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.

ObjectiveTo observe the clinical efficacy and safety of hot ironing with Haitongpi Formula （海桐皮方， HF） in the treatment of lumbar disc herniation （LDH） of cold-dampness obstruction type. MethodsA total of 70 patients with cold-dampness obstruction type LDH were randomly divided into a treatment group and a control group， with 35 cases in each group. Both groups received three movements technique of Qinggong Spinal Manipulation （QSM） as the basis for treatment. In addition， the treatment group received hot ironing with HF， while the control group applied Diclofenac Sodium Gel externally. The treatment duration for both groups was 14 days. The clinical efficacy was compared between groups. Japanese Orthopedic Association （JOA） score， visual analog scale （VAS） for pain， pain pressure threshold （PPT） for lumbar positive response points， and traditional Chinese medicine （TCM） symptom scores were compared， on day 7， and day 14 of treatment， as well as on day 7 and day 14 of follow-up. The lumbar curvature index （LCI） was also compared before treatment and on day 14 of treatment. Adverse reactions during the study were recorded for both groups. ResultsA total of 35 patients in the treatment group and 34 patients in the control group were included for final analysis. The clinical total effective rate of the treatment group （91.43%， 32/35） was significantly higher than that of the control group （82.35%， 28/34， P＜0.05）. Both the JOA score and PPT of the two groups increased on day 7 and day 14 of treatment， and on day 7 and day 14 of follow-up. VAS scores and TCM symptom scores both decreased. The LCI of both groups increased on day 14 of treatment （P＜0.01）. Compared with the control group at the same time points， on day 14 of treatment and day 7 and day 14 of follow-up， the treatment group had higher JOA scores and PPT， and lower VAS scores and TCM symptom scores. The LCI of the treatment group increased on day 14 of treatment （P＜0.05 or P＜0.01）. One case in the control group showed mild skin allergy， with no other adverse reactions observed in either group. ConclusionBased on three movements technique of QSM， hot ironing with HF shows better clinical efficacy than external Diclofenac Sodium Gel in the treatment of cold-dampness obstruction type LDH. It can significantly reduce lumbar pain， increase pain pressure threshold， improve clinical symptoms， lumbar function， and lumbar curvature， with good safety.

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

This study employed Mendelian randomization (MR) analysis to confirm the association between breast cancer and the risk of anxiety and depression, and to explore the molecular mechanisms by which lipid nanoparticles of ketamine (LNP@Ket) modulate these behaviors in a mouse model of breast cancer. Through single-cell transcriptomic analysis, the study aimed to clarify nuclear factor erythroid 2-related factor 2 (Nrf2)'s role in the development of anxiety and depression in these mice. Analysis of patient data from genome-wide association study (GWAS) databases supported the link between breast cancer, anxiety, and depression. In vivo experiments demonstrated that treating breast cancer mice with LNP@Ket significantly reduced anxiety and depression behaviors. The synthesis of LNP@Ket and its subsequent analysis highlighted its inhibitory effects on these behaviors. Single-cell transcriptomic sequencing identified key cells and genes affected by LNP@Ket treatment, particularly emphasizing Nrf2. Upregulation of Nrf2 in astrocytes increased the expression of antioxidant enzymes and reduced pro-inflammatory cytokines, alleviating anxiety and depression symptoms by inhibiting neuroinflammation and neurodegeneration. This comprehensive study highlights the pivotal role of Nrf2 in the therapeutic efficacy of LNP@Ket for treating anxiety and depression in breast cancer mice.

OBJECTIVES: The objective of this study is to measuring the morphology and position of bilateral temporomandibular joints in patients with unilateral and bilateral molar scissor bite and simulating the deformation of the mandible during occlusion, in order to provide thesis for the diagnosis of temporomandibular joint disease in patients with unilateral and bilateral molar scissor bite. METHODS: This study was a retrospective study. A total of 10 patients with unilateral molar scissor bite (the unilateral molar scissor bite group) and 10 patients with bilateral molar scissor bite (the bilateral molar scissor bite group) were selected as the experimental group, and 20 adult patients with classⅠ of angle classification of similar ages were selected as the control group. All patients underwent cone beam computed tomography scans, by measuring the width of the fossa, height of the fossa, articular eminence inclination, long axis of the condyle, minor axis of the condyle, horizontal angle of the condyle and the space of the temporomandibular joint, compare temporomandibular joint morphology and position. The three-dimensional finite element analysis of the mandible morphology was carried out to evaluate the force and deformation of the mandible by using software to simulate the occlusion of the patients. It was further explored the relationship between the force of the mandible morphology and the possible temporomandibular joint disorder symptoms of the patients. RESULTS: Intergroup comparisons for the unilateral molar scissor bite group and left sides of the other groups revealed that the superior articular space in the group with unilateral molar scissor bite was shorter than that in the control group (P<0.05); the long axis of the condyle in the unilateral and bilateral molar scissor bite group were both shorter than that of the control group (P<0.05); among which the unilateral group was larger than the bilateral group, and the minor axis of the condyle in bilateral molar scissor bite group was smaller than in the control group (P<0.05), and the unilateral and bilateral condylar groups were larger than the control group (P<0.05); and the condylar horizontal angle in the unilateral and bilateral groups were larger than that in the control group (P<0.05). The normal sides of the unilateral molar scissor bite group and right sides of the other groups had smaller superior articular space than the control group (P<0.05); and the condylar long-axis in bilateral group was smaller than the control group (P<0.05); and the normal side of the condylar short-axis unilateral group was larger than that of the bilateral condylar group. Three-dimensional finite element analysis: the condyle of patients with molar scissor bite was a concentrated area of deformation during the bite of the mandible, when the first molar occlusion of the scissors bite side was simulated, the maximum deformation was located in the condyle in the X-axis and Z-axis directions. The amount of deformation was greater than that of the scissor bite side in the X-axis direction, while in the Z-axis direction, the normal side was greater than the scissor bite side. The maximum sites of local deformation in the X-axis direction were located in anterior and posterior the transverse crest of scissor bite side, and the minimum sites of local deformation was at 1/3 of the anterior slope of the inner pole of the normal side, the maximum local deformation sites in the Z-axis direction were located in the outer pole and below the outer pole of the normal side. The X-axis deformation value was the largest in the molars occlusion on the normal side, the Y-axis deformation value was in the premolars occlusion on the normal side, and the Z-axis deformation value was the largest in the centric occlusion, the deformation value of the condyle was not most significant in molar scissor bite. CONCLUSIONS Unilateral and bilateral molar scissor bite resulting in a short condyle morphology, and the bilateral group had a shorter condylar morphology than the unilateral group. The condyle of the patient with molar scissor bite is a concentrated area of poor occlusal deformation, and the largest sites of deformation are distributed near the transverse ridge of the inner and outer poles of the condyle. Different occlusion conditions have an effect on condylar deformation values, but do not indicate whether there is a clear association between them.
Humans ; Finite Element Analysis ; Retrospective Studies ; Temporomandibular Joint/pathology* ; Cone-Beam Computed Tomography ; Mandible/pathology* ; Imaging, Three-Dimensional ; Adult ; Temporomandibular Joint Disorders/diagnostic imaging* ; Mandibular Condyle/diagnostic imaging* ; Female ; Male ; Molar

Post-stroke depression （PSD） represents a common and debilitating complication following stroke， substantially impeding neurorehabilitation outcomes and exerting a profound negative impact on patients' quality of life， while concurrently contributing to increased mortality rates. Despite a growing understanding of PSD， contemporary clinical management continues to encounter multifaceted challenges. This systematic review synthesizes extant literature to delineate pathophysiological mechanisms underlying PSD and to identify evidence-based interventions. By establishing a theoretical foundation， it aims to optimize early diagnostic protocols and personalized therapeutic regimens， thereby enhancing rehabilitation and therapeutic outcomes in stroke patients. Through rigorous evaluation of 14 original studies， this analysis comprehensively examines genetic factors， neurobiological aberrations， immunological factors， and psychosocial stressors contributing to PSD onset and progression， offering critical insights for developing comprehensive treatment strategies.［Funded by Science and Technology Plan Project of Yunnan Provincial Department of Science and Technology （number， 202101AY070001-048）］

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.

AIM: To investigate the preventive effect and optimal drug dose of lipoic acid-niacin(N2L)against blue light-induced retinal damage in SD rats, and to explore its possible protective mechanism.METHODS: A total of 36 specific pathogen free-grade male SD rats of 150-200 g were selected and randomly divided into normal control group, blue light injury group, N2L low-dose group(1.0 mg/kg), N2L medium-dose group(2.5 mg/kg), N2L high-dose group(5.0 mg/kg), and physiological saline group, with 6 rats in each group. The normal control group was reared in a 12 h dark and light cycle, and the rest of the groups received 9 h of daily light exposure, 3 h of blue light irradiation with a wavelength of 455 nm and an intensity of 3000±50 lx, and 12 h of darkness to establish the injury model, and were exposed to light exposure for 14 d. For 14 consecutive durations, a 1 mL dose of the corresponding drug was injected intraperitoneally. The rats were reared for another 5 d with a regular 12 h light-dark cycle and were examined by electroretinography. Specimens were prepared by over anesthesia, HE staining, and the thickness of the outer nuclear layer was observed under a optical microscope; superoxide dismutases(SOD)activity was detected by CheKineTM SOD Activity Assay Kit; and the retinal Caspase-3, quinone oxidoreductase 1(NQO1), glutathione S transferase(GST), Bcl-2, and Bax protein expression in rat retina were detected by Western blot.RESULTS: The amplitude of b-wave in dark-vision ERG 3.0 and 10.0(cd·s)/m2 stimulated light, b-wave in bright-vision ERG 3.0(cd·s)/m2 stimulated light, and the amplitude of the 2nd wave peak of oscillatory potential were significantly lower in blue light injury group than that in the normal control group(all P<0.01), while the amplitude was significantly higher in the N2L medium-dose group than in the blue light injury group(all P<0.05), and was not statistically different from that of the normal control group; the thickness of the retina in the blue light injury group was decreased in the ONL compared with that of the normal control group(P<0.001), while in the N2L medium dose group, it was thicker than that of the blue light injury group(P<0.001), and there was no statistically significant difference from the normal control group; SOD activity was significantly higher in the N2L medium-dose group than in the remaining 5 groups(P<0.05); the expression of Caspase-3, Bax, and NQO1 in the blue light injury group was higher than that of the normal control group(all P<0.01), and expression of Bax and Caspase-3 was significantly lower in the N2L medium-dose group compared with the blue light injury group(all P<0.001), whereas GST, NQO1 and Bcl-2 were significantly increased(all P<0.01).CONCLUSION:A concentration of 2.5 mg/kg N2L can effectively antagonize the damaging effect of blue light on the retina of SD rats, and it is expected to be a preventive and curative drug for it.

Very early onset inflammatory bowel disease (VEO-IBD) in children refers to an IBD with the onset age of less than 6 years old, clinically characterized by recurrent colitis, perianal lesions, and nutrient absorption disorders.Different from adults, single gene mutation plays an important role in the pathogenesis of VEO-IBD.To date, about 70 single gene defects have been identified involving the pathogenesis of VEO-IBD, including epithelial barrier, neutrophil and phagocyte function, immune cell selection and activation, immunosuppressive mechanism, or apoptosis.Interleukin-10 (IL-10) is an anti-inflammatory cytokine that regulates innate and adaptive immunity, influences the expression of pro-inflammatory molecules and the function of multiple immune cells, and plays a vital role in the development and progression of IBD.Patients with defects in the IL-10 signaling pathway (IL-10 or IL-10 receptor deficiency) may develop life-threatening colitis as early as childhood.This article reviews the progress in the pathogenesis and treatment of VEO-IBD caused by IL-10 signaling pathway defects.