With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease.

Objective To investigate the effect of silencing alpha tubulin acetyltransferase 1(α-TAT1)on migration behavior of endothelial cells induced by hepatopulmonary syndrome(HPS).Methods Online database Tabula Muris was used to analyze the expression of α-TAT1 in various cell subsets in the lungs.Twenty-four male SD rats were randomly divided into control group(Sham group,n=6)and common bile duct ligation group(HPS group,n=18).The rats in HPS group were euthanasized at 2 and 4 weeks after modelling,and then the expression of α-TAT1 in pulmonary vascular endothelial cells was detected by immunofluorescence colocalization.The sera from the Sham and HPS rats were used to stimulate human umbilical vein endothelial cells(HUVECs)for 12 and 24 h,respectively.Then the obtained HUVECs were divided into 4 groups:Sham serum+siRNA NC group,Sham serum+siRNA α-TAT1 group,HPS serum+siRNA NC group,HPS serum+siRNA α-TAT1 group.The expression levels of α-TAT1 and Ace-α-tubulin in HUVECs were detected by Western blotting.Immunofluorescence assay was applied to observe the levels of polymerized microtubules of α-Tubulin in HUVECs after nocodazole(10 μmol/L)pretreatment to evaluate the stability of microtubule structure.Cell scratch assay combined with cell immunofluorescence assay was employed to observe the nuclear localization of Golgi apparatus and cell migration ability of HUVECs.The angiogenesis ability of HUVECs was tested by in vitro angiogenesis test.Results In vivo and in vitro experiments showed that the expression of α-TAT1 in endothelial cells was significantly increased after HPS inducement.The expression levels of α-TAT1 and Ace-α-tubulin were significantly down-regulated,and the stability of microtubules was weakened in the siRNA α-TAT1 interference group(P＜0.01).In addition,the distribution of GM 130 labeled Golgi apparatus in the protrusion of HUVECs was down-regulated in the siRNAα-TAT1 interference group,as well as the migration ability(P＜0.01).And the length of angiogenesis and network level were also significantly declined(P＜0.01).Conclusion Silencing α-TAT1 reduces the migrαtion and angiogenesis of endothelial cells in HPS,which was associated with weakened stabilization of microtubule.

Objective To compare the effect of palliative mitral valve surgeries and medication therapies for secondary non-ischemic mitral regurgitation. Methods The clinical data of patients with non-ischemic functional mitral regurgitation treated in our hospital between 2009 and 2019 were retrospectively analyzed. Patients with a left ventricular ejection fraction (LVEF)＜40% underwent a dobutamine stress test, and a positive result was determined when the LVEF improved by more than 15% compared to the baseline value. Positive patients were divided into a surgery group and a medication group. The surgery group underwent surgical mitral valve repair or replacement, while the medication group received simple medication treatment. Follow-up on survival and cardiac function status through outpatient or telephone visits every six months after surgery, and patients underwent cardiac ultrasound examination one year after surgery. The main research endpoint was a composite endpoint of all-cause death, heart failure readmission, and heart transplantation, and the differences in cardiac function and cardiac ultrasound parameters between the two groups were compared. Results Ultimately 41 patients were collected, including 28 males and 13 females with an average age of 55.5±11.1 years. Twenty-five patients were in the surgery group and sixteen patients in the medication group. The median follow-up time was 16 months, ranging 1-96 months. The occurrence of all-cause death in the surgery group was lower than that in the medication group (HR=0.124, 95%CI 0.024-0.641, P=0.034). The difference between the two groups was not statistically significant in the composite endpoint (HR=0.499, 95%CI 0.523-1.631, P=0.229). The New York Heart Association (NYHA) grade of the surgery group was better (NYHA Ⅰ-Ⅱ accounted for 68.0% in the surgury group and 18.8% in the medication group, P<0.01) as well as the grade of mitral valve regurgitation (87.5% of the patients in the medication group had moderate or above regurgitation at follow-up, while all the patients in the surgery group had moderate below regurgitation, P<0.01). There was no statistical difference in preoperative and follow-up changes in echocardiograph parameters between the two groups (P＞0.05). Conclusion For non-ischemic functional mitral regurgitation, if the cardiac systolic function is well reserved, mitral valve surgery can improve survival and quality of life compare to simple medication therapy.

Objective:To design and synthesize 89Zr-deferoxamine(DFO)-G4C2, a novel molecular probe targeting programmed cell death receptor 1(PD-1), and evaluate its in vivo biodistribution and microPET/CT imaging characteristics in tumor-bearing mice. Methods:DFO-G4C2 was prepared by coupling DFO with G4C2, a monoclonal antibody targeting PD-1. The affinity and binding specificity of this amalgamation were subsequently assessed through the implementation of flow cytometry and surface plasmon resonance techniques. The molecular probe 89Zr-DFO-G4C2 was achieved by labeling DFO-G4C2 with the radioisotope 89Zr, and the labeling efficiency and in vitro stability of 89Zr-DFO-G4C2 were determined. Mouse models laden with CT26 colorectal cancer cells expressing PD-1 were established, followed by in vivo biodistribution and microPET/CT imaging studies, to explore the potential clinical value of 89Zr-DFO-G4C2. Additionally, the validity of this molecular probe was verified in 4T1 breast cancer models, affirming its efficacy as an imaging tool across different tumor models. Independent-sample t test was used to analyze the data. Results:DFO-G4C2 exhibited an affinity constant KD of (0.55±0.02) μmol/L, indicating a strong binding affinity. The binding rate to mouse PD-1 protein was determined to be (61.82±8.49)%. The labeling rate of 89Zr-DFO-G4C2 reached a high level of (98.76±0.51)%. Furthermore, the labeling rates in lysate and human serum after 144 h were measured to be (93.07±2.16)% and (83.42±3.21)%, respectively. MicroPET/CT imaging of CT26 tumor-bearing mice injected with 89Zr-DFO-G4C2 showcased pronounced radioactivity uptake in the tumor tissue. At 72 h post-injection, the tumor uptake value reached (10.47±0.34) percentage activity of injection dose per gram of tissue (%ID/g). The tumor uptake observed in the blocked experimental group, wherein an excess of unlabeled antibody was administered, was significantly lower at (6.26±1.03) %ID/g in comparison to the non-blocked group ( t=6.67, P=0.003). The in vivo biodistribution results were consistent with the observed microPET/CT imaging outcomes. MicroPET/CT imaging observations in the 4T1 breast cancer bearing mouse model were analogous to those obtained from the CT26 model. Conclusion:ImmunoPET based on the 89Zr-DFO-G4C2 molecular probe can non-invasively and visually assess the PD-1 expression level of tumors in vivo, and it is expected to be a new molecular imaging technique for immunotherapy monitoring of PD-1 inhibitors.

Acute pancreatitis （AP） is a gastrointestinal disease that requires early intervention， and when it progresses to moderate-severe AP （MSAP） or severe AP （SAP）， there will be a significant increase in the mortality rate of patients. Machine learning （ML） has achieved great success in the early prediction of AP using clinical data with the help of its powerful computational and learning capabilities. This article reviews the research advances in ML in predicting the severity， complications， and death of AP， so as to provide a theoretical basis and new insights for clinical diagnosis and treatment of AP through artificial intelligence.

OBJECTIVE: To establish a machine learning model based on extreme gradient boosting (XGBoost) algorithm for early prediction of severe acute pancreatitis (SAP), and explore its predictive efficiency. METHODS: A retrospective cohort study was conducted. The patients with acute pancreatitis (AP) who admitted to the First Affiliated Hospital of Soochow University, the Second Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University from January 1, 2020 to December 31, 2021 were enrolled. Demography information, etiology, past history, and clinical indicators and imaging data within 48 hours of admission were collected according to the medical record system and image system, and the modified CT severity index (MCTSI), Ranson score, bedside index for severity in acute pancreatitis (BISAP) and acute pancreatitis risk score (SABP) were calculated. The data sets of the First Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University were randomly divided into training set and validation set according to 8 : 2. Based on XGBoost algorithm, the SAP prediction model was constructed on the basis of hyperparameter adjustment by 5-fold cross validation and loss function. The data set of the Second Affiliated Hospital of Soochow University was served as independent test set. The predictive efficacy of the XGBoost model was evaluated by drawing the receiver operator characteristic curve (ROC curve), and compared it with the traditional AP related severity score; variable importance ranking diagram and Shapley additive explanation (SHAP) diagram were drawn to visually explain the model. RESULTS: A total of 1 183 AP patients were enrolled finally, of which 129 (10.9%) developed SAP. Among the patients from the First Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University, there were 786 patients in the training set and 197 in the validation set; 200 patients from the Second Affiliated Hospital of Soochow University were used as the test set. Analysis of all three datasets showed that patients who advanced to SAP exhibited pathological manifestation such as abnormal respiratory function, coagulation function, liver and kidney function, and lipid metabolism. Based on the XGBoost algorithm, an SAP prediction model was constructed, and ROC curve analysis showed that the accuracy for prediction of SAP reached 0.830, the area under the ROC curve (AUC) was 0.927, which was significantly improved compared with the traditional scoring systems including MCTSI, Ranson, BISAP and SABP, the accuracy was 0.610, 0.690, 0.763, 0.625, and the AUC was 0.689, 0.631, 0.875, and 0.770, respectively. The feature importance analysis based on the XGBoost model showed that the top ten items ranked by the importance of model features were admission pleural effusion (0.119), albumin (Alb, 0.049), triglycerides (TG, 0.036), Ca²⁺ (0.034), prothrombin time (PT, 0.031), systemic inflammatory response syndrome (SIRS, 0.031), C-reactive protein (CRP, 0.031), platelet count (PLT, 0.030), lactate dehydrogenase (LDH, 0.029), and alkaline phosphatase (ALP, 0.028). The above indicators were of great significance for the XGBoost model to predict SAP. The SHAP contribution analysis based on the XGBoost model showed that the risk of SAP increased significantly when patients had pleural effusion and decreased Alb. CONCLUSIONS A SAP prediction scoring system was established based on the machine automatic learning XGBoost algorithm, which can predict the SAP risk of patients within 48 hours of admission with good accuracy.
Humans ; Pancreatitis ; Acute Disease ; Retrospective Studies ; Hospitalization ; Algorithms

In the American Heart Association’s Scientific Sessions 2021, the results of six clinical trials related to cardiovascular surgery were revealed. The PALACS trial demonstrated that posterior left pericardiotomy during open heart surgery was associated with a significant reduction in postoperative atrial fibrillation; the EPICCURE study found that injection of mRNA encoding vascular endothelial growth factor (VEGF-A mRNA) directly into the myocardium of patients undergoing elective coronary artery bypass grafting (CABG) improved patients’ heart function; the VEST trial once again proved the safety and potential value of external stent for vein graft. This article will interpret the above-mentioned three studies.

Objective:To compare the effects of laparoscopic and surgical catheterization on catheter-related complications and microinflammation in uremic peritoneal dialysis (PD) patients.Methods:According to different catheterization methods, 98 uremic patients who were scheduled to undergo peritoneal dialysis in the First People's Hospital of Jiande from January 2014 to March 2019 were divided into group A (38 cases), group B (60 cases). Laparoscopic catheterization was used in group A, and incision catheterization was used in group B. Surgical parameters, catheter complications, microinflammation and survival rate of early catheterization were observed in the two groups.Results:The operation time of group A was (35.00±3.14)min, which was shorter than that of group B [(50.00±5.17)min], and the operation cost of group A was (5 800.0±318.9)CNY, which was higher than that of group B [(3 400.0±297.4)CNY], and the visual analogue score (VAS) of group A was (2.33±0.31)points, which was lower than that of group B [(3.25±0.49)points], there were statistically significant differences between the two groups ( t=11.540, 9.317, 10.328, 36.578, all P<0.05). The incidence of catheter-related complications in group A was 10.53%(4/38), which was significantly lower than 28.33%(17/60) in group B (χ 2=4.383, P<0.05). There were no statistically significant differences in high-sensitivity C-reactive protein (hs-CRP), interleukin-6(IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels between group A and group B before catheterization (all P>0.05). After catheterization, the levels of hs-CRP, IL-6 and TNF-alpha in group B were (12.52±3.75)mg/L, (12.02±3.76)ng/L, (15.92±5.72)ng/L, respectively, which were higher than those in group A [(9.63±2.36)mg/L, (9.11±3.54)ng/L, (13.41±5.61)ng/L] ( t=4.244, 4.081, 4.510, all P<0.05). After 2 months of follow-up, the survival rate of dialysis tube technique was 89.47%(34/38) in group A and 71.67%(43/60) in group B, there was statistically significant difference between the two groups (χ 2=4.382, P<0.05). Conclusion:Application of laparoscopic catheterization in uremic PD patients has satisfactory effect, light pain, fewer complications, mild inflammation and high survival rate of early catheterization technology, which is worthy of clinical promotion.

Objective To investigate the clinical features of cutaneous adverse reactions to tyrosine kinase inhibitors.Methods Thirty patients with cutaneous adverse reactions to tyrosine kinase inhibitors were enrolled from the First Affiliated Hospital of Guangzhou Medical University between January 2015 and December 2016,and their laboratory test results,histopathological findings and treatment response data were collected and analyzed retrospectively.Results Of the 30 patients,15 presented with acneiform eruptions,10 with eczematoid eruptions,2 with morbilliform rashes,1 with telangiectasia,1 with hand-foot skin reaction,9 with xerosis,7 with nail changes and 4 with hair changes.A patient with grade 4 acneiform eruptions showed a markedly elevated alanine transaminase (ALT) level (315 U/L).Mild ALT abnormalities (48.5-88.1 U/L) were found in 3 patients with grade 3 acneiform eruptions,1 with grade 2 acneiform eruptions,1 with grade 1 acneiform eruptions and 1 with eczematoid eruptions complicated by fever.Two patients with eczematoid eruptions and 1 with morbilliform rashes showed elevated proportions of peripheral blood eosinophils (0.057-0.303).Pathological changes of the acneiform eruptions included hyperkeratosis and dilation of hair follicles and neutrophilic infiltration.Pathological manifestations of eczematoid eruptions included different degrees of spongiosis,thickened spinous layer,irregular elongation of rete ridges and liquefaction degeneration of basal cells in the epidermis,and perivascular infiltration of lymphocytes and eosinophils in the superficial dermis.Patients with grade 1-3 acneiform eruptions received oral minocycline for 6 weeks,skin lesions gradually regressed,but relapse occurred after the withdrawal.After withdrawal of targeted antineoplastic agents and 2-week treatment with systemic glucocorticoids,skin lesions gradually regressed in patients with grade 4 acneiform eruptions,those with eczematoid eruptions complicated by fever,and those with morbilliform rashes.Skin rashes also resolved in patients with mild morbilliform rashes and those with mild eczematoid eruptions after 2 weeks of treatment with antianaphylactic agents and topical glucocorticoids.Oral antibiotics were effective for the treatment of periungual erythematous swelling or granulomas.Conclusion Tyrosine kinase inhibitor-related cutaneous adverse reactions include a constellation of disorders,and hepatic function can be impaired.

Objective To observe the inhibitory effect of quercetin on the biofilm formation of Streptococcus mutans(Sm),to preliminarily reveal the possible underlying mechanisms,and to evaluate the cytotoxicity of quercetion to human dental pulp cells so as to provide the theoretical basis for the application of quercetin in oral biomaterials.Methods Quercetin storage solution was diluted to 0,3.125,6.25,12.5,25,50,100,200,400 and 800 mg/L,and added into Sm medium for 4 h and 24 h,crystal violet staining was used to evaluate the biofilm volume.In subsequent detections,three groups were set:control(0 mg/L),200 mg/L quercetin and 400 mg/L quercetin.Confocal laser scanning microscopy was used to observe the morphology of the biofilm;qPCR for gtfB,gtfC,comD,comE,and luxS were assessed to preliminarily investigate the mechanisms.Finally,the methyl thiazolyl tetrazolium(MTT) test using human dental pulp cells was used to investigate cytotoxicity.Results Quercetin could significantly inhibit up to (86.16±0.45)％ of the biofilm formation of Sm (Compared with the control group P=0.00) and effectively removed (43.04±0.53)％ of the mature biofilm(Compared with the control group P=0.00).Confocal laser scanning microscopy photographs showed that after co-incubated for 24 h,the dense biofilm structures of the experimental group were destroyed by quercetin both at 200 mg/L and 400 mg/L.Quercetin suppressedover 50％ of the expression of gtfB,gtfC,comD,comE(compared with the control group P＜0.05) and promoted the expression of luxS up to 2.18 ±0.24 and 2.84±0.26 after 4 h and 24 h,respectively(compared with the control group P＜0.05).Quercetin also exhibited acceptable compatibility for human dental pulp cells.Conclusions Quercetin could effectively reduce the biofilm formation of Sm by inhibiting the expression of the related genes,and exhibited no cytotoxicity for human dental pulp cells.Quercetin has good potential to be applied in oral biological materials.