Compared efficacy of University of Wisconsin and histidine-tryptophan-ketoglutarate solutions in ex-situ liver resection and autotransplantation for end-stage hepatic alveolar echinococcosis patients

Background: The University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are the two most frequently used liver graft preservation fluids. The present study aimed to compare their efficacy in end-stage hepatic alveolar echinococcosis patients who underwent ex-situ liver resection and autotransplantation (ELRA). Methods: A total of 81 patients received ELRA from August 2010 to March 2018. They were allocated into UW ( n = 48) and HTK groups ( n = 33) based on the type of solutions used. Demographic and operational data were retrospectively analyzed. Primary outcomes included 90-day mortality, incidence of early graft loss, primary dysfunction, and postoperative complications. Results: Demographic and operational characteristics were similarly distributed in the two groups. No statistically significant differences were observed with regard to 90-day mortality (12.77% vs. 12.12%) and early graft loss rate (8.51% vs. 9.09%) between the two groups. Patients in the UW and HTK groups showed a primary dysfunction rate of 27.66% and 27.27%, respectively. The UW group exhibited a higher incidence tendency of biliary complications, albeit with no statistical significance. Conclusions: This is the largest cohort study comparing the efficacy of the UW and HTK organ-preserving solutions in end-stage hepatic alveolar echinococcosis patients in ELRA settings. UW and HTK solutions presented similar efficacy and safety. A randomized clinical trial with larger scale is needed for further investigation in future clinical applications.

Multi-modality measurement and comprehensive analysis of hepatocellular carcinoma using synchrotron-based microscopy and spectroscopy

The visualization and data mining of tumor multidimensional information may play a major role in the analysis of the growth,metastasis,and microenvironmental changes of tumors while challenging traditional imaging and data processing techniques.In this study,a general trans-scale and multi-modality measurement method was developed for the quantitative diagnosis of hepatocellular carcinoma(HCC)using a combination of propagation-based phase-contrast computed tomography(PPCT),scanning transmission soft X-ray microscopy(STXM),and Fourier transform infrared micro-spectroscopy(FTIR).Our experimental results reveal the trans-scale micro-morpho-logical HCC pathology and facilitate quantitative data analysis and comprehensive assessment.These results include some visualization features of PPCT-based tissue microenvironments,STXM-based cellular fine structures,and FTIR-based bio-macromolecular spectral characteris-tics during HCC tumor differentiation and proliferation.The proposed method provides multidimensional feature data support for constructing a high-accuracy machine learning algorithm based on a gray-level histogram,gray-gradient co-occurrence matrix,gray-level co-occurrence matrix,and back-propagation neural network model.Multi-dimensional information analysis and diagnosis revealed the morphological pathways of HCC pathological evolution and we explored the relationships between HCC-related feature changes in inflammatory microenviron-ments,cellular metabolism,and the stretching vibration peaks of biomolecules of lipids,proteins,and nucleic acids.Therefore,the proposed methodology has strong potential for the visualization of complex tumors and assessing the risks of tumor differentiation and metastasis.

Clinical implication of naive and memory T cells in locally advanced cervical cancer:A proxy for tumor biology and short-term response prediction

Background:This study was designed to investigate the feasibility of tumor-infiltrating immune cells with different phenotypic characteristics for predicting short-term clinical responses in patients with locally advanced cervical cancer(LACC).Methods:Thirty-four patients who received concurrent chemoradiotherapy and twenty-one patients who merely underwent radiotherapy were enrolled in this study.We retrospectively analyzed the T cell markers(i.e.,CD3,CD4,CD8),memory markers(i.e.,CD45,CCR7),and differentiation markers(i.e.,CD27)in the peripheral blood and tumor tissues of patients with LACC before treatment based on flow cytometry.We also analyzed the relationship of T cell subsets between peripheral blood and tumor tissues,and their correlation with complete response or partial response.Results:The percentage of central memory CD8^(+)TCM(CD8^(+)CD45RA^(−)CD27^(+)CCR7^(+))cells in LACC patients was significantly lower than that of the control group.The percentage of CD8^(+)TN in the peripheral blood of LACC patients was significantly higher than that of tumor tissues.CD8^(+)TEM in the peripheral blood was significantly lower than that of tumor tissues.The percentage of CD8^(+)TN and CD8^(+)TCM in human papillomavirus(HPV)positive samples was significantly higher than that of HPV-negative samples.Similarly,the percentage of CD8^(+)TCM in tumor tissues was significantly higher in cancer tissue samples with lymph nodes compared with those without.Conclusion:A higher proportion of CD4^(+)TCM and a lower proportion of CD8^(+)TN in the tumor microenvironment of LACC may contribute to the therapy response prediction.

Single-Cell RNA Sequencing Reveals Potential for Endothelial-to-Mesenchymal Transition in Tetralogy of Fallot

Background:Tetralogy of Fallot(TOF)is a very common cyanotic congenital heart disease.Endothelial-to-mesenchymal transition(EndoMT)is recognized as a physiological mechanism involved in embryonic heart development and endothelial formation.However,there is still a gap in the reports related to the mechanism of EndoMT development in TOF.Methods:First,transcriptomic data of single cell nuclei of TOF and Donor were obtained based on the Gene Expression Omnibus(GEO)database,and the data were normalized and clus-tered by dimensionality reduction using the Seurat package.Subsequently,differentially expressed genes(DEGs)between TOF and Donor were screened using the“FindMarkers”function,and the gene sets of interest were enriched.Finally,to characterize the dynamics of EndoMT occurrence in TOF,we performed pseudotime cell tra-jectory inference as well as utilized SCENIC analysis to probe the gene regulatory networks(GRNs)dominated by transcription factors(TFs)in endothelial cells.Results:We identified a total of six cell clusters based on single-cell nuclear transcriptome data from TOF and Donor.We found that 611 genes with up-regulated expression within TOF showed conversion to mesenchyme.By subdividing endothelial cell subtypes,endothelial cells 2 were shown to be involved in cell adhesion,migration and extracellular matrix processes.Pseudo-time and SCENIC analyses showed that endothelial cell 2 has EndoMT potential.In addition,ERG and TEAD1 are TFs that play key reg-ulatory roles in this subtype,and both of their target genes are also highly expressed in TOF.This demonstrates that ERG and TEAD1 effectively promote the EndoMT process.Conclusion:Our study reveals the molecular mechanisms underlying the development of EndoMT in TOF,which demonstrates that manipulating the endothelial-to-mesenchymal transition may offer unprecedented therapeutic potential for the treatment of TOF.

Portal vein embolization combined with ex vivo liver resection and autotransplantation: A novel treatment strategy for end-stage and metastatic hepatic alveolar echinococcosis

Alveolar echinococcosis(AE)is a lethal parasitic disease caused by Echinococcus multilocularis larvae,and more than 90%of pri-mary AE lesions occur in the liver.Most of the affected individ-uals remain asymptomatic and the disease is often diagnosed at an advanced stage.The infection may spread to organs adjacent to the liver or distant locations,eventually causing end-stage multi-ple organ AE.Brain metastasis of AE is the most fatal with an inci-dence rate of 0.2%[1].

Insight into the history and trends of liver transplantation for echinococcosis:A bibliometric analysis

BACKGROUND Liver transplantation(LT)has demonstrated favorable efficacy in managing endstage alveolar echinococcosis.Nevertheless,the current research focal points and advancement trends remain ambiguous.AIM To map the research landscape to underscore critical areas of focus,influential studies,and future directions of LT for echinococcosis treatment.METHODS Publications on LT for echinococcosis treatment published between 1900 and 2023 were searched in the Web of Science database and analyzed using bibliometrics.RESULTS A total of 14 countries/regions,75 institutions,and 499 authors have published research articles,with China,Turkey,and France being the three most productive countries.The four institutions with the most contributions were Sichuan University,Xinjiang Medical University,the University de Franche Comte,and Inonu University.The three authors who contributed the most were Wen Hao,Wang Wentao,and Bresson Hadni Solange.The four most common keywords were alveolar echinococcosis,LT,ex-vivo liver resection and autotransplantation,and echinococcosis multilocularies.CONCLUSION Our study found that the treatment of complications after LT for echinococcosis treatment and the preoperative surgical plan based on the anatomical relationship between the lesion and the blood vessel are early research hotspots.Recent research focuses on the treatment of complications after ex-vivo liver resection and autotransplantation,especially vascular complications.

Complex inferior vena cava reconstruction during ex vivo liver resection and autotransplantation:A case report

BACKGROUND Ex vivo liver resection and autotransplantation(ELRA)is an essential approach for treating patients with end-stage hepatic alveolar echinococcosis(AE),and its surgical indications involve severe invasion of important hepatic vessels,which makes in vivo resection impossible.Revascularization is a major step in the process of ELRA,which is extremely challenging when the invaded vessels have huge defects.CASE SUMMARY Herein,we have reported the case of a 26-year-old patient with hepatic AE in an autologous liver graft who underwent complex inferior vena cava(IVC)reconstruction using disease-free IVC,autologous portal vein fragments,and umbilical vein within the ligamentum teres hepatis.The patient showed good surgical recovery without vascular-related complications during the long-term follow-up.CONCLUSION We reviewed three studies that have reported complex revascularization of the IVC.This case report and systematic review showed that the use of autologous perihepatic vessels prevents donor-area trauma,immune rejection,and other adverse reactions.When the blood vessel is severely invaded and a single vascular material cannot repair and reconstruct the defect,ELRA may provide a safe and feasible surgical approach,which has good prospects for clinical application.

Human papillomavirus distribution and cervical cancer epidemiological characteristics in rural population of Xinjiang,China

Background:Cervical cancer remains a major public health issue for the Uyghur women and other women living mainly in rural areas of Xinjiang.This study aims to investigate the distribution of human papillomavirus(HPV)infection and cervical cancer in rural areas of Xinjiang,China.Methods:Cervical cancer screening was performed on rural women aged 35 to 64 years from Xinjiang,China in 2017 through gynecological examination,vaginal discharge smear microscopy,cytology,and HPV testing.If necessary,colposcopy and biopsy were performed on women with suspicious or abnormal screening results.Results:Of the 216,754 women screened,15,518 received HPV testing.The HPV-positive rate was 6.75%(1047/15,518).Compared with the age 35-44 years group,the odds ratios(ORs)of HPV positivity in the age 45-54 years and 55-64 years groups were 1.18(95%confidence interval[Cl]:1.02-1.37)and 1.84(95%Cl:1.53-2.21),respectively.Compared with women with primary or lower education level,the ORs for HPV infection rates of women with high school and college education or above were 1.37(95%Cl:1.09-1.72)and 1.62(95%Cl:1.23-2.12),respectively.Uyghur women were less likely to have HPV infection than Han women,with an OR(95%Cl)of 0.78(0.61-0.99).The most prevalent HPV types among Xinjiang women were HPV 16(24.00%),HPV 33(12.70%),and HPV 52(11.80%).The detection rate of cervical intraepithelial neoplasia(CIN)2+was 0.14%and the early diagnosis rate of cervical cancer was 85.91%.The detection rates of vaginitis and cervicitis were 19.28%and 21.32%,respectively.Conclusions:The HPV infection rate in Xinjiang is low,but the detection rate of cervical cancer and precancerous lesions is higher than the national average level.Cervical cancer is a prominent public health problem in Xinjiang,especially in southern Xinjiang.

Genomic Epidemiology of Carbapenemaseproducing Klebsiella pneumoniae in China

The rapid spread of carbapenemase-producing Klebsiella pneumoniae(cpKP)poses serious threats to public health;however,the underlying genetic basis for its dissemination is still unknown.We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates collected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009–2017 by short-/long-read sequencing.The results showed that most cpKP isolates were categorized into clonal group 258(CG258),in which ST11 was the dominant clone.Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates.Additionally,carbapenemase gene analysis indicated that blaKPC was dominant in the cpKP isolates,and most blaKPC genes were located in five major incompatibility(Inc)groups of blaKPC-harboring plasmids.Importantly,three advantageous combinations of host–blaKPC-carrying plasmid(Clade 3.1+3.2–IncFIIpHN7A8,Clade 3.1+3.2–IncFIIpHN7A8:IncR,and Clade 3.3–IncFIIpHN7A8:IncpA1763-KPC)were identified to confer cpKP isolates the advantages in both genotypes(strong correlation/coevolution)and phenotypes(resistance/growth/competition)to facilitate the nationwide spread of ST11/CG258 cpKP.Intriguingly,Bayesian skyline analysis illustrated that the three advantageous combinations might be directly associated with the strong population expansion during 2007–2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008.We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections.Thus,the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China,and much emphasis should be given to the close monitoring of advantageous cpKP–plasmid combinations.

Recent advances in the development of activatable multifunctional probes for in vivo imaging of caspase-3

Caspases are a family of proteases that play critical roles in controlling inflammation and cell death.Apoptosis is a caspase-3 mainly controlled behavior to avoid inflammation and damage to surrounding cells,whereas anomalistic cell apoptosis may be associated with many diseases.The detection and imaging of caspase-3 will be of great significance in evaluating the early therapeutic effect of tumors.Developing smart fluorescent probes may be helpful for the visualization of the rapeutic effect compared with "always on" probes.Thus,more and more works toward activatable fluorescent probes for caspase-3 imaging have been reported.In addition,multifunctional probes have also been designed to further improve the imaging of caspase-3.Herein,this review systematically summarized the representative wo rk of caspase-3 from the perspective of molecular design that it will play a guiding role in the design of probes that respond to caspase-3.Also,challenges and perspectives toward the field for imaging of cell apoptosis(caspase-3) are also discussed.

Integrating 16S sequencing and metabolomics study on anti-rheumatic mechanisms against collagen-induced arthritis of Wantong Jingu Tablet

Wantong Jingu Tablet(WJT),a mixture of traditional Chinese medicine,was reported to relieve the symptoms of rheumatoid arthritis(RA),but its pharmacological mechanism was not completely understood.The aim of this study was to investigate the therapeutic mechanisms of WJT for RA in vivo.The effects of WJT on joint pathology,as well as the levels of Bax,Bcl-2,caspase-3,cleaved-caspase-3,ERK1/2,pERK1/2,TNF-α,IL-1β,and IL-6 were measured using collagen-induced arthritis(CIA)rats.The intestinal flora composition and the metabolites alteration were analyzed by 16S rDNA sequencing and metabolomics method,respectively.We found that WJT ameliorated the severity of the CIA rats which might be mediated by inducing apoptosis,inactivating the MEK/ERK signals and reducing the production of pro-inflammatory cytokines.WJT,in part,relieved the gut microbiota dysbiosis,especially bacterial phylum Bacteroidetes,Tenericutes and Deferribacteres,as well as bacterial genus Vibrio,Macrococcus and Vagococcus.3’-N-debenzoyl-2’-deoxytaxol,tubulysin B,and magnoline were significantly associated with the specific genera.We identified serotonin,glutathione disulfide,N-acetylneuraminic acid,naphthalene and thromboxane B2 as targeted molecules via metabolomics.Our findings contributed to the understanding of RA pathogenesis,and WJT played essential roles in gut microbiota health and metabolite modulation in the CIA rats.

Click chemistry and natural products

The 2022 Nobel Prize in Chemistry was awarded to American scientists Carolyn Bertozzi,K.Barry Sharpless,and Danish scientist Morten P.Merdahl for their contributions to the development of click chemistry and bioorthogonal chemistry.

Dog vaccination with EgM proteins against Echinococcus granulosus

Background:Dogs play a pivotal role in the transmission of cystic echinococcosis(CE),a zoonosis caused by the tapeworm Echinococcus granulosus.We showed previously that dogs vaccinated with two E.granulosus adult-worm specific proteins,EgM9 and EgM123,emulsified with Freund’s adjuvants induced significant protective efficacy in terms of reduction in worm burden and egg production after 45 days post-infection.It was not known whether this protection can be sustained using adjuvants suitable for use in dogs.Methods:Recombinant EgM9 and EgM123 were mixed with Quil A or ISCOMs for vaccinating dogs.After three vaccine injections,all the dogs were orally challenge-infected with 200000 protoscoleces of E.granulosus.After 45 days of infection,all the dogs were euthanized and necropsied for collecting and counting E.granulosus worms.Immunoglobins,including the IgG subclasses IgG1 and IgG2,were detected in the sera of vaccinated dogs by ELISA.To determine whether the protection efficacy could be maintained after 45 days post-infection,we implemented a longevity trial to count eggs in dog faeces for 170 days after infection.Results:The dogs vaccinated with EgM9 and EgM123 mixed with Quil A and ISCOMs showed similar protective efficacy as the proteins emulsified with Freund’s adjuvants in our previous study in terms of reduction of worms and eggs at 45 days post-infection.The longevity trial showed that EgM9 protein-vaccinated group released lower number of eggs per gram compared with the egg counts in the control dogs during the dog trial study.Conclusion:EgM9 and EgM123 are thus suitable vaccine candidates against E.granulosus infection in dogs.

Breaking-then-curing strategy for efficient cystic echinococcosis therapy

Cystic echinococcosis(CE)is one of the most harmful and life-threatening helminths.As the essential therapeutics,chemotherapy is always difficult to achieve desired anti-echinococcal effect due to the problems that the echinococcus granulosus cyst laminated layer makes the drug difficult to infiltrate and the poor solubility of drugs.In this study,we established a“breaking-then-curing”anti-echinococcal treatment strategy for efficient CE therapy.The photodynamic therapy(PDT)was used as a breaker to produce toxic reactive oxygen species(ROS)and damage the laminated layer of protoscolices(PSCs),leading to enhanced infiltration of albendazole sulfoxide nanoparticles(ABZSO NPs).Then,ABZSO NP was worked as curer for efficient anti-echinococcal treatment.As a result,the breaking-then-curing treatment strategy could generate more intracellular ROS in PSCs induced by plenty of ABZSO NPs,greatly increasing the mortality rate of PSCs in a shorter time than using ABZSO NPs alone,leading to the attenuation of laminated layer and finally disintegrating PSCs.We believe the“breaking-then-curing”strategy will suggest great potential in the treatment of CE and provide a new sight for anti-echinococcal treatment.