BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

In response to the current situation and teaching status of the medical image processing course on the background of"new medical science",a teaching software which is highly compatible with the teaching process of medical image processing is developed.The teaching software allows for linear grayscale transformation,windowing display,scaling,rotation,mirroring,median filtering,differential sharpening,edge detection,histogram acquisition,and histogram equalization of medical images.Additionally,it enables parameter adjustments within a certain range for linear grayscale transformation,windowing display,scaling,rotation,median filtering,differential sharpening,and edge detection.Meanwhile,it employs different algorithms to achieve the scaling of medical images.The teaching software is used in the theoretical and experimental teaching of medical image processing courses at Baotou Medical College.It can improve students'initiative and enthusiasm in learning,strengthen their understanding of the examination points for radiology technicians,lay a solid foundation for subsequent courses,and ultimately achieve the goal of in-depth integration of"Medical Engineering"and"Medical Science"in the medical image technology major at Baotou Medical College under the background of"new medical science".

The relationship between dosage form and efficacy is an important aspect of traditional Chinese medicine pharmacy research.However,there is a lack of systematic analysis of how ancient physicians understood the functional characteristics of decoction.By analyzing the advantages and effects of using decoction in the Jingui Yuhan Jing,it can be observed that ancient people's understanding of the therapeutic effect of decoction did not solely stem from medical practice,but also understood and elaborated on the function of decoction through the characteristics of water.This article starts with a discussion on the application of decoction in Jingui Yuhan Jing and uses metaphorical cognitive theory to analyze how ancient physicians understood and constructed the cleansing,opening,guiding,dispersing,nourishing,and moisturizing effects of decoction in the aspects of water cleanliness,connectivity,fluidity,impact,and moisturizing.This has formed a relatively complete set of explanations on the functional characteristics of decoction based on the"water metaphor".This has affected the widespread application of decoction and selection of solvents and has developed a new thinking system for the understanding and research of ancient dosage forms.

Metabotropic glutamate receptor 5 (mGluR5) encephalitis is a rare type of anti-cell surface antigen antibody encephalitis mediated by autoimmune mechanisms. This article reported a case of anti-mGluR5 encephalitis. The patient was a 25-year-old young man with a history of Hodgkin′s lymphoma. Due to tumor recurrence, he developed encephalitis symptoms including fever, headache, mental and behavioral abnormalities, memory loss, consciousness disturbance, and seizures after checkpoint immunosuppressive therapy. He was finally diagnosed as anti-mGluR5 encephalitis by positive serum anti-mGluR5 antibodies. Finally, the symptoms alleviated after treatment with hormones and gamma globulin.

Objective:To investigate the antibacterial and osteogenic properties of biomimetic mineralized iodine-loaded coating with micro-nano topography on the surface of bone implants.Methods:After the fiber network structure of sodium hydrogen titanate was constructed by alkali thermal reaction on the surface of Ti6Al4V (noted as AT), it was biomimetically mineralized in the modified simulated body fluid to form a micro-nano topology with high specific surface area (noted as AT-CaP), and finally loaded with PVPI to construct a novel antibacterial osseointegration coating (noted as AT-CaP-PVPI). The study was conducted in AT, AT-CaP, and AT-CaP-PVPI groups, in each of which 3 parallel experiments were performed. The morphology and colony counting of Staphylococcus aureus on the coating surface were observed to detect the in vitro antibacterial performance of the coating. Fifteen male SD rats were randomly divided into 3 groups ( n=5): AT, AT-CaP, and AT-CaP-PVPI. After intramedullary injection of Staphylococcus aureus into the lower end of the femur in the SD rats, titanium rods coated with AT, AT-CaP, and AT-CaP-PVPI were inserted into the marrow cavity. The osteogenesis, volume ratio of new bone mass and number of trabeculae on the surface of the femoral implants were compared between the 3 groups 4 weeks after operation. Results:In AT and AT-CaP groups, a large number of bacteria grew in their inherent elliptical or spherical shape on the implant surface and a large number of colonies were seen on the plate; in AT-CaP-PVPI group, the bacteria on the coating surface exhibited membrane deformation and depression, some of them were completely broken and dissolved, and a large number died. There was almost no new bone formation around the implants in AT group; new bone scattered around the implants with discontinuous distribution in AT-CaP group; a great amount of new bone was seen around the implants with even distribution but no signs of infection in AT-CaP-PVPI group. The volume ratio of new bone mass and the number of trabeculae on the implant surface in AT-CaP-PVPI group were 0.453±0.206 and 6.055±0.536, respectively, significantly higher than those in AT group (0.046±0.028 and 1.667±1.249) and AT-CaP group (0.188±0.052 and 3.804±0.889) ( P<0.05). Conclusion:Biomimetic mineralized iodine-loaded coating with micro-nano topography on the surface of bone implants shows good antibacterial and osteogenic properties.

Humans ; Critical Illness ; Critical Care ; Intensive Care Units ; Surveys and Questionnaires

OBJECTIVE: The compatibility of Eucommia ulmoides (Eu) and Psoralea corylifolia (Pc) on the pharmacokinetic (PK) properties in the rat was explored in this study. METHODS: Eu extract, Pc extract and the combined extracts (crude drug ratio was 2:1) was administered by gavage, respectively. Two PK experiments were conducted. In first one, the blood samples were collected via the occuli chorioideae vein to get the PK properties of the components. In second one, the blood samples were simultaneously collected via the internal jugular vein or portal vein at different time points and the concentrations of target ingredients were detected by LC/MS/MS to clear the location where the interaction of Eu and Pc took place in vivo. RESULTS: Eight of 11 ingredients in Eu and Pc extract were determined in rat plasma. The exposure levels of geniposidic acid (GPA), aucubin (AU), geniposide (GP), pinoresinol diglucoside (PDG), psoralen glycosides (PLG) and isopsoralen glycosides (IPLG) were decreased 1/5-2/3 after administration of combined extracts. Comparing to the combined administration, the exposure of GPA and AU in plasma of single Eu administration collected via the portal vein were decreased 1/3-2/3, and the values of AUC_0-24h and AUC_0-∞ of GP collected from the portal vein or internal jugular vein were double increased. The other components' parameters were not significantly changed. CONCLUSION In summary, the Pc and Eu combined administration could affect the exposure of the main components of Eu extract in rats due to the changed intestinal absorption. The research on the compatibility of Pc and Eu was helpful to guide the clinical administration of Eu and Pc simultaneously.