BACKGROUND:The number of patients receiving total knee arthroplasty has been increasing globally each year.Pain management is a crucial aspect following total knee arthroplasty,as effective pain control can facilitate early mobilization,reduce complications,enhance patient satisfaction,and accelerate the rehabilitation process.OBJECTIVE:To construct a visual map of post-total knee arthroplasty pain,understand the international research status and trends in this field,and provide a reference for future studies.METHODS:Relevant research articles on post-total knee arthroplasty pain were retrieved from the CNKI,WanFang Data,and Web of Science core databases,covering the period from January 2000 to December 2023.The CiteSpace software(version 6.2.3)was used to analyze the annual publication output,authors,institutions,countries,keywords,and references.Utilizing R programming language(version 4.4.1),a database was established to create line charts and bar graphs.RESULTS AND CONCLUSION:(1)Our analysis included 3 796 publications,predominantly in Chinese(3 509 articles)with the remainder in English(287 articles).(2)The United States was the most productive country in English literature,with Harvard University leading institutional output.Guangzhou University of Chinese Medicine was the top publishing institution in Chinese literature.(3)Keyword clustering identified"quality of life,""phobia,"and"acupuncture"as emerging focal points in Chinese literature,while"satisfaction"and"psychological factors"were prominent in English literature over the past five years.Co-occurrence and clustering analysis revealed dense internal connections among institutions,authors,and publications,but sparse external collaborations.(4)The study's bias on visualization analysis may have introduced bias by excluding less influential papers.(5)Regarding research hotspots,domestic research emphasized the efficacy and exploration of analgesic methods,in contrast to international research that focused on pain mechanism subtyping and analgesic drug innovation.Future research is expected to trend towards traditional Chinese medicine for postoperative pain,multimodal analgesia,and the investigation and prevention of pain typing mechanisms.

BACKGROUND:The number of patients receiving total knee arthroplasty has been increasing globally each year.Pain management is a crucial aspect following total knee arthroplasty,as effective pain control can facilitate early mobilization,reduce complications,enhance patient satisfaction,and accelerate the rehabilitation process.OBJECTIVE:To construct a visual map of post-total knee arthroplasty pain,understand the international research status and trends in this field,and provide a reference for future studies.METHODS:Relevant research articles on post-total knee arthroplasty pain were retrieved from the CNKI,WanFang Data,and Web of Science core databases,covering the period from January 2000 to December 2023.The CiteSpace software(version 6.2.3)was used to analyze the annual publication output,authors,institutions,countries,keywords,and references.Utilizing R programming language(version 4.4.1),a database was established to create line charts and bar graphs.RESULTS AND CONCLUSION:(1)Our analysis included 3 796 publications,predominantly in Chinese(3 509 articles)with the remainder in English(287 articles).(2)The United States was the most productive country in English literature,with Harvard University leading institutional output.Guangzhou University of Chinese Medicine was the top publishing institution in Chinese literature.(3)Keyword clustering identified"quality of life,""phobia,"and"acupuncture"as emerging focal points in Chinese literature,while"satisfaction"and"psychological factors"were prominent in English literature over the past five years.Co-occurrence and clustering analysis revealed dense internal connections among institutions,authors,and publications,but sparse external collaborations.(4)The study's bias on visualization analysis may have introduced bias by excluding less influential papers.(5)Regarding research hotspots,domestic research emphasized the efficacy and exploration of analgesic methods,in contrast to international research that focused on pain mechanism subtyping and analgesic drug innovation.Future research is expected to trend towards traditional Chinese medicine for postoperative pain,multimodal analgesia,and the investigation and prevention of pain typing mechanisms.

Non-alcoholic fatty liver disease （NAFLD） is one of the most prevalent forms of liver diseases globally. Its progression can lead to cirrhosis and end-stage liver disease， and there is currently a lack of effective pharmacological treatments. Adenosine monophosphate-activated protein kinase （AMPK）， as a regulatory hub for maintaining cellular energy homeostasis， can coordinate key cellular processes such as adipogenesis， glucose metabolism， and mitochondrial functions. Its activation exerts metabolic regulatory effects through pathways including inhibiting lipogenesis， enhancing mitochondrial β-oxidation， regulating inflammation and oxidative stress， and promoting autophagy. Accordingly， AMPK emerges as a potential target for the prevention and treatment of NAFLD. Traditional Chinese Medicine （TCM）， with low toxicity， high accessibility， and multi-component， multi-target synergistic effects， has demonstrated unique value in NAFLD treatment， particularly showing notable advantages in regulating the AMPK signaling pathway. Sichuan is known as the treasure house of TCM， and the active components of its authentic medicinal materials such as Coptidis Rhizoma not only reflect regional characteristics in AMPK signaling regulation but also form a multi-level metabolic regulatory network through crosstalk with pathways such as sirtuin 1 （SIRT1） and peroxisome proliferator-activated receptor α （PPARα）. They can achieve specific regulation by directly activating AMPK and modulating upstream and downstream targets， exerting prominent effects in ameliorating hepatic steatosis and inflammation. This study systematically reviews the research findings on TCM for the prevention and treatment of NAFLD over the past five years， elaborating the mechanisms by which TCM treats NAFLD through regulating the AMPK signaling pathway. It aims to provide new perspectives and references for clinical diagnosis and treatment， basic research， and drug development.

Objective To explore the mechanism of Luzhongjiangu Decoction in treating Osteonecrosis of the femoral head(ONFH).Methods Animal experiments were conducted to validate the therapeutic effect of Luzhongjiangu Decoction on ONFH.Network pharmacology was employed to screen potential targets,and molecular docking was used to verify the affinity between ligands and receptors.Fifty rats were randomly divided into blank group,model group,high-dose Luzhongjiangu Decoction groups,medium-dose Luzhongjiangu Decoction groups and low-dose Luzhongjiangu Decoction groups.After treatment,the therapeutic effect was evaluated by bone histomorphometry,bone histopathology and the expression of osteogenic related proteins.The serum metabolic differences were detected by UHPLC-QE-MS non-targeted metabonomics technique,followed by metabolic pathway enrichment analysis.Network pharmacology and metabolomics were integrated,and molecular docking was employed to further investigate the underlying mechanisms..Results The experimental results showed that Luzhongjiangu Decoction can significantly increase the expression of OCN,OPN and other osteogenic related factors,increase bone mineral density,alleviate the destruction of bone trabeculae,compared with that in the model group(P<0.01).The metabolomics test showed that compared with model group,Luzhongjiangu Decoction could callback 34 kinds of serum metabolic differences,involving 21 metabolic pathways,the main metabolic pathways were arachidonic acid metabolism,steroid hormone biosynthesis,primary bile acid biosynthesis,lysine degradation and so on.Network pharmacological results suggested that 185 active components and 1040 targets,551 disease targets and 76 intersection targets were obtained.The key pathways of Luzhongjiangu Decoction in the treatment of ONFH,which were analyzed by KEGG,involved HIF-1 signaling pathway,thyroid hormone signaling pathway,Calcium signaling pathway and so on.Integrated analysis showed that Luzhongjiangu Decoction may treat ONFH through seven metabolic pathways including arginine and proline metabolism,arachidonic acid metabolism,and steroid hormone biosynthesis;the molecular docking results also revealed correlation between potential pharmacodynamic substances and core target genes.Conclusion Luzhongjiangu Decoction can regulate the balance between proliferation and apoptosis of bone cells in a hypoxic environment by affecting the metabolic pathways such as arachidonic acid metabolism and HIF-1 signaling pathway,thereby exerting a therapeutic effect on osteonecrosis of the femoral head.

Purpose To analyze the expression of SNAP23 in esophageal squamous cell carcinoma(ESCC)and its influence on invasion of ESCC cells.Methods A total of 41 cases of ESCC and paired normal adjacent tissue(NAT)were collected.The expression and localization of SNAP23 were detected by immunohistochemical EnVision method.The differences of SNAP23 expression levels between ESCC tissues and NAT tissues were compared to analyze the relationship between SNAP23 expression and clinicopathological characteristics.The expression level of SNAP23 in human immortalized esophageal epithelial cells SHEE and ESCC cell lines TE-1,TE-13 and KYSE150 were detected by Western blot.Lentiviral vector transfection technique was used to construct stable transfection cell lines with knock-down and overexpression of SNAP23 gene.The effect of SNAP23 on invasion of ESCC cell line TE-13 was evaluated by cell invasion experiment.Results The expression of SNAP23 in ESCC was significantly higher(53.7％,22/41)than that in the NAT group(19.5％,8/41),the difference was statistically significant(x2=10.303,P＜0.01).The expression level of SNAP23 in ESCC tissues was significantly correlated with maximum tumor diameter(x2=4.193,P＜0.05)and invasion depth(x2=7.264,P＜0.05),but was not correlated with patient gender,age,tumor site,tumor type,pathologic grade,vascular embolus,nerve invasion and lymph node metastasis(P＞0.05).Compared with human immortalized esophageal epithelial cells SHEE,SNAP23 was highly expressed in ESCC cell lines(P＜0.000 1).Compared with the sh-NT group,the invasion of ESCC cell line TE-13 was inhibited when SNAP23 expression was knocked down(P＜0.000 1);compared with the Vector group,the invasion of ESCC cell line TE-13 was enhanced after overexpression of SNAP23(P＜0.000 1).Conclusion SNAP23 is highly expressed in ESCC tis-sue and cell lines,and its expression level in ESCC tissues is positively correlated with tumor maximum diameter and invasion depth;SNAP23 promotes the invasion of ESCC cells.

Respiratory viral infections such as influenza and respiratory syncytial virus infections continue to rapidly increase in patients worldwide.Host immune responses to respiratory viruses play a key role in the pathogenesis and clinical manifestations of the disease.Respiratory viruses not only activate antiviral immune responses,but also may lead to uncontrolled inflammatory re-sponses,characterized by significant release of pro-inflammatory cytokines in severely infected patients,resulting in lymphopenia,lymphocyte dysfunction,and abnormalities in immune cells such as neutrophils and macrophages.These respiratory virus-induced im-mune abnormalities may lead to microbial infection,septic shock,and severe multiorgan dysfunction.Therefore,clarifying the immu-nopathogenic mechanisms of patients with respiratory viral infections can guide clinical treatment and patient prognosis;in addition,rational regulation of the immune response of respiratory viruses in the host,including enhancing antiviral immunity while suppressing systemic inflammation,may be the key to successful treatment.This review mainly discusses the immunomodulation and related clini-cal treatment strategies for respiratory viral infections to help develop new therapeutic strategies for respiratory viral infections and pa-tient prognosis.

Objective To comprehensively and systematically evaluate the clinical effect of Chuanzhi Tongluo capsule combined with western medical treatment in patients with cerebral infarction using meta-analysis.Methods Domestic databases were searched,including China Knowledge Network,Wanfang,and Wipu databases,and foreign databases were mainly PubMed.The qualified literature was screened according to the inclusion and exclusion criteria,and was evaluated using the software of RevMan5.3 and Stata14.0 after quality assessment.Results Eight randomized controlled trials(RCTs)on the combination of Chuanzhi Tongluo capsule and western medicine were included,with a total of 728 patients with cerebral infarction,among which 365 cases were in the group of Chuanzhi Tongluo capsule combined with western medicine and 363 cases were in the group of western medicine alone.The results were analyzed in terms of the total effective rate,neurological deficit score such as the National Institutes of Health Stroke Scale(NIHSS),daily living scores,such as the Barthel Index and Activities of Daily Living(ADL)scores and inflammation level(Inflammatory mediator IL-6,ultrasensitive C-reactive protein)as the outcome indexes.Meta-analysis results showed that the total effective rate[95%CI,1.18(1.12,1.25),P<0.00001],neurological function impairment score[95%CI,-1.37(-2.08,-0.67),P=0.0001],daily life score[95%,0.88(0.51,1.25),P<0.00001],and inflammation level[95%CI,-0.75(-0.96,-0.54),P<0.00001]were better than those of the control group and showed significant differences.The incidence of adverse events[95%CI,0.89(0.37,2.15),P=0.80],and the difference was not statistically significant with that of western medicine treatment alone.Conclusion Compared with the control group which only used western medicine,the treatment effect of Chuanzhi Tongluo capsule combined with western medicine in the treatment of cerebral infarction is more significant,and the combined treatment can improve the neurological function of the patients,enhance the quality of daily life,and reduce the level of inflammation more effectively.

Objective To investigate the expression pattern of six-transmembrane epithelial antigen of prostate 1(STEAP1)in pulmonary hypertension(PH)rat model and explore its potential clinical value.Methods A hypoxia-induced pulmonary arte-rial smooth muscle cell(PASMC)model was established,and the expression levels of STEAP1 in the hypoxia cell model were detected using Western blot and immunofluorescence analysis.Nine patients diagnosed with PH through right heart catheteriza-tion during hospitalization in the Division of Cardiovascular Surgery at Tongji Hospital,Tongji Medical College,Huazhong Uni-versity of Science and Technology,were selected as the PH group.Four organ donors without pulmonary disease were selected as the control group.Western blot analysis was used to detect STEAP1 expression levels in lung tissue from both groups.A rat PH model was established by Sugen5416 couple with chronic hypoxia treatment(SuHx,and control rats were housed in an at-mospheric environment).Hematoxylin-eosin staining and immunohistochemistry staining were used to detect α-SMA expression in lung tissue,and the degree of pulmonary artery perivascular cluster lesions and vascular muscularization in model rats was as-sessed.Dual-color immunofluorescence staining was used to co-stain α-SMA and STEAP1 to detect the expression levels and tis-sue localization of STEAP1 in the lung tissue of model rats.Bioinformatics methods were employed to analyze the potential downstream regulatory mechanisms of STEAP1.Results STEAP1 expression level was significantly upregulated in the hypoxi-a-induced PASMCs.STEAP1 expression level was also upregulated in the lung tissue of PH patients.Compared with the control group,the pulmonary arteries of rats with PH showed significant remodeling,particularly with marked thickening of the pulmo-nary arterial smooth muscle layer;STEAP1 expression was significantly upregulated in the thickened pulmonary arterial smooth muscle layer of rats with PH(P＜0.01).Bioinformatic analysis suggested that the downstream regulatory mechanisms of STEAP1 were enriched in signaling pathways such as apoptosis.Conclusion STEAP1 expression level is upregulated in the thickened pulmonary arterial smooth muscle layer in PH,suggesting that it may be associated with the pathological mechanisms of pulmonary vascular remodeling and may participate in the development of PH through signaling pathways such as apopto-sis.Further exploration of STEAP1 may uncover new targets for basic research and clinical prevention and treatment.

Objective To explore the mechanism of Luzhongjiangu Decoction in treating Osteonecrosis of the femoral head(ONFH).Methods Animal experiments were conducted to validate the therapeutic effect of Luzhongjiangu Decoction on ONFH.Network pharmacology was employed to screen potential targets,and molecular docking was used to verify the affinity between ligands and receptors.Fifty rats were randomly divided into blank group,model group,high-dose Luzhongjiangu Decoction groups,medium-dose Luzhongjiangu Decoction groups and low-dose Luzhongjiangu Decoction groups.After treatment,the therapeutic effect was evaluated by bone histomorphometry,bone histopathology and the expression of osteogenic related proteins.The serum metabolic differences were detected by UHPLC-QE-MS non-targeted metabonomics technique,followed by metabolic pathway enrichment analysis.Network pharmacology and metabolomics were integrated,and molecular docking was employed to further investigate the underlying mechanisms..Results The experimental results showed that Luzhongjiangu Decoction can significantly increase the expression of OCN,OPN and other osteogenic related factors,increase bone mineral density,alleviate the destruction of bone trabeculae,compared with that in the model group(P<0.01).The metabolomics test showed that compared with model group,Luzhongjiangu Decoction could callback 34 kinds of serum metabolic differences,involving 21 metabolic pathways,the main metabolic pathways were arachidonic acid metabolism,steroid hormone biosynthesis,primary bile acid biosynthesis,lysine degradation and so on.Network pharmacological results suggested that 185 active components and 1040 targets,551 disease targets and 76 intersection targets were obtained.The key pathways of Luzhongjiangu Decoction in the treatment of ONFH,which were analyzed by KEGG,involved HIF-1 signaling pathway,thyroid hormone signaling pathway,Calcium signaling pathway and so on.Integrated analysis showed that Luzhongjiangu Decoction may treat ONFH through seven metabolic pathways including arginine and proline metabolism,arachidonic acid metabolism,and steroid hormone biosynthesis;the molecular docking results also revealed correlation between potential pharmacodynamic substances and core target genes.Conclusion Luzhongjiangu Decoction can regulate the balance between proliferation and apoptosis of bone cells in a hypoxic environment by affecting the metabolic pathways such as arachidonic acid metabolism and HIF-1 signaling pathway,thereby exerting a therapeutic effect on osteonecrosis of the femoral head.

Objective To comprehensively and systematically evaluate the clinical effect of Chuanzhi Tongluo capsule combined with western medical treatment in patients with cerebral infarction using meta-analysis.Methods Domestic databases were searched,including China Knowledge Network,Wanfang,and Wipu databases,and foreign databases were mainly PubMed.The qualified literature was screened according to the inclusion and exclusion criteria,and was evaluated using the software of RevMan5.3 and Stata14.0 after quality assessment.Results Eight randomized controlled trials(RCTs)on the combination of Chuanzhi Tongluo capsule and western medicine were included,with a total of 728 patients with cerebral infarction,among which 365 cases were in the group of Chuanzhi Tongluo capsule combined with western medicine and 363 cases were in the group of western medicine alone.The results were analyzed in terms of the total effective rate,neurological deficit score such as the National Institutes of Health Stroke Scale(NIHSS),daily living scores,such as the Barthel Index and Activities of Daily Living(ADL)scores and inflammation level(Inflammatory mediator IL-6,ultrasensitive C-reactive protein)as the outcome indexes.Meta-analysis results showed that the total effective rate[95%CI,1.18(1.12,1.25),P<0.00001],neurological function impairment score[95%CI,-1.37(-2.08,-0.67),P=0.0001],daily life score[95%,0.88(0.51,1.25),P<0.00001],and inflammation level[95%CI,-0.75(-0.96,-0.54),P<0.00001]were better than those of the control group and showed significant differences.The incidence of adverse events[95%CI,0.89(0.37,2.15),P=0.80],and the difference was not statistically significant with that of western medicine treatment alone.Conclusion Compared with the control group which only used western medicine,the treatment effect of Chuanzhi Tongluo capsule combined with western medicine in the treatment of cerebral infarction is more significant,and the combined treatment can improve the neurological function of the patients,enhance the quality of daily life,and reduce the level of inflammation more effectively.