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This study aimed to investigate the safety and effect of omitting chest tubes after thoracoscopic lobectomy in children with congenital lung malformation. A multicenter retrospective study was performed with 632 thoracoscopic lobectomy CLM patients in four hospitals between 2014.1 and 2023.1, which were divided into non-chest tube (NCT)group and chest tube (CT)group. Baseline data, operation and follow-up outcomes were compared. In total, 312 patients were included in the NCT group, and 320 in the CT group. There were no statistically significant differences in baseline data between the two groups. The FLACC scale score in the NCT group was less than the CT group (2.7 ± 0.43 vs. 5.8 ± 0.26 p = 0.027). The median length of postoperative hospital stay in the CT group was significantly longer than the NCT group (5 d vs.3 d, p = 0.045). Eight (2.5%) patients developed chest tube related infections in the CT group(p = 0.004). Six patients developed atelectasis in the NCT group, which was significantly less than the 18 patients in the CT group(p = 0.014). No chest tube placement in selected CLM pediatric patients may be safe and avoid chest tube-related complications, which may also contribute to a rapid recovery., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Statement of informed consent: Informed consent was obtained from all individual participants included in the study. Ethics approval: This study was approved by the Institutional Review Board and Ethical Committee of West China Hospital of Sichuan University in China (No.1284)., (© 2024. The Author(s).)

Up to half of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage, for which effective treatment options are lacking, resulting in a poor prognosis. Over the past few years, the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has proven highly efficacious in treating advanced HCC, significantly extending patients' survival and providing a potential for sequential curative surgery. After sequential curative hepatectomy or liver transplantation following conversion therapy, patients can receive long-term survival benefits. In order to improve the long-term survival rate of the overall population with liver cancer and achieve the goal of a 15% increase in the overall 5-year survival rate outlined in the Healthy China 2030 blueprint, the Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association, Chinese Society of Liver Cancer, and the Liver Study Group of Surgery Committee of Beijing Medical Association organized in-depth discussions among relevant domestic experts in the field. These discussions focused on the latest progress since the release of the Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2021 Edition) and resulted in a new consensus on the modifications and supplements to related key points. This consensus aims to further guide clinical practice, standardize medical care, and promote the development of the discipline.

Background: Indocyanine green (ICG) is a near-infrared fluorescent dye widely used for intraoperative navigation during liver surgeries because of its non-radioactive nature, high safety, and minimal impact on liver function. However, variability in its dosage and concentration and its low imaging success rates have limited its widespread application. To address these issues, we developed a novel ICG-human serum albumin (ICG-HSA) complex to enhance fluorescence visualization during laparoscopic anatomical liver resection., Methods: This prospective, double-blind, single-center, randomized controlled trial will compare the fluorescence navigation effects of the novel ICG-HSA complex with the guideline-recommended ICG administration scheme. The study will involve patients aged 18 to 75 years with malignant liver tumors. The participants will undergo evaluations at specified time points, and data will be collected using an internet-based electronic data capture system. The primary outcome will be the effectiveness of intraoperative fluorescence imaging, assessed by three independent experts. The secondary outcomes will be conversion to open surgery, the total operative time, intraoperative blood loss, and long-term survival rates., Discussion: The aim of using this novel ICG-HSA complex will be to improve the success rate of fluorescence navigation in liver resection by ensuring better stability and a longer liver retention time compared with free ICG. This study seeks to validate the clinical value of ICG-HSA in enhancing surgical precision and outcomes, ultimately promoting its broader clinical application. The results are expected to provide high-level evidence supporting the safety and efficacy of this new fluorescence imaging agent., Trial Registration: ClinicalTrial.gov NCT06219096. Registered on 1 December 2024., Competing Interests: Declarations. Ethics approval and consent to participate: This prospective study was approved by the Medical Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (Ethics number: 2023 review (2121)). All methods were carried out in accordance with relevant guidelines and regulations. Research involving human participants, human material, or human data is conducted in accordance with the Declaration of Helsinki. The authors confirmed that informed consent was obtained from all subjects. Consent for publication: Not applicable. Competing interests: All of the results will be published. There are no financial interests in this trial and none of the parties concerned has right of veto., (© 2024. The Author(s).)

Background: The intensifying global aging population exacerbates the serious shortage of nurses, placing immense pressure on the healthcare system worldwide. Overwhelming workloads, limited career development opportunities, and high turnover rates among nurses compound these challenges. Career aspiration is closely related to individual active work behavior and career orientation, and is significant for stabilizing the nursing team. Identifying different subgroups of career aspiration among intern nursing students and analyzing the influencing factors can provide tailored support and interventions for their career development, contributing to addressing the global nursing shortage and shaping the future of the nursing profession., Aims: To identify different subgroups of career aspiration among intern nursing students and to analyze the related factors of the different subgroups., Methods: This secondary analysis relied upon a cross-sectional study conducted in China among 521 nursing students during clinical practice. Latent profile analysis was used to identify subgroups of career aspiration among intern nursing students, and multivariate logistic regression was used to analyze factors influencing their career aspiration. The Career Aspiration Scale, General Demographic Information Questionnaire, and the Nursing Students Clinical Practice Poor Adaptation Scale were utilized as measures., Results: There were four different subgroups of career aspiration, namely the "Moderate career aspiration type (33.7%)", "High leadership expectations-low effort type (11.6%)", "High professional development-low educational aspiration type (28.9%)", "High aspiration multidimensional leader-scholar type (25.8%)". School classification and clinical practice poor adaptation were significantly related factors for the four subgroups (all p < 0.05). Female significantly influenced the "high professional development-low educational aspiration type" (p < 0.001). Students' origin, grade point average, and student leadership experience significantly influenced the "high aspiration multidimensional leader-scholar type" (all p < 0.05)., Conclusions: This study has identified four distinct subgroups of career aspiration among Chinese intern nursing students and their influencing factors. These findings demonstrate the heterogeneity within the intern nursing student population, provide an effective supplement with a more in-depth analysis to the previous research and underscore the need for tailored educational approaches in clinical practice. By nurturing nursing students' career aspiration, a stable and competent nursing workforce will be cultivated to meet future healthcare demands and propel the advancement of the nursing profession., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Minimally invasive surgeries are increasingly central to modern medicine, particularly in liver transplantation. These techniques, which offer reduced trauma, precise operations, minimal bleeding, and swift recovery, are, however, unevenly adopted across China. Only a limited number of centers routinely perform minimally invasive donor hepatectomies, indicating a significant imbalance in the development and application of these advanced procedures. Additionally, there lacks a set of standardized guidelines that are tailored to meet China's unique healthcare challenges and conditions., Methods: In August 2023, the Branch of Organ Transplant of Chinese Medical Association and the Branch of Organ Transplant Physicians of Chinese Medical Doctor Association convened a group of national liver transplantation experts to establish a guideline development committee. This committee conducted a thorough review of relevant literature, evaluated existing guidelines and consensus, and assessed factors such as the evidence base, patient preferences, and the cost-effectiveness of interventions within China. After multiple rounds of discussions, both online and offline, the committee finalized the guidelines., Results: This collaborative effort led to the creation of the "Chinese guidelines for minimally invasive donor hepatectomy in living donor liver transplantation (2024 edition)". These guidelines address crucial aspects such as the safety and advantages of minimally invasive surgery for living donor liver transplantation, donor selection criteria, anesthesia strategies, surgical technical details, and learning curves associated with these procedures, resulting in a comprehensive set of 26 recommendations., Conclusions: The formulation of these guidelines represents a significant advancement towards standardizing minimally invasive liver transplantation surgeries in China. They are designed to enhance outcomes for both donors and recipients by synthesizing expert consensus with contemporary research and clinical practices. Moreover, they serve as a crucial reference for surgeons and medical institutions, promoting the refinement and adoption of minimally invasive surgical techniques in liver transplantation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-329/coif). S.D. serves as an unpaid editorial board member of HepatoBiliary Surgery and Nutrition. Z.G. serves as an unpaid Assistant Editor of HepatoBiliary Surgery and Nutrition. Jiayin Yang reports grants from National Key R&D Program of China (No. 2022YFC2304705); National Natural Science Foundation of China (No. 82270691); Sichuan Province Key Research and Development Project (No. 2023YFS0026); and Chengdu Province Key Research and Development Project (No. 2022YF0900009SN). The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Preaxial polydactyly (PPD) is a congenital limb malformation, previously reported to be caused primarily by variants in the ZRS and upstream preZRS regions. This study investigated genetic variations associated with PPD, focusing on point variants and copy number variations (CNVs) in the ZRS and preZRS regions. Comprehensive genetic analyses were conducted on 102 patients with PPD, including detailed clinical examinations and Sanger sequencing of the ZRS and preZRS regions. Additionally, real-time quantitative PCR (qPCR) was used to detect CNVs in the ZRS region. The evolutionary conservation and population frequencies of identified variants were also evaluated. Six point variants were identified, among which four are likely pathogenic novel variants: 93G > T (g.156584477G > T), 106G > A (g.156584464G > A), 278G > A (g.156584292G > A), and 409A > C (g.156585378A > C). Additionally, qPCR analysis revealed that 66.67% of patients exhibited ZRS duplications. Notably, these duplications were also present in cases with newly identified potential pathogenic point variants. These findings suggest the possible interaction of point variants in ZRS and preZRS through a common pathogenic mechanism, leading jointly to PPD. The findings expand the variant spectrum associated with non-syndromic polydactyly and highlight that, despite different classifications, anterior polydactyly caused by variants in ZRS and nearby regions may share common pathogenic mechanisms. The incorporation of various variant types in genetic screening can effectively enhance the rate of pathogenic variant detection and contribute to the cost-effectiveness of genetic testing for limb developmental defects, thereby promoting healthy births., Competing Interests: Declarations Conflict of interest The authors declare no competing interests. Consent to publish The authors affirm that human research participants provided informed consent for publication of the images in Fig. 1b., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging. Furthermore, we observed that IgG could induce a pro-senescent state in macrophages and microglia, thereby exacerbating tissue aging, and that targeted reduction of IgG mitigated aging across various tissues in male mice. This study provides a high-resolution spatial depiction of aging and indicates the pivotal role of immunoglobulin-associated senescence during the aging process., Competing Interests: Declaration of interests Y.G., C.N., Y.S., Z.L., H.D., and F.W. are employees of BGI. J.C.I.B. and C.R.E. are employees of Altos Labs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Current biliary dilatation (BD) classifications are complex and based on cases including secondary BD, leading to unclear distinctions. Notably, congenital and secondary BD differ in etiology, symptoms, and prognosis., Objective: To propose a more concise and more suitable classification of congenital biliary dilatation (CBD), and exploring the feasibility and effectiveness of this classification in diagnosis and treatment., Methods: Based on the preoperative imaging data of patients with CBD admitted to the Department of Pediatric Surgery of West China Hospital of Sichuan University, from January 2015 to December 2018, a new classification of CBD was accomplished according to the site of bile duct dilatation lesions, which was named HUAXI CBD classification. The CBD was classified into 4 types: type I (distal extra-hepatic bile duct dilatation), type II (distal extra-hepatic combined with right and left primary hepatic bile duct dilatation), type III (extra-hepatic combined with secondary and above hepatic bile duct dilatation), and type IV (intra-hepatic bile duct dilatation). Meanwhile, the feasibility and reliability of the HUAXI CBD classification were analyzed by analyzing the clinical treatment strategies, perioperative complications and long-term follow-up results of different subtypes., Results: A total of 300 patients with CBD were included in this study. According to the HUAXI CBD classification method, 240 cases were type I, 48 cases were type II, 10 cases were type III, and 2 cases were type IV. After treatment, patients with type I had a normal hepatobiliary function after surgery and a good prognosis; patients with type II had good recovery of liver function in 37 cases (77.1%), but 11 cases (22.9%) had postoperative complications during follow-up; patients with type III and IV had high incidence of cholangitis (6/10, 2/2, respectively) and choledocholithiasis (5/10, 2/2, respectively) after surgery, especially those with diffuse intrahepatic dilatation having a poor prognosis, eventually developing cirrhosis and necessitating liver transplantation., Conclusions: The HUAXI CBD classification is consistent with treatment principles, concise and easy to remember, and more suitable for CBD clinical application., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the ethics committee of West China hospital of Sichuan university (approval no.202411). We certify that the study was performed in accordance with the 1964 declaration of HELSINKI and later amendments. Consent for publication Written informed consent was obtained from the patient for publication of this study and any accompanying images. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study aimed to investigate the feasibility and efficacy of near-infrared fluorescence-guided laparoscopic anatomical hepatectomy (LAH) using a novel indocyanine green (ICG)-human serum albumin complex (HSA) in patients with hepatocellular carcinoma., Methods: Clinical data of hepatocellular carcinoma patients who underwent ICG-HSA fluorescence-guided LAH at our center from January 2024 to April 2024 were prospectively collected and analyzed. Ultraviolet absorption spectroscopy was used to test the absorption and stability of ICG-HSA complex solutions under different conditions. After determining the optimal ratio, the complex was administered intravenously during surgery to perform negative staining via Glissonean pedicle isolation. LAH was performed along the fluorescence-demarcated boundaries., Results: Thirty-one patients were included (24 men; mean age, 54.61 ± 13.54 years). The median maximum tumor diameter was 2.80 (interquartile range [IQR], 2.00-4.00) cm. S8 segmentectomy (22.6%) and right posterior segmentectomy (19.4%) were the most common resections performed. Successful fluorescence negative staining was achieved in all patients using ICG and HSA at a 1:6 molar ratio at room temperature. Mean operation time was 297.58 ± 85.53 min, Median intraoperative blood loss was 100.0 mL (IQR, 50.0-200.0). The median surgical margin distance was 0.90 cm (IQR, 0.40-1.50). The postoperative complication rate was 45.2% (35.5% Clavien-Dindo grade I and 9.7% grade II). The median length of hospital stay was 5.0 days (IQR, 4.0-5.0)., Conclusion: ICG-HSA-assisted LAH is safe and feasible. Compared with free ICG, the novel ICG-HSA complex exhibits better optical properties and in vivo stability, which can improve the accuracy of intraoperative liver segment localization and optimize the anatomical dissection plane. It has the potential to become an ideal fluorescent imaging agent for anatomical hepatectomy., (© 2024. The Author(s).)

Background: Congenital lung malformation (CLM) is usually characterized by single-lobe involvement and multilobe involvement is uncommon. There is a lack of experience in the clinical features and surgical treatment of unilateral multilobar CLM. Therefore, this study aims to summarize the clinical characteristics and evaluate the safety and feasibility of thoracoscopic lung sparing resection in the treatment of unilateral multilobar CLM., Methods: A retrospective study was conducted on 34 patients with unilateral multilobar CLM, and 34 unilobar patients were randomly selected as the control group in West China Hospital of Sichuan University from 2014.1 to 2021.1. Clinical, operation and follow-up outcomes were compared between the two groups., Results: Twelve (35.2%) patients developed preoperative symptoms in the multilobar group more than 4(11.7%) the unilobar group (p = 0.02), the main preoperative symptom was infection; The multilobar group and unilobar group showed significant differences in mean intraoperative blood loss (13.3 mL vs. 7.5 mL; p = 0.02) and mean surgical time (95.6 min vs. 47.5 min; p = 0.037). The median length of postoperative hospital stay and the median chest tube placement time in the multilobar group were significantly longer (5 d vs.3 d, p = 0.045; 2 d vs.1 d, p = 0.031). There were one (2.9%) patient in unilobar group and 4(11.7%) patients in multilobar group developed complications postoperatively, which is no significant differences between the two groups(p = 0.16). No complications such as thoracic deformity, mediastinal deviation, scoliosis or recurrence were observed in either group at follow-up., Conclusions: Unilateral multilobar CLM cases are more susceptible to develop symptoms than unilobar cases. Thoracoscopic lung sparing resection in the treatment of unilateral multilobar CLM has high safety and can effectively avoid serious complications of unilateral multiple lobectomy or pneumonectomy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Gallbladder cancer (GBC) is a highly aggressive malignancy, with limited survival profiles after curative surgeries. This study aimed to develop a practical model for predicting the postoperative overall survival (OS) in GBC patients., Methods: Patients from three hospitals were included. Two centers (N = 102 and 100) were adopted for model development and internal validation, and the third center (N = 85) was used for external testing. Univariate and stepwise multivariate Cox regression were used for feature selection. A nomogram for 1-, 3-, and 5-year postoperative survival rates was constructed accordingly. Performance assessment included Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. Kaplan-Meier curves were utilized to evaluate the risk stratification results of the nomogram. Decision curves were used to reflect the net benefit., Results: Eight factors, TNM stage, age-adjusted Charlson Comorbidity Index (aCCI), body mass index (BMI), R0 resection, blood platelet count, and serum levels of albumin, CA125, CA199 were incorporated in the nomogram. The time-dependent C-index consistently exceeded 0.70 from 6 months to 5 years, and time-dependent ROC revealed an area under the curve (AUC) of over 75% for 1-, 3-, and 5-year survival. The calibration curves, Kaplan-Meier curves and decision curves also indicated good prognostic performance and clinical benefit, surpassing traditional indicators TNM staging and CA199 levels. The reliability of results was further proved in the independent external testing set., Conclusions: The novel nomogram exhibited good prognostic efficacy and robust generalizability in GBC patients, which might be a promising tool for aiding clinical decision-making., (© 2024. The Author(s).)

Background: The Nurses' Cancer Pain Management Competency Scale (NCPMCS) is a tool to explore nurses' competencies and subjective experiences in cancer pain management, and to help nurses understand their current shortcomings in cancer pain management. The scale, currently available only in English and translated into Chinese for wider adoption abroad, provides a tool for Chinese nurses to assess their level of cancer pain management. Furthermore, based on the scale's specific score, they can evaluate their lack of understanding about cancer pain management, advance research into this area, and enhance their capacity to control cancer pain while providing patient care., Objective: The purpose of this study was to translate and localize the new scale, and to measure its reliability and validity. The study was also to provide a way to quickly and accurately measure the competency of cancer pain management among nursing staff in China., Methods: The Bristling translation approach was used to translate, translate back, and culturally modify the English version of the cancer pain management competency scale for nurses to create the Chinese version. A convenience sample was used for the study, 220 clinical nurses from three Grade III hospitals in Zhengzhou, Henan Province, China, were chosen by convenience sampling. The Chinese version of the scale was used for this investigation., Results: The Cancer Pain Management Competency Scale for Nurses has 14 items over 4 dimensions in its Chinese form. From the exploratory factor analysis, four common components were recovered; the cumulative variance rate was 81.994%, the scale's Cronbach's α coefficient was 0.902, and the Cronbach's α coefficient for each dimension ranged from 0.800 to 0.938. Retest reliability was 0.915, scale content validity was 0.865, and Spearman-Brown's broken half reliability was 0.808., Conclusion: Nurses' cancer pain management competency in clinics can be assessed using the Chinese version of the Nurses' Cancer Pain Management Competency Scale, which has strong validity and reliability., (Copyright © 2024. Published by Elsevier Inc.)

Background and Aims: The practice of intraoperative blood salvage and autotransfusion (IBSA) during deceased donor liver transplantation for hepatocellular carcinoma (HCC) can potentially reduce the need for allogeneic blood transfusion. However, implementing IBSA remains debatable due to concerns about its possible detrimental effects on oncologic recurrence., Methods: This study retrospectively enrolled nationwide recipients of deceased donor liver transplantation for HCC between 2015 and 2020. The focus was on comparing the cumulative recurrence rate and the recurrence-free survival rate. Propensity score matching was conducted repeatedly for further subgroup comparison. Recipients were categorized based on the Milan criteria, macrovascular invasion, and pretransplant α-Fetoprotein (AFP) level to identify subgroups at risk of HCC recurrence., Results: A total of 6196 and 329 patients were enrolled in the non-IBSA and IBSA groups in this study. Multivariable competing risk regression analysis identified IBSA as independent risk factors for HCC recurrence ( P <0.05). Postmatching, the cumulative recurrence rate and recurrence-free survival rate revealed no significant difference in the IBSA group and non-IBSA group (22.4 vs. 16.5%, P =0.12; 60.3 vs. 60.9%, P =0.74). Recipients beyond Milan criteria had higher, albeit not significant, risk of HCC recurrence if receiving IBSA (33.4 vs. 22.5%, P =0.14). For recipients with macrovascular invasion, the risk of HCC recurrence has no significant difference between the two groups (32.2 vs. 21.3%, P =0.231). For recipients with an AFP level <20 ng/ml, the risk of HCC recurrence was comparable in the IBSA group and the non-IBSA group (12.8 vs. 18.7%, P =0.99). Recipients with an AFP level ≥20 ng/ml, the risk of HCC recurrence was significantly higher in the IBSA group. For those with an AFP level ≥400 ng/ml, the impact of IBSA on the cumulative recurrence rate was even more pronounced (49.8 vs. 21.9%, P =0.011)., Conclusions: IBSA does not appear to be associated with worse outcomes for recipients with HCC exceeding the Milan criteria or with macrovascular invasion. IBSA could be confidently applied for recipients with a pretransplant AFP level <20 ng/ml. For recipients with AFP levels ≥20 ng/ml, undertaking IBSA would increase the risk of HCC recurrence., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The recent focus on the roles of N-linked glycoproteins in carcinogenesis across various malignancies has prompted our exploration of aberrantly expressed glycoproteins responsible for HCC progression and potential therapeutic strategy., Methods: Mass spectrometry was applied to initially identify abnormally expressed glycoproteins in HCC, which was further assessed by immunohistochemistry (IHC) staining. The role of selected glycoprotein on HCC development and underlying mechanism was systematically investigated by colony formation, mouse xenograft, RNA-sequencing and western blot assays, etc. Chromatin immunoprecipitation (ChIP) and luciferase assays were performed to explore potential transcription factors (TFs) of selected glycoprotein. The regulation of repaglinide (RPG) on expression of lumican and downstream effectors was assessed by western blot and IHC, while its impact on malignant phenotypes of HCC was explored through in vitro and in vivo analyses, including a murine NASH-HCC model established using western diet and carbon tetrachloride (CCl 4 )., Results: Lumican exhibited upregulation in both serum and tumor tissue, with elevated expression associated with an inferior prognosis in HCC patients. Knockdown of lumican resulted in significantly reduced growth of HCC in vitro and in vivo. Mechanically, lumican promoted HCC malignant phenotypes by inhibiting the p53/p21 signaling pathway. Forkhead Box O3 (FOXO3) was identified as the TF of lumican that transcriptionally enhanced its expression. Without silencing FOXO3, RPG blocked the binding of FOXO3 to the promoter region of lumican, thereby inhibiting the activation of lumican/p53/p21 axis. Mice treated with RPG developed fewer and smaller HCCs than those in the control group at 24 weeks after establishment., Conclusion: Our results indicate that RPG prevented the development and progression of HCC via alteration of FOXO3/lumican/p53 axis., (© 2024. Springer Nature Switzerland AG.)

Hypophosphatemic vitamin D-resistant rickets typically presents in infancy or early childhood with skeletal deformities and growth plate abnormalities. In this report, the SMUSHi005-A human induced pluripotent stem cell (hiPSC) line was successfully established from the PBMCs of a female patient carrying the PHEX mutation with c.1586-1586+1 delAG. The iPSC line has been confirmed to have a normal karyotype. The displayed cells clearly exhibit characteristics similar to embryonic stem cells, expressing pluripotency markers and demonstrating the ability to differentiate into three germ layers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Portal hypertension (PHT) has been proven to be closely related to the development of hepatocellular carcinoma (HCC). Whether PHT before liver transplantation (LT) will affect the recurrence of HCC is not clear., Methods: 110 patients with depressurization of the portal vein (DPV) operations (Transjugular Intrahepatic Portosystemic Shunt-TIPS, surgical portosystemic shunt or/and splenectomy) before LT from a HCC LT cohort, matched with 330 preoperative non-DPV patients; this constituted a nested case-control study. Subgroup analysis was based on the order of DPV before or after the occurrence of HCC., Results: The incidence of acute kidney injury and intra-abdominal bleeding after LT in the DPV group was significantly higher than that in non-DPV group. The 5-year survival rates in the DPV and non-DPV group were 83.4% and 82.7% respectively (P = 0.930). In subgroup analysis, patients in the DPV prior to HCC subgroup may have a lower recurrence rate (4.7% vs.16.8%, P = 0.045) and a higher tumor free survival rate (88.9% vs.74.4%, P = 0.044) after LT under the up-to-date TNMI-II stage, while in TNM III stage, there was no difference for DPV prior to HCC subgroup compared with the DPV after HCC subgroup or the non-DPV group., Conclusion: Compared with DPV after HCC, DPV treatment before HCC can reduce the recurrence rate of HCC after early transplantation (TNM I-II). DPV before LT can reduce the recurrence of early HCC., (© 2024. The Author(s).)

Background: Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC., Methods: In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; < 60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon's two-stage design, > 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy., Results: Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6-51.9) and 90.3% (56/62, 95% CI, 80.1-96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8-not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7-94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients., Conclusions: Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC., Trial Registration: ClinicalTrials.gov (NCT04401800)., (© 2024. The Author(s).)

Background: Impact of preoperative infection on liver transplantation (LT) needs further investigation., Materials and Methods: From 1 January 2015 to 31 December 2022, 24 122 eligible patients receiving LT were enrolled from the China Liver Transplant Registry database. The outcomes of LT were compared after using the propensity score-matched analysis., Results: Compared to the noninfection group, patients in the infection group were more likely to have postoperative effusion, infection, abdominal bleeding, and biliary complications (all P <0.01), and they had shorter 30-day, 90-day survival, and overall survival (all P <0.01). Cox proportional hazards regression analysis revealed that MELD score and cold ischemia time were risk factors for the overall survival in the infection group (both P <0.05). Besides, compared to the nonpulmonary group, patients in the pulmonary group were more likely to have postoperative effusion and infection (both P <0.0001), and less likely to have postoperative abscess and early allograft dysfunction (both P <0.05). Patients in the nonabdominal group also had a higher proportion of postoperative infection than those in the abdominal group ( P <0.05). Furthermore, compared to the number=1 group, patients in the number ≥2 group were more prone to postoperative effusion and infection (both P <0.01), and they also had shorter 30-day and 90-day survival (both P <0.05)., Conclusion: Preoperative infection can result in a higher incidence of early postoperative complications and shorter survival in liver transplant recipients. The types and number of infection sites will also influence the prognosis of liver transplant recipients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

CRISPR/Cas9 technology, combined with somatic cell nuclear transplantation (SCNT), represents the primary approach to generating gene-edited pigs. The inefficiency in acquiring gene-edited nuclear donors is attributed to low editing and delivery efficiency, both closely linked to the selection of CRISPR/Cas9 forms. However, there is currently no direct method to evaluate the efficiency of CRISPR/Cas9 editing in porcine genomes. A platform based on fluorescence reporting signals and micropattern arrays was developed in this study, to visually assess the efficiency of gene editing. The optimal specifications for culturing porcine cells, determined by the quantity and state of cells grown on micropattern arrays, were a diameter of 200 µm and a spacing of 150 µm. By visualizing the area of fluorescence loss and measuring the gray value of the micropattern arrays, it was quickly determined that the mRNA form targeting porcine cells exhibited the highest editing efficiency compared to DNA and Ribonucleoprotein (RNP) forms of CRISPR/Cas9. Subsequently, four homozygotes of the β4GalNT2 gene knockout were successfully obtained through the mRNA form, laying the groundwork for the subsequent generation of gene-edited pigs. This platform facilitates a quick, simple, and effective evaluation of gene knockout efficiency. Additionally, it holds significant potential for swiftly testing novel gene editing tools, assessing delivery methods, and tailoring evaluation platforms for various cell types., (© 2024 Wiley‐VCH GmbH.)

Recent studies suggest that circular RNA (circRNA)-mediated post-translational modification of RNA-binding proteins (RBP) plays a pivotal role in metastasis of hepatocellular carcinoma (HCC). However, the specific mechanism and potential clinical therapeutic significance remain vague. This study attempts to profile the regulatory networks of circRNA and RBP using a multi-omics approach. Has&#95;circ&#95;0006646 (circ0006646) is an unreported circRNA in HCC and is associated with a poor prognosis. Silencing of circ0006646 significantly hinders metastasis in vivo. Mechanistically, circ0006646 prevents the interaction between nucleolin (NCL) and the E3 ligase tripartite motif-containing 21 to reduce the proteasome-mediated degradation of NCL via K48-linked polyubiquitylation. Furthermore, the change of NCL expression is proven to affect the phosphorylation levels of multiple proteins and inhibit p53 translation. Moreover, patient-derived tumor xenograft and lentivirus injection, which is conducted to simulate clinical treatment confirmed the potential therapeutic value. Overall, this study describes the integrated multi-omics landscape of circRNA-mediated NCL ubiquitination degradation in HCC metastasis and provides a novel therapeutic target., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Introduction: Gene-edited pigs have become prominent models for studying human disease mechanisms, gene therapy, and xenotransplantation. CRISPR (clustered regularly interspaced short palindromic repeats)/CRISPR-associated 9 (CRISPR/Cas9) technology is a widely employed tool for generating gene-edited pigs. Nevertheless, delivering CRISPR/Cas9 to pre-implantation embryos has traditionally posed challenges due to its reliance on intricate micromanipulation equipment and specialized techniques, resulting in high costs and time-consuming procedures. This study aims to introduce a novel one-step approach for generating genetically modified pigs by transducing CRISPR/Cas9 components into pre-implantation porcine embryos through oviductal injection of recombinant adeno-associated viruses (rAAV). Methods: We first used rAAV-1, rAAV-6, rAAV-8, rAAV-9 expressing EGFP to screen for rAAV serotypes that efficiently target porcine embryos, and then, to achieve efficient expression of CRISPR/Cas9 in vivo for a short period, we packaged sgRNAs targeting the GHR genes to self-complementary adeno-associated virus (scAAV), and Cas9 proteins to single-stranded adeno-associated virus (ssAAV). The efficiency of porcine embryos -based editing was then validated in vitro . The feasibility of this one-step method to produce gene-edited pigs using rAAV-CRISPR/Cas9 oviductal injection into sows within 24 h of conception was then validated. Results: Our research firstly establishes the efficient delivery of CRISPR/Cas9 to pig zygotes, both in vivo and in vitro , using rAAV6. Successful gene editing in pigs was achieved through oviductal injection of rAAV-CRISPR/Cas9. Conclusion: This method circumvents the intricate procedures involved in in vitro embryo manipulation and embryo transfers, providing a straightforward and cost-effective approach for the production of gene-edited pigs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gao, He, Zhu, Peng, Zhou, Deng, Liao, Ni, Li, Gao, Bu, Yang, Yang, Yang and Bao.)

Adrenal glands, vital for steroid secretion and the regulation of metabolism, stress responses and immune activation, experience age-related decline, impacting systemic health. However, the regulatory mechanisms underlying adrenal aging remain largely uninvestigated. Here we established a single-nucleus transcriptomic atlas of both young and aged primate suprarenal glands, identifying lipid metabolism and steroidogenic pathways as core processes impacted by aging. We found dysregulation in centripetal adrenocortical differentiation in aged adrenal tissues and cells in the zona reticularis region, responsible for producing dehydroepiandrosterone sulfate (DHEA-S), were highly susceptible to aging, reflected by senescence, exhaustion and disturbed hormone production. Remarkably, LDLR was downregulated in all cell types of the outer cortex, and its targeted inactivation in human adrenal cells compromised cholesterol uptake and secretion of dehydroepiandrosterone sulfate, as observed in aged primate adrenal glands. Our study provides crucial insights into endocrine physiology, holding therapeutic promise for addressing aging-related adrenal insufficiency and delaying systemic aging., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: Sex-specific differences are observed in various liver diseases, but the influence of sex on the outcomes of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains to be determined. This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC., Methods: Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed. The associations between donor, recipient, or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching (PSM). The survival associated with different sex-based donor-recipient transplant patterns was further studied., Results: Among 3,769 patients enrolled in this study, the 1-, 3-, and 5-year overall survival (OS) rates of patients with HCC after LT were 96.1%, 86.4%, and 78.5%, respectively, in female recipients, and 95.8%, 79.0%, and 70.7%, respectively, in male recipients after PSM ( P = 0.009). However, the OS was comparable between recipients with female donors and male donors. Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival (HR = 1.381, P = 0.046). Among the donor-recipient transplant patterns, the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival ( P < 0.05)., Conclusions: Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients, and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival. Livers from male donors may provide the most benefit to female recipients. Our results indicate that sex should be considered as a critical factor in organ allocation., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2024 The Authors.)

Objective: The acquisition of real-time portal vein pressure (PVP) is important for portal hypertension (PH) discrimination to monitor disease progress and select treatment options. To date, the PVP evaluation approaches are either invasive or noninvasive but with less stability and sensitivity., Methods: We customized an open ultrasound scanner to explore in vitro and in vivo the ultrasound contrast agent SonoVue microbubbles' subharmonic characteristics with acoustic pressure and local ambient pressure, and obtained promising results of PVP measurements in canine models with induced PH by ligation or embolization of portal vein., Results: In in vitro experiments, the highest correlations between the subharmonic amplitude of SonoVue microbubbles and ambient pressure were observed at acoustic pressures of 523 kPa and 563 kPa (r = -0.993, -0.993, P<0.05, respectively). The correlation coefficients between absolute subharmonic amplitudes and PVP (10.7-35.4 mmHg) were the highest among existing studies using microbubbles as pressure sensors (r values ranged from -0.819 to -0.918). The PH (>16 mmHg) diagnostic capacity also achieved a high level (563 kPa, sensitivity = 93.3%, specificity = 91.7%, accuracy = 92.6%)., Conclusion: This study proposes a promising measurement for PVP with the highest accuracy, sensitivity, and specificity in an in vivo model compared to existing studies. Future investigations are planned to assess the feasibility of this technique in clinical practice., Significance: This is the first study that comprehensively investigates the role of the subharmonic scattering signals from SonoVue microbubbles in evaluating PVP in vivo. It represents a promising alternative to invasive measurements for portal pressure.

Metastasis of hepatoblastoma (HB) is a key factor that impairs the prognosis and treatment of children. The suppressor of cytokine signaling 2 (SOCS2) is a classical negative feedback protein that regulates cytokine signal transduction and has been known to be downregulated in several tumor, but the molecular mechanisms of its involvement in HB metastasis are unknown. We found that SOCS2 was a gene down-regulated in hepatoblastoma and associated with HB metastasis through bioinformatics. The qRT-PCR, Western blot and IHC showed that SOCS2 was significantly lower in HB tissues. Clinicopathological correlation analysis revealed that low expression of SOCS2 was significantly correlated with tumor metastasis (P = 0.046) and vascular invasion (P = 0.028), associated with poor prognosis. Overexpression of SOCS2 inhibited the migration and invasion of hepatoblastoma cells, while knockdown of SOCS2 expression promoted these malignant phenotypes. In vivo studies revealed overexpression of SOCS2 inhibited the formation of lung metastasis. Up-regulation of SOCS2 in HB cell inhibited EMT and JAK2/STAT5. Conversely, down-regulation of SOCS2 promoted EMT and JAK2/STAT5. The addition of the JAK2 inhibitor Fedratinib partially reversed the effects of si-SOCS2 on HB cells. SOCS2 may inhibit the migration and invasion of HB cells by inhibiting the JAK2/STAT5 signaling pathway. These results may provide guiding significance for the clinical treatment of HB., (© 2023. The Author(s).)

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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Salvage liver transplantation (SLT) has been reported to be an efficient treatment option for patients with recurrent hepatocellular carcinoma (HCC) after liver resection (LR). However, for recipients who underwent liver transplantation (LT) due to recurrent HCC after LR in China, the selection criteria are not well established., Methods: In this study, data from the China Liver Transplant Registry (CLTR) of 4,244 LT performed from January 2015 to December 2019 were examined, including 3,498 primary liver transplantation (PLT) and 746 SLT recipients. Propensity score matching (PSM) analysis was used to minimize between-group imbalances. The overall survival (OS) and disease-free survival (DFS) between PLT and SLT in recipients fulfilling the Milan or Hangzhou criteria were compared based on the multivariate analysis, nomograms were plotted to further classify the SLT group into low- and high-risk groups., Results: In this study, the 1-, 3- and 5-year OS and DFS of SLT recipients fulfilling Milan criteria (OS, P=0.01; DFS, P<0.001) or Hangzhou criteria (OS, P=0.03; DFS, P=0.003) were significantly reduced when compared to that of PLT group after PSM analysis. Independent risk factors, including preoperative transarterial chemoembolization (TACE), alpha fetoprotein (AFP) level, tumor maximum size and tumor total diameter were selected to draw a prognostic nomogram. The low-risk SLT recipients (1-year, 95.34%; 3-year, 84.26%; 5-year, 77.20%) showed a comparable OS with PLT recipients fulfilling Hangzhou criteria (P=0.107)., Conclusions: An optimal nomogram model for prognosis stratification and clinical decision guidance of SLT was established. The low-risk SLT recipients based on the nomograms showed comparable survival with those fulfilling Hangzhou criteria in PLT group., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-22-304/coif). Q.X. serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare., (2023 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Aims: Serum uric acid (SUA) levels have been previously linked to a higher risk of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D) according to various observational studies. However, whether this association is causally linked or simply influenced by confounding factors is unclear. Therefore, this study utilized Mendelian randomization (MR) analysis to explore the causality between SUA levels and the risk of CVD in individuals with T2D., Methods: Our study cohort consisted of 5723 participants who were diagnosed with T2D in the National Health and Nutrition Examination Survey (NHANES) from 1999-2018. The study assessed the association between SUA levels and the risk of CVD using a multivariable logistic regression model. To further examine causality between SUA levels and CVD, a two-sample MR study was conducted utilizing genetic data from genome-wide association studies (GWAS) involving over 140,000 individuals. The main MR analysis employed the inverse-variance-weighted (IVW) method. Additionally, several sensitivity analyses were performed to evaluate the robustness and pleiotropy of the results., Results: In the cross-sectional study, after multivariable adjustment, participants with SUA levels >6.7 mg/dL exhibited odds ratios (ORs) of 1.51 (95% CI: 1.01-2.26, p=0.049) for heart failure, 1.02 (95% CI: 0.69-1.50, p=0.937) for coronary heart disease, 1.36 (95% CI: 0.78-2.38, p=0.285) for angina, and 1.22 (95% CI: 0.80-1.85, p=0.355) for myocardial infarction when compared to participants with SUA levels ≤ 4.6 mg/dL. However, in the IVW analysis, no causality between SUA levels and the risk of heart failure was observed (OR = 1.03, 95% CI: 0.97-1.09, p = 0.293). The secondary analysis yielded similar results (OR = 1.05, 95% CI: 0.96-1.14, p = 0.299). The sensitivity analyses further supported our primary findings., Conclusion: Based on the MR study, we did not find supporting evidence for a causal association between SUA levels and the risk of heart failure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 He, Feng, Zhang, Wu, Zhou, He, Zheng and Yang.)

Background/purpose: Congenital biliary dilatation (CBD) is a bile duct malformation often associated with pancreaticobiliary maljunction. Different subtypes of CBD have been noted for clinical differences, but their pathogenic mechanisms are unclear., Methods: To elucidate the genetic basis of CBD, we performed lncRNA and mRNA sequencing and bioinformatic analysis on 18 cystic and 18 fusiform CBD samples., Results: We identified differentially expressed mRNAs and lncRNAs between the two types of CBD, and constructed coexpression modules that correlated with clinical characteristics of CBD using weighted gene coexpression network analysis. We found that the brown module was the highest positive correlation with fusiform CBD (R = 0.67, p = 7.9e-6) and contained the most genes. We then built a lncRNA-mRNA coexpression network to identify potential target genes of lncRNAs in CBD, and a protein-protein interaction network to investigate the hub genes from the target genes and the brown module. Finally, we performed enrichment analyses and found differences between cystic and fusiform CBD in hepatobiliary system development, liver and pancreas development involving hub genes ONECUT1 and HNF1B that could be regulated by corresponding lncRNAs., Conclusion: Our study suggests that lncRNAs may modulate pancreaticobiliary duct development differently in cystic and fusiform CBD, providing new insights for etiology studies and clinical treatment., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Introduction: Hepatoblastoma (HB) is a malignant liver tumor predominantly found in children and tumor metastasis is one of the main causes of poor prognosis in affected patients. The precise molecular mechanisms responsible for HB metastasis remain incompletely understood. However, there is evidence suggesting a connection between the dysregulation of microRNAs (miRNAs) and the progression of tumor metastasis in HB., Methods: The study utilized weighted gene co-expression network analysis (WGCNA) to analyze a miRNA microarray dataset of HB. The expression of miR-181b-5p in HB tissues and cells was detected using quantitative real-time PCR. The impact of miR-181b-5p on the metastatic capacity of HB was evaluated through scratch and Transwell assays. The effects of exogenously expressing miR-181b on the metastatic phenotypes of HB cells were evaluated in vivo . Furthermore, a luciferase reporter assay was performed to validate a potential target of miR-181b-5p in HB., Results: We found that miR-181b-5p was highly expressed in HB tissues and HB cell lines. Overexpression of miR-181b enhanced scratch healing, cell migration, and invasion abilities in vitro , as well as enhancing HB lung metastasis potential in vivo . Dual-luciferase reporter assays showed that Suppressor Of Cytokine Signaling 2 (SOCS2) was a direct target of miR-181b. The overexpression of miR-181b resulted in the suppression of SOCS2 expression, subsequently activating the epithelial-mesenchymal transition and JAK2/STAT5 signaling pathways. The rescue experiment showed that SOCS2 overexpression attenuated the effects of miR-181b on HB cells., Conclusion: Our study showed that miR-181b promotes HB metastasis by targeting SOCS2 and may be a potential therapeutic target for HB., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.)

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary liver cancer with a high mortality rate and imposes a huge burden on patients and society. Recently, ubiquitin‑specific protease 35 (USP35) was found to be involved in cell proliferation and mitosis, but its role in HCC remains largely unknown. The expression of USP35 in HCC and its association with patient prognosis in the study cohort and public databases was analyzed in the present study. The effects of USP35 on the malignant biological behavior of HCC were analyzed by cellular functional experiments. Mechanistically, the effect of USP35 deubiquitylation on the M2 splice isoform of pyruvate kinase (PKM2) and on the Warburg effect of tumor cells were verified by western blotting and ubiquitination assay. The results of the present study demonstrated that USP35 is highly expressed in HCC and its high expression is significantly associated with poor prognosis of patients with HCC. In the present study, it was also demonstrated that inhibiting the expression of USP35 can impair the malignant properties (proliferation, migration and invasion) of HCC tumor cells by elevating the ubiquitination level of PKM2, the deubiquitinated form of which is critical for glycolysis in tumor cells. The present study therefore indicated that USP35 may be a target in the treatment of HCC.

Background: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear., Methods: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted., Results: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways., Conclusions: GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Objective: To investigate the relationship between thrombin-antithrombin complex (TAT), plasmin-α 2 -plasmininhibitor complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (tPAIC) and postoperative complications in the early stage after liver transplantation (LT)., Methods: We analyzed the perioperative clinical data, including plasma TAT, PIC, sTM, and tPAIC, of 130 post-LT patients admitted to the intensive care unit (ICU), West China Hospital, Sichuan University between December 2021 and November 2022. Patients were divided into two groups, a complication group and a non-complication group, according to whether they experienced complications of Clavien-Dindo (CD) grade Ⅲb and above within 30 days after the surgery. Univariate analysis and binary multivariate logistic regression models were used to determine the risk factors for complications within 30 days post-LT., Results: The incidence of complications of CD grade Ⅲb and above within 30 days post-LT was 33.1% (43/130). Patients in the complication group had significantly higher scores for the Model for End-Stage Liver Disease (MELD), operative time, intraoperative red blood cell transfusion volume, intraoperative plasma transfusion volume, and plasma TAT, PIC, sTM and tPAIC measured at the time of admission to ICU after the operation than those in the non-complication group did (all P <0.05). Logistic regression showed that for every single U of red blood cells transfused during the transplant surgery, the probabilities of complications within 30 days post-LT increased by 15.1% (95% confidence interval [ C I ]: 1.070-1.239, P <0.001) and for the increase of every single TU/mL of plasma sTM measured upon post-LT admission to ICU, the probabilities of complications increased by 13.7% (95% CI : 1.060-1.220, P <0.001)., Conclusion: Plasma sTM measured upon admission to ICU after LT is an independent risk factor for complications within 30 days post-LT, and additional assessment of sTM may help predict complications in the early stage post-LT., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Lipoprotein(a) (Lp[a]) is a particle consisting of a low-density lipoprotein (LDL)-like core connected to an apolipoprotein(a) chain, which is an established risk factor for cardiovascular disease. However, studies addressing the relationship between atrial fibrillation (AF) and Lp(a) demonstrated conflicted results. Thus, we sought to evaluate this relationship by conducting this systemic review and meta-analysis. We performed a comprehensive systematic search of health science databases, including PubMed, Embase, Cochrane Library, Web of Science, MEDLINE, and ScienceDirect, to identify all relevant literature from their inception to March 1, 2023. We identified nine related articles, which were eventually included in this study. Our study showed no association between Lp(a) with new-onset AF (HR = 1.45, 95% confidence interval [CI]: 0.57-3.67, p = .432). In addition, genetically elevated Lp(a) was not associated with the risk of atrial fibrillation (OR = 1.00, 95% CI: 1.00-1.00, p = .461). Different stratification of Lp(a) levels may have different outcomes. Also, higher Lp(a) levels may be inversely associated with the risk of developing AF compared to those with lower levels. Lp(a) levels were not associated with incident AF. Further research is needed to identify the mechanism underlying these results and better understand Lp(a) stratification for AF and the possible inverse association between Lp(a) and AF., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background and Aims: Warm ischaemic injury (WII) stems from incorrect energy metabolism and is the main cause of graft dysfunction. Mitochondria, as the centre of cellular metabolic activities, may be the key in identifying accurate indicators for evaluating the quality of grafts. Our research focuses on the screening, clinical application, and mechanism of the optimal WII mitochondrion biomarker., Approach and Results: Using a 100% hepatic warm ischaemia mouse model, without reperfusion, transmission electron microscopy demonstrated evident morphological changes of hepatic mitochondria at 15 min of ischaemia. However, all 13 mt-mRNAs could not display continuously upregulated consistency at 0-15-30-60 min during WII. High-throughput analysis of miRNA expression in both purified mitochondria and liver tissues suggested miR-23b-5p was a potential mitochondrial microRNA (mitomiR) biomarker with high sensitivity and 0-15-30-60 min change consistency. Fluorescence in-situ hybridization and reverse transcription quantitative polymerase chain reaction (RT-qPCR) further confirmed the results. Through overexpression and inhibition, the functionality of this mitomiR during WII was identified as a protective regulator in vitro and then verified in Dicer1 fl/fl Alb Cre mice by downregulation of other miRNAs and supplementation of mature mitomiR-23b-5p. Dual-luciferase reporter assay and the Seahorse XF analyzer determined that mitomiR-23b-5p reduced mitochondrial respiratory function by silencing mt-RNR2 (16S). Clinically, mitomiR-23b-5p was positively correlated with serum alanine aminotransferase levels 3 days after the operation ( P =0.032), and the C-statistic for 90-day graft survival rate was 0.698., Conclusions: MitomiR-23b-5p plays a protective regulatory role and implements a special mitochondrial regulation mechanism not yet reported in WII. These clinical results further support the experimental result that the expression of MitomiR-23b-5p is closely related to the prognosis of clinical liver transplantation patients. This is a promising new biomarker for WII evaluation of donor livers., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Inattention has been given to the pathogenesis of adolescent and young adult (AYA) hepatocellular carcinoma (HCC). Due to the more advanced tumor progression and poorer prognosis of AYA-HCC, together with a better tolerance ability, noncirrhotic background, and a stronger willingness to treat AYA-HCC, clinical and molecular biology studies are urgent and necessary, especially for those with hepatitis B infection., Methods: For clinical aspects, the overall survival, the recurrence-free survival, and the Cox analyses were performed. Then, functional analysis, gene clustering, metabolic-related analysis, immune infiltration and competing endogenous RNA (ceRNA) construction were carried out using whole transcriptome sequencing technique., Results: Based on the clinical information of our HCC cohort, the overall survival and recurrence-free survival rates were worse in the AYA group than in the elderly group as previously described. According to our whole transcriptome sequencing results, functional analysis revealed that metabolism-related pathways as well as protein translation and endoplasmic reticulum processing were enriched. Then the hub metabolism-related genes were screened by metabolite-protein interactions (MPIs) and protein-protein interactions (PPIs). Fatty acid metabolism is a crucial component of metabolic pathways, abnormalities of which may be the reason for the worse prognosis of HBV-AYA HCC. Finally, the relationship of disrupted expression of metabolism-related genes with immune infiltration was also analyzed, and the lncRNA‒miRNA‒mRNA-related ceRNA network for HBV-AYA HCC was constructed, which may provide new cues for HBV-AHA HCC prevention., Conclusion: The worse prognosis and recurrence rate of HBV-AYA HCC may be related to abnormalities in metabolism-related pathways, especially disorders of fatty acid metabolism., (© 2023. The Author(s).)

Competing Interests: Declaration of interests None declared.

Background: This study aimed to find effective treatments for the patient within UCSF criteria., Methods: This study enrolled 1006 patients meeting UCSF criteria, undergoing hepatic resection (HR), divided into two groups: single tumor group and multiple tumors group. We compared and analyzed the risk factors between these two groups' long-term outcomes, through log-rank test, cox proportional hazards model and using neural network analysis to identify the independent risk factors., Results: The 1-, 3-, and 5-year OS rates in single tumor were significantly higher than multiple tumors (95.0%, 73.2% and 52.3% versus 93.9%, 69.7% and 38.0%, respectively, p < 0.001). The 1-, 3- and 5-year RFS rates were 90.3%, 60.7%, and 40.1% in single tumor and 83.4%, 50.7% and 23.8% in multiple tumors, respectively (p < 0.001). And tumor type, anatomic resection and MVI were the independent risk factors for the patient within UCSF criteria. MVI was the most important risk factor affecting OS and RFS rates in neural network analysis. The method of hepatic resection and the number of tumors were also affected OS and RFS rates., Conclusion: Anatomic resections should be applied to patients within UCSF criteria, especially for patients with single MVI negative tumours., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Liver transplantation (LT) is a highly curative therapy for patients with hepatocellular carcinoma (HCC). However, due to the shortage of donor livers and rapid progression of HCC, a majority of patients are dropped out from the waitlist. Recently, immunotherapy has shown great promise in the treatment of advanced HCC. However, the use of immunotherapy is limited in LT mainly due to the potentially increasing risk of graft rejection. One of the main challenges for researchers is the protection of donor graft from an immunotherapy-boosted immune response mounted by the host. Besides, the safety, availability, and costs of immunotherapy are other challenges that need to be addressed. Here, we reviewed the literature involving patients who received immunotherapy prior to transplant to avoid waitlist dropouts and following transplantation to prevent the progression of tumor recurrence and metastasis. Statistically, the incidence of rejection was 25.0% pre-transplant and 18.5% post-transplant. Based on the review of these clinical studies, we can conclude that conducting clinical trials on the safety and efficacy of currently available immunotherapy drugs and identifying novel immunotherapy targets through extensive research may be promising for patients who do not meet the selection criteria for LT and who experience post-transplant recurrence. To date, the clinical experience on the use of immunotherapy before or after LT comes from individual case studies. Although some of the reported results are promising, they are not sufficient to support the standardized use of immunotherapy in clinical practice., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Aims: To determine the relationship between microvascular invasion (MVI) and the clinical features of hepatocellular carcinoma (HCC) and provide a method to evaluate MVI status by neutral network analysis., Methods: The patients were divided into two groups (MVI-positive group and MVI-negative group). Univariate analysis and multivariate logistic regression analysis were carried out to identify the independent risk factors for MVI positivity. Neural network analysis was used to analyze the different importance of the risk factors in MVI prediction., Results: We enrolled 1697 patients in this study. We found that the independent prognostic factors were age, NEU, multiple tumors, AFP level and tumor diameter. By neural network analysis, we proposed that the level of AFP was the most important risk factor for HCC in predicting MVI status (the AUC was 0.704). However, age was the most important risk factor for early-stage HCC with a single tumor (the AUC was 0.605)., Conclusion: Through the neutral network analysis, we could conclude that the level of AFP is the most important risk factor for MVI-positive patients and the age is the most important risk factor for early-stage HCC with a single tumor., (© 2023. The Author(s).)

Hepatocellular carcinoma (HCC) remains a global health challenge with a low early diagnosis rate and high mortality. The Rab GTPase (RAB) family plays an essential role in the occurrence and progression of HCC. Nonetheless, a comprehensive and systematic investigation of the RAB family has yet to be performed in HCC. We comprehensively assessed the expression landscape and prognostic significance of the RAB family in HCC and systematically correlated these RAB family genes with tumor microenvironment (TME) characteristics. Then, three RAB subtypes with distinct TME characteristics were determined. Using a machine learning algorithm, we further established a RAB score to quantify TME features and immune responses of individual tumors. Moreover, to better evaluate patient prognosis, we established a RAB risk score as an independent prognostic factor for patients with HCC. The risk models were validated in independent HCC cohorts and distinct HCC subgroups, and their complementary advantages guided clinical practice. Furthermore, we further confirmed that the knockdown of RAB13, a pivotal gene in risk models, suppressed HCC cell proliferation and metastasis by inhibiting the PI3K/AKT signaling pathway, CDK1/CDK4 expression, and epithelial-mesenchymal transition. In addition, RAB13 inhibited the activation of JAK2/STAT3 signaling and the expression of IRF1/IRF4. More importantly, we confirmed that RAB13 knockdown enhanced GPX4-dependent ferroptosis vulnerability, highlighting RAB13 as a potential therapeutic target. Overall, this work revealed that the RAB family played an integral role in forming HCC heterogeneity and complexity. RAB family-based integrative analysis contributed to enhancing our understanding of the TME and guided more effective immunotherapy and prognostic evaluation.

Leucine-rich repeat kinase 2 (LRRK2), also known as Dardarin (derived from the Basque word "dardara," meaning tremor), is a protein kinase encoded by the PARK8 gene. This protein is mainly distributed in the cytoplasm; however, it is also present in the mitochondrial outer membrane. Mutations in the LRRK2 protein cause Parkinson's disease (PD). We generated a human induced pluripotent stem cell (iPSC) line (CIBi014-A) expressing pluripotency markers. This cell line exhibited a normal karyotype and could be differentiated into three germ layers in vitro. This line will be valuable for investigating the mechanism underlying PD and identifying potential therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Mutations in PARK7 and the resulting alterations in its production protein (DJ-1) are tightly associated with Parkinson's disease. We generated a human induced pluripotent stem cell (iPSC) line (CIBi013-A) from a patient with young-onset Parkinson's disease (YOPD) who carried a novel homozygous PARK7 (DJ-1) mutation (chr1:8037723, c.334C>G). The generated iPSCs will be used for investigating phenotype and underlying molecular mechanisms in patient-derived cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)