PCSK9 inhibitors and osteoporosis: mendelian randomization and meta-analysis.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent an effective strategy for reducing cardiovascular disease risk. Yet, PCSK9's impact on osteoporosis remains unclear. Hence, we employed Mendelian randomization (MR) analysis for examining PCSK9 inhibitor effects on osteoporosis. METHODS: Single nucleotide polymorphisms (SNPs) for 3-hydroxy-3-methylglutaryl cofactor A reductase (HMGCR) and PCSK9 were gathered from available online databases for European pedigrees. Four osteoporosis-related genome-wide association studies (GWAS) data served as the main outcomes, and coronary artery disease (CAD) as a positive control for drug-targeted MR analyses. The results of MR analyses examined by sensitivity analyses were incorporated into a meta-analysis for examining causality between PCSK9 and HMGCR inhibitors and osteoporosis. RESULTS: The meta-analysis involving a total of 1,263,102 subjects, showed that PCSK9 inhibitors can increase osteoporosis risk (P < 0.05, I2, 39%). However, HMGCR inhibitors are not associated with osteoporosis risk. Additionally, a replication of the analysis was conducted with another exposure-related GWAS dataset, which led to similar conclusions. CONCLUSION: PCSK9 inhibitors increase osteoporosis risk. However, HMGCR inhibitors are unremarkably linked to osteoporosis.

Establishment and evaluation of a modified mouse model of renal subcapsular transplantation of microvolume cells.

The renal subcapsular space provides an easily accessible, nutrition-rich pocket that supports engraftment, and as such, is often used as a site for stem and cancer cell transplantation. Renal capsule transplantation requires high technical requirements, the recipient mice have greater surgical damage, the mouse kidney is small and the kidney capsule is fragile, and the operation is easy to fail. The conventional method is not suitable for microvolume cell transplantation to this site in animals with a small kidney, such as mice, due to high risks of cell loss or dislocation or injury to the capsule. In this study, we developed and validated a modified approach for the mouse model of renal subcapsular transplantation of microvolume mouse skeletal stem cells (SSCs). We used a pipette with a refined tip to separate the capsule from the parenchyma. Moreover, we used cells suspended in Matrigel rather than a liquid carrier for transplantation. Using the modified method, we were able to transplant microvolume mouse SSCs as low as 0.2 µL beneath the mouse renal capsule with excellent reproducibility. After 4 weeks of in vivo culture, the implanted mouse SSCs formed grafts on the surface of the parenchyma at the target site of transplantation. Histological staining of the grafts indicated osteogenic, fibrogenic, and lipogenic differentiation. Micro-CT imaging of the grafts revealed bone formation. This modified model could be used to effectively transplant different types of microvolume cells to the renal subcapsular space when the donor cells are difficult to acquire or the recipient mice have a very small size kidney.

Cellular Mechanism Underlying the Facilitation of Contractile Response Induced by Tumor Necrosis Factor-α in Mouse Tracheal Smooth Muscle.

The proinflammatory cytokine tumor necrosis factor-α (TNF-α) augments intracellular Ca2+ signaling and contractile responses of airway smooth muscles, leading to airway hyperresponsiveness. However, the underlying mechanism has not been fully elucidated. This study aimed to investigate the cellular mechanism of the potentiated contraction of mouse tracheal smooth muscle induced by TNF-α. The results showed that TNF-α triggered facilitation of mouse tracheal smooth muscle contraction in an epithelium-independent manner. The TNF-α-induced hypercontractility could be suppressed by the protein kinase C inhibitor GF109203X, the tyrosine kinase inhibitor genistein, the Src inhibitor PP2, or the L-type voltage-dependent Ca2+ channel blocker nifedipine. Following TNF-α incubation, the α1C L-type Ca2+ channel (CaV1.2) was up-regulated in cultured primary mouse tracheal smooth muscle cells. Pronounced phosphotyrosine levels were observed in mouse tracheas. In conclusion, this study shows that TNF-α enhanced airway smooth muscle contraction via protein kinase C-Src-CaV1.2 pathways, which provides novel insights into the pathologic role of proinflammatory cytokines in mediating airway hyperresponsiveness.

Construction of Zr-Metal-Organic Frameworks-Based Composite Materials toward Anhydrous Proton Conduction and Photocatalytic CO2 Reduction.

Metal-organic frameworks constructed from Zr usually possess excellent chemical and physical stability. Therefore, they have become attractive platforms in various fields. In this work, two families of hybrid materials based on ZrSQU have been designed and synthesized, named Im@ZrSQU and Cu@ZrSQU, respectively. Im@ZrSQU was prepared through the impregnation method and employed for proton conduction. Im@ZrSQU exhibited terrific proton conduction performance in an anhydrous environment, with the highest proton conduction value of 3.6 × 10-2 S cm-1 at 110 °C. In addition, Cu@ZrSQU was synthesized via the photoinduction method for the photoreduction of CO2, which successfully promoted the conversion of CO2 into CO and achieved the CO generation rate of up to 12.4 µmol g-1 h-1. The photocatalytic performance of Cu@ZrSQU is derived from the synergistic effect of Cu NPs and ZrSQU. Based on an in-depth study and discussion toward ZrSQU, we provide a versatile platform with applications in the field of proton conduction and photocatalysis, which will guide researchers in their further studies.

Ginkgetin Alleviates Intervertebral Disc Degeneration by Inhibiting Apoptosis, Inflammation, and Disturbance of Extracellular Matrix Synthesis and Catabolism via Inactivation of NLRP3 Inflammasome.

BACKGROUND: Apoptosis, inflammation, and the extracellular matrix (ECM) synthesis and catabolism are compromised with intervertebral disc degeneration (IDD). Ginkgetin (GK) has been demonstrated to alleviate several diseases; however, its effect on IDD remains unknown. METHODS: The nucleus pulposus cells (NPCs) were stimulated with interleukin (IL)-1ß to construct the IDD models in vitro. Rats were used for the construction of the IDD models in vivo via the fibrous ring puncture method. The effect and mechanism of GK on IDD were determined by cell counting kit-8 (CCK-8), flow cytometry, western blot, real-time quantitative polymerase chain reaction (RT-qPCR), enzyme­linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) and safranine O staining, and immunohistochemistry (IHC) assays, respectively. RESULTS: GK increased the cell viability and upregulated the expressions of anti-apoptosis and ECM synthesis markers in NPCs treated with IL-1ß. GK also decreased apoptosis rate, and downregulated the expressions of proteins related to pro-apoptosis, ECM catabolism, and inflammation in vitro. Mechanically, GK reduced the expression of nucleotide binding oligomeric domain like receptor protein 3 (NLRP3) inflammasome-related proteins. Overexpression of NLRP3 reversed the effect of GK on the proliferation, apoptosis, inflammation, and ECM degradation in IL-1ß-induced NPCs. Moreover, GK attenuated the pathological manifestations, inflammation, ECM degradation, and NLRP3 inflammasome expression in IDD rats. CONCLUSION: GK suppressed apoptosis, inflammation, and ECM degradation to alleviate IDD via the inactivation of NLRP3 inflammasome.

Genetically predicted triglycerides mediate the relationship between type 2 diabetes Mellitus and intervertebral disc degeneration.

BACKGROUND: To validate the causal relationship between type 2 diabetes mellitus (T2DM) and intervertebral disc degeneration (IVDD) and to identify and quantify the role of triglycerides (TGs) as potential mediators. METHODS: A two-sample Mendelian randomization (MR) analyses of T2DM (61,714 cases and 1178 controls) and IVDD (20,001 cases and 164,682 controls) was performed using genome-wide association studies (GWAS). Moreover, two-step MR was employed to quantify the proportionate impact of TG-mediated T2DM on IVDD. RESULTS: MR analysis showed that T2DM increased IVDD risk (OR: 1.0466, 95% CI 1.0049-1.0899, P = 0.0278). Reverse MR analyses demonstrated that IVDD does not affect T2DM risk (P = 0.1393). The proportion of T2DM mediated through TG was 11.4% (95% CI 5.5%-17.4%). CONCLUSION: This work further validates the causality between T2DM and IVDD, with a part of the effect mediated by TG, but the greatest impacts of T2DM on IVDD remain unknown. Further studies are needed to identify other potential mediators.

Research relating to three-dimensional (3D) printing in spine surgery: a bibliometric analysis.

PURPOSE: Although numerous publications on three-dimensional printing (3DP) in spine surgery have been published, bibliometric analysis studies are scarce. Thus, this study aimed to present a bibliometric analysis of the status, hot spots, and frontiers of 3DP in spine surgery and associated research disciplines. METHODS: All publications relating to the utilization of 3DP in spine surgery from 1999 to May 9, 2022, were retrieved from the Web of Science. The bibliometric analysis was performed using CiteSpace software, and information on the country, institution, author, journal, and keywords for each publication was collected. RESULTS: A total of 270 articles were identified. From 2016 onward, a significant increase in publications on spinal surgery was observed. China was the most productive and influential country (98 publications) and H-index (22), followed by the USA and Australia. The most productive institution was Capital Medical University (9 publications). P. S. D'urso (8 publications, 46 citations) and R. J. Mobbs (8 publications, 39 citations) were the most prolific authors. European Spine Journal contributed the highest number of publications. The eight main clusters were: "rapid prototyping" #0, "3D printed" #1, "spine fusion" #2, "scoliosis" #3, "spine surgery" #4, "patient-specific" #5, "nervous system" #6, and "neuronavigation" #7. The strongest keyword bursts in 3DP in spine surgery were "fixation," "drill template," "instrumentation," "fusion," "complication," and "atlantoaxial instability." CONCLUSION: This analysis provides information on research trends and frontiers in the application of 3DP in spine surgery, as well as research and collaboration partners, institutions, and countries.

Compare the clinical value of two minimally invasive approaches to locating radial nerve in the posterior humeral approach.

PURPOSE: To compare the clinical value between locating radial nerve (RN) guided by Color Doppler ultrasonography and posterior antebrachial cutaneous nerve (PACN) in the posterior humeral approach. METHODS: The five fresh adult cadavers (ten upper arms) were selected to compare the two methods of locating the RN in the posterior humeral approach (guided by ultrasound and PACN) by measuring the operation time, the length of incision, and the area of subcutaneous free. And the comparison between the two groups was statistically analyzed by paired t-test. RESULTS: The results of this study demonstrated that the length of incision and the area of subcutaneous free in the ultrasound group were smaller than that in the PACN group (P < 0.05), while the operation time was just the opposite (P < 0.05). However, after excluding the time of ultrasound location, the operation time in the ultrasound group was shorter than that in the PANC group, and the difference was statistically significant (P < 0.05). CONCLUSION: The RN can be quickly and safely exposed by both methods. The ultrasound approach requires a long learning curve, but is more minimally invasive and can help determine whether the intraoperative nerve is compressed by the plate. And the PACN method requires a longer incision and a wider area of subcutaneous free, while specialized equipment and professional training for surgeons are not required. In a word, these two methods have advantages and disadvantages, so they should be selected based on the exact situation.

Leukoreduced PRP enhanced proliferation and ECM production yet inhibited senescence, inflammation, and multi-differentiation potential of AFSCs by downregulating HMGB1.

BACKGROUND: This study assessed the role and potential mechanism of platelet-rich plasma (PRP) in the progression of intervertebral disk degeneration (IVDD). METHODS: Annulus fibrosus (AF)-derived stem cells (AFSCs) from New Zealand white rabbits received the transfection with high mobility group box 1 (HMGB1) plasmids and the subsequent treatment with bleomycin, 10% leukoreduced PRP or leukoconcentrated PRP. Dying cells were indicated by immunocytochemistry analysis for senescence-associated ß-galactosidase (SA-ß-gal) staining. The proliferation of these cells was evaluated based on the population doubling time (PDT). The expressions of HMGB1, pro-aging and anti-aging molecules, extracellular matrix (ECM)-related catabolic/anabolic factors, and inflammatory genes at the molecular or transcriptional levels were quantified via Western blot or reverse transcription-quantitative PCR (RT-qPCR). Besides, the adipocytes, osteocytes, and chondrocytes were separately dyed by Oil Red O, Alizarin Red S, and Safranin O staining. RESULTS: Bleomycin enhanced the senescent morphological changes and increased the PDT and the expressions of SA-ß-gal, pro-aging molecules, ECM-related catabolic factors, inflammatory genes, and HMGB1 while suppressing the expressions of anti-aging and anabolic molecules. Leukoreduced PRP reversed the effects of bleomycin and inhibited the differentiation of AFSCs into adipocytes, osteocytes, and chondrocytes. Besides, HMGB1 overexpression offset the roles of leukoreduced PRP in AFSCs. CONCLUSION: Leukoreduced PRP promotes cell proliferation and ECM production of AFSCs, while inhibiting their senescence, inflammation, and multi-differentiation potentials via downregulating HMGB1 expression.

Letter to the editor regarding "Full­endoscopic (bi­portal or uni­portal) versus microscopic lumbar decompression laminectomy in patients with spinal stenosis: systematic review and meta­analysis".

A recent article entitled "Full­endoscopic (bi­portal or uni­portal) versus microscopic lumbar decompression laminectomy in patients with spinal stenosis: systematic review and meta­analysis" written by Pairuchvej et al. (Eur J Orthop Surg Traumatol 30(4):595-611, 2019) published in "European Journal of Orthopaedic Surgery & Traumatology" has aroused our great interest. The authors concluded that compared with minimally invasive decompression surgery, full endoscopic spinal surgery had better pain relief (back pain and leg pain) in the treatment of lumbar spinal stenosis and had a lower complication rate, but no statistical difference in oswestry disability index score and operative time between both groups. Comparing to minimally invasive spinal surgery, bi-portal endoscopic spinal surgery had better back pain relief in the early stage, while uni-portal full endoscopic spinal surgery had better pain relief in the leg and a lower rate of complications.

Targeted gene next-generation sequencing reveals genomic profile in a cohort of 46 Chinese patients with breast cancer.

BACKGROUND: The present study aimed to explore the genomic profile in a cohort of Chinese patients with breast cancer (BC), as well as provide potential strategies for clinic treatment in specific subset of BC patients. METHODS: Paired samples from 46 BC patients were subjected to DNA extraction and 537 gene targeted next-generation sequencing. RESULTS: In total, 742 somatic mutations were detected in these patients, which involved 303 genes. TP53 and PIK3CA were the most frequently mutated genes, with a mutation rate of 45.65% and 26.09%. C>T, T>C and C>A comprised the main single nucleotide base variation for this Chinese cohort. Triple negative breast cancer (TNBC) group had more TP53-mutated patients than the Non-TNBC group (p = 0.0229). In addition, the cohort was also divided into 'Young' and 'Old' groups based on the age of onset. Compared with the 'Young' group, the 'Old' group had more frameshift mutations (p = 0.0190), less missense mutations (p = 0.0269) and more HOXA11-mutated patients (p = 0.0197). Additionally, the HOXA11mt (HOXA11 gene mutated) group had more frameshift mutations than the HOXA11wt (HOXA11 gene without mutation) group (p < 0.0001). In KEGG (i.e. Kyoto Encyclopedia of Genes and Genomes) analysis, the HOXA11wt group had more gene mutations involved in the T cell receptor signaling pathway (p = 0.0197), Jak-STAT signaling pathway (p = 0.0380) and the HIF-1 signaling pathway (p = 0.0489) than the HOXA11mt group. In the present study, the heterogeneity of somatic mutations was revealed between different tumor subgroups, including TNBC/Non-TNBC, age of onset (Young/Old) and HOXA11 mutation (HOXA11mt /HOXA11wt ). CONCLUSIONS: The present study revealed the heterogeneity of gene mutation and clinical variables among BC subtypes and might provide guidance for developing a potential target for clinical treatment.

GPVI (Glycoprotein VI) Interaction With Fibrinogen Is Mediated by Avidity and the Fibrinogen αC-Region.

OBJECTIVE: GPVI (glycoprotein VI) is a key molecular player in collagen-induced platelet signaling and aggregation. Recent evidence indicates that it also plays important role in platelet aggregation and thrombus growth through interaction with fibrin(ogen). However, there are discrepancies in the literature regarding whether the monomeric or dimeric form of GPVI binds to fibrinogen at high affinity. The mechanisms of interaction are also not clear, including which region of fibrinogen is responsible for GPVI binding. We aimed to gain further understanding of the mechanisms of interaction at molecular level and to identify the regions on fibrinogen important for GPVI binding. Approach and Results: Using multiple surface- and solution-based protein-protein interaction methods, we observe that dimeric GPVI binds to fibrinogen with much higher affinity and has a slower dissociation rate constant than the monomer due to avidity effects. Moreover, our data show that the highest affinity interaction of GPVI is with the αC-region of fibrinogen. We further show that GPVI interacts with immobilized fibrinogen and fibrin variants at a similar level, including a nonpolymerizing fibrin variant, suggesting that GPVI binding is independent of fibrin polymerization. CONCLUSIONS: Based on the above findings, we conclude that the higher affinity of dimeric GPVI over the monomer for fibrinogen interaction is achieved by avidity. The αC-region of fibrinogen appears essential for GPVI binding. We propose that fibrin polymerization into fibers during coagulation will cluster GPVI through its αC-region, leading to downstream signaling, further activation of platelets, and potentially stimulating clot growth. Graphic Abstract: A graphic abstract is available for this article.

Ag Nanoparticle-Modified Polyoxometalate-Based Metal-Organic Framework for Enhanced CO2 Photoreduction.

The photoreduction deposition method is employed to fabricate a family of silver nanoparticle (Ag NP)-modified polyoxometalate-based metal-organic framework (NENU-5) photocatalysts, named Ag/NENU-5. The title photocatalysts, Ag/NENU-5, can be used for the photocatalytic reduction of CO2 and are observed to efficiently reduce CO2 into CO, in which the highest reduction rate is 22.28 µmol g-1 h-1, 3 times greater than that of NENU-5. Photocatalytic reduction performances of CO2 have been extremely improved after the incorporation of Ag NPs as the cocatalyst. The enhancement of the photocatalytic reduction of CO2 has been attributed to the synergistic effects of Ag NPs and NENU-5, inhibiting the charge recombination during the photocatalytic process and increasing the reaction active sites. Furthermore, the influence of Ag NPs on the photocatalytic activity has also been investigated. The experimental results clearly reveal that the size of Ag NPs could exert a main effect on the photocatalytic activity, and the reasonable size of Ag NPs is able to enhance the photocatalytic reduction activity toward CO2 significantly.

A pilot study of endoscope-assisted MITLIF with fluoroscopy-guided technique: intraoperative objective and subjective evaluation of disc space preparation.

BACKGROUND: Adequate discectomy and endplate preparation are extremely crucial steps for spinal interbody fusion. Minimally invasive transforaminal lumbar interbody fusion MITLIF technique is safe and effective. However, concerns exist regarding sufficient disc space preparation from unilateral access. The purpose of this study, was to demonstrate our preliminary experience in objective and subjective evaluation of disc space preparation intraoperatively during endoscope-assisted MITLIF with fluoroscopy-guided, describing some of its possible advantages, and analyzing its safety and feasibility. METHODS: From March 2018 to July 2019, three patients with degenerative spinal stenosis with radiculopathy and instability underwent endoscope-assisted MITLIF with fluoroscopy-guided. Patients' demographic data, clinical parameters, subsidence, and fusion were collected. RESULTS: Patients were successfully treated by endoscope-assisted MITLIF with fluoroscopy-guided at single-level or two-level. Symptoms improved postoperatively in all patients, and no complications occurred during follow-up. No cage subsidence was observed. At 6-month postoperatively, there was bony fusion observed on computed tomography in two patients. CONCLUSION: Endoscope-assisted MITLIF with fluoroscopy-guided is a safe and feasible technique to improve visualization during discectomy and endplate preparation objectively and subjectively, possibly increasing fusion rate and early time to fusion.

Bibliometric analysis and visualization of research trends on oblique lumbar interbody fusion surgery.

PURPOSE: To determine trends and hot subjects in the field of oblique lumbar interbody fusion (OLIF) research during the last decade using bibliometric analysis and visualization tools, in order to assist researchers in exploring new directions for future research in that field. METHODS: Articles published from January 1, 2012, to August 15, 2021, were screened in the Web of Science database. The data were analyzed with CiteSpace software, which generated visualization knowledge maps. All literature was assessed for the following parameters: the number of total publications, distribution, h-index, institutions, journals, authors, co-occurrence state, and research hotspots. RESULTS: A total of 173 articles were identified. The country with the largest number of articles was China (41.04%), followed by South Korea (20.81%), the USA (15.61%), Japan (9.83%), and Thailand (2.89%). South Korea and the USA had the highest h-index (9), followed by China (8), Japan (7), and Thailand (2). Catholic University of Korea was the organization that produced the most literature. World Neurosurgery published the most papers about OLIF (12.50%), but articles in Spine were most frequently cited (151). Kim JS was the most productive author, whereas Silvestre C was the most cited author. The main research hotspots are anatomy, discectomy, approach, injure, and diseases. CONCLUSIONS: The number of publications in the field of OLIF has increased considerably in recent years. The USA, China, South Korea, and Japan have made substantial contributions to this field. Anatomy, complications, decompression surgery, and application in various degenerative lumbar diseases have been the research hotspots in recent years.

Effects of 5.8 GHz microwave on hippocampal synaptic plasticity of rats.

OBJECTIVE: 5.8 GHz spectrum is gaining more attention in wireless technology. To explore the potential hazards, we investigated the effect of exposure to 5.8 GHz microwave on learning and memory ability of rats. Methods: Morris Water maze (MWM), Novel object recognition (NOR) and Fear conditioning test (FCT) were used to evaluate the ability of spatial and non-spatial memory of rats. The hippocampal morphology, the level of brain injury factors in serum and the mitochondrial membrane potential of hippocampal neurons was examined to evaluate the damage of hippocampal neurons. The density of dendritic spines, the ultrastructure of synapses and the level of PSD95, Synaptophysin, p-CREB and CREB were detected to evaluate the hippocampal synaptic plasticity. RESULTS: Compared with Sham group, there was no significant difference in the performance of ethology (in MWM, NOR, FCT) in Microwave 2 h group or Microwave 4 h group. The hippocampal morphology, the serum level of brain injury factors and the content of mitochondrial JC-1 monomer in Microwave 2 h group or Microwave 4 h group did not change obviously, compared with Sham group. The density of dendritic spines, the ultrastructure of synapse and the level of PSD95, Synaptophysin, p-CREB and CREB in hippocampus in Microwave 2 h group or Microwave 4 h group did not significantly change, compared with Sham group. CONCLUSION: Under this experimental condition, exposure to 5.8 GHz microwave could not affect the hippocampal synaptic plasticity of rats.

Postoperative Pain Management after Full Endoscopic Lumbar Discectomy: An Observational Study.

Background: Surgical incision pain, rebound pain, and recurrence can manifest themselves in different forms of postoperative pain after full endoscopic lumbar discectomy (FELD). This study aims to evaluate various postoperative pains after FELD and summarize their characteristics. Methods: Data about the demographic characteristics of patients, pain intensity, and functional assessment results were collected from January 2016 to September 2019. Clinical outcomes including Oswestry Disability Index (ODI) and visual analog scale (VAS) scores, were obtained. Results: A total of 206 patients were enrolled. ODI and VAS of the patients significantly decreased after FELD at 12-month follow-up. A total of 193 (93.7%) patients had mild surgical incision pain after FELD and generally a VAS < 4, and it mostly resolved on its own within 3 days. A total of 12 (5.8%) patients experienced rebound pain, which was typically characterized by pain (mainly leg pain with or without back pain), generally occurring within 2 weeks after FELD and lasting < 3 weeks. The pain levels of rebound pain were equal to or less than those of preoperative pain, and generally scored a VAS of < 6. The recurrence rate was 4.4%. Recurrence often occurs within three months after surgery, with the pain level of the recurrence being greater than or equal to the preoperative pain. Conclusions: Different types of postoperative pain have their own unique characteristics and durations, and treatment options are also distinct. Conservative treatment and analgesia may be indicated for rebound pain and surgical incision pain, but recurrence usually requires surgical treatment.

Is Biportal Endoscopic Spine Surgery More Advantageous Than Uniportal for the Treatment of Lumbar Degenerative Disease? A Meta-Analysis.

Background and Objectives: To estimate the clinical outcomes of uniportal and biportal full-endoscopic spine surgery for the treatment of lumbar degenerative disease (LDD), and to provide the latest evidence for clinical selection. Materials and Methods: Relevant literatures published in PubMed, Web of Science, Embase, CNKI, and WanFang Database before 21 November 2021 were searched systematically. Two researchers independently screened the studies, extracted data, and evaluated the risk of bias of the included studies. The systematic review and meta-analysis were performed using the Review Manager software (version 5.4; The Cochrane Collaboration). Results: A total of seven studies were included in this meta-analysis, including 198 patients in a uniportal endoscopy group and 185 patients in a biportal endoscopy group. The results of this meta-analysis demonstrated that the biportal endoscopy group experienced less intraoperative estimated blood loss (WMD = -2.54, 95%CI [-4.48, -0.60], p = 0.01), while the uniportal endoscopy group displayed significantly better recovery results in Visual Analog Scale (VAS) assessments of the back within 3 days of surgery (WMD = 0.69, 95%CI [0.02, 1.37], p = 0.04). However, no significant differences in operation time, length of hospital stay, complication rates, Oswestry Disability Index (ODI) (within 3 months), ODI (last follow-up), VAS for back (within 3 months), VAS for back (last follow-up), and VAS for leg (within 3 days, within 3 months, last follow-up) were identified between the two groups. Conclusions: According to our meta-analysis, patients who underwent the uniportal endoscopic procedure had more significant early postoperative back pain relief than those who underwent the biportal endoscopic procedure. Nevertheless, both surgical techniques are safe and effective.

ß2-Adrenoceptor Activation Stimulates IL-6 Production via PKA, ERK1/2, Src, and Beta-Arrestin2 Signaling Pathways in Human Bronchial Epithelia.

OBJECTIVE: ß2-Adrenoceptor agonists are widely used to treat asthma because of their bronchial-dilation effects. We previously reported that isoprenaline, via the apical and basolateral ß2-adrenoceptor, induced Cl- secretion by activating cyclic AMP (cAMP)-dependent pathways in human bronchial epithelia. Despite these results, whether and how the ß2-adrenoceptor-mediated cAMP-dependent pathway contributes to pro-inflammatory cytokine release in human bronchial epithelia remains poorly understood. METHODS: We investigated ß2-adrenoceptor-mediated signaling pathways involved in the production of two pro-inflammatory cytokines, interleukin (IL)-6 and IL-8, in 16HBE14o- human bronchial epithelia. The effects of isoprenaline or formoterol were assessed in the presence of protein kinase A (PKA), exchange protein directly activated by cAMP (EPAC), Src, and extracellular signal-regulated protein kinase (ERK)1/2 inhibitors. The involvement of ß-arrestin2 was examined using siRNA knockdown. RESULTS: Isoprenaline and formoterol (both ß2 agonists) induced IL-6, but not IL-8, release, which could be inhibited by ICI 118,551 (ß2 antagonist). The PKA-specific inhibitor, H89, partially inhibited IL-6 release. Another intracellular cAMP receptor, EPAC, was not involved in IL-6 release. Isoprenaline-mediated IL-6 secretion was attenuated by dasatinib, a Src inhibitor, and PD98059, an ERK1/2 inhibitor. Isoprenaline treatment also led to ERK1/2 phosphorylation. In addition, knockdown of ß-arrestin2 by siRNA specifically suppressed cytokine release when a high concentration of isoprenaline (1 mM) was used. CONCLUSION: Our results suggest that activation of the ß2-adrenoceptor in 16HBE14o- cells stimulated the PKA/Src/ERK1/2 and/or ß-arrestin2 signaling pathways, leading to IL-6 release. Therefore, our data reveal that ß2-adrenoceptor signaling plays a role in the immune regulation of human airway epithelia.

The correlation of intraoperative distraction of intervertebral disc with the postoperative canal and foramen expansion following oblique lumbar interbody fusion.

PURPOSE: To examine the correlation of intraoperative distraction of intervertebral disc with the postoperative central canal and foramen expansion by oblique lumbar interbody fusion (OLIF) with indirect decompression. METHODS: Patients who underwent OLIF between October 2013 and April 2017 were included. Clinical outcomes included back and leg pain evaluated by visual analog scale (VAS) and Oswestry Disability Index (ODI). Intraoperative radiographic parameters of height ratio [(HR) = disc height/intervertebral body height)] and cage location were evaluated on intraoperative fluoroscopic images. Disc height (DH), foraminal height (FH), cross-sectional area of spinal canal (CSAC), and CSA of the foramen (CSAF) were measured. RESULTS: A total of 47 patients involving 62 levels were enrolled in this study. Mean follow-up was 43.8 ± 12.0 months. These patients reported an improvement of 61.7% in VAS back, 68.1% in VAS leg, and 46% in ODI (all p < 0.01). Radiographic parameters including HR, DH, FH, CSAC, and CSAF were also significantly increased by 32.6%, 48.2%, 21.4%, 44.0%, and 40.1% (left-side CSAF) or 45.4% (right-side CSAF), respectively (p < 0.05). HR increment was correlated with CSA (canal and foramen) increment. Slightly higher improvements of HR, DH, FH, CSAC, and CSAF (both sides) were noted when cage was located at middle rather than anterior (p > 0.05). CONCLUSIONS: The ligamentotaxis effect of OLIF is capable of supporting indirect decompression of central canal and neural foramina and clinical improvement. HR is a reliable intraoperative assessment method. In addition, intraoperative HR increment was correlated with postoperative neural elements expansion.