Objective: To analyze the changes in classroom lighting environment of schools in Suzhou and their impact on refractive progression among primary and secondary school students, so as to provide the basis for accurate provention and control of myopia. Methods: A baseline investigation was conducted in October 2022 by using a stratified cluster random sampling method to recruit primary and secondary school students from Suzhou. A follow up visit was performed in October 2023. A total of 12 302 students and 360 classrooms that participated in both surveys were included analysis. The visual acuity progression over one year and classroom lighting conditions were assessed. Group comparisons were performed by using the Wilcoxon or Kruskal-Wallis rank-sum, and Chi-square tests. Multivariate Logistic regression was employed to identify the major factors influencing refractive changes. Results: The compliance rate of average illuminance on classroom blackboard surface increased from 72.22% to 75.28%, while the compliance rate of average illuminance on desks decreased from 89.44% to 87.22%, the overall myopia rate among students rose from 59.63% to 66.99% from 2022 to 2023. The average annual progression of equivalent spherical power(SE) in the right eye of students was -0.25(-0.75,0.06)D. Significant statistical differences were observed in the annual mean changes across different school levels, regions, baseline refractive statuses, and classroom lighting environment change groups ( Z/H =316.59, -8.27, 38.80 , 51.01, all P <0.05). Multivariate Logistic regression analysis showed that pre myopia, low myopia, junior high school, senior high school, vocational high school, and improved classroom lighting environment were protective factors of reducing the risk of rapid progression in refractive error ( OR =0.58, 0.69, 0.81, 0.50, 0.28, 0.82, all P <0.05). Conversely, female students and rural students had higher risks of rapid myopia progression ( OR =1.09, 1.42, both P <0.05). Conclusions Over one year follow up, the complance rate of classroom lighting indicators in Suzhou remaines stable, while students refractive status shows a trend toward myopia. Improving classroom lighting environment can reduce the risk of rapid myopia progression.

Glaucoma is the leading cause of irreversible blindness worldwide, with its primary risk factor arising from elevated intraocular pressure (IOP) due to an imbalance between aqueous humor production and outflow. This study aims to establish quantitative correlations among IOP, iris mechanical properties, channel microstructures, and aqueous humor dynamics through three-dimensional modeling and finite element analysis, overcoming the limitations of conventional experimental techniques in studying aqueous flow within the trabecular meshwork (TM) outflow pathway. A three-dimensional fluid-structure interaction (FSI) model incorporating the layered TM structure, Schlemm's canal (SC), iris, and other anterior segment tissues was developed based on human ocular anatomy. FSI simulations were performed to quantify the effects of IOP variations and iris Young's modulus on tissue morphology and aqueous humor dynamics parameters. The computational results demonstrated that axial iris deformation showed significant correlations with IOP and iris Young's modulus. Although elevated IOP exhibited minimal effects on hydrodynamic parameters in the anterior and posterior chambers, it markedly suppressed aqueous flow velocity in the TM region. Additionally, wall shear stress in SC and collector channels displayed high sensitivity to IOP variations. These findings reveal that the tissue mechanics-FSI mechanism modulates outflow resistance by regulating aqueous humor dynamics, offering valuable references for developing clinical therapies targeting IOP reduction in glaucoma management.
Humans ; Trabecular Meshwork/anatomy & histology* ; Finite Element Analysis ; Aqueous Humor/metabolism* ; Intraocular Pressure/physiology* ; Glaucoma/physiopathology* ; Iris/anatomy & histology* ; Computer Simulation ; Models, Biological

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
Animals ; Microglia/immunology* ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/immunology* ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotective Agents/administration & dosage* ; Interleukin-1beta/genetics* ; STAT3 Transcription Factor/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Nitric Oxide Synthase Type II/genetics* ; Lipopolysaccharides

Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

Objective To explore whether hepatocyte Perilipin-2(Plin2)is involved in the development of fatty liver related to comparative gene identification-58(CGI-58)deficiency mice and compare the effects of Plin2 and Plin3 on lipid droplet formation and lipid accumulation.Methods Based on CGI-58Flox/Flox mice as animal model,the adeno-associated viruses targeting mouse liver,CGI-58 knockout and Plini2 knockdown were achieved by co-expression Cre protein and micro-RNA targeting Plin2(Mi-KD).Then CGI-58 deficiency mice were used as control(NC)to detect the differences in metabolic phenotype and liver pathology.AML-12 mouse hepatocytes were used as cellular model and interfered with siRNA to achieve Plin2/Plin3 knockdown in AML-12 cells.Lipid droplet formation and lipid accumulation were compared with Bodipy staining and enzyme colorimetry in basal condition or lipid-overloaded condition(OA inducement)after Plin2/Plin3 knockdown.Results Plin2 knockdown(Mi-KD)reduced PLIN2 protein level by＞99％in mouse livers.Mi-KD decreased hepatomegaly(P=0.019 5)and liver injury(P=0.000 4),while reduced the histological NAS score(P=0.000 2)and hepatic triglyceride content(P=0.016 6)in the CGI-58 deficiency female mice.Mi-KD prevented microvesicular hepatic steatosis in the CGI-58 deficient female mice.Plin3 knockdown significantly reduced the triglyceride content in basal condition of hepatocytes(P=0.001 4),and Plin2 knockdown just showed a decreased trend.Plin2 or Plin3 knockdown significantly reduced the triglyceride content separately in lipid-overloaded hepatocytes(P＜0.05).Conclusion Hepatocyte Plin2 is essential in the development of microvesicular hepatic steatosis caused by CGI-58 deficiency.Both Plin2 and Plin3 are involved in lipid droplet formation and lipid accumulation in hepatocytes,and Plin3 shows a stronger effect.

Objective:To investigate the neuroprotective effect of hesperidin combined with enriched environment on ferroptosis in collagenase-induced intracerebral hemorrhage(ICH) mouse model as well as the ferroptosis mechanism.Methods:ICH model was established by injecting collagenase Ⅶ into caudate putamen nucleus. Ninty C57BL/6J mice were randomly divided into 6 groups according to a random number table: sham group, intracerebral hemorrhage group, enriched environment group, hesperidin group, enriched environment and hesperidin group (combination group), and combination group + Nrf2 specific inhibitor ML385 (inhibitor group), with 15 mice in each group. The mice in inhibitor group, intracerebral hemorrhage group, enriched environment group, hesperidin group and combination group were injected with 0.5 μL collagenase type Ⅶ solution (0.075 U/μL, dissolved with 0.9% NaCl solutin) for ICH modeling, and the mice in sham group were injected with 0.9% normal saline. The hesperidin group, combination group, and inhibitor group were given hesperidin solution (dissolved in 0.5% carboxymethyl cellulose sodium) by gavage within 6 hours after the modeling surgery. The sham group, intracerebral hemorrhage group, and enriched environment group were given equal volumes of 0.5% carboxymethyl cellulose sodium solution by gavage. The inhibitor group was intraperitoneally injected with Nrf2 specific inhibitor ML385 (30 mg/kg, dissolved in 5% DMSO), while the other groups were intraperitoneally injected with an equal volume of 5% DMSO. Both gastric perfusion and intraperitoneal injection were completed within 6 hours after the end of modeling operation, once a day for 14 days. After the postoperative recovery of the mice, the enriched environment group, combination group, and inhibitor group were placed in enriched environment cages, while the sham group, intracerebral hemorrhage group, and hesperidin group were placed in regular cages. After all intervention were completed, all mice were evaluated using the modified neurological severity score (mNSS). Then the mice were subjected to brain water content detection, Prussian blue staining, ELISA detection of changes in malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase 4 (Gpx4), PCR and Western blot detection of nuclear factor E2 related factor 2 (Nrf2) and Gpx4 at the mRNA level and protein level. The GraphPad Prism 9 software was used for statistical analysis. ANOVA was used for multi-group comparison, and Tukey test was used for multiple comparisons.Results:(1) There was a statistically significant difference in mNSS scores among the 6 groups ( F=66.35, P<0.001). The mNSS score of the intracerebral hemorrhage group(8.00±1.46) was higher than that of the sham group(0.86±0.83)( P<0.05). The mNSS scores of the enriched environment group (6.47±1.13) and hesperidin group (6.13±1.25) were lower than that of the intracerebral hemorrhage group, but higher than that of the combination group (4.53±1.30)(all P<0.05). (2) There was a statistically significant difference in the percentage of brain water content among the 6 groups ( F=33.29, P<0.001). The percentage of brain water content in the intracerebral hemorrhage group was higher than that in the sham group.The percentage of brain water content in the enriched environment group and hesperidin group were lower than that in the intracerebral hemorrhage group, but higher than that in the combination group (all P<0.05). (3) The result of Prussian blue staining showed that iron deposition in the intracerebral hemorrhage group was higher than that in the sham group, while the iron depositions in the enriched environment group and hesperidin groups were lower than that in the intracerebral hemorrhage group, but higher than that in the combination group(all P<0.05). (4) There were statistically significant differences in the expression levels of Nrf2 and Gpx4 mRNA and protein among the 6 groups ( F=27.73, 31.24, 26.79, 13.79, all P<0.001). The mRNA and protein levels of Nrf2 and Gpx4 in the combination group were higher than those in the enriched environment group, hesperidin group, but higher than those in the inhibitor group(all P<0.05). (5) The results of ELISA showed that the levels of MDA, Gpx4, ROS, and SOD in the brain tissues of 6 groups were statistically significant ( F=111.20, 21.53, 29.45, 22.75, all P<0.001). Among them, the MDA and ROS in the combination group ((14.05±0.57) nmol/mL, (75.46±3.40) ng/mL) were lower than those in the enriched environment group ((18.17±2.51) nmol/mL, (97.23±3.43) ng/mL), hesperidin group ((17.24±0.68) nmol/mL, (90.02±9.46) ng/mL) and the inhibitor group ((17.08±0.64) nmol/mL, (101.07±3.38) ng/mL), while Gpx4 and SOD ((340.40±31.21) pg/mL, (62.55±2.81) ng/mL) were higher than those in the enriched environment group ((267.81±27.17) pg/mL, (50.47±8.38) ng/mL), hesperidin group ((271.55±34.36) pg/mL, (50.55±8.19) ng/mL) and the inhibitor group ((235.65±72.54)pg/mL, (52.67±3.56)ng/mL)(all P<0.05). Conclusion:Enriched environment and hesperidin can inhibit ferroptosis after ICH by activating the Nrf2/GPX4 pathway, exerting neuroprotective effects on ICH mouse models, and the combined treatment of the enriched environment and hesperidin has a more significant effect.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.