Phakic intraocular lens implantation has become one of the important means of correcting refractive errors today. Among them,the implantable collamer lens(ICL)is favored for its wide range of correction, excellent optical quality, and high safety, but the risks of postoperative complications such as glaucoma and anterior subcapsular opacification still exist. Vault is an important indicator for evaluating the safety after ICL implantation, and its ideal state is crucial for preventing complications. Studies have shown that iris morphology has a significant impact on vault. In order to further optimize surgical outcomes and improve surgical safety, this review comprehensively reviews the research progress of iris-related parameters in ICL implantation and discusses the importance of various parameters in preoperative evaluation and postoperative follow-up.

OBJECTIVES: To investigate the role and mechanism of copper overload-mediated endoplasmic reticulum stress (ERS) in vascular endothelial injury in Kawasaki disease (KD). METHODS: Four-week-old male C57BL/6 mice were randomly divided into four groups: control, KD, KD plus copper chelator tetrathiomolybdate (TTM), and KD plus ERS inhibitor AMG PERK 44 (AMG) (n=20 per group). A KD mouse model was established using Candida albicans extract. Human umbilical vein endothelial cells (HUVECs) were divided into control (intervention with healthy children's serum), KD (intervention with KD patients' serum), and KD+TTM (intervention with KD patients' serum plus 20 µmol/L TTM). Copper deposition in mouse heart tissue was assessed using rubeanic acid staining. Vascular pathological changes were observed using hematoxylin-eosin staining and measurement of abdominal aortic diameter and area. ERS activation was detected by transmission electron microscopy and immunofluorescence. HUVEC viability, apoptosis, and functional changes were evaluated using CCK8, flow cytometry, cell scratch assay, and angiogenesis experiments. ERS marker protein expression levels were measured by Western blot. RESULTS: Compared to the KD group, the KD+TTM and KD+AMG groups showed reduced copper deposition in the vascular wall, decreased swelling of coronary endothelial cells and endoplasmic reticulum, reduced inflammatory cell infiltration, and less abdominal aortic lesion expansion. The abdominal aortic diameter and area, and the fluorescence intensity of ERS marker proteins (GRP78 and CHOP) were significantly lower (P<0.05). Compared to the KD group, the KD+TTM group exhibited increased cell viability, tube number, and scratch healing rate, along with decreased apoptosis rate and expression of ERS marker proteins (GRP78, CHOP, ATF6, and p-PERK) (P<0.05). CONCLUSIONS Copper overload aggravates vascular endothelial injury in KD by activating the ERS pathway. TTM can exert protective effects on the endothelium by regulating copper metabolism and inhibiting the ERS pathway.
Endoplasmic Reticulum Stress ; Copper/toxicity* ; Male ; Mucocutaneous Lymph Node Syndrome/metabolism* ; Animals ; Humans ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Mice ; Human Umbilical Vein Endothelial Cells ; Apoptosis ; Endothelium, Vascular/injuries*

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

Objective To develop a preoperative question prompt list(QPL)for older patients with benign prostatic hyperplasia(BPH)and evaluate its effectiveness in application.Methods This trial adopted a randomized controlled design.The QPL was developed by literature review,expert discussions,and Delphi consultation.Convenience sampling was used to subject 76 older BPH inpatients treated in our department,and then they were randomly divided into control(routine communication,n=38)and intervention(QPL-assisted communication,n=38)groups.Number of the questions patient asking,communication duration,information recall,and communication quality were compared between the 2 groups.Results In the 2 rounds of expert consultation,the response rate of questionnaire was 94.44%and 100%,the authority coefficient was 0.89 and 0.93,the coefficient of variation was 0.05～0.22 and 0～0.11,and Kendall's coefficients was 0.645(Chi-square=87.782,P<0.001)and 0.733(Chi-square=74.789,P<0.001),respectively.The final QPL included 3 themes and 7 questions.The intervention group asked more questions(4.03±1.89 vs 2.11±1.27,P<0.05)but spent similar time for communication(8.18±2.11 vs 7.67±1.72 min,P>0.05).At 1 d before discharge,better information recall(8.74±1.12 vs 6.49±1.68,P<0.001)and communication quality(60.06±6.25 vs 54.86±7.98,P<0.05)were observed in the intervention group when compared with the control group.Conclusion Our developed preoperative communication QPL is of scientificalness and effectiveness for elderly BPH patients.This tool can not only encourage question-asking behavior,but also improve information recall and communication quality in the patients.

A new method was developed for simultaneous and efficient determination of linear perfluorooctanoic acid(n-PFOA)and linear perfluorooctane sulfonate(n-PFOS),and their typical branched isomers in seawater by online solid phase extraction-liquid chromatography-tandem mass spectrometry(Online SPE-LC-MS/MS).Only centrifugation of the seawater sample was required to remove the particulate matter,and then the seawater sample was directly injected and analyzed by online SPE-LC-MS/MS.An Eclipse Plus-C18 guard column was selected as SPE column for online enrichment of linear and branched isomers,and a F5 PFP column(150 mm×2.1 mm,2.7 μm)was used as the analytical column.Under the optimized experimental conditions,the separation and detection of all PFOA and PFOS linear and branched isomers could be completed within 20 min.The spiked recoveries of various target compounds ranged from 82.9%to 107.7%with detection limits and limits of quantification of 0.10-1.05 ng/L and 0.30-2.11 ng/L,respectively.The method was characterized by good precision(RSD≤9.10%)and linearity(R2≥0.990).Subsequently,linear and branched isomers of PFOA and PFOS in surface and bottom seawater samples collected from the Laizhou Bay of China were determined.The results showed that the detection rate of all the four branched PFOA isomers were 100%,with the highest average concentration of 25.85 ng/L found for 6m-PFOA,which accounted for 11.79%of the∑PFOA.For the five branched isomers of PFOS,the highest detection rate of 90.84%was found for 5m-PFOS.The highest average concentration of 0.64 ng/L was observed for 3m-PFOS,accounting for 19.88%of ∑PFOS.The proposed method provided an effective detection tool for qualitative and quantitative detection of PFOA and PFOS isomers in the marine aquatic environment.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Objective To investigate the effect of Euphorbia helioscopia on biological behaviors of non-small cell lung cancer(NSCLC)cells.Methods NSCLC cell lines PC-9 and A549 treated with different concentrations of Euphorbia helioscopia preparations were examined for changes in proliferation,apoptosis,invasion and migration using CCK-8 assay,colony formation assay,flow cytometry,wound healing assay and Transwell assay.Western blotting was performed to detect the changes in protein expressions of Bax,Bcl-2,E-cadherin,vimentin,MMP2,and MMP9 in the treated cells.PC-9 cells were injected subcutaneously into BALB/C nude mice to establish a nude mouse subcutaneous tumor model.According to the growth of subcutaneous tumors,mice were randomly divided into control group:gavaged daily with saline;Euphorbia helioscopia-treated group:gavaged daily with Euphorbia helioscopia 65 mg/mL,and Euphorbia helioscopia granules were dissolved in saline;cisplatin-treated group:injected intraperitoneally with cisplatin 4 mg/kg every 5 days,6 mice per group.The subcutaneous tumor volume and mass changes of mice were measured,and the toxic effects of Euphorbia helioscopia on heart,liver,spleen,lung and kidney as well as the therapeutic effects of Euphorbia helioscopia were observed in the mice bearing tumor.Results Euphorbia helioscopia granules concentration-dependently inhibited the proliferation and survival of PC-9 and A549 cells,significantly promoted cell apoptosis,suppressed invasion and migration abilities of the cells,up-regulated the expression levels of E-cadherin and Bax,and down-regulated the expressions of Bcl-2,vimentin,MMP2,and MMP9.In the tumor-bearing mice,treatment with Euphorbia helioscopia significantly inhibited tumor growth without producing obvious toxicity in the vital organs.Conclusion Euphorbia helioscopia can inhibit proliferation,invasion,and migration and induces apoptosis of NSCLC cells in vitro.

Objective Traditional Chinese medicine(TCM)has precise traits and advantages in the scientific prevention and remedy practice of diabetic gastroparesis(DGP).The review gathered and reviewed the research on the therapy of DGP with TCM in current years.It was once located that it performed an essential function by regulating Cajal interstitial cells,enteric nervous system,gastrointestinal hormones and gut microbiota.The research development of the mechanism and effect of TCM in the treatment of DGP were respectively reviewed from the above factors,providing thoughts and scientific foundation for the prevention and treatment of DGP.

Objective To explore the influencing factors of microcirculation dysfunction in patients with anterior wall acute myocardial infarction(AMI)and to establish a relevant prediction model.Methods A total of 130 patients with anterior wall AMI,whose microcirculation function was assessed by caIMR after receiving percutaneous coronary intervention(PCI)at Shanghai Sixth People's Hospital of China from January 2017 to September 2020,were enrolled in this study.The patients were divided into abnormal microcirculation resistance group(n=52)and normal microcirculation resistance group(n=78).The clinical data were compared between the two groups.The regression analysis was used to analyze the influencing factors of microcirculation dysfunction.Results In the abnormal microcirculation resistance group the contrast agent consumption,the onset-to-operation time,the Gensini total score and the LAD Gensini score were(121.92±31.37)mL,(10.51±5.12)min,(97.91±31.77)points and(69.36±13.15)points respectively,which were significantly higher than(109.03±28.2)mL,(4.94±2.94)min,(81.05±35.22)points and(54.45±23.48)points respectively in the normal microcirculation resistance group,the differences in the above indexes between the two groups were statistically significant(all P＜0.05).A prediction model covering interventional strategies was established,and its accuracy was higher than that of a conventional model,its AUC compared with the conventional model was 0.91 to 0.87,indicating that this model could well predict the risk of microcirculation dysfunction in patients with AMI after receiving PCI.Conclusion This prediction model can promptly identify high-risk microcirculation dysfunction patients with anterior wall AMI after receiving PCI.