Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

Experimental Research on Anti-tumor Metastasis Effect of Basil Polysaccharide in vivo

Objective: To study the effects of basil polysaccharide (BP) in inhibiting tumor growth and metastasis in vivo. Methods: One hundred and fifty mice were randomly divided into five groups to observe the effect on tumor growth after H22 cancer cells had been transplanted subcutaneously into their right armpit region and treated with different dosages (5 mg/kg, 2. 5 mg/kg and 1. 25 mg/kg) of BP for 14 days, with Mi-tomycin (Mit-C) used as control. Another 150 mice were randomly divided into three groups, models of tumor metastasis in the lung by various paths (lymphatic, blood circulatory and spontaneous) were established respectively. They were treated with BP or Mit-C to observe the influence of treatments on tumor metastasis by various paths. Results: BP of various dosages showed no effect on tumor growth, but in high and middle dosage, it could significantly reduce the number or metastasis nodules ( P<0. 05). Conclusion: BP has a tumor metastasis inhibitory effect, which might be one of the candidates for new anti-tumor metastasis agents. Its mechanism may be blocking the function of platelets in the tumor metastasis progress.

Immunization with autologous T cells enhances in vivo anti-tumor immune responses accompanied by up-regulation of GADD45β

Immunization with inactivated autoreactive T cells may induce idiotype anti-idiotypic reactions to deplete autoreactive T cells, which are involved in autoimmune diseases. However, it is unknown whether attenuated activated healthy autologous T-cell immunization could increase anti-tumor immune responses. To this end, C57B1/6 mice were immunized with attenuated activated autologous T cells. The splenocytes from immunized mice showed a higher proliferative ability than that from naive mice. The special phenotype analysis showed that there were more CD8+ T cells and CD62L+ T cells in immunized mice after 24 h of culture with 10% fetal calf serum complete medium in vitro (P〈0.01). These results demonstrated that this immunization may activate T cells in vivo. Furthermore, the splenocytes from immunized mice revealed resistance to activation-induced cell death (AICD) in vitro. To further study the relative genes that are responsible for the higher proliferation and resistance to AICD, the expression of Fas/Fas ligand (FasL) and GADD4513 was measured by real-time PCR. The results indicated that GADD45β transcription was higher in the splenocytes from immunized mice than that in the naive mice. In addition, the Fas expression showed a parallel higher, but FasL did not change obviously. To investigate the biologic functions induced by immunization in vivo, a tumor model was established by EL-4 tumor cell inoculation in C57/B1 mice. Mice receiving autologous T-cell immunization had significantly inhibited tumor growth in vivo (P〈0.01). This study implicated that immunization with attenuated activated autologous T cells enhances anti-tumor immune responses that participate in tumor growth inhibition.

Anti-tumor Effects of a Recombinant Fowlpox Virus Expressing Apoptin on Human Cervical Carcinoma in Vivo and in Vitro

Apoptin is a chicken anemia virus-derived,p53-independent,bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis of various human tumor cells,but not of normal diploid cells.To explore the application of apoptin in tumor gene therapy,we used a recombinant fowlpox virus expressing apoptin protein （vFV-Apoptin） to investigate the anti-tumor effectes of vFV-Apoptin on human cervical carcinoma（HeLa） cells in vivo and in vitro through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide（MTT） assay,acridine orage/ethidium bromide（AO/EB） and annexin V staining test,respectively.The results show that vFV-Apoptin inhibites the proliferation of HeLa cells in vitro through inducing the apoptosis of HeLa cells,and the inhibition effect of vFV-Apoptin has a dose-effect and time-effect relationship.The results of animal models show that vFV-Apoptin significantly inhibits tumor growth,extends the lifespan of animals and improves the mean survival.Experimental results indicate that vFV-Apoptin has a potential application in the tumor gene therapy.

Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1

Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host immunity.The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs,specifically the paired use of Huangqi and Danggui.Methods:Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs.Using the MTT assay and a transplanted tumor mice model,the anti-tumor effects of combination TCMs were investigated in vitro and in vivo.High content analysis and flow cytometry were then used to evaluate cellular immunity,followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms.Finally,the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments.Results:There is an optimal combination of Huangqi and Danggui that,administered as an aqueous extract,can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo.Based on network pharmacology analysis,PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui.Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract(quercetin,jaranol,isorhamnetin,kaempferol,calycosin,and suchilactone)that bind to PIK3R1.Jaranol is the most important component against breast cancer.The suchilactone/jaranol combination and,especially,the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract.Conclusions:The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

Anti-tumor activities of macromolecular fractions of fresh gecko vivo and their induction of Bel-7402 cell differentiation

Objective:To investigate the anti-tumor effect of macromolecular fractions of fresh gecko (M-AG) in vivo and their differentiation-inducing activity in Bel-7402 cells in vitro.Methods:An H22 hepatocarcinoma-bearing mouse model was used to evaluate the anti-tumor activity of M-AG samples.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was applied to analyze cell viability.Cell morphology was observed by phase contrast microscopy.The quantity of the alpha-fetoprotein was detected by a radioimmunoassay.Chromatometry was used to assay the albumin quantity.Activities of alkaline phosphatase and γ-glutamyl trans-peptidase were measured by biochemical methods.Finally,western blotting was applied to assess proteins in the mitogen-activated protein kinase (MAPK) signaling pathway.Results:Macromolecular fractions of fresh gecko exerted a significant anti-tumor effect in mice.The inhibition rate of tumor growth was 63% in the moderate M-AG dose group.Cells treated with M-AG displayed a differentiated state.The treatment lowered alphafetoprotein secretion and significantly decreased the activities of γ-glutamyl trans-peptidase and alkaline phosphatase in Bel-7402 cells.In contrast,M-AG increased the amount of albumin in the cell culture medium.All biochemical indices demonstrated that M-AG induced Bel7402 cell differentiation.Western blotting showed no changes in the quantities of extracellular signal-regulated kinase (ERK) 1/2,p38MAPK,or c-Jun N-terminal protein kinase 1/2.However,M-AG significantly activated the phosphorylation of ERK1/2 in a dose-dependent manner.In addition,M-AG had no significant influence on the expression of nuclear factor-kappa B.Conclusion:Macromolecular fractions of fresh gecko has an anti-tumor activity in H22 hepatocarcinoma-bearing mice in vivo and inhibits Bel-7402 cell proliferation in vitro by inducing cell differentiation related to activation of ERK1/2.

Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic patients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.

Extracellular vesicles in anti-tumor drug resistance: Mechanisms and therapeutic prospects

Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy.Prior research has illuminated reasons behind drug resistance,including increased drug efflux,alterations in drug targets,and abnormal activation of oncogenic pathways.However,there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment(TME).Recent studies on extracellular vesicles(EVs)have provided valuable insights.EVs are membrane-bound particles secreted by all cells,mediating cell-to-cell communication.They contain functional cargoes like DNA,RNA,lipids,proteins,and metabolites from mother cells,delivered to other cells.Notably,EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs.This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance,covering therapeutic approaches like chemo-therapy,targeted therapy,immunotherapy and even radiotherapy.Detecting Ev-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance.Additionally,targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance.We highlight the importance of conducting in-depth mechanistic research on EVs,their cargoes,and functional ap-proaches specifically focusing on EV subpopulations.These efforts will significantly advance the devel-opment of strategies to overcome drug resistance in anti-tumor therapy.

Acute effect of foot strike patterns on in vivo tibiotalar and subtalar joint kinematics during barefoot running

Background:Foot kinematics,such as excessive eversion and malalignment of the hindfoot,are believed to be associated with running-related injuries.The maj ority of studies to date show that different foot strike patterns influence these specific foot and ankle kinematics.However,technical deficiencies in traditional motion capture approaches limit knowledge of in vivo joint kinematics with respect to rearfoot and forefoot strike patterns(RFS and FFS,respectively).This study uses a high-speed dual fluoroscopic imaging system(DFIS)to determine the effects of different foot strike patterns on 3D in vivo tibiotalar and subtalar joints kinematics.Methods:Fifteen healthy male recreational runners underwent foot computed tomography scanning for the construction of 3-dimensional models.A high-speed DFIS(100 Hz)was used to collect 6 degrees of freedom kinematics for participants’tibiotalar and subtalar joints when they adopted RFS and FFS in barefoot condition.Results:Compared with RFS,FFS exhibited greater internal rotation at 0%-20%of the stance phase in the tibiotalar joint.The peak internal rotation angle of the tibiotalar joint under FFS was greater than under RFS(p<0.001,Cohen’s d=0.92).RFS showed more dorsiflexion at 0%-20%of the stance phase in the tibiotalar joint than FFS.RFS also presented a larger anterior translation(p<0.001,Cohen’s d=1.28)in the subtalar joint at i nitial contact than FFS.Conclusion:Running with acute barefoot FFS increases the internal rotation of the tibiotalar joint in the early stance.The use of high-speed DFIS to quantify the movement of the tibiotalar and subtalar joint was critical to revealing the effects of RF S and FFS during running.

Treatment of primary nasal tuberculosis with anti-tumor necrosis factor immunotherapy:A case report

BACKGROUND Primary nasal tuberculosis(TB)is a rare form of extrapulmonary TB,particularly in patients receiving anti-tumor necrosis factor(TNF)immunotherapy.As a result,its diagnosis remains challenging.CASE SUMMARY A 58-year-old male patient presented to the ear,nose,and throat department with right-sided nasal obstruction and bloody discharge for 1 month.He was diagnosed with psoriatic arthritis and received anti-TNF immunotherapy for 3 years prior to presentation.Biopsy findings revealed chronic granulomatous inammation and a few acid-fast bacilli,suggestive of primary nasal TB.He was referred to our TB management department for treatment with oral anti-TB agents.After 9 months,the nasal lesions had disappeared.No recurrence was noted during follow-up.CONCLUSION The diagnosis of primary nasal TB should be considered in patients receiving TNF antagonists who exhibit thickening and crusting of the nasal septum mucosa or inferior turbinate,particularly when pathological findings suggest granulomatous inflammation.

In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia

General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective.Results revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of consciousness.Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia.Notably,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness.Furthermore,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups.These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

Evaluation of Biological Effects of Nanosystems of Directed Transport in Experiments <i>in Vivo</i>and Their Application Possibilities in Anti-Tumor Therapy

The aim of the investigations was to evaluate benefits of the directed transport system - a nanocomposite, based on cisplatin and magnetite combined with local action of constant magnetic field on the tumor, in experiments in vivo in animals with transplantable Guerin carcinoma. Animals were divided into 5 groups according to the type of agent. We showed that nanocomposite in combination with static magnetic field exercises more prominent anti-tumor activity than cisplatin alone. It should be noted that regardless of the therapeutic agent, in Guerin carcinoma we observed </

Ex vivo liver resection and auto-transplantation and special systemic therapy in perihilar cholangiocarcinoma treatment

This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastrointestinal Surgery.It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation(ELRAT)and systemic therapy,underlying molecular mechanisms for targeted therapy in perihilar cho-langiocarcinoma(pCCA)management.pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis.The only curative option is radical surgery.Surgical excision and reconstruction become extremely com-plicated and not always could be performed even in localized disease.On the other hand,ELRAT takes its place among surgical options for carefully selected pCCA patients.In advanced disease,systemic therapy becomes a viable option to prolong survival.This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with ki-nase inhibitors and immunotherapy in both palliative and adjuvant settings.Fi-broblast grow factor and fibroblast grow factor receptor,human epidermal grow-th factor receptor 2,isocitrate dehydrogenase,and protein kinase cAMP activated catalytic subunit alpha(PRKACA)and beta(PRKACB)pathways have been ac-tively investigated in CCA in last years.Several agents were introduced and approved by the Food and Drug Administration.They all demonstrated mean-ingful activity in CCA patients with no global change in outcomes.That is why every successfully treated patient counts,especially those with advanced disease.In conclusion,pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options.ELRAT also brings some hope,but it could be performed in very carefully selected patients.Advanced disease requires systemic anticancer treatment,which is supposed to be individualized according to the genetic and molecular features of cancer cells.Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.

Preclinical Verification of Modulated Electro-Hyperthermia—Part II. In Vivo Research

The treatments of malignant diseases nowadays are rapidly developing. One of the groups of novel therapies applies electromagnetic fields to destroy the malignant lesions. The thermal (heating) and nonthermal (polarization, molecular excitations) processes are combined in novel methods. The non-ionizing energy absorption from the electric field may produce substantial heat, increasing the targeted lesion’s temperature and inducing hyperthermic effects. The modulated electro-hyperthermia (mEHT) uses thermal conditions to optimize and accelerate the chemical reactions induced by the nonthermal excitation of the electric field. The mEHT cooperates with the body’s homeostatic control and harmonizes the mutual efforts to destroy the malignancy. Our objective is to show in vivo proof of the combined complementary electromagnetic impact on various tumors produced by mEHT. Furthermore, we present evidence of the increasing efficacy of the complementary application of mEHT with conventional treatments.

Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

SWIR FluorescenceImaging In Vivo Monitoring and Evaluating Implanted M2 Macrophages in Skeletal Muscle Regeneration

Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders.Owing to their significant role in tissue regeneration,implantation of M2 macrophages(M2MФ)has great potential for improving skeletal muscle regeneration.Here,we present a short-wave infrared(SWIR)fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2MФtransplantation.SWIR fluorescence imaging was employed to track implanted M2MФin the injured skeletal muscle of mouse models.It is found that the implanted M2MФaccumulated at the injury site for two weeks.Then,SWIR fluorescence imaging of blood vessels showed that M2MФimplantation could improve the relative perfusion ratio on day 5(1.09±0.09 vs 0.85±0.05;p=0.01)and day 9(1.38±0.16 vs 0.95±0.03;p=0.01)post-injury,as well as augment the degree of skeletal muscle regencration on day 13 post-injury.Finally,multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration.These results provide more in vivo details about M2MФin skeletal muscle regeneration and confirm that M2MФcould promote angiogenesis and improve the degree of skeletal muscle repair,which will guide the research and development of M2MФimplantation to improve skeletal muscle regeneration.

Anti-Tumor and Anti-Diabetic Effects of Sarsasapogenin

In this paper,the pharmacological effects and molecular mechanisms of sarsasapogenin,such as anti-oxidant,anti-inflammatory and anti-diabetic effects,are reviewed in order to provide a theoretical basis for the subsequent development and clinical application of sarsasapogenin.

Preparation of kakkatin derivatives and their anti-tumor activity

BACKGROUND Modern pharmacological studies have confirmed that plant-derived compounds from Puerariae flos(PF)has significant biological activities against liver damage,tumors and inflammation.Kakkatin is an isoflavone polyphenolic compound isolated from PF flower.However,the effect of kakkatin and its derivatives on anti-tumor has not been well explored.AIM To design and synthesize a kakkatin derivative[6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one(HK)]to explore its anti-tumor biological activity.METHODS Hept-6-yn-1-yl ethanesulfonate was introduced to replace hydrogen at the hydroxyl position of kakkatin phenol,and the derivative of kakkatin was prepared;the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to detect cell viability,a clone formation assay was adopted to detect cell proliferation,apoptosis,necrosis,and cell cycles were analyzed by Annexin V/propidium iodide staining and flow cytometry.Cell migration and invasion ability were evaluated by cell scratch assay and transwell assay.The potential mechanism of HK on hepatocellular carcinoma(HCC)SMMC-7721 cells was explored through network pharmacology and molecular docking,and finally real-time PCR assays was used to verify the potential targets and evaluate the biological activity of HK.RESULTS Compared with kakkatin,the modified HK did not significantly increase the inhibitory activity of gastric cancer MGC803 cells,but the inhibitory activity of HCC SMMC-7721 cells was increased by about 30 times,with an IC50 value of 2.5μM,and the tumor inhibition effect was better than cisplatin,which could significantly inhibit the cloning,invasion and metastasis of HCC SMMC-7721 cells,and induce apoptosis and G2/M cycle arrest.Its mechanism of action is mainly related to the upregulation of PDE3B and NFKB1 target proteins in the cAMP pathway.CONCLUSION HK have a significant inhibitory effect on HCC SMMC-7721 cells,and the targets of their action may be PDE3B and NFKB1 proteins in the cAMP pathway,making it a good lead drug for the treatment of HCC.

Implantable Electrochemical Microsensors for In Vivo Monitoring of Animal Physiological Information

In vivo monitoring of animal physiological information plays a crucial role in promptly alerting humans to potential diseases in animals and aiding in the exploration of mechanisms underlying human diseases.Currently,implantable electrochemical microsensors have emerged as a prominent area of research.These microsensors not only fulfill the technical requirements for monitoring animal physiological information but also offer an ideal platform for integration.They have been extensively studied for their ability to monitor animal physiological information in a minimally invasive manner,characterized by their bloodless,painless features,and exceptional performance.The development of implantable electrochemical microsensors for in vivo monitoring of animal physiological information has witnessed significant scientific and technological advancements through dedicated efforts.This review commenced with a comprehensive discussion of the construction of microsensors,including the materials utilized and the methods employed for fabrication.Following this,we proceeded to explore the various implantation technologies employed for electrochemical microsensors.In addition,a comprehensive overview was provided of the various applications of implantable electrochemical microsensors,specifically in the monitoring of diseases and the investigation of disease mechanisms.Lastly,a concise conclusion was conducted on the recent advancements and significant obstacles pertaining to the practical implementation of implantable electrochemical microsensors.

Rotational Intravascular Multidirectional Ultrasound Catheter for Sonothrombolysis of Retracted Clots:An in Vitro and in Vivo Study

Thromboembolism in blood vessels poses a serious risk of stroke,heart attack,and even sudden death if not properly managed.Sonothrombolysis combined with ultrasound contrast agents has emerged as a promising approach for the effective treatment of thromboembolism.Recent reports have highlighted the potential of intravascular sonothrombolysis as a safe and effective treatment modality for deep vein thrombosis(DVT).However,its efficiency has not been validated through in vivo testing of retracted clots.This study aimed to develop a miniaturized multidirectional transducer featuring two 4-layer lead zir-conate titanate(PZT-5A)stacks with an aperture size of 1.4 mm1.4 mm,enabling both forward-and side-looking treatment.Integrated into a custom two-lumen 10-French(Fr)catheter,the capability of this device for intravascular sonothrombolysis was validated both in vitro and in vivo.With low-dose tissue plasminogen activators and nanodroplets,the rotational multidirectional transducer reduced the retracted clot mass(800 mg)by an average of 52%within 30 min during in vitro testing.The lysis rate was significantly higher by 37%than that in a forward-viewing transducer without rotation.This improvement was particularly noteworthy in the treatment of retracted clots.Notably,a long-retracted clot(>10 cm)was successfully treated within 40 min in vivo by creating a flow channel with a diameter>4 mm in a porcine DVT model.In conclusion,these findings strongly suggest the potential of this technique for clinical applications in sonothrombolysis,offering a feasible solution for effectively treating thromboembolism,particularly in challenging cases involving retracted clots.