Objective: To explore the dynamic developmental trajectories of college students class belongingness during their college years and its longitudinal predictive effects on depressive symptoms, so as to provide targeted insights for precise campus psychological interventions. Methods: In October 2021 (T1), a total of 4 720 college students from a university in Shandong Province were selected by cluster sampling method and followed up for 3 years. Surveys were conducted annually (T2: October 2022, T3: October 2023, T4: October 2024). The Class Belongingness Scale and Patient Health Questionnaire-9 (PHQ-9) were used to assess students class belongingness and depressive symptoms. Latent growth mixture modeling was employed to identify trajectories of class belonging, and multinomial Logistic regression analysis was used to examine the predictive effects of these trajectory classes on depressive symptoms. Results: Mean scores of class belongingness across T1-T4 were (73.24±11.95, 74.76±12.25, 75.25±12.38, 77.64±11.63), and the scores of depressive symptoms were [1.00 (0, 5.00), 0 (0, 3.00), 0 (0, 2.00), 0 (0, 2.00)]. The developmental trajectories of class belongingness were categorized into three types: the high-starting ascending group ( 56.61 %), the low-starting descending group (11.91%), and the medium-starting stable group (31.48%). Multinomial Logistic regression analysis showed that, compared to the medium-starting stable group, the high-starting ascending group had a lower probability of developing mild depressive symptoms ( OR=0.27, 95%CI =0.15-0.47) and moderate or above depressive symptoms ( OR=0.29, 95% CI = 0.14-0.60) (both P <0.05). Conversely, the low-starting descending group had a higher probability of developing mild depressive symptoms ( OR=2.31, 95%CI =1.65-3.22) and moderate or above depressive symptoms ( OR=7.49, 95%CI = 3.82-14.69) (both P <0.05). Conclusion Declining trajectory of class belongingness is a risk factor for depressive symptoms, while sustained upward trend may mitigate such risks.

Ecoflex is a commercial designation for elastomers developed based on the principles of environmental sustainability and flexibility. Various manufacturers offer different types of Ecoflex products with distinct compositions and functions. Among these, the platinum-catalyzed silicone rubber Ecoflex series has demonstrated considerable applicability in various fields of oral medicine due to its excellent flexibility, biocompatibility, stability across a wide temperature range, and tunable mechanical properties. In tissue engineering, it can simulate the mechanical behavior of oral mucosa, and is used in cleft lip surgical training models and preoperative evaluation for temporal bone defect reconstruction. In the field of wearable devices, leveraging its encapsulation protection and flexible characteristics, highly sensitive sensors constructed from Ecoflex can monitor signals such as oral bite force and masticatory muscle activity, thereby aiding in the diagnosis of temporomandibular joint disorders and postoperative evaluation of cleft lip and palate. Moreover, when combined with bio-waste materials, it promotes the functionalization and sustainability of oral wearable devices.In drug delivery systems, its conformability and controlled-release capability address challenges in localized oral drug administration. Designs such as flexible microneedles and temperature-responsive composite systems provide precise solutions for treating periodontitis and oral ulcers. In minimally invasive surgical instruments, its softness enables the development of soft robots and magnetically controlled microfluidic valves, enhancing surgical safety and precision. In the field of oral rehabilitation, Ecoflex soft liner materials, inspired by the suction cup structure of octopus tentacles, improve denture retention. Their low modulus reduces mucosal irritation, ensuring both comfort and durability. Although Ecoflex shows great potential in biomedical applications, it still faces certain challenges, particularly regarding long-term stability after implantation, mechanical fatigue resistance, and microbial colonization, which require further investigation. In the future, with advancements in 3D printing technology, Ecoflex is expected to achieve more precise clinical translation across multiple fields and drive innovation in intelligent biomaterials.

The liver is the largest visceral organ in the human body, responsible for multiple important functions such as metabolism, detoxification, nutrient storage, and immune regulation. Hepatocytes located along the portal-central vein axis have heterogeneity in gene expression and function, which led to the concept of liver zonation. Cells in different regions play different roles in metabolic processes, and the coordination and cooperation between these cells are crucial for maintaining normal liver function. In recent years, the advancements in single-cell genomics and spatial transcriptomics technologies have significantly improved our understanding of liver zonation. This article summarizes the important role of metabolic zonation in maintaining liver function and its relationship with disease and aging, providing a theoretical basis for further research and therapeutic strategies.

BACKGROUND:U937 cells can be used as a cell model for studying the biological characteristics,signaling pathways,and therapeutic targets of acute myeloid leukemia.Although it has been reported that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia,its biological function in U937 cells remains unclear,and its mechanism of action in the occurrence and development of acute myeloid leukemia needs to be further clarified. OBJECTIVE:To investigate the expression level of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia and its effect on the proliferation and apoptosis of U937 cells. METHODS:RNA-sequencing was used to analyze the bone marrow monocyte samples from acute myeloid leukemia patients,and the differentially expressed gene long non-coding RNA KIAA0125 was screened.The expression of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia was detected by qRT-PCR.The relationship between long non-coding RNA KIAA0125 mRNA expression and prognosis in bone marrow cells of 173 acute myeloid leukemia patients and 70 healthy people was statistically analyzed by GEPIA database.Subsequently,recombinant lentivirus technology and CRISPR/Cas9-SAM technology were used to construct U937 cell lines with knockdown/overexpression of long non-coding RNA KIAA0125.qRT-PCR was used to detect the knockdown/overexpression efficiency of long non-coding RNA KIAA0125.Next,CCK-8 assay,flow cytometry,and western blot assay were used to detect the effects of knockdown/overexpression of long non-coding RNA KIAA0125 on the proliferation and apoptosis of U937 cells.Finally,western blot assay was used to detect the effect of knockdown/overexpressed long non-coding RNA KIAA0125 on Wnt/β-catenin signaling pathway-related proteins. RESULTS AND CONCLUSION:(1)The results of qRT-PCR showed that long non-coding RNA KIAA0125 was highly expressed in peripheral blood of acute myeloid leukemia patients.The results of GEPIA database showed that long non-coding RNA KIAA0125 was highly expressed in bone marrow cells of acute myeloid leukemia patients,and the high expression group had worse overall survival.(2)The knockdown efficiency of long non-coding RNA KIAA0125 in knockdown group was 70%,and the U937 cells that stably down-regulated long non-coding RNA KIAA0125 expression were successfully constructed.The expression of long non-coding RNA KIAA0125 in overexpression group was four times that of vector group,and stable U937 cells were successfully constructed.(3)Knockdown of long non-coding RNA KIAA0125 inhibited the proliferation of U937 cells and promoted their apoptosis.Overexpression of long non-coding RNA KIAA0125 promoted the proliferation of U937 cells but had no significant effect on the apoptosis of U937 cells.(4)Knockdown of long non-coding RNA KIAA0125 inhibited the activity of Wnt/β-catenin signaling pathway,while overexpression of long non-coding RNA KIAA0125 activated Wnt/β-catenin signaling pathway.These results confirm that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia peripheral blood.Long non-coding RNA KIAA0125 may affect the proliferation and apoptosis of U937 cells by regulating the Wnt/β-catenin signaling pathway,and may be a potential prognostic marker for acute myeloid leukemia.

Objective:To explore the relationship between gut microbiota and giant cell arteritis (GCA), and to identifyits potential therapeutic strategies.Methods:Gut microbiota data were obtained from the MiBioGen consortium genome-wide association study (GWAS), and GCA data were obtained from the FinnGen consortium public GWAS. Causal associations between gut microbiota and GCA were assessed using two-sample Mendelian randomization (MR) analyses, including inverse-variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods. Heterogeneity and horizontal pleiotropy were evaluated, and false positive results were excluded by using the Benjamini-Hochberg (BH) method of multiple hypothesis testing. All analyses were completed using the TwoSampleMR and MRPRESSO software packages (version 4.3.0) in R language. The analysis of the intestinal flora data, followed by conducting network pharmacology analysis were carried out by Cytoscape 3.9.1 and perform molecular docking verification was performed with AutoDock Vina software.Results:IVW simulations revealed 13 gut microbiota taxa were associated with GCA, of which Lachnospiraceae was significantly negatively associated with GCA risk[nSNP=16, OR(95% CI)=0.32(0.16, 0.63), β=-1.15, Se=0.35, P=0.001, FDR<0.05], and there was no heterogeneity (Cochran′s Q test, Q=13.42, P=0.490) as well as horizontal pleiotropy ( P=0.370). Further literature search and computer simulation docking analysis showed that genistein binds to MMP2 with a binding energy of -43.1 kJ/mol. Conclusion:Lachnospiraceae in the gut microbiota was is negatively associated with GCA, and genistein may be able to regulate the abundance of Lachnospiraceae through the MMP2 target to treat GCA, providing a new therapeutic approach for giant cell arteritis.

Objective To investigate the mechanism by which AGE receptor(RAGE)antagonist FPS-ZM1 inhibits AGE accumulation and promotes wound repair in rats with diabetic foot ulcer(DFU).Methods A total of 30 SD rats were divided into normal control(Con)group,sham operation group(Sham),DFU group,FPS-ZM1 treatment group(DFU+FPS-ZM1),and phosphate buffer saline treatment group(DFU+PBS),with 6 rats in each group.Masson staining was used to evaluate the wound surface structure.ELISA was used to detect the expression of AGE,TNF-α,matrix metalloproteinase 9(MMP-9),and VEGF proteins in serum and tissues,and Western blot method was used to test the expression of RAGE,VEGF receptor(VEGFR),CD31,and nuclear factor κB(NF-κB)proteins.Results Compared with the Con and Sham groups,the collagen fibers had less indigo staining,disordered arrangement and sparse distribution in DFU group.Compared with the DFU and DFU+PBS groups,the DFU+FPS-ZM1 group showed obvious blue staining of collagen fibers in the wound granulation tissue,and the number of deposition layers was relatively neat and orderly.Compared with Sham group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues were increased(P<0.05),and the expressions of VEGF protein and CD31 and VEGFR proteins in serum and tissues were decreased in DFU group(P<0.05).Compared with DFU group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues decreased(P<0.05),and the expression of VEGF protein and CD31 and VEGFR proteins in serum and tissues increased in DFU+FPS-ZM1 group(P<0.05).Compared with DFU+FPS-ZM1 group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues increased(P<0.05),and the expressions of VEGF protein,CD31 and VEGFR proteins in serum tissues decreased in DFU+PBS group(P<0.05).Conclusions The RAGE antagonist FPS-ZM1 down-regulates MMP-9 and up-regulates VEGF by inhibiting the NF-κB inflammatory signaling pathway,and promotes DFU wound healing.

Schizophrenia is a chronic and debilitating mental disorder.Around 20%to 40%of patients do not respond well to normal antipsychotic medication,and are ultimately diagnosed with treatment-resistant schizophrenia(TRS),representing the most severe and challenging form of schizophrenia.Currently,clozapine is the standard treatment for TRS.Early identification and standardized treatment can be beneficial to patients with TRS by controlling acute-phase symptoms as soon as possible,reducing suicidal rate and improving their quality of life.Under the guidance of the Steering Committee,this consensus was formed after multiple discussions by 30 psychiatric experts and anonymous Delphi surveys including 17 consensus opinions on treatment-resistant schizophrenia,which cover risk factors and prevention,diagnosis and evaluation,standardized clozapine treatment and management of adverse reactions,treatment regimens for clozapine resistance and intolerance,and psychosocial intervention,etc.The consensus-making process also incorporated evidence-based medicine to help standardize and guide diagnosis and treatment for adults with TRS in China.

Objective To investigate the mechanism by which AGE receptor(RAGE)antagonist FPS-ZM1 inhibits AGE accumulation and promotes wound repair in rats with diabetic foot ulcer(DFU).Methods A total of 30 SD rats were divided into normal control(Con)group,sham operation group(Sham),DFU group,FPS-ZM1 treatment group(DFU+FPS-ZM1),and phosphate buffer saline treatment group(DFU+PBS),with 6 rats in each group.Masson staining was used to evaluate the wound surface structure.ELISA was used to detect the expression of AGE,TNF-α,matrix metalloproteinase 9(MMP-9),and VEGF proteins in serum and tissues,and Western blot method was used to test the expression of RAGE,VEGF receptor(VEGFR),CD31,and nuclear factor κB(NF-κB)proteins.Results Compared with the Con and Sham groups,the collagen fibers had less indigo staining,disordered arrangement and sparse distribution in DFU group.Compared with the DFU and DFU+PBS groups,the DFU+FPS-ZM1 group showed obvious blue staining of collagen fibers in the wound granulation tissue,and the number of deposition layers was relatively neat and orderly.Compared with Sham group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues were increased(P<0.05),and the expressions of VEGF protein and CD31 and VEGFR proteins in serum and tissues were decreased in DFU group(P<0.05).Compared with DFU group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues decreased(P<0.05),and the expression of VEGF protein and CD31 and VEGFR proteins in serum and tissues increased in DFU+FPS-ZM1 group(P<0.05).Compared with DFU+FPS-ZM1 group,the expressions of AGE,TNF-α and MMP-9 proteins,NF-κB and RAGE proteins in serum and tissues increased(P<0.05),and the expressions of VEGF protein,CD31 and VEGFR proteins in serum tissues decreased in DFU+PBS group(P<0.05).Conclusions The RAGE antagonist FPS-ZM1 down-regulates MMP-9 and up-regulates VEGF by inhibiting the NF-κB inflammatory signaling pathway,and promotes DFU wound healing.

Schizophrenia is a chronic and debilitating mental disorder.Around 20%to 40%of patients do not respond well to normal antipsychotic medication,and are ultimately diagnosed with treatment-resistant schizophrenia(TRS),representing the most severe and challenging form of schizophrenia.Currently,clozapine is the standard treatment for TRS.Early identification and standardized treatment can be beneficial to patients with TRS by controlling acute-phase symptoms as soon as possible,reducing suicidal rate and improving their quality of life.Under the guidance of the Steering Committee,this consensus was formed after multiple discussions by 30 psychiatric experts and anonymous Delphi surveys including 17 consensus opinions on treatment-resistant schizophrenia,which cover risk factors and prevention,diagnosis and evaluation,standardized clozapine treatment and management of adverse reactions,treatment regimens for clozapine resistance and intolerance,and psychosocial intervention,etc.The consensus-making process also incorporated evidence-based medicine to help standardize and guide diagnosis and treatment for adults with TRS in China.

The liver is the largest visceral organ in the human body, responsible for multiple important functions such as metabolism, detoxification, nutrient storage, and immune regulation. Hepatocytes located along the portal-central vein axis have heterogeneity in gene expression and function, which led to the concept of liver zonation. Cells in different regions play different roles in metabolic processes, and the coordination and cooperation between these cells are crucial for maintaining normal liver function. In recent years, the advancements in single-cell genomics and spatial transcriptomics technologies have significantly improved our understanding of liver zonation. This article summarizes the important role of metabolic zonation in maintaining liver function and its relationship with disease and aging, providing a theoretical basis for further research and therapeutic strategies.