Risk prediction models for postoperative pulmonary complications (PPCs) can assist healthcare professionals in assessing the likelihood of PPCs occurring after surgery, thereby supporting rapid decision-making. This study evaluated the merits, limitations, and challenges of these models, focusing on model types, construction methods, performance, and clinical applications. The findings indicate that current risk prediction models for PPCs following lung cancer surgery demonstrate a certain level of predictive effectiveness. However, there are notable deficiencies in study design, clinical implementation, and reporting transparency. Future research should prioritize large-scale, prospective, multi-center studies that utilize multiomics approaches to ensure robust data for accurate predictions, ultimately facilitating clinical translation, adoption, and promotion.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

BACKGROUND:Human periodontal stem cells have a certain inhibitory effect on the pro-inflammatory function of M1-type macrophages,and it is not clear whether icariin,which has anti-inflammatory and other pharmacological activities,can enhance the inhibitory effect of human periodontal stem cells on M1-type macrophages. OBJECTIVE:To investigate the effect of icariin on M1 macrophages after pretreatment of human periodontal stem cells. METHODS:Primary human periodontal stem cells were isolated,cultured and characterized.THP-1 was induced and M1-type macrophages were identified by immunofluorescence staining and PCR.Human periodontal stem cells were cultured with α-MEM complete medium containing concentrations of 10-7,10-6,10-5,and 10-4 mol/L icariin,and the cytotoxicity of Icariin on human periodontal stem cells was detected by the CCK-8 assay at 1,3,5,and 7 days,respectively.α-MEM complete medium,untreated α-MEM conditioned medium for human periodontal stem cells and α-MEM conditioned medium for human periodontal stem cells pretreated with icariin for 24 hours were conditioned with RPMI-1640 complete medium in a 1:1 ratio for M1-type macrophages in the control,untreated,and pretreated groups,and 24 hours later,the mRNA expression of inflammatory factors in M1 macrophages was detected by RT-PCR.The protein expression of inflammatory factors in M1 macrophages was detected by ELISA.The expression of surface markers and nuclear factor-κB pathway-related proteins in M1/M2 macrophages was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that 10-7,10-6,10-5,10-4 mol/L icariin was not cytotoxic to the human periodontal stem cells,and from day 5 onwards,all the concentrations increased the cell viability,and promoted the cell proliferation.10-4 mol/L icariin was selected for follow-up experiment.(2)RT-PCR and ELISA results showed that compared with the control group,the untreated group and the pretreated group both decreased the expression and secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α of M1-type macrophages(P<0.05),and the pretreated group was lower than the untreated group(P<0.05).(3)Western blot assay results showed that compared with the untreated group,the expression of CD86 was significantly lower in the pretreated group(P<0.05);compared with the control group,the expression of CD206,a surface marker of M2-type macrophages,was elevated in both the untreated and pretreated groups(P<0.01),and it was significantly higher in the pretreated group than in the untreated group(P<0.01).In M1-type macrophages after 24 hours of conditioned culture,compared with the control group,the expression of nuclear factor-κB/P65 was decreased in the untreated group and the pretreated group(P<0.01),and the expression of p-IκBα was decreased only in the pretreated group(P<0.01);the expression of both nuclear factor-κB/P65 and p-IκBα was significantly reduced in the pretreated group compared with the untreated group(P<0.05),while the difference of IκBα in the three groups was not statistically significant.(4)These results indicated that icariin enhanced the inhibitory effect of human periodontal stem cells on M1-type macrophages,and this effect may be related to the inhibition of the nuclear factor-κB signaling pathway of macrophages.

Gadopiclenol was used in adults and pediatric patients 2 years of age and older during magnetic resonance imaging(MRI)to detect and view lesions of the central nervous system(brain,spine,and associated tissues)and body(head and neck,chest,abdomen,pelvis,and musculoskeletal system)with abnormal vascular properties.Gadopiclenol is a new type of macrocyclic gadolinium-based contrast agent(GBCA).In this article,the molecular structure,principle of action,pharmacodynamics,pharmacokinetics,clinical studies,safety and other aspects of Gadopiclenol were reviewed,in order to introduce the current research status and existing achievements of Gadopiclenol.

Reducing the consumption of attentional resources and improving human performance in dynamic visual sustained attention tasks is a key issue in sustained attention research. The multiple object tracking (MOT) task is a widely used paradigm for studying individual sustained attention. In a classic MOT paradigm, observers need to maintain their attention on specific targets among a set of distractors and track their movement. To further utilize attentional resources and improve tracking performance, researchers have proposed studying the additivity problem of grouping effects in attention tracking. Grouping effects during MOT is the phenomenon that moving items can be perceived into larger moving units based on featural cues of themselves or task requirements. This article reviewed previous studies about attention resources, classification, additivity, and neural mechanisms of grouping effects in MOT. Based on previous research, we concluded that grouping effects in MOT can be classified into three categories, i.e., spatiotemporal-based grouping, object-based grouping, and feature-based grouping, according to different grouping cues (spatiotemporal continuity, global perception and organization of objects, and surface featural similarity). Grouping based on multiple cues will produce greater effects compared with one cue, this is the additive effect. The study of additivity is important for understanding the cognitive mechanisms of different grouping effects, the attentional mechanisms, and resource allocation in individual dynamic visual tracking. This study summarized previous behavioral and neuroimaging research and systematically explored the non-additivity based on different surface features and the additivity based on surface features and specific spatiotemporal features. Exploring the mechanism of additivity effects provides us with new insight into understanding grouping effects. For future studies, researchers need to thoroughly investigate the neural mechanisms of different kinds of groupings. This can not only provide explanations for the additivity of groupings but also provide substantial evidence for the classification of groupings.

Chronic heart failure （CHF） is a clinical syndrome resulting from damage to the myocardium， leading to changes in the function or structure of the heart and causing reduced pumping and/or filling capacity. Its pathogenesis is complex， potentially involving myocardial fibrosis， apoptosis and autophagy of cardiomyocytes， inflammatory responses， oxidative stress， and myocardial remodeling. Our team believes that the fundamental pathogenesis of CHF is heart-Qi deficiency， with the disease location in the heart， which is closely related to other organs. Due to heart-Qi deficiency， blood circulation weakens， leading to blood stasis， which in turn generates water-dampness and phlegm turbidity that accumulate over time and become toxic. The interaction between water stasis， Qi stagnation， blood stasis， and phlegm toxicity further weakens the body， creating a vicious cycle （deficiency， stasis， water retention， and toxicity） that is difficult to resolve. Under physiological conditions， the nuclear factor-κB （NF-κB） signaling pathway functions normally， maintaining vital activities and immune responses. However， in pathological states， the NF-κB signaling pathway becomes imbalanced， triggering inflammatory responses and other issues. Research has shown that traditional Chinese medicine （TCM） can regulate the NF-κB signaling pathway through multiple pathways， targets， and effects， effectively improving the progression of CHF. As a result， this has become a research hotspot for the prevention and treatment of the disease. Guided by TCM theory， this research group reviewed the literature to summarize the activation pathways of the NF-κB pathway and its interactions with other pathways. Additionally， the group summarized the research progress on the regulation of the NF-κB pathway in the treatment of CHF using Chinese medicines， their active ingredients， Chinese medicine compounds， and Chinese patent medicines. This study is expected to clarify the mechanisms and targets by which TCM treats CHF by regulating the NF-κB pathway， thereby guiding clinical treatment and drug development for CHF.

Background Gastric carcinogenesis is a multifactorial and complex process, in which long non-coding RNAs (lncRNAs) play important roles as oncogenes or antioncogenes. Research has found that the expression of lncRNA LINC02859 is down-regulated in gastric cancer tissues and correlated with the degree of tumor differentiation and TNM stage, and also plays an important role in the development of malignant transformation of cells induced by environmental carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but its mechanism of action is still unclear. Objective To explore the role and potential regulatory mechanism of gastric cancer-associated lncRNA LINC02859 in MNNG-induced malignant transformation of human normal gastric mucosal cells (GES-1). Methods A total of 110 gastric cancer patients from a high incidence area of gastric cancer in Gansu Province were selected, and their cancer tissues and normal gastric mucosa tissues adjacent to the cancer were collected to detect the expression level of LINC02859 by real-time quantitative PCR (RT-qPCR). High-throughput sequencing and bioinformatics analysis of the tissues were used to identify the potential signaling pathways regulated by the genes co-expressed with LINC02859. GES-1 cells at 70%-80% cell fusion with low cell passage number and normal morphology were incubated with 0, 0.25 and 0.5 μmol·L⁻¹ MNNG solution for 48 h and the LINC02859 expression level was detected. Cell proliferation activity was detected by Cell Counting Kit-8 (CCK-8), clone formation was detected by plate clone formation assay, and cell migration ability was detected by scratch assay to evaluate the effects of MNNG on cell morphology and function. The expression levels of key proteins of Wnt signaling pathway were detected by RT-qPCR and Western blotting. Results The RT-qPCR results showed that LINC02859 was lowly expressed in the gastric cancer tissues compared with the paracancerous tissues, and the difference was statistically significant (P < 0.05). The pathway enrichment analysis showed that LINC02859 potentially regulated the Wnt pathway. The in vitro malignant transformation assay suggested that after the MNNG exposure, the malignant cells of passage 5 (MC-5) had altered morphology, increased number of colony formation, and higher proliferation and migration ability than the control cells; compared with the normal GES-1 cells, LINC02859 gene expression levels were reduced in the 0.25 μmol·L⁻¹ and the 0.5 μmol·L⁻¹ MNNG-exposed GES-1 cells; the expression levels of key proteins of the Wnt pathway, transcription factor 7 (TCF7), Axis inhibitor (Axin1), phosphorylation of glycogen synthase kinase-3 beta (p-GSK-3β), casein kinase 1 (CK1), and β-catenin, were elevated in the cells after 0.5 μmol·L⁻¹ MNNG exposure (P < 0.05); whereas, overexpression of LINC02859 suppressed the activating effect of MNNG on the Wnt pathway. Conclusion LINC02859 is lowly expressed in the cancer tissues of gastric cancer patients. MNNG exposure induces morphological and functional changes in GES-1 cells, down-regulated expression of LINC02859, and activation of the Wnt signaling pathway; overexpression of LINC02859 inhibits the activation of the Wnt signaling pathway in the gastric carcinogenesis induced by MNNG exposure.

The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

Exploring the action targets (groups) of traditional Chinese medicine (TCM) is an important proposition to promote the innovation and development of TCM, but it has attracted a lot of attention as to whether it is related to the efficacy or the disease. Our team found that the metabolomic signature molecules in the development of diabetes mellitus (DM) were significantly associated with the clinical efficacy of Yuquan Pill through a large clinical sample study. Taking this as a clue, our team intends to expand the information on the omics features of DM development, and discover the key targets (groups) and their lead compounds for the hypoglycemic effect of Yuquan Pill. The project includes: ① Based on the retrospective clinical trials, using omics technology integrated with generative artificial intelligence, mining the characteristic information of proteome and microbiome, forming driving factors together with metabolome characteristic molecules, and characterizing the molecular trajectories of diabetes evolution and their interference by Yuquan Pill; ② Taking the evolving molecular trajectories as a link and pointer, using anthropomorphic modeling and molecular biology techniques such as chemical proteomics to discover the key targets (groups) of Yuquan Pill's hypoglycemic effect, with the prospective clinical samples for validation; ③ Evaluate the overall response of key targets (groups) using graph neural network technology, and search for drug-derived/endogenous lead compounds with proven clinical pathologies and clear mechanisms of action, so as to provide a new paradigm and technology for the discovery of complex active ingredient targets (groups) of TCM that are related to their clinical efficacy, as well as for the discovery of innovative medicines.

Background: Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease is associated with coronary artery lesion development.Purpose: This study aimed to explore the factors associated with IVIG-resistance and construct and validate an interpretable machine learning (ML) prediction model in clinical practice. Methods: Between December 2014 and November 2022, 602 patients were screened and risk factors for IVIG-resistance investigated. Five ML models are used to establish an optimal prediction model. The SHapley Additive exPlanations (SHAP) method was used to interpret the ML model. Results: Na+, hemoglobin (Hb), C-reactive protein (CRP), and globulin were independent risk factors for IVIG-resistance. A nonlinear relationship was identified between globulin level and IVIG-resistance. The XGBoost model exhibited excellent performance, with an area under the receiver operating characteristic curve of 0.821, accuracy of 0.748, sensitivity of 0.889, and specificity of 0.683 in the testing set. The XGBoost model was interpreted globally and locally using the SHAP method. Conclusion Na+, Hb, CRP, and globulin levels were independently associated with IVIG-resistance. Our findings demonstrate that ML models can reliably predict IVIG-resistance. Moreover, use of the SHAP method to interpret the established XGBoost model's findings would provide evidence of IVIG-resistance and guide the individualized treatment of Kawasaki disease.