The mitochondrial unfolded protein response(UPRmt)represents a crucial intracellular stress response mechanism that plays a fundamental role in maintaining mitochondrial and cellular homeostasis. Growing evidence suggests that dysregulation of UPRmt contributes significantly to the pathogenesis of various systemic disorders, including neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, as well as age-related pathologies. Emerging research has particularly highlighted the involvement of UPRmt in ocular diseases, including cataracts, glaucoma, and diabetic retinopathy. This comprehensive review examines the physiological functions of UPRmt and its regulatory mechanisms in age-related eye diseases. The roles of key UPRmt downstream effector molecules in ocular cell populations such as lens epithelial cells, retinal pigment epithelial cells, and retinal ganglion cells are systematically analyzed. Importantly, the dual regulatory nature of UPRmt in ocular pathophysiology is discussed, that is, its moderate activation promotes mitochondrial homeostasis, mitigates oxidative stress, and suppresses inflammatory responses, its chronic or excessive activation triggers apoptotic pathways, induces metabolic dysfunction, and ultimately accelerates disease progression. By elucidating these mechanisms, our review provides novel insights into ocular disease pathogenesis and proposes potential therapeutic strategies targeting UPRmt modulation for the prevention and treatment of age-related eye disorders.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

Objective To investigate the role of scar epithelial cells and its potential molecular mechanisms in the efficacy of low-energy CO2 fractional laser treating post-burn scars.Methods The model of post-major burn scars on the back of rat was established.Three rats with post-major burn scars received 30 mJ low-energy CO2 fractional laser treatment to detect the activation of scar epidermal cells.Epidermal tissue of scars was isolated for RNA sequencing to screen activated pathways.Subsequently,18 rats with post-major burn scars were randomly divided into 3 groups(n=6):the control group without laser treatment,the laser group receiving 30 mJ CO2 fractional laser treatment,and the laser+inhibitor group receiving laser treatment and intra-scar injection of IWR-1(a Wnt/β-catenin pathway inhibitor),to verify the activation status and effects of the selected pathways.Hematoxylin-eosin staining,Masson staining,and Western blotting were used to detect the proliferation of epithelial cells and fibroblasts,the activation of Wnt/β-catenin pathway,as well as the improvement of scar profiles.Results After low-energy laser treatment,there was a significant increase in the number of Ki67-positive,proliferating cell nuclear antigen(PCNA)-positive,cytokeratin 19(CK19)-positive,and p63-positive cells in the scar epithelial tissue.RNA sequencing coupled with literature analysis identified Wnt/β-catenin pathway as a potential candidate pathway.In the confirmatory experiment,compared to the control group,the Wnt/β-catenin pathway was activated in scar epithelial cells in the laser group 5 d post-laser intervention.After 30 d laser intervention,dermal collagen exhibited a more loosened arrangement,with reduced dermal thickness and significantly less α-smooth muscle actin(α-SMA)-positive fibroblasts compared to the control group.CollagenⅠ,collagen Ⅲ,and the relative ratio of collagen Ⅰ to Ⅲ in the laser group were at a lower level than those in the control group.Administration of the Wnt/β-catenin pathway inhibitor blocked the activation of the Wnt/β-catenin pathway induced by low-energy laser,the proliferation of scar epithelial cells and the improvement of scar profiles.Conclusion Low-energy CO2 fractional laser treatment can activate the Wnt/β-catenin pathway of scar epithelial cells,thereby activating epithelial cells and yielding significant scar improvements.

Objective To compare the clinical efficacy of pulmonary artery thrombus aspiration plus catheter-directed thrombolysis and pulmonary artery thrombus aspiration plus peripheral venous thrombolysis in treating acute intermediate-high-risk pulmonary embolism.Methods The clinical data of patients with acute intermediate-high-risk pulmonary embolism,who received pulmonary artery thrombosis aspiration combined with catheter-directed thrombolysis or peripheral venous thrombolysis at the Affiliated Hospital of Nantong University and the Qidong Municipal People's Hospital from January 2017 to May 2024,were retrospectively analyzed.Based on the propensity score matching(PSM)method,the clinical efficacy of the two treatments was compared.The observation indicators included technical success rate,clinical success rate,changes in cardiopulmonary function,and incidence of complications.Results After propensity score matching,the pulmonary artery thrombosis aspiration combined with catheter-directed thrombolysis group(group A)and the pulmonary artery thrombosis aspiration combined with peripheral venous thrombolysis group(group B)had 40 patients each.In group A and group B,the technical success rate was 100％and 100％respectively,the clinical success rate was 97.5％and 87.5％respectively,and the clinical success rate was 97.5％and 87.5％respectively(P=0.201);the postoperative one-week mean oxygen partial pressure was(98.4±16.4)mmHg and(95.5±14.7)mmHg respectively(P＜0.001);the postoperative one-week mean pulmonary artery pressure was(26.3±10.5)mmHg and(28.5±11.8)mmHg respectively(P=0.005);the mean reduction value of B-type natriuretic peptide(BNP)level was(767.2±1 005.5)ng/L and(831.0±1 371.8)ng/L respectively(P＜0.001).No statistically significant difference in the incidence of surgery-related complications existed between the two groups(P＞0.05).Conclusion In treating patients with acute intermediate-high-risk pulmonary embolism,pulmonary artery thrombosis aspiration combined with catheter-directed thrombolysis is superior to pulmonary artery thrombosis aspiration combined with peripheral venous thrombolysis in better short-term efficacy.

Background::Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods::GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice ( Grk2?SM22), and littermate controls ( Grk2flox/flox) were grouped into control and hypoxia mice ( n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results::The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2?SM22 mice compared with littermate controls. The amelioration of PH in Grk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion::Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

Objective:A dose verification system of two-dimensional semiconductor matrix(SRS MapCHECK)was used to verify the dose of the clinical treatment plan of patients who underwent CyberKnife(CK),which realized rapid verification for individualization of radiotherapy plans of patients through analyzed the γ-passing rates of them.Methods:A total of 253 patients with tumor who received CK clinical treatment in the First Medical Center of Chinese PLA General Hospital from March 2021 to May 2023 were selected.Among of them,121 cases received CK treatment on head,and 30 cases received that on lung,and 102 cases received CK treatment on abdomen and other metastatic tumor.In the MultiPlan treatment plan system,the plan of patient was mapped to the integrated model composed of StereoPHAN model and SRS MapCHECK matrix dose verification system by the means of the plan image center overlap.The dose verification was conducted on the plan of each patient on the basis of ensuring the consistency of the number of beam,direction of beam and the monitor unit.The different γ analysis standards(1%/1 mm,2%/1 mm,3%/1 mm,1%/2 mm,2%/2 mm,3%/2 mm,1%/3 mm,2%/3 mm and 3%/3 mm)were adopted to conduct global analysis of absolute dose for each verification plan,and the threshold(TH)of low dose was set as 10%.Results:The γ passing rates of phantom verification plans of 253 patients were respectively(88.64±5.91)%,(95.43±3.40)%,(97.90±2.06)%,(96.51±2.35)%,(98.15±1.68)%,(99.06±1.12)%,(98.30±1.39)%,(99.09±0.97)%and(99.52±0.63)%under different analysis standards.The γ passing rates of other standards of patients with tumor on different parts were larger than 95%except the analysis result of 1%1 mm standard.The overall analysis result of the deviation of central point dose was(-1.30±2.17)%,among of which the tumor of head,abdominal tumors and other metastatic tumor were about approximately-2%,while that of lung tumors were approximately-3%.The deviation of abdominal and other metastatic tumor was the minimum.The correlation analysis showed that the target volume and the size of the minimum collimator were respectively correlated to the dose deviation of the center.Conclusion:SRS MapCHECK dose verification system can conveniently and quickly realize the individualized verification for the plan of patients who receive CK treatment.

Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.

Objective:To evaluate the efficacy and safety of sodium hyaluronate gel in preventing adhesion after prophylactic enterostomy.Methods:One hundred and twenty four patients from 6 hospitals were enrolled in this prospective multi-center randomized controlled trial. Patients were randomized into the study group ( n=59) or the control group ( n=65).All patients underwent prophylactic enterostomy. Patients of study group received odium hyaluronate gel for adhesion-prevention,while those in control group did not receive any adhesion-prevention treatment. The incidence of moderate to severe adhesion around the incision in the stoma area were evalutated during stoma reduction surgery. Results:The incidence of moderate to severe adhesion around the incision in the stoma area was 6.3% in the study group, the difference was statistically significant ( P<0.05) compared to that of the control group (32.6%). Conclusion:Sodium hyaluronate gel can safely and effectively reduce the incidence of moderate and severe adhesions after abdominal surgery.

Purpose: Various types of trauma can cause retinal hemorrhages in children, including accidental and nonaccidental head trauma. We used animal eyes and a finite element model of the eye to examine stress patterns produced during purely linear and angular accelerations, along with stresses attained during simulated repetitive shaking of an infant. Methods: Using sheep and primate eyes, sclerotomy windows were created by removing the sclera, choroid, and retinal pigment epithelium to expose the retina. A nanofiber square was glued to a 5 mm2 area of retina. The square was pulled and separated from vitreous while force was measured. A finite element model of the pediatric eye was used to computationally measure tension stresses during shaking. Results: In both sheep and primate eyes, tension stress required for separation of retina from vitreous range from 1 to 5 kPa. Tension stress generated at the vitreoretinal interface predicted by the computer simulation ranged from 3 to 16 kPa during a cycle of shaking. Linear acceleration generated lower tension stress than angular acceleration. Angular acceleration generated maximal tension stress along the retinal vasculature. Linear acceleration produced more diffuse force distribution centered at the poster pole. Conclusions The finite element model predicted that tension stress attained at the retina during forcible shaking of an eye can exceed the minimum threshold needed to produce vitreoretinal separation as measured in animal eyes. Furthermore, the results show that movements that involve significant angular acceleration produce strong stresses localized along the vasculature, whereas linear acceleration produces weaker, more diffuse stress centered towards the posterior pole of the eye.

Objective:To compare the prognosis of patients with unilateral sporadic medullary thyroid carcinoma treated by different surgical selection, and analyze the independent risk factors affecting the prognosis.Methods:One hundred and twenty-six patients at Tianjin Medical University Cancer Institute and Hospital from Feb 2011 to Oct 2018 were retrospectively divided into group A (total thyroiclectomy) and group B (unilateral lobectomy).Results:There were no significant differences in postoperative recurrence rate ( χ2=0.394, P=0.530), mortality ( χ2=3.175, P=0.146), biochemical cure rate ( χ2=0.613, P=0.434), progression free survival and overall survival ( P=0.278, 0.175) between group A and group B; Tumor diameter ≥4 cm and lateral cervical lymph node metastasis were independent risk factors affecting the overall survival. The incidence of postoperative temporary hypocalcemia ( χ2=5.068, P=0.024) and permanent hypocalcemia ( χ2=6.590, P=0.010) in group A was higher than that in group B. Conclusions:Ipsolateral thyroidectomy can be applied to patients with unilateral sporadic medullary thyroid carcinoma with similar long term prognosis and tower incidence of temporary hypocalcemia and permanent hypocalcemia compared to total thyroidectomy.