Anomalous valley Hall effect in two-dimensional valleytronic materials

The anomalous valley Hall effect(AVHE)can be used to explore and utilize valley degrees of freedom in materials,which has potential applications in fields such as information storage,quantum computing and optoelectronics.AVHE exists in two-dimensional(2D)materials possessing valley polarization(VP),and such 2D materials usually belong to the hexagonal honeycomb lattice.Therefore,it is necessary to achieve valleytronic materials with VP that are more readily to be synthesized and applicated experimentally.In this topical review,we introduce recent developments on realizing VP as well as AVHE through different methods,i.e.,doping transition metal atoms,building ferrovalley heterostructures and searching for ferrovalley materials.Moreover,2D ferrovalley systems under external modulation are also discussed.2D valleytronic materials with AVHE demonstrate excellent performance and potential applications,which offer the possibility of realizing novel low-energy-consuming devices,facilitating further development of device technology,realizing miniaturization and enhancing functionality of them.

A novel approach to Parkinson's disease treatment with a potentially dual-acting therapeutic agent that targetsα-synuclein aggregation and neuron death

Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy bodies.While the current standards of therapy have been successful in providing some symptom relief,they fail to address the underlying pathophysiology of PD and as a result,they have no effect on disease progression.

Progress on two-dimensional ferrovalley materials

The electron's charge and spin degrees of freedom are at the core of modern electronic devices. With the in-depth investigation of two-dimensional materials, another degree of freedom, valley, has also attracted tremendous research interest. The intrinsic spontaneous valley polarization in two-dimensional magnetic systems, ferrovalley material, provides convenience for detecting and modulating the valley. In this review, we first introduce the development of valleytronics.Then, the valley polarization forms by the p-, d-, and f-orbit that are discussed. Following, we discuss the investigation progress of modulating the valley polarization of two-dimensional ferrovalley materials by multiple physical fields, such as electric, stacking mode, strain, and interface. Finally, we look forward to the future developments of valleytronics.

Intertwined depressive and cognitive trajectories and the risk of dementia and death in older adults:a competing risk analysis

Background Depressive symptoms and cognitive impairment often interact,rendering their associations controversial.To date,their joint trajectories and associations with dementia and death remain underexplored.Aims To explore the interactions between depressive symptoms and cognitive function,their developmental trajectories and the associations with all-cause dementia,Alzheimer’s disease(AD)and all-cause death in older adults.Methods Data were from the Health and Retirement Study.Depressive symptoms and cognitive function were measured using the 8-item Centre for Epidemiologic Studies Depression Scale and the Telephone Interview of Cognitive Status,respectively.All-cause dementia and AD were defined by self-reported or proxy-reported physician diagnoses.All-cause death was determined by interviews.The restricted cubic spline,group-based trajectory modelling and subdistribution hazard regression were used.Results Significant interactions between depressive symptoms and cognitive function in 2010 in their association with new-onset all-cause dementia and AD from 2010 to 2020 were found,especially in women(p for interaction<0.05).Independent trajectory analysis showed that emerging or high(vs no)depressive trajectories and poor or rapidly decreased cognitive trajectories(vs very good)from 1996 to 2010 were at significantly higher risk of subsequent all-cause dementia,AD and all-cause death.15 joint trajectories of depressive symptoms and cognitive function from 1996 to 2010 were determined,where rapidly decreased cognitive function was more common in those with no depressive symptoms.Compared with older adults with the trajectory of no depressive symptoms and very good cognitive function,those with the trajectory of no depressive symptoms but rapidly decreased cognitive function were much more likely to develop new-onset all-cause dementia and death,with subdistribution hazard ratios(95%confidence intervals)of 4.47(2.99 to 6.67)and 1.84(1.43 to 2.36),especially in women.Conclusions To effectively mitigate the risk of dementia and death,it is crucial to acknowledge the importance of preventing cognitive decline in older adults without depressive symptoms,particularly in women.

Valleytronic topological filters in silicene-like inner-edge systems

Inner edge state with spin and valley degrees of freedom is a promising candidate for designing a dissipationless device due to the topological protection. The central challenge for the application of the inner edge state is to generate and modulate the polarized currents. In this work, we discover a new mechanism to generate fully valley-and spin–valley-polarized current caused by the Bloch wavevector mismatch(BWM). Based on this mechanism, we design some serial-typed inner-edge filters. By using once of the BWM, the coincident states could be divided into transmitted and reflected modes, which can serve as a valley or spin–valley filter. In particular, while with twice of the BWM, the incident current is absolutely reflected to support an off state with a specified valley and spin, which is different from the gap effect.These findings give rise to a new platform for designing valleytronics and spin-valleytronics.

Recent progress on valley polarization and valley-polarized topological states in two-dimensional materials

Valleytronics, using valley degree of freedom to encode, process, and store information, may find practical applications in low-power-consumption devices. Recent theoretical and experimental studies have demonstrated that twodimensional(2D) honeycomb lattice systems with inversion symmetry breaking, such as transition-metal dichalcogenides(TMDs), are ideal candidates for realizing valley polarization. In addition to the optical field, lifting the valley degeneracy of TMDs by introducing magnetism is an efficient way to manipulate the valley degree of freedom. In this paper, we first review the recent progress on valley polarization in various TMD-based systems, including magnetically doped TMDs,intrinsic TMDs with both inversion and time-reversal symmetry broken, and magnetic TMD heterostructures. When topologically nontrivial bands are empowered into valley-polarized systems, valley-polarized topological states, namely valleypolarized quantum anomalous Hall effect can be realized. Therefore, we have also reviewed the theoretical proposals for realizing valley-polarized topological states in 2D honeycomb lattices. Our paper can help readers quickly grasp the latest research developments in this field.

Fully spin-polarized, valley-polarized and spin-valley-polarized electron beam splitters utilizing zero-line modes in a three-terminal device

Topological zero-line modes(ZLMs) with spin and valley degrees of freedom give rise to spin, valley and spinvalley transport, which support a platform for exploring quantum transport physics and potential applications in spintronic/valleytronic devices. In this work, we investigate the beam-splitting behaviors of the charge current due to the ZLMs in a three-terminal system. We show that with certain combinations of ZLMs, the incident charge current along the interface between different topological phases can be divided into different polarized currents with unit transmittance in two outgoing terminals. As a result, fully spin-polarized, valley-polarized and spin-valley-polarized electron beam splitters are generated. The mechanism of these splitters is attributed to the cooperative effects of the distribution of the ZLMs and the intervalley and intravalley scatterings that are modulated by the wave-vector mismatch and group velocity mismatch. Interestingly, half-quantized transmittance of these scatterings is found in a fully spin-valley-polarized electron beam splitter.Furthermore, the results indicate that these splitters can be applicable to graphene, silicene, germanene and stanene due to their robustness against the spin–orbit coupling. Our findings offer a new way to understand the transport mechanism and investigate the promising applications of ZLMs.

Audits of Death in HIV-Infected Children and Adolescents Followed up in the Pediatric Department of the Regional Teaching Hospital of Borgou/Alibori from 2005 to 2020

Introduction: Human immunodeficiency virus (HIV) is a major public health problem with high morbidity and mortality among children. The objective of this work was to audit the deaths of children and adolescents with HIV infection followed up in the pediatric department of the Regional Teaching Hospital of Borgou/Alibori (CHUDB/A) the from 2005 to 2020. Patients and Method: This was a retrospective and descriptive study conducted in the pediatric department of CHUD/B-A in Parakou. All children with HIV infection who died from January 1, 2005 to August 31, 2020 were included. Data collection was carried out in three stages: a phase of medical records processing, a phase of community survey and a phase of death audits. The variables studied were sociodemographic, clinical, biological, therapeutic and evolutionary. Results: Over the study period, the data of 464 infected children were recorded, including 92 deaths, representing a case fatality rate of 19.83%. Severe acute malnutrition (69.23%), gastro-intestinal tract infections (43.58%) and serious opportunistic pulmonary infections (24.36% pulmonary tuberculosis and 19.23% pneumocystis) were the main causes of death. The main dysfunctions found were: the delayed diagnosis of HIV infection (79.35%), the absence or delay in consultation when the child’s clinical condition deteriorates (32.61% and 47.83%), delayed initiation of antiretroviral treatment (42.39%) and non-adherence to treatment (38.04%). Non-adherence to treatment was predominant in adolescents (90.49%). Conclusion: Specific interventions for early detection, adequate nutritional care, psychosocial support for adolescents and mothers of children are necessary to reduce mortality due to HIV among children and adolescents.

Effects of Maternal Death on Children Living in the Sagnarigu Municipality

Introduction: The greatest effect of maternal mortality is renowned in children aged 2 - 5 months whose mothers had died. Children whose mothers died due to maternal complications were likely to record a higher mortality in infancy compared to children of surviving mothers. Motherless children mostly suffer a lot due to lack of day-to-day care, isolation, lack of motivation as well as economic cost associated with mother’s death. Thus, the purpose of this study was to ascertain the lives of children whose mothers passed away during childbirth at the Sagnarigu Municipality. Methods: This quantitative cross-sectional study was carried out at the Sagnarigu Municipal. The study recruited 297 respondents. To assess the effects of maternal death on the lives of children, families that experienced maternal death were assessed. The number of pregnancies experienced by the deceased woman, pregnancy-related complaints experienced, determinants of maternal death, number of children alive, and their standard of living were assessed with the aid of a structured questionnaire. Results: The data showed that negligence, illiteracy, poor road access, poverty, ignorance, delays in recognizing the problem, delays in making appropriate decisions, delays in the health facility, delays in giving the appropriate treatments, and traditional beliefs were some of the factors that led to maternal death in the Sagnarigu Municipality. Conclusion: The study concluded that determinants of maternal death in the Sagnarigu Municipal included the following;negligence, illiteracy, poverty, and delays in recognizing the problem. The study findings also demonstrated that the effects of maternal death on children are diverse and cut across different areas of a child’s life including livelihood sustenance, healthcare, education, and emotional and psychological development.

The 2022 Extreme Heatwave in Shanghai,Lower Reaches of the Yangtze River Valley:Combined Influences of Multiscale Variabilities

In the summer of 2022,China(especially the Yangtze River Valley,YRV)suffered its strongest heatwave(HW)event since 1961.In this study,we examined the influences of multiscale variabilities on the 2022 extreme HW in the lower reaches of the YRV,focusing on the city of Shanghai.We found that about 1/3 of the 2022 HW days in Shanghai can be attributed to the long-term warming trend of global warming.During mid-summer of 2022,an enhanced western Pacific subtropical high(WPSH)and anomalous double blockings over the Ural Mountains and Sea of Okhotsk,respectively,were associated with the persistently anomalous high pressure over the YRV,leading to the extreme HW.The Pacific Decadal Oscillation played a major role in the anomalous blocking pattern associated with the HW at the decadal time scale.Also,the positive phase of the Atlantic Multidecadal Oscillation may have contributed to regulating the formation of the double-blocking pattern.Anomalous warming of both the warm pool of the western Pacific and tropical North Atlantic at the interannual time scale may also have favored the persistency of the double blocking and the anomalously strong WPSH.At the subseasonal time scale,the anomalously frequent phases 2-5 of the canonical northward propagating variability of boreal summer intraseasonal oscillation associated with the anomalous propagation of a weak Madden-Julian Oscillation suppressed the convection over the YRV and also contributed to the HW.Therefore,the 2022 extreme HW originated from multiscale forcing including both the climate warming trend and air-sea interaction at multiple time scales.

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity.At embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction.The LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three dosages.Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS group.Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS group.Quercetin significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS induction.Quercetin significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of AMPKα1,LC3-I,and LC3-II.Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy,programmed cell death,and myocardiocytes permeability.

Effect of the Implementation of Emonc in the Reduction of Maternal Deaths in the Department of Collines from 2018 to 2022

Background: Maternal and neonatal mortality remains a public health problem in Benin. Each year, approximately 1500 maternal deaths and more than 12,000 newborn deaths are recorded there. In order to correct the situation, strategies such as the implementation of Emergency Obstetric and Neonatal Care (EmONC) were initiated. Objective: Determine the rates of maternal deaths in EmONC centers in the Collines department from 2018 to 2022. Framework and Methods: The study took place in Benin precisely in the Collines department. This was a descriptive cross-sectional study. Data collection was carried out during the first two weeks of January 2023 and covered data from the 09 Basic Emergency Obstetric and Neonatal Care centers (BEMONC) and the Obstetric and Neonatal Care centers of Complete Emergency (CEmONC) of the Collines department from 2018 to 2022. An estimate of the ratios of maternal deaths occurring at the level of the EmONC centers of the Collines department from 2018-2022 was carried out followed by constructive suggestions. Results: During the five years (2018 to 2022), the Collines department recorded 42,582 live births with 148 maternal deaths, i.e. a ratio of 348 maternal deaths per 100,000 live births. Between 2018 and 2022, the highest maternal death ratio was recorded in 2019, i.e. 425 maternal deaths per 100,000 live births for all EmONC centers and 607 maternal deaths per 100,000 live births in EmONC centers. The highest maternal death ratio at the BEmONC center level was recorded in 2020, i.e. 129 maternal deaths per 100,000 births. Conclusion: These results suggest that despite the implementation of EmONC in the Collines department, maternal deaths have not decreased. To improve these outcomes for a reduction in maternal deaths, urgent action must be taken.

Epidemiological Aspects of Stillbirth and Neonatal Deaths in the Delivery Room at the Libreville Mother-Child University Hospital from 2019 to 2022

Introduction: Stillbirths are estimated at 2 million each year, of which more than 40% occur during labour. Our objective was to study the epidemiological aspects of stillbirth and neonatal deaths in the delivery room in our health facility. Patients and methods: Prospective, descriptive and analytical study, conducted at the Jeanne Ebori Foundation Mother-Child University Hospital over 4 years (January 2019-December 2022). All neonatal deaths in the delivery room or foetal death in utero, were included. Results: Among the 18,346 deliveries performed, 512 newborns were declared dead in the delivery room (27.9‰ live births), divided into in utero foetal death (19.0‰) and immediate neonatal death (8.9‰). The mean age was 34.3 weeks of amenorrhea. The rate of preterm birth was 60.4%. The sex ratio was 1.1. The average weight was 2186.6. The main causes were vascular (46.1%), foetal (20.2%), adnexal (17.1%) and asphyxia per partum (16.6%). Foetal causes were more likely to result in IUFD than other causes (OR = 6.4 [2.4 - 15.7], p < 0.001). After birth, partum asphyxia was more likely to lead to death before 15 minutes of life than other causes (OR = 11 [6.1 - 18.9], p Conclusion: The causes of stillbirth and early neonatal mortality are dominated by maternal vascular pathologies. However, the proportion of childbirth-related causes remains worrying. Better monitoring of pregnancy and labour will minimize this prevalence in our hospital.

Protocol of Investigation on Sudden Death at Autopsy, Including Molecular, Genetic and Toxicology Testing

The role of the autopsy: 1) Whether the death is ascribable to a natural or unnatural cause and when natural, if cardiac or extra-cardiac;2) The nosology of the cardiac diseases and the mechanism of cardiac death, whether arrhythmic or mechanical;3) If the cardiac disease is inherited, screening and counselling of the next of kin is required. About 30% of sudden deaths is ascribable to genetically determined morbid entities, mostly transmissible with the autosomal dominant pattern of inheritance, so that 50% of the first degree relatives are genetically affected (“carriers”) and exposed at risk;4) If toxic or illicit drug abuse was involved.

Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy

Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.

Challenging situation of coronary artery anomaly associated with ischemia and/or risk of sudden death

Coronary artery anomaly is known as one of the causes of angina pectoris and sudden death and is an important clinical entity that cannot be overlooked.The incidence of coronary artery anomalies is as low as 1%-2%of the general population,even when the various types are combined.Coronary anomalies are practically challenging when the left and right coronary ostium are not found around their normal positions during coronary angiography with a catheter.If there is atherosclerotic stenosis of the coronary artery with an anomaly and percutaneous coronary intervention(PCI)is required,the suitability of the guiding catheter at the entrance and the adequate back up force of the guiding catheter are issues.The level of PCI risk itself should also be considered on a caseby-case basis.In this case,emission computed tomography in the R-1 subtype single coronary artery proved that ischemia occurred in an area where the coronary artery was not visible to the naked eye.Meticulous follow-up would be crucial,because sudden death may occur in single coronary arteries.To prevent atherosclerosis with full efforts is also important,as the authors indicated admirably.

Review of Maternal Deaths over 3 and a Half Years at the Kara University Hospital Center, Northern Togo: About 65 Cases

Objective: To analyze maternal deaths, identify causes and dysfunctions leading to these deaths in order to contribute to the implementation of strategies to reduce maternal mortality at CHU Kara. Method: Cross-sectional descriptive study involving 65 cases of maternal deaths recorded at CHU-Kara from January 1, 2018 to June 30, 2021. Results: Our study focused on 65 cases of maternal deaths recorded at the maternity ward of CHU-Kara. The average age was 30 years, with a range of 15 to 45 years. They were mostly housewives (52.3%), uneducated (38.5%), multiparous (41.5%), and referred (86.2%). The causes were mainly direct obstetric causes (81.54%), with preeclampsia and its complications (28.30%) and immediate postpartum hemorrhage (20.75%) being the most common. However, uterine rupture (20.5%) and post-abortion sepsis (16.4%) were the most lethal etiologies. Delayed evacuation (46.43%), inadequate transportation (91%), and insufficient prenatal care (72.31%) were the dysfunctions before referral. Within the CHU Kara, delays in management (58.46%), unavailability of blood and labile products (18%), and insufficient monitoring were the dysfunctions identified. Ninety-five point four percent (95.4%) of the deaths were preventable. Conclusion: The magnitude of intrahospital maternal deaths, the various dysfunctions observed in the occurrence of maternal deaths before referral/evacuation and within the hospital highlight the importance of effectively implementing recommendations from audits in the fight against maternal mortality. The majority of the deaths were preventable (95.38%).

Topological edge and corner states of valley photonic crystals with zipper-like boundary conditions

We present a stable valley photonic crystal(VPC)unit cell with C_(3v)symmetric quasi-ring-shaped dielectric columns and realize its topological phase transition by breaking mirror symmetry.Based on this unit cell structure,topological edge states(TESs)and topological corner states(TCSs)are realized.We obtain a new type of wave transmission mode based on photonic crystal zipper-like boundaries and apply it to a beam splitter assembled from rectangular photonic crystals(PCs).The constructed beam splitter structure is compact and possesses frequency separation functions.In addition,we construct a box-shaped triangular PC structures with zipper-like boundaries and discover phenomena of TCSs in the corners,comparing its corner states with those formed by other boundaries.Based on this,we explore the regularities of the electric field patterns of TESs and TCSs,explain the connection between the characteristic frequencies and locality of TCSs,which helps better control photons and ensures low power consumption of the system.

The Impact of Finerenone on Changes in Pulse Wave Velocity, Arterial Pressure and Heart Related Deaths in Hemodialysis Patients—Study Perspective

The description in the abstract lacks clear logic and a comprehensive summary of this study, so please revise and improve it according to the design theme and main content of this study, and describe it in the order of (research background), purpose/aim, method, results and conclusions. The introduction of the abstract and preface is rather lengthy, but the summary of the whole study and the presentation of the research background are not perfect (mainly because the logic of the context is not clear and orderly), so it will appear a bit messy. Hope to be able to modify (this has been mentioned in the preliminary opinion). Cardiovascular events (CVE) pose a significant threat to individuals with end-stage renal disease (ESRD), yet these patients are often excluded from cardiovascular clinical trials, leaving prognostic factors associated with CVE in ESRD patients largely unexplored. Recent human studies have demonstrated elevated circulating aldosterone levels in ESRD patients, correlating with left ventricular hypertrophy. Additionally, animal models have shown improvements in uremic cardiomyopathy with spironolactone therapy, prompting interest in assessing the efficacy of spironolactone or eplerenone in reducing mortality and improving cardiovascular function in dialysis patients. Clinicians have historically been cautious about prescribing mineralocorticoid receptor antagonists (MRAs) to congestive heart failure patients with chronic kidney disease (CKD) due to hyperkalemia risk. However, the emergence of finerenone, a novel MR antagonist with a favorable safety profile and lower hyperkalemia risk, has renewed interest in MRA therapy in this population. Heart disease, including coronary artery disease, hypertension, and left ventricular failure, is alarmingly prevalent in dialysis patients, contributing significantly to elevated mortality rates compared to the general population. Arterial stiffness, as indicated by pulse wave velocity (PWV), progressively worsens with advancing CKD stages, peaking in severity among ESRD patients undergoing dialysis. High PWV serves as a crucial risk stratification tool in ESRD. Elevated NT-proBNP and BNP levels in ESRD patients are well-documented, with significant associations observed between baseline peptide concentrations and cardiovascular morbidity and mortality. By incorporating finerenone into our study, we aim to investigate its potential benefits in reducing arterial stiffness, lowering blood pressure, and ultimately mitigating heart-related mortality among hemodialysis patients. This study holds substantial implications for hypertension and cardiovascular risk management in this vulnerable patient population. Eligible participants must have been on chronic hemodialysis for at least three months, with ACE inhibitors or angiotensin receptor blockers included in their therapy at maximum tolerable doses. Serum potassium levels 5.7 mmol/L, left ventricular ejection fraction 50%, and PWV higher than age-estimated values are also prerequisites for study entry. Randomized allocation will be conducted using a permuted block design, stratified by center, with allocation communicated via signed study forms during initial examinations. All steps of this research will be conducted in accordance with the principles of the Helsinki Declaration.

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.