Efficacy and safety of different anti-osteoporotic drugs for the spinal fusion surgery: A network meta-analysis.

BACKGROUND: Administering anti-osteoporotic agents to patients perioperatively is a widely accepted approach for improving bone fusion rates and reducing the risk of complications. The best anti-osteoporotic agents for spinal fusion surgery remain unclear. AIM: To investigate the efficacy and safety of different anti-osteoporotic agents in spinal fusion surgery via network meta-analysis. METHODS: Searches were conducted in four electronic databases (PubMed, EMBASE, Web of Science, the Cochrane Library and China National Knowledge Infrastructure (CNKI) from inception to November 2022. Any studies that compared anti-osteoporotic agents vs placebo for spinal fusion surgery were included in this network meta-analysis. Outcomes included fusion rate, Oswestry disability index (ODI), and adverse events. Network meta-analysis was performed by R software with the gemtc package. RESULTS: In total, 13 randomized controlled trials were included in this network meta-analysis. Only teriparatide (OR 3.2, 95%CI: 1.4 to 7.8) was more effective than placebo in increasing the fusion rate. The surface under the cumulative ranking curve (SUCRA) of teriparatide combined with denosumab was the highest (SUCRA, 90.9%), followed by teriparatide (SUCRA, 74.0%), zoledronic acid (SUCRA, 43.7%), alendronate (SUCRA, 41.1%) and risedronate (SUCRA, 35.0%). Teriparatide (MD -15, 95%CI: -28 to -2.7) and teriparatide combined with denosumab (MD -20, 95%CI: -40 to -0.43) were more effective than placebo in decreasing the ODI. The SUCRA of teriparatide combined with denosumab was highest (SUCRA, 90.8%), followed by teriparatide (SUCRA, 74.5%), alendronate (SURCA, 52.7), risedronate (SURCA, 52.1%), zoledronic acid (SURCA, 24.2%) and placebo (SURCA, 5.6%) for ODI. The adverse events were not different between groups. CONCLUSION: This network meta-analysis suggests that teriparatide combined with denosumab and teriparatide alone significantly increase the fusion rate and decrease the ODI without increasing adverse events. Based on current evidence, teriparatide combined with denosumab or teriparatide alone is recommended to increase the fusion rate and to reduce ODI in spinal fusion patients.

[Effect and Involved Mechanism of RSL3-induced Ferroptosis in Acute Leukemia Cells MOLM13 and Drug-resistant Cell Lines].

OBJECTIVE: To investigate the effect and involved mechanism of RSL3 on ferroptosis action in acute leukemia cells MOLM13 and its drug-resistant cells. METHODS: After MOLM13 treated with RSL3, CCK-8 assay was performed to detect cell viability, flow cytometry was used to detect the reactive oxygen species (ROS) level of the cells, RT-qPCR and Western blot were used to detect the expression of glutathione peroxidase 4 (GPX4). After MOLM13/IDA and MOLM13/Ara-C, the drug-resistant cell lines were constructed, the ferroptosis induced by RSL3 was observed. Bone marrow samples were collected from patients with acute monocytic leukemia. RT-qPCR and Western blot were performed to detect the expression of related genes and proteins involved in ferroptosis pathway. RESULTS: RSL3 significantly inhibited the cell viability of MOLM13 and increased the intracellular ROS level, which were partially reversed by ferrostatin-1. The mRNA and protein expression of GPX4 decreased in MOLM13 treated with RSL3. RSL3 inhibited the viability of MOLM13/IDA and MOLM13/Ara-C cells more strongly than that of non-drug resistant cells, also increased the intracellular ROS level . The cytotoxic effects were partially reversed by ferrostatin-1. The mRNA and protein expressions of GPX4 in MOLM13/IDA and MOLM13/Ara-C cells were higher than those in non-drug resistant cells. The mRNA and protein levels of GPX4 in bone marrow of relapsed/refractory acute mononuclear leukemia patients were higher than those of ordinary acute mononuclear leukemia patients. CONCLUSION: RSL3 can induce non-drug resistant cells MOLM13 ferroptosis by inhibiting GPX4 activity. MOLM13/IDA and MOLM13/Ara-C are more sensitive to RSL3 compared with non-drug resistant cells MOLM13, which may be caused by the differences in GPX4 expression. The expressions of GPX4 mRNA and protein in relapsed/refractory acute mononuclear leukemia are higher than those in ordinary acute mononuclear leukemia.

[Analysis of lumbosacral sagittal balance parameter variation in minimally invasive transforaminal lumbar interbody fusion with real-time 3D navigation techniques].

OBJECTIVE: To explore the dynamic changes of lumbosacral sagittal parameters after real-time three-dimensional navigation assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and traditional open TLIF for treatment of lumbar degenerative disease. METHODS: The clinical data of 61 patients with lumbar degenerative disease underwent single-segment surgery from September 2017 to September 2019 were retrospectively analyzed. Among them, 31 cases underwent MIS-TLIF with 3D navigation techniques (MIS-TLIF group) and another 30 cases underwent conventional open TLIF (traditional open TLIF group). The basic information, operative time and intraoperative blood loss were collected. The sagittal radiologic parameters were measured before surgery and 3 months after surgery, including lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), anterior disc height (ADH), posterior disc height(PDH).And the average disc height(DH) and pelvic incidence to lumbar lordosis mismatch (PI-LL) were calculated. RESULTS: Operative time and intraoperative blood loss in MIS-TLIF group were significantly less than in traditional open TLIF group(P<0.05). In MIS-TLIF group, LL, SL, PI-LL, and DH were significantly improved at 3 months after surgery (P<0.05), while PI, PT, and SS were not statistically different from those before surgery (P>0.05). LL, PI-LL, and DH of patients in the traditional open TLIF group were significantly improved at 3 months after surgery (P<0.05), while the PI, PT, SS, and SL were not statistically different from those before surgery (P>0.05). LL change showed a significant correlation with SL change (r= 0.433, P<0.001). Change in SL closely correlated to change in ADH (r=0.621, P<0.05) and PDH(r=0.527, P<0.05). CONCLUSION: Real-time navigation-assisted MIS-TLIF and traditional open TLIF can recover DH in a short term for lumbar degenerative diseases, improve LL and PI-LL, and make the arrangement of the sagittal plane of the lumbosacral region more coordinated after surgery. But only the navigation assisted MIS -TLIF can significantly improve SL. Compared with traditional open TLIF, real-time navigation assisted MIS-TLIF in the treatment of degenerative lumbar diseases has the advantages of short operation time and less intraoperative bleeding.

Non-uniform model of relationship between surface strain and rust expansion force of reinforced concrete.

When operating within the environments rich with sodium chloride, steel bars of reinforced concrete structures are often subject to corrosion caused by surrounding erosive materials, and the associated rust expansion force due to corrosion takes a critical role in determining the durability of relevant reinforced concrete structures. By investigating the corrosion course of steel reinforcement with theory of elasticity, a numerical rust expansion model is established for the moment of concrete surface rupture based on non-uniform sin function. Cuboid reinforced concrete specimen with squared cross sections is tested to analyze the rust expansion when concrete cracks due to corrosive forces. The utility of the established expansion model is validated by numerical simulation with Abaqus through the comparison between the associated outcomes. The impacts of steel bar diameter and concrete cover thickness on the magnitude of rust expansion force are discussed.

Noninvasive tools based on immune biomarkers for the diagnosis of central nervous system graft-vs-host disease: Two case reports and a review of the literature.

BACKGROUND: Central nervous system graft-vs-host disease (CNS-GVHD) is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation. Currently, establishing a diagnosis of CNS-GVHD is challenging because the diagnostic criteria and diagnostic methods are not well defined and many confounding factors need to be ruled out. CASE SUMMARY: Here, we present two patients with CNS-GVHD. Both patients with a history of acute GVHD or chronic GVHD developed neurological symptoms that could not be explained by other causes, and had abnormal cerebrospinal fluid (CSF) studies as determined by CSF and blood immune biomarker examinations, suggestive of suspected CNS-GVHD. Due to the lack of specific magnetic resonance imaging abnormalities and the rapid clinical deterioration of the patients, we did not attempt to perform a brain biopsy, but prompted the initiation of empirical immunosuppressive therapy. In view of the rapid and favorable response to local and systematic immunosuppressive treatment and the aforementioned neurologic manifestations together with CSF abnormalities and other negative findings, a final diagnosis of CNS-GVHD was made. CONCLUSION: CSF and blood immune biomarker examinations facilitated the diagnosis of CNS-GVHD, which are particularly suitable for patients who are critically ill and require urgent treatment and for those who are unsuitable for invasive diagnostic procedures.

[Expression and Significance of HIF-1α in Erythropoiesis of Secondary Iron Overload Disease after Irradiation Damage].

OBJECTIVE: To study the expression of hypoxia inducible factor 1α(HIF-1α) of iron-overloaded in irradiated mice and its effect on erythropoiesis. METHODS: Twenty mice were randomly divided into 4 groups: Ctrl (control group), IR (irradiation group), IO (irradiation + iron overload group), and RAPA (rapamycin treatment group). The iron overload model was verified. The CFU-E (colony forming unit-erythroid) and BFU-E(burst colony forming unit-erythroid) were cultured; flow cytometry was used to detect the ratios of early stage (Ter119+CD71-) to late stage (Ter119+CD71+) of primitive erythroblasts; RT-PCR was used to detect the mRNA expression of HIF-1α and its related signal molecules in bone marrow cells. RESULTS: The expression of HIF-1α in IR and IO group was significantly higher than that in Ctrl group, and that in IO group was significantly higher than IR group (P<0.05). The ratio of late stage primitive erythroblasts, the number of CFU-E and BFU-E in both IR and IO group were lower than those in Ctrl group, and those in IO group were significantly lower than those in IR group (P<0.05). Compared with Ctrl group, the expression of HIF-1α related signal pathway molecules in both IR and IO group was significantly decreased (P<0.05). Compared with IO group, the expression of HIF-1α and its related signal molecules in RAPA(mTOR inhibitor) group was decreased significantly (P<0.05), the number of BFU-E was increased significantly(P<0.05). CONCLUSION: Irradiation induces the increase of HIF-1α and the decrease of the ability of hematopoietic colony formation and the ratio of late stage primitive erythroblasts. Iron overload can aggravate the injury. mTOR inhibitor rapamycin can partially alleviate the injury, suggesting that iron overload can lead to injury of erythropoiesis through HIF-1α.

[Effects of Iron Overload on the Apoptosis and Function of Splenic CD8+ T Cells in Mice].

OBJECTIVE: To investigate the effects of iron overload on apoptosis and function of splenic CD8+ T cells in mice. METHODS: Forty C57BL/6 mice were randomly divided into control groups, Iron overload (IO), IO+NAC and IO+DFX groups. The iron overload model was established by intraperitoneal injection of iron dextran, and saline was injected as the control. The levels of intracellular reactive oxygen species (ROS) and labile iron pool (LIP) were analyzed by measuring the mean fluorescence intensity (MFI) of 2-7 dichlorofluorescein (DCF) or calcein. The ratio of CD8+ T cells and the levels of IFN-γ, TNF-α, Granzyme-B, and perforin in CD8+ T cells were detected by flow cytometry. The CD8+ T cell apoptosis was determined by flow cytometry with Annexin V/PI double staining. Real-time PCR was used to detect the expression of IFN-γ, TNF-α, Granzyme-B, perforin, BCL-2, and bax at mRNA level in CD8+ T cells. RESULTS: Iron overload was found by spleen iron staining and flow cytometry. The level of intracellular ROS in iron overload (IO) groups was higher than that of the control groups (P<0.01). The percentage of CD8+ T cells in spleen from mice with IO was lower than that in control groups (P<0.05). The expression of IFN-γ and Granzyme-B in CD8+ T cells in IO group were lower than that in control group, the expression of IFN-γ and Granzyme-B at mRNA level in CD8+ T cells was lower than that of control group (P<0.05). CD8+ T cell apoptosis in iron overload group was significantly higher than that in control groups (P<0.01); the expression of BCL-2 at mRNA level was lower than that in control group, but the expression of BAX at mRNA level was higher than that in control group (P<0.05). These effects could be reversed after treating iron-overloaded mice with DFX or NAC. CONCLUSION: Iron overload can inhibit the ratio of CD8+ T cells of splenic cells in mice, decrease the expression of IFN-γ, Granzyme-B, increase the apoptosis of CD3+ CD8+/CD8-. These effects may be regulated through increasing the intracellular ROS level, and can be partially reversed after treating iron-overloaded mice with DFX or NAC.

Specialised emission pattern of leaf trace in a late Permian (253 million-years old) conifer.

Leaf traces are important structures in higher plants that connect leaves and the stem vascular system. The anatomy and emission pattern of leaf traces are well studied in extant vascular plants, but remain poorly understood in fossil lineages. We quantitatively analysed the leaf traces in the late Permian conifer Ningxiaites specialis from Northwest China based on serial sections through pith, primary and secondary xylems. A complete leaf traces emission pattern of a conifer is presented for the first time from the late Palaeozoic. Three to five monarch leaf traces are grouped in clusters, arranged in a helical phyllotaxis. The leaf traces in each cluster can be divided into upper, middle and lower portions, and initiate at the pith periphery and cross the wood horizontally. The upper leaf trace increases its diameter during the first growth increment and then diminishes completely, which indicates leaf abscission at the end of the first year. The middle trace immediately bifurcates once or twice to form two or three vascular bundles. The lower trace persists as a single bundle during its entire length. The intricate leaf trace dynamics indicates this fossil plant had a novel evolutionary habit by promoting photosynthetic capability for the matured plant.

Height measurement of microchip connecting pins by use of stereovision.

A stereovision method for estimating the height of connecting pins on a microchip is described. The technique uses a centroidal method to simplify the calculation. A few seconds are required for a Pentium 586 PC to calculate the heights of 300 connecting pins on a 50 mm x 50 mm microchip. The method is described, and experimental results are presented. The optical system, which consists of two CCD cameras with long-focal-length lenses and a two-channel digital image grabber, is capable of in situ measurement.

Shape measurement by use of liquid-crystal display fringe projection with two-step phase shifting.

The use of an optical fringe projection method with two-step phase shifting for three-dimensional (3-D) shape measurement of small objects is described. In this method, sinusoidal linear fringes are projected onto an object's surface by a programmable liquid-crystal display (LCD) projector and a long-working-distance microscope (LWDM). The image of the fringe pattern is captured by another LWDM and a CCD camera and processed by a phase-shifting technique. Usually a minimum of three phase-shifted fringe patterns is necessary for extraction of the object shape. In this method, a new algorithm based on a two-step phase-shifting technique produces the 3-D object shape. Unlike in the conventional method, phase unwrapping is performed directly by use of an arccosine function without the need for a wrapped phase map. Hence, shape measurement can be speeded up greatly with this approach. A small coin is evaluated to demonstrate the validity of the proposed measurement method, and the experimental results are compared with those of the four-step phase-shifting method and the conventional mechanical stylus method.

Proposed algorithm for phase unwrapping.

A new, to our knowledge, two-dimensional phase-unwrapping algorithm is proposed. The algorithm, which is based on the global continuity of physical information (e.g. the three-dimensional surface profile of an object) being measured, uses the principle of least-phase difference to rectify errors caused by an erroneous 2pi-phase jump in the initial unwrapped phase map obtained by the conventional phase-unwrapping method. Experimental results show that the proposed algorithm works well on a phase map that contains error sources, such as noises, phase discontinuity of more than pi, and insufficient sampling. Moreover, the algorithm is most suitable for unwrapping a phase map generated during shape measurement with a step-change surface on the test object, which is usually a critical problem in shape measurement.