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

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 clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective Aberrant expression of ATP binding cassette subfamily B member 1(ABCB1)plays a key role in several cancers.However,influence of G protein coupled receptor family C group 5 type A(GPRC5A)-regulated ABCB1 expression on lung adenocarcinoma proliferation remains unclear.Therefore,this study investigated the effect of GPRC5A regulated ABCB1 expression on the proliferation of lung adenocarcinoma. Methods ABCB1 expressions in lung adenocarcinoma cell lines,human lung adenocarcinoma tissues,and tracheal epithelial cells and lung tissues of GPRC5A knockout mice and wild-type mice were analyzed with RT-PCR,Western blot,or immunohistochemical analysis.Cell counting kit-8 assay was performed to analyze the sensitivity of tracheal epithelial cells from GPRC5A knockout mice to chemotherapeutic agents.Subcutaneous tumor formation assay was performed to confirm whether down-regulation of ABCB 1 could inhibit the proliferation of lung adenocarcinoma in vivo.To verify the potential regulatory relationship between GPRC5A and ABCB1,immunofluorescence and immunoprecipitation assays were performed. Results ABCB1 expression was up-regulated in lung adenocarcinoma cell lines and human lung adenocarcinoma tissues.ABCB1 expression in the tracheal epithelial cells and lung tissues of GPRC5A deficient mice was higher than that in the wild type mice.Tracheal epithelial cells of GPRC5A knockout mice were much more sensitive to tariquidar and doxorubicin than those of GPRC5A wild type mice.Accordingly,28 days after injection of the transplanted cells,the volume and weight of lung tumor in ABCB1 knockout cell-transplanted GPRC5A-/-C57BL/6 mice were significantly smaller than those in wild type cell-transplanted mice(P=0.0043,P=0.0060).Furthermore,immunofluorescence and immunoprecipitation assays showed that GPRC5A regulated ABCB1 expression by direct binding. Conclusion GPRC5A reduces lung adenocarcinoma proliferation via inhibiting ABCB1 expression.The pathway by which GPRC5A regulates ABCB1 expression needs to be investigated.

Objective:To evaluate the diagnostic performance of the Prostate Imaging Reporting and Data System version 2.1(PI-RADS v2.1)for clinically significant prostate cancer(CSPCa)in the peripheral zone(PZ),transitional zone(TZ)and multiple zones(MZs).Methods:We retrospectively studied the clinical data on 108 patients undergoing multiparametric magnetic resonance imaging(mpMRI)and transperineal prostate biopsy in our hospital from January 2021 to January 2023.Using PI-RADS v2.1,we ex-amined the MR images of the patients with suspected PCa,compared the PI-RADS v2.1 scores with the results of prostate biopsy,and analyzed the correlation of the PI-RADS v2.1 scores with CSPCa.We calculated the area under the receiver operating characteristic(ROC)curve(AUC),and described the diagnostic performance of PI-RADS v2.1 for CSPCa in the PZ,TZ and MZs.Results:Transperineal prostate puncture biopsy was successfully completed in all the patients,which revealed 66(61.11％)cases of CSPCa with Gleason score(GS)7-10.Suspected CSPCa was observed in 45(95.74％)of the 47 PZ lesions,8(47.06％)of the 17 TZ le-sions,and 40(90.91％)of the 44 MZ lesions.The PZ,TZ and MZ lesions diagnosed by PI-RADS v2.1 were significantly correlated with CSPCa(r=0.492,P＜0.001).The AUCs of PI-RADS v2.1 for PZ,TZ and MZs were 0.644,0.732 and 0.811,with specificities of 66.8％,57.6％and 62.1％,and sensitivities of 57.2％,78.4％and 93.2％,respectively.The negative predictive values were 46.5％,85.7％and 79.2％,and the positive predictive values 76.2％,43.4％and 84.8％,respectively.Conclusion:The PI-RADS v2.1 score has a high diagnostic value for CSPCa in the PZ,TZ and MZs,with the best performance for that in the MZs.

Objective: To investigate how plasma exchange (PE) and double plasma molecular adsorption combined with half-volume plasma exchange (DPMAS + half-volume PE) affect the curative effect and short-term survival rate in liver failure. Methods: Data from 181 cases of liver failure caused by different etiologies from January 1, 2017 to September 31, 2020, were selected. Patients were divided into a PE treatment alone group and a DPMAS + half-dose PE treatment group. The laboratory indicators with different models of artificial liver before and after treatment and the survival rates of 7, 14, 28, and 90 days after discharge were observed in the two groups. Measurement data were analyzed by t-tests and rank sum tests. Categorical data were analyzed by χ (2) test. Results: Non-biological artificial liver therapy with different models improved the liver and coagulation function in the two groups of patients with liver failure (P < 0.05 in PTA% intra-group). The coagulation function was significantly improved in the PE treatment alone group compared with that in the DPMAS + half-dose PE group [PT after treatment: (20.15 ± 0.88) s in the PE treatment alone group, (23.43 ± 1.02) s, t = -2.44, P = 0.016 in the DPMAS+half-dose PE group; PTA: 44.72% ± 1.75% in the PE treatment alone group, 35.62% ± 2.25%, t = 3.215 P = 0.002 in the DPMAS + half-dose PE group]. Bilirubin levels were significantly decreased in the DPMAS+half-dose PE group compared to the PE treatment alone group [total bilirubin after treatment: (255.30 ± 15.64) μmol/L in the PE treatment alone group, (205.46 ± 9.03) μmol/L, t = 2.74, P = 0.07 in the DPMAS + half-dose PE group; direct bilirubin after treatment: (114.74 ± 7.11) μmol/L in the PE treatment alone group, (55.33 ± 3.18) μmol/L, t = 7.54, P < 0.001) in the DPMAS + half-dose PE group]. However, there was no significant effect on leukocytes and neutrophils after treatment with different models of artificial liver (P > 0.05) in the two groups, and platelets decreased after treatment, with no statistically significant difference between the groups (t = -0.15, P = 0.882). The inflammatory indexes of the two groups improved after treatment with different models of artificial liver (P < 0.05], and the 28 and 90 d survival rates were higher in the DPMAS+half-dose PE group than those of the PE treatment alone group (28 d: 60.3% vs. 75.0%, χ (2) = 4.315, P = 0.038; 90 d: 56.2% vs. 72.5%. χ (2) = 10.355 P < 0.001). DPMAS + half-dose PE group plasma saving was 1385 ml compared with PE treatment alone group (Z = -7.608, P < 0.05). Conclusion: Both DPMAS+half-dose PE and PE treatment alone have a certain curative effect on patients with liver failure. In DPMAS+half-dose PE, the 28-day survival rate is superior to PE treatment alone, and it saves plasma consumption and minimizes blood use in clinic.