1.Low dose metformin delays silicosis-induced pulmonary fibrosis in mice
Yuanting LIANG ; Zhijia WU ; Qiying NONG ; Na ZHAO
China Occupational Medicine 2023;50(5):524-528
{L-End}Objective To investigate the effect and mechanism of low dose metformin in delaying pulmonary fibrosis in silicosis mice. {L-End}Methods The specific pathogen free C57BL/6 male mice were randomly divided into four groups,with six mice in each group. Mice in the silicosis model group and the metformin intervention group were given 20 μL of a mass concentration of 250 g/L silica suspension, and mice in the blank control group and the drug control group were given 20 μL of 0.9% sodium chloride solution, using tracheal exposure method. After 72.0 hours of dust exposure, the mice of drug control group and metformin intervention group were intraperitoneally injected with metformin at a dose of 65 mg/kg body mass, while the mice in the blank control group and the silicosis model group were given 0.9% sodium chloride solution at the same volume, once every other day for 28 days. After the treatment, histopathological change of the lungs was observed, lung organ coefficient was calculated, degree of pulmonary fibrosis was evaluated with Ashcroft score, and mRNA expression of fibronectin (Fn)1 and collagen typeⅠ(COLⅠ) alpha 1 (Col1a1) in lung tissues were detected by real-time fluorescence quantitative polymerase chain reaction. The relative expression of FN and COLⅠ in lung tissues was determined by Western blot. {L-End}Results The results of histopathological examination of the lungs showed that there were no inflammation and fibrosis in the lungs of mice in the blank control group and the drug control group; mice in silicosis model group had inflammation and fibrosis in lung; the degree of lung inflammation and fibrosis was reduced in the mice of metformin intervention group compared with the silicosis model group. The lung organ coefficient, Ashcroft score, the relative expression of Fn1 and Col1a1 mRNA, the relative expression of FN and COLⅠprotein in lung tissues increased in silicosis model group (all P<0.05), compared with those in both blank control group and drug control group. The indexes above decreased of mice in the metformin intervention group than those in the silicosis model group (all P<0.05). {L-End}Conclusion Low-dose metformin can delay the progression of pulmonary fibrosis in silicosis mice. The mechanism may be related to metformin's improving excessive deposition of extracellular matrix induced by silica.
2.Preoperative intravenous injection of tranexamic acid combined with postoperative local use of elastic bandage to reduce blood loss for complex tibial plateau fractures: a prospective controlled clinical trial
Peng ZOU ; Zhimeng WANG ; Junsong YANG ; Xiaoqiang HUANG ; Yuanting ZHAO
Chinese Journal of Orthopaedic Trauma 2020;22(8):676-681
Objective:To assess the effects of preoperative intravenous injection of tranexamic acid and postoperative local use of elastic bandage on blood loss in complex tibial plateau fractures (Schatzker types Ⅴ-Ⅵ).Methods:A sequence randomly generated by computer was used to randomize a cohort of 40 patients into 2 groups who were to receive surgery at Department of Orthopaedics and Trauma, Hong Hui Hospital from June 2018 to January 2019 for complex tibial plateau fractures. They were 24 men and 16 women, aged from 35 to 55 years (average, 46.0 years). In group A, intravenous injection of normal saline was conducted 5 to 10 min before surgical incision and no elastic bandage was used after surgery. In group B, a dose of 15 mg/kg tranexamic acid was intravenously given 5 to 10 min before surgical incision and elastic bandage was used to bandage the knee with compression after surgery. The 2 groups were compared in terms of total blood loss, hidden blood loss, transfusion rate, 48-h drainage flow, venous thromboembolism, postoperative wound complications, postoperative visual analogue scale (VAS), and D-dimer value 24 h after surgery.Results:There were no significant differences between the 2 groups in age, gender, body mass index, smoking history, concomitant medical conditions, American Society of Anesthesiologists (ASA) score, preoperative hemoglobin, preoperative hematocrit, preoperative D-dimerization or fibrin degradation products, showing comparability ( P>0.05). In groups A and B, hemoglobin values 24 h after surgery were 104.6 g/L ± 10.4 g/L versus 113.3 g/L ± 11.9 g/L, drainage volumes 48 h after surgery 277.1 mL ± 229.2 mL versus 207.1 mL ± 124.3 mL, hidden blood loss volumes 318.0 mL ± 83.4 mL versus 266.2 mL ± 60.9 mL, total blood loss volumes 792.8 mL ± 202.8 mL versus 692.2 mL ± 124.9 mL, D-dimer values 24 h after surgery 5.1 mg/L ± 1.3 mg/L versus 4.1 mg/L ± 0.7 mg/L, postoperative VAS scores 5.2 ± 0.9 versus 3.9 ± 1.1, lower limb cross-section diameters 24 h after surgery 35.5 cm ± 3.0 cm versus 34.4 cm ± 2.6 cm, lower limb cross-section diameters 72 h after surgery 33.8 cm ± 2.1 cm versus 32.8 cm ± 2.3 cm, postoperative rates of wound ecchymosis hematoma 20.0% (4 cases) versus 0 (0 cases), and hospital stays 6.6 d ± 1.0 d versus 6.2 d ± 1.2 d. There were significant differences between the 2 groups in all the above items ( P<0.05). However, there were no significant differences between the 2 groups in incidence of postoperative DVT, pulmonary embolism or other wound complications ( P>0.05). Conclusions:Preoperative intravenous injection of tranexamic acid and postoperative local use of elastic bandage is reasonable and safe for complex tibial plateau fractures, because it significantly reduces intraoperative blood loss but does not increase the risk of venous thromboembolism, and thus has a positive role in accelerating the recovery of patients.
3.Exploring the mechanism of action of curcumin in the treatment of silicosis based on network pharmacology and molecular docking
Zhijia WU ; Jiayun WU ; Yuanting LIANG ; Meimei ZHONG ; Wei WEI ; Yiru QIN ; Na ZHAO
China Occupational Medicine 2023;50(4):361-369
Objective To explore the mechanism of action of curcumin in the treatment of silicosis by network pharmacology combined with molecular docking technology. Methods The targets prediction network of curcumin in treating silicosis was established based on the collection of targets of curcumin and silicosis in multiple databases, cross-targets were submitted to the STRING database, and their connectivity was analyzed by Cytoscape software. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the top 20 genes. The molecular docking was performed on the key targets to study the mechanism of action of curcumin in treating silicosis. Results A total of 311 targets related to curcumin, 270 targets related to silicosis, and 74 cross-targets were obtained from the databases. GO function analysis revealed 2 665 related pathways, and KEGG pathway enrichment analysis revealed 188 related pathways. Molecular docking results showed that curcumin had good binding ability with the targets of mitogen-activated protein kinase 3 (MAPK3), interleukin (IL) 6, serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), signal transducer and activator of transcription 3, albumin, Jun proto-oncogene, tumor necrosis factor (TNF), IL1B, tumor protein p53, C-C motif chemokine ligand 2 and fibronectin 1. Conclusion The therapeutical effects of curcumin on silicosis were implemented through multi-targets and multi-pathways. Curcumin may play a role in the treatment of silicosis by binding to the core targets MAPK3, IL6, AKT1, VEGFA and TNF and regulating the MAPK, IL6, TNF, phosphatidylinositol 3-kinase/protein kinase B and VEGF signaling pathways.
4.Foundation of acute symptomatic osteoporotic thoracolumbar fracture classification system and its validity examination and clinical application evaluation
Dingjun HAO ; Jianan ZHANG ; Junsong YANG ; Tuanjiang LIU ; Xiaohui WANG ; Peng LIU ; Liang YAN ; Yuanting ZHAO ; Qinpeng ZHAO ; Dageng HUANG ; Jijun LIU ; Shichang LIU ; Yunfei HUANG ; Yuan TUO ; Ye TIAN ; Lulu BAI ; Heng LI ; Zilong ZHANG ; Peng ZOU ; Pengtao WANG ; Qingda LI ; Xin CHAI ; Baorong HE
Chinese Journal of Trauma 2021;37(3):250-260
Objective:To establish the acute symptomatic osteoporotic thoracolumbar fracture (ASOTLF) classification system, and to examine the reliability and evaluate the effect of clinical application.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 293 patients with osteoporotic thoracolumbar fracture(OTLF) admitted to Honghui Hospital from January 2016 to December 2018. There were 514 males and 779 females, aged 57-90 years [(71.4±6.3)years]. The T value of bone mass density was -5.0--2.5 SD [(-3.1±-0.4)SD]. According to the clinical symptoms a and fracture morphology, OTLF was divided into 4 types, namely type I(I occult fracture), type II(compressed fracture), type III (burst fracture) and type IV(unstable fracture). The type II was subdivided into three subtypes (type IIA, IIB, IIC), and the Type III into two subtypes (type IIIA, IIIB). of all patients, 75 patients (5.8%) were with type I, 500 (38.7%) with type II A, 134 (10.4%) with type IIB, 97 (7.5%) with type IIC, 442 (34.2%) with type IIIA, 27(2.1%) with type IIIB and 18 (1.4%) with type IV. After testing the validity of the classification, different treatment methods were utilized according to the classification, including percutaneous vertebroplasty (PVP) for Type I, PVP after postural reduction for Type II, percutaneous kyphoplasty (PKP) for Type IIIA, posterior reduction and decompression, bone graft fusion and bone cement-augmented screw fixation for Type IIIB, and posterior reduction, bone graft fusion and bone cement-augmented screw fixation for Type IV. The visual analog score (VAS), Oswestry disability index (ODI), Frankel grade of spinal cord injury, local Cobb Angle, and vertebral body angle (vertebral body angle) were recorded in all patients and in each type of patients before surgery, at 1 month after surgery and at the last follow-up. The neurological function recovery and complications were also recorded.Results:The patients were followed up for 24-43 months [(29.9±5.1)months]. A total of 3 000 assessments in two rounds were conducted by three observers. The overall κ value of inter-observer credibility was 0.83, and the overall κ value of intra-observer credibility was 0.88. The VAS and ODI of all patients were (5.8±0.7)points and 72.5±6.6 before surgery, (1.8±0.6)points and 25.0±6.3 at 1 month after surgery, and (1.5±0.6)points and 19.5±6.2 at the last follow-up, respectively (all P<0.05). The Cobb angle and vertebral body angle of all patients were (13.0±9.1)° and (8.0±4.6)° before surgery, (7.9±5.2)° and (4.6±2.9)° at 1 month after surgery, and (9.1±6.0)° and (5.8±3.0)° at the last follow-up, respectively (all P<0.05). At the last follow-up, VAS, ODI, Cobb Angle and VBA of each type of patients were significantly improved compared with those before surgery (all P<0.05). The spinal cord compression symptoms were found 1 patient with type IV and 5 patients with type IIIB preoperatively. At the last follow-up, neurological function improved from grade C to grade E in 1 patient and from grade D to grade E in 5 patients ( P<0.05). The lower limb radiation pain or numbness in 3 patients with type IV and 22 patients with type III preoperatively were fully recovered after surgical treatment at the last follow-up except for three patients. Conclusions:The ASOTLF classification is established and has high consistency and reliability. The classification-oriented treatment strategy has achieved a relatively satisfactory effect, indicating that the classification has a certain guiding significance for treatment of OTLF.
5.Causes of residual back pain at early stage after percutaneous vertebroplasty
Junsong YANG ; Hao CHEN ; Peng LIU ; Tuanjiang LIU ; Jijun LIU ; Zhengping ZHANG ; Baorong HE ; Liang YAN ; Haiping ZHANG ; Yuanting ZHAO ; Jianan ZHANG ; Dageng HUANG ; Dingjun HAO
Chinese Journal of Orthopaedics 2020;40(10):625-634
Objective:To explore the risk factors of residual back pain (RBP) in patients undergone PVP within 1 month and further analyze the correlation.Methods:Between March 2013 and January 2015, 1 316 patients with OVCF were treated by PVP. RBP after PVP was defined as a visual analogue scale (VAS) score of > 4 both 1 week and 1 month post-operatively. According to the pain relief, the patients were divided into two groups, the satisfied group and the unsatisfied group. All patients were scheduled for follow-up at1 week, 1 month, 3 months, and 1 year post-operatively, during which radiography and magnetic resonance imaging (T1-weighted, T2-weighted, and short time inversion recovery (STIR) sequences) were recommended to detect the existence of secondary OVCF. VAS scores and Oswestry disability index (ODI) were recorded. Demographic data, surgical information, anesthesia method, number of OVCF, injection amount of cement of single vertebral bone, imaging data and other comorbidity informations of patients in the two groups were analyzed by Logistic regression for the factors related to RBP after PVP.Results:Among 1 316 patients, 60 cases complained RBP, and the prevalence was 4.6%. VAS score and ODI of the two groups were significantly different at 1 week, 1 month and 3 months after surgery, suggesting there was a certain degree of residual pain in the lower back of patients in the unsatisfied group, which was more severe than that in the satisfied group. However, the above differences disappeared in the follow-up of 12 months after surgery.Univariate analysesshowed that preoperative bone mineral density (BMD), number of fracture, cement distribution and volume injected per level and lumbodorsal fascia contusion were associated with RBP after PVP ( P< 0.01, retrospectively). Multivariate analysis revealed that the absolute value of pre-operative BMD(odds ratio ( OR)=3.577, P=0.029), combined withlumbodorsal fascia contusion ( OR=3.805, P=0.002), number of fracture ( OR=3.440, P<0.001), satisfactory cement distribution ( OR=3.009, P=0.013) and combined with depression ( OR=3.426, P=0.028) were positively correlated with RBP after PVP, and these were risk factors. The injection amount of cement of single vertebral bone ( OR=0.079, P<0.001) was negatively correlated with RBP after PVP, which was a protective factor. Conclusion:Pre-operative low BMD, lumbodorsal fascial injury, multiple segment OVCF, insufficient cement injected volume, unsatisfactory cement distribution and depression were risk factors associated with RBP after PVP in patients with OVCF.