Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of cancers worldwide,ranking fifth among men and seventh among women,resulting in more than 7 million deaths annually.With the development of medical tech-nology,the 5-year survival rate of HCC patients can be increased to 70%.How-ever,HCC patients are often at increased risk of cardiovascular disease(CVD)death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients.Moreover,CVD and cancer have become major disease burdens worldwide.Thus,further research is needed to lessen the risk of CVD death in HCC patient survivors.METHODS This study was conducted on the basis of the Surveillance,Epidemiology,and End Results database and included HCC patients with a diagnosis period from 2010 to 2015.The independent risk factors were identified using the Fine-Gray model.A nomograph was constructed to predict the CVM in HCC patients.The nomograph performance was measured using Harrell’s concordance index(C-index),calibration curve,receiver operating characteristic(ROC)curve,and area under the ROC curve(AUC)value.Moreover,the net benefit was estimated via decision curve analysis(DCA).RESULTS The study included 21545 HCC patients,of whom 619 died of CVD.Age(<60)[1.981(1.573-2.496),P<0.001],marital status(married)[unmarried:1.370(1.076-1.745),P=0.011],alpha fetoprotein(normal)[0.778(0.640-0.946),P=0.012],tumor size(≤2 cm)[(2,5]cm:1.420(1.060-1.903),P=0.019;>5 cm:2.090(1.543-2.830),P<0.001],surgery(no)[0.376(0.297-0.476),P<0.001],and chemotherapy(none/unknown)[0.578(0.472-0.709),P<0.001]were independent risk factors for CVD death in HCC patients.The discrimination and calibration of the nomograph were better.The C-index values for the training and validation sets were 0.736 and 0.665,respectively.The AUC values of the ROC curves at 2,4,and 6 years were 0.702,0.725,0.740 in the training set and 0.697,0.710,0.744 in the validation set,respectively.The calibration curves showed that the predicted probab-ilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities.DCA demonstrated that the prediction model has a high net benefit.CONCLUSION Risk factors for CVD death in HCC patients were investigated for the first time.The nomograph served as an important reference tool for relevant clinical management decisions.

Effects of thrombopoietin pre-treatment on peri-liver transplantation thrombocytopenia in a mouse model of cirrhosis with hypersplenism

BACKGROUND During cirrhosis,the liver is impaired and unable to synthesize and clear thrombopoietin properly.At the same time,the spleen assumes the function of hemofiltration and storage due to liver dysfunction,resulting in hypersplenism and excessive removal of platelets in the spleen,further reducing platelet count.When liver function is decompensated in cirrhotic patients,the decrease of thrombopoietin(TPO)synthesis is the main reason for the decrease of new platelet production.This change of TPO leads to thrombocytopenia and bleeding tendency in cirrhotic patients with hypersplenism.AIM To investigate the clinical efficacy of recombinant human TPO(rhTPO)in the treatment of perioperative thrombocytopenia during liver transplantation in cirrhotic mice with hypersplenism.METHODS C57BL/6J mice and TPO receptor-deficient mice were used to establish models of cirrhosis with hypersplenism.Subsequently,these mice underwent orthotopic liver transplantation(OLT).The mice in the experimental group were given rhTPO treatment for 3 consecutive days before surgery and 5 consecutive days after surgery,while the mice in the control group received the same dose of saline at the same frequency.Differences in liver function and platelet counts were determined between the experimental and control groups.Enzyme-linked immunosorbent assay was used to assess the expression of TPO and TPO receptor(c-Mpl)in the blood.RESULTS Preoperative administration of rhTPO significantly improved peri-OLT thrombocytopenia in mice with cirrhosis and hypersplenism.Blocking the expression of TPO receptors exacerbated peri-OLT thrombocytopenia.The concentration of TPO decreased while the concentration of c-Mpl increased in compensation in the mouse model of cirrhosis with hypersplenism.TPO pre-treatment significantly increased the postoperative TPO concentration in mice,which in turn led to a decrease in the c-Mpl concentration.TPO pre-treatment also significantly enhanced the Janus kinase(Jak)/signal transducers and activators of transcription pathway protein expressions in bone marrow stem cells of the C57BL/6J mice.Moreover,the administration of TPO,both before and after surgery,regulated the levels of biochemical indicators,such as alanine aminotransferase,alkaline phosphatase,and aspartate aminotransferase in the C57BL/6J mice.CONCLUSION Pre-treatment with TPO not only exhibited therapeutic effects on perioperative thrombocytopenia in the mice with cirrhosis and hypersplenism,who underwent liver transplantation but also significantly enhanced the perioperative liver function.

Knowledge,attitudes and experiences of genetic testing for autism spectrum disorders among caregivers,patients,and health providers:A systematic review

BACKGROUND Several genetic testing techniques have been recommended as a first-tier diagnostic tool in clinical practice for diagnosing autism spectrum disorder(ASD).However,the actual usage rate varies dramatically.This is due to various reasons,including knowledge and attitudes of caregivers,patients,and health providers toward genetic testing.Several studies have therefore been conducted worldwide to investigate the knowledge,experiences,and attitudes toward genetic testing among caregivers of children with ASD,adolescent and adult ASD patients,and health providers who provide medical services for them.However,no systematic review has been done.AIM To systematically review research on knowledge,experiences,and attitudes towards genetic testing among caregivers of children with ASD,adolescent and adult ASD patients,and health providers.METHODS We followed the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines and searched the literature in three English language databases(PubMed,Web of Science,and PsychInfo)and two Chinese databases(CNKI and Wanfang).Searched literature was screened independently by two reviewers and discussed when inconsistency existed.Information on characteristics of the study,characteristics of participants,and main findings regarding knowledge,experience,and attitudes of caregivers of children with ASD,adolescent and adult ASD patients,and health providers concerning ASD genetic testing were extracted from included papers into a charting form for analysis.RESULTS We included 30 studies published between 2012 and 2022 and conducted in 9 countries.Most of the studies(n=29)investigated caregivers of children with ASD,one study also included adolescent and adult patients,and two covered health providers.Most(51.0%-100%)of the caregivers/patients knew there was a genetic cause for ASD and 17.0%to 78.1%were aware of ASD genetic testing.However,they lacked full understanding of genetic testing.They acquired relevant and necessary information from physicians,the internet,ASD organizations,and other caregivers.Between 9.1%to 72.7%of caregivers in different studies were referred for genetic testing,and between 17.4%to 61.7%actually obtained genetic testing.Most caregivers agreed there are potential benefits following genetic testing,including benefits for children,families,and others.However,two studies compared perceived pre-test and post-test benefits with conflicting findings.Caregivers concerns included high costs,unhelpful results,negative influences(e.g.,causing family conflicts,causing stress/risk/pain to children etc.)prevented some caregivers from using genetic testing.Nevertheless,46.7%to 95.0%caregivers without previous genetic testing experience intended to obtain it in the future,and 50.5%to 59.6%of parents previously obtaining genetic testing would recommend it to other parents.In a single study of child and adolescent psychiatrists,54.9%of respondents had ordered ASD genetic testing for their patients in the prior 12 mo,which was associated with greater knowledge of genetic testing.CONCLUSION Most caregivers are willing to learn about and use genetic testing.However,the review showed their current knowledge is limited and usage rates varied widely in different studies.

Interleukin-22 contributes to liver regeneration in micewith concanavalin A-induced hepatitis after hepatectomy

AIM: To investigate the therapeutic effects and mechanisms of interleukin(IL)-22 in liver regeneration in mice with concanavalin A(Con A)-induced liver injury following 70% hepatectomy.METHODS: Mice were injected intravenously with Con A at 10 μg/g body weight 4 d before 70% hepatectomy to create a hepatitis model, and recombinant IL-22 was injected at 0.125 μg/g body weight 30 min prior to 70% hepatectomy to create a therapy model. Control animals received an intravenous injection of an identical volume of normal saline.RESULTS: IL-22 treatment prior to 70% hepatectomy performed under general anesthesia resulted in reductions in the biochemical and histological evidence of liver injury, earlier proliferating cell nuclear antigen expression and accelerated recovery of liver mass. IL-22 pretreatment also significantly induced signal transducer and activator of transcription factor 3(STAT3) activation and increased the expression of a variety of mitogenic proteins, such as Cyclin D1. Furthermore, alpha fetal protein m RNA expression was significantly elevated after IL-22 treatment.CONCLUSION: In this study, we demonstrated that IL-22 is a survival factor for hepatocytes and prevents and repairs liver injury by enhancing pro-growth pathways via STAT3 activation. Treatment with IL-22 protein may represent a novel therapeutic strategy for preventing liver injury in patients with liver disease who have undergone hepatectomy.

Overexpression of Csk-binding protein decreases growth,invasion,and migration of esophageal carcinoma cells by controlling Src activation

AIM:To investigate the mechanisms by which Cskbinding protein(CBP)inhibits tumor progression in esophageal carcinoma.METHODS:A CBP overexpressing esophageal carcinoma cell line(TE-1)was established.The growth,invasion,and migration of CBP-TE-1 cells,as well as the expression of Src were then determined and compared with those in normal TE-1 cells.RESULTS:The expression of Src was decreased by the overexpression of CBP in TE-1 cells.The growth,invasion,and migration of TE-1 cells were decreased by the overexpression of CBP.CONCLUSION:This study indicates that CBP may decrease the metastasis of esophageal carcinoma by inhibiting the activation of Src.CBP may be a potential tumor suppressor and targeting the CBP gene may be an alternative strategy for the development of therapies for esophageal carcinoma.

Application value of mixed reality in hepatectomy for hepatocellular carcinoma

BACKGROUND As a new digital holographic imaging technology,mixed reality(MR)technology has unique advantages in determining the liver anatomy and location of tumor lesions.With the popularization of 5 G communication technology,MR shows great potential in preoperative planning and intraoperative navigation,making hepatectomy more accurate and safer.AIM To evaluate the application value of MR technology in hepatectomy for hepatocellular carcinoma(HCC).METHODS The clinical data of 95 patients who underwent open hepatectomy surgery for HCC between June 2018 and October 2020 at our hospital were analyzed retrospectively.We selected 95 patients with HCC according to the inclusion criteria and exclusion criteria.In 38 patients,hepatectomy was assisted by MR(Group A),and an additional 57 patients underwent traditional hepatectomy without MR(Group B).The perioperative outcomes of the two groups were collected and compared to evaluate the application value of MR in hepatectomy for patients with HCC.RESULTS We summarized the technical process of MR-assisted hepatectomy in the treatment of HCC.Compared to traditional hepatectomy in Group B,MR-assisted hepatectomy in Group A yielded a shorter operation time(202.86±46.02 min vs 229.52±57.13 min,P=0.003),less volume of bleeding(329.29±97.31 mL vs 398.23±159.61 mL,P=0.028),and shorter obstructive time of the portal vein(17.71±4.16 min vs 21.58±5.24 min,P=0.019).Group A had lower alanine aminotransferas and higher albumin values on the third day after the operation(119.74±29.08 U/L vs 135.53±36.68 U/L,P=0.029 and 33.60±3.21 g/L vs 31.80±3.51 g/L,P=0.014,respectively).The total postoperative complications and hospitalization days in Group A were significantly less than those in Group B[14(37.84%)vs 35(60.34%),P=0.032 and 12.05±4.04 d vs 13.78±4.13 d,P=0.049,respectively].CONCLUSION MR has some application value in three-dimensional visualization of the liver,surgical planning,and intraoperative navigation during hepatectomy,and it significantly improves the perioperative outcomes of hepatectomy for HCC.

Development and validation of novel nomograms to predict survival of patients with tongue squamous cell carcinoma

BACKGROUND There is no unified standard to predict postoperative survival in patients with tongue squamous cell carcinoma(TSCC),hence the urgency to develop a model to accurately predict the prognosis of these patients.AIM To develop and validate nomograms for predicting overall survival(OS)and cancer-specific survival(CSS)of patients with TSCC.METHODS A cohort of 3454 patients with TSCC from the Surveillance,Epidemiology,and End Results(SEER)database was used to develop nomograms;another independent cohort of 203 patients with TSCC from the Department of Oral and Maxillofacial Surgery,First Affiliated Hospital of Zhejiang University School of Medicine,was used for external validation.Univariate and multivariate analyses were performed to identify useful variables for the development of nomograms.The calibration curve,area under the receiver operating characteristic curve(AUC)analysis,concordance index(C-index),net reclassification index(NRI),and decision curve analysis(DCA)were used to assess the calibration,discrimination ability,and clinical utility of the nomograms.RESULTS Eight variables were selected and used to develop nomograms for patients with TSCC.The Cindex(0.741 and 0.757 for OS and CSS in the training cohort and 0.800 and 0.830 in the validation cohort,respectively)and AUC indicated that the discrimination abilities of these nomograms were acceptable.The calibration curves of OS and CSS indicated that the predicted and actual values were consistent in both the training and validation cohorts.The NRI values(training cohort:0.493 and 0.482 for 3-and 5-year OS and 0.424 and 0.402 for 3-and 5-year CSS;validation cohort:0.635 and 0.750 for 3-and 5-year OS and 0.354 and 0.608 for 3-and 5-year CSS,respectively)and DCA results indicated that the nomograms were significantly better than the tumor-node-metastasis staging system in predicting the prognosis of patients with TSCC.CONCLUSION Our nomograms can accurately predict patient prognoses and assist clinicians in improving decision-making concerning patients with TSCC in clinical practice.

Porous carbon nanofibers derived from low-softening-point coal pitch towards all-carbon potassium ion hybrid capacitors

Potassium ion hybrid capacitors(PIHC)have promising applications in medium and large-scale energy storage systems due to their high energy/power density,abundant potassium resource and low cost.However,the slow kinetics of battery-type anodes originating from the large-size K+results in a mismatch between the two electrodes,rendering the modest energy density of PIHC.Herein,we first develop an electrospinning strategy to successfully synthesize fibrous precursor by using the HNO_(3)pre-oxidized low-softening-point coal pitch as the low-cost raw material.With further carbonization or KOH activation,the two types of carbon nanofibers(CNF)are fabricated as anode and cathode materials,respectively,towards the dual-carbon PIHC devices.Thanks to its threedimensional interconnected porous conducting network and large layer spacing,the resulted CNF anode material is endowed with high reversible capacities,excellent rate and long cycle stability.Meanwhile,the activated CNF cathode with a large surface area of 2169 m^(2)·g^(-1)exhibits excellent capacitive performance.A PIHC constructed with the two fibrous electrodes delivers an energy density of110.0 Wh·kg^(-1)at 200.0 W kg^(-1),along with a capacitance retention of 83.5%after 10,000 cycles at 1.0 A·g^(-1).The contribution here provides a cost-efficiency avenue and platform for advanced dual-carbon PIHC.

A retrospective study of the occurrence of ischemic-type biliary lesions post liver transplantation

Dear Editors,Ischemic-type biliary lesions(ITBLs)significantly reduce patient and graft survival rates.Research data regarding the causes of ITBL are rare.ITBLs is an important cause of post liver transplantation graft loss and patient death.The exact cause of this type of biliary complication remains unclear.To establish strategies for ITBL treatment or prevention,the risk factors of ITBL must be elucidated.The objective of this single-center retrospective study was to investigate the risk factors of ITBL in orthotopic liver transplantation(OLT)patients.