BACKGROUND Death anxiety(DA)is a prevalent psychological challenge among oncology nurses that affects their emotional well-being and professional competence in coping with death-related situations.Death-related attitu...BACKGROUND Death anxiety(DA)is a prevalent psychological challenge among oncology nurses that affects their emotional well-being and professional competence in coping with death-related situations.Death-related attitudes and resilience are critical factors that may mediate the relationship between DA and coping with death competence(CDC).However,few studies have examined the chain-mediating effect of these factors among Chinese oncology nurses.This study aimed to investigate the association between DA and CDC among Chinese oncology nurses,with a focus on the mediating roles of death attitude and resilience.AIM To investigate the association between DA and CDC among Chinese oncology nurses.using an electronic questionnaire distributed in Wenjuanxing,China.In total,615 valid responses were obtained.The participants completed the Templer death anxiety scale,death attitude profile-revised,Connor-Davidson resilience scale,and coping with death scale.A chain mediation analysis was performed using the PROCESS macro in SPSS to examine the relationships between these variables.RESULTS The findings indicated that DA had a significant direct effect on CDC[effect=0.201,95%confidence interval(CI):0.112-0.322].In addition to this direct effect,three significant indirect pathways were observed:(1)Death attitude(effect=0.118,95%CI:0.056-0.163);(2)Resilience(effect=0.108,95%CI:0.032-0.176);and(3)A sequential mediation pathway involving both death attitude and resilience(effect=0.071,95%CI:0.042-0.123).The total indirect effects of the three mediation paths accounted for 29.7%of the relationship between DA and CDC.CONCLUSION Using a chain mediation model,this study explored the mechanisms linking DA,death attitude,resilience,and CDC among Chinese oncology nurses.These findings highlighted the crucial role of death attitude and resilience in mediating the relationship between DA and CDC.Interventions aimed at fostering adaptive attitudes toward death and enhancing resilience may improve nurses’ability to cope with death-related stressors,ultimately benefiting their psychological well-being and professional competence.展开更多
Hepatocellular carcinoma(HCC)is the predominant form of primary liver cancer,accounting for 90%of all cases.Currently,early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection,B-ultrasound,and c...Hepatocellular carcinoma(HCC)is the predominant form of primary liver cancer,accounting for 90%of all cases.Currently,early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection,B-ultrasound,and computed tomography scanning;however,their specificity and sensitivity are suboptimal.Despite significant advancements in HCC biomarker detection,the prognosis for patients with HCC remains unfavorable due to tumor heterogeneity and limited understanding of its pathogenesis.Therefore,it is crucial to explore more sensitive HCC biomarkers for improved diagnosis,monitoring,and management of the disease.Long non-coding RNA(lncRNA)serves as an auxiliary carrier of genetic information and also plays diverse intricate regulatory roles that greatly contribute to genome complexity.Moreover,investigating gene expression regulation networks from the perspective of lncRNA may provide insights into the diagnosis and prognosis of HCC.We searched the PubMed database for literature,comprehensively classified regulated cell death mechanisms and systematically reviewed research progress on lncRNA-mediated cell death pathways in HCC cells.Furthermore,we prospectively summarize its potential implications in diagnosing and treating HCC.展开更多
BACKGROUND In recent years,emerging clinical research has prioritized assessment of combined therapeutic efficacy and safety parameters when programmed death 1 or its ligand(PD-1/L1)inhibitors are incorporated into fi...BACKGROUND In recent years,emerging clinical research has prioritized assessment of combined therapeutic efficacy and safety parameters when programmed death 1 or its ligand(PD-1/L1)inhibitors are incorporated into first-line standard-of-care(SOC)therapy for metastatic colorectal cancer(mCRC).However,data obtained from these trials demonstrated conflicting evidence concerning survival benefits and clinical outcomes.AIM To evaluate the therapeutic impact and safety parameters of combining PD-1/L1 inhibitors with SOC protocols as first-line treatment for mCRC.METHODS Four biomedical databases(PubMed,Embase,Cochrane Library,Web of Science)were systematically interrogated to identify eligible studies published up to October 12,2024.The analysis focused on evaluating the primary outcome of overall survival(OS)in the mCRC population with secondary outcomes of progression-free survival(PFS),overall response rate(ORR),and incidence rate of grade≥3 adverse events.Additionally,we performed exploratory analyses in the microsatellite stable/mismatch repair-proficient(MSS/pMMR)subpopulation,based on a subset of the included studies.Subgroup analyses according to PD-1/L1 inhibitor use were conducted in both the overall population and the MSS/pMMR subgroup.RESULTS This pooled analysis incorporated six randomized controlled trials involving 675 patients with mCRC receiving first-line therapy.The combination of PD-1/L1 inhibitors with SOC regimens demonstrated a significant PFS advantage over SOC monotherapy in intention-to-treat populations[hazard ratio(HR)=0.8,95%confidence interval(CI):0.65-0.98,P=0.033].Nevertheless,the MSS/pMMR subgroup showed no PFS benefit(HR=0.83,95%CI:0.67-1.03,P=0.091),and no cohort exhibited OS improvement(intention-to-treat:HR=0.84,95%CI:0.66-1.05,P=0.124;MSS/pMMR:HR=0.79,95%CI:0.60-1.03,P=0.083).Comparable outcomes were observed for ORR(risk ratio=1.03,95%CI:0.90-1.17,P=0.711)and incidence rate of grade≥3 adverse events(risk ratio=1.12,95%CI:0.93-1.36,P=0.245)between treatment arms.CONCLUSION The findings indicated that integrating PD-1/L1 blocking agents with SOC regimens for mCRC as first-line treatment failed to demonstrate significant improvements in ORR.Existing clinical data remain inadequate to establish OS advantages,particularly in patients with MSS/pMMR,despite exhibiting manageable toxicity profiles.Subsequent confirmation through rigorously designed phase III clinical trials remains essential to verify these therapeutic outcomes.展开更多
Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.Thi...Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.This is primarily due to the fact the eye is an immunologically privileged organ,and it fails to achieve the efficacy of immune checkpoint inhibitors(ICIs)comparable to that for CM.However,approaches utilizing specific melanomaassociated antigens are being developed for metastatic forms of CM and UM.The most promising to date are gp100 and tyrosinase related protein 1(TYRP1),primarily for the design of targeting chimeric molecules and for autologous T-/NK-cell products with a chimeric antigen receptor.The difference in the mutational profile of apoptosis-related genes in CM and UM also makes counterproductive the use of the same drugs re-activators of the intrinsic pathway of apoptosis.Therefore,the discovery of novel pathways of regulated cell death such as ferroptosis and cuproptosis may help in the development of new drugs for melanomas resistant to already available inducers of regulated cell death.Here we consistently discuss the latest advances in the therapy of melanomas,and above all-UM,which is classified as an orphan disease.展开更多
This editorial focuses on the recent article by Yang et al in the World Journal of Gastrointestinal Oncology,which highlights the role of interlukin-17A in promoting hepatocellular carcinoma(HCC)progression by up-regu...This editorial focuses on the recent article by Yang et al in the World Journal of Gastrointestinal Oncology,which highlights the role of interlukin-17A in promoting hepatocellular carcinoma(HCC)progression by up-regulated programmed cell death protein-1(PD-1)/programmed cell death protein ligand-1(PD-L1)expression.Previous,the high PD-1/PD-L1 level was due to hepatitis virus infection leading to systemic innate immune tolerance and cluster of differen-tiation 8+T cells exhaustion,ultimately leading to HCC.Recently,interesting studies have found that the malignant progression of metabolic dysfunction-associated steatotic/fatty liver disease(MASLD/MAFLD),that is former nonalcoholic fatty liver disease,was achieved by up-regulated PD-L1 level that was activated the cGAS-STING pathway under lipid accumulation with mito-chondrial DNA overflow and up-regulated PD-1/PD-L1 to promote MASLD malignant transformation via immune escape.These data suggested that PD-1 or PD-L1 should be a promising target for preventing or delaying non-viral liver disease malignant progression except of antiviral therapy for HCC.展开更多
BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both brea...BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both breast cancer(BC)clinicopathological characteristics and tumor sensitivity to chemotherapy.However,the concordance of PDCD1 LG1 expression scoring with immunohistochemical(IHC)tests approved for clinical use and with the polymerase chain reaction(PCR)method has not been previously studied.AIM To evaluate the concordance of methods for assessing PD-L1 expression,IHC tests with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and PCR.METHODS This prospective single-center observational cohort study included 148 patients with BC.PD-L1 expression in immune cells was assessed by the IHC method with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and by PCR.The concordance of PD-L1 scores between tests was assessed with positive percentage agreement(PPA)and negative percentage agreement(NPA).The strength of the agreement between the methods was calculated via the Cohen kappa index.P<0.05 was considered statistically significant.RESULTS Regardless of the method used to assess marker expression,PD-L1 expression was significantly more often detected in patients with negative estrogen receptor status,human epidermal growth factor receptor-2-positive(HER2+)status,luminal B HER+BC,nonluminal HER+BC and triple-negative BC.PPA and NPA were 38.3%and 70.4%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(SP142);26.3%and 63.3%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(PCR);and 36.5%and 74.4%,respectively,for PD-L1(SP142)and PD-L1(PCR).Cohen's kappa index for PD-L1(PDCD1 LG1)and PD-L1(SP142)was 0.385(95%CI:0.304–0.466),that for PD-L1(PDCD1 LG1)and PD-L1(PCR)was 0.207(95%CI:0.127–0.287),and that for PD-L1(SP142)and PD-L1(PCR)was 0.389(95%CI:0.309–0.469).CONCLUSION Thus,all three markers of PD-L1 expression are associated with the characteristics of aggressive BC,demonstrating moderate concordance between the tests.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in th...BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.展开更多
BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and com...BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a ...BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.展开更多
BACKGROUND Acute pancreatitis in pregnancy is a rare but serious condition that can lead to high maternal mortality and fetal loss.Instances of pregnancy complicated by severe acute pancreatitis,particularly with subs...BACKGROUND Acute pancreatitis in pregnancy is a rare but serious condition that can lead to high maternal mortality and fetal loss.Instances of pregnancy complicated by severe acute pancreatitis,particularly with subsequent respiratory and cardiac arrest,are rarely reported.CASE SUMMARY We present the case of a 35-year-old woman,at 36+5 weeks of gestation,who presented with paroxysmal epigastric pain accompanied by low back pain,nausea,and vomiting.According to the clinical symptoms,B-ultrasound imaging and biochemical indicators,the patient was diagnosed with acute pancreatitis and initially managed conservatively.However,3 hours after admission,the patient experienced respiratory and cardiac arrest,and the fetus died.In this case,the adverse outcomes occurred due to the lack of aggressive fluid resuscitation and an active surgical intervention.CONCLUSION Implementing aggressive fluid resuscitation to sustain tissue perfusion,alongside the proactive evaluation of pharmacological agents that suppress gastric acid secretion and inhibit pancreatic enzyme activity,may be beneficial in mitigating the risk of a severely adverse prognosis.Effective management of acute pancreatitis during pregnancy requires careful timing of surgical intervention,a thorough evaluation of the risks and benefits regarding the continuation or termination of pregnancy,and a focus on safeguarding both maternal and fetal health.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment opti...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.展开更多
Introduction: The objective of this work was to study maternal deaths noted on arrival in the Gynecology and Obstetrics Department at Fousseyni Daou Hospital in Kayes over a period of 10 years. Materials and Methods: ...Introduction: The objective of this work was to study maternal deaths noted on arrival in the Gynecology and Obstetrics Department at Fousseyni Daou Hospital in Kayes over a period of 10 years. Materials and Methods: This was a cross-sectional, descriptive study with data collection over a period of 10 years;The data collection was retrospective over nine years from January 1, 2013 to December 31, 2021 and prospective over one year from January 1, 2022 to December 31, 2022. This study focused on all patients whose death was noted on arrival during pregnancy, labor or in the postpartum period in the Gynecology-Obstetrics Department of Fousseyni Daou Hospital. Confidentiality and anonymity were respected. The processing and analysis of statistical data were carried out using SPSS 20.0 software. Results: During the study period, we recorded 93 cases of death noted on arrival out of a total of 606 maternal deaths, i.e., a frequency of 15.34%. The average age was 27 years with the extremes of 20 years and 34 years. They came mainly from rural areas at 74%, were married at 82%, uneducated at 51.6%, housewives at 87.1%. The profession of the spouses is worker at 37.6%. In our sample, evacuated patients were the most represented with 75.3%. Postpartum hemorrhage was the most frequent reason for admission with 22.6%. The deceased patients had no medical history at 86%. In our series, 59.5% of the deceased patients had not had antenatal consultations (CPN). Patients who died on arrival and who had given birth at home were the most represented with 54.8%. Deaths from immediate postpartum hemorrhage complicated by shock were the most frequent with 25.8% followed by severe anemia 8.6%. Deaths were mainly due to direct obstetric causes at 76.3%. In these deaths observed on arrival, the 2nd delay was identified at 48.4%. Conclusion: Maternal deaths observed on arrival remain frequent in the Kayes region. The main causes are immediate postpartum hemorrhage and anemia, which are almost all preventable causes of maternal death following the 1st and 2nd delay.展开更多
Exploring the concept of death within Judaism may seem audacious,yet it is encouraged by the tradition of inquiry intrinsic to Jewish thought.Despite the caution urged by rabbinic authorities,Jewish texts ranging from...Exploring the concept of death within Judaism may seem audacious,yet it is encouraged by the tradition of inquiry intrinsic to Jewish thought.Despite the caution urged by rabbinic authorities,Jewish texts ranging from the Torah to mystical writings offer rich perspectives on death,the soul,and the afterlife.This article examines how death is represented in Jewish belief and practice,considering diverse expressions from ritual law,poetic literature,Kabbalistic cosmology,and esoteric traditions.Emphasis is placed on ritual practices,mourning customs,and metaphysical understandings of the soul,including Sheol,Gehenna,and Eden.The evolution of these beliefs is explored through rabbinic,mystical,and popular sources,across historical and cultural contexts.展开更多
BACKGROUND Death anxiety is a common emotional response to death,and it varies in intensity across cultures and regions.However,there is a paucity of research on death anxiety among nursing students during their clini...BACKGROUND Death anxiety is a common emotional response to death,and it varies in intensity across cultures and regions.However,there is a paucity of research on death anxiety among nursing students during their clinical internship,especially in relation to their emotional experiences and behavioral responses.AIM To explore the relationship between empathy and death anxiety as well as to identify factors influencing students’empathetic skills during their initial clinical experiences.METHODS This cross-sectional study included 473 nursing students enrolled from across vocational colleges in Quanzhou(Fujian Province,China)during June–July 2023.These students were trained at three Grade-A general hospitals.The Empathy Scale and Death Anxiety Scale were applied to assess their empathetic skills and death anxiety levels during the early stages of the clinical internship.Data ana-lyses employed descriptive statistics,correlation analyses,independent sample t-tests,one-way analysis of variance,and multiple linear regression analysis.RESULTS The mean death anxiety score was 46.33±6.29,with 95.6%of participants exhi-biting high death anxiety.The mean scores across dimensions were as follows:Cognitive-affective,18.08±3.15;pain and illness,13.25±2.41;awareness of the passage of time,5.58±1.40;stimuli related to death,9.40±1.56.The mean empathy score was 63.78±11.49.Regression analysis revealed that students’subject major,total death anxiety level,and pain and stress dimensions acted as significant predictors of their empathetic skills during early clinical practice(P<0.05).CONCLUSION Vocational nursing students,especially those in midwifery with higher death anxiety,exhibited lower empathetic skills during the early stages of their clinical internship.Nursing educators should take measures to enhance the empathetic skills of students through appropriate training and support for students with high death anxiety levels.展开更多
Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss a...Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss and irreversible blindness.Elevated intraocular pressure(IOP)remains the most important risk factor for glaucoma,but the exact mechanism responsible for the death of RGCs is currently unknown.Neurotrophic factor deficiency,impaired mitochondrial structure and function,disrupted axonal transport,disturbed Ca2+homeostasis,and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma.This review was conducted using Web of Science,PubMed,Project,and other databases to summarize the relevant mechanisms of death of RGCs in glaucoma,in addition to outlining protective treatments to improve the degradation of RGCs.展开更多
The challenge of protecting the brain resides in the unique characteristics of neurons,as they are postmitotic,long-lived,excitable,and polarized cells with long and fragile axons and dendrites.The complexity of the m...The challenge of protecting the brain resides in the unique characteristics of neurons,as they are postmitotic,long-lived,excitable,and polarized cells with long and fragile axons and dendrites.The complexity of the multiple potential cell death pathways further complicates this issue.In addition,the immature brain is prone to a“cell death continuum,”which involves intricate molecular interconnections between cell death processes.展开更多
Ferroptosis in combination with immune therapy emerges as a promising approach for cancer therapy.Herein,dual-responsive metal-polyphenol coordinated nanomedicines were developed for pH/glutathione(GSH)-responsive syn...Ferroptosis in combination with immune therapy emerges as a promising approach for cancer therapy.Herein,dual-responsive metal-polyphenol coordinated nanomedicines were developed for pH/glutathione(GSH)-responsive synergistic ferroptosis and immunotherapy.Our innovative strategy involves the development of a manganese-polyphenol coordinated nanostructure,leveraging the biocompatibility of bovine serum albumin(BSA)as a template to encapsulate the anticancer drug sorafenib.The tumor microenvironment(pH/GSH)prompts the disassembly of MnO_(2)and epigallocatechin gallate(EGCG),thereby releases the anticancer payload.Concurrently,MnO_(2)acts to deplete intracellular GSH,which in turn suppresses glutathione peroxidase activity,leading to an accumulation of lipid peroxides with cell ferroptosis.Additionally,the release of Mn^(2+)ions bolster the cyclic guanosine monophosphlic acid(GMP)-adenosine monophosphlic acid(AMP)synthase-stimulator of interferon gene(cGAS-STING)pathway,which,in conjunction with the immunogenic cell death(ICD)effect induced by tumor cell apoptosis,significantly promotes dendritic cell(DC)maturation and enhances the presentation of tumor antigens.This successively ignites a robust innate and adaptive immune response.Both in vitro and in vivo experiments have demonstrated that the concurrent administration of ferroptosis-inducing and immune-stimulating therapies can significantly inhibit tumor growth.展开更多
Sensorineural hearing loss(SNHL),the most commonly-occurring form of hearing loss,is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea.Numerous environmental and physiolog...Sensorineural hearing loss(SNHL),the most commonly-occurring form of hearing loss,is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea.Numerous environmental and physiological factors have been shown to cause acquired SNHL,such as ototoxic drugs,noise exposure,aging,infections,and diseases.Several programmed cell death(PCD)pathways have been reported to be involved in SNHL,especially some novel PCD pathways that have only recently been reported,such as ferroptosis,necroptosis,and pyroptosis.Here we summarize these PCD pathways and their roles and mechanisms in SNHL,aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.展开更多
The intestinal tract,a complex organ responsible for nutrient absorption and digestion,relies heavily on a balanced gut microbiome to maintain its integrity.Disruptions to this delicate microbial ecosystem can lead to...The intestinal tract,a complex organ responsible for nutrient absorption and digestion,relies heavily on a balanced gut microbiome to maintain its integrity.Disruptions to this delicate microbial ecosystem can lead to intestinal inflammation,a hallmark of inflammatory bowel disease(IBD).While the role of the gut microbiome in IBD is increasingly recognized,the underlying mechanisms,particularly those involving endoplasmic reticulum(ER)stress,autophagy,and cell death,remain incompletely understood.ER stress,a cellular response to various stressors,can trigger inflammation and cell death.Autophagy,a cellular degradation process,can either alleviate or exacerbate ER stress-induced inflammation,depending on the specific context.The gut microbiome can influence both ER stress and autophagy pathways,further complicating the interplay between these processes.This review delves into the intricate relationship between ER stress,autophagy,and the gut microbiome in the context of intestinal inflammation.By exploring the molecular mechanisms underlying these interactions,we aim to provide a comprehensive theoretical framework for developing novel therapeutic strategies for IBD.A deeper understanding of the ER stress-autophagy axis,the gut microbial-ER stress axis,and the gut microbial-autophagy axis may pave the way for targeted interventions to restore intestinal health and mitigate the impact of IBD.展开更多
The abundance of live and dead Oithona similis in Jiaozhou Bay,Shandong,China,was investigated monthly from December 2008 to November 2009 via the neutral red staining method.The annual variation in total abundance wa...The abundance of live and dead Oithona similis in Jiaozhou Bay,Shandong,China,was investigated monthly from December 2008 to November 2009 via the neutral red staining method.The annual variation in total abundance was similar for females,males,and copepodites,with a main numerical peak from February to July and a minor peak in November,but the variations in carcass abundance and death proportion were different.The monthly average abundance of male and copepodite carcasses significantly increased with their total abundance(P<0.001),whereas no such correlation was observed for females.The abundance of female carcasses peaked at 12.4 inds./m^(3) in November but remained below 3.0 inds./m^(3) in all other months.The monthly average death proportion ranged 0.3%-4.9% for females,3.6%-25.7% for males,and 2.6%-8.4% for copepodites.On average,the death proportion of males was 9.2 times greater than that of females and 3.5 times greater than that of copepodites.Therefore,significant sexual difference exists in the non-predatory mortality of O.similis and this difference is an important cause of the female-skewed sex ratios observed in the field.展开更多
基金Supported by the Hunan Provincial Natural Science Foundation of China,No.2025JJ80410.
文摘BACKGROUND Death anxiety(DA)is a prevalent psychological challenge among oncology nurses that affects their emotional well-being and professional competence in coping with death-related situations.Death-related attitudes and resilience are critical factors that may mediate the relationship between DA and coping with death competence(CDC).However,few studies have examined the chain-mediating effect of these factors among Chinese oncology nurses.This study aimed to investigate the association between DA and CDC among Chinese oncology nurses,with a focus on the mediating roles of death attitude and resilience.AIM To investigate the association between DA and CDC among Chinese oncology nurses.using an electronic questionnaire distributed in Wenjuanxing,China.In total,615 valid responses were obtained.The participants completed the Templer death anxiety scale,death attitude profile-revised,Connor-Davidson resilience scale,and coping with death scale.A chain mediation analysis was performed using the PROCESS macro in SPSS to examine the relationships between these variables.RESULTS The findings indicated that DA had a significant direct effect on CDC[effect=0.201,95%confidence interval(CI):0.112-0.322].In addition to this direct effect,three significant indirect pathways were observed:(1)Death attitude(effect=0.118,95%CI:0.056-0.163);(2)Resilience(effect=0.108,95%CI:0.032-0.176);and(3)A sequential mediation pathway involving both death attitude and resilience(effect=0.071,95%CI:0.042-0.123).The total indirect effects of the three mediation paths accounted for 29.7%of the relationship between DA and CDC.CONCLUSION Using a chain mediation model,this study explored the mechanisms linking DA,death attitude,resilience,and CDC among Chinese oncology nurses.These findings highlighted the crucial role of death attitude and resilience in mediating the relationship between DA and CDC.Interventions aimed at fostering adaptive attitudes toward death and enhancing resilience may improve nurses’ability to cope with death-related stressors,ultimately benefiting their psychological well-being and professional competence.
基金Supported by Science Project of Hunan Provincial Healthy Commission,No.20230844.
文摘Hepatocellular carcinoma(HCC)is the predominant form of primary liver cancer,accounting for 90%of all cases.Currently,early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection,B-ultrasound,and computed tomography scanning;however,their specificity and sensitivity are suboptimal.Despite significant advancements in HCC biomarker detection,the prognosis for patients with HCC remains unfavorable due to tumor heterogeneity and limited understanding of its pathogenesis.Therefore,it is crucial to explore more sensitive HCC biomarkers for improved diagnosis,monitoring,and management of the disease.Long non-coding RNA(lncRNA)serves as an auxiliary carrier of genetic information and also plays diverse intricate regulatory roles that greatly contribute to genome complexity.Moreover,investigating gene expression regulation networks from the perspective of lncRNA may provide insights into the diagnosis and prognosis of HCC.We searched the PubMed database for literature,comprehensively classified regulated cell death mechanisms and systematically reviewed research progress on lncRNA-mediated cell death pathways in HCC cells.Furthermore,we prospectively summarize its potential implications in diagnosing and treating HCC.
文摘BACKGROUND In recent years,emerging clinical research has prioritized assessment of combined therapeutic efficacy and safety parameters when programmed death 1 or its ligand(PD-1/L1)inhibitors are incorporated into first-line standard-of-care(SOC)therapy for metastatic colorectal cancer(mCRC).However,data obtained from these trials demonstrated conflicting evidence concerning survival benefits and clinical outcomes.AIM To evaluate the therapeutic impact and safety parameters of combining PD-1/L1 inhibitors with SOC protocols as first-line treatment for mCRC.METHODS Four biomedical databases(PubMed,Embase,Cochrane Library,Web of Science)were systematically interrogated to identify eligible studies published up to October 12,2024.The analysis focused on evaluating the primary outcome of overall survival(OS)in the mCRC population with secondary outcomes of progression-free survival(PFS),overall response rate(ORR),and incidence rate of grade≥3 adverse events.Additionally,we performed exploratory analyses in the microsatellite stable/mismatch repair-proficient(MSS/pMMR)subpopulation,based on a subset of the included studies.Subgroup analyses according to PD-1/L1 inhibitor use were conducted in both the overall population and the MSS/pMMR subgroup.RESULTS This pooled analysis incorporated six randomized controlled trials involving 675 patients with mCRC receiving first-line therapy.The combination of PD-1/L1 inhibitors with SOC regimens demonstrated a significant PFS advantage over SOC monotherapy in intention-to-treat populations[hazard ratio(HR)=0.8,95%confidence interval(CI):0.65-0.98,P=0.033].Nevertheless,the MSS/pMMR subgroup showed no PFS benefit(HR=0.83,95%CI:0.67-1.03,P=0.091),and no cohort exhibited OS improvement(intention-to-treat:HR=0.84,95%CI:0.66-1.05,P=0.124;MSS/pMMR:HR=0.79,95%CI:0.60-1.03,P=0.083).Comparable outcomes were observed for ORR(risk ratio=1.03,95%CI:0.90-1.17,P=0.711)and incidence rate of grade≥3 adverse events(risk ratio=1.12,95%CI:0.93-1.36,P=0.245)between treatment arms.CONCLUSION The findings indicated that integrating PD-1/L1 blocking agents with SOC regimens for mCRC as first-line treatment failed to demonstrate significant improvements in ORR.Existing clinical data remain inadequate to establish OS advantages,particularly in patients with MSS/pMMR,despite exhibiting manageable toxicity profiles.Subsequent confirmation through rigorously designed phase III clinical trials remains essential to verify these therapeutic outcomes.
基金supported by the Russian Science Foundation,project no.23-14-00285。
文摘Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.This is primarily due to the fact the eye is an immunologically privileged organ,and it fails to achieve the efficacy of immune checkpoint inhibitors(ICIs)comparable to that for CM.However,approaches utilizing specific melanomaassociated antigens are being developed for metastatic forms of CM and UM.The most promising to date are gp100 and tyrosinase related protein 1(TYRP1),primarily for the design of targeting chimeric molecules and for autologous T-/NK-cell products with a chimeric antigen receptor.The difference in the mutational profile of apoptosis-related genes in CM and UM also makes counterproductive the use of the same drugs re-activators of the intrinsic pathway of apoptosis.Therefore,the discovery of novel pathways of regulated cell death such as ferroptosis and cuproptosis may help in the development of new drugs for melanomas resistant to already available inducers of regulated cell death.Here we consistently discuss the latest advances in the therapy of melanomas,and above all-UM,which is classified as an orphan disease.
基金Supported by National Natural Science Foundation of China,No.81673241 and No.32470985.
文摘This editorial focuses on the recent article by Yang et al in the World Journal of Gastrointestinal Oncology,which highlights the role of interlukin-17A in promoting hepatocellular carcinoma(HCC)progression by up-regulated programmed cell death protein-1(PD-1)/programmed cell death protein ligand-1(PD-L1)expression.Previous,the high PD-1/PD-L1 level was due to hepatitis virus infection leading to systemic innate immune tolerance and cluster of differen-tiation 8+T cells exhaustion,ultimately leading to HCC.Recently,interesting studies have found that the malignant progression of metabolic dysfunction-associated steatotic/fatty liver disease(MASLD/MAFLD),that is former nonalcoholic fatty liver disease,was achieved by up-regulated PD-L1 level that was activated the cGAS-STING pathway under lipid accumulation with mito-chondrial DNA overflow and up-regulated PD-1/PD-L1 to promote MASLD malignant transformation via immune escape.These data suggested that PD-1 or PD-L1 should be a promising target for preventing or delaying non-viral liver disease malignant progression except of antiviral therapy for HCC.
基金Supported by Russian Science Foundation,No.23-25-00183.
文摘BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both breast cancer(BC)clinicopathological characteristics and tumor sensitivity to chemotherapy.However,the concordance of PDCD1 LG1 expression scoring with immunohistochemical(IHC)tests approved for clinical use and with the polymerase chain reaction(PCR)method has not been previously studied.AIM To evaluate the concordance of methods for assessing PD-L1 expression,IHC tests with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and PCR.METHODS This prospective single-center observational cohort study included 148 patients with BC.PD-L1 expression in immune cells was assessed by the IHC method with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and by PCR.The concordance of PD-L1 scores between tests was assessed with positive percentage agreement(PPA)and negative percentage agreement(NPA).The strength of the agreement between the methods was calculated via the Cohen kappa index.P<0.05 was considered statistically significant.RESULTS Regardless of the method used to assess marker expression,PD-L1 expression was significantly more often detected in patients with negative estrogen receptor status,human epidermal growth factor receptor-2-positive(HER2+)status,luminal B HER+BC,nonluminal HER+BC and triple-negative BC.PPA and NPA were 38.3%and 70.4%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(SP142);26.3%and 63.3%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(PCR);and 36.5%and 74.4%,respectively,for PD-L1(SP142)and PD-L1(PCR).Cohen's kappa index for PD-L1(PDCD1 LG1)and PD-L1(SP142)was 0.385(95%CI:0.304–0.466),that for PD-L1(PDCD1 LG1)and PD-L1(PCR)was 0.207(95%CI:0.127–0.287),and that for PD-L1(SP142)and PD-L1(PCR)was 0.389(95%CI:0.309–0.469).CONCLUSION Thus,all three markers of PD-L1 expression are associated with the characteristics of aggressive BC,demonstrating moderate concordance between the tests.
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.
基金Science and Technology Program of Guangzhou,No.202102010077International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2020-ZD-03.
文摘BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.
文摘BACKGROUND Acute pancreatitis in pregnancy is a rare but serious condition that can lead to high maternal mortality and fetal loss.Instances of pregnancy complicated by severe acute pancreatitis,particularly with subsequent respiratory and cardiac arrest,are rarely reported.CASE SUMMARY We present the case of a 35-year-old woman,at 36+5 weeks of gestation,who presented with paroxysmal epigastric pain accompanied by low back pain,nausea,and vomiting.According to the clinical symptoms,B-ultrasound imaging and biochemical indicators,the patient was diagnosed with acute pancreatitis and initially managed conservatively.However,3 hours after admission,the patient experienced respiratory and cardiac arrest,and the fetus died.In this case,the adverse outcomes occurred due to the lack of aggressive fluid resuscitation and an active surgical intervention.CONCLUSION Implementing aggressive fluid resuscitation to sustain tissue perfusion,alongside the proactive evaluation of pharmacological agents that suppress gastric acid secretion and inhibit pancreatic enzyme activity,may be beneficial in mitigating the risk of a severely adverse prognosis.Effective management of acute pancreatitis during pregnancy requires careful timing of surgical intervention,a thorough evaluation of the risks and benefits regarding the continuation or termination of pregnancy,and a focus on safeguarding both maternal and fetal health.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.
文摘Introduction: The objective of this work was to study maternal deaths noted on arrival in the Gynecology and Obstetrics Department at Fousseyni Daou Hospital in Kayes over a period of 10 years. Materials and Methods: This was a cross-sectional, descriptive study with data collection over a period of 10 years;The data collection was retrospective over nine years from January 1, 2013 to December 31, 2021 and prospective over one year from January 1, 2022 to December 31, 2022. This study focused on all patients whose death was noted on arrival during pregnancy, labor or in the postpartum period in the Gynecology-Obstetrics Department of Fousseyni Daou Hospital. Confidentiality and anonymity were respected. The processing and analysis of statistical data were carried out using SPSS 20.0 software. Results: During the study period, we recorded 93 cases of death noted on arrival out of a total of 606 maternal deaths, i.e., a frequency of 15.34%. The average age was 27 years with the extremes of 20 years and 34 years. They came mainly from rural areas at 74%, were married at 82%, uneducated at 51.6%, housewives at 87.1%. The profession of the spouses is worker at 37.6%. In our sample, evacuated patients were the most represented with 75.3%. Postpartum hemorrhage was the most frequent reason for admission with 22.6%. The deceased patients had no medical history at 86%. In our series, 59.5% of the deceased patients had not had antenatal consultations (CPN). Patients who died on arrival and who had given birth at home were the most represented with 54.8%. Deaths from immediate postpartum hemorrhage complicated by shock were the most frequent with 25.8% followed by severe anemia 8.6%. Deaths were mainly due to direct obstetric causes at 76.3%. In these deaths observed on arrival, the 2nd delay was identified at 48.4%. Conclusion: Maternal deaths observed on arrival remain frequent in the Kayes region. The main causes are immediate postpartum hemorrhage and anemia, which are almost all preventable causes of maternal death following the 1st and 2nd delay.
文摘Exploring the concept of death within Judaism may seem audacious,yet it is encouraged by the tradition of inquiry intrinsic to Jewish thought.Despite the caution urged by rabbinic authorities,Jewish texts ranging from the Torah to mystical writings offer rich perspectives on death,the soul,and the afterlife.This article examines how death is represented in Jewish belief and practice,considering diverse expressions from ritual law,poetic literature,Kabbalistic cosmology,and esoteric traditions.Emphasis is placed on ritual practices,mourning customs,and metaphysical understandings of the soul,including Sheol,Gehenna,and Eden.The evolution of these beliefs is explored through rabbinic,mystical,and popular sources,across historical and cultural contexts.
基金Supported by 2021 Annual Routine Project of the 14th Five-Year Plan of Fujian Education Science,No.FJJKGZ21-110.
文摘BACKGROUND Death anxiety is a common emotional response to death,and it varies in intensity across cultures and regions.However,there is a paucity of research on death anxiety among nursing students during their clinical internship,especially in relation to their emotional experiences and behavioral responses.AIM To explore the relationship between empathy and death anxiety as well as to identify factors influencing students’empathetic skills during their initial clinical experiences.METHODS This cross-sectional study included 473 nursing students enrolled from across vocational colleges in Quanzhou(Fujian Province,China)during June–July 2023.These students were trained at three Grade-A general hospitals.The Empathy Scale and Death Anxiety Scale were applied to assess their empathetic skills and death anxiety levels during the early stages of the clinical internship.Data ana-lyses employed descriptive statistics,correlation analyses,independent sample t-tests,one-way analysis of variance,and multiple linear regression analysis.RESULTS The mean death anxiety score was 46.33±6.29,with 95.6%of participants exhi-biting high death anxiety.The mean scores across dimensions were as follows:Cognitive-affective,18.08±3.15;pain and illness,13.25±2.41;awareness of the passage of time,5.58±1.40;stimuli related to death,9.40±1.56.The mean empathy score was 63.78±11.49.Regression analysis revealed that students’subject major,total death anxiety level,and pain and stress dimensions acted as significant predictors of their empathetic skills during early clinical practice(P<0.05).CONCLUSION Vocational nursing students,especially those in midwifery with higher death anxiety,exhibited lower empathetic skills during the early stages of their clinical internship.Nursing educators should take measures to enhance the empathetic skills of students through appropriate training and support for students with high death anxiety levels.
基金Supported by National Natural Science Foundation of China(No.82070964)Shaanxi Provincial Outstanding Youth Science Foundation Project(No.2022JC-60)+1 种基金Shaanxi International Science and Technology Cooperation Program Project(No.2024GHYBXM-20)Shaanxi Provincial Education Department Youth Innovation Team Research Project(No.23JP151).
文摘Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss and irreversible blindness.Elevated intraocular pressure(IOP)remains the most important risk factor for glaucoma,but the exact mechanism responsible for the death of RGCs is currently unknown.Neurotrophic factor deficiency,impaired mitochondrial structure and function,disrupted axonal transport,disturbed Ca2+homeostasis,and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma.This review was conducted using Web of Science,PubMed,Project,and other databases to summarize the relevant mechanisms of death of RGCs in glaucoma,in addition to outlining protective treatments to improve the degradation of RGCs.
基金supported by grants from the Swiss National Science Foundation(310030-182332 and 310030L-208141)(to JP)。
文摘The challenge of protecting the brain resides in the unique characteristics of neurons,as they are postmitotic,long-lived,excitable,and polarized cells with long and fragile axons and dendrites.The complexity of the multiple potential cell death pathways further complicates this issue.In addition,the immature brain is prone to a“cell death continuum,”which involves intricate molecular interconnections between cell death processes.
基金supported by the National Key R&D Program of China(No.2022YFC2304205)National Natural Science Foundation of China(Nos.51903062,52273128)the Plan on Enhancing Scientific Research in GMU(No.02-410-2405033).
文摘Ferroptosis in combination with immune therapy emerges as a promising approach for cancer therapy.Herein,dual-responsive metal-polyphenol coordinated nanomedicines were developed for pH/glutathione(GSH)-responsive synergistic ferroptosis and immunotherapy.Our innovative strategy involves the development of a manganese-polyphenol coordinated nanostructure,leveraging the biocompatibility of bovine serum albumin(BSA)as a template to encapsulate the anticancer drug sorafenib.The tumor microenvironment(pH/GSH)prompts the disassembly of MnO_(2)and epigallocatechin gallate(EGCG),thereby releases the anticancer payload.Concurrently,MnO_(2)acts to deplete intracellular GSH,which in turn suppresses glutathione peroxidase activity,leading to an accumulation of lipid peroxides with cell ferroptosis.Additionally,the release of Mn^(2+)ions bolster the cyclic guanosine monophosphlic acid(GMP)-adenosine monophosphlic acid(AMP)synthase-stimulator of interferon gene(cGAS-STING)pathway,which,in conjunction with the immunogenic cell death(ICD)effect induced by tumor cell apoptosis,significantly promotes dendritic cell(DC)maturation and enhances the presentation of tumor antigens.This successively ignites a robust innate and adaptive immune response.Both in vitro and in vivo experiments have demonstrated that the concurrent administration of ferroptosis-inducing and immune-stimulating therapies can significantly inhibit tumor growth.
基金supported by grants from the National Key Research and Development Program of China(2023YFA1801804,2022YFA0807000,2021YFA1101300,2021YFA1101800,and 2020YFA0112503)the National Natural Science Foundation of China(82171149,82371166,81970892,82330033,82030029,92149304,82071053,and 82171144)+5 种基金the Shenzhen Science and Technology Program(JCYJ20230807114700001,JCYJ20210324125608022,and JCYJ20190814093401920)the Guangdong Basic and Applied Basic Research Foundation(2024A1515010548)the Science and Technology Department of Sichuan Province(2021YFS0371)the Jiangsu Provincial Scientific Research Center of Applied Mathematics(BK20233002)the Open Research Fund of Guangdong Academy of Medical Sciences(YKY‐KF202201)the Taishan Scholars Project-Young Experts Program of Shandong Province(tsqn202211357).
文摘Sensorineural hearing loss(SNHL),the most commonly-occurring form of hearing loss,is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea.Numerous environmental and physiological factors have been shown to cause acquired SNHL,such as ototoxic drugs,noise exposure,aging,infections,and diseases.Several programmed cell death(PCD)pathways have been reported to be involved in SNHL,especially some novel PCD pathways that have only recently been reported,such as ferroptosis,necroptosis,and pyroptosis.Here we summarize these PCD pathways and their roles and mechanisms in SNHL,aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
基金supported by the fund for the Project of the National Key Research and Development Program of China(2024YFD1300203)Project support was provided by the Fund opened from Key Laboratory of Fujian Universities Preventive Veterinary Medicine and Biotechnology,Longyan University(grant No.2021KF01)the Cyanine Project of Yangzhou University(2020)。
文摘The intestinal tract,a complex organ responsible for nutrient absorption and digestion,relies heavily on a balanced gut microbiome to maintain its integrity.Disruptions to this delicate microbial ecosystem can lead to intestinal inflammation,a hallmark of inflammatory bowel disease(IBD).While the role of the gut microbiome in IBD is increasingly recognized,the underlying mechanisms,particularly those involving endoplasmic reticulum(ER)stress,autophagy,and cell death,remain incompletely understood.ER stress,a cellular response to various stressors,can trigger inflammation and cell death.Autophagy,a cellular degradation process,can either alleviate or exacerbate ER stress-induced inflammation,depending on the specific context.The gut microbiome can influence both ER stress and autophagy pathways,further complicating the interplay between these processes.This review delves into the intricate relationship between ER stress,autophagy,and the gut microbiome in the context of intestinal inflammation.By exploring the molecular mechanisms underlying these interactions,we aim to provide a comprehensive theoretical framework for developing novel therapeutic strategies for IBD.A deeper understanding of the ER stress-autophagy axis,the gut microbial-ER stress axis,and the gut microbial-autophagy axis may pave the way for targeted interventions to restore intestinal health and mitigate the impact of IBD.
基金Supported by the Shandong Provincial Natural Science Foundation(No.ZR2020QC043)。
文摘The abundance of live and dead Oithona similis in Jiaozhou Bay,Shandong,China,was investigated monthly from December 2008 to November 2009 via the neutral red staining method.The annual variation in total abundance was similar for females,males,and copepodites,with a main numerical peak from February to July and a minor peak in November,but the variations in carcass abundance and death proportion were different.The monthly average abundance of male and copepodite carcasses significantly increased with their total abundance(P<0.001),whereas no such correlation was observed for females.The abundance of female carcasses peaked at 12.4 inds./m^(3) in November but remained below 3.0 inds./m^(3) in all other months.The monthly average death proportion ranged 0.3%-4.9% for females,3.6%-25.7% for males,and 2.6%-8.4% for copepodites.On average,the death proportion of males was 9.2 times greater than that of females and 3.5 times greater than that of copepodites.Therefore,significant sexual difference exists in the non-predatory mortality of O.similis and this difference is an important cause of the female-skewed sex ratios observed in the field.
