Chemical Constituents, Hypolipidemic, and Hypoglycemic Activities of Edgeworthia gardneri Flowers.

The flowers of Edgeworthia gardneri are used as herbal tea and medicine to treat various metabolic diseases including hyperglycemia, hypertension, and hyperlipidemia. This paper investigate the chemical constituents and biological activities of ethanolic extract and its different fractions from E. gardneri flowers. Firstly, the E. gardneri flowers was extracted by ethanol-aqueous solution to obtain crude extract (CE), which was subsequently fractionated by different polar organic solution to yield precipitated crystal (PC), dichloromethane (DCF), ethyl acetate (EAF), n-butanol (n-BuF), and residue water (RWF) fractions. UHPLC-ESI-HRMS/MS analysis resulted in the identification of 25 compounds, and the main compounds were flavonoids and coumarins. The precipitated crystal fraction showed the highest phenolic and flavonoid contents with 344.4 ± 3.38 mg GAE/g extract and 305.86 ± 0.87 mg RE/g extract. The EAF had the strongest antioxidant capacity and inhibitory effect on α-glucosidase and pancreatic lipase with IC50 values of 126.459 ± 7.82 and 23.16 ± 0.79 µg/mL. Besides, both PC and EAF significantly regulated the glucose and lipid metabolism disorders by increasing glucose consumption and reducing TG levels in HepG2 cells. Molecular docking results suggested that kaempferol-3-O-glucoside and tiliroside had good binding ability with enzymes, indicating that they may be potential α-glucosidase and pancreatic lipase inhibitors. Therefore, the E. gardneri flowers could be served as a bioactive agent for the regulation of metabolic disorders.

Mechanism and endoscopic-treatment-induced evolution of biliary non-anastomotic stricture after liver transplantation revealed by single-cell RNA sequencing.

BACKGROUND: Biliary complications, especially non-anastomotic stricture (NAS), are the main complications after liver transplantation. Insufficient sampling and no recognized animal models obstruct the investigation. Thus, the mechanisms and alterations that occur during endoscopic treatment (ET) of NAS remain unclear. METHODS: Samples were obtained with endoscopic forceps from the hilar bile ducts of NAS patients receiving continuous biliary stent implantation after diagnosis. Retrospective analysis of multiple studies indicated that the duration of ET for NAS was approximately 1-2 years. Thus, we divided the patients into short-term treatment (STT) and long-term treatment (LTT) groups based on durations of less or more than 1 year. Samples were subjected to single-cell RNA sequencing. Transcriptomic differences between STT and normal groups were defined as the NAS mechanism. Similarly, alterations from STT to LTT groups were regarded as endoscopic-treatment-induced evolution. RESULTS: In NAS, inflammation and immune-related pathways were upregulated in different cell types, with nonimmune cells showing hypoxia pathway upregulation and immune cells showing ATP metabolism pathway upregulation, indicating heterogeneity. We confirmed a reduction in bile acid metabolism-related SPP1+ epithelial cells in NAS. Increases in proinflammatory and profibrotic fibroblast subclusters indicated fibrotic progression in NAS. Furthermore, immune disorders in NAS were exacerbated by an increase in plasma cells and dysfunction of NK and NKT cells. ET downregulated multicellular immune and inflammatory responses and restored epithelial and endothelial cell proportions. CONCLUSIONS: This study reveals the pathophysiological and genetic mechanisms and evolution of NAS induced by ET, thereby providing preventive and therapeutic insights into NAS. HIGHLIGHTS: For the first time, single-cell transcriptome sequencing was performed on the bile ducts of patients with biliary complications. scRNA-seq analysis revealed distinct changes in the proportion and phenotype of multiple cell types during Nonanastomotic stricture (NAS) and endoscopic treatment. A reduction in bile acid metabolism-related SPP1+ epithelial cells and VEGFA+ endothelial cells, along with explosive infiltration of plasma cells and dysfunction of T and NK cells in NAS patients. SPP1+ macrophages and BST2+ T cells might serve as a surrogate marker for predicting endoscopic treatment.

Region-specific cellular and molecular basis of liver regeneration after acute pericentral injury.

Liver injuries often occur in a zonated manner. However, detailed regenerative responses to such zonal injuries at cellular and molecular levels remain largely elusive. By using a fate-mapping strain, Cyp2e1-DreER, to elucidate liver regeneration after acute pericentral injury, we found that pericentral regeneration is primarily compensated by the expansion of remaining pericentral hepatocytes, and secondarily by expansion of periportal hepatocytes. Employing single-cell RNA sequencing, spatial transcriptomics, immunostaining, and in vivo functional assays, we demonstrated that the upregulated expression of the mTOR/4E-BP1 axis and lactate dehydrogenase A in hepatocytes contributes to pericentral regeneration, while activation of transforming growth factor ß (TGF-ß1) signaling in the damaged area mediates fibrotic responses and inhibits hepatocyte proliferation. Inhibiting the pericentral accumulation of monocytes and monocyte-derived macrophages through an Arg-Gly-Asp (RGD) peptide-based strategy attenuates these cell-derived TGF-ß1 signalings, thus improving pericentral regeneration. Our study provides integrated and high-resolution spatiotemporal insights into the cellular and molecular basis of pericentral regeneration.

Novel 3D morphological characteristics for congenital biliary dilatation diagnosis: A case-control study.

BACKGROUND: Congenital biliary dilatation (CBD) necessitates the timely removal of dilated bile ducts. Accurate differentiation between CBD and secondary biliary dilatation (SBD) is crucial for treatment decisions, and identification of CBD with intrahepatic involvement is vital for surgical planning and supportive care. This study aimed to develop quantitative models based on bile duct morphology to distinguish CBD from SBD and further identify CBD with intrahepatic involvement. MATERIALS AND METHODS: The retrospective study included 131 CBD and 209 SBD patients between December 2014 and December 2021 for model development, internal validation and testing. A separate cohort of 15 CBD and 34 SBD patients between January 2022 and December 2022 was recruited for temporally-independent validation. Quantitative shape-based (Shape) and diameter-based (Diam) morphological characteristics of bile ducts were extracted to build a CBD diagnosis model to distinguish CBD from SBD and an intrahepatic involvement identification model to classify CBD with/without intrahepatic involvement. The diagnostic performance of the models was compared with that of experienced hepatobiliary surgeons. RESULTS: The CBD diagnosis model using clinical, Shape, and Diam characteristics showed good performance with an AUROC of 0.942 [95% CI: 0.890-0.994], AUPRC of 0.917 [0.855-0.979], accuracy of 0.891, sensitivity of 0.950 and F1-score of 0.864. The model outperformed two experienced surgeons in accuracy, sensitivity, and F1-score. The intrahepatic involvement identification model using clinical, Shape, and Diam characteristics yielded outstanding performance with an AUROC of 0.944 [0.879-1.000], AUPRC of 0.982 [0.947-1.000], accuracy of 0.932, sensitivity of 0.971 and F1-score of 0.957. The models demonstrated generalizable performance on the temporally-independent validation cohort. CONCLUSIONS: This study developed two robust quantitative models for distinguishing CBD from SBD and identifying CBD with intrahepatic involvement, respectively, based on morphological characteristics of the bile ducts, showing great potential in risk stratification and surgical planning of CBD.

Efficacy of radiotherapy in combined treatment of hepatocellular carcinoma patients with portal vein tumor thrombus: a real-world study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) has an extremely poor prognosis. A previous study proved that low-dose radiotherapy (RT) could prolong the prognosis of HCC patients with PVTT. This study aims to explore the sensitivity of PVTT to RT treatment. METHODS: Patients were selected based on imaging diagnosis of HCC accompanied by PVTT and received combined treatment of radiotherapy, antiangiogenic drugs and immune checkpoint inhibitors, followed by hepatectomy or liver transplantation from January 2019 to August 2022. The efficacy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and pathological assessment. The sensitivity of tumor cells to the treatment was compared between the primary tumor (PT)and PVTT by analyzing their residual tumor and pathologic complete remission (PCR) incidence. RESULTS: Data from 14 patients were collected in the study. After combined treatment, the size of PVTT decreased more significantly than that of the primary tumor in the imaging study (p < 0.05). The residual cancer was significantly more restrictive than that of primary tumor in paired patients based on pathological measurement (p = 0.008). The PCR incidence of the primary tumor (21.42%) was significantly lower (p = 0.008) than that of PVTT in the pathologic study (78.57%). CONCLUSION: PVTT is more sensitive to radiotherapy treatment than the primary tumor in patients with HCC. This combination therapy might be an effective option as a downstaging therapy for patients with HCC with PVTT.

Cucumber mosaic virus impairs the physiological homeostasis of Panax notoginseng and induces saponin-mediated resistance.

As an important medicinal plant, Panax notoginseng often suffers from various abiotic and biotic stresses during its growth, such as drought, heavy metals, fungi, bacteria and viruses. In this study, the symptom and physiological parameters of cucumber mosaic virus (CMV)-infected P. notoginseng were analyzed and the RNA-seq was performed. The results showed that CMV infection affected the photosynthesis of P. notoginseng, caused serious oxidative damage to P. notoginseng and increased the activity of several antioxidant enzymes. Results of transcriptome analysis and corresponding verification showed that CMV infection changed the expression of genes related to plant defense and promoted the synthesis of P. notoginseng saponins to a certain extent, which may be defensive ways of P. notoginseng against CMV infection. Furthermore, pretreatment plants with saponins reduced the accumulation of CMV. Thus, our results provide new insights into the role of saponins in P. notoginseng response to virus infection.

Comparing iodized oil with polyvinyl alcohol for portal vein embolization in promoting liver remnant increase before partial hepatectomy.

BACKGROUND: To compare the efficacy and safety of iodized oil versus polyvinyl alcohol (PVA) particles in portal vein embolization (PVE) before partial hepatectomy. METHODS: From October 2016 to December 2021, 86 patients who planned to undergo hepatectomy after PVE were enrolled, including 61 patients post-PVE with PVA particles + coils and 25 patients post-PVE with iodized oil + coils. All patients underwent CT examination before and 2-3 weeks after PVE to evaluate the future liver remnant (FLR). The intercohort comparison included the degree of liver volume growth, changes in laboratory data, and adverse events. RESULTS: There was no significant difference in the resection rate between the iodized oil group and the PVA particle group (68 % vs. 70 %, p = 0.822). In terms of the degree of hypertrophy (9.52 % ± 13.47 vs. 4.03 % ± 10.55, p = 0.047) and kinetic growth rate (4.07 % ± 5.4 vs. 1.55 % ± 4.63, p = 0.032), the iodized oil group was superior to the PVA group. The PVE operation time in the PVA particle group was shorter than that in the iodized oil group (121. 72 min ± 34.45 vs. 156. 2 min ± 71.58, p = 0.029). There was no significant difference in the degree of hypertrophy between the high bilirubin group and the control group (5.32 % ± 9.21 vs. 6.1 % ± 14.79, p = 0.764). Only 1 patient had a major complication. CONCLUSIONS: Compared with PVA particles, iodized oil PVE can significantly increase liver volume and the degree of hypertrophy without any significant difference in safety.

Targeting metabolic reprogramming in hepatocellular carcinoma to overcome therapeutic resistance: A comprehensive review.

Hepatocellular carcinoma (HCC) poses a heavy burden on human health with high morbidity and mortality rates. Systematic therapy is crucial for advanced and mid-term HCC, but faces a significant challenge from therapeutic resistance, weakening drug effectiveness. Metabolic reprogramming has gained attention as a key contributor to therapeutic resistance. Cells change their metabolism to meet energy demands, adapt to growth needs, or resist environmental pressures. Understanding key enzyme expression patterns and metabolic pathway interactions is vital to comprehend HCC occurrence, development, and treatment resistance. Exploring metabolic enzyme reprogramming and pathways is essential to identify breakthrough points for HCC treatment. Targeting metabolic enzymes with inhibitors is key to addressing these points. Inhibitors, combined with systemic therapeutic drugs, can alleviate resistance, prolong overall survival for advanced HCC, and offer mid-term HCC patients a chance for radical resection. Advances in metabolic research methods, from genomics to metabolomics and cells to organoids, help build the HCC metabolic reprogramming network. Recent progress in biomaterials and nanotechnology impacts drug targeting and effectiveness, providing new solutions for systemic therapeutic drug resistance. This review focuses on metabolic enzyme changes, pathway interactions, enzyme inhibitors, research methods, and drug delivery targeting metabolic reprogramming, offering valuable references for metabolic approaches to HCC treatment.

Microscale tissue engineering of liver lobule models: advancements and applications.

The liver, as the body's primary organ for maintaining internal balance, is composed of numerous hexagonal liver lobules, each sharing a uniform architectural framework. These liver lobules serve as the basic structural and functional units of the liver, comprised of central veins, hepatic plates, hepatic sinusoids, and minute bile ducts. Meanwhile, within liver lobules, distinct regions of hepatocytes carry out diverse functions. The in vitro construction of liver lobule models, faithfully replicating their structure and function, holds paramount significance for research in liver development and diseases. Presently, two primary technologies for constructing liver lobule models dominate the field: 3D bioprinting and microfluidic techniques. 3D bioprinting enables precise deposition of cells and biomaterials, while microfluidics facilitates targeted transport of cells or other culture materials to specified locations, effectively managing culture media input and output through micro-pump control, enabling dynamic simulations of liver lobules. In this comprehensive review, we provide an overview of the biomaterials, cells, and manufacturing methods employed by recent researchers in constructing liver lobule models. Our aim is to explore strategies and technologies that closely emulate the authentic structure and function of liver lobules, offering invaluable insights for research into liver diseases, drug screening, drug toxicity assessment, and cell replacement therapy.

The public-private partnerships in healthcare sector in China.

This manuscript is a narrative review on experience in the healthcare public-private partnerships (PPP) field project in China. The PPP model allows healthcare officials to share the risk of building new facilities with the private sector. The objective of this study is to evaluate and to review the PPP of healthcare sector in China, and to investigate the critical success factors and best practice of PPP. We adapted the PPP evaluation framework of the World Bank Independent Evaluation Group as our conceptual framework to summarize the literatures. The current study systematically reviewed the evolution and current status of public and private hospitals development in China, and to investigate factors related to the successful and less successful deployment and performance of PPP in the healthcare sector of China, and to develop best practice models of PPP among hospitals of China. We found that the PPP organizations providing finance and political risk coverage, thus enabling specific PPP transactions to reach financial closure-potentially setting demonstration effects. Such PPPs may then contribute to improving access to infrastructure and social services, which drives economic growth and other optimal outcomes.

Effectiveness and Safety of the PD-1 Inhibitor Lenvatinib Plus Radiotherapy in Patients with HCC with Main PVTT: Real-World Data from a Tertiary Centre.

Background: Patients with hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT), especially type Vp-4, usually have a poor prognosis. However, the vast majority of Phase III clinical trials exclude this population based on the inclusion criteria. Lenvatinib plus a PD-1 inhibitor has shown promising antitumour activity and tolerable safety in patients with unresectable HCC in Asian populations. Radiotherapy has also demonstrated high response rates and favourable survival for HCC patients with PVTT. This study aimed to explore the preliminary clinical efficacy and safety of lenvatinib plus the PD-1 inhibitor combined with radiotherapy for HCC patients with main portal vein tumour thrombus. Methods: Between 1 March 2018 and 31 October 2020, HCC patients with main PVTT who received lenvatinib plus a PD-1 inhibitor (pembrolizumab, nivolumab or sintilimab) combined with radiotherapy from Beijing Tsinghua Changgung Hospital in China were reviewed for eligibility. The efficacy was evaluated by the survival and PVTT response rate, and the safety was evaluated by the frequency of key adverse events (AEs). Results: In total, 39 eligible HCC patients with type Vp-4 PVTT who received triple therapy were included in this study. The 2-year OS rate was 15.4%, which was the primary end-point of our study. The median overall survival (OS) and progression-free survival (PFS) were 9.4 months (range 2.3 to 57.1) and 4.9 months (range 1.4 to 36.1), respectively. The objective response rate (ORR) of PVTT based on mRECIST was 61.5%. AFP dropped to normal 3 months after radiotherapy and was an independent risk factor associated with OS. All AEs were controlled, and no treatment-related deaths occurred. Conclusion: Lenvatinib plus PD-1 inhibitor combined with radiotherapy had a significant therapeutic effect and manageable AEs in HCC patients with type Vp-4 PVTT and may be a potential treatment option for advanced HCC.

Incorporation of protein induced by vitamin K absence or antagonist-II into transplant criteria expands beneficiaries of liver transplantation for hepatocellular carcinoma: a multicenter retrospective cohort study in China.

INTRODUCTION: In order to maximize the utilization of precious donor liver, precisely determining potential hepatocellular carcinoma (HCC) candidates who will benefit from liver transplantation (LT) is essential. As a crucial diagnostic biomarker for HCC, protein induced by vitamin K absence or antagonist-II (PIVKA-II) has become one of the key indicators for assessing tumor recurrence risk after LT. This study aims to investigate the role of PIVKA-II in recipient selection and prognostic stratification. METHODS: The clinicopathologic data of HCC patients undergoing LT from 2015 to 2020 in six Chinese transplant centers were collected. Univariate and multivariate analyses were performed to determine risk factors for disease free survival (DFS). Based on these risk factors, survival analysis was made by Kaplan-Meier method and their value in prognostic stratification was assessed. RESULTS: A total of 522 eligible HCC patients with pre-LT PIVKA-II records were finally included in this study. Tumor burden>8 cm, α-fetoprotein>400 ng/ml, histopathologic grade III and PIVKA-II>240 mAU/ml were identified as independent risk factors for DFS. DFS of patients with PIVKA-II≤240 mAU/ml ( N =288) were significantly higher than those with PIVKA-II>240 mAU/ml ( N =234) (1-year, 3-year, and 5-year DFS: 83.2, 77.3, and 75.9% vs. 75.1, 58.5, and 50.5%; P <0.001). Compared with Hangzhou criteria ( N =305), incorporating PIVKA-II into Hangzhou criteria (including tumor burden, α-fetoprotein, and histopathologic grade) increased the number of patients with eligibility for LT by 21.6% but achieved comparable DFS and overall survival. CONCLUSIONS: Incorporating PIVKA-II into existing LT criteria could increase the number of eligible HCC patients without compromising post-LT outcomes.

Lipid droplet deposition in the regenerating liver: A promoter, inhibitor, or bystander?

Liver regeneration (LR) is a complex process involving intricate networks of cellular connections, cytokines, and growth factors. During the early stages of LR, hepatocytes accumulate lipids, primarily triacylglycerol, and cholesterol esters, in the lipid droplets. Although it is widely accepted that this phenomenon contributes to LR, the impact of lipid droplet deposition on LR remains a matter of debate. Some studies have suggested that lipid droplet deposition has no effect or may even be detrimental to LR. This review article focuses on transient regeneration-associated steatosis and its relationship with the liver regenerative response.

Predicting the outcomes of hepatocellular carcinoma downstaging with the use of clinical and radiomics features.

BACKGROUND: Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment. METHODS: Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes. RESULTS: Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively. CONCLUSIONS: The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment.

Genome-wide identification, characterization and transcriptional profile of the SWEET gene family in Dendrobium officinale.

BACKGROUND: Dendrobium officinale Kimura et Migo (D. officinale) is a well-known traditional Chinese medicine with high content polysaccharides in stems. The SWEET (Sugars Will Eventually be Exported Transporters) family is a novel class of sugar transporters mediating sugar translocation among adjacent cells of plants. The expression patterns of SWEETs and whether they are associated with stress response in D. officinale remains uncovered. RESULTS: Here, 25 SWEET genes were screened out from D. officinale genome, most of which typically contained seven transmembrane domains (TMs) and harbored two conserved MtN3/saliva domains. Using multi-omics data and bioinformatic approaches, the evolutionary relationship, conserved motifs, chromosomal location, expression patterns, correlationship and interaction network were further analyzed. DoSWEETs were intensively located in nine chromosomes. Phylogenetic analysis revealed that DoSWEETs were divided into four clades, and conserved motif 3 specifically existed in DoSWEETs from clade II. Different tissue-specific expression patterns of DoSWEETs suggested the division of their roles in sugar transport. In particular, DoSWEET5b, 5c, and 7d displayed relatively high expression levels in stems. DoSWEET2b and 16 were significantly regulated under cold, drought, and MeJA treatment, which were further verified using RT-qPCR. Correlation analysis and interaction network prediction discovered the internal relationship of DoSWEET family. CONCLUSIONS: Taken together, the identification and analysis of the 25 DoSWEETs in this study provide basic information for further functional verification in D. officinale.

Highly Tough and Biodegradable Poly(ethylene glycol)-Based Bioadhesives for Large-Scaled Liver Injury Hemostasis and Tissue Regeneration.

Conventional tissue adhesives face challenges for hemostasis and tissue regeneration in large-scaled hemorrhage and capillary hypobaric bleeding due to weak adhesion, and inability to degrade at specific sites. Herein, convenient and injectable poly(ethylene glycol) (PEG)-based adhesives are developed to address the issues for liver hemostasis. The PEG-bioadhesives are composed of tetra-armed PEG succinimide glutarate (PEG-SG), tetra-armed PEG amine (PEG-NH2 ), and tri-lysine. By mixing the components, the PEG-bioadhesives can be rapidly formulated for use of liver bleeding closure in hepatectomy. The PEG-bioadhesives also possess mechanical compliance to native tissues (elastic modulus ≈40 kPa) and tough tissue adhesion (≈28 kPa), which enables sufficient adhering to the injured tissues and promotes liver regeneration with the PEG-bioadhesive degradation. In both rats of liver injury and pigs of large-scaled hepatic hemorrhage, the PEG-bioadhesives show effective hemostasis with superior blood loss than conventional tissue adhesives. Due to biocompatibility and degradability, the PEG-bioadhesive is advantageous for liver regeneration, while commercial adhesives (e.g., N-octyl cyanoacrylate) display adhesion failure and limited liver reconstructions. These PEG-bioadhesive components are FDA-approved, and demonstrate excellent adhesion to various tissues not only for liver hemostasis, it is a promising candidate in biomedical translations and clinical applications.

Identification, molecular characterization and phylogenetic analysis of a novel nucleorhabdovirus infecting Paris polyphylla var. yunnanensis.

A novel betanucleorhabdovirus infecting Paris polyphylla var. yunnanensis, tentatively named Paris yunnanensis rhabdovirus 1 (PyRV1), was recently identified in Yunnan Province, China. The infected plants showed vein clearing and leaf crinkle at early stage of infection, followed by leaf yellowing and necrosis. Enveloped bacilliform particles were observed using electron microscopy. The virus was mechanically transmissible to Nicotiana bethamiana and N. glutinosa. The complete genome of PyRV1 consists of 13,509 nucleotides, the organization of which was typical of rhabdoviruses, containing six open reading frames encoding proteins N-P-P3-M-G-L on the anti-sense strand, separated by conserved intergenic regions and flanked by complementary 3'-leader and 5'-trailer sequences. The genome of PyRV1 shared highest nucleotide sequence identity (55.1%) with Sonchus yellow net virus (SYNV), and the N, P, P3, M, G, and L proteins showed 56.9%, 37.2%, 38.4%, 41.8%, 56.7%, and 49.4% amino acid sequence identities with respective proteins of SYNV, suggesting RyRV1 belongs to a new species of the genus Betanucleorhabdovirus.

Hotspots and difficulties of biliary surgery in older patients.

ABSTRACT: With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.

Data-Driven Assisted Decision Making for Surgical Procedure of Hepatocellular Carcinoma Resection and Prognostic Prediction: Development and Validation of Machine Learning Models.

Background: Currently, surgical decisions for hepatocellular carcinoma (HCC) resection are difficult and not sufficiently personalized. We aimed to develop and validate data driven prediction models to assist surgeons in selecting the optimal surgical procedure for patients. Methods: Retrospective data from 361 HCC patients who underwent radical resection in two institutions were included. End-to-end deep learning models were built to automatically segment lesions from the arterial phase (AP) of preoperative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Clinical baseline characteristics and radiomic features were rigorously screened. The effectiveness of radiomic features and radiomic-clinical features was also compared. Three ensemble learning models were proposed to perform the surgical procedure decision and the overall survival (OS) and recurrence-free survival (RFS) predictions after taking different solutions, respectively. Results: SegFormer performed best in terms of automatic segmentation, achieving a Mean Intersection over Union (mIoU) of 0.8860. The five-fold cross-validation results showed that inputting radiomic-clinical features outperformed using only radiomic features. The proposed models all outperformed the other mainstream ensemble models. On the external test set, the area under the receiver operating characteristic curve (AUC) of the proposed decision model was 0.7731, and the performance of the prognostic prediction models was also relatively excellent. The application web server based on automatic lesion segmentation was deployed and is available online. Conclusions: In this study, we developed and externally validated the surgical decision-making procedures and prognostic prediction models for HCC for the first time, and the results demonstrated relatively accurate predictions and strong generalizations, which are expected to help clinicians optimize surgical procedures.

Free-breathing simultaneous water-fat separation and T1 mapping of the whole liver (SWALI) with isotropic resolution using 3D golden-angle radial trajectory.

Background: Conventional liver T1 mapping techniques are typically performed under breath-holding conditions; they have limited slice coverage and often rely on multiple acquisitions. Furthermore, liver fat affects the accuracy of T1 quantification. Therefore, we aim to propose a free-breathing technique for simultaneous water-fat separation and T1 mapping of the whole liver (SWALI) in a single scan. Methods: The proposed SWALI sequence included an inversion recovery (IR) preparation pulse followed by a series of multiecho three-dimensional (3D) golden-angle radial acquisitions. For each echo time (TE), a series of images containing a mix of water and fat were reconstructed using a sliding window method. For each inversion time (TI), water and fat were separated, and then water and fat T1 estimation was conducted. The fat fraction (FF) was calculated based on the last TI image. The FF and water T1 quantification accuracy were compared with the gold standard sequences in the phantom. The in vivo feasibility was tested in 9 healthy volunteers, 2 patients with fatty liver, and 3 patients with hepatocellular carcinoma (HCC). The reproducibility was evaluated in the patients with fatty liver and in the healthy volunteers. Results: The mean FF and the mean water T1 values obtained by the SWALI sequence showed good agreements with chemical shift-encoded magnetic resonance imaging (CSE-MRI; r=0.998; P<0.001) and fat-suppressed (FS) IR-spin echo (SE; r=0.997; P<0.001) in the phantom. For the patients with fatty liver and the healthy volunteers, the SWALI sequence showed no significant difference with CSE-MRI in FF quantification (P=0.53). In T1 quantification, comparable T1 values were obtained with the SWALI sequence and modified Look-Locker inversion recovery (MOLLI; P=0.10) in healthy volunteers, while the water T1 estimated by the SWALI sequence was significantly lower than the water-fat compound T1 estimated by MOLLI (P<0.001) in patients with fatty liver. In the reproducibility study, the intraclass correlation coefficients (ICCs) for the estimated FF and water T1 were 0.997 and 0.943, respectively. Water T1 of the patients with HCC calculated using the SWALI sequence showed a significant reduction after the contrast administration (P<0.001). Conclusions: Free-breathing water-fat separation and T1 mapping of the whole liver with 2.5 mm isotropic spatial resolution were achieved simultaneously using the SWALI sequence in a 5-min scan.