Bergamottin (Ber) ameliorates the progression of osteoarthritis via the Sirt1/NF-κB pathway.

Osteoarthritis (OA) is a common chronic disease characterized by progressive cartilage degeneration and secondary synovial inflammation. Bergamottin (Ber) is an important natural derivative of the furanocoumarin compound, extracted from natural foods, such as the pulp of grapefruits and pomelos. Ber exhibits several characteristicsthat are beneficial to human health, such as anti-inflammation, antioxidant, and anti-cancer effects. However, the role of Ber in the treatment of OA has not been elucidated to date. Therefore, in the present study, in vitro experiments were conducted, which demonstrated that Ber reduces the secretion of inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) under the stimulation of interleukin-1ß (IL-1ß). Ber also reversed the IL-1 ß-mediated aggrecan and type II collagen degradation within the extracellular matrix (ECM). In addition, in vivo experiments were conducted, in which Ber ameliorated the progression of OA in mice. It was revealed that Ber exerted its cellular effect by activating the Sirt1/NF-kB pathways. In conclusion, the present study demonstrated the therapeutic potential of Ber in the context of OA.

Intraoperative pain prediction of percutaneous kyphoplasty under local anesthesia by preoperative experimental pain assessment.

BACKGROUND: Percutaneous kyphoplasty (PKP) is the preferred treatment for osteoporotic vertebral compression fractures (OVCF) Currently, the preoperative anesthesia methods for PKP are mainly local anesthesia and tracheal intubation general anesthesia. OBJECTIVE: To assess whether patient sensitivity to pain measured preoperatively could predict the patients' pain response during PKP treatment under local anesthesia, to facilitate the development of an optimal preoperative anesthesia plan for patients. METHODS: Fifty-five female patients diagnosed with osteoporotic single vertebral fracture who were treated with PKP under local anesthesia were selected. The patients' pain sensitivities, including pain threshold and pain tolerance threshold, were evaluated with a pain test device on the day before the operation in the ward. Heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SpO2) were recorded before anesthesia, post-anesthesia, after needle puncture, and after balloon dilatation. At the same time, blood was drawn at the above time points to determine the level of norepinephrine (NA) as an indicator of intraoperative pain stress response. The numerical rating scale (NRS) during surgery was recorded at the end of the surgery. RESULTS: The preoperative pain tolerance threshold of 55 surgical patients was correlated with the intraoperative NRS score (r=-0.768, P< 0.001), as well as with the preoperative and intraoperative changes in HR (r=-0.791, P< 0.001), MAP (r=-0.819, P< 0.001), and NA (r=-0.553, P< 0.001). Thus, the lower the preoperative pain tolerance threshold, the more severe the patient's response to pain during PKP treatment under local anesthesia, and the greater the hemodynamic changes. Consequently, the intraoperative experience becomes worse. However, there was no correlation between preoperative pain threshold and NRS scores (r=-0.069, P= 0.616) nor between the preoperative and intraoperative changes in HR (r= 0.103, P= 0.453), MAP (r= 0.086, P= 0.535), and NA (r=-0.058, P= 0.674). CONCLUSION: The results indicated that preoperative pain assessment could predict the level of pain response in OVCF patients during PKP surgery under local anesthesia.

Procyanidin B2 regulates the Sirt1/Nrf2 signaling pathway to improve random-pattern skin flap survival.

Random-pattern skin flaps have been widely used in the reconstruction of damaged tissues. Ischemia-reperfusion injury occurring in the distal regions of the flap is a common issue, which often leads to flap necrosis and restricts its clinical applications. Procyanidin B2 (PB2), a naturally occurring flavonoid in large quantities in various fruits, has been demonstrated to exhibit several significant pharmacological properties. However, the effect of PB2 on flap viability is not clearly known. Here, using Western blot analysis, immunohistochemistry, and immunofluorescence staining, we observed that PB2 significantly reduced oxidative stress and inflammation and enhanced angiogenesis. Mechanically, we provided evidence for the first time that the beneficial effects of PB2 occur through the activation of the Sirt1/Nrf2 signaling pathway. Moreover, co-administration of PB2 and EX527, a selective inhibitor of Sirt1, resulted in down-regulation of the expression of Sirt1, Nrf2, and downstream antioxidants. In summary, our study showed that PB2 might be a novel therapeutic strategy for improving the survival of random-pattern skin flaps.

Comparison of unipedicular and bipedicular kyphoplasty for treating acute osteoporotic vertebral compression fractures in the lower lumbar spine: a retrospective study.

BACKGROUND: Unipedicular and bipedicular approaches for percutaneous kyphoplasty are reportedly both effective in treating osteoporotic vertebral compression fractures (OVCFs). However, most studies have reported thoracolumbar fractures, with few reports describing the treatment of the lower lumbar spine. Here, we compared the clinical and radiological results of unipedicular and bipedicular approaches for percutaneous kyphoplasty for treating osteoporotic vertebral compression fractures. METHODS: We retrospectively reviewed the records of 160 patients who underwent percutaneous kyphoplasty for lower lumbar (L3-L5) osteoporotic vertebral compression fractures between January 2016 and January 2020. Patient characteristics, surgical outcomes, operation time, blood loss, clinical and radiological features, and complications were compared between two groups. Cement leakage, height restoration, and cement distribution were calculated from the radiographs. Visual pain analog scale (VAS) and Oswestry Disability Index (ODI) were calculated before surgery, immediately post-surgery, and 2 years after surgery. RESULTS: The mean age, sex, body mass index, injury time, segmental distribution, and morphological classification of fractures before surgery did not differ significantly between the groups. The results showed significant improvements in the VAS score, ODI score, and vertebral height restoration in each group (p < 0.05), with no significant differences between the two groups (p > 0.05). The mean operation time and extent of blood loss were lower in the unipedicular group than those in the bipedicular group (p < 0.05). Different types of bone cement leakage were observed in both groups. Leakage rate was higher in the bipedicular group than in the unipedicular group. Patients in the bipedicular group showed greater improvement in bone cement distribution than those in the unipedicular group (p < 0.05). CONCLUSIONS: The clinical and radiological results of unipedicular percutaneous kyphoplasty for treating osteoporotic vertebral compression fractures in the lower lumbar region were similar to those of bipedicular percutaneous kyphoplasty. However, the unipedicular approach resulted in shorter surgical time, less blood loss, and less bone cement leakage. Thus, the unipedicular approach may be preferable owing to its several advantages.

Percutaneous mesh-container-plasty versus percutaneous kyphoplasty for the treatment of Kümmell's disease: a retrospective cohort study.

BACKGROUND: Both percutaneous kyphoplasty (PKP) and percutaneous mesh-container-plasty (PMCP) were important procedures for the treatment of Kümmell's disease. This study aimed to compare the clinical and radiological results of PKP and PMCP for the treatment of Kümmell's disease. METHODS: This study included patients with Kümmell's disease treated at our center between January 2016 and December 2019. A total of 256 patients were divided into two groups according to the surgical treatment they received. Clinical, radiological, epidemiological, and surgical data were compared between the two groups. Cement leakage, height restoration, deformity correction, and distribution were evaluated. The visual analog scale (VAS), Oswestry Disability Index (ODI), and short-form 36 health survey domains "role-physical" (SF-36 rp) and "bodily pain" (SF-36 bp) were calculated preoperatively, immediately after surgery, and 1-year postoperatively. RESULTS: The VAS and ODI scores improved in the PKP [preoperative: 6 (6-7), 68.75 ± 6.64; postoperative: 2 (2-3), 23.25 ± 3.50, respectively] (p < 0.05) and the PMCP [preoperative: 6 (5-7), 67.70 ± 6.50; postoperative: 2 (2-2), 22.24 ± 3.55, respectively] groups (p < 0.05). There were significant differences between the two groups. The mean cost in the PKP group was lower than that in the PMCP group (3697 ± 461 vs. 5255 ± 262 USD, p < 0.05). The cement distribution in the PMCP group was significantly higher than that in the PKP group (41.81 ± 8.82% vs. 33.65 ± 9.24%, p < 0.001). Cement leakage was lower in the PMCP group (23/134) than in the PKP group (35/122) (p < 0.05). The anterior vertebral body height ratio (AVBHr) and Cobb's angle improved in the PKP (preoperative: 70.85 ± 16.62% and 17.29 ± 9.78°; postoperative: 80.28 ± 13.02% and 13.05 ± 8.40°, respectively) and PMCP (preoperative: 70.96 ± 18.01% and 17.01 ± 10.53°; postoperative: 84.81 ± 12.96% and 10.76 ± 9.23°, respectively) groups (p < 0.05). There were significant differences in vertebral body height recovery and segmental kyphosis improvement between the two groups. CONCLUSIONS: PMCP had advantages over PKP in terms of pain relief and functional recovery for the treatment of Kümmell's disease. Moreover, PMCP is more effective than PKP in preventing cement leakage, increasing cement distribution, and improving vertebral height and segmental kyphosis, despite its higher cost.

Sitagliptin attenuates neuronal apoptosis via inhibiting the endoplasmic reticulum stress after acute spinal cord injury.

Regulation of endoplasmic reticulum stress (ER) stress-induced apoptosis and nerve regeneration is a hopeful way for acute spinal cord injury (SCI). Sitagliptin (Sita) is one of dipeptidyl peptidase-4 (DPP-4) inhibitor, which is beneficial neurons damaged diseases. However, its protective mechanisms of avoiding nerve injury remain unclear. In this study, we further investigated the mechanism of the anti-apoptotic and neuroprotective effects of Sita in promoting locomotor recovery from SCI. In vivo results showed that Sita treatment reduced neural apoptosis caused by SCI. Moreover, Sita effectively attenuated the ER tress and associated apoptosis in rats with SCI. A striking feature was the occurrence of nerve fiber regeneration at the lesion site, which eventually led to significant locomotion recovery. In vitro results showed that the PC12 cell injury model induced by Thapsigargin (TG) also showed similar neuroprotective effects. Overall, sitagliptin showed potent neuroprotective effects by targeting the ER stress-induced apoptosis both in vivo and vitro, thus facilitating the regeneration of the injured spinal cord.

Percutaneous mesh-container-plasty versus percutaneous kyphoplasty in the treatment of malignant thoracolumbar compression fractures: a retrospective cohort study.

OBJECTIVE: This study aimed to compare the clinical and radiological results of percutaneous mesh-container-plasty versus percutaneous kyphoplasty in the treatment of malignant thoracolumbar compression fractures. METHODS: Patients with malignant thoracolumbar compression fractures treated in a single tertiary care center between January 2011 and December 2020 were retrospectively reviewed and included in the study. Ninety-four patients who were diagnosed by pathological biopsy were divided into 2 groups according to the type of surgical treatment: the percutaneous kyphoplasty group (50 patients: 24 male, 26 female; mean age=73.02 ± 7.79 years) and the percutaneous mesh-container-plasty group (44 patients: 21 male, 23 female; mean age=74.68 ± 7.88 years). The epidemiological data, surgical outcomes, and clinical and radiological features were compared between the 2 groups. Cement leakage, height restoration, deformity correction, and cement distribution were calculated from the radiographs. The visual analog scale, Oswestry disability index, Karnofsky performance scale scores, and short-form 36 health survey domains role physi cal and bodily pain were calculated preoperatively, immediately, and 1 year postoperatively. RESULTS: The visual analog scale score improved from 5 (range=4-6) preoperatively to 2 (range=2-3) immediately postoperatively in the percutaneous kyphoplasty group and from 5 (range=4-6) preoperatively to 2 (range=2-2) immediately postoperatively in the percutane ous mesh-container-plasty group; there was a significant difference between the 2 groups (P=.018). Although Oswestry disability index, Karnofsky performance scale, short-form 36 health survey domains bodily pain and role physical significantly improved in both groups after surgery compared to the preoperative period, there was no significant difference between the 2 groups (P > .05). The mean cost in the percutaneous kyphoplasty group was lower than that in the percutaneous mesh-container-plasty group (5563 ± 439 vs. 6569 ± 344 thousand dollars, P < .05). There was no difference between the cement volume in the 2 groups, and cement distribution in the percutaneous mesh-container-plasty group was higher than that in the percutaneous kyphoplasty group (44.30% ± 10.25% vs. 32.54% ± 11.76%, P < .05). Cement leakage was found to be lesser in the percutaneous mesh-container-plasty group (7/44) than in the percutane ous kyphoplasty group (18/50, P < .05). There were no statistically significant differences in the recovery of vertebral body height and improvement of segmental kyphosis between the 2 groups (P > .05). CONCLUSION: Percutaneous kyphoplasty and percutaneous mesh-container-plasty both have significant abilities in functional recovery, height restoration, and segment kyphosis improvement in treating malignant thoracolumbar compression fractures. Percutaneous mesh container-plasty may be better able to relieve pain, inhibit cement leakage, and improve cement distribution than percutaneous kypho plasty. However, percutaneous mesh-container-plasty requires a relatively longer procedure and is more expensive than percutaneous kyphoplasty. LEVEL OF EVIDENCE: Level III, Therapeutic Study.

[Analysis of the effect of double button plate combined with strengthened anchor in the treatment of acromioclavicular dislocation].

OBJECTIVE: To evaluate the efficacy and prognosis of double button plate combined with strengthened anchor technique and clavicular hook plate internal fixation for complete acromioclavicular joint dislocation. METHODS: From July 2017 to September 2020, a total of 42 patients with acromioclavicular joint dislocation treated by surgery were choosen as study objects and divided into observation group (21 cases) and control group (21 cases). In the observation group, there were 14 males and 7 females, aged 21 to 63 years old, with an average of (45.05±8.70) years old. In the control group, there were 16 males and 5 females, aged 25 to 68 years old, with an average of(45.00±9.44) years old. The patients in the observation group were treated with double button plate combined with strengthened anchor technique, whereas those in the control group received clavicular hook plate internal fixation. The two groups were compared in terms of operating time, intraoperative blood loss, postoperative hospital stay, shoulder pain(visual analogue scale, VAS) score, shoulder function Constant-Murley score and postoperative complications. RESULTS: There was no significant difference between the two groups in intraoperative blood loss or postoperative hospital stay(P>0.05). The operating time of double button plate combined with strengthened anchor technique group (65.24±5.36) min was significantly longer than that of the clavicular hook plate group (48.81±4.72) min, and the difference was statistically significant (P<0.05). There was no significant difference in shoulder function or pain degree between the two groups before operation (P>0.05). After 1 month, 3 months and 6 months, the Constant-Murley score of the observation group was 73.29±2.15, 85.43±1.47, 93.86±1.24 separately, which were significantly higher than those of the control group;and the VAS score was 2.76±0.62, 1.71±0.64, 0.57±0.51 separately, which were significantly lower than those of the control group (P<0.05). One instance of shoulder discomfort was found in the observation group, while 5 cases of shoulder pain, 2 cases of restricted shoulder mobility, and 1 case of subacromial bone absorption were found in the control group. In both group, there was no loss of reduction. CONCLUSION: In the treatment of complete acromioclavicular joint dislocation double button plate combined with strengthened anchor technique achieves favorable clinical result. Internal fixation does not need to be removed. The recovery of shoulder joint function and pain relief are superior than clavicular hook plate internal fixation, which is more worthy of clinical promotion.

Analysis of Related Influencing Factors of Deep Vein Thrombosis after Lumbar Internal Fixation and Treatment Strategy.

Lumbar internal fixation is a traditional surgical method for the treatment of degenerative diseases of the lumbar spine. However, due to its large surgical trauma, it easily causes complications such as deep venous thrombosis (DVT) after the operation. DVT refers to the abnormal coagulation of blood in deep veins, blocking the lumen, causing venous blood return disorder, causing venous blood return disorder to cause swelling and pain, which affects the recovery of the patient's lumbar spine function. In severe cases, even complicated pulmonary embolism endangers the life and health of the patient. Therefore, it is extremely important to explore the related influencing factors and effective treatment of DVT. The purpose of this study was to investigate the influencing factors and effective treatment of DVT after lumbar internal fixation. Univariate analysis and multivariate a logistic regression model were used to analyze the related factors affecting DVT after lumbar internal fixation. Conventional treatments such as anticoagulation, promotion of venous blood return, and improvement of limb circulation were given to patients with DVT, and functional exercise was guided to compare the hypercoagulability and hyperviscosity of blood in patients with DVT before and after treatment. The results showed that the incidence of DVT after lumbar internal fixation was related to age, BMI, and bed time. Getting out of bed for functional exercise in time after surgery can effectively prevent the formation of DVT. Preoperative grading examination, intraoperative intervention, postoperative physical exercise, and other preventive guidance can be carried out according to different individuals during the perioperative period to prevent the formation of postoperative DVT.

Safety and efficacy studies of kyphoplasty, mesh-container-plasty, and pedicle screw fixation plus vertebroplasty for thoracolumbar osteoporotic vertebral burst fractures.

BACKGROUND: Percutaneous kyphoplasty (PKP), percutaneous mesh-container-plasty (PMCP), and pedicle screw fixation plus vertebroplasty (PSFV) were three methods for osteoporotic vertebral burst fractures (OVBF). The purpose of the current study was to evaluate the clinical safety and efficacy of PKP, PMCP, and PSFV for OVBFs. METHODS: This retrospective study included 338 consecutive patients with thoracolumbar OVBFs who underwent PKP (n = 111), PMCP (n = 109), or PSFV (n = 118) and compared their epidemiological data, surgical outcomes, and clinical and radiological features. Clinical evaluations of VAS and ODI and radiological evaluations of height restoration, deformity correction, cement leakage, and canal compromise were calculated preoperatively, postoperatively, and 2 years postoperatively. RESULTS: Cement leakage (31/111 vs. 13/109 and 16/118, P < 0.05) was significantly higher in group PKP than in groups PSFV and PMCP. VAS and ODI scores improved postoperatively from 7.04 ± 1.15 and 67.11 ± 13.49 to 2.27 ± 1.04 and 22.00 ± 11.20, respectively, in group PKP (P < 0.05); from 7.04 ± 1.29 and 67.26 ± 12.79 to 2.17 ± 0.98 and 21.01 ± 7.90, respectively, in group PMCP (P < 0.05); and from 7.10 ± 1.37 and 67.36 ± 13.11 to 3.19 ± 1.06 and 33.81 ± 8.81, respectively, in the PSFV group (P < 0.05). Moreover, postoperative VAS and ODI scores were significantly higher in group PSFV than in groups PKP and PMCP (P < 0.05). However, VAS scores were not significantly different in the three groups 2 years postoperatively (P > 0.05). Postoperative anterior (81.04 ± 10.18% and 87.51 ± 8.94% vs. 93.46 ± 6.42%, P < 0.05) and middle vertebral body height ratio (83.01 ± 10.16% and 87.79 ± 11.62% vs. 92.38 ± 6.00%, P < 0.05) were significantly higher in group PSFV than in groups PMCP and PKP. Postoperatively, Cobb angle (10.04 ± 4.26° and 8.16 ± 5.76° vs. 4.97 ± 4.60°, P < 0.05) and canal compromise (20.76 ± 6.32 and 19.85 ± 6.18 vs. 10.18 ± 6.99, P < 0.05) were significantly lower in group PSFV than in groups PMCP and PKP. CONCLUSION: Despite relatively worse radiological results, PMCP is a safe and minimally invasive surgical method that can obtain better short-term clinical results than PKP and PSFV for OVBFs.

Critical roles of sphingosine kinase 1 in the regulation of neuroinflammation and neuronal injury after spinal cord injury.

BACKGROUND: The pathological process of traumatic spinal cord injury (SCI) involves excessive activation of microglia leading to the overproduction of proinflammatory cytokines and causing neuronal injury. Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P), plays an important role in mediating inflammation, cell proliferation, survival, and immunity. METHODS: We aim to investigate the mechanism and pathway of the Sphk1-mediated neuroinflammatory response in a rodent model of SCI. Sixty Sprague-Dawley rats were randomly assigned to sham surgery, SCI, or PF543 (a specific Sphk1 inhibitor) groups. Functional outcomes included blinded hindlimb locomotor rating and inclined plane test. RESULTS: We discovered that Sphk1 is upregulated in injured spinal cord tissue of rats after SCI and is associated with production of S1P and subsequent NF-κB p65 activation. PF543 attenuated p65 activation, reduced inflammatory response, and relieved neuronal damage, leading to improved functional recovery. Western blot analysis confirmed that expression of S1P receptor 3 (S1PR3) and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) are activated in microglia of SCI rats and mitigated by PF543. In vitro, we demonstrated that Bay11-7085 suppressed NF-κB p65 and inhibited amplification of the inflammation cascade by S1P, reducing the release of proinflammatory TNF-α. We further confirmed that phosphorylation of p38 MAPK and activation of NF-κB p65 is inhibited by PF543 and CAY10444. p38 MAPK phosphorylation and NF-κB p65 activation were enhanced by exogenous S1P and inhibited by the specific inhibitor SB204580, ultimately indicating that the S1P/S1PR3/p38 MAPK pathway contributes to the NF-κB p65 inflammatory response. CONCLUSION: Our results demonstrate a critical role of Sphk1 in the post-traumatic SCI inflammatory cascade and present the Sphk1/S1P/S1PR3 axis as a potential target for therapeutic intervention to control neuroinflammation, relieve neuronal damage, and improve functional outcomes in SCI.

[Effects of tranexamic acid combined with temporary drain clamping on postoperative blood loss in total knee arthroplasty].

OBJECTIVE: To evaluate the efficacy and safety of one dose tranexamic acid combined with temporary drain lamping in primary unilateral total knee arthroplasty. METHODS: Total 160 patients undergoing unilateral primary total knee arthroplasty between January 2012 and December 2013 were randomly divided into four groups(40 cases in each group):group A (the drain was clamped for 2 hours after the operation and the patients received 20 ml physiological saline), group B(the drain was clamped for 2 hours after the operation and the patients received 10 ml tranexamic acid and 10 ml physiological saline), group C (the drain was clamped for 4 hours after the operation and the patients received 20 ml physiological saline) and group D(the drain was clamped for 4 hours after the operation and the patients received 10 ml tranexamic acid and 10 ml physiological saline). The postoperative hemoglobin level, maximum hemoglobin loss, wound drainage, blood loss, the volume of blood transfusion, the number of patients inquiring blood transfusion, venous thrombo embolism rate, and ecchymosis rate were recorded and compared among the four groups. RESULTS: There was no incision infection, severe hypoxia, and symptomatic pulmonary embolism in these groups. There were significant differences in hemoglobin content one day after operation in each group(F=12.26, P=0.000), in the hemoglobin content 7 days after operation in each group(F=20.74, P=0.000), in postoperative drainage in each group(F=38.71, P=0.000);in the amount of invisible red blood cell loss in each group(F=83.41, P=0.000), and in total red blood cell loss in each group(F=102.68, P=0.000). Color Doppler ultrasound examination found that the total incidence of VTE was 3%(5/160) and there were no significant differences in each group(P=0.892). There were no significant differences in postoperative subcutaneous ecchymosis area>1% incidence(P=0.143). CONCLUSIONS: Topical tranexami acid treatment combined with temporary clamping of drain for 4 hours could reduce postoperative blood loss, blood transfusion, and ecchymosis rate without increasing the risk of thromboembolic event after total knee arthroplasty.