Intraoperative capsule protection can reduce the potential risk of adjacent segment degeneration acceleration biomechanically: an in silico study.

BACKGROUND: The capsule of the zygapophyseal joint plays an important role in motion segmental stability maintenance. Iatrogenic capsule injury is a common phenomenon in posterior approach lumbar interbody fusion operations, but whether this procedure will cause a higher risk of adjacent segment degeneration acceleration biomechanically has yet to be identified. METHODS: Posterior lumbar interbody fusion (PLIF) with different grades of iatrogenic capsule injury was simulated in our calibrated and validated numerical model. By adjusting the cross-sectional area of the capsule, different grades of capsule injury were simulated. The stress distribution on the cranial motion segment was computed under different loading conditions to judge the potential risk of adjacent segment degeneration acceleration. RESULTS: Compared to the PLIF model with an intact capsule, a stepwise increase in the stress value on the cranial motion segment can be observed with a step decrease in capsule cross-sectional areas. Moreover, compared to the difference between models with intact and slightly injured capsules, the difference in stress values was more evident between models with slight and severe iatrogenic capsule injury. CONCLUSION: Intraoperative capsule protection can reduce the potential risk of adjacent segment degeneration acceleration biomechanically, and iatrogenic capsule damage on the cranial motion segment should be reduced to optimize patients' long-term prognosis.

Anterior direct decompression significantly relieves spinal cord high signal in patients with ossification of the posterior longitudinal ligament: a case-control study.

BACKGROUND: In patients with cervical spondylotic myelopathy caused by ossification of the posterior longitudinal ligament, high cord signal (HCS) is frequently observed. However, limited research has investigated the variations in HCS improvement resulting from different surgical approaches. This study aims to explore the potential relationship between the choice of surgical approach and the postoperative improvement of intramedullary high signal in ossification of the posterior longitudinal ligament (OPLL) patients. METHODS: We extensively reviewed the patients' medical records, based on which demographic information such as gender, age, and body mass index (BMI) were recorded, and assessed the severity of the patients' neurological status preoperatively and postoperatively by using the Japanese Orthopedic Association score (JOAs), focusing on consecutive preoperative and postoperative Magnetic resonance imaging (MRI) T2WI measurements, to study the statistical correlation between the improvement of HCS and the choice of surgical approach. RESULTS: There were no significant differences in demographic, imaging parameters, and clinical symptoms between patients undergoing anterior and posterior surgery (p > 0.05, Table 1). However, both improvement in JOAs (Recovery2) and improvement in HCS (CR2) were significantly better in the anterior surgery group two years after surgery (p < 0.05, Table 1). Multifactorial logistic regression analysis revealed that posterior surgery and higher preoperative signal change ratio (SCR) were identified as risk factors for poor HCS improvement at the two-year postoperative period (p < 0.05, Table 2). Table 1 Differences in demographic, imaging parameters, and clinical symptoms in patients with anterior and posterior approach Anterior approach Posterior approach P-Values Demographic data  Sex (male/female) 10/12 6/17 0.175  Age 58.59 ± 5.68 61.43 ± 9.04 0.215  Hypertension 14/8 14/9 0.848  Diabetes 16/6 19/4 0.425  BMI 25.58 ± 4.72 26.95 ± 4.58 0.331  Smoking history 19/3 16/7 0.175 Preoperative measured imaging parameters  Preoperative SCR 1.615 ± 0.369 1.668 ± 0.356 0.623  CR1 0.106 ± 0.125 0.011 ± 0.246 0.08  CNR 0.33 ± 0.073 0.368 ± 0.096 0.15  C2-7 Cobb angle 8.977 ± 10.818 13.862 ± 13.191 0.182  SVA 15.212 ± 8.024 17.46 ± 8.91 0.38  mK-line INT 3.694 ± 3.291 4.527 ± 2.227 0.323 Imaging follow-up  6 months postoperative SCR 1.45 ± 0.44 1.63 ± 0.397 0.149  2 years postoperative SCR 1.26 ± 0.19 1.65 ± 0.35 0.000**  CR2 0.219 ± 0.14 - 0.012 ± 0.237 0.000** Clinical symptoms  Preoperative JOAs 10.64 ± 1.59 10.83 ± 1.47 0.679  6 months postoperative JOAs 11.82 ± 1.37 11.65 ± 1.4 0.69  2 years postoperative JOAs 14.18 ± 1.01 12.52 ± 2.06 0.001**  Recovery1 0.181 ± 0.109 0.128 ± 0.154 0.189  Recovery2 0.536 ± 0.178 0.278 ± 0.307 0.001** *, statistical significance (p < 0.05). **, statistical significance (p < 0.01) BMI = body mass index. SCR = the signal change ratio between the localized high signal and normal spinal cord signal at the C7-T1 levels. CR1 = the regression of high cord signals at 6 months postoperatively (i.e., CR1 = (Preoperative SCR-SCR at 6 months postoperatively)/ Preoperative SCR). CR2 = the regression of high cord signal at 2 years postoperatively (i.e., CR2 = (Preoperative SCR-SCR at 2 years postoperatively)/ Preoperative SCR). CNR = canal narrowing ratio. SVA = sagittal vertical axis. mK-line INT = modified K-line interval. JOAs = Japanese Orthopedic Association score. Recovery1 = degree of JOAs recovery at 6 months postoperatively (i.e., Recover1 = (JOAs at 6 months postoperatively-Preoperative JOAs)/ (17- Preoperative JOAs)). Recovery2 = degree of JOAs recovery at 2 years postoperatively (i.e., Recover2 = (JOAs at 2 years postoperatively-Preoperative JOAs)/ (17-Preoperative JOAs)) Table 2 Linear regression analyses for lower CR2 values 95% CI P value Uni-variable analyses Demographic data  Sex (male/female) - 0.01 0.221 0.924  Age - 0.015 0.003 0.195  Hypertension - 0.071 0.204 0.334  Diabetes - 0.195 0.135 0.716  BMI - 0.375 0.422 0.905  Smoking history - 0.249 0.077 0.295  Surgical approach - 0.349 - 0.113 0.000# Preoperative measured imaging parameters  C2-7 Cobb angle - 0.009 0.002 0.185  SVA - 0.008 0.008 0.995  mK-line INT - 0.043 0.005 0.122  Preoperative SCR 0.092 0.445 0.004#  CR1 0.156 0.784 0.004#  CNR - 0.76 0.844 0.918 Multi-variable analyses  Surgical approach - 0.321 - 0.118 0.000**  Preoperative SCR 0.127 0.41 0.000**  CR1 - 0.018 0.501 0.067 #, variables that achieved a significance level of p < 0.1 in the univariate analysis *statistical significance (p < 0.05). **statistical significance (p < 0.01) BMI = body mass index. SCR = the signal change ratio between the localized high signal and normal spinal cord signal at the C7-T1 levels. CR1 = the regression of high cord signals at 6 months postoperatively (i.e., CR1 = (Preoperative SCR-SCR at 6 months postoperatively)/ Preoperative SCR). CR2 = the regression of high cord signal at 2 years postoperatively (i.e., CR2 = (Preoperative SCR-SCR at 2 years postoperatively)/ Preoperative SCR). CNR = canal narrowing ratio. SVA = sagittal vertical axis. mK-line INT = modified K-line interval CONCLUSIONS: For patients with OPLL-induced cervical spondylotic myelopathy and intramedullary high signal, anterior removal of the ossified posterior longitudinal ligament and direct decompression offer a greater potential for regression of intramedullary high signal. At the same time, this anterior surgical strategy improves clinical neurologic function better than indirect decompression in the posterior approach.

Bibliometric analysis on the progress of immunotherapy in renal cell carcinoma from 2003-2022.

The incidence and mortality rates of renal cell carcinoma (RCC) have been increasing annually due to obesity and environmental pollution. Although immunotherapy of RCC has been studied for decades, few comprehensive bibliometric analyses exist on the treatment. Therefore, the purpose of this bibliometric analysis was to identify scientific achievements of the global research on RCC immunotherapy from 2003 to 2022 and discuss research trends. Data were retrieved from the Clarivate Web of Science Core Collection using a set retrieval strategy. The Bibliometrics tool Cite Space 6.2 R2 (Chaomei Chen, Drexel University) was used to analyze 4,841 articles. The USA had the most publications (n = 1,864); Harvard University was identified as the leading institution (n = 264); and Dr. Toni K. Choueiri, was the most productive researcher in the field (n = 55). Keyword analysis showed that nivolumab, immune checkpoint inhibitors, tumor microenvironment, everolimus, cabozantinib, resistance, pembrolizumab and ipilimumab were the main hotspots and frontier directions of RCC. By analyzing the results of bibliometrics, national and international researchers can better understand the current research status of RCC immunotherapy and identify new directions for future research. However, the analysis also identified pockets of insularity, highlighting a need for greater collaboration and cooperation among researchers to advance the field of RCC immunotherapy.

Metabolic reprogramming of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a malignancy that exhibits metabolic reprogramming as a result of genetic mutations. This reprogramming accommodates the energy and anabolic needs of the cancer cells, leading to changes in glucose, lipid, and bio-oxidative metabolism, and in some cases, the amino acid metabolism. Recent evidence suggests that ccRCC may be classified as a metabolic disease. The metabolic alterations provide potential targets for novel therapeutic interventions or biomarkers for monitoring tumor growth and prognosis. This literature review summarized recent discoveries of metabolic alterations in ccRCC, including changes in glucose, lipid, and amino acid metabolism. The development of metabolic drugs targeting these metabolic pathways was also discussed, such as HIF-2α inhibitors, fatty acid synthase (FAS) inhibitors, glutaminase (GLS) inhibitors, indoleamine 2,3-dioxygenase (IDO) inhibitors, and arginine depletion. Future trends in drug development are proposed, including the use of combination therapies and personalized medicine approaches. In conclusion, this review provides a comprehensive overview of the metabolic alterations in ccRCC and highlights the potential for developing new treatments for this disease.

Identification of miR-192 target genes in porcine endometrial epithelial cells based on miRNA pull-down.

INTRODUCTION: MicroRNAs (miRNAs)-a class of small endogenous non-coding RNAs-are widely involved in post-transcriptional gene regulation of numerous physiological processes. High-throughput sequencing revealed that the miR-192 expression level appeared to be significantly higher in the blood exosomes of sows at early gestation than that in non-pregnant sows. Furthermore, miR-192 was hypothesized to have a regulatory role in embryo implantation; however, the target genes involved in exerting the regulatory function of miR-192 required further elucidation. METHODS: In the present study, potential target genes of miR-192 in porcine endometrial epithelial cells (PEECs) were identified through biotin-labeled miRNA pull-down; functional and pathway enrichment analysis was performed via gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Bioinformatic analyses were concurrently used to predict the potential target genes associated with sow embryo implantation. In addition, double luciferase reporter vectors, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and Western blot were performed to verify the targeting and regulatory roles of the abovementioned target genes. RESULTS: A total of 1688 differentially expressed mRNAs were identified via miRNA pull-down. Through RT-qPCR, the accuracy of the sequencing data was verified. In the bioinformatics analysis, potential target genes of miR-192 appeared to form a dense inter-regulatory network and regulated multiple signaling pathways, such as metabolic pathways and the PI3K-Akt, MAPKs, and mTOR signaling pathways, that are relevant to the mammalian embryo implantation process. In addition, CSK (C-terminal Src kinase) and YY1 (Yin-Yang-1) were predicted to be potential candidates, and we validated that miR-192 directly targets and suppresses the expression of the CSK and YY1 genes. CONCLUSION: We screened 1688 potential target genes of miR-192 were screened, and CSK and YY1 were identified as miR-192 target genes. The outcomes of the present study provide novel insights into the regulatory mechanism of porcine embryo implantation and the identification of miRNA target genes.

Uniaxial MEMS-based 3D reconstruction using pixel refinement.

A uniaxial micro-electro-mechanical systems (MEMS) micro-vibration mirror can be used to construct a new type of fringe projection profilometry (FPP) system. In FPP system calibration, some pixels may be calibrated worse than other pixels due to various error sources, which will affect the final reconstruction accuracy. In addition, there are some difficulties in calibrating the MEMS-based system because a projector using the uniaxial vibration mirror does not have focusing optics and can only project unidirectional fringes. In this paper, we developed an FPP system using a uniaxial MEMS micro-vibration mirror. To solve the calibration problems, we propose a calibration model suitable for the MEMS-based system and a pixel refinement method. These pixels with relatively large calibration errors are called outlier-pixels, which will significantly increase the error of the following 3D mapping. Therefore, the pixel refinement method classifies all pixels based on a frequency distribution histogram of calibration errors during calibration and prevents outlier-pixels from participating in the following 3D mapping. The experimental results show that the proposed method can improve the accuracy of 3D reconstruction, and the feasibility of the self-developed system is verified.

Peltier thermoelectric cooler improves both the signal-to-noise ratio and warm-up time of high-power LED induced fluorescence detector and application to aflatoxins.

High-power LED induced fluorescence detector (HP-LED-IF) suffers from problems of large noise and poor baseline stability. In this study, a Peltier thermoelectric cooler (PTC) was utilized to stabilize the HP-LED junction temperature of a HP-LED-IF to reduce the baseline noise for the first time. Compared with traditional fan cooling, the signal-to-noise ratio was improved to 3.8 times, and the warm-up time was shortened by 64.4%. For application, a 365/450 nm HP-LED-IF was constructed and coupled with HPLC for detection of aflatoxins. The limits of detections (LODs, 3 times peak-to-peak noise) for aflatoxin G2 and B2 were 1.2 and 1.0 pg/mL, respectively. In-situ photochemical derivatization reaction of G1 and B1 in 28 µL detection cell within 2.1 s flow time was found surprisingly for the first time, which enhanced the fluorescence signal by about 10 times. The LODs for aflatoxin G1 and B1 were 3.4 and 2.4 pg/mL, respectively. These LODs are among the lowest values that have been reported. This study provides a key technique to improve both the signal-to-noise ratio and warm-up time of HP-LED-IFs and a novel in-situ derivatization method for aflatoxins G1 and B1.

Identification of differentially expressed miRNAs in serum extracellular vesicles (EVs) of Kazakh sheep at early pregnancy.

MiRNAs-containing extracellular vesicles (EVs) possess the unique function of mediating intercellular communication and participating in many biological processes such as post-transcriptional gene regulation of embryo implantation and placental development. In the present study, Illumina small-RNA sequencing was used to identify differentially expressed (DE) miRNAs in serum EVs of pregnant (P) and non-pregnant (NP) Kazakh sheep at Day 17 from mating. The specifically and differentially expressed miRNAs at early pregnancy in sheep were verified by using RT-PCR. The target genes of DE miRNAs were predicted by bioinformatics software, and the functional and pathway enrichment analysis was performed on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. A total of 562 miRNAs (210 novel miRNAs) were identified by sequencing, of which 57 miRNAs were differentially expressed, 49 were up-regulated, 8 were down-regulated and 22 novel miRNAs were specifically expressed in the pregnant sheep. Eight highly expressed known miRNA (miR-378-3p, miR-320-3p, miR-22-3p, let-7b, miR-423-3p, miR-221, miR-296-3p, miR-147-3p) in pregnant group were down-regulated in the control group. miRNAs-containing pregnancy-related terms and regulatory pathways regulation were enriched using both GO and KEGG analyses. Moreover, we also envisioned a miRNA-mRNA interaction network to understand the function of miRNAs involved in the early pregnancy serum regulatory network. The results of RT-PCR verification confirmed the reliability of small-RNA sequencing. Among them, miR-22-3p and miR-378-3p were significantly differentially expressed (DE) between pregnant sheep and non-pregnant group (p <  0.01). The site at which oar-miR-22-3p binds MAPK3 was determined with a dual-luciferase system. This is the first integrated analysis of the expression profiles of EV-miRNAs and their targets during early pregnancy in ewes. These data identify key miRNAs that influence the implantation of sheep in the early stage of pregnancy, and provide theoretical basis for further molecular regulatory mechanisms research.

Recombinant H7 hemagglutinin expressed in glycoengineered Pichia pastoris forms nanoparticles that protect mice from challenge with H7N9 influenza virus.

Cases of H7N9 human infection caused by an avian-origin H7N9 virus emerged in eastern China in 2013, leading to the urgent requirement of developing an effective vaccine to reduce its pandemic potential. In this report, the full-length recombinant H7 protein (rH7) of A/Hangzhou/1/2013 (H7N9) virus was expressed by a glycoengineered Pichia pastoris system. The rH7 protein underwent complex glycosylation modifications and polymerized to nanoparticles of 30-50 nm in diameter. Recombinant H7 (1.9 µg) elicited a > 1:40 hemagglutination inhibition titer, and 3.75 µg rH7 protected 100% of the mice in the mice challenge model with 10-fold 50% lethal dose of the A/Shanghai/2/2013 (H7N9) rat lung-adapted strain. In conclusion, rH7 produced by the glycoengineered P. pastoris can be used for vaccination against the H7N9 virus, and provides an effective platform for the rapid production of future influenza vaccines.