Objective: To investigate the current status of benefit finding among young and middle-aged patients with type 2 diabetes mellitus (T2DM) and analyze its influencing factors, so as to provide a reference for improving the level of benefit finding in this population. Methods: From November 2022 to May 2023, young and middle-aged patients with T2DM aged 18-59 years hospitalized in the endocrinology departments of 2 tertiary hospitals in Hengyang City, Hunan Province were selected as survey subjects by a convenience sampling method. Basic demographic information was collected using a general questionnaire survey. Benefit finding, resourcefulness, and stigma were evaluated using the Benefit Finding Scale, the Chinese Version of the Resourcefulness Scale, and the Type 2 Diabetes Stigma Assessment Scale, respectively. A multiple linear regression model was used to analyze the influencing factors of benefit finding among young and middle-aged patients with T2DM. Results: A total of 305 young and middle-aged patients with T2DM were investigated, including 222 males (72.79%) and 83 females (27.21%). There were 231 cases aged 45-59 years, accounting for 75.74%. The scores for benefit finding, resourcefulness, and stigma were (42.86±6.06), (75.12±11.30), and (41.20±10.10), respectively. Multiple linear regression analysis showed that young and middle-aged patients with T2DM who were male (β′=0.088), aged 18-<45 years (β′=0.083), absence of diabetes complications (β′=0.124), and had higher resourcefulness scores (β′=0.679) had higher levels of benefit finding, while patients with higher stigma scores (β′=-0.097) had lower levels of benefit finding. Conclusion The level of benefit finding among young and middle-aged patients with T2DM was moderate, and was related to gender, age, diabetes complications, resourcefulness, and stigma.

Objective To investigate the relationship between cyclin A2 (CCNA2) and the prognosis of colon cancer, and its possible mechanism from the perspective of immune infiltration. Methods We downloaded the transcriptome data of colon cancer patients from The Cancer Genome Atlas database. Clinicopathological feature analysis and survival analysis were performed based on the expression levels of CCNA2. A total of 75 specimens of colon cancer and normal tissues were collected, and the expression level of CCNA2 was analyzed using immunohistochemical methods. Multivariate analysis was conducted to explore its relationship with clinicopathological features. Gene Set Enrichment Analysis (GSEA) was used to assess the potential molecular functions of CCNA2 in colon cancer. CIBERSORT algorithm was applied to calculate the correlation between CCNA2 and immune-cell infiltration in colon cancer. Results Database and immunohistochemical analyses indicated that CCNA2 was expressed at a significantly higher level in colon cancer tissues than normal tissues (P<0.001). The overall survival, disease-specific survival, and progression-free interval were all longer in the group with high CCNA2 expression than the group with low expression (all P<0.05). In tumor tissues, the expression level of CCNA2 decreased with increased pathological and TNM stages (P<0.05). The expression level of CCNA2 in normal tissues was consistently lower than that in colon cancer tissues across all clinical stages (all P<0.001). GSEA suggested that Wnt/β-catenin, KRAS, and other signaling pathways were enriched when CCNA2 was lowly expressed. CIBERSORT analysis revealed an increase in the infiltration of immune cells such as regulatory T cells and macrophages M0 when CCNA2 expression was low. Conclusion CCNA2 is highly expressed in colon cancer and closely associated with grade of pathology and TNM stage. It may recruit regulatory T cells through the KRAS and Wnt/β-catenin pathways, thereby reducing immune-cell infiltration and promoting colon cancer progression, leading to poor prognosis.

Objective To explore the clinical and immunological significance of CCDC97 in hepatocellular carcinoma (HCC). Methods Clinical data and RNA sequencing results from HCC patients were retrieved from TCGA and ICGC databases. Bioinformatics analysis and in vitro experiments were performed to investigate the role of CCDC97 in HCC. Results The expression level of CCDC97 was elevated in HCC patients and HCC cells, closely associated with pathological features and prognosis. CCDC97 was identified as a novel prognostic biomarker. It is linked to the spliceosome pathway, which is significantly active in tumors and potentially promotes carcinogenesis. CCDC97 is also highly expressed in various immune cells and is associated with microenvironment. Furthermore, knocking down CCDC97 in vitro suppressed cell migration, invasion, and proliferation. Conclusion CCDC97 plays a critical role in HCC progression and the immune microenvironment, making it a potential target for prognosis and therapeutic intervention.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Tumor Microenvironment/genetics* ; Cell Movement/genetics* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/genetics* ; Male

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective This study aims to compare the accuracy of self-developed universal implant guide(SDG),3D printed digital guide(DG),and free hand(FH)simulated implantation in the posterior tooth area of dental models.Methods Ten junior dentists were selected to place three implants in the 35,37,and 46 tooth sites of the mandibular models(35,36,37,and 46 missing teeth)by using SDG,DG,and FH,and the process was repeated again to take the av-erage value.Cone beam computed tomography(CBCT)was used to evaluate the global coronal deviation,global apical deviation,depth deviation,and angular deviation between the actual position and preoperative planned position.Re-sults The coronal deviation and apical deviation of the three implant sites in the SDG group were not significantly dif-ferent from those in the two other groups(P>0.05).The depth deviation and angular deviation in the SDG group were smaller than those in the DG group(P<0.05)and FH group(P<0.05),respectively.All deviations at site 37 in the SDG group were not different from those at site 35(P>0.05),while the depth and angular deviation at site 37 in the DG group were higher than those at site 35(P<0.05).Conclusion The precision of the self-developed universal dental im-plant guide can meet the requirements of clinical posteri-or implantation.

Osteosarcoma,which primarily affects children and adolescents,is a highly malignant bone tumor with high rates of disability and mortality.Therefore,the exploration of biological markers related to its occurrence,development,and prognosis is crucial.Genome-wide association studies have revealed the vital role of genetic polymorphisms in the pathogenesis of osteosarcoma.This study aims to provide new insights into reliable biomarkers of osteosarcoma through the analysis of the functional single-nucleotide polymor-phisms of tumor-related genes.

Insulin resistance （IR） is an important pathological and physiological mechanism of type 2 diabetes （T2DM）， and the treatment of IR has become the key to the prevention and treatment of T2DM. IR is a state of insensitivity or reduced sensitivity of insulin-stimulated tissue cells to glucose， resulting in cells that are unable to efficiently take up glucose in the bloodstream and thus causing hyperglycemia. Adenosine monophosphate-activated protein kinase （AMPK） is an energy-sensing enzyme that can regulate multiple metabolic pathways and maintain the stability of adenosine triphosphate （ATP） in the cell. In recent years， traditional Chinese medicine （TCM） has played an increasingly important role in the prevention and treatment of T2DM. The research on exploring the AMPK signaling pathway of TCM intervention in the progress of T2DM has gradually increased. Many pharmacological studies have shown that TCM has advantages such as safety and high efficiency in the prevention and treatment of T2DM. AMPK signaling pathway is one of the key pathways for the active ingredients of TCM and TCM extracts to improve IR. Active ingredients such as phenols， flavonoids， polysaccharides， alkaloids， and saponins， as well as other herbal extracts can improve IR by activating the AMPK signaling pathway cascade response， thereby improving IR by regulating glucolipid metabolism， inhibiting inflammatory response， anti-oxidative stress and maintaining mitochondrial homeostasis. Based on this， this paper reviews the pharmacological and experimental research results of TCM intervening the AMPK signaling pathway to improve IR in recent years， expecting to provide reference for further research， development and application of TCM in intervening IR and treating T2DM.

OBJECTIVE To investigate the mechanism of catalpol affecting the differentiation of helper T cell 17 （Th17） by interfering the expressions of pyruvate kinase M2 （PKM2） and lactate dehydrogenase A （LDHA）. METHODS The naive CD4+ T cells were selected from the spleen of C57BL/6 mice， and were differentiated into Th17 cells by adding directional differentiation stimulants for 72 hours. At the same time， the cells were treated with 0 （directed control）， 20， 40 and 80 μg/mL catalpol. The flow cytometry was used to detect the proportion of Th17 cell differentiation in cells； the colorimetric method was adopted to detect the levels of pyruvate and lactate in cell culture supernatant； mRNA expressions of retinoid-related orphan nuclear receptor gamma t （RORγt）， PKM2 and LDHA were detected by qRT-PCR method； Western blot was used to detect the expression levels of PKM2， LDHA， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated STAT3 （p-STAT3） proteins in cells. RESULTS Compared with the directed control group， after 72 hours of treatment with 20， 40， 80 μg/mL catalpol， the differentiation ratio of Th17 cells were decreased by 6.74%， 8.41%， 9.24%， and the levels of pyruvate and lactate in the cell culture supernatant， the mRNA expressions of PKM2， LDHA and RORγt as well as the protein expressions of PKM2 and LDHA and the phosphorylation of STAT3 were significantly reduced （P＜0.05）. CONCLUSIONS Catalpol can reduce the glycolysis level by down-regulating the expressions of PKM2 and LDHA， thereby inhibiting the differentiation of Th17 cells.

This study was designed to explore the correlation between alterations in NLRP3 levels and Th17/Treg imbalance in asthmatic mice undergoing epithelial-mesenchymal transition(EMT).A murine model of asthma was established by intraperitoneal injection combined with nebulization of ovalbumin(OVA).Mice were randomly grouped into asthma model group and normal control group.The airway reactivity was detected with non-invasive lung function instrument.Hematoxylin and Eosin(HE)and Masson's trichrome staining were applied to evaluate the histopathological injury of lung tissue and the extent of lung fibrosis;RT-qPCR was applied to detect EMT-related biomarkers(Snail,E-Cadherin,N-Cadherin),the specific transcription factors of T cell subsets(RoRγt,Foxp3)and NLRP3 in lung tissue of mice;Western blot was used to detect the protein expression of E-cadherin,N-Cadherin and NLRP3 in lung tissue of mice.The Th17 and Treg cell populations in the spleen were enumerated via flow cytometry.Furthermore,the expression levels of NLRP3,IL-17 and IL-10 in bronchoalveolar lavage fluid(BALF)were analyzed by Giemsa staining.Compared with the control group,the asthma model group showed higher level of airway resistance,coupled with an obviously decrease in pulmonary ventilation compliance.Pathological alterations in lung tissue were evident,characterized by thickening of the airway epithelium,airway stenosis,infiltration of inflammatory cells,higher expression levels of N-Cadherin and NLRP3 proteins(P<0.05),lower expression level of E-Cadherin(P<0.001)and higher levels of marker genes(Snail and N-Cadherin)in lung tissue.Furthermore,model mice demonstrated higher level of NLRP3 in BALF(P<0.05),higher level of Th17 in spleen,and higher levels of retinoic acid orphan receptor(ROR)-γt mRNA(P<0.05)and Th17-related cytokines(IL-17)(P<0.01).Concurrently,model mice also showed an obviously decrease in the prevalence of Treg cells,Forkhead box Foxp3 mRNA(P<0.001),and Treg-related cytokine IL-10(P<0.05).The results of the Pearson correlation analysis indicated that the level of NLRP3 mRNA was positively correlated the ratio of RoR γt mRNA,but negatively correlated with Foxp3 mRNA in the lung tissue of asthmatic mice.Additionally,NLRP3 in BALF demonstrated a positive correlation with IL-17 and a negative correlation with IL-10.In conclusion,These findings suggest that NLRP3 may trigger bronchial EMT by exacerbating the immune imbalance of Th17/Treg cells.

Dendrobium is one of the valuable Chinese herbs in China,and Dendrobium officinale is the top grade of Dendrobium,which is recorded in many ancient medical texts as having the efficacy of treating diabetes.Modern pharmacological research shows that Dendrobium has the effects of anti-tumor,anti-fatigue,immune regulation,anti-aging,and regulation of glycolipid metabolism.In clinical application,Dendrobium officinale also has the function of balancing glucose and lipid metabolism,improving insulin resistance,promoting insulin secretion,improving the function of islet cells,and has a certain role in the prevention and treatment of diabetic complications.At present,there is a lack of systematic review of the pharmacological mechanism of Dendrobium officinale in the treatment of diabetes.In order to understand the pharmacological action of Dendrobium officinale in the treatment of diabetes more comprehensively,and to provide a reference for further pharmacological research,so that it can be better applied in clinics,this paper reviews the research progress of the pharmacological mechanism of Dendrobium officinale in the treatment of diabetes.