Associations between multi-metal joint exposure and decreased estimated glomerular filtration rate (eGFR) in solar greenhouse workers: a study of a unique farmer group.

BACKGROUND: Solar greenhouse workers, a unique farmer group, have been reported to have a higher risk of chronic kidney disease (CKD) compared to the general population, possible due to exposure to multiple metals. OBJECTIVE: This study aimed to investigate the associations between exposure to multiple metals and the estimated glomerular filtration rate (eGFR). METHODS: A cross-sectional study was conducted in the Northwest China. Urine samples were tested for concentration of 14 metals, including chromium, manganese, iron, et al. Blood creatinine was measured to calculate eGFR, which was to evaluate the kidney function. Linear model and the Bayesian Kernel Machine Regression (BKMR) models were used to evaluate the associations between metals exposure and eGFR. RESULT: The study included 281 solar greenhouse workers, with 128 (45.6%) males and 153 (54.4%) females. The highest median concentrations of metals were zinc (418.55 µg/L), strontium (368.77 µg/L), and iron (55.73 µg/L), respectively. The linear model analysis showed that urinary levels of copper and zinc were negatively associated with eGFR [ß = -0.021, 95% CI (-0.048, -0.007); ß = -0.018, 95% CI (-0.068, -0.005)] considering a false discovery rate. BKMR results indicated a significant overall negative effect of 14 metals exposure on the eGFR when all metal levels were above the 50th percentile compared to the median value. CONCLUSIONS: The decrease in eGFR among solar greenhouse workers was related to mixed metal exposure. Reducing exposure to the metals of copper, zinc, and lead could effectively protects kidney function. Further prospective studies are needed to resolve concerns about reverse causality.

Quantum 2-Player Games and Realizations with Circuits.

Game theory problems are widely applied in many research areas such as computer science and finance, with the key issue being how to quickly make decisions. Here, we present a novel quantum algorithm for game theory problems based on a continuous quantum walk. Our algorithm exhibits quantum advantage compared to classical game algorithms. Furthermore, we exploit the analogy between the wave function of the Schrödinger equation and the voltage in Kirchhoff's law to effectively translate the design of quantum game trees into classical circuit networks. We have theoretically simulated the quantum game trees and experimentally validated the quantum functionality speedup on classical circuit networks. Due to the robust scalability and stability inherent in classical circuit networks, quantum game trees implemented within this framework hold promise for addressing more intricate application scenarios.

Dual-Anionic Coordination Manipulation Induces Phosphorus and Boron-Rich Gradient Interphase Towards Stable and Safe Sodium Metal Batteries.

High-voltage sodium metal batteries (SMBs) present a viable pathway towards high-energy-density sodium-based batteries due to the competitive cost advantage and abundant supply of sodium resources. However, they still suffer from severe capacity decay induced by the notorious decomposition of the electrolyte under high voltage and unstable cathode/electrolyte interphase (CEI). In addition, the high reactivity of Na metal and flammable electrolytes push SMBs to their safety limits. Herein, a special dual-anion aggregated Na+ solvation structure is designed in a nonflammable trimethyl phosphate-based localized high-concentration electrolyte, and a gradient CEI enriched with phosphorus and boron compounds is formed on the cathode. This thin and stable interphase effectively suppresses the parasitic reaction, improves the interfacial stability of the cathode, and facilitates Na+ transport through the interface by the synergistic effect of multi-components, thus optimizing the cycling stability and safety of SMBs. The Na0.95Ni0.4Fe0.15Mn0.3Ti0.15O2//Na batteries employing such electrolyte provide a discharge capacity of 167.5 mA h g-1 and high retention in the capacity of 85.2% after 800 cycles at 1 C. This approach offers a general strategy for the design of flame-retardant high-voltage electrolytes and the practical application of SMBs.

[Zhongfeng Xingnao Decoction alleviates intracerebral haemorrhage-induced brain injury via inhibiting neuronal ferroptosis].

Zhongfeng Xingnao Decoction(ZFXN) has been utilized for treating intracerebral hemorrhage(ICH) in China, while the pharmacological mechanism of ZFXN remains unclear. Exploring the pharmacological roles of ZFXN is critical for guiding the treatment of cerebrovascular diseases. In this study, a rat model of ICH was constructed by injection of Ⅶ collagenase in the right caudate nucleus. SD rats were randomly assigned into five groups, and the neurological function of rats was evaluated based on the Bederson score. Magnetic resonance imaging(MRI) was used to assess the volume of ICH. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were employed to observe the pathological and ultrastructural changes in the brain tissue. The levels of reactive oxygen species(ROS) were measured by flow cytometry. The immunofluorescence assay was employed to detect the expression of glutathione peroxidase 4(GPX4) in neurons surrounding the hematoma. Finally, Western blot was employed to determine the expression of ferroptosis-related proteins upstream frameshift 1(UPF1), ferroportin(FPN), acyl-CoA ligase 4(ACSL4), cyclooxyge-nase-2(COX-2), GPX4, NADPH oxidase 1(NOX1), and solute carrier family 7 member 11(SLC7A11) after ICH. Compared with the model(ICH) group, ZFXN treatment for 5 days attenuated neurological dysfunction, reduced the hematoma volume, and alleviated the pathological changes induced by ICH. Meanwhile, ZFXN lowered the levels of Fe~(2+) and oxidative stress and up-regulated the expression of proteins inhibiting ferroptosis. ZFXN improved the prognosis of ICH in rats by inhibiting neuronal ferroptosis, which provided a valuable guide for the clinical application of ZFXN. ZFXN may inhibit ferroptosis by promoting the expression of SLC7A11 and FPN.

Harmonizing soft tissue subnasale and chin position in a forehead-based framework: interracial commonalities and differences between Asian and Caucasian females.

OBJECTIVES: To establish a reference system for assessing the anteroposterior (A-P) position of the subnasal and lower-facial soft tissues for whole facial harmony. MATERIALS AND METHODS: Forty Asian and 40 Caucasian females with attractive profiles were selected as the "attractive" samples, with "ordinary" samples for comparison. Each profile was analyzed, and comparisons were made to reveal the interracial commonalities and differences. Esthetically essential parameters were established. An averaged attractive profile for each race was created by digital morphing and then modified into 30 variations based on combined variations of the esthetically essential parameters. Assessments were performed to investigate the esthetic ranges. RESULTS: A-P position of the subnasal and lower-facial landmarks harmonized with the forehead for female profile esthetics. In addition to balanced soft tissue subnasale (sSn)- and soft titssue pogonion (Pos)-to-forehead A-P relations, harmonizing lower-facial soft tissues to sSn was indispensable for profile attractiveness. sSn-to-glabella, Pos-to-glabella, and Pos-to-sSn A-P relations were esthetically essential. Perceived by orthodontists, the attractive Asian female profiles had sSn-to-glabella A-P relations ranging from 0.5 mm to 4.5 mm, Pos-to-sSn from -9.0 mm to -5.5 mm, and Pos-to-glabella from -8.5 mm to -1.0 mm. Compared with Asians, the attractive Caucasian female profiles had more anteriorly and widely distributed sSn relative to the forehead, wider ranges of Pos-to-sSn A-P relations, and more prominent chins. CONCLUSIONS: A reference system comprising sSn-glabella, Pos-sSn, and Pos-glabella horizontal distances was constructed for facial profile analysis. This system could aid treatment planning for surgical or orthopedic repositioning of the maxilla and chin.

Suppression of overactivated immunity in the early stage is the key to improve the prognosis in severe burns.

Background: Severe burns can lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) due to inflammation-immunity dysregulation. This study aimed to identify key immune-related molecules and potential drugs for immune regulation in severe burn treatment. Method: Microarray datasets GSE77791 and GSE37069 were analyzed to identify immune-related differentially expressed genes (DEGs), enriched pathways and prognosis-related genes. The DGIdb database was used to identify potentially clinically relevant small molecular drugs for hub DEGs. Hub DEGs were validated by total RNA from clinical blood samples through qPCR. The efficacy of drug candidates was tested in a severe burn mouse model. Pathologic staining was used to observe organ damage. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the serum IL-1b, IL-6, TNF-a and MCP-1 contents. Activation of the NF-κB inflammatory pathway was detected by western blotting. Transcriptome sequencing was used to observe inflammatory-immune responses in the lung. Results: A total of 113 immune-related DEGs were identified, and the presence of immune overactivation was confirmed in severe burns. S100A8 was not only significantly upregulated and identified to be prognosis-related among the hub DEGs but also exhibited an increasing trend in clinical blood samples. Methotrexate, which targets S100A8, as predicted by the DGIdb, significantly reduces transcription level of S100A8 and inflammatory cytokine content in blood, organ damage (lungs, liver, spleen, and kidneys) and mortality in severely burned mice when combined with fluid resuscitation. The inflammatory-immune response was suppressed in the lungs. Conclusion: S100A8 with high transcription level in blood is a potential biomarker for poor severe burn prognosis. It suggested that methotrexate has a potential application in severe burn immunotherapy. Besides, it should be emphasized that fluid resuscitation is necessary for the function of methotrexate.

Postoperative rehabilitation management self-efficacy and its relationship with symptoms in the patients with lung cancer: A latent profile analysis.

Objective: To identify the potential subgroups of postoperative rehabilitation management self-efficacy in patients with lung cancer and explore the association between these subgroups and symptom burden. Methods: This cross-sectional study enrolled 231 lung cancer patients who underwent surgery between May and August 2023. Latent profile analysis, univariate analysis, and disordered multinomial logistic regression were performed to explore postoperative rehabilitation management self-efficacy profiles and identify interindividual variability. ANOVA, LSD, and Tamhane's T2 method were used for multiple comparisons between symptom burden and self-efficacy subgroups. Results: The three subgroups of postoperative rehabilitation management self-efficacy identified included low level group (17.7%), medium level group (63.2%), and high level group (19.0%). Patients with junior high school education were more likely to be classified as medium level groups, and patients with higher levels of social support and better resilience were more likely to be classified as medium and high level groups. Symptom severity and symptom interference of lung cancer patients after surgery varied considerably among the three classes. In the lung cancer module, the high level group had fewer symptoms than the medium level group (P < 0.05). Conclusions: Postoperative rehabilitation management self-efficacy has different classification features among patients with lung cancer. Educational background, resilience, and social support were the influencing factors of postoperative rehabilitation management self-efficacy. Lung cancer patients with higher self-efficacy in postoperative rehabilitation management showed fewer symptom burdens. Medical staff should actively pay attention to patients with low self-efficacy and provide precise interventions for patients with different subgroups.

Quality control of elbow joint radiography using a YOLOv8-based artificial intelligence technology.

BACKGROUND: To explore an artificial intelligence (AI) technology employing YOLOv8 for quality control (QC) on elbow joint radiographs. METHODS: From January 2022 to August 2023, 2643 consecutive elbow radiographs were collected and randomly assigned to the training, validation, and test sets in a 6:2:2 ratio. We proposed the anteroposterior (AP) and lateral (LAT) models to identify target detection boxes and key points on elbow radiographs using YOLOv8. These identifications were transformed into five quality standards: (1) AP elbow positioning coordinates (XA and YA); (2) olecranon fossa positioning distance parameters (S17 and S27); (3) key points of joint space (Y3, Y4, Y5 and Y6); (4) LAT elbow positioning coordinates (X2 and Y2); and (5) flexion angle. Models were trained and validated using 2,120 radiographs. A test set of 523 radiographs was used for assessing the agreement between AI and physician and to evaluate clinical efficiency of models. RESULTS: The AP and LAT models demonstrated high precision, recall, and mean average precision for identifying boxes and points. AI and physicians showed high intraclass correlation coefficient (ICC) in evaluating: AP coordinates XA (0.987) and YA (0.991); olecranon fossa parameters S17 (0.964) and S27 (0.951); key points Y3 (0.998), Y4 (0.997), Y5 (0.998) and Y6 (0.959); LAT coordinates X2 (0.994) and Y2 (0.986); and flexion angle (0.865). Compared to manual methods, using AI, QC time was reduced by 43% for AP images and 45% for LAT images (p < 0.001). CONCLUSION: YOLOv8-based AI technology is feasible for QC of elbow radiography with high performance. RELEVANCE STATEMENT: This study proposed and validated a YOLOv8-based AI model for automated quality control in elbow radiography, obtaining high efficiency in clinical settings. KEY POINTS: QC of elbow joint radiography is important for detecting diseases. Models based on YOLOv8 are proposed and perform well in image QC. Models offer objective and efficient solutions for QC in elbow joint radiographs.

Baseline CT radiomics features to predict pathological complete response of advanced esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy using paclitaxel and cisplatin.

PURPOSE: To develop a CT radiomics model to predict pathological complete response (pCR) of advanced esophageal squamous cell carcinoma (ESCC) toneoadjuvant chemotherapy using paclitaxel and cisplatin. MATERIALS AND METHODS: 326 consecutive patients with advanced ESCC from two hospitals undergoing baseline contrast-enhanced CT followed by neoadjuvant chemotherapy using paclitaxel and cisplatin were enrolled, including 115 patients achieving pCR and 211 patients without pCR. Of the 271 cases from 1st hospital, 188 and 83 cases were randomly allocated to the training and test cohorts, respectively. The 55 patients from a second hospital were assigned as an external validation cohort. Region of interest was segmented on the baseline thoracic contrast-enhanced CT. Useful radiomics features were generated by dimension reduction using least absolute shrinkage and selection operator. The optimal radiomics features were chosen using support vector machine (SVM). Discriminating performance was assessed with area under the receiver operating characteristic curve (ROC) and F-1score. The calibration curves and Brier score were used to evaluate the predictive accuracy. RESULTS: Eight radiomics features were selected to create radiomics models related to pCR of advanced ESCC (P-values < 0.01 for both the training and test cohorts). SVM model showed the best performance (AUCs = 0.929, 0.868 and 0.866, F-1scores = 0.857, 0.847 and 0.737 in the training, test and external validation cohorts, respectively). The calibration curves and Brier scores indicated goodness-of-fit and its great predictive accuracy. CONCLUSION: CT radiomics models could well help predict pCR of advanced ESCC, and SVM model could be a suitable predictive model.

Electrical Control of Magnetic Resonance in Phase Change Materials.

Metal-insulator transitions (MITs) in resistive switching materials can be triggered by an electric stimulus that produces significant changes in the electrical response. When these phases have distinct magnetic characteristics, dramatic changes in the spin excitations are also expected. The transition metal oxide La0.7Sr0.3MnO3 (LSMO) is a ferromagnetic metal at low temperatures and a paramagnetic insulator above room temperature. When LSMO is in its metallic phase, a critical electrical bias has been shown to lead to an MIT that results in the formation of a paramagnetic resistive barrier transverse to the applied electric field. Using spin-transfer ferromagnetic resonance spectroscopy, we show that even for electrical biases less than the critical value that triggers the MIT, there is magnetic phase separation, with the spin-excitation resonances varying systematically with applied bias. Therefore, voltage-triggered MITs in LSMO can alter magnetic resonance characteristics, offering an effective method for tuning synaptic weights in neuromorphic circuits.

Enhancing Patient Outcomes: A Novel Nomogram Prediction Model Based on Systemic Immune-Inflammation Index for Esophageal Stricture After Endoscopic Submucosal Dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a widely utilized treatment for early esophageal cancer. However, the rising incidence of postoperative esophageal stricture poses a significant challenge, adversely affecting patients' quality of life and treatment outcomes. Developing precise predictive models is urgently required to enhance treatment outcomes. MATERIALS AND METHODS: This study retrospectively analyzed clinical data from 124 patients with early esophageal cancer who underwent ESD at Ningbo Medical Center Lihuili Hospital. Patients were followed up to assess esophageal stricture incidence. Binary logistic regression analysis was used to identify factors associated with post-ESD esophageal stricture. A novel nomogram prediction model based on Systemic Immune-inflammation Index (SII) was constructed and evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: ROC curve analysis showed that the optimal value of SII for predicting esophageal stricture was 312.67. Both univariate and multivariate analyses identified lesion infiltration depth (< M2 vs. ≥ M2, p = 0.002), lesion longitudinal length (< 4 cm vs. ≥ 4 cm, p = 0.008), circumferential resection range (< 0.5, 0.5-0.75, ≥ 0.75, p = 0.014), and SII (< 312.67 vs. ≥ 312.67, p = 0.040) as independent risk factors for post-ESD esophageal stricture. A novel nomogram prediction model incorporating these four risk factors was developed. Validation using ROC curve analysis demonstrated satisfactory model performance, while calibration curves indicated good agreement between model-predicted risk and observed outcomes. CONCLUSION: We successfully constructed a novel nomogram prediction model based on SII, which can accurately and intuitively predict the occurrence of esophageal stricture after ESD, providing guidance for clinicians and improving treatment outcomes.

Robust chelated lead octahedron surface for efficient and stable perovskite solar cells.

PbI6 octahedron as a fundamental framework endows the perovskite with excellent photoelectric properties, but also the defective and flimsy surface. Here, we report that the treatment of perovskite surface by bidentate ligands molecules N, N'-Dimethyl-1,2-ethanediamine can in-situ form a lead iodide chelates layer with excellently robust chelated lead octahedron, leading to effectively stabilize and passivate the underlying perovskite. The strong chelation with the lead enables the surface to largely inhibit the defects generation, iodide ion migration and skeleton collapse under external stimuli. It also prolongs the carrier lifetime and adjusts the surface energy-level of perovskite. The resultant perovskite solar cells deliver a power conversion efficiency of 25.7% (certified 25.04%) and retain >90% of their initial value after almost 1000 hours aging at maximum power point under simulated AM1.5 illumination.

Glycosylation in aging and neurodegenerative diseases.

Aging, a complex biological process, involves the progressive decline of physiological functions across various systems, leading to increased susceptibility to neurodegenerative diseases. In society, demographic aging imposes significant economic and social burdens due to these conditions. This review specifically examines the association of protein glycosylation with aging and neurodegenerative diseases. Glycosylation, a critical post-translational modification, influences numerous aspects of protein function that are pivotal in aging and the pathophysiology of diseases such as Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. We highlight the alterations in glycosylation patterns observed during aging, their implications in the onset and progression of neurodegenerative diseases, and the potential of glycosylation profiles as biomarkers for early detection, prognosis, and monitoring of these age-associated conditions, and delve into the mechanisms of glycosylation. Furthermore, this review explores their role in regulating protein function and mediating critical biological interactions in these diseases. By examining the changes in glycosylation profiles associated with each part, this review underscores the potential of glycosylation research as a tool to enhance our understanding of aging and its related diseases.

Novel computed tomography-based nomograms for the pretherapeutic prediction of response to neoadjuvant chemotherapy with S-1 and oxaliplatin with or without the addition of docetaxel in patients with advanced gastric cancer.

Background: Selecting the appropriate preoperative neoadjuvant chemotherapy (NACT) regimen for patients with advanced gastric cancer (GC) is critical to effective treatment. The aim of this study was to develop nomograms based on pretherapeutic computed tomography (CT) features to predict response to NACT with S-1 and oxaliplatin (SOX) or that with docetaxel and SOX (DOS) in patients with advanced GC. Methods: This study enrolled 311 consecutive patients with confirmed advanced GC undergoing contrast-enhanced CT before and after the three cycles of NACT with DOS (n=152) or SOX (n=159), who were randomized into a training cohort (TC) (NACT with DOS: n=111; NACT with SOX: n=120) and validation cohort (VC) (NACT with DOS: n=41; NACT with SOX: n=39). The objective response rate (ORR) was used to evaluate the response to NACT. In the TC, ORR was compared between the DOS and SOX regimens, and independent predictors including CT features and tumor differentiation were determined by univariate and binary logistic regression analyses. Individual nomograms were constructed for the SOX and DOS regimens in the TC, and the predictive accuracy was validated in the VC. Results: After NACT, the percentage of ORR was higher in patients receiving DOS than in those receiving SOX in TC (P value <0.05). The independent predictors after DOS and SOX were pretherapeutic cT stage [odds ratio (OR) =7.364; OR =8.848], cN stage (OR =1.027; OR =1.345), degree of differentiation (OR =7.127; OR =7.835), and gross tumor volume (OR =8.960; OR =8.161) (all P values <0.05). The concordance indexes of the individual nomograms developed using these predictors were 0.940 and 0.932 after DOS or SOX in the TC, respectively, which was validated by calibration plots with a slope close to 45° in the TC and VC. Conclusions: Despite there being a superior response to DOS compared with SOX, nomograms for predicting response to both NACT regimens were similar, with each demonstrating good predictive performance.

Confined Cu Single Sites in ZSM-5 for Photocatalytic Hydroxylation of Benzene to Phenol.

Zeolites with band-like charge transport properties have exhibited their potential activities in sensing, optics, and electronics. Herein, a precisely designed Cu@ZSM-5 catalyst is presented with an ultra-wide bandgap of 4.27 eV, showing excellent photocatalytic activity in hydroxylation of benzene with benzene conversion 27.9% and phenol selectivity 97.6%. The SXRD and Rietveld refinement results illustrate that Cu@ZSM-5 has an average of 0.8 Cu atoms per unit cell and the single Cu atoms located in the cross-section of the sinusoidal and straight channels. XANES and EXAFS further demonstrate that the Cu atoms have an oxidation state of +2, coordinated with three OMFI-framework atoms and one ─OH group. Detailed characterizations demonstrate that the Cu@ZSM-5 with tailored bandgap is able to enhance the photoinduced electron-hole separation and hence promote selective hydroxylation of benzene to phenol via the superoxide radical route. This work may open a new way for designing electrically conductive zeolite-supported photocatalysts.

Restoration of ARA metabolic disorders in vascular smooth muscle cells alleviates intimal hyperplasia.

Intimal hyperplasia (IH) is an innegligible issue for patients undergoing interventional therapy. The proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor-BB (PDGF-BB) are critical events in the development of IH. While the exact mechanism and effective target for IH needs further investigation. Metabolic disorders of arachidonic acid (ARA) are involved in the occurrence and progression of various diseases. In this study, we found that the expressions of soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) were significantly increased in the VSMCs during balloon injury-induced IH. Then, we employed a COX-2/sEH dual inhibitor PTUPB to increase the concentration of epoxyeicosatrienoic acids (EETs) while prevent the release of pro-inflammatory prostaglandins. Results showed that PTUPB treatment significantly reduced neointimal thickening induced by balloon injury in rats in vivo and inhibited PDGF-BB-induced proliferation and migration of VSMCs in vitro. Our results showed that PTUPB may reverse the phenotypic transition of VSMCs by inhibiting Pttg1 expression. In conclusion, we found that the dysfunction of ARA metabolism in VSMCs contributes to IH, and the COX-2/sEH dual inhibitor PTUPB attenuates IH progression by reversing the phenotypic switch in VSMC through the Sirt1/Pttg1 pathway.

Different etiological entities of liver cancer across populations: Implications from age-period-cohort analysis on incidence trends.

BACKGROUND: The incidence of liver cancer has shown different temporal trends across populations, while the underlying reasons remain unclear. METHODS: We examined temporal trends in the incidence of liver cancer in Hong Kong, Sweden, and the United States since the 1970s through 2021 using joinpoint regression and age-period-cohort analysis. RESULTS: The age-standardized incidence rate of liver cancer in Hong Kong steadily decreased (average annual percentage change [AAPC] -2.2%, 95% confidence interval [CI] -2.8% to -1.7% in men; AAPC -2.1%, 95%CI -3.1% to -1.1% in women) in 1983-2020. The rate in Sweden increased on average by 0.8% (95%CI 0.2% to 1.4%) per year in men and was stable in women (AAPC 0.2%, 95%CI -0.9% to 1.4%) in 1970-2021. The rate in the United States increased by 2.1% (95%CI 1.5% to 2.8%) per year in men and by 2.1% (95%CI 1.6% to 2.5%) in women in 1975-2020, but decreasing trends were noted in 2015-2020 (AAPC -6.6%, 95%CI -8.3% to -4.9% in men; AAPC -4.2%, 95%CI -7.5% to -0.5% in women). Stratified analysis by histological type showed such decrease in recent years was limited to hepatocellular carcinoma, rather than intrahepatic cholangiocarcinoma. We observed distinct changes in trends across age groups and different trends across birth cohorts. CONCLUSION: The incidence of liver cancer has decreased in Hong Kong but increased in Sweden and the United States since the 1980s, despite decreasing incidence in the United States since 2015. Such disparities may be explained by different etiology and implementation of preventive measures across populations.

Olaparib combined with CDK12-IN-3 to promote genomic instability and cell death in ovarian cancer.

Large-scale phase III clinical trials of Olaparib have revealed benefits for ovarian cancer patients with BRCA gene mutations or homologous recombination deficiency (HRD). However, fewer than 50% of ovarian cancer patients have both BRCA mutations and HRD. Therefore, improving the effect of Olaparib in HR-proficient patients is of great clinical value. Here, a combination strategy comprising Olaparib and CDK12-IN-3 effectively inhibited the growth of HR-proficient ovarian cancer in cell line, patient-derived organoid (PDO), and mouse xenograft models. Furthermore, the combination strategy induced severe DNA double-strand break (DSB) formation, increased NHEJ activity in the G2 phase, and reduced HR activity in cancer cells. Mechanistically, the combination treatment impaired Ku80 poly(ADP-ribosyl)ation (PARylation) and phosphorylation, resulting in PARP1-Ku80 complex dissociation. After dissociation, Ku80 occupancy at DSBs and the resulting Ku80-primed NHEJ activity were increased. Owing to Ku80-mediated DNA end protection, MRE11 and Rad51 foci formation was inhibited after the combination treatment, suggesting that this treatment suppressed HR activity. Intriguingly, the combination strategy expedited cGAS nuclear relocalization, further suppressing HR and, conversely, increasing genomic instability. Moreover, the inhibitory effect on cell survival persisted after drug withdrawal. These findings provide a rationale for the clinical application of CDK12-IN-3 in combination with Olaparib.

Preoperative identification of small metastatic lymph nodes in esophageal squamous cell carcinoma using CT radiomics of lymph nodes.

PURPOSE: To propose and validate a CT radiomics model utilizing radiomic features from lymph nodes (LNs) with maximum short axis diameter (MSAD) < 1 cm for predicting small metastatic LN (sMLN) in patients with resectable esophageal squamous cell carcinoma (ESCC). METHODS: A total of 196 resectable patients with ESCC undergoing surgery were retrospectively enrolled, among whom 25% had sMLN. 146 out of 196 patients (from hospital 1) were randomly divided into the training (n = 116) and testing cohorts (n = 30) at an 8:2 ratio, while the remaining 50 patients from hospital 2 constituted the external validation cohort. Least absolute shrinkage and selection operator binary logistic regression was employed for radiomics feature dimensionality reduction and selection, and multivariable logistic regression analysis was used to construct the radiomics prediction model. The clinical features were statistically selected to develop the clinical model. And both the selected radiomics and clinical features were used to develop the combined model. The predictive value of models was assessed using the area under the receiver operating characteristic curves (AUC). RESULTS: The LN radiomics model was constructed with 9 radiomics features, the clinical model was developed with 3 clinical features, and the combined model was developed using both the LN radiomics and clinical features. However, no statistical radiomics features from ESCC were extracted in dimensionality reduction. Compared to the clinical model, the combined model exhibited superior predictive ability (AUC: 0.893 vs. 0.766, P = 0.003), and the LN radiomics model showed slightly better predictive ability (AUC: 0.860 vs. 0.766, P = 0.153). It was validated in the test and external validation cohorts. CONCLUSION: The combined model could assist in preoperatively identifying sMLN in resectable ESCC. It is beneficial for more accurate N staging and clinical comprehensive staging of ESCC, thereby facilitating the clinical physician to make more personalized and standardized treatment strategies.