Establishment of a nomogram model for predicting therapy complications in patients with polycythemia and deep venous thrombosis

BACKGROUND Patients with deep venous thrombosis(DVT)residing at high altitudes can only rely on anticoagulation therapy,missing the optimal window for surgery or thrombolysis.Concurrently,under these conditions,patient outcomes can be easily complicated by high-altitude polycythemia(HAPC),which increases the difficulty of treatment and the risk of recurrent thrombosis.To prevent reaching this point,effective screening and targeted interventions are crucial.Thus,this study analyzes and provides a reference for the clinical prediction of thrombosis recurrence in patients with lower-extremity DVT combined with HAPC.AIM To apply the nomogram model in the evaluation of complications in patients with HAPC and DVT who underwent anticoagulation therapy.METHODS A total of 123 patients with HAPC complicated by lower-extremity DVT were followed up for 6-12 months and divided into recurrence and non-recurrence groups according to whether they experienced recurrence of lower-extremity DVT.Clinical data and laboratory indices were compared between the groups to determine the influencing factors of thrombosis recurrence in patients with lowerextremity DVT and HAPC.This study aimed to establish and verify the value of a nomogram model for predicting the risk of thrombus recurrence.RESULTS Logistic regression analysis showed that age,immobilization during follow-up,medication compliance,compliance with wearing elastic stockings,and peripheral blood D-dimer and fibrin degradation product levels were indepen-dent risk factors for thrombosis recurrence in patients with HAPC complicated by DVT.A Hosmer-Lemeshow goodness-of-fit test demonstrated that the nomogram model established based on the results of multivariate logistic regression analysis was effective in predicting the risk of thrombosis recurrence in patients with lowerextremity DVT complicated by HAPC(χ^(2)=0.873;P>0.05).The consistency index of the model was 0.802(95%CI:0.799-0.997),indicating its good accuracy and discrimination.CONCLUSION The column chart model for the personalized prediction of thrombotic recurrence risk has good application value in predicting thrombotic recurrence in patients with lower-limb DVT combined with HAPC after discharge.

Challenging anticoagulation therapy for multiple primary malignant tumors combined with thrombosis:A case report and review of literature

BACKGROUND Venous thromboembolism significantly contributes to patient deterioration and mortality.Management of its etiology and anticoagulation treatment is intricate,necessitating a comprehensive consideration of various factors,including the bleeding risk,dosage,specific anticoagulant medications,and duration of therapy.Herein,a case of lower extremity thrombosis with multiple primary malignant tumors and high risk of bleeding was reviewed to summarize the shortcomings of treatment and prudent anticoagulation experience.CASE SUMMARY An 83-year-old female patient was admitted to the hospital due to a 2-wk history of left lower extremity edema that had worsened over 2 d.Considering her medical history and relevant post-admission investigations,it was determined that the development of left lower extremity venous thrombosis and pulmonary embolism in this case could be attributed to a combination of factors,including multiple primary malignant tumors,iliac venous compression syndrome,previous novel coronavirus infection,and inadequate treatment for prior thrombotic events.However,the selection of appropriate anticoagulant medications,determination of optimal drug dosages,and establishment of an appropriate duration of anticoagulation therapy were important because of concurrent thrombocytopenia,decreased quantitative fibrinogen levels,and renal insufficiency.CONCLUSION Anticoagulant prophylaxis should be promptly initiated in cases of high-risk thrombosis.Individualized anticoagulation therapy is required for complex thrombosis.

Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

Use of MLC901 in cerebral venous sinus thrombosis:Three case reports

BACKGROUND Cerebral venous sinus thrombosis(CVT)is rare cause of cerebrovascular disease.The incidence is 0.5%of all stroke.The majority of affected patients are young adults(mean age:35-40 years)with mild to moderate disabilities.Poor outcome with severe disability is seen in 13%of cases.Early diagnosis and treatment are important for good outcomes and preventing complications.Treatment options are limited and mostly based on consensus.NeuroAiD II™(MLC901;Moleac Pte,Ltd,Singapore)has a potential beneficial role in post-stroke recovery,by aiding the natural brain recovery process.CASE SUMMARY MLC901 consists of nine natural herbal ingredients.Studies have shown its safety profile and aid in post stroke recovery.The aim of this case series was to demonstrate the potential role of MLC901 in stroke recovery of patients with cerebral venous sinus thrombosis(CVST)who received MLC901 in addition to standard of care.The prescribed dose of MLC901 is 400 mg/cap two capsules,three times a day.Data from these patients were prospectively collected at baseline and at monthly visits,for a duration of 3 mo.Outcome measures included adherence to therapy,side effects,National Institutes of Health Stroke Scale,Glasgow Coma Scale,modified Rankin Scale,and the Short Orientation-Memory-Concentration Test.MLC901 was well tolerated and no side effects were reported.All patients were stable with improved condition.CONCLUSION This case series highlights the potential therapeutic effects of MLC901 on CVST and provides support for further studies.

Left ventricular thrombosis caused cerebral embolism during venoarterial extracorporeal membrane oxygenation support: A case report

BACKGROUND Venoarterial(VA)extracorporeal membrane oxygenation(ECMO),an effective short-term circulatory support method for refractory cardiogenic shock,is widely applied.However,retrospective analyses have shown that VA-ECMO-assisted cases were associated with a relatively high mortality rate of approximately 60%.Embolization in important organs caused by complications of left ventricular thrombosis(LVT)during VA-ECMO is also an important reason.Although the incidence of LVT during VA-ECMO is not high,the consequences of embolization are disastrous.CASE SUMMARY A 37-year-old female patient was admitted to hospital because of fever for 4 d and palpitations for 3 d.After excluding the diagnosis of coronary heart disease,we established a diagnosis of“clinically explosive myocarditis”.The patient still had unstable hemodynamics after drug treatment supported by VA-ECMO,with heparin for anticoagulation.On day 4 of ECMO support,a left ventricular thro-mbus attached to the papillary muscle root of the mitral valve was found by transthoracic echocardiography.Left ventricular decompression was performed and ECMO was successfully removed,but the patient eventually died of multiple cerebral embolism.CONCLUSION LVT with high mobility during VA-ECMO may cause embolism in important organs.Therefore,a"wait and see"strategy should be avoided.

Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes

BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

Giant cavernous aneurysms occluded by aneurysmal thrombosis,calcification,parent artery occlusion:A case report and review of literature

BACKGROUND Patients with giant intracranial aneurysms(GIAs)are at a high risk of rupture,morbidity,and mortality even after surgical or endovascular treatment.We described a case of a spontaneously occluded GIA secondary to gradual growth of the GIA,continuously progressed aneurysmal thrombosis,complete aneurysmal calcification and complete occlusion of the parent artery-the right internal carotid artery(RICA).CASE SUMMARY A 72-year-old female patient complained of sudden pain in her right eye upon admission to our hospital.She had been diagnosed with a GIA[30 mm(axial)×38 mm(coronal)×28 mm(sagittal)]containing an aneurysmal thrombus located in the cavernous sinus segment of RICA diagnosed by magnetic resonance imaging(MRI),enhanced MRI,and magnetic resonance angiography more than 14 years ago.Later,with slow growth of the cavernous carotid GIA,aneurysmal thrombosis progressed continuously,spontaneous occlusion of the RICA,complete aneurysmal calcification,and occlusion of the GIA occurred gradually.She had no history of subarachnoid hemorrhage but missed the chance for endovascular therapy at an early stage.As a result,she was left with severe permanent sequelae from the injuries to the right cranial nerves Ⅱ,Ⅲ,Ⅳ,V1/V2,and Ⅴ.CONCLUSION The risk of rupture of the cavernous carotid GIAs was relatively low and possibly further be reduced by the stasis flow and spontaneous occlusion of the parent artery internal carotid artery(ICA)induced by the mass effect of the cavernous carotid GIAs and the extremely rare aneurysmal calcification.However,nowadays,it is advisable to recommend early endovascular treatment for the cavernous carotid GIAs to prevent injuries to the surrounding intracranial nerves and occlusion of the ICA,mainly caused by the mass effect of the cavernous carotid GIAs.

Research Progress of Atomizers and Drugs Used in Atomization Therapy

At present,the commonly used treatment methods for chronic respiratory diseases are drug,oxygen,interventional and atomization therapy.Atomization therapy is the most widely used because of its characteristics of fast effect,high local drug concentration,less drug dosage,convenient application and few systemic adverse reactions.In this paper,the mechanism,characteristics,commonly used drugs and clinical application of atomization therapy are discussed.

Research Progress of Drug Therapy for Diabetes

Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including diabetes type 1 and diabetes type 2,of which diabetes type 2 accounts for more than 90%.The incidence rate of diabetes is high,the course of disease is long,and it is difficult to cure.Most patients need long-term medication.This study analyzed the clinical manifestations and predisposing factors of diabetes,and explored the progress of drug treatment of diabetes,which is summarized as follows.

Observation on the Clinical Effect of Applying Venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.

Advances in Transdermal Drug Delivery for Cancer Therapy

Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.

Should antiplatelet therapy be interrupted in drug eluting stent recipients throughout the periendoscopic period？ A very late stent thrombosis case re-port and review of the literature

In-stent thrombosis after cessation of antiplatelet medications in patients with drug-eluting stents （DES） is a significant problem in medical practice, particularly in the perioperative period. We report a case of an 87-year-old man with a medical history of hypertension, coronary artery disease and chronic atrophic gastritis. Very late thrombosis of a sirolimus-eluting stent occurred 1207 days after implantation, seven months after discontinuation of clopidogrel, and the interruption of aspirin 13 days in preparation of an elective endoscopic gastroin-testinal procedure presented with acute myocardial infarction. The patient was treated with thrombectomy and successfully revascularized with superimposition of two sirolimus-eluting stents. Medications administered in the catheterization laboratory included low molecular weight heparin and nitroglycerin. Flow was defined as grade 2 according to the thrombolysis in myocardial infarction scale. Electrocardio-gram after the procedure revealed persistent, but decreased, ST-segment elevation in the anterolateral leads. The patient recovered and was discharged on aspirin and clopidogrel indefinitely. There was no cardiac event during the two year follow-up period. This case underlines the importance of maintaining the balance of thrombosis and bleeding during perioperation of non-cardiac procedure and the possible need for continuation of aspirin therapy during periendoscopic procedures among patients with low bleeding risks who received DES.

Ionizable drug delivery systems for efficient and selective gene therapy

Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.

Consensus among Chinese experts on standard interventional therapy for deep venous thrombosis of lower extremity(second edition)

This is an update on the first edition of the expert consensus. This document discusses the indications and contraindications of interventional treatment methods for deep venous thrombosis such as anticoagulation, catheter-directed thrombolysis, percutaneous mechanical thrombectomy, percutaneous transluminal angioplasty and stent implantation. The operational procedures, considerations, preoperative management, and prevention of complications were also updated, supplemented, and revised. Emphasis is placed on the interventional treatment of acute and subacute deep venous thrombosis to effectively reduce the incidence of post-thrombosis syndrome.

Anticoagulation therapy prevents portal-splenic vein thrombosis after splenectomy with gastroesophageal devascularization

AIM:To compare the incidence of early portal or splenic vein thrombosis(PSVT) in patients treated with irregular and regular anticoagulantion after splenectomy with gastroesophageal devascularization.METHODS:We retrospectively analyzed 301 patients who underwent splenectomy with gastroesophageal devascularization for portal hypertension due to cirrhosis between April 2004 and July 2010.Patients were categorized into group A with irregular anticoagulation and group B with regular anticoagulation,respectively.Group A(153 patients) received anticoagulant monotherapy for an undesignated time period or with aspirin or warfarin without low-molecular-weight heparin(LMWH) irregularly.Group B(148 patients) received subcutaneous injection of LMWH routinely within the first 5 d after surgery,followed by oral warfarin and aspirin for one month regularly.The target prothrombin time/international normalized ratio(PT/INR) was 1.25-1.50.Platelet and PT/INR were monitored.Color Doppler imaging was performed to monitor PSVT as well as the effectiveness of thrombolytic therapy.RESULTS:The patients' data were collected and analyzed retrospectively.Among the patients,94 developed early postoperative mural PSVT,including 63 patients in group A(63/153,41.17%) and 31 patients in group B(31/148,20.94%).There were 50(32.67%) patients in group A and 27(18.24%) in group B with mural PSVT in the main trunk of portal vein.After the administration of thrombolytic,anticoagulant and antiaggregation therapy,complete or partial thrombus dissolution achieved in 50(79.37%) in group A and 26(83.87%) in group B.CONCLUSION:Regular anticoagulation therapy can reduce the incidence of PSVT in patients who undergo splenectomy with gastroesophageal devascularization,and regular anticoagulant therapy is safer and more effective than irregular anticoagulant therapy.Early and timely thrombolytic therapy is imperative and feasible for the prevention of PSVT.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province,China,2014–2020

Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

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.

MATHEMATICAL MODELING AND BIFURCATION ANALYSIS FOR A BIOLOGICAL MECHANISM OF CANCER DRUG RESISTANCE

Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.

Research progress in tumor angiogenesis and drug resistance in breast cancer

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.

Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay

Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.