AIM:To investigate the effect of fibroblast growth factor 21(FGF21)on high glucose-induced oxidative stress in retinal pigment epithelial(RPE)cells and to clarify the underlying molecular mechanisms.METHODS:Single-cell sequencing data from the GEO database were analyzed to determine the expression profile of the FGF21 receptor FGFR1 in RPE cells. Human ARPE-19 cells were cultured and randomly assigned to control, high glucose(30 mmol/L), and high glucose+FGF21 analog treatment groups, with additional siFGFR1 and PI3K inhibitor groups. Cell viability in different treatment groups was assessed using CCK-8 assay, intracellular reactive oxygen species(ROS)levels were quantified using DCFH-DA fluorescent probing combined with immunofluorescence staining and flow cytometry. Transcriptome sequencing was performed on cells from the high glucose group and high glucose+FGF21 group to analyze the enrichment level of the PI3K/Akt signaling pathway. Western blotting was performed to detect phosphorylation levels of PI3K/Akt pathway components.RESULTS:Single-cell sequencing revealed specific expression of FGFR1 in RPE cells of retinal tissues from diabetic model mice. Under In vitro experiments, high glucose(30 mmol/L)exposure reduced ARPE-19 cell viability by 49.7% and increased ROS levels by approximately 2-fold. Whereas treatment with the FGF21 analog(60 ng/mL)restored cell viability and attenuated high glucose-induced ROS accumulation. Mechanistic studies demonstrated that FGFR1 knockdown inhibited the antioxidative stress of FGF21. Further validation of the molecular mechanism revealed that high glucose significantly suppressed the PI3K/Akt pathway activation(the levels of p-Akt and p-PI3K were decreased by 33.9% and 36.6%, respectively), while FGF21 effectively reversed this inhibitory effect and restored the expression of p-Akt and p-PI3K. Treatment with the PI3K inhibitor LY294002 inhibited the cytoprotective effect of FGF21 and significantly increased the ROS-positive cells, these findings confirm that PI3K/Akt signaling is indispensable downstream mechanism for FGF21 to exert its effects.CONCLUSION:FGF21 alleviates high glucose-induced oxidative stress and cellular injury in RPE cells by activating the PI3K/Akt signaling pathway through its receptor FGFR1.

Preoperative localization of pulmonary small nodules can effectively improve the safety and success rate of video-assisted thoracoscopic surgery(VATS),but there are still controversies regarding the selection of relevant techniques.Interventional Oncology Committee of the Chinese Anti-Cancer Association organized domestic interventional radiology experts engaged in treatment of pulmonary malignancies,based on clinical experience and evidence-based medical evidence to formulate this Chinese expert consensus on preoperative auxiliary localization techniques for VATS of pulmonary small nodules.

Preoperative localization of pulmonary small nodules can effectively improve the safety and success rate of video-assisted thoracoscopic surgery(VATS),but there are still controversies regarding the selection of relevant techniques.Interventional Oncology Committee of the Chinese Anti-Cancer Association organized domestic interventional radiology experts engaged in treatment of pulmonary malignancies,based on clinical experience and evidence-based medical evidence to formulate this Chinese expert consensus on preoperative auxiliary localization techniques for VATS of pulmonary small nodules.

Depression is a chronic brain dysfunctional disease mainly due tomood disorders.Currently,the pathogenesis of depression is unclear,and its pathogenesis,pathophysiology and treatment have consistently been a major focus of academic research.This review provides an overview of the role of serum inflammatory factors in the pathogenesis,diagnosis,and treatment of depression.The inflammatory factor pathway provides a theoretical basis for the development of diagnostic and therapeutic methods for depression.It is expected to provide accurate personalized treatment for patients with depression through the treatment of inflammatory factors,improve the treatment outcomest,and reduce the risk of disease progression.

Objective To explore the role and potential mechanisms of plasma-activated solution(PAS)in alleviating dextran sulfate sodium salt(DSS)-induced ulcerative colitis.Methods We constructed a DSS-induced ulcerative colitis mouse model and evaluated the effect of PAS in vivo by observing mouse weight,calculating disease activity indexes,detecting inflammatory factors and oxidative stress indicators through ELISA.We also evaluated the effect of PAS on colon cell proliferation and migration ability through clone formation experiments,scratch experiments,and used Western blotting to determine the expression levels of proliferation-related proteins.Results PAS significantly reversed DSS-induced weight loss and increased disease activity indexes in mice(P＜0.05).The serum inflammatory cytokine levels(TNF-α,IL-6 and IL-1β)in PAS group were significantly reduced compared to those in DSS group(P＜0.05).PAS treatment could improve the imbalance of colonic redox homeostasis including changes of malondialdehyde,catalase and superoxide dismutase caused by DSS(P＜0.05).After the use of endothelial nitric oxide synthase inhibitors,changes in various indicators caused by in vivo PAS disappeared(P＜0.001).The clone formation ability of colon cells was stronger in the group treated with PAS,and the expression of proliferation-related proteins increased.Cell scratch experiments suggested that intervention with PAS could reverse the decrease in cell migration ability caused by lipopolysaccharide(P＜0.001).After the application of endothelial nitric oxide synthase inhibitors,the pro-proliferative and migratory effects of PAS disappeared(P＜0.05).Conclusion PAS alleviate DSS-induced colitis in mice and promote colonic epithelial cell repair through the eNOS pathway.

Objective To explore the application of plasma-activated solution(PAS)in the treatment of peritoneal metastasis in mice.Methods A mice model of peritoneal tumor transplantation was established,and PAS was prepared for intervention in the mice.The growth of the peritoneally transplanted tumor was assessed using in vivo imaging technology,while the apoptosis level was evaluated through flow cytometry,immunofluorescence,and Western blotting.Results At the in vitro level,there was no significant impact on tumor cell apoptosis level under adherent conditions observed when utilizing PAS(P＞0.05).Under non-adherent condition,PAS significantly augmented tumor cell apoptosis level(P＜0.05),substantially increased the proportion of deceased cells(P＜0.05),and markedly elevated intracellular total and mitochondrial reactive oxygen species levels(P＜0.05).In vivo level,using PAS following peritoneal transplanted tumor formation exhibited no noteworthy influence on peritoneal transplanted tumor growth(P＞0.05),while immediate utilization of PAS during model conducting effectively reduced abdominal tumor spread(P＜0.05).Conclusion PAS inhibits tumor peritoneal dissemination in mice by promoting tumor cell anoikis.

The effectiveness of reperfusion therapy in patients with mild non-disabling stroke still lacks sufficient evidence. Especially for patients with mild non-disabling stroke who have multiple risk factors or large vessel occlusion, whether they can benefit from intravenous thrombolysis and endovascular treatment remains an important issue to be addressed in current clinical research. This article reviews the research progress on reperfusion therapy for acute mild non-disabling stroke.

Objective:To investigate the factors influencing the metastasis of right-sided lymph nodes posterior to right recurrent laryngeal nerve (LN-prRLN) in patients with papillary thyroid microcarcinoma (PTMC) at cN 0 stage, to construct a nomogram prediction model for metastasis of right-sided LN-prRLN in patients with PTMC at cN 0 stage and to provide the decision reference for the dissection of right-sided LN-prRLN. Methods:A retrospective case-controlled study was conducted. The clinical data of patients receiving right-sided LN-prRLN dissection in Baoding No.1 Central Hospital between January 2023 and June 2024 were collected. All patients were divided into the metastatic group and the normal group according to whether metastasis of right-sided LN-prRLN would happen after the postoperative pathological examination. The differences in the clinicopathological characteristics between the 2 groups were compared, and multivariate logistic regression model was used to screen out the independent risk factors influencing right-sided LN-prRLN. A nomogram prediction model for metastasis of right-sided LN-prRLN based on independent risk factors was built; taking the postoperative pathological examination results as the gold standard, the receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the model in determining the metastasis of right-sided LN-prRLN. Bootstrap internal validation method was used for random sampling to calculate the consistency index (CI) of the model. The calibration curves and clinical decision curves were drawn to respectively verify the calibration degree of the model and the clinical application ability of the model.Results:All 235 patients included 57 males (24.3%) and 178 females (75.7%). The age was (39±13) years old and 47 cases (20.0%) out of 235 patients had the metastasis of right-sided LN-prRLN. The proportion of patients characterized by male, right-sided tumors, tumor diameter > 0.5 cm, extrathyroidal invasion, metastasis of right-sided lymph nodes anterior to right recurrent laryngeal nerve (LN-arRLN) in the metastatic group was higher than that in the normal group, and the differences were statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that male ( OR = 3.705, 95% CI: 1.133-12.116, P = 0.030), right-sided tumors ( OR = 5.610, 95% CI: 1.811-17.381, P = 0.003), the increased tumor diameter ( OR = 3.504, 95% CI: 1.169-10.507, P = 0.025), extrathyroidal invasion ( OR = 2.812, 95% CI: 1.026-7.708, P = 0.044) and right-sided LN-arRLN metastasis ( OR = 10.522, 95% CI: 3.237-34.199, P < 0.001) were independent risk factors of the metastasis of LN-prRLN in PTMC patients at cN 0 stage; based on the above independent risk factors, a nomogram prediction model was established. The ROC curve showed that the area under the curve of the nomogram prediction model for determining the metastasis of right-sided LN-prRLN in PTMC patients at cN 0 stage was 0.864 (95% CI: 0.794-0.935), Youden index was 0.735, the optimal cut-off value was 4.562, the corresponding sensitivity was 87.0%, and the corresponding specificity was 86.5%, which indicated a high predictive value of the nomogram model. Bootstrap test internal validation showed that the CI was 0.810 (95% CI: 0.763-0.917). Calibration curves showed that bias-corrected line was close to the ideal line, indicating a good consistency ( P = 0.347). Decision curve showed a good clinical efficacy. Conclusions:Male, right-sided tumors, the increased tumor diameter, extrathyroidal invasion and right-sided LN-arRLN metastasis are independent risk factors for right-sided LN-prRLN metastases in patients with PTMC at cN 0 stage. The nomogram prediction model based on the above factors has a good predictive performance, which is helpful for surgeons to make clinical decisions.

Depression is a chronic brain dysfunctional disease mainly due tomood disorders.Currently,the pathogenesis of depression is unclear,and its pathogenesis,pathophysiology and treatment have consistently been a major focus of academic research.This review provides an overview of the role of serum inflammatory factors in the pathogenesis,diagnosis,and treatment of depression.The inflammatory factor pathway provides a theoretical basis for the development of diagnostic and therapeutic methods for depression.It is expected to provide accurate personalized treatment for patients with depression through the treatment of inflammatory factors,improve the treatment outcomest,and reduce the risk of disease progression.

The primary intravenous anesthetics employed in clinical practice encompass dexmedetomidine (Dex), propofol, ketamine, etomidate, midazolam, and remimazolam. Apart from their established sedative, analgesic, and anxiolytic properties, an increasing body of research has uncovered neuroprotective effects of intravenous anesthetics in various animal and cellular models, as well as in clinical studies. However, there also exists conflicting evidence pointing to the potential neurotoxic effects of these intravenous anesthetics. The role of intravenous anesthetics for neuro on both sides of protection or toxicity has been rarely summarized. Considering the mentioned above, this work aims to offer a comprehensive understanding of the underlying mechanisms involved both in the central nerve system (CNS) and the peripheral nerve system (PNS) and provide valuable insights into the potential safety and risk associated with the clinical use of intravenous anesthetics.
Animals ; Humans ; Anesthetics, Intravenous/adverse effects* ; Neuroprotective Agents/pharmacology* ; Propofol ; Neurotoxicity Syndromes/prevention & control* ; Central Nervous System/drug effects* ; Dexmedetomidine