Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Mycobacterium tuberculosis ( Mtb) is the causative agent of tuberculosis in humans and animals. Mtb invades the host′s lungs via airborne transmission, infects macrophages and causes tuberculosis. In some cases, the infection can spread to other tissues and organs. Despite the availability of several drugs for the treatment of tuberculosis, the emergence of multi-drug-resistant tuberculosis has led to high morbidity and mortality rates worldwide. Therefore, there is an urgent need for researchers to develop new anti-tuberculosis drugs that can treat tuberculosis more efficiently. Recent studies have shown that the virulence factors of Mtb play a crucial role in its pathogenicity. These factors primarily include secreted proteins, transcription factors, proteases, stress response proteins, metabolism-associated proteins, and cell-surface components. By evading the host′s immune surveillance through mechanisms such as anti-oxidative stress, regulating nutrient synthesis and metabolism, and modulating host cells apoptosis, Mtb is able to achieve long-term survival and spread with in the host. Understanding the mechanisms of Mtb virulence factors can provide new directions for targeted tuberculosis therapy. Therefore, knowledge of these virulence factors is essential for the development of new vaccines and anti-tuberculosis drugs. In this review, we summarize the latest research progress in the virulence factors of Mtb to provide a reference for targeted treatment of tuberculosis.

Tuberculosis(TB),a chronic infectious disease caused by infection with the Mycobacterium tuberculosis complex(MTBC),has re-emerged as the leading cause of death from a single infectious agent worldwide.Because of widespread use and mis-use of anti-tuberculosis drugs,the emergence of multidrug-resistant TB(MDR-TB)and extensively drug-resistant TB(XDR-TB)is increasing,thus posing a serious threat to global health.The current problem of drug resistance is a major prevention and treatment challenge;therefore,the search for new drug targets is urgently needed.In recent years,substantial progress has been made in re-search on anti-tuberculosis drug targets and novel therapeutic strategies.Herein,we summarize recent research progress in anti-tuberculosis drug targets,primarily cell wall synthesis,nucleic acid replication and transcription,and energy metabolism.We also provide an overview of research progress regarding two novel therapeutic strategies,to provide a theoretical basis and research ideas for the development of new clinical drugs.

Objective To study the effect of Liangxue Tuizi Formula(LXTZF)on reactive oxygen species(ROS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation in Henoch-Sch?nlein purpura(HSP)rats,and to explore its possible mechanism in the treatment of HSP.Methods Twenty-four rats were divided randomly into four groups:control,model,LXTZF,and compound glycyrrhizin(CG)groups.Except for the control group,a model of HSP was established in the other groups by heat drugs combined with egg albumin.After successful modeling,rats in the LXTZF group were given LXTZF solution 7.47 g/kg,rats in the CG group were given CG solution 13.5 mg/kg by gavage,and rats in the control and model groups were given normal saline solution by gavage once a day for 4 weeks.Samples were collected 8 hours after the last gavage.Skin histopathology changes were observed by hematoxylin and eosin(HE)staining.Serum interleukin(IL)-18 and IL-1βlevels were detected by enzyme-linked immunosorbent assay(ELISA).Changes in ROS levels in the skin were detected by immunofluorescence.Apoptosis-associated speckle-like protein(ASC),NLRP3,cysteinyl aspartate-specific protease-1(Caspase-1)mRNA and protein expression levels in rat skin were detected by real-time quantitative polymerase chain reaction(RT-PCR)and immunohistochemistry and Western blot,respectively.Results The skin pathology in the model group showed obvious inflammatory cell infiltration compared with the control group.Serum IL-18 and IL-1β levels were significantly increased(P＜0.05),skin ROS levels were significantly increased(P＜0.05),and skin ASC,NLRP3,Caspase-1 mRNA and protein expression levels were significantly increased(P＜0.05).Inflammatory cell infiltration in the skin tissues of rats was alleviated in the LXTZF and CG groups compared with the model group,while serum levels of IL-18 and IL-1β were significantly decreased(P＜0.05).ROS levels in the skin were significantly decreased(P＜0.05),and mRNA and protein levels of ASC,NLRP3,and Caspase-1 in the skin were significantly decreased(P＜0.05).Conclusions The mechanism of LXTZF in HSP may be related to the inhibition of ROS-mediated NLRP3 inflammasome activation.

Objective To study the effect of Liangxue Tuizi Formula(LXTZF)on reactive oxygen species(ROS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation in Henoch-Sch?nlein purpura(HSP)rats,and to explore its possible mechanism in the treatment of HSP.Methods Twenty-four rats were divided randomly into four groups:control,model,LXTZF,and compound glycyrrhizin(CG)groups.Except for the control group,a model of HSP was established in the other groups by heat drugs combined with egg albumin.After successful modeling,rats in the LXTZF group were given LXTZF solution 7.47 g/kg,rats in the CG group were given CG solution 13.5 mg/kg by gavage,and rats in the control and model groups were given normal saline solution by gavage once a day for 4 weeks.Samples were collected 8 hours after the last gavage.Skin histopathology changes were observed by hematoxylin and eosin(HE)staining.Serum interleukin(IL)-18 and IL-1βlevels were detected by enzyme-linked immunosorbent assay(ELISA).Changes in ROS levels in the skin were detected by immunofluorescence.Apoptosis-associated speckle-like protein(ASC),NLRP3,cysteinyl aspartate-specific protease-1(Caspase-1)mRNA and protein expression levels in rat skin were detected by real-time quantitative polymerase chain reaction(RT-PCR)and immunohistochemistry and Western blot,respectively.Results The skin pathology in the model group showed obvious inflammatory cell infiltration compared with the control group.Serum IL-18 and IL-1β levels were significantly increased(P＜0.05),skin ROS levels were significantly increased(P＜0.05),and skin ASC,NLRP3,Caspase-1 mRNA and protein expression levels were significantly increased(P＜0.05).Inflammatory cell infiltration in the skin tissues of rats was alleviated in the LXTZF and CG groups compared with the model group,while serum levels of IL-18 and IL-1β were significantly decreased(P＜0.05).ROS levels in the skin were significantly decreased(P＜0.05),and mRNA and protein levels of ASC,NLRP3,and Caspase-1 in the skin were significantly decreased(P＜0.05).Conclusions The mechanism of LXTZF in HSP may be related to the inhibition of ROS-mediated NLRP3 inflammasome activation.

Tuberculosis(TB),a chronic infectious disease caused by infection with the Mycobacterium tuberculosis complex(MTBC),has re-emerged as the leading cause of death from a single infectious agent worldwide.Because of widespread use and mis-use of anti-tuberculosis drugs,the emergence of multidrug-resistant TB(MDR-TB)and extensively drug-resistant TB(XDR-TB)is increasing,thus posing a serious threat to global health.The current problem of drug resistance is a major prevention and treatment challenge;therefore,the search for new drug targets is urgently needed.In recent years,substantial progress has been made in re-search on anti-tuberculosis drug targets and novel therapeutic strategies.Herein,we summarize recent research progress in anti-tuberculosis drug targets,primarily cell wall synthesis,nucleic acid replication and transcription,and energy metabolism.We also provide an overview of research progress regarding two novel therapeutic strategies,to provide a theoretical basis and research ideas for the development of new clinical drugs.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Mycobacterium tuberculosis ( Mtb) is the causative agent of tuberculosis in humans and animals. Mtb invades the host′s lungs via airborne transmission, infects macrophages and causes tuberculosis. In some cases, the infection can spread to other tissues and organs. Despite the availability of several drugs for the treatment of tuberculosis, the emergence of multi-drug-resistant tuberculosis has led to high morbidity and mortality rates worldwide. Therefore, there is an urgent need for researchers to develop new anti-tuberculosis drugs that can treat tuberculosis more efficiently. Recent studies have shown that the virulence factors of Mtb play a crucial role in its pathogenicity. These factors primarily include secreted proteins, transcription factors, proteases, stress response proteins, metabolism-associated proteins, and cell-surface components. By evading the host′s immune surveillance through mechanisms such as anti-oxidative stress, regulating nutrient synthesis and metabolism, and modulating host cells apoptosis, Mtb is able to achieve long-term survival and spread with in the host. Understanding the mechanisms of Mtb virulence factors can provide new directions for targeted tuberculosis therapy. Therefore, knowledge of these virulence factors is essential for the development of new vaccines and anti-tuberculosis drugs. In this review, we summarize the latest research progress in the virulence factors of Mtb to provide a reference for targeted treatment of tuberculosis.

Objective:To observe and verify the changes of transcriptome in hyperoxia-induced acute lung injury (HALI), and to further clarify the changes of pathways in HALI.Methods:Twelve healthy male C57BL/6J mice were randomly divided into normoxia group and HALI group according to the random number table, with 6 mice in each group. The mice in the normoxia group were fed normally in the room, and the mice in the HALI group was exposed to 95% oxygen to reproduce the HALI animal model. After 72 hours of hyperoxia exposure, the lung tissues were taken for transcriptome sequencing, and then Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analysis was performed. The pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to verify the key molecules in the signal pathways closely related to HALI identified by transcriptomics analysis.Results:Transcriptomic analysis showed that hyperoxia induced 537 differentially expressed genes in lung tissue of mice as compared with the normoxia group including 239 up-regulated genes and 298 down-regulated genes. Further KEGG pathway enrichment analysis identified 20 most significantly enriched pathway entries, and the top three pathways were ferroptosis signaling pathway, p53 signaling pathway and glutathione (GSH) metabolism signaling pathway. The related genes in the ferroptosis signaling pathway included the up-regulated gene heme oxygenase-1 (HO-1) and the down-regulated gene solute carrier family 7 member 11 (SLC7A11). The related genes in the p53 signaling pathway included the up-regulated gene tumor suppressor gene p53 and the down-regulated gene murine double minute 2 (MDM2). The related gene in the GSH metabolic signaling pathway was up-regulated gene glutaredoxin 1 (Grx1). The light microscope showed that the pulmonary alveolar structure of the normoxia group was normal. In the HALI group, the pulmonary alveolar septum widened and thickened, and the alveolar cavity shrank or disappeared. RT-RCR and Western blotting confirmed that compared with the normoxia group, the mRNA and protein expressions of HO-1 and p53 in lung tissue of the HALI group were significantly increased [HO-1 mRNA (2 -ΔΔCt): 2.16±0.17 vs. 1.00±0.00, HO-1 protein (HO-1/β-actin): 1.05±0.01 vs. 0.79±0.01, p53 mRNA (2 -ΔΔCt): 2.52±0.13 vs. 1.00±0.00, p53 protein (p53/β-actin): 1.12±0.02 vs. 0.58±0.03, all P < 0.05], and the mRNA and protein expressions of Grx1, MDM2, SLC7A11 were significantly decreased [Grx1 mRNA (2 -ΔΔCt): 0.53±0.05 vs. 1.00±0.00, Grx1 protein (Grx1/β-actin): 0.54±0.03 vs. 0.93±0.01, MDM2 mRNA (2 -ΔΔCt): 0.48±0.03 vs. 1.00±0.00, MDM2 protein (MDM2/β-actin): 0.57±0.02 vs. 1.05±0.01, SLC7A11 mRNA (2 -ΔΔCt): 0.50±0.06 vs. 1.00±0.00, SLC7A11 protein (SLC7A11/β-actin): 0.72±0.03 vs. 0.98±0.01, all P < 0.05]. Conclusions:HALI is closely related to ferroptosis, p53 and GSH metabolism signaling pathways. Targeting the key targets in ferroptosis, p53 and GSH metabolism signaling pathways may be an important strategy for the prevention and treatment of HALI.

The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.
Animals ; Rats ; Interleukin-6 ; Network Pharmacology ; Animal Experimentation ; Tumor Necrosis Factor-alpha ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Liver Cirrhosis/genetics* ; Medicine, Chinese Traditional ; Capsules ; Class I Phosphatidylinositol 3-Kinases ; Collagen ; Drugs, Chinese Herbal/pharmacology*