Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

BACKGROUND:Bone marrow mesenchymal stem cells play a pivotal role in tissue engineering and bone regeneration.However,promoting the osteogenic differentiation of bone marrow mesenchymal stem cells poses a significant challenge.OBJECTIVE:To examine the influence of Fe3O4@ZIF-8 nanoparticles on the osteogenic differentiation of bone marrow mesenchymal stem cells under magnetic stimulation.METHODS:Zeolite imidazolate skeleton(ZIF-8)was synthesized by hydrothermal method,and magnetic Fe3O4@ZIF-8 nanoparticles were synthesized by one-pot method(2.5,5,10,and 20 μg Fe3O4 were added to the preparation materials,respectively).The Fe3O4@ZIF-8 nanoparticles were characterized by scanning electron microscopy,X-ray photoelectron spectroscopy,X-ray diffraction,and vibration sample magnetometer detection,and suitable materials were selected for subsequent experiments.Bone marrow mesenchymal stem cells of 4-week-old SD rats were extracted and co-cultured with Fe3O4@ZIF-8 nanoparticle solution with different mass concentrations(25,50,75,100,and 125 μg/mL),respectively.Cell proliferation was detected by CCK-8 assay,and the optimal material solution mass concentration was selected.After the mass concentration of the material solution was screened,magnetic stimulation was applied(magnetic field intensity was 0,50,100,and 150 MT,respectively).Cell proliferation was detected by CCK-8 assay,and the best magnetic field intensity and Fe3O4@ZIF-8 nanoparticles were selected for the experiment of induced differentiation of bone marrow mesenchymal stem cells.SD rat bone marrow mesenchymal stem cells were co-cultured with ZIF-8,Fe3O4@ZIF-8,and Fe3O4@ZIF-8(magnetic field intervention)nanoparticle solution,respectively.The single cultured cells were used as blank controls.Lipid induction was followed by oil red O staining.After osteogenesis induction,alkaline phosphatase,alizarin red staining and Runx2 protein concentration were detected.RESULTS AND CONCLUSION:(1)Under scanning electron microscopy,Fe3O4@ZIF-8 nanoparticles showed a dodecahedral structure.With the increase of Fe3O4 content in the material,the particle size of the nanoparticles increased.Fe3O4@ZIF-8 nanoparticles(5 and 10 μg Fe3O4 was added to the material preparation)with a particle size of about 250 nm(stable functional and biosafety of nanoparticles at this particle size)were selected.(2)The results of CCK-8 assay showed that 50 μg/mL Fe3O4@ZIF-8 nanoparticles(with 10 μg Fe3O4 added to the preparation of the material)could significantly promote the proliferation of bone marrow mesenchymal stem cells under a 100 MT magnetic field.The nanoparticles under this condition were selected for the osteogenic induction differentiation experiment of bone marrow mesenchymal stem cells.(3)After osteogenic induction,the alkaline phosphatase activity,extracellular matrix mineralization degree,and Runx2 protein mass concentration of bone marrow mesenchymal stem cells in Fe3O4@ZIF-8(magnetic field intervention)group were higher than those in other three groups(P<0.05).After adipogenic induction,the lipid droplet formation of bone marrow mesenchymal stem cells in Fe3O4@ZIF-8(magnetic field intervention)group was lower than that in the other three groups(P<0.05).(4)The results show that Fe3O4@ZIF-8 nanoparticles can promote osteogenic differentiation of bone marrow mesenchymal stem cells under specific magnetic field conditions.

AIM To investigate the effects of rice wine type and wine processing method on chemical constituents and anti-coagulation effect of Angelicae sinensis Radix.METHODS Wine-washed products and wine-stir-fried products were prepared by different types and ages of rice wine,respectively,after which HPLC was adopted in the content determination of tryptophan,chlorogenic acid,vanillic acid,phthalic acid,ferulic acid,senkyunolide I,senkyunolide H,coniferyl ferulate and ligustilide,and PT,APTT,TT were detected in rabbit plasma.RESULTS Phenolic acids and volatile constituents demonstrated lower contents in the wine-stir-fried products than those in the raw product(P＜0.05),while those in the wine-washed products displayed no obvious changes(except for senkyunolide I)(P＞0.05).The contents of volatile constituents in the wine-washed products were higher than those in the wine-stir-fried products(P＜0.05).After being processed with dry rice wine,various constituents exhibited increased contents as compared with those after being processed with sweet rice wine(P＜0.05).Compared with the raw product,prolonged PT,APTT and TT were observable in the processed products prepared by 3-year semi-dry rice wine(P＜0.05).CONCLUSION The optimal rice wine type is determined to be 3-year semi-dry.Wine-washed Angelicae sinensis Radix shows high contents of ferulic acid and volatile constituents,whose activating blood and resolving stasis effect may be stronger.

This study was aimed at understanding the prevalence and drug resistance status of Salmonella of waterfowl ori-gin in the Guangdong region in the past decade,to guide prevention and control efforts.The drug-sensitive paper slide method was used to conduct drug susceptibility testing on 314 waterfowl-originating Salmonella strains isolated from 238 waterfowl farms in the Guangdong region from 2013 to 2023.The isolated Salmonella strains were most resistant to penicillin,amoxicil-lin,cefradine,and cefazolin in the β-lactam group;sulphadoxine dimethylpyrimidine in the sulphonamide group;and tetracy-cline in the tetracycline group.The resistance rates ranged from 73.57％to 89.49％.The highest sensitivity was observed to amikacin,gentamicin,and kanamycin in the aminoglycoside group,and norfloxacin in the quinolone group,with susceptibility rates all exceeding 50％.The 280 strains of Salmonella showed multi-drug resistance to six classes of antimicrobial drugs and high resistance(as much as 60.83％)to five drug classes.Correlation analysis revealed the highest correlations for florfenicol with gentamicin,and for amoxicillin with penicillin(r=0.650 for both),followed by gentamicin with kanamycin(r=0.620).Salmonella resistance in waterfowl in Guangdong Province was generally severe and showed a complex pattern of drug resist-ance.Detection of waterfowl pathogens should be strengthened to prevent the spread of drug-resistant bacteria and support ra-tional use of antibiotics.This work provides a reference for Salmonella prevention and control in waterfowl farms.

Objective:To explore the hemodynamic characteristics of the middle cerebral artery (MCA) in atherosclerotic stenosis using four-dimensional flow (4D Flow) MRI, and combining high-resolution magnetic resonance vessel wall imaging (HR VW-MRI) to analyze the relationship between hemodynamics and the degree of stenosis, as well as the morphological characteristics of plaques.Methods:The study was a cross-sectional study. A total of 24 patients with middle cerebral artery(MCA) M1 atherosclerotic stenosis and 10 age and sex matched healthy controls (HC group) were prospectively recruited from September 2018 to March 2021 at Beijing Tiantan Hospital, Capital Medical University. All subjects underwent MRI examination. The hemodynamic of MCA were collected by 4D Flow MRI, and the hemodynamic parameters of proximal and distal MCA stenosis were calculated by blood flow post-processing software, including average blood flow rate (FR avg), average blood flow velocity (V avg), peak blood flow velocity (V pk), time average wall shear stress (TAWSS), minimum wall shear stress (WSS min) and oscillatory shear index (OSI). The differences in hemodynamic parameters among the proximal and distal ends of MCA stenosis and the HC group were compared using one-way ANOVA or Kruskal-Wallis H test. The stenosis rate and characteristics of MCA plaque were analyzed by HR VW-MRI, including remodeling index (RI), normalized wall index (NWI) and plaque length. Pearson or Spearman correlation analysis was used to explore the correlation between stenosis rate and hemodynamic parameters. Taking the stenosis rate as the control variable, partial correlation analysis was used to explore the correlation between plaque morphological characteristics and hemodynamic parameters. Results:There were statistically significant differences in FR avg, V avg, V pk, TAWSS, OSI, WSS min among the proximal and distal stenosis of MCA and HC groups ( P<0.05). The proximal end of the MCA stenosis had significantly higher FR avg, V avg, TAWSS and WSS min than those of the distal end of the stenosis ( P<0.01). The FR avg, V avg, V pk, TAWSS, and WSS min in the distal end of MCA stenosis were lower than those in the HC group, while the OSI was higher than that in the HC group ( P<0.01). The correlation analysis results showed that the MCA proximal V pk ( r=-0.425, P=0.027) and distal V pk ( r=-0.538, P=0.004) were negatively correlated with the diameter stenosis rate. When the stenosis rate was taken as the control factor, in the MCA proximal stenosis, V avg ( r=0.553, P=0.003), TAWSS ( r=0.543, P=0.004) and WSS min ( r=0.547, P=0.004) were positively correlated with RI, proximal OSI was negatively correlated with RI ( r=-0.492, P=0.011), and was positively correlated with the plaque length ( r=0.437, P=0.026). At the distal end of the stenosis, V pk was negatively correlated with NWI ( r=-0.556, P=0.003), OSI was negatively correlated with RI ( r=-0.511, P=0.008), NWI ( r=-0.390, P=0.049). TAWSS was positively correlated with RI ( r=0.393, P=0.047). Conclusions:The 4D Flow MRI demonstrates characteristic hemodynamic changes in the proximal and distal ends of the stenotic MCA. The local hemodynamic characteristics of the stenotic MCA are correlated with plaque morphological parameters, including lumen stenosis, plaque load, and RI. It suggests an interaction between the occurrence and development of MCA plaque and local hemodynamic changes.

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.

Aim To study the difference in hepatotox-icity of psoralen on normal rats and Yin-deficiency rats from the perspective of lipid metabolism,so as to help explain the mechanism of psoralen cautiously used in patients with Yin deficiency recorded in ancient books.Methods SD rats were randomly divided into the nor-mal control group(carboxymethyl cellulose-Na,CMC-Na),normal administration group(CMC-Na+psor-alen),Yin-deficiency control group(CMC-Na+thy-roxine)and Yin-deficiency administration group(CMC-Na+thyroxine+psoralen).The model of Yin-deficiency was established by thyroxine(1 mg·kg-1)for ten days,and then psoralen(200 mg·kg-1)was given for three days.The serum indexes related to liver injury were detected by automatic biochemical analy-zer,the morphological changes of liver tissue were ob-served using HE and oil red O staining,and the relative transcription levels of lipid metabolism related enzymes and mRNA of transporter and endoplasmic reticulum stress related factors were detected using Real-time PCR.Results After intragastric administration of psoralen for three days,compared with the normal group,the levels of serum alanine aminotransferase(ALT),aspartate transaminase(AST),total bile acid(TBA)and triglyeride(TG)in Yin deficiency group increased more significantly,while TC,ALB and TP de-creased more significantly,and liver HE and oil red O staining showed more obvious lipid degeneration.TG synthesis factors adrenocortical carcinoma(ACC),fatty acid synthase(FASN)and sterolregulatory element binding protein-1(SREBP-1)were down-regulated more significantly,TG transport factors mili-total pro-tein(MTP)and lipoprotein pipase(LPL)were down-regulated more evidently,fatty acid β-oxidation related factors carnitine palmitoyltransferase 1A(CPT1A),carnitine/organic cation transporter 2(OCTN2)and peroxisome proliferators-activated receptors-alpha(PPARα)were down-regulated more apparently,TC transporter adenosine triphosphate binding cassette transporter G8(ABCG8)and bile acid receptor farne-soid X receptor(FXR)were down-regulated more ob-viously,and endoplasmic reticulum stress factor activa-ting transcription factor 4(ATF4)was up-regulated more significantly.Conclusions Psoralen can cause more severe hepatotoxicity in Yin deficiency rats than that in normal administration group,and its mechanism may be related to the disorder of hepatic lipid metabo-lism,aggravation of hepatic cholestasis and steatosis,and activation of endoplasmic reticulum stress re-sponse.

Objective To analyze the characteristics of intestinal flora of personnel stationed on an island,so as to lay the foundation for maintaining the intestinal microecological balance of personnel stationed on island and provide accurate medical security.Methods Several subjects stationed on an island and several subjects from coastal areas were enrolled by random and sampling method,and their fecal samples were sequenced by 16S rRNA high-throughput sequencing.Diversity and composition of gut microbiota in 2 cohorts of personnel were compared.Results Alpha diversity analysis of intestinal flora showed that the abundance of intestinal flora in subjects stationed on the island was significantly higher than that of subjects from coastal areas.Beta diversity analysis indicated significant differences in the composition of intestinal microbial communities between the subjects stationed on the island and those from coastal areas(P=0.001).The abundance of the Bacteroidota in the intestinal tract of subjects stationed on the island was significantly lower than that of subjects from coastal areas(30.8%vs 48.3%,P＜0.001),while the abundance of the Proteobacteria was significantly higher than that of subjects from coastal areas(28.3%vs 10.2%,P＜0.001).After multiple hypothesis testing correction,it was found that the abundance of the Bacteroides,Roseburia,Alistipes,and Parabacteroides in the intestines of subjects stationed on the island decreased significantly,while the abundance of the Prevotella,Escherichia-Shigella,Citrobacter,and Eubacterium_coprostanoligenes increased significantly.Conclusion The special environment of islands affects the characteristics of intestinal flora of personnel,and the intestinal microecological health needs precise maintenance.

Objective To explore the correlation between glycolysis related indexes of peripheral blood mononuclear cells(PBMCs)[glucose transporter 1(GLUT1),fructose-2,6-diphosphatase 3(PFKFB3)and lactate kinase M2(PKM2)]and intracranial pressure and clinical prognosis of patients with hypertensive cerebral hemorrhage(HICH)who broke into the ventricle.Methods 85 HICH patients hospitalized in our hospital from January 2021 to June 2022 were retrospectively collected as the research participants.The levels of PKM2,GLUT1 and PFKFB3 in PBMCs were analyzed by enzyme-linked immunosorbent assay kit.Six months after the onset of HICH,the short-term outcome was evaluated by modified Rankin scale(mRS),and the patients were divided into good prognosis(mRS score≤2)and poor prognosis(mRS score≥3).Results The levels of PKM2,PFKFB3 and GLUT1 in PBMCs of HICH patients with ventricular rupture were further lower than those of the patients without ventricular rupture(P<0.05).Six months after discharge,8 patients(22.9%)with HICH in non-ventricular rupture group had poor prognosis,while 28 patients(56.0%)with HICH in ventricular rupture group had poor prognosis,and the difference was statistically significant(χ2=9.263,P=0.002).Compared with the group with good prognosis,the levels of PKM2 and GLUT1 in PBMCs of HICH patients with poor prognosis were lower(P<0.05).Compared with the good prognosis group,the levels of PKM2 and GLUT1 in PBMCs of HICH patients with poor prognosis group were lower in HICH patients with ventricular rupture(P<0.05).In HICH patients who broke into the ventricle,the AUC of PKM2 and GLUT1 in predicting the poor prognosis of HICH patients were 0.879(95%CI:0.807～0.951)and 0.897(95%CI:0.831～0.963),respectively.Conclusion The levels of PKM2 and GLUT1 in PBMCs of patients with HICH breaking into ventricles decrease significantly,and are negatively correlated with intracranial pressure,which can be used to predict the short-term prognosis of the patients.

Immunotherapy has been widely used in cancer treatment in recent years and functions by stimulating the immune system to kill tumor cells. Radiation therapy (RT) uses radiation to induce DNA damage and kill tumor cells. However, this activates the body's immune system, promoting the release of tumor-related antigens from inactive dendritic cells, which stimulates the recurrence and metastasis of tumors in immune system tissues. The combination of RT and immunotherapy has been increasingly evaluated in recent years, with studies confirming the synergistic effect of the two antitumor therapies. Particularly, the combination of RT by dose adjustment with different immunotherapies has positive implications on antitumor immunity as well as disease prognosis compared with respective monotherapies. This review summarizes the current research status, progress, and prospects of RT combined with immunotherapy in cancer treatment. It additionally discusses the prevalent concerns regarding the dose, time window, and toxicity of this combination therapy.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Combined Modality Therapy ; Radiotherapy/methods*