Inhibition of GBP5 activates autophagy to alleviate inflammatory response in LPS-induced lung injury in mice.

BACKGROUND: Pulmonary emphysema is a condition that causes damage to the lung tissue over time. GBP5, as part of the guanylate-binding protein family, is dysregulated in mouse pulmonary emphysema. However, the role of GBP5 in lung inflammation in ARDS remains unveiled. METHODS: To investigate whether GBP5 regulates lung inflammation and autophagy regulation, the study employed a mouse ARDS model and MLE-12 cell culture. Vector transfection was performed for the genetic manipulation of GBP5. Then, RT-qPCR, WB and IHC staining were conducted to assess its transcriptional and expression levels. Histological features of the lung tissue were observed through HE staining. Moreover, ELISA was conducted to evaluate the secretion of inflammatory cytokines, autophagy was assessed by immunofluorescent staining, and MPO activity was determined using a commercial kit. RESULTS: Our study revealed that GBP5 expression was altered in mouse ARDS and LPS-induced MLE-12 cell models. Moreover, the suppression of GBP5 reduced lung inflammation induced by LPS in mice. Conversely, overexpression of GBP5 diminished the inhibitory impact of LPS on ARDS during autophagy, leading to increased inflammation. In the cell line of MLE-12, GBP5 exacerbates LPS-induced inflammation by blocking autophagy. CONCLUSION: The study suggests that GBP5 facilitates lung inflammation and autophagy regulation. Thus, GBP5 could be a potential therapeutic approach for improving ARDS treatment outcomes, but further research is required to validate these findings.

Primary Epithelioid Angiosarcoma of the Jejunal Mesentery Causing Abdominal Bleeding: Case Report and Literature Review.

Gastrointestinal angiosarcoma is an extremely rare malignant tumor of the digestive tract, characterized by a very poor prognosis, with few patients surviving more than 1 year after diagnosis. This case report describes a 71-year-old female patient with a 3-year history of intermittent abdominal pain and significant exacerbation of abdominal pain and bloating 2 weeks prior to treatment. After surgical treatment, the pathological and immunohistochemical diagnosis was primary epithelioid angiosarcoma of the jejunal mesentery. The patient refused postoperative adjuvant chemotherapy and died 4 months after diagnosis due to widespread systemic metastasis. In addition, this article reviews 38 previously reported cases of primary gastrointestinal angiosarcoma, aiming to further understand angiosarcoma and thus guide clinical practitioners in providing more comprehensive treatment approaches.

Optimization of the fermentation process and antioxidant activity of mixed lactic acid bacteria for honeysuckle beverage.

The aim of the research was to obtain a high healthcare honeysuckle beverage with strong antioxidant activity. Honeysuckle (Lonicera japonica Thunb) was used as the raw material in this experiment. The effects of fermentation temperature, fermentation time, lactic acid bacteria inoculation amount, and sugar addition amount on the sensory quality of honeysuckle beverage were investigated by single factor test and orthogonal test, and the best process was obtained. The physicochemical indexes and antioxidant activity of honeysuckle beverages fermented with lactic acid bacteria were studied. The results showed that the fermentation temperature of the beverage was 37 °C, the fermentation time was 24 h, the inoculation amount of Lactiplantibacillus plantarum and Lactobacillus acidophilus mixed starter (1:1) was 3%, and 8% white granulated sugar was added. The highest sensory score was 87.30 ± 0.17, which was the optimal process. The honeysuckle liquid mixed inoculation with Lactiplantibacillus plantarum and Lactobacillus acidophilus was fermented for 24 h. The number of viable bacteria reached 9.84 ± 0.02 lg cfu/mL, the pH value was 3.10 ± 0.01, and the total polyphenol content was 7.53 ± 0.03 mg GAE/g. The number of lactic acid bacteria, pH, total polyphenol content, and free radical scavenging rate were significantly increased (p < 0.05) compared with the non-inoculated and single-inoculated lactic acid bacteria. To sum up, it was concluded that a better quality beverage could be obtained by fermenting a solution of honeysuckle with Lactiplantibacillus plantarum and Lactobacillus acidophilus mixed fermentation agent, providing a new approach and new ideas for the development of deep processing and fermented beverages using honeysuckle.

High expression of CASP1 induces atherosclerosis.

Atherosclerosis is a chronic, progressive vascular disease. The relationship between CASP1 gene expression and atherosclerosis remains unclear. The atherosclerosis dataset GSE132651 and GSE202625 profiles were downloaded from gene expression omnibus. Differentially expressed genes (DEGs) were screened. The construction and analysis of protein-protein interaction network, functional enrichment analysis, gene set enrichment analysis, and Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEG. 47 DEGs were identified. According to gene ontology analysis, they were mainly enriched in the regulation of stimulus response, response to organic matter, extracellular region, extracellular region, and the same protein binding. Kyoto Encyclopedia of Gene and Genome analysis results showed that the target cells were mainly enriched in the PI3K-Akt signaling pathway, Ras signaling pathway, and PPAR signaling pathway. In the enrichment project of Metascape, vascular development, regulation of body fluid levels, and positive regulation of cell motility can be seen in the gene ontology enrichment project. Eleven core genes (CASP1, NLRP3, MRC1, IRS1, PPARG, APOE, IL13, FGF2, CCR2, ICAM1, HIF1A) were obtained. IRS1, PPARG, APOE, FGF2, CCR2, and HIF1A genes are identified as core genes. Gene expression heatmap showed that CASP1 was highly expressed in atherosclerosis samples and low expressed in normal samples. NLRP3, MRC1, IRS1, PPARG, APOE, IL13, FGF2, CCR2, ICAM1, HIF1A were low expressed in atherosclerosis samples. CTD analysis showed that 5 genes (CASP1, NLRP3, CCR2, ICAM1, HIF1A) were found to be associated with pneumonia, inflammation, cardiac enlargement, and tumor invasiveness. CASP1 gene is highly expressed in atherosclerosis. The higher the CASP1 gene, the worse the prognosis.

Three-dimensional chromatin landscapes in hepatocellular carcinoma associated with hepatitis B virus.

BACKGROUND: Three-dimensional (3D) chromatin architecture frequently altered in cancer. However, its changes during the pathogenesis of hepatocellular carcinoma (HCC) remained elusive. METHODS: Hi-C and RNA-seq were applied to study the 3D chromatin landscapes and gene expression of HCC and ANHT. Hi-C Pro was used to generate genome-wide raw interaction matrices, which were normalized via iterative correction (ICE). Moreover, the chromosomes were divided into different compartments according to the first principal component (E1). Furthermore, topologically associated domains (TADs) were visualized via WashU Epigenome Browser. Furthermore, differential expression analysis of ANHT and HCC was performed using the DESeq2 R package. Additionally, dysregulated genes associated with 3D genome architecture altered were confirmed using TCGA, qRT-PCR, immunohistochemistry (IHC), etc. RESULTS: First, the intrachromosomal interactions of chr1, chr2, chr5, and chr11 were significantly different, and the interchromosomal interactions of chr4-chr10, chr13-chr21, chr15-chr22, and chr16-chr19 are remarkably different between ANHT and HCC, which resulted in the up-regulation of TP53I3 and ZNF738 and the down-regulation of APOC3 and APOA5 in HCC. Second, 49 compartment regions on 18 chromosomes have significantly switched (A-B or B-A) during HCC tumorigenesis, contributing to up-regulation of RAP2A. Finally, a tumor-specific TAD boundary located on chr5: 6271000-6478000 and enhancer hijacking were identified in HCC tissues, potentially associated with the elevated expression of MED10, whose expression were associated with poor prognosis of HCC patients. CONCLUSION: This study demonstrates the crucial role of chromosomal structure variation in HCC oncogenesis and potential novel biomarkers of HCC, laying a foundation for cancer precision medicine development.

High-performance and functional fully bio-based polylactic acid/polypropylene carbonate blends by in situ multistep reaction-induced interfacial control.

Using a solvent-free radical grafting technique, glycidyl methacrylate (GMA) and maleic anhydride (MAH) were used as functionalized graft monomers, styrene (St) as a copolymer monomer, and grafted onto polylactic acid (PLA). A series of PLA-g-(GMA/MAH-co-St) graft copolymers were prepared by adjusting the GMA/MAH ratio. Subsequently, the prepared graft copolymers were used as a compatibilizer with PLA and polypropylene carbonate (PPC) for melt blending to prepare PLA/PPC/PLA-g-(GMA/MAH-co-St) blends. The effects of changes in the GMA/MAH ratio in the graft copolymer on the thermodynamics, rheology, optics, degradation performance, mechanical properties, and microstructure of the blend were studied. The results found that GMA, MAH, and St were successfully grafted onto PLA, and the PLA-g-(GMA/MAH-co-St) graft copolymer obtained from the reaction had a good toughening effect on the PLA/PPC blend system, which significantly improved the mechanical properties of the PLA/PPC/PLA-g-(GMA/MAH-co-St) blend without reducing its degradation performance, resulting in a biodegradable blend material with excellent comprehensive performance. In the PLA-g-(GMA/MAH-co-St) grafting reaction system, when GMA/MAH = 1.5/1.5 (w/w), the grafting degree of the graft copolymer increased most significantly, from 0.83 phr to 1.51 phr. This composition of graft copolymer can effectively improve the compatibility between PLA and PPC. The resulting PLA/PPC blend can maintain good melt flow properties (MFR of 14.51 g/10 min), high transparency, and low haze (light transmittance of 91.56 %, haze of 20.5 %), while significantly improving its thermal stability (T95%, Tmax, and Et increased by 12.87 °C, 20.33 °C, and 32.00 kJ/mol, respectively). Moreover, when introducing PLA-g-(GMA/MAH-co-St) (GMA/MAH = 1.5/1.5 (wt/wt)) graft copolymer into the system, the toughness of the PLA/PPC/PLA-g-(GMA/MAH-co-St) blend system is optimal, with the notch impact strength and fracture elongation increasing to 184.6 % and 535.4 % of the PLA/PPC blend, respectively, at which point the fracture surface of the impact sample shows a wrinkled fracture feature indicative of toughness.

Improving the properties of polylactic acid/polypropylene carbonate blends through cardanol-induced compatibility enhancement.

Cardanol (CD) is used as a reactive compatibilizer, and blended with polylactic acid (PLA) and polypropylene carbonate (PPC) resin (70/30(w/w)) to obtain a series of PLA/PPC/CD blends. The systematic study was conducted on the thermal properties, optical properties, rheological properties, mechanical properties, and microscopic morphology of the blend, by varying amounts of CD added to the blends. A detailed explanation and comprehensive analysis of the reaction mechanism between CD and PLA/PPC have been made. The study found that CD acts as a "bridge" between the PLA and PPC, forming the structure of a block copolymer (PLA-b-CD-b-PPC), and the copolymer can greatly improve the compatibility of PLA and PPC. When the amount of CD reaches 8 wt%, only one Tg is observed in the blend, simultaneously, PLA/PPC has already transitioned from a partially compatible system to a completely compatible system. At the same time, the addition of CD does not have any negative impact on the thermal stability of the PLA/PPC blend under processing temperature conditions, and the thermal stability of the PLA/PPC/CD blends can even be improved under extreme conditions. In addition, the addition of CD allows the PLA/PPC/CD blends to maintain a high light transmittance while reducing the opacity of the blend (the light transmittance remains above 92 %, and the opacity is reduced from 37 % to about 24 %), demonstrating excellent optical properties. Moreover, the elongation at break and impact strength of the PLA/PPC/CD blend both show a trend of first increasing and then decreasing with the increase of CD amount. When the CD amount varies within the range of 6- 8 wt%, the blends undergoes a brittle-ductile transition, and its toughness is greatly improved while the rigidity can also meet practical needs. When the amount of CD in the system increases to 12 wt%, the toughness of the blend reaches its peak, and its elongation at break and impact strength reach 513.24 % and 9211.5 J/m2 respectively (increased to 2442.84 % and 270.73 % of the PLA/PPC blend). Concurrently, the fracture surface of the blend exhibits large-scale plastic flow in the direction of the applied force, with marked shear yield phenomena, showing obvious characteristics of tough fracture.

Inhibitory mechanism of quercetin on Alicyclobacillus acidoterrestris.

In this the antibacterial of quercetin against Alicyclobacillus acidoterrestris was evaluated by measuring the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Subsequently, the effect of quercetin on A. acidoterrestris cell membrane was evaluated through scanning electron microscopy (SEM), surface hydrophobicity determination, diacetate fluorescein staining and propidium iodide (PI) staining. Additionally, the effects of quercetin on intracellular macromolecules and cell metabolism were explored by measuring the culture medium protein, bacterial protein and intracellular sodium and potassium adenosine triphosphate (ATP) enzyme activity. The results revealed that quercetin exhibited the MIC and MBC values of 100 ug/mL and 400 ug/mL, respectively, against A. acidoterrestris. The SEM results revealed that quercetin could induce irreversible damage to the cell membrane effectively. Moreover, quercetin could enhance the surface hydrophobicity of A. acidoterrestris. The results of flow cytometry and fluorescence microscopy analyses revealed that quercetin could promote cell damage by altering the cell membrane permeability of A. acidoterrestris, inducing the release of nucleic acid substances from the cells. Furthermore, the determination of protein content in the culture medium, bacterial protein content, and the Na(+)/K(+)-ATPase activity demonstrated that quercetin could reduce the intracellular protein content and impedes protein expression and ATPase synthesis effectively, leading to apoptosis.

[Phage antibody library technology in tumor therapy: a review].

Tumor is a serious threat to human health. At present, surgical resection, chemoradiotherapy, targeted therapy and immunotherapy are the main therapeutic strategies. Monoclonal antibody has gradually become an indispensable drug type in the clinical treatment of cancer due to its high efficiency and low toxicity. Phage antibody library technology (PALT) is a novel monoclonal antibody preparation technique. The recombinant immunoglobulin variable region of heavy chain (VH)/variable region of light chain (VL) gene is integrated into the phage vector, and the antibody is expressed on the phage surface in the form of fusion protein to obtain a diverse antibody library. Through the process of adsorption-elution-amplification, the antibody library can be screened to obtain the antibody molecule with specific binding antigen as well as its gene sequence. PALT has the advantages of short antibody production cycle, strong plasticity of antibody structure, large antibody yield, high diversity and direct production of humanized antibodies. It has been used in screening tumor markers and preparation of antibody drugs for breast cancer, gastric cancer, lung cancer and liver cancer. This article reviews the recent progress and the application of PALT in tumor therapy.

Improvement of properties of polylactic acid/polypropylene carbonate blends using epoxy soybean oil as an efficient compatibilizer.

Epoxidized soybean oil (ESO) was used as a compatibilizer and blended with polylactic acid (PLA) and polypropylene carbonate (PPC) resin to prepare a series of PLA/PPC/ESO blends with varying compositions. The influence of the variation in the amount of ESO added to the blend system on the thermal properties, optical properties, rheological properties, mechanical properties, and microscopic morphology of the blends was studied. The research indicates that ESO can react with PLA and PPC to form a chemical bond interface, which improves the compatibility of PLA and PPC to a certain extent. With the increase in the amount of ESO added to the blend (1- 5 phr), the complete decomposition temperature, storage modulus, loss modulus, complex viscosity, notched impact strength, and elongation at break of the blend all show a trend of continuous increase. At the same time, the melt flow rate, light transmittance, and tensile strength of the blend do not show significant fluctuations. When the amount of ESO in the system is 5 phr, compared with the PLA/PPC blend, the notched impact strength and elongation at break of the PLA/PPC/ESO blend increase from 4270.3 J/m2, 43.89 % to 8560.4 J/m2, 211.28 %, respectively, and its tensile strength and transmittance still remain around 63 MPa, 92 %. This improves the toughness of the blend while maintaining its rigidity, demonstrating excellent mechanical and optical properties. At this time, the microscopic morphology of the fracture surface of the impact sample also shows obvious characteristics of tough fracture. However, when the amount of ESO added to the blend is excessive (6 phr), the compatibility of the blending system decreases, which will degrade the performance of the blending material and ultimately destroy the phase morphology of the blend and reduce its mechanical properties.

Lifestyle factors, serum parameters, metabolic comorbidities, and the risk of kidney stones: a Mendelian randomization study.

Background and objective: The early identification of modifiable risk factors is important for preventing kidney stones but determining causal associations can be difficult with epidemiological data. We aimed to genetically assess the causality between modifiable factors (lifestyle factors, serum parameters, and metabolic comorbidities) and the risk of kidney stones. Additionally, we aimed to explore the causal impact of education on kidney stones and its potential mediating pathways. Methods: We conducted a two-sample Mendelian randomization (MR) study to explore the causal association between 44 modifiable risk factors and kidney stones. The FinnGen dataset initially explored the causal relationship of risk factors with kidney stones and the UK Biobank dataset was used as the validation set. Then, a meta-analysis was conducted by combining discovery and validation datasets. We used two-step MR to assess potential mediators and their mediation proportions between education and kidney stones. Results: The combined results indicated that previous exposures may increase the risk of kidney stones, including sedentary behavior, urinary sodium, the urinary sodium/potassium ratio, the urinary sodium/creatinine ratio, serum calcium, 25-hydroxyvitamin D (25OHD), the estimated creatinine-based glomerular filtration rate (eGFRcrea), GFR estimated by serum cystatin C (eGFRcys), body mass index (BMI), waist circumference, type 2 diabetes mellitus (T2DM), fasting insulin, glycated hemoglobin, and hypertension. Coffee intake, plasma caffeine levels, educational attainment, and the urinary potassium/creatinine ratio may decrease the risk of kidney stones. Ranked by mediation proportion, the effect of education on the risk of kidney stones was mediated by five modifiable risk factors, including sedentary behavior (mediation proportion, 25.7%), smoking initiation (10.2%), BMI (8.2%), T2DM (5.8%), and waist circumference (3.2%). Conclusion: This study provides MR evidence supporting causal associations of many modifiable risk factors with kidney stones. Sedentary lifestyles, obesity, smoking, and T2DM are mediating factors in the causal relationship between educational attainment and kidney stones. Our results suggest more attention should be paid to these modifiable factors to prevent kidney stones.

The Effect of Functionalized SEBS on the Properties of PP/SEBS Blends.

Styrene (St) was used as comonomer and glycidyl methacrylate (GMA) as grafting monomer to prepare SEBS-g-(GMA-co-St) graft copolymers via melt grafting. Then, the graft copolymers were employed as a compatibilizer for melt blending polypropylene (PP) and hydrogenated styrene-butadiene-styrene (SEBS) triblock copolymers. The effects of the amount of GMA in the graft copolymers on thermal properties, rheology, crystallization, optical and mechanical properties, and microstructure of the blends were investigated. The results show that GMA and St were successfully grafted onto SEBS. The GMA amount in the graft copolymer significantly influenced the comprehensive properties of PP/SEBS/SEBS-g-(GMA-co-St) blends. The epoxy groups of GMA reacted with PP and SEBS, forming interfacial chemical bonds, thereby enhancing the compatibility between PP and SEBS to varying extents. After introducing SEBS-g-(GMA-co-St) into PP/SEBS blends, crystallinity decreased, crystal size increased while transmittance remained above 91% with rising GMA amount in the graft copolymers, indicating excellent optical properties. Notched impact strength and elongation at break of the blends showed a trend of first increasing and then decreasing with increased amounts of GMA in the graft copolymers. When the amount of GMA in the graft copolymers was 3 wt%, the blends exhibited optimal toughness with notched impact strength and elongation at break of 30,165.82 J/m2 and 1445.40%, respectively. This was attributed to the tightest dispersion interface adhesion and maximum matrix plastic deformation, consistent with the mechanical performance results.

Patient-Reported Outcome Measures following Coblation Nucleoplasty for Cervical Discogenic Dizziness.

BACKGROUND: There is little research in the literature comparing the efficacy of coblation nucleoplasty with conservative treatment in the treatment of cervical discogenic dizziness and reporting the achieved rate of minimal clinically important differences (MCID) and patient acceptable symptom state (PASS) after surgery. This retrospective study aims to explore the patient-reported outcome measures (PROM) following coblation nucleoplasty for cervical discogenic dizziness and to compare the therapeutic effect of coblation nucleoplasty with prolonged conservative treatment. METHODS: Sixty-one patients with cervical discogenic dizziness and a positive intradiscal diagnostic test eligible for single-level cervical coblation nucleoplasty were included in the study. Among these 61 patients, 40 patients underwent cervical coblation nucleoplasty, while the remaining 21 patients refused surgery and received continued conservative treatment. The primary PROMs were the intensity and frequency of dizziness and secondary PROMs were related to the neck disability index (NDI) and visual analog scale (VAS) for neck pain (VAS-neck) during a 12-month follow-up period. Moreover, the achieved rate of MCID and PASS in both groups was assessed 12 months after surgery. RESULTS: Dizziness intensity, dizziness frequency, VAS-neck score, and NDI score were significantly improved from the baseline at all follow-up time points in both treatment groups, except for showing no significant improvement in dizziness frequency in the conservative treatment group at 6 and 12 months after surgery. However, at each follow-up time point, the above indexes were lower in the surgery group than in the conservative treatment group. In addition, the achieved rates for PASS and MCID in all indexes in the surgery group were significantly higher than those in the conservative treatment group at 12 months after surgery. CONCLUSIONS: Cervical coblation nucleoplasty significantly improved the intensity and frequency of dizziness, neck pain, and NDI in patients with cervical discogenic dizziness, and the results were superior to those from prolonged conservative treatment. Meanwhile, cervical coblation nucleoplasty is a good choice for patients with chronic neck pain and refractory cervical discogenic dizziness who have not demonstrated the indications for open surgery and have not responded well to conservative treatment.

[Biomarkers for early screening and diagnosis of breast cancer: a review].

The estimated new cases of breast cancer (BC) patients were 2.26 million in 2020, which accounted for 11.7% of all cancer patients, making it the most prevalent cancer worldwide. Early detection, diagnosis and treatment are crucial to reduce the mortality, and improve the prognosis of BC patients. Despite the widespread use of mammography screening as a tool for BC screening, the false positive, radiation, and overdiagnosis are still pressing issues that need to be addressed. Therefore, it is urgent to develop accessible, stable, and reliable biomarkers for non-invasive screening and diagnosis of BC. Recent studies indicated that the circulating tumor cell DNA (ctDNA), carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), extracellular vesicles (EV), circulating miRNAs and BRCA gene from blood, and the phospholipid, miRNAs, hypnone and hexadecane from urine, nipple aspirate fluid (NAF) and volatile organic compounds (VOCs) in exhaled gas were closely related to the early screening and diagnosis of BC. This review summarizes the advances of the above biomarkers in the early screening and diagnosis of BC.

[Advances of glioma biomarkers].

Glioma is the most common primary brain tumor, accounting for 81% of intracranial tumors. The diagnosis and prognosis assessment of glioma are mainly based on imaging. However, imaging cannot be fully used as the basis for diagnosis and prognosis assessment due to the infiltrative growth characteristics of glioma. Therefore, the discovery and identification of novel biomarkers is particularly important for the diagnosis, treatment and prognosis assessment of glioma. The latest findings suggest that a variety of biomarkers in the tissues and blood of glioma patients can be used for the auxiliary diagnosis and prognosis assessment of glioma. Among them, IDH1/2 gene mutation, BRAF gene mutation and fusion, p53 gene mutation, increased telomerase activity, circulating tumor cells and non-coding RNA can be used as diagnostic markers. Prognostic markers include 1p/19p codeletion, MGMT gene promoter methylation, upregulation of matrix metalloproteinase-28, insulin-like growth factor-binding protein-2 and CD26, and downregulation of Smad4. This review highlights the latest advances of biomarkers in the diagnosis and prognosis assessment of glioma.

Preoperative computed tomography-based tumoral radiomic features prediction for overall survival in resectable non-small cell lung cancer.

Objectives: The purpose of this study was to evaluate whether preoperative radiomics features could meliorate risk stratification for the overall survival (OS) of non-small cell lung cancer (NSCLC) patients. Methods: After rigorous screening, the 208 NSCLC patients without any pre-operative adjuvant therapy were eventually enrolled. We segmented the 3D volume of interest (VOI) based on malignant lesion of computed tomography (CT) imaging and extracted 1542 radiomics features. Interclass correlation coefficients (ICC) and LASSO Cox regression analysis were utilized to perform feature selection and radiomics model building. In the model evaluation phase, we carried out stratified analysis, receiver operating characteristic (ROC) curve, concordance index (C-index), and decision curve analysis (DCA). In addition, integrating the clinicopathological trait and radiomics score, we developed a nomogram to predict the OS at 1 year, 2 years, and 3 years, respectively. Results: Six radiomics features, including gradient_glcm_InverseVariance, logarithm_firstorder_Median, logarithm_firstorder_RobustMeanAbsoluteDeviation, square_gldm_LargeDependenceEmphasis, wavelet_HLL_firstorder_Kurtosis, and wavelet_LLL_firstorder_Maximum, were selected to construct the radiomics signature, whose areas under the curve (AUCs) for 3-year prediction reached 0.857 in the training set (n=146) and 0.871 in the testing set (n=62). The results of multivariate analysis revealed that the radiomics score, radiological sign, and N stage were independent prognostic factors in NSCLC. Moreover, compared with clinical factors and the separate radiomics model, the established nomogram exhibited a better performance in predicting 3-year OS. Conclusions: Our radiomics model may provide a promising non-invasive approach for preoperative risk stratification and personalized postoperative surveillance for resectable NSCLC patients.

Phosphoglycerate mutase 5 facilitates mitochondrial dysfunction and neuroinflammation in spinal tissues after spinal cord injury.

Spinal cord injury (SCI) is a high incidence worldwide that causes a heavy physical and psychological burden to patients. It is urgent to further reveal the pathological mechanism and effective treatment of SCI. Mitochondrial dysfunction plays an important role in the disease progression of SCI. As a mitochondrial membrane protein, phosphoglycerate mutase 5 (PGAM5) is mainly involved in mitochondrial function and mitosis to modulate cellular physiological functions, but the roles of PGAM5 in spinal tissues remain to be unreported after SCI. The purpose of this study was to evaluate the role of PGAM5 in SCI mice and its relationship with neuroinflammation. The results showed that the mitochondrial membrane protein PGAM5 was involved in microglia activation after SCI, and PGAM5 deletion could improve mitochondrial dysfunction (including abnormal mtDNA, ATP synthases, and ATP levels, Cyt C expression, and ROS and rGSH levels) in spinal cord tissue after SCI, Arg1/iNOS mRNA level, iNOS expression, and pro-inflammatory cytokines TNF-α, IL-1ß, and IL-18 levels. In vitro, H2O2 increased TNF-α, IL-1ß, and IL-18 levels in BV2 cells, and PGAM5-sh and Nrf2 activators significantly reversed H2O2-induced iNOS expression and proinflammatory cytokine production. Furthermore, IP/Western blotting results revealed that PGAM5-sh treatment significantly reduced the interaction of PGAM5 with Nrf2 and enhanced the nuclear translocation of Nrf2 in BV2 cells. The data suggested that PGAM5 was involved in the cascade of oxidative stress and inflammatory response in microglia via facilitating the expression level of Nrf2 in the nucleus after SCI. It provided a reference for clarifying the pathological mechanism and therapeutic target of SCI.

A nomogram for predicting postoperative urosepsis following retrograde intrarenal surgery in upper urinary calculi patients with negative preoperative urine culture.

Retrograde intrarenal surgery (RIRS) is one of the main surgical methods for upper urinary calculi, but severe complications of infection may occur after surgery. This study aimed to establish and validate a preoperative nomogram for predicting postoperative urosepsis following retrograde intrarenal surgery to treat upper urinary calculus in patients with a negative preoperative urine culture. We retrospectively recruited 1767 patients with negative preoperative urine cultures who underwent retrograde intrarenal surgery to treat upper urinary calculi from January 2017 to April 2022. The independent risk factors for urosepsis include a solitary kidney, positive urine nitrite, operative time ≥ 75 min, history of recurrent urinary tract infections, and history of diabetes were identified by univariate analysis and multivariate binary logistic regression analysis, which construct a nomogram. The receiver operating characteristic curve of the nomogram for predicting urosepsis was 0.887 in the training cohort and 0.864 in the validation cohort, respectively. The calibration curve and decision curve analysis demonstrated great consistency and clinical utility of the nomogram. Therefore, the nomogram combining preoperative independent risk factors can predict the probability of a postoperative urosepsis following retrograde intrarenal surgery in patients with a negative preoperative urine culture, which could help urologists take preventive measures in advance after surgery to avoid more serious complications of infection.

Anterior Cervical Decompression and Fusion Surgery for Cervical Spondylosis with Concomitant Tinnitus: A Multicenter Prospective Cohort Study.

OBJECTIVE: Cervical spondylosis is often accompanied by tinnitus. Up to now, there is a lack of large samples and prospective studies to investigate the effect of anterior cervical decompression and fusion (ACDF) on tinnitus associate with cervical spondylosis. To this end, we performed a prospective cohort study to assess the effectiveness of ACDF on the relief of tinnitus. METHODS: This was a multicenter, prospective, cohort clinical study. Between August 2017 and August 2018, 174 patients with cervical spondylosis accompanied by tinnitus were enrolled, with a follow-up of 12 months. Among the 174 patients, 142 received anterior cervical surgery (surgery group) and 32 received conservative treatment (conservative group). The primary end point was the mean change in scores on the tinnitus functional index (TFI). The secondary end points included tinnitus loudness, modified Japanese orthopaedic association scores (mJOA) for spinal cord function, and visual analogue scale (VAS) for neck pain. All the above indexes were measured before treatments and at 1, 3, 6, and 12 months after treatments. One-way analysis of variance and paired samples t-test was adopted for statistical analysis. RESULTS: The TFI score was reduced immediately after cervical decompression surgery (from 54.7 ± 15.6 to 32.3 ± 12.5, P < 0.001) and this was sustained at 12 months (P < 0.001). The TFI score of the conservative group also decreased (from 53.9 ± 16.8 to 45.2 ± 13.6, P < 0.001), but the effect was not maintained at 12 months (P = 0.069). There was a significant improvement in tinnitus loudness (from 5.2 ± 1.6 to 2.6 ± 1.9, P < 0.001), mJOA (from 12.0 ± 1.6 to 14.2 ± 1.6, P < 0.001), and VAS for neck pain (from 58.5 ± 9.6 to 22.0 ± 16.4, P < 0.001) in the surgical group. Improvements in the surgical group were statistically significantly greater than that in the conservative group (P < 0.001). CONCLUSION: This study indicates that anterior cervical surgery can relieve tinnitus in patients with cervical spondylosis and that tinnitus is an accompanying manifestation of cervical spondylosis.