BACKGROUND:LncRNA-TNFRSF13C,an important factor in B cell development and function,is expressed in periodontal tissues of patients with periodontitis,but the specific mechanism is still unclear. OBJECTIVE:To investigate the mechanism of lncRNA-TNFRSF13C regulating miR-1246 on hypoxia-inducible factor 1α in periodontal cells. METHODS:Human periodontal ligament cells(hPDLCs)were treated with lipopolysaccharide and divided into group A(hPDLCs cell lines without transfection),group B(hPDLCs cell lines transfected with TNFRSF13C NC-siRNA),group C(hPDLCs cell lines transfected with TNFRSF13C-siRNA),group D(hPDLCs cell line transfected with miR-1246 mimics),group E(hPDLCs cell line transfected with miR-1246 siRNA),group F(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 mimics),and group G(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 siRNA).The relative expression of lncRNA-TNFRSF13C and miR-1246 in each group was detected by qRT-PCR.Cell counting kit-8 assay was used to detect cell viability.Apoptosis was detected by flow cytometry.Expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins was detected by western blot.The correlation between lncRNA-TNFRSF13C and miR-1246 was analyzed by Pearson,and the targeting relationship was analyzed by dual-luciferase reporter assay. RESULTS AND CONCLUSION:There was no significant difference in human periodontal ligament cell activity,apoptosis rate and protein indexes between groups A and B(P>0.05).Compared with group B,hPDLCS cell activity in group C was increased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were decreased(P<0.05).Compared with group C,hPDLCS cell activity in group D was decreased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were increased(P<0.05).Compared with group D,the cell activity of group E was increased(P<0.05).The cell activity in group F was lower than that in group E,and the apoptosis rate was reduced in both groups E and F(P<0.05).Compared with group F,the cell activity of group G was increased,and the apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor were decreased(P<0.05).LncRNA-TNFRSF13C was positively correlated with miR-1246(P<0.05).Compared with the TNFRSF13C-siRNA group,the fluorescence activity of miR-1246-wt in the TNFRSF13C-NC group was reduced(P>0.05);compared with the miR-1246-NC group,the fluorescence activities of hypoxia-inducible factor 1α-wt and vascular endothelial growth factor-wt in the miR-1246 mimics group were increased(P<0.05).To conclude,down-regulation of lncRNA-TNFRSF13C can promote the activity of periodontal cells treated with lipopolysaccharide,reduce apoptosis,and inhibit hypoxia-inducible factor 1α and vascular endothelial growth factor.The mechanism is related to the regulation of miR-1246 activity.

Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

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.

Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Aim To investigate the effects of 2-dode-cyl-6-methoxycyclohexa-2 , 5-diene-l, 4-dione ( DM-DD) on resisting hepatic fibrosis induced by carbon tetrachloride ( CC14 ) in rats and the underlying mechanisms , with a specific focus on the TGF-pi/Smads signaling pathway. Methods The hepatic fibrosis model was replicated using 50% CC14. Various parameters, including levels of aspartate transferase ( AST) , ala-nine transferase ( ALT ) , albumin/globulin ( A/G ) , total protein (TP) , total bilirubin (T-BIL) , hyaluron-ic acid ( HA ) , laminin ( LN ) , collagen type Ж ( Col Ж) , and collagen type IV(ColIV) in the blood, were measured. Liver tissue lesions and fiber formation were observed using HE and Masson staining. The expression levels of a smooth muscle actin (a-SMA) , collagen type I ( Col I ) , transformed growth factor (TGF-pi), Smad2, and Smad7 proteins were assessed using immunohistochemistry. a-SMA, Coll, TGF-pi, and Smad7 mRNA levels in liver tissue were measured by RT-PCR. Additionally, the expression levels of TGF-pi, Smad4, and Smad7 proteins in liver tissue were determined by Western blot. Results In comparison to the normal control group, the model group exhibited significantly elevated levels of AST, ALT, TP, T-BIL, HA, LN, Col Ш and Col IV in serum. But A/G level notably decreased. Successful modeling was confirmed by the presence of extensive fiber formations observed through HE and Massonstaining in liver tissue. The DMDD administration group demonstrated a notable decrease levels of AST, ALT, TP, T-BIL, HA, LN, Col III, and CollV, but A/G was significantly elevated when compared to the model group. Furthermore, a-SMA, Coll, TGF-f31, Smad2 and Smad4 mRNA and protein levels in the DMDD administration group were significantly reduced, while Smad7 significantly declined. HE and Masson staining results reflected a marked reduction in fibrous hyper-plasia. Conclusion DMDD exhibits a protective effect against CCl4-induced hepatic fibrosis, and its mechanism appears to be associated with the TGF-fJl/ Smads signaling pathway.

Objective To investigate the predictive value of tissue plasminogen activator(t-PA),chro-mogranin A(CgA),and lipoprotein related phospholipase A2(LP-PLA2)in serum for major adverse cardio-vascular event(MACE)after percutaneous coronary intervention(PCI).Methods A total of 120 patients with coronary heart disease who underwent PCI in the hospital from August 2020 to August 2022 were en-rolled in the study.According to whether MACE occurred within 1 year after PCI,the patients were divided into MACE group(33 cases)and non-MACE group(87 cases).The levels of serum t-PA,CgA,LP-PLA2 and clinical data were compared between the MACE group and the non-MACE group.Multivariate Logistic regres-sion was used to analyze the risk factors of MACE after PCI.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of t-PA,CgA and LP-PLA2 alone or in combination for MACE after PCI.Results The proportion of patients with smoking history,NT-proBNP,CgA,LP-PLA2,and the propor-tion of patients with hypertension in the MACE group were higher than those in the non-MACE group(P＜0.05),while left ventricular ejection fraction(LVEF)and t-PA were lower than those in the non-MACE group(P＜0.05).There were no significant differences in age,gender composition,serum creatinine,triglyc-erides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),drinking history,NYHA cardiac function classification,combined diabetes,application of aspirin,and application of clopidogrel between the two groups(P＞0.05).Multivariate Logistic regression analysis showed that smoking history,increased NT-proBNP,hypertension,decreased LVEF,decreased t-PA,increased CgA and increased LP-PLA2 were risk factors for MACE after PCI(P＜0.05).ROC curve analysis showed that the areas under the curves(AUCs)of serum t-PA,CgA and LP-PLA2 alone or in combination for predicting MACE after PCI were 0.785(95％CI:0.693-0.877),0.678(95％CI:0.564-0.791),0.730(95％CI:0.636-0.824),0.888(95％CI:0.830-0.946),respectively.The efficacy of combined prediction was bet-ter than those of single detections(P＜0.05).Conclusion The lower the serum t-PA level is and the higher the CgA and LP-PLA2 levels are,the greater the risk of MACE after PCI is.The combination of the three in-dicators has higher value in predicting MACE after PCI.

Objective To evaluate the change of cardiac structure and function in patients with hypertrophic obstructive cardiomyopathy(HOCM)after ultrasound-guided percutaneous intramyocardial septal radiofrequency ablation(PIMSRA)via cardiac magnetic resonance(CMR).Methods Patients with HOCM who underwent PIMSRA,echocardiography and CMR preoperative scanning and one year after surgery were analyzed retrospectively.Myocardial structural and functional parameters were measured by Circle cardiovascular imaging post-processing software.The changes of myocardial parameters before and after surgery were compared by using paired sample t-test and Chi-square test.Results Compared with the preoperative assessment,patients'clinical symptoms and the cardiac function were significantly improved one year after surgery.The left ventricular outflow tract pressure gradient(LVOT-PG)was significantly decreased and length of mitral regurgitation was shortened one year after surgery compared with before surgery via ultrasound(P<0.05).Compared with the preoperative assessment,CMR showed that patients with end-systolic volume of left atrium,minimum volume of left atrium,transverse diameter of left atrium,thickness of ventricular septum and free wall of left ventricular at end-systolic section were significantly reduced,and left ventricular mass(LVM)was significantly decreased one year after surgery,with statistical significance between before and after surgery(P<0.001).One year after surgery,the left atrium ejection fraction(LAEF)was significantly increased(P<0.05),the maximum slope and the maximum signal intensity of the ventricular septum and the left ventricular free wall of the papillary muscle were significantly increased(P<0.001),and the peak time was significantly decreased(P<0.001)compared with before surgery.Conclusion After PIMSRA treatment,the systolic function of left atrium in HOCM patients is improved,and the microcirculation perfusion of left ventricular is significantly improved.

BACKGROUND:Graphene is the thinnest,strongest,and toughest type of two-dimensional new crystal material,demonstrating significant advantages in biomedical applications.Angiogenesis and vascularization of bone are key factors in tissue repair and regeneration,and are effective ways to address vascular and osteogenic issues. OBJECTIVE:To review the characteristics and mechanisms of graphene and its derivatives in promoting angiogenesis activity and vascularizing bone,in order to provide a reference for their clinical application in vascular tissue repair and regeneration. METHODS:Using a computer to search for relevant literature included in PubMed,ScienceDirect,CNKI,and Wanfang databases,the Chinese search terms were"grapheme","angiogenesis,vascularization","vascularized bone",and"endothelial cells",while the English search terms were"graphene""angiogenesis OR vascularization""vascularized bone""endothelial cells".After excluding literature unrelated to the topic of the article,according to the inclusion and exclusion criteria,62 articles were ultimately included for result analysis. RESULTS AND CONCLUSION:(1)At present,graphene oxide has been studied more and is the most widely used in graphene and its derivatives.(2)Graphene and its derivatives are suitable for heart,bone,nerve,and wound healing related diseases.(3)Graphene and its derivatives have excellent physical and chemical properties and biological properties,but they have potential cytotoxicity.We should pay attention to its biological safety in application.(4)The application of graphene and its derivatives requires further research to demonstrate the optimal size and concentration and measures to reduce toxicity.(5)On the cellular level,graphene and its derivatives can promote angiogenic activity by tip endothelial cell phenotype,mesenchymal stem cell adhesion and proliferation, and vascular smooth muscle cell growth.(6)On the molecular level,graphene and its derivatives can increase the expression of vascular endothelial growth factor,basic fibroblast growth factor,hepatocyte growth factor and activate reactive oxygen species/nitric oxide synthase/nitric oxide signaling pathway,lysophosphatilate R6/Hippo-YAP pathway,stromal cell-derived factor-1/vascular endothelial growth factor and ZEB 1/Notch1 pathway.(7)Grapheme oxide and graphene oxide-copper phosphorylated extracellular regulatory protein kinase and activated hypoxia-inducible factor-1,thereby promoting the up-regulation of vascular endothelial growth factor and bone morphogenetic protein-2 expression,and promoting angiogenesis and vascularized bone.(8)In summary,graphene and its derivatives,especially graphene oxide,have great application prospects in the repair and regeneration of vascularized tissues due to their excellent biological properties,good angiogenesis and vascularized bone ability.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.