Myosteatosis is one of the common complications in patients with end-stage liver disease, which is significantly associated with poor outcomes after liver transplantation. Currently, diagnostic criteria of myosteatosis have not been established, and CT is the most commonly used for diagnosis. The pathogenesis of myosteatosis is multifactorial, and the pathophysiological mechanisms linking it to end-stage liver disease are not fully understood. An increasing number of scholars have recognized that the severity of myosteatosis is closely related to its clinical consequences, but there are no effective treatment options available. This article reviews the pathophysiological mechanisms and diagnostic methods of myosteatosis, and its impact on the prognosis of liver transplant recipients, and discusses current treatment strategies to provide references for the perioperative management of liver transplant recipients.

ObjectiveTo investigate the mechanisms by which Renshentang treats atherosclerosis （AS） in mice， focusing on the regulation of endothelial inflammatory responses mediated by transient receptor potential vanilloid subtype 1 （TRPV1）. MethodsAn AS model was established in apolipoprotein E knockout （ApoE^-/-） mice fed a high-fat diet. The mice were randomly divided into a simvastatin group （0.02 g·kg^-1·d^-1） and low-， medium-， and high-dose Renshentang groups （1.77， 3.54， 7.08 g·kg^-1·d^-1）， with 12 mice in each group. ApoE^-/- mice were fed a high-fat diet and treated simultaneously. C57BL/6J mice fed a normal diet served as the normal group （n=9）. After continuous administration for 12 weeks， mice were anesthetized and the aortas were collected. Oil Red O staining was used to observe lipid plaque formation in the aorta. Hematoxylin-eosin （HE） staining was performed to examine pathological changes in the aortic root. Immunohistochemistry was used to analyze the levels of pro-inflammatory factors tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， as well as the expression of TRPV1， phosphorylated phosphoinositide 3-kinase （p-PI3K）， and phosphorylated protein kinase B （p-Akt） in the aortic root. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect endothelial nitric oxide synthase （eNOS） mRNA expression in the aorta， and Western blot was used to detect TRPV1 protein expression. ResultsCompared with the normal group， the model group showed a significant increase in aortic plaque formation （P<0.01） and significantly elevated levels of TNF-α and IL-1β in the aortic root （P<0.01）. The expression levels of TRPV1， p-PI3K， and p-Akt were decreased （P<0.05， P<0.01）， and eNOS mRNA expression was reduced （P<0.05， P<0.01）. Compared with the model group， all Renshentang groups significantly reduced aortic plaque formation （P<0.01）， significantly decreased TNF-α and IL-1β levels （P<0.01）， and markedly increased the expression levels of TRPV1， p-PI3K， p-Akt， and eNOS mRNA （P<0.05， P<0.01）. ConclusionRenshentang may inhibit endothelial inflammation and suppress the formation of AS by increasing TRPV1 protein expression and up-regulating the PI3K/Akt/eNOS signaling pathway， which may be one of the molecular mechanisms underlying its therapeutic effect against AS.

Objective To investigate serum HCV-RNA detection rate in patients with positive hepatitis C virus (HCV) immunoglobulin G (IgG) antibody, and to analyze the related factors of HCV-RNA detection in patients with positive HCV IgG antibody by logistic regression analysis. Methods A retrospective study was conducted on 500 patients with positive HCV IgG antibody. The positive rate of HCV-RNA was counted. Logistic regression analysis was adopted to analyze the related factors of HCV-RNA detection in HCV IgG antibody positive population. Results A total of 317 patients with positive HCV-RNA detection were included in serum HCV-RNA positive group (n=317), and 183 patients with negative HCV-RNA detection were enrolled as serum HCV-RNA negative group (n=183). The diagnosis rate of HCV infection was 63.40% (317/500). Logistic regression analysis showed that abnormal levels of serum ALT, AST, GGT, TBIL, HCV IgG antibody, prothrombin time, and the presence of clinical symptoms were independently correlated with the detection of HCV-RNA in HCV IgG antibody positive individuals (P<0.05). Established 7-factor prediction models and created a nomogram. The chi-square value was 0.586, and P = 0.89 > 0.05. The ROC curve was plotted using pROC, and the area under the ROC curve was 0.912. Conclusion Among the population positive for HCV IgG antibody, the detection rate of serum HCV-RNA is high. Abnormal levels of ALT, AST, GGT, TBIL, IgG antibody, prothrombin time and clinical symptoms are the related factors for the detection of HCV-RNA. These indicators provide a reference for the clinical judgment of the real infection risk of HCV IgG positive individuals.

Hepatobiliary and pancreatic tumors are common types of digestive system disorders， and their complex pathogeneses have led to difficulties in early diagnosis and a high metastasis rate， with persistently high incidence and mortality rates in China， which greatly affects the quality of life and prognosis of patients. Studies have shown that heparanase （HPSE）， as a key effector molecule in matrix remodeling， plays a crucial regulatory role in tumor invasion and metastasis and microenvironment remodeling， and it is significantly associated with clinical prognosis. This article reviews the molecular mechanism of HPSE in hepatobiliary and pancreatic tumors， in order to provide a strong scientific basis for developing diagnostic markers and targeted interventions for hepatobiliary and pancreatic tumors.

Membrane protein degradation is a cutting-edge field in targeted protein degradation (TPD). Herein, we developed glypican-3 (GPC3)-mediated lysosome-targeting chimeras (GLTACs) as a novel strategy for the targeted degradation of tumor-specific membrane proteins. GLTACs utilize tumor-specific expression and endocytosis properties of GPC3 to degrade membrane proteins. By conjugating a GPC3-targeting peptide with the ligand of protein of interest (POI), GLTACs induce the formation of a ternary complex that is internalized into lysosomes, leading to the degradation of the POI. The effectiveness and specificity of GLTACs were validated by designing PD-L1, c-Met, and FGFR1 degraders. In particular, GLTAC WP0 potently degraded PD-L1 and induced T-cell-mediated tumor killing against HepG2 cells, highlighting the potential therapeutic applications. The development of GLTAC technology expands the scope of TPD strategies and opens new avenues for discovering novel therapeutic modalities against challenging protein targets.

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

Objective:To construct a perioperative pain nursing protocol for thoracoscopic surgery patients, providing a reference for clinical pain nursing practice.Methods:An evidence-based approach was used to search relevant guidelines and extract the best evidence. The initial draft was created through discussions among the research team, followed by two rounds of Delphi expert consultations. Based on the experts' suggestions, the protocol was revised and the best plan was finalized.Results:A total of 10 guidelines were included, and 22 experts participated in two rounds of consultations. The response rate for the consultation questionnaires was 100.00% (22/22) , with expert authority coefficients of 0.94 and 0.95 for the two rounds, respectively. The coefficient of variation for all indicators in the second round ranged from 0.04 to 0.24. The final pain nursing protocol included four primary indicators: personnel preparation, pain assessment, pain education, and pain intervention, with 10 secondary indicators and 27 tertiary indicators.Conclusions:The constructed perioperative pain nursing protocol for thoracoscopic surgery patients is significant, scientific, comprehensive, and targeted. It provides theoretical support and practical guidance for pain management, helping to reduce postoperative pain in patients.

Objective:To evaluate the causal relationship between IL-7 and IL-7Rα and ankylosing spondylitis(AS)using the Mendelian randomization(MR)method.Methods:This study was based on gene-wide association study(GWAS)summary data,con-structing instrumental variables(IV)using single nucleotide polymorphisms(SNPs).We respectively adopt Inverse variance weighted(IVW),MR-Egger mode and Weighted median(WM)mode to assess the causal relation between IL-7/IL-7Rα and AS.In addition,we also conducted sensitivity tests,including the heterogeneity test,the pleiotropy test,the leave-one-out approach and the MR-PRESSO test.Results:IL-7 and IL-7Rα were respectively included in 9 and 5 IVs that could be used for MR analysis.Results of IVW analysis revealed a reliable causal relationship between IL-7 and IL-7Rα and AS[IL-7:P=0.025 2,OR(95%CI)=0.999 4(0.989 1～0.999 9);IL-7Rα:P=0.008 3,OR(95%CI)=1.000 6(1.000 2～1.001 0)].Cochranes Q test(IL-7:P=0.999 7;IL-7Rα:P=0.946 9)showed that all studies had good homogeneity.The results of a leave-one-out sensitivity analysis suggested that causal associations were not strongly influenced by any selected IVs.The intercept of the MR-Egger regression further showed that pleiotropy did not bias the causal effect in this study.Conclusion:Both IL-7 and IL-7Rα have a strong causal relationship with AS,among which IL-7 is a protec-tive factor for AS,and IL-7Rα is a risk factor for AS.