The year 2025 is a crucial one for the leapfrog development of basic research in liver transplantation in China. This article systematically reviews and summarizes the major original contributions made by Chinese scholars in the field of liver transplantation during the year. In the field of xenotransplantation, our research teams have successively completed the world's first gene-modified pig-human in situ and auxiliary liver transplantation, marking that China is leading globally in the clinical transformation of xenogeneic organs. In the aspect of donor liver source expansion and repair, the deep integration of domestic bionic oxygenation machine perfusion system with cell-loaded microgels and 3D bioprinting technology has successfully achieved the dynamic functional repair of marginal donor livers and the preliminary construction of artificial liver tissues. Regarding elderly donor livers, the mechanism of the interaction-driven network between senescent hepatic sinusoidal endothelial cells and hepatocytes was revealed for the first time, promoting the transformation from "passive treatment" to "active management of aging risks". In addition, domestic research has systematically revealed the multi-dimensional pathological mechanisms of ischemia-reperfusion injury, including acetylation regulation and cell pyroptosis, ferroptosis, etc. and innovatively proposed cutting-edge strategies such as "hibernation mechanism-driven organ protection" and "donor-specific thymus vaccine". In the aspects of liver transplantation for hepatocellular carcinoma and precise management, the deep integration of multi-omics technology and artificial intelligence has demonstrated high accuracy in postoperative complication prediction and tumor recurrence prediction, providing solid evidence-based basis for enhancing the international discourse power of "Chinese standards". Through this annual academic review, this article aims to showcase the core breakthroughs in basic research on liver transplantation in China, and contribute wisdom to promoting the transformation of clinical diagnosis and treatment paradigms and achieving international academic alignment.

Temporomandibular joint (TMJ) is the only synovial joint in the oral and maxillofacial region, with its disc being a critical fibrocartilaginous structure that distributes stress and maintains the stability of joint movement. Various factors can lead to TMJ disc destruction, resulting in TMJ dysfunction and facial deformities. In recent years, research on TMJ disc destruction has become a frontier in the field of oral and maxillofacial surgery. Previous research and literature reviews have mainly focused on diagnosis and treatment, with a lack of reviews on the progress of basic research related to disc destruction. This review summarizes current progress in the etiology, pathological features, molecular mechanisms, and tissue-engineered repair materials of TMJ disc destruction, providing reference for basic research and clinical prevention and treatment. Studies have shown that the causes of TMJ disc destruction include mechanical damage (e.g. anterior disc displacement, malocclusion, trauma), chronic inflammation (e.g. TMJ osteoarthritis, rheumatoid arthritis), and susceptibility factors such as age and sex, as well as psychosocial factors. Its main manifestations are alterations in the ultrastructure and mechanical properties of collagen fibers. Its molecular mechanisms include abnormal angiogenesis, imbalanced fibrocartilage cell homeostasis under mechanical or inflammatory stimulation, and abnormal stem cell differentiation. The present study focuses on the development and optimization of tissue engineered biomaterials through cell sources, scaffold materials, and growth factors. Future studies should focus on the molecular mechanisms of TMJ disc destruction, regulation of disc development during embryonic and postnatal stages, development and translation of novel biomaterials, as well as the application of artificial intelligence in material design, molecular target screening, and clinical decision-making.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective To screen the independent influencing factors for gastrointestinal bleeding(GIB)in hospitalized patients with coronary heart disease(CHD)and to construct and validate a no-mogram prediction model.Methods A total of 440 CHD patients who developed GIB during hospi-talization were selected as GIB group,and another 320 CHD patients hospitalized in the department of cardiovascular medicine were randomly selected as non-GIB group.The clinical data of the two groups were analyzed and compared.Multivariate logistic regression analysis was used to screen the indepen-dentinfluencing factors for GIB.Based on these factors,a nomogram prediction model for the risk of GIB in hospitalized CHD patients was constructed.The entire dataset was randomly divided into train-ing set(n=532)and validation set(n=228)in a 7∶3 ratio.The performance of the nomogram model was evaluated using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Multivariate logistic regression analysis showed that body mass index(BMI),history of digestive system diseases,CHD classification,albumin,white blood cell count,monocyte-to-lymphocyte ratio(MLR),and low-density lipoprotein were all independent influencing factors for GIB in CHD patients(P＜0.05).ROC curve analysis indicated that the nomo-gram model(excluding low-density lipoprotein)constructed based on independent influencing factors exhibited good discrimination in both the training set(area under the curve:0.839,95％CI,0.805 to 0.873)and the validation set(area under the curve:0.810,95％CI,0.751 to 0.868).Calibration curve analysis demonstrated good consistency between the predicted probabilities and the observed incidence of GIB in hospitalized CHD patients in both the training and validation sets.DCA results revealed that the nomogram model had a good clinical net benefit.Conclusion The nomogram model constructed based on independent influencing factors has good predictive performance for the risk of GIB in hospitalized CHD patients and can provide a basis for clinicians to promptly identify GIB and adjust medication regimens.

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.

Objective:Periprosthetic joint infection (PJI) is one of the most severe complications following hip and knee arthroplasty and is a leading cause of revision surgery. Pathogens and their antibiotic susceptibility are key factors in the successful treatment of PJI. This study retrospectively analyzes the pathogen characteristics and antimicrobial susceptibility of PJI patients treated at our center, aiming to establish an empirical antibiotic regimen for PJI in the region, providing a reference for empirical antibiotic therapy in the clinical management of PJI.Methods:This study retrospectively reviewed PJI patients treated at our center from January 2018 to October 2024. In each case, preoperative arthrocentesis fluid, and synovium tissue from at least three sites during surgery were collected for aerobic and anaerobic blood culture. The positive culture rate, distribution of pathogens based on Gram staining, methicillin resistance, mixed infections, and multidrug resistance were analyzed. Effective coverage parameters were constructed based on antimicrobial sensitivity and coverage rates, and appropriate empirical antimicrobial regimens were proposed.Results:A total of 233 PJI patients were included in the analysis. There were 99 males and 134 females with an average age of 67.0±10.1 years (ranging from 32 to 93 years). The study included 130 hip and 103 knee arthroplasty patients. Among the patients, 202 (86.7%) had positive cultures, with a total of 301 pathogen strains isolated: 268 Gram-positive bacteria (89.4%), 25 Gram-negative bacteria (8.3%), and 7 fungal strains (2.3%). The most common Gram-positive bacteria were coagulase-negative staphylococci (196 strains, 65.1%), epidermal staphylococci (77 strains, 25.6%), Staphylococcus aureus (39 strains, 13.0%), and Streptococcus spp. (19 strains, 6.3%). The most common Gram-negative bacteria were Enterobacteriaceae (14 strains, 4.7%). In hip joint infections, the most prevalent pathogens were epidermal Staphylococci (48 strains, 28.1%) and Staphylococcus aureus (27 strains, 15.8%), while in knee joint infections, epidermal Staphylococci (29 strains, 22.3%) were most common. Regarding antibiotic resistance, 48.5% of staphylococcal strains were methicillin-resistant Staphylococcus, and 51.5% were multidrug-resistant strains. Staphylococci were 100% susceptible to vancomycin, teicoplanin, daptomycin, linezolid, and tigecycline, but exhibited high resistance to β-lactams and quinolone antibiotics. Analysis of empirical antibiotic regimens revealed that vancomycin combined with meropenem, linezolid combined with meropenem, vancomycin combined with imipenem, vancomycin combined with piperacillin/tazobactam, and vancomycin combined with ceftriaxone had effective coverage rates of 97.0%, 97.0%, 96.0%, 94.9%, and 90.9%, respectively.Conclusion:The main pathogens in PJI in this region are Gram-positive bacteria, with high rates of methicillin resistance and multidrug resistance. Based on antimicrobial susceptibility data, we recommend vancomycin combined with meropenem as the empirical treatment regimen for culture-negative PJI in this region, with linezolid combined with meropenem as an alternative.

Objective:Periprosthetic joint infection (PJI) is one of the most severe complications following hip and knee arthroplasty and is a leading cause of revision surgery. Pathogens and their antibiotic susceptibility are key factors in the successful treatment of PJI. This study retrospectively analyzes the pathogen characteristics and antimicrobial susceptibility of PJI patients treated at our center, aiming to establish an empirical antibiotic regimen for PJI in the region, providing a reference for empirical antibiotic therapy in the clinical management of PJI.Methods:This study retrospectively reviewed PJI patients treated at our center from January 2018 to October 2024. In each case, preoperative arthrocentesis fluid, and synovium tissue from at least three sites during surgery were collected for aerobic and anaerobic blood culture. The positive culture rate, distribution of pathogens based on Gram staining, methicillin resistance, mixed infections, and multidrug resistance were analyzed. Effective coverage parameters were constructed based on antimicrobial sensitivity and coverage rates, and appropriate empirical antimicrobial regimens were proposed.Results:A total of 233 PJI patients were included in the analysis. There were 99 males and 134 females with an average age of 67.0±10.1 years (ranging from 32 to 93 years). The study included 130 hip and 103 knee arthroplasty patients. Among the patients, 202 (86.7%) had positive cultures, with a total of 301 pathogen strains isolated: 268 Gram-positive bacteria (89.4%), 25 Gram-negative bacteria (8.3%), and 7 fungal strains (2.3%). The most common Gram-positive bacteria were coagulase-negative staphylococci (196 strains, 65.1%), epidermal staphylococci (77 strains, 25.6%), Staphylococcus aureus (39 strains, 13.0%), and Streptococcus spp. (19 strains, 6.3%). The most common Gram-negative bacteria were Enterobacteriaceae (14 strains, 4.7%). In hip joint infections, the most prevalent pathogens were epidermal Staphylococci (48 strains, 28.1%) and Staphylococcus aureus (27 strains, 15.8%), while in knee joint infections, epidermal Staphylococci (29 strains, 22.3%) were most common. Regarding antibiotic resistance, 48.5% of staphylococcal strains were methicillin-resistant Staphylococcus, and 51.5% were multidrug-resistant strains. Staphylococci were 100% susceptible to vancomycin, teicoplanin, daptomycin, linezolid, and tigecycline, but exhibited high resistance to β-lactams and quinolone antibiotics. Analysis of empirical antibiotic regimens revealed that vancomycin combined with meropenem, linezolid combined with meropenem, vancomycin combined with imipenem, vancomycin combined with piperacillin/tazobactam, and vancomycin combined with ceftriaxone had effective coverage rates of 97.0%, 97.0%, 96.0%, 94.9%, and 90.9%, respectively.Conclusion:The main pathogens in PJI in this region are Gram-positive bacteria, with high rates of methicillin resistance and multidrug resistance. Based on antimicrobial susceptibility data, we recommend vancomycin combined with meropenem as the empirical treatment regimen for culture-negative PJI in this region, with linezolid combined with meropenem as an alternative.

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.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective:To explore the relationship and underlying mechanisms between servant leadership and satisfaction of medical staff in tertiary hospitals, and to provide references for improving satisfaction of medical personnel.Methods:From January to June 2023, a questionnaire survey was conducted among on-duty medical staff at a tertiary hospital in Guangzhou using a simple random sampling method. Data corresponding to four key variables: servant leadership, hospital management level, affective commitment, and satisfaction of medical staff were collected. SPSS 25.0 software was used to perform independent samples t-tests and one-way analysis of variance (ANOVA) to examine group differences, and Pearson correlation analysis was conducted to explore the relationships among multiple variables. Amos 24.0 software was employed to construct a structural equation model to conduct confirmatory factor analysis of the four key variables, analyze potential mediating effects, and use multi-group analysis to examine differences in path parameters and structure among groups. Results:A total of 632 valid questionnaires were obtained. The satisfaction score of medical staff was (4.50±0.66)(maximum score was 5 points). Age, years of work experience, and job category had statistically significant effects on satisfaction of medical staff ( F = 5.799, 6.483, 7.671; P = 0.001). All four key variables were significantly positively correlated ( P<0.001). Servant leadership, hospital management level, and affective commitment all had direct positive effects on satisfaction of medical staff, with path coefficients of 0.207, 0.386, and 0.345, respectively ( P <0.05, critical ratio>1.96). Hospital management level and affective commitment each had independent partial mediating effects between servant leadership and satisfaction of medical staff (path coefficients of 0.353 and 0.067, respectively; P = 0.007, 0.018). They also jointly exerted a chain mediating effect (path coefficient of 0.243, P = 0.013). Differences in path effects among different job categories (clinical doctors, nurses, and administrative support staff) were statistically significant ( χ2 = 43.344, df = 24, P = 0.009). Conclusions:The servant leadership in tertiary hospitals can directly influence the satisfaction of medical staff, as well as indirectly influence it through emotional commitment and hospital management level. Moreover, the mechanisms of influence vary among medical staff of different professional categories. Tertiary hospitals should introduce and promote servant leadership styles, enhance the servant leadership behaviors of management personnel, and strengthen the synergistic effects of servant leadership, hospital management level, and affective commitment. Differential adjustment mechanisms should be implemented for different job categories.