Pro-oncogene FBI-1 inhibits the ferroptosis of prostate carcinoma PC-3 cells via the microRNA-324-3p/GPX4 axis.

Ferroptosis has been characterized as non-apoptotic programmed cell death and is considered a novel strategy for antitumor treatment. The factor that binds to inducer of short transcripts-1 (FBI-1) is an important proto-oncogene playing multiple roles in human malignancies and the development of resistance to therapy. However, the roles of FBI-1 in ferroptosis of endocrine independent prostate carcinoma are still unknown. The results of this study showed that FBI-1 inhibited the ferroptosis of prostate carcinoma PC-3 cells (a typical endocrine-independent prostate carcinoma cell line) via the miR-324-3p/glutathione peroxidase 4 (miR-324-3p/GPX4) axis. Overexpression of FBI-1 enhanced the expression levels of GPX4. In contrast, knockdown of FBI-1 decreased the expression of GPX4 and induced the ferroptosis of PC-3 cells. The miR-324-3p decreased the expression of GPX4 by targeting the 3'-untranslated region of GPX4 to induce ferroptosis. Notably, FBI-1 increased the expression of GPX4 by repressing the levels of miR-324-3p. The transcription of miR-324-3p was mediated by specificity protein 1 (SP1), and FBI-1 repressed the expression of miR-324-3p by repressing the activation of SP1. In clinical specimens, the endogenous levels of FBI-1 were positively associated with Glutathione Peroxidase 4 (GPX4) and negatively related with the expression of miR-324-3p. Therefore, the results indicated that the miR-324-3p/GPX4 axis participates in the FBI-1-mediated ferroptosis of prostate carcinoma cells.

Prediction of tumor regression grade in far-advanced gastric cancer after preoperative immuno-chemotherapy using dual-energy CT-derived extracellular volume fraction.

OBJECTIVES: This study examines the effectiveness of dual-energy CT (DECT) delayed-phase extracellular volume (ECV) fraction in predicting tumor regression grade (TRG) in far-advanced gastric cancer (FAGC) patients receiving preoperative immuno-chemotherapy. MATERIALS AND METHODS: A retrospective analysis was performed on far-advanced gastric adenocarcinoma patients treated with preoperative immuno-chemotherapy at our institution from August 2019 to March 2023. Patients were categorized based on their TRG into pathological complete response (pCR) and non-pCR groups. ECV was determined using the delayed-phase iodine maps. In addition, tumor iodine densities and standardized iodine ratios were meticulously analyzed using the triple-phase enhanced iodine maps. Univariate analysis with five-fold cross-validation and Spearman correlation determined DECT parameters and clinical indicators association with pCR. The predictive accuracy of these parameters for pCR was evaluated using a weighted logistic regression model with five-fold cross-validation. RESULTS: Of the 88 patients enrolled (mean age 60.8 ± 11.1 years, 63 males), 21 (23.9%) achieved pCR. Univariate analysis indicated ECV's significant role in differentiating between pCR and non-pCR groups (average p value = 0.021). In the logistic regression model, ECV independently predicted pCR with an average odds ratio of 0.911 (95% confidence interval, 0.798-0.994). The model, incorporating ECV, tumor area, and IDAV (the relative change rate of iodine density from venous phase to arterial phase), showed an average area under curves (AUCs) of 0.780 (0.770-0.791) and 0.766 (0.731-0.800) for the training and validation sets, respectively, in predicting pCR. CONCLUSION: DECT-derived ECV fraction is a valuable predictor of TRG in FAGC patients undergoing preoperative immuno-chemotherapy. CLINICAL RELEVANCE STATEMENT: This study demonstrates that DECT-derived extracellular volume fraction is a reliable predictor for pathological complete response in far-advanced gastric cancer patients receiving preoperative immuno-chemotherapy, offering a noninvasive tool for identifying potential treatment beneficiaries.

Balancing interlayer spacing, pore structures and conductivity endows hard carbon with high capacity for rechargeable aluminum batteries.

As a key configuration, hard carbon (HC) is widely regarded as a promising cathode for rechargeable aluminum batteries (RABs), because of its enlarged interlayer spacing and well-developed pore structures. However, the trade-off between the pore structure, interlayer spacing and conductivity easily leads to an unsatisfactory electrochemical performance in terms of capacity and cycling stability. Hence, N-doped hard carbon (P-M) is synthesized at a relatively low temperature (700 °C) and anion intercalation associated with the energy storage process is investigated. The results demonstrate that the introduction of a N-doping agent not only expands the layer spacing and creates rich pore structures, but also boosts the conductivity. Compared with HC without N-doping, the expanded interlayer spacing in P-M can increase ion storage ability, and the rich pore channels contribute to electron transfer. Besides, compared with HC annealed at a higher temperature (900 °C), the enhanced conductivity in P-M is conducive to accelerating ion diffusion. Benefiting from these structure merits, the optimized P-M cathode delivers a high capacity (323 mA h g-1 at 500 mA g-1) and a prolonged cycle lifespan over 1000 cycles at 1 A g-1 retaining 109 mA h g-1. This work can provide a guidance for developing other high-performance hard carbon cathodes.

Identification of potent pan-ephrin receptor kinase inhibitors using DNA-encoded chemistry technology.

EPH receptors (EPHs), the largest family of tyrosine kinases, phosphorylate downstream substrates upon binding of ephrin cell surface-associated ligands. In a large cohort of endometriotic lesions from individuals with endometriosis, we found that EPHA2 and EPHA4 expressions are increased in endometriotic lesions relative to normal eutopic endometrium. Because signaling through EPHs is associated with increased cell migration and invasion, we hypothesized that chemical inhibition of EPHA2/4 could have therapeutic value. We screened DNA-encoded chemical libraries (DECL) to rapidly identify EPHA2/4 kinase inhibitors. Hit compound, CDD-2693, exhibited picomolar/nanomolar kinase activity against EPHA2 (Ki: 4.0 nM) and EPHA4 (Ki: 0.81 nM). Kinome profiling revealed that CDD-2693 bound to most EPH family and SRC family kinases. Using NanoBRET target engagement assays, CDD-2693 had nanomolar activity versus EPHA2 (IC50: 461 nM) and EPHA4 (IC50: 40 nM) but was a micromolar inhibitor of SRC, YES, and FGR. Chemical optimization produced CDD-3167, having picomolar biochemical activity toward EPHA2 (Ki: 0.13 nM) and EPHA4 (Ki: 0.38 nM) with excellent cell-based potency EPHA2 (IC50: 8.0 nM) and EPHA4 (IC50: 2.3 nM). Moreover, CDD-3167 maintained superior off-target cellular selectivity. In 12Z endometriotic epithelial cells, CDD-2693 and CDD-3167 significantly decreased EFNA5 (ligand) induced phosphorylation of EPHA2/4, decreased 12Z cell viability, and decreased IL-1ß-mediated expression of prostaglandin synthase 2 (PTGS2). CDD-2693 and CDD-3167 decreased expansion of primary endometrial epithelial organoids from patients with endometriosis and decreased Ewing's sarcoma viability. Thus, using DECL, we identified potent pan-EPH inhibitors that show specificity and activity in cellular models of endometriosis and cancer.

Effectiveness of a Teach-Back Education Program on Perioperative Pain in Patients With Lung Cancer: An Intervention Study Using Behavior Change Wheel.

OBJECTIVE: To assess the effect of a teach-back educational intervention using Behavior Change Wheel (BCW) framework on perioperative pain among patients with lung cancer. METHODS: A prospective quasi-experimental study was conducted in 88 patients with lung cancer from a tertiary hospital in China. According to the order of admission, they were allocated to either control group or intervention group, with 44 patients in each group. Patients in the control group received routine nursing care, while patients in the intervention group were given a teach-back education program based on BCW framework. The visual analog scale (VAS) was adopted to evaluate patients' pain on the day of surgery (T0), 1 (T1), 2 (T2), and 3 (T3) days after surgery. We also recorded the use of patient-controlled analgesia (PCA), the length of hospital stay, and the degree of patients' satisfaction. RESULTS: Rest pain, pain when coughing, and pain during activity that patients in the intervention group experienced were significantly less severe than those in the control group on T0 and T1. The pain when coughing in the intervention group was also significantly milder on T2 and T3. In addition, the number of self-control time, use duration, and total dose of PCA were significantly lower in the intervention group. Moreover, patients' satisfaction of nursing service was significantly higher in the intervention group. CONCLUSION: A teach-back education program based on BCW framework was effective in pain management among the perioperative patients with lung cancer. This study demonstrates the application of teach-back method and the BCW in the development of patient education intervention to mitigate perioperative pain.

A noise robust sparse time-frequency representation method for measuring underwater gas leakage rate.

Passive acoustic monitors analyze sound signals emitted by seafloor gas bubbles to measure leakage rates. In scenarios with low-flux gas leaks, individual bubble sounds are typically non-overlapping. Measurement methods for these bubble streams aim to estimate the frequency peak of each bubble sound, which correlates with the bubble's size. However, the presence of ocean ambient noise poses challenges to accurately estimating these frequency peaks, thereby affecting the measurement of gas leakage rates in shallow sea environments using passive acoustic monitors. To address this issue, we propose a robust measurement method that includes a noise-robust sparse time-frequency representation algorithm and an adaptive thresholding approach for detecting bubble frequencies. We demonstrate the effectiveness of our proposed method using experimental data augmented with ocean ambient noise and ship-transit noise recorded from a bay area.

Therapeutic stapled peptides: Efficacy and molecular targets.

Peptide stapling, by employing a stable, preformed alpha-helical conformation, results in the production of peptides with improved membrane permeability and enhanced proteolytic stability, compared to the original peptides, and provides an effective solution to accelerate the rapid development of peptide drugs. Various reviews present peptide stapling chemistries, anchoring residues and one- or two-component cyclization, however, therapeutic stapled peptides have not been systematically summarized, especially focusing on various disease-related targets. This review highlights the latest advances in therapeutic peptide drug development facilitated by the application of stapling technology, including different stapling techniques, synthetic accessibility, applicability to biological targets, potential for solving biological problems, as well as the current status of development. Stapled peptides as therapeutic drug candidates have been classified and analysed mainly by receptor- and ligand-based stapled peptide design against various diseases, including cancer, infectious diseases, inflammation, and diabetes. This review is expected to provide a comprehensive reference for the rational design of stapled peptides for different diseases and targets to facilitate the development of therapeutic peptides with enhanced pharmacokinetic and biological properties.

TGF-ß1/SMAD3-driven GLI2 isoform expression contributes to aggressive phenotypes of hepatocellular carcinoma.

Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-ß1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-ß1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified. Phospho-SMAD3 interacted with active GLI2 isoforms to transactivate downstream genes in modulation of stemness, epithelial-mesenchymal transition, chemo-resistance and metastasis in poorly-differentiated hepatoma cells. Non-canonical activation of hedgehog signaling was confirmed in a transgenic HBV-associated HCC mouse model. Inhibition of TGF-ß/SMAD3 signaling reduced lung metastasis in a mouse in situ hepatic xenograft model. In another cohort of 55 HCC patients, subjects with high GLI2 expression had a shorter disease-free survival than those with low expression. Moreover, co-positivity of GLI2 with SMAD3 was observed in 87.5% of relapsed HCC patients with high GLI2 expression, indicating an increased risk of post-resection recurrence of HCC. The findings underscore that suppressing the non-canonical hedgehog signaling pathway may confer a potential strategy in the treatment of HCC.

Comparison between oral dydrogesterone versus micronized vaginal progesterone gel in clinical outcome within the first HRT-FET cycle: a retrospective analysis.

OBJECTIVE: The purpose of this study is to compare the clinical efficacy of oral dydrogesterone and micronized vaginal progesterone (MVP) gel during the first HRT-FET cycle. METHODS: A retrospective cohort study based on a total of 344 women undergoing their first HRT-FET cycles without Gonadotropin-Releasing Hormone agonist (GnRH-a) pretreatment was conducted. All the cycles were allocated to two groups in the reproductive medical center at the University of Hong Kong-Shenzhen Hospital. One group (n = 193) received oral dydrogesterone 30 mg/d before embryo transfer, while the other group (n = 151) received MVP gel 180 mg/d. RESULTS: The demographics and baseline characteristics of two groups were comparable. We found no statistically significant difference in live birth rate (24.35% vs. 31.13%, P = 0.16), clinical pregnancy rate (34.72% vs. 36.42%, P = 0.74), embryo implantation rate (25.09% vs. 28.36%, P = 0.43), positive pregnancy rate (42.49% vs 38.41%, P = 0.45), miscarriage rate (9.33% vs 3.97%, P = 0.05), or ectopic pregnancy rate (0.52% vs. 0.66%, P = 0.86) between the oral dydrogesterone group and MVP gel group. In the multivariate logistic regression analysis for covariates, medication used for luteal support was not associated with live birth rate (OR = 0.73, 95% CI: 0.32-1.57, P = 0.45). And the different luteal support medication did not have a significant positive association with the live birth rate in the cycles with day 2 embryo transferred (OR = 1.39, 95% CI:0.66-2.39, P = 0.39) and blastocyst transferred (OR = 1.31 95% CI:0.64-2.69, P = 0.46). CONCLUSION: 30 mg/d oral dydrogesterone and 180 mg/d MVP gel revealed similar reproductive outcomes in HRT-FET cycles in the study.

5-Aza-2'-Deoxycytidine Ameliorates Choroidal Neovascularization by Inhibiting the Wnt/ß-Catenin Signaling Pathway.

Purpose: Choroidal neovascularization (CNV) can constitute the final pathology of many ocular diseases and result in severe vision loss. Studies have demonstrated that DNA methylation is critical in retinal development, aging, and disorders. The current work investigated the effects and underlying mechanism of 5-Aza-2'-deoxycytidine (5-aza-dC), a suppressor of DNA methylation, in the pathological progression of CNV. Methods: The DNA methylation profiles of retinal pigment epithelial (RPE)/choroidal complexes in normal and laser-induced CNV mice were assessed by Arraystar Mouse RefSeq Promoter Arrays. The CNV area and blood flow density and intensity were observed by optical coherence tomography angiography, and fluorescence leakage was examined by fundus fluorescein angiography in CNV mice with systemic administration of 5-aza-dC. The effects of 5-aza-dC on the biological functions of bEnd.3 cells were estimated by related assays. Notum gene promoter methylation was measured using bisulfite sequencing PCR. Methyltransferases and Wnt signaling-related genes were detected in animal and cell culture experiments by real-time PCR and immunoblot. Results: Methyltransferases were upregulated, but Notum (a secretion inhibitor of Wnt signaling) was downregulated in the RPE/choroidal complexes of mice with experimental CNV. Intraperitoneal injection of 5-aza-dC inactivated the Wnt pathway and ameliorated the lesion area and the intensity and density of blood flow, as well as the degree of leakage in CNV. In vitro, vascular endothelial growth factor A (VEGFA) stimulation promoted methyltransferases expression and suppressed Notum expression, consequently activating Wnt signaling, whereas exogenous 5-aza-dC reversed VEGFA-induced hyperpermeability, proliferation, migration, and tube formation in bEnd.3 cells via demethylation of Notum promoter. Conclusions: We observed that 5-aza-dC attenuates the growth of CNV by inhibiting the Wnt signaling pathway via promoter demethylation of the Wnt antagonist Notum. These findings provide a theoretical basis for methylation-based treatment with the Notum gene as a potential target for CNV treatment.

EBV-Associated Smooth Muscle Tumors With Autoimmune Hemolytic Anemia and Hepatitis B Infection: Report of a Previously Undescribed Neoplasm With Review.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is rare in adults. The presence of intratumoral T lymphocytes and primitive rounded cells characterized this neoplasm. We report a 24-year-old Chinese man who developed EBV-SMT in the right adrenal gland with hepatitis B infection and autoimmune hemolytic anemia without a history of HIV infection, primary immune deficiency, organ transplantation, or malignant tumor. This patient had an unknown immunodeficient state. EBV-SMTs are commonly located in the liver, lung, and gastrointestinal tract but rarely in the adrenal gland. We reviewed 10 reported literature on EBV-SMT in the adrenal gland. It is imperative to distinguish EBV-SMT from conventional somatic smooth muscle tumors. The discovery of EBV-SMT forces the clinician to conduct a thorough evaluation of immune function and immune status surveillance, and these patients are vulnerable to subsequent malignant tumors.

Temporal variability of air-water gas exchange of carbon dioxide in clam and fish aquaculture ponds.

The growing trend of land-based aquaculture has heightened the significance of comprehensively assessing air-water carbon dioxide (CO2) gas exchange in these inland waters, given their potential impact on carbon neutral strategies. However, temporal variations of partial pressure of CO2 (pCO2) and CO2 flux in clam and fish aquaculture ponds were barely investigated. We assessed the water surface pCO2 in one to five months intervals by deploying a lab-made buoy in three clam ponds and three fishponds located in tropical and subtropical climates. Measurements were conducted over a 24 h period each time, spanning from April 2021 to June 2022, covering the stocking, middle, and harvesting stages of the culture cycle. Diurnal pCO2 variations were dominantly controlled by biologically driven changes in dissolved inorganic carbon and total alkalinity (~97 %), while temperature and salinity effects were minor (~3 %). Clam ponds acted as a sink of atmospheric CO2 during stocking stages and transitioned to a source during middle to harvesting stages. In contrast, fishponds acted as a source of atmospheric CO2 throughout culture cycles and CO2 flux strengthened when reaching harvesting stages. Overall, clam ponds acted as a weak sink for atmospheric CO2 (-2.8 ± 17.3 mmol m-2 d-1), whereas fishponds acted as a source (16.8 ± 21.7 mmol m-2 d-1). CO2 emission was stronger during daytime coinciding with higher windspeeds compared to nighttime in fishponds. We suggest incorporating high temporal resolution measurements to account for diurnal and culture-stage variations, enabling more accurate estimates of air-water CO2 flux in aquaculture ponds. Moreover, the findings of this study highlight the importance of feeding, aeration, and biological activities (photosynthesis, remineralization, and calcification) in controlling the air-water CO2 flux in aquaculture ponds and such information can be used in implementing better strategies to achieve carbon neutral goals.

Cadmium promotes the binding and centrosomal translocation of CCDC85C and PLK4 via ROS-GCLM pathway to trigger centrosome amplification in colon cancer cells.

Cadmium (Cd) is a prevalent heavy metal contaminant that can cause centrosome amplification (CA) and cancer. Since CA can initiate tumorigenesis, it is plausible that cadmium initiates tumorigenesis via CA. The present study investigated the signaling pathways underlying CA by Cd. Our findings confirmed that sub-toxic concentrations of Cd could induce CA in the HCT116 colon cancer cells, and revealed that reactive oxygen species (ROS), GCLM, CCDC85C and PLK4 were the signaling molecules that formed a pathway of ROS-GCLM-CCDC85C-PLK4. Cd not only increased the protein levels of CCDC85C and PLK4, but also promoted their distribution to the centrosomes. Molecular docking analysis revealed that CCDC85C and PLK4 had the binding potential. Indeed, antibodies against CCDC85C and PLK4 were able to pull down PLK4 and CCDC85C, respectively. Knockdown of CCDC85C decreased the Cd-promoted centrosomal distribution of PLK4. Similarly, knockdown of PLK4 reduced the centrosomal distribution of CCDC85C. Our results suggest that Cd activates ROS-GCLM pathway that triggers the expression of and binding between CCDC85C and PLK4, and promotes the translocation of CCDC85C-PLK4 complex to the centrosomes, which eventually leads to CA.

Hesperitin attenuates alcoholic steatohepatitis by regulating TLR4/NF-κB signaling in mice.

In the peel of citrus (Rutaceae) fruit, hesperitin (Hesp), a flavanone glycoside chemical, is found naturally. Hesp has been found to have a wide range of pharmacological actions, including anti-inflammatory, antioxidant, antiviral, and anticancer properties, according to earlier research. However, nothing is known regarding its function in alcoholic liver steatosis and inflammation. In this study, we employed a network pharmacology approach to identify the TLR4 signaling pathway as a primary target of Hesp for the treatment of alcoholic steatohepatitis (ASH). Molecular docking results showed that Hesp bound to the representative target TLR4 and exhibited good affinity. In addition, Hesp inhibits the TLR4 target and consequently the NF-κB signaling pathway, which in turn slows the evolution of alcoholic steatohepatitis, according to further in vitro and in vivo tests. The results of this study preliminarily indicate that Hesp is an ideal drug candidate for the treatment of ASH.

The Characteristics of Extracranial Internal Carotid Artery and Their Relationship With Surgical Outcomes in Patients With Moyamoya Disease: A Combined Head-and-Neck Vessel Wall MR Imaging Study.

BACKGROUND: The features of intracranial arteries in patients with Moyamoya disease (MMD) have been widely investigated. However, the MR characteristics of extracranial internal carotid artery (EICA) and their effect on outcomes of revascularization treatment are not fully understood. PURPOSE: To investigate the characteristics of EICA and their relationship with outcomes of revascularization treatment in adult patients with MMD based on higher-resolution MRI (HRMRI). STUDY TYPE: Prospective interventional outcomes. SUBJECTS: Two hundred eighty-eight consecutive patients with MMD (mean age: 43.7 ± 11.2 years; 140 male). FIELD STRENGTH/SEQUENCE: Turbo inversion recovery magnitude T1-weighted imaging and turbo spin echo (TSE) T2-weighted imaging, three-dimensional time-of-flight MR angiography, T2-fluid attenuated inversion recovery, and 3D T1-SPACE vessel wall imaging at 3.0 T. ASSESSMENT: The HRMRI characteristics of EICA were determined. The relationship between the characteristics of EICA (proximal stenosis, diffuse wall thickening, carotid plaques, and luminal thrombosis) and stroke outcomes of revascularization treatment in patients with MMD was analyzed. The discriminative ability of EICA characteristics in combination with intracranial carotid artery features (involvement of vessel segments, bilateral involvement, and Suzuki stage) to determine stroke outcomes was compared with that of intracranial artery features alone during a mean 8.0 months follow-up period. STATISTICAL TESTS: Cox proportional hazards models and Kaplan-Meier curves to calculate the hazard ratios (HRs) for stroke with 95% confidence intervals (CIs). Area under the receiver operating characteristic curve (AUC) for assessing discriminative performance. A P value <0.05 was considered statistically significant. RESULTS: During a mean 8.0 ± 2.2 months follow-up, of the 288 participants, 137 had proximal stenosis (47.6%), 106 had diffuse wall thickening (36.8%), 60 had carotid plaques (20.8%), and 27 had luminal thrombosis (9.4%) of EICA. Of these features, proximal stenosis (HR = 2.86; 95% CI = 1.13-7.29) and diffuse wall thickening (HR = 2.62; 95% CI = 1.16-5.94) of EICA were significantly associated with stroke after surgery, before and after adjusting for confounding factors. In discriminating the stroke outcomes after surgery, combining characteristics of EICA with features of intracranial arteries resulted in a significant incremental improvement (DeLong test, P < 0.05) in the AUC over that obtained with features of intracranial arteries alone (AUC: 0.73 vs. 0.60-0.64). CONCLUSION: Proximal stenosis and diffuse wall thickening of EICA were significantly associated with stroke outcomes after surgery in patients with MMD. Our findings suggest that understanding the characteristics of EICA has added value for intracranial vessels in predicting future events after surgery in patients with MMD. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 4.

[Robot-assisted PVP for the treatment of osteoporotic fractures of the upper thoracic vertebra].

OBJECTIVE: To investigate the clinical effect of "Tianji" orthopedic robot-assisted percutaneous vertebro plasty(PVP) surgery in the treatment of upper thoracic osteoporotic fracture. METHODS: A retrospective analysis was performed on 32 patients with upper thoracic osteoporotic fracture who underwent PVP surgery in Shenzhen Hospital of Traditional Chinese Medicine from August 2016 to June 2022. There were 8 males and 24 females, ranging in age from 58 to 90 years old, with a mean of (67.75±12.27) years old. Fifteen patients were treated with robot-assisted PVP surgery (robot group), including 3 males and 12 females, with an average age of (68.5±10.3) years. Fracture location:1 case of T2 fracture, 1 case of T3 fracture, 3 cases of T4 fracture, 3 cases of T5 fracture, and 7 cases of T6 fracture. The follow-up period ranged from 1.0 to 3.0 months, with a mean of (1.6±0.7) months. Seventeen patients underwent routine PVP surgery (conventional group), including 5 males and 12 females, with an average age of (66.8±11.6) years old. Fracture location:1 case of T1 fracture, 5 cases of T4 fracture, 2 cases of T5 fracture and 9 cases of T6 fracture. The follow-up period ranged from 0.5 to 4.0 months, with a mean of (1.5±0.6) months. Preoperative and postoperative visual analogue scale(VAS) and Oswestry disability index(ODI) scores were compared between the two groups, and the number of punctures, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage, and intraoperative radiation dose were compared between the two groups. RESULTS: Number of punctures times, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage and intraoperative radiation dose in the robot group were all significantly better than those in the conventional group(P<0.05). VAS of 2.03±0.05 and ODI of (22.16±4.03) % in the robot group were significantly better than those of the robot group before surgery, which were (8.67±0.25) score and (79.40±7.72)%(t=100.869, P<0.001;t=25.456, P<0.001). VAS of 2.17±0.13 and ODI of (23.88±6.15)% in the conventional group were significantly better than those before surgery, which were (8.73±0.18) score and (80.01±7.59)%(t=121.816, P<0.001;t=23.691, P<0.001). There was no significant difference in VAS and ODI between the two groups after operation (t=-3.917, P=0.476;t=-0.922, P=0.364). CONCLUSION: Robot-assisted PVP in the treatment of upper thoracic osteoporotic fractures can further improve surgical safety, reduce bone cement leakage, and achieve satisfactory clinical efficacy.

A CT-based nomogram established for differentiating gastrointestinal heterotopic pancreas from gastrointestinal stromal tumor: compared with a machine-learning model.

OBJECTIVE: To identify CT features and establish a nomogram, compared with a machine learning-based model for distinguishing gastrointestinal heterotopic pancreas (HP) from gastrointestinal stromal tumor (GIST). MATERIALS AND METHODS: This retrospective study included 148 patients with pathologically confirmed HP (n = 48) and GIST (n = 100) in the stomach or small intestine that were less than 3 cm in size. Clinical information and CT characteristics were collected. A nomogram on account of lasso regression and multivariate logistic regression, and a RandomForest (RF) model based on significant variables in univariate analyses were established. Receiver operating characteristic (ROC) curve, mean area under the curve (AUC), calibration curve and decision curve analysis (DCA) were carried out to evaluate and compare the diagnostic ability of models. RESULTS: The nomogram identified five CT features as independent predictors of HP diagnosis: age, location, LD/SD ratio, duct-like structure, and HU lesion/pancreas A. Five features were included in RF model and ranked according to their relevance to the differential diagnosis: LD/SD ratio, HU lesion/pancreas A, location, peritumoral hypodensity line and age. The nomogram and RF model yielded AUC of 0.951 (95% CI: 0.842-0.993) and 0.894 (95% CI: 0.766-0.966), respectively. The DeLong test found no statistically significant difference in diagnostic performance (p > 0.05), but DCA revealed that the nomogram surpassed the RF model in clinical usefulness. CONCLUSION: Two diagnostic prediction models based on a nomogram as well as RF method were reliable and easy-to-use for distinguishing between HP and GIST, which might also assist treatment planning.

Duodenal neuroendocrine neoplasms on enhanced CT: establishing a diagnostic model with duodenal gastrointestinal stromal tumors in the non-ampullary area and analyzing the value of predicting prognosis.

OBJECTIVE: To identify CT features and establish a diagnostic model for distinguishing non-ampullary duodenal neuroendocrine neoplasms (dNENs) from non-ampullary duodenal gastrointestinal stromal tumors (dGISTs) and to analyze overall survival outcomes of all dNENs patients. MATERIALS AND METHODS: This retrospective study included 98 patients with pathologically confirmed dNENs (n = 44) and dGISTs (n = 54). Clinical data and CT characteristics were collected. Univariate analyses and binary logistic regression analyses were performed to identify independent factors and establish a diagnostic model between non-ampullary dNENs (n = 22) and dGISTs (n = 54). The ROC curve was created to determine diagnostic ability. Cox proportional hazards models were created and Kaplan-Meier survival analyses were performed for survival analysis of dNENs (n = 44). RESULTS: Three CT features were identified as independent predictors of non-ampullary dNENs, including intraluminal growth pattern (OR 0.450; 95% CI 0.206-0.983), absence of intratumoral vessels (OR 0.207; 95% CI 0.053-0.807) and unenhanced lesion > 40.76 HU (OR 5.720; 95% CI 1.575-20.774). The AUC was 0.866 (95% CI 0.765-0.968), with a sensitivity of 90.91% (95% CI 70.8-98.9%), specificity of 77.78% (95% CI 64.4-88.0%), and total accuracy rate of 81.58%. Lymph node metastases (HR: 21.60), obstructive biliary and/or pancreatic duct dilation (HR: 5.82) and portal lesion enhancement ≤ 99.79 HU (HR: 3.02) were independent prognostic factors related to poor outcomes. CONCLUSION: We established a diagnostic model to differentiate non-ampullary dNENs from dGISTs. Besides, we found that imaging features on enhanced CT can predict OS of patients with dNENs.

HKDC1 reprograms lipid metabolism to enhance gastric cancer metastasis and cisplatin resistance via forming a ribonucleoprotein complex.

As essential modulators of transcription and translation, RNA-binding proteins (RBPs) are frequently dysregulated in cancer. Bioinformatics study reveals that the RNA-binding protein hexokinase domain component 1 (HKDC1) is overexpressed in gastric cancer (GC). As HKDC1 plays a role in lipid homeostasis in the liver and glucose metabolism in certain cancers, the exact mechanism of action of HKDC1 in GC remains largely unknown. Upregulation of HKDC1 correlates with chemoresistance and poor prognosis in GC patients. HKDC1 enhances invasion, migration and resistance to cisplatin (CDDP) in GC cells in vitro and in vivo. Comprehensive transcriptomic sequencing and metabolomic analysis reveal that HKDC1 mediates abnormal lipid metabolism in GC cells. Herein, we identify a number of HKDC1-binding endogenous RNAs in GC cells, including protein kinase, DNA-activated, catalytic subunit (PRKDC) mRNA. We further validate that PRKDC is a crucial downstream effector of HKDC1 induced-GC tumorigenesis depends on lipid metabolism. Interestingly, G3BP1, a well-known oncoprotein, can be bound by HKDC1. HKDC1 cooperates with G3BP1 to enhance the stability of PRKDC transcript. Our results reveal a novel HKDC1/G3BP1-PRKDC regulatory axis that induces GC metastasis and chemoresistance via reprogramming lipid metabolism, which may provide an effective therapeutic strategy for a subset of GC with HKDC1 overexpression.

Circulating neutrophils activated by cancer cells and M2 macrophages promote gastric cancer progression during PD-1 antibody-based immunotherapy.

Aims: To analyze the correlation between the neutrophil-to-lymphocyte ratio (NLR) and prognosis of advanced gastric cancer (AGC) patients treated by PD-1 antibody-based therapy and to delineate molecular characteristics of circulating neutrophils by single-cell RNA sequencing (scRNA-seq). Methods: The clinicopathological information of 45 AGC patients receiving PD-1 antibody-based regimens at the Department of Oncology, Ruijin Hospital, was reviewed. Treatment outcomes including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were recorded. The correlation between NLR and efficacy of PD-1 antibody-based treatment was analyzed. Single-cell RNA sequencing (scRNA-seq) analysis was performed based on multisite biopsy samples from two AGC patients to explore the molecular characteristics of circulating neutrophils and their pro-tumor mechanisms. Tissue samples from 88 gastric cancer patients who underwent radial gastrectomy were collected for immunochemistry staining. Results: A high posttreatment NLR was associated with poor outcomes of AGC patients receiving PD-1 antibody-based regimens. scRNA-seq analysis showed that an increased number of circulating neutrophils were found in peripheral blood samples after treatment in which neutrophil cluster 1 (NE-1) was the major subcluster. NE-1 was featured with a neutrophil activation phenotype with the high expression of MMP9, S100A8, S100A9, PORK2, and TGF-ß1. NE-1 displayed an intermediate state in pseudotime trajectory analysis with gene function enrichment found in neutrophil activation, leukocyte chemotaxis, and negative regulation of MAP kinase activity. Cellular interaction analysis showed that the chemokine signaling pathway is the major interactional pathway of NE-1 between subclusters of malignant epithelial cells (EP-4) and M2 macrophages (M2-1 and M2-2). In turn, the MAPK signaling pathway and Jak-STAT signaling pathway of EP-4, including IL1B/IL1RAP, OSM/OSMR, and TGFB1/TGFBR2 axes, were identified as interacting pathways between EP-4 and NE-1. The high expression of OSMR in tumor cells was closely correlated with lymph node metastasis of gastric cancer. Conclusion: The posttreatment NLR could be a poor prognostic marker of AGC patients treated with immune checkpoint inhibitors (ICIs). Subclusters of circulating neutrophils activated by tumor cells and M2 macrophages could participate in gastric cancer progression through signaling interactions with tumor cells.