05, P<0.01), indicating the induction of endoplasmic reticulum stress, activation of the IRE1/RIDD signaling pathway, and initiation of the apoptosis process. Compared with the blank group, the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes, as well as in both early and late apoptosis rates (P<0.01). The expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 proteins were significantly increased, while the expression level of Bcl-2 protein was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group (P<0.05). The expression levels of Bid, Bax, and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group (P<0.05, P<0.01). The high-dose ETH group significantly reduced the expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 (P<0.05, P<0.01) and significantly increased the expression level of Bcl-2 (P<0.05). The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins in the high-dose ETH group were significantly decreased (P<0.05, P<0.01). ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.
4.Analysis of red blood cell RhAG protein, Rh D, and Rh CE antigens expression in carriers of RHAG 808A: a common variant in the Chinese population
Yalin LUO ; Mingming SUN ; Jizhi WEN ; Zhijian LIAO ; Yanli JI
Chinese Journal of Blood Transfusion 2025;38(5):660-664
Objective: To investigate the impact of RHAG
808A variant, commonly identified in the Chinese population, on RhAG protein, RhD and RhCE antigens expression through in vivo and in vitro expression analysis. Methods: A missense mutation of RHAG gene (c. 808G>A, p. Val270Ile) with high frequency was found in KMxD database. Bioinformatics analysis was performed using Polyphen-2 and Provean software. High resolution melting (HRM) method was utilized to screen for the variant carriers in the blood donors. The expression of RhAG protein, RhD and RhCE antigens on the surface of red cells of variant carriers were detected via flow cytometry. Wild-type and mutant vectors of RHAG were constructed and transfected into HEK 293T cells for in vitro expression analysis. Then, the expression of RhAG protein, RhD and RhCE antigens were analyzed by flow cytometry. Results: Polyphen-2 and Provean software suggested that the amino acid change (p. Val270Ile) of RhAG protein may be harmful or neutral respectively. Among the 999 blood donors from Guangzhou Blood Center, 4 homozygous carriers and 99 heterozygous carriers of RHAG
808A mutant allele were identified. The frequency of this allele was 5.4% (107/1 998). No significant differences in RhAG protein, RhD and RhCE antigens expression level was identified between the homozygous carriers, heterozygous carriers of RHAG
808A variant allele and the wild-type individuals. In vitro analysis for antigen expression study obtained the similar results. Conclusion: The RHAG
808A variant allele commonly identified in the Chinese population has no effect on the expression of RhAG protein, RhD and RhCE antigens, so the variant should be a population polymorphism site.
5.Combination of CT/MRI LI-RADS With Second-Line Contrast-Enhanced Ultrasound Using Sulfur Hexafluoride or Perfluorobutane for Diagnosing Hepatocellular Carcinoma in High-Risk Patients
Yu LI ; Sheng LI ; Qing LI ; Kai LI ; Jing HAN ; Siyue MAO ; Xiaohong XU ; Zhongzhen SU ; Yanling ZUO ; Shousong XIE ; Hong WEN ; Xuebin ZOU ; Jingxian SHEN ; Lingling LI ; Jianhua ZHOU
Korean Journal of Radiology 2025;26(4):346-359
Objective:
The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).
Materials and Methods:
This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.
Results:
In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%).
Conclusion
The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.
6.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.
7.Ultrasound-guided attenuation parameter for identifying metabolic dysfunction-associated steatotic liver disease: a prospective study
Yun-Lin HUANG ; Chao SUN ; Ying WANG ; Juan CHENG ; Shi-Wen WANG ; Li WEI ; Xiu-Yun LU ; Rui CHENG ; Ming WANG ; Jian-Gao FAN ; Yi DONG
Ultrasonography 2025;44(2):134-144
Purpose:
This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard.
Methods:
Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated.
Results:
Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001).
Conclusion
Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.
8.Endovascular Treatment for Acute Posterior Circulation Tandem Lesions: Insights From the BASILAR and PERSIST Registries
Wei LI ; Mohamed F. DOHEIM ; Zhongming QIU ; Tan WANG ; Zhibin CHEN ; Wenjie ZI ; Qingwu YANG ; Haitao GUAN ; Hongyu QIAO ; Wenhua LIU ; Wei HU ; Xinfeng LIU ; Jinbo HUANG ; Zhongkui HAN ; Zhonglun CHEN ; Zhenqiang ZHAO ; Wen SUN ; Raul G. NOGUEIRA
Journal of Stroke 2025;27(1):75-84
Background:
and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT.
Methods:
Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery.
Results:
A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24).
Conclusion
Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.
10.Bioactive metabolites: A clue to the link between MASLD and CKD?
Wen-Ying CHEN ; Jia-Hui ZHANG ; Li-Li CHEN ; Christopher D. BYRNE ; Giovanni TARGHER ; Liang LUO ; Yan NI ; Ming-Hua ZHENG ; Dan-Qin SUN
Clinical and Molecular Hepatology 2025;31(1):56-73
Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

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