BACKGROUND:During tissue repair and regeneration,macrophages exhibit multiple activities such as promoting inflammation,anti-inflammation,fibrosis,and wound healing at various stages of tissue damage.The heterogeneity and balanced polarization of macrophages are decisive in organ repair. OBJECTIVE:To explore the research hotspots and development trends in the field of macrophage polarization in tissue repair through visualization analysis methods,as well as the research level of global scientific and clinical workers in this field. METHODS:Using bibliometric analysis methods,this study employed Citespace literature visualization analysis software and VOSviewer tools,retrieving related literature from 2013 to 2023 in the Web of Science Core Collection's Science Citation Index Expanded(SCI-Expanded)and Social Sciences Citation Index Expanded(SSCI-Expanded)databases.The analysis results were presented in a dynamic map format,revealing the main trends and focuses of the research. RESULTS AND CONCLUSION:The number of publications in this field had dramatically increased from 2013 to 2023,with a significant rise starting in 2017.Chinese researchers had the highest number of publications,with 642 papers,while American researchers began focusing on this field early on.Professor Elisseeff Hennifer H had made a substantial contribution to the research in this area.Shanghai Jiao Tong University had produced the most publications.In recent years,keywords such as"hyaluronic acid"and"regulation"had been prevalent.Macrophage polarization research in tissue repair primarily concentrates on its multifunctional regulatory mechanisms,interactions with other cell types,and its behavior under specific pathological conditions.The main research areas include the role of macrophages in wound healing,cardiovascular diseases,chronic inflammation,tumor microenvironments,and regenerative medicine.A deeper understanding of the multifunctionality and polarization mechanisms of macrophages can lead to the development of new therapeutic strategies to enhance tissue repair and regeneration,thereby improving patient treatment outcomes.

ObjectiveTo investigate the value of noninvasive imaging detection （FibroScan）， two serological models of gamma-glutamyl transpeptidase-to-platelet ratio （GPR） score and S index， and two inflammatory factors of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B （CHB）， as well as the consistency of liver biopsy in pathological staging， and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients， and related examinations were performed before liver biopsy， including total bilirubin， alanine aminotransferase， platelet count， gamma-glutamyl transpeptidase， albumin， IL-6， TNF-α， liver stiffness measurement （LSM）， and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy， and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic （ROC） curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsIn the consistency check， inflammation degree based on liver biopsy had a Kappa value of 0.807 （P<0.001）， and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 （P<0.001）， suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM， GPR score， S index， IL-6， and TNF-α （all P<0.05）， and GPR score， S index， IL-6， and TNF-α were positively correlated with LSM （all P<0.05）. GPR score， S index， IL-6， and TNF-α were all independent risk factors for diagnosing significant liver fibrosis （≥S2） and progressive liver fibrosis （≥S3） （all P<0.05）. As for each indicator alone， GPR score had the highest value in the diagnosis of significant liver fibrosis （≥S2）， followed by S index， IL-6， and TNF-α， while S index had the highest value in the diagnosis of progressive liver fibrosis （≥S3）， followed by GPR score， TNF-α， and IL-6. The joint model had a higher predictive value than each indicator alone （all P<0.05）. ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score， S index， IL-6， and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB， and the combined prediction model established by them can better diagnose liver fibrosis.

Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

ObjectiveTo investigate the influencing factors for hepatic hydrothorax （HH） before intervention for primary hepatic carcinoma （PHC）， and to construct and assess the nomogram risk prediction model. MethodsA retrospective analysis was performed for the clinical data of 353 hospitalized patients who attended the Third People’s Hospital of Kunming for the first time from October 2012 to October 2021 and there diagnosed with PHC， and according to the presence or absence of HH， they were divided into HH group with 153 patients and non-HH group with 200 patients. General data and the data of initial clinical testing after admission were collected from all PHC patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. After the multicollinearity test was performed for the variables with statistical significance determined by the univariate analysis， the multivariate Logistic regression analysis was used to identify independent influencing factors. The “rms” software package was used to construct a nomogram risk prediction model， and the Hosmer-Lemeshow test and the receiver operating characteristic （ROC） curve were used to assess the risk prediction model； the “Calibration Curves” software package was used to plot the calibration curve， and the “rmda” software package was used to plot the clinical decision curve and the clinical impact curve. ResultsAmong the 353 patients with PHC， there were 153 patients with HH， with a prevalence rate of 43.34%. Child-Pugh class B （odds ratio ［OR］=2.652， 95% confidence interval ［CI］： 1.050 — 6.698， P=0.039）， Child-Pugh class C （OR=7.963， 95%CI： 1.046‍ ‍—‍ ‍60.632， P=0.045）， total protein （OR=0.947， 95%CI： 0.914‍ ‍—‍ ‍0.981， P=0.003）， high-sensitivity C-reactive protein （OR=1.007， 95%CI： 1.001‍ ‍—‍ ‍1.014， P=0.025）， and interleukin-2 （OR=0.801， 95%CI： 0.653‍ ‍—‍ ‍0.981， P=0.032） were independent influencing factors for HH before PHC intervention， and a nomogram risk prediction model was established based on these factors. The Hosmer-Lemeshow test showed that the model had a good degree of fitting （χ²=5.006， P=0.757）， with an area under the ROC curve of 0.752 （95%CI： 0.701‍ ‍—‍ ‍0.803）， a sensitivity of 78.40%， and a specificity of 63.50%. The calibration curve showed that the model had good consistency in predicting HH before PHC intervention， and the clinical decision curve and the clinical impact curve showed that the model had good clinical practicability within a certain threshold range. ConclusionChild-Pugh class， total protein， interleukin-2， and high-sensitivity C-reactive protein are independent influencing factors for developing HH before PHC intervention， and the nomogram model established based on these factors can effectively predict the risk of developing HH.

This paper comprehensively discusses on the potential neurobiological mechanisms of acupuncture in the treatment of tobacco dependence， focusing on three important aspects， including acupuncture's regulation of tobacco dependence behavior， effects of acupuncture on withdrawal syndrome， and the role of acupuncture in preventing relapse. It is found that acupuncture can inhibit drug-seeking behavior by regulating the reward pathway and related neurons， such as dopamine， thus modulating tobacco dependence behavior. It also alleviates withdrawal symptoms by improving the oral environment of smokers and reducing negative emotions after quitting. Furthermore， acupuncture can prevent relapse by decreasing brain network activity related to smoking cravings and improving cognitive brain functions like addiction memory. Currently， research on the specific neurobiological mechanism of acupuncture in treating tobacco dependence and the involved neural circuits is limited. Future research directions are proposed， including the evaluation of clinical effects， exploration of specific therapeutic mechanisms， investigation of brain pathology， and strengthening the exploration of brain functions. Additionally， combining modern technologies to clarify the neural circuits involved in acupuncture intervention will provide a basis for acupuncture treatment of tobacco addiction.

ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 （ACSL4） signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group， sham-operation group， model group， trimetazidine group （5.4 mg·kg^-1）， low-， medium-， and high-dose group （3.51， 7.02，14.04 g·kg^-1） of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome， and continuous treatment for 7 d was conducted， while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed， and indicators such as electrocardiogram， echocardiography， and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin （HE） staining， and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid （12-HETE） and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe²⁺， lipid peroxidation （LPO）， glutathione （GSH）， and T-GSH/glutathione disulfide （GSSG） in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species （ROS）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， ACSL4， and ly-sophosphatidylcholine acyltransferase3 （LPCAT3） in myocardial tissue. ResultsCompared with those in the normal group， the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage， bow-back elevation of the ST segments， elevated T waves， J-point elevation， and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）. Blood rheology showed that the viscosity of the whole blood （low， medium， and high rate of shear） was significantly increased （P<0.01）. HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken， and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles， and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased （P<0.01）. The content of Fe²⁺， LPO， and ROS in myocardial tissue was significantly increased （P<0.01）. The content of GSH was significantly decreased （P<0.01）， and T-GSH/GSSG was decreased （P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased （P<0.05， P<0.01）， while those of ACSL4 and LPCAT3 increased significantly （P<0.01）. Compared with the model group， the general macroscopic symptoms and electrocardiogram results of rats in low-， medium- and high-dose groups of Xuefu Zhuyutang were alleviated， and the differences in LVEF/LVFS ratios were all significantly increased （P<0.05， P<0.01）. The differences in whole-blood viscosity （low， medium， and high rate of shear） were all significantly decreased （P<0.01）. The results of HE staining and transmission electron microscopy showed that the morphology， structure， and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. The content of Fe²⁺， LPO， and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and the content of GSH and T-GSH/GSSG was significantly increased （P<0.05， P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and ACSL4 and LPCAT3 were decreased to different degrees in the low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway， thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.

ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January， 2019 to December， 2022 were enrolled， among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group， and 154 patients without recompensation were enrolled as control group. Related clinical data were collected， and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and the receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis， 63 （29.03%） had recompensation. There were significant differences between the recompensation group and the control group in HIV history （χ²=4.566， P=0.034）， history of partial splenic embolism （χ²=6.687， P=0.014）， Child-Pugh classification （χ²=11.978， P=0.003）， grade of ascites （χ²=14.229， P<0.001）， albumin （t=4.063， P<0.001）， prealbumin （Z=-3.077， P=0.002）， high-density lipoprotein （t=2.854， P=0.011）， high-sensitivity C-reactive protein （Z=-2.447， P=0.014）， prothrombin time （Z=-2.441， P=0.015）， carcinoembryonic antigen （Z=-2.113， P=0.035）， alpha-fetoprotein （AFP） （Z=-2.063， P=0.039）， CA125 （Z=-2.270， P=0.023）， TT3 （Z=-3.304， P<0.001）， TT4 （Z=-2.221， P=0.026）， CD45⁺ （Z=-2.278， P=0.023）， interleukin-5 （Z=-2.845， P=0.004）， tumor necrosis factor-α （Z=-2.176， P=0.030）， and portal vein width （Z=-5.283， P=0.005）. The multivariate analysis showed that history of partial splenic embolism （odds ratio ［OR］=3.064， P=0.049）， HIV history （OR=0.195， P=0.027）， a small amount of ascites （OR=3.390， P=0.017）， AFP （OR=1.003， P=0.004）， and portal vein width （OR=0.600， P<0.001） were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history， grade of ascites， history of partial splenic embolism， AFP， portal vein width， and the combined predictive model of these indices had an area under the ROC curve of 0.556， 0.641， 0.560， 0.589， 0.745， and 0.817， respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis， those with a history of partial splenic embolism， a small amount of ascites， and an increase in AFP level are more likely to experience recompensation， while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.