Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

Estimation of cancer cell migration in biomimetic random/oriented collagen fiber microenvironments

Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment,playing a crucial role in pathological processes such as tumor invasion and metastasis.However,conventional two-dimensional cell culture and animal models have limitations in studying the influence of tumor microenvironment on cancer cell migration.Fortunately,the further development of microfluidic technology has provided solutions for the study of such questions.We utilize microfluidic chip to build a random collagen fiber microenvironment(RFM)model and an oriented collagen fiber microenvironment(OFM)model that resemble early stage and late stage breast cancer microenvironments,respectively.By combining cell culture,biochemical concentration gradient construction,and microscopic imaging techniques,we investigate the impact of different collagen fiber biochemical microenvironments on the migration of breast cancer MDA-MB-231-RFP cells.The results show that MDA-MB-231-RFP cells migrate further in the OFM model compared to the RFM model,with significant differences observed.Furthermore,we establish concentration gradients of the anticancer drug paclitaxel in both the RFM and OFM models and find that paclitaxel significantly inhibits the migration of MDA-MB-231-RFP cells in the RFM model,with stronger inhibition on the high concentration side compared to the low concentration side.However,the inhibitory effect of paclitaxel on the migration of MDA-MB-231-RFP cells in the OFM model is weak.These findings suggest that the oriented collagen fiber microenvironment resembling the late-stage tumor microenvironment is more favorable for cancer cell migration and that the effectiveness of anticancer drugs is diminished.The RFM and OFM models constructed in this study not only provide a platform for studying the mechanism of cancer development,but also serve as a tool for the initial measurement of drug screening.

Hypoxic tumor microenvironment:Destroyer of natural killer cell function

In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer(NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment(TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.

New roles of tumor-derived exosomes in tumor microenvironment

Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.

Microenvironmental effects on growth response of Pinus massoniana to climate at its northern boundary in the Tongbai Mountains,Central China

The Tongbai Mountains is an ecologically sensi-tive region and the northern boundary of Pinus massoniana Lamb.To analyze the effect of different microenvironments on tree growth response to climate factors,we developed standard chronologies for earlywood width(EWW),late-wood width(LWW),and total ring width(TRW)of P.massoniana at two sampling sites on slopes with different orientations,then analyzed characteristics of the chronolo-gies and their correlations with climate variables from five stations in the region and with a regional normalized differ-ence vegetation index(NDVI).Statistical results showed that the TRW/EWW/LWW chronology consistency and charac-teristics(mean sensitivity,signal to noise ratio,expressed population signal)for trees growing on the southeastern slope were much higher than for trees on the northeastern slope.Correlations indicated that temperature in current March and August has a significant positive effect on TRW/EWW/LWW formation,and the effect on the northeastern slope was weaker than on the southeastern slope.Compared to temperature,precipitation has more complicated effects on tree growth,but the effect on the northeastern slope was also generally weaker than on the southeastern slope.Step-wise linear regression analyses showed that temperature in August was the main limiting factor at the two sampling sites.Similarly,the response of tree growth on the southeast-ern slope as determined by the NDVI is better than on the northeastern slope,and the TRW/EWW/LWW chronologies for the southeastern slope explained over 50%of the total NDVI variances in June.Overall,the results indicate that the difference in the climate response of P.massoniana at two sampling sites is clearly caused by differences in the microenvironment,and such differences should be properly considered in future studies of forest dynamics and climate reconstructions.

Development of a toroidal soft x-ray imaging system and application for investigating three-dimensional plasma on J-TEXT

A toroidal soft x-ray imaging(T-SXRI)system has been developed to investigate threedimensional(3D)plasma physics on J-TEXT.This T-SXRI system consists of three sets of SXR arrays.Two sets are newly developed and located on the vacuum chamber wall at toroidal positionsφof 126.4°and 272.6°,respectively,while one set was established previously atφ=65.50.Each set of SXR arrays consists of three arrays viewing the plasma poloidally,and hence can be used separately to obtain SXR images via the tomographic method.The sawtooth precursor oscillations are measured by T-SXRI,and the corresponding images of perturbative SXR signals are successfully reconstructed at these three toroidal positions,hence providing measurement of the 3D structure of precursor oscillations.The observed 3D structure is consistent with the helical structure of the m/n=1/1 mode.The experimental observation confirms that the T-SXRI system is able to observe 3D structures in the J-TEXT plasma.

DNA Damage-driven Inflammatory Cytokines:Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy

DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor progression.Accumulating evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines.These cytokines possess multifaced functions in the anti-tumor immune response.Thus,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor therapies.This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines.We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.

Computer-assisted three-dimensional individualized extreme liver resection for hepatoblastoma in proximity to the major liver vasculature

BACKGROUND The management of hepatoblastoma(HB)becomes challenging when the tumor remains in close proximity to the major liver vasculature(PMV)even after a full course of neoadjuvant chemotherapy(NAC).In such cases,extreme liver resection can be considered a potential option.AIM To explore whether computer-assisted three-dimensional individualized extreme liver resection is safe and feasible for children with HB who still have PMV after a full course of NAC.METHODS We retrospectively collected data from children with HB who underwent surgical resection at our center from June 2013 to June 2023.We then analyzed the detailed clinical and three-dimensional characteristics of children with HB who still had PMV after a full course of NAC.RESULTS Sixty-seven children diagnosed with HB underwent surgical resection.The age at diagnosis was 21.4±18.8 months,and 40 boys and 27 girls were included.Fifty-nine(88.1%)patients had a single tumor,39(58.2%)of which was located in the right lobe of the liver.A total of 47 patients(70.1%)had PRE-TEXT III or IV.Thirty-nine patients(58.2%)underwent delayed resection.After a full course of NAC,16 patients still had close PMV(within 1 cm in two patients,touching in 11 patients,compressing in four patients,and showing tumor thrombus in three patients).There were 6 patients of tumors in the middle lobe of the liver,and four of those patients exhibited liver anatomy variations.These 16 children underwent extreme liver resection after comprehensive preoperative evaluation.Intraoperative procedures were performed according to the preoperative plan,and the operations were successfully performed.Currently,the 3-year event-free survival of 67 children with HB is 88%.Among the 16 children who underwent extreme liver resection,three experienced recurrence,and one died due to multiple metastases.CONCLUSION Extreme liver resection for HB that is still in close PMV after a full course of NAC is both safe and feasible.This approach not only reduces the necessity for liver transplantation but also results in a favorable prognosis.Individualized three-dimensional surgical planning is beneficial for accurate and complete resection of HB,particularly for assessing vascular involvement,remnant liver volume and anatomical variations.

Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS

The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.

Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.

Glycogen metabolism-mediated intercellular communication in the tumor microenvironment influences liver cancer prognosis

Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.

Prognostic and predictive role of immune microenvironment in colorectal cancer

Colorectal cancer(CRC)represents a molecularly heterogeneous disease and one of the most frequent causes of cancer-related death worldwide.The traditional classification of CRC is based on pathomorphological and molecular character-istics of tumor cells(mucinous,ring-cell carcinomas,etc.),analysis of mechanisms of carcinogenesis involved(chromosomal instability,microsatellite instability,CpG island methylator phenotype)and mutational statuses of commonly altered genes(KRAS,NRAS,BRAF,APC,etc.),as well as expression signatures(CMS 1-4).It is also suggested that the tumor microenvironment is a key player in tumor progression and metastasis in CRC.According to the latest data,the immune microenvironment can also be predictive of the response to immune checkpoint inhibitors.In this review,we highlight how the immune environment influences CRC prognosis and sensitivity to systemic therapy.

Action of circulating and infiltrating B cells in the immune microenvironment of colorectal cancer by single-cell sequencing analysis

BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.

Three-dimensional stability calculation method for high and large composite slopes formed by mining stope and inner dump in adjacent open pits

The 2D limit equilibrium method is widely used for slope stability analysis.However,with the advancement of dump engineering,composite slopes often exhibit significant 3D mechanical effects.Consequently,it is of significant importance to develop an effective 3D stability calculation method for composite slopes to enhance the design and stability control of open-pit slope engineering.Using the composite slope formed by the mining stope and inner dump in Baiyinhua No.1 and No.2 open-pit coal mine as a case study,this research investigates the failure mode of composite slopes and establishes spatial shape equations for the sliding mass.By integrating the shear resistance and sliding force of each row of microstrip columns onto the bottom surface of the strip corresponding to the main sliding surface,a novel 2D equivalent physical and mechanical parameters analysis method for the strips on the main sliding surface of 3D sliding masses is proposed.Subsequently,a comprehensive 3D stability calculation method for composite slopes is developed,and the quantitative relationship between the coordinated development distance and its 3D stability coefficients is examined.The analysis reveals that the failure mode of the composite slope is characterized by cutting-bedding sliding,with the arc serving as the side interface and the weak layer as the bottom interface,while the destabilization mechanism primarily involves shear failure.The spatial form equation of the sliding mass comprises an ellipsoid and weak plane equation.The analysis revealed that when the coordinated development distance is 1500 m,the error rate between the 3D stability calculation result and the 2D stability calculation result of the composite slope is less than 8%,thereby verifying the proposed analytical method of equivalent physical and mechanical parameters and the 3D stability calculation method for composite slopes.Furthermore,the3D stability coefficient of the composite slope exhibits an exponential correlation with the coordinated development distance,with the coefficient gradually decreasing as the coordinated development distance increases.These findings provide a theoretical guideline for designing similar slope shape parameters and conducting stability analysis.

Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status

Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage.The recent description of the tumor microenvironment(TME)in HCC has provided a new concept of immunogenicity within the HCC.Virusrelated HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells.This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors(ICIs).In addition,the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity.Therefore,data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.

Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma:A comprehensive review

The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits.However,recent studies have shown that lymphatic endothelial cells(LECs)and blood endothelial cells(BECs)also play multifaceted roles in the tumor microenvironment beyond their structural functions,particularly in hepatocellular carcinoma(HCC).This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC,including their involvement in angiogenesis,immune modulation,lymphangiogenesis,and metastasis.By providing a detailed account of the complex interplay between LECs,BECs,and tumor cells,this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.

Computed tomography three-dimensional reconstruction in the diagnosis of bleeding small intestinal polyps:A case report

BACKGROUND Computed tomography(CT)small bowel three-dimensional(3D)reconstruction is a powerful tool for the diagnosis of small bowel disease and can clearly show the intestinal lumen and wall as well as the outside structure of the wall.The horizontal axis position can show the best adjacent intestinal tube and the lesion between the intestinal tubes,while the coronal position can show the overall view of the small bowel.The ileal end of the localization of the display of excellent,and easy to quantitative measurement of the affected intestinal segments,the sagittal position for the rectum and the pre-sacral lesions show the best,for the discovery of fistulae is also helpful.Sagittal view can show rectal and presacral lesions and is useful for fistula detection.It is suitable for the assessment of inflammatory bowel disease,such as assessment of disease severity and diagnosis and differential diagnosis of the small bowel and mesenteric space-occupying lesions as well as the judgment of small bowel obstruction points.CASE SUMMARY Bleeding caused by small intestinal polyps is often difficult to diagnose in clinical practice.This study reports a 29-year-old male patient who was admitted to the hospital with black stool and abdominal pain for 3 months.Using the combination of CT-3D reconstruction and capsule endoscopy,the condition was diagnosed correctly,and the polyps were removed using single-balloon enteroscopyendoscopic retrograde cholangiopancreatography without postoperative complications.CONCLUSION The role of CT-3D in gastrointestinal diseases was confirmed.CT-3D can assist in the diagnosis and treatment of gastrointestinal diseases in combination with capsule endoscopy and small intestinal microscopy.

Research on Quantitative Identification of Three-Dimensional Connectivity of Fractured-Vuggy Reservoirs

The fractured-vuggy carbonate oil resources in the western basin of China are extremely rich.The connectivity of carbonate reservoirs is complex,and there is still a lack of clear understanding of the development and topological structure of the pore space in fractured-vuggy reservoirs.Thus,effective prediction of fractured-vuggy reservoirs is difficult.In view of this,this work employs adaptive point cloud technology to reproduce the shape and capture the characteristics of a fractured-vuggy reservoir.To identify the complex connectivity among pores,fractures,and vugs,a simplified one-dimensional connectivity model is established by using the meshless connection element method(CEM).Considering that different types of connection units have different flow characteristics,a sequential coupling calculation method that can efficiently calculate reservoir pressure and saturation is developed.By automatic history matching,the dynamic production data is fitted in real-time,and the characteristic parameters of the connection unit are inverted.Simulation results show that the three-dimensional connectivity model of the fractured-vuggy reservoir built in this work is as close as 90%of the fine grid model,while the dynamic simulation efficiency is much higher with good accuracy.

Application of three-dimensional speckle tracking technique in measuring left ventricular myocardial function in patients with diabetes

BACKGROUND Diabetic cardiomyopathy is considered as a chronic complication of diabetes mellitus(DM).Therefore,early detection of left ventricular systolic function(LVSF)damage in DM is essential.AIM To explore the use of the three-dimensional speckle tracking technique(3D-STI)for measuring LVSF in DM patients via meta-analysis.METHODS The electronic databases were retrieved from the initial accessible time to 29 April 2023.The current study involved 9 studies,including 970 subjects.We carried out this meta-analysis to estimate myocardial function in DM compared with controls according to myocardial strain attained by 3D-STI.RESULTS Night articles including 970 subjects were included.No significant difference was detected in the left ventricular ejection fraction between the control and the diabetic group(P>0.05),while differences in global longitudinal strain,global circumferential strain,global radial strain,and global area strain were markedly different between the controls and DM patients(all P<0.05).CONCLUSION The 3D-STI could be applied to accurately measure early LVSF damage in patients with DM.