Differentially Expressed Proteins in the Serum of Elderly Patients Who Experienced Perioperative Neurocognitive Disorders Following Transurethral Resection of the Prostate.

OBJECTIVE: Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency surgical procedures. The etiologies are not fully understood. This study endeavored to investigate novel targets and prediction methods for the occurrence of PND. METHODS: A total of 229 elderly patients diagnosed with prostatic hyperplasia who underwent transurethral resection of the prostate (TURP) combined with spinal cord and epidural analgesia were included in this study. The patients were divided into two groups, the PND group and non-PND group, based on the Z-score method. According to the principle of maintaining consistency between preoperative and intraoperative conditions, three patients from each group were randomly chosen for serum sample collection. isobaric tags for relative and absolute quantification (iTRAQ) proteomics technology was employed to analyze and identify the proteins that exhibited differential expression in the serum samples from the two groups. Bioinformatics analysis was performed on the proteins that exhibited differential expression. RESULTS: Among the 1101 serum proteins analyzed in the PND and non-PND groups, eight differentially expressed proteins were identified in PND patients. Of these, six proteins showed up-regulation, while two proteins showed down-regulation. Further bioinformatics analysis of the proteins that exhibited differential expression revealed their predominant involvement in cellular biological processes, cellular component formation, as well as endocytosis and phagocytosis Additionally, these proteins were found to possess the RING domain of E3 ubiquitin ligase. CONCLUSION: The iTRAQ proteomics technique was employed to analyze the variation in protein expression in serum samples from patients with PND and those without PND. This study successfully identified eight proteins that exhibited differential expression levels between the two groups. Bioinformatics analysis indicates that proteins exhibiting differential expression are primarily implicated in the biological processes associated with microtubules. Investigating the microtubule formation process as it relates to neuroplasticity and synaptic formation may offer valuable insights for enhancing our comprehension and potential prevention of PND. CLINICAL TRIAL REGISTRATION: Registered (ChiCTR2000028836). Date (20190306).

Schistosoma japonicum cystatin alleviates paraquat poisoning caused acute lung injury in mice through activating regulatory macrophages.

BACKGROUND: Paraquat (PQ) is a widely used herbicide that poisons human by accident or intentional ingestion. PQ poisoning causes systemic inflammatory response syndrome (SIRS) resulting in acute lung injury (ALI) with an extremely high mortality rate. Blood trematode Schistosoma japonicum-produced cystatin (Sj-Cys) is a strong immunomodulatory protein that has been experimentally used to treat inflammation related diseases. In this study, Sj-Cys recombinant protein (rSj-Cys) was used to treat PQ-induced lung injury and the immunological mechanism underlying the therapeutic effect was investigated. METHODS: PQ-induced acute lung injury mouse model was established by intraperitoneally injection of 20 mg/kg of paraquat. The poisoned mice were treated with rSj-Cys and the survival rate was observed up to 7 days compared with the group without treatment. The pathological changes of PQ-induced lung injury were observed by examining the histochemical sections of affected lung tissue and the wet to dry ratio of lung as a parameter for inflammation and edema. The levels of the inflammation related cytokines IL-6 and TNF-α and regulatory cytokines IL-10 and TGF-ß were measured in sera and in affected lung tissue using ELISA and their mRNA levels in lung tissue using RT-PCR. The macrophages expressing iNOS were determined as M1 and those expressing Arg-1 as M2 macrophages. The effect of rSj-Cys on the transformation of inflammatory M1 to regulatory M2 macrophages was measured in affected lung tissue in vivo (EKISA and RT-PCR) and in MH-S cell line in vitro (flow cytometry). The expression levels of TLR2 and MyD88 in affected lung tissue were also measured to determine their role in the therapy of rSj-Cys on PQ-induced lung injury. RESULT: We identified that treatment with rSj-Cys significantly improved the survival rate of mice with PQ-induced lung injury from 30 % (untreated) to 80 %, reduced the pathological damage of poisoning lung tissue, associated with significantly reduced levels of proinflammatory cytokines (IL-6 from 1490 to 590 pg/ml, TNF-α from 260 to 150 pg/ml) and increased regulatory cytokines (IL-10 from360 to 550 pg/ml, and TGF-ß from 220 to 410 pg/ml) in both sera (proteins) and affected lung tissue (proteins and mRNAs). The polarization of macrophages from M1to M2 type was found to be involved in the therapeutic effect of rSj-Cys on the PQ-induced acute lung injury, possibly through inhibiting TLR2/MyD88 signaling pathway. CONCLUSIONS: Our study demonstrated the therapeutic effect of rSj-Cys on PQ poisoning caused acute lung injury by inducing M2 macrophage polarization through inhibiting TLR2/MyD88 signaling pathway. The finding in this study provides an alternative approach for the treatment of PQ poisoning and other inflammatory diseases.

Integrated analysis of tertiary lymphoid structures and immune infiltration in ccRCC microenvironment revealed their clinical significances: a multicenter cohort study.

BACKGROUND: Tertiary lymphoid structures (TLSs) serve as organized lymphoid aggregates that influence immune responses within the tumor microenvironment. This study aims to investigate the characteristics and clinical significance of TLSs and tumor-infiltrating lymphocytes (TILs) in clear cell renal cell carcinoma (ccRCC). METHODS: TLSs and TILs were analyzed comprehensively in 754 ccRCC patients from 6 academic centers and 532 patients from The Cancer Genome Atlas. Integrated analysis was performed based on single-cell RNA-sequencing datasets from 21 ccRCC patients to investigate TLS heterogeneity in ccRCC. Immunohistochemistry and multiplex immunofluorescence were applied. Cox regression and Kaplan-Meier analyses were used to reveal the prognostic significance. RESULTS: The study demonstrated the existence of TLSs and TILs heterogeneities in the ccRCC microenvironment. TLSs were identified in 16% of the tumor tissues in 113 patients. High density (>0.6/mm2) and maturation of TLSs predicted good overall survival (OS) (p<0.01) in ccRCC patients. However, high infiltration (>151) of scattered TILs was an independent risk factor of poor ccRCC prognosis (HR=14.818, p<0.001). The presence of TLSs was correlated with improved progression-free survival (p=0.002) and responsiveness to therapy (p<0.001). Interestingly, the combination of age and TLSs abundance had an impact on OS (p<0.001). Higher senescence scores were detected in individuals with immature TLSs (p=0.003). CONCLUSIONS: The study revealed the contradictory features of intratumoral TLSs and TILs in the ccRCC microenvironment and their impact on clinical prognosis, suggesting that abundant and mature intratumoral TLSs were associated with decreased risks of postoperative ccRCC relapse and death as well as favorable therapeutic response. Distinct spatial distributions of immune infiltration could reflect effective antitumor or protumor immunity in ccRCC.

Integrin αVß3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVß3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVß3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVß3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL. METHODS: OPLL or control ligament samples were collected in surgery. For OPLL samples, RNA-sequencing results revealed activation of the integrin family, particularly integrin αVß3. Integrin αVß3 expression was detected by qPCR, Western blotting, and immunohistochemical analysis. Fluorescence microscopy was used to observe the targeted inhibition of integrin αVß3 by the c(RGDyk) peptide on ligaments fibroblasts (LFs) derived from patients with OPLL and endothelial cells (ECs). The effect of c(RGDyk) peptide on the ossification of pathogenic LFs was detected using qPCR, Western blotting. Alkaline phosphatase staining or alizarin red staining were used to test the osteogenic capability. The effect of the c(RGDyk) peptide on angiogenesis was determined by EC migration and tube formation assays. The effects of the c(RGDyk) peptide on heterotopic bone formation were evaluated by micro-CT, histological, immunohistochemical, and immunofluorescence analysis in vivo. RESULTS: The results indicated that after being treated with c(RGDyk), the osteogenic differentiation of LFs was significantly decreased. Moreover, the c(RGDyk) peptide inhibited the migration of ECs and thus prevented the nutritional support required for osteogenesis. Furthermore, the c(RGDyk) peptide inhibited ectopic bone formation in mice. Mechanistic analysis revealed that c(RGDyk) peptide could inhibit osteogenesis and angiogenesis in OPLL by targeting integrin αVß3 and regulating the FAK/ERK pathway. CONCLUSIONS: Therefore, the integrin αVß3 appears to be an emerging therapeutic target for OPLL, and the c(RGDyk) peptide has dual inhibitory effects that may be valuable for the new therapeutic strategy of OPLL.

Comprehensiveness cuproptosis related genes study for prognosis and medication sensitiveness across cancers, and validation in prostate cancer.

Cuproptosis-related genes (CRGs) are important for tumor development. However, the functions of CRGs across cancers remain obscure. We performed a pan-cancer investigation to reveal the roles of CRGs across cancers. In an analysis of 26 cancers, 12 CRGs were differentially expressed, and those CRGs were found to have prognostic value across different cancer types. The expression of CRGs exhibited varied among tumors of 6 immune subtypes and were significantly correlated with the 16 sensitivities of drugs. The expression of CRGs were highly correlated with immunological subtype and tumor microenvironment (TME) of prostate cancer. We also established CRGs-related prognostic signatures that closely correlated with prognosis and drug sensitivity of prostate cancer patients. Single-cell RNA-seq revealed that several CRGs were enriched in the cancer cells. Finally, an in vitro experiment showed that elesclomol, a cuproptosis inducer, targets ferredoxin 1 and suppress cell viability in prostate cancer cells. In conclusion, we carried out a comprehensive investigation for determining CRGs in differential expression, prognosis, immunological subtype, TME, and cancer treatment sensitivity across 26 malignancies; and validated the results in prostate cancer. Our research improves pan-cancer knowledge of CRGs and identifies more effective immunotherapy strategies.

MRI-based vertebral bone quality score in cervical ossification of the posterior longitudinal ligament: a comparison with cervical spondylotic myelopathy using propensity score matching.

BACKGROUND: Bone mineral density plays a key role in the assessment of operative instrumentation complications and clinical outcomes. The MRI-based vertebral bone quality (VBQ) score has been introduced as a novel marker of bone quality. However, few studies have investigated the relationship between VBQ score and patients associated with cervical ossification of the posterior longitudinal ligament (OPLL). PURPOSE: The aims of the study were (1) to reveal bone mineral density between cervical OPLL and cervical spondylotic myelopathy (CSM) group by VBQ score, (2) to compare the VBQ score of cervical OPLL between male and female group, (3) to explore the relationship between segmental VBQ scores associated with OPLL. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Consecutive series of 425 patients at a single academic institution. OUTCOME MEASURES: MRI based measurements of C2-C7 VBQ scores. METHODS: Preoperative noncontrast T1-weighted MRIs of the cervical spine was used to measure the VBQ score. The VBQ score was defined as the mean value of the signal intensity of the vertebrae divided by that of the cerebrospinal fluid (CSF) space at the cisterna magna. Patients with cervical OPLL and CSM were matched based on age, sex, body mass index (BMI), comorbidity, medication history, diet habit, smoking, alcohol consumption via propensity score matching (PSM). Normality of each VBQ score was tested by the Shapiro-Wilk test. Wilcoxon's rank-sum test was used to compare matched cohorts. Kruskal-Wallis test was performed to compare the VBQ scores between segments. Multivariate logistic regression analysis was used to evaluate factors associated with the development of cervical OPLL. RESULTS: A total of 425 patients were assessed. For final analysis, 135 paired patients were compared between the cervical OPLL and CSM groups, and 22 paired patients were compared between male and female group associated with cervical OPLL. There were no statistically significant differences in age, sex, BMI, comorbidity, medication history, diet habit, smoking, alcohol between the matched cohorts. OPLL group was associated with lower VBQ score compared with CSM group at C3, while there were no differences in VBQ score for the other levels between the two groups. There were no differences between male and female group associated with OPLL in C2-C7 VBQ scores. VBQ scores of cervical OPLL are variable between segments, with significantly lower scores at C6, C7 compared with C1-C5. Multivariate logistic regression analysis showed that BMI was correlated with the development of OPLL (regression coefficient, 0.162; 95% confidence interval, 0.010-0.037). Additional risk factors included hypertension, calcium supple history and smoking. CONCLUSIONS: This study demonstrates that cervical OPLL is associated with lower VBQ score at C3, with no differences for the other levels when compared with CSM derived from measurements on MRI. No differences were found between male and female group associated with OPLL in C2-C7 VBQ scores. Cervical OPLL were found to have smaller VBQ score at C6, C7 compared with C1-C5. Our findings provide new insight for bone density assessment in cervical OPLL patient.

Decanoylcarnitine Inhibits Triple-Negative Breast Cancer Progression via Mmp9 in an Intermittent Fasting Obesity Mouse.

Purpose: Treatment of triple-negative breast cancer (TNBC) remains challenging. Intermittent fasting (IF) has emerged as a promising approach to improve metabolic health of various metabolic disorders. Clinical studies indicate IF is essential for TNBC progression. However, the molecular mechanisms underlying metabolic remodeling in regulating IF and TNBC progression are still unclear. Methods: In this study, we utilized a robust mouse model of TNBC and exposed subjects to a high-fat diet (HFD) with IF to explore its impact on the metabolic reprogramming linked to cancer progression. To identify crucial serum metabolites and signaling events, we utilized targeted metabolomics and RNA sequencing (RNA-seq). Furthermore, we conducted immunoblotting, real-time quantitative polymerase chain reaction (RT-qPCR), cell migration assays, lentivirus-mediated Mmp9 overexpression, and Mmp9 inhibitor experiments to elucidate the role of decanoylcarnitine/Mmp9 in TNBC cell migration. Results: Our observations indicate that IF exerts notable inhibitory effects on both the proliferation and cancer metastasis. Utilizing targeted metabolomics and RNA-seq, we initially identified pivotal serum metabolites and signaling events in the progression of TNBC. Among the 349 serum metabolites identified, decanoylcarnitine was picked out to inhibit TNBC cell proliferation and migration. RNA-seq analysis of TNBC cells treated with decanoylcarnitine revealed its suppressive effects on extracellular matrix-related protein components, with a notable reduction observed in Mmp9. Further investigations confirmed that decanoylcarnitine could inhibit Mmp9 expression in TNBC cells, primary tumors, lung, and liver metastasis tissues. Mmp9 overexpression abolished the inhibitory effect of decanoylcarnitine on cell migration. Conclusion: This study pioneers the exploration of IF intervention and the role of decanoylcarnitine/Mmp9 in the progression of TNBC in obese mice, enhancing our comprehension of the potential roles of various dietary patterns in the process of cancer treatment.

Analysis of Diffusion-Weighted and T2-Weighted Imaging in the Prediction of Distinct Granulation Patterns of Somatotroph Adenomas.

OBJECTIVE: The heterogeneity of the somatotroph adenomas, especially for sparsely granulated (SG) and densely granulated (DG) subtypes, has attracted great attention in identifying their imaging biomarker. The purpose of the current study was to compare the diagnostic performance of diffusion-weighted and T2-weighted magnetic resonance imaging (MRI) sequences for preoperatively distinguishing the granulation patterns of somatotroph adenomas. METHODS: Thirty-two patients with a clinical diagnosis of somatotroph adenomas from October 2018 to March 2023 were included in this study. Coronal diffusion-weighted imaging (DWI) and T2-weighted MRI sequence data were collected from 3.0T MRI and compared between SG and DG groups. The immunohistochemistry was used to confirm the electron microscopy pathologic subtypes and Ki67 expression levels of somatotroph adenomas postoperatively. RESULTS: Patients in the SG group had significantly higher signal intensity (SI) ratio of DWI (rDWI) (P < 0.001), lower SI ratio of apparent diffusion coefficient (rADC) (P < 0.001), and higher SI ratio of T2-weighted imaging (P = 0.011). The combined diagnosis index of rDWI and rADC had the highest diagnostic efficiency in predicting SG adenomas (sensitivity, 93.3%; specificity, 88.2%; P < 0.001). The rDWI and rADC values had positive and negative correlations with the Ki67 index and tumor maximum diameter, respectively. Lower rADC×103 was an independent predictor for SG adenomas. CONCLUSIONS: Our results indicated that compared with previously used T2-weighted imaging, the DWI sequence, especially the combined diagnosis index of rDWI and rADC, could more efficiently distinguish the granulation patterns of somatotroph adenomas preoperatively.

Prognostic model of kidney renal clear cell carcinoma using aging-related long noncoding RNA signatures identifies THBS1-IT1 as a potential prognostic biomarker for multiple cancers.

Aging is responsible for the main intrinsic triggers of cancers; however, the studies of aging risk factors in cancer animal models and cancer patients are rare and insufficient to be represented in cancer clinical trials. For a better understanding of the complex regulatory networks of aging and cancers, 8 candidate aging related long noncoding RNAs (CarLncs) identified from the healthy aging models, centenarians and their offsprings, were selected and their association with kidney renal clear cell carcinoma (KIRC) was explored by series of cutting edge analyses such as support vector machine (SVM) and random forest (RF) algorithms. Using data downloaded from TCGA and GTEx databases, a regulatory network of CarLncs-miRNA-mRNA was constructed and five genes within the network were screened out as aging related feature genes for developing KIRC prognostic models. After a strict filtering pipeline for modeling, a formula using the transcript per million (TPM) values of feature genes "LncAging_score = 0.008* MMP11 + 0.066* THBS1-IT1 + (-0.014)* DYNLL2 + (-0.030)* RMND5A+ 0.008* PEG10" was developed. ROC analysis and nomogram suggest our model achieves a great performance in KIRC prognosis. Among the 8 CarLncs, we found that THBS1-IT1 was significantly dysregulated in 12 cancer types. A comprehensive pan-cancer analysis demonstrated that THBS1-IT1 is a potential prognostic biomarker in not only KIRC but also multiple cancers, such as LUSC, BLCA, GBM, LGG, MESO, PAAD, STAD and THCA, it was correlated with tumor microenvironment (TME) and tumor immune cell infiltration (TICI) and its high expression was related with poor survival.

A novel hybrid algorithm based on Harris Hawks for tumor feature gene selection.

Background: Gene expression data are often used to classify cancer genes. In such high-dimensional datasets, however, only a few feature genes are closely related to tumors. Therefore, it is important to accurately select a subset of feature genes with high contributions to cancer classification. Methods: In this article, a new three-stage hybrid gene selection method is proposed that combines a variance filter, extremely randomized tree and Harris Hawks (VEH). In the first stage, we evaluated each gene in the dataset through the variance filter and selected the feature genes that meet the variance threshold. In the second stage, we use extremely randomized tree to further eliminate irrelevant genes. Finally, we used the Harris Hawks algorithm to select the gene subset from the previous two stages to obtain the optimal feature gene subset. Results: We evaluated the proposed method using three different classifiers on eight published microarray gene expression datasets. The results showed a 100% classification accuracy for VEH in gastric cancer, acute lymphoblastic leukemia and ovarian cancer, and an average classification accuracy of 95.33% across a variety of other cancers. Compared with other advanced feature selection algorithms, VEH has obvious advantages when measured by many evaluation criteria.

A pan-cancer analysis of DDR1 in prognostic signature and tumor immunity, drug resistance.

Disk-like domain receptor 1 (DDR1) is a crucial regulator of pro-inflammatory mediators and matrix-degrading enzymes. Although mounting evidence supports a vital role for DDR1 in the tumorigenesis of some cancers, no pan-cancer analysis of DDR1 has been reported. Therefore, we aimed to explore the prognostic value of DDR1 in 33 cancer types and investigate its potential immune function. We used a range of bioinformatics approaches to explore the potential carcinogenic role of DDR1 in multiple cancers. We found that DDR1 was expressed at high levels in most cancers. DDR1 expression was positively or negatively associated with prognosis in different cancers. DDR1 expression was significantly associated with DNA methylation in 8 cancers, while there was a correlation between DDR1 expression and RNA methylation-related genes and mismatch repair gene in most cancers. Furthermore, DDR1 expression was significantly associated with microsatellite instability in 6 cancers and tumor mutation burden in 11 cancers. In addition, DDR1 expression was also significantly correlated with immune cell infiltration, tumor microenvironment, immune-related genes, and drug resistance in various cancers. In conclusion, DDR1 can serve as a potential therapeutic target and prognostic marker for various malignancies due to its vital role in tumorigenesis and tumor immunity.

Selective leaching process for efficient and rapid recycling of spent lithium iron phosphate batteries.

With the continuous development of new energy vehicles, the number of decommissioned lithium iron phosphate (LiFePO4) batteries has been constantly increasing. Therefore, it is necessary to recover metal from spent LiFePO4 batteries due to the high potential for environmental protection and high resource value. In this study, sodium persulfate (Na2S2O8) was selected as the oxidant to regulate and control the oxidation state and proton activity of the leaching solution through its high oxidizing ability. Selective recovery of lithium from LiFePO4 batteries was achieved by oxidizing LiFePO4 to iron phosphate (FePO4) during the leaching process. This paper reports an extensive investigation of the effects of various factors, including the acid concentration, initial volume fraction of the oxidant, reaction temperature, solid-liquid ratio, and reaction time, on lithium leaching. Li+ reached a high leaching rate of 93.3% within 5 minutes even at a low concentration of sulphuric acid (H2SO4), and high-purity lithium carbonate (Li2CO3) was obtained through impurity removal and precipitation reactions. In addition, the leaching mechanism was analysed by both X-ray diffraction and X-ray photoelectron spectroscopy characterization. The results show that the obtained high lithium-ion (Li+) leaching efficiency and fast Li+ leaching time can be ascribed to the superior oxidizing properties of Na2S2O8 and the stability of the crystal structure of LiFePO4 during the oxidative leaching process. The adopted method has significant advantages in terms of safety, efficiency and environmental protection, which are conducive to the sustainable development of lithium batteries.

The hindgut microbiome contributes to host oxidative stress in postpartum dairy cows by affecting glutathione synthesis process.

BACKGROUND: Dairy cows are susceptible to postpartum systemic oxidative stress (OS), which leads to significant production loss and metabolic disorders. The gut microbiota has been linked to host health and stress levels. However, to what extent the gut microbiota is associated with postpartum OS remains unknown. In this study, the contribution of the fecal microbiota to postpartum systemic OS and its underlying mechanisms were investigated by integrating 16S rRNA gene sequencing, metagenomics, and metabolomics in postpartum dairy cattle and by transplanting fecal microbiota from cattle to mice. RESULTS: A strong link was found between fecal microbial composition and postpartum OS, with an explainability of 43.1%. A total of 17 significantly differential bacterial genera and 19 species were identified between cows with high (HOS) and low OS (LOS). Among them, 9 genera and 16 species showed significant negative correlations with OS, and Marasmitruncus and Ruminococcus_sp._CAG:724 had the strongest correlations. The microbial functional analysis showed that the fecal microbial metabolism of glutamine, glutamate, glycine, and cysteine involved in glutathione synthesis was lower in HOS cows. Moreover, 58 significantly different metabolites were identified between HOS and LOS cows, and of these metabolites, 19 were produced from microbiota or cometabolism of microbiota and host. Furthermore, these microbial metabolites were enriched in the metabolism of glutamine, glutamate, glycine, and cysteine. The mice gavaged with HOS fecal microbiota had significantly higher OS and lower plasma glutathione peroxidase and glutathione content than those orally administered saline or LOS fecal microbiota. CONCLUSIONS: Integrated results suggest that the fecal microbiota is responsible for OS and that lower glutathione production plays a causative role in HOS. These findings provide novel insights into the mechanisms of postpartum OS and potential regulatory strategies to alleviate OS in dairy cows. Video Abstract.

Comparison of the outcome after anterior cervical ossified posterior longitudinal ligament en bloc resection versus posterior total laminectomy and fusion in patients with ossification of the cervical posterior longitudinal ligament: a prospective randomized controlled trial.

The optimal procedure for the treatment of ossification of the posterior longitudinal ligament (OPLL) remains controversial. The aim of this study was to compare the outcome of anterior cervical ossified posterior longitudinal ligament en bloc resection (ACOE) with posterior laminectomy and fusion with bone graft and internal fixation (PTLF) for the surgical management of patients with this condition. Between July 2017 and July 2019, 40 patients with cervical OPLL were equally randomized to undergo surgery with an ACOE or a PTLF. The clinical and radiological results were compared between the two groups. The Japanese Orthopaedic Association (JOA) score and recovery rate in the ACOE group were significantly higher than those in the PTLF group during two years postoperatively, provided that the canal occupying ratio (COR) was > 50%, or the K-line was negative. There was no significant difference in JOA scores and rate of recovery between the two groups in those in whom the COR was < 50%, or the K-line was positive. There was no significant difference in the Cobb angle between C2 and C7, sagittal vertical axis, cervical range of motion (ROM), and complications between the two groups. Compared with PTLF, ACOE is a preferred surgical approach for the surgical management of patients with cervical OPLL in that it offers a better therapeutic outcome when the COR is > 50%, or the K-line is negative, and it also preserves better cervical curvature and sagittal balance. The prognosis of ACOE is similar to that of PTLE when the COR is < 50%, or the K-line is positive.

Association of RNA-modification "writer" genes with prognosis and response to immunotherapy in patients with low-grade glioma.

RNA modification is a key regulatory mechanism involved in tumorigenesis, tumor progression, and the immune response. However, the potential role of RNA modification "writer" genes in the immune microenvironment of gliomas and their effect on the response to immunotherapy remains unclear. The purpose of this study was to evaluate the role of RNA modification "writer" gene in the prognosis and immunotherapy response of low-grade glioma (LGG). The consensus non-negative matrix factorization (CNMF) method was used to identify different RNA modification subtypes. We used a novel eigengene screening method, the variable neighborhood learning Harris Hawks optimizer (VNLHHO), to screen for eigengenes among the RNA modification subtypes. We constructed a principal components analysis score(PCA_score)-based prognostic prediction model and validated it using an independent cohort. We also analyzed the association between PCA_score and the immune and molecular features of LGG. The results suggested that LGG can be divided into two different RNA modification-based subtypes with distinct prognostic and molecular features. High PCA_score was significantly associated with a poor prognosis in LGG and was an independent prognostic factor. A nomogram containing PCA_score and clinical features was constructed, and it showed a significant predictive value. PCA_score was negatively correlated with tumor purity and the abundance of CD4+ T cells in LGG patients. LGG patients with high PCA_score had lower Tumor Immune Dysfunction and Exclusion scores and showed an immunotherapy response. In conclusion, we report a novel RNA modification-based prognostic model for LGG that lays the foundation for evaluating LGG prognosis and developing more effective therapeutic strategies for these tumors.

Glutathione inhibited starch digestion: Structural and kinetic analysis of substrate and α-amylase.

Glutathione (GSH) is a natural antioxidant that helps fight free radicals. Whether it will affect the activity of amylase and starch digestion remains unknown. This research disclosed that GSH could interact with starch through hydrogen bonds, which accelerated the swelling of starch granules and promoted the formation of ordered double-helix crystalline, and therefore inhibited starch digestion. Moreover, pig pancreas α-amylase (PPA) which was incubated with GSH displayed a less stable conformation and decreased activity. However, in a crowded media constructed by sodium caseinate (NaCas), an antagonistic effect existed between GSH and NaCas. As the rate and extent of starch digestion have been linked with health aspects, this study suggests that GSH can be used in the formulation of diet foods. It also reminds us to consider the synergistic or antagonistic effects caused by the coexisted components in the complexed food matrix.

Lyophilized bovine acellular tendon linear fiber material for the reconstruction of attachment structure of paraspinous muscles: an animal in vivo study.

Low back pain is common after lumbar spine surgery and the injury from extensive detachment of paraspinal muscles during the surgery may play a vital role. Previously, we prepared a bovine acellular tendon fiber (ATF) material through lyophilization and proved that it could retain its original fibrillar structure and mechanical properties. The objective of this study is to evaluate the effectiveness of this new fiber material used for attachment structure reconstruction of paraspinal muscle. Defect of spinous process, interspinous and supraspinous ligament was established on lumbar spine in rabbit and rat and ATF linear material was implanted to reconstruct the attachment structure. Ultrasound showed the cross-sectional area of the paraspinal muscle in ATF group was larger than that of control group in rats. MRI showed the irregular shape and high signal changes in control group, but regular shape and uniform signal in the ATF group in rabbit. For Electromyogram, the frequency of evoked potential in control group was lower than ATF group and normal rats. HE and Masson staining showed good tissue healing, and immunohistochemical results showed the immune rejection of ATF is significantly lower than that of suture. Reconstruction of the attachment structure of paraspinous muscles with ATF linear material could maintain the morphology, volume and function of paraspinal muscle. ATF material has the potential to be used to manufacture personalized ligaments and other tissue engineering scaffolds. Graphical abstract.

Factors affecting titanium mesh cage subsidence in single-level anterior cervical corpectomy and fusion for ossification of the posterior longitudinal ligament.

PURPOSE: To analyze risk factors of titanium mesh cage (TMC) subsidence in single-level anterior cervical corpectomy and fusion (ACCF) for cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: TMC subsidence is defined as the reduction of the adjacent vertebral bodies by ≥ 2 mm. Patients with cervical OPLL who were treated with single-level ACCF between January 2019 and May 2021 were retrospectively analyzed in two groups: patients with TMC subsidence as Group S and patients with no TMC subsidence as Group N during the one-year follow-up period. The degree of distraction of surgical segment and correction of the cervical curvature was measured to analyze their relationship with TMC subsidence. RESULTS: A total of 128 patients were included in Group S, and 138 patients were included in Group N. There was no significant difference in patient demographics and complications between the two groups. The degree of distraction in Group S was significantly higher than that in Group N (11.4% ± 7.6% vs. 4.7% ± 9.7%, P < 0.01). The change of C2 to C7 Cobb angle (α) in Group S was significantly greater than that in Group N (5.7 ± 2.7 vs. 1.4 ± 4.7, P < 0.01), and the change of interspinous process distance (SPD) in Group S was also significantly greater than that in Group N (7.0 ± 4.2 vs. 4.1 ± 2.7, P < 0.01). The JOA score and JOA recovery rate were not statistically different between the two groups. CONCLUSIONS: Intraoperative selection of overlength TMC in single-level ACCF for OPLL, over-distraction and excessive correction of the cervical curvature may cause TMC subsidence after surgery. No significant impact of TMC subsidence on the surgical outcome was observed during the 1-year follow-up period.

A novel prognostic model for cutaneous melanoma based on an immune-related gene signature and clinical variables.

Abundant evidence has indicated that the prognosis of cutaneous melanoma (CM) patients is highly complicated by the tumour immune microenvironment. We retrieved the clinical data and gene expression data of CM patients in The Cancer Genome Atlas (TCGA) database for modelling and validation analysis. Based on single-sample gene set enrichment analysis (ssGSEA) and consensus clustering analysis, CM patients were classified into three immune level groups, and the differences in the tumour immune microenvironment and clinical characteristics were evaluated. Seven immune-related CM prognostic molecules, including three mRNAs (SUCO, BTN3A1 and TBC1D2), three lncRNAs (HLA-DQB1-AS1, C9orf139 and C22orf34) and one miRNA (hsa-miR-17-5p), were screened by differential expression analysis, ceRNA network analysis, LASSO Cox regression analysis and univariate Cox regression analysis. Their biological functions were mainly concentrated in the phospholipid metabolic process, transcription regulator complex, protein serine/threonine kinase activity and MAPK signalling pathway. We established a novel prognostic model for CM integrating clinical variables and immune molecules that showed promising predictive performance demonstrated by receiver operating characteristic curves (AUC ≥ 0.74), providing a scientific basis for predicting the prognosis and improving the clinical outcomes of CM patients.

Exosomal miR-140-5p inhibits osteogenesis by targeting IGF1R and regulating the mTOR pathway in ossification of the posterior longitudinal ligament.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is a disabling disease whose pathogenesis is still unclear, and there are no effective cures or prevention methods. Exosomal miRNA plays an important role in the osteogenesis of ectopic bone. Therefore, we focused on the downregulation of miR-140-5p in OPLL cell-derived exosomes to explore the mechanism by which exosomal miR-140-5p inhibits osteogenesis in OPLL. RESULTS: Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and exosomal markers. Exosomal RNA was extracted to perform miRNA sequencing and disclose the differentially expressed miRNAs, among which miR-140-5p was significantly downregulated. Confocal microscopy was used to trace the exosomal miR-140-5p delivered from OPLL cells to human mesenchymal stem cells (hMSCs). In vitro, we verified that exosomal miR-140-5p inhibited the osteoblast differentiation of hMSCs by targeting IGF1R and suppressing the phosphorylation of the IRS1/PI3K/Akt/mTOR pathway. In vivo, we verified that exosomal miR-140-5p inhibited ectopic bone formation in mice as assessed by micro-CT and immunohistochemistry. CONCLUSIONS: We found that exosomal miR-140-5p could inhibit the osteogenic differentiation of hMSCs by targeting IGF1R and regulating the mTOR pathway, prompting a further potential means of drug treatment and a possible target for molecular therapy of OPLL.