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.

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

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.

Nanoparticle delivery systems have good application prospects in the field of precision therapy, but the preparation process of nanomaterial has problems such as short in vivo circulation time, easy recognition, and clearance by the immune system in the body. In recent years, biomimetic nanoparticle delivery systems mediated by natural cell membranes have become a research hotspot to address these issues. The natural membrane biomimetic nanoparticle delivery system cleverly integrates the advantages of natural biofilm "autologous" and "artificial" functional carriers by using endogenous cell membranes to modify the surface of nanocarriers, endowing them with characteristics such as tumor targeting, low immunogenicity, and long blood circulation. Currently, biomimetic nanoparticle delivery systems have been used in the treatment of malignant tumors, cardiovascular diseases, bacterial infections, and other diseases. This paper analyzes the development status and current research hotspots of natural cell membrane camouflaged biomimetic nanoparticle delivery systems mainly reviews the latest research progress of red blood cell membrane camouflaged biomimetic nanoparticle delivery systems in the field of disease treatment in recent years. It focuses on exploring the advantages, future development prospects, and limitations of biomimetic nanoparticle delivery systems based on red blood cell membrane camouflage in improving drug delivery, to provide a reference for the in-depth research and development of this system.

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.

Objective:To analyze the efficacy of distal tibial osteotomy and bone transport in the treatment of infected bone defects at the proximal tibia.Methods:A retrospective study was conducted to analyze the clinical data of 25 patients with infected bone defects at the proximal tibia who had been treated by distal osteotomy and bone transport at Department of Microprosthetic Surgery, The First Hospital Affiliated to Xinjiang Medical University from May 2015 to June 2023. There were 20 males and 5 females with an age of (45.9±7.1) years. The length of bone defects was (7.5±3.9) cm, the number of operations 3 (2, 4) times, the distance from bone defects to the tibial plateau (4.1±1.9) cm, and the length of bone defects (7.5±3.9) cm. Six patients finished debridement and osteotomy in one operation. Staged surgery was conducted in 19 patients. At first, the original fixator was removed, followed by debridement and injection of the antibiotic bone cement. Next, the bone cement was removed to clean the lesion completely, and then the medullary cavity was penetrated by an electric drill to install an external fixator after flushing. Bone transport started 7 to 10 days later, at a speed of 1 mm/d, and was carried out in 4 times. The healing index, external fixation time, and external fixation index were recorded. The visual analog scale (VAS) for pain, knee range of motion (ROM), and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were compared between preoperation, 1-month postoperation, and the last follow-up. Fracture healing was evaluated using the Paley criteria, and complications were documented.Results:In this cohort, the healing index was (68.9±35.6) points, the external fixation time 13.0 (8.5, 21.8) months, and the external fixation index (2.43±1.24) points. All patients were followed up for 13.0 (8.5, 21.7) months. The VAS score, knee ROM, and AOFAS ankle-hindfoot score at the last follow-up were significantly improved compared with preoperation and 1-month postoperation ( P<0.05). According to the Paley criteria, fracture healing was excellent in 14, good in 9 and poor in 2 cases, giving an excellent and good rate of 92.0%. The incidences of ankle and knee movement limitations were 92.0% (23/25) and 76.0% (19/25), respectively, being the highest. The incidences of foot drop, clubfoot and claw toe were 68.0% (17/25), 24.0% (6/25) and 20.0% (5/25), respectively. The incidences of pin tract infection and nonunion at the junction were 56.0% (14/25) and 60.0% (15/25), respectively. All these complications were improved by dressing change or surgery. Conclusions:Distal tibial osteotomy and bone transport can effectively treat infected bone defects at the proximal tibia, and the complications during the treatment need to be treated accordingly.

OBJECTIVE To explore the expression levels of microribonucleic acid-21(miR-21)and helper T cell(Th)1/Th2 cytokines in peripheral blood of the asthma children complicated with respiratory tract infections of vi-ruses and analyze the significance.METHODS A total of 90 asthma children with respiratory tract infections of vi-ruses(the infection group)and 43 asthma children without respiratory tract infections of viruses(the no infection group)who were treated in the 904th Hospital of the Joint Logistics Support Force of The People's Liberation Ar-my of China were enrolled in the study,and the clinical data were collected from the enrolled patients.The distri-bution of viruses from the children of the infection group was analyzed.The levels of peripheral blood miR-21,Th1 cytokines[interferon-γ(IFN-γ),interleukin(IL)-2]and Th2 cytokines[IL-4,IL-5]were compared between the two groups.The children of the infection group were divided into the mild group,the moderate group and the severe group according to the severity of disease.The levels of the above indexes were compared among the chil-dren with the various degree of illness condition.The association of the illness condition with miR-21,IFN-γ,IL-2,IL-4 and IL-5 was analyzed.RESULTS Respiratory syncytial virus was dominant among the respiratory tract vi-ruses in the infection group,accounting for 32.22％.The levels of IFN-γ and IL-2 of the infection group were low-er than those of the no infection group(P＜0.05),the levels of miR-21,IL-4 and IL-5 of the infection group were higher than those of the no infection group(P＜0.05).The levels of IFN-γ and IL-2 of the severe group were lower than those of the mild group and the moderate group(P＜0.05),while the levels of miR-21,IL-4 and IL-5 of the severe group were higher than those of the mild group and the moderate group(P＜0.05);the levels of IFN-γ and IL-2 of the moderate group were lower than those of the mild group(P＜0.05),and the levels of miR-21,IL-4 andIL-5 of the moderate group were higher than those of the mild group(P＜0.05).Spearman correlation analysis showed that the illness condition of the children was positively correlated with miR-21,IL-4 and IL-5(P＜0.05),which was negatively correlated with IFN-γ and IL-2(P＜0.05).CONCLUSIONS The respiratory tract infections of viruses may aggravate the abnormal rise of peripheral blood miR-21 and the imbalance of Th1/Th2.The above indexes are closely associated with the illness condition of the children.

Objective:To investigate whether systemic immune inflammation index(SII)-C-reactive protein/albumin(CRP/Alb)can predict postoperative survival in non-small cell lung cancer(NSCLC)patients.Methods:A total of 262 patients with NSCLC who underwent surgery in Hebei Provincial People's Hospital from January 2017 to November 2020 were included.SII and CRP/Alb expressions in patients after surgery were analyzed by K-M survival curve analysis,Cox multivariate risk regression analysis and ROC curve analysis.Results:Patients with high SII expression(>961.78)and high CRP/Alb expression(>0.025)had worse outcomes than patients with low SII and CRP/Alb expressions,respectively(P<0.001).SII-CRP/Alb score(P=0.032),age≥60 years(P=0.038)and T stage T2～T3(P<0.001)were significantly associated with shorter overall survival.AUC of SII-CRP/Alb scores were larger than SII and CRP/Alb scores,respectively.Conclusion:SII-CRP/Alb score can effectively evaluate postoperative survival status of patients with NSCLC,and SII-CRP/Alb score are independent predictors of postoperative overall survival in NSCLC patients.