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 analyze the association between dietary diversity and cognitive function among the elderly using group-based trajectory model, so as to provide the basis for formulating dietary intervention strategies to prevent cognitive impairment. Methods: Based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) project, demographic information, lifestyle behaviors, psychological well-being, and activities of daily living of elderly individuals aged ≥65 years from 2008 to 2018 were collected. Dietary diversity was assessed using a food frequency questionnaire, with a score of <7 points defined as low dietary diversity. Cognitive function was evaluated using the Chinese version of the Mini-Mental State Examination (MMSE). A group-based trajectory model was established based on cognitive function scores from 2008 to 2018 to analyze the trajectories of cognitive function change. The association between dietary diversity and cognitive function was analyzed using a multinomial logistic regression model. Results: A total of 1 613 individuals were collected, with a median age was 72.00 (interquartile range, 10.00) years. There were 810 males (50.22%) and 803 females (49.78%). The group-based trajectory model analysis categorized the participants into three groups: the low-level normal group, the high-level normal group, and the slow-then-rapid decline group, comprising 796 (49.35%), 585 (36.27%), and 232 (14.38%) individuals, respectively. Among these groups, the numbers of individuals with low dietary diversity were 497 (62.44%), 311 (53.16%), and 166 (71.55%), respectively, with a statistically significant difference (P<0.05). Multinomial logistic regression analysis showed that after adjusting for demographic information, lifestyle behaviors, psychological well-being, and activities of daily living, compared with the high-level normal group, low dietary diversity was statistically associated with cognitive function in the slow-then-rapid decline group (OR=1.622, 95%CI: 1.103-2.384). Conclusion Low dietary diversity may increase the risk of cognitive impairment among the elderly.

Objective: To investigate the effects of “Three Methods and Three Acupoints” (TMTP) Tuina therapy on spinal microcirculation in sciatic nerve injury (SNI). Methods: Thirty-six Sprague–Dawley rats were randomly assigned to four groups: normal, sham operation, model, and TMTP Tuina. Successful model induction was confirmed by observable hind limb lameness. After 20 sessions, hind limb grip strength and motor nerve conduction velocity (MNCV) were measured at baseline and following the 10th and 20th intervention. CD31 and α-SMA in the ventral horn of SNI model rats were detected using immunofluorescence. Motor neurons in the ventral horn were detected by Nissl staining. PTEN levels in the ventral horn were measured by ELISA, and PI3K, Akt, BDNF, VEGF, and HIF-1α expression was determined by RT-PCR. Spinal cord microcirculation was evaluated by western blotting analysis of the levels of Akt, p-Akt, BDNF, and VEGF. Results: Hind limb grip strength and MNCV significantly improved in the TMTP Tuina group compared to the model group (both P < .001). Morphology of ventral horn motor neurons in the TMTP Tuina group improved compared to the model group, with increased expressions of α-SMA (P = .002) and CD31 (P = .006). Western blot analysis indicated increased expression of VEGF (P = .005), p-Akt (P < .001), and BDNF (P = .008) in the ventral horn following Tuina treatment. RT-PCR analysis revealed increased expression of PI3K, Akt, BDNF, VEGF and HIF-1α (all P < .05). In contrast, expression of PTEN decreased compared to the model group (P < .001). Conclusion TMTP Tuina therapy may restore motor function in rats, enhance ventral horn motor neuron morphology, and promote angiogenesis and vascular smooth muscle proliferation. The mechanism may involve the activation of the PI3K/Akt signaling pathway.

Objective:To explore the relationship between parental neglect and adolescents' internalizing problem behaviors and aggressive behaviors using network analysis methods,as well as the influence of gender on their relationship.Methods:A survey was conducted in 889 middle and high school students with the Child Psycho-logical Abuse and Neglect Scale,Chinese Short Version of Depression Anxiety and Stress Scale(DASS-21),and Buss-Perry Aggression Questionnaire.Include different dimensions of parental neglect and internalizing problem be-haviors and aggressive behaviors as nodes,and use R software for network analysis.Results:In the total sample,the strength of emotional neglect(strength=1.14),anxiety(strength=0.99)and anger(strength=1.06)was high-est.the strength of emotional neglect(strength=1.14)was the highest in parental neglect,the strength of anxiety(strength=0.99)was the highest in internalizing problem behaviors,and the strength of anger(strength=1.06)was the highest in aggressive behaviors.In the male group,the bridge strength of anger(bridge strength=0.44)was the highest.In the female group,the bridge strength of stress(bridge strength=0.27)was the highest.Conclusion:There is a positive correlation between parental neglect,internalizing problem behaviors and aggressive behaviors,and significant gender differences were observed in network structures.

Objective To explore the characteristics and prognosis of follicular lymphoma(FL)with bulky disease under rituximab-based first-line treatment.Methods A retrospective analysis was conducted on 525 FL patients diagnosed between September 2009 and September 2021 who received rituximab as a first-line treat-ment[342 patients received rituximab combined with chemotherapy(R-chemo),183 patients received rituximab plus lenalidomide(R2)].The clinicopathologic characteristics,gene mutations,and prognosis of bulky FL patients were analyzed.Results Compared to non-bulky FL patients,bulky FL patients had a significantly higher proportion of lymph node≥5 sites,≥2 extranodal involvement,bone marrow involvement,elevated LDH,and a higher proportion in the high-risk group of FLIPI1 and FLIPI2.Gene sequencing revealed a significantly higher mutation rate of ZNF608 in bulky FL patients compared to non-bulky FL patients.In patients receiving R-chemo as the first-line treatment,there was no significant difference in progression-free survival(PFS)and overall survival(OS)between bulky and non-bulky FL patients.However,in patients treated with R2,the PFS and OS of bulky FL patients was significantly shorter.Conclusions Bulky FL patients compared to non-bulky FL patients have a significantly higher proportion of high-risk baseline characteristics.For bulky FL at diagnosis,chemo-free regimens require further exploration on the basis of R2.

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.

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.