Objective To investigate effects of Cordyceps sinensis(CS)on high glucose(HG)induced podocyte injury by regulating the adenylate activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Mouse podocytes were cultured in vitro and divided into the normal glucose(NG)group,the HG group,the HG+CS group,the HG+CS+autophagy inhibitor(HG+CS+3MA)group and the HG+CS+AMPK inhibitor(HG+CS+Compound C)group.Podocyte viability was detected by CCK-8 method.Western blot assay was used to detect the expression levels of podocyte marker proteins podocin and nephrin,autophagy-related proteins Beclin-1 and P62,and pathway related proteins p-AMPK and p-mTOR.Results Compared with the NG group,the cell viability of podocytes decreased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were decreased,and the expression levels of P62 and p-mTOR protein were increased in the HG group(P＜0.05).Compared with the HG group,the cell viability of podocytes was increased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were significantly increased(P＜0.05),and the expression levels of P62 and p-mTOR protein were decreased in the HG+CS group(P＜0.05).Compared with the HG+CS group,the cell viability decreased in the HG+CS+3MA group and the HG+CS+Compound C group(P＜0.05).Compared with the HG+CS group,the HG+CS+3MA group and the HG+CS+Compound C group showed decreased expression levels of podocin,nephrin and Beclin-1 protein,and increased expression of P62 protein(P＜0.05).Compared with the HG+CS group,the expression of p-AMPK protein decreased and the expression of p-mTOR protein increased in the HG+CS+Compound C group(P＜0.05).Conclusion Cordyceps sinensis may play a protective role in diabetic nephropathy by up-regulating AMPK/mTOR signaling pathway to induce podocyte autophagy,alleviate high glucose induced podocyte injury and apoptosis.

The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.

Recent years have witnessed significant advancements in myopia control research through the application of diffuse optical technology(DOT)spectacle lenses. Myopia has emerged as a global public health challenge, affecting nearly half of the world's population, with childhood and adolescent myopia rates continuing to rise. DOT lenses represent an innovative myopia control intervention based on retinal contrast signal theory. These lenses incorporate micro-light scattering dots distributed across the lens surface to reduce retinal imaging contrast and modulate the influence of visual input on axial elongation, thereby slowing myopia progression. The core mechanism operates through refractive index differences between the lens substrate(1.53)and scattering dots(1.50), which generate optical scattering effects. This design maintains clear vision through a central 5 mm optical zone while effectively reducing contrast signal intensity in the peripheral retina. Large-scale randomized controlled trials, including the CYPRESS study, have demonstrated significant myopia control efficacy in children aged 6-10 years: 12-month follow-up data revealed a 74% reduction in myopia progression and a 50% reduction in axial elongation, with sustained safety and visual quality maintained over 4-year long-term follow-up. However, several aspects of DOT technology remain contentious and require further clinical validation, including its applicability across different age groups, optimal scattering dot density configurations, combined application effects with other myopia control methods, and long-term visual adaptation during extended use. This review systematically examines the theoretical foundations, design characteristics, clinical application progress, and future development directions of DOT technology, providing scientific evidence for clinical myopia prevention and control strategy formulation.

Objective To investigate effects of Cordyceps sinensis(CS)on high glucose(HG)induced podocyte injury by regulating the adenylate activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Mouse podocytes were cultured in vitro and divided into the normal glucose(NG)group,the HG group,the HG+CS group,the HG+CS+autophagy inhibitor(HG+CS+3MA)group and the HG+CS+AMPK inhibitor(HG+CS+Compound C)group.Podocyte viability was detected by CCK-8 method.Western blot assay was used to detect the expression levels of podocyte marker proteins podocin and nephrin,autophagy-related proteins Beclin-1 and P62,and pathway related proteins p-AMPK and p-mTOR.Results Compared with the NG group,the cell viability of podocytes decreased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were decreased,and the expression levels of P62 and p-mTOR protein were increased in the HG group(P＜0.05).Compared with the HG group,the cell viability of podocytes was increased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were significantly increased(P＜0.05),and the expression levels of P62 and p-mTOR protein were decreased in the HG+CS group(P＜0.05).Compared with the HG+CS group,the cell viability decreased in the HG+CS+3MA group and the HG+CS+Compound C group(P＜0.05).Compared with the HG+CS group,the HG+CS+3MA group and the HG+CS+Compound C group showed decreased expression levels of podocin,nephrin and Beclin-1 protein,and increased expression of P62 protein(P＜0.05).Compared with the HG+CS group,the expression of p-AMPK protein decreased and the expression of p-mTOR protein increased in the HG+CS+Compound C group(P＜0.05).Conclusion Cordyceps sinensis may play a protective role in diabetic nephropathy by up-regulating AMPK/mTOR signaling pathway to induce podocyte autophagy,alleviate high glucose induced podocyte injury and apoptosis.

Colonoscopy serves as a modality for the early detection and removal of colorectal lesions,playing a pivotal role in colorectal cancer prevention.Health education for patients can enhance the compliance of colonoscopy,improve the participation rate,and optimize the intestinal cleanliness.High-quality bowel preparation is an important guarantee for colonoscopy and is associated with a higher detection rate of colorectal lesions.In recent years,the academic field has put forward that education should not be restricted to patients only.Educating endoscopists also plays a vital role in improving the quality of colonoscopy.The concept of"peri-colonoscopy period"encompasses the continuous process of"before,during,and after colonoscopy".This article reviewed the role and current research status of doctor-patient joint education during the peri-colonoscopy period,aiming to deepen the understanding of colonoscopy for both doctors and patients,so as to improve the quality of colonoscopy and standardize colonoscopy management.

Background:Colonoscopy is the gold standard for diagnosis of colorectal cancer,and the success of colonoscopy is highly depended on the quality of bowel preparation.Aims:To investigate the impact of the last defecation time before colonoscopy on qualities of bowel preparation and colonoscopy.Methods:Consecutive outpatients who underwent painless colonoscopy from June 2023 to December 2023 at 5 medical centers in Jiangsu Province and met the inclusion criteria were enrolled in this multicenter cross-sectional study.These patients were divided into 3 groups according to the time interval between the last defecation and the start of colonoscopy.The time interval was≤2 h,2-5 h,and≥5 h in group A,B,and C,respectively.The primary outcome was the score of the Boston Bowel Preparation Scale(BBPS),and the secondary outcomes included the cecal intubation time(CIT),withdrawal time(WT),cecal intubation length(CIL),adenoma detection rate(ADR),and polyp detection rate(PDR).Results:A total of 298 patients underwent painless colonoscopy were enrolled in the study.There were no significant differences in gender,age,body mass index,abdominal circumference,comorbidities,surgical histories,and other baseline data among the three groups.The total BBPS score declined gradually from 8.27±0.58 in group A to 8.21±0.53 in group B and 8.05±0.37 in group C(P<0.05).Segment-specific analysis showed that significant difference in bowel cleanliness only existed in right colon among the three groups(BBPS score:2.48±0.50,2.40±0.49,and 2.18±0.39,respectively,P<0.05).There were no significant differences in CIT,WT and CIL among the three groups,while the highest ADR and PDR were seen in group B(ADR:45.2%,57.5%,and 35.4%,respectively,P<0.05;PDR:53.4%,63.8%,and 43.1%,respectively,P<0.05).Conclusions:When the time interval between the last defecation and the start of colonoscopy is less than 5 h,more effective bowel preparation and higher ADR and PDR can be achieved.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

AIM: To study the early outcomes of anterior segment parameters after implantation of an implantable collamer lens with a central hole(ICL V4c)in patients with high myopia.METHODS:A total of 82 cases(160 eyes)with high myopia, including 42 males(82 eyes)and 40 females(78 eyes), aged 26.0±4.6(21 to 37)years, who underwent ICL V4c implantation at our institution from February 2019 to September 2022 and were followed up for 1 a, were included. The general characteristics of the anterior segment of the eye were measured preoperatively: spherical equivalent, mean horizontal corneal curvature, white-to-white(WTW), and axial length(AL); intraocular pressure(IOP), endothelial cell density(ECD), central anterior chamber depth(CACD), anterior chamber volume(ACV)and anterior chamber angle(ACA)were measured preoperatively and at 1 d, 1 wk, 1, 3 and 6 mo postoperatively. Furthermore, the distance from the centre of the posterior surface of the ICL V4c optical zone to the anterior surface of the lens(vault)was measured at 1 d, 1 wk, 1, 6 mo, and 1 a after surgery.RESULTS: The mean preoperative spherical equivalent of the patients was -7.56±2.55 D, mean horizontal corneal curvature was 42.89±1.47 D, WTW was 11.64±0.37 mm, and AL was 26.64±0.93 mm. The baseline IOP was 15.97±2.13 mmHg, and the differences in IOP at each time point after ICL V4c implantation compared to preoperative were not statistically significant(F=0.875, P=0.504); ECD was 2 989.30±140.78 cells/mm2 at baseline, and ECD at 6 mo after ICL V4c implantation was not statistically significant compared with preoperative ECD(t=1.475, P=0.142); CACD was 3.19±0.21 mm at baseline, and ACV was 210.30±27.7 mm3, and CACD and ACV were significantly lower than preoperative at all postoperative time points(F=111.10, 288.38, all P<0.001). The baseline ACA was 35.44°±11.27°, and the ACA at each time point after ICL V4c implantation was significantly lower than preoperatively(F=21.23, P<0.001). The vault was 665.32±184.03 μm at 1 d postoperatively, and continued to be significantly reduced at 1 wk, 1, 6 mo, and 1 a postoperatively compared with 1 d(F=52.10, P<0.001). However, it remained stable at 6 mo and 1 a postoperatively, and the difference was not statistically significant compared with vault at 1 mo postoperatively(P>0.05).CONCLUSION: ICL V4c has certain safety and efficiency in 1 a postoperative follow-up, and the parameters of the anterior segment of the eye stabilized in the early period.

Myopia is a common ophthalmic disease that endangers the health of eyes all over the world. The incidence rate of myopia is high in China. Myopia has become the most prominent problem affecting the health of young people's eyes. Myopia prevention and control work has become urgent. Periretinal hyperopia defocusing is one of the main causes of myopia, and the defocusing soft lenses involved based on this principle have played a good role in myopia prevention and control. This article summarizes the working principle of defocusing soft lenses for controlling myopia and its impact on corneal and visual function, and evaluates the prevention and control effect of defocusing soft lenses on myopia based on current research.

Objective In this study,we analyzed the transcriptome sequences of Kupffer cells exposed to simulated microgravity for 3 d and conducted biological experiments to determine how microgravity initiates apoptosis in Kupffer cells. Methods Rotary cell culture system was used to construct a simulated microgravity model.GO and KEGG analyses were conducted using the DAVID database.GSEA was performed using the R language.The STRING database was used to conduct PPI analysis.qPCR was used to measure the IL1B,TNFA,CASP3,CASP9,and BCL2L11 mRNA expressions.Western Blotting was performed to detect the level of proteins CASP3 and CASP 9.Flow cytometry was used to detect apoptosis and mitochondrial membrane cells.Transmission electron microscopy was used to detect changes in the ultrastructure of Kupffer cells. Results Transcriptome Sequencing indicated that simulated microgravity affected apoptosis and the inflammatory state of Kupffer cells.Simulated microgravity improved the CASP3,CASP9,and BCL2L11 expressions in Kupffer cells.Annexin-V/PI and JC-1 assays showed that simulated microgravity promoted apoptosis in Kupffer cells.Simulated microgravity causes M1 polarization in Kupffer cells. Conclusion Our study found that simulated microgravity facilitated the apoptosis of Kupffer cells through the mitochondrial pathway and activated Kupffer cells into M1 polarization,which can secrete TNFA to promote apoptosis.