Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

OBJECTIVES: To compare the efficacy of toric implantable collamer lens (Toric-ICL) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for myopia correction in patients with moderate to high myopia complicated with astigmatism. METHODS: We retrospectively collected data from 64 patients (aged 18-42 years) with moderate to high myopia complicated with astigmatism (128 eyes) undergoing either Toric-ICL (28 patients/56 eyes) or FS-LASIK (36 patients/72 eyes) at our department between January, 2019 and December, 2020. The changes of uncorrected distance visual acuity (UCVA), spherical equivalent (SE), mean astigmatism correction index (CI), corneal endothelial cell density (ECD) and intraocular pressure (IOP) following the procedures were compared between the two groups. RESULTS: In FS-LASIK group, all the eyes (72/72) achieved an UCVA≥1.0, similar to the rate in Toric-ICL group (55/56 eyes; P=0.2374). The postoperative SE was also comparable between FS-LASIK and Toric-ICL groups [0.43±0.06 D (range: -1.0 to 1.50 D) vs 0.38±0.05 D (range: -0.75 to 1.00 D); P=0.56]. The mean astigmatism CI was significantly higher in FS-LASIK group than in Toric-ICL group (0.8561 vs 0.7176; P<0.0001), and 88.89% of the eyes in FS-LASIK group and 69.64% in Toric-ICL group had postoperative astigmatism ≤0.50 D. No significant changes were observed in postoperative corneal ECD in FS-LASIK group, whereas ECD decreased significantly after the procedure in Toric-ICL group (P=0.0057). The patients undergoing Toric-ICL exhibited no significant changes of postoperative IOP, but the patients receiving FS-LASIK had significantly reduced IOP after the procedure (P<0.001). CONCLUSIONS Although the patients included in Toric-ICL group had higher myopia and astigmatism, Toric-ICL still showed better predictability and efficacy for astigmatic correction in Toric-ICL group. Toric-ICL is an effective and safe equivalent of FS-LASIK for correcting moderate myopia but can be more advantageous for correcting high myopia with astigmatism.
Humans ; Astigmatism/complications* ; Myopia/complications* ; Keratomileusis, Laser In Situ/methods* ; Retrospective Studies ; Adult ; Visual Acuity ; Adolescent ; Young Adult ; Treatment Outcome ; Male ; Lens Implantation, Intraocular/methods* ; Female ; Phakic Intraocular Lenses ; Intraocular Pressure

The organoid co-culture model, as a novel tool for recreating a three-dimensional microenvironment to study cell-cell interactions, has demonstrated significant application potential in biomedical research in recent years. By simulating the in vivo tissue microenvironment, this model provides a more precise experimental platform for investigating complex cellular interactions, particularly in areas such as tumor immune evasion mechanisms, drug sensitivity testing, and the pathological characterization of neurodegenerative diseases, where it has demonstrated significant value. However, the organoid co-culture model still faces several challenges in terms of standardized procedures, large-scale cultivation, ethical guidelines, and future development. In particular, in the field of laboratory animal science, how to effectively combine organoids with traditional animal models, and how to select the most appropriate model for different research needs while exploring its potential for replacement, remain pressing issues. In the context of ethical approval and the replacement of animal experiments, the organoid co-culture model offers an experimental approach that better aligns with the "3R" principle (Replacement, Reduction, Refinement), potentially becoming an important tool for replacing traditional animal models. To this end, this paper reviews the latest advances and key challenges in this field, providing a detailed description of the construction methods for organoid co-culture models and discussing their applications in disease mechanism research and drug screening. The paper also systematically compares the organoid co-culture models with traditional animal models, exploring the criteria for selecting the appropriate model for specific applications. Furthermore, this paper discusses the potential value of organoid co-culture models as alternatives to animal experiments and anticipates future development trends of this technology. Through these discussions, the paper aims to promote the innovation and development of organoid co-culture technology and provide new perspectives and scientific evidence for future research.

The organoid co-culture model, as a novel tool for recreating a three-dimensional microenvironment to study cell-cell interactions, has demonstrated significant application potential in biomedical research in recent years. By simulating the in vivo tissue microenvironment, this model provides a more precise experimental platform for investigating complex cellular interactions, particularly in areas such as tumor immune evasion mechanisms, drug sensitivity testing, and the pathological characterization of neurodegenerative diseases, where it has demonstrated significant value. However, the organoid co-culture model still faces several challenges in terms of standardized procedures, large-scale cultivation, ethical guidelines, and future development. In particular, in the field of laboratory animal science, how to effectively combine organoids with traditional animal models, and how to select the most appropriate model for different research needs while exploring its potential for replacement, remain pressing issues. In the context of ethical approval and the replacement of animal experiments, the organoid co-culture model offers an experimental approach that better aligns with the "3R" principle (Replacement, Reduction, Refinement), potentially becoming an important tool for replacing traditional animal models. To this end, this paper reviews the latest advances and key challenges in this field, providing a detailed description of the construction methods for organoid co-culture models and discussing their applications in disease mechanism research and drug screening. The paper also systematically compares the organoid co-culture models with traditional animal models, exploring the criteria for selecting the appropriate model for specific applications. Furthermore, this paper discusses the potential value of organoid co-culture models as alternatives to animal experiments and anticipates future development trends of this technology. Through these discussions, the paper aims to promote the innovation and development of organoid co-culture technology and provide new perspectives and scientific evidence for future research.

The liver is one of the organs most commonly affected by rheumatic diseases. Hepatic abnormalities in patients with rheumatic diseases can result from a variety of factors， including direct liver involvement by the disease itself， coexistence with primary liver disease， and drug-induced liver injury. When liver indicators are abnormal， a thorough differential diagnosis is required. For unexplained liver dysfunction， routine testing for autoantibodies should be performed to facilitate early identification of underlying autoimmune liver disease. If the etiology remains unclear， a liver biopsy is recommended for a final diagnosis if feasible. Alongside active management of rheumatic diseases， it is necessary to closely monitor liver function， avoid the use of agents that may exacerbate hepatic damage， particularly anti-rheumatic drugs with strong hepatotoxicity， and tailor treatment strategies according to personal specific conditions， so as to minimize liver damage and improve long-term outcome.

Rheumatic diseases are chronic inflammatory autoimmune diseases that can affect multiple organs and systems. In clinical practice， most patients with rheumatic diseases present with asymptomatic liver function abnormalities during the course of the disease， and the etiology of such diseases may be associated with the rheumatic disease itself， medications， metabolism， viruses， or the presence of other chronic liver diseases. Immune-mediated inflammatory responses play a significant role in liver involvement （including hepatocyte injury， intrahepatic vascular lesions， and hepatic fibrosis） in rheumatic diseases. This article discusses the clinical features and management of liver involvement secondary to rheumatic diseases， in order to enhance the understanding of this condition among specialists in related fields.

Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.

The liver is one of the organs most commonly affected by rheumatic diseases.Hepatic abnormalities in patients with rheumatic diseases can result from a variety of factors,including direct liver involvement by the disease itself,coexistence with primary liver disease,and drug-induced liver injury.When liver indicators are abnormal,a thorough differential diagnosis is required.For unexplained liver dysfunction,routine testing for autoantibodies should be performed to facilitate early identification of underlying autoimmune liver disease.If the etiology remains unclear,a liver biopsy is recommended for a final diagnosis if feasible.Alongside active management of rheumatic diseases,it is necessary to closely monitor liver function,avoid the use of agents that may exacerbate hepatic damage,particularly anti-rheumatic drugs with strong hepatotoxicity,and tailor treatment strategies according to personal specific conditions,so as to minimize liver damage and improve long-term outcome.

Rheumatic diseases are chronic inflammatory autoimmune diseases that can affect multiple organs and systems.In clinical practice,most patients with rheumatic diseases present with asymptomatic liver function abnormalities during the course of the disease,and the etiology of such diseases may be associated with the rheumatic disease itself,medications,metabolism,viruses,or the presence of other chronic liver diseases.Immune-mediated inflammatory responses play a significant role in liver involvement(including hepatocyte injury,intrahepatic vascular lesions,and hepatic fibrosis)in rheumatic diseases.This article discusses the clinical features and management of liver involvement secondary to rheumatic diseases,in order to enhance the understanding of this condition among specialists in related fields.

Objective:To analyze the clinical characteristics and treatment of eosinophilic angiocentric fibrosis (EAF) involving the orbit.Methods:We described a case and review the literature of EAF involving the orbit.Results:The literature review has shown 34 similar cases. Nineteen patients combined with other site involvement (17 cases had nasal involvement), whereas 15 had primary orbital involvement. Ocular swelling (18 cases) and epiphora (4 cases) were the most common initial presenting symptoms. The typical histopathologic findings include a perivascular, eosinophil-rich infiltrate and a "onion-skin" type of fibrosis concentrated around small vessels and all cases in this group conformed the above typical characteristics. In this series, 20 patients provided immunohistochemical results for IgG4, among them, 16 cases were positive while 4 cases were negative. No manifestations of obliterative phlebitis and storiform fibrosis were observed. The age, gender, and lesion locations (single or multiple) of the IgG4 staining positive group and the negative group were analyzed. There was no statistically significant difference in the age of onset, gender ratio and lesion the two groups ( P>0.05). Conclusion:For patients presented with ocular swelling, epiphora, with or without nasal lesions, EAF should be considered. The diagnosis of EAF is based largely on histopathologic findings. Although some cases were positive for IgG4 by immunohistochemistry, storiform fibrosis and obliterative phlebitis is not seen in our series, which aid in distinguishing EAF from IgG4-related disease.