Repeat biopsy versus initial biopsy in terms of complication risk factors and clinical outcomes for patients with non-small cell lung cancer: a comparative study of 113 CT-guided needle biopsy of lung lesions.

Objectives: The safety and feasibility of repeat biopsy after systemic treatment for non-small cell lung cancer have received extensive attention in recent years. The purpose of this research was to compare complication rates between initial biopsy and rebiopsy in non-small cell lung cancer patients with progressive disease and to assess complication risk factors and clinical results after rebiopsy. Methods: The study included 113 patients initially diagnosed with non-small cell lung cancer who underwent lung biopsy at initial biopsy and rebiopsy after progression while on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and/or chemotherapy from January 2018 to December 2021. We compared the incidence of complications between the initial biopsy and rebiopsy and analyzed the predictors factors that influenced complications in patients who underwent rebiopsy. Results: The successful rate of rebiopsy was 88.5% (100/113). With the exception of two cases where lung adenocarcinoma changed into small cell lung cancer with gefitinib treatment, 98 individuals retained their initial pathological type. The secondary EGFR T790M mutation accounts for 55.6% of acquired resistance. The total number of patients with complications in initial biopsy was 25 (22.1%) and 37 (32.7%) in the rebiopsy. The incidence of pulmonary hemorrhage increased from 7.1% at the initial biopsy to 10.6% at rebiopsy, while the incidence of pneumothorax increased from 14.2% to 20.4%. Compared with the initial biopsy, the incidence of overall complications, parenchymal hemorrhage, and pneumothorax increased by 10.6%, 3.5%, and 6.2%, respectively. In all four evaluations (pneumorrhagia, pneumothorax, pleural reaction, and overall complication), there were no significant differences between the rebiopsy and initial biopsy (all p > 0.05). The multivariate logistic regression analysis suggested that male sex (odds ratio [OR] = 5.064, p = 0.001), tumor size ≤ 2 cm (OR = 3.367, p = 0.013), EGFR-TKIs with chemotherapy (OR = 3.633, p =0.023), and transfissural approach (OR = 7.583, p = 0.026) were independent risk factors for overall complication after rebiopsy. Conclusion: Compared with the initial biopsy, the complication rates displayed a slight, but not significant, elevation in rebiopsy. Male sex, tumor size ≤ 2 cm, transfissural approach, and EGFR-TKIs combined with chemotherapy were independent risk factors for rebiopsy complications.

Case report: Retroperitoneal solid pseudopapillary neoplasm associated with multiple hepatic metastases.

Solid pseudopapillary neoplasm (SPN) is a rare tumor mostly occurring in the pancreas. They are low-grade malignant tumors of the exocrine pancreas that occasionally metastasize, usually to the liver or peritoneum. Additionally, multiple metastases of extrapancreatic SPN to the liver are extremely rare and have been reported before. This study presents a case of a 13-year-old male patient with retroperitoneal SPN and multiple hepatic metastases. The patient presented with abdominal trauma and underwent enhanced CT, which revealed upper pancreatic occupancy and three hypodense foci in the right lobe of the liver. Moreover, increased spleen size was noted. The patient's serum tumor marker CA125 was increased to 39.00 U/mL (N < 35.0 U/mL), and circulating tumor cells were elevated to 10.2 FU/3 mL (N < 8.7 FU/3 mL). The patient underwent retroperitoneal occupancy resection and splenectomy, followed by resection of liver metastases 7 months after the surgery. Furthermore, multiple liver metastases from retroperitoneal SPN were confirmed postoperatively. The patient recovered for 1 year without tumor recurrence. This case emphasizes the importance of evaluating serum tumor markers and medical imaging in young patients as well as the fact that surgery appears to be the preferred treatment option for multiple metastases in SPN.

Utility of spectral CT with orthopedic metal artifact reduction algorithms for 125I seeds implantation in mediastinal and hepatic tumors.

Background: Virtual monochromatic image (VMI) combined with orthopedic metal artifact reduction algorithms (VMI + O-MAR) can effectively reduce artifacts caused by metal implants of different types. Nevertheless, so far, no study has systematically evaluated the efficacy of VMI + O-MAR in reducing various types of metal artifacts induced by 125I seeds. The aim of this study was to assess the effectiveness of combining spectral computed tomography (CT) images with O-MAR in reducing metal artifacts and improving the image quality affected by artifacts in patients after 125I radioactive seeds implantation (RSI). Methods: A total of 45 patients who underwent dual-layer detector spectral CT (DLCT; IQon, Philips Healthcare) scanning of mediastinal and hepatic tumors after 125I RSI were retrospectively included. Spectral data were reconstructed into conventional image (CI), VMI, CI combined with O-MAR (CI + O-MAR), and VMI + O-MAR to evaluate the de-artifact effect and image quality improvement. Objective indicators included signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and artifact index (AI) of lesions affected by artifacts. Subjective indicators included assessment of overcorrected artifacts and new artifacts, different morphology of artifacts, and overall image quality. Results: In artifact-affected lesion areas, SNR and CNR in the CI/VMI + O-MAR groups were better than those in CI groups (all P values <0.05). The AI showed a downward trend as VMI keV increased (all P values <0.001). The AI values of the CI/VMI (50-150 keV) group were all higher than the groups of CI/VMI + O-MAR (50-150 keV) (P<0.001). Overcorrection artifacts and new artifacts were concentrated in the VMI50/70 keV groups. In the evaluation of artifact morphology, as the VMI keV increased, the number of near-field banding artifacts in hyperdense artifacts gradually decreased, whereas the number of minimal or no artifacts increased, and the total number of hyperdense artifacts were decreased. The diagnostic and image quality scores of hyperdense artifacts were higher than those of hypodense artifacts as VMI keV increased. Conclusions: High VMI level combined with O-MAR substantially improve objective and subjective image quality, lesion display ability, and diagnostic confidence of CT follow-up after 125I RSI, especially at the VMI + O-MAR 150 keV level.

UCP2 promotes NSCLC proliferation and glycolysis via the mTOR/HIF-1α signaling.

BACKGROUND: Metabolic disturbance is a hallmark of cancers. Targeting key metabolic pathways and metabolism-related molecular could be a potential therapeutic approach. Uncoupling protein 2 (UCP2) plays a pivotal part in the malignancy of cancer and its capacity to develop resistance to pharmaceutical interventions. However, it is unclear about the mechanism of how UCP2 acts in the tumor growth and metabolic reprogramming process in non-small cell lung cancer (NSCLC). METHODS: Here, we conducted qRT-PCR to investigate the expression of UCP2 in both NSCLC tissues and cell lines. Subsequent functional studies including colony formation assay, CCK-8 assay, and glycolysis assay were conducted to investigate the functions of UCP2 in NSCLC. The regulatory mechanism of UCP2 toward the mammalian target of rapamycin (mTOR) and hypoxia-inducible factor-1 alpha (HIF-1α) signaling in NSCLC was confirmed through western blotting. RESULTS: We observed a significant upregulation of UCP2 in both NSCLC tissues and cell lines. The increased expression of UCP2 has a strong association with a worse outlook. Silencing UCP2 remarkably dampened NSCLC cell proliferation and glycolysis capacities. Mechanically, UCP2 promoted NSCLC tumorigenesis partially via regulating the mTOR/HIF-1α axis. CONCLUSION: Taken together, we explored the functions as well as the mechanisms of the UCP2/mTOR/HIF-1α axis in NSCLC progression, uncovering potential biological signatures and targets for NSCLC treatment.

Synthesis of lipoic acid ferulate and evaluation of its ability to preserve fish oil from oxidation during accelerated storage.

Lipoic acid ferulate (LAF) was synthesized and its anti-free radical ability in vitro was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonicacid) (ABTS) assays. Protective effects of LAF in stabilizing fish oil were tested, compared to antioxidants such as lipoic acid, ferulic acid and tert-butylhydroxyquinone (TBHQ) by measuring peroxide values, thiobarbituric acid reactants, p-anisidine values, nuclear magnetic resonance (NMR) spectra and gas chromatography-mass spectrometry (GC-MS) spectra of fish oil during accelerated storage (12 days, 80 °C). The inhibitory effect of these antioxidants on fish oil oxidation followed the order TBHQ ≧ LAF > ferulic acid > lipoic acid. In addition, the omega-3 polyunsaturated fatty acids were the first to be oxidized. The formation of oxidation products followed a first-order kinetic model, and the addition of LAF effectively reduced the reaction rate constants. Therefore, LAF can effectively slow down the formation of oxidative products and prolong the shelf life of fish oil.

Reprogramming of Treg cells in the inflammatory microenvironment during immunotherapy: a literature review.

Regulatory T cells (Treg), as members of CD4+ T cells, have garnered extensive attention in the research of tumor progression. Treg cells have the function of inhibiting the immune effector cells, preventing tissue damage, and suppressing inflammation. Under the stimulation of the tumor inflammatory microenvironment (IM), the reprogramming of Treg cells enhances their suppression of immune responses, ultimately promoting tumor immune escape or tumor progression. Reducing the number of Treg cells in the IM or lowering the activity of Treg cells while preventing their reprogramming, can help promote the body's anti-tumor immune responses. This review introduces a reprogramming mechanism of Treg cells in the IM; and discusses the regulation of Treg cells on tumor progression. The control of Treg cells and the response to Treg inflammatory reprogramming in tumor immunotherapy are analyzed and countermeasures are proposed. This work will provide a foundation for downregulating the immunosuppressive role of Treg in the inflammatory environment in future tumor immunotherapy.

circROBO1 promotes prostate cancer growth and enzalutamide resistance via accelerating glycolysis.

Background and aim: As non-coding RNAs, circular RNAs (circRNAs) contribute to the progression of malignancies by regulating various biological processes. In prostate cancer, however, there is still a lack of understanding regarding the potential molecular pathways and roles of circRNAs. Methods: Loss-off function experiments were performed to investigate the potential biological function of circRNA in the progression of prostate cancer. Western blot, qRT-PCR, and IHC assay were used to examine the expression level of different genes or circRNAs. Further molecular biology experiments were conducted to uncover the molecular mechanism underlying circRNA in prostate cancer using dual luciferase reporter and RNA immunoprecipitation (RIP) assays. Results: A novel circRNA (hsa_circ_0124696, named circROBO1) was identified as a significantly upregulated circRNA in both prostate cancer cells and tissues. Suppression of circROBO1 significantly attenuated the proliferation of prostate cancer cells. In addition, we found that the knockdown of circROBO1 remarkably increased the sensitivity of prostate cancer to enzalutamide treatment. A deceleration in glycolysis rate was observed after inhibition of circROBO1, which could suppress prostate cancer growth and overcome resistance to enzalutamide. Our results revealed that circROBO1 promotes prostate cancer growth and enzalutamide resistance via accelerating glycolysis. Conclusion: Our study identified the biological role of the circROBO1-miR-556-5p-PGK1 axis in the growth and enzalutamide resistance of prostate cancer, which is the potential therapeutic target of prostate cancer.

Interleukin-21 knockout reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis.

Estrogen deficiency accelerates osteoporosis in elderly women. However, the role of IL-21 in postmenopausal osteoporosis remains unclear. Female wild-type (WT) C57BL/6 and IL-21 knockout (KO) mice were used for ovariectomy (OVX). Here, IL-21 levels were significantly increased in the serum and bone tissues of WT-OVX mice. The trabecular bone space of the femur was significantly increased, and the bone mass was reduced in OVX mice, accompanied by a significant decrease in the maximum load, energy absorption, and elastic modulus indices. In contrast, IL-21 knockout effectively alleviated the effects of OVX on bone mass. Serum TRACP-5b and receptor activator of nuclear factor kappa B ligand (RANKL) levels and osteoclastogenesis were significantly higher in OVX mice than in sham mice, while serum TRACP-5b and RANKL levels and osteoclastogenesis were significantly decreased in IL-21 KO + OVX mice compared to WT + OVX mice. IL-21 knockdown reduces TRACP-5b, RANKL, and osteoclastogenesis, effectively preventing bone resorption and alleviating the progression of OVX-induced osteoporosis.

Optimal choice of stapler and digestive tract reconstruction method after distal gastrectomy for gastric cancer: A prospective case-control study.

BACKGROUND: Gastric cancer is the most common cause of cancer-related deaths, and is classified according to its location in the proximal, middle, or distal stomach. Surgical resection is the primary approach for treating gastric cancer. This prospective study aimed to determine the best reconstruction method after distal gastrectomy for gastric cancer. AIM: To explore the efficacy of different staplers and digestive tract reconstruction (DTR) methods after radical gastrectomy and their influence on prognosis. METHODS: Eighty-seven patients who underwent radical gastrectomy for distal gastric cancer at our institution between April 2017 and April 2020 were included in this study, with a follow-up period of 12-26 mo. The patients were assigned to four groups based on the stapler and DTR plan as follows: Billroth Ⅰ (B-I) reconstruction + linear stapler group (group A, 22 cases), B-I reconstruction + circular stapler group (group B, 22 cases), Billroth II (B-II) reconstruction + linear stapler group (group C, 22 cases), and B-II reconstruction + circular stapler group (group D, 21 cases). The pathological parameters, postoperative gastrointestinal function recovery, postoperative complications, and quality of life (QOL) were compared among the four groups. RESULTS: No significant differences in the maximum diameter of the gastric tumors, total number of lymph nodes dissected, drainage tube removal time, QLQ (QOL questionnaire)-C30 and QLQ-STO22 scores at 1 year postoperatively, and incidence of complications were observed among the four groups (P > 0.05). However, groups A and C (linear stapler) had significantly lower intraoperative blood loss and significantly shorter anastomosis time, operation time, first fluid diet intake time, first exhaust time, and length of postoperative hospital stay (P < 0.05) than groups B and D (circular stapler). CONCLUSION: Linear staplers offer several advantages for postoperative recovery. B-I and B-II reconstruction methods had similar effects on QOL. The optimal solution can be selected according to individual conditions and postoperative convenience.

Identification and validation of a nomogram predicting cancer-specific survival for elderly patients with adult fibrosarcoma: a multicenter retrospective study.

Background: Due to the low incidence of adult fibrosarcoma (AFS), it is difficult for clinicians to assess cancer-specific survival (CSS) in elderly patients based on this study. The study aimed to develop nomograms capable of accurately predicting 3-, 5-, and 8-year CSS in patients over 40 years of age with AFS. Methods: Data were collected from The Surveillance, Epidemiology, and End Results (SEER) registry. 586 patients were included in this study. Univariate as well as multivariate Cox regression analyses were applied to identify independent risk factors. A nomogram was constructed and validated to predict the 3-, 5-, and 8-year CSS of patients. Results: Five variables including age, sex, stage, grade, and chemotherapy status were considered independent risk factors and were used to construct the nomogram. The nomogram was well validated. The C-indexes of the training cohort and the validation cohort are 0.766 and 0.780, respectively. In addition, the area under the curves for 3-, 5- and 8-year CSS are 0.824, 0.846 and 0.840 in the training cohort, 0.835, 0.806 and 0.829 in the validation cohort. Calibration curves were also plotted to show that predicted endings have a well fit for the true endings. Finally, decision curve analysis demonstrates that the nomogram can bring a high benefit to patients. Conclusion: We successfully constructed a highly accurate nomogram to predict the CSS of AFS patients at 3-, 5-, and 8 years. The nomogram can greatly help clinicians and patients with AFS.

SNHG3/hsa-miR-455-5p Axis-mediated High Expression of MTHFD2 Correlates with Tumor Immune Infiltration and Endometrial Carcinoma Progression.

Purpose: Endometrial carcinoma (EC) is one of the three most common female genital tract cancers, and it contributes to the leading deaths of gynecologic cancer. MTHFD2 was reported up-regulated and associated with poor prognosis in many malignancies. However, its biological functions and mechanisms in EC are unclear. The present study aimed to identify the biological functions and potential molecular mechanisms of MTHFD2 in EC. Methods: The gene expression and information of patients used in this study were derived from TCGA, GEO and HPA databases. KM survival analysis was used to explore the clinical outcomes of EC patients and correlation analysis was applied to find the correction between MTHFD2 expression level and immune infiltration in EC. We used GO and GSEA analysis to explore the biological functions and mechanisms of MTHFD2. The CCK8 assay, the colony formation assay and the transwell migration assay were conducted to validate the function of MTHFD2 in EC cells. We applied STRING to find the protein that interacted with MTHFD2. Finally, ENCORI was used to explore the potential upstream regulation of MTHFD2 in EC and it was validated in EC cells. Results: In the present study, we found that MTHFD2 was up-regulated in EC and its high expression level was associated with patients' poor prognosis and adverse clinical parameters. MTHFD2 level was shown to be correlated with immune infiltration. Knockdown of MTHFD2 inhibited the malignant phenotype of HEC-1A and Ishikawa cells, including proliferation, colony formation and migration. Furthermore, we found the SNHG3/hsa-miR-455-5p axis as the potential upstream of MTHFD2. Conclusion: SNHG3/hsa-miR-455-5p axis-mediated high expression of MTHFD2, and the MTHFD2 expression level was associated with tumor immune infiltration and endometrial carcinoma progression. Knockdown of MTHFD2 significantly inhibited the malignant phenotype of EC cells. MTHFD2 may be a valuable predictive biomarker, and targeting MTHFD2 may be an effective way to improve the therapeutic effect in EC.

Insight into three water additives: Revealing the protective effects on survival and stress response under cold stress for Pacific white shrimp Litopenaeus vannamei.

The reproduction, development and growth of shrimp were hindered by cold stress, and even death was caused in severe cases. Moreover, huge economic losses to the shrimp aquaculture industry were caused every year by cold currents. The purpose of this study was to investigate the potential protective effects of water additives on the cold stress resistance of Pacific white shrimp (Litopenaeus vannamei) and their ability to improve the survival and stress response of the shrimp. Three potential cold-resistant additives adenosine triphosphate (A), soybean phospholipid (SP) and Clostridium butyricum (CB) on Pacific white shrimp under cold stress were added to the water with three concentrations for each additive. The mortality, activities of antioxidation enzymes and expression of anti-stress related genes in each group under cold stress were detected. The results showed that the cumulative mortality of low concentration for adenosine triphosphate (AL) and soybean phospholipid (SPL), medium concentration for soybean phospholipid (SPM) and high concentration for Clostridium butyricum (CBH) groups were significantly lower than that of the control (C) group when temperature maintained at 13 °C for 6 days. Total antioxidant capacity (T-AOC) content in shrimp plasma was significantly higher, while malondialdehyde (MDA) content was significantly lower than that in the C group. Gene expression analysis showed that 0.4 mg/L of adenosine triphosphate could regulate the immune defense ability and decrease apoptosis level of Pacific white shrimp under cold stress. Soybean phospholipid (2 mg/L) could enhance the immune ability of hepatopancreas, and Clostridium butyricum (10 mg/L) could significantly increase the expression of stress-related genes in shrimp intestine. Overall, these findings suggested that adenosine triphosphate and soybean phospholipid have the potential to be used as cold-resistant additives in Pacific white shrimp culture. This study provided valuable insights into addressing the problem of cold stress in shrimp culture.

The direct and gut microbiota-mediated effects of dietary bile acids on the improvement of gut barriers in largemouth bass (Micropterus salmoides).

Fish gut barrier damage under intensive culture model is a significant concern for aquaculture industry. This study aimed to investigate the effects of bile acids (BAs) on gut barriers in Micropterus salmoides. A germ-free (GF) zebrafish model was employed to elucidate the effects of the direct stimulation of BAs and the indirect regulations mediated by the gut microbiota on gut barrier functions. Four diets were formulated with BAs supplemented at 0, 150, 300 and 450 mg/kg, and these 4 diets were defined as control, BA150, BA300 and BA450, respectively. After 5 weeks of feeding experiment, the survival rate of fish fed with BA300 diet was increased (P < 0.05). Histological analysis revealed an improvement of gut structural integrity in the BA150 and BA300 groups. Compared with the control group, the expression of genes related to chemical barrier (mucin, lysozyme and complement 1) and physical barrier (occludin and claudin-4) was increased in the BA150 and BA300 groups (P < 0.05), and the expression of genes related to immunological barrier (interleukin [IL]-6, tumor growth factor ß, IL-10, macrophage galactose-type lectin and immunoglobulin M [IgM]) was significantly increased in the BA300 group (P < 0.05), but the expression of genes related to chemical barrier (hepcidin) and immunological barrier (IL-1ß, tumor necrosis factor-α, IL-6 and arginase) was significantly decreased in the BA450 group (P < 0.05). Gut microbiota composition analysis revealed that the abundance of Firmicutes was augmented prominently in the BA150 and BA300 groups (P < 0.05), while that of Actinobacteriota and Proteobacteria showed a downward trend in the BA150 and BA300 groups (P > 0.05). The results of the gut microbiota transferring experiment demonstrated an upregulation of gut barrier-related genes, including immunoglobulin Z/T (IgZ/T), IL-6, IL-1ß and IL-10, by the gut microbiota transferred from the BA300 group compared with the control (P < 0.05). Feeding the BA300 diet directly to GF zebrafish resulted in enhanced expression of IgM, IgZ/T, lysozyme, occludin-2, IL-6 and IL-10 (P < 0.05). In conclusion, BAs can improve the gut barriers of fish through both direct and indirect effects mediated by the gut microbiota.

Activated P2X receptors can up-regulate the expressions of inflammation-related genes via NF-κB pathway in spotted sea bass (Lateolabrax maculatus).

P2X receptors, including seven subtypes, i.e., P2X1-7, are the ligand-gated ion channels activated by the extracellular ATP playing the critical roles in inflammation and immune response. Even though the immune functions of P2X receptors have been characterized extensively in mammals, their functions in fish remain largely unknown. In this study, four P2X receptor homologues were characterized in spotted sea bass (Lateolabrax maculatus), which were named LmP2X2, LmP2X4, LmP2X5, and LmP2X7. Their tissue distributions and expression patterns were then investigated by real-time quantitative PCR (qPCR). Furthermore, their functions in regulating the expressions of inflammation-associated genes and possible signaling pathway were examined by qPCR and luciferase assay. The results showed that they share similar topological structures, conserved genomic organization, and gene synteny with their counterparts in other species previously investigated. And the four P2X receptors were expressed constitutively in the tested tissues. In addition, the expression of each of the four receptor genes was significantly induced by stimulation of Edwardsiella tarda and/or pathogen-associated molecular patterns (PAMPs) in vivo. Also, in primary head kidney leukocytes of spotted sea bass, LmP2X2 and LmP2X5 were induced by using PAMPs and/or ATP. Notably, the expressions of CCL2, IL-8, and TNF-α recognized as the pro-inflammatory cytokines, and of the four apoptosis-related genes, i.e., caspase3, caspase6, caspase7, and P53, were differentially upregulated in the HEK 293T cells with over-expressed LmP2X2 and/or LmP2X7 following ATP stimulation. Also, the over-expression of LmP2X4 can upregulate the expressions of IL-8, caspase6, caspase7, and P53, and LmP2X5 upregulates of IL-8, TNF-α, caspase7, and P53. Then in the present study it was demonstrated that the activation of any one of the four receptors significantly upregulated the activity of NF-κB promoter, suggesting that the activated LmP2Xs may regulate the expressions of pro-inflammatory cytokines via the NF-κB pathway. Taken together, the four P2X receptors were identified firstly from fish species in Perciformes, and they participate in innate immune response of spotted sea bass possibly by regulating the expressions of the inflammation-related genes. Our study provides the new evidences for the P2X receptors' involvement in fish immunity.

A Simple-to-Use Nomogram for Predicting Postoperative Early Death Risk in Elderly Patients with Spinal Tumors: A Population-Based Study.

Background: For elderly patients with primary spinal tumors, surgery is the best option for many elderly patients, in addition to palliative care. However, due to the unique physical function of elderly patients, the short-term prognosis is often unpredictable. It is therefore essential to develop a novel nomogram as a clinical aid to predict the risk of early death for elderly patients with primary spinal tumors who undergo surgery. Materials and Methods: In this study, clinical data were obtained from 651 patients through the SEER database, and they were retrospectively analyzed. Logistic regression analyses were used for risk-factor screening. Predictive modeling was performed through the R language. The prediction models were calibrated as well as evaluated for accuracy in the validation cohort. The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate the functionality of the nomogram. Results: We identified four separate risk factors for constructing nomograms. The area under the receiver operating characteristic curve (training set 0.815, validation set 0.815) shows that the nomogram has good discrimination ability. The decision curve analysis demonstrates the clinical use of this nomogram. The calibration curve indicates that this nomogram has high accuracy. At the same time, we have also developed a web version of the online nomogram for clinical practitioners to apply. Conclusions: We have successfully developed a nomogram that can accurately predict the risk of early death of elderly patients with primary spinal tumors undergoing surgery, which can provide a reference for clinicians.

Nuclease treatment enhanced the ameliorative effect of yeast culture on epidermal mucus, hepatic lipid metabolism, inflammation response and gut microbiota in high-fat diet-fed zebrafish.

As a functional feed additive, yeast cultures are rich in nucleotides, and adding extra nuclease can significantly increase the content of nucleotides in yeast culture. In this experiment, the effects on growth, epidermal mucus, liver and intestinal health of zebrafish were evaluated by supplementing the yeast culture or nuclease-treated yeast culture with a high-fat diet (HFD). One-month-old zebrafish were fed four diets: normal diet (NORM), HFD, yeast culture diet (YC), and nuclease-treated yeast culture diet (YC (N)) for three weeks. Results showed that the complement 4 activity of the epidermal mucus in YC (N) group was significantly higher than those in HFD and YC groups (P < 0.05). The YC and YC (N) significantly reduced the content of hepatic triglyceride caused by HFD (P < 0.05). Moreover, compared with the YC group, the YC (N) significantly increased the expression of lipolysis genes, such as PPARα, PGC1α, ACOX3 (P < 0.05). Compared with the YC group, the YC (N) group significantly increased the expression of liver pro-inflammatory factors TNFα, IL-6, IL-1ß and anti-inflammatory factors TGFß, IL-10 (P < 0.05). The diet YC and YC (N) significantly improved the height of the intestinal villus (P < 0.05). Compared with the HFD group, the YC (N) group significantly increased the expression of intestinal pro-inflammatory factors TNFα, IL-6 and anti-inflammatory factors TGFß, IL-10 (P < 0.05). The YC (N) group significantly decreased the abundance of intestinal Proteobacteria and Acinetobacter, and increased the abundance of intestinal Actinobacteria, Mycobacterium and Rhodobacter (P < 0.05). In conclusion, compared with the supplement of yeast culture, nuclease treated yeast culture can further alleviate the adverse effects of HFD on liver and intestinal health, and be used as feed additives for the nutritional and immune regulation of fish.

CT and CEA-based machine learning model for predicting malignant pulmonary nodules.

Computed tomography (CT), an efficient radiological technology, is used to detect lung cancer in the clinic. Carcinoembryonic antigen (CEA), a common tumor biomarker, is applied in the detection of various tumors. To highlight the advantages of two-dimensional techniques and assist clinicians in optimizing lung cancer diagnostic schemes, we established a favorable model combining CT and CEA. In the study, univariate analysis was performed to screen independent predictors in a training cohort of 271 patients with malignant pulmonary nodules (MPNs) and 92 with benign pulmonary nodules (BPNs). Six machine learning-based models involving five CT predictors (mediastinal lymph node enlargement, lobulation, vascular notch sign, spiculation, and nodule number) and lnCEA were constructed and validated in an independent cohort of 129 participants (92 MPNs and 37 BPNs) by SPSS Modeler. A nomogram and the Delong test were generated by R software. Finally, the model established by logistic regression had highest diagnostic efficiency (area under the curve [AUC] = 0.912). Moreover, the diagnostic ability of the logistic model in the validation cohort (AUC = 0.882, 80.4% sensitivity, 75.7% specificity) was higher than that of the Peking University model (AUC = 0.712, 68.5% sensitivity, 70.3% specificity) and the Mayo model (AUC = 0.745, 62.0% sensitivity, 75.7% specificity). Interestingly, for the participants with intermediate (10-30 mm) and CEA-negative nodule, the model reached an AUC of 0.835 (72.3% sensitivity, 83.3% specificity). The AUC for the early lung cancer was as high as 0.822 with 67.3% sensitivity and 78.9% specificity. As a conclusion, this promising model presents a new diagnostic strategy for the clinic to distinguish MPNs from BPNs.

Functional characterization of MEKK3 in the intestinal immune response to bacterial challenges in grass carp (Ctenopharyngodon idella).

Mitogen-activated protein kinase kinase kinase 3 (MEKK3) is an evolutionarily conserved Ser/Thr protein kinase of the MEKK family that is essential for the host immune response to pathogen challenges in mammals. However, the immune function of MEKK3s in lower vertebrate species, especially in bony fish, remains largely unknown. In this study, a fish MEKK3 (designated CiMEKK3) gene was cloned and identified from grass carp (Ctenopharyngodon idella). The present CiMEKK3 cDNA encoded a 620 amino acid polypeptide containing a conserved S-TKc domain and a typical PB1 domain. Several potential immune-related transcription factor-binding sites, including activating protein 1 (AP-1), nuclear factor kappa B (NF-κB) and signal transducer and activator of downstream transcription 3 (STAT3), were observed in the 5' upstream DNA sequence of CiMEKK3. A phylogenetic tree showed that CiMEKK3 exhibits a close evolutionary relationship with MEKK3s from Cyprinus carpio and Carassius auratus. Quantitative real-time PCR analysis revealed that CiMEKK3 transcripts were widely distributed in all selected tissues of healthy grass carp, with a relatively high levels observed in the gill, head kidney and intestine. Upon in vitro challenge with bacterial pathogens (Aeromonas hydrophila and Aeromonas veronii) and pathogen-associated molecular patterns (PAMPs) (lipopolysaccharide (LPS), peptidoglycan (PGN), L-Ala-γ-D-Glu-mDAP (Tri-DAP) and muramyl dipeptide (MDP)), the expression levels of CiMEKK3 in the intestinal cells of grass carp were shown to be significantly upregulated in a time-dependent manner. In vivo injection experiments revealed that CiMEKK3 transcripts were significantly induced by MDP challenge in the intestine; however, these effects could be inhibited by the nutritional dipeptides carnosine and Ala-Gln. Moreover, subcellular localization analysis and luciferase reporter assays indicated that CiMEKK3 could act as a cytoplasmic signal-transducing activator involved in the regulation of NF-κB and MAPK/AP-1 signaling cascades in HEK293T cells. Taken together, these findings strongly suggest that CiMEKK3 plays vital roles in the intestinal immune response to bacterial challenges, which will aid in understanding the pathogenesis of inflammatory bowel disease in bony fish.

Derivation and validation of a prediction model for patients with lung nodules malignancy regardless of mediastinal/hilar lymphadenopathy.

BACKGROUND: Clinical prediction models to classify lung nodules often exclude patients with mediastinal/hilar lymphadenopathy, although the presence of mediastinal/hilar lymphadenopathy does not always indicate malignancy. Herein, we developed and validated a multimodal prediction model for lung nodules in which patients with mediastinal/hilar lymphadenopathy were included. METHODS: A single-center retrospective study was conducted. We developed and validated a logistic regression model including patients with mediastinal/hilar lymphadenopathy. Discrimination of the model was assessed by area under the operating curve. Goodness of fit test was performed via the Hosmer-Lemeshow test, and a nomogram of the logistic regression model was drawn. RESULTS: There were 311 cases included in the final analysis. A logistic regression model was developed and validated. There were nine independent variables included in the model. The aera under the curve (AUC) of the validation set was 0.91 (95% confidence interval [CI]: 0.85-0.98). In the validation set with mediastinal/hilar lymphadenopathy, the AUC was 0.95 (95% CI: 0.90-0.99). The goodness-of-fit test was 0.22. CONCLUSIONS: We developed and validated a multimodal risk prediction model for lung nodules with excellent discrimination and calibration, regardless of mediastinal/hilar lymphadenopathy. This broadens the application of lung nodule prediction models. Furthermore, mediastinal/hilar lymphadenopathy added value for predicting lung nodule malignancy in clinical practice.

Establishment and validation of a clinical model for diagnosing solitary pulmonary nodules.

OBJECTIVES: The main purpose of this study was to develop and validate a clinical model for estimating the risk of malignancy in solitary pulmonary nodules (SPNs). METHODS: A total of 672 patients with SPNs were retrospectively reviewed. The least absolute shrinkage and selection operator algorithm was applied for variable selection. A regression model was then constructed with the identified predictors. The discrimination, calibration, and clinical validity of the model were evaluated by the area under the receiver-operating-characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: Ten predictors, including gender, age, nodule type, diameter, lobulation sign, calcification, vascular convergence sign, mediastinal lymphadenectasis, the natural logarithm of carcinoembryonic antigen, and combination of cytokeratin 19 fragment 21-1, were incorporated into the model. The prediction model demonstrated valuable prediction performance with an AUC of 0.836 (95% CI: 0.777-0.896), outperforming the Mayo (0.747, p = 0.024) and PKUPH (0.749, p = 0.018) models. The model was well-calibrated according to the calibration curves. The DCA indicated the nomogram was clinically useful over a wide range of threshold probabilities. CONCLUSION: This study proposed a clinical model for estimating the risk of malignancy in SPNs, which may assist clinicians in identifying the pulmonary nodules that require invasive procedures and avoid the occurrence of overtreatment.