Effects of circulating inflammatory proteins on osteoporosis and fractures: evidence from genetic correlation and Mendelian randomization study.

Objective: There is a controversy in studies of circulating inflammatory proteins (CIPs) in association with osteoporosis (OP) and fractures, and it is unclear if these two conditions are causally related. This study used MR analyses to investigate the causal associations between 91 CIPs and OP and 9 types of fractures. Methods: Genetic variants data for CIPs, OP, and fractures were obtained from the publicly available genome-wide association studies (GWAS) database. We used inverse variance weighted (IVW) as the primary analysis, pleiotropy, and heterogeneity tests to analyze the validity and robustness of causality and reverse MR analysis to test for reverse causality. Results: The IVW results with Bonferroni correction indicated that CXCL11 (OR = 1.2049; 95% CI: 1.0308-1.4083; P = 0.0192) can increase the risk of OP; IL-4 (OR = 1.2877; 95% CI: 1.1003-1.5070; P = 0.0016), IL-7 (OR = 1.2572; 95% CI: 1.0401-1.5196; P = 0.0180), IL-15RA (OR = 1.1346; 95% CI: 1.0163-1.2668; P = 0.0246), IL-17C (OR = 1.1353; 95% CI: 1.0272-1.2547; P = 0.0129), CXCL10 (OR = 1.2479; 95% CI: 1.0832-1.4377; P = 0.0022), eotaxin/CCL11 (OR = 1.1552; 95% CI: 1.0525-1.2678; P = 0.0024), and FGF23 (OR = 1.9437; 95% CI: 1.1875-3.1816; P = 0.0082) can increase the risk of fractures; whereas IL-10RB (OR = 0.9006; 95% CI: 0.8335-0.9730; P = 0.0080), CCL4 (OR = 0.9101; 95% CI: 0.8385-0.9878; P = 0.0242), MCP-3/CCL7 (OR = 0.8579; 95% CI: 0.7506-0.9806; P = 0.0246), IFN-γ [shoulder and upper arm (OR = 0.7832; 95% CI: 0.6605-0.9287; P = 0.0049); rib(s), sternum and thoracic spine (OR = 0.7228; 95% CI: 0.5681-0.9197; P = 0.0083)], ß-NGF (OR = 0.8384; 95% CI: 0.7473-0.9407; P = 0.0027), and SIRT2 (OR = 0.5167; 95% CI: 0.3296-0.8100; P = 0.0040) can decrease fractures risk. Conclusion: Mendelian randomization (MR) analyses indicated the causal associations between multiple genetically predicted CIPs and the risk of OP and fractures.

Biomechanical evaluation of different oblique lumbar interbody fusion constructs: a finite element analysis.

BACKGROUND: Finite element analysis (FEA) was performed to investigate the biomechanical differences between different adjunct fixation methods for oblique lumbar interbody fusion (OLIF) and to further analyze its effect on adjacent segmental degeneration. METHODS: We built a single-segment (Si-segment) finite element model (FEM) for L4-5 and a double-segment (Do-segment) FEM for L3-5. Each complete FEM was supplemented and modified, and both developed two surgical models of OLIF with assisted internal fixation. They were OLIF with posterior bilateral percutaneous pedicle screw (TINA system) fixation (OLIF + BPS) and OLIF with lateral plate system (OLIF + LPS). The range of motion (ROM) and displacement of the vertebral body, cage stress, adjacent segment disc stress, and spinal ligament tension were recorded for the four models during flexion/extension, right/left bending, and right/left rotation by applying follower load. RESULTS: For the BPS and LPS systems in the six postures of flexion, extension, right/left bending, and right/left rotation, the ROM of L4 in the Si-segment FEM were 0.32°/1.83°, 0.33°/1.34°, 0.23°/0.47°, 0.24°/0.45°, 0.33°/0.79°, and 0.34°/0.62°; the ROM of L4 in the Do-segment FEM were 0.39°/2.00°, 0.37°/1.38°, 0.23°/0.47°, 0.21°/0.44°, 0.33°/0.57°, and 0.31°/0.62°, and the ROM of L3 in the Do-segment FEM were 6.03°/7.31°, 2.52°/3.50°, 4.21°/4.38°, 4.21°/4.42°, 2.09°/2.32°, and 2.07°/2.43°. BPS system had less vertebral displacement, less cage maximum stress, and less spinal ligament tension in Si/Do-segment FEM relative to the LPS system. BPS system had a smaller upper adjacent vertebral ROM, greater intervertebral disc stress in terms of left and right bending as well as left and right rotation compared to the LPS system in the L3-4 of the Do-segment FEM. There was little biomechanical difference between the same fixation system in the Si/Do-segment FEM. CONCLUSIONS: Our finite element analysis showed that compared to OLIF + LPS, OLIF + BPS (TINA) is more effective in reducing interbody stress and spinal ligament tension, and it better maintains the stability of the target segment and provides a better fusion environment to resist cage subsidence. However, OLIF + BPS (TINA) may be more likely to cause adjacent segment degeneration than OLIF + LPS.

Identification of postnatal development dependent genes and proteins in porcine epididymis.

BACKGROUND: The epididymis is a highly regionalized tubular organ possesses vectorial functions of sperm concentration, maturation, transport, and storage. The epididymis-expressed genes and proteins are characterized by regional and developmental dependent pattern. However, a systematic and comprehensive insight into the postnatal development dependent changes in gene and protein expressions of porcine epididymis is still lacking. Here, the RNA and protein of epididymis of Duroc pigs at different postnatal development stages were extracted by using commercial RNeasy Midi kit and extraction buffer (7 M Urea, 2 M thiourea, 3% CHAPS, and 1 mM PMSF) combined with sonication, respectively, which were further subjected to transcriptomic and proteomic profiling. RESULTS: Transcriptome analysis indicated that 198 and 163 differentially expressed genes (DEGs) were continuously up-regulated and down-regulated along with postnatal development stage changes, respectively. Most of the up-regulated DEGs linked to functions of endoplasmic reticulum and lysosome, while the down-regulated DEGs mainly related to molecular process of extracellular matrix. Moreover, the following key genes INSIG1, PGRMC1, NPC2, GBA, MMP2, MMP14, SFRP1, ELN, WNT-2, COL3A1, and SPARC were highlighted. A total of 49 differentially expressed proteins (DEPs) corresponding to postnatal development stages changes were uncovered by the proteome analysis. Several key proteins ACSL3 and ACADM, VDAC1 and VDAC2, and KNG1, SERPINB1, C3, and TF implicated in fatty acid metabolism, voltage-gated ion channel assembly, and apoptotic and immune processes were emphasized. In the integrative network, the key genes and proteins formed different clusters and showed strong interactions. Additionally, NPC2, COL3A1, C3, and VDAC1 are located at the hub position in each cluster. CONCLUSIONS: The identified postnatal development dependent genes and proteins in the present study will pave the way for shedding light on the molecular basis of porcine epididymis functions and are useful for further studies on the specific regulation mechanisms responsible for epididymal sperm maturation.

House ammonia exposure causes alterations in microbiota, transcriptome, and metabolome of rabbits.

Introduction: Pollutant gas emissions in the current production system of the livestock industry have negative influences on environment as well as the health of farm staffs and animals. Although ammonia (NH3) is considered as the primary and harmful gas pollutant in the rabbit farm, less investigation has performed to determine the toxic effects of house ammonia exposure on rabbit in the commercial confined barn. Methods: In this study, we performed multi-omics analysis on rabbits exposed to high and low concentration of house ammonia under similar environmental conditions to unravel the alterations in nasal and colonic microbiota, pulmonary and colonic gene expression, and muscular metabolic profile. Results and discussion: The results showed that house ammonia exposure notably affected microbial structure, composition, and functional capacity in both nasal and colon, which may impact on local immune responses and inflammatory processes. Transcriptome analysis indicated that genes related to cell death (MCL1, TMBIM6, HSPB1, and CD74) and immune response (CDC42, LAMTOR5, VAMP8, and CTSB) were differentially expressed in the lung, and colonic genes associated with redox state (CAT, SELENBP1, GLUD1, and ALDH1A1) were significantly up-regulated. Several key differentially abundant metabolites such as L-glutamic acid, L-glutamine, L-ornithine, oxoglutaric acid, and isocitric acid were identified in muscle metabolome, which could denote house ammonia exposure perturbed amino acids, nucleotides, and energy metabolism. In addition, the widespread and strong inter-system interplay were uncovered in the integrative correlation network, and central features were confirmed by in vitro experiments. Our findings disclose the comprehensive evidence for the deleterious effects of house ammonia exposure on rabbit and provide valuable information for understanding the underlying impairment mechanisms.

Seasonal Variations in Production Performance, Health Status, and Gut Microbiota of Meat Rabbit Reared in Semi-Confined Conditions.

In this study, we investigated the variations in production performance, health status, and gut microbiota of meat rabbits raised in the semi-confined barn during summer and winter. Compared to summer, rabbits reared in winter possessed significantly higher slaughter weight and carcass weight. Rabbits fed in the summer were more vulnerable to different stressors, which led to increased protein levels of HSP90, IL-1α, IL-1ß, IL-2, and concentrations of MDA, but declined GSH and SOD activities. Additionally, significant differences in gut microbial communities were observed. Compared to the winter, rabbits fed in the summer had significantly lower and higher alpha and beta diversity. Both Firmicutes and Verrucomicrobiota were the dominant phyla, and they accounted for greater proportions in the winter than in the summer. At lower microbial taxa levels, several seasonal differentially enriched microbes were identified, such as Akkermansia muciniphila, the Oscillospiraceae NK4A214 group, the Christensenellaceae R-7 group, Alistipes, and Muribaculaceae. Functional capacities linked to microbial proliferation, nutrient metabolism, and environmental adaptive responses exhibited significantly different abundances between summer and winter. Moreover, strong interactions among different indicators were presented. Based on our findings, we not only proposed several potential strategies to ameliorate the undesirable effects of seasonal changes on the productivity and health of meat rabbits but also underscored the directions for future mechanistic studies of adaptation physiology.

Single-stage posterior-only debridement, decompression and interbody fusion for the treatment of thoracolumbar spinal tuberculosis complicated with psoas abscesses.

BACKGROUND: To explore the clinical safety and efficacy of single-stage posterior-only debridement, decompression, allograft bone using titanium mesh and interbody fusion combined for the treatment of thoracolumbar spinal tuberculosis complicated with psoas abscesses. METHODS: A total of 38 patients diagnosed with thoracolumbar spinal tuberculosis complicated with psoas abscesses underwent surgery via single-stage posterior-only debridement, decompression, allograft bone using titanium mesh and interbody fusion from January 2010 to September 2016 were enrolled in the study. The clinical efficacy of the approach was assessed based on parameters including operating time, blood loss, Cobb angle, visual analogue scale (VAS) scores, Frankel grade, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). RESULTS: The surgery duration was 224.4 ± 71.1 min with a blood loss of 731.8 ± 585.8 ml. The Cobb angle was corrected from 16.0 ± 15.4° preoperatively to 8.1 ± 7.4° postoperatively (P < 0.001, t = - 4.38), and returned to a level of 11.0 ± 8.5° at the final follow-up (P = 0.002, t = 3.38). Back pain was relieved, with the mean preoperative VAS of 3.5 ± 1.1 decreased to 0.7 ± 0.8 postoperatively (P < 0.001, t = 23.21) and then to 0.6 ± 0.5 at the final follow-up (P < 0.001, t = 17.07). Neurological function was improved in various degrees and psoas abscesses disappeared in all patients. The ESR and CRP decreased gradually after surgery and returned to normal at the final follow-up in all patients. All patients achieved bone fusion thoroughly and no recurrence of TB or surgical related complications was found at the final follow-up. CONCLUSION: Single-stage posterior-only debridement, decompression, allograft bone using titanium mesh and interbody fusion is a safe and effective approach for the management of thoracolumbar spinal tuberculosis complicated with psoas abscesses.

Posterior-only approach with titanium mesh cages versus autogenous iliac bone graft for thoracic and lumbar spinal tuberculosis.

Objective: This study aimed to compare the effectiveness of titanium mesh cages (TMCs) with autogenous iliac bone grafts (AIBG) in posterior-only surgery for thoracic and lumbar spinal tuberculosis.Design: Retrospective investigative design.Setting: The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.Participants: A total of 146 patients with thoracic or lumbar tuberculosis.Interventions: All patients underwent a posterior-only approach with either a TMC (86 cases) or AIBG (60 cases).Outcomes measures: Operation duration, intraoperative blood loss, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS), and related complications were used to compare the effectiveness and feasibility of the two techniques. Frankel grading system, Cobb angle, and loss of angular correction were employed to assess neurological and kyphotic improvements.Results: There were significant improvements in ESR, CRP, VAS, Frankel grade, and Cobb angle at the last follow-up (P < 0.05) when compared with the preoperative state. The TMC group was superior in operation duration (P < 0.001), intraoperative blood loss (P = 0.007), VAS (P < 0.001), loss of angular correction (P < 0.001), and surgical complications as compared with the AIBG group. There were no significant differences in the improvement of the Frankel grade and Cobb angle between the TMC and AIBG groups (P > 0.05). A recurrence of tuberculosis was not found in either of the groups.Conclusion: Compared to autogenous iliac bone grafts, titanium mesh cages could serve as a superior material in posterior-only operative therapy for thoracic and lumbar spinal tuberculosis.

Is there cervical spine muscle weakness in patients with Hirayama disease? A morphological study about cross-sectional areas of muscles on MRI.

PURPOSE: Patients with Hirayama disease (HD) present with a larger range of neck flexion and show signs of cervical spine instability. Cervical spine stability largely relies on cervical spine muscles. The purpose of this study was to compare the cross-sectional areas (CSAs) of cervical spine muscles between patients with HD and healthy controls, providing some insights into whether there is cervical spine muscle weakness and incongruence in HD patients. METHODS: In this retrospective study, cervical spine muscles CSAs of 44 HD patients, as well as that of 44 age- and sex-matched healthy counterparts, were measured on the T2-weighted axial MR images. The ratios of cervical spine muscles CSA to the corresponding vertebral body areas, defined as R-CSAs, and the flexor/extensor CSA ratios were computed and compared between two groups. RESULTS: Compared with healthy counterparts, R-CSAs of total cervical spine muscles, total extensors, superficial extensors, and deep flexors were significantly lower in HD patients. HD patients also demonstrated a significantly greater superficial flexor/superficial extensor CSA ratio than the healthy counterparts, indicating a mismatch between superficial flexors CSA and superficial extensors CSA in HD patients. CONCLUSIONS: In this pioneering study, HD patients had decreased size in most cervical spine muscles and a mismatch between CSAs of superficial flexor and that of superficial extensors. These results indicate generalized weakness and incongruence of cervical spine muscles, which may predispose cervical spine of HD patients to a less stable situation. These slides can be retrieved under Electronic Supplementary Material.

Anterior debridement, decompression, fusion and instrumentation for lower cervical spine tuberculosis.

BACKGROUND: Antituberculosis chemotherapy have been widely used for lower cervical spine tuberculosis and brought out favorable outcomes. However, the contribution of surgical treatment is not well investigated yet. Therefore, this study aimed to evaluate the clinical efficacy and feasibility of surgical treatment for lower cervical spine tuberculosis by anterior debridement, decompression, fusion and instrumentation. METHODS: From April 2011 to July 2016, 17 patients (9 males and 8 females, average age, 45.7 ± 16.8 years) with lower cervical spine tuberculosis (C4-C7) underwent anterior debridement, decompression, fusion and instrumentation. Frankel grading and visual analogue scale were used to assess neurological function and neck pain, respectively. Operating time, blood loss, erythrocyte sedimentation rate, C-reactive protein, kyphosis angle and postoperative complications were used to evaluate the clinical outcomes of surgery. RESULTS: The surgery duration time range from 78 to 322 min (average 136.2 ± 61.1 min) and the blood loss range from 50 to 500 ml (average 127.7 ± 110.9 ml). Kyphosis angle was 10.8 ± 11.8°on average preoperative and returned to -6.3 ± 10.4° postoperative (P < 0.001, t = 12.3) and remained -4.4 ± 9.9°at final follow-up (P < 0.001, t = 11.8). The average preoperative and final follow-up visual analogue scale scores were 4.6 ± 1.3 and 0.6 ± 0.5 respectively (P < 0.001, t = 13.5). The erythrocyte sedimentation rate and C-reactive protein decreased gradually postoperative and returned to normal at final follow-up. No postoperative severe complications and no recurrence of tuberculosis occurred in all cases and neurologic function was improved in various degrees. CONCLUSION: Anterior debridement, decompression, fusion and instrumentation could serve as an effective treatment in the management of the lower cervical spine tuberculosis.

Perioperative Management of Spinal Tuberculosis in Patients with End-Stage Renal Disease: A Preliminary Report on A Patient Series.

OBJECTIVE: To present a preliminary experience of perioperative management for patients with spinal tuberculosis (STB) and end-stage renal disease (ESRD) and discuss strategic factors that should be considered. METHODS: A retrospective study of 6 patients with STB and ESRD who underwent spine surgeries in our hospital from January 2010 to May 2017 was carried out. Medical records were reviewed for clinical manifestations, laboratory examinations, radiologic findings, perioperative management, clinical outcomes, and complications. RESULTS: Except for 1 patient who died of cardiac arrest 5 days after surgery, this case series was followed with a mean follow-up period of 17.0 months (range, 9-23). There were no patients reporting major side effects related to an adjusted antituberculosis chemotherapy regimen. Postoperatively, surgical incision healed primarily, whereas delirium and pneumonia were noted in 2 patients. At final follow-ups, solid bony fusion was achieved in 4 patients, whereas fusion was indefinite in the patient who underwent surgery at L3/4 level. Visual analogue scale score improved from preoperative 5.2 ± 0.37 to 2.6 ± 0.55 at the final follow-ups. CONCLUSIONS: Perioperative management of patients with STB and ESRD is a complicated issue, with multiple factors to be considered. Spinal surgery can achieve acceptable outcomes in these patients if meticulous management is performed.

Could Allograft Bones Combined with Poly-Ether-Ether-Ketone Cages or Titanium Mesh Cages be an Alternative Grafting Method in the Management of Cervical Spinal Tuberculosis?

OBJECTIVE: To investigate the effectiveness of allograft bones combined with poly-ether-ether-ketone (PEEK) cages or titanium mesh cages (TMCs) in the management of cervical spinal tuberculosis. METHODS: A total of 16 patients with cervical spinal tuberculosis who underwent anterior debridement, reconstruction with allograft bones combined with PEEK cages or TMCs, and anterior plate fixation between 2013 and 2016 were retrospectively studied. Neck pain, neurologic status, operating time, intraoperative blood loss, cervical spine alignment, bony fusion, and self-reported clinical outcomes were reviewed. RESULTS: Six patients underwent 1 level reconstruction using PEEK cages and 10 patients received TMCs reconstruction. Patients received a mean follow-up time of 45.9 ± 13.1 months. Neck pain was greatly relieved, as visual analog scale scores decreased from 4.6 ± 1.3 preoperatively to 0.7 ± 0.5 at the final follow-up (P < 0.05). Neurologic status was improved in all patients with neurologic deficits, with 9 patients improving by 1 grade and 1 patient by 2 grades. Kyphosis angle was corrected from 1.3 ± 12.0 degrees preoperatively to -5.4 ± 10.2 degrees postoperatively (P < 0.05) and remained at -3.6 ± 9.6 degrees at the final follow-up (P < 0.05). Bony fusion was achieved in all patients, with a mean time to the fusion of 3.8 ± 1.3 months. There was no implant failure or signs of cervical spinal tuberculosis recurrence. Excellent results, good results, and fair results were reported in 37.5%, 56.25%, and 6.25% of patients, respectively. CONCLUSIONS: Allograft bone combined with PEEK cages and TMCs could bring about favorable clinical results in patients with cervical spinal tuberculosis. This method could be an alternative to autologous bone grafting method in the management of certain cases.

Anterior Cervical Surgery for the Treatment of Hirayama Disease.

OBJECTIVE: To provide a quantitative assessment of clinical outcomes of anterior cervical surgery for patients with Hirayama disease. METHODS: Nineteen patients undergoing anterior cervical surgery were retrospectively collected, and preoperative and postoperative clinical and radiographic data were compared. RESULTS: All patients had a mean follow-up time of 72.5 ± 30.6 months. Tremor in 6 of 14 patients and cold paralysis in 8 patients were resolved after operation. Grip strength of upper extremities was significantly improved (preoperative 15.67 ± 2.74 kg vs. postoperative 19.82 ± 2.89 kg, P < 0.001). Postoperative cervical lordosis was significantly increased to 6.41 ± 4.39 mm from 2.70 ± 4.61 mm (P < 0.001). The overall range of cervical flexed motion was significantly decreased (preoperative 33.10° ± 10.60° vs. postoperative 13.55° ± 6.69°, P < 0.001), with segmental range of C5-6 (preoperative 12.52° ± 7.13° vs. postoperative 7.04° ± 3.75°, P = 0.002) and C6-7 (preoperative 9.01° ± 5.01° vs. postoperative 5.73° ± 2.74°, P = 0.014) contributing significantly to the improvement. Postoperative angle mobility of C3-4 to C6-7 was significantly decreased (P < 0.001). Postoperative neutral magnetic resonance imaging showed the transverse area of spinal cord of C6 (P = 0.016) and C7 (P = 0.021) was significantly increased. CONCLUSIONS: Anterior cervical surgery can provide clinical efficacy and imaging improvement, including reduced range of cervical flexed motion and angle mobility of lower cervical spine and increased cervical lordosis and spinal cord area.

One-Stage Surgical Treatment for Consecutive Multisegment Thoracic Spinal Tuberculosis with Kyphosis by Posterior-Only Debridement, Interbody Fusion, and Instrumentation.

OBJECTIVE: To evaluate the clinical efficacy and feasibility of one-stage surgical treatment for consecutive multisegment thoracic spinal tuberculosis with kyphosis by posterior-only debridement, interbody fusion, and instrumentation. METHODS: Sixty-two patients who underwent posterior debridement, interbody fusion, and instrumentation were reviewed for radiographic fusion, region kyphosis, neurologic status, and clinical outcomes. Thoracic Cobb's angle and Frankel grading system were used to assess kyphosis and neurologic improvements, respectively. Operation time, blood loss, erythrocyte sedimentation rate, C-reactive protein, visual analogue scale score, and postoperative complications were recorded to evaluate efficacy and feasibility. RESULTS: The surgery duration was 234.5 ± 91.3 minutes, with blood loss of 761.3 ± 598.5 mL. The levels of erythrocyte sedimentation rate and C-reactive protein in all patients decreased gradually to normal within 3 months after the surgery. Kyphosis angle was corrected from 16.9 ± 10.9° preoperatively to 10.4 ± 6.3° postoperatively (P < 0.001, t = 5.2) and remained at 12.0 ± 6.6° at final follow-up (P < 0.001, t = 4.6). Twenty-seven patients obtained neurologic improvement by 1-3 grades. The average visual analogue scale score decreased from preoperative 3.7 ± 1.0 to postoperative 0.7 ± 0.9 (P < 0.001, t = 16.4), and then to 0.5 ± 0.3 at final follow-up (P < 0.001, t = 21.5). All patients achieved bony fusion. Recurrence of tuberculosis was not found in all patients. CONCLUSIONS: One-stage posterior surgery of debridement, interbody fusion and instrumentation could serve as an efficient way to cure patients with consecutive multisegment thoracic spinal tuberculosis.

Correction: Preserving Posterior Complex Can Prevent Adjacent Segment Disease following Posterior Lumbar Interbody Fusion Surgeries: A Finite Element Analysis.

[This corrects the article DOI: 10.1371/journal.pone.0166452.].