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.

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.

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.

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.

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.

Association of blood culture with carbapenem use in pyogenic liver abscess: a two-center retrospective study.

BACKGROUND: Highly empiric use of carbapenem in pyogenic liver abscess (PLA) is widespread problem. However, few studies have examined the association between blood culture and carbapenem use in patients with PLA in China. Thus, we conducted this observational study. METHODS: The data of patients diagnosed with PLA at two comprehensive tertiary care centers from 2014 to 2020 were retrospectively collected. Demographic and clinical data were analyzed, and univariate and multivariate analyses were performed to investigate the association between blood culture and carbapenem use. Subgroup analysis was conducted to explore whether the effect is different in sepsis. RESULTS: Blood culture was performed in 110 (46.0%) patients, of whom 44 (40.0%) patients had positive results for bacterial culture. Extended-spectrum beta-lactamase (ESBL)-positive blood culture isolates were detected in 8 (7.3%) patients. The positivity rate of blood culture in sepsis was higher than in non-sepsis (58.1% vs. 32.9%, P = 0.015). Fewer patients who had a blood culture received carbapenem treatment in comparison to patients without blood culture (19.1% vs. 31.8%, P = 0.026). Multivariate analysis showed that blood culture was independently associated with less carbapenem exposure (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI]: 0.16-0.68, P = 0.003), and this effect remained significant in the sepsis subgroup (adjusted OR = 0.17, 95% CI: 0.05-0.53, P = 0.002). CONCLUSION: Blood culture had a high positivity rate and was associated with less carbapenem use in PLA, especially those who developed sepsis. More attention should be paid to performing early blood culture and less carbapenem use in PLA.

SENP3 in monocytes/macrophages up-regulates tissue factor and mediates lipopolysaccharide-induced acute lung injury by enhancing JNK phosphorylation.

The mechanisms underlying coagulation abnormalities in sepsis and septic acute lung injury remain unclear. Tissue factor (TF) initiates coagulation; its production can be regulated by reactive oxygen species (ROS); and monocytes/macrophages produce pathological TF during sepsis. The SUMO2/3 protease SENP3 is redox-sensitive, and SENP3 accumulation in lipopolysaccharide (LPS)-activated macrophages is ROS-dependent. To explore whether SENP3 contributes to LPS-activated coagulation, we used mice with Senp3 conditional knockout (cKO) in myeloid cells. In the model of LPS-induced sepsis, SENP3 cKO mice exhibited less severe acute lung injury than SENP3 fl/fl mice. SENP3 cKO mice exhibited decreased TF expression in monocytes and alveolar macrophages, with consequently compromised coagulation in their blood and lungs. In vitro results showed that ROS-induced SENP3 accumulation contributed to LPS-induced TF expression, which was reduced by JNK inhibitor SP600125. Furthermore, mice injected with LPS following SP600125 (75 mg/kg) treatment showed decreased monocytes/macrophages TF production and alleviated coagulation activation, with less severe lung injury and higher survival rates. Collectively, the results suggest that SENP3 mediates LPS-induced coagulation activation by up-regulating monocyte/macrophage TF production in a JNK-dependent manner. This work provides new insights into ROS regulation of LPS-activated coagulation and reveals a link between SUMOylation and coagulation.

Percutaneous fine-needle aspiration for pyogenic liver abscess (3-6 cm): a two-center retrospective study.

BACKGROUND: The role of ultrasonography-guided percutaneous fine-needle aspiration (PNA) for pyogenic liver abscess (PLA) remains without consensus, especially in abscesses 3 to 6 cm in diameter. The objective of this study was to evaluate the comparative effectiveness and safety of PNA combined with antibiotics. METHODS: This was a retrospective study of patients with PLA that were from 3 to 6 cm in diameter who treated at two medical centers in Shanghai, China, from January 2014 to March 2019. Patients were divided into groups treated by PNA plus antibiotics or antibiotics alone. Patients demographics and clinical data related diagnosis, antibiotic treatment, and patient outcomes were analyzed. RESULTS: Out of a total of 94 PLA patients, 42 (44.7%) patients received PNA combined with antibiotics, and 52 (55.3%) received antibiotics alone. There were no complications related to PNA. In the PNA group, 13 (31.7%) patients with negative blood culture and 8 (19.5%) patients without blood culture were microbiologically confirmed via aspiration. The time for temperature normalization (P < 0.001) and the reduction rate of C-reactive protein within the first week (P = 0.031) were significantly lower in the PNA group. In the multivariate analysis, treatment with PNA was more likely to result in clinical improvement of PLA (odds ratio = 0.33, 95% confidence intervals (CI): 0.11-0.96, P = 0.043). CONCLUSIONS: PNA combined with antibiotics appears to be a safe, effective, and promising treatment for PLA of 3-6 cm in size. Furthermore, the technique allows for direct microbial sample, which can improve the selection of antibiotics.

Predictive value of circulating plasma mitochondrial DNA for Sepsis in the emergency department: observational study based on the Sepsis-3 definition.

BACKGROUND: The definition of sepsis is regularly updated; however, there is no standard diagnostic test. To improve diagnosis and prognostic prediction, the aim of this study was to determine the predictive value of circulating plasma mitochondrial DNA (mtDNA) levels in patients admitted to the emergency department (ED) with sepsis. METHODS: A total of 107 patients hospitalized from June 2018 to January 2019 were divided into the sepsis (n = 72) and septic shock (n = 35) groups based on the sepsis-3 definition. Clinical and laboratory data were measured within 24 h of admission. The mtDNA concentrations in clarified plasma were estimated by quantitative polymerase chain reaction. Binary logistic regression analysis and the receiver operating characteristic (ROC) curve were used to determine predictive value of mtDNA and other markers for sepsis outcome (28-day mortality). RESULTS: The median plasma mtDNA levels on admission were significantly higher in the septic shock patients than in the sepsis patients (134,252(IQR 70215-203,184) vs. 59,945(IQR 13274-95,319) copies/µL, P < 0.01), and were also higher in non-survivors than in survivors within 28 days (165,291(IQR 89919-272,228)vs. 63,025(IQR 17031-98,401)copies/µL, P < 0.01). Binary logistic regression showed that plasma lactate and mtDNA levels were independent risk factors for 28-day mortality [odds ratio (OR) 1.341, 95% confidence interval (CI) 1.035-1.736, P = 0.026 and OR 13.299, 95%CI 2.765-63.956, P = 0.001, respectively). The area under the ROC curve values for plasma mtDNA levels, lactate concentration, and their combined were 0.781 (p < 0.001, 95%CI 0.671-0.891), 0.733 (p < 0.001, 95%CI 0.635-0.832), and 0.799 (p < 0.001, 95%CI 0.698-0.901), respectively. The calibration test for the combined variable showed X2 of 2.559 and P = 0.923. CONCLUSION: A higher plasma mtDNA level was associated with a poor prognosis of sepsis in the emergency room, and could serve as a predictor of sepsis for 28-day mortality.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.