Tianxiangdan(TXD),a traditional Chinese herbal remedy,demonstrates efficacy in mitigating myocardial ischemia-reperfusion(I/R)-induced damage.This study employed network pharmacology to evaluate the therapeutic target...Tianxiangdan(TXD),a traditional Chinese herbal remedy,demonstrates efficacy in mitigating myocardial ischemia-reperfusion(I/R)-induced damage.This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R.Highperformance liquid chromatography-mass spectrometry(HPLC-MS)identified 86 compounds in TXD.Network pharmacological analysis predicted potential target genes and their modes of action.Cardiac function,ischaemic ST changes,lactate dehydrogenase(LDH),malondialdehyde(MDA),superoxide dismutase(SOD)activity,myocardial fiber,and infarct size were assessed using in vivo and in vitro I/R injury models.Estrogen receptor alpha(ERα)protein expression and estradiol(E2)levels were measured to confirm TXD's impact on estrogen levels and ERαexpression.To examine if TXD reduces I/R injury through ERα,an AZD group(300 nmol·L^(-1)AZD9496 and 15%TXD serum)was compared to a TXD group(15%TXD serum).The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway.I/R injury-induced ferroptosis was identified using a Fer-1 group(1.0μmol·L^(-1)Fer-1 and 15%TXD serum)to elucidate the potential association between ferroptosis and ERαproteins.A DCFH-DA probe detected reactive oxygen species(ROS)and Fe^(2+),while Western blotting assessed target protein expression.Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels,improving cardiac injury biomarkers(LDH,MDA,and SOD),alleviating pathological features,and preventing I/R-induced loss of cell viability in vitro.The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells.The TXD group showed significantly decreased ROS and Fe^(2+)levels,while the AZ group(treated with AZD9496)exhibited increased levels.The TXD group demonstrated enhanced expression of ERαand glutathione peroxidase 4(GPX4),with reduced levels of P53 protein and ferritinheavy polypeptide 1(FTH1).The AZ group exhibited contrasting effects on these expression levels.The literature indicated a novel connection between ERαand ferroptosis.TXD activates the ERαsignaling pathway,promoting protection against I/R-induced myocardial cell ferroptosis.This study provides evidence supporting TXD use for myocardial ischemia treatment,particularly in older female patients who may benefit from its therapeutic outcomes.展开更多
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 th...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.展开更多
OBJECTIVE:To investigate the role of toll-like receptor 4(TLR4)/mutant myeloid differentiation primary response 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway-mediated inflammation in diabetes mellitus with...OBJECTIVE:To investigate the role of toll-like receptor 4(TLR4)/mutant myeloid differentiation primary response 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway-mediated inflammation in diabetes mellitus with Northwest dryness syndrome.METHODS:Rats were randomly divided into the normal control,type 2 diabetes(T2DM)model,Northwest dryness syndrome+T2DM(Northwest dryness),and simple internal dampness+T2DM(internal dampness)groups.Enzyme-linked immunosorbent assay was used to detect biochemical indexes and inflammatory factors.The histopathological observation was performed.Quantitative real-time polymerase chain reaction and Western blot analysis were used to detect the mRNA and protein expression levels,respectively.RESULTS:Compared with the T2DM group,the glycosylated hemoglobin A1c,insulin,glucose tolerance,the homeostasis model assessment of insulin resistance,tumor necrosis factor-α,interleukin 1β,interleukin 16,malondialdehyde,blood lipid,alanine aminotransferase,and aspartate aminotransferase were significantly elevated in the internal dampness group.Their levels were significantly elevated in the Northwest dryness group than in the T2DM and internal dampness groups.The superoxide dismutase,glutathione peroxidase,liver glycogen,and organ-to-weight ratio were significantly declined in the internal dampness group and the Northwest dryness group than in the T2DM group.However,these levels were elevated in the Northwest dryness group than in the internal dampness group.Moreover,the mRNA expression levels of interferon regulatory factor 5 and NF-κB p65,and the protein expression levels of TLR4,MyD88,and NF-κB were significantly higher in the internal dampness and the Northwest dryness groups than the T2DM group.Additionally,the mRNA and protein levels were significantly higher in the Northwest dryness group than in the internal dampness group.CONCLUSION:Northwest dryness syndrome-mediated TLR4/MyD88/NF-κB pathway and chronic inflammation might be associated with the occurrence and development of T2DM.展开更多
Objective:Alternative splicing affects gene expression during placental development.The present study aimed to identify poly(ADP-ribose)polymerase 1(PARP1)-regulated alternative splicing events in HTR-8/Svneo cells.Me...Objective:Alternative splicing affects gene expression during placental development.The present study aimed to identify poly(ADP-ribose)polymerase 1(PARP1)-regulated alternative splicing events in HTR-8/Svneo cells.Methods:Decidual tissues were collected from women with induced abortion and spontaneous abortion.PARP1 transcription was quantified by RT-qPCR.Small interfering RNA(siRNA)was used to knock down the PARP1 expression in HTR-8/Svneo cells.The transfection efficiency was verified by RT-qPCR and Western blotting.Total RNA was extracted,and the RNA-sequencing approach was used to identify alternative splicing events and transcriptomes.The PARP1 knockdown-induced differentially expressed genes with changes in alternative splicing events were quantified by RT-qPCR.Functional analysis,which included the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways,was performed.Results:The PARP1 mRNA expression increased in decidual tissues in the spontaneous abortion group,when compared to the induced abortion group.However,the PARP1 knockdown significantly downregulated 1491 genes and upregulated 881 genes in HTR-8/Svneo cells.Furthermore,227 genes that underwent alternative splicing were identified,and these were differentially expressed in siPARP1 cells,when compared to siNC cells.Conclusion:The functional analysis revealed that these alternative splicing genes affected the functional phenotypes of extravillous cytotrophoblasts.Furthermore,the PARP1 knockdown led to alterations in gene expression and specific alternative splicing patterns in extravillous trophoblasts.展开更多
Triple-negative breast cancer (TNBC) is an aggressive and often fatal disease, especially since the brain metastasis of TNBC has been a particularly severe manifestation. However, brain metastasis in TNBC at early sta...Triple-negative breast cancer (TNBC) is an aggressive and often fatal disease, especially since the brain metastasis of TNBC has been a particularly severe manifestation. However, brain metastasis in TNBC at early stages often lacks noticeable symptoms, making it challenging to detect. Near-infrared II (NIR-II) fluorescence microscopic imaging obtains long wavelength, which enables reduced scattering, high spatial resolution and minimal autofluorescence, it is also a favorable imaging method for tumor diagnosis. PbS@CdS quantum dots (QDs) are one of the popular NIR-II fluorescence nanoprobes for well brightness. In this study, NIR-II emissive PbS@CdS QDs were utilized and further encapsulated with thiol-terminated poly(ethylene oxide) (SH-PEG, MW = 5000) to form PbS@CdS@PEG QDs nanoparticles (NPs). The obtained PbS@CdS@PEG QDs NPs were then characterized and further studied in detail. The PbS@CdS@PEG QDs NPs had large absorption spectra, exhibited strong NIR-II fluorescence emission at approximately 1300nm, and possessed good NIR-II fluorescence properties. Then, the mice model of early-stage brain metastases of TNBC was established, and the PbS@CdS@PEG QDs NPs were injected into the tumor-bearing mice for NIR-II fluorescence microscopic bioimaging. The brain vessels and tumors of the living mice were detected with high spatial resolution under the NIR-II fluorescence microscopic imaging system with irradiation of 808nm laser. The tumor tissues were further restricted and prepared as thin slices. The NIR-II fluorescence signals were collected from the tumor slices with high spatial resolution and signal-to-background ratio (SBR). Thus, the PbS@CdS@PEG QDs NPs-assisted NIR-II fluorescence microscopic system can effectively achieve targeting brain metastases of TNBC imaging, offering a novel and promising approach for TNBC-specific diagnosis.展开更多
BACKGROUND Bletilla striata polysaccharides(BSP)have antioxidant,immune regulation,and anti-fibrotic activities.However,the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-assoc...BACKGROUND Bletilla striata polysaccharides(BSP)have antioxidant,immune regulation,and anti-fibrotic activities.However,the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-associated steatotic liver disease(MASLD)have not been fully understood.AIMTo investigate the therapeutic effects and mechanisms of BSP on MASLD by centering on the hepatocyte nuclearfactor kappa B p65(RelA)/hepatocyte nuclear factor-1 alpha(HNF1α)signaling.METHODSA mouse model of MASLD was induced by feeding with a high-fat-diet(HFD)and a hepatocyte model of steatosiswas induced by treatment with sodium oleate(SO)and sodium palmitate(SP).The therapeutic effects of BSP onMASLD were examined in vivo and in vitro.The mechanisms underlying the action of BSP were analyzed for theireffect on lipid metabolism disorder,endoplasmic reticulum(ER)stress,and the RelA/HNF1αsignaling.RESULTSHFD feeding reduced hepatocyte RelA and HNF1αexpression,induced ER stress,lipid metabolism disorder,andnecroptosis in mice,which were significantly mitigated by treatment with BSP.Furthermore,treatment with BSP orBSP-containing conditional rat serum significantly attenuated the sodium oleate/sodium palmitate(SO/SP)-induced hepatocyte steatosis by decreasing lipid accumulation,and lipid peroxidation,and enhancing theexpression of RelA,and HNF1α.The therapeutic effects of BSP on MASLD were partially abrogated by RELAsilencing in mice and RELA knockout in hepatocytes.RELA silencing or knockout significantly down-regulatedHNF1αexpression,and remodeled ER stress and oxidative stress responses during hepatic steatosis.CONCLUSIONTreatment with BSP ameliorates MASLD,associated with enhancing the RelA/HNF1αsignaling,remodeling ERstress and oxidative stress responses in hepatocytes.展开更多
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 i...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.展开更多
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 stud...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.展开更多
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 ...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.展开更多
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...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.展开更多
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 adva...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.展开更多
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...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.展开更多
BACKGROUND Echinococcosis,caused by Echinococcus parasites,includes alveolar echinococcosis(AE),the most lethal form,primarily affecting the liver with a 90%mortality rate without prompt treatment.While radical surger...BACKGROUND Echinococcosis,caused by Echinococcus parasites,includes alveolar echinococcosis(AE),the most lethal form,primarily affecting the liver with a 90%mortality rate without prompt treatment.While radical surgery combined with antiparasitic therapy is ideal,many patients present late,missing hepatectomy opportunities.Ex vivo liver resection and autotransplantation(ELRA)offers hope for such patients.Traditional surgical decision-making,relying on clinical experience,is prone to bias.Machine learning can enhance decision-making by identifying key factors influencing surgical choices.This study innovatively employs multiple machine learning methods by integrating various feature selection techniques and SHapley Additive exPlanations(SHAP)interpretive analysis to deeply explore the key decision factors influencing surgical strategies.AIM To determine the key preoperative factors influencing surgical decision-making in hepatic AE(HAE)using machine learning.METHODS This was a retrospective cohort study at the First Affiliated Hospital of Xinjiang Medical University(July 2010 to August 2024).There were 710 HAE patients(545 hepatectomy and 165 ELRA)with complete clinical data.Data included demographics,laboratory indicators,imaging,and pathology.Feature selection was performed using recursive feature elimination,minimum redundancy maximum relevance,and least absolute shrinkage and selection operator regression,with the intersection of these methods yielding 10 critical features.Eleven machinelearning algorithms were compared,with eXtreme Gradient Boosting(XGBoost)optimized using Bayesian optimization.Model interpretability was assessed using SHAP analysis.RESULTS The XGBoost model achieved an area under the curve of 0.935 in the training set and 0.734 in the validation set.The optimal threshold(0.28)yielded sensitivity of 93.6%and specificity of 90.9%.SHAP analysis identified type of vascular invasion as the most important feature,followed by platelet count and prothrombin time.Lesions invading the hepatic vein,inferior vena cava,or multiple vessels significantly increased the likelihood of ELRA.Calibration curves showed good agreement between predicted and observed probabilities(0.2-0.7 range).The model demonstrated high net clinical benefit in Decision Curve Analysis,with accuracy of 0.837,recall of 0.745,and F1 score of 0.788.CONCLUSION Vascular invasion is the dominant factor influencing the choice of surgical approach in HAE.Machine-learning models,particularly XGBoost,can provide transparent and data-driven support for personalized decision-making.展开更多
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 an...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].展开更多
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 bioorthog...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.展开更多
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 th...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.展开更多
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...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.展开更多
Objective:To establish an acute canine coronary artery occlusion model by implanting a mixed thrombus prepared in vitro into the coronary artery by percutaneous coronary intervention(PCI).Methods:This study included 1...Objective:To establish an acute canine coronary artery occlusion model by implanting a mixed thrombus prepared in vitro into the coronary artery by percutaneous coronary intervention(PCI).Methods:This study included 14 healthy Beagle dogs aged 10-13 months.First,5 ml of canine venous blood was drawn to prepare the coronary artery thrombus in vitro.The thrombus was then implanted into the canine coronary artery by PCI to establish an animal model of acute coronary artery occlusion.Dogs were randomly divided into two experimental groups:group A,in which dogs were assessed for 2 h after coronary occlusion,and group B,in which dogs were assessed for 4 h after surgery.Baseline and postoperative assess-ment included cardiac troponin T(cTnT)levels,electrocardiography(ECG),plain and contrast echocardiography,and large-scale digital subtraction angiography(DSA).Results:Canine venous blood was successfully used to prepare a mixed thrombus with reticular fibrin structure and activated platelets in vitro.After the mixed thrombus was implanted into the coronary artery,large-scale DSA showed no contrast medium perfusion,confirming complete occlusion of the coronary artery.After the coronary artery occlusion,dogs in both groups showed ST segment elevation>0.5 MV,a 0.9μg/L increase in CTnT(p<0.001),and increased EDV and ESV.Dogs also showed decreased left ventricular EF and FS and decreased MBF in the infarcted area(p<0.05).Conclusions:An experimental model of acute coronary artery occlusion in dogs was successfully established by implanting a mixed thrombus developed in vitro into the coronary artery using minimally invasive PCI.展开更多
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 ge...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.展开更多
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)...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.展开更多
基金supported by the National Natural Science Foundation of China (No. 8196140154)the Natural Science Foundation of Xinjiang Uygur Autonomous Region (Nos.2023D01C139 and 2023D01C63)the State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund (No. SKL-HIDCA-2020-8)。
文摘Tianxiangdan(TXD),a traditional Chinese herbal remedy,demonstrates efficacy in mitigating myocardial ischemia-reperfusion(I/R)-induced damage.This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R.Highperformance liquid chromatography-mass spectrometry(HPLC-MS)identified 86 compounds in TXD.Network pharmacological analysis predicted potential target genes and their modes of action.Cardiac function,ischaemic ST changes,lactate dehydrogenase(LDH),malondialdehyde(MDA),superoxide dismutase(SOD)activity,myocardial fiber,and infarct size were assessed using in vivo and in vitro I/R injury models.Estrogen receptor alpha(ERα)protein expression and estradiol(E2)levels were measured to confirm TXD's impact on estrogen levels and ERαexpression.To examine if TXD reduces I/R injury through ERα,an AZD group(300 nmol·L^(-1)AZD9496 and 15%TXD serum)was compared to a TXD group(15%TXD serum).The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway.I/R injury-induced ferroptosis was identified using a Fer-1 group(1.0μmol·L^(-1)Fer-1 and 15%TXD serum)to elucidate the potential association between ferroptosis and ERαproteins.A DCFH-DA probe detected reactive oxygen species(ROS)and Fe^(2+),while Western blotting assessed target protein expression.Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels,improving cardiac injury biomarkers(LDH,MDA,and SOD),alleviating pathological features,and preventing I/R-induced loss of cell viability in vitro.The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells.The TXD group showed significantly decreased ROS and Fe^(2+)levels,while the AZ group(treated with AZD9496)exhibited increased levels.The TXD group demonstrated enhanced expression of ERαand glutathione peroxidase 4(GPX4),with reduced levels of P53 protein and ferritinheavy polypeptide 1(FTH1).The AZ group exhibited contrasting effects on these expression levels.The literature indicated a novel connection between ERαand ferroptosis.TXD activates the ERαsignaling pathway,promoting protection against I/R-induced myocardial cell ferroptosis.This study provides evidence supporting TXD use for myocardial ischemia treatment,particularly in older female patients who may benefit from its therapeutic outcomes.
基金Supported by National Natural Science Foundation of China,No.82260411 and No.82270632.
文摘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.
基金the State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia-funded Project:Correlation Study on Chronic Inflammation Mediated by Tolllike Receptor 4/Mutant Myeloid Differentiation Primary Response 88/Nuclear Factor Kappa-B Signaling Pathway(No.SKL-HIDCA-2021-ZY5)。
文摘OBJECTIVE:To investigate the role of toll-like receptor 4(TLR4)/mutant myeloid differentiation primary response 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway-mediated inflammation in diabetes mellitus with Northwest dryness syndrome.METHODS:Rats were randomly divided into the normal control,type 2 diabetes(T2DM)model,Northwest dryness syndrome+T2DM(Northwest dryness),and simple internal dampness+T2DM(internal dampness)groups.Enzyme-linked immunosorbent assay was used to detect biochemical indexes and inflammatory factors.The histopathological observation was performed.Quantitative real-time polymerase chain reaction and Western blot analysis were used to detect the mRNA and protein expression levels,respectively.RESULTS:Compared with the T2DM group,the glycosylated hemoglobin A1c,insulin,glucose tolerance,the homeostasis model assessment of insulin resistance,tumor necrosis factor-α,interleukin 1β,interleukin 16,malondialdehyde,blood lipid,alanine aminotransferase,and aspartate aminotransferase were significantly elevated in the internal dampness group.Their levels were significantly elevated in the Northwest dryness group than in the T2DM and internal dampness groups.The superoxide dismutase,glutathione peroxidase,liver glycogen,and organ-to-weight ratio were significantly declined in the internal dampness group and the Northwest dryness group than in the T2DM group.However,these levels were elevated in the Northwest dryness group than in the internal dampness group.Moreover,the mRNA expression levels of interferon regulatory factor 5 and NF-κB p65,and the protein expression levels of TLR4,MyD88,and NF-κB were significantly higher in the internal dampness and the Northwest dryness groups than the T2DM group.Additionally,the mRNA and protein levels were significantly higher in the Northwest dryness group than in the internal dampness group.CONCLUSION:Northwest dryness syndrome-mediated TLR4/MyD88/NF-κB pathway and chronic inflammation might be associated with the occurrence and development of T2DM.
基金supported by the State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund(No.SKL-HIDCA-2020-JZ11).
文摘Objective:Alternative splicing affects gene expression during placental development.The present study aimed to identify poly(ADP-ribose)polymerase 1(PARP1)-regulated alternative splicing events in HTR-8/Svneo cells.Methods:Decidual tissues were collected from women with induced abortion and spontaneous abortion.PARP1 transcription was quantified by RT-qPCR.Small interfering RNA(siRNA)was used to knock down the PARP1 expression in HTR-8/Svneo cells.The transfection efficiency was verified by RT-qPCR and Western blotting.Total RNA was extracted,and the RNA-sequencing approach was used to identify alternative splicing events and transcriptomes.The PARP1 knockdown-induced differentially expressed genes with changes in alternative splicing events were quantified by RT-qPCR.Functional analysis,which included the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways,was performed.Results:The PARP1 mRNA expression increased in decidual tissues in the spontaneous abortion group,when compared to the induced abortion group.However,the PARP1 knockdown significantly downregulated 1491 genes and upregulated 881 genes in HTR-8/Svneo cells.Furthermore,227 genes that underwent alternative splicing were identified,and these were differentially expressed in siPARP1 cells,when compared to siNC cells.Conclusion:The functional analysis revealed that these alternative splicing genes affected the functional phenotypes of extravillous cytotrophoblasts.Furthermore,the PARP1 knockdown led to alterations in gene expression and specific alternative splicing patterns in extravillous trophoblasts.
基金supported by the National Natural Science Foundation of China(NSFC)under Grant Nos.62035011,82202220 and 82060326State Key Laboratory of Pathogenesis,Prevention and treat ment of High Incident Diseases in central Asia(Nos.SKL-HIDCA-2022-3 and SKL-HIDCA-2022-GJ1)+3 种基金the Xinjiang Uygur Autonomous Region Regional Collaborative Innovation Special Science and Technology Assistance Program(No.2022E02130)Xinjiang Uygur Autonomous Region Natural Sci ence Foundation Key Project(No.2022D01D40)Outstanding Youth Project(2023D01E06)Y.Gao and C.Zhang authors contributed equally to this work.
文摘Triple-negative breast cancer (TNBC) is an aggressive and often fatal disease, especially since the brain metastasis of TNBC has been a particularly severe manifestation. However, brain metastasis in TNBC at early stages often lacks noticeable symptoms, making it challenging to detect. Near-infrared II (NIR-II) fluorescence microscopic imaging obtains long wavelength, which enables reduced scattering, high spatial resolution and minimal autofluorescence, it is also a favorable imaging method for tumor diagnosis. PbS@CdS quantum dots (QDs) are one of the popular NIR-II fluorescence nanoprobes for well brightness. In this study, NIR-II emissive PbS@CdS QDs were utilized and further encapsulated with thiol-terminated poly(ethylene oxide) (SH-PEG, MW = 5000) to form PbS@CdS@PEG QDs nanoparticles (NPs). The obtained PbS@CdS@PEG QDs NPs were then characterized and further studied in detail. The PbS@CdS@PEG QDs NPs had large absorption spectra, exhibited strong NIR-II fluorescence emission at approximately 1300nm, and possessed good NIR-II fluorescence properties. Then, the mice model of early-stage brain metastases of TNBC was established, and the PbS@CdS@PEG QDs NPs were injected into the tumor-bearing mice for NIR-II fluorescence microscopic bioimaging. The brain vessels and tumors of the living mice were detected with high spatial resolution under the NIR-II fluorescence microscopic imaging system with irradiation of 808nm laser. The tumor tissues were further restricted and prepared as thin slices. The NIR-II fluorescence signals were collected from the tumor slices with high spatial resolution and signal-to-background ratio (SBR). Thus, the PbS@CdS@PEG QDs NPs-assisted NIR-II fluorescence microscopic system can effectively achieve targeting brain metastases of TNBC imaging, offering a novel and promising approach for TNBC-specific diagnosis.
基金National Natural Science Foundation of China,No.32260089Science and Technology Research Foundation of Guizhou Province,No.QKHJC-ZK(2022)YB642+3 种基金Science and Technology Research Foundation of Hubei Province,No.2022BCE030Science and Technology Research Foundation of Changzhou City,No.CE20225040Science and Technology Research Foundation of Zunyi City,No.ZSKHHZ(2022)344 and No.ZSKHHZ(2022)360WBE Liver Fibrosis Foundation,No.CFHPC2025028.
文摘BACKGROUND Bletilla striata polysaccharides(BSP)have antioxidant,immune regulation,and anti-fibrotic activities.However,the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-associated steatotic liver disease(MASLD)have not been fully understood.AIMTo investigate the therapeutic effects and mechanisms of BSP on MASLD by centering on the hepatocyte nuclearfactor kappa B p65(RelA)/hepatocyte nuclear factor-1 alpha(HNF1α)signaling.METHODSA mouse model of MASLD was induced by feeding with a high-fat-diet(HFD)and a hepatocyte model of steatosiswas induced by treatment with sodium oleate(SO)and sodium palmitate(SP).The therapeutic effects of BSP onMASLD were examined in vivo and in vitro.The mechanisms underlying the action of BSP were analyzed for theireffect on lipid metabolism disorder,endoplasmic reticulum(ER)stress,and the RelA/HNF1αsignaling.RESULTSHFD feeding reduced hepatocyte RelA and HNF1αexpression,induced ER stress,lipid metabolism disorder,andnecroptosis in mice,which were significantly mitigated by treatment with BSP.Furthermore,treatment with BSP orBSP-containing conditional rat serum significantly attenuated the sodium oleate/sodium palmitate(SO/SP)-induced hepatocyte steatosis by decreasing lipid accumulation,and lipid peroxidation,and enhancing theexpression of RelA,and HNF1α.The therapeutic effects of BSP on MASLD were partially abrogated by RELAsilencing in mice and RELA knockout in hepatocytes.RELA silencing or knockout significantly down-regulatedHNF1αexpression,and remodeled ER stress and oxidative stress responses during hepatic steatosis.CONCLUSIONTreatment with BSP ameliorates MASLD,associated with enhancing the RelA/HNF1αsignaling,remodeling ERstress and oxidative stress responses in hepatocytes.
基金supported by grants from Xinjiang Uyghur Autonomous Region Key Laboratory Open Research Program(No.2018D03002)the National Natural Science Foundation of China(No.81560329)+1 种基金Xinjiang Uyghur Autonomous Region Key Scientific Research Program(No.201430123–2)State Key Laboratory of Pathogenesis,Prevention,Treatment of High Incidence Diseases in Central Asia Fund(No.SKL-HIDCA-2017-Y2)
文摘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.
文摘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.
基金financially supported by the National Natural Science Foundation of China(Nos.22074050,22022404,21804033)Wuhan Scientific and Technological Projects(No.2019020701011441)+2 种基金Open Research Fund supported by the Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund(No.SKL-HIDCA-2019-11)State Key Laboratory of Elemento-Organic Chemistry,Nankai University(No.201901)the ministry of education Key laboratory for the Synthesis and Application of Organic Functional Molecules,Hubei University(No.KLSAOFM2011).
文摘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.
基金supported by the Natural Science Foundation of Shandong Province,China(No.ZR2020MA088)Natural Science Foundation of Xinjiang Uygur Autonomous Region,China(No.2019D01C188)+1 种基金National Key Research and Development Program of China(No.2018YFC1200204)National Natural Science Foundation of China(No.12175127).
文摘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.
基金the Project of the Central Government Guiding Local Science and Technology under Grant Number ZYYD2022B18the Institutional Ethics Committee of Affiliated Cancer Hospital of Xinjiang Medical University(No.K-2019001).
文摘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.
基金supported by The National Natural Science Foundation of China(No.82160050)State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia(No.SKL-HIDCA-2021-24).
文摘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.
基金Supported by Natural Science Foundation of Xinjiang Uygur Autonomous Region,No.2022D01D17State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,No.SKL-HIDCA-2024-2.
文摘BACKGROUND Echinococcosis,caused by Echinococcus parasites,includes alveolar echinococcosis(AE),the most lethal form,primarily affecting the liver with a 90%mortality rate without prompt treatment.While radical surgery combined with antiparasitic therapy is ideal,many patients present late,missing hepatectomy opportunities.Ex vivo liver resection and autotransplantation(ELRA)offers hope for such patients.Traditional surgical decision-making,relying on clinical experience,is prone to bias.Machine learning can enhance decision-making by identifying key factors influencing surgical choices.This study innovatively employs multiple machine learning methods by integrating various feature selection techniques and SHapley Additive exPlanations(SHAP)interpretive analysis to deeply explore the key decision factors influencing surgical strategies.AIM To determine the key preoperative factors influencing surgical decision-making in hepatic AE(HAE)using machine learning.METHODS This was a retrospective cohort study at the First Affiliated Hospital of Xinjiang Medical University(July 2010 to August 2024).There were 710 HAE patients(545 hepatectomy and 165 ELRA)with complete clinical data.Data included demographics,laboratory indicators,imaging,and pathology.Feature selection was performed using recursive feature elimination,minimum redundancy maximum relevance,and least absolute shrinkage and selection operator regression,with the intersection of these methods yielding 10 critical features.Eleven machinelearning algorithms were compared,with eXtreme Gradient Boosting(XGBoost)optimized using Bayesian optimization.Model interpretability was assessed using SHAP analysis.RESULTS The XGBoost model achieved an area under the curve of 0.935 in the training set and 0.734 in the validation set.The optimal threshold(0.28)yielded sensitivity of 93.6%and specificity of 90.9%.SHAP analysis identified type of vascular invasion as the most important feature,followed by platelet count and prothrombin time.Lesions invading the hepatic vein,inferior vena cava,or multiple vessels significantly increased the likelihood of ELRA.Calibration curves showed good agreement between predicted and observed probabilities(0.2-0.7 range).The model demonstrated high net clinical benefit in Decision Curve Analysis,with accuracy of 0.837,recall of 0.745,and F1 score of 0.788.CONCLUSION Vascular invasion is the dominant factor influencing the choice of surgical approach in HAE.Machine-learning models,particularly XGBoost,can provide transparent and data-driven support for personalized decision-making.
基金This study was supported by the grants from the National Natural Science Foundation of China(81960377)Open Project of State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia(SKL-HIDCA-2020-BC and SKL-HIDCA-2021-4)Xinjiang Uygur Autonomous Region University Scientific Research Project(XJEDU2021I016).
文摘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].
基金supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2022D01D38)the National Natural Science Foundation of China(Nos.82173681,21977116,82104004,81973223)+1 种基金the Open Project of State Key Laboratory of Natural Medicines(No.SKLNMZZ202213)the State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund(No.SKL-HIDCA-2021-1).
文摘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.
基金the State Key Laboratory of Pathogenesis,Prevention and Treatment of Central Asia High Incidence Diseases fund(Nos.SKL-HIDCA-2019–7 and SKL-HIDCA2020–1)。
文摘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.
基金Supported by Key Laboratory Opening Topic Fund Subsidization:The Regulation of Sympathetic Nerve in Liver Regeneration in Hepatic Alveolar Echinococcosis,No.2021D04024.
文摘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.
基金Natural Science Foundation of Xinjiang Uygur Autonomous Region,Grant/Award Number:2022D01C254State Key Laboratory Pathogenesis,Prevention,Treatment of High Incidence Diseases in Central Asia,Grant/Award Number:SKLHIDCA-2017-Y13China Utrasound Doctor Science and Technology Star Program,Grant/Award Number:2017001。
文摘Objective:To establish an acute canine coronary artery occlusion model by implanting a mixed thrombus prepared in vitro into the coronary artery by percutaneous coronary intervention(PCI).Methods:This study included 14 healthy Beagle dogs aged 10-13 months.First,5 ml of canine venous blood was drawn to prepare the coronary artery thrombus in vitro.The thrombus was then implanted into the canine coronary artery by PCI to establish an animal model of acute coronary artery occlusion.Dogs were randomly divided into two experimental groups:group A,in which dogs were assessed for 2 h after coronary occlusion,and group B,in which dogs were assessed for 4 h after surgery.Baseline and postoperative assess-ment included cardiac troponin T(cTnT)levels,electrocardiography(ECG),plain and contrast echocardiography,and large-scale digital subtraction angiography(DSA).Results:Canine venous blood was successfully used to prepare a mixed thrombus with reticular fibrin structure and activated platelets in vitro.After the mixed thrombus was implanted into the coronary artery,large-scale DSA showed no contrast medium perfusion,confirming complete occlusion of the coronary artery.After the coronary artery occlusion,dogs in both groups showed ST segment elevation>0.5 MV,a 0.9μg/L increase in CTnT(p<0.001),and increased EDV and ESV.Dogs also showed decreased left ventricular EF and FS and decreased MBF in the infarcted area(p<0.05).Conclusions:An experimental model of acute coronary artery occlusion in dogs was successfully established by implanting a mixed thrombus developed in vitro into the coronary artery using minimally invasive PCI.
基金supported by the National Natural Science Foundation of China(Grant No.31770870)the National Science and Technology Major Projects of China(Grant No.2018ZX10302-301-004-003).
文摘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.
基金the Tianshan Youth Project Foundation of Xinjiang,China(No.2017Q056).
文摘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.
