Early efficacy observation of the unilateral biportal endoscopic technique in the treatment of multi-level lumbar spinal stenosis.

BACKGROUND: To explore the early curative effect of unilateral biportal endoscopy (UBE) in the treatment of multi-level lumbar spinal stenosis with the help of multiple small incisions. METHODS: A retrospective analysis was performed on 26 patients with multi-level lumbar spinal stenosis treated by UBE in our hospital from August 1, 2021, to March 1, 2022. We collect patients' basic medical records and independently design surgical incisions. The visual analog score (VAS) and Oswestry Disability Index (ODI) were compared before surgery, 7 days after surgery and 6 months after surgery. Spinal canal diameters on CT were compared before surgery and 7 days after surgery. The modified MacNab standard was used to evaluate the efficacy satisfaction at 6 months after operation. RESULTS: In this study, 26 patients were operated according to the predetermined surgical plan. The operative time was 145 ± 40.11 min, the intraoperative blood loss was 156.25 ± 44.32 ml, and the postoperative hospital stay was 4.79 ± 1.31 days. The VAS scores of postoperative lumbago and leg pain were lower than those before surgery (P < 0.05). The postoperative ODI score was significantly different from that before surgery (P < 0.05). The postoperative CT sagittal diameter was significantly different from that before surgery (P < 0.05). The curative effect of modified MacNab was 76.92% when followed up 7 days after surgery. The curative effect of modified MacNab was 92.31% when followed up 6 months after surgery, which was significantly improved compared with 7 days after surgery. CONCLUSION: Under multiple small incision channels, UBE can effectively treat multi-level lumbar spinal stenosis, significantly relieve the clinical symptoms of patients, and significantly improve the quality of life of patients. It is a safe and feasible minimally invasive surgical treatment method for multi-level lumbar spinal stenosis.

Predicting surgical outcome and sagittal alignment change in patients with cervical spondylosis and degenerative kyphosis after anterior cervical discectomy and fusion.

The aim of this study was to forecast the risk factors of poor outcomes and postoperative loss of lordosis or recurrence of kyphosis. In this retrospective study, 101 patients with cervical spondylosis and preoperative kyphosis who underwent anterior cervical discectomy and fusion (ACDF) were enrolled, between June 2015 and June 2019. Patients were grouped according to the recovery rate of Japanese Orthopaedic Association (JOA) score whether more than 50%, and the change of postoperative cervical Cobb angle. There were 22 cases with less than 50% of recovery rate and 35 cases with the worsening of postoperative sagittal alignment (WPSA). Multivariate linear-regression analysis was conducted with the data. Advanced age (p = 0.019), longer duration of symptoms (p = 0.003) and loss of local Cobb angle (LCA) after surgery (p = 0.031) was significantly associated with a poor clinical outcome. A whole kyphosis (p = 0.009), aggravated neck pain after surgery (p = 0.012), preoperative lower thoracic 1 (T1) (p < 0.001), bigger change of C2-7 sagittal vertical axis (SVA) (p = 0.008) and adjacent segment degeneration (ASD) (p = 0.024) was significantly associated with the WPSA. Preoperative health education, nutritional support and early postoperative rehabilitation intervention, in perioperative period, were recommended for patients with advance age, longer duration of symptoms, whole cervical kyphosis and lower T1. Postoperative sagittal malalignment was related to neck pain and ASD after surgery.

[Progress in prolactin receptor research].

Prolactin (PRL) is secreted by lactotrophs in the anterior pituitary and some extra-pituitary tissues such as breast, lacrimal gland, uterus, thymus and spleen, etc. Since PRL is closely related to growth hormone (GH) and placental lactogens (PL), it has been broadly accepted that PRL, GH and PL are resulted from the duplication of an ancestral gene. PRL regulates hundreds of biological functions by endocrine, paracrine and autocrine manners. Prolactin initiates its effects by binding to its receptor (PRLR). PRLR belongs to the class I cytokine receptor superfamily. Up to now, three membrane--PRLRs have been clarified. They are long form (LF), intermediate form (IF) and short form (SF) including SFla and SFlb. All PRLRs are derived from a primary transcript of common gene through alternative splicing mechanism. Although the extracellular domain (ECD) and the transmembrane domain (TD) of LF, IF and SF are equal, different isoforms of PRLR exert different function through different intracellular domain. It has been well documented that abnormity of PRLR is closely related to the pathogenesis, progression and prognosis of cancers including breast cancer. Several PRLR antagonists have been well designed and evidenced to have the potential to be important therapeutics.

Biomechanical Characterization of Unilateral and Bilateral Posterior Lumbar Interbody Fusion Constructs.

Objectives: To compare the biomechanical stability of two-level PLIF constructs with unilateral and bilateral pedicle screw fixations. Methods: Six cadaveric lumbar segments were evaluated to assess biomechanical stability in response to pure moment loads applied in flexion-extension (FE), lateral bending (LB), and axial rotation (AR). Each specimen was tested in six sequential configurations: (1) intact baseline; (2) facetectomy; (3) unilateral pedicle screws (UPS); (4) bilateral pedicle screws (BPS); (5) unilateral pedicle screws and cage (UPSC); and (6) bilateral pedicle screws and cage (BPSC). Results: Significant reductions in motion were observed when comparing all instrumented conditions to the intact and facetectomy stages of testing. No significant differences in motion between UPS, BPS, UPSC, or BPSC were observed in response to FE range of motion (ROM) or neutral zone (NZ). ROM was significantly higher in the UPS stage compared to BPS in response to LB and AT loading. ROM was significantly higher in UPSC compared to BPSC in response to LB loading only. Similarly, NZ was significantly higher in UPSC compared to BPSC in response to only LB loading. In response to AT loading, ROM was significantly higher during UPS than BPS or BPSC; however, no significant differences were noted between UPSC and BPSC with respect to AT ROM or NZ. Conclusion: BPS fixation is biomechanically superior to UPS fixation in multilevel PLIF constructs. This was most pronounced during both LB loading. Interbody support did contribute significantly to immediate stability.

Minimally invasive injectable lumbar interbody fusion with mineralized collagen-modified PMMA bone cement: A new animal model.

This study was to develop a feasible and safe animal model for minimally invasive injectable lumbar interbody fusion using a novel biomaterial, mineralized collagen-polymethylmethacrylate bone cement (MC-PMMA), with unilateral pedicle screw fixation in an in vivo goat model. Eight goats (Capra aegagrus hircus) were divided into three groups: MC-PMMA, unmodified commercial-polymethylmethacrylate bone cement (UC-PMMA), and a control group (titanium cage filled with autogenous bone, TC-AB). Each group of goats was treated with minimally invasive lumbar interbody fusion at the L3/L4 and L5/L6 disc spaces (injected for MC-PMMA and UC-PMMA, implanted for TC-AB). The pedicle screws were inserted at the L3, L4, L5, and L6 vertebrae, respectively, and fixed on the left side. The characteristics of osteogenesis and bone growth were assessed at the third and the sixth month, respectively. The methods of evaluation included the survival of each animal, X-ray imaging, and 256-layer spiral computed tomography (256-CT) scanning, imaged with three-dimensional microfocus computed tomography (micro-CT), and histological analysis. The results showed that PMMA bone cement can be extruded smoothly after doping MC, the MC-PMMA integrates better with bone than the UC-PMMA, and all goats recovered after surgery without nerve damage. After 3 and 6 months, the implants were stable. New trabecular bone was observed in the TC-AB group. In the UC-PMMA group a thick fibrous capsule had formed around the implants. The MC-PMMA was observed to have perfect osteogenesis and bone ingrowth to adjacent bone surface. Minimally invasive injectable lumbar interbody fusion using MC-PMMA bone cement was shown to have profound clinical value, and the MC-PMMA showed potential application prospects.

The protective effect of oleanolic acid on NMDA-induced MLE-12 cells apoptosis and lung injury in mice by activating SIRT1 and reducing NF-κB acetylation.

Overactivation of the N-methyl-d-aspartate (NMDA) receptor promotes oxidative stress, aggravates the inflammatory response and induces excitotoxic lung injury. NMDA is a synthetic agonist that selectively activates the NMDA receptor. Oleanolic acid (OA) is a natural anti-inflammatory and antioxidant compound. This study investigated the effect and possible mechanism of OA on NMDA-induced acute lung injury (ALI) in mice. OA pretreatment alleviated NMDA-induced histological lung changes and ameliorated pulmonary oedema and pulmonary permeability. At the same time, OA inhibited inflammatory cell infiltration and decreased the levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß in the lung and bronchoalveolar lavage fluid (BALF). OA markedly decreased malondialdehyde (MDA) production and increased the superoxide dismutase (SOD) and glutathione (GSH) contents of the lung in vivo. Meanwhile, we first found that NMDA increased LDH activity and decreased cell viability, and induced oxidative stress and apoptosis in mouse lung epithelial (MLE)-12 cells. By employing SRT1720 and sirtinol, the activator and inhibitor of sirtuin 1 (SIRT1), we found that SRT1720 partially eliminated the increase in ROS，and sirtinol further promoted the increase in ROS caused by NMDA. OA increased MLE-12 cells viability and attenuated oxidative stress after NMDA challenge in vitro. OA suppressed NMDA-induced MLE-12 cells apoptosis, while sirtinol inhibited the effect of OA. In addition, OA significantly upregulated the levels of SIRT1, nuclear-related factor 2(Nrf2) and Bcl-2 protein and downregulated the levels of acetylated nuclear factor-kappa B (NF-κB), NLRP3 and Bax protein. In conclusion, OA attenuated NMDA-induced excitotoxic lung injury, potentially through its anti-inflammatory, antioxidative stress and anti-apoptotic effects. The mechanism may be related to activating SIRT1 and reducing NF-κB acetylation.

NMDA receptor activation inhibits the protective effect of BM­MSCs on bleomycin­induced lung epithelial cell damage by inhibiting ERK signaling and the paracrine factor HGF.

Endoplasmic reticulum (ER) stress in alveolar epithelial cells (AECs) is associated with the pathogenesis of pulmonary fibrosis. Bone marrow­derived mesenchymal stromal cells (BM­MSCs) can exert protective effects on ER­stressed AECs via paracrine signaling. In the present study, mouse lung epithelial (MLE)­12 cells were directly stimulated with various concentrations of bleomycin (BLM). MLE­12 cell apoptosis was detected by flow cytometry, and Ki67 expression was detected by immunofluorescence to reflect cell proliferation. The results revealed that BLM increased the protein expression levels of X­box binding protein 1 and immunoglobulin heavy chain­binding protein, thus inducing ER stress, and caused cell dysfunction by inhibiting proliferation and promoting apoptosis. In addition, MSC­derived conditioned medium (MSC­CM) protected MLE­12 cells from BLM­induced injury, by reducing ER stress, promoting cell proliferation and inhibiting cell apoptosis. Our previous studies reported that N­methyl­D­aspartate (NMDA) receptor activation partially inhibits the antifibrotic effect of BM­MSCs on BLM­induced pulmonary fibrosis through downregulating the paracrine factor hepatocyte growth factor (HGF). In the present study, the synthesis and secretion of HGF were detected by western blotting and ELISA, respectively. Results further demonstrated that NMDA inhibited the synthesis and secretion of HGF in BM­MSCs, and NMDA­preconditioned MSC­CM had no protective effects on BLM­induced injury in MLE­12 cells. In addition, activation of the NMDA receptor decreased the phosphorylation levels of extracellular signal­regulated kinase (ERK)1/2 in BM­MSCs. Using Honokiol and FR180204, the activator and inhibitor of ERK1/2, respectively, it was then revealed that Honokiol partially eliminated the decrease in HGF expression, whereas FR180204 further promoted the reduction in HGF caused by NMDA. Collectively, these findings suggested that NMDA receptor activation may downregulate HGF by inhibiting ERK signaling in BM­MSCs, thus weakening their protective effects on BLM­induced lung epithelial cell damage.

An excessive increase in glutamate contributes to glucose-toxicity in ß-cells via activation of pancreatic NMDA receptors in rodent diabetes.

In the nervous system, excessive activation of NMDA receptors causes neuronal injury. Although activation of NMDARs has been proposed to contribute to the progress of diabetes, little is known about the effect of excessive long-term activation of NMDARs on ß-cells, especially under the challenge of hyperglycemia. Here we thoroughly investigated whether endogenous glutamate aggravated ß-cell dysfunction under chronic exposure to high-glucose via activation of NMDARs. The glutamate level was increased in plasma of diabetic mice or patients and in the supernatant of ß-cell lines after treatment with high-glucose for 72 h. Decomposing the released glutamate improved GSIS of ß-cells under chronic high-glucose exposure. Long-term treatment of ß-cells with NMDA inhibited cell viability and decreased GSIS. These effects were eliminated by GluN1 knockout. The NMDAR antagonist MK-801 or GluN1 knockout prevented high-glucose-induced dysfunction in ß-cells. MK-801 also decreased the expression of pro-inflammatory cytokines, and inhibited I-κB degradation, ROS generation and NLRP3 inflammasome expression in ß-cells exposed to high-glucose. Furthermore, another NMDAR antagonist, Memantine, improved ß-cells function in diabetic mice. Taken together, these findings indicate that an increase of glutamate may contribute to the development of diabetes through excessive activation of NMDARs in ß-cells, accelerating ß-cells dysfunction and apoptosis induced by hyperglycemia.

NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury.

BACKGROUND: Glutamate is a major neurotransmitter in the central nervous system (CNS). Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor (NMDAR), causing neuronal injury and death. Recently, NMDAR has been reported to be found in the lungs. The aim of this study is to examine the effects of memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice. METHODS: C57BL/6 mice were intratracheally injected with bleomycin (BLM) to induce lung injury. Mice were randomized to receive saline, memantine (Me), BLM, BLM plus Me. Lungs and BALF were harvested on day 3 or 7 for further evaluation. RESULTS: BLM caused leukocyte infiltration, pulmonary edema and increase in cytokines, and imposed significant oxidative stress (MDA as a marker) in lungs. Memantine significantly mitigated the oxidative stress, lung inflammatory response and acute lung injury caused by BLM. Moreover, activation of NMDAR enhances CD11b expression on neutrophils. CONCLUSIONS: Memantine mitigates oxidative stress, lung inflammatory response and acute lung injury in BLM challenged mice.

Endogenous hydrogen sulfide mediates the cardioprotection induced by ischemic postconditioning in the early reperfusion phase.

Hydrogen sulfide (H(2)S), produced by cystanthionine-γ-lysase (CSE) in the cardiovascular system, has been suggested to be the third gasotransmitter in addition to nitric oxide (NO) and carbon monoxide (CO). The present study aimed to investigate the role of H(2)S in ischemic postconditioning (IPO) during the early period of reperfusion. IPO with 6 episodes of 10 sec reperfusion followed by 6 episodes of 10 sec ischemia (IPO 2') was administered when reperfusion was initiated. Cardiodynamics and the concentration of H(2)S were measured at 1, 2, 3, 4, 5, 10, 20, 30, 60, 90 and 120 min of reperfusion. Lactate dehydrogenase (LDH) levels and infarct size were determined at the end of the reperfusion. The concentration of H(2)S was stable during the whole experiment in the control group, whereas it reached a peak at the first minute of reperfusion in the ischemia-reperfusion (IR) group. The concentration of H(2)S at the first minute of reperfusion in the IPO 2' group was higher compared to that of the IR group, which correlated with cardioprotection including improved heart contractile function and reduced infarct size and LDH levels. However, the above effects of IPO 2' were attenuated by pre-treatment with blockade of endogenous H(2)S production with DL-propargylglycine for 20 min prior to global ischemia. Furthermore, we found that other forms of IPO, IPO commencing at 1 min after reperfusion (delayed IPO) or lasting only for 1 min (IPO 1'), failed to increase the concentration of H(2)S and protect the myocardium. We conclude that the peak of endogenous H(2)S in the early reperfusion phase is the key to cardioprotection induced by IPO.