In recent years, the incidence of myopia has been increasing alongside the growing global population, emerging as a significant public health challenge worldwide. Individuals with myopia exhibit an elongated axial length, which leads to various structural and functional ocular changes, resulting in the risk of related eye diseases and, in severe cases, blindness. Unfortunately, once myopia develops, it is irreversible. The only way to prevent or slow its progression is through appropriate treatment. The current focal point in myopia prevention and control is the peripheral myopic defocus theory. This paper summarizes the relevant research on defocus incorporated multiple segments(DIMS)lenses, following a systematic analysis of the literature. It analyzes the advantages and disadvantages of DIMS compared to other myopia control methods, and discusses the application prospects and future directions of defocus lenses represented by DIMS, aiming to provide reference and guidance for the control of myopia progression in children and adolescents.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To explore the impact of pembrolizumab combined with chemotherapy on angiogenesis and circulating endothelial cells in patients with advanced non-small cell lung cancer (NSCLC) .Methods:The retrospective analysis of clinical data from 121 patients diagnosed with advanced NSCLC who were admitted to the Second Affiliated Hospital of Xingtai Medical College from August 2021 to January 2023 was conducted. These patients were divided into a control group ( n=57) and an observation group ( n=64) based on the designated treatment protocol. Specifically, individuals in the control group received standard chemotherapy (cisplatin+paclitaxel), while those in the observation group underwent penpilimab therapy in conjunction with conventional chemotherapy. The comparative assessment encompassed short-term clinical efficacy, quality of life, immune function parameters, angiogenic factors [including endostatin, insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF) ], circulating endothelial cells, and adverse reactions within the two groups. Results:After 6 courses of treatment, the objective response rate [67.19% (43/64) vs. 49.12% (28/57) ] and disease control rate [87.50% (56/64) vs. 70.18% (40/57) ] in observation group were higher than those in control group, with statistically significant differences ( χ2=4.06, P=0.044; χ2=5.52, P=0.019). The quality of life score of observation group [ (56.77±6.81) points] was significantly higher than that of control group [ (47.73±8.23) points], with a statistically significant difference ( t=6.61, P<0.001) ; The T cell subgroup CD3 + levels [ (63.59±9.00) % vs. (53.06±8.80%), t=6.49, P<0.001], CD4 + levels [ (46.54±8.20) % vs. (30.74±7.32) %, t=11.13, P<0.001] and CD4 +/CD8 + ratio (1.90±0.36 vs. 1.21±0.28, t=11.66, P<0.001) in observation group were significantly higher than those in control group, with statistically significant differences; Endostatin in observation group [ (48.99±3.43) μmol/L] was significantly higher than that in control group [ (31.35±3.87) μmol/L], with a statistically significant difference ( t=26.58, P<0.001), IGF-1 [ (102.31±20.35) μg/L vs. (134.98±19.02) μg/L] and VEGF [ (31.70±4.32) pg/ml vs. (58.71±5.99) pg/ml] were significantly lower in observation group than those in control group, with statistically significant differences ( t=18.73, P<0.001; t=28.14, P<0.001). The number of circulating endothelial cells in observation group [ (58.77±10.03) /ml] was significantly lower than that in control group [ (87.01±8.01) /ml], with a statistically significant difference ( t=17.20, P<0.001). During treatment, there were no statistically significant differences in the incidence of gastrointestinal reaction ( χ2=0.01, P=0.908), leukopenia ( χ2=0.64, P=0.424), thrombocytopenia ( χ2=0.28, P=0.597), anemia ( χ2=1.66, P=0.197), nephrotoxicity ( χ2=0.64, P=0.424), skin rash ( χ2=1.33, P=0.249) between the two groups. Conclusion:The combination therapy of pembrolizumab and chemotherapy for the treatment of advanced NSCLC has demonstrated noteworthy effectiveness. This regimen has the potential to enhance patients' immune functionality, ameliorate their overall quality of life, suppress angiogenesis, and exhibits a commendable profile of safety and reliability.

Objective To study the brain functional connectivity(FC)changes in patients with normal tension glau-coma(NTG)and healthy volunteers using FC technique of resting-state functional magnetic resonance imaging(rs-fMRI)based on V1 region seed point(ROI),so as to explore the pathogenesis and early diagnosis of NTG.Methods Fourteen NTG patients(NTG group)who met the inclusion criteria and 14 healthy controls(HCs group)were enrolled.The clinical data of all subjects were collected,and rs-fMRI was performed in both groups.The magnetic resonance data was pre-pro-cessed by software,and bilateral A1 regions were taken as the ROI to analyze their correction with the whole brain voxel time series and obtain the FC value between the ROI and the whole brain by comparison of FC values in resting state be-tween the groups.Pearson correlation analysis was used to explore the relationship between FC value in the brain regions with significant differences with the ROI and clinical variables in the NTG group.Results Compared with the subjects in the HCs group,there were no statistically significant differences in age,gender,body weight,cup-disc ratio and 24 h mean intraocular pressure of patients in the NTG group(all P＞0.05),and there were statistically significant differences in the best corrected visual acuity(BCVA)of both eyes and peripapillary retinal nerve fiber layer thickness(RNFLT)(all P＜0.05).The Pearson correlation analysis showed that FC value of the brain regions with abnormal FC to V1 region were cor-related with RNFLT in the NTG group(P＜0.05).ROI1-left superior frontal gyrus,ROI1-right superior frontal gyrus,ROI2-left cingulate gyrus and ROI2-right middle frontal gyrus were significantly positively correlated with RNFLT(all P＜0.05).Compared with the HCs group,the brain regions with reduced FC to the right ROI in the NTG group were the left superior frontal gyrus and right superior frontal gyrus;the brain regions with reduced FC to the left ROI were the left cingulate gyrus and right middle frontal gyrus.Conclusion Compared to healthy individuals,NTG patients have significant changes in the functional connections between certain specific brain regions and V1 region,including bilateral superior frontal gyrus,left cingulate gyrus,and middle frontal gyrus.The changes in brain functional activity may be caused by visual dysfunction caused by NTG,leading to functional impairment of the visual and cognitive emotion processing brain regions,which may be one of the potential neuropathological mechanisms in NTG patients.

AIM:Given the uncertain impact of osmotic pressure on embryoid body(EB)differentiation,this study aimed to investigate the effects of increased osmotic pressure on EB differentiation and explore the potential relation-ship between this process and cadherin.METHODS:Polhethylene glycol 300(PEG 300)was used to increase the os-motic pressure of the culture medium used for cultivating EBs under both high osmotic pressure and standard culture condi-tions.The experimental design included a control group,an experimental group(hypertonic group),groups treated with varying concentrations of PEG 300,and an experimental group treated with an inhibitor.Western blot,RT-qPCR,AM/PI staining,CCK-8,and immunocytochemical staining was used to analyze the cell viability and the expression of CDH1 and CDH2 markers of the three germ layers,and pluripotency markers within the EBs.RESULTS:Hypertonicity did not af-fect cell viability.Significant differences were observed in the expression of the cadherin proteins CDH1 and CDH2 in EBs between the experimental and control groups;however,no cleartrend towards an EMT shift was observed.Specifically,CDH2 expression was significantly down-regulated in experimental group,showing a clear correlation with variations in os-motic pressure.Moreover,compared with control group,pluripotency markers in the EBs from experimental group exhibited significantly higher expression levels from the 2nd day to the 5th day.A substantial increase in the expression of mesoder-mal markers was also observed;however,a downward trend was observed for ectodermal markers in experimental group.Intervention using SB431542,which up-regulates CDH2 expression by affecting TGF-β signaling,reversed the expression trend of mesodermal and ectodermal markers in experimental group.CONCLUSION:Elevated osmotic pressure appears to enhance the mesodermal differentiation efficiency in EBs,possibly correlating with CDH1 and CDH2 changes induced by osmotic pressure.Therefore,this study emphasizes the significant role of osmotic pressure in stem cell applications.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Abstract Prevention and control of myopia requires comprehensive measures. Based on the system established earlier, the system is revised and upgraded. The original system emphasizes comprehensive measures and proposes to focus on both the symptoms and root causes. These measures are summarized into six aspects, three address the root cause measures including health education, glasses optics and visual environment, and three address symptoms measures including eye exercises, physical therapy and drugs. The paper is comprehensively supplemented and analyzes the primary and the secondary, and promotes physical therapy from treating the symptoms to treat both the symptoms and the root causes. These improvement measures will help promote the prevention and control of myopia in children and adolescents.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.