Objective:To explore and analyze the efficacy of preoperative intravenous tranexamic acid (TXA) in reducing bleeding and alleviating early postoperative pain in elderly patients with proximal humeral fractures (PHF) who underwent minimally invasive plate osteosynthesis (MIPO) approach with open reduction and locking plate internal fixation.Methods:A retrospective analysis was conducted on the data of 165 elderly patients with partial or partial PHF who underwent open reduction and locking plate internal fixation via MIPO approach at the Yixing People′s Hospital from June 2018 to June 2021. According to whether TXA was used intravenously 30 minutes before surgery, patients were divided into a TXA group (77 cases) and a control group (88 cases). The surgical time, hemoglobin decrease, total blood loss (TBL), intraoperative blood loss (IBL), postoperative drainage volume, visible blood loss (VBL), hidden blood loss (HBL), blood transfusion status, Visual Analogue Scale (VAS) score for surgical site pain 24 hours after surgery, postoperative hospital stay, shoulder Constant-Murley function score at 1 and 3 months after surgery, and complications were recorded and compared between the two groups.Results:The TBL, VBL, IBL, HBL, postoperative drainage volume, hemoglobin decrease, transfusion rate, postoperative VAS score at the surgical site, and hospital stay in the TXA group were all lower than those in the control group, and the differences were statistically significant (all P<0.05). The VAS score at the surgical site 24 hours after surgery was positively correlated with TBL and HBL in two groups of patients ( r=0.402, 0.418, P<0.001). Compared with the control group, the TXA group had a higher shoulder Constant-Murley function score at 1 month after surgery, and the difference was statistically significant ( P=0.002). There was no statistically significant difference in shoulder Constant-Murley function score and incidence of complications between the two groups at 3 months after surgery (all P>0.05). Conclusions:For elderly patients with partial or partial PHF who underwent open reduction and locking plate internal fixation using MIPO approach, intravenous infusion of TXA 30 minutes before surgery can help alleviate postoperative pain at the surgical site, reduce intraoperative and postoperative bleeding, lower transfusion rates, shorten hospital stay, and do not increase the incidence of complications such as incision abnormalities and thrombosis, which is beneficial for promoting early and rapid recovery of patients.

Objective:Observing the effect of exosomes derived from hypoxic Bone marrow mesenchymal stem cells (BMSCs) on the function of chondrocytes, and exploring the role and mechanism of exosomal miR-196b-5p. Evaluating the application prospects of hypoxic BMSCs exosomes and miR-196b-5p for cartilage regeneration.Methods:Chondrocytes were cultured in the supernatant of BMSCs cultured under normoxia or hypoxia, respectively. The proliferation of chondrocytes was detected by CCK-8 assay and the expressions of Collagen type 2 (Col2), Col1, Aggrecan and SOX9 were detected by qPCR to evaluate the effect of hypoxic BMSCs paracrine on chondrocyte functions. Obtaining normoxic and hypoxic exosomes through ultracentrifugation, and testing their effects on the proliferation and anabolic-related genes of chondrocytes through CCK-8 assay and qPCR. Verifying the expression of miR-196b-5p in hypoxic exosomes based on exosomal miRNA array. Knocking out miR-196b-5p in hypoxic BMSCs, and detecting the effect of hypoxic exosomal miR-196b-5p on the functions of chondrocytes by loss-of-function assay. Predicting the downstream of miR-196b-5p through bioinformatics tools, and exploring the mechanism of hypoxic exosomal miR-196b-5p by gain-of-function assays. Hypoxic exosomes and miR-196b-5p-knockout hypoxic exosomes were loaded on silk fibroin hydrogel and subcutaneously into nude mice. After 4 weeks of culture, histological staining of saffron O, Masson and biochemical content of sGAG and collagen were performed to assess the application prospect of hypoxic exosomes and hypoxic exosomal miR-196b-5p on cartilage regeneration. Results:The results of CCK-8 assay and qPCR indicated that the supernatant of hypoxic BMSCs significantly promoted the proliferation of chondrocytes 1.20±0.07 and the expression of cartilage-related markers (Col2 2.95±0.17, Aggrecan 2.45±0.27, SOX9 2.92±0.29) compared to normoxic BMSCs (0.94±0.04, 1.89±0.09, 1.67±0.21, 1.76±0.16), the differences were statistically significant ( P<0.05). The result of CCK-8 assay showed that hypoxic exosomes (1.28±0.04) promoted the proliferation of chondrocytes compared to normoxic exosomes 1.05±0.06, the differences were statistically significant ( P<0.05). CCK-8 assay revealed that the down-regulation of miR-196b-5p in hypoxic exosomes 0.99±0.06 attenuated the proliferation of chondrocytes compared to control group 1.20±0.07, the differences were statistically significant ( P<0.05); the expression of Col2 0.56±0.04, Aggrecan 0.74±0.09, and SOX9 0.45±0.05 in chondrocytes was reduced in the miR-196b-5p knockdown group compared to the control group (1.00±0.09, 1.00±0.12, 1.00±0.07), the differences were statistically significant ( P<0.05). Co-transfection of pmirGLO-BACH1-WT reporter vector with miR-196b-5p mimics decreased the luciferase activity 0.73±0.06, the differences were statistically significant ( P<0.05). Co-transfection of pmirGLO-BACH1-MUT reporter vector with miR-196b-5p mimics showed no change in luciferase activity. BACH1 is the target of miR-196b-5p. Subcutaneous culture in nude mice showed that hypoxic exosomes significantly promoted the deposition of sGAG 383.2±21.54 and collagen 67.40±3.45, while reducing the expression of miR-196b-5p in hypoxic exosomes weakened the deposition of sGAG 258.4±19.50 and collagen 57.15±4.95, the differences were statistically significant ( P<0.05). Conclusion:Hypoxic exosomes promoted the functions of chondrocytes by inhibiting the expression of BACH1 through miR-196b-5p. Hypoxic exosomes can be applied in cartilage regeneration.

Objective:To explore the independent risk factors for the occurrence and aggravation of lower back pain (LBP) in patients with Parkinson′s disease (PD), in order to provide reference for clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the case data of 309 PD patients who visited the Affiliated Yixing Hospital of Jiangsu University from June 2018 to May 2020. The KING Parkinson′s Disease Pain Scale (KPPS) was used to quantitatively evaluate the LBP of PD patients, who were divided into LBP group and Non LBP group. The general clinical data, PD related data, and imaging data of the two groups were compared and analyzed. Binary logistic regression analysis was used to evaluate independent risk factors for LBP in PD patients. Pearson correlation analysis was conducted between KPPS scores and various factors, and linear regression analysis was used to identify the relevant risk factors that exacerbate LBP in PD patients.Results:Compared with the Non LBP group, the LBP group had lower bone mineral density (BMD) and a lower proportion of patients who engaged in daily exercise. The difference between the two groups was statistically significant (all P<0.05). Compared with the Non LBP group, patients in the LBP group had a longer course of illness, higher stiffness scores, a higher proportion of patients with fluctuating symptoms, higher UPDRS-Ⅲ scores, and a higher proportion of patients with thoracolumbar fascial injury (TLFI) and lumbar sagittal imbalance. The differences between the two groups were statistically significant (all P<0.05). The results of binary logistic regression analysis showed that combined TLFI ( OR=2.773, 95% CI: 1.219-6.309, P=0.015), combined lumbar sagittal imbalance ( OR=4.835, 95% CI: 2.244-10.421, P<0.001), and lower BMD ( OR=2.818, 95% CI: 1.767-4.493, P<0.001) were risk factors for LBP in PD patients. The KPPS score was correlated with BMD and TLFI ( r=-0.146, 0.294, all P<0.05). The linear regression results showed that the merged TLFI ( B=2.271, β=0.285, P<0.001) was positively correlated with KPPS score, indicating a risk factor. Conclusions:The combination of TLFI, lumbar sagittal imbalance, and lower BMD is closely related to the occurrence of LBP in PD patients, and the combination of TLFI is an independent risk factor for exacerbating LBP symptoms. Clinical attention should be paid to the prevention and treatment of TLFI in PD patients.

Objective:To investigate the mechanism by which baicalein alleviates osteoarthritis by regulating Sirtuin (Sirt) to inhibit the senescence of fibroblast-like synoviocytes (FLS).Methods:FLS were extracted from synovium of non-osteoarthritis patients (3 patients) and osteoarthritis patients (3 patients), and assessed the senescence of FLS in osteoarthritis patients by Western blot, β-galactosidase staining and immunofluorescence, and examined the changing levels of Sirt family proteins and mRNAs in FLS. The relative expression level of Sirt1 in FLS was knocked down by transfection with Sirt1 siRNA, and the antioxidative capacity and senescence degree of FLS were analyzed. Chondrocytes were co-cultured with FLS and functional changes in chondrocytes were detected by Western blot. After inducing FLS senescence with bleomycin (BLM), different concentrations of baicalein were administered to detect the expression levels of Sirt1, p16, and p21 proteins and intracellular reactive oxygen species (ROS). The expression level of Sirt1 in FLS was knocked down, and BLM and baicalein treatments were applied. The relative expression levels of Sirt1 and ROS were detected using Western blot and ROS assays. After BLM-induced FLS senescence, baicalein and Compound C were added. The relative expression levels of phosphorylated AMP-activated protein kinase (pAMPK), nuclear factor erythroid 2-related factor 2 (NRF2), p16, p21, and ROS were detected by Western blot and ROS assays.Results:The relative expression of p16 and p21 in FLS in the osteoarthritic group were 3.66±0.38 and 3.55±0.34, which were higher than those in non-osteoarthritis group 1.00±0.07 and 1.00±0.09 ( t=11.860, P<0.001; t=12.520, P<0.001). The relative expression levels of Sirt1 and Sirt6 in FLS in the osteoarthritis group were 0.30±0.04 and 0.16±0.01, which were smaller than those in the non-osteoarthritis group 1.00 ± 0.03 and 1.00±0.04 ( t=23.840, P<0.001; t=34.130, P<0.001). After baicalein treatment, the relative expression of ROS was 2.58±0.28, 1.65±0.14 and 1.00±0.24 in the BLM, BLM+Bai and control groups, respectively, with statistically significant differences between the groups ( F=35.700, P<0.001), which was greater in the BLM and BLM+Bai than in the control group, and lower in the BLM+Bai than in the BLM group ( P<0.05). The relative expression of pAMPK and NRF2 was 0.28±0.02 and 0.38±0.09 after Compound C+Baicalein treatment, which was lower than that of 0.56±0.07 and 0.60±0.08 in the BLM+Bai group ( P<0.05). The relative expression of ROS increased from 1.75±0.16 to 3.45±0.12 ( P<0.001). The proportion of positivity in the BLM+Bai+Compound C, BLM+Bai and control groups was 47.30%±4.29%, 18.18%±3.89% and 7.70%±3.53% ( F=109.700, P<0.001), respectively, with the BLM+Bai+Compound C group being higher than that in the BLM+Bai group ( P<0.05). Conclusion:The downregulation of Sirt1 expression in patients with osteoarthritis leads to FLS senescence and accelerates the progression of osteoarthritis. Baicalein can inhibit FLS senescence by activating Sirt1/AMPK/NRF2 pathway, which may delay the progression of osteoarthritis and improve the function of chondrocytes.