Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Liver Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Animals ; Humans ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Amphibian Venoms/therapeutic use* ; Cell Line, Tumor ; Neoplasm Metastasis ; Cell Survival/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Neoplasm Invasiveness ; Mice, Inbred BALB C ; Mice, Nude ; Mice ; Male ; Bufanolides/therapeutic use* ; Protein Precursors ; Prothrombin ; Biomarkers

OBJECTIVE: To elucidate the mechanism of Banxia Houpo Decoction (BHD) in treating gastroesophageal reflux disease (GERD) by integrating and utilizing the compound analysis, network pharmacology, and empirical verification. METHODS: Ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was utilized to identify the primary compounds in BHD. Network pharmacology was employed to retrieve target genes. A GERD rat model was developed and 32 SD rats were randomly divided into model, BHD-L (3 g/kg), BHD-H (6 g/kg), and mosapride (0.75 mg/kg) groups using a random number table, 8 rats in each group. Eight rats without the construction of a GERD model were selected as the blank group. Esophageal damage was evaluated through visualization and histopathology evaluation. 5-hydroxytryptamine (5-HT) levels in serum and lower esophageal sphincter (LES) were determined by ELISA. LES contractility was measured with a force transducer, and serotonin transporter (SERT) and 5-HT4R expressions in LES were assessed by RT-PCR, Western blot, and immunofluorescence staining, respectively. RESULTS: UPLC-HRMS analysis identified 37 absorption peaks and 157 compounds in BHD. Functional enrichment identified SERT as a significant target for LES contractility. Histopathological findings indicated less severe esophageal mucosal damage in the BHD-H group compared with the model group. Although serum 5-HT levels showed no significant difference, 5-HT concentration in LES tissue was notably higher in the BHD-H group (P<0.05). Within the range from 10^-10 to 10^-7 mmol/L, LES contractility in the BHD-H and mosapride groups was significantly increased (P<0.05). Within the range from 3 × 10^-7 to 3 × 10^-6 mmol/L 5-HT, LES contractility in the BHD-H group was increased (P<0.05). No significant difference was detected within the range from 10^-5 to 10^-4 mmol/L 5-HT. Notably, SERT expression in the BHD-H group assessed by RT-PCR, Western blot, and immunofluorescence staining were significantly lower than that in the model group (all P<0.01); while 5-HT4R expression remained unchanged. CONCLUSION BHD may increase LES contractility by inhibiting SERT expression in LES tissue.
Animals ; Gastroesophageal Reflux/physiopathology* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Network Pharmacology ; Male ; Serotonin/metabolism* ; Rats ; Disease Models, Animal ; Serotonin Plasma Membrane Transport Proteins/metabolism* ; Esophagus/drug effects*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

BACKGROUND:Remyelination in the central nervous system is a basic repair process triggered by demyelinating events,mainly through the proliferation,migration,and differentiation of oligodendrocyte precursor cells into oligodendrocytes.The process of remyelination is affected by many factors such as astrocytes,myelin debris,microglia,macrophages,endothelial cells,pericytes,T cells,and age.OBJECTIVE:Astrocytes play an important role in regulating synaptic activity,nutritional support,and tissue repair in the central nervous system.This review aims to provide potential therapeutic targets for demyelinating diseases of central nervous system by reviewing the role of astrocytes in remyelination.METHODS:A search was conducted on relevant literature collected from CNKI,PubMed,and Web of Science from 2014 tO 2024.The search terms were"astrocytes,oligodendrocyte precursor cells,remyelination"in both Chinese and English.Finally,66 articles were included after screening and summarized.RESULTS AND CONCLUSION:(1)The treatment of demyelinating diseases,such as multiple sclerosis,is limited to disease-modifying therapies,and there is no available method to overcome the failure of remyelination.Therefore,it is necessary to explore targets related to remyelination to promote myelin repair.(2)Remyelination is a process in which oligodendrocyte precursor cells proliferate,migrate,differentiate,and mature into oligodendrocytes,and the latter produce myelin to wrap axons to form myelin sheath.(3)Astrocytes regulate remyelination by phagocytosis of myelin debris,participating in inflammatory response,transforming into oligodendrocyte lineage cells,providing energy supply for oligodendrocyte lineage cells,releasing neurotrophic factors,and secreting extracellular matrix components.(4)The drugs screened in this paper use astrocytes and their derived factors as intervention targets to regulate the remyelination.Some drugs have satisfactory effects,but their effectiveness and safety still need more basic research and clinical trials to verify.(5)The mechanism of action of astrocytes in remyelination has not been fully elucidated,and the related molecular targets and signaling pathways can be further studied.

Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

BACKGROUND:Remyelination in the central nervous system is a basic repair process triggered by demyelinating events,mainly through the proliferation,migration,and differentiation of oligodendrocyte precursor cells into oligodendrocytes.The process of remyelination is affected by many factors such as astrocytes,myelin debris,microglia,macrophages,endothelial cells,pericytes,T cells,and age.OBJECTIVE:Astrocytes play an important role in regulating synaptic activity,nutritional support,and tissue repair in the central nervous system.This review aims to provide potential therapeutic targets for demyelinating diseases of central nervous system by reviewing the role of astrocytes in remyelination.METHODS:A search was conducted on relevant literature collected from CNKI,PubMed,and Web of Science from 2014 tO 2024.The search terms were"astrocytes,oligodendrocyte precursor cells,remyelination"in both Chinese and English.Finally,66 articles were included after screening and summarized.RESULTS AND CONCLUSION:(1)The treatment of demyelinating diseases,such as multiple sclerosis,is limited to disease-modifying therapies,and there is no available method to overcome the failure of remyelination.Therefore,it is necessary to explore targets related to remyelination to promote myelin repair.(2)Remyelination is a process in which oligodendrocyte precursor cells proliferate,migrate,differentiate,and mature into oligodendrocytes,and the latter produce myelin to wrap axons to form myelin sheath.(3)Astrocytes regulate remyelination by phagocytosis of myelin debris,participating in inflammatory response,transforming into oligodendrocyte lineage cells,providing energy supply for oligodendrocyte lineage cells,releasing neurotrophic factors,and secreting extracellular matrix components.(4)The drugs screened in this paper use astrocytes and their derived factors as intervention targets to regulate the remyelination.Some drugs have satisfactory effects,but their effectiveness and safety still need more basic research and clinical trials to verify.(5)The mechanism of action of astrocytes in remyelination has not been fully elucidated,and the related molecular targets and signaling pathways can be further studied.

Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.