A food-grade and senescent cell-targeted fisetin delivery system based on whey protein isolate-galactooligosaccharides Maillard conjugate

Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.

Targeted multi-agent communication algorithm based on state control

As an important mechanism in multi-agent interaction,communication can make agents form complex team relationships rather than constitute a simple set of multiple independent agents.However,the existing communication schemes can bring much timing redundancy and irrelevant messages,which seriously affects their practical application.To solve this problem,this paper proposes a targeted multiagent communication algorithm based on state control(SCTC).The SCTC uses a gating mechanism based on state control to reduce the timing redundancy of communication between agents and determines the interaction relationship between agents and the importance weight of a communication message through a series connection of hard-and self-attention mechanisms,realizing targeted communication message processing.In addition,by minimizing the difference between the fusion message generated from a real communication message of each agent and a fusion message generated from the buffered message,the correctness of the final action choice of the agent is ensured.Our evaluation using a challenging set of Star Craft II benchmarks indicates that the SCTC can significantly improve the learning performance and reduce the communication overhead between agents,thus ensuring better cooperation between agents.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.

Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

Research Progress in Targeted Therapy for Esophageal Cancer

Esophageal cancer (EC) is a prevalent malignant tumor that affects the digestive system and is often linked to a poor prognosis. The absence of effective early screening methods results in the diagnosis of esophageal cancer (EC) patients at advanced or metastatic stages. While historically considered incurable, ongoing advancements in medical research have led to the integration of various treatment modalities as primary approaches for managing advanced endometrial cancer. These modalities include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Notably, the introduction of targeted therapy and immunotherapy has significantly enhanced the survival rates of individuals with EC. Immunotherapy has appeared as the predominant treatment for advanced esophageal cancer, while targeted therapy faces certain obstacles. Consequently, this review primarily focuses on the advancements in targeted therapy for esophageal cancer (EC), evaluating the effectiveness and safety of relevant medications, and aiming to provide guidance for the comprehensive management of EC based on current research findings.

Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments

BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.

Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.

Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Value of combining targeted emergency nursing with psychological nursing in children with febrile convulsions

BACKGROUND Febrile convulsions are a common pediatric emergency that imposes significant psychological stress on children and their families.Targeted emergency care and psychological nursing are widely applied in clinical practice,but their value and impact on the management of pediatric febrile convulsions are unclear.AIM To determine the impact of targeted emergency nursing combined with psychological nursing on satisfaction in children with febrile convulsions.METHODS Data from 111 children with febrile convulsions who received treatment at Nantong Maternal and Child Health Care Hospital between June 2021 and October 2022 were analyzed.The control group consisted of 44 children who received conventional nursing care and the research group consisted of 67 children who received targeted emergency and psychological nursing.The time to fever resolution,time to resolution of convulsions,length of hospital stays,Pittsburgh Sleep Quality Index,patient compliance,nursing satisfaction of the parents,occurrence of complications during the nursing process,and parental anxiety and depression were compared between the control and research groups.Parental anxiety and depression were assessed using the Hamilton Rating Scale for Depression(HAMD)and the Hamilton Rating Scale for Anxiety(HAMA).RESULTS The fever resolution,convulsion disappearance,and hospitalization times were longer in the control group compared with the research group(P<0.0001).The time to falling asleep,sleep time,sleep quality,sleep disturbance,sleep efficiency,and daytime status scores were significantly better in the research group compared with the control group(P<0.0001).The HAMD and HAMA scores for parents of children in the research group were lower than the scores in the control group after nursing(P<0.05).Compliance with treatment of children in the research group was higher than in the control group(P<0.05).Parental satisfaction with nursing in the research group was higher than in the control group(P<0.05).The total complication rate of children in the control group was higher than in the research group(P<0.05).CONCLUSION Combining psychological nursing with targeted emergency nursing improved the satisfaction of children’s families and compliance with treatment and promoted early recovery of clinical symptoms and improvement of sleep quality.

Covalent targeted radioligands potentiate radionuclide therapy

Targeted radionuclide therapy,in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation,has addressed unmet clinical needs and improved outcomes for patients with cancer1-4.A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue,which remains a major challenge5,6.A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution.Here we installed a sulfur(VI)fluoride exchange(SuFEx)chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance.When the engineered radiopharmaceutical binds to the tumour-specific protein,the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the'click'SuFEx reaction.

Strategies for Cultivating Public Funded Targeted Normal Students Based on Goal Management Theory : A Case Study of East, West and North Guangdong

Public funded targeted normal students are an important component of China s teacher team construction.Since its implementation in 2007,a large number of outstanding rural teachers who have been striving on the front line of education have been trained.Based on the theory of goal management,this paper explores the problems and countermeasures in the training of public funded targeted normal students.It strives to solve the problems of low willingness to teach and high default rates among public funded normal students,and hopes that the suggestions proposed in this paper can further promote the effective implementation of policies for public funded normal students.

Analysis of the Effectiveness of Targeted Nursing in Children with Severe Viral Encephalitis Complicated with Respiratory Failure

Objective:To explore and analyze the effectiveness of targeted nursing in children with severe viral encephalitis complicated with respiratory failure.Methods:From April 2021 to April 2023,74 children with severe viral encephalitis complicated with respiratory failure admitted to the Department of Pediatrics of our hospital were selected as the research objects and divided into the target group(n=37)and the reference group(n=37).Targeted nursing was given to the target group,while general nursing was given to the reference group.Physical rehabilitation,motor scores,and lung function were compared between the groups.Results:The recovery time of limb abnormalities,convulsions,abnormal consciousness,and cranial nerve disorders in the target group was significantly better than that in the reference group(P<0.05).The motor function,joint activity and pain,sensory function,and total score of the target group were significantly lower than those of the reference group(P<0.05).After the intervention,lung function indicators including VC(vital capacity),FVC(forced vital capacity),and MVV(maximum voluntary ventilation)of the target group were better than those of the reference group(P<0.05).Conclusion:Targeted nursing can shorten the recovery period of severe viral encephalitis complicated with respiratory failure in children,speed up the recovery of motor function,and improve lung function.This nursing model has a significant application effect in children with severe viral encephalitis complicated with respiratory failure.

Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients

BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a normal weight or are not obese.They are said to have lean-type MAFLD,and few studies of such patients are available.Because MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.MAFLD and analyze metabolic pathways.UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD patients.RESULTS Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P<0.05).Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy indi-viduals(P<0.01).The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals(P<0.05)and the expression of triglycerides and fasting blood glucose were increased(P<0.01).A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P<0.05 and variable importance in projection>1.The levels of PA,OA,LA,and AA were significantly increased compared with healthy individuals.CONCLUSION The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified biomarkers.PA,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

Resistance to targeted therapy in metastatic colorectal cancer:Current status and new developments

Colorectal cancer(CRC)is one of the most lethal and common malignancies in the world.Chemotherapy has been the conventional treatment for metastatic CRC(mCRC)patients.However,the effects of chemotherapy have been unsatisfactory.With the advent of targeted therapy,the survival of patients with CRC have been prolonged.Over the past 20 years,targeted therapy for CRC has achieved substantial progress.However,targeted therapy has the same challenge of drug resistance as chemotherapy.Consequently,exploring the resistance mechanism and finding strategies to address the resistance to targeted therapy,along with searching for novel effective regimens,is a constant challenge in the mCRC treatment,and it is also a hot research topic.In this review,we focus on the current status on resistance to existing targeted therapies in mCRC and discuss future developments.

Effects of mixed fertilizers formed by the compounding of two targeted controlled-release nitrogen fertilizers on yield,nitrogen use efficiency,and ammonia volatilization in double-cropping rice

One-time application of mixed fertilizer formed by the compounding of two controlled-release nitrogen fertilizers(CRUs)with targeted N supply during the periods from transplantation(TS)to panicle initiation(PI)and from PI to heading(HS)is expected to synchronize the double-peak N demand of rice.However,its effects on the yield and N use efficiency(NUE)of labor-intensive double-cropping rice were unknown.Two targeted CRU(CRU_(A)and CRU_(B))were compounded in five ratios(CRU_(A):CRU_(B)=10:0,7:3,5:5,3:7,and 0:10)to form five mixed fertilizers(BBFs):BBF1-5.A field experiment was performed to investigate the characteristics of N supply in early and late seasons under different BBFs and their effects on N uptake,yield,and ammonia volatilization(AV)loss from paddy fields of double-cropping rice.Conventional high-yield fertilization(CK,three split applications of urea)and zero-N treatments were established as controls.The N supply dropped significantly with the increased compound ratio of CRU_(B)during the period from TS to PI,but increased during the period from PI to HS.With the exception of the period from TS to PI in the late rice season,the N uptake of early and late rice maintained close synchronicity with the N supply of BBFs during the double-peak periods.Excessive N supply(BBF1 and BBF2)in the late rice season during the period from TS to PI increased N loss by AV.The effect of BBF on grain yield increase varied widely between seasons,irrespective of year.Among the BBFs,the BBF2 treatment of early rice not only stabilized the spikelets per panicle but also ensured a high number of effective panicles by promoting N uptake during the period from TS to PI and a high grain-filling percentage by appropriately reducing the N supply at the later PI stage,resulting in the highest rice yield.While stabilizing the effective panicle number,the BBF4 treatment of late rice increased the number of spikelets per panicle by promoting N uptake during the period from PI to HS,resulting in the highest rice yield.The two-year average yield and apparent N recovery efficiency of the BBF2 treatment during the early rice season were 9.6 t ha 1 and 45.3%,while those of late rice in BBF4 were 9.6 t ha 1 and 43.0%,respectively.The yield and NUE indexes of BBF2 in early rice and BBF4 in late rice showed no significant difference from those of CK.The AVs of BBF2 during the early rice season and of BBF4 during the late rice season were 50.0%and 76.8%lower,respectively,than those of CK.BBF2 and BBF4 could effectively replace conventional urea split fertilization in early and late rice seasons,ensuring rice yield and NUE and reducing AV loss in paddy fields.

Lipid metabolism of hepatocellular carcinoma impacts targeted therapy and immunotherapy

Hepatocellular carcinoma(HCC)is a common malignant tumor that affecting many people's lives globally.The common risk factors for HCC include being overweight and obese.The liver is the center of lipid metabolism,synthesizing most cholesterol and fatty acids.Abnormal lipid metabolism is a significant feature of metabolic reprogramming in HCC and affects the prognosis of HCC patients by regulating inflammatory responses and changing the immune microenvironment.Targeted therapy and immunotherapy are being explored as the primary treatment strategies for HCC patients with unresectable tumors.Here,we detail the specific changes of lipid metabolism in HCC and its impact on both these therapies for HCC.HCC treatment strategies aimed at targeting lipid metabolism and how to integrate them with targeted therapy or immunotherapy rationally are also presented.

Neutrophils in the era of single-cell RNA sequencing: functions and targeted therapies in cancer

Introduction Neutrophils,a crucial component of the innate immune system,are the most abundant bone marrow-derived eukaryotic cell in human blood.The functional importance of neutrophils is often overlooked because neutrophils are short-lived,terminally differentiated,and do not proliferate.Although traditionally considered anti-bacterial cells,research has demonstrated the multifaceted roles of neutrophils in cancer.Studies have suggested that neutrophils with normal functions co-exist with pathologically activated neutrophils that support tumorprogression and metastasis in the context of cancer.

Predictive Value of Peripheral Blood Markers in Hepatocellular Carcinoma Patients Treated with Anti-PD-1 in Combination with Targeted Therapy

Background: There are currently no recognised biomarkers that identify predictive groups of benefit in patients with hepatocellular carcinoma receiving immune-combined targeted therapy, for which we explored the value of peripheral blood markers as markers of their prognosis. Methods: Patients who underwent anti-PD-1 combination targeted therapy for hepatocellular carcinoma from 1 January 2019 to 31 December 2021 at the First Affiliated Hospital of Chongqing Medical University were retrospectively analysed. The data collected were analysed by R software. Results: A total of 41 cases were included in our study. The optimal threshold values of peripheral blood markers were obtained by plotting ROC curves and grouping patients. Survival analysis of the grouped patients showed statistically significant differences in survival between the different groups for Platelet-lymphocyte ratio (PLR, P = 0.0022), Monocyte-lymphocyte ratio (MLR, P = 0.042), Fibrinogen-Lymphocyte Ratio (FLR, P = 0.0009), Prognostic nutritional index (PIN, P = 0.0005), and Fibrinogen-albumin ratio (FAR, P = 0.0144). An ANOVA was performed on the basic conditions of the patients between the different groups, except for the statistically significant difference in BCLC stage (P = 0.0128) between the high MLR and low MLR groups, there was no statistically significant difference in age, gender, BCLC stage, and hepatitis status between the groups. COX regression analysis showed that BCLC stage, FAR, FLR and PIN were risk factors associated with the prognosis of patients receiving targeted combination immunotherapy for hepatocellular carcinoma, and FLR was an independent risk factor associated with the prognosis of patients receiving targeted combination immunotherapy for hepatocellular carcinoma. Conclusions: We found that peripheral blood markers are promising biomarkers for predicting the prognosis of patients with hepatocellular carcinoma receiving anti-PD-1 combined with targeted therapy, and this study identified FLR as an independent risk factor for the prognosis of patients having advanced hepatocellular carcinoma treated with anti-PD-1 combined with targeted therapy.

CLDN18.2-targeted molecular imaging and precision therapy of gastrointestinal tumors

Claudin-18.2(CLDN18.2)is a tight junction protein that is typically expressed only in normal gastric mucosal cells.When malignancy occurs,cell polarity is lost,intercellular adhesion structures are destroyed,and CLDN18.2 is therefore exposed to the surface of tumor cells[1].CLDN18.2 is specifically expressed in approximately 40%of human epidermal growth factor receptor 2(HER2)-negative gastrointestinal cancers,making it a promising emerging therapeutic target.As recently reported,zolbetuximab,an CLDN18.2 targeting antibody,has shown amazing efficacy in patients with CLDN18.2-positive and HER2-negative gastric cancers[2].In clinical practice,the assessment of CLDN18.2 expression status is crucial to the determination of treatment regimen for patients.Molecular imaging can be used as a non-invasive test for diagnosis,staging,and efficacy monitoring.The results of molecular imaging of CLDN18.2 have been published continuously,and the development of CLDN18.2 molecular probe is of great significance for the development of tumor targeted therapy(Fig.1).