Lung cancer remains one of the most prevalent and deadly malignancies worldwide, with persistently low five-year survival rates. This poor prognosis is primarily attributed to challenges such as difficulties in early diagnosis, high tumor heterogeneity, and strong therapeutic resistance. Although recent advances in targeted therapies and immune checkpoint inhibitors have significantly improved the prognosis of some patients, the majority still encounter primary or secondary resistance. Galectin-3, a multifunctional glycan-binding protein, is constitutively expressed in pulmonary tissues. Its expression encompasses bronchial and alveolar epithelial cells, the pulmonary vasculature, and resident immune cells. Galectin-3 plays a central role in lung cancer progression by regulating tumor cell proliferation, immune evasion, and angiogenesis. The complex immunosuppressive mechanisms within the tumor microenvironment not only facilitate tumor growth and metastasis but also partially limit the efficacy of cancer immunotherapies. Overcoming these barriers requires the exploration of novel regulatory targets to break through therapeutic bottlenecks. This review systematically elucidates the mechanisms by which galectin-3 interacts with immune cells (e.g., T cells, macrophages) in the tumor microenvironment and evaluates its potential as a therapeutic target, including inhibitor development and combination immunotherapy strategies. The findings aim to provide a theoretical foundation for advancing galectin-3 as a novel therapeutic target in lung cancer and offer new perspectives for overcoming current immunotherapy resistance.
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Humans ; Lung Neoplasms/pathology* ; Tumor Microenvironment/immunology* ; Galectin 3/genetics* ; Animals ; Immunomodulation ; Immunotherapy

Immune checkpoint blockade (ICB) therapy has demonstrated significant efficacy in the treatment of various cancers. However, a subset of patients develops hyper-progressive disease (HPD) following ICB, which is characterized by accelerated tumor growth and poor clinical outcomes. This review outlines the clinical features, potential mechanisms, and possible intervention strategies of HPD, with the aim of informing clinical practice and providing relevant recommendations.
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Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Neoplasms/therapy* ; Disease Progression ; Animals ; Immunotherapy

OBJECTIVE: To investigate the association between fluid balance trajectories within the first 3 days of intensive care unit (ICU) admission and 28-day mortality as well as the incidence of continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients were extracted from the Medical Information Mart of Intensive Care-IV (MIMIC-IV). Group-based trajectory modeling (GBTM) was used to analyze the daily fluid balance of patients within 3 days of ICU admission, and grouping them accordingly. Univariate and multivariate Logistic regression analyses were performed to assess the association between fluid balance trajectory and 28-day mortality and ICU CRRT in SAP patients. RESULTS: A total of 251 SAP patients were included, with 33 deaths within 28 days, and a 28-day mortality of 13.15%; 49 patients (19.52%) continued to receive bedside CRRT after 3 days of ICU admission. The fluid balance on the 3rd day, cumulative fluid balance within 3 days of ICU admission, and incidence of CRRT in the death group were significantly higher than those in the survival group. According to GBTM groups, there were 127 cases in the moderate fluid resuscitation with rapid reduction (MF group), 44 cases in the large fluid resuscitation with rapid reduction (LF group), 20 cases in the moderate fluid resuscitation with slow reduction (MS group), and 60 cases in the small fluid resuscitation with slow reduction (SS group). The cumulative fluid balance within 3 days of ICU admission of the MF group, LF group, MS group, and SS group were 8.60% (5.15%, 11.70%), 16.70% (13.00%, 21.02%), 23.40% (19.38%, 25.45%), and 0.65% (-2.35%, 2.20%), respectively, and the incidence of CRRT during ICU hospitalization were 11.02%, 29.55%, 85.00%, and 8.33%, respectively, with statistically significant differences among the groups (both P < 0.05); the 28-day mortality were 11.02%, 18.18%, 20.00%, and 11.67%, respectively, with no statistically significant difference among the groups (P > 0.05). Kaplan-Meier survival curve analysis showed there was no statistically significant difference in 28-day cumulative survival rate among groups with different fluid balance trajectories (Log-rank test: χ ² = 2.31, P = 0.509). Multivariate Logistic regression analysis showed that cumulative fluid balance within 3 days of ICU admission was an independent risk factor for 28-day mortality [odds ratio (OR) = 1.071, 95% confidence interval (95%CI) was 1.005-1.144, P = 0.040] and CRRT requirement (OR = 1.233, 95%CI was 1.125-1.372, P < 0.001); early aggressive fluid resuscitation on day 1 reduced CRRT risk (OR = 0.866, 95%CI was 0.756-0.978, P = 0.030). CONCLUSIONS Dynamic fluid management is essential in SAP patients. While early aggressive fluid resuscitation may reduce CRRT demand, excessive cumulative fluid balance is associated with increased 28-day mortality and CRRT incidence.
Humans ; Male ; Female ; Middle Aged ; Water-Electrolyte Balance ; Continuous Renal Replacement Therapy ; Intensive Care Units ; Aged ; Adult ; Pancreatitis/mortality* ; Logistic Models ; Retrospective Studies ; Renal Replacement Therapy

Prostaglandin E2(PGE2)regulates a variety of cells in tumor microenvironment(TME)and plays an important role in tumor growth,metastasis and immunity.PGE2 activates different downstream signaling pathways through its key receptor prostaglandin E receptor(EP4),regulating inflammation,immune cell function and angiogenesis to promote or inhibit tumor development.EP4 shows potential application values in adjuvant chemotherapy and immunotherapy as an emerging anti-tumor target.However,future studies on the roles of EP4 in tumor microenvironment,develo-pment of safer and more effective EP4 drugs,and its application in personalized immunotherapy are needed.

Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

Objective To discuss the correlation between free prostate specific antigen(fPSA),serum ferritin(SF),blood uric acid(SUA)levels and Gleason grading in patients with prostate cancer(PCa).Methods The clinical data of 61 patients with prostate biopsy treated in 411 Hospital of Shanghai University from January to December of 2023 were retrospectively analyzed.According to the results of puncture,the patients were divided into benign prostatic hyperpla-sia(BPH)group(31 cases)and PCa group(30 cases).The levels of fPSA,SF and SUA in patients and Gleason grade in biopsy cases were analyzed.The correlation between fPSA,SF and SUA levels and Gleason grade was analyzed by the method of Spearman.And the diagnostic efficacy of fPSA,SF and SUA levels on PCa was analyzed by receiver operating characteristic curve(ROC).Results The levels of fPSA,SF and SUA in PCa group were significantly higher than those in BPH group(P＜0.05).There were statistically significant differences in levels of fPSA SF and SUA in PCA patients with different Gleason grades(P＜0.05).With the specificity reaching 96.08％and sensitivity reaching 94.35％,the ar-ea under the curve(AUC)of the combined fPSA,SF and SUA levels in the diagnosis of PCa was 0.982,which was higher than that of the single fPSA,SF and SUA levels(P＜0.05).SF and SUA levels in PCa patients were positively correlated with Gleason grade(P＜0.05),while fPSA levels were not correlated with Gleason grade(P＞0.05).Conclusion The levels of SF and SUA in PCa patients are positively correlated with Gleason grade,which can be used as an important index to predict Gleason grade in PCa patients.

Objective:To investigate the important clinical features and prognosis of febrile infection-related epilepsy syndrome(FIRES).Methods:A retrospective analysis was performed for the data of 15 children with FIRES who were hospitalized and treated in Peking University First Hospital from March 2022 to June 2024,including clinical features,treatment regimens,and prognosis,and follow-up was performed by telephone.Results:The median duration of status epilepticus was 15 days for all children.Of all 15 children,14(93.3%)were comorbid with disturbance of consciousness,8(53.3%)were comorbid with respiratory failure and underwent endotra-cheal incubation,and 13(86.7%)had been admitted to the intensive care unit.In the acute stage,7 children underwent the examination of various inflammatory factors in blood and cerebrospinal fluid,including interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,and tumor necrosis factor-α,and all 7 children had significant increases in the levels of inflammatory factors in cerebrospinal fluid,which were significantly higher than the levels of inflammatory factors in serum.Of all 15 children,12(80%)had diffuse slow wave changes on electroencephalography,and migrating focal seizures were detected in 7 children(46.7%).Cranial magnetic resonance im-aging(MRI)manifestations in the acute stage included temporal and insular cortical edema(60%),abnormal white matter signal(33.3%),and claustrum sign(13.3%),and MRI features in the chronic stage included the deepening of cerebral sulci(75%)and ventricular dilatation(33.3%).The treatment in the acute stage in-cluded intravenous drip of gamma-globulin and high-dose methyl-prednisolone in 15 children(effective in 2 children),ketogenic diet in 4 children(effective in 1 child),tocilizumab in 5 children(effective in 3 children),and anakinra in 2 children(effective in 1 child).As of the last follow-up,the median duration of disease was 14.0 months(4-65 months)for all patients,and only 2 children achieved complete seizure control,while the remaining 13 children had refractory epilepsy.Cognitive impairment was observed in 93.3%of the children.Conclusion:FIRES often has acute and severe conditions,and first-line immunotherapies often have a poor therapeutic ef-fect.Tocilizumab and anakinra may be effective in some patients with seizures in the acute stage.

Objective:To investigate the cranial magnetic resonance imaging(MRI)characteristics of children with febrile infection-related epilepsy syndrome(FIRES).Methods:A retrospective analysis was performed for the imaging characteristics of children with FIRES who were admitted to Department of Pediatrics,Peking University First Hospital,from November 2020 to August 2024,includ-ing the characteristic manifestation of claustrum sign on cranial MRI.Results:A total of 86 children with a confirmed diagnosis of FIRES were included,among whom there were 65 boys(75.6%)and 21 girls(24.4%),with a median age of onset of 6.35(4.4,8.32)years.Among these children,14(16.3%)had normal cranial MRI findings in the acute stage,with T2 FLAIR changes as the most common abnormal manifestation(39.5%),and 30 children(34.9%)experienced brain atrophy,with a median time of 44(34,72)days for the onset of brain atrophy for the first time.There were 22 children(25.6%)with positive bilateral claustrum sign on cranial MRI,which manifested as symmetrical T2 FLAIR hyperintensity with limited diffusion in the bilateral claustrum,and the median time to the first appearance of claustrum sign was 11(7,15)days,while the median time to negative conversion of claustrum sign was 33(24,50)days.The claustrum sign disappeared after the relief of status epilepticus in the acute stage in most children.Among the children in this study,71 entered the chronic stage during follow-up,3 had normal cranial MRI results during the course of the disease,and 34 had brain atrophy for the first time in the chronic stage,with a median time of 186(115,429)days to the first appearance of brain atrophy on cranial MRI,while of all 86 children,64(80.0%)experienced brain atrophy on cranial MRI in the acute stage and the chronic stage.Conclusion:Children with FIRES have diverse cranial MRI characteristics.There might be normal MRI manifestations at the beginning of the disease,and positive bilateral claustrum sign might be the specific manifestation in the acute stage.Changes in the claustrum disappear after the relief of status epilepticus in most cases,and most patients may progress to brain atrophy in the chronic stage.

Objective:To investigate the efficacy and safety of ketogenic diet,anakinra,and tocilizumab in the treatment of febrile infection-related epilepsy syndrome(FIRES)through a meta-analysis.Methods:With FIRES,ketogenic diet,anakinra,and tocili-zumab as search terms,the databases of PubMed,Embase,Web of Science,the Cochrane Library,Clinicalttrials.gov,CNKI,Wanfang Data,and VIP were searched for related articles published up to December 13,2024.Two reviewers independently screened the ar-ticles according to the inclusion and exclusion criteria and assessed the risk of bias of the studies included.Review Manager was used to perform the meta-analysis.Results:Among the 549 studies,45 case reports and case series met the inclusion criteria,and there were 45 retrospective studies in total,among which 25,8,and 17 were included in the ketogenic diet group,the tocilizumab group,and the anakinra group,respectively,with 66 patients in the ketogenic diet group,8 in the the tocilizumab group,and 54 in the anakinra group.There were 3 case reports,in which all 3 patients were treated with tocilizumab and anakinra.The meta-analysis showed that in the treatment of FIRES in the acute stage,ketogenic diet,anakinra,and tocilizumab showed a response raet of 68%(95%CI=51%-85%,I 2=71%,P<0.01),57%(95%CI=35%-80%,I 2=71%,P<0.01),and 100%(95%CI=79%-100%,I 2=0%,P=1.00),respec-tively,with no statistical differences between studies.The survival rate was 96%(95%CI=89%-100%,I 2=0%,P=1.00)in the keto-genic diet group,96%(95%CI=89%-100%,I 2=0%,P=1.00)in the FIRES,and ketogenic diet and anakinra treatment have a relatively high incidence rate of adverse reactions.Hypoglycemia and infec-tion are adverse reactions commonly observed during treatment.

Objective:To investigate the effect of aucubin(AU)on mitochondrial autophagy in the hippocampus of ischemic stroke(IS)rats by regulating the pten-induced kinase protein 1(PINK1)/cytoplasmic E3-ubiquitin ligase(Parkin)signaling pathway.Methods:The IS rat model was established by middle cerebral artery occlusion(MCAO),and was randomly divided into IS group,low-dose AU group(AU-L),medium-dose AU group(AU-M),high-dose AU group(AU-H),and high-dose AU combined with 3-MA group(AU-H+3-MA).The rats without liga-tion were used as the Sham surgery group.Zea Longa score was used to evaluate the neurological function of rats.TTC staining was used to detect the percentage of cerebral infarction volume.The microstructures of mitochondria were observed by transmission electron microscopy,and the changes of autophagy protein-microtubule associated protein light chain 3B(LC3B)and p62 were detected by immunohistochemistry.Hippocampal apoptosis was detected by TUNEL.PINK1/Parkin-related protein expression in hippocampus was detected by Western blot.Results:Neurological function score of IS rats was increased(P＜0.05),cerebral infarction was observed by TTC staining,the expression of mito-chondrial autophagy protein p62 in hippocampus was up-regulated(P＜0.05),the expression of LC3B was down-regu-lated(P＜0.05),the number of autophagosomes was decreased(P＜0.05),and apoptosis in hippocampus was in-creased(P＜0.05),the expression of PINK1 and ARKIN protein in hippocampus was down-regulated(P＜0.05).After AU intervention,the neural function score of rats was decreased,the percentage of cerebral infarction volume was reduced,the positive expression of p62 in hippocampus was down-regulated(P＜0.05),the positive expression of LC3B was up-regulated(P＜0.05),and the number of autophagosomes was increased(P＜0.05),the apoptosis of hippocampus was decreased(P＜0.05),and the expression of PINK1 and ARKIN protein in hippocampus was in-creased(P＜0.05).3-MA blocked the therapeutic effect of AU and aggravated the nerve injury in rats.Conclusion:AU promotes hippocampal mitochondrial autophagy and improves neurological damage in IS rats by activating the PINK1/Parkin signaling pathway.