Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death / 生物医学与环境科学（英文）

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

The Progression of Postmortem Biochemistry Analysis in Forensic Discrimination of Cause of Death / 中山大学学报(医学科学版)

The discrimination of the cause of death is an important part in forensic medicine. With the advantages of simple operation， high test efficiency， and easy sensitivity to the death mechanism of the deceased， postmortem biochemistry analysis has become a significant auxiliary analysis method for discrimination of the cause of death. In this paper， we discuss the development status， advantages and current problems of postmortem biochemical analysis， and then describe the application prospect of postmortem biochemistry in the discrimination of the cause of death by posing feasible solutions， so that to provide an idea for this research.

Individual and interactive effects of atmospheric PM2.5 and O3 on mortality of circulatory system diseases in Ningxia / 环境与职业医学

Background The impact of atmospheric fine particulate matter (PM2.5) and ozone (O3) on the mortality of circulatory system diseases cannot be ignored. However, whether the interaction between PM2.5 and O3 can affect population health is rarely reported and requires study. Objective To investigate the individual and interactive impacts of atmospheric PM2.5 and O3 on the mortality of circulatory system diseases in the population of Ningxia region. Methods The data of 119647 deaths due to circulatory system diseases, daily average concentrations of atmospheric pollutants, and meteorological data in Ningxia from 2013 to 2020 were retrieved. PM2.5 was divided into low, medium, and high concentrations according to the primary and secondary national limits (35 and 75 μg·m−3) of the Ambient air quality standards. Similarly, O3 was divided into low, medium, and high concentrations according to the national limits (100 and 160 μg·m−3). Using a generalized additive mixed model based on quasi Poisson distribution, the impacts of atmospheric PM2.5 and O3 as well as their interaction on the mortality of circulatory system diseases were analyzed using the population data of Ningxia region. Results During the target period, males and the ≥ 65 year group accounted for larger proportions of deaths due to circulatory system diseases (55.47% and 79.87% respectively). The daily average concentration of PM2.5 (40.25 μg·m−3) exceeded the national primary limit. In the single pollution model, the highest cumulative lag effects for mortality from circulatory system diseases were PM2.5 exposure over previous 1 d (lag01) and O3 exposure for previous 2 d (lag02), and their excess risk (ER) values were 1.03% (95%CI: 0.67%, 1.40%) and 1.02% (95%CI: 0.57%, 1.50%), respectively. The results of concentration stratification analysis showed that the most significant risks of death from circulatory system diseases [ER (95%CI): 1.12% (0.32%, 1.92%) and 0.95% (0.13%, 1.79%) respectively] were found at medium PM2.5 and O3 concentrations. The interaction analysis revealed that under, a synergistic effect on the risk of death from circulatory system diseases was identified (relative excess risk due to interaction=3.08%, attributable proportion of interaction=2.90%, synergy index=1.89) when considering the coexistence of PM2.5 and O3 above the primary limit. As the concentrations of PM2.5 and O3 increased, the synergistic effect increased the risk of death from circulatory system diseases in the general population, men, women, and the ≥ 65 years group. Conclusion Both atmospheric PM2.5 and O3 can increase the risk of death from circulatory system diseases, and the two pollutants have a synergistic effect on the risk of death from circulatory system diseases.

Research advances in traditional Chinese medicine regulation of programmed cell death in intervening against hepatic fibrosis / 临床肝胆病杂志

Hepatic fibrosis （HF） is a pathological process of abnormal repair of liver tissue structure caused by chronic liver injury， and its pathogenesis has not been fully clarified. Related studies have shown that programmed cell death may be associated with the onset of HF， and traditional Chinese medicine （TCM） has a significant effect in regulating programmed cell death to intervene against HF. This article reviews the main mechanism of the influence of programmed cell death on HF and discusses the possible mechanism of TCM regulation of programmed cell death in improving HF， which provides new ideas for TCM prevention and treatment of HF.

Construction and self-activation detection of yeast two-hybrid bait plasmid of human programmed cell death ligand 1 immunoglobulin variable region domain gene / 中国生物制品学杂志

@#Objective To construct a yeast two-hybrid recombinant bait plasmid of human programmed cell death ligand 1(PD-L1)immunoglobulin variable region(IgV)domain gene,detect its expression in yeast and detect the cytotoxicity and self-activation of PD-L1 IgV protein as well as the interaction between PD-L1 IgV and human thioredoxin(hTrx).Methods Human PD-L1 was analyzed by bioinformatics method,and primers were designed to amplify PD-L1 IgV domain based on the coding region of PD-L1 gene registered in NCBI GenBank database. PCR amplification was carried out with pENTERPD-L1 plasmid as template,and then cloned into yeast two-hybrid bait vector pGBKT7. The recombinant bait plasmid and pGBKT7 empty vector were transformed into Y2HGold yeast cells respectively,and the PD-L1 IgV gene and its expression were detected by PCR and Western blot;Meanwhile,the protein toxicity and self-activation of PD-L1 IgV were detected,and the interaction between PD-L1 IgV and hTrx was detected by drip plate method.Results The bioinformatics analysis results of PD-L1 were consistent with related reports. The recombinant bait plasmid pGBKT7-PD-L1 IgV was correctly constructed,and Y2HGold positive clone was obtained,in which PD-L1 IgV was stably expressed. The empty vector pGBKT7 and recombinant bait plasmid pGBKT7-PD-L1 IgV grew well on SD/-Trp and SD/-Trp/X-α-Gal plates with the same colony size and number and white colony,but they did not grow on SD/-Trp/X-α-Gal/AbA plates,which indicated that PD-L1 IgV protein had no toxicity and no self-activation effect on yeast. The results of drip plates test showed that all experimental groups grew well on SD/-Trp/-Leu plate,while only positive control group grew on SD/-Trp/-Leu/X-α-Gal/AbA plate and showed blue color,which indicated that bait protein PD-L1 IgV and hTrx did not self-activate,and there was no interaction between them.Conclusion Recombinant human PD-L1 IgV bait plasmid was successfully constructed. PD-L1 IgV protein showed no toxicity and self-activation effect on yeast cells,and there was no interaction between PD-L1 IgV and hTrx. Subsequently,hTrx can be used to construct a peptide aptamer library,from which peptide aptamers that specifically bind to PD-L1 IgV can be screened.

Probability and trend of premature death of four major chronic diseases in Linyi City in 2013-2021 / 公共卫生与预防医学

Objective To analyze the mortality rate and probability of premature death caused by four major noninfectious chronic diseases (NCDs)in Linyi City from 2013 to 2021, and to provide data support for scientific formulation of chronic disease prevention and control strategy. Methods The mortality data of major chronic diseases in Linyi City from 2013 to 2021 were analyzed. The crude mortality, age-standardized mortality and premature death probability were calculated. The annual percent change (APC) was adopted to analyze the temporal trend of mortality and probability of premature death. Results The average annual crude mortality of four major NCDs was 538.98/100,000, and the age-standardized mortality was 387.3/100,000. The crude mortality rate increased from 517.37/100 000 in 2013 to 563.13/100 000 in 2021 (APC=0.89％, P=0.01). The age-standardized mortality rate decreased from 410.19/100,000 to 364.92/100,000 (APC=-1.8％, P=0.01). The crude mortality and age-standardized mortality of four major NCDs in males were higher than those in females (P<0.05). The average annual probability of premature death caused by four major NCDs was 13.37%. The probability of premature death decreased from 14.49％ in 2013 to 12.32％ in 2021（APC=-2.1％, P=0.00）. From 2013 to 2021, the probability of premature death from malignant tumors, cardiovascular and cerebrovascular diseases, and chronic respiratory diseases in Linyi City dropped from 6.14%, 7.47%, and 1.21% to 5.52%, 6.46%, and 0.5%, respectively (APCs were -1.2%, -2.1%, and -11.3%, respectively, and P values were 0.04, 0.00, and 0.00, respectively). The probability of premature death from diabetes remained stable. The probability of premature death caused by four major NCDs in males was higher than that in females (P<0.05). Conclusion The probability of premature death of the four major NCDs in Linyi has showed a downward trend during 2013-2021. It is suggested to strengthen the prevention and control of diabetes in the next step.

Relationship between air pollution and HIV/AIDS death in Wuhan City / 公共卫生与预防医学

Objective To explore the correlation between air pollutants (PM2.5, NO2, and CO) and the mortality rate of HIV/AIDS patients in Wuhan. Methods The death data of HIV/AIDS patients from January 1, 2017, to December 31, 2019, and the daily average atmospheric pollutant concentration during the study period were collected. A time-stratified case-control study design was used to explore the correlation between atmospheric pollutant concentration and patient mortality. Results For every 10 µg/m3 increase in CO concentration within 0-4 days of cumulative lag, AIDS-related mortality in HIV/AIDS patients increased by 1.79% (95% CIs: 0.04, 3.56). There was no statistical correlation between PM3 and NO3 concentrations and mortality in patients with HI and AIDS. Conclusion CO is positively correlated with the risk of AIDS-related death in HIV/AIDS patients. This study can provide relevant epidemiological evidence for public health authorities to develop more effective prevention measures for HIV/AIDS patients.

Deaths of children under 5 years old in Changsha in 2016 - 2021 / 公共卫生与预防医学

Objective To analyze the death status and main causes of death among children under 5 years old in Changsha from 2016 to 2021, and to provide a scientific basis for formulating preventive measures for children's health care. Methods The data of 1 761 deaths of children under 5 years old in Changsha City from 2016 to 2021 were collected, and the mortality trend, the order of causes of death and the utilization of pre-death medical care services were retrospectively analyzed. Results The 7-day neonatal mortality, 28-day neonatal mortality, 0-1-year-old neonatal mortality, and the mortality rate of children under 5 years old (U5MR) in Changsha City from 2016 to 2021 were 0.76‰, 1.28‰, 2.41‰, and 3.86‰, respectively. All the mortality rates showed a decreasing trend (P<0.05). U5MR in males was significantly higher than that in females (P<0.05), and U5MR in rural areas was significantly higher than that in urban areas (P<0.05). The top five causes of U5MR were drowning, premature delivery or low birth weight, pneumonia, other congenital anomalies, and accidental asphyxia, respectively. The death places of children under 5 years old were mainly medical and health institutions, and 81.72% of them were treated in hospitals before death. Conclusion From 2016 to 2021, the mortality rate of children under the age of 5 in Changsha City has gradually decreased. Preventing congenital malformations, reducing preterm birth or low birth weight, improving the treatment level of pneumonia, and preventing accidents such as drowning and accidental suffocation are the key to reducing the mortality rate of children under 5 years old.

Trends of heart disease death and prediction of life expectancy without cause of death in Qidong City in 1990-2019 / 公共卫生与预防医学

Objective To analyze the trend of heart disease death and the life expectancy without cause of death in Qidong City, Jiangsu Province from 1990 to 2019, and to provide reference for the prevention and control of heart disease. Methods Data on heart disease deaths among residents in Qidong City from 1990 to 2019 were collected through the Qidong City Death Registration and Monitoring System. The crude mortality rate (CR) and Chinese age-standardized mortality rate (CASR), potential years of life loss (PYLL), average years of life loss (AYLL), potential life loss years rate (PYLLR), life expectancy, and life expectancy without cause of death were calculated, and the annual percentage change (APC) was used to analyze the trend of heart disease death. Using SAS9.2 software, the death trend prediction was conducted by the ARIMA model in time series analysis. Results From 1990 to 2019, 27,762 residents died of heart disease in Qidong City, with a CR of 81.20/100 000 and an APC of 3.734%. There were 12 358 deaths of heart disease in men, with a CR of 73.24/100 000 and an APC of 3.86%, while there were 15 404 deaths of heart disease in women, with a CR of 88.95/100 000 and an APC of 3.63%. CR showed an upward trend (all P < 0.001). The PYLL for heart disease was 66 192.00 person-years, the AYLL was 13.23 person-years, and the PYLLR was 2.16‰. The life expectancy loss from heart disease was gradually increasing: 0.89 years in 1990 to 1.85 years in 2019, with an APC of 0.405% (P<0.001, a statistically significant trend). The prediction results showed that in 2029, the life expectancy after heart disease would reach 88.17 years. Conclusion From 1990 to 2019, the crude mortality rate of heart disease in Qidong City has showed an increasing trend, leading to an increasing loss of life due to heart disease year by year. The mortality rate and life loss of heart disease in women are higher than those in men. Targeted intervention measures should be further adopted to reduce the mortality rate of heart disease among residents in Qidong.

Research progress in RIPK3 and its inhibitors / 中国药理学通报

Receptor-interacting serine/threonine-protein kinase 3(RIPK3),a member of the RIP kinase family,plays an important role in cell death,especially in necroptosis. In addition,RIPK3 is also involved in apoptosis and pyroptosis,suggesting that RIPK3 may be the intersection of multiple cell death and it possesses the potential to be a target for precise regulation of cell death. According to the kinase binding mode,current RIPK3 inhibitors can be classified into type ,type Ⅱ and other types. This review summarizes the research progress in the role of RIPK3 in cell death and its inhibitors,which is of great significance in seeking drugs for the treatment of injury-related diseases.

Research progress in ferroptosis pathways and ubiquitination modification of ferroptosis-related molecules / 中国药理学通报

Ferroptosis is an iron-dependent cell death caused by phospholipid peroxidation damage of polyunsaturated fatty acids on cell membranes and involves several pathways, including the iron homeostasis regulatory pathway, the cystine glutamate reverse transporter (system Xc) pathway and the voltage-dependent anion channel (VDAC) pathway. Ferroptosis is involved in the development of several diseases (e. g. myocardial infarction, stroke, cancer and degenerative diseases). The ubiquitination is an important post-translational modification of various protein molecules in the organism. Studies have shown that regulating the ubiquitination of ferroptosis pathway-related molecules can control cellular ferroptosis. Targeting the ubiquitination of ferroptosis pathway-related molecules can effectively promote or inhibit ferroptosis, which is expected to be a new strategy for the treatment of cancer or cardiovascular diseases. In this paper we review the progress of the ferroptosis pathways and the ubiquitination modification of ferroptosis-related molecules.

Disease burden due to PM2.5 pollution before and after air quality improvement in Shijiazhuang / 环境与职业医学

Background Air pollution has gradually become a major environmental and public health problem faced by countries around the world. Hazy weather not only affects the health of the population, but also poses a threat to social and public safety. China has successively promulgated policies such as the "Ten Articles on Atmosphere" and the Three-year action plan to fight air pollution, aiming to improve ambient air quality. It is clear that the Beijing-Tianjin-Hebei region has accomplished the set targets and improved air quality according to the environmental monitoring data of 2017. Objective To assess air quality improvements through the evaluation of the disease burden due to fine particulate matter (PM2.5) pollution in Shijiazhuang City before and after the air quality improvement from 2014 to 2021, including fatalities and health economic losses attributed to PM2.5 pollution. Methods Data on causes of death, PM2.5 concentrations, the number of permanent residents at the end of the year, gross regional product, and disposable income per capita in urban areas of Shijiazhuang were collected from 2014 to 2021. Total, non-accidental, circulatory, and respiratory deaths due to PM2.5 pollution were estimated by global exposure mortality models (GEMM). Health and economic losses due to selected diseases were calculated by value of statistical life (VOSL). Results During the study period, the average annual concentration of PM2.5 in Shijiazhuang was highest in 2014, and began to decline year by year in 2017, but all exceeded the current national limit of the second level of ambient air quality standards (35 μg·m−3). The total deaths, non-accidental deaths, circulatory disease deaths, and respiratory disease deaths attributed to PM2.5 pollution from 2014 to 2021 were 41326, 40246, 21792, and 5022, respectively; the associated health economic losses were 37.362, 36.369, 19.695, and 4.535 billion yuan, respectively. From the perspective of improved air quality, both the number of attributed deaths and health economic losses had declined in a volatile manner since 2017, with a significant decrease in 2019. If the average annual concentration of PM2.5 reached the second-level limit of China's ambient air quality standard (35 μg·m−3), the total deaths, non-accidental deaths, and deaths from circulatory diseases and respiratory diseases due to PM2.5 pollution would deducted by about 17000, 16000, 9000, and 2000, respectively; the corresponding health and economic losses would decreased by 15.201, 14.761, 7.959, and 1.859 billion yuan, respectively. If the average annual concentration of PM2.5 reached the latest PM2.5 air quality guidelines (5 μg·m−3) proposed by the World Health Organization, the total deaths, non-accidental deaths, circulatory disease deaths, and respiratory disease deaths due to PM2.5 pollution would deducted by 36000, 35000, 19000, and 4000, respectively, and the corresponding health and economic losses would reduced by 32.673, 31.796, 17.211, and 3.969 billion yuan, respectively. Conclusion PM2.5 pollution can lead to severe mortality burden and economic loss. Under the implementation of the State Council's "Ten Articles on Atmosphere" and the Three-year action plan to fight air pollution, Shijiazhuang's PM2.5 concentration and health economic losses have been significantly reduced, and further control of PM2.5 pollution can achieve greater health benefits and economic gains, affirming the positive results of local air pollution prevention work.

The Ethical Value of Hospice Narrative Doulas in the Context of Great Health / 中国医学伦理学

Death is the last transitional rite in the life process. Whether for the life state, family ethics or social relations of both the dead or the living, death indicates a major change and hides a certain crisis. The bio-health narrative concept puts forward that any transitional rite of life process requires narrative intervention and narrative care, as does death. Under the guidance of the concept, the profession of narrative death-doula came into being. Using the narrative concept as a framework, hospice narrative doulas provide emotional, physical, mental support to the terminal stage subjects and their families by accompanying the dying at close range, listening to their life stories, helping them record and dictate their autobiographies, reconstructing and repairing interpersonal narrative connections, and even planning funeral details with the dying. The death narrative doulas will create a personalized and humanized ritual and process around death, restore the spirituality and humanity which has been lost in the modern medical context to death itself.

Experience and Reflection on the Ethical Review of Organ Donation and Transplantation after Citizens’ Death in Medical Institution / 中国医学伦理学

In order to explore the ethical review experience of organ donation and transplantation after the death of citizens, and provide reference value for medical institutions to carry out corresponding ethical review. By using descriptive research, purpose sampling method and the principle of data saturation, 10 members and secretaries of ethics committee on clinical application of organ transplantation technology were finally selected as respondents for semi-structured interviews. The Colaizzi 7-step analysis method was adopted to analyze, summarize and refine the theme. The results showed that the ethical review experience of organ donation and transplantation after the death of citizens included four themes: the responsibilities of ethics committee, the key points of ethics review, the form of ethics review conference and its advantages and disadvantages, and the construction of the ethics committee of organ transplantation. Therefore, there are defects in the ethical review of organ donation and transplantation in medical institutions at present. These can be remedied by enriching elements of the ethical review following the four principles of medical ethics, refining the laws related to organ donation after citizens’ death, constructing a reasonable and efficient pattern of ethical review conference, and establishing a robust and appropriate operation mode of organ transplantation ethics committee.

Qualitative Study on the Cognition Status of Organ Donors’ Family Members to Advance Care Planning / 中国医学伦理学

Discussing the cognition, attitude and influencing factors of the family members of organ donors towards advance care planning (ACP) to provide a basis for the further promotion of ACP in the field of organ donation. Using qualitative research methods, 8 family members of organ donors were selected purposefully for semi-structured interviews, and the 7-step of Colaizzi was used to analyze and summarize the themes of the interview data. The results showed that the cognition status of the family members of organ donors of ACP could be summarized into 3 themes: problems faced by ACP implementation, positive recognition of the implementation of ACP, factors affecting the promotion of ACP. Organ donors’ family members are unfamiliar with the concept of ACP and have unclear cognition, but think that the implementation of ACP is of positive significance. It is suggested to further strengthen the publicity of ACP, medical autonomy, death education, so as to promote the development of ACP and improve the willing to donate organ.

Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses

Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Distribuição de óbitos devido ao câncer do colo do útero nos municípios de extrema pobreza, Brasil, 2000 a 2018 / Distribution of deaths due to cervical cancer in extreme poverty municipalities, Brazil, from 2000 to 2018

Resumo Introdução: O câncer do colo uterino (CCU) permanece uma importante causa de morte nas regiões mais pobres do mundo. Objetivo: Analisar tendências da distribuição relativa de óbitos por CCU ocorridos nos municípios de extrema pobreza (EP) do Brasil, de 2000 a 2018. Método: A distribuição relativa de óbitos por CCU nos municípios de EP foi avaliada em relação ao total de óbitos observados em cada Unidade Federativa (UF). Uma modelagem autorregressiva foi usada para avaliar as tendências temporais da distribuição relativa de óbitos de 2000 a 2018. Resultados: De 2000 a 2018, houve 94.065 óbitos por CCU no Brasil, e 10,7% deles ocorreram nos municípios de EP. Seis estados (Amazonas, Roraima, Pará, Amapá, Tocantins e Mato Grosso do Sul) tiveram 100% dos seus municípios de EP reportando a ocorrência desses óbitos. As tendências na distribuição de óbitos nos municípios de EP em relação ao total de óbitos de cada UF seguiram em elevação em onze estados brasileiros. Conclusões: O CCU é doença prioritária das políticas públicas do Brasil, e as tendências desses óbitos observadas nos municípios mais pobres apontam que mais atenção deve ser dada a estas unidades de análise, a fim de melhorar a saúde das pessoas mais pobres.

Abstract Background: Cervical cancer (CC) remains a major cause of death in the poorest regions of the world. Objective: To analyze trends in relative distribution of CC deaths occurred in extreme poverty municipalities, Brazil, from 2000 to 2018. Method: The relative distribution of CC deaths occurred in extreme poverty municipalities was evaluated in relation to total number of CC deaths observed in each Federative Unit (FU). An autoregressive modeling was used to assess the temporal trends in the death distribution, 2000-2018. Results: From 2000 to 2018, there were 94,065 CC deaths, and 10.7% of them were recorded in extreme poverty municipalities. There were six states (Amazonas, Roraima, Pará, Amapá, Tocantins, and Mato Grosso do Sul) with 100.0% of extreme poverty municipalities reporting the occurrence of these deaths. The trends of death distribution in extreme poverty municipalities in relation to the total of deaths in each FU followed in increasing trends in eleven Brazilian FU. Conclusions: CC is a disease prioritized by public policies in Brazil, and the trends of these deaths observed in the poorest municipalities point out that more attention should be given to these units of analysis, in order to improve the health of the poorest people.

Predicting the outcome of death by CALL Score in COVID-19 patients

SUMMARY OBJECTIVE: The aim of this study was to assess the performance of the CALL Score tool in predicting the death outcome in COVID-19 patients. METHODS: A total of 897 patients were analyzed. Univariate and multivariate logistic regression analyses were conducted to determine the association between characteristics of the CALL Score and the occurrence of death. The relationship between CALL Score risk classification and the occurrence of death was also examined. Receiver operating characteristic curve analysis was performed to identify optimal cutoff points for the CALL Score and the outcome. RESULTS: The study revealed that age>60 years, DHL>500, and lymphocyte count ≤1000 emerged as independent predictors of death. Higher risk classifications of the CALL Score were associated with an increased likelihood of death. The optimal CALL Score cutoff point for predicting the death outcome was 9.5 (≥9.5), with a sensitivity of 70.4%, specificity of 80.3%, and accuracy of 80%. CONCLUSION: The CALL Score showed promising discriminatory ability for death outcomes in COVID-19 patients. Age, DHL level, and lymphocyte count were identified as independent predictors. Further validation and external evaluation are necessary to establish the robustness and generalizability of the CALL Score in diverse clinical settings.

Nursing care for parents who have experienced fetal demise: integrative review / Cuidado de enfermería a padres que han experimentado la pérdida fetal: revisión integradora / O cuidado de enfermagem aos pais que vivenciaram o óbito fetal: revisão integrativa

ABSTRACT Objectives: to identify scientific evidence regarding nursing care for parents who have experienced grief following fetal demise. Methods: an integrative review of original studies was conducted across six databases. The studies were classified according to the level of evidence. Results: the qualitative analysis of the nine studies comprising the sample involved thematic categories, exploring the impact of perinatal loss on families, inadequate communication by healthcare professionals, and the importance of a holistic approach in care. The role of the nurse is highlighted in making a positive contribution to the team, emphasizing participation in training and the provision of essential information. Final Considerations: grieving affects not only family dynamics but also the social environment, emphasizing the urgency of a more empathetic and comprehensive approach. Care should be holistic, going beyond technical nursing assistance, and addressing the biopsychosocial context of the parents.

RESUMEN Objetivos: identificar evidencia científica sobre el cuidado de enfermería a padres que han experimentado el duelo ante la pérdida fetal. Métodos: revisión integradora de estudios originales realizada en seis bases de datos y clasificados según el nivel de evidencia. Resultados: el análisis cualitativo de los nueve estudios que conformaron la muestra abordó categorías temáticas, explorando el impacto de la pérdida perinatal en las familias, la comunicación inadecuada por parte de los profesionales de la salud y la importancia de un enfoque holístico en la atención. Se destaca la importancia del papel del enfermero en la contribución positiva al equipo, haciendo hincapié en la participación en capacitaciones y la provisión de información esencial. Consideraciones Finales: la experiencia del duelo afecta no solo la dinámica familiar, sino también el entorno social, evidenciando la urgencia de un enfoque más empático y comprensivo. El cuidado debe ser holístico, trascendiendo la asistencia técnica de enfermería, con un enfoque en el contexto biopsicosocial de los padres.

RESUMO Objetivos: identificar evidências científicas acerca do cuidado de enfermagem aos pais que vivenciaram o luto diante do óbito fetal. Métodos: revisão integrativa de estudos originais realizada em seis bases de dados e classificados quanto ao nível de evidência. Resultados: a análise qualitativa dos nove estudos que compuseram a amostra envolveu categorias temáticas, explorando o impacto da perda perinatal nas famílias, a comunicação inadequada por parte dos profissionais de saúde e a importância de uma abordagem holística na assistência. Destaca-se a importância do papel do enfermeiro na contribuição positiva para a equipe, enfatizando a participação em capacitações e o fornecimento de informações essenciais. Considerações Finais: a vivência do luto impacta não apenas a dinâmica familiar, mas o meio social, evidenciando a urgência de uma abordagem mais empática e compreensiva. O cuidado deve ocorrer de forma holística, transcendendo a assistência técnica de enfermagem, com abordagem do contexto biopsicossocial dos pais.