AIM: To compare the efficacy of different intraocular lens(IOL)fixation in aphakic patients lacking capsule support.METHODS:Retrospective study. Totally 120 cases(120 eyes)of aphakia patients who lacked capsule support admitted to our hospital from June 2019 to June 2024 were selected as the study subjects and randomly assigned into group A and group B, with 60 cases in each group. Group A underwent subcapsular IOL deep scleral fixation, while group B underwent IOL suture suspension fixation in the ciliary groove. The surgery time, uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), intraocular pressure(IOP), corneal endothelial cell density(CECD), corneal endothelial cell loss rate, and postoperative complications were compared between the two groups before and at 1, 3, 6 mo after surgery.RESULTS:The operation time of the group A was lower than that of the group B(24.69±2.69 vs. 32.75±3.75 min, t=11.937, P<0.05). The UCVA and BCVA in both groups were better than those before operation, and the group A was better than the group B(all P<0.05). The loss rates of corneal endothelial cells in the group A were lower than those in the group B at 1, 3 and 6 mo after surgery, the IOP in the group A was lower than that in the group B at 1 mo after surgery, and the CECD in the group A was higher than the group B(all P<0.05). The 3 eyes(5.0%)of the postoperative IOL ectopic in the group A were less than 11 eyes in the group B(18.3%, P=0.023).CONCLUSION:Subcapsular IOL deep scleral fixation has prominent curative effects on aphakic patients who lack capsule support. It helps improve vision, with less operation time, and fewer postoperative complications.

The Golgi apparatus (GA) is a key membranous organelle in eukaryotic cells, acting as a central component of the endomembrane system. It plays an irreplaceable role in the processing, sorting, trafficking, and modification of proteins and lipids. Under normal conditions, the GA cooperates with other organelles, including the endoplasmic reticulum (ER), lysosomes, mitochondria, and others, to achieve the precise processing and targeted transport of nearly one-third of intracellular proteins, thereby ensuring normal cellular physiological functions and adaptability to environmental changes. This function relies on Golgi protein quality control (PQC) mechanisms, which recognize and handle misfolded or aberrantly modified proteins by retrograde transport to the ER, proteasomal degradation, or lysosomal clearance, thus preventing the accumulation of toxic proteins. In addition, Golgi-specific autophagy (Golgiphagy), as a selective autophagy mechanism, is also crucial for removing damaged or excess Golgi components and maintaining its structural and functional homeostasis. Under pathological conditions such as oxidative stress and infection, the Golgi apparatus suffers damage and stress, and its homeostatic regulatory network may be disrupted, leading to the accumulation of misfolded proteins, membrane disorganization, and trafficking dysfunction. When the capacity and function of the Golgi fail to meet cellular demands, cells activate a series of adaptive signaling pathways to alleviate Golgi stress and enhance Golgi function. This process reflects the dynamic regulation of Golgi capacity to meet physiological needs. To date, 7 signaling pathways related to the Golgi stress response have been identified in mammalian cells. Although these pathways have different mechanisms, they all help restore Golgi homeostasis and function and are vital for maintaining overall cellular homeostasis. It is noteworthy that the regulation of Golgi homeostasis is closely related to multiple programmed cell death pathways, including apoptosis, ferroptosis, and pyroptosis. Once Golgi function is disrupted, these signaling pathways may induce cell death, ultimately participating in the occurrence and progression of diseases. Studies have shown that Golgi homeostatic imbalance plays an important pathological role in various major diseases. For example, in Alzheimer’s disease (AD) and Parkinson’s disease (PD), Golgi fragmentation and dysfunction aggravate the abnormal processing of amyloid β-protein (Aβ) and Tau protein, promoting neuronal loss and advancing neurodegenerative processes. In cancer, Golgi homeostatic imbalance is closely associated with increased genomic instability, enhanced tumor cell proliferation, migration, invasion, and increased resistance to cell death, which are important factors in tumor initiation and progression. In infectious diseases, pathogens such as viruses and bacteria hijack the Golgi trafficking system to promote their replication while inducing host defensive cell death responses. This process is also a key mechanism in host-pathogen interactions. This review focuses on the role of the Golgi apparatus in cell death and major diseases, systematically summarizing the Golgi stress response, regulatory mechanisms, and the role of Golgi-specific autophagy in maintaining homeostasis. It emphasizes the signaling regulatory role of the Golgi apparatus in apoptosis, ferroptosis, and pyroptosis. By integrating the latest research progress, it further clarifies the pathological significance of Golgi homeostatic disruption in neurodegenerative diseases, cancer, and infectious diseases, and reveals its potential mechanisms in cellular signal regulation.

T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.

Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)％,(6.28±0.20)％,(24.96±1.18)％,(12.36±0.49)％,(18.76±0.68)％and(4.59±0.26)％;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.

Objective To study the pharmacokinetic characteristics of lamotrigine tablets in Chinese healthy subjects under fasting and fed conditions,and to evaluate the bioequivalence and safety profiles between the domestic test preparation and the original reference preparation.Methods Twenty-four Chinese healthy male and female subjects were enrolled under fasting and fed conditions,18 male and 6 female subjects under fasting conditions,17 male and 7 female subjects under fed conditions.A random,open,single-dose,two preparations,two sequences and double-crossover design was used.Plasma samples were collected over a 72-hour period after give the test or reference preparations 50 mg under fasting and fed conditions.The concentration of lamotrigine in plasma was detected by liquid chromatography-tandem mass spectrometry,and the main pharmacokinetic parameters were calculated to evaluate the bioequivalence by WinNonLin 8.1 program.Results The main pharmacokinetic parameters of single-dose the tested and reference preparations were as follows:The fasting condition Cmax were(910.93±248.02)and(855.87±214.36)ng·mL-1;tmax were 0.50(0.25,4.00)and 1.00(0.25,3.50)h;t1/2 were(36.1±9.2)and(36.0±8.2)h;AUC0_72h were(27 402.40±4 752.00)and(26 933.90±4 085.80)h·ng·mL-1.The fed condition Cmax were(701.62±120.67)and(718.95±94.81)ng·mL-1;tmax were 4.00(1.00,5.00)and 4.00(0.50,5.00)h;t1/2 were(44.2±12.4)and(44.0±12.0)h;AUC0-72h were(30 253.20±7 018.00)and(30 324.60±6 147.70)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax and AUC0-72 hfor the test preparation and reference preparation were all between 80.00％and 125.00％under fasting and fed conditions.Conclusion Two kinds of lamotrigine tablets are bioequivalent,and have similar safety in Chinese healthy male and female subjects under fasting and fed conditions.

Objective To explore the effect of Shexiang Baoxin pill on cardiac tissue angiogenesis in spontaneously hypertensive rats(SHR).Method Twenty 12 week old male SHR were randomly divided into experimental group and model group,with 12 week old male SD rats as the normal control group.The experimental group rats were orally administered with Shexiang Baoxin pill(45 mg·kg-1)daily,and their blood pressure was monitored using a non-invasive tail artery blood pressure gauge every four weeks.Eight weeks later,cardiac tissue was taken for platelet endothelial cell adhesion molecule-1(PECAM-1/CD31)immunofluorescence staining to observe CD31 expression level.Use protein blotting to detect the expression levels of myocardial endothelial growth factor(VEGF),myocardial endothelial growth factor receptor 2(VEGF-R2),basic fibroblast growth factor(bFGF)and phosphorylated protein kinase B(p-Akt)/protein kinase B(Akt)proteins.Result There was significant increase in blood pressure between the experimental group,model group and normal group at the same time point(all P＜0.01),but there was no statistically significant difference in blood pressure changes between the experimental group and model group at the same time point(all P＞0.05).The CD31 expression rates of the normal group,model group and experimental group were(3.79±0.84)％,(2.54±0.42)％and(3.56±0.49)％;VEGF levels were 0.95±0.10,0.73±0.08 and 0.94±0.15;VEGF-R2 levels were 0.85±0.10,0.61±0.14 and 0.80±0.10;bFGF levels were 0.84±0.04,0.51±0.21 and 0.74±0.14;p-Akt/Akt levels were 0.85±0.15,0.57±0.13 and 0.80±0.20,respectively.The differences between the normal group and the model group,as well as the experimental group and the model group,were statistically significant(all P＜0.05).Conclusion Shexiang Baoxin pill can promote the neovascularization of microvessels in the heart tissue of spontaneously hypertensive rats,and its mechanism may be related to the activation of PI3K/Akt phosphorylation,upregulation of bFGF,VEGF and their receptor VEGF-R2 in myocardial tissue.

Objective To explore the toxicity of Polygonum multiflorum alcohol extract on 3D hepatospheres.Methods Variations in culture conditions and cell ratios were implemented,followed by the assessment of cell sphere diameter,density,and roundness,aiming to explore the optimal culture conditions.The 3D hepatocyte spheres were divided into control group and experimental-L,-M,-H groups.The experimental-L,-M,-H groups were treated with 0.25,1.00 and 2.50 mg·mL-1 Polygounm multiforum alcohol extract,and the control group was given the same amount of culture medium.The cell viability of the cell spheroids was tested by CellTiter-Glo reagent,the expression level of liver function related genes was detected by fluorescent quantitative polymerase chain reaction(RT-qRCR).The toxicity of cell spheres was detected by double fluorescent staining of living and dead cells.Results The ideal culture condition of cell sphere was 500 cells per micropore,and the cell ratio was HepG2-Huvec-LX-2=8∶1∶1.It displayed the values of 0.91±0.07 for circularity,0.91±0.02 for firmness,1.12±0.14 for aspect ratio,and(170.97±14.79)μm for diameter.On the 3rd,7th,10th and 14th days,the expression levels of albumin(ALB)mRNA were 1.00±0.02,0.96±0.02,0.54±0.07,0.52±0.07,and the expression levels of cytochrome P450 1A2(CYP1A2)mRNA were 1.00±0.10,2.15±0.16,2.45±0.33,1.30±0.03,respectively.The expression levels of multidrug resistance protein 2(MPR2)in the control group and the experimental-L,-M,-H groups were 1.00±0.31,1.38±0.24,1.48±0.06 and 1.90±0.08,respectively;spheroid viability were(98.19±0.49)％,(88.53±0.90)％,(71.60±2.91)％and(56.65±5.41)％.There were statistically significant differences in the above indexes between the experimental-L,-M,-H groups and the control group(all P＜0.05).Conclusion The established hepatocyte sphere co-culture model showed varying degrees of expression of phase Ⅰ/Ⅱ drug metabolism enzymes,transporters,and liver cell specific marker molecule albumin and can be used to evaluate the toxicity of multiflorum multiflorum,which provides further reference for the clinical application of multiflorum multiflorum.

This paper outlines the common aspects of constructing integrated urban medical groups,focusing on governance,organizational restructuring,operational modes,and mechanism synergy.It then delves into the challenges in China's group construction,highlighting issues with power-responsibility alignment,capacity evolution,incentive alignment,and performance evaluation.Finally,the paper suggests strategies to enhance China's compact urban medical groups,focusing on governance reform,capacity building,benefit integration,and performance evaluation.

Gene editing technology utilizes artificial nucleases to insert, replace, or delete specific sequences in desired genomic regions. The discovery of CRISPR/Cas9 nucleases was a milestone in the development of advanced gene editing tools, which revolutionized the field due to their simplicity and versatility. However, the limited precision of Cas9 nucleases remains a notable obstacle. Recently, derivative technologies such as prime editing have earned considerable attention for their enhanced efficiency and precision. The prime editing system consists of two components: the SpCas9 nickase (H840A) fused with reverse transcriptase (MLV-RT) and an engineered prime editing guide RNA (pegRNA). This system can irreversibly introduce various types of genetic changes into the genome, including 12 possible types of point mutations, as well as insertions, deletions and their combinations, without the need for DNA double-strand breaks (DSBs) or donor DNA templates. Prime editing offers several advantages in terms of editing accuracy, versatility, PAM constraints, and off-target effects. The editing results of prime editing system is highly accurate and can be tailored to specific needs. In addition, the system can be edited near or far from PAM sites, making it less constrained by PAM site restrictions. Moreover, it demonstrates high genome-wide specificity. The system also supports a variety of edits, demonstrating immense potential, especially in large DNA fragment editing—an area that relied heavily on CRISPR/Cas9 nucleases before. The development of prime editing, especially bi-direction prime editor, shed new light on large DNA fragment manipulations, including deletions, insertions, replacements, gene integration, as well as chromosomal translocations, inversions, and tandem duplications. Despite the significant progress made with prime editing technology, its application still faces challenges, especially low editing efficiency, which limits its potential in broader research and clinical settings. Consequently, researchers are exploring strategies to enhance the efficiency of prime editing. This review highlights several approaches to improving prime editing efficiency. These include optimizing pegRNA by refining PBS and RT parameters, increasing pegRNA stability and expression levels, and developing automated pegRNA design software. Additionally, efforts are being made to optimize the prime editing system proteins, such as screening for Cas9 and reverse transcriptase variants and performing codon optimization. The final aspect is the regulation of endogenous factors, including the inhibition of mismatch repair mechanisms and the modulation of chromatin environment. These approaches significantly enhance the practicality of prime editing in research and clinical contexts. In conclusion, prime editing represents a major advancement in the field of gene editing, offering powerful tools and methods for both basic research and clinical applications. This review will introduce the discovery, improvement and applications of prime editors, with a focus on prime editing mediated large DNA fragment manipulations. Hopefully, these insights will serve as valuable references for future research and applications of prime editing technology.

Objective To explore the clinical value of fibrinogen-albumin-ratio (FAR) in adult extracorporeal membrane oxygenation (ECMO) hemorrhage. Methods The clinical data of adult patients receiving ECMO in the West China Hospital from 2018 to 2020 were analyzed retrospectively. Patients were divided into a bleeding group and a non-bleeding group based on whether they experienced bleeding after ECMO. Logistic regression analysis was used to study the relationship between FAR and bleeding, as well as risk factors for death. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive ability of FAR. According to the optimal cut-off value of FAR for predicting hemorrhage, patients were divided into a high-risk group and a low-risk group, and the occurrence of bleeding was compared between the two groups. Results A total of 125 patients were enrolled in this study, including 85 males and 40 females, aged 46.00 (31.50, 55.50) years. Among them, 58 patients received veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and 67 patients received veno-venous extracorporeal membrane oxygenation (VV-ECMO). There were 49 patients having bleeding, and the lactate level was higher (P=0.026), the platelet count before ECMO initiation and 24 h after ECMO initiation was lower (P=0.031, 0.020), the fibrinogen level 24 h after ECMO initiation was lower (P=0.049), and the proportion of myocarditis patients was higher (P=0.017) in the bleeding group than those of the non-bleeding group. In the subgroup analysis of ECMO mode, the higher D-Dimer, lactate level and lower FAR before and 24 h after ECMO initiation were associated with bleeding in the VA-ECMO group (P=0.017, 0.011, 0.033, 0.005). The 24 h FAR was independently correlated with bleeding (P=0.048), and AUC was 0.714. The cut-off value was 55.73. According to this optimal cut-off value, 25 patients were divided into the high-risk group (≤55.73) and 33 into the low-risk group (>55.73). There was a higher incidence of bleeding in the high-risk group compared to the low-risk group (unadjusted P=0.002; P=0.013 for multivariable adjustment). In the VV-ECMO group, the relationship between FAR and bleeding events was not significant (P>0.05). Conclusion Low 24 h FAR is an independent risk factor for bleeding in VA-ECMO patients, and the diagnostic cut-off value is 55.73.