The connection between tendons and bones is called the tendon bone connection. With the continuous improvement of national sports awareness, excessive exercises and the related intensity are prone to damage the tendon bone connection. Tendon bone healing is a complex repair and healing process involving multiple factors, and good tendon bone healing is a prerequisite for its physiological function. The complexity of tendon bone structure also poses great challenges to the repair of tendon bone injuries. In recent years, researches have found that stem cells, growth factors, macrophages, and other factors are closely related to the healing process of tendon bone injuries, among which macrophages play an important role in the healing process. The authors reviewed relevant research literature in recent years and summarized the role of macrophages in tendon bone healing, in order to provide new ideas and directions for treatment strategies to promote tendon bone healing.
Humans ; Macrophages/metabolism* ; Wound Healing ; Animals ; Tendons/physiology* ; Bone and Bones/injuries* ; Tendon Injuries

Objective To investigate the effects of exosomes (Exo) derived from high glucose-stimulated glomerular mesangial cells (GMC) on the kidneys of C57BL/6 mice and the intervention mechanism of Tongluo Yishen Formula (TLYSF). Methods The rat GMC were divided into a normal glucose group (NG, with 5.6 mmol/L glucose) and a high glucose group (HG, with 30 mmol/L glucose). After 24 hours of culture, the supernatant was collected, and exosomes were extracted using the ultracentrifugation method. The exosomes were then identified by transmission electron microscopy and Western blot analysis. Male C57BL/6 mice were divided into three groups: NO-Exo group, NG-Exo group, and HG-Exo group. These groups were respectively administered tail vein injections of PBS buffer, exosomes derived from GMC cultured in normal glucose, and exosomes derived from GMC cultured in high glucose, three times a week for a total of 8 weeks. After 8 weeks, the mice in the HG-Exo group were randomly divided into three subgroups: the HG-Exo group [gavaged with saline], the HG-Exo+TLYSF group [gavaged with TLYSF at 34.32 g/(kg.d)], and the HG-Exo + VAL group [gavaged with valsartan suspension at 10.4 mg/(kg.d)], and the intervention lasted for 4 weeks. Urinary microalbumin (mALb), urinary N-acetyl-β-D-aminoglucosidase (NAG), glycated hemoglobin (HbA1c), serum creatinine (Scr) and urea nitrogen (BUN) were detected. Transmission electron microscopy was used to observe the ultrastructure of renal tissues. TUNEL was used to detect the DNA damage of renal tissue cells. Immunofluorescence was used to detect the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and wilms tumor 1(WT-1). RT-PCR was used to detect the mRNA levels of NLRP3, cysteinyl aspartate-specific proteinase 1 (caspase-1), interleukin-1 beta (IL-1β), miR-200c-3p and miR-148a-3p. Western Blot was employed to detect the protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 and IL-1β. Results Compared with the NG-Exo group, mice in the HG-Exo group exhibited significantly increased levels of mALb, urinary NAG, Scr and BUN. Transmission electron microscopy revealed ruptured podocyte membranes and swollen mitochondria. The positive rate of cells stained by the TUNEL increased, with elevated optical density of NLRP3 and decreased optical density of WT-1. Additionally, there was a significant increase in the level of NLRP3, caspase-1, IL-1β mRNA, as well as miR-200c-3p and miR-148a-3p. The protein expression of NLRP3, ASC, caspase-1, and IL-1β also increased. Compared with HG-Exo group, mice in the HG-Exo+TLYSF group showed decreased levels of mALb, urinary NAG, Scr, and BUN. The podocyte membranes were relatively intact, and mitochondrial damage was alleviated. The positive rate of cells stained by the TUNEL decreased, along with a reduction in the optical density of NLRP3 and an increase in the optical density of WT-1. Furthermore, the mRNA expression levels of NLRP3, caspase-1, IL-1β, miR-200c-3p, and miR-148a-3p were all downregulated to varying degrees. The protein expression levels of NLRP3, ASC, caspase-1, and IL-1β also decreased. Conclusion Exosomes derived from GMC stimulated by high glucose can damage the kidneys of mice and induce podocyte pyroptosis. TLYSF may ameliorate podocyte pyroptosis by downregulating the expression of exosomal miR-200c-3p and miR-148a-3p and inhibiting the activation of the NLRP3/ASC/caspase-1 pathway.
Animals ; Exosomes/ultrastructure* ; Glucose/pharmacology* ; Male ; Podocytes/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred C57BL ; Mice ; Mesangial Cells/metabolism* ; Pyroptosis/drug effects* ; Rats ; MicroRNAs/genetics*

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

OBJECTIVE: Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. METHODS: We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro. RESULTS: SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells. CONCLUSION Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals ; Apoptosis/drug effects* ; Particulate Matter/adverse effects* ; Mice ; Male ; Inflammation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Myocardial Ischemia/drug therapy* ; Cell Line

Objective:To investigate the effect of tofacitinib on early atherosclerosis of patients with systemic lupus erythematosus and explore the possible relationship between lupus nephritis and early atherosclerosis of systemic lupus erythematosus.Methods:Sixteen 8-week-old female MRL/lpr mice with a body weight of 20~25 g were selected and randomly divided into the treatment group and placebo group, with 8 mice in each group. The treatment group diluted tofacitinib by normal saline, and given at a dose of 10 mg·kg -1·d -1, and the placebo group (starch tablets) administered the medication in the same way as the treatment group for a total of 8 weeks. The ELISA method was applied to detect serum anti-dsDNA antibody levels in the two groups of mice. Bradford method protein concentration was used to determine the level of urine protein in mice. Automatic biochemical analyzer was used to detect blood lipids, urea nitrogen, serum creatinine, complement C3, complement C4 levels. Western blotting was used to determine the protein expression levels of monocyte chemoattractant protein-1 (MCP-1), non-receptor protein tyrosine kinase family 1 (JAK1), signal transducer and activator of transcription 1 (STAT1) and signal transducer and activator of transcription 2 (STAT2) in aortic and kidney tissues. After the aortic arch section were prepared, oil red O was used to stain the sections, and the vascular plaque area and intimal thickness were evaluated by ImageJ software. The kidneys were dissected and stained with HE, and the active lesions of lupus nephritis were evaluated using the glomerular activity scoring system. SPSS 23.0 software was used for statistical analysis, in which the between-group comparison was performed using two independent samples t-test, and the correlation analysis was performed using the Spearman method. Results:①The serum anti-dsDNA antibody expression level in the treatment group [(5.2±1.0) U/ml] was lower than that in the placebo group [(6.9±1.2) U/ml], ( Z=-3.07, P=0.008), and the levels of complement C3 and complement C4 were higher than those in the placebo group [(293±10) mg/L vs. (260±19) mg/L, Z=2.72, P=0.017]; (16±6) mg/L vs. (8±9) mg/L, Z=3.78, P=0.006]. There was no significant difference in serum BUN and Scr between the treatment group and the placebo group [(10.6±0.7) mmol/L vs. (11.5±1.1) mmol/L, Z=-1.96, P=0.071; (17±5) μmol/L vs. (22±6) μmol/L, Z=-1.79, P=0.095]. ② Compared with the placebo group, the levels of LDL, TC and TG in the treatment group decreased [(0.83±0.15) mmol/L vs. (1.08±1.05) mmol/L, Z=-3.95, P=0.001; (2.90±0.08) mmol/L vs. (1.81±0.97) mmol/L, Z=-5.17, P=0.001; (1.10±0.08) mmol/L vs. (1.60±0.42) mmol/L, Z=-3.23, P=0.013], and HDL level increased [(2.02±0.99) mmol/L vs. (1.81±0.97) mmol/L, Z=4.42, P=0.001]. ③ Compared with the placebo group, the levels of aortic MCP-1, JAK1, STAT1 and STAT2 in the treatment group were reduced [(0.17±0.30) vs. (0.23±0.05), Z=-3.06, P=0.009; (0.83±0.09) vs. (1.05±0.19), Z=-3.07, P=0.008; (0.77±0.07) vs. (0.94±0.13), Z=-2.83, P=0.014; (0.70±0.07) vs. (0.82±0.09), Z=-2.83, P=0.013], the aortic plaque area and aortic intimal thickness were lower than those in the placebo group [(12±31) μm 2vs. (1 242±1 101) μm 2, Z=-3.12, P=0.016; (63±7) μm vs. (82.10±8.06) μm, Z=-5.13, P<0.001]. ④ Compared with the placebo group, the urine protein level and glomerulonephritis activity score in the treatment group were decreased [(0.08±0.03) mg/mL vs. (0.20±0.11) mg/mL, Z=-3.08, P=0.015; (1.79±0.38) vs. (2.79±0.14) points, Z=-7.08, P<0.001)], and renal tissue MCP-1, JAK1, STAT1.Compared with the placebo group, STAT2 levels were reduced [(0.364±0.040) vs. (0.425±0.021), Z=-3.85, P=0.003; (0.689±0.074) vs. (0.838±0.068), Z=-4.19, P=0.001; (0.508±0.070) vs. (0.646±0.019), Z=-2.85, P=0.015; (0.618±0.062) vs. (0.740±0.101), Z=-2.94, P=0.013. ⑤ The glomerular mobility scores of the two groups were positively correlated with LDL, TCHO, TG, aortic plaque area and aortic intimal thickness ( r=0.51, P=0.043; r=0.79, P<0.001; r=0.64, P=0.008; r=0.82, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.53, P=0.036). The urine protein levels in the two groups were positively correlated with LDL, TC, TG, aortic plaque area and aortic intimal thickness ( r=0.67, P=0.004; r=0.68, P=0.004; r=0.53, P=0.033; r=0.80, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.57, P=0.021). Conclusion:The severity of lupus nephritis is correlated with atherosclerosis and dyslipidemia in the early stage of systemic lupus erythematosus. Tofacitinib may reduce the degree of early arteriosclerosis and lupus nephritis in MRL/LPR mice, and reduce blood lipid levels, which may be effective in improving the prognosis of SLE and improving the survival rate of patients.

Objective To explore the efficacy and safety of"ditching and ridge removal"with 450 nm semiconductor blue laser in the treatment of large volume benign prostatic hyperplasia(BPH),in order to promote the clinical application of this method.Methods A retrospective study was conducted on 30 patients with large volume BPH treated with"ditching and ridge removal"with 450 nm semiconductor blue laser in Yingsheng Branch of Tai'an Central Hospital during Sep.and Dec.2023.The laser operation time,level of hemoglobin before and after operation,bladder irrigation time after operation,urinary catheter indwelling time,postoperative hospital stay,and intraoperative and postoperative complications were recorded.The changes of international prostate symptom score(IPSS),quality of life scale(QoL)score,maximum urinary flow rate(Qmax)and post-void residual volume(PVR)were compared before and 1 month after operation.Results The volume of prostate was(104.5±14.52)mL,the laser operation time was(20.13±2.98)min,and the bladder irrigation time was(20.27±2.56)h.The catheter was removed in all patients 2 days after operation,and all patients were discharged 3 days after operation.One month after operation,the IPSS,QoL,Qmax and PVR were significantly improved as compared with those before operation(P＜0.05).No complications occurred during the follow-up.Conclusion"Ditching and ridge removal"with 450 nm semiconductor blue laser is a new,safe and effective method in the treatment of large volume BPH.