Comparison of the clinical effects of dual-modality endoscopy and traditional laparotomy for the treatment of intra-and extrahepatic bile duct stones

BACKGROUND Bile duct stones(BDSs)may cause patients to develop liver cirrhosis or even liver cancer.Currently,the success rate of surgical treatment for intrahepatic and extrahepatic BDSs is not satisfactory,and there is a risk of postoperative complic-ations.AIM To compare the clinical effects of dual-modality endoscopy(duodenoscopy and laparoscopy)with those of traditional laparotomy in the treatment of intra-and extrahepatic BDSs.METHODS Ninety-five patients with intra-and extrahepatic BDSs who sought medical services at Wuhan No.1 Hospital between August 2019 and May 2023 were selected;45 patients in the control group were treated by traditional laparotomy,and 50 patients in the research group were treated by dual-modality endoscopy.The following factors were collected for analysis:curative effects,safety(incision infection,biliary fistula,lung infection,hemobilia),surgical factors[surgery time,intraoperative blood loss(IBL)volume,gastrointestinal function recovery time,and length of hospital stay],serum inflammatory markers[tumor necrosis factor(TNF)-α,interleukin(IL)-6,and IL-8],and oxidative stress[glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),malondialdehyde(MDA),and advanced protein oxidation products(AOPPs)].RESULTS The analysis revealed markedly better efficacy(an obviously higher total effective rate)in the research group than in the control group.In addition,an evidently lower postoperative complication rate,shorter surgical duration,gastrointestinal function recovery time and hospital stay,and lower IBL volume were observed in the research group.Furthermore,the posttreatment serum inflammatory marker(TNF-α,IL-6,and IL-8)levels were significantly lower in the research group than in the control group.Compared with those in the control group,the posttreatment GSH-Px,SOD,MDA and AOPPs in the research group were equivalent to the pretreatment levels;for example,the GSH-Px and SOD levels were significantly higher,while the MDA and AOPP levels were lower.CONCLUSION Dual-modality endoscopy therapy(duodenoscopy and laparoscopy)is more effective than traditional laparotomy in the treatment of intra-and extrahepatic BDSs and has a lower risk of postoperative complications;significantly shortened surgical time;shorter gastrointestinal function recovery time;shorter hospital stay;and lower intraop-erative bleeding volume,while having a significant inhibitory effect on excessive serum inflammation and causing little postoperative oxidative stress.

High-speed all-optic optical coherence tomography and photoacoustic microscopy dual-modal system for microcirculation evaluation

We propose a high-speed all-optic dual-modal system that integrates spectral domain optical coherence tomography and photoacoustic microscopy(PAM).A 3*3 coupler-based interfer-ometer is used to remotely detect the surface vibration caused by photoacoustic(PA)waves.Three outputs of the interferometer are acquired simultaneously with a multi-channel data ac-quisition card.One channel data with the highest PA signal detection sensitivity is selected for sensitivity compensation.Experiment on the phantom demonstrates that the proposed method can sucessfully compensate for the loss of intensity caused by sensitivity variation.The imaging speed of the PAM is improved compared to our previous system.The total time to image a sample with 256×256 pixels is~20s.Using the proposed system,the microvasculature in the mouse auricle is visualized and the blood flow state is accessed.

IN VIVO VALIDATION OF DUAL-MODALITY SYSTEM FOR SIMULTANEOUS POSITRON EMISSION TOMOGRAPHY AND OPTICAL TOMOGRAPHIC IMAGING

We report on tests of combined positron emission tomography(PET)andfluorescence molecular tomography(FMT)imaging system for in vivo investigation on small animals.A nude mouse was inoculated with MD-MB-231 breast cancer cells which expressed redfluorescent protein(RFP).For FMT system,reflective illumination mode was adopted with full-angle data acquisition.[18F]-Fluorodeoxyglucose([18F]-FDG)was used as radioactive tracer for PET.Both data were acquired simultaneously and then reconstructed separately before fusion.Fluorescent tomography results showed exactly where the tumor was located while PET results offered more metabolic information.Results confirmed feasibility for tumor detection and showed superiority to single modality imaging.

Fe3O4-based Nanoparticles for pH-responsive Dual-modality Imaging and Photothermal Therapy

The study designed a polyacrylic acid(PAA)modified Fe3O4@MnO2 nanoparticles(Fe3O4@MnO2@PAA)for T1/T2 dualmode imaging.In addition,this nano-drug has pH response and anti-tumor photothermal therapy.First,using Fe3O4 as the core can significantly reduce the signal of Fe3O4@MnO2@PAA nanoparticles.MnO2 nanoshells can be decomposed into paramagnetic Mn2+under the acidic environment in the tumor,which enhanced the T1 signal.The pH-responsive T1/T2 dual-mode magnetic resonance imaging(MRI)contrast agent had good sensitivity and specificity,providing more comprehensive and detailed information for tumor diagnosis.In addition,Fe3O4@MnO2@PAA nanoparticles showed excellent absorption capacity in the near-infrared region(NIR),which could be used as a good photothermal conversion material to mediate photothermal treatment of tumors.Therefore,the pHresponsive dual-mode MRI nanoparticle-mediated photothermal therapy showed good application potential in tumor treatment and diagnosis.

Colorimetric and Photothermal Dual-modal Visual Detection of Iodide Ion Based on G-Quadruplex-Hemin Cascade Signal Amplification

The insufficient internal resorption of iodide ions(I−)leads to thyroid disorders,such as goiter,hypothyroidism,and cretinism in adults.In this paper,a portable point-of-care testing(POCT)platform was developed for the dual-modal analysis of I^(−),seamlessly integrating both colorimetric and photothermal thermometer techniques.The quantification of results was achieved using a standard thermometer or smartphone.G-Quadruplex/Hemin(G4/Hemin)is the DNAzyme with peroxidase-like activity.The catalytic efficacy of G-quadruplex structures can be enhanced with the help of I^(−),manifesting as multicolor transitions from colorless to green and then blue,and accompanied by the increase of temperature,which can be used for the quantitative detection of I^(−).Additionally,digital analysis according to the three-color channels(R/G/B)by a cellphone eliminated the requirement for intricate instruments.This dual-modal method for portable I^(−)determination is cost-effectiveness,simplicity,remarkable sensitivity(0.5 nmol/L)and selectivity.Besides,it was applied to determining the concentration of I^(−)in spiked serum samples.

Aggregation-induced Emission Probe for Fluorescence/Photoacoustic Dual-modality Imaging and Photodynamic/Photothermal Treatment

The combination of near-infrared(NIR)fluorescence imaging(FLI)and photoacoustic imaging(PAI)can effectively compensate for each other’s inherent limitations,which can provide reliable and rich information on tumor biology.Therefore,the development of FL/PA dual-modality imaging probes is beneficial for achieving precision cancer diagnosis and treatment.Herein,we designed an efficient phototherapy agent methoxy bithiophene indene(OTIC),which was based on aggregation-induced emission(AIE)active fluorophores.To improve the water dispersion and enrichment of OTIC at the tumor site,OTIC nanoparticles(OTIC NPs)were prepared by a nanoprecipitation method.The balance between radiation and non-radiation energy dissipation was regulated by the strong donor-acceptor interaction and intramolecular motion.So OTIC NPs exhibited bright NIR fluorescence,photoacoustic signals,efficient generation of reactive oxygen species,and high photothermal conversion efficiency under NIR irradiation.Accurate imaging of the tumor and mice sentinel lymph nodes(SLNs)with OTIC NPs was visualized by NIR FL/PA dual-modal imaging.With the comprehensive imaging information provided by OTIC NPs in vivo,tumors were ablated under laser irradiation,which greatly improved the therapeutic efficacy.OTIC NPs would be possible to realize the precise guidance of FL/PA imaging for tumor treatment in the future clinical application.

Recent advances in photoelectrochemistry-coupled dual-modal biosensors:From constructions to biosensing applications

Precise and sensitive bioanalysis has been the major and urgent pursuit in pathologic diagnosis,food safety,environment monitoring,and drug evaluation.Photoelectrochemical(PEC)bioanalysis,as one of the most promising detection technologies,has rapidly expanded within the field of analysis.However,most of reported PEC analysis approaches still suffer from weak external anti-interference ability,high background,and the risk of false positive or negative errors due to their inherent single-signal readout.To overcome these shortcomings,new PEC-coupled dual-modal analysis approaches have been developed,where a dual-response signal can be derived through two completely different mechanisms and independent signal transduction pathways.This review introduces the basic principles of PEC biosensing and enumerates and classifies the substrate or probe selections,constructions,and applications of PEC-coupled dual-modal biosensors.Furthermore,the challenges and developmental prospects of PEC-coupled dual-mode sensing technologies are evaluated and discussed.We hope that this review will provide valuable insights into the latest advancements and practical applications of dual-mode PEC bioanalysis,which will be of great interest to those seeking to stay informed in this field.

A dual-modality hydrogen sulfide-specific probe integrating chemiluminescence with NIR fluorescence for targeted cancer imaging

Taking apart in numerous physiological and pathological activities,hydrogen sulfide(H_(2)S)has been selected as an excellent target spot for the early diagnosis of cancer.So far,there are many mature probes that apply single optical imaging to monitor endogenous H_(2)S.Nevertheless,a single modality is not an ideal method to afford accurate diagnostic information in comprehensive biological organisms.Herein,we developed a dual-modal imaging probe BWS.This designed probe showed a specific response to H_(2)S with both chemiluminescence and NIR fluorescence light-up.The concurrence of fluorescence and chemiluminescence signal provided“double insurances”for highly accurate monitoring of H_(2)S.Satisfactorily,this dual-modal imaging probe performed precise visualization of endogenous H_(2)S in living cells and in vivo.We envisaged that this chemiluminescence/fluorescence real-time dual-modality strategy for H_(2)S detection will expand and optimize the multimodal imaging methods for efficient diagnosis and treatment of cancer.

Gadolinium-containing semiconducting polymer nanoparticles for magnetic resonance/fluorescence dual-modal imaging and photothermal therapy of oral squamous cell carcinoma

Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the oral and maxillofacial region.Due to its unique location,earlier and more accurate diagnosis and more minimally invasive treatment of OSCC is of major importance.Herein,gadolinium-containing semiconductor polymer nanoparticles(SPN-Gd)were designed and prepared.The nanoparticles consist of a near-infrared(NIR)absorption semiconductor polymer(PCPDTBT)served as fluorescence signal source and a photothermal conversion agent(PTA)and a gadolinium-grafted triblock amphiphilic copolymer(F127-DTPA-Gd)served as a magnetic resonance imaging(MRI)contrast agent and nanocarrier.The experiments in vivo showed that SPN-Gd could act as an MRI contrast agent and optical image agent with a long retention time,and it had a significant inhibiting effect on tumors of OSCC mice model through photothermal therapy(PTT).Thus our study provides a simple nanotheranostic platform composed of two components for efficient MR/fluorescence dual-modal imaging-guided PTT.

Polymeric dual-modal imaging nanoprobe with two-photon aggregation-induced emission for fluorescence imaging and gadolinium-chelation for magnetic resonance imaging

Nanoprobes that offer both fluorescence imaging(FI)and magnetic resonance imaging(MRI)can provide supplementary information and hold synergistic advantages.However,synthesis of such dual-modality imaging probes that simultaneously exhibit tunability of functional groups,high stability,great biocompatibility and desired dual-modality imaging results remains challenging.In this study,we used an amphiphilic block polymer from(ethylene glycol)methyl ether methacrylate(OEGMA)and N-(2-hydroxypropyl)methacrylamide(HPMA)derivatives as a carrier to conjugate a MR contrast agent,Gd-DOTA,and a two-photon fluorophore with an aggregation-induced emission(AIE)effect,TPBP,to construct a MR/two-photon fluorescence dual-modality contrast agent,Gd-DOTA-TPBP.Incorporation of gadolinium in the hydrophilic chain segment of the OEGMA-based carrier resulted in a high r_(1)value for Gd-DOTA-TPBP,revealing a great MR imaging resolution.The contrast agent specifically accumulated in the tumor region,allowing a long enhancement duration for vascular and tumor contrast-enhanced MR imaging.Meanwhile,coupling TPBP with AIE properties to the hydrophobic chain segment of the carrier not only improved its water solubility and reduced its cytotoxicity,but also significantly enhanced its imaging performance in an aqueous phase.Gd-DOTA-TPBP was also demonstrated to act as an excellent fluorescence probe for two-photon-excited bioimaging with higher resolution and greater sensitivity than MRI.Since high-resolution,complementary MRI/FI dual-modal images were acquired at both cellular and tissue levels in tumor-bearing mice after application of Gd-DOTA-TPBP,it has great potential in the early phase of disease diagnosis.

MRI/PAI Dual-modal Imaging-guided Precise Tracking of Bone Marrow-derived Mesenchymal Stem Cells Labeled with Nanoparticles for Treating Liver Cirrhosis

Background and Aims:Stem cell transplantation is a potential treatment option for liver cirrhosis(LC).Accurately and noninvasively monitoring the distribution,migration,and prognosis of transplanted stem cells using imaging methods is important for in-depth study of the treatment mechanisms.Our study aimed to develop Au-Fe3O4 silica nanoparticles(NPs)as tracking nanoplatforms for dualmodal stem cell imaging.Methods:Au-Fe3O4 silica NPs were synthesized by seed-mediated growth method and co-precipitation.The efficiency and cytotoxicity of the NPslabeled bone marrow-derived mesenchymal stem cells(BMMSCs)were evaluated by Cell Counting Kit-8 assays,ICPMS,phenotypic characterization,and histological staining.The biodistribution of labeled BM-MSCs injected through different routes(the hepatic artery or tail vein)into rats with LC was detected by magnetic resonance imaging(MRI),photoacoustic imaging(PAI),and Prussian blue staining.Results:Synthesized Au-Fe3O4 silica NPs consisted of a core(star-shaped Au NPs)and an outside silica layer doped with Fe3O4 NPs.After 24 h coincubation with 2.0 OD concentration of NPs,the viability of BM-MSCs was 77.91%±5.86%and the uptake of Au and Fe were(22.65±1.82)µg/mL and(234.03±11.47)µg/mL,respectively.The surface markers of labeled BM-MSCs unchanged significantly.Labeled BMMSCs have osteogenic and adipogenic differentiation potential.Post injection in vivo,rat livers were hypointense on MRI and hyperintense on PAI.Prussian blue staining showed that more labeled BM-MSCs accumulated in the liver of the hepatic artery group.The severity of LC of the rats in the hepatic artery group was significantly alleviated.Conclusions:Au-Fe3O4 silica NPs were suitable MRI/PAI dual-modal imaging nanoplatforms for stem cell tracking in regenerative medicine. Transhepatic arterial infusion of BMMSCs was the optimal route for the treatment of LC.

One stone two birds:electrochemical and colorimetric dual-mode biosensor based on copper peroxide/covalent organic framework nanocomposite for ultrasensentive norovirus detection

Norovirus(NoV)is regarded as one of the most common causes of foodborne diarrhea in the world.It is urgent to identify the pathogenic microorganism of the diarrhea in short time.In this work,we developed an electrochemical and colorimetric dual-mode detection for NoV based on the excellent dual catalytic properties of copper peroxide/COF-NH_(2)nanocomposite(CuO_(2)@COF-NH_(2)).For the colorimetric detection,NoV can be directly detected by the naked eye based on CuO_(2)@COF-NH_(2)as a laccase-like nonazyme using“peptide-NoV-antibody”recognition mode.The colorimetric assay displayed a wide and quality linear detection range from 1 copy/mL to 5000 copies/mL of NoV with a low limit of detection(LOD)of 0.125 copy/mL.For the electrochemical detection of NoV,CuO_(2)@COF-NH_(2)showed an oxidation peak of copper ion from Cu^(+)to Cu^(2+)using“peptide-NoV-antibody”recognition mode.The electrochemical assay showed a linear detection range was 1-5000 copies/mL with a LOD of 0.152 copy/mL.It's worthy to note that this assay does not need other electrical signal molecule,which provide the stable and sensitive electrochemial detection for NoV.The electrochemical and colorimetric dual-mode detection was used to detect NoV in foods and faceal samples,which has the potential for improving food safety and diagnosing of NoV-infected diarrhea.

A compact fluorescence/circular dichroism dual-modality probe for detection, differentiation, and detoxification of multiple heavy metal ions via bond-cleavage cascade reactions

Selective detection of multiple analytes in a compact design with dual-modality and theranostic features presents great challenges. Herein, we wish to report a coumarin-thiazolidine masked D-penicillamine based dual-modality fluorescent probe COU-DPA-1 for selective detection, differentiation, and detoxification of multiple heavy metal ions(Ag^(+), Hg^(2+), Cu^(2+)). The probe shows divergent fluorescence(FL)/circular dichroism(CD) responses via divergent bond-cleavage cascade reactions(metal ion promoted C-S cleavage and hydrolysis at two distinctive cleavage sites): FL “turn-off” and CD “turn-on” for Ag+(no hydrolysis), FL “turn-on” and CD “turn-off” for Hg^(+)(imine hydrolysis), and FL “self-threshold ratiometric” and CD “turn-off” for excess Cu^(2+)(lactone and imine hydrolysis), providing the first example of a fluorescence/CD dual-modality probe for multiple species with complimentary responses. Moreover, the bond-cleavage cascade reactions also lead to the formation of D-penicillamine heavy metal ion complexes for potential detoxification treatments.

Novel multifunctional theranostic nanoagents based on Ho^(3+) for CT/MRI dual-modality imaging-guided photothermal therapy

Because of the intrinsic defects of traditional treatment of cancer,it is quite needed to construct novel theranostic nanoagents that can not only improve the accuracy of imaging diagnosis but also achieve highly efficient therapy of cancer.Herein,we fabricated polydopamine-functionalized ammonium holmium fluoride nanocomposites(AHF@PDA)for dual-modality bioimaging(magnetic resonance imaging(MRI)and computed tomography(CT))owing to the high X-ray attenuation feature and magnetic property of Ho^(3+).Moreover,PDA shell endows AHF@PDA with excellent photothermal conversion performances and robust biocompatibility,leading to good treatment effect in vitro and in vivo.All above positive results certify that AHF@PDA have good potential as theranostic agents for clinical application in the future.

FOLATE-TARGETED OPTICAL AND MAGNETIC RESONANCE DUAL-MODALITY PCL-b-PEG MICELLES FOR TUMOR IMAGING

A biodegradable tumor targeting nano-probe based on poly（ε-caprolactone）-b-poly（ethylene glycol） block copolymer （PCL-b-PEG）micelle functionalized with a magnetic resonance imaging （MRI） contrast agent diethylenetriaminepentaacetic acid-gadolinium （DTPA-Gd＋） on the shell and a near-infrared （NIR） dye in the core for magnetic resonance and optical dual-modality imaging was prepared. The longitudinal relaxivity （rl） of the PCL-b-PEG- DTPA-Gd3＋ micelle was 13.4 （mmol/L）^-1s^-1, three folds of that of DTPA-Gd3＋, and higher than that of many polymeric contrast agents with similar structures. The in vivo optical imaging of a nude mouse bearing xenografied breast tumor showed that the dual-modality micelle preferentially accumulated in the tumor via the folic acid-mediated active targeting and the passive accumulation by the enhanced permeability and retention （EPR） effect. The results indicated that the dualmodality micelle is a promising nano-probe for cancer detection and diagnosis.

Perfluorooctyl bromide nanoemulsions holding MnO_(2) nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death

Tumor-targeted immunotherapy is a remarkable breakthrough,offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity.However,existing platforms suffer from low efficacy,inability to induce strong immunogenic cell death(ICD),and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones.Here,an innovative platform,perfluorooctyl bromide(PFOB)nanoemulsions holding MnO_(2) nanoparticles(MBP),was developed to orchestrate cancer immunotherapy,serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD.By simultaneously depleting the GSH and eliciting the ICD effect via highintensity focused ultrasound(HIFU)therapy,the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells(DCs)and facilitating the activation of CD8^(+)and CD4^(+)T cells.The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis.Together,these findings inaugurate a new strategy of tumor-targeted immunotherapy,realizing a novel therapeutics paradigm with great clinical significance.

Dual-modal Colorimetric and Fluorometric Method for Glucose Detection Using MnO2 Sheets and Carbon Quantum Dots

A novel dual-modal fluorometric and colorimetric method was developed for glucose detection using MnO2 sheets and carbon quantum dots(CQDs). The glucose could be oxidized by glucose oxidase, in accompanied witli the fbnnation of H2O2 intennediate, which resulted in the decomposition of MnO2 sheets, as well as tlie MnO2 sheets(brown) changed to Mn^2+ ions(colorless), which induced the absorption of MnO2 sheet decreased and the fluorescence of CQDs increased, consequently. The linear detection ranges of glucose are 5-1000 μmol/L by fluorescent method and 5-60 μmol/L by colorimetric method. The limits of detection of these two measurements are 2.11 and 2.18 μmol/L, respectively. This method is easy to conduct, has reasonable sensitive and selectivity, and could be applied for the glucose detection in real human senim.

Facile preparation of holmium(Ⅲ)-doped carbon nanodots for fluorescence/magnetic resonance dual-modal bioimaging

In this work, we report the synthesis of holmium（III）-doped carbon nanodots（Ho BCDs） as fluorescence/magnetic resonance（FL/MR） dual-modal imaging probes via a facile hydrothermal process using citrate acid（CA）, branched-polyethylenimine（BPEI） and diethylenetriamine pentaacetic acid hydrate holmium（III） dihydrogen salt（Ho-DTPA） as carbon source, passivating reagent and holmium source, respectively.The thus prepared Ho BCDs exhibited ultra-small particle size（~4 nm）, high water solubility and bright fluorescence with an absolute quantum yield of 8%. Additionally, grey-scaled T_1-weighted images of Ho BCDs solution appeared to be apparently brighter than that of deionized water and un-doped blue carbon nanodots（BCDs） solution. In addition, in vitro toxicity assay validated superior biocompatibility of Ho BCDs. Using He La cells as models, Ho BCDs-treated cells were observed to emit blue fluorescence located both in plasma and nucleus, and presented positive contrast enhancement in T_1-weighted images, suggesting their potentials for practical biomedical applications.

A dual-modal probe for NIR fluorogenic and ratiometric photoacoustic imaging of Cys/Hcy in vivo

Biothiols, such as cysteine(Cys) and homocysteine(Hcy), play vital roles in biological homeostasis and are closely related to various pathological and physiological processes in the living systems. Therefore, the in vivo detection of biothiols is of great importance for early diagnosis of diseases and assessment of disease progression. In this work, we developed a near-infrared(NIR) fluorescence and photoacoustic dual-modal molecular probe(NIR-S) that can be specifically activated by Cys or Hcy. The aryl-thioether substituted cyanine probe can undergo nucleophilic substitution and Smiles rearrangement reaction, resulting in specific turn-on NIR fluorescence and ratiometric photoacoustic responses for Hcy/Cys. Thus, NIR-S not only realizes the specific NIR fluorescence and photoacoustic dual mode imaging to detect Hcy/Cys in solution, but also can be applied to living cells and mice to detect Hcy/Cys. This work provided a practical tool to detect Hcy/Cys levels in vivo, which would be beneficial for the early diagnosis and progress of diseases.

Dual-modal photoacoustic/CT imaging system

Photoacoustic(PA) tomography(PAT) breaks the barrier for high-resolution optical imaging in a strong lightscattering medium, having a great potential for both clinical implementation and small animal studies. However,many organs and tissues lack enough PA contrast or even hinder the propagation of PA waves. Therefore, it is challenging to interpret pure PAT images, especially three-dimensional(3 D) PA images for deep tissues, without enough structural information. To overcome this limitation, in this study, we integrated PAT with X-ray computed tomography(CT) in a standalone system. PAT provides optical contrast and CT gives anatomical information. We performed agar, tissue phantom, and animal studies, and the results demonstrated that PAT/CT imaging systems can provide accurate spatial registration of important complementary contrasts.