Development and validation of a machine learning-based nomogram for predicting HLA-B27 expression.

BACKGROUND: HLA-B27 positivity is normal in patients undergoing rheumatic diseases. The diagnosis of many diseases requires an HLA-B27 examination. METHODS: This study screened totally 1503 patients who underwent HLA-B27 examination, liver/kidney function tests, and complete blood routine examination in First Affiliated Hospital of Guangxi Medical University. The training cohort included 509 cases with HLA-B27 positivity whereas 611 with HLA-B27 negativity. In addition, validation cohort included 147 cases with HLA-B27 positivity whereas 236 with HLA-B27 negativity. In this study, 3 ML approaches, namely, LASSO, support vector machine (SVM) recursive feature elimination and random forest, were adopted for screening feature variables. Subsequently, to acquire the prediction model, the intersection was selected. Finally, differences among 148 cases with HLA-B27 positivity and negativity suffering from ankylosing spondylitis (AS) were investigated. RESULTS: Six factors, namely red blood cell count, human major compatibility complex, mean platelet volume, albumin/globulin ratio (ALB/GLB), prealbumin, and bicarbonate radical, were chosen with the aim of constructing the diagnostic nomogram using ML methods. For training queue, nomogram curve exhibited the value of area under the curve (AUC) of 0.8254496, and C-value of the model was 0.825. Moreover, nomogram C-value of the validation queue was 0.853, and the AUC value was 0.852675. Furthermore, a significant decrease in the ALB/GLB was noted among cases with HLA-B27 positivity and AS cases. CONCLUSION: To conclude, the proposed ML model can effectively predict HLA-B27 and help doctors in the diagnosis of various immune diseases.

MEG3 alleviates ankylosing spondylitis by suppressing osteogenic differentiation of mesenchymal stem cells through regulating microRNA-125a-5p-mediated TNFAIP3.

Osteoblasts are important regulators of bone formation, but their roles in ankylosing spondylitis (AS) remain unclear. This study aims to explore the role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) MEG3 in AS. Serum from AS patients as well as AS mesenchymal stem cells (ASMSCs) and healthy donors mesenchymal stem cells (HDMSCs) was collected. Accordingly, poorly expressed MEG3 and TNF alpha induced protein 3 (TNFAIP3) as well as overexpressed microRNA-125a-5p (miR-125a-5p) were noted in the serum of AS patients and in ASMSCs during the osteogenic induction process. Meanwhile, the interaction among MEG3, miR-125a-5p, and TNFAIP3 was determined and their effect on osteoblast activity was examined in vitro and in vivo. Overexpression of MEG3 and TNFAIP3 or inhibition of miR-125a-5p was found to inactivate the Wnt/ß-catenin pathway, thus suppressing osteogenic differentiation of MSCs. MEG3 competitively bound to miR-125a-5p to increase TNFAIP3 expression, thereby inactivating the Wnt/ß-catenin pathway and repressing the osteogenic differentiation of MSCs. In proteoglycan (PG)-induced AS mouse models, MEG3 also reduced osteogenic activity of MSCs to inhibit AS progression through the miR-125a-5p/TNFAIP3/Wnt/ß-catenin axis. Therefore, up-regulation of MEG3 or depletion of miR-125a-5p holds potential of alleviating AS, which sheds light on a new therapeutic strategy for AS treatment.

Application of machine learning in prediction of bone cement leakage during single-level thoracolumbar percutaneous vertebroplasty.

BACKGROUND: In the elderly, osteoporotic vertebral compression fractures (OVCFs) of the thoracolumbar vertebra are common, and percutaneous vertebroplasty (PVP) is a common surgical method after fracture. Machine learning (ML) was used in this study to assist clinicians in preventing bone cement leakage during PVP surgery. METHODS: The clinical data of 374 patients with thoracolumbar OVCFs who underwent single-level PVP at The First People's Hospital of Chenzhou were chosen. It included 150 patients with bone cement leakage and 224 patients without it. We screened the feature variables using four ML methods and used the intersection to generate the prediction model. In addition, predictive models were used in the validation cohort. RESULTS: The ML method was used to select five factors to create a Nomogram diagnostic model. The nomogram model's AUC was 0.646667, and its C value was 0.647. The calibration curves revealed a consistent relationship between nomogram predictions and actual probabilities. In 91 randomized samples, the AUC of this nomogram model was 0.7555116. CONCLUSION: In this study, we invented a prediction model for bone cement leakage in single-segment PVP surgery, which can help doctors in performing better surgery with reduced risk.

STAT3 and SPI1, may lead to the immune system dysregulation and heterotopic ossification in ankylosing spondylitis.

OBJECTIVE: This study was aimed to identify the biomarkers for diagnosis and reveal the immune microenvironment changes in ankylosing spondylitis (AS). METHODS: GSE73754 was downloaded for the co-expression network construction and immune cell analyses. Flow cytometric analysis was performed to validate the results of bioinformatics analysis. Gene set enrichment analysis (GSEA) was performed to investigate the potential biological characteristic between different phenotypes. Pearson correlation analysis between the hub genes and the xCell score of immune cell types was performed. RESULTS: Signal transducer and activator of transcription 3 (STAT3) and Spi-1 proto-oncogene (SPI1) was identified as the hub genes in the datasets GSE73754. And the t-test showed that the expression level of STAT3 and SPI1 in the GSE73754 was significantly higher in AS and human leukocyte antigen (HLA)-B27(+) groups. Flow cytometric analysis showed that natural killer T cells (NKT) cells were upregulated, while Th1 cells were down-regulated in AS, which was consistent with the results obtained from bioinformatics analysis. STAT3 and SPI1 was correlated with the NKT cells and Th1 cells. CONCLUSION: STAT3 and SPI1 may be a key cytokine receptor in disease progression in AS.

Pulmonary embolism following the third thoracic tuberculosis surgery: A case report and literature review.

BACKGROUND: The study aimed to analyze the clinical effects of pulmonary embolism succeeding a third surgery conducted for multiple recurrences in thoracic tuberculosis (TB). CASE REPORT: A 74-year-old female patient developed thoracic tuberculosis and was subsequently treated in our hospital in March 2019, October 2020, and February 2021. The third surgical intervention included anterolateral thoracic lesion resection, internal fixation, posterior spinal tuberculous sinus resection, and debridement with suture. The operative time was 172 min resulting in a substantial intraoperative blood loss (2321 ml). Postoperative re-examination of chest CTPA indicated a strip filling defect and pulmonary embolism in the external branch of the right middle lobe of the lung. After completing the active treatment, the D-dimer quantification, WBC, CRP, and ESR values were 1261 ng/ml, 7.71 × 109 /L, 74.66 mg/L, and 63 mm, respectively. Chest CTPA re-examination after the treatment showed no signs of pulmonary embolism. CONCLUSION: Patients with a long-term history of multiple operations, high BMI, cerebral infarction, diabetes, and older age group were more likely to develop pulmonary embolism after spinal tuberculosis surgery. Thus, the possibility of postoperative pulmonary embolism should be thoroughly analyzed before any subsequent surgical treatment in patients with recurrent spinal tuberculosis.

Suitability of 3.5-mm screw for the atlas in children: a retrospective computed tomography analysis.

BACKGROUND: The growth and development of the atlas in children has not been studied to date using a large sample size. OBJECTIVE: To study whether a 3.5-mm screw is suitable for the atlas in children, to explore the anatomical size and development of the atlas in 0-14-year-old children, and to provide morphological basis for lateral mass screw internal fixation. METHODS: A Computed Tomography (CT) morphometric analysis was performed on 420 pediatric atlases. In the atlas, D1, D2, D3, D4, and α of the atlas lateral mass were measured. Statistical analysis was performed using one-way ANOVA and Students' t test. The least square method was used for the regression analysis of the change trend in anatomical structure. The curve with the greatest goodness of fit was used as the anatomic trend regression curve. RESULTS: D1, D2, D3, and D4 generally showed an increasing trend with age. The ranges of averages of D1, D2, D3, D4, and α in 0-14 year-old children were as follows: 4.576-9.202 mm, 9.560-25.100 mm, 3.414-10.554 mm, 11.150-27.895, and 12.41°-20.97°, respectively. The trends of the fitting curves of L1 and L3 were power functions, and those of L2 and L4 were logarithmic curves. CONCLUSIONS: CT examination could help in preoperative decision-making, and 3.5-mm screw was found to be suitable for lateral mass screw internal fixation in children aging 2 years and older. D1-D4 increased with age. This provided a certain reference to perform posterior atlantoaxial fusion in children and is of great significance to design posterior atlantoaxial screw in children.

Blood transfusion risk prediction in spinal tuberculosis surgery: development and assessment of a novel predictive nomogram.

OBJECTIVE: The present study attempted to predict blood transfusion risk in spinal tuberculosis surgery by using a novel predictive nomogram. METHODS: The study was conducted on the clinical data of 495 patients (167 patients in the transfusion group and 328 patients in the non-transfusion group) who underwent spinal tuberculosis surgery in our hospital from June 2012 to June 2021. The least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression analyses were used to screen out statistically significant parameters, which were included to establish a novel predictive nomogram model. The receiver operating characteristic (ROC) curve, calibration curves, C-index, and decision curve analysis (DCA) were used to evaluate the model. Finally, the nomogram was further assessed through internal validation. RESULTS: The C-index of the nomogram was 0.787 (95% confidence interval: 74.6%-.82.8%). The C-value calculated by internal validation was 0.763. The area under the curve (AUC) of the predictive nomogram was 0.785, and the DCA was 0.01-0.79. CONCLUSION: A nomogram with high accuracy, clinical validity, and reliability was established to predict blood transfusion risk in spinal tuberculosis surgery. Surgeons must prepare preoperative surgical strategies and ensure adequate availability of blood before surgery.

Feasibility of 3.5 mm C2 pedicle screws in children: A computerized tomography analysis.

There have been no studies with large sample sizes on growth of the pedicle of C2 in children. In the present study we measured the pedicle of C2 through computed tomography (CT) imaging in children aged less than 14 years and evaluated the suitability of the 3.5-mm screw for the pedicle in such children. The study was conducted on CT morphometric images of 420 children in our hospital between June 2018 and June 2020. The width (D1), length (D2), height (D3), inclination angle (α), and tail angle (ß) of the C2 pedicle were measured. One-way analysis of variance and Student's t test were used for statistical analyses. The least-square method was used to analyze the curve fitting the trend of anatomical change in the pedicle. The largest degree of goodness of fit determined the best-fitting curve. The size of the pedicle of C2 increased with age. The median ranges of D1, D2, D3, α, and ß were 3.312-5.431 mm, 11.732-23.645 mm, 3.597-8.038 mm, 32.583°-36.640°, and 24.867°-31.567°, respectively. The curves fitting the trends of D1 and D3 were power functions, whereas D2 was fitted by a logarithmic curve. However, no curve fitted α or ß. A 3.5-mm screw can be placed in the pedicle of C2 in children aged more than 1 year. The growth and development trend of this pedicle can provide an anatomical reference for deciding on posterior cervical surgery and for selecting and designing pedicle screws for children.

Rapid characterization and pharmacokinetic study of aristolochic acid analogues using ion mobility mass spectrometry.

Aristolochic acid analogues (AAAs), naturally existing in herbal Aristolochia and Asarum genera, were once widely used in traditional pharmacopeias because of their anti-inflammatory properties, but lately they were identified as potential nephrotoxins and mutagens. A method for rapid characterization of AAAs in serum was developed using ion mobility spectrometry coupled with mass spectrometry (IMS-MS). Five AAAs, containing four aristolochic acids and one aristolactam, were separated and identified within milliseconds. AAAs were separated in gas phase based on the difference of their ion mobility (K0), and then identified based on their K0 values, m/z, and product ions from MS/MS. Quantitative analysis of AAAs was performed using an internal standard with a satisfactory sensitivity. Limits of detection (signal-to-noise = 3) and quantification (signal-to-noise = 10) were 1-5 ng/mL and 3-8 ng/mL, respectively. The method was validated and successfully applied to the pharmacokinetics study of AAAs in rats, offering a promising way for fast screening and evaluation of AAAs in biological samples.

A Retrospective Study of Factors Associated with Restoration of Thoracic Kyphosis in 43 Patients with Adolescent Idiopathic Scoliosis with Lenke Type 1 Curvature.

BACKGROUND This retrospective study aimed to identify the factors associated with successful surgical correction of thoracic kyphosis (TK) in 43 patients with adolescent idiopathic scoliosis (AIS) with Lenke type 1 curvature, in which the major curve with the largest Cobb angle was mainly in the thoracic region. MATERIAL AND METHODS We collected data from patients with Lenke 1 AIS. The following parameters were measured: Cobb angle, side-bending Cobb angle, cervical lordosis (CL), TK, lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), the sagittal vertical axis (SVA), the center of a C7 plumb line to the center sacral vertical line (C7-CSVL), correction rate, Ponte osteotomy, flexibility, and screw density. Univariate analysis and multivariate logistic regression analyses were performed. RESULTS Among the 43 cases analyzed, the mean postoperative Cobb angle at the last follow-up, C7-CSVL, SVA, CL, TK, LL, PI, SS, and PT were respectively 21.33±9.47°, 10.41±8.45 mm, 19.68±14.33 mm, 16.19±7.45°, 23.12±7.45°, 50.33±11.37°, 49.70±9.83°, 39.42±8.11°, and 10.16±6.63°. Univariate analysis suggested that preoperative TK, preoperative LL, and Ponte osteotomy were statistically significant (P<0.05), and multivariate analysis suggested that preoperative LL and Ponte osteotomy were statistically significant (P<0.05). CONCLUSIONS The results of this study demonstrated that preoperative TK, preoperative LL, and Ponte osteotomy were related factors for maintaining normal TK. Multivariate analysis suggested that preoperative LL and the use of Ponte osteotomy with full-thickness segmental resection of the spinal posterior column resulted in the successful surgical correction of TK in patients with AIS with Lenke type 1 curvature.

Is there a correlation between upper lumbar disc herniation and multifidus muscle degeneration? A retrospective study of MRI morphology.

BACKGROUND: The purpose of the study is to investigate the correlation between upper lumbar disc herniation (ULDH) and multifidus muscle degeneration via the comparison of width, the cross-sectional area and degree of fatty infiltration of the lumbar multifidus muscle. METHODS: Using the axial T2-weighted images of magnetic resonance imaging as an assessment tool, we retrospectively investigated 132 patients with ULDH and 132 healthy individuals. The total muscle cross-sectional area (TMCSA) and the pure muscle cross-sectional area (PMCSA) of the multifidus muscle at the L1/2, L2/3, and L3/4 intervertebral disc levels were measured respectively, and in the meantime, the average multifidus muscle width (AMMW) and degree of fatty infiltration of bilateral multifidus muscle were evaluated. The resulting data were analyzed to determine the presence/absence of statistical significance between the study and control groups. Multivariate logistical regression analyses were used to evaluate the correlation between ULDH and multifidus degeneration. RESULTS: The results of the analysis of the two groups showed that there were statistically significant differences (p < 0.05) between TMCSA, PMCSA, AMMW and degree of fatty infiltration. The multivariate logistic regression analysis indicated that the TMCSA, PMCSA, AMMW and the degree of fatty infiltration of multifidus muscle were correlated with ULDH, and the differences were statistically significant (P < 0.05). CONCLUSIONS: A correlation could exist between multifidus muscles degeneration and ULDH, that may be a process of mutual influence and interaction. Lumbar muscle strengthening training could prevent and improve muscle atrophy and degeneration.

Risk Factors for Recurrent L5-S1 Disc Herniation After Percutaneous Endoscopic Transforaminal Discectomy: A Retrospective Study.

BACKGROUND This retrospective study aimed to investigate the risk factors associated with the recurrence of L5-S1 disc herniation after percutaneous endoscopic transforaminal discectomy (PETD). MATERIAL AND METHODS There were 484 patients L5-S1 disc herniation who underwent PETD who were divided into the recurrence group (n=46) and the non-recurrence group (n=438). Transforaminal endoscopic approaches included modifications of the Yeung endoscopy spine system (YESS) (the intraforaminal intradiscal approach) and the transforaminal endoscopic spine system (TESSYS) (intraforaminal extradiscal approach). Demographic and clinical characteristics and imaging data were analyzed. The two study groups were compared to determine the factors associated with the recurrence of L5-S1 disc herniation. The patients underwent postoperative follow-up for between one and four years. RESULTS At follow-up, 9.504% of patients (46/484) with the recurrence of L5-S1 disc herniation following PETD when compared with the non-recurrence group showed no significant difference for time to return to work, gender, history of diabetes mellitus, trauma, duration of symptoms, smoking and alcohol history, hypertension, location of disc herniation, transverse process length, intervertebral space height, and pelvic incidence angle (P>0.05). However, age, body mass index (BMI), the degree of disc degeneration, sagittal range of motion, lumbar lordosis angle, and sacral slope were significantly associated with the recurrence of L5-S1 disc herniation following PETD (P<0.05). Logistic regression analysis supported these main associations. CONCLUSIONS The recurrence of L5-S1 disc herniation following PETD was significantly associated with increased age and BMI, more severe disc degeneration, increased sagittal range of motion, increased lumbar lordosis, and sacral slope.

Retroperitoneal laparoscopic resection of adrenal tumor in pregnant woman with cushing's syndrome.

Cushing's syndrome (CS) during pregnancy is rare. It causes the clinical disorder by overproduction of cortisol. Hypercortisolemia in pregnancy can lead to severe complications, both for the mother and the fetus, including spontaneous abortion, perinatal death, prematurity, maternal hypertension, heart failure, diabetes and opportunistic infections. The most common cause of hypercortisolemia in pregnancy is a cortisol-secreting adrenal tumor. Herein we present a 31 year-old female patient, at 20 weeks' gestation, with CS secondary to a left adrenal tumor. A brief review of reported similar cases is included.

ErbB4 Gene Polymorphism Is Associated With the Risk and Prognosis of Congestive Heart Failure in a Northern Han Chinese Population.

BACKGROUND: There has been no research evaluating the association between human Neuregulin (NRG) 1/ErbB2/ErbB4 gene polymorphisms and heart failure risk. METHODS AND RESULTS: Genotyping of 13 single nucleotide polymorphisms (SNPs) in the NRG-1/ErbB2/ErbB4 genes was performed in 569 unrelated heart failure patients and 682 healthy controls from a Northern Han Chinese population with the use of iPlex SNP Genotyping analysis on a Sequenom Massarray System. In the ErbB4 gene, the variants rs10932374 and rs1595064 were associated with reduced risk of heart failure under allelic, recessive and additive genetic models, and the variants rs13003941 and rs1595065 were associated with increased risk of heart failure under allelic, dominant, and additive models. The G-G-C-C-T haplotype of rs10932374-rs13003941-rs1595064-rs1595065-rs3748960 in the ErbB4 gene increased the risk of heart failure (odd ratio 1.35, 95% confidence interval [CI] 1.06-1.70; P = .014). The T variant of rs13003941 was associated with larger left ventricle (dominant model, P = .014; additive model, P = .048), and increased risk of overall death (relative risk [RR] 1.48, 95% CI 1.01-2.18; P = .045) and cardiovascular death (RR 1.56, 95% CI 1.04-2.33; P = .03) after adjusting for age and sex. NRG-1/ErbB2 gene polymorphisms were not associated with heart failure risk or prognosis. CONCLUSION: ErbB4 gene polymorphisms were associated with the risk, severity, and prognosis of heart failure in a Northern Han Chinese population.

[Reference value and clinical correlates of soluble ST2 in healthy community-based Chinese population].

OBJECTIVE: This study was designed to investigate the plasma level of soluble ST2 (sST2) and related influencing factors, and establish its reference value in the healthy community-based population in Beijing area of China. METHODS: We measured plasma sST2 level by enzyme-linked immunosorbent assay between March 2012 and August 2012 in 1 334 healthy subjects in communities, including 597 males and 737 females. Empiric and quantile regression methods were used to determine the reference range of plasma sST2. A multiple linear regression model was established to analyze the factors that might affect the level of plasma sST2. RESULTS: Gender is the most important factor affecting the plasma level of sST2 in healthy people. Plasma level of sST2 is significantly higher in men than in women (P < 0.01). Within each age strata, i.e. < 45, 45-54, 55-64, ≥ 65 years old, the plasma levels of sST2 were significantly higher in men than age-matched female (all P < 0.01). Age, body mass index (BMI), systolic blood pressure, diastolic blood pressure, and smoking did not affect plasma sST2 level. Reference range of sST2 was 5.7-53.5 µg/L for men and 4.4-42.4 µg/L for women (95% nonparametric reference interval). The one-side upper 95th percentile value of sST2 to discriminate the cardiovascular disease from healthy state was 47.2 µg/L for men and 37.2 µg/L for women. CONCLUSIONS: This study established the normal reference range of plasma sST2 in healthy community-based population. The major influencing factor of sST2 level in healthy population is gender.

Ketamine inhibits proliferation of neural stem cell from neonatal rat hippocampus in vitro.

BACKGROUND/AIMS: Ketamine is a widely used anesthetic in obstetric and pediatric anesthesia. In the developing brain, the widespread neuron apoptosis triggered by ketamine has been demonstrated. However, little is known about its effect on neural stem cells (NSCs) function. This study aimed to investigate the effect of ketamine on proliferation of NSCs from neonatal rat hippocampus. METHODS: Neural stem cells were isolated from the hippocampus of Sprague-Dawley rats on postnatal day 3. In dose-response experiments, cultured neural stem cells (NSCs) were exposed to different concentrations of ketamine (0-1000 µM) for 24 hrs. The proliferative activity of NSCs was evaluated by 5-Bromo-2'-deoxyuridine (BrdU) incorporation assay. Apoptosis of neural stem cells were assessed using caspase-3 by western blot. The intracellular Ca(2+) concentration ([Ca(2+)]i) in NSCs was analyzed by flow cytometry. The activation of protein kinase C-α (PKCα) and the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) were measured by western blot analysis. RESULTS: Clinical relevant concentration of ketamine (10, 20 and 50 µM) did not markedly alter the proliferation of NSCs from neonatal rat hippocampus in vitro. However, ketamine (200, 500, 800 and 1000µM) significantly inhibited the proliferation of NSCs and did not affect the expression of caspase-3. Meanwhile, ketamine (200, 500, 800 and 1000µM) also markedly decreased [Ca(2+)]i as well as suppressed PKCα activation and ERK1/2 phosphorylation in NSCs. A combination of subthreshold concentrations of ketamine (100 µM) and Ca(2+) channel blocker verapamil (2.5 µM), PKCα inhibitor chelerythrine (2.5 µM) or ERK1/2 kinase inhibitor PD98059 (5 µM) significantly produced suprathreshold effects on PKCα activation, ERK1/2 phosphorylation and NSC proliferation. CONCLUSION: Ketamine inhibited proliferation of NSCs from neonatal rat hippocampus in vitro. Suppressing Ca(2+)-PKCα-ERK1/2 signaling pathway may be involved in this inhibitory effect of ketamine on NSCs proliferation.

Age and flexors as risk factors for cervical radiculopathy: A new machine learning method.

This study aimed to investigate the risk factors for cervical radiculopathy (CR) along with identifying the relationships between age, cervical flexors, and CR. This was a retrospective cohort study, including 60 patients with CR enrolled between December 2018 and June 2020. In this study, we measured C2 to C7 Cobb angle, disc degeneration, endplate degeneration, and morphology of paraspinal muscles and evaluated the value of predictive methods using receiver operating characteristic curves. Next, we established a diagnostic model for CR using Fisher discriminant model and compared different models by calculating the kappa value. Age and cervical flexor factors were used to construct clinical predictive models, which were further evaluated by C-index, receiver operating characteristic curve, calibration curve, and decision curve analysis. Multivariate analysis showed that age and cervical flexors were potential risk factors for CR, while the diagnostic model indicated that both exerted the best diagnostic effect. The obtained diagnostic equation was as follows: y1 = 0.33 × 1 + 10.302 × 2-24.139; y2 = 0.259 × 1 + 13.605 × 2-32.579. Both the C-index and AUC in the training set reached 0.939. Moreover, the C-index and AUC values in the external validation set reached 0.961. We developed 2 models for predicting CR and also confirmed their validity. Age and cervical flexors were considered potential risk factors for CR. Our noninvasive inspection method could provide clinicians with a more potential diagnostic value to detect CR accurately.

Disparate processing of numerosity and associated continuous magnitudes in rats.

The studies of number sense in different species are severely hampered by the inevitable entanglement of non-numerical attributes inherent in nonsymbolic stimuli representing numerosity, resulting in contrasting theories of numerosity processing. Here, we developed an algorithm and associated analytical methods to generate stimuli that not only minimized the impact of non-numerical magnitudes in numerosity perception but also allowed their quantification. We trained number-naïve rats with these stimuli as sound pulses representing two or three numbers and demonstrated that their numerical discrimination ability mainly relied on numerosity. Also, studying the learning process revealed that rats used numerosity before using magnitudes for choices. This numerical processing could be impaired specifically by silencing the posterior parietal cortex. Furthermore, modeling this capacity by neural networks shed light on the separation of numerosity and magnitudes extraction. Our study helps dissect the relationship between magnitude and numerosity processing, and the above different findings together affirm the independent existence of innate number and magnitudes sense in rats.

HMGB1 Mediates Inflammation-Induced DMT1 Increase and Dopaminergic Neurodegeneration in the Early Stage of Parkinsonism.

Both neuroinflammation and iron accumulation play roles in the pathogenesis of Parkinson's disease (PD). However, whether inflammation induces iron dyshomeostasis in dopaminergic neurons at an early stage of PD, at which no quantifiable dopaminergic neuron loss can be observed, is still unknown. As for the inflammation mediators, although several cytokines have been reported to increase in PD, the functions of these cytokines in the SN are double-edged and controversial. In this study, whether inflammation could induce iron dyshomeostasis in dopaminergic neurons through high mobility group protein B1 (HMGB1) in the early stage of PD is explored. Lipopolysaccharide (LPS), a toxin that primarily activates glia cells, and 6-hydroxydopamine (6-OHDA), the neurotoxin that firstly impacts dopaminergic neurons, were utilized to mimic PD in rats. We found a common and exceedingly early over-production of HMGB1, followed by an increase of divalent metal transporter 1 with iron responsive element (DMT1+) in the dopaminergic neurons before quantifiable neuronal loss. HMGB1 neutralizing antibody suppressed inflammation in the SN, DMT1+ elevation in dopaminergic neurons, and dopaminergic neuronal loss in both LPS and 6-OHDA administration- induced PD models. On the contrary, interleukin-1ß inhibitor diacerein failed to suppress these outcomes induced by 6-OHDA. Our findings not only demonstrate that inflammation could be one of the causes of DMT1+ increase in dopaminergic neurons, but also highlight HMGB1 as a pivotal early mediator of inflammation-induced iron increase and subsequent neurodegeneration, thereby HMGB1 could serve as a potential target for early-stage PD treatment.

The efficacy of thoracolumbar interfascial plane block for lumbar spinal surgeries: a systematic review and meta-analysis.

BACKGROUND: The intent of this meta-analysis was to examine the efficacy of thoracolumbar interfascial plane block (TLIP) for pain control after lumbar spinal surgery. METHODS: Randomized controlled trials (RCTs) published on PubMed, CENTRAL, Scopus, Embase, and Web of Science databases up to February 10, 2023, comparing TLIP with no or sham block or wound infiltration for lumbar spinal surgeries were included. Pain scores, total analgesic consumption, and postoperative nausea and vomiting (PONV) were analyzed. RESULTS: Seventeen RCTs were eligible. Comparing TLIP with no block or sham block, the meta-analysis showed a significant decrease of pain scores at rest and movement at 2 h, 8 h, 12 h, and 24 h. Pooled analysis of four studies showed a significant difference in pain scores at rest between TLIP and wound infiltration group at 8 h but not at 2 h, 12 h, and 24 h. Total analgesic consumption was significantly reduced with TLIP block as compared to no block/sham block and wound infiltration. TLIP block also significantly reduced PONV. GRADE assessment of the evidence was moderate. CONCLUSION: Moderate quality evidence indicates that TLIP blocks are effective in pain control after lumbar spinal surgeries. TLIP reduces pain scores at rest and movement for up to 24 h, reduces total analgesic consumption, and the incidence of PONV. However, evidence of its efficacy as compared to wound infiltration of local anesthetics is scarce. Results should be interpreted with caution owing low to moderate quality of the primary studies and marked heterogeneity.