In epidemiological statistics, the incidence rate and mortality rate of malignant lung tumors rank among the top. Non-small cell lung cancer (NSCLC) constitutes an important part of lung cancer and has become a key focus of clinical research and treatment. Among the genomic characteristics of NSCLC, the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is one of the main tumor drivers, accounting for approximately 25% of all NSCLC cases. The existence of this mutation is closely related to the treatment response and prognosis of patients. Therefore, the treatment strategy for KRAS-mutated NSCLC is an important topic in the field of tumor research. In the current era, immunomodulatory therapy has rapidly gained popularity and developed rapidly in oncology due to its unique mechanism of action and remarkable clinical efficacy. The treatment strategies targeting the KRAS-mutated of NSCLC have gradually become a research hotspot. The advent of immune checkpoint inhibitors (ICIs) has opened up a new therapeutic avenue for patients with such cancers, and clinical studies have shown significant effects in improving survival rates. Nevertheless, there are still many challenges in the application of immunotherapy, such as the complexity of the tumor microenvironment, individual differences among patients, and drug resistance mechanisms. This article reviews the progress of immunotherapy for KRAS-mutated NSCLC, focusing on the specific application of immunotherapy, the exploration of combination therapies, and the results of related clinical trials. At the same time, it discusses the possible future development directions of KRAS-mutated NSCLC treatment, providing a reference for clinical treatment practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/immunology* ; Lung Neoplasms/immunology* ; Proto-Oncogene Proteins p21(ras)/immunology* ; Immunotherapy/methods* ; Mutation ; Animals

OBJECTIVE: To establish a three-dimensional finite element model of a digital wire loop space maintainer for the mandible and primary tooth loss, in order to investigate the stress, deformation, and shear force experienced by patients with the loss of the second primary molar when wearing the wire loop space maintainer. METHODS: Cone beam computed tomography (CBCT) scans were performed on the patients to create a digital model of the mandible with the absence of the second primary molar using Mimics 21.0 software. A digital model integrating the crown's retention and the wire loop structure of the full crown and ring wire loop space maintainer was constructed using pediatric space maintainer design software, utilizing three different materials: cobalt-chromium alloy, polyether ether ketone (PEEK), and titanium alloy. In ANSYS Work Beach 2023 R2 software, vertical loads of 70 N, tilted 45° along the long axis of the tooth loads of 70 N, and a 10 N load on the surface of the wire loop were applied to the occlusal surfaces of models 46 and 84, simulating centric and lateral occlusions during chewing with the wire loop space maintainer in place. The stress states of the wire loop space maintainer and supporting teeth were analyzed. RESULTS: Under various loading conditions, the maximum principal stress of the ring wire loop space maintainer was significantly lower than that of the full crown. Stress contour maps indicated that the peak of the maximum principal stress occurred at the junction of the wire loop and crown structure, indicating that this area was more susceptible to fracture. The ring wire loop space maintainer made from PEEK material exhibited the lowest maximum shear stress on the internal organizational surfaces, with equivalent stresses of 23.18 MPa and 36.35 MPa for models 46 and 84, respectively. Stress contour maps demonstrated that the maximum stress on tooth 46 was located at its mesial, while the maximum stress on tooth 84 was situated near the root area on its distal, in contact with the wire loop space maintainer. CONCLUSION In cases of second primary molar loss, wearing the digital ring wire loop space maintainer can effectively distribute stress, and the ring wire loop space maintainer made from PEEK material reduces the stress experienced by supporting teeth to some extent, demonstrating its superiority in clinical application.
Finite Element Analysis ; Humans ; Tooth, Deciduous ; Cone-Beam Computed Tomography ; Space Maintenance, Orthodontic/methods* ; Imaging, Three-Dimensional ; Orthodontic Wires ; Dental Stress Analysis ; Mandible ; Stress, Mechanical

Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCD^SS) and the VCD depression resilient group (VCD^RES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective To explore the efficacy of bilateral facial muscle training combined with visual electromyography biofeedback on facial nerve function recovery in patients with idiopathic facial nerve palsy. Methods Patients with idiopathic facial nerve palsy admitted to Shanghai Fifth People’s Hospital, Fudan University from July 2022 to July 2024 were selected and randomly divided into a control group and an intervention group. The control group received conventional physical factor therapy, while the intervention group received bilateral facial muscle training combined with visual electromyography biofeedback therapy based on the control group’s regimen. After 20 treatment sessions, the total effective rate, the House-Brackmann (H-B) facial nerve grading system, the Sunnybrook Facial Grading System (SFGS) score, and the average value ratio of maximal amplitudes of bilateral frontalis and zygomaticus muscles were compared between the two groups. Results A total of 90 patients were included, 45 in each group. After 20 treatment sessions, the total effective rate was significantly higher in the intervention group than in the control group (84.4% vs 75.6%, P＝0.003). Compared with the control group, the intervention group demonstrated a significantly lower H-B grade (P＝0.003) and a higher SFGS score (P＝0.001). The average value ratios of maximal amplitudes of the affected versus healthy side frontalis (P＝0.013) and zygomatic (P＝0.022) muscles were higher in the intervention group than in the control group. Conclusions Bilateral facial muscle training combined with visual electromyography biofeedback is an effective approach for treating idiopathic facial nerve palsy, effectively promoting the recovery of facial nerve function, and improving facial symmetry and facial muscle function.

Objective: To analyse associated factors of campus bullying in schools, and to construct a nomogram model to predict the risk of campus bullying, so as to provide a theoretical basis for campus bullying prevention and control. Methods: In September 2023, 89 117 middle and high school students were selected by stratified cluster random sampling method within 12 cities (103 counties) in Inner Mongolia, and were surveyed with self administered questionnaire. Among them, there were 62 381 participants in the training set and 26 736 participants in the testing set. Statistical analysis was conducted using χ 2 test and multiple Logistic regression, and a nomogram model was drawn for predicting campus bullying. Results: The prevalence of campus bullying was 3.49%. Living in a suburban county, living in an unstable family, not the only child, having a father with a college degree or above, sometimes or never eating breakfast, being overweight or obese, living on campus, being scolded by parents in the past 30 days, smoking, Internet addiction, experiencing depression, anxiety symptoms, recreational soluble solvents use, cough medicine abuse, nonprescribed use of sedatives were all positively correlated with campus bullying ( OR =1.18, 1.40, 1.12, 1.33, 1.13, 1.72 , 1.12, 1.17, 1.82, 1.32, 1.83, 3.92, 2.40, 2.25, 1.51, 1.63, P <0.01).There were a negative correlation between high school students, female students, and the number of physical education classes per week (2-3, ≥4) with campus bullying ( OR =0.67, 0.58, 0.72, 0.83, P <0.01). The prediction model of campus bullying risk was established by nomogram model. The area under curve (AUC) was 0.82, and the calibration curve showed that the predicted value was close to the actual value. Conclusions Bullying among middle and high school students are related to family intimacy, poor daily behaviour and psychological factors. Targets of bullying intervention in schools should be identified, and preventive and control measures against bullying in secondary schools should be formulated, so as to reduce the occurrence of campus bullying.

Objective:To analyze the prevalence and clinical features of respiratory syncytial virus (RSV) in Chengde city.Methods:From August 2022 to June 2023, throat swabs and clinical data of 478 hospitalized children with respiratory tract infection in the Chengde Central Hospital were collected. Real-time quantitative PCR was used to detect the molecular epidemiology of RSV-A and RSV-B subtypes and analyze the clinical features of patients with RSV infection.Results:Among the hospitalized children, 67.57% (323/478) tested positive for RSV. The outbreak of RSV infection was caused by RSV-A subtype. The peaks of RSV-A infection occurred from November to December, 2022 and May to June, 2023. There were 86.07% (278/323) of the RSV-A-positive cases had mixed infection with other pathogens, primarily bacterial pathogens with Streptococcus pneumoniae being the most common, followed by Klebsiella pneumoniae. Influenza virus A was the most common viral pathogens causing mixed infection. The level of lactate dehydrogenase was higher in the patients with single RSV-A infection than in those with mixed infection ( Z=2.396, P=0.017), and higher than the normal upper limit. Compared with the single infection group, the mixed infection group had higher white blood cell count ( Z=2.417, P=0.016), neutrophil ratio ( Z=3.218, P=0.001), C-reactive protein level ( Z=1.998, P=0.046) and creatinine level ( Z=2.107, P=0.035), and lower lymphocyte ratio ( Z=3.205, P=0.001), but they were all within the normal range. There were no significant differences in the clinical features between RSV-A-positive patients co-infected with bacteria or other viruses (all P>0.05). Conclusions:RSV-A is the leading cause of respiratory tract infection in children in Chengde from 2022 to 2023, and often co-detected with bacteria. The mixed infection with other respiratory pathogens is related to the clinical features of patients with RSV-A infection.

Immunotherapy has become the cornerstone of current malignant tumor treatment.However,the response of different patients to immunotherapy is highly heterogeneous,and not all patients can benefit from it.There is an urgent need to find biomarkers that can effectively predict the efficacy of immunotherapy.C-C chemokine ligand 4(CCL4)is a cytokine,belonging to the inflammatory CCL subfamily.It is mainly secreted by immune cells and tumor cells and shows low or no expression in normal tissues but abnormally high expression in various malignant tumor tissues.After binding to CCL4 and its receptor C-C chemokine receptor type 5(CCR5),it can recruit and mediate immune cell migration,destroy the stabili-ty of the tumor microenvironment(TME),participate in carcinogenesis and promote the development of tumors.In the tumor immune microenvironment,CCL4 can mediate and recruit the directed migration of key immune cells such as monocytes,macrophages,natural killer(NK)cells,and T cells,which makes it a potentially important element affecting the efficacy of im-munotherapy and has specific value.This paper reviews the research progresses of CCL4's effects on immune escape in TME,in order to provide clues and references for basic research and clinical diagnosis and treatment.

Objective:To invastigate the targets and signaling pathways of Gubiao Fanggan Modified Formula in regulating the defense against influenza A virus in immunosuppressed mice by network pharmacology,and the key targets were verified by immuno-suppressive mice model.Methods:TCMSP database was used to search the active ingredients of Gubiao Fanggan Modified Formula,and GeneCard,OMIM,PharmGkb databases were used to obtain the potential targets of the active ingredients to prevent influenza,and take their intersection targets were taken;STRING11.5 database was used to make protein-protein interaction network analyzed and finded the core targets;Cytoscape3.8.1 was used to build a traditional Chinese medicine-ingredient-disease target network,and GO enrichment analysis and KEGG enrichment analysis were performed.Intraperitoneal injection of cyclophosphamide was used to construct a mouse model of immune function suppression,normal group,model control group,Gubiao Fanggan Modified Formula group and oseltamivir group were set up,followed by prophylactic administration,and influenza virus intervention was performed on the fourth day.After 7 days of intragastric administration,the key targets were verified by mouse spleen index,HE staining,RT-qPCR and immunohistochemistry.Results:There were 82 active ingredients in five traditional Chinese medicines in Gubiao Fanggan Modi-fied Formula,and 72 common targets of drugs and diseases such as IL-6,TNF-α,IL-2,etc,mainly involving IL-17,TNF and AGE-RAGE signaling pathway.Gubiao Fanggan Modified Formula could increase spleen index and significantly reduce mRNA and protein expressions of IL-6 and TNF-α in spleen tissue of mice(P<0.05 or P<0.01).Conclusion:Gubiao Fanggan Modified Formula may regulate body's immune function through targets such as IL-6 and TNF-α,thereby preventing influenza virus infection.

Objective To investigate the inhibitory effect of gallic acid(GA)on lipopolysaccharide(LPS)-induced inflammatory responses in human THP1 macrophages.Methods THP1 monocytes were differentiated into macrophages with phorbol myristate acetate.A macrophage inflammation model was established with LPS induction,and GA was added at different concentrations.The safe concentrations of LPS and GA for THP1 cells were screened using the CCK-8 method,and a normal group,model group(100 μg/L LPS),and GA group(100 μg/L LPS+different concentrations of GA)were set up.ELISA was used to detect the levels of interleukin(IL)-6,tumor necrosis factor-α(TNF-α),and IL-1β in the cell culture media of each group.The microplate method was used to detect lactate dehydrogenase(LDH)activity and NO content in the cell cultures,and fluorescence staining was used to detect the reactive oxygen species(ROS)levels,cell damage,and changes in mitochondrial transmembrane potential in each group.Western blot was performed to detect the levels of cyclooxygenase-2(COX-2),HMGB1,c-Jun amino-terminal kinase(JNK),extracellular-regulated protein kinase(ERK),P38 mitogen-activated protein kinase(P38),nuclear transcription factor-KB(NF-κB),NOD-like receptor protein 3(NLRP3),Caspase-1,IL-1β,and gasdermin D(GSDMD).Results Compared with the normal group,the model cell group's secretion of IL-6,TNF-α,IL-1β,and NO was increased(P＜0.05);the secretion of COX-2,HMGB1,p-ERK,p-JNK,and p-P38 and expression of p-NF-KB,NLRP3,Caspase-1,IL-1β were elevated(P＜0.05);expression of GSDMD protein activation fragment was reduced(P＜0.05);ROS generation and cellular damage were significantly increased;mitochondrial transmembrane potential was significantly lower;and LDH activity was elevated(P＜0.05).In comparison with the model group,the GA group cells'secretion of IL-6,TNF-α,IL-1β,and NO was decreased(P＜0.05);expression of COX-2,HMGB1,p-ERK,p-JNK,p-P38,p-NF-κB,NLRP3,Caspase-1,and IL-1β was decreased(P＜0.05);GSDMD protein activation fragment expression level was increased(P＜0.05);ROS generation and cellular damage were decreased;mitochondrial transmembrane potential gradually increased;and LDH activity was decreased(P＜0.05).Conclusions GA had an inhibitory effect on the LPS-induced inflammatory response in THP1 macrophages,and its anti-inflammatory mechanism may involve the MAPK and NF-κB signaling pathways.