Harnessing nanomaterials for copper-induced cell death.

Copper (Cu), an essential micronutrient with redox properties, plays a pivotal role in a wide array of pathological and physiological processes across virtually all cell types. Maintaining an optimal copper concentration is critical for cellular survival: insufficient copper levels disrupt respiration and metabolism, while excess copper compromises cell viability, potentially leading to cell death. Similarly, in the context of cancer, copper exhibits a dual role: appropriate amount of copper can promote tumor progression and be an accomplice, yet beyond befitting level, copper can bring about multiple types of cell death, including autophagy, apoptosis, ferroptosis, immunogenic cell death, pyroptosis, and cuproptosis. These forms of cell death are beneficial against cancer progression; however, achieving precise copper regulation within tumors remains a significant challenge in the pursuit of effective cancer therapies. The emergence of nanodrug delivery systems, distinguished by their precise targeting, controlled release, high payload capacity, and the ability to co-deliver multiple agents, has revitalized interest in exploiting copper's precise regulatory capabilities. Nevertheless, there remains a dearth of comprehensive review of copper's bidirectional effects on tumorigenesis and the role of copper-based nanomaterials in modulating tumor progression. This paper aims to address this gap by elucidating the complex role in cancer biology and highlighting its potential as a therapeutic target. Through an exploration of copper's dualistic nature and the application of nanotechnology, this review seeks to offer novel insights and guide future research in advancing cancer treatment.

Deceased Donor Program in India: Listing and Allocation Practices and the Legal Process With Respect to Liver Transplantation.

India is the country with the third largest transplantation activity in the world but has one of the lowest deceased donation rates. The Transplantation of Human Organs Act was first enacted as law 29 years ago, its implementation has been non-uniform and growth in deceased donation has been slow and heterogenous. This review discusses the concept of brain death, ethics of deceased donation and organ allocation, Indian legislation in this area and the regulatory structure of the National Organ transplantation program. We also discuss current status of deceased donation and deceased donor liver transplantation in the country, identify variation in liver allocation policies across Indian states and identify areas of need and potential solutions.

Actitudes ante la muerte en profesionales de enfermería latinoamericanos: una revisión integrativa

Introducción: La muerte es parte de los tabúes sociales existentes y puede fomentar actitudes que distan de su abordaje explícito en relación con los cuidados. Objetivo: Analizar las actitudes ante la muerte en profesionales de enfermería de acuerdo con las publicaciones científicas en el contexto latinoamericano en el período 2018 a 2022. Metodología: Se realizó una revisión de literatura integrativa de las publicaciones científicas latinoamericanas respecto de las actitudes ante la muerte en el contexto de la enfermería, empleando los siguientes términos estandarizados: actitud, muerte, enfermería y cuidados de enfermería. Se incluyeron 8 artículos publicados en el período definido, en idioma español y portugués, en los que se abordó explícitamente la temática de la revisión. La información de los artículos fue analizada tomando como referencia los conceptos de la teoría de las transiciones. Resultados: Se encontraron diseños tanto cuantitativos (50 %) como cualitativos (50 %), elaborados en su totalidad en el ámbito hospitalario. Los principales resultados dan cuenta del predominio de la indiferencia ante la muerte en el contexto de los cuidados. En relación con la teoría de las transiciones, la mayoría de los artículos abordan las condiciones en que estas se dan, además de los conceptos de terapéutica de enfermería y patrones de respuesta. Conclusiones: La producción de investigaciones sobre la actitud ante la muerte en profesionales de enfermería es escasa en Latinoamérica. Las experiencias de pérdidas cercanas, la capacitación y el soporte institucional son la base para contribuir a una mejor actitud hacia la muerte

Introdução: A morte faz parte dos tabus sociais existentes e pode fomentar atitudes que se distanciam de sua abordagem explícita em relação aos cuidados. Objetivo: analisar as atitudes diante da morte em profissionais de enfermagem de acordo com as publicações científicas no contexto latino-americano no período de 2018 a 2022. Metodologia: Foi realizada uma revisão de literatura integrativa de publicações científicas latino-americanas sobre atitudes diante da morte no contexto da enfermagem, utilizando os seguintes termos padronizados: atitude, morte, enfermagem e cuidados de enfermagem. Foram incluídos 8 artigos publicados no período definido, em espanhol e português, nos quais o tema da revisão foi abordado explicitamente. As informações dos artigos foram analisadas tendo como referência os conceitos da teoria das transições. Resultados: Foram identificados desenhos quantitativos (50 %) e qualitativos (50 %), elaborados totalmente no âmbito hospitalar. Os principais resultados mostram a predominância da indiferença diante da morte no contexto do cuidado. Em relação à teoria das transições, a maioria dos artigos aborda as condições em que as transições ocorrem, além dos conceitos de terapêutica de enfermagem e padrões de resposta. Conclusões: A produção de pesquisas sobre atitudes diante da morte em profissionais de enfermagem é escassa na América Latina. As experiências de perdas próximas, a capacitação e o apoio institucional são a base para contribuir para uma melhor atitude em relação à morte

Introduction: Death is part of the existing social taboos and can foster attitudes that are far from its explicit approach in relation to care. Objective: To analyze attitudes towards death in nursing professionals according to scientific publications in the Latin American context in the period 2018 to 2022. Methodology: An integrative literature review was conducted of Latin American scientific publications regarding attitudes towards death in the context of Nursing, using the following standardized terms: attitude, death, nursing and nursing care. Eight articles published in the defined period were included, in Spanish and Portuguese, in which the subject of the review was explicitly addressed. The information in the articles was analyzed using the concepts of the theory of transitions as a reference. Results: Both quantitative (50 %) and qualitative (50 %) designs were found, all of them elaborated in the hospital setting. The main results show the predominance of indifference to death in the context of care. In relation to the theory of transitions, most of the articles address the conditions under which these occur, in addition to the concepts of nursing therapeutics and response patterns. Conclusions: The production of research on the attitude towards death in nursing professionals is scarce in Latin America. Experiences of close losses, training and institutional support are the basis for contributing to a better attitude towards death

Desfechos obstétricos adversos durante a COVID-19: uma série de casos retrospectiva / Adverse obstetric outcomes during COVID-19: a retrospective case series / Resultados obstétricos adversos durante el COVID-19: serie de casos retrospectiva

Objetivo: analisar as características e os desfechos obstétricos adversos em gestantes/puérperas infectadas pelo SARS-CoV-2 em serviço de referência. Método: série de casos retrospectiva entre gestantes com Covid-19 em um hospital universitário em Minas Gerais, Brasil, atendidas no serviço de 2020 a 2021, coletados em abril de 2022, empregando-se estatística descritiva para análise dos dados através do Statistical Package for the Social Science. Resultados: incluídas 26 gestantes, em sua maioria brancas, que tiveram como principais desfechos obstétricos adversos a internação em UTI (43,5%), parto prematuro (34,6%), dado reestratificado de semanas para dias para investigar o encurtamento da gestação, onde constatou-se média de 38,6 dias potenciais de gravidez perdidos dos 280 dias ideais, e ainda 15,4% evoluíram para óbito materno. Conclusão: o estudo proporcionou evidenciar a necessidade de vigilância e atenção às gestantes com foco nos principais desfechos adversos, podendo-se intervir em tempo oportuno para diminuir adversidades.

Objective: to analyze the characteristics and adverse obstetric outcomes in pregnant/puerperal women infected by SARS-CoV-2 at a reference service. Method: a retrospective case series conducted among pregnant women with Covid-19 in a university hospital from Minas Gerais, Brazil, treated at the service from 2020 to 2021. The cases were collected in April 2022 employing descriptive statistics for data analysis in the Statistical Package for the Social Science. Results: a total of 26 pregnant women were included, mostly white-skinned, whose main adverse obstetric outcomes were admission to the ICU (43.5%), premature birth (34.6%) and data restratified from weeks to days to investigate shortening of pregnancy, where a mean of 38.6 potential days of pregnancy were lost out of the ideal 280 days, and 15.4% resulted in maternal death. Conclusion: the study provided evidence of the need for surveillance and care for pregnant women with a focus on the main adverse outcomes, enabling timely intervention to reduce adversities.

Objetivo: analizar las características y resultados obstétricos adversos en gestantes/puérperas infectadas por SARS-CoV-2 en un servicio de referencia. Método: serie de casos retrospectiva entre gestantes con Covid-19 en un hospital universitario de Minas Gerais, Brasil, atendidas en el servicio de 2020 a 2021. Los datos se recolectaron en abril de 2022, se utilizó estadística descriptiva para analizar los datos mediante el Statistical Package for the Social Science. Resultados: se incluyeron 26 gestantes, la mayoría de raza blanca, cuyos principales resultados obstétricos adversos fueron ingreso a UCI (43,5%), parto prematuro (34,6%), dato reestratificado de semanas a días para investigar el acortamiento de la gestación, que arrojó como resultado un promedio de 38,6. Se comprobó que se perdieron en promedio 38,6 días potenciales de embarazo de los 280 días ideales, y muerte materna (15,4%). Conclusión: la evidencia que proporcionó el estudio indica que es necesario vigilar y atender a las gestantes enfocándose en los principales resultados adversos, lo que permite intervenir de forma oportuna para reducir adversidades.

[A Study on the Life Attitudes, Fear of Death, and Dying Care Abilities of Nursing Assistants in Long-Term Care Institutions].

BACKGROUND: End-of-life care in long-term care institutions is increasingly important. Nursing assistants are the primary care workforce, and their end-of-life care capabilities affect the quality of care provided to residents as well as residents' physical and mental health. PURPOSE: This study was designed to explore the life attitudes, fear of death status, end-of-life care abilities and experience, and coping styles of nursing assistants in long-term care institutions in the eastern region and the effects of these variables on care. METHODS: A cross-sectional, mixed-methods research design was used. The study included 165 nursing assistants working in long-term care facilities in Taitung and Hualien counties. The study questionnaire included items covering life attitudes, fear of death, and dying care abilities. In addition, in-depth interviews were conducted with 12 of the participants. RESULTS: Most of the participants held positive attitudes toward life and reported having a low to moderate fear of death. A significant and positive correlation between life attitude and dying care ability was identified (r = .426, p < .001). Although average ability to provide physical care to residents at end of life was found to be relatively good, ability to provide emotional support and allow residents to express their emotions was generally poor. The scales of fear of death, life attitude toward love and care, ideals, and high school education were identified as significant predictors of dying care ability, together explaining 22.8% of the variance. The interview results were summarized into five major themes that also echoed the quantitative results. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Attitudes toward life and fear of death partially were shown to influence the dying care ability of the nursing assistants in this study. Dying care skills should be strengthened in nursing assistants, and they should be encouraged to explore the meanings of life and death through on-the-job education. Also, long-term care institutions should show concern for and support their nursing assistants by sponsoring case discussions, care experience sharing sessions, and support groups.

Perinatal mortality among term births: Informing decisions about singleton early term births in Western Australia.

BACKGROUND: To minimise the risk of perinatal mortality, clinicians and expectant mothers must understand the risks and benefits associated with continuing the pregnancy. OBJECTIVES: Report the gestation-specific risk of perinatal mortality at term. METHODS: Population-based cohort study using linked health data to identify all singleton births at gestations 37-41 weeks, in Western Australia (WA) from 2009 to 2019. Lifetable analysis was used to combine the risk of each type of perinatal mortality and calculate the cumulative risk of perinatal mortality, termed the perinatal risk index (PRI). Rates of antepartum and intrapartum stillbirth and neonatal death, as well as the PRI, were examined for each gestational week at term by non-Aboriginal and Aboriginal ethnicity. For non-Aboriginal women, rates were also examined by time-period (pre- vs. post-WA Preterm Birth Prevention Initiative (the Initiative) rollout), primiparity, and obstetric risk. RESULTS: There were 332,084 singleton term births, including 60 perinatal deaths to Aboriginal mothers (3.2 deaths per 1000 births to Aboriginal mothers) and 399 perinatal deaths to non-Aboriginal mothers (1.3 deaths per 1000 births to non-Aboriginal mothers). For non-Aboriginal women, the PRI was at its lowest (PRI 0.80, 95% CI 0.61, 1.00) at 39 weeks gestation. For Aboriginal women, it was at its lowest at 38 weeks (PRI 2.43, 95% CI 0.48, 4.39) with similar risk at 39 weeks (PRI 2.68, 95% CI 1.22, 4.14). The PRI increased steadily after 39 weeks gestation. The risk of perinatal mortality was higher among Aboriginal women. The gestation-specific perinatal mortality rates were similar by the time-period, primiparity and obstetric risk. CONCLUSIONS: The gestational ages at term associated with the lowest risk of perinatal mortality reinforce that the recommendation not to deliver before 39 weeks without medical indication is applicable to both Aboriginal and non-Aboriginal women giving birth in WA. There was no increase in the perinatal mortality rate associated with the introduction of the Initiative.

The Negative Impact of Prolonged Desiccation on the Recovery of Selaginella bryopteris: Insights Into Autophagy and Cellular Protection Strategies.

Desiccation tolerance is a complex biological phenomenon that allows certain plants to survive extreme dehydration and revive upon rehydration. Although significant progress has been made in understanding the physiological and molecular mechanisms involved in desiccation tolerance, recovery mechanisms after prolonged desiccation periods are enigmatic. Combining physiological, biochemical, transcriptomic and metabolomic approaches, we investigated the role of prolonged desiccation on recovery of Selaginella bryopteris. Prolonged desiccation causes a decline in the antioxidant system, leading to accumulation of ROS that hinder recovery by inducing cellular damage. Transcriptome and WGCNA analysis revealed the significance of protective proteins, alternative respiration and protein homeostasis in cellular protection and recovery after short and long-term desiccation. Metabolomic analysis exhibited an increased accumulation of antioxidant compounds, which can be substituted for antioxidant enzymes to maintain cellular protection during prolonged desiccation. The significant role of autophagy and autophagic components was evaluated by H2O2 treatment and phylogenetic analysis of ATG4 and ATG8, which unveiled their substantial role in desiccation tolerance and remarkable conservation of the autophagy-related genes across plant species. Our data demonstrated that prolonged desiccation leads to ROS-induced cell death by extensive autophagy due to enormous loss of protective proteins, antioxidant enzymes and energy resources during desiccation.

Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis.

Inflammasomes are multi-protein complexes that assemble within the cytoplasm of mammalian cells in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), driving the secretion of the pro-inflammatory cytokines IL-1ß and IL-18, and pyroptosis. The best-characterized inflammasome complexes are the NLRP3, NAIP-NLRC4, NLRP1, AIM2, and Pyrin canonical caspase-1-containing inflammasomes, and the caspase-11 non-canonical inflammasome. Newer inflammasome sensor proteins have been identified, including NLRP6, NLRP7, NLRP9, NLRP10, NLRP11, NLRP12, CARD8, and MxA. These inflammasome sensors can sense PAMPs from bacteria, viruses and protozoa, or DAMPs in the form of mitochondrial damage, ROS, stress and heme. The mechanisms of action, physiological relevance, consequences in human diseases, and avenues for therapeutic intervention for these novel inflammasomes are beginning to be realized. Here, we discuss these emerging inflammasome complexes and their putative activation mechanisms, molecular and signaling pathways, and physiological roles in health and disease.

A Robust ROS Generation and Ferroptotic Lipid Modulation Nanosystem for Mutual Reinforcement of Ferroptosis and Cancer Immunotherapy.

Ferroptosis initiation is often utilized for synergistic immunotherapy. While, current immunotherapy is limited by an immunosuppressive tumor microenvironment (TME), and ferroptosis is limited by insufficient reactive oxygen species (ROS) and ferroptotic lipids in tumor cells. Here, an arachidonic acid (AA) loaded nanosystem (CTFAP) is developed to mutually reinforce ferroptosis and cancer immunotherapy by augmenting ROS generation and modulating ferroptotic lipids. CTFAP is composed of acid-responsive core calcium peroxide (CaO2) nanoparticles, ferroptotic lipids sponsor AA, tetracarboxylic porphyrin (TCPP) and Fe3+ based metal-organic framework structure, and biocompatible mPEG-DSPE for improved stability. Once endocytosed by tumor cells, CTFAP can release oxygen (O2) and hydrogen peroxide (H2O2) in the acidic TME, facilitating TCPP-based sonodynamic therapy and Fe3+-mediated Fenton-like reactions to generate substantial ROS for cell ferroptosis initiation. The immunogenic cell death (ICD) after ferroptosis promotes interferon γ (IFN-γ) secretion to up-regulate the expression of long-chain family member 4 (ACSL4), cooperating with the released AA from CTFAP to accelerate the accumulation of lipid peroxidation (LPO) and thereby promoting ferroptosis in cancer cells.CTFAP with ultrasound treatment efficiently suppresses tumor growth, has great potential to challenges in cancer immunotherapy.

Proapoptotic and antimigration properties of osthole in combination with LY294002 against human glioma cells.

Anaplastic astrocytoma and glioblastoma multiforme are infiltrating and vascularized gliomas with a high degree of chemoresistance and metastasis. Our previous studies have shown that osthole may be of great importance in the treatment of gliomas. Therefore, in this work, for the first time, coumarin was used in combination with LY294002-an inhibitor of the PI3K-Akt/PKB-mTOR pathway, which is overly active in gliomas. MOGGCCM and T98G cells were incubated with osthole and LY294002, alone and in combination. Staining with specific fluorochromes was used to visualize cell death and the scratch test to assess the migration. The level of proteins was estimated by immunoblotting. Forming protrusions were visualized by SEM, and immunocytochemistry was used to determine the localization of proteins. Additionally, the expression of Bcl-2, beclin 1 and Raf kinase was silenced using specific siRNA. The obtained results showed that osthole in combination with LY294092 effectively inhibited the migration of glioma cells by reducing the level of metaloproteinases and Rho family proteins, as well as decreasing the level of N-cadherin. In addition, the combination of compounds induced apoptosis. New combination of compounds shows a high pro-apoptotic potential and also inhibits the migration of gliomas cells.

Chronically Low NMNAT2 Expression Causes Sub-lethal SARM1 Activation and Altered Response to Nicotinamide Riboside in Axons.

Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is an endogenous axon survival factor that maintains axon health by blocking activation of the downstream pro-degenerative protein SARM1 (sterile alpha and TIR motif containing protein 1). While complete absence of NMNAT2 in mice results in extensive axon truncation and perinatal lethality, the removal of SARM1 completely rescues these phenotypes. Reduced levels of NMNAT2 can be compatible with life; however, they compromise axon development and survival. Mice born expressing sub-heterozygous levels of NMNAT2 remain overtly normal into old age but develop axonal defects in vivo and in vitro as well as behavioural phenotypes. Therefore, it is important to examine the effects of constitutively low NMNAT2 expression on SARM1 activation and disease susceptibility. Here we demonstrate that chronically low NMNAT2 levels reduce prenatal viability in mice in a SARM1-dependent manner and lead to sub-lethal SARM1 activation in morphologically intact axons of superior cervical ganglion (SCG) primary cultures. This is characterised by a depletion in NAD(P) and compromised neurite outgrowth. We also show that chronically low NMNAT2 expression reverses the NAD-enhancing effect of nicotinamide riboside (NR) in axons in a SARM1-dependent manner. These data indicate that low NMNAT2 levels can trigger sub-lethal SARM1 activation which is detectable at the molecular level and could predispose to human axonal disorders.

Label-Free Detection of Programmed Death-Ligand 1 for Prognosis Using a Truncated Aptamer and SYBR Green I.

The rapid and accurate detection of programmed death-ligand 1 (PD-L1) expression is of great value in the diagnosis and treatment of tumors. ELISA-based traditional method is the gold standard for protein detection, but there are still some shortcomings, especially the antigen-antibody dependence, greatly increased the detection time and cost. This work constructed a label-free fluorescent probe for rapid and sensitive detection of PD-L1 using a truncated aptamer as recognition molecules and double-stranded DNA specific dyes (SYBR Green I) as signal units. After a series of optimization conditions, this probe has good detection capability for PD-L1 in buffer solution with the detection limit as low as 0.68 ng/mL. Due to the specific recognition ability of aptamer and target, this method also has good selectivity for PD-L1 detection. The recovery of PD-L1 in human serum samples ranges from 86.20 to 96.36%. Compared with other methods, this strategy does not need to be marked, and does not need other complex design and purification process, but simple operation process and strong anti-interference ability. The whole detection process can be completed within 20 min and has good application prospect. This work will provide reference for drug dosage and prognosis evaluation of specific tumor therapy.

BAP1 regulates HSF1 activity and cancer immunity in pancreatic cancer.

BACKGROUND: The vast majority of pancreatic cancers have been shown to be insensitive to single-agent immunotherapy. Exploring the mechanisms of immune resistance and implementing combination therapeutic strategies are crucial for PDAC patients to derive benefits from immunotherapy. Deletion of BAP1 occurs in approximately 27% of PDAC patients and is significantly correlated with poor prognosis, but the mechanism how BAP1-deletion compromises survival of patients with PDAC remain a puzzle. METHODS: Bap1 knock-out KPC (KrasG12D/+; LSLTrp53R172H/+; Pdx-1-Cre) mice and control KPC mice, syngeneic xenograft models were applied to analysis the correlation between BAP1 and immune therapy response in PDAC. Immunoprecipitation, RT-qPCR, luciferase and transcriptome analysis were combined to revealing potential mechanisms. Syngeneic xenograft models and flow cytometry were constructed to examine the efficacy of the inhibitor of SIRT1 and its synergistic effect with anti-PD-1 therapy. RESULT: The deletion of BAP1 contributes to the resistance to immunotherapy in PDAC, which is attributable to BAP1's suppression of the transcriptional activity of HSF1. Specifically, BAP1 competes with SIRT1 for binding to the K80 acetylated HSF1. The BAP1-HSF1 interaction preserves the acetylation of HSF1-K80 and promotes HSF1-HSP70 interaction, facilitating HSF1 oligomerization and detachment from the chromatin. Furthermore, we demonstrate that the targeted inhibition of SIRT1 reverses the immune insensitivity in BAP1 deficient PDAC mouse model. CONCLUSION: Our study elucidates an unrevealed mechanism by which BAP1 regulates immune therapy response in PDAC via HSF1 inhibition, and providing promising therapeutic strategies to address immune insensitivity in BAP1-deficient PDAC.

A single exposure to brivaracetam or perampanel does not cause cell death in neonatal rats.

Introduction: Exposure to a range of anti-seizure medications (ASMs) during early brain development adversely impacts neurodevelopmental outcomes in both animal models and in clinical studies. Many ASMs, including phenobarbital, phenytoin, valproate (VPA), and benzodiazepines, are associated with acute neurotoxicity (cell death), impaired synaptic development, and long-term behavioral changes following gestational or neonatal exposure in animals. This is mirrored in clinical studies which show lasting neurodevelopmental deficits following early-life or gestational exposure to these drugs. Brivaracetam (BRV) and perampanel (PER) are two newer generation anti-seizure medications and are of interest based on their mechanisms of action (SV2A modulator, AMPA antagonist, respectively), as other drugs with these mechanisms of action do not trigger acute neurotoxicity. Both BRV and PER show anti-seizure efficacy in developing animals, but potential neurotoxicity of these drugs is unexplored. Methods: To address this gap, we treated postnatal day (P)7 Sprague-Dawley rats with BRV (20, 40, 80 mg/kg) and PER (0.1, 0.9, 2.7 mg/kg), and assessed the induction of cell death across a range of vulnerable brain regions 24 h after exposure. Cell death was assessed using pathogreen staining. Results: In each of the regions examined (dorsal striatum, nucleus accumbens, motor cortex, cingulate cortex, lateral thalamus, septum, hippocampus), VPA, which served as a positive control, significantly increased cell death as measured by the numer of pathogreen positive cells. By contrast, neither BRV nor PER increased the number of pathogreen positive cells in any region examined. Discussion: Our results suggest that BRV and PER may have a positive safety profile-at least with respect to acute induction of cell death - and therefore may offer a safer option for the treatment of early life seizures.

Roles of the tumor microenvironment in the resistance to programmed cell death protein 1 inhibitors in patients with gastric cancer.

Despite the continuous developments and advancements in the treatment of gastric cancer (GC), which is one of the most prevalent types of cancer in China, the overall survival is still poor for most patients with advanced GC. In recent years, with the progress in tumor immunology research, attention has shifted toward immunotherapy as a therapeutic approach for GC. Programmed cell death protein 1 (PD-1) inhibitors, as novel immunosuppressive medications, have been widely utilized in the treatment of GC. However, many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy. To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy, to maximize the clinical activity of immunosuppressive drugs, and to elicit a lasting immune response, it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients. This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment, aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.

The role of pyroptosis in the occurrence and development of pregnancy-related diseases.

Pyroptosis is a form of programmed cell death that is crucial in the development of various diseases, including autoimmune diseases, atherosclerotic diseases, cancer, and pregnancy complications. In recent years, it has gained significant attention in national and international research due to its association with inflammatory immune overactivation and its involvement in pregnancy complications such as miscarriage and preeclampsia (PE). The mechanisms discussed include the canonical pyroptosis pathway of gasdermin activation and pore formation (caspase-1-dependent pyroptosis) and the non-canonical pyroptosis pathway (cysteoaspartic enzymes other than caspase-1). These pathways work on various cellular and factorial levels to influence normal pregnancy. This review aims to summarize and analyze the pyroptosis pathways associated with abnormal pregnancies and pregnancy complications. The objective is to enhance pregnancy outcomes by identifying various targets to prevent the onset of pyroptosis.

Reconceptualization of immune checkpoint inhibitor-associated gastritis.

In recent years, with the extensive application of immunotherapy in clinical practice, it has achieved encouraging therapeutic effects. While enhancing clinical efficacy, however, it can also cause autoimmune damage, triggering immune-related adverse events (irAEs). Reports of immunotherapy-induced gastritis have been increasing annually, but due to its atypical clinical symptoms, early diag-nosis poses a certain challenge. Furthermore, it can lead to severe complications such as gastric bleeding, elevating the risk of adverse outcomes for solid tumor patients if immunotherapy is interrupted. Therefore, gaining a thorough under-standing of the pathogenesis, clinical manifestations, diagnostic criteria, and treatment of immune-related gastritis is of utmost importance for early identification, diagnosis, and treatment. Additionally, the treatment of immune-related gastritis should be personalized according to the specific condition of each patient. For patients with grade 2-3 irAEs, restarting immune checkpoint inhibitors (ICIs) therapy may be considered when symptoms subside to grade 0-1. When restarting ICIs therapy, it is often recommended to use different types of ICIs. For grade 4 irAEs, permanent discontinuation of the medication is necessary.