Compared with traditional therapies for chronic liver disease （CLD）， Bifidobacterium has the characteristics of multi-target intervention， high biosafety， and good host compatibility and provides new strategies for intervention of CLD progression in terms of microecological regulation. Various studies have shown that Bifidobacterium regulates liver homeostasis and exerts a therapeutic effect on CLD by regulating intestinal flora， maintaining antioxidation， promoting energy consumption， alleviating inflammation， improving glycolipid metabolism， and exerting an antitumor effect. This article systematically reviews the studies on Bifidobacterium in the treatment of CLD in China and globally， explores their different mechanisms， and elaborates on the interaction between related signaling pathways （such as the nuclear factor erythroid 2-related factor 2 signaling pathway and the adenosine monophosphate-activated protein kinase signaling pathway） and the liver， in order to provide a basis for probiotic intervention in liver pathology， as well as new ideas for the comprehensive treatment of CLD.

Objective To explore the application value of computed tomography (CT) three-dimensional reconstruction in total knee arthroplasty (TKA). Methods A total of 102 patients who underwent TKA in our hospital between April 2022 and April 2025 were enrolled and divided using a random number table into a traditional group (51 cases, routine preoperative evaluation) and a study group (51 cases, CT three-dimensional reconstruction-assisted surgery). The therapeutic efficacy at 3 months postoperatively and perioperative indicators were compared between the two groups. The hip-knee-ankle (HKA) angle was measured preoperatively and at 3 months postoperatively. The Hospital for Special Surgery (HSS) knee score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were recorded preoperatively and at 3 and 6 months postoperatively. Complications were documented. Results The excellent/good rate in the study group (92.16%) was higher than that in the traditional group (74.51%) (P<0.05). The operation time, intraoperative blood loss, postoperative drainage volume, and hospital stay in the study group were (69.52 ± 7.11) min, (102.69 ± 8.54) mL, (167.33 ± 12.35) mL, and (10.93 ± 2.37) days, respectively, which were shorter than those in the traditional group [(78.45 ± 5.98) min, (108.36 ± 10.02) mL, (175.96 ± 14.93) mL, and (12.04 ± 1.95) days] (P<0.05). At 3 months postoperatively, the HKA angle was 178.02° ± 1.05° in the study group and 177.45° ± 1.34° in the traditional group, both were significantly improved compared with those before operation, with the study group showing better improvement (P<0.05). The HSS knee and WOMAC scores in both groups at 3 and 6 months postoperatively were improved compared with preoperative scores (P<0.05). At 3 and 6 months postoperatively, the study group showed higher HSS knee score and lower WOMAC score than the traditional group (P<0.05). The incidence of complications in the study group (3.92%) was lower than that in the traditional group (17.65%) (P<0.05). Conclusion TKA guided by CT three-dimensional reconstruction improved the excellent/good rate, optimized HKA angle and knee function, shortened operation time and hospital stay, reduced intraoperative blood loss and postoperative drainage volume, and decreased the incidence of complications.

Objective To explore the application value of computed tomography (CT) three-dimensional reconstruction in total knee arthroplasty (TKA). Methods A total of 102 patients who underwent TKA in our hospital between April 2022 and April 2025 were enrolled and divided using a random number table into a traditional group (51 cases, routine preoperative evaluation) and a study group (51 cases, CT three-dimensional reconstruction-assisted surgery). The therapeutic efficacy at 3 months postoperatively and perioperative indicators were compared between the two groups. The hip-knee-ankle (HKA) angle was measured preoperatively and at 3 months postoperatively. The Hospital for Special Surgery (HSS) knee score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were recorded preoperatively and at 3 and 6 months postoperatively. Complications were documented. Results The excellent/good rate in the study group (92.16%) was higher than that in the traditional group (74.51%) (P<0.05). The operation time, intraoperative blood loss, postoperative drainage volume, and hospital stay in the study group were (69.52 ± 7.11) min, (102.69 ± 8.54) mL, (167.33 ± 12.35) mL, and (10.93 ± 2.37) days, respectively, which were shorter than those in the traditional group [(78.45 ± 5.98) min, (108.36 ± 10.02) mL, (175.96 ± 14.93) mL, and (12.04 ± 1.95) days] (P<0.05). At 3 months postoperatively, the HKA angle was 178.02° ± 1.05° in the study group and 177.45° ± 1.34° in the traditional group, both were significantly improved compared with those before operation, with the study group showing better improvement (P<0.05). The HSS knee and WOMAC scores in both groups at 3 and 6 months postoperatively were improved compared with preoperative scores (P<0.05). At 3 and 6 months postoperatively, the study group showed higher HSS knee score and lower WOMAC score than the traditional group (P<0.05). The incidence of complications in the study group (3.92%) was lower than that in the traditional group (17.65%) (P<0.05). Conclusion TKA guided by CT three-dimensional reconstruction improved the excellent/good rate, optimized HKA angle and knee function, shortened operation time and hospital stay, reduced intraoperative blood loss and postoperative drainage volume, and decreased the incidence of complications.

Objective To explore the application value of computed tomography (CT) three-dimensional reconstruction in total knee arthroplasty (TKA). Methods A total of 102 patients who underwent TKA in our hospital between April 2022 and April 2025 were enrolled and divided using a random number table into a traditional group (51 cases, routine preoperative evaluation) and a study group (51 cases, CT three-dimensional reconstruction-assisted surgery). The therapeutic efficacy at 3 months postoperatively and perioperative indicators were compared between the two groups. The hip-knee-ankle (HKA) angle was measured preoperatively and at 3 months postoperatively. The Hospital for Special Surgery (HSS) knee score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were recorded preoperatively and at 3 and 6 months postoperatively. Complications were documented. Results The excellent/good rate in the study group (92.16%) was higher than that in the traditional group (74.51%) (P<0.05). The operation time, intraoperative blood loss, postoperative drainage volume, and hospital stay in the study group were (69.52 ± 7.11) min, (102.69 ± 8.54) mL, (167.33 ± 12.35) mL, and (10.93 ± 2.37) days, respectively, which were shorter than those in the traditional group [(78.45 ± 5.98) min, (108.36 ± 10.02) mL, (175.96 ± 14.93) mL, and (12.04 ± 1.95) days] (P<0.05). At 3 months postoperatively, the HKA angle was 178.02° ± 1.05° in the study group and 177.45° ± 1.34° in the traditional group, both were significantly improved compared with those before operation, with the study group showing better improvement (P<0.05). The HSS knee and WOMAC scores in both groups at 3 and 6 months postoperatively were improved compared with preoperative scores (P<0.05). At 3 and 6 months postoperatively, the study group showed higher HSS knee score and lower WOMAC score than the traditional group (P<0.05). The incidence of complications in the study group (3.92%) was lower than that in the traditional group (17.65%) (P<0.05). Conclusion TKA guided by CT three-dimensional reconstruction improved the excellent/good rate, optimized HKA angle and knee function, shortened operation time and hospital stay, reduced intraoperative blood loss and postoperative drainage volume, and decreased the incidence of complications.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

ObjectiveTo investigate the whole genomic characteristics and phylogenetic relationships of clinical isolates of enteroaggregative Escherichia coli (EAEC) in diarrhea outpatients in Pudong New Area, Shanghai. MethodsBased on the diarrheal disease surveillance network in Pudong New Area, Shanghai, whole-genome sequencing was performed on a total of 55 EAEC strains isolated from fecal samples of the diarrhea outpatients from January 2015 to December 2019. The genome analyses based on raw sequencing data encompassed genome size, coding genes, dispersed repeat sequences, genomic islands, and protein coding regions, and pan-genome analyses were conducted simultaneously. Contigs sequences assays were performed to analyze molecular characteristics including serotypes, antibiotic resistance genes, and virulence factors. The phylogenetic clusters and multilocus sequence typing (MLST) were identified, and a phylogenetic tree was constructed. ResultsEAEC exhibited an open pan-genome. The predominant serotype of EAEC in diarrhea outpatients in Pudong New Area was O130:H27, and the carriage rate of β-lactam resistance genes was the highest (67.27%, 37/55). A total of 29 virulence factors and 106 virulence genes were identified, phylogenic group B1 was the predominant group, and clonal group CC31 was the dominant clonal group. The strain distribution was highly heterogeneous. ConclusionThe genomic characteristics of EAEC displayed significant strain polymorphism. It is necessary to develop effective strategies for differential diagnosis and improve detection capabilities for infection with EAEC of different serotypes and genotypes.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis. Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) can lead to a spectrum of diseases, collectively known as ribosomopathy. Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture. The formation of membraneless organelles and intracellular structures, including ribosomes and nucleoli, cannot occur without the involvement of phase separation. Here, ribosome structure, biogenesis, and their relationship with ribosomopathy are systematically reviewed. The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed, which may offer some clues for understanding the mechanisms of ribosomopathy. Then, some new ideas for the prevention, diagnosis, and treatment of ribosomopathy are provided.
Humans ; Ribosomes/physiology* ; Ribosomal Proteins/metabolism* ; Mutation ; Animals ; Cell Nucleolus/metabolism* ; Protein Biosynthesis ; Phase Separation

Artificial intelligence (AI) has emerged as a transformative technology in accelerating drug discovery and development within natural medicines research. Natural medicines, characterized by their complex chemical compositions and multifaceted pharmacological mechanisms, demonstrate widespread application in treating diverse diseases. However, research and development face significant challenges, including component complexity, extraction difficulties, and efficacy validation. AI technology, particularly through deep learning (DL) and machine learning (ML) approaches, enables efficient analysis of extensive datasets, facilitating drug screening, component analysis, and pharmacological mechanism elucidation. The implementation of AI technology demonstrates considerable potential in virtual screening, compound optimization, and synthetic pathway design, thereby enhancing natural medicines' bioavailability and safety profiles. Nevertheless, current applications encounter limitations regarding data quality, model interpretability, and ethical considerations. As AI technologies continue to evolve, natural medicines research and development will achieve greater efficiency and precision, advancing both personalized medicine and contemporary drug development approaches.
Biological Products/pharmacology* ; Artificial Intelligence ; Humans ; Drug Discovery/methods* ; Machine Learning ; Deep Learning

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.