Clinical efficacy and kinematic analysis of Chinese knotting technique-assisted posterior cruciate ligament reconstruction: A retrospective analysis.

To investigate the clinical efficacy and knee joint kinematic changes of posterior cruciate ligament (PCL) reconstruction assisted by Chinese knotting technique (CKT). A retrospective analysis was conducted on 88 cases of PCL reconstructive surgery admitted between September 2016 and September 2020. All patients were operated on by the same senior doctor and his team. The patients were divided into 2 groups according to whether the CKT was applied, with 44 cases in each group. Both groups received active rehabilitation treatment after surgery. All patients were followed up for more than 2 years. International knee documentation committee, hospital for special surgery (HSS), and Lysholm scores were used to evaluate the clinical efficacy of the 2 methods at 3, 12, and 24 months after surgery. The motion cycle and kinematic indices of the knee joint were measured by the Opti_Knee three-dimensional motion measurement system before surgery and at 3, 12, and 24 months after surgery. A secondary arthroscopic examination was performed at 12 months after surgery, MAS score was used to evaluate the secondary endoscopic examination of PCL. All the patients had wound healing in stage I without infection. International Knee in both sets Documentation Committee scores, HSS scores and Lysholm scores were gradually improved at all time points (P < .05); compared with the traditional group, the HSS score was higher in the reduction group 12 months after surgery (P < .05), but there was no significant difference at 24 months after surgery. 12 months and 24 months after 3 dimensional motion measurement system using Opti_Knee showed a reduction group before and after displacement and displacement of upper and lower range than the traditional group (P < 0. 05). One year after surgery, the good and good rate of MAS score reduction group was higher than traditional group. CKT assisted PCL reconstruction can improve the subjective function score of the affected knee joint and the results of secondary microscopy. Satisfactory knee kinematic function can be obtained in the early stage, and the anteroposteric relaxation of the knee joint can be reduced.

Elucidation of the key therapeutic targets and potential mechanisms of Andrographolide multi-targets against osteoarthritis via network pharmacological analysis and experimental validation.

OBJECTIVE: Our purpose is to unveil Andrographolide's potential multi-target and multi-mechanism therapeutic effects in treating OA via systematic network pharmacological analysis and cell experimental validation. MATERIALS AND METHODS: Initially, we gathered data from Andrographolide and OA-related databases to obtain information on Andrographolide's biological properties and the targets linked with OA. We developed a bioinformatic network about Andrographolide and OA, whereby we analyzed the network to identify potential therapeutic targets and mechanisms of action of Andrographolide. Subsequently, we used molecular docking to analyze the binding sites of Andrographolide to the target proteins. At the same time, SDF-1 was used to construct an OA cell model to verify the therapeutic effect of Andrographolide on OA and its effect on target proteins. RESULTS: Our experimental results show that Andrographolide has excellent pharmaceutical properties, by Lipinski's rules for drugs, suggesting that this compound can be considered to have a high therapeutic potential in drug development. 233 targets were preliminarily investigated, the mechanisms through which Andrographolide targets OA primarily involve the TNF signaling pathway, PI3K-AKT signaling pathway, IL-17 signaling pathway, and TLR signaling pathway. These mechanisms target OA by influencing immune and inflammatory responses in the joints, regulating apoptosis to prevent chondrocyte death. Finally, TNF-α, STAT3, TP53, IL-6, JUN, IL-1ß, HIF-1α, TGF-ß1, and AKT1 were identified as 9 key targets of Andrographolide anti-OA. In addition, our molecular docking analyzes with cell experimental validation further confirm the network pharmacology results. According to our molecular docking results, Andrographolide can bind to all the hub target proteins and has a good binding ability (binding energy < -5 kcal/mol), with the strongest binding affinity to AKT1 of -9.2 kcal/ mol. The results of cell experiments showed that Andrographolide treatment significantly increased the cell viability and the expression of COL2A1 and ACAN proteins. Moreover, 30 µM Andrographolide significantly reversed SDF-1-induced increases in the protein expression of TNF-α, STAT3, TP53, IL-6, JUN, IL-1ß, HIF-1α, and TGF-ß1, and decreases in the protein expression of AKT1. CONCLUSION: This study provides a comprehensive understanding of the potential therapeutic targets and mechanisms of action of Andrographolide in OA treatment. Our findings suggest that Andrographolide is a promising candidate for drug development in the management of OA.

Tumor keratin 15 expression links with less extent of invasion and better prognosis in papillary thyroid cancer patients receiving tumor resection.

OBJECTIVE: Keratin 15 (KRT15) is identified as a useful biomarker in several solid tumors, while its clinical role in papillary thyroid cancer (PTC) remains unknown. Herein, this study is intended to explore the correlation of tumor KRT15 with clinical features and survival in PTC patients who received tumor resection. METHODS: This study retrospectively screened 350 PTC patients who received tumor resection and 50 thyroid benign lesions (TBL) patients. KRT15 in formalin-fixed paraffin-embedded lesion specimens of all subjects was detected by immunohistochemistry (IHC). RESULTS: KRT15 was reduced in PTC patients compared to TBL patients (P < 0.001). Furthermore, KRT15 was negatively associated with tumor size (P = 0.017), extrathyroidal invasion (P = 0.007), pathological tumor (pT) stage (P < 0.001), and postoperative radioiodine application (P = 0.008) in PTC patients. Regarding prognostic value, high KRT15 (cut-off by an IHC value of 3) is linked with prolonged accumulating disease-free survival (DFS) (P = 0.008) and overall survival (OS) (P = 0.008) in PTC patients. Also, the multivariate Cox regression model showed that high KRT15 (vs. low) was an independent factor for longer DFS (hazard ratio = 0.433, P = 0.049), but not for OS (P > 0.050) in PTC patients. Subgroup analyses revealed that KRT15 possessed a better prognostic value in PTC patients with age ≥ 55 years, tumor size > 4 cm, pathological node stage 1, or pathological tumor-node-metastasis stage ≤ 2 (all P < 0.050). CONCLUSION: Increased tumor KRT15 associates with a lower invasive degree, prolonged DFS, and OS, revealing its prognostic utility in PTC patients undergoing tumor resection.

Quinolines: A Promising Heterocyclic Scaffold for Cancer Therapeutics.

The quinoline scaffold is a widely recognized heterocycle with applications across various disease categories, ranging from malaria and viral infections to bacterial infections, high cholesterol, and even tumors. Consequently, quinoline plays a crucial role in the development of new drugs, and the field greatly benefits from advancements in computer-aided drug design. This review aims to provide insights into the evolution of quinoline and its derivatives, offering a comprehensive exploration of both marketed and developing drugs. Furthermore, the function and mechanism of quinoline compounds are introduced. Many studies rely on cell experiments to demonstrate drug cytotoxicity. In the concluding section of this review, the interaction between quinoline compounds and targets is simulated using computer-aided drug design methods. A thorough analysis is conducted on the potential influencing factors affecting the binding state between quinoline compounds and targets. Notably, the Pi-Alkyl interaction emerges as a significant contributor, while hydrogen bonding is identified as a pivotal bond in these interactions. This review serves as a valuable overview of the potential contributions of quinoline compounds to cancer treatment. It seamlessly combines the essential functions of marketed quinoline drugs with the promise held by emerging quinoline-based compounds. Additionally, the simulation of interactions between quinoline compounds and proteins through computer-aided design enhances our understanding of these compounds' efficacy.

Complementary Alu sequences mediate enhancer-promoter selectivity.

Enhancers determine spatiotemporal gene expression programs by engaging with long-range promoters1-4. However, it remains unknown how enhancers find their cognate promoters. We recently developed a RNA in situ conformation sequencing technology to identify enhancer-promoter connectivity using pairwise interacting enhancer RNAs and promoter-derived noncoding RNAs5,6. Here we apply this technology to generate high-confidence enhancer-promoter RNA interaction maps in six additional cell lines. Using these maps, we discover that 37.9% of the enhancer-promoter RNA interaction sites are overlapped with Alu sequences. These pairwise interacting Alu and non-Alu RNA sequences tend to be complementary and potentially form duplexes. Knockout of Alu elements compromises enhancer-promoter looping, whereas Alu insertion or CRISPR-dCasRx-mediated Alu tethering to unregulated promoter RNAs can create new loops to homologous enhancers. Mapping 535,404 noncoding risk variants back to the enhancer-promoter RNA interaction maps enabled us to construct variant-to-function maps for interpreting their molecular functions, including 15,318 deletions or insertions in 11,677 Alu elements that affect 6,497 protein-coding genes. We further demonstrate that polymorphic Alu insertion at the PTK2 enhancer can promote tumorigenesis. Our study uncovers a principle for determining enhancer-promoter pairing specificity and provides a framework to link noncoding risk variants to their molecular functions.

A review on CRISPR/Cas: a versatile tool for cancer screening, diagnosis, and clinic treatment.

Cancer is one of the leading causes of death worldwide and it has the trend of increase incidence. However, in the past decades, as quickly developed new technologies and modified old techniques for cancer screening, diagnosis, and treatment, the cancer-caused mortality rates dropped quickly, and the survival times of cancer patients are enhanced. However, the current death rate is still about 50% and the survival patients always suffer from the side effect of current cancer treatments. Recently developed Nobel Prize-winning CRISPR/Cas technology provides new hope on cancer screening, early diagnosis, and clinic treatment as well as new drug development. Currently, four major CRISPR/Cas9-derived genome editors, CRISPR/Cas9 nucleotide sequence editor, CRISPR/Cas base editor (BE), CRISPR prime editor (PE), and CRISPR interference (CRISPRi) (including both CRISPRa and CRISPRr), were well developed and used to various research and applications, including cancer biology study and cancer screening, diagnosis, and treatment. Additionally, CRISPR/Cas12 and CRISPR/Cas13 genome editors were also widely used in cancer-related basic and applied research as well as treatment. Cancer-associated SNPs and genetic mutations as well as both oncogenes and tumor suppressor genes are perfect targets for CRISPR/Cas-based gene therapy for cancer treatment. CRISPR/Cas is also employed to modify and generate new Chimeric antigen receptor (CAR) T-cells for improving its safety, efficiency, and longer-time last for treating various cancers. Currently, there are many clinic trails of CRISPR-based gene therapy for cancer treatments. Although all CRISPR/Cas-derived genome and epigenome tools are promising methods for cancer biology study and treatment, the efficiency and long term-safety are still the major concerns for CRISPR-based gene therapy. Developing new CRISPR/Cas delivery methods and reducing the potential side effects, including off-target impacts, will enhance CRISPR/Cas application in cancer-related research, diagnosis, and therapeutical treatment.

Integrating DOI in T classification improves the predictive performance of laryngeal cancer staging.

It has been recognized that depth of invasion (DOI) is closely associated with patient survival for most types of cancer. The purpose of this study was to determine the DOI optimal cutoff value and its prognostic value in laryngeal squamous carcinoma (LSCC). Most importantly, we evaluated the prognostic performance of five candidate modified T-classification models in patients with LSCC. LSCC patients from Harbin Medical University Cancer Hospital and Chinese Academy of Medical Sciences Cancer Hospital were divided into training group (n = 412) and validation group (n = 147). The primary outcomes were overall survival (OS) and relapse-free survival (RFS), and the effect of DOI on prognosis was analyzed using a multivariable regression model. We identified the optimal model based on its simplicity, goodness of fit and Harrell's consistency index. Further independent testing was performed on the external validation queue. The nomograms was constructed to predict an individual's OS rate at one, three, and five years. In multivariate analysis, we found significant associations between DOI and OS (Depth of Medium-risk invasion HR, 2.631; P < .001. Depth of high-risk invasion: HR, 5.287; P < .001) and RFS (Depth of high-risk invasion: HR, 1.937; P = .016). Model 4 outperformed the American Joint Committee on Cancer (AJCC) staging system based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan-Meier curves. Inclusion of DOI in the current AJCC staging system can improve the differentiation of T classification in LSCC patients.

Cellular retinol-binding protein 1: a therapeutic and diagnostic tumor marker.

Cellular Retinol Binding Protein 1 (CRBP1) gene is a protein coding gene located on human chromosome 3q21, which codifies a protein named CRBP1. CRBP1 is widely expressed in many tissues as a chaperone protein to regulate the uptake, subsequent esterification and bioavailability of retinol. CRBP1 combines retinol and retinaldehyde with high affinity to protect retinoids from non-specific oxidation, and transports retinoids to specific enzymes to promote the biosynthesis of retinoic acid. The vital role of CRBP1 in retinoids metabolism has been gradually discovered, which has been implicated in tumorigenesis. However, the precise functions of CRBP1 in different diseases are still poorly understood. The purpose of this review is to provide an overview of the role of CRBP1 in various diseases, especially in both the promotion and inhibition of cancers, which may also offer a novel biomarker and potential therapeutic target for human diseases.

Reminiscence therapy care program as a potential nursing intervention to relieve anxiety, depression, and quality of life in older papillary thyroid carcinoma patients: A randomized, controlled study.

Objective: Reminiscence therapy (RT) ameliorates psychological problems and quality of life in cancer patients. However, no study reports its effect on older papillary thyroid carcinoma (PTC) patients. This study intended to investigate the effect of the RT-care program (CP) on anxiety, depression, quality of life, and survival in older PTC patients. Methods: Eighty-six postoperative older PTC patients were enrolled and randomly assigned to RT-CP group (N = 44) and usual (U)-CP group (N = 42) as a 1:1 ratio for a 6-month intervention. Hospital Anxiety and Depression Scale (HADS) and Quality of Life Questionnaire-Core 30 (QLQ-C30) scores were assessed at baseline, month (M)1, M2, M4, and M6. Results: HADS and QLQ-C30 scores at baseline were not different between two groups. Additionally, HADS-anxiety score at M6 (p = 0.029), and HADS-depression score at M2 (p = 0.030), M4 (p = 0.029), M6 (p = 0.012) were reduced in RT-CP group versus U-CP group. Meanwhile, anxiety and depression rates from M1 to M6 were slightly decreased in RT-CP group versus U-CP group but did not reach statistical significance. Furthermore, depression severity at M6 was reduced in RT-CP group versus U-CP group (p = 0.049). Besides, QLQ-C30 global health status was increased at M2 (p = 0.023) and M6 (p = 0.033), QLQ-C30 function score was elevated at M2 (p = 0.040) and M4 (p = 0.035), while QLQ-C30 symptom score was decreased at M2 (p = 0.046) in RT-CP group versus U-CP group. Moreover, disease-free survival and overall survival were not different between two groups. Conclusion: RT-CP may be a potential intervention for ameliorating anxiety, depression, and quality of life in older PTC patients.

System analysis based on the ER stress-related genes identifies WFS1 as a novel therapy target for colon cancer.

BACKGROUND: Colon cancer (COAD) is the third-largest common malignant tumor and the fourth major cause of cancer death in the world. Endoplasmic reticulum (ER) stress has a great influence on cell growth, migration, proliferation, invasion, angiogenesis, and chemoresistance of massive tumors. Although ER stress is known to play an important role in various types of cancer, the prognostic model based on ER stress-related genes (ERSRGs) in colon cancer has not been constructed yet. In this study, we established an ERSRGs prognostic risk model to assess the survival of COAD patients. METHODS: The COAD gene expression profile and clinical information data of the training set were obtained from the GEO database (GSE40967) and the test set COAD gene expression profile and clinical informative data were downloaded from the TCGA database. The endoplasmic reticulum stress-related genes (ERSRGs) were obtained from Gene Set Enrichment Analysis (GSEA) website. Differentially expressed ERSRGs between normal samples and COAD samples were identified by R "limma" package. Based on the univariate, lasso, and multivariate Cox regression analysis, we developed an ERSRGs prognostic risk model to predict survival in COAD patients. Finally, we verified the function of WFS1 in COAD through in vitro experiments. RESULTS: We built a 9-gene prognostic risk model based on the univariate, lasso, and multivariate Cox regression analysis. Kaplan-Meier survival analysis and Receiver operating characteristic (ROC) curve revealed that the prognostic risk model has good predictive performance. Subsequently, we screened 60 compounds with significant differences in the estimated half-maximal inhibitory concentration (IC50) between high-risk and low-risk groups. In addition, we found that the ERSRGs prognostic risk model was related to immune cell infiltration and the expression of immune checkpoint molecules. Finally, we determined that knockdown of the expression of WFS1 inhibits the proliferation of colon cancer cells. CONCLUSIONS: The prognostic risk model we built may help clinicians accurately predict the survival of patients with COAD. Our findings provide valuable insights into the role of ERSRGs in COAD and may provide new targets for COAD therapy.

Plastic biodegradation by in vitro environmental microorganisms and in vivo gut microorganisms of insects.

Traditional plastics, such as polyethylene (PE), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyurethane (PUR), and other plastic polymers, are difficult to degrade and are gradually accumulated in the environment to cause a serious environmental problem, which is urgently needed to develop novel treatments or control technology. The biodegradation of plastics has gained great attention due to the advantages of green and safe characteristics. Microorganisms play a vital role in the biodegradation of plastics, including environmental microbes (in vitro) and gut microbes of insects (in vivo). Microbial degradation in environmental conditions in vitro is extremely slow for major plastics at degradation rates on the basis of a month or even a year time, but recent discoveries show that the fast biodegradation of specific plastics, such as PS, PE, and PUR, in some invertebrates, especially insects, could be enhanced at rates on basis of hours; the biodegradation in insects is likely to be gut microbial-dependent or synergetic bioreactions in animal digestive systems. This review comprehensively summarizes the latest 7-year (2016-2022) publications on plastic biodegradation by insects and microorganisms, elucidates the mechanism of plastic degradation in insects and environmental microbes, and highlights the cutting-edge perspectives for the potential applications of plastic biodegradation.

Assessment of immune status of laryngeal squamous cell carcinoma can predict prognosis and guide treatment.

BACKGROUND: In the past few years, immunotherapy has changed the way we treat solid tumors. People pay more and more attention to the immune microenvironment of laryngeal squamous cell carcinoma (LSCC). In this study, our immunotherapy research took advantage of the clinical database and focused our in-depth analysis on the tumor microenvironment (TME). METHODS: This study evaluated the relationship between the clinical outcome and the local tissue and overall immune status in 412 patients with primary LSCC. We constructed and validated a risk model that could predict prognosis, assess immune status, identify high-risk patients, and develop personalized treatment plans through bioinformatics. In addition, through immunohistochemical analysis, we verified the differential expression of CTSL and KDM5D genes with the largest weight coefficients in the model in LSCC tissues and their influence on the prognosis and tumor-infiltrating lymphocytes (TILs). RESULTS: We found that interstitial tumor-infiltrating lymphocytes, tumor parenchymal-infiltrating lymphocyte volume, tumor infiltrates lymphocytes of frontier invasion, and the platelet-to-lymphocyte ratio (PLR) were independent factors affecting the prognosis of patients with LSCC. A novel risk model can guide clinicians to accurately predict prognosis, identify high-risk patients, and formulate personalized treatment plans. The differential expression of genes such as CTSL and KDM5D has a significant correlation with the TILs of LSCC and the prognosis of patients. CONCLUSION: Local and systemic inflammatory markers in patients with laryngeal squamous cell carcinoma are reliable prognostic factors. The risk model and CTSL, KDM5D gene have important potential research value.

Alternatively spliced ANLN isoforms synergistically contribute to the progression of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality. Anilin actin-binding protein (ANLN) has been reported to be associated with carcinogenesis in multiple tumors. However, the expression pattern and functional effects of ANLN in HNSCC remain to be unclear. Clinical data and online databases were used to analyze the expression of ANLN and its relationship with HNSCC patient survival. Expression of two major splice variants of ANLN was assessed in HNSCC tissues and cell lines. The functional effects and related mechanisms of ANLN isoforms were investigated in HNSCC in vitro and in vivo. Our study showed that patients with high expression of ANLN had a poor prognosis. The two primary isoforms of ANLN transcripts ANLN-201 and ANLN-210 were highly expressed in HNSCC tissues and cell lines. Knockout of ANLN restrained cell proliferation, migration, and invasion of SCC-9 cells. Mechanically, ANLN-201 could interact with c-Myc to keep its protein stability, thereby playing a oncogenic role in HNSCC. ANLN-210 could be transferred to macrophages via exosomes by binding to RNA-binding protein hnRNPC. Exosomal ANLN-210 promoted macrophage polarization via PTEN/PI3K/Akt signaling pathway, thus stimulating tumor growth of HNSCC. ANLN was an independent prognostic factor in patients with HNSCC. Alternatively spliced ANLN isoforms collaboratively promote HNSCC tumorigenesis in vitro and in vivo, which might provide the in-depth role and mechanism of ANLN in HNSCC development.

LncRNA LINC-PINT Inhibits Malignant Behaviors of Laryngeal Squamous Cell Carcinoma Cells via Inhibiting ZEB1.

Objective: Laryngeal squamous cell carcinoma (LSCC) belongs to head and neck squamous cell carcinoma (HNSCC), with dismal prognosis. Here, this study aims to disclose the role of LINC-PINT in cancer development, which may contribute to improving the clinical outcomes of LSCC treatment. Methods: LINC-PINT expression in LSCC tissues and in TU-177 and Hep-2 cells was quantified, and subsequently, the association between LINC-PINT and LSCC malignancies was analyzed. pcDNA3.1-LINC-PINT or pcDNA3.1-EZH2 was introduced into Hep-2 and TU-177 cells. qRT-PCR and Western blot analyses examined the levels of proteins related to the AKT/mTOR pathway and their phosphorylated proteins in Hep-2 and TU-177 cells. The viability as well as migration and invasion abilities of Hep-2 and TU-177 cells were determined. Also, the distribution of LINC-PINT in Hep-2 cells was investigated as well as the interplay between LINC-PINT and EZH2. The downstream genes that might interact with EZH2 were screened. Results: LINC-PINT expression was inhibited in LSCC tissues and in Hep-2 and TU-177 cells, whose downregulation was associated with unsatisfactory prognosis. LINC-PINT overexpression suppressed the proliferative, migratory and invasive capacities of Hep-2 and TU-177 cells. LINC-PINT, mainly expressing in nuclei, could enrich EZH2 to silence ZEB1. In Hep-2 and TU-177 cells, the inhibition of LINC-PINT or overexpression of ZEB1 could enhance cell proliferation, migration and invasion. The phosphorylated levels of proteins related to the AKT/mTOR pathway were declined in cells with LINC-PINT overexpression, and the levels of these phosphorylated proteins were increased in cells with LINC-PINT inhibition. Conclusion: LINC-PINT enriches EZH2 to silence ZEB1 and thus inhibits the proliferative, migratory, and invasive capacities of Hep-2 and TU-177 cells. In addition, LINC-PINT might exert its biological function through the AKT/mTOR pathway.

High Iodine Nutrition May Be a Risk Factor for Cervical Lymph Node Metastasis in Papillary Thyroid Cancer Patients.

PURPOSE: The aim of this study was to retrospectively identify the effect of iodine on the papillary thyroid cancer (PTC) process and investigate the risk clinicopathologic characteristics of cervical lymph node metastasis (CLNM) for achieving a better preventive strategy of PTC. METHODS: Totally 187 patients with CLNM and 279 without CLNM (NCLNM) were enrolled, and their urinary iodine concentration (UIC) and serum iodine concentration (SIC) were measured. Logistic regressions were used to reveal the effects of iodine nutrition on the CLNM status of PTC. RESULTS: The levels of thyroid-stimulating hormone (TSH) and thyroglobulin (TG) were higher in the CLNM group than in the NCLNM group. UIC and SIC were positively correlated, and both of them were correlated with TSH, free thyroxine, and TG. The proportions of UIC >300 µg/L and of SIC >90 µg/L were higher in the CLNM than in the NCLNM. Logistic analysis showed that SIC >90 µg/L was an independent predictor for CLNM in PTC. Additionally, age ≥45, female, TG, multifocality, and diameter of cancer invasion >1 cm also affected CLNM status in PTC, and their logistic regression model showed a certain diagnostic accuracy (area under the receiver-operating characteristic curve = 0.72). CONCLUSIONS: Relatively high iodine nutrition seemed to be a significant risk factor for the occurrence of CLNM in PTC and may promote lymphatic metastasis in PTC.

Identification of Immune-Related LncRNA Pairs for Predicting Prognosis and Immunotherapeutic Response in Head and Neck Squamous Cell Carcinoma.

Long noncoding RNAs (lncRNAs) have multiple functions with regard to the cancer immunity response and the tumor microenvironment. The prognosis of head and neck squamous cell carcinoma (HNSCC) is still poor currently, and it may be effective to predict the clinical outcome and immunotherapeutic response of HNSCC by immunogenic analysis. Therefore, by using univariate COX analysis and Lasso Cox regression, we identified a signature consisting of 21 immune-related lncRNA pairs (IRLPs) that predicted clinical outcome and Immunotherapeutic response in HNSCC. Specifically, it was associated with immune cell infiltration (i.e., T cells CD4 memory resting, CD8 T cells, macrophages M0, M2, and NK cells), and more importantly this signature was strongly related with immune checkpoint inhibitors (ICIs) [such as PDCD1 (r = -0.35, P < 0.001), CTLA4 (r = -0.26, P < 0.001), LAG3 (r = -0.22, P < 0.001) and HAVCR2 (r = -0.2, P < 0.001)] and immunotherapy-related biomarkers (MMR and HLA). The present study highlighted the value of the 21 IRLPs signature as a predictor of prognosis and immunotherapeutic response in HNSCC.

Prognostic value of platelet distribution width and mean platelet volume in patients with laryngeal cancer.

Aims: To investigate the prognostic relevance of platelet volume indices for survival in laryngeal cancer. Patients & methods: The study included 640 patients with laryngeal cancer. We analyzed the optimal cutoff values through receiver operating characteristic analysis, then analyzed the univariate factor and multivariate variables. Kaplan-Meier curves and log-rank tests were conducted to compare the overall survival (OS) and recurrence-free survival rates between the groups. Results: In multivariate analysis, elevated platelet distribution width (PDW) and PDW/platelet count ratio were significantly correlated with poor prognosis for OS; however, elevated mean platelet volume (MPV) and MPV/platelet count ratio suggested a notable correlation with favorable prognosis for OS. Meanwhile, elevated PDW and decreased MPV were significantly correlated with poor prognosis for recurrence-free survival. Conclusions: Our findings indicate that elevated PDW and decreased MPV could serve as independent biomarkers for worse survival in laryngeal cancer.

A novel full endoscopic annular repair technique combined with autologous conditioned plasma intradiscal injection: a new safe serial therapeutic model for the treatment of lumbar disc herniation.

BACKGROUND: Recurrent intervertebral disc herniation and an exacerbated degenerative process have been identified as the most important factors contributing to persistent pain and disability after surgical discectomy. Defects in the annulus fibrosus remain a surgical challenge, as the preference for minimally invasive surgical approaches for lumbar microdiscectomy, surgical access, and the specifics of anatomy limit the types of devices that permit annulus fibrosus repair. Furthermore, the intervertebral disc is a relatively avascular structure, and surgical procedures can accelerate the degenerative disc process. This study aimed to evaluate the clinical safety and efficacy of a novel microdiscectomy annular repair technique combined with an autologous conditioned plasma (ACP) intradiscal injection for the treatment of lumbar disc herniation (LDH). METHODS: From July 2017 to December 2018 this study recruited 75 patients with LDH (single segment) and randomly divided these patients into the following three groups: group A, full endoscopic discectomy; group B: full endoscopic discectomy and annular repair; group C, full endoscopic discectomy annular repair and ACP intradiscal injection. The pre- and postoperative neurological function and pain status were evaluated by the visual analog scale (VAS) score and the Oswestry disability index (ODI). Patients were followed up once preoperatively, and at 1, 3, and 6 months postoperatively. RESULTS: The procedure was successfully performed in all cases. No cases required conversion to an open procedure. The preoperative symptoms were alleviated significantly after surgery. The VAS scores for lower back and lower limb pain and ODI score were significantly difference at 1 month, 3 months, 6 months post operation compared to pre-operation scores (P<0.05). For VAS scores of the lower back, the difference between group A and group C was statistically significant (A>C), as was the difference between group B and group C (B>C). CONCLUSIONS: Early results showed that the use of the novel full endoscopic annular repair technique and ACP intradiscal injection serial therapeutic model are beneficial for short term outcomes and demonstrates a reduction in symptomatic disc reherniation with low postoperative complication rates. This new serial therapeutic model may significantly improve the symptoms of postoperative lower back pain.

Prognostic Significance of Lactate Dehydrogenase in Patients Undergoing Surgical Resection for Laryngeal Squamous Cell Carcinoma.

The aim is to estimate the prognostic value of lactate dehydrogenase (LDH) in patients undergoing surgical resection for laryngeal squamous cell carcinoma (LSCC). A total of 640 resected LSCC patients were included. Preoperative lactate dehydrogenase (LDH) was assessed. Kaplan-Meier survival analysis and Cox regression analysis were conducted for overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis, univariate analysis and multivariate analysis demonstrated significant prognostic value for preoperative LDH. Although LDH was predictor of OS, it failed to be a predictor of RFS. The univariate HR and 95% CI of LDH were 0.484 and 0.357-0.658 (P < 0.0001). The multivariate analysis showed that LDH (HR = 0.518, 95% CI: 0.380-0.705, p < 0.0001) was related to OS. Elevated preoperative LDH >132 IU/L was significantly associated with better survival. Preoperative LDH might be an independent prognostic marker of OS in LSCC patients undergoing surgical resection.

Expressions and relationship of Krüppel-like factor 15 and endothelial nitric oxide synthase in experimental deep venous thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) is an early postoperative complication. Thrombosis formation, which is potentially life-threatening, seriously affects the rehabilitation of patients after surgery. We aimed to establish a C57 mouse model of DVT and to examine the changes in the expression of Krüppel-like factor 15 (KLF15) and endothelial nitric oxide synthase (eNOS) in venous wall tissues, and we also investigated the regulatory relationship of KLF15 and eNOS in the thrombin-induced human umbilical vein endothelial cell (HUVEC) injury cell model. METHODS: The DVT model was established using the inferior vena cava (IVC) stenosis method. The expression levels of KLF15 and eNOS were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In cell experiments, the expression of KLF15 and eNOS was analyzed in the model of thrombin-induced HUVEC injury with KLF15 siRNA. RESULTS: Compared to the control and sham-operated groups, KLF15 in the DVT group was upregulated, while eNOS was downregulated. The results of cell experiments revealed that KLF15 was downregulated in the thrombin+KLF15 siRNA group compared with the thrombin group. Meanwhile, eNOS was upregulated in the thrombin+KLF15 siRNA group compared with the thrombin group. These findings suggested that KLF15 regulated the expression of eNOS in the DVT model. CONCLUSIONS: We successfully constructed a DVT mouse model. In the early stage of DVT formation, KLF15 regulated the expression and inhibited the antithrombotic effect of eNOS, resulting in thrombi formation.