Mini-open Pedicle Subtraction Osteotomy versus Standard Posterior Approach for Ankylosing Spondylitis-related Spinal Kyphosis: A Comparative Study.

OBJECTIVE: Surgical strategy for spinal kyphosis in patients with ankylosing spondylitis (AS) has been challenging. Pedicle subtraction osteotomy (PSO) through a minimally invasive (MI) approach has been developed with promising clinical outcomes. We aimed to compare the effectiveness and safety of PSO via an MI approach and a standard posterior approach (SPA) for treating AS-related spinal kyphosis. METHODS: A total of 41 patients with AS-related spinal kyphosis who underwent PSO through an MI approach (MI surgery [MIS] group: n = 25) or SPA (SPA group: n = 16) between January 2015 and July 2020 were retrospectively included. Spinopelvic parameters were evaluated before the surgery, immediately after the surgery, and at the 2-year follow-up. Clinical data including operative time, estimated blood loss, blood transfusion, level of fusion, incision length, bed rest period, length of hospitalization, and surgical complications were compared between the two groups. The Scoliosis Research Society outcomes instrument-22 (SRS-22) was administered to assess patients' quality of life at the latest follow-up. Comparisons between the two groups were performed using independent sample t-test or Chi-square test. RESULTS: Characteristics and baseline kyphosis of the two groups were matched. At the 2-year follow-up, in the MIS group, the average correction values of the sagittal vertical axis and global kyphosis (GK) were 9.5 cm and 44.3°, respectively. Compared with the SPA group, the MIS group had similar correction values and correction losses after surgery. No obvious differences were observed in any radiographic parameters, except for GK, immediately after surgery and at the 2-year follow-up between the two groups (p > 0.05). The MIS group had a significantly shorter operative time, lesser blood loss, lesser transfusion volume, shorter fusion level, and lesser time to mobilization than did the SPA group. Higher average functional activity scores of SRS-22 were obtained in the MIS group than in the SPA group. CONCLUSION: Mini-open PSO may be an effective alternative to the SPA for treating AS-related spinal kyphosis, with comparable correction effect, lesser surgical trauma and faster recovery. This comparative study may provide valuable guidance for surgical decision-making and patient counseling.

Herbal Formula Modified Bu-Shen-Huo-Xue Decoction Attenuates Intervertebral Disc Degeneration via Regulating Inflammation and Oxidative Stress.

OBJECTIVE: This study aims to clarify the potential mechanism of modified Bu-Shen-Huo-Xue decoction (MBSHXD) in treating intervertebral disc degeneration (IDD) with methods of network pharmacology and molecular docking. METHODS: An MBSHXD and IDD-related common target gene set was established through TCMSP, UniProt, and two disease gene databases. GO and KEGG enrichment analysis and protein-protein interaction (PPI) networks were performed through the R platform and STRING to discover the potential mechanism. Molecular docking between the active ingredients and the core genes is used to calculate the binding energy. RESULTS: A total of 147 active ingredients and 79 common genes (including 10 core genes, TNF, VEGFA, IL6, MAPK3, AKT1, MAPK8, TP53, JUN, MMP9, and CXCL8) were identified. The results of GO and KEGG enrichment analysis showed that MBSHXD plays an essential role in regulating inflammation and oxidative stress. The meaningful pathways are the AGE-RAGE signaling pathway in diabetic complications, the IL-17 signaling pathway, the TNF signaling pathway, the PI3K-Akt signaling pathway, the MAPK signaling pathway, and apoptosis. In addition, the PPI network and molecular docking further demonstrated the roles that nine bioactive ingredients of MBSHXD play in IDD treatment through their interference with core target proteins. CONCLUSION: This study reveals that MBSHXD has the characteristics of a "multi-component, multi-target, and multi-pathway" in the treatment of IDD by regulating inflammation and oxidative stress, and network pharmacology may provide a feasible method to verify the molecular mechanism of MBSHXD for IDD by combining with molecular docking.

Prospective study of preoperative autologous blood donation for patients with high risk of allogeneic blood transfusion in lumbar fusion surgery: a study protocol of a randomised controlled trial.

INTRODUCTION: Preoperative autologous blood donation (PABD) can be used to reduce the exposure of allogeneic blood transfusion in patients undergoing elective surgery. Better blood management to avoid anaemia and reduce allogeneic blood transfusion after spine surgery become increasingly important with development of enhanced recovery after surgery. We present here the design of a randomised controlled trial with three groups to verify the clinical effectiveness of PABD in patients at high risk of transfusion for lumbar fusion surgery and explore the optimal timing of autologous blood donation. METHOD AND ANALYSIS: Patients (age 18-70 years) who will receive lumbar fusion surgery for degenerative disease with haemoglobin over 110 g/L and 'high risk' of allogeneic blood transfusion are eligible, unless they refuse participation or are diagnosed with malignant metastases, infection, cardiovascular and cerebrovascular diseases, haematological disorders or relevant drug history and critical illnesses. A total of 1200 patients will be recruited and randomised into three groups. Patients in group A will not receive PABD and be regarded as control group. PABD will be performed for patients in groups B and C. Blood donation will be finished at 1 week (±3 day) before surgery in group B and 2 weeks (±3 day) before surgery in group C. Primary outcome measures will include haemoglobin decline, incidence and amount of allogeneic blood transfusion. Secondary outcome measures will include days of hospitalisation after surgery, haematocrit level and incidence of complications. This study is a single-centre and open-label randomised controlled trial. The sample size is calculated with reference to the retrospective data and previous studies. ETHICS AND DISSEMINATION: This trial has been approved by the Peking University Third Hospital Medical Science Research Ethic Committee (no: 2020-262-02). Results of the trial will be submitted for publication in a peer-reviewed journal and as conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2000039824, preresults.

Pharmacological Mechanism of Danggui-Sini Formula for Intervertebral Disc Degeneration: A Network Pharmacology Study.

BACKGROUND: Intervertebral disc degeneration (IVDD) is the most significant cause of low back pain, the sixth-largest disease burden globally, and the leading cause of disability. This study is aimed at investigating the molecular biological mechanism of Danggui-Sini formula (DSF) mediated IVDD treatment. METHODS: A potential gene set for DSF treatment of IVDD was identified through TCMSP, UniProt, and five disease gene databases. A protein interaction network of common targets between DSF and IVDD was established by using the STRING database. GO and KEGG enrichment analyses were performed using the R platform to discover the potential mechanism. Moreover, AutoDock Vina was used to verify molecular docking and calculate the binding energy. RESULTS: A total of 119 active ingredients and 136 common genes were identified, including 10 core genes (AKT1, IL6, ALB, TNF, VEGFA, TP53, MAPK3, CASP3, JUN, and EGF). Enrichment analysis results showed that the therapeutic targets of DSF for diseases mainly focused on the AGE-RAGE signaling pathway involved in diabetic complications, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, apoptosis, cellular senescence, PI3K-Akt signaling pathway, and FoxO signaling pathway. These biological processes are induced mainly in response to oxidative stress and reactive oxygen species and the regulation of apoptotic signaling pathways. Molecular docking showed that there was a stable affinity between the core genes and the key components. CONCLUSIONS: The combination of network pharmacology and molecular docking provides a practical way to analyze the molecular biological mechanism of DSF-mediated IVDD treatment, which confirms the "multicomponent, multitarget and multipathway" characteristics of DSF and provides an essential theoretical basis for clinical practice.

Hounsfield units value is a better predictor of pedicle screw loosening than the T-score of DXA in patients with lumbar degenerative diseases.

PURPOSE: To compare the performance of using Hounsfield units (HU) value derived from computed tomography and T-score of dual-energy X-ray absorptiometry (DXA) to predict pedicle screw loosening. METHODS: We reviewed 253 patients aged ≥ 50 years undergoing pedicle screw fixation for lumbar degenerative diseases (LDD). The evaluation of screw loosening: radiolucent zones of ≥ 1 mm thick in X-ray. The criterion for osteoporosis: the lowest T-score ≤ - 2.5. The average HU value of L1-L4 was used to represent lumbar bone mineral density (BMD). The area under receiver operating characteristics curve (AUC) was used to evaluate the performance of predicting screw loosening. RESULTS: One patient underwent reoperation for screw loosening at 9 months follow-up. At 12 months follow-up, the loosening rate was 30.6% (77/252) in the remaining 252 patients. Osteoporotic patients had higher loosening rate than non-osteoporotic patients (39.3% vs. 25.8%, P = 0.026). The T-score showed no significant difference between loosening group and non-loosening group (- 2.1 ± 1.5 vs. - 1.7 ± 1.6, P = 0.074), and so is the lowest lumbar BMD of DXA (0.83 ± 0.16 g/cm2 vs. 0.88 ± 0.19 g/cm2, P = 0.054). The HU value was lower in the loosening group (106.8 ± 34.4 vs. 129.8 ± 45.7, P < 0.001). The HU value (OR, 0.980; 95%CI 0.968-0.993; P = 0.002) was the independent influencing factor of screw loosening. The AUC of predicting screw loosening was 0.666 (P < 0.001) for HU value and 0.574 (P = 0.062) for T-score. CONCLUSIONS: HU value is a better predictor of pedicle screw loosening than T-score of DXA in patients aged ≥ 50 years with LDD. We should not only focus on the DXA measurements when making surgical plans concerning lumbar fixation. These slides can be retrieved under Electronic Supplementary Material.

Characteristics of vertebral CT Hounsfield units in elderly patients with acute vertebral fragility fractures.

OBJECTIVE: To explore the characteristics of vertebral CT Hounsfield units (HU) in elderly patients with acute vertebral fragility fractures. METHODS: A total of 299 patients aged ≥ 65 years with acute vertebral fragility fractures were retrospectively reviewed, and 77 patients of them were age- and sex-matched with 77 control patients without any fractures. The vertebral HU value of L1(L1-HU) was measured, and T12 and L2 were used as alternatives for L1 in the case of L1 fracture. RESULTS: There were 460 thoracic and lumbar vertebral fractures in the 299 elderly patients, including 349 acute vertebral fragility fractures and 111 chronic fractures. The average L1-HU value was 66.0 ± 30.6 HU and showed significant difference among patients having different numbers of vertebral fractures (one fracture: 73.3 ± 27.0 HU, two fractures: 58.7 ± 32.5 HU, three or more fractures: 40.7 ± 28.8 HU; P < 0.001). As for the 1:1 age- and sex-matched patients, the L1-HU of the 77 patients with fractures was lower than that of the control patients (70.6 ± 23.4 HU vs. 101.5 ± 36.2 HU, P < 0.001). The area under the receiver operating characteristic curve of using L1-HU to differentiate patients with fractures from controls was 0.77(95% CI 0.70-0.85, P < 0.001). The cutoff value had high specificity of 90% or high sensitivity of 90% to identify patients with fractures of 60 HU and 100 HU, respectively. CONCLUSIONS: The elderly patients with acute vertebral fragility fractures have much lower HU values than those without fractures. Moreover, the lower the vertebral HU value is, the more likely the patients have more than one vertebral fracture. These slides can be retrieved under Electronic Supplementary Material.

The use of CT Hounsfield unit values to identify the undiagnosed spinal osteoporosis in patients with lumbar degenerative diseases.

PURPOSES: Our purpose was to use computed tomography (CT) Hounsfield unit (HU) values to identify the undiagnosed spinal osteoporosis in patients with lumbar degenerative diseases. METHODS: A total of 334 patients with lumbar degenerative diseases were retrospectively reviewed and divided into two groups according to the degree of lumbar degenerative changes in preoperative lumbar CT images. Patients who had at least three vertebrae with severe degeneration at L1-L4 were placed in the degenerative group, and others were placed in the control group. HU value of trabecular bone in middle axial CT image of vertebral body, T-score and bone mineral density (BMD) at L1-L4 and hips were measured. CT HU thresholds for osteoporosis were obtained from control group and then applied to identify undiagnosed spinal osteoporosis. RESULTS: There were 182 patients in the degenerative group and 152 patients in the control group. CT HU value had a positive correlation with T-score and BMD of lumbar spine in both groups (P < 0.001), while the correlation coefficients at L1-L4 were higher in the control group (> 0.7) than in the degenerative group (< 0.7). T-score and BMD of lumbar spine were higher in the degenerative group (P < 0.05), while CT HU value, T-score and BMD of hips had no significant difference between two groups. According to the linear regression equations of vertebral T-score and CT HU value in the control group, the thresholds matching T-score of - 2.5 were 110, 100, 85 and 80HU for L1, L2, L3 and L4, respectively. Defining CT osteoporosis as L1 ≤ 110HU or L2 ≤ 100HU or L3 ≤ 85HU or L4 ≤ 80HU was 88.5% (69/78) specific and 60.8% (45/74) sensitive for distinguishing DXA osteoporosis of lumbar spine in the control group. The rate of undiagnosed spinal osteoporosis was higher in the degenerative group than in the control group according to CT HU thresholds (38.7% vs. 11.5%, P < 0.05). CONCLUSIONS: Degenerative changes in the lumbar spine can increase BMD and T-score provided by lumbar DXA, leading to an underestimation of vertebral osteoporosis. Thresholds for osteoporosis based on CT HU values can be used as a complementary method to identify undiagnosed spinal osteoporosis in patients with lumbar degenerative diseases. These slides can be retrieved under Electronic Supplementary Material.

Protective effects of kaempferol on lipopolysaccharide-induced mastitis in mice.

Kaempferol isolated from the root of Zingiberaceae plants galangal and other Chinese herbal medicines have been reported to have anti-inflammatory properties. However, the anti-inflammatory effects of kaempferol on lipopolysaccharide (LPS)-induced mastitis are unknown and their underlying molecular mechanisms remain to be explored. The aim of this study was to evaluate the effects of kaempferol on LPS-induced mouse mastitis. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. Kaempferol was injected 1 h before and 12 h after induction of LPS intraperitoneally. The present results showed that kaempferol markedly reduced infiltration of neutrophilic granulocyte, activation of myeloperoxidase (MPO), expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in a dose-dependent manner, which were increased in LPS-induced mouse mastitis. Furthermore, kaempferol suppressed the phosphorylation of nuclear factor-κB (NF-κB) p65 subunit and the degradation of its inhibitor IκBα. All results suggest that anti-inflammatory effects of kaempferol against the LPS-induced mastitis possibly through inhibition of the NF-κB signaling pathway. Kaempferol may be a potential therapeutic agent for mastitis.