Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Various dynasties of herbs and prescription books recorded the specifications, processing, and clinical application of Schisandrae Chinensis Fructus. The clinical application of Schisandrae Chinensis Fructus mainly focuses on astringency, tonifying qi and generating fluids, nourishing the kidneys and calming the heart. There have been few reports on the exploration on textual study on other functions and usage precautions of Schisandrae Chinensis Fructus; at present, the classic prescriptions containing Schisandrae Chinensis Fructus do not clearly indicate their specific specifications and processing in the prescription composition. Textual study has found that different processed products of Schisandrae Chinensis Fructus have different clinical therapeutic effects. For raw use, it is more suitable to use light agents to bring adversely risen qi downward, steam to produce light agents to increase transparency, honey to produce leveling agents is better for moistening the lungs and nourishing yin, wine honey to produce leveling agents can supplement deficiency and promote blood circulation, wine to produce heavy agents can strengthen acid absorption. It is suggested further in-depth research on steamed products, honey products, and honey wine products to broaden clinical application options and improve the accuracy of clinical medication. The clinical application of Schisandrae Chinensis Fructus has different emphases and evolution in different dynasties. In the Tang Dynasty, Schisandrae Chinensis Fructus could reduce the qi of the upper, middle, and lower energizers, and eliminate deficiency heat; during the Five Dynasties period, Schisandrae Chinensis Fructus could nourish qi, improve eyesight, warm the middle, and bring adversely risen qi downward; During the Jin and Yuan dynasties, Schisandrae Chinensis Fructus was used to warm water and treat cholera, as well as to improve muscle function; in the Ming Dynasty, Schisandrae Chinensis Fructus was proposed to reduce qi and strengthen yin, treating the critical condition of yin and yang deficiency; during the Qing Dynasty, Schisandrae Chinensis Fructus could prevent summer heat, and external application to sores could astringent and invigorate the muscles. Schisandrae Sphenantherae Fructus has records of dispersing phlegm and fire, and dispelling wind pathogens. This article reviewed the relevant records of Schisandrae Chinensis Fructus in traditional Chinese herbs and prescriptions throughout history, summarized the efficacy characteristics of Schisandrae Chinensis Fructus under different processing methods, clinical applications under historical evolution, and main contraindications for use, proposed recommendations for the application of Schisandrae Chinensis Fructus in classic and commonly used prescriptions, which can provide scientific basis for the precise selection of different specifications and processed products of Schisandrae Chinensis Fructus and Schisandrae Sphenantherae Fructus, as well as scientific guidance for their rational application in drug development.

Objective:To explore the efficacy and safety of brain radiotherapy combined with pyrotinib and capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases.Methods:Clinical data of 30 HER2-positive breast cancer patients with brain metastases treated at the Fourth Hospital of Hebei Medical University between January 2018 and January 2024 were retrospectively analyzed. According to the timing of drug administration, patients were divided into the concurrent radiotherapy and medication group ( n=20) and the sequential group receiving pyrotinib plus capecitabine within 1 month before or after radiotherapy ( n=10). Intracranial progression-free survival (iPFS), intracranial and extracranial objective response rates (ORR), overall survival (OS), and treatment safety were analyzed. Survival curves were plotted using the Kaplan-Meier method, and survival differences were compared by log-rank test. Results:The median follow-up time was 23.5 months (range, 5.2-37.8), with a median iPFS of 13.0 months (range, 1.7-27.3) and a median OS of 28.2 months (range, 7.3-46.2). The 1-year iPFS and OS in the concurrent radiotherapy with pyrotinib and capecitabine group were numerically higher than those in the sequential group treated within 1 month before or after radiotherapy, but the differences were not statistically significant ( P=0.825, 0.724, respectively). The intracranial and extracranial ORRs were 83.3% and 64.3%, respectively. The most common grade ≥3 treatment-related adverse reactions were diarrhea (27%) and neutropenia (23%). Conclusions:Radiotherapy combined with pyrotinib and capecitabine provides prolonged survival benefits with acceptable safety in patients with HER2-positive breast cancer brain metastases. Compared to concurrent administration, pyrotinib plus capecitabine given within 1 month before or after radiotherapy does not appear to affect prognosis.

Objective To explore the factors affecting the occurrence of transient arrhythmia after percuta-neous coronary intervention(PCI)in patients with acute coronary syndromes(ACS),to establish a risk prediction model,and to test the prediction effect.Methods 480 ACS patients who underwent PCI in Western Theater Air Force Hospital of PLA from August 2022 to February 2024 were selected as study subjects and were divided into 336 cases in the construct group and 144 cases in the validation group according to the ratio of 7:3.The data of the construct group were used to construct the model,and the validation group was used to validate the model.The patients in the constructed group were divided into 84 cases in the occurrence group and 252 cases in the non-occurrence group according to whether they had experienced postoperative transient arrhythmia,and the validation group was divided into 36 cases in the occurrence group and 108 cases in the non-occurrence group.The baseline data of the study subjects in the two groups were observed,and the predictive value of continuous variables was analyzed using the ROC experiment;the influencing factors of the occurrence of transient arrhythmia after PCI in ACS patients were analyzed using multifactorial logistic regression;the Nomogram prediction model was constructed using the R language;and the model was evaluated and validated using calibration curves and decision curves.Results The results of a one-way analysis of the constructed group showed that older age,the presence of a history of diabetes mellitus,the time from onset to admission≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS(P<0.05),and the prediction model established accordingly had an AUC of 0.865 and a 95%CI of 0.804～0.927,which was effective in predicting the occurrence of transient arrhythmia after PCI in patients with ACS.The model performed well in predicting the occurrence of transient arrhythmia after PCI,with a C-index of 0.858(0.753～0.865),and provided a good stan-dardized net benefit when its risk threshold was between 0.10 to 0.96.The validation group ROC curve and calibra-tion curve results are good,with an AUC of 0.846 and a C-index of 0.840(0.737～0.851),suggesting that the model has a good external predictive efficacy.The results of the validation group decision curve analysis indicated that the model could provide better standardized net returns when the risk threshold was between 0.06 and 0.94.Conclusion The results of univariate analysis showed that older age,the presence of a history of diabetes melli-tus,onset-to-admission time≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS,and the Nomogram model constructed on the basis of these four influenc-ing factors could effectively predict the risk of transient arrhythmia after PCI in patients with ACS.

A 36-year-old male developed unconsciousness and no response to voice stimuli after taking approximately 2 050 mg felodipine (the specific time was unknown). Two hours later, he was sent to the department of emergency by his family and admitted to the hospital. His vital signs showed body temperature 35.1 ℃, pulse 148 times/min, respiration 32 times/min, and blood pressure 65/34 mmHg. Acute drug poisoning, acute toxic cardiomyopathy, acute toxic shock, acute type Ⅱ respiratory failure, acute toxic encephalopathy, and acute renal failure were diagnosed based on the patient′s clinical manifestations combined with laboratory tests results, cardiac ultrasound, chest and abdominal CT scans. Endotracheal intubation connected to a ventilator for invasive assisted ventilation, pressure boosting, and fluid resuscitation were given. At the same time, repeated gastric lavage and enema were performed to remove toxins. Blood perfusion was intermittently and repeatedly administered, and continuous renal replacement therapy was used. The blood concentration of felodipine was 1 298 μg/L at 2 hours after admission, and cardiac arrest occurred at 4 hours. Venous-arterial extracorporeal membrane oxygenation (V-A ECMO) treatment was administered immediately. After 48 hours of ECMO operation, sedatives were discontinued and the patient′s consciousness was improved after 4 hours. On the 5th day of ECMO treatment, his heart rate was 72 beats per minute, and blood pressure was 127/65 mmHg. The blood concentration of felodipine decreased to 2 μg/L. The patient′s vital signs were significantly improved and ECMO supportive treatment was withdrawn. After 26 days of hospitalization, the patient recovered and was discharged.

Flow diverter (FD) devices have gradually become the mainstream approach for interventional treatment of intracranial aneurysms. In-stent stenosis (ISS) is a common complication after FD implantation, which can lead to ischemic events and affect the prognosis of patients. Current studies have shown that ISS occurrence is closely related to hemodynamic changes. From the perspective of hemodynamics, this article reviews the research progress of mechanisms, evaluation methods and treatments of ISS after FD implantation, in order to provide reference for clinical practice.

A 36-year-old male developed unconsciousness and no response to voice stimuli after taking approximately 2 050 mg felodipine (the specific time was unknown). Two hours later, he was sent to the department of emergency by his family and admitted to the hospital. His vital signs showed body temperature 35.1 ℃, pulse 148 times/min, respiration 32 times/min, and blood pressure 65/34 mmHg. Acute drug poisoning, acute toxic cardiomyopathy, acute toxic shock, acute type Ⅱ respiratory failure, acute toxic encephalopathy, and acute renal failure were diagnosed based on the patient′s clinical manifestations combined with laboratory tests results, cardiac ultrasound, chest and abdominal CT scans. Endotracheal intubation connected to a ventilator for invasive assisted ventilation, pressure boosting, and fluid resuscitation were given. At the same time, repeated gastric lavage and enema were performed to remove toxins. Blood perfusion was intermittently and repeatedly administered, and continuous renal replacement therapy was used. The blood concentration of felodipine was 1 298 μg/L at 2 hours after admission, and cardiac arrest occurred at 4 hours. Venous-arterial extracorporeal membrane oxygenation (V-A ECMO) treatment was administered immediately. After 48 hours of ECMO operation, sedatives were discontinued and the patient′s consciousness was improved after 4 hours. On the 5th day of ECMO treatment, his heart rate was 72 beats per minute, and blood pressure was 127/65 mmHg. The blood concentration of felodipine decreased to 2 μg/L. The patient′s vital signs were significantly improved and ECMO supportive treatment was withdrawn. After 26 days of hospitalization, the patient recovered and was discharged.

Objective To explore the factors affecting the occurrence of transient arrhythmia after percuta-neous coronary intervention(PCI)in patients with acute coronary syndromes(ACS),to establish a risk prediction model,and to test the prediction effect.Methods 480 ACS patients who underwent PCI in Western Theater Air Force Hospital of PLA from August 2022 to February 2024 were selected as study subjects and were divided into 336 cases in the construct group and 144 cases in the validation group according to the ratio of 7:3.The data of the construct group were used to construct the model,and the validation group was used to validate the model.The patients in the constructed group were divided into 84 cases in the occurrence group and 252 cases in the non-occurrence group according to whether they had experienced postoperative transient arrhythmia,and the validation group was divided into 36 cases in the occurrence group and 108 cases in the non-occurrence group.The baseline data of the study subjects in the two groups were observed,and the predictive value of continuous variables was analyzed using the ROC experiment;the influencing factors of the occurrence of transient arrhythmia after PCI in ACS patients were analyzed using multifactorial logistic regression;the Nomogram prediction model was constructed using the R language;and the model was evaluated and validated using calibration curves and decision curves.Results The results of a one-way analysis of the constructed group showed that older age,the presence of a history of diabetes mellitus,the time from onset to admission≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS(P<0.05),and the prediction model established accordingly had an AUC of 0.865 and a 95%CI of 0.804～0.927,which was effective in predicting the occurrence of transient arrhythmia after PCI in patients with ACS.The model performed well in predicting the occurrence of transient arrhythmia after PCI,with a C-index of 0.858(0.753～0.865),and provided a good stan-dardized net benefit when its risk threshold was between 0.10 to 0.96.The validation group ROC curve and calibra-tion curve results are good,with an AUC of 0.846 and a C-index of 0.840(0.737～0.851),suggesting that the model has a good external predictive efficacy.The results of the validation group decision curve analysis indicated that the model could provide better standardized net returns when the risk threshold was between 0.06 and 0.94.Conclusion The results of univariate analysis showed that older age,the presence of a history of diabetes melli-tus,onset-to-admission time≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS,and the Nomogram model constructed on the basis of these four influenc-ing factors could effectively predict the risk of transient arrhythmia after PCI in patients with ACS.