Genetic association analysis of dietary intake and idiopathic pulmonary fibrosis: a two-sample mendelian randomization study.

BACKGROUND: IPF is a complex lung disease whose aetiology is not fully understood, but diet may have an impact on its development and progression. Therefore, we investigated the potential causal connection between dietary intake and IPF through TSMR to offer insights for early disease prevention recommendations. METHODS: The study incorporated 29 dietary exposure factors, oily fish intake, bacon intake, processed meat intake, poultry intake, beef intake, pork intake, lamb/mutton intake, non-oily fish intake, fresh fruit intake, cooked vegetable intake, baked bean intake, fresh tomato intake, tinned tomato intake, salad/raw vegetable intake, Fresh fruit intake, coffee intake, tea intake, water intake, red wine intake, average weekly beer plus cider intake, alcoholic drinks per week, cereal intake, bread intake, whole-wheat intake, whole-wheat cereal intake, cheese intake, yogurt intake, salt added to food and whole egg intake. The study explored the causal link between diet and IPF using TSMR analysis, predominantly the IVW method, and performed sensitivity analyses to validate the results. RESULT: The study revealed that consuming oily fish, yogurt, and dried fruits had a protective effect against IPF, whereas the consumption of alcoholic beverages and beef was linked to an increased risk of IPF. CONCLUSION: In this MR study, it was discovered that the consumption of oily fish, yogurt, and dried fruits exhibited a protective effect against IPF, whereas the intake of alcoholic beverages and beef was associated with an elevated risk of IPF. These findings underscore the significance of making informed and timely dietary decisions in IPF prevention.

GLRaV-2 protein p24 suppresses host defenses by interaction with a RAV transcription factor from grapevine.

Grapevine leafroll-associated virus 2 (GLRaV-2) is a prevalent virus associated with grapevine leafroll disease, but the molecular mechanism underlying GLRaV-2 infection is largely unclear. Here, we report that 24-kDa protein (p24), an RNA-silencing suppressor (RSS) encoded by GLRaV-2, promotes GLRaV-2 accumulation via interaction with the B3 DNA-binding domain of grapevine (Vitis vinifera) RELATED TO ABSCISIC ACID INSENSITIVE3/VIVIPAROUS1 (VvRAV1), a transcription factor belonging to the APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) superfamily. Salicylic acid-inducible VvRAV1 positively regulates the grapevine pathogenesis-related protein 1 (VvPR1) gene by directly binding its promoter, indicating that VvRAV1 may function in the regulation of host basal defense responses. p24 hijacks VvRAV1 to the cytoplasm and employs the protein to sequester 21-nt double-stranded siRNA together, thereby enhancing its own RSS activity. Moreover, p24 enters the nucleus via interaction with VvRAV1 and weakens the latter's binding affinity to the VvPR1 promoter, leading to decreased expression of VvPR1. Our results provide a mechanism by which a viral RSS interferes with both the antiviral RNA silencing and the AP2/ERF-mediated defense responses via the targeting of one specific host factor.

Discovery of New Heterocyclic/Benzofuran Hybrids as Potential Anti-Inflammatory Agents: Design, Synthesis, and Evaluation of the Inhibitory Activity of Their Related Inflammatory Factors Based on NF-κB and MAPK Signaling Pathways.

NF-κB and MAPK are classic inflammation signaling pathways which regulate inflammation signal transmission and induce the expression of many inflammatory factors. Based on the potent anti-inflammatory activity of benzofuran and its derivatives, several new heterocyclic/benzofuran hybrids were first designed and synthesized by molecular hybridization. Their structure was confirmed by 1H NMR, 13C NMR, HRMS or X-single crystal diffraction. The anti-inflammatory activity of these new compounds was screened by compounds; compound 5d exhibited an excellent inhibitory effect on the generation of NO (IC50 = 52.23 ± 0.97 µM), and low cytotoxicity (IC50 > 80 µM) against the RAW-264.7 cell lines. To further elucidate the possible anti-inflammatory mechanisms of compound 5d, the hallmark protein expressions of the NF-κB and MAPK pathways were studied in LPS-stimulated RAW264.7 cells. The results indicate that compound 5d not only significantly inhibits the phosphorylation levels of IKKα/IKKß, IKßα, P65, ERK, JNK and P38 in the classic MAPK/NF-κB signaling pathway in a dose-dependent manner, but also down-regulates the secretion of pro-inflammatory factors such as NO, COX-2, TNF-α and IL-6. Further, the in vivo anti-inflammatory activity of compound 5d indicated that it could regulate the involvement of neutrophils, leukocytes and lymphocytes in inflammation processes, and reduce the expression of IL-1ß, TNF-α and IL-6 in serum and tissues. These results strongly suggest that the piperazine/benzofuran hybrid 5d has a good potential for developing an anti-inflammatory lead compound, and the anti-inflammatory mechanism might be related to the NF-κB and MAPK signaling pathways.

Narrow linewidth semiconductor laser with a multi-period-delayed feedback photonic circuit.

A multi-period-delayed feedback (MPDF) photonic circuit constructed by a Sagnac ring and two coupled rings was designed. By coupling a distributed feedback (DFB) laser diode (LD) with the MPDF, a narrow linewidth semiconductor laser was demonstrated. The linewidth of the DFB-LD with MPDF was narrowed to be around 2 kHz, which is reduced by three orders of magnitude, and the linewidth reduction capability could be maintained when the wavelength of the DFB-LD was tuned in a range wider than 3 nm. The laser frequency stability can also be improved using the proposed technique, and the frequency fluctuation was reduced for nearly 8 times in comparison with the DFB-LD.

Changes of Physicochemical, Bioactive Compounds and Antioxidant Capacity during the Brewing Process of Zhenjiang Aromatic Vinegar.

Zhenjiang aromatic vinegar (ZAV) is a kind of traditional fermented food worldwide. In this study, the changes of physicochemical properties, total phenolic content (TPC), total flavonoid content (TFC), and total antioxidant activity (TAA) were evaluated during the brewing process of ZAV. In addition, the correlation between phenolic compound contents and antioxidant activities was investigated during the aging process (AP) of ZAV. The results showed that total acids, non-volatile acids, and amino nitrogen increased gradually during the brewing process. Reducing sugar decreased sharply at the early fermentation stage and then increased during the AP. Meanwhile, TPC, TFC, and TAA kept a very low level at the stage of alcohol fermentation (AF), and increased to the highest level at the sixth year of the AP. TAA has a high positive correlation with TPC and TFC during the brewing process of ZAV. In addition, the contents of p-hydroxybenzoic acid, vanillic acid, and catechin were higher than other phenolic compounds and reached the highest level at the sixth year of the AP, and were the main composition of phenolic compounds during the AP. Moreover, gallic acid, ferulic acid, and sinapic acid had the higher contribution at the early stage of the AP, and then declined to a lower level. Catechin, vanillic acid, and syringic acid had a higher contribution during the AP. These findings would be helpful in controlling the quality of vinegar and improving its functional properties.

Continuous-wave single-frequency laser with dual wavelength at 1064 and 532 nm.

A continuous-wave high-power single-frequency laser with dual-wavelength output at 1064 and 532 nm is presented. The dependencies of the output power on the transmission of the output coupler and the phase-matching temperature of the LiB(3)O(5) (LBO) crystal are studied. An output coupler with transmission of 19% is used, and the temperature of LBO is controlled to the optimal phase-matching temperature of 422 K; measured maximal output powers of 33.7 W at 1064 nm and of 1.13 W at 532 nm are obtained with optical-optical conversion efficiency of 45.6%. The laser can be single-frequency operated stably and mode-hop-free, and the measured frequency drift is less than 15 MHz in 1 min. The measured Mx2 and My2 for the 1064 nm laser are 1.06 and 1.09, respectively. The measured Mx2 and My2 for the 532 nm laser are 1.12 and 1.11, respectively.

Effect of pharmaconutrition-supplemented parenteral nutrition for severe acute pancreatitis: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of pharmaconutrition-supplemented parenteral nutrition (PN) for severe acute pancreatitis (SAP). METHODS: A comprehensive search of abstracts was performed in the MEDLINE, OVID, Springer, and Cochrane Library database. Published data of randomized clinical trials (RCTs) comparing the clinically relevant outcomes of pharmaconutrition-supplemented PN versus PN for patients with SAP were analyzed. The analyzed outcome variables included infection, mortality, intensive care unit (ICU) stay, hospital stay, and leukocytes change. Statistical analyses were performed using the Cochrane Collaboration's RevMan 5.1 software. RESULTS: Four RCTs published in 1998 or later were included in this meta-analysis, in which 76 patients with pharmaconutrition-supplemented PN and 77 patients with PN. Pharmaconutrition-supplemented PN showed significantly better results in terms of infection (OR, 0.42; 95% CI, 0.20-0.91; P =0.03) and leukocytes change (before treated: mean different, 0.93; 95% CI, 0.21-1.65; P =0.01; after treated: mean different, -0.77; 95% CI, -1.47- -0.08; P =0.03). No significant difference could be found in mortality (OR, 0.30; 95% CI, 0.07-1.19; P =0.09), ICU stay (mean different, -3.65; 95% CI, -9.39-2.10; P =0.21), and hospital stay (mean different, -1.20; 95% CI, -9.89-7.48; P =0.79). CONCLUSIONS: The current meta-analysis indicates that pharmaconutrition-supplemented PN only show advantages in infection and leukocytes change.

Repair of refractory wounds through grafting of artificial dermis and autologous epidermis aided by vacuum-assisted closure.

BACKGROUND: This study aimed to investigate the clinical efficacy of vacuum-assisted closure (VAC) combined with grafting of artificial dermis and autologous epidermis in the repair of refractory wounds. METHODS: Patients with refractory wounds underwent debridement. Then the VAC device was used to culture wound granulation tissue. After the wound granulation tissue began to grow, artificial dermis was grafted on the wounds with VAC treatment. Then autologous epidermis was grafted on the artificial dermis to repair the wounds after survival of the artificial epidermis. The study mainly observed length of the hospital stay, survival of the artificial dermis, time required for culture of the granulation tissue using VAC before grafting of the artificial dermis, survival time of the artificial dermis, survival conditions of the autologous epidermis, influence on functions of a healed wound at a functional part, healing conditions of donor sites, and recurrence conditions of the wounds. RESULTS: Healing was successful for 22 patients (95.7%), but treatment failed for 1 child. The 22 patients were followed up for 6 to 24 months. According to follow-up findings, the skin grafts had good color and a soft texture. They were wear resistant and posed no influence on function. The appearance of the final results was the same as that of the full-thickness skin graft. Mild or no pigmentation and no scar formation occurred at the donor sites, and the wounds did not recur. CONCLUSION: Vacuum-assisted closure combined with grafting of artificial dermis and autologous epidermis is an effective means for repairing refractory wounds and is worth clinical popularizing and application. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Diffusion models in text generation: a survey.

Diffusion models are a kind of math-based model that were first applied to image generation. Recently, they have drawn wide interest in natural language generation (NLG), a sub-field of natural language processing (NLP), due to their capability to generate varied and high-quality text outputs. In this article, we conduct a comprehensive survey on the application of diffusion models in text generation. We divide text generation into three parts (conditional, unconstrained, and multi-mode text generation, respectively) and provide a detailed introduction. In addition, considering that autoregressive-based pre-training models (PLMs) have recently dominated text generation, we conduct a detailed comparison between diffusion models and PLMs in multiple dimensions, highlighting their respective advantages and limitations. We believe that integrating PLMs into diffusion is a valuable research avenue. We also discuss current challenges faced by diffusion models in text generation and propose potential future research directions, such as improving sampling speed to address scalability issues and exploring multi-modal text generation. By providing a comprehensive analysis and outlook, this survey will serve as a valuable reference for researchers and practitioners interested in utilizing diffusion models for text generation tasks.

Advanced postoperative tissue antiadhesive membranes enabled with electrospun nanofibers.

Tissue adhesion is one of the most common postoperative complications, which is frequently accompanied by inflammation, pain, and even dyskinesia, significantly reducing the quality of life of patients. Thus, to prevent the formation of tissue adhesions, various strategies have been explored. Among these methods, placing anti-adhesion membranes over the injured site to separate the wound from surrounding tissues is a simple and prominently favored method. Recently, electrospun nanofibers have been the most frequently investigated antiadhesive membranes due to their tunable porous structure and high porosities. They not only can act as an essential barrier and functional carrier system but also allow for high permeability and nutrient transport, showing great potential for preventing tissue adhesion. Herein, we provide a short review of the most recent applications of electrospun nanofibrous antiadhesive membranes in tendons, the abdominal cavity, dural sac, pericardium, and meninges. Firstly, each section highlights the most representative examples and they are sorted based on the latest progress of related research. Moreover, the design principles, preparation strategies, overall performances, and existing problems are highlighted and evaluated. Finally, the current challenges and several future ways to develop electrospun nanofibrous antiadhesive membranes are proposed. The systematic discussion and proposed directions can shed light on ideas and guide the reasonable design of electrospun nanofibrous membranes, contributing to the development of exceptional tissue anti-adhesive materials in the foreseeable future.

Gibberellin Positively Regulates Tomato Resistance to Tomato Yellow Leaf Curl Virus (TYLCV).

Tomato yellow leaf curl virus (TYLCV) is a prominent viral pathogen that adversely affects tomato plants. Effective strategies for mitigating the impact of TYLCV include isolating tomato plants from the whitefly, which is the vector of the virus, and utilizing transgenic lines that are resistant to the virus. In our preliminary investigations, we observed that the use of growth retardants increased the rate of TYLCV infection and intensified the damage to the tomato plants, suggesting a potential involvement of gibberellic acid (GA) in the conferring of resistance to TYLCV. In this study, we employed an infectious clone of TYLCV to inoculate tomato plants, which resulted in leaf curling and growth inhibition. Remarkably, this inoculation also led to the accumulation of GA3 and several other phytohormones. Subsequent treatment with GA3 effectively alleviated the TYLCV-induced leaf curling and growth inhibition, reduced TYLCV abundance in the leaves, enhanced the activity of antioxidant enzymes, and lowered the reactive oxygen species (ROS) levels in the leaves. Conversely, the treatment with PP333 exacerbated TYLCV-induced leaf curling and growth suppression, increased TYLCV abundance, decreased antioxidant enzyme activity, and elevated ROS levels in the leaves. The analysis of the gene expression profiles revealed that GA3 up-regulated the genes associated with disease resistance, such as WRKYs, NACs, MYBs, Cyt P450s, and ERFs, while it down-regulated the DELLA protein, a key agent in GA signaling. In contrast, PP333 induced gene expression changes that were the opposite of those caused by the GA3 treatment. These findings suggest that GA plays an essential role in the tomato's defense response against TYLCV and acts as a positive regulator of ROS scavenging and the expression of resistance-related genes.

Causal effects between gut microbiota and pulmonary arterial hypertension: A bidirectional Mendelian randomization study.

BACKGROUND: Multiple studies have highlighted a potential link between gut microbes and the onset of Pulmonary Arterial Hypertension (PAH). Nonetheless, the precise cause-and-effect relationship remains uncertain. OBJECTIVES: In this investigation, we utilized a two-sample Mendelian randomization (TSMR) approach to probe the presence of a causal connection between gut microbiota and PAH. METHODS: Genome-wide association (GWAS) data for gut microbiota and PAH were sourced from MiBioGen and FinnGen research, respectively. Inverse variance weighting (IVW) was used as the primary method to explore the causal effect between gut flora and PAH, supplemented by MR-Egger, weighted median (WM). Sensitivity analyses examined the robustness of the MR results. Reverse MR analysis was used to rule out the effect of reverse causality on the results. RESULTS: The results indicate that Genus Ruminococcaceae UCG004 (OR = 0.407, P = 0.031) and Family Alcaligenaceae (OR = 0.244, P = 0.014) were protective factors for PAH. Meanwhile Genus Lactobacillus (OR = 2.446, P = 0.013), Class Melainabacteria (OR = 2.061, P = 0.034), Phylum Actinobacteria (OR = 3.406, P = 0.010), Genus Victivallis (OR = 1.980, P = 0.010), Genus Dorea (OR = 3.834, P = 0.024) and Genus Slackia (OR = 2.622, P = 0.039) were associated with an increased Prevalence of PAH. Heterogeneity and pleiotropy were not detected by sensitivity analyses, while there was no reverse causality for these nine specific gut microorganisms. CONCLUSIONS: This study explores the causal effects of eight gut microbial taxa on PAH and provides new ideas for early prevention of PAH.

Arginine-Proline Metabolism as a Mediator in the Association Between Coal Dust Exposure and Lung Function: A Retrospective Analysis.

OBJECTIVES: To investigate the mediating role of the activation degree of arginine-proline metabolism in the association of coal dust and decreased lung function. METHODS: CDE represented coal dust exposure, while the Hyp/Arg in BALF gauged arginine-proline metabolism activation. Pulmonary function indicators, including FVC%pred, FEV1/FVC%, and FEV1%pred, DLCO%pred, P(A-a) O2 and 6MWT, were assessed. RESULTS: Findings revealed a significant association between elevated CDE and increased Hyp/Arg, increased P(A-a) O2, decreased 6MWT, DLCO%pred, and decreased FVC%pred. However, no statistically significant association was found between CDE and FEV1%pred or FEV1/FVC%. The mediating effect of Hyp/Arg was significant for CDE's impact on P(A-a) O2 and DLCO%pred but not on 6MWT and FVC%pred. CONCLUSIONS: These results highlight the role of Hyp/Arg in mediating the association between CDE and lung function parameters, shedding light on potential therapeutic avenues for mitigating coal dust-induced lung function impairment.

Exploring a Potential Causal Link Between Dietary Intake and Chronic Obstructive Pulmonary Disease: A Two-Sample Mendelian Randomization Study.

Background: Chronic Obstructive Pulmonary Disease (COPD), the most prevalent chronic respiratory condition, significantly impairs patients' quality of life. The pivotal element in disease management lies in prevention, underscoring the paramount importance of employing a scientific approach to investigate early prevention strategies for COPD. Methods: This study delved into the causal link between 28 dietary intakes and COPD employing two-sample Mendelian randomization. We primarily utilized the Inverse Variance Weighted (IVW) method as the main outcome, complemented by Weighted Median (WM), MR-Egger method, along with several sensitivity analysis techniques, all accompanied by visual representations. Results: We identified higher odds of COPD following exposure to green beans (OR=1.381, 95% CI=1.119-1.704, P=0.003) and pork intake (OR=2.657, 95% CI=1.203-5.868, P=0.016). In contrast, the odds of developing COPD were lower following exposure to dried fruit (OR=0.481, 95% CI=0.283-0.819, P=0.007), cereal (OR=0.560, 95% CI=0.356-0.880, P=0.012), and whole egg consumption (OR=0.700, 95% CI=0.504-0.972, P=0.033). Conclusion: In light of our study's findings, we anticipate that strategically modifying dietary choices may offer an avenue for early COPD prevention in the future.

Genetically predicted the causal relationship between gut microbiota and infertility: bidirectional Mendelian randomization analysis in the framework of predictive, preventive, and personalized medicine.

Objective: Several studies have reported the association between gut microbiota and infertility; however, the causal association between them remains unclear. This study aimed to explore the causal relationship between gut microbiota and infertility and evaluate how specific gut microbiota can support early monitoring and prevention of infertility in the context of predictive, preventive, and personalized medicine (PPPM/3PM). Methods: The gut microbiota GWAS data included 18,340 individuals. Female infertility (6481 cases and 68,969 controls) and male infertility data (680 cases and 72,799 controls) were obtained from the FinnGen consortium. The inverse variance weighting (IVW), MR-Egger, weighted median (WM), Cochran Q tests, MR-PRESSO, and leave-one-out were used as a supplement to Mendelian randomization (MR) results and sensitivity analysis. Results: The results of MR analysis indicated a significant causal association between Eubacterium oxidoreducens (OR = 2.048, P = 0.008), Lactococcus (OR = 1.445, P = 0.042), Eubacterium ventriosum (OR = 0.436, P = 0.018), Eubacterium rectale (OR = 0.306, P = 0.002), and Ruminococcaceae NK4A214 (OR = 0.537, P = 0.045) and male infertility. Genetically predicted Eubacterium ventriosum (OR = 0.809, P = 0.018), Holdemania (OR = 0.836, P = 0.037), Lactococcus (OR = 0.867, P = 0.020), Ruminococcaceae NK4A214 (OR = 0.830, P < 0.050), Ruminococcus torques (OR = 0.739, P = 0.022), and Faecalibacterium (OR = 1.311, P = 0.007) were associated with female infertility. Sensitivity analysis did not detect heterogeneity and pleiotropy (P > 0.05). Conclusions: Our results provided evidence for the causal relationship between some gut microbiota and male and female infertility. These findings might be valuable in providing personalized treatment options for preventing infertility and improving reproductive function by monitoring and regulating the gut microbiota of infertility patients in the context of PPPM. Moreover, detecting the abundance of microbiota in feces can support preventive and personalized strategies, which may benefit more infertility patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00332-6.

WAVE3 Facilitates the Tumorigenesis and Metastasis of Tongue Squamous Cell Carcinoma via EMT.

Wiskott-Aldrich syndrome protein family verprolin-homologous domain-containing protein 3 (WAVE3) is reported as an oncogene regulating cell proliferation and motility in multiple malignancies, while its role in tongue squamous cell carcinoma (TSCC) remains unknown. This study aimed to explore the expression and mechanism of WAVE3 in TSCC. We enrolled 64 TSCC patients admitted between June 2013 and February 2014 and collected their cancerous and adjacent normal tissues to determine WAVE3 expression by immunohistochemistry. The correlation of WAVE3 expression with TSCC patients' pathological characteristics was analyzed. Then, a 7-year follow-up was conducted to observe the value of WAVE3 in evaluating patient outcomes. In addition, human TSCC SCC9, SCC25, and CAL27 cells were purchased and detected by Cell Counting Kit-8 (CCK-8), Transwell, and scratch-wound assays for their proliferation, invasion, and migration capacities, while real-time quantitative PCR (qRT-PCR) and Western blotting were utilized to quantify WAVE3 and epithelial-mesenchymal transition (EMT)-related protein expression, respectively. The most active cell lines were selected to be infected with lentiviral vectors that silenced WAVE3 (named WAVE3-sh group) and overexpressed WAVE3 cDNA (named WAVE3-OE group) to observe the impacts of interfering WAVE3 expression on TSCC cell biological behavior. The positive expression of WAVE3 in TSCC tissue was found to be obviously enhanced and predominantly located in the cytoplasm. In addition, close correlations were identified between WAVE3 and T staging, clinical staging, lymphatic metastasis, distant metastasis, and differentiation degree (P < 0.05). Increased WAVE3 expression predicted an elevated risk of death, as indicated by the follow-up analysis (P < 0.05). SCC9 was selected for subsequent experiments among various TSCC cell lines studied because it showed the most potent ability to proliferate, invade, and migrate (P < 0.05). Silencing WAVE3 expression in SCC9 cells decreased cell proliferation, invasion, migration, and EMT-related protein expression (P < 0.05), while increasing WAVE3 expression promoted SCC9 viability. WAVE3, which was highly expressed in TSCC, promoted EMT in tumor cells and accelerated their proliferation, invasion, and migration, which might provide a new theoretical basis for molecular targeted therapy of TSCC in the future.

Brucea javanica oil inhibits tongue squamous cell invasion and metastasis by regulating miR-138-EZH2 pathway.

Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors of head and neck. Its incidence is on the rise, and the proportion of young patients is gradually increasing, which is prone to tumor recurrence and metastasis. At present, there is no effective method to completely treat TSCC. Studies have shown that brucea javanica oil (BJO) has good antitumor activity against lung cancer and gastrointestinal tumors, but its therapeutic effect on TSCC is not clear. We have previously confirmed that oleic acid, the main component of BJO, can induce apoptosis of TSCC and reduce its invasion and metastasis ability. However, the anticancer effect and mechanism of BJO in TSCC remain unclear. In order to further explore the effects of BJO on the biological characteristics of TSCC cells, we studied the effects of different concentrations of BJO on the migration, invasion ability and epithelial mesenchymal transition (EMT) progression of TSCC cells and the possible mechanisms through in vitro experiments. We found that BJO could inhibit the invasion and metastasis of TSCC and up-regulate miR-138. After BJO treatment, the expression of E-cad was significantly increased, while the expression of EZH2, Slug, p-ERK1/2 and Vimentin was significantly decreased. EZH2 is a miR-138 target gene involved in TSCC. BJO inhibits TSCC invasion and metastasis by regulating the miR-138-EZH2 pathway. In vivo experiments have also well demonstrated the targeting effect of this pathway. This study provides a new therapeutic strategy for the treatment of TSCC.

Prognostic biomarker replication factor C subunit 5 and its correlation with immune infiltrates in acute myeloid leukemia.

OBJECTIVE: To determine the role of replication factor C subunit 5 (RFC5) in acute myeloid leukemia (AML) from four aspects: expression, prognosis, biological functions, and its effects on the immune system. METHODS: The RFC5 gene expression and survival analyses, biological function analyses including functional enrichment analysis of genes co-expressed with RFC5, RFC5-interacted gene network construction, gene set enrichment analysis (GSEA), and immune infiltration analysis were performed using data based on GDC TCGA and GEO. The CIBERSORT algorithm was employed to quantify immune cell fractions. All the statistical analyses were performed in SPSS software, GraphPad Prism, and R software. RESULTS: RFC5 expression was abnormally expressed in AML (P <0.05). Notably, differential RFC5 expression was observed among different FAB AML subtypes and hematopoietic lineages (all P <0.05). More importantly, high RFC5 expression served as an independent prognostic factor for the poor overall survival of AML patients (P <0.001). Enrichment analyses revealed that RFC5 was involved in cell cycle-related pathways in AML. CIBERSORT analysis showed high proportions of M2 macrophages in the high RFC5 expression group. CONCLUSIONS: RFC5 might serve as an effective and robust biomarker for the diagnosis and prognosis of AML. RFC5 might be involved in the AML progression via cell cycle regulation. Moreover, the correlation between RFC5 and immune cells might provide potential assistance for AML treatment.

[Comparison of nano-hydroxyapatite/polyamide 66 bioactive support and autologous iliac bone in bone grafting and fusion for elderly patients with lumbar tuberculosis].

Objective: To investigate the safety of nano-hydroxyapatite/polyamide 66 (n-HA/PA66) bioactive support in bone grafting and fusion for elderly patients with lumbar tuberculosis, and to analyze its effectiveness and advantages by comparing with autologous iliac bone grafting. Methods: A retrospective analysis was performed on 48 elderly patients with lumbar tuberculosis who met the selection criteria between January 2017 and January 2020. The patients all underwent one-stage posterior pedicle screw internal fixation combined with anterior lesion removal and bone grafting and fusion, of which 23 cases applied n-HA/PA66 bioactive support+allogeneic bone graft (n-HA/PA66 group) and 25 cases applied autologous iliac bone graft (autologous iliac bone group). There was no significant difference between the two groups in gender, age, bone density, disease duration, lesion segment, and preoperative pain visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and Cobb angle ( P>0.05). The operation time, intraoperative blood loss, and postoperative complications, as well as the VAS score, JOA score, American Spinal Injury Association (ASIA) spinal cord injury grading, Cobb angle, and bone fusion were recorded and compared between the two groups. Results: The operations were completed successfully in both groups. n-HA/PA66 group had significantly less operation time and intraoperative blood loss than the autologous iliac bone group ( P<0.05). All patients were followed up 12-24 months, with an average of 15.7 months. And the difference in follow-up time between the two groups was not significant ( P>0.05). Postoperative complications occurred in 3 cases (13%) in the n-HA/PA66 group and 10 cases (40%) in the autologous iliac group, and the difference in the incidence of complications between the two groups was significant ( χ 2=4.408, P=0.036). The postoperative VAS scores and JOA scores significantly improved when compared with the preoperative scores in both groups ( P<0.05), and the difference was significant ( P<0.05) between 2 weeks after operation and the last follow-up. The difference in VAS score at 2 weeks after operation was significant between the two groups ( P<0.05), and there was no significant difference ( P>0.05) at the other time points. At last follow-up, according to the ASIA grading, the effective improvement rate was 86% (18/21) in the n-HA/PA66 group and 90% (18/20) in the autologous iliac group, with no significant difference ( χ 2=0.176, P=0.675). Imaging review showed that grade Ⅰ bony fusion was obtained in both groups, and the fusion time of bone graft in the n-HA/PA66 group was significantly longer than that in the autologous iliac bone group ( P<0.05). There was no significant difference in the Cobb angle at each time point between the two groups ( P>0.05). No recurrence of tuberculosis, loosening or fracture of the internal fixator, or displacement of the bone graft was observed during follow-up. Conclusion: In elderly patients with lumbar spine tuberculosis, the n-HA/PA66 bioactive support combined with allogeneic bone graft can effectively restore and maintain the fusion segment height and physiological curvature of the lumbar spine, and the fusion rate of bone graft is similar to that of autologous iliac bone, which can achieve better effectiveness.

Multi-modal Neuroelectrophysiological Monitoring in the Treatment of Thoracic Tuberculosis with Debridement and Bone Grafting and Posterior Pedicle Screw Fixation via Costal Transverse Process Approach.

OBJECTIVE: To explore the value of multi-mode neuroelectrophysiological monitoring (MIOM) in evaluating spinal cord and nerve root function in the treatment of thoracic tuberculosis via costal transverse process approach. METHODS: From December 2017 to September 2019, a retrospective study of thoracic tuberculosis patients in our hospital was conducted. This study included 25 patients (14 men and 11 women). The average age of patients at the time of surgery was 63.3 years (range, 20-83 years). All patients (three cases with the destruction of a single vertebral body, 13 cases with the destruction of two vertebral bodies, and nine cases with the destruction of three or more vertebral bodies) underwent costal transverse process approach with debridement and bone grafting and internal fixation combined with intraoperative multimodal neuroelectrophysiological monitoring. During the operation, somatosensory evoked potential (SEP), transcranial electrical stimulation motor evoked potential (TES-MEP), and spontaneous electromyography (EMG) were used to monitor progress. ESR, visual analogue scale (VAS), Cobb angle, and Oswestry disability index (ODI) were statistically analyzed to evaluate the treatment effects and patient satisfaction. RESULTS: All 25 patients were successfully monitored. The follow-up time ranged from 12 to 21 months, with an average of 15.3 months. SEP waveform abnormalities occurred in five patients during the operation, the incidence rate was 28%. Of these five patients, three patients changed their instruments and postures, and adjusted the flushing water flow in time; one patient received pressure therapy in time; the operation was suspended for 10 min for one patient. There were seven cases with abnormal TES-MEP waveform, the incidence rate was 28%. Among these seven cases, five cases adjusted the nail path during the operation and adjusted the nail position in time. One case adjusted the inclination angle of the operating table in time; one case completed the contralateral nail stick correction in time; five of them had abnormal TES-MEP waveforms, and EMG burst potential was also detected, the incidence rate was 20%. After prompt treatment, the abnormal waveforms of all patients returned to normal; no abnormal waveforms, recurrence of tuberculosis, loosening of internal fixation, nerve and spinal cord dysfunction, etc. The VAS score, erythrocyte sedimentation rate (ESR), Cobb angle, and ODI scores of the patients 1 year after operation were significantly improved compared with 1 week after operation (P < 0.05). CONCLUSION: Multi-mode intraoperative electrophysiological detection combined with costal transverse process approach for the treatment of thoracic tuberculosis could avoid intraoperative nerve and blood vessel damage, reduce surgical risk, improve surgical efficiency, and ensure curative effect.