Outcomes of COVID-19 in multiple myeloma patients treated with daratumumab.

Despite concerns about an increased risk of adverse outcomes following coronavirus disease (COVID-19) in multiple myeloma patients treated with anti-CD38 Abs, the impact of COVID-19 on this group of patients is unclear. We tried to evaluate the clinical outcomes of these patients. We collected data from 1036 patients with multiple myeloma and enrolled 509 cases with COVID-19. We divided enrolled patients into daratumumab or nondaratumumab cohorts based on whether they had received daratumumab-based treatment within 6 months of COVID-19 infection. We applied a propensity score matching method to reduce the bias of baseline characteristics, and then compared the incidence of adverse outcomes between these two cohorts. A total of 117 patients were enrolled in the daratumumab cohort, and 392 patients in the nondaratumumab cohort. After propensity score matching, 204 patients were matched. The proportions of patients who developed COVID-19 pneumonia (59.8% vs. 34.3%, p < 0.001), were hospitalized (33.3% vs. 11.8%, p < 0.001) and developed severe disease (23.5% vs. 6.9%, p = 0.001) were higher in the matched daratumumab cohort. By multivariate analysis, daratumumab exposure was an independent risk factor for severe disease. An ECOG performance status >2 and history of chronic kidney disease were independent risk factors for COVID-19-related mortality among patients who received daratumumab-based therapy. This study suggested that multiple myeloma patients exposed to daratumumab were at a higher risk of adverse outcomes from COVID-19.

Alternating current stimulation promotes neurite outgrowth and plasticity in neurons through activation of the PI3K/AKT signaling pathway.

As a commonly used physical intervention, electrical stimulation (ES) has been demonstrated to be effective in the treatment of central nervous system disorders. Currently, researchers are studying the effects of electrical stimulation on individual neurons and neural networks, which are dependent on factors such as stimulation intensity, duration, location, and neuronal properties. However, the exact mechanism of action of electrical stimulation remains unclear. In some cases, repeated or prolonged electrical stimulation can lead to changes in the morphology or function of the neuron. In this study, immunofluorescence staining and Sholl analysis are used to assess changes in the neurite number and axon length to determine the optimal pattern and stimulation parameters of ES for neurons. Neuronal death and plasticity are detected by TUNEL staining and microelectrode array assays, respectively. mRNA sequencing and bioinformatics analysis are applied to predict the key targets of the action of ES on neurons, and the identified targets are validated by western blot analysis and qRT-PCR. The effects of alternating current stimulation (ACS) on neurons are more significant than those of direct current stimulation (DCS), and the optimal parameters are 3 µA and 20 min. ACS stimulation significantly increases the number of neurites, the length of axons and the spontaneous electrical activity of neurons, significantly elevates the expression of growth-associated protein-43 (GAP-43) without significant changes in the expression of neurotrophic factors. Furthermore, application of PI3K/AKT-specific inhibitors significantly abolishes the beneficial effects of ACS on neurons, confirming that the PI3K/AKT pathway is an important potential signaling pathway in the action of ACS.

MicroRNA-140-3p alleviates intervertebral disc degeneration via KLF5/N-cadherin/MDM2/Slug axis.

MicroRNAs (miRNAs) are associated with healing or deteriorating degenerated intervertebral disc (IVD) tissues in spinal cord diseases, including intervertebral disc degeneration (IDD). IDD represents a chronic process of extracellular matrix destruction, but the relevant molecular mechanisms implicated in the regenerative effects of miRNAs are unclear. Here, we investigated the regenerative effects of microRNA-140 (miR-140-3p) in an IDD model induced by annulus needle puncture. Bioinformatics analysis was conducted to identify regulatory factors (KLF5/N-cadherin/MDM2/Slug) linked to miR-140-3p effects in IDD. Mesenchymal stem cells (MSCs) were extracted from degenerated IVD nucleus pulposus (NP), and the expression of miR-140-3p/KLF5/N-cadherin/MDM2/Slug was manipulated to explore their effects on cell proliferation, migration, apoptosis and differentiation. The results showed that miR-140-3p was under-expressed in the degenerated IVD NP, whereas its overexpression alleviated IDD. Mechanistic studies suggested that miR-140-3p targeted KLF5 expression, and high KLF5 expression impeded the migration and differentiation of MSCs. In degenerated IVD NP-derived MSCs, MiR-140-3p-mediated KLF5 downregulation simultaneously elevated N-cadherin expression and transcriptionally inhibited MDM2, thus upregulating Slug expression. The experimental data indicated that miR-140-3p enhanced the proliferation, migration and differentiation of degenerated IVD NP-derived MSCs and repressed their apoptosis. The in vivo validation experiment also demonstrated that miR-140-3p inhibited IDD by modulating the KLF5/N-cadherin/MDM2/Slug axis. Collectively, our results uncovered the regenerative role of miR-140-3p in IDD via regulation of the KLF5/N-cadherin/MDM2/Slug axis, which could be a potential therapeutic target for IDD.Abbreviations: miR-140-3p: microRNA-140-3p; IDD: intervertebral disc degeneration; MSCs: Mesenchymal stem cells; IVD: intervertebral disc; MSCs: mesenchymal stem cells; KLF5: Kruppel-like factor 5; MDM2: mouse double minute 2; NC: negative control; DHI: disc height index.

Long noncoding RNA LINC01278 favors the progression of osteosarcoma via modulating miR-133a-3p/PTHR1 signaling.

As one of the most aggressive malignancies, osteosarcoma has high risks of death. Although long noncoding RNAs (lncRNAs) may promote the osteosarcoma progression as verified, the potential molecular mechanism of lncRNAs in osteosarcoma remains unknown. Herein, we analyzed lncRNA microarray of osteosarcoma and selected LINC01278 as the study object. Then, we found that the expression of LINC01278 tested by quantitative reverse-transcription polymerase chain reaction was enhanced in tumor tissues compared with the para-carcinoma tissues and related to clinical stage, distant metastasis in osteosarcoma. In addition, the clinical outcomes were poor in osteosarcoma patients with high LINC01278 level. Moreover, LINC01278 promoted proliferation and restrained apoptosis in osteosarcoma cells. Afterward, mechanistic studies turned out that LINC01278 was a competing endogenous RNA of parathyroid hormone type 1 receptor (PTHR1) in osteosarcoma by sponging miR-133a-3p, which was considered as a tumor inhibitor in osteosarcoma. Furthermore, PTHR1 downregulation restored the impacts of inhibited miR-133a-3p on the processes in osteosarcoma cells. Our findings clarified that the carcinogenic effect of LINC01278 in osteosarcoma was mediated through miR-133a-3p/PTHR1 signaling, creating a novel insight into good targets for the therapy and prognosis of osteosarcoma.

N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High-Magnitude Compression.

BACKGROUND/AIMS: Mechanical load can regulate disc nucleus pulposus (NP) biology in terms of cell viability, matrix homeostasis and cell phenotype. N-cadherin (N-CDH) is a molecular marker of NP cells. This study investigated the role of N-CDH in maintaining NP cell phenotype, NP matrix synthesis and NP cell viability under high-magnitude compression. METHODS: Rat NP cells seeded on scaffolds were perfusion-cultured using a self-developed perfusion bioreactor for 5 days. NP cell biology in terms of cell apoptosis, matrix biosynthesis and cell phenotype was studied after the cells were subjected to different compressive magnitudes (low- and high-magnitudes: 2% and 20% compressive deformation, respectively). Non-loaded NP cells were used as controls. Lentivirus-mediated N-CDH overexpression was used to further investigate the role of N-CDH under high-magnitude compression. RESULTS: The 20% deformation compression condition significantly decreased N-CDH expression compared with the 2% deformation compression and control conditions. Meanwhile, 20% deformation compression increased the number of apoptotic NP cells, up-regulated the expression of Bax and cleaved-caspase-3 and down-regulated the expression of Bcl-2, matrix macromolecules (aggrecan and collagen II) and NP cell markers (glypican-3, CAXII and keratin-19) compared with 2% deformation compression. Additionally, N-CDH overexpression attenuated the effects of 20% deformation compression on NP cell biology in relation to the designated parameters. CONCLUSION: N-CDH helps to restore the cell viability, matrix biosynthesis and cellular phenotype of NP cells under high-magnitude compression.

Cross-Coupling Effects of Silencing of Cyclooxygenase-2 (COX-2)/Aggrecanase-1 and Over-Expressed Insulin-Like Growth Factor 1 (IGF-1) in an Osteoarthritis Animal Model.

BACKGROUND This study aimed to observe the effect of lentivirus-mediated cyclooxygenase-2 and aggrecanase-1 silencing and insulin-like growth factor-1 overexpression in human bone marrow mesenchymal stem cells after injection into model osteoarthritic knees. MATERIAL AND METHODS Using genetic recombination technique, the genes of cyclooxygenase-2, aggrecanase-1, and insulin-like growth factor-1 were recombined into the lentiviral vectors, and we transfected the human bone marrow stem cells in vitro. The BMSC transfected with lentivirus without genes served as a blank-virus group, and saline was used for another control group. One week later, the cytokines PGE2, aggrecanase-1, hIGF-1, and IL-1 were detected and compared between groups. RESULTS Compared with blank-virus group, the expression of COX-2 (85.81±5.12 ng/L) and aggrecanase1 (6.256±1.66) were decreased in the virus group (p<0.05), while the expression of hIGF-1 (17.46±1.86) was increased (p<0.05). The concentrations of PGE2 (85.81±5.12 ng/L), aggrecanase1 (51.34±5.463 ng/L), and IL-1 (82.31±4.321 ng/L) decreased (p<0.05) within the knee, but the concentration of hIGF-1 (44.33±0.7194 ng/L) increased (p<0.05). Compared with the other groups, the results of histological and immunohistochemical examinations demonstrated that the abrasion of articular cartilage was significantly improved and repaired. CONCLUSIONS Lentivirus-mediated RNAi can inhibit the expression of COX-2 mRNA and aggrecanase-1mRNA, and enhance the hIGF-1 mRNA expression, thereby influencing the concentration of cytokines in the early osteoarthritic model knee joints.

Innovations in 3D printed individualized bone prosthesis materials: revolutionizing orthopedic surgery: a review.

The advent of personalized bone prosthesis materials and their integration into orthopedic surgery has made a profound impact, primarily as a result of the incorporation of three-dimensional (3D) printing technology. By leveraging digital models and additive manufacturing techniques, 3D printing enables the creation of customized, high-precision bone implants tailored to address complex anatomical variabilities and challenging bone defects. In this review, we highlight the significant progress in utilizing 3D printed prostheses across a wide range of orthopedic procedures, including pelvis, hip, knee, foot, ankle, spine surgeries, and bone tumor resections. The integration of 3D printing in preoperative planning, surgical navigation, and postoperative rehabilitation not only enhances treatment outcomes but also reduces surgical risks, accelerates recovery, and optimizes cost-effectiveness. Emphasizing the potential for personalized care and improved patient outcomes, this review underscores the pivotal role of 3D printed bone prosthesis materials in advancing orthopedic practice towards precision, efficiency, and patient-centric solutions. The evolving landscape of 3D printing in orthopedic surgery holds promise for revolutionizing treatment approaches, enhancing surgical outcomes, and ultimately improving the quality of care for orthopedic patients.

Micro-transplantation in an elderly patient with very high risk MDS:A case report and literature review.

Introduction: The prognosis of patients with myelodysplastic syndromes (MDS) (very high risk) is poor.HLA-mismatched allogeneic T-cell infusion which is called micro-transplantation can not only shorten the time of bone marrow suppression, but also improve the treatment response of patients. Case presentation: A 74-year-old woman presented with fatigue and showed pancytopenia on routine blood count. She was diagnosed with MDS (very high risk) after bone marrow examination,then she received 4 cycles of micro-transplantation. The progression-free survival was 22 months and overall survival was 33 months. Discussion: The patient showed good tolerance to micro-transplantation with manageable toxicities and short myelosuppression time.

An Implantable Self-Driven Diaphragm Pacing System Based on a Microvibration Triboelectric Nanogenerator for Phrenic Nerve Stimulation.

Spinal cord injury poses considerable challenges, particularly in diaphragm paralysis. To address limitations in existing diaphragm pacing technologies, we report an implantable, self-driven diaphragm pacing system based on a microvibration triboelectric nanogenerator (MV-TENG). Leveraging the efficient MV-TENG, the system harvests micromechanical energy and converts this energy into pulses for phrenic nerve stimulation. In vitro tests confirm a stable MV-TENG output, while subcutaneous implantation of the device in rats results in a constant amplitude over 4 weeks with remarkable energy-harvesting efficacy. The system effectively induces diaphragmatic motor-evoked potentials, triggering contractions of the diaphragm. This proof-of-concept system has potential clinical applications in implantable phrenic nerve stimulation, presenting a novel strategy for advancing next-generation diaphragm pacing devices.

Defect detection and identification for aircraft cable insulation layer based on deep forest.

Due to the special internal environment of aircraft, cable damage is inevitable, which usually starts from insulation layer defects and may cause major economic losses, and even seriously threaten the life of people on board. According to the above issue, a defect detection system for aircraft cable insulation layer based on ultrasonic guided waves (UGWs) is built in this paper. In order to ensure the complete coupling between the sensor and the insulation layer of the aircraft cable, the macro fiber composite (MFC) flexible sensor is employed in the system. Both simulation and experimental results show that this method can simultaneously monitor four different types (abrasion, cut, semi-stripping and full-stripping) of cable insulation layer defects at different locations on the same cable. The reflection signals of different types of defects are extremely similar and difficult to distinguish directly. In this paper, a classification method for four types of defects based on the deep forest method is proposed. This method requires a small sample size, and the classification performance is not affected by network structure and parameters. The recognition accuracy can reach 100%, avoiding the problem of traditional deep learning classification relying on a large number of samples and requiring parameter adjustment. The proposed method in this paper is proven to be able to effectively carry out online monitoring and accurately classify defect types, which has guiding significance for aircraft maintenance personnel to take corresponding measures in time.

The LIM Domain Protein BmFHL2 Inhibits Egg Production in Female Silkworm, Bombyx mori.

The female Bombyx mori accumulates a large amount of egg proteins, mainly Vg and 30K, during egg formation to provide nutrition for embryo development. The synthesis and transport of Vg have been extensively studied, particularly the regulation of Vg transcription induced by 20E; however, the mechanism of 30K protein synthesis is poorly studied. As a model organism of the order Lepidoptera, B. mori has high reproduction potential. In the present study, we found that the FHL2 homologous gene (BmFhl2) in B. mori is involved in inhibiting female egg formation by influencing the synthesis of 30K protein. Interference of BmFhl2 expression in silkworm females increased 30K protein synthesis, accelerated ovarian development, and significantly increased the number of eggs produced and laid; however, the 20E pathway was inhibited. The transcription levels of Vg and 30Kc19 were significantly downregulated following BmFhl2 overexpression in the silkworm ovarian cell line BmN. The Co-IP assay showed that the potential binding protein of BmFHL2 included three types of 30K proteins (30Kc12, 30Kc19, and 30Kc21). These results indicate that BmFHL2 participates in egg formation by affecting 30K protein in female B. mori.

Use of pedicled latissimus dorsi myocutaneous flap to reconstruct the upper limb with large soft tissue defects.

OBJECTIVE: To report the technique of reconstruction of large skin and soft tissue defects in the upper extremity using pedicled latissimus dorsi myocu-taneous flaps. METHODS: Six patients with large skin and soft tissue defects were included in this report. There were 5 trauma patients and the rest one needed to receive plastic surgery for his extremity scar. All wounds were in the upper extremity. The sizes of defects ranged from 15 cm multiply 6 cm to 30 cm multiply 18 cm. Pedicled latissimus dorsi myocutaneous flaps were designed according to the defect area and raised with part of latissimus dorsi. The thoracodorsal artery and its perforators were carefully protected during surgery. RESULTS: All flaps healed primarily without flap congestion, margin necrosis or infection. The skin donor sites either received split-thickness skin graft (3 cases, mostly from the anterior thigh) or was closed primarily (3 cases) and had minimal morbidity. Follow-up of 6-12 months showed that the contour of flap was aesthetic and the function of limb was excellent. CONCLUSION: Our experience indicates that the pedicled latissimus dorsi myocutaneous flap is favorable for reconstruction of large skin and soft tissue defects in the upper extremity.

Melatonin Attenuates Spinal Cord Injury in Mice by Activating the Nrf2/ARE Signaling Pathway to Inhibit the NLRP3 Inflammasome.

BACKGROUND: Spinal cord injury (SCI) is a central nervous system (CNS) trauma involving inflammation and oxidative stress, which play important roles in this trauma's pathogenesis. Therefore, controlling inflammation is an effective strategy for SCI treatment. As a hormone, melatonin is capable of producing antioxidation and anti-inflammation effects. In the meantime, it also causes a neuroprotective effect in various neurological diseases. Nrf2/ARE/NLRP3 is a well-known pathway in anti-inflammation and antioxidation, and Nrf2 can be positively regulated by melatonin. However, how melatonin regulates inflammation during SCI is poorly explored. Therefore, it was investigated in this study whether melatonin can inhibit the NLRP3 inflammasome through the Nrf2/ARE signaling pathway in a mouse SCI model. METHODS: A model of SCI was established in C57BL/6 mice and PC12 cells. The motor function of mice was detected by performing an open field test, and Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling were carried out to evaluate the survival of neurons. Mitochondrial dysfunction was detected by transmission electron microscopy (TEM) and by assessing the mitochondrial membrane potential. In addition, the expression of NLRP3 inflammasome and oxidative-stress-related proteins were detected through Western blot and immunofluorescence double staining. RESULTS: By inhibiting neuroinflammation and reducing neuronal death, melatonin promotes the recovery of neuromotor function. Besides this, melatonin is able to reduce the damage that causes neuronal mitochondrial dysfunction, reduce the level of reactive oxygen species (ROS) and malondialdehyde, and enhance the activity of superoxide dismutase and the production of glutathione peroxidase. Mechanically, melatonin inhibits the activation of NLRP3 inflammasomes and reduces the secretion of pro-inflammatory factors through the Nrf2/ARE signaling. CONCLUSIONS: In conclusion, melatonin inhibits the NLRP3 inflammasome through stimulation of the Nrf2/ARE pathway, thereby suppressing neuroinflammation, reducing mitochondrial dysfunction, and improving the recovery of nerve function after SCI.

Treatment of Scoliosis with One-Stage Posterior Pedicle Screw System by Paraspinal Intermuscular Approach: A Minimum of Two Years of Follow-Up.

OBJECTIVE: To evaluate the clinical efficacy of the treatment of scoliosis with a pedicle screw system through paraspinal intermuscular approach (PIA). METHODS: This is a retrospective case series study. A total of 10 patients diagnosed with scoliosis had surgical indications and treated with a pedicle screw system in one-stage posterior surgery by PIA from March 2013 to April 2015 at the First Hospital of Jilin University were enrolled in this study. The average age of the patients was 14.9 years, including one male and nine females. The operative information and surgical results, including Cobb angle correction, correction loss, global balance (including Frontal Plane Balance [FPB] and Sagittal Plane Balance [SPB]), and fusion rate were reviewed. Functional outcomes including visual analog scale (VAS) back pain score, leg pain score, and Scoliosis Research Society-22 questionnaire (SRS-22) were used to evaluate the quality of life of patients preoperatively and at last follow-up. RESULTS: Each patient was followed up at least six times. The average follow-up time was 43.2 months. Mean scoliosis and kyphosis improved from 68.5° ± 18.1°to 18.7° ± 11.8° and from 34.4° ± 17.9°to 24.0° ± 6.7°, respectively (p < 0.05); at last follow-up, it was 20.1° and 24.7°, respectively (p > 0.05). During the follow-up, mean coronal and sagittal correction loss was 1.4° ± 1.2°and 0.7° ± 0.8°, respectively (p > 0.05). Mean FPB improved from 32.7 to 11.7 mm (p < 0.05); Mean SPB changed from 0.3 to -0.7 mm (p > 0.05). No dural tears were observed during the corrective surgery or wound infection or implant-related complications. No pseudoarthrosis was identified according to the last follow-up three-dimensional (3D) CT scan. All the domains in SRS-22 questionnaire show statistically significant improvement at the last follow-up (p < 0.05). The VAS back pain scores improved from a mean preoperative score of 1.7 to a mean postoperative score of 0.2 (p < 0.05). CONCLUSION: This original one-stage posterior PIA is safe and effective in the treatment of scoliosis, which is characterized with less blood loss, shorter operation time, and satisfactory bony fusion.

Circ0007042 alleviates intervertebral disc degeneration by adsorbing miR-369 to upregulate BMP2 and activate the PI3K/AKt pathway.

BACKGROUND: To identify regulatory ncRNA molecules that can cause differential expression of CDH2 in intervertebral disc degeneration (IDD) and explore whether there are other ways to affect the progression of IDD. METHODS: A primary culture of human nucleus pulposus (NP) cells was established and identified by immunofluorescence. An in vitro IDD model was constructed by compressing human NP cells, and the MTT assay was used to measure cell viability. Changes in the ncRNA group were analysed by RNA-seq. The expression levels of hsa_circ_7042, CDH2, and miR-369-3p were detected by qPCR. Cell apoptosis, senescence, and extracellular matrix (ECM) metabolism were detected by flow cytometry, ß-galactosidase staining, and Western blotting. hsa_circ_7042, miR-369-3p, and bone morphogenetic protein 2 (BMP2) were verified by luciferase and RNA immunoprecipitation (RIP) analyses. The PI3K/Akt pathway was validated by transfection of BMP2 siRNA. Furthermore, a mouse model of lumbar spine instability was constructed. circ_7042 adenovirus was packaged and injected into the intervertebral discs of mice, and the influence of circ_7042 overexpression on intervertebral disc degeneration was determined. RESULTS: Western blotting, qPCR, and flow cytometry analyses confirmed that overexpression of circ_7042 could downregulate miR-369-3p and upregulate the expression of CDH2 and BMP2 in IDD cell and animal models. Additionally, the levels of apoptotic and senescent cells decreased, and ECM degradation decreased. The PI3K/Akt pathway was significantly activated after circ_7042 was overexpressed. The injection of circ_7042-overexpressing adenovirus effectively reduced ECM degradation and the level of apoptosis in NP tissue. CONCLUSIONS: circ_7042 could upregulate the expression of CDH2 and BMP2 by absorbing miR-369-3p, and the increased BMP2 activated the PI3K/Akt pathway, thus improving IDD.

Combined analysis of silk synthesis and hemolymph amino acid metabolism reveal key roles for glycine in increasing silkworm silk yields.

Rearing silkworms (Bombyx mori) using formula feed has revolutionized traditional mulberry feed strategies. However, low silk production efficiencies persist and have caused bottlenecks, hindering the industrial application of formula feed sericulture. Here, we investigated the effects of formula feed amino acid composition on silk yields. We showed that imbalanced amino acids reduced DNA proliferation, decreased Fib-H, Fib-L, and P25 gene expression, and caused mild autophagy in the posterior silk gland, reducing cocoon shell weight and ratio. When compared with mulberry leaves, Gly, Ala, Ser, and Tyr percentages of total amino acids in formula feed were decreased by 5.26%, while Glu and Arg percentages increased by 9.56%. These changes increased uric acid and several amino acids levels in the hemolymph of silkworms on formula feed. Further analyses showed that Gly and Thr (important synthetic Gly sources) increased silk yields, with Gly increasing amino acid conversion efficiencies to silk protein, and reducing urea levels in hemolymph. Also, Gly promoted endomitotic DNA synthesis in silk gland cells via phosphoinositide 3-kinase (PI3K)/Akt/target of rapamycin (TOR) signaling. In this study, we highlighted the important role of Gly in regulating silk yields in silkworms.

Attenuation of the upregulation of NF­κB and AP­1 DNA­binding activities induced by tunicamycin or hypoxia/reoxygenation in neonatal rat cardiomyocytes by SERCA2a overexpression.

The present study aimed to investigate the effects of the overexpression of sarco/endoplasmic reticulum Ca2+­ATPase (SERCA2a) on endoplasmic reticulum (ER) stress (ERS)­associated inflammation in neonatal rat cardiomyocytes (NRCMs) induced by tunicamycin (TM) or hypoxia/reoxygenation (H/R). The optimal multiplicity of infection (MOI) was 2 pfu/cell. Neonatal Sprague­Dawley rat cardiomyocytes cultured in vitro were infected with adenoviral vectors carrying SERCA2a or enhanced green fluorescent protein genes, the latter used as a control. At 48 h following gene transfer, the NRCMs were treated with TM (10 µg/ml) or subjected to H/R to induce ERS. The results of electrophoretic mobility shift assay (EMSA) revealed that overexpression of SERCA2a attenuated the upregulation of nuclear factor (NF)­κB and activator protein­1 (AP­1) DNA­binding activities induced by TM or H/R. Western blot analysis and semi­quantitative RT­PCR revealed that the overexpression of SERCA2a attenuated the activation of the inositol­requiring 1α (IRE1α) signaling pathway and ERS­associated apoptosis induced by TM. The overexpression of SERCA2a also decreased the level of phospho­p65 (Ser536) in the nucleus, as assessed by western blot analysis. However, the overexpression of SERCA2a induced the further nuclear translocation of NF­κB p65 and higher levels of tumor necrosis factor (TNF)­α transcripts in the NRCMs, indicating the occurrence of the ER overload response (EOR). Therefore, the overexpression of SERCA2a has a 'double­edged sword' effect on ERS­associated inflammation. On the one hand, it attenuates ERS and the activation of the IRE1α signaling pathway induced by TM, resulting in the attenuation of the upregulation of NF­κB and AP­1 DNA­binding activities in the nucleus, and on the other hand, it induces EOR, leading to the further nuclear translocation of NF­κB and the transcription of TNF­α. The preceding EOR may precondition the NRCMs against subsequent ERS induced by TM. Further studies using adult rat cardiomyocytes are required to prevent the interference of EOR. The findings of the present study may enhance the current understanding of the role of SERCA2a in cardiomyocytes.

A Preoperative Predictive Model of Lower Lumbar Spine Instability Based on Three-Dimensional Computed Tomography: A Retrospective Case-Control Pilot Study.

OBJECTIVE: This study aimed to build a predictive model of lower lumbar instability. METHODS: This retrospective study included 199 patients. Patients were divided into the lower lumbar instability group (LLIG) (n = 98) and lower lumbar stability group (LLSG) (n = 101). All participants of LLIG were recruited over a 2-year period (2015-2017) from the patients who accept lumbar surgery at the First Hospital of Jilin University. The LLSG was selected from outpatients who had underwent lumbar spine computed tomography (CT) and Flexion and extension radiographs (FER) at the First Hospital of Jilin University from 2015 to 2017. Several lower lumbar parameters were measured, including Lordosis angle (LA), intervertebral height (IH), ratio of anterior height to posterior height (APR), angle between endplate and anterior edge of vertebral body (AEPVa), sagittal slip ratio (SSR), and angle between the upper endplate and z-axis on sagittal plane (AUEZS). These parameters were keyed into the SPSS software to create a predictive model for classification. Sensitivity, specificity, predictive accuracy, and Kappa value were used to evaluate the predictive model. RESULTS: Compared with LLSG, the LA of LLIG decreased by 3.49° (126.54° vs 130.3°). Similarly, the IH of LLIG decreased by 1.23°mm, 1.66°mm, and 0.71°mm at L3-4, L4-5, and L5-S1. Compared with LLSG, the SSR of LLIG is higher at L3-4, L4-5, and L5-S1 (0.54 vs 0.51, 0.57 vs 0.46, and 0.59 vs 0. 47). Moreover, the APR of LLIG is higher than those of LLSG at L3-4, L4-5, and L5-S1 (1.97 vs 1.81, 2.40 vs 1.97, and 2.69 vs 2.26). The LLIG has bigger AEPVa than LLIG at L3-4, L4-5, and L5-S1. Compared with LLSG, the AUEZS of LLIG is bigger at L3-4 (91.75° vs 90.81°) and smaller at L4-5 and L5-S1(84.63° vs 85.85° and 73.27° vs 75.01°). The SSR (L4) show highest predictive accuracy (83%) when every parameter was fed to LDA classifier to generate a univariate model. All parameters represent a statistically significant difference (P < 0.05) between LLSG and LLIG. The model including LA, APR (L5-S1), IH (L4-5), SSR (L5), AUEZS (L5) has highest predictive accuracy of 88.2%. The sensitivity, specificity, and Kappa value are 88.7%, 93.1%, and 0.77. CONCLUSION: The predictive model has good classification performance and can be an auxiliary tool for clinicians to evaluate lumbar instability in preoperative patients with severe pain aggravated by lumbar movement.

The application of machine learning algorithms in predicting the length of stay following femoral neck fracture.

PURPOSE: Femoral neck fracture is a frequent cause of hospitalization, and length of stay is an important marker of hospital cost and quality of care provided. As an extension of traditional statistical methods, machine learning provides the possibility of accurately predicting the length of hospital stay. The aim of this paper is to retrospectively identify predictive factors of the length of hospital stay (LOS) and predict the postoperative LOS by using machine learning algorithms. METHOD: Based on the admission and perioperative data of the patients, linear regression was used to analyze the predictive factors of the LOS. Multiple machine learning models were developed, and the performance of different models was compared. RESULT: Stepwise linear regression showed that preoperative calcium level (P = 0.017) and preoperative lymphocyte percentage (P = 0.007), in addition to intraoperative bleeding (p = 0.041), glucose and sodium chloride infusion after surgery (P = 0.019), Charlson Comorbidity Index (p = 0.007) and BMI (P = 0.031), were significant predictors of LOS. The best performing model was the principal component regression (PCR) with an optimal MAE (1.525) and a proportion of prediction error within 3 days of 90.91%. CONCLUSION: Excessive intravenous glucose and sodium chloride infusion after surgery, preoperative hypocalcemia, preoperative high percentages of lymphocytes, excessive intraoperative bleeding, lower BMI and higher CCI scores were related to prolonged LOS by using linear regression. Machine learning could accurately predict the postoperative LOS. This information allows hospital administrators to plan reasonable resource allocation to fulfill demand, leading to direct care quality improvement and more reasonable use of scarce resources.

Non-Ablative Chemotherapy Followed by HLA-Mismatched Allogeneic CD3+ T-Cells Infusion Causes An Augment of T-Cells With Mild CRS: A Multi-Centers Single-Arm Prospective Study on Elderly Acute Myeloid Leukemia and int-2/High Risk Myelodysplastic Syndrome Patients.

OBJECTIVE: To evaluate the efficacy and safety of standard or low-dose chemotherapy followed by HLA-mismatched allogeneic T-cell infusion (allo-TLI) for the treatment of elderly patients with acute myeloid leukemia (AML) and patients with intermediate-2 to high-risk myelodysplastic syndrome (MDS). METHODS: We carried out a prospective, multicenter, single-arm clinical trial. Totally of 25 patients were enrolled, including 17 AML patients and 8 MDS patients. Each patient received four courses of non-ablative chemotherapy, with HLA-mismatched donor CD3+ allo-TLI 24 h after each course. AML patients received chemotherapy with decitabine, idarubicin, and cytarabine, and MDS patients received decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor. RESULTS: A total of 79 procedures were performed. The overall response rates of the AML and MDS patients were 94% and 75% and the 1-year overall survival rates were 88% (61-97%) and 60% (13-88%), respectively. The overall 60-day treatment-related mortality was 8%. Compared with a historical control cohort that received idarubicin plus cytarabine (3 + 7), the study group showed significantly better overall response (94% vs. 50%, P=0.002) and overall survival rates (the 1-year OS rate was 88% vs. 27%, P=0.014). Post-TLI cytokine-release syndrome (CRS) occurred after 79% of allo-TLI operations, and 96% of CRS reactions were grade 1. CONCLUSION: Elderly AML patients and intermediate-2 to high-risk MDS patients are usually insensitive to or cannot tolerate regular chemotherapies, and may not have the opportunity to undergo allogeneic stem cell transplantation. Our study showed that non-ablative chemotherapy followed by HLA-mismatched allo-TLI is safe and effective, and may thus be used as a first-line treatment for these patients. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.aspx?proj=20112.