Cascaded controlled delivering growth factors to build vascularized and osteogenic microenvironment for bone regeneration.

The process of bone regeneration is intricately regulated by various cytokines at distinct stages. The establishment of early and efficient vascularization, along with the maintenance of a sustained osteoinductive microenvironment, plays a crucial role in the successful utilization of bone repair materials. This study aimed to develop a composite hydrogel that would facilitate the creation of an osteogenic microenvironment for bone repair. This was achieved by incorporating an early rapid release of VEGF and a sustained slow release of BMP-2. Herein, the Schiff base was formed between VEGF and the composite hydrogel, and VEGF could be rapidly released to promote vascularization in response to the early acidic bone injury microenvironment. Furthermore, the encapsulation of BMP-2 within mesoporous silica nanoparticles enabled a controlled and sustained release, thereby facilitating the process of bone repair. Our developed composite hydrogel released more than 80% of VEGF and BMP-2 in the acidic medium, which was significantly higher than that in the neutral medium (about 60%). Moreover, the composite hydrogel demonstrated a significant improvement in the migratory capacity and tube formation ability of human umbilical vein endothelial cells (HUVECs). Furthermore, the composite hydrogel exhibited an augmented ability for osteogenesis, as confirmed by the utilization of ALP staining, alizarin red staining, and the upregulation of osteogenesis-related genes. Notably, the composite hydrogel displayed substantial osteoinductive properties, compared with other groups, the skull defect in the composite hydrogels combined with BMP-2 and VEGF was full of new bone, basically completely repaired, and the BV/TV value was greater than 80%. The outcomes of animal experiments demonstrated that the composite hydrogel effectively promoted bone regeneration in cranial defects of rats by leveraging the synergistic effect of an early rapid release of VEGF and a sustained slow release of BMP-2, thereby facilitating vascularized bone regeneration. In conclusion, our composite hydrogel has demonstrated promising potential for vascularized bone repair through the enhancement of angiogenesis and osteogenic microenvironment.

Pyruvate Kinase M2 Nuclear Translocation Regulate Ferroptosis-Associated Acute Lung Injury in Cytokine Storm.

Cytokine storm (CS) is linked with macrophage dysfunction and acute lung injury (ALI), which can lead to patient mortality. Glycolysis is preferentially exploited by the pro-inflammatory macrophages, in which pyruvate kinase M2 (PKM2) is a critical enzyme. The mechanism underlying the link between CS and ALI involves cell death, with the recently discovered programmed cell death known as ferroptosis being involved. However, the relationship between the glycolysis and ferroptosis in the context of CS-related ALI remains unclear. CS-associated ALI induced by poly I:C (10 mg/kg, i.v) and LPS (5 mg/kg, i.p) (IC: LPS) exhibit significant ferroptosis. Ferrostatin-1 (ferroptosis inhibitor) treatment attenuated IC:LPS­induced mortality and lung injury. Moreover, Alveolar macrophage (AM) from IC:LPS model exhibited enhanced glycolysis and PKM2 translocation. The administration of ML-265(PKM2 monomer/dimer inhibitor) resulted in the formation of a highly active tetrameric PKM2, leading to improved survival and attenuation of ALI. Furthermore, ML-265 treatment decreased ferroptosis and restored the balance between anaerobic glycolysis and oxidative phosphorylation. Notably, in patients with lung infection, intracellular expression level of PKM2 were correlated with circulating inflammation. Enhanced ferroptosis and PKM2 nuclear translocation was noticed in CD14+ blood monocytes of lung infection patients with CS. In conclusion, PKM2 is a key regulatory node integrating metabolic reprograming with intra-nuclear function for the regulation of ferroptosis. Targeting PKM2 could be explored as a potential means in the future to prevent or alleviate hyper-inflammatory state or cytokines storm syndrome with aberrant ferroptotic cell death.

PD-1/PD-L1 governed cross-talk of exhausted CD8+ T and memory B cells in systemic lupus erythematosus.

BACKGROUND: Indeterminate readout of the quantitative interferon-γ release test (QFT) for Mycobacterium tuberculosis screening is a specific laboratory finding for systemic lupus erythematosus (SLE), which may be due to T-cell exhaustion and abnormal programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) signalling. METHODS: We enrolled 104 patients with SLE and 225 with other rheumatic musculoskeletal diseases (RMDs) who presented to the outpatient clinic between 2020 and 2023. Twenty healthy donors served as the controls. The QFT was performed in all participants, and those with indeterminate results were compared among the groups. Immunophenotyping and functional assays were performed using blood mononuclear cells. Interferon (IFN)-γ was detected in vitro and ex vivo in patients with SLE with indeterminate or negative QFT results, before or after rituximab therapy. RESULTS: 104 patients with SLE had a significantly higher rate of indeterminate QFT results was significantly higher (17.31%) than that of 225 patients with RMD (3.56%). Patients with SLE with indeterminate QFT had more active disease (SLEDAI-2K, mean 10.94 vs 4.02, p<0.0001), including a higher incidence of active nephritis (55.56% vs 29.07%). Indeterminate QFT in SLE is mainly caused by an insufficient IFN-γ response in CD8+T cells with exhausted immunophenotypes. The abnormal interaction between exhausted PD-1 high CD8+ T cells and activated PD-L1 low memory B cells in SLE can be reversed with a PD-1 agonist or increased PD-L1 expression. Rituximab treatment indirectly reversed this IFN-γ response. CONCLUSION: The PD-1/PD-L1 signalling pathway, which governs the crosstalk between exhausted CD8+ T cells and activated memory B cells, is a mechanistic explanation for insufficient interferon-γ response in patients with SLE.

SENP3 facilitates M1 macrophage polarization via the HIF-1α/PKM2 axis in lipopolysaccharide-induced acute lung injury.

M1/M2 macrophage polarization plays a pivotal role in the development of acute lung injury (ALI). The hypoxia-inducible factor-1α/pyruvate kinase M2 (HIF-1α/PKM2) axis, which functions upstream of macrophage polarization, has been implicated in this process. The function of HIF-1α is known to be tightly regulated by SUMOylation. Upregulation of SUMO-specific peptidase 3 (SENP3), a deSUMOylation enzyme, is induced by reactive oxygen species (ROS), which are abundantly produced during ALI. To explore the links between SENP3, macrophage polarization, and lung injury, we used mice with Senp3 conditional knockout in myeloid cells. In the lipopolysaccharide (LPS)-induced ALI model, we found that in vitro and in vivo SENP3 deficiency markedly inhibited M1 polarization and production of pro-inflammatory cytokines and alleviated lung injury. Further, we demonstrated that SENP3 deficiency suppressed the LPS-induced inflammatory response through PKM2 in a HIF-1α-dependent manner. Moreover, mice injected with LPS after PKM2 inhibitor (shikonin) treatment displayed inhibition of M1 macrophage polarization and reduced lung injury. In summary, this work revealed that SENP3 promotes M1 macrophage polarization and production of proinflammatory cytokines via the HIF-1α/PKM2 axis, contributing to lung injury; thus, SENP3 may represent a potential therapeutic target for ALI treatment.

Magnetosome yield characteristics modeling of acidithiobacillus ferrooxidans in airlift bioreactor using response surface methodology.

Bacterial magnetosomes had been proved to have great application potential in medicine and biotechnology. The objective of the present study was to obtain high yield of magnetosomes from Acidithiobacillus ferrooxidans (A. ferrooxidans) BYM in an airlift bioreactor using response surface methodology (RSM). The magnetosomes from A. ferrooxidans BYM were characterized using a transmission electron microscope and scanning electron microscopy. The maximum magnetosome yield of 0.4267 mg/L was achieved at ventilation capacity of 3.6 L/min and gluconic acid concentration of 10 mmol/L at 25oC. The correlation coefficient (R2) value of 0.8676 of the obtained model suggested a good correlation between the actual and predicted magnetosome yield. The confirmation experiment confirmed that the actual magnetosome yield of 0.391 mg/L obtained were in agreement with the predicted value of 0.398 mg/L. These results suggested that RSM can be employed to find out the optimum conditions for magnetosome formation in airlift bioreactor.

Differences in sex- and age-associated mortality in patients with anti-MDA5-positive dermatomyositis.

OBJECTIVES: The effect of sex and age on the outcomes of patients with anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (MDA5+ DM) remains unclear. This study aimed to investigate the impact of sex and age on the prognosis of patients with MDA5+ DM. METHODS: We included 251 patients (women, 156; men, 95), who were newly diagnosed with MDA5+ DM between 2014 and 2021. The outcome was 6-month all-cause mortality after the diagnosis of interstitial lung disease. Cox regression analysis was used to assess the mortality. Adjusted restricted cubic spline analysis was performed to explore the non-linear relationship between age and outcomes. RESULTS: The 6-month mortality rates of women and men were 36.5% and 46.3%, respectively. Multivariate Cox regression revealed that ≥60 years of age was significantly associated with the risk of death (hazard ratio, 2.43; 95% confidence interval, 1.02-5.78). The trend of the risk of 6-month mortality in men was relatively flat until 54 years and increased rapidly afterwards (hazard ratio, 1.14; 95% confidence interval, 1.01-1.29). In contrast, the 6-month mortality rate showed a low linear increasing trend with age among females. CONCLUSIONS: Patients with MDA5+ DM, who received contemporary treatment, had unfavourable outcomes. The 6-month mortality risk increased with age, particularly in male patients aged >54 years.

Bone Cement and Pedicle Screw for the Treatment of Spinal Tumors with Spinal Cord Compression and Posterior Wall Defects.

OBJECTIVE: To compare the safety and efficacy of posterior internal fixation with open vertebroplasty (VP) and posterior internal fixation with open kyphoplasty (KP) in the treatment of metastatic epidural spinal cord compression (MESCC) with posterior wall destruction. METHODS: This retrospective study, conducted between January 2016 and May 2019, equally divided 60 patients with MESCC and posterior wall destruction into two groups based on the surgical method: open vertebroplasty with pedicle screw fixation (VP group) and open kyphoplasty with pedicle screw fixation (KP group). Visual analogue scale (VAS), SF-36 scores, middle vertebral height (MVH), and posterior vertebral height (PVH) were evaluated for the two groups preoperatively, postoperatively, and 1 year after surgery. Spinal Instability Neoplastic Score, Frankel grades and complications were recorded and evaluated. RESULTS: Five patients were excluded from the analysis, and our study cohort consisted of 55 adult patients who met the inclusion criteria. The VAS and SF-36 scores of these two groups of patients significantly improved, when compared with those before the surgery (P < 0.05). There were significant differences in total cost (8835 ± 1468 vs 9540 ± 053 USD) and cement volume (4.51 ± 0.96 ml vs 6.35 ± 1.09 ml) between two groups (P < 0.05). The MVH and PVH of these two groups of patients significantly improved, when compared with those before the surgery (P < 0.05). The MVH was significantly larger in the KP group than in the VP group postoperatively (20.15 ± 4.86 vs 17.70 ± 3.78, P < 0.05) and at the final follow-up (20.42 ± 5.59 vs 17.28 ± 3.23, P < 0.05). However, the PVH of the two groups did not significantly differ at the two postoperative follow-ups (P > 0.05). No significant differences were found in surgery time, time from surgery to discharge, blood loss and complications between both groups postoperatively (P > 0.05). CONCLUSION: In the short term, both approaches are effective and safe in patients with MESCC and posterior wall destruction. The posterior internal fixation with open VP may be a good choice of surgical method in patients with MESCC and posterior wall defects.

Identification of osteoporosis based on gene biomarkers using support vector machine.

Osteoporosis is a major health concern worldwide. The present study aimed to identify effective biomarkers for osteoporosis detection. In osteoporosis, 559 differentially expressed genes (DEGs) were enriched in PI3K-Akt signaling pathway and Foxo signaling pathway. Weighted gene co-expression network analysis showed that green, pink, and tan modules were clinically significant modules, and that six genes (VEGFA, DDX5, SOD2, HNRNPD, EIF5B, and HSP90B1) were identified as "real" hub genes in the protein-protein interaction network, co-expression network, and 559 DEGs. The sensitivity and specificity of the support vector machine (SVM) for identifying patients with osteoporosis was 100%, with an area under curve of 1 in both training and validation datasets. Our results indicated that the current system using the SVM method could identify patients with osteoporosis.

Proteomic comparison between physiological degeneration and needle puncture model of disc generation disease.

BACKGROUND: The completeness of the intervertebral disc proteome is fundamental to the integrity and functionality of the intervertebral disc. METHODS: The 20 experimental rats were placed into two groups randomly, normal group (NG) and acupuncture pathological degeneration group-2 weeks (APDG-2w). The ten 24-month-old rats were grouped into physiological degeneration group (PDG). Magnetic resonance imaging, X-ray examination, histological staining (hematoxylin & eosin, safranin-O cartilage, and alcian blue staining), and immunohistochemical examination were carried out for assessing the degree of disc degradation. Intervertebral disc was collected, and protein composition was determined by LC- MS, followed by bioinformatic analysis including significance analysis, subcellular localization prediction, protein domain prediction, GO function and KEGG pathway analysis, and protein interaction network construction. LC-PRM was done for protein quantification. RESULTS: Physiological degeneration and especially needle puncture decreased T2 signal intensity and intervertebral disc height. Results from hematoxylin & eosin, safranin-O, and alcian blue staining revealed that the annulus fibrosus apparently showed the wavy and collapsed fibrocartilage lamellas in APDG-2w and PDG groups. The contents of the nucleus pulposus were decreased in physiological degeneration group and APDG-2w group compared with NG. Results from immunohistochemical analysis suggested the degeneration of intervertebral disc and inflammation in APDG-2w and PDG groups. The protein composition and expression between needle puncture rat models and the physiological degeneration group showed significant difference. CONCLUSIONS: Our studies produced point-reference datasets of normal rats, physiological degeneration rats, and needle puncture rat models, which is beneficial to subsequent pathological studies. There is differential expression of protein expression in degenerative discs with aging and acupuncture, which may be used as a potential discriminating index for different intervertebral degenerations.

Comparing the Bridge-Type Zero-Profile Anchored Spacer (ROI-C) Interbody Fusion Cage System and Anterior Cervical Discectomy and Fusion (ACDF) with Plating and Cage System in Cervical Spondylotic Myelopathy.

OBJECTIVE: To compare the clinical efficacy and radioactivity of the bridge-type zero-profile anchored spacer (ROI-C) interbody fusion cage and anterior cervical discectomy and fusion with plating and cage system (ACDF) for cervical spondylotic myelopathy (CSM). METHODS: This is a retrospective contrastive study. We recruited 35 patients who received ROI-C (ROI-C group) and 34 patients who received ACDF (ACDF group), between January 2014 to January 2019, at our treatment center. The ROI-C group comprised of 11 males and 24 females with a mean age of 61.59 ± 8.21 years (range, 51-71 years). The ACDF group comprised of 12 males and 22 females with a mean age of 60.15 ± 7.52 years (range, 52-74 years). Neck Disability Index (NDI), Japanese Orthopaedic Association score (JOA), Odom's score, cervical Cobb angle, fusion rate, adjoining ossification, and dysphagia. RESULTS: A total of 69 patients met the inclusion criteria, and these patients received more than two years of follow-up. There were significant differences in surgical duration (101 ± 22 min vs. 118 ± 29 min) and blood loss (102 ± 46 ml vs. 145 ± 58 ml) between two groups (P < 0.05). The JOA and NDI of these two groups of patients significantly improved, when compared with those before the operation (P < 0.05). Twenty-nine of 35 patients in the ROI-C group and 27 of 34 patients in ACDF group achieved good or excellent outcomes according to Odom's criteria. The cervical lordosis of both two groups significantly increased, when compared with those before the operation (P < 0.05). In the ROI-C group, the postoperative fusion rate was 85.7% at the 3-month follow-up and 100% at the final follow-up. In the ACDF group, the postoperative fusion rate was 82.4% at the 3-month follow-up and 100% at the final follow-up. The dysphagia incidence of the ACDF group was higher than that of the ROI-C group postoperatively and at the one month after surgery (P < 0.05), but no significant difference was found in the incidence of dysphagia at final follow-up (P > 0.05). CONCLUSION: Both ROI-C and ACDF achieved good therapeutic effects. However, ROI-C can reduce the operation time and postoperative complications.

Platelet Transfusion in Patients With Sepsis and Thrombocytopenia: A Propensity Score-Matched Analysis Using a Large ICU Database.

PURPOSE: Sepsis with thrombocytopenia is highly prevalent in critically ill intensive care unit (ICU) patients and is associated with adverse outcomes. Platelet transfusion is the primary treatment of choice. However, evidence for the beneficial effects of platelet transfusion in patients with sepsis and thrombocytopenia is scarce and low in quality. This study aimed to evaluate the association between platelet transfusion and mortality among ICU patients with sepsis and thrombocytopenia. PATIENTS AND METHODS: Using the Medical Information Mart for Intensive Care III database (v. 1.4), the outcomes of sepsis patients with platelet counts of ≤ 150,000/µL were compared between those who did and did not receive platelet transfusion. The primary outcomes were 28- and 90-day all-cause mortalities. The secondary outcomes were red blood cell (RBC) transfusion, ICU-free days, and hospital-free days. Propensity score matching was employed to assemble a cohort of patients with similar baseline characteristics. RESULTS: Among 7,765 eligible patients, 677 received platelet transfusion and were matched with 677 patients who did not receive platelet transfusion according to propensity scores. Platelet transfusion, as compared with no platelet transfusion, was associated with an increased risk of 28-day all-cause mortality [36.9 vs. 30.4%, odds ratio (OR), 1.21; 95% confidence interval (CI), 1.01-1.46; p = 0.039], increased risk of 90-day all-cause mortality (50.8 vs. 44.6%, OR, 1.13; 95% CI, 1.00-1.31; p = 0.048), fewer mean (standard deviation) 28-day ICU-free days (15.88 ± 8.97 vs. 18.64 ± 8.33 days, p < 0.001), and fewer hospital-free days (10.29 ± 8.49 vs. 11.43 ± 8.85 days, p = 0.017). The rate of RBC transfusion was not significantly different between the platelet transfusion and non-transfusion groups (p = 0.149). The results were maintained across several subgroup and sensitivity analyses. CONCLUSION: In this study, platelet transfusion was associated with higher 28- and 90-day all-cause mortalities. These results suggest the potential hazards of platelet transfusion in ICU patients with sepsis and thrombocytopenia.

Resveratrol inhibits the progression of premature senescence partially by regulating v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) and sirtuin 1 (SIRT1).

OBJECTIVE: To explore the effect of resveratrol in premature senescence and reveal its anti-premature senescence mechanisms through network pharmacology. METHODS: In this study, the H2O2-induced bone marrow mesenchymal stem cells (BMMSCs) premature senescence model is applied. Cell counting kit-8 assay, ß-galactosidase staining and flow cytometry are conducted to detect the proliferation, senescence and apoptosis of BMMSCs. Bioinformatics analyses are used to screen and validate molecular targets of resveratrol acting on premature senescence. Dual-luciferase reporter assay is conducted to verify the interaction between v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) and sirtuin 1 (SIRT1). RT-qPCR and western blot are adopted to detect mRNA and protein levels of RELA, SIRT1, senescence-related genes and apoptosis-related genes. RESULTS: First, we proved that resveratrol alleviated the H2O2-induced senescence of BMMSCs. Then, bioinformatics analysis revealed that RELA was the downstream target of resveratrol and SIRT1 was the downstream target of RELA, respectively, involved in premature aging. RELA/SIRT1 may be the potential target of resveratrol for premature senescence. Notably, rescue experiments indicated that resveratrol inhibited premature senescence partially through targeting regulation RELA/SIRT1. CONCLUSION: In our study, we confirm the functional role of the resveratrol-RELA- SIRT1 axis in the progression of premature senescence, which provides a latent target for premature senescence treatment.

Similarity and difference between aging and puncture-induced intervertebral disc degeneration.

The purpose of our study was to investigate the changes in micromorphology and mechanical properties of intervertebral discs degeneration induced by aging and puncture. Normal group (NG), 2 weeks post-puncture degeneration group (PDG) and aging degeneration group (ADG) each included 10 rats. Plain film, magnetic resonance imaging, and histological testing were utilized to assess intervertebral disc degeneration. Atomic force microscope was utilized to analyze the microstructure and elastic modulus of the intervertebral disc, while immunohistochemistry was employed to assess alterations in the cell matrix using collagen I, collagen II, matrix metalloproteinase-3 (MMP-3), and tumour necrosis factor-α (TNF-α). The results showed that the disc height ratio between PDG and ADG decreased. In the PDG and ADG group, histological scores both increased, the gray value of the T2 signal decreased, the proportion of MMP-3 and TNF-positive cells in intervertebral disc tissues was higher (p < 0.05) and the IOD values of COL-2 lower in intervertebral disc tissues (p < 0.05). The elastic modulus of PDG and ADG annulus fibers (AF) increased compared to the NG (p < 0.05); when compared to PDG, the elastic modulus of ADG AF decreased (p < 0.05). The elastic modulus of PDG and ADG collagen increased in the nucleus pulposus (NP, p < 0.05); ADG had a greater AF diameter than NG and PDG (p < 0.05). The results indicated that ADG fiber diameter thickens, and chronic inflammation indicators rise; PDG suffers from severe extracellular matrix loss. The degeneration of the ADG and PDG intervertebral discs is different. The results provide foundation for clinical research.

Does the Relationship Between Bone Cement and the Intravertebral Cleft of Kummell Disease Affect the Efficacy of PKP?

OBJECTIVE: To study the relationship between distribution of bone cement and intravertebral cleft of patients with Kummell disease on the clinical effect of percutaneous kyphoplasty (PKP). METHODS: According to the relationship between the distribution of bone cement and the cleft in the vertebrae, a total of 92 patients with Kummell disease who underwent PKP in our hospital were divided into 2 groups. Specifically, the bone cement of patients in group A was localized in the cleft of the vertebrae and did not infiltrate around the cleft, while that of group B patients not only filled the cleft of the vertebrae, but also distributed diffusely around the cleft of the vertebrae. The amount of bone cement injected, leakage rate, visual analogue scale (VAS) score, Oswestry Disability Index (ODI), and vertebral imaging changes before operation, and 2 days and 1 year after operation were compared between the 2 groups. RESULTS: The amount of bone cement injected and the permeability of bone cement in group B were higher than those in group A (P < 0.05). The scores of VAS and ODI in both groups were significantly improved after operation, but the two scores in group B were better than those in group A one year after operation. The height of anterior vertebral body and Cobb's angle of kyphosis in the 2 groups were significantly improved after operation, but 1 year after operation, those in group B were better than those in group A. CONCLUSIONS: PKP was an effective method for treating Kummell disease. At the same time, the relationship between the distribution of bone cement and the cleft in the vertebral body was an important factor affecting the curative effect after PKP. The effect of the distribution pattern of bone cement filled with intravertebral cleft and diffusely distributed around the fissures was better than that of bone cement confined in the vertebral cleft.

EZH2 upregulates the expression of MAPK1 to promote intervertebral disc degeneration via suppression of miR-129-5p.

BACKGROUND: This study was designed to verify whether enhancer of zeste homolog 2 (EZH2) affects intervertebral disc degeneration (IVDD) development through regulation of microRNA (miR)-129-5p/MAPK1. METHODS: Initially, we collected lumbar nucleus pulposus (NP) tissue samples from patients with juvenile idiopathic scoliosis (n = 14) and IVDD (n = 34). We measured the expression of related genes in clinical IVDD tissues and a lipopolysaccharide (LPS)-induced NP cell model. After loss- and gain-of-function assays, NP cell proliferation and senescence were examined. The targeting relationship between miR-129-5p and MAPK1 was explored by dual luciferase reporter gene and RNA immunoprecipitation (RIP) assays. The enrichment of EZH2 and H3K27me3 in miR-129-5p promoter was verified by chromatin immunoprecipitation (ChIP). Finally, an IVDD rat model was established to test the effects of transduction with lentiviral vector carrying miR-129-5p agomir and/or oe-EZH2 in vivo. RESULTS: miR-129-5p was underexpressed, and EZH2 and MAPK1 levels were overexpressed in lumbar nucleus pulposus from human IVDD patients and in LPS-induced NP cells. miR-129-5p overexpression or silencing of MAPK1 promoted proliferation of NP cells, while inhibiting their senescence. EZH2 inhibited miR-129-5p through H3K27me3 modification in the miR-129-5p promoter. miR-129-5p could target the downregulation of MAPK1 expression. EZH2 overexpression increased the release of inflammatory factors and cell senescence factors, which was reversed by miR-129-5p agomir in vivo. CONCLUSIONS: Taken together, EZH2 inhibits miR-129-5p through H3K27me3 modification, which upregulates MAPK1, thereby promoting the development of IVDD.

Impact of Platelet Transfusion Thresholds on Outcomes of Patients With Sepsis: Analysis of the MIMIC-IV Database.

BACKGROUND: The benefits of platelet thresholds for transfusion remain unclear. This study assessed the effect of two transfusion thresholds on the survival outcomes of patients with sepsis and thrombocytopenia. METHODS: In this retrospective cohort study, data of patients with sepsis admitted to an intensive care unit (ICU) and who had received platelet transfusion were extracted from the Medical Information Mart for Intensive Care IV database. Patients were classified into the lower-threshold group (below 20,000/µL) and higher-threshold group (20,000-50,000/µL), based on thresholds calculated from their pretransfusion platelet count. The endpoints included 28- and 90-day mortality, red blood cell (RBC) transfusion, ICU-free days, and hospital-free days. RESULTS: There were 76 and 217 patients in the lower-threshold and higher-threshold groups, respectively. The higher-threshold group had a higher rate of surgical ICU admission (35.0% vs. 9.2%) and lower quick Sequential Organ Failure Assessment (qSOFA) score than the lower-threshold group. In the higher-threshold group, 94 (43.3%) and 132 (60.8%) patients died within 28 and 90 days, compared to 51 (67.1%) and 63 (82.9%) patients in the lower-threshold group (adjusted odds ratio, 1.96; 95% confidence interval, 1.16 to 3.03; P = 0.012; adjusted odds ratio, 2.04; 95% confidence interval, 1.16 to 3.57; P = 0.012, respectively). After stratification by mortality risk, the subgroup analysis showed a consistent trend favoring higher-threshold transfusion but reached statistical significance only in the low-risk group. There were no differences in red blood cell transfusion, ICU-free days, and hospital-free days between the groups. The E-value analysis suggested robustness to unmeasured confounding. CONCLUSIONS: In patients with sepsis and thrombocytopenia, platelet transfusion at a higher threshold was associated with a greater reduction in the 28- and 90-day mortalities than that at a lower threshold.

Performance of Procalcitonin to Distinguish Fungal from Bacterial Infections in Patients with Systemic Lupus Erythematosus.

PURPOSE: To evaluate the performance of serum procalcitonin (PCT) concentrations to diagnose fungal infection in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: From January 2017 to October 2020, SLE patients hospitalized for serious infection with an identified single bacterial or fungal pathogen, as well as PCT measured within 24h after admission were included. The diagnostic performance of PCT was evaluated independently and in combination with the white blood cell (WBC) count, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). The analysis included the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and the crude and adjusted area under the receiver operating characteristic curve (AUROC). RESULTS: Sixty-nine patients were included; 26 had a fungal infection (38%) and 43 had a bacterial infection (22 gram-positive and 21 gram-negative). Fungal infection patients were mainly distributed in the respiratory group (88.5%), and bacterial infection distribution were more prevalent in respiratory group (44.2%) and abdominal/urinary group (23.3%). The PCT concentration was significantly lower in fungal infections than bacterial infections (fungal: 0.22 ng/mL, interquartile range [IQR], 0.09-0.44 vs bacterial: 0.60 ng/mL, IQR, 0.16-5.74; p = 0.016) and differed significantly between different infection sites (p = 0.022). PCT had better diagnostic performance for predicting fungal infection (AUROC = 0.731) than the WBC count (AUROC = 0.581), the CRP level (AUROC = 0.716), and ESR (AUROC = 0.583). PCT and ESR together had the best diagnostic performance, with 46.2% sensitivity and 88.4% specificity. Further, the AUROC increased compared to PCT alone but was statistically insignificant (p = 0.693). CONCLUSION: For SLE patients with serious infection, the PCT concentration had better diagnostic accuracy for predicting fungal infection than the WBC count, the CRP level, and ESR. Combining PCT and ESR obtained the highest AUROC and provided an acceptable discrimination performance.

Clinical comparison of febrile and afebrile patients with pyogenic liver abscess: A two-centre retrospective study.

BACKGROUND: : Limited research has been conducted on afebrile pyogenic liver abscess (PLA). This poses a challenge in rapid diagnosis and early tailored care to physicians. In his study, we aimed to compare the clinical characteristics of afebrile and febrile patients with PLA. METHODS: : We retrospectively analyzed the data of patients with PLA who were admitted to the emergency departments of two university hospitals between January 2014 and March 2020. Patients were classified into afebrile and febrile groups by using body temperature higher than 38°C as the reference standard. The demographic, clinical, and laboratory characteristics of both groups were compared. The primary outcome was all-cause in-hospital mortality and length of hospital stay. Multivariate analysis was performed to define factors associated with afebrile PLA. RESULTS: : Of the 239 patients included in this study, 51 patients (21.3%) were afebrile and 188 patients (78.7%) were febrile. There were no differences between the abscess characteristics, laboratory manifestations, and disease severity of both groups; however, age and Charlson score differed between the groups (P = 0.009 and P = 0.011). The all-cause in-hospital mortality rate was much higher in the afebrile PLA group than in the febrile PLA group (9.8% vs. 2.1%, P = 0.011). Regarding the length of stay, no significant differences were noted in the febrile PLA group compared with the afebrile PLA group (18.5% vs 17.3%, P = 0.514). In multivariate analyses, only age greater than 65 years was significantly associated with afebrile PLA. CONCLUSIONS: : Afebrile patients with PLA tend to be older, have higher Charlson scores, and in-hospital mortality rate than those with febrile patients. PLA patients older than 65 years are more likely to present without fever (<38°C) at the time of the emergency visit.

Comparison of Clinical Outcomes Following Anterior Cervical Discectomy and Fusion with Zero-Profile Anchored Spacer-ROI-C-Fixation and Combined Intervertebral Cage and Anterior Cervical Discectomy and Fusion: A Retrospective Study from a Single Center.

BACKGROUND The aim of this study was to compare the outcomes following anterior cervical discectomy and fusion with zero-profile anchored spacer-ROI-C-fixation (ROI-C) vs combined intervertebral cage and anterior cervical discectomy and fusion (ACDF). MATERIAL AND METHODS We retrospectively analyzed 87 patients who underwent operations between January 2015 and January 2019, including 42 patients that underwent ROI-C treatment (group A) and 45 that were treated by the ACDF approach (group B). Operative duration, blood loss, dysphagia, Neck Disability Index scores (NDI), Japanese Orthopaedic Association scores (JOA), and other complications were compared between these groups. In addition, implant settlement, fusion, and cervical Cobb angle were assessed via imaging analyses. RESULTS Patients in group A and group B were followed for 22.6±3.3 months and 27.1±3.5 months, respectively (range: 13-30 months). Relative to preoperative values, JOA scores were increased and NDI scores were reduced in both groups following treatment (P<0.05), with comparable outcomes between groups (P>0.05). However, operative duration, intraoperative blood loss, and postoperative complications did differ significantly between these groups (P<0.05). Specifically, rates of short-term dysphagia were lower and recovery time was faster in group A relative to group B (P<0.05). CONCLUSIONS The findings from this study showed that ROI-C fixation achieved satisfactory outcomes, improved cervical curvature, restored intervertebral height, and was associated with shorter operative duration, reduced blood loss, and less dysphagia.

Combining C reactive protein and serum albumin to predict 90-day mortality in systemic lupus erythematosus with serious community-acquired infections.

OBJECTIVE: Serious infections in SLE are common and have emerged as the major cause of death. However, effective methods to identify poor prognosis are still lacking. Therefore, we aimed to determine the predictive value of C reactive protein (CRP) plus albumin (ALB) in SLE with serious infections. METHODS: From May 2015 to December 2018, consecutive patients with SLE presenting with serious infections in our emergency department were prospectively recruited. Serum CRP and ALB were measured within 24 hours of admission. The outcome was defined as mortality rate at 90 days. A CRP plus ALB score (2-6) was assigned based on the CRP and ALB concentrations. We performed univariate and multivariate regression analyses to detect the independent effects of CRP plus ALB on 90-day mortality (all-cause and infection-related). Subgroup analyses were used to show the effects stratified by lupus nephritis. RESULTS: A total of 150 patients were included, and the all-cause 90-day mortality rate was 38% (n=57), 41 of which was infection-related. The predominant infection sites were pulmonary (79.3%) and bloodstream infection (20.7%). Serum CRP and ALB levels were significantly different in non-surviving patients compared with those in surviving patients (p=0.002 and p<0.001, respectively). In the fully adjusted logistic regression model, the CRP plus ALB score was associated with decreased 90-day survival (adjusted OR 1.52; 95% CI 1.08 to 2.13; p=0.017). CONCLUSIONS: CRP plus ALB was associated with the risk of all-cause and infection-related 90-day mortality in SLE with serious infections. Although this finding requires further verification, the two parameters may be useful for predicting poor outcomes in such patients.