Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxid...Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.展开更多
Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells.The rapid development and dissemination of ant...Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells.The rapid development and dissemination of antimicrobial–resistant strains have exacerbated this dilemma.With the increasing knowledge of host–pathogen interactions,especially bacterial strategies for survival and proliferation within host cells,host-directed therapy(HDT)has attracted increased interest and has emerged as a promising antiinfection method for treating intracellular infection.Herein,we applied a cell-based screening approach to a US Food and Drug Administration(FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium(S.Typhimurium).This screening allowed us to identify the antidiarrheal agent loperamide(LPD)as a potent inhibitor of S.Typhimurium intracellular proliferation.LPD treatment of infected cells markedly promoted the host autophagic response and lysosomal activity.A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B(GPNMB)induced by LPD.In addition,LPD treatment effectively protected against S.Typhimurium infection in Galleria mellonella and mouse models.Thus,our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial pathogens.Moreover,LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.展开更多
Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explo...Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.展开更多
Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,whi...Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,which can progress to severe respiratory distress syndrome and multiple organ failure.In severe cases,these complications may even lead to death.One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response.Therefore,suppressing the overactive immune response may be an effective strategy for treating COVID-19.Mesenchymal stem cells(MSCs)and their derived exosomes(MSCs-Exo)have potent homing abilities,immunomodulatory functions,regenerative repair,and antifibrotic effects,promising an effective tool in treating COVID-19.In this paper,we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19.We also summarize relevant recent clinical trials,including the source of cells,the dosage and the efficacy,and the clinical value and problems in this field,providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.展开更多
Gastric peroral endoscopic myotomy(G-POME)is an emerging minimally invasive endoscopic technique involving the establishment of a submucosal tun-nel around the pyloric sphincter.In 2013,Khashab et al used G-POME for t...Gastric peroral endoscopic myotomy(G-POME)is an emerging minimally invasive endoscopic technique involving the establishment of a submucosal tun-nel around the pyloric sphincter.In 2013,Khashab et al used G-POME for the first time in the treatment of gastroparesis with enhanced therapeutic efficacy,prov-iding a new direction for the treatment of gastroparesis.With the recent and rapid development of G-POME therapy technology,progress has been made in the treatment of gastroparesis and other upper digestive tract diseases,such as congenital hypertrophic pyloric stenosis and gastric sleeve stricture,with G-POME.This article reviews the research progress and future prospects of G-POME for the treatment of upper digestive tract gastrointestinal diseases.展开更多
This editorial discusses the article“Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis”published in the latest edition of the World Journal of Gastroint...This editorial discusses the article“Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis”published in the latest edition of the World Journal of Gastrointestinal Surgery.Immunotherapy has achieved outstanding success in tumor treatment.However,the presence of liver metastasis(LM)restrains the efficacy of immunotherapy in various tumors,including lung cancer,colorectal cancer,renal cell carcinoma,melanoma,and gastric cancer.A decrease in CD8+T cells and nature killer cells,along with an increase in macrophages and regulatory T cells,was observed in the microenvironment of LM,leading to immunotherapy resistance.More studies are necessary to determine the best strategy for enhancing the effectiveness of immunotherapy in patients with LM.展开更多
Objective:To study the effective value of introducing the concept of early oral exercise in the process of nursing intervention for preterm infants in the neonatal intensive care unit(NICU).Methods:96 cases of preterm...Objective:To study the effective value of introducing the concept of early oral exercise in the process of nursing intervention for preterm infants in the neonatal intensive care unit(NICU).Methods:96 cases of preterm infants diagnosed from January 2022 to August 2022 were selected and randomly divided into two groups:the general practice group(general nursing intervention),and the early practice group(early oral exercise intervention),and the effect of intervention on preterm infants in the two groups was observed.Results:After nursing care,the mean value of the non-nutritive sucking ability assessment(76.54±5.82),the mean value of the intellectual development degree assessment(104.57±8.45),the mean value of the psychomotor development degree assessment(102.33±6.74),and the mean value of behavioral neural reflexes ability assessment(38.71±2.40)in the early practice group were better than that as compared to the general practice group(P<0.05);the mean value of oral feeding start time of preterm infants in the early practice group(35.42±7.63)weeks,the mean value of all oral feeding time(34.12±5.28)weeks,and the mean time of hospital intervention(15.33±4.25)days were lesser than compared to those of the general practice group at 37.4±5.82 weeks,37.46±3.55 weeks,and 20.46±2.91 days,respectively(P<0.05);the rate of adverse reactions in preterm infants in the early practice group significantly lower than that of the general practice group(P<0.05).Conclusion:The introduction of the concept of early oral exercise intervention among NICU nurses improved the feeding effect,sucking ability of preterm infants,and intellectual development.Hence,early oral motor care should be popularized.展开更多
Background:The purpose of this study is to evaluate the quality of life(QoL)of hospitalized patients in China suffering from digestive system malignancies and to identify potential risk factors for a decrease in QoL.M...Background:The purpose of this study is to evaluate the quality of life(QoL)of hospitalized patients in China suffering from digestive system malignancies and to identify potential risk factors for a decrease in QoL.Methods:The European Organization for Research and Treatment Core Quality of Life questionnaire(EORTC QLQ-C30)was applied to evaluate the QoL of 23,519 patients with six digestive malignancies(esophageal cancer,gastric cancer,colorectal cancer,liver cancer,biliary tract cancer,and pancreatic cancer).A t test or analysis of variance was employed to analyze the total EORTC QLQ-C30 scale scores and domain scores of the EORTC QLQ-C30 scale among patients in different subgroups.Results:The average QoL score was 50.4±10.8.The tumor type,age,sex,and TNM stage all had an impact on QoL ratings.Colorectal cancer patients had a better total QoL score(49.3±10.3)and scores in the domains of functioning,withmilder symptoms,except for diarrhea.Patients with biliary tract cancer(54.2±12.3)and pancreatic cancer(54.2±12.3)reported a poorer QoL,significant functional impairment,and more pronounced symptoms.Patients with esophageal cancer experienced the most severe financial difficulties(35.2±27.5).Patients aged≥65 years,women,and those with TNM stage III/IV reported lower QoL.In addition,the disparities in total QoL scores and scores in specific domains were significant among patients with some types of tumors,and based on ethnicity,educational level,occupation,treatment(s)received,and place of residence.Conclusions:There is a need to focus on elderly individuals,those with low educational levels,and patients with progressivemalignant tumors and to improve routine disease monitoring and symptom management to enhance the quality of life for patients with malignancies of the digestive system.展开更多
Background: Otitis media (OM) is highly prevalent and is one of the most important causes of preventable hearing loss in developing countries and it may have long-term impacts on the children. Several hospital-based c...Background: Otitis media (OM) is highly prevalent and is one of the most important causes of preventable hearing loss in developing countries and it may have long-term impacts on the children. Several hospital-based cross-sectional studies have been conducted in East African countries to assess the prevalence of OM;however, no similar studies have been conducted in Somalia. Therefore, we conducted a hospital-based cross-sectional study to identify the prevalence and the underlying risk factors of OM among children under the age of five in Mogadishu, Somalia. Methodology: A hospital-based cross-sectional study was conducted from July 2022 to November 2022 at three main hospitals in Mogadishu, Somalia. A total of 384 children aged less than 5 years were included. Parents of these children were interviewed with a questionnaire and a clinical examination was performed for each child. The Statistical Package for Social Sciences, SPSS (Version 22, IBM, Inc.), was used for the statistical analysis. Result: The prevalence of otitis media among the 384 children recruited was 31.25% (120/384). Otitis media was significantly associated with age less than one year (P = 0.006), malnutrition (P Conclusion: In summary, the present study found that otitis media was highly prevalent (31.25%) in Mogadishu, Somalia. The majority of the affected children were younger than one year. Age of the child, malnutrition, upper respiratory tract infections, feeding in lying position, and dripping something into a child’s ear were found to significantly increase the risk of developing otitis media in children. In contrast, breastfeeding for more than one year has been found to reduce the risk of developing otitis media in children.展开更多
Background:Hepatocellular carcinoma(HCC)is the sixth most common cancer globally,with limited therapies and unsatisfactory prognosis once in the advanced stages.With promising advances in locoregional and systematic t...Background:Hepatocellular carcinoma(HCC)is the sixth most common cancer globally,with limited therapies and unsatisfactory prognosis once in the advanced stages.With promising advances in locoregional and systematic treatments,fast development of targeted drugs,the success of immunotherapy,as well as the emergence of the therapeutic alliance,conversion therapy has recently become more well developed and an effective therapeutic strategy.This article aimed to review recent developments in conversion therapy in liver transplantation(LT)for HCC.Data sources:We searched for relevant publications on Pub Med before September 2022,using the terms“HCC”,“liver transplantation”,“downstaging”,“bridging treatment”and“conversion therapy.”Results:Conversion therapy was frequently represented as a combination of multiple treatment modalities to downstage HCC and make patients eligible for LT.Although combining various local and systematic treatments in conversion therapy is still controversial,growing evidence has suggested that multimodal combined treatment strategies downstage HCC in a shorter time,which ultimately increases the opportunities for LT.Moreover,the recent breakthrough of immunotherapy and targeted therapy for HCC also benefit patients with advanced-stage tumors.Conclusions:In the era of targeted therapy and immunotherapy,applying the thinking of transplant oncology to benefit HCC patients receiving LT is a new topic that has shed light on advanced-stage patients.With the expansion of conversion therapy concepts,further investigation and research is required to realize the full potential of conversion treatment strategies,including accurately selecting candidates,determining the timing of surgery,improving the conversion rate,and guaranteeing the safety and long-term efficacy of treatment.展开更多
The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrop...The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.展开更多
BACKGROUND At present,many studies have reported the risk factors for postoperative intracranial reinfection,including age,sex,time to surgery,duration of postoperative catheterization,emergency procedures,type of dis...BACKGROUND At present,many studies have reported the risk factors for postoperative intracranial reinfection,including age,sex,time to surgery,duration of postoperative catheterization,emergency procedures,type of disease and cerebrospinal fluid leakage,but the academic community has not reached a unified conclusion.AIM To find factors influencing the surveillance of re-emerging intracranial infections in elective neurosurgical patients.METHODS Ninety-four patients who underwent elective craniotomy from January 1,2015 to December 31,2022 in the Department of Neurosurgery,First Hospital of Jilin University,were included in this study.Of those,45 patients were enrolled in the infection group,and 49 were enrolled in the control group.The clinical data of the patients were collected and divided into three categories,including preoperative baseline conditions,intraoperative characteristics and postoperative infection prevention.The data were analyzed using SPSS 26.0 software.RESULTS There were 23 males and 22 females in the infection group with a mean age of 52.8±15.1 years and 17 males and 32 females in the control group with a mean age of 48.9±15.2 years.The univariate analysis showed that the infection group had higher systolic blood pressures and postoperative temperatures,fewer patients who underwent a supratentorial craniotomy,more patients with a history of hypertension and higher initial postoperative white blood cell counts than the control group,with statistically significant differences(P<0.05).The multifactorial logistic regression analysis showed that a history of hypertension and a high postoperative body temperature were independent risk factors for postoperative infection in neurosurgical patients.CONCLUSION The results obtained in this study indicated that a history of hypertension and a high postoperative body temperature were independent risk factors for postoperative neurological symptoms.展开更多
Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-c...Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.展开更多
Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke trea...Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.展开更多
This editorial discusses the article written by Zheng et al that was published in the latest edition of the World Journal of Gastrointestinal Surgery.Our primary focus is on the causes,location,diagnosis,histological ...This editorial discusses the article written by Zheng et al that was published in the latest edition of the World Journal of Gastrointestinal Surgery.Our primary focus is on the causes,location,diagnosis,histological classification,and therapy of ectopic pancreas.Ectopic pancreas refers to the presence of pancreatic tissue that is situated in a location outside its usual anatomical placement,and is not connected to the normal pancreas in terms of blood supply or anatomical struc-ture.Currently,the embryological origin of ectopic pancreas remains uncertain.The most prevalent form of ectopic pancreatic is gastric ectopic pancreas.Endoscopic ultrasonography examination can visualize the morphological charac-teristics of the ectopic pancreatic lesion and pinpoint its anatomical location.The histological categorization of ectopic pancreas evolves.Endoscopic treatment has been widely advocated in ectopic pancreas.展开更多
Background The Global Leadership Initiative on Malnutrition(GLIM)recently developed a new set of diagnostic criteria for identifying patients with malnutrition.Because the GLIM criteria were only introduced a little o...Background The Global Leadership Initiative on Malnutrition(GLIM)recently developed a new set of diagnostic criteria for identifying patients with malnutrition.Because the GLIM criteria were only introduced a little over 3 years ago,additional validation and reliability testing are needed in a variety of populations.Methods We performed an observational,multicenter cohort study.From July 2013 to October 2018,lung cancer patients were recruited from the Daping Hospital of Army Medical University and the First Hospital of Jilin University as part of the INSCOC project.Previously-established cut-off values for the calf circumference(CC,male<30 cm,female<29.5 cm)were applied as the reduced muscal mass of phenotypic criteria to establish the GLIM diagnosis.Multivariate Cox regression analyses were performed to analyze the association between the GLIM criteria and survival.Results A total of 1219 patients with lung cancer were studied as subjects.Their age was 58.81±9.92 years old,and 820 were male and 399 were female.According to the GLIM diagnostic criteria using the CC as a muscle mass measurement,303 patients(24.9%)were categorized as malnourished,142 patients(23.1%)in the adult group(18≤age<60)and 161 patients(26.7%)in the older group(age≥60 years).The patients with malnutrition had a higher incidence of anemia than the nourished patients(P=0.012).The QLQ-C30 score and KPS score indicating that the malnourished patients had a consistently worse quality of life compared to the nourished group(all P<0.001).The median survival of the malnutrition group was 42(95%CI:34-50)months,which was much shorter than the 62(95%CI:57-66)months in the nourished group(P<0.001).In the adult group,the median survival decreased from 65(95%CI:55-72)months in nourished group to 34(95%CI:25-48)months in the patients with malnutrition(P<0.001).In the older group,it decreased from 61(95%CI:55-67)months to 48(95%CI:39-59)months(P=0.001).A Cox regression analysis showed that GLIM-diagnosed malnutrition was associated with an increased risk of death among adult group(HR=1.670,95%CI:1.29-2.16),older group(HR=1.332,95%CI:1.05-1.69)and overall(HR=1.453,95%CI:1.22-1.72).Conclusion All of these results demonstrate that GLIM-diagnosed malnutrition is associated with a poorer survival for all lung cancer patients,independent of age.展开更多
Kirsten rat sarcoma viral oncogene homolog(KRAS)is the most frequently mutated oncogene,occurring in various tumor types.Despite extensive efforts over the past 40 years to develop inhibitors targeting KRAS mutations,...Kirsten rat sarcoma viral oncogene homolog(KRAS)is the most frequently mutated oncogene,occurring in various tumor types.Despite extensive efforts over the past 40 years to develop inhibitors targeting KRAS mutations,resistance to these inhibitors has eventually emerged.A more precise understanding of KRAS mutations and the mechanism of resistance development is essential for creating novel inhibitors that target specifically KRAS mutations and can delay or overcome resistance.Immunotherapy has developed rapidly in recent years,and in-depth dissection of the tumor immune microenvironment has led researchers to shift their focus to patients with KRAS mutations,finding that immune factors play an essential role in KRAS-mutant(KRAS-Mut)tumor therapy and targeted drug resistance.Breakthroughs and transitions from targeted therapy to immunotherapy have provided new hope for treating refractory patients.Here,we reviewed KRAS mutation-targeted treatment strategies and resistance issues,focusing on our in-depth exploration of the specific immune status of patients with KRAS mutations and the impact of body immunity following KRAS inhibition.We aimed to guide innovative approaches combining RAS inhibition with immunotherapy,review advances in preclinical and clinical stages,and discuss challenges and future directions.展开更多
Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compen...Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice.However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.展开更多
Pancreatic cancer(PC),a highly lethal tumor with nearly identical incidence and mortality rates,has become the sixth leading cause of cancer-related deaths.Hypoxia is an important malignant factor in PC,as it regulate...Pancreatic cancer(PC),a highly lethal tumor with nearly identical incidence and mortality rates,has become the sixth leading cause of cancer-related deaths.Hypoxia is an important malignant factor in PC,as it regulates angiogenesis,metabolic reprogramming,tumor progression,and metastasis.Disrupting the hypoxic microenvironment can enhance the efficacy of antitumor therapy and improve the prognosis of patients with PC.With the advent of bioinformatics,hypoxia-related PC models have emerged in recent years.They provide a reference for estimating the prognosis and immune microenvironment of patients with PC and identify potential biomarkers for targeting hypoxic microenvironment.However,these findings based on bioinformatic analysis may not be completely reliable without further experimental evidence and clinical cohort validation.The application of these models and biomarkers in clinical practice to predict survival time and develop anti hypoxic therapeutic strategies for patients with PC remains in its infancy.In this editorial,we review the current status of hypoxia-related prognostic models in PC,analyze their similarities and differences,discuss several existing challenges,and provide potential solutions and directions for further studies.This editorial will facilitate the optimization,validation,and determination of the molecular mechanisms of related models.展开更多
In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer(NK) cells, which are an important subset of innate lymphoc...In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer(NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment(TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.展开更多
基金supported by the National Natural Science Foundation of China,No.82071442 (to LS)a grant from the Jilin Provincial Department of Finance,No.JLSWSRCZX2021-004 (to LS)。
文摘Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.
基金supported by the National Key Research and Development Program of China(2021YFD1801000)the Natural Science Foundation of China(32373066)+1 种基金the Natural Science Foundation of Jilin Province(20230101142JC)the Fundamental Research Funds for the Central Universities.
文摘Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells.The rapid development and dissemination of antimicrobial–resistant strains have exacerbated this dilemma.With the increasing knowledge of host–pathogen interactions,especially bacterial strategies for survival and proliferation within host cells,host-directed therapy(HDT)has attracted increased interest and has emerged as a promising antiinfection method for treating intracellular infection.Herein,we applied a cell-based screening approach to a US Food and Drug Administration(FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium(S.Typhimurium).This screening allowed us to identify the antidiarrheal agent loperamide(LPD)as a potent inhibitor of S.Typhimurium intracellular proliferation.LPD treatment of infected cells markedly promoted the host autophagic response and lysosomal activity.A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B(GPNMB)induced by LPD.In addition,LPD treatment effectively protected against S.Typhimurium infection in Galleria mellonella and mouse models.Thus,our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial pathogens.Moreover,LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.
文摘Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.
基金Supported by Science and Technology Department Project of Jilin Province,China,No.20230101163JCthe Outstanding Youth Fund Project of Jilin Provincial Department of Education,China,No.JJKH20241324KJ.
文摘Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,which can progress to severe respiratory distress syndrome and multiple organ failure.In severe cases,these complications may even lead to death.One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response.Therefore,suppressing the overactive immune response may be an effective strategy for treating COVID-19.Mesenchymal stem cells(MSCs)and their derived exosomes(MSCs-Exo)have potent homing abilities,immunomodulatory functions,regenerative repair,and antifibrotic effects,promising an effective tool in treating COVID-19.In this paper,we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19.We also summarize relevant recent clinical trials,including the source of cells,the dosage and the efficacy,and the clinical value and problems in this field,providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.
文摘Gastric peroral endoscopic myotomy(G-POME)is an emerging minimally invasive endoscopic technique involving the establishment of a submucosal tun-nel around the pyloric sphincter.In 2013,Khashab et al used G-POME for the first time in the treatment of gastroparesis with enhanced therapeutic efficacy,prov-iding a new direction for the treatment of gastroparesis.With the recent and rapid development of G-POME therapy technology,progress has been made in the treatment of gastroparesis and other upper digestive tract diseases,such as congenital hypertrophic pyloric stenosis and gastric sleeve stricture,with G-POME.This article reviews the research progress and future prospects of G-POME for the treatment of upper digestive tract gastrointestinal diseases.
基金Supported by Initiation Project of Science and Technology Department of Inner Mongolia Minzu University,No.KYQD23014.
文摘This editorial discusses the article“Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis”published in the latest edition of the World Journal of Gastrointestinal Surgery.Immunotherapy has achieved outstanding success in tumor treatment.However,the presence of liver metastasis(LM)restrains the efficacy of immunotherapy in various tumors,including lung cancer,colorectal cancer,renal cell carcinoma,melanoma,and gastric cancer.A decrease in CD8+T cells and nature killer cells,along with an increase in macrophages and regulatory T cells,was observed in the microenvironment of LM,leading to immunotherapy resistance.More studies are necessary to determine the best strategy for enhancing the effectiveness of immunotherapy in patients with LM.
文摘Objective:To study the effective value of introducing the concept of early oral exercise in the process of nursing intervention for preterm infants in the neonatal intensive care unit(NICU).Methods:96 cases of preterm infants diagnosed from January 2022 to August 2022 were selected and randomly divided into two groups:the general practice group(general nursing intervention),and the early practice group(early oral exercise intervention),and the effect of intervention on preterm infants in the two groups was observed.Results:After nursing care,the mean value of the non-nutritive sucking ability assessment(76.54±5.82),the mean value of the intellectual development degree assessment(104.57±8.45),the mean value of the psychomotor development degree assessment(102.33±6.74),and the mean value of behavioral neural reflexes ability assessment(38.71±2.40)in the early practice group were better than that as compared to the general practice group(P<0.05);the mean value of oral feeding start time of preterm infants in the early practice group(35.42±7.63)weeks,the mean value of all oral feeding time(34.12±5.28)weeks,and the mean time of hospital intervention(15.33±4.25)days were lesser than compared to those of the general practice group at 37.4±5.82 weeks,37.46±3.55 weeks,and 20.46±2.91 days,respectively(P<0.05);the rate of adverse reactions in preterm infants in the early practice group significantly lower than that of the general practice group(P<0.05).Conclusion:The introduction of the concept of early oral exercise intervention among NICU nurses improved the feeding effect,sucking ability of preterm infants,and intellectual development.Hence,early oral motor care should be popularized.
基金supported by the National KeyResearch and Development Program(No.2022YFC2009600 andNo.2022YFC2009601).
文摘Background:The purpose of this study is to evaluate the quality of life(QoL)of hospitalized patients in China suffering from digestive system malignancies and to identify potential risk factors for a decrease in QoL.Methods:The European Organization for Research and Treatment Core Quality of Life questionnaire(EORTC QLQ-C30)was applied to evaluate the QoL of 23,519 patients with six digestive malignancies(esophageal cancer,gastric cancer,colorectal cancer,liver cancer,biliary tract cancer,and pancreatic cancer).A t test or analysis of variance was employed to analyze the total EORTC QLQ-C30 scale scores and domain scores of the EORTC QLQ-C30 scale among patients in different subgroups.Results:The average QoL score was 50.4±10.8.The tumor type,age,sex,and TNM stage all had an impact on QoL ratings.Colorectal cancer patients had a better total QoL score(49.3±10.3)and scores in the domains of functioning,withmilder symptoms,except for diarrhea.Patients with biliary tract cancer(54.2±12.3)and pancreatic cancer(54.2±12.3)reported a poorer QoL,significant functional impairment,and more pronounced symptoms.Patients with esophageal cancer experienced the most severe financial difficulties(35.2±27.5).Patients aged≥65 years,women,and those with TNM stage III/IV reported lower QoL.In addition,the disparities in total QoL scores and scores in specific domains were significant among patients with some types of tumors,and based on ethnicity,educational level,occupation,treatment(s)received,and place of residence.Conclusions:There is a need to focus on elderly individuals,those with low educational levels,and patients with progressivemalignant tumors and to improve routine disease monitoring and symptom management to enhance the quality of life for patients with malignancies of the digestive system.
文摘Background: Otitis media (OM) is highly prevalent and is one of the most important causes of preventable hearing loss in developing countries and it may have long-term impacts on the children. Several hospital-based cross-sectional studies have been conducted in East African countries to assess the prevalence of OM;however, no similar studies have been conducted in Somalia. Therefore, we conducted a hospital-based cross-sectional study to identify the prevalence and the underlying risk factors of OM among children under the age of five in Mogadishu, Somalia. Methodology: A hospital-based cross-sectional study was conducted from July 2022 to November 2022 at three main hospitals in Mogadishu, Somalia. A total of 384 children aged less than 5 years were included. Parents of these children were interviewed with a questionnaire and a clinical examination was performed for each child. The Statistical Package for Social Sciences, SPSS (Version 22, IBM, Inc.), was used for the statistical analysis. Result: The prevalence of otitis media among the 384 children recruited was 31.25% (120/384). Otitis media was significantly associated with age less than one year (P = 0.006), malnutrition (P Conclusion: In summary, the present study found that otitis media was highly prevalent (31.25%) in Mogadishu, Somalia. The majority of the affected children were younger than one year. Age of the child, malnutrition, upper respiratory tract infections, feeding in lying position, and dripping something into a child’s ear were found to significantly increase the risk of developing otitis media in children. In contrast, breastfeeding for more than one year has been found to reduce the risk of developing otitis media in children.
基金supported by grants from the National Natural Science Foundation of China(U20A20360)the National Key R&D Program of China(2018YFC1312102)+1 种基金the Development and Reform Commission of Jilin Province(2014G074)the Jilin Provincial Department of Finance(JLSWSRCZX2021-016)。
文摘Background:Hepatocellular carcinoma(HCC)is the sixth most common cancer globally,with limited therapies and unsatisfactory prognosis once in the advanced stages.With promising advances in locoregional and systematic treatments,fast development of targeted drugs,the success of immunotherapy,as well as the emergence of the therapeutic alliance,conversion therapy has recently become more well developed and an effective therapeutic strategy.This article aimed to review recent developments in conversion therapy in liver transplantation(LT)for HCC.Data sources:We searched for relevant publications on Pub Med before September 2022,using the terms“HCC”,“liver transplantation”,“downstaging”,“bridging treatment”and“conversion therapy.”Results:Conversion therapy was frequently represented as a combination of multiple treatment modalities to downstage HCC and make patients eligible for LT.Although combining various local and systematic treatments in conversion therapy is still controversial,growing evidence has suggested that multimodal combined treatment strategies downstage HCC in a shorter time,which ultimately increases the opportunities for LT.Moreover,the recent breakthrough of immunotherapy and targeted therapy for HCC also benefit patients with advanced-stage tumors.Conclusions:In the era of targeted therapy and immunotherapy,applying the thinking of transplant oncology to benefit HCC patients receiving LT is a new topic that has shed light on advanced-stage patients.With the expansion of conversion therapy concepts,further investigation and research is required to realize the full potential of conversion treatment strategies,including accurately selecting candidates,determining the timing of surgery,improving the conversion rate,and guaranteeing the safety and long-term efficacy of treatment.
基金supported by grants from the National Natural Science Foundation of China(81800245,81970228,82102306,81900779)the China Postdoctoral Science Foundation(2020M670030ZX)+1 种基金the Shaoguan Science and Technology Program(2019sn078)the Start-up Fund for RAPs under the Strategic Hiring Scheme(P0035913)。
文摘The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.
文摘BACKGROUND At present,many studies have reported the risk factors for postoperative intracranial reinfection,including age,sex,time to surgery,duration of postoperative catheterization,emergency procedures,type of disease and cerebrospinal fluid leakage,but the academic community has not reached a unified conclusion.AIM To find factors influencing the surveillance of re-emerging intracranial infections in elective neurosurgical patients.METHODS Ninety-four patients who underwent elective craniotomy from January 1,2015 to December 31,2022 in the Department of Neurosurgery,First Hospital of Jilin University,were included in this study.Of those,45 patients were enrolled in the infection group,and 49 were enrolled in the control group.The clinical data of the patients were collected and divided into three categories,including preoperative baseline conditions,intraoperative characteristics and postoperative infection prevention.The data were analyzed using SPSS 26.0 software.RESULTS There were 23 males and 22 females in the infection group with a mean age of 52.8±15.1 years and 17 males and 32 females in the control group with a mean age of 48.9±15.2 years.The univariate analysis showed that the infection group had higher systolic blood pressures and postoperative temperatures,fewer patients who underwent a supratentorial craniotomy,more patients with a history of hypertension and higher initial postoperative white blood cell counts than the control group,with statistically significant differences(P<0.05).The multifactorial logistic regression analysis showed that a history of hypertension and a high postoperative body temperature were independent risk factors for postoperative infection in neurosurgical patients.CONCLUSION The results obtained in this study indicated that a history of hypertension and a high postoperative body temperature were independent risk factors for postoperative neurological symptoms.
基金supported by funds from the National Natural Science Foundation of China(Grant Nos.81830002,81830004,82070168,and 32070951)the Translational Research grant of NCRCH(Grant No.2020ZKZC04)National Key R&D Program of China(Grant No.2021YFA1100800)。
文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.
基金supported by the National Natural Science Foundation of China,No.81971105(to ZNG)the Science and Technology Department of Jilin Province,No.YDZJ202201ZYTS677(to ZNG)+3 种基金Talent Reserve Program of the First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)Science and Technology Department of Jilin Province,Nos.YDZJ202302CXJD061,20220303002SF(to YY)Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY).
文摘Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.
文摘This editorial discusses the article written by Zheng et al that was published in the latest edition of the World Journal of Gastrointestinal Surgery.Our primary focus is on the causes,location,diagnosis,histological classification,and therapy of ectopic pancreas.Ectopic pancreas refers to the presence of pancreatic tissue that is situated in a location outside its usual anatomical placement,and is not connected to the normal pancreas in terms of blood supply or anatomical struc-ture.Currently,the embryological origin of ectopic pancreas remains uncertain.The most prevalent form of ectopic pancreatic is gastric ectopic pancreas.Endoscopic ultrasonography examination can visualize the morphological charac-teristics of the ectopic pancreatic lesion and pinpoint its anatomical location.The histological categorization of ectopic pancreas evolves.Endoscopic treatment has been widely advocated in ectopic pancreas.
基金supported by the National Natural Science Foundation of China(No.81673167 to Hongxia Xu)the Chongqing Technology Innovation and Application Demonstration Project for Social Livelihood(cstc2018jscx-msybX0094 to Jie Liu).
文摘Background The Global Leadership Initiative on Malnutrition(GLIM)recently developed a new set of diagnostic criteria for identifying patients with malnutrition.Because the GLIM criteria were only introduced a little over 3 years ago,additional validation and reliability testing are needed in a variety of populations.Methods We performed an observational,multicenter cohort study.From July 2013 to October 2018,lung cancer patients were recruited from the Daping Hospital of Army Medical University and the First Hospital of Jilin University as part of the INSCOC project.Previously-established cut-off values for the calf circumference(CC,male<30 cm,female<29.5 cm)were applied as the reduced muscal mass of phenotypic criteria to establish the GLIM diagnosis.Multivariate Cox regression analyses were performed to analyze the association between the GLIM criteria and survival.Results A total of 1219 patients with lung cancer were studied as subjects.Their age was 58.81±9.92 years old,and 820 were male and 399 were female.According to the GLIM diagnostic criteria using the CC as a muscle mass measurement,303 patients(24.9%)were categorized as malnourished,142 patients(23.1%)in the adult group(18≤age<60)and 161 patients(26.7%)in the older group(age≥60 years).The patients with malnutrition had a higher incidence of anemia than the nourished patients(P=0.012).The QLQ-C30 score and KPS score indicating that the malnourished patients had a consistently worse quality of life compared to the nourished group(all P<0.001).The median survival of the malnutrition group was 42(95%CI:34-50)months,which was much shorter than the 62(95%CI:57-66)months in the nourished group(P<0.001).In the adult group,the median survival decreased from 65(95%CI:55-72)months in nourished group to 34(95%CI:25-48)months in the patients with malnutrition(P<0.001).In the older group,it decreased from 61(95%CI:55-67)months to 48(95%CI:39-59)months(P=0.001).A Cox regression analysis showed that GLIM-diagnosed malnutrition was associated with an increased risk of death among adult group(HR=1.670,95%CI:1.29-2.16),older group(HR=1.332,95%CI:1.05-1.69)and overall(HR=1.453,95%CI:1.22-1.72).Conclusion All of these results demonstrate that GLIM-diagnosed malnutrition is associated with a poorer survival for all lung cancer patients,independent of age.
基金supported by National Natural Science Foundation of China—Youth Fund Project (No.32000617)Jilin Provincial Science and Technology Department (No.20200602032ZP and No.20210 303002SF)+1 种基金Jilin Provincial Development and Reform Commission (No.2021C10)Changchun Science and Technology Bureau (No.21ZGY28)
文摘Kirsten rat sarcoma viral oncogene homolog(KRAS)is the most frequently mutated oncogene,occurring in various tumor types.Despite extensive efforts over the past 40 years to develop inhibitors targeting KRAS mutations,resistance to these inhibitors has eventually emerged.A more precise understanding of KRAS mutations and the mechanism of resistance development is essential for creating novel inhibitors that target specifically KRAS mutations and can delay or overcome resistance.Immunotherapy has developed rapidly in recent years,and in-depth dissection of the tumor immune microenvironment has led researchers to shift their focus to patients with KRAS mutations,finding that immune factors play an essential role in KRAS-mutant(KRAS-Mut)tumor therapy and targeted drug resistance.Breakthroughs and transitions from targeted therapy to immunotherapy have provided new hope for treating refractory patients.Here,we reviewed KRAS mutation-targeted treatment strategies and resistance issues,focusing on our in-depth exploration of the specific immune status of patients with KRAS mutations and the impact of body immunity following KRAS inhibition.We aimed to guide innovative approaches combining RAS inhibition with immunotherapy,review advances in preclinical and clinical stages,and discuss challenges and future directions.
文摘Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice.However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.
基金Supported by National Natural Science Foundation of China,No.82373664Scientific and Technological Development Program of Jilin Province,No.20240402015GH.
文摘Pancreatic cancer(PC),a highly lethal tumor with nearly identical incidence and mortality rates,has become the sixth leading cause of cancer-related deaths.Hypoxia is an important malignant factor in PC,as it regulates angiogenesis,metabolic reprogramming,tumor progression,and metastasis.Disrupting the hypoxic microenvironment can enhance the efficacy of antitumor therapy and improve the prognosis of patients with PC.With the advent of bioinformatics,hypoxia-related PC models have emerged in recent years.They provide a reference for estimating the prognosis and immune microenvironment of patients with PC and identify potential biomarkers for targeting hypoxic microenvironment.However,these findings based on bioinformatic analysis may not be completely reliable without further experimental evidence and clinical cohort validation.The application of these models and biomarkers in clinical practice to predict survival time and develop anti hypoxic therapeutic strategies for patients with PC remains in its infancy.In this editorial,we review the current status of hypoxia-related prognostic models in PC,analyze their similarities and differences,discuss several existing challenges,and provide potential solutions and directions for further studies.This editorial will facilitate the optimization,validation,and determination of the molecular mechanisms of related models.
文摘In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer(NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment(TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.
