Liver injury has become an increasingly serious global health problem， and existing chemical drugs face the limitations in efficacy and adverse reactions， resulting in the urgent need to develop safe and effective drugs. Recent studies have highlighted the potential of flavonoids from natural medicinal plants in the prevention and treatment of liver injury. As a typical natural flavonoid， luteolin shows a good protective effect against liver injury due to various etiologies， but there is still a lack of systematic elaboration on its mechanism of action. This article summarizes related research advances in China and globally and reviews the mechanism of action of luteolin in inhibiting oxidative stress， exerting an anti-inflammatory effect， regulating cell death， alleviating hepatic fibrosis， modulating lipid metabolism disorders， and regulating the gut-liver axis， as well as the application prospect of luteolin in the treatment of liver injury， in order to provide a scientific reference for further research on this compound.

Liver injury has become an increasingly serious global health problem， and existing chemical drugs face the limitations in efficacy and adverse reactions， resulting in the urgent need to develop safe and effective drugs. Recent studies have highlighted the potential of flavonoids from natural medicinal plants in the prevention and treatment of liver injury. As a typical natural flavonoid， luteolin shows a good protective effect against liver injury due to various etiologies， but there is still a lack of systematic elaboration on its mechanism of action. This article summarizes related research advances in China and globally and reviews the mechanism of action of luteolin in inhibiting oxidative stress， exerting an anti-inflammatory effect， regulating cell death， alleviating hepatic fibrosis， modulating lipid metabolism disorders， and regulating the gut-liver axis， as well as the application prospect of luteolin in the treatment of liver injury， in order to provide a scientific reference for further research on this compound.

OBJECTIVE To evaluate the cost-effectiveness of cefiderocol versus best available therapy （BAT） or standard-of- care （SOC） for the treatment of confirmed or suspected carbapenem-resistant Gram-negative bacterial （CRGNB） serious infections from the perspective of the Chinese healthcare system， and to explore its reasonable pricing. METHODS A decision tree model was constructed based on data from two phase Ⅲ clinical trials （CREDIBLE-CR and GAME CHANGER） to simulate the cost- effectiveness of cefiderocol in two scenarios： salvage therapy for confirmed CRGNB infection （scenario 1） and empirical therapy for suspected CRGNB infection （scenario 2）. The primary outcome measure was the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） was set at 1 to 3 times China’s per capita GDP in 2024. To verify the robustness of the results， one- way and probabilistic sensitivity analyses were conducted， and based on these， a reasonable price range for cefiderocol in the Chinese market was explored. RESULTS The results for scenario 1 showed that the clinical cure rate in the cefiderocol group was higher than that in the BAT group （47.50% vs. 34.21%）， but its ICER was 415 065.03 yuan per cured case， exceeding three times China’s GDP per capita. Scenario 2 revealed that the ICER for cefiderocol relative to SOC was as high as 1 362 446.16 yuan per cured case， far exceeding the WTP. Sensitivity analysis indicated that the treatment duration and price of cefiderocol were key factors affecting its cost-effectiveness. In the two scenarios described above， the unit price of cefiderocol must fall below 683.47 and 242.00 yuan/g， respectively， to be considered cost-effective. CONCLUSIONS Based on the current market price， cefiderocol lacks sufficient cost-effectiveness for treating confirmed or suspected CRGNB serious infections within China’s healthcare system. To improve its accessibility， price negotiations or a tiered medical insurance payment strategy are required.

Diabetic kidney disease （DKD） is a microvascular complication of diabetes， with a complex pathogenesis， in which mitochondrial dysfunction is considered to be the core of DKD development. Taking mitochondria as a target to regulate mitochondrial energy metabolism， mitochondrial oxidative stress， mitophagy， and mitochondrial dynamic function represents a promising strategy for the DKD prevention and treatment， with good prospects in clinical application. Traditional Chinese medicine （TCM） has great potential to mediate mitochondrial dysfunction in the DKD prevention and treatment. This article deeply explores the intrinsic relationship between various forms of mitochondrial dysfunction and DKD， and summarizes the current research status of various Chinese herbal compounds and Chinese herbal formulas in targeting mitochondrial dysfunction for the DKD prevention and treatment. This article aims to provide new targets and strategies for the DKD prevention and treatment， and the research and development of TCM.

Background Silicosis, caused by inhalation of silica (SiO₂) dust, remains the most prevalent occupational pneumoconiosis in China. While galectin-3 (Gal-3) is known to play pro-inflammatory and pro-fibrotic roles in various diseases, its specific mechanism in the pathogenesis of silicosis has not been fully clarified. Objective To investigate the role and underlying mechanisms of Gal-3 in silicosis using clinical samples of silicosis and a silicosis mouse model. Methods Lung nodule biopsy samples were collected from patients with stage III pneumoconiosis. Concurrently a silicosis mouse model was constructed via non-exposed tracheal intubation with instillation of a SiO₂ suspension. The expression levels of Gal-3 mRNA and protein in the lung tissues of the silicosis model mice were then detected using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) staining. Single-cell transcriptomic sequencing (scRNA-seq) was performed on both human and murine lung samples to analyze the expression of the Gal-3-encoding gene Lgals3 across different cell types. In vitro, RAW264.7 macrophages were treated with varying concentrations of SiO₂ suspension for 24 h and 48 h; the expression levels of Gal-3 mRNA and protein were measured by RT-qPCR and Western blot. The Gal-3 inhibitor TD139 was used to intervene in the SiO₂-induced in vitro macrophage model, and Western blot was used to detect the intracellular expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Finally, mouse embryonic lung fibroblasts NIH/3T3 and Mlg2908 were treated with varying concentrations of recombinant mouse Gal-3 protein (rmGal-3) for 48 h, and Western blot was used to detect the expression of fibrosis markers [(Collagen I, Collagen III, Fibronectin, and α smooth muscle actin (α-SMA)] and proteins associated with the TGF-β1/Smads signaling pathway. Results RT-qPCR and IHC staining showed that both the gene and protein expression levels of Gal-3 were significantly elevated at all consecutive time points in the silicosis mouse model (P < 0.05). scRNA-seq revealed that Lgals3 was aberrantly highly expressed in lung tissues from pneumoconiosis patients and silicosis mouse models, with the highest expression observed in macrophages. After treatment of macrophages with different concentrations of SiO₂ for 24 h and 48 h, the mRNA and protein expression levels of Gal-3 were significantly upregulated compared with the control group (P < 0.05). Following TD139 intervention, the protein expression levels of IL-1β, TNF-α, and TGF-β1 in dust-exposed macrophages were markedly downregulated (P < 0.0001). After 48 h of stimulation with rmGal-3, the protein expression levels of Collagen I, Fibronectin, and α-SMA in mouse embryonic lung fibroblasts (NIH/3T3 and Mlg2908) were significantly increased in all treatment groups compared with the control group (P < 0.01). Moreover, Gal-3 treatment markedly upregulated TGF-β1 protein expression in Mlg2908 cells and enhanced the phosphorylation levels of Smad2 and Smad3 (P < 0.0001). Conclusion Gal-3 is abnormally expressed in silicotic lung tissues, which primarily originates from macrophages, and inhibition of Gal-3 suppresses SiO₂-induced inflammatory and pro-fibrotic responses. In addition, Gal-3 promotes fibroblast differentiation and extracellular matrix production by activating the TGF-β1/Smads signaling pathway.

Background Silicosis, caused by inhalation of silica (SiO₂) dust, remains the most prevalent occupational pneumoconiosis in China. While galectin-3 (Gal-3) is known to play pro-inflammatory and pro-fibrotic roles in various diseases, its specific mechanism in the pathogenesis of silicosis has not been fully clarified. Objective To investigate the role and underlying mechanisms of Gal-3 in silicosis using clinical samples of silicosis and a silicosis mouse model. Methods Lung nodule biopsy samples were collected from patients with stage III pneumoconiosis. Concurrently a silicosis mouse model was constructed via non-exposed tracheal intubation with instillation of a SiO₂ suspension. The expression levels of Gal-3 mRNA and protein in the lung tissues of the silicosis model mice were then detected using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) staining. Single-cell transcriptomic sequencing (scRNA-seq) was performed on both human and murine lung samples to analyze the expression of the Gal-3-encoding gene Lgals3 across different cell types. In vitro, RAW264.7 macrophages were treated with varying concentrations of SiO₂ suspension for 24 h and 48 h; the expression levels of Gal-3 mRNA and protein were measured by RT-qPCR and Western blot. The Gal-3 inhibitor TD139 was used to intervene in the SiO₂-induced in vitro macrophage model, and Western blot was used to detect the intracellular expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Finally, mouse embryonic lung fibroblasts NIH/3T3 and Mlg2908 were treated with varying concentrations of recombinant mouse Gal-3 protein (rmGal-3) for 48 h, and Western blot was used to detect the expression of fibrosis markers [(Collagen I, Collagen III, Fibronectin, and α smooth muscle actin (α-SMA)] and proteins associated with the TGF-β1/Smads signaling pathway. Results RT-qPCR and IHC staining showed that both the gene and protein expression levels of Gal-3 were significantly elevated at all consecutive time points in the silicosis mouse model (P < 0.05). scRNA-seq revealed that Lgals3 was aberrantly highly expressed in lung tissues from pneumoconiosis patients and silicosis mouse models, with the highest expression observed in macrophages. After treatment of macrophages with different concentrations of SiO₂ for 24 h and 48 h, the mRNA and protein expression levels of Gal-3 were significantly upregulated compared with the control group (P < 0.05). Following TD139 intervention, the protein expression levels of IL-1β, TNF-α, and TGF-β1 in dust-exposed macrophages were markedly downregulated (P < 0.0001). After 48 h of stimulation with rmGal-3, the protein expression levels of Collagen I, Fibronectin, and α-SMA in mouse embryonic lung fibroblasts (NIH/3T3 and Mlg2908) were significantly increased in all treatment groups compared with the control group (P < 0.01). Moreover, Gal-3 treatment markedly upregulated TGF-β1 protein expression in Mlg2908 cells and enhanced the phosphorylation levels of Smad2 and Smad3 (P < 0.0001). Conclusion Gal-3 is abnormally expressed in silicotic lung tissues, which primarily originates from macrophages, and inhibition of Gal-3 suppresses SiO₂-induced inflammatory and pro-fibrotic responses. In addition, Gal-3 promotes fibroblast differentiation and extracellular matrix production by activating the TGF-β1/Smads signaling pathway.

Ribonucleic acid(RNA)molecules with repeat expansion sequences can liquid-liquid phase separate into droplet-like condensates,which usually have good fluidity and can dynamically exchange matter and energy with the outside world,so as to play physiological functions.However,when the conditions are changed,the droplets will undergo a phase transition,forming gel-like or solid-like condensates.The change in the morphology of the condensates is closely related to many diseases.In this work,the effects of the RNA repeat length,concentration,cation and pH value on the liquid-liquid phase separation(LLPS)of RNA with CAG repeats were systematically studied,and the molecular structure of the condensates formed by LLPS was analyzed by Raman spectroscopy.This study revealed the molecular basis of the formation of different condensates from the perspective of structural biology,and provided new insights for in-depth understanding of the molecular assembly of RNA phase separation and phase transition.

Objective To investigate the predictive value of serum lactate dehydrogenase(LDH)level com-bined with high-throughput sequencing in children with severe Mycoplasma pneumoniae pneumonia(SMPP).Methods The clinical data of 99 children with Mycoplasma pneumoniae pneumonia(MPP)admitted to Hua-zhong University of Science and Technology Union Hospital from October 2023 to March 2024 were retro-spectively analyzed.According to the severity of the disease,the children were divided into mild group(33 ca-ses)and severe group(66 cases).Spearman correlation analysis was used for correlation analysis,Logistic re-gression was used to analyze the influencing factors of SMPP,and the receiver operating characteristic(ROC)curve was used to evaluate the value of LDH in predicting SMPP.Results The level of LDH in the severe group was higher than that in the mild group(P<0.05).The results of high-throughput sequencing showed that the proportions of virulence positive and drug resistance gene A2063G mutation in the severe group were higher than those in the mild group(P<0.05).Multivariate Logistic regression analysis showed that LDH level and drug resistance gene A2063G mutation were related to the SMPP(P<0.05).ROC curve analysis showed that LDH combined with high-throughput sequencing detection of drug resistance gene A2063G muta-tion had a high value in predicting SMPP,and the area under the curve was 0.724.Conclusion Serum LDH combined with high-throughput sequencing detection of drug resistance gene A2063G mutation can be used as an effective indicator to predict SMPP.

Abstract In April 2021, type Ⅰ vaccine-derived poliovirus (VDPV) was detected from two fecal samples of a male infant with acute flaccid paralysis (AFP) in Zhejiang Province when he was admitted to the Children's Hospital Affiliated to Fudan University in Shanghai, with 12 and 14 nucleotide mutations in the VP1 region, respectively. The case had a history of immunization with three doses of poliovirus vaccines, and grade Ⅲ proximal muscle strength and grade Ⅱ distal muscle strength of the right lower limb. After symptomatic treatment, the activity of the right lower limb and the muscle strength was significantly restored, thus he was discharged. VDPV was not detected from subsequent (the 8th to 12th) fecal samples of the case and fecal samples of close contacts. No similar cases were found in medical institutions in the county, surrounding areas, neighboring villages or towns. Since the case did not exhibit clinical symptoms of poliomyelitis caused by VDPV, poliomyelitis was excluded, and the case was diagnosed with hemophilia type A based on the epidemiological investigation, laboratory tests, and the history of poliomyelitis vaccination. This event involved cross-provincial (municipal) cooperation and was responsed promptly, preventing further spread of the virus. It suggested that the sensitivity of the AFP case surveillance system should be maintained, environmental monitoring methods should be increased, and the poliomyelitis vaccination should be promoted to prevent the spread of the virus.

ObjectiveTo explore the mechanism of the Wenyang Jieyu prescription in regulating depression-like behavior in mice after maternal-infant separation combined with secondary stress. MethodsAfter birth， the rats were randomly divided into blank （NC） group， maternal-infant separation （MS） group， restraint stress （RS） group， maternal-infant separation combined with restraint stress （MRS） group， Wenyang group， Jieyu group， Wenyang Jieyu （XSF） group， and minocycline group. Maternal-infant separation was performed on day 5 （PD5）， followed by weaning at PD21 and prophylactic administration. The dose of Wenyang group， Xiaoyao group， XSF group and minocycline group were 5.85， 12.03， 16.71 g·kg^-1 and 50 mg·kg^-1， respectively. Restraint stress was applied on PD90. The model was evaluated using glucose， social interaction， open field， and O-maze behavior tests， as well as high-performance liquid chromatography to measure serotonin， dopamine， and other neurotransmitters. The expression level of ionized calcium-binding adaptor molecule-1 （Iba-1） protein， a marker of hippocampal microglia， was detected by immunohistochemistry. Protein expression levels of Janus kinase 2 （JAK2） and signal transducer and activator of transcription 3 （STAT3） in the hippocampus were analyzed by an automatic protein expression analysis system. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of M1 markers， JAK2/STAT3 pathway-related genes， and cytokines in hippocampal microglia in each group. ResultsCompared with the NC group， the MRS group exhibited depression-like behavior， with significantly decreased levels of neurotransmitters in the hippocampus （P<0.05， P<0.01）， increased expression of Iba-1 （P<0.01）， and elevated protein levels of JAK2 and STAT3 （P<0.05）. The mRNA expression levels of CD68， CD11b， IL-1β， JAK2， and STAT3 were significantly increased （P<0.01）， while IL-10 mRNA expression was significantly decreased （P<0.01）. Compared with the MRS group， the XSF and minocycline groups showed some improvement in depression-like behavior. In these groups， the hippocampal neurotransmitter content was significantly increased （P<0.05， P<0.01）， and Iba-1 expression was significantly decreased （P<0.01）. The protein levels of JAK2 and STAT3 in the XSF group showed a downward trend. The mRNA expression levels of CD68， CD11b， JAK2， STAT3， and IL-1β in the hippocampus were significantly decreased in the XSF and minocycline groups （P<0.05， P<0.01）， while IL-10 mRNA expression was significantly increased （P<0.05， P<0.01）. ConclusionWenyang Jieyu prescription can regulate depression-like behavior in maternal-infant separation mice combined with secondary stress by inhibiting the polarization of hippocampal microglia to the M1 phenotype. The regulation of hippocampal microglia polarization by Wenyang Jieyu prescription may be associated with the JAK2/STAT3 pathway.