Bovine lactoferrin inhibits inflammatory response and apoptosis in lipopolysaccharide-induced acute lung injury by targeting the PPAR-γ pathway.

BACKGROUND: Lactoferrin (LF) is an iron-binding multifunctional cationic glycoprotein. Previous studies have demonstrated that LF may be a potential drug for treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In this study, we explored the anti-inflammatory effect and mechanism of bovine lactoferrin (bLF) in ALI using the RNA sequencing (RNA-seq) technology and transcriptome analysis. METHODS AND RESULTS: Based on the differentially expressed genes (DEGs) obtained from RNA-seq of the Lung from mouse model, the bioinformatics workflow was implemented using the BGISEQ-500 platform. The protein-protein interaction (PPI) network was obtained using STRING, and the hub gene was screened using Cytoscape. To verify the results of transcriptome analysis, the effects of bLF on Lipopolysaccharide (LPS)-induced BEAS-2B cells and its anti-reactive oxygen species (ROS), anti-inflammatory, and antiapoptotic effects were studied via Cell Counting Kit-8 (CCK-8) test, active oxygen detection test, ELISA, and western blot assay. Transcriptome analysis revealed that two hub gene modules of DEGs were screened via PPI analysis using the STRING and MCODE plug-ins of Cytoscape. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these core modules are enriched in the PPAR (peroxisome proliferator-activated receptor) and AMPK (AMP-activated protein kinase) signaling pathways. Through cell experiments, our study shows that bLF can inhibit ROS, inflammatory reaction, and LPS-induced BEAS-2B cell apoptosis, which are significantly antagonized by the PPAR-γ inhibitor GW9662. CONCLUSION: This study has suggested that the PPAR-γ pathway is the critical target of bLF in anti-inflammatory reactions and apoptosis of ALI, which provides a direction for further research.

A novel MRI-based Cervical-Endplate Bone Quality score independently predicts cage subsidence after Anterior Cervical Discectomy and Fusion.

INTRODUCTION: Postoperative cage subsidence after Anterior Cervical Discectomy and Fusion (ACDF) often has adverse clinical consequences and is closely related to Bone Mineral Density (BMD). Previous studies have shown that cage subsidence can be better predicted by measuring site-specific bone density. MRI-based Endplate Bone Quality (EBQ) scoring effectively predicts cage subsidence after lumbar interbody fusion. However, there is still a lack of studies on the practical application of EBQ scoring in the cervical spine. PURPOSE: To create a similar MRI-based scoring system for Cervical-EBQ (C-EBQ) and to assess the correlation of the C-EBQ with endplate Computed Tomography (CT)-Hounsfield Units (HU) and the ability of this scoring system to independently predict cage subsidence after ACDF, comparing the predictive ability of the C-EBQ with the Cervical-Vertebral Bone Quality (C-VBQ) score. METHODS: A total of 161 patients who underwent single-level ACDF for degenerative cervical spondylosis at our institution from 2012 to 2022 were included. Demographics, procedure-related data, and radiological data were collected, and Pearson correlation test was used to determine the correlation between C-EBQ and endplate HU values. Cage subsidence was defined as fusion segment height loss of ≥ 3 mm. Receiver operating characteristic analysis and area-under-the-curve values were used to assess the predictive ability of C-EBQ and C-VBQ. A multivariate logistic regression model was developed to identify potential risk factors associated with subsidence. RESULTS: Cage subsidence was present in 65 (40.4%) of 161 patients. The mean C-EBQ score was 1.81 ± 0.35 in the group without subsidence and 2.59 ± 0.58 in the group with subsidence (P < 0.001). Multivariate analysis showed that a higher C-EBQ score was significantly associated with subsidence (OR = 5.700; 95%CI = 3.435-8.193; P < 0.001), was the only independent predictor of cage subsidence after ACDF, had a predictive accuracy of 93.7%, which was superior to the C-VBQ score (89.2%), and was significantly negatively correlated with the endplate HU value (r = -0.58, P < 0.001). CONCLUSIONS: Higher C-EBQ scores were significantly associated with postoperative cage subsidence after ACDF. There was a significant negative correlation between C-EBQ and endplate HU values. The C-EBQ score may be a promising tool for assessing preoperative bone quality and postoperative cage subsidence and is superior to the C-VBQ.

S1 vertebral bone quality score independently predicts pedicle screw loosening following surgery in patients with adult degenerative scoliosis.

BACKGROUND CONTEXT: MRI-based vertebral bone quality (VBQ) score is an effective predictor of pedicle screw loosening after lumbar fusion surgery and has been recognized as a valuable tool for assessing preoperative bone quality. Due to the lateral curvature of lumbar spine of degenerative scoliosis, accurate measurement of VBQ score by conventional measurement methods that capture MRI signal intensity at L1-4 may be limited under certain conditions. To this end, a new simplified S1 VBQ score method has been proposed, which is comparable to the previous L1-4 VBQ score or S1 Hounsfield unit (HU) value, and has high accuracy and reliability. PURPOSE: To evaluate the predictive value of MRI-based S1 VBQ score for pedicle screw loosening following surgery for adult degenerative scoliosis (ADS). STUDY DESIGN/SETTING: Retrospective single-center cohort. PATIENT SAMPLE: We reviewed 92 patients who underwent posterior lumbar interbody fusion (PLIF) with pedicle screw fixation for ADS between January 2017 and January 2020. OUTCOME MEASURES: Association between S1 VBQ score and pedicle screw loosening following surgery for ADS. METHODS: We retrospectively reviewed the records of all patients who performed PLIF between January 2017 and January 2020. The clear zone around pedicle screws≥1 mm can be identified as screw loosening. The S1 VBQ score is calculated from the S1 central-based non-contrast T1-weighted magnetic resonance imaging (MRI). The signal intensity (SI) of the cerebrospinal fluid (CSF) was then measured using ROI placed at the L3 level to normalize the results. Multivariate logistic regression analysis was performed to identify independent risk factors for screw loosening. Then, constructed a receiver operating characteristic (ROC) curve and determined the threshold (cut-off) of VBQ score with high sensitivity and specificity based on Youden Index. RESULTS: A total of 92 patients were included, including 34 males and 58 females. The mean age of the patients was 61.23±1.23 years old. At 1-year follow-up, the screw loosening rate was 56.5% (52/92). The age and levels of fixation were higher in the loosening group than in the non-loosening group (p=.036, p=.025). Patients in the loosening group had a greater VBQ score compared to patients in the non-loosening group (3.31±0.41 vs 3.01±0.28, p=.001). Multivariate logistic regression analysis showed that advanced age (OR, 1.090; 95% CI 1.005-1.183; p=.039) and higher VBQ score (OR, 5.778; 95% CI 2.889-16.177; p=.001) were independent risk factors for screw loosening. In addition, the ROC curve were created to assess the role of VBQ score as predictors of screw loosening with a diagnostic accuracy of 74.6% (95% CI 64.2%-85.1%).The most suitable threshold for the VBQ score as determined by the Youden Index was 3.175 (sensitivity: 76.0%, specificity: 83.3%). CONCLUSIONS: Higher S1 VBQ score was significantly associated with pedicle screw loosening following surgery for ADS. The S1 VBQ score can be used as an effective preoperative predictor, which has the potential clinical application.

Long-term Outcome of Isobar TTL System for the Treatment of Lumbar Degenerative Disc Diseases.

OBJECTIVE: The Isobar TTL dynamic fixation system has demonstrated favorable outcomes in the short-term treatment of lumbar degenerative disc diseases (LDDs). However, there is a paucity of extensive research on the long-term effects of this system on LDDs. This study aimed to evaluate the long-term clinical and radiological outcomes of patients with LDDs who underwent treatment utilizing the Isobar TTL dynamic fixation system. METHODS: The study analyzed the outcomes of 40 patients with LDDs who underwent posterior lumbar decompression and received single-segment Isobar TTL dynamic internal fixation at our hospital between June 2010 and December 2016. The evaluation of clinical therapeutic effect involved assessing postoperative pain levels using the visual analogue scale (VAS) and Oswestry disability index (ODI), both before surgery, 3 months after, and the final follow-up. To determine the preservation of functional motion in dynamically stable segments, we measured the range of motion (ROM) and disc height of stabilized and adjacent segments preoperatively and during the final follow-up. Additionally, we investigated the occurrence of adjacent segment degeneration (ASD). RESULTS: Forty patients were evaluated, with an average age of 44.65 years and an average follow-up period of 79.37 months. Fourteen patients belonged to the spondylolisthesis group, while the remaining 26 were categorized under the stenosis or herniated disc group. The preoperative ROM of the stabilized segment exhibited a significant reduction from 8.15° ± 2.77° to 5.00° ± 1.82° at the final follow-up (p < 0.001). In contrast, there was a slight elevation in the ROM of the adjacent segment during the final follow-up, increasing from 7.68° ± 2.25° before surgery to 9.36° ± 1.98° (p < 0.001). The intervertebral space height (IH) in the stabilized segment exhibited a significant increase from 10.56 ± 1.99 mm before surgery to 11.39 ± 1.90 mm at the one-week postoperative follow-up (p < 0.001). Conversely, there was a notable decrease in the IH of the adjacent segment from 11.09 ± 1.82 mm preoperatively to 10.86 ± 1.79 mm at the one-week follow-up after surgery (p < 0.001). The incidence of ASD was 15% (6/40) after an average follow-up period of 79.37 months, with a rate of 15.38% (4/26) in the stenosis or herniated disc group and 14.29% (2/14) in the spondylolisthesis group; however, no statistically significant difference was observed in the occurrence of ASD among these groups (p > 0.05). CONCLUSION: The Isobar TTL dynamic fixation system is an effective treatment for LDDs, improving pain relief, quality of life (QoL) and maintaining stabilized segmental motion. It has demonstrated excellent long-term clinical and radiographic results.

Health-related Quality of Life (HRQOL) Outcomes of Selective/Nonselective Thoracic Fusion for Lenke 1C Adolescent Idiopathic Scoliosis (AIS) Patients with a Minimum 4-year Follow-up.

OBJECTIVE: Both the selective thoracic fusion (STF) and nonselective thoracic fusion (NSTF) are treatments for Lenke 1C adolescent idiopathic scoliosis (AIS). To date, the impacts of the two surgical strategies on patients' long-term quality of life remain unclear. Therefore, the purpose of this study was to explore the long-term effects of STF/NSTF on the quality of life in Lenke 1C AIS patients through a 4-10-year follow-up. METHODS: From January 2011 to April 2018, according to the inclusion and exclusion criteria, a retrospective single-center study of 75 surgical patients with Lenke 1C curves was performed (n = 75). They all underwent posterior fusion, and patients were divided into the selective thoracic fusion (STF) group (n = 42) and the nonselective thoracic fusion (NSTF) group (n = 33) based on their surgical approach. All participants received the survey of the visual analogue scale (VAS), SRS30, SF12, and Oswestry disability index (ODI) scales. Patients' gender, age, body mass index (BMI), surgical approach (STF/NSTF), surgical segments (UIV and LIV), follow-up time, complications, preoperative, postoperative, and last follow-up Cobb angles, and health-related quality of life (HRQOL) outcomes were collected, and analyzed through the Shapiro-Wilks test, Wilcoxon rank-sum test, t-test, and χ2 test. RESULTS: The mean follow-up of the entire cohort was 73 ± 5.6 months. The lumbar Cobb angle in the STF group improved from 31.8 ± 6.5° to 11.5 ± 5.1° after the operation and 10.3 ± 6.9° at the last follow-up. The postoperative correction rate of the lumbar curve was 63.8%, which increased to 67.7% at the last follow-up. In the NSTF group, the lumbar Cobb angle improved from 34.3 ± 11.3° to 4.3 ± 3.7° after the operation, and was 5.1 ± 3.1° at the last follow-up. The postoperative correction rate of the lumbar curve was 87.4%, and 85.1% at the last follow-up. At the last follow-up, the STF group had higher overall HRQOL scores than the NSTF group, and there were statistically differences between the different groups (STF/NSTF) in SRS-30-Mental health (p = 0.03), SRS-30-Satisfaction with management (p = 0.02), SRS-30-Pain (p = 0.03), ODI (p = 0.01), SF-12 PCS (p = 0.03), VAS back pain (p = 0.005) and VAS leg pain (p = 0.001). No statistically differences were found in SF12 MCS, SRS-30-Self-image/Appearance and SRS-30 Function/activity. CONCLUSION: After 4-10 years of follow-up, we found that the STF group achieved satisfactory correction results, and compared with the NSTF group, their overall HRQOL scores were higher, especially in terms of pain and satisfaction, where the STF group shows a significant advantage.

The Quality of Life of the Patients with Thoracic Ossification of the Ligamentum Flavum after Surgery Using EQ-5D-5L.

OBJECTIVE: There is a lack of studies on the quality of life (QoL) after posterior laminectomy in patients with thoracic ossification of the ligamentum flavum (TOLF), and risk factors associated with poor prognosis remain controversial. Therefore, the present study was conducted to illustrate the QoL for TOLF patients after surgery and determine its relationship with their demographic, surgery-related, clinical characteristics and imaging data. METHODS: One hundred and eighteen patients diagnosed with thoracic myelopathy because of TOLF were enrolled in this retrospective study. They all underwent posterior decompressive laminectomy from August 2010 to January 2022. The QoL was evaluated based on the EQ-5D-5L. Collecting gender, age, number of operations, compressed segments, Frankel grade, complications, body mass index (BMI), symptoms and duration, modified Japanese Orthopaedic Association (mJOA) score (preoperative), follow-up time and type of ossification, increased signal on Sagittal T2-weighted Images (ISST2I), occupancy rate and analyzing by Mann-Whitney U-test, Kruskal-Wallis test, the χ2 -test, and logistic regression tests. RESULTS: Average follow-up 70.8 months (18-149), the mean age was 59.74 ± 9.81 years and the mean score for the QoL based on the EQ-5D-5 L and visual analogue scale (VAS) score were 0.71 ± 0.28 and 78.88 ± 10.21 at the final follow-up. Moderate and severe problems were found in the pain/discomfort in 22.0% of the patients. These mobility and usual activities numbers were slightly higher (24.6% and 30.4%, respectively). The mean scores for QoL and VAS were significantly higher in patients with mild and moderate neurological impairment, normal BMI, <60 years of age, no dural tears, symptom relief at hospital discharge, unilateral and bilateral ossification on axial CT scan, ≤ 50% spinal canal occupancy on CT and MRI, and none or fuzzy on ISST2I. CONCLUSION: QoL after posterior laminectomy in TOLF patients is generally satisfactory compared to preoperative levels. Preoperative mJOA score, Age, comorbid diabetes, the major symptom is activity limitation, BMI, ISST2I, Intraoperative dural tears and spinal canal occupancy rate correlate significantly with the corresponding dimensions and are predictive. Age, spinal canal occupancy rate, ISST2I, preoperative mJOA score, BMI are significantly associated with and have predictive value for overall postoperative QoL.

Preoperative albumin-to-globulin ratio and prognostic nutritional index predict the prognosis of colorectal cancer: a retrospective study.

The immunonutritional status has important effects on outcomes for cancer patients. Albumin-to-globulin ratio (AGR) and the prognostic nutrition index (PNI) are often used to assess the immunonutritional status of cancer patients. However, the clinical significance of these factors in colorectal cancer (CRC) remains unclear. We aimed to evaluate the clinical significance of the AGR and PNI in CRC. We reviewed the clinical data of 511 patients with CRC in two hospitals. Data from one institution was used as the training cohort. The optimal cutoff values for AGR and PNI in the training cohort were 1.4 and 48.65, respectively. Patients in both the low AGR and low PNI groups had poor overall survival (OS) and progression-free survival (PFS), while those in the low AGR-low PNI group had the lowest OS and PFS. Multivariate analysis revealed that preoperative AGR, preoperative PNI, gross type, and TNM stage were independent prognostic factors influencing OS in patients with CRC. Preoperative AGR, preoperative PNI, and TNM stage were independently associated with PFS in patients with CRC. According to the results of multivariate analysis in the training cohort, we developed the nomograms for OS and PFS and performed internal and external validation, which showed good prediction ability of the nomograms. In conclusion, preoperative AGR and PNI can be used as effective indicators to predict survival for patients with CRC. AGR and PNI may help develop effective adjuvant-therapy schedules.

Pan-immune-inflammation value is associated with the clinical stage of colorectal cancer.

Objective: We investigated the clinical significance of preoperative pan-immune-inflammation value (PIV) in patients with colorectal cancer (CRC). Methods: In this retrospective study, 366 cases who underwent surgery for CRC were enrolled. Their clinical data were collected. PIV was calculated with the formula PIV = [neutrophil count (109/L)× platelet count (109/L) × monocyte count (109/L) /lymphocyte count (109/L). Patients were divided into high PIV (> median PIV) and low PIV (< median PIV) groups. The relationship between PIV and clinicopathological features of CRC was investigated. Receiver operating characteristic (ROC) curve was plotted to indicate the value of immune-inflammatory biomarkers (IIBs) in predicting the TNM stage of CRC, and the area under the curve (AUC) was calculated to evaluate the actual clinical value of IIBs. AUC > 0.5 and closer to 1 indicated the better predictive efficacy. The influencing factors of PIV in CRC were analyzed. Results: We found that PIV was positively correlated with tumor size (r = 0.300, p < 0.05), carcinoembryonic antigen (CEA) (r = 0.214, p < 0.05) and carbohydrate antigen 125 (CA-125) (r = 0.249, p < 0.05), but negatively correlated with albumin (Alb) (r = -0.242, p < 0.05). PIV was significantly different in patients with different tumor locations (left or right), surgical methods (laparotomy versus laparoscopic surgery) (p < 0.05), and patients with different pathological T stages, N-stage and TNM stages (p < 0.05). ROC curve analysis of IIBs showed the AUC of PIV was greater than other markers when combined with CEA or carbohydrate antigen 19-9 (CA19-9). Multivariate regression analysis identified T stage, CEA, Alb, and tumor size as the independent influential factors of PIV in CRC. Conclusion: PIV is associated with the tumor stage in patients with CRC, which may be useful in preoperative assessment of CRC.

[Visual analysis of influenza treated by traditional Chinese medicine based on CiteSpace].

OBJECTIVE: To analyze the research status, research hotspots and frontier trends of traditional Chinese medicine (TCM) in the treatment of influenza in the past 20 years through the knowledge graph, so as to provide reference basis for further research. METHODS: The related literatures of TCM in the treatment of influenza were collected in China National Knowledge Infrastructure (CNKI) from 2000 to 2019. The relevant graphs of authors, research institutions and key words were drawn by CiteSpace 5.6, the distribution and cooperation of main research forces in this field were analyzed, and the research frontiers and hot spot information in this field were discussed. RESULTS: A total of 3 048 related literatures were obtained, involving 949 authors and 242 research institutions. The analysis of the number of articles showed that the volume of articles related to the treatment of influenza with TCM fluctuated greatly in the past 20 years, which was obviously affected by the sudden hot spots around 2010, but showed an overall upward trend, with an average annual volume of about 152 articles. The analysis of the author's cooperation map showed that a total of 77 core authors had published more than 5 articles, accounting for only 8.1% of all authors, and 5 authors had published more than 30 articles. Five major teams had been formed with Gu Ligang, Liu Qingquan, Lu Fangguo, Cui Xiaolan and Zhang Fengxue as the core. The analysis of the cooperation map of research institutions showed that the cooperation among institutions was not good, and only the scientific research institutes in Beijing and Guangzhou had formed a closely related cooperation network. The keyword co-occurrence map showed that 8 keywords appeared more than 100 times, especially ultra-high-frequency keywords, influenza virus ranked first (n = 518). There were 14 key nodes, such as influenza virus, TCM treatment, viral pneumonia and so on, which supported the current research field of TCM in the treatment of influenza. Fourteen clusters were formed to classify the current research hotspots, including the nomenclature of influenza, virus type, TCM treatment, western medicine knowledge, etc., and the map showed that the clustering was reasonable and the structure was significant. Timeline graph showed that parainfluenza virus, virus disease, pharmacodynamics, heat-clearing and detoxifying drugs, bacteriostasis and experimental research had all been studied for more than 8 years, revealing the research hotspots and trends of TCM in the treatment of influenza. CONCLUSIONS: The overall research related to the treatment of influenza with TCM is relatively perfect. In the future, the close cooperation among authors and institutions should be strengthened. The molecular mechanism research, clinical and animal trials of TCM should be further studied, so as to improve the research system of TCM treatment of influenza.

Zacopride Exerts an Antiarrhythmic Effect by Specifically Stimulating the Cardiac Inward Rectifier Potassium Current in Rabbits: Exploration of a New Antiarrhythmic Strategy.

BACKGROUND: Zacopride, a potent antagonist of 5-HT3 receptors and an agonist of 5-HT4 receptors, is a gastrointestinal prokinetic agent. In a previous study, we discovered that zacopride selectively stimulated the inward rectifier potassium current (IK1) in the rat and that agonizing IK1 prevented or eliminated aconitine-induced arrhythmias in rats. OBJECTIVE: Our aims were to confirm that the antiarrhythmic effects of zacopride are mediated by selectively enhancing IK1 in rabbits. METHODS: The effects of zacopride on the function of the main ion channels were investigated using a whole-cell patch-clamp technique in rabbits. Effects of zacopride on cardiac arrhythmias were also explored experimentally both in vivo and in vitro. RESULTS: Zacopride moderately enhanced cardiac IK1 but had no apparent action on voltage-gated sodium current (INa), L- type calcium current (ICa-L), sodium-calcium exchange current (INa/Ca), transient outward potassium current (Ito), or delayed rectifier potassium current (IK) in rabbits. Zacopride also had a marked antiarrhythmic effect in vivo and in vitro. We proved that the resting membrane potential (RMP) was hyperpolarized in the presence of 1 µmol/L zacopride, and the action potential duration (APD) at 90% repolarization (APD90) was shortened by zacopride (0.1-10 µmol/L) in a concentration- dependent manner. Furthermore, zacopride at 1 µmol/L significantly decreased the incidence of drug-induced early afterdepolarization (EAD) in rabbit ventricular myocytes. CONCLUSION: Zacopride is a selective agonist of rabbit cardiac IK1 and that IK1 enhancement exerts potential antiarrhythmic effects.

[Yield loss model and yield loss mechanism of high-yielding summer maize infected by Physoderma maydis].

A total of 21 different disease-grading summer maize groups were formed by fixed-point natural infection of maize brown spot in the field, and mass loss estimation models of single ear mass and 100-grain mass were constructed by stepwise regression with DPS software. The mass loss estimation models of single ear and 100-grain were Y = -4.012 + 0.377X1 - 0.228X2 + 0.694X3 - 0.144X4 and Y = -4.536 + 0.173X1 + 0.188X2 + 0.248X3 - 0.034X4, respectively, where Y was yield loss rate, X1 was the disease index at flowering stage, X2 was the disease index at pollination stage, X3 was the disease index at filling stage, and X4 was the disease index at dough stage. The measured relationships between the disease indices at different growth stages and the mass loss for single ear and 100-grain coincided well with the modeling results. Maize brown spot directly affected the net photosynthetic rate of ear height leaf and the activities of RuBP carboxylase and PEP carboxylase. The higher the disease-grade, the lower the net photosynthetic rate and the activities of the two enzymes were.