Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy

Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.

Minimally invasive interventional therapy for pain

Pain interventional therapy,known as the most promising medical technology in the 21st century,refers to clinical treatment technology based on neuroanatomy,neuroimaging,and nerve block technology to treat pain diseases.Compared with traditional destructive surgery,interventional pain therapy is considered a better and more economical choice of treatment.In recent years,a variety of minimally invasive pain interventional therapy techniques,such as neuroregulation,spinal cord electrical stimulation,intervertebral disc ablation,and intrasheath drug infusion systems,have provided effective solutions for the treatment of patients with post-herpetic neuralgia,complex regional pain syndrome,cervical/lumbar disc herniation,and refractory cancer pain.

An investigation of the morphodynamic change of reef islands under monochromatic waves

The persistence and habitability of coral reef islands in future extreme oceanographic conditions has received increasing attention in the recent decade,concerning that the sea level rise(SLR)and more frequent and intense storms in the context of global climate change are expected to destabilize those islands.Here,we conduct a set of wave-flume laboratory experiments focusing on the morphodynamic change of reef islands to varying ocean forcing conditions(wave height and SLR).Subsequently,a phase-resolving XBeach numerical model is adopted to simulate the monochromatic wave process and its associated sediment dynamics.The adopted model is also firstly validated by laboratory experimental results as reported in this study.It is then used to examine the impacts of island morphological factors(island width,island height,island location and island side slope)on the island migration.The combined laboratory/physical and numerical experiment outputs suggest that reef islands can accrete vertically in response to the sea level rise and the increased storminess.

An Interdisciplinary Perspective from the Earth Scientist's Periodic Table:Similarity and Connection between Geochemistry and Metallurgy

In 2003,Railsback proposed the Earth Scientist's Periodic Table,which displays a great deal of elemental geology information in accordance with the natural environment of the earth.As an applied science,metallurgy is based on mineral composition and element behavior,that is similar to geochemistry.In this paper,connections and similarities between geology and metallurgy are identified,based on geochemical laws and numerous metallurgical cases.An obvious connection is that simple cations w让h high and low ionic potential are commonly extracted by hydrometallurgy,while those with intermediate ionic potential are extracted by pyrometallurgy.In addition,element affinity in geology is associated with element migration in metallurgic phases.To be specific,in pyrometallurgy,lithophile elements tend to gather in slags,chalcophile elements prefer the matte phase,siderophile elements are easily absorbed into metal melt,and atmophile elements readily enter the gas phase.Furthermore,in hydrometallurgy,the principles of hard/soft acids and bases(HSABs)offer an explanation of how precipitation and dissolution occur in different solutions,especially for fluoride and chloride.This article provides many metallurgical examples based on the principles of geochemistry to verify these similarities and connections.

Precision interventional radiology

The recent interest in precision medicine among interventionists has led to the establishment of the concept of precision interventional radiology(PIR).This concept focuses not only on the accuracy of interventional operations using traditional image-guided techniques,but also on the comprehensive evaluation of diseases.The invisible features extracted from CT,MRI,or US improve the accuracy and specificity of diagnosis.The integration of multi-omics and molecule imaging provides more information for interventional operations.The development and application of drugs,embolic materials,and devices broaden the concept of PIR.Integrating medicine and engineering brings new image-guided techniques that increase the efficacy of interventional operations while reducing the complications of interventional treatment.In all,PIR,an important part of precision medicine,emphasizing the whole disease management process,including precision diagnosis,comprehensive evaluation,and interventional therapy,maximizes the benefits of patients with limited damage.

Fucoidan-based dual-targeting mesoporous polydopamine for enhanced MRI-guided chemo-photothermal therapy of HCC via P-selectin-mediated drug delivery

The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin(FMPDA/Gd^(3+)/DOX)was prepared as an effective theranostic agent for magnetic resonance imaging(MRI)-guided chemo-photothermal therapy of HCC.It was found that FMPDA/Gd^(3+)/DOX had a high photothermal conversion efficiency of 33.4%and excellent T1-MRI performance with a longitudinal relaxivity(r1)value of 14.966 m M^(-1)·s^(-1).Moreover,the results suggested that FMPDA/Gd^(3+)/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells,which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors.The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd^(3+)/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality.Overall,our study demonstrated that FMPDA/Gd^(3+)/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.

One-year status of hepatic venous pressure gradient measurement from 85 hospitals in China

Aims:Surveys and research on the applications of the hepatic venous pressure gradient(HVPG)are important for understanding the current status and future development of this technology in China.This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022.Methods:We investigated the overall status of HVPG technology in China-including hospital distribution,hospital level,annual number of cases,catheters used,average cost,indications,and current challenges by using online questionnaire.By counting the number and percentages of cases of these results,we hope to clarify the current status of HVPG measurements in China.Results:According to the survey,85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces.A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022,of which 2813 cases(56.4%)were measured alone.The average cost of HVPG measurement was 5646.8±2327.9 CNY.Of the clinical teams who performed the measurements(sometimes multiple per hospital),94.3%(82/87)used the balloon method,and the majority of the teams(72.4%,63/87)used embolectomy catheters.Conclusions:This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology.It is still necessary to continue promoting and popularizing this technology in the future.

Sialic acid-engineered mesoporous polydopamine nanoparticles loaded with SPIO and Fe3+as a novel theranostic agent for T1/T2 dual-mode MRI-guided combined chemo-photothermal treatment of hepatic cancer

diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer.Herein,we aimed to develop a novel mesoporous polydopamine(MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging(MRI)-guided cancer chemo-photothermal therapy.Superparamagnetic iron oxide(SPIO)-loaded MPDA NPs(MPDA@SPIO)was firstly prepared,followed by modifying with a targeted molecule of sialic acid(SA)and chelating with Fe^(3+)(SA-MPDA@SPIO/Fe^(3+) NPs).After that,doxorubicin(DOX)-loaded SA-MPDA@SPIO/Fe^(3+) NPs(SA-MPDA@SPIO/DOX/Fe^(3+))was prepared for tumor theranostics.The prepared SAPEG-MPDA@SPIO/Fe^(3+) NPs were water-dispersible and biocompatible as evidenced by MTT assay.In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability,with relaxivity of being r1=4.29 mM1s1 and r2=105.53 mM1s1,respectively.SAPEG-MPDA@SPIO/Fe^(3+) NPs could effectively encapsulate the DOX,showing dual pH-and thermal-triggered drug release behavior.In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe^(3+) NPs could effectively target to the hepatic tumor tissue,which was possibly due to the specific interaction between SA and the overexpressed E-selectin.This behavior also endowed SA-MPDA@SPIO/DOX/Fe^(3+)NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification.In addition,SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs displayed a superior therapeutic effect,which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy.These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs is an effective targeted nanoplatform for tumor theranostics,having potential value in the effective treatment of hepatic cancer.

Tolerance and acceptance of hepatic venous pressure gradient measurement in cirrhosis(CHESS1904):An international multicenter study

Aim:To determine the tolerance and acceptance of hepatic venous pressure gradient(HVPG)measurements in patients with liver cirrhosis.Methods:This prospective international multicenter study included 271 patients with cirrhosis who were scheduled to undergo HVPG measurement between October 2019 and June 2020.Data related to the tolerance and acceptance of HVPG measurements were collected using descriptive questionnaires.Results:HVPG measurements were technically successful in all 271 patients,with 141(52.0%)undergoing HVPG measurement alone.The complication rate was 0.4%.Postoperative pain was significantly lower than preoperative expected pain(p<0.001)and intraoperative pain(p<0.001),and intraoperative pain was also significantly lower than preoperative expected pain(p=0.036).No,mild,moderate,severe,and intolerable discomfort scores were reported by 36.9%,44.6%,11.1%,6.3%,and 0.4%of these patients,respectively,during HVPG measurement and by 54.6%32.5%,11.4%,1.5%,and 0%,respectively,after HVPG measurement.Of these patients,39.5%had little understanding and 10%had no understanding of the value of HVPG measurement,with 35.1%and 4.1%regarding HVPG measurements as being of little or no help,respectively.Most patients reported that they would definitely(15.5%),probably(46.9%),or possibly(29.9%)choose to undergo additional HVPG measurements again,and 62.7%regarded the cost of the procedure as acceptable.Conclusion:HVPG measurement was safe and well‐tolerated in patients with cirrhosis,but patient education and communication are warranted to improve the acceptance of this procedure.

Pull-through capacity of bolted thin steel plate

The loading capacity in the axial direction of a bolted thin steel plate was investigated.A refined numerical model of bolt was first constructed and then validated using existing experiment results.Parametrical analysis was performed to reveal the influences of geometric parameters,including the effective depth of the cap nut,the yield strength of the steel plate,the preload of the bolt,and shear force,on the ultimate loading capacity.Then,an analytical method was proposed to predict the ultimate load of the bolted thin steel plate.Results derived using the numerical and analytical methods were compared and the results indicated that the analytical method can accurately predict the pull-through capacity of bolted thin steel plates.The work reported in this paper can provide a simplified calculation method for the loading capacity in the axial direction of a bolt.