Objective: To investigate the impact of RhE antigen-matched transfusion during liver transplantation on early postoperative recovery and complications. Methods: In this retrospective cohort study, ninety-five patients undergoing liver transplantation at Kunming First People's Hospital between January 2022 and July 2025 were enrolled. Patients were divided into two groups: Group 1 (RhE-mismatched transfusion, n=57) and Group 2 (RhE-matched transfusion, n=38). The baseline data, complete blood counts, hepatic and renal function, coagulation parameters, and complication rates between the two groups were compared at postoperative days 1, 3, 5, 7, and 10. Survival analysis was performed using the Kaplan-Meier method. Results: The baseline characteristics were well-balanced and comparable between the two groups (all P>0.05). The early postoperative mortality rate in the mismatched group (31.58%, 18/57) was significantly higher than that in the matched group (10.53%, 4/38) (P=0.017). The incidence of postoperative hepatic encephalopathy was significantly higher in the mismatched group (50.88%, 29/57) than in the matched group (10.53%, 4/38) (P<0.001). The incidence of postoperative haemorrhage in the mismatched group (24.56%, 14/57) was higher than that in the matched group (5.26%, 2/38), with a statistically significant difference (P=0.014). The incidence of perioperative infection in the mismatched group (28.07%, 16/57) was higher than that in the matched group (10.53%, 4/38), with a statistically significant difference (P=0.04). Corresponding odds ratios (OR) and 95% confidence intervals indicated a lower risk of these adverse events in the matched group. On postoperative day 1, the change in activated partial thromboplastin time (-1.6, 20.5) in the mismatched group was greater than in the matched group (-0.2, 5.5). The change in international normalised ratio (-0.56, 1.22) in the mismatched group was greater than in the matched group (-0.18, 0.32), while the change in albumin (-4.0, 4.8) was smaller in the mismatched group than in the matched group (-2.5, 8.8). On postoperative day 5, the change in albumin (-0.41±7.83) in the mismatched group was smaller than in the matched group (2.68±4.53). At postoperative day 7, the change in albumin in the mismatched group (-0.61±7.38) was smaller than that in the matched group (2.51±5.85), while the change in D-dimer in the mismatched group (0.73, 7.4) was greater than that in the matched group (-1.6, 4.3). On postoperative day 10, the mismatched group exhibited significantly higher fibrinogen levels (-1.21, 1.78) than the matched group (-0.49, 0.97), and significantly longer prothrombin times (-11.3, -2.7) than the matched group (-6.2, -0.8) (all P<0.05). The matched group exhibited a mean overall survival (OS) of 32.803 months (95% CI:29.171-36.436 months), significantly exceeding the mismatched group's 28.996 months (95% CI:24.202-33.790 months). The log-rank test yielded statistically significant results (χ =4.307, P=0.038). Conclusion: Implementing RhE blood group-matched transfusion during liver transplantation may help reduce early postoperative mortality and the incidence of major complication rates, promote faster recovery of coagulation and liver function, and thereby improve short-term patient outcomes.

Panvascular diseases represent systemic vascular disorders characterized by atherosclerosis as their core pathological feature. Their incidence rates continue to rise， posing significant challenges for clinical management. Based on Traditional Chinese Medicine （TCM） theory of ''positive deficiency phlegm stasis''， this study delved into the pivotal role of mitochondrial homeostasis dysregulation in the pathogenesis and progression of pan-vascular diseases， along with its intrinsic connection to TCM pathogenesis. Mitochondrial homeostasis dysregulation pervades the entire course of these diseases， with mitochondrial oxidative stress serving as the initiating factor. Excessive reactive oxygen species （ROS） trigger endothelial dysfunction， lipid accumulation， and inflammatory initiation. Additionally， the imbalance between mitochondrial autophagy and apoptosis constitutes a pivotal link in disease progression. Excessive or insufficient autophagy may lead to the accumulation of damaged mitochondria and excessive cellular apoptosis， thereby promoting plaque instability. Furthermore， mitochondrial metabolic reprogramming impairs energy supply and function in vascular wall cells， hindering subsequent vascular repair. These pathological processes constitute the microscopic manifestation of the core pathogenesis， which is characterized by ''the intermingle of phlegm and stasis and the deficiency of healthy Qi''. Specifically， the endogenous phlegm-turbidity drives mitochondrial oxidative stress injuries， the mutual entanglement of phlegm and stasis induces an imbalance between mitochondrial autophagy and apoptosis， while deficiency of healthy Qi propels mitochondrial energy metabolism disorders and reprogramming. In view of this， this study proposed to employ phlegm-resolving and turbidity-clearing methods to mitigate mitochondrial oxidative stress injuries， phlegm-resolving and blood-activating methods to regulate mitochondrial autophagy and apoptosis， and spleen-tonifying and kidney-nourishing methods to modulate mitochondrial metabolic reprogramming. This approach can prevent and treat panvascular diseases by multi-target regulation of mitochondrial homeostasis， providing a theoretical framework and therapeutic strategies for the prevention and treatment of panvascular diseases through integrated Chinese and Western medicine.

Many triterpenoid compounds have been successfully heterologously synthesized in Saccharomyces cerevisiae. To increase the yield of triterpenoids, various metabolic engineering strategies have been developed. One commonly applied strategy is to enhance the supply of precursors, which has been widely used by researchers. Squalene, as a precursor to triterpenoid biosynthesis, plays a crucial role in the synthesis of these compounds. This study primarily investigates the effect of different squalene levels in chassis strains on the synthesis of triterpenoids(oleanolic acid and ursolic acid), and the underlying mechanisms are further explored using real-time quantitative PCR(qPCR) analysis. The results demonstrate that the chassis strain CB-9-5, which produces high levels of squalene, inhibits the synthesis of oleanolic acid and ursolic acid. In contrast, chassis strains with moderate to low squalene production, such as Y8-1 and CNPK, are more conducive to the synthesis of oleanolic acid and ursolic acid. The qPCR analysis reveals that the expression levels of ERG1, βAS, and CrCYP716A154 in the oleanolic acid-producing strain CB-OA are significantly lower than those in the control strains C-OA and Y-OA, suggesting that high squalene production in the chassis strains suppresses the transcription of certain genes, leading to a reduced yield of triterpenoids. Our findings indicate that when constructing S. cerevisiae strains for triterpenoid production, chassis strains with high squalene content may suppress the expression of certain genes, ultimately lowering their production, whereas chassis strains with moderate squalene levels are more favorable for triterpenoid biosynthesis.
Squalene/analysis* ; Saccharomyces cerevisiae/genetics* ; Triterpenes/metabolism* ; Metabolic Engineering ; Oleanolic Acid/biosynthesis* ; Ursolic Acid

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

Objective To investigate the biomechanical characteristics of clear aligners combined with Class Ⅱelastics during retraction of upper anterior teeth,and compare the differences between two traction methods.Methods A case with a molar distal relationship and extraction of four first premolars was selected.The finite element method was applied to analyze tooth displacement,force distribution,and periodontal ligament(PDL)stress during 0.2 mm en-masse retraction of the anterior teeth.Three working conditions were defined:en-masse retraction without elastics(Condition 1),120 g Class Ⅱ elastics with aligner-cut hooks on upper canines and lower first molars(Condition 2),120 g Class Ⅱ elastics with aligner windows and bonded buttons on upper canines and lower first molars(Condition 3).Results Class Ⅱ elastics significantly enhanced lingual movement of the upper anterior teeth and mesial movement of the lower posterior teeth,while reducing mesial movement of the upper posterior teeth and lingual movement of the lower anterior teeth.In the transverse direction,the forces exerted on the teeth in all three conditions were minimal.In the sagittal direction,in Condition 2,the mesial force of the upper posterior teeth was effectively reduced by an average of 0.13 N,and the mesial force of the lower posterior teeth was increased by an average of 0.31 N.In Condition 3,the distal force of the upper canine teeth and the mesial force of the lower first molar were significantly increased by 0.40 N and 1.14 N,respectively.In the vertical direction,In condition 2,the average extrusive force of the upper teeth and the extrusive force of the lower molars were increased by 0.22 N and 0.20 N,respectively.In Condition 3,the upper canine extrusive force was increased by 0.91 N,while the lower molar intrusive force and the second molar extrusive force were reduced by 0.27 N and 0.25 N,respectively.The PDL stress distribution in the three conditions was generally similar.In Condition 3,the maximum principal stress distribution area on the lower first molars expanded slightly,but the magnitude did not increase significantly.Conclusions Condition 2 optimized the lower posterior teeth mesialization through balanced force distribution and protected the upper posterior teeth anchorage.Condition 3 significantly increased extrusive and distal forces on the upper canines and mesial forces on the lower first molars but did not substantially elevate periodontal risks for these teeth.

Objective To investigate the value of intraoperative ultrasound radiomics for predicting isocitrate dehydrogenase 1(IDH1)mutation of high-grade glioma.Methods Ninety-five patients with high-grade glioma(WHO grade Ⅲ and Ⅳ)who underwent craniotomy glioma resection and ultrasound assisted tumor localization during operation and then confirmed by pathology were retrospectively enrolled.The patients were divided into training set(n=66,including 24 IDH1 mutation type and 42 IDH1 wild type)and validation set(n=29,including 11 IDH1 mutation type and 18 IDH1 wild type)at the ratio of 7∶3.Based on intraoperative ultrasound,radiomics features were extracted,the best ones were screened,and a radiomics model was established for predicting IDH1 mutation of high-grade glioma using random forest algorithm.Receiver operating characteristic(ROC)curve was plotted,the area under the curve(AUC)was calculated to evaluate the predictive efficacy of the model,and decision curve analysis(DCA)was used to evaluate the clinical value of the model.Results A total of 851 radiomics features were extracted based on intraoperative ultrasound,and finally 5 best ones were screened out to construct a radiomics model.The AUC of the radiomics model for predicting IDH1 mutation of high-grade glioma in training and validation sets was 0.902 and 0.707,respectively,with no significant difference(P=0.097).DCA maps showed that the clinical net benefit of the radiomics model was high.Conclusion Intraoperative ultrasound radiomics could effectively predict IDH1 mutation of high-grade glioma.

Aim To investigate the interventional effects of polysaccharides from Dicliptera chinensis(L.)Juss.(DCP)on acute liver failure(ALF)in-duced by lipopolysaccharide(LPS)combined with D-galactosamine(D-GalN)in mice,and on LPS-induced inflammatory responses in RAW264.7 cells,based on the TLR-4/MyD88/NF-κB signaling pathway.Meth-ods Mice were randomly divided into the control,model,silymarin,DCP low,medium,and high dose groups,and toxicity test groups.After 10 consecutive days of treatment,ALF models were established by in-jecting mice with LPS+D-GalN.Additionally,an in-flammatory response model was established by stimula-ting RAW264.7 cells with LPS.Results Biochemical assays showed that compared with the model group,the medium-and high-dose DCP groups exhibited de-creased serum ALT,AST,ALP,TBIL,and γ-GT activi-ties(P＜0.05),reduced levels of ROS,MPO and MDA in liver(P＜0.05),increased activities of SOD,GSH-Px,CAT,and elevated T-AOC levels(P＜0.05).ELISA revealed lower levels of ICAM-1,VCAM-1,IL-6,IL-1β,and TNF-α in liver(P＜0.05).HE staining indicated reduced inflammatory cell infiltration and improved hepatocyte necrosis in liv-er after DCP administration.The use of DCP alone showed no significant organ toxicity.qRT-PCR and Western blot results indicated that DCP inhibited the expression of key factors in TLR-4/MyD88/NF-κB sig-naling pathway(P＜0.05).Cell validation experi-ments also confirmed that this pathway was inhibited by DCP.Conclusion DCP alleviates ALF primarily by inhibiting oxidative stress and blocking the activation of the TLR-4/MyD88/NF-κB signaling pathway.

Objective To validate the diagnostic performance and risk stratification ability of an AI-based recognition system(PE-AI)for pulmonary embolism(PE)using computed tomography pulmonary angiography(CTPA)so as to analyze its diagnostic value in clinical practice.Methods A total of 416 patients with suspected PE who underwent CTPA from January 1,2023 to December 10,2023 at our hospital were included in this study.Two junior radiologists and PE-AI separately detected and diagnosed emboli in the collected cases by double-blind method,and recorded the diagnosis time respectively.Three senior radiologists reviewing with clinical follow-up results were used as the gold standard in this study.Diagnostic performance was evaluated by using the receiver operating characteristic(ROC)curve analysis and Delong-t test.For positive cases,the pulmonary artery obstruction index(PAOI)calculated by AI and manually were collected respectively and consistency analysis was performed.Results The area under the curve(AUC)of PE-AI,manual and combined diagnosis was 85.6％,90.8％and 95.1％,respectively,which differed significantly(P＜0.05).The reading time of PE-AI[(0.16±0.07)min]was significantly lower than the time of manual[(4.42±1.85)min,P＜0.001]and combined diagnosis[(4.58±1.84)min,P＜0.001].The PAOI measured by PE-AI and manually had high consistency(intraclass correlation efficient,ICC=0.80)in the subgroup analysis of confirmed cases.Conclusion AI can quickly identify pulmonary artery emboli in a short time and assist radiologists to improve diagnostic efficiency.At the same time,through the intelligent detection of PAOI,it is helpful for the risk stratification of patients with PE and optimizing the diagnosis and treatment pathway for pulmonary embolism.