Oxygen-defect bismuth oxychloride nanosheets for ultrasonic cavitation effect enhanced sonodynamic and second near-infrared photo-induced therapy of breast cancer.

Sonodynamic therapy (SDT) relies heavily on the presence of oxygen to induce cell death. Its effectiveness is thus diminished in the hypoxic regions of tumor tissue. To address this issue, the exploration of ultrasound-based synergistic treatment modalities has become a significant research focus. Here, we report an ultrasonic cavitation effect enhanced sonodynamic and 1208 nm photo-induced cancer treatment strategy based on thermoelectric/piezoelectric oxygen-defect bismuth oxychloride nanosheets (BNs) to realize the high-performance eradication of tumors. Upon ultrasonic irradiation, the local high temperature and high pressure generated by the ultrasonic cavitation effect combined with the thermoelectric and piezoelectric effects of BNs create a built-in electric field. This facilitates the separation of carriers, increasing their mobility and extending their lifetimes, thereby greatly improving the effectiveness of SDT and NIR-Ⅱ phototherapy on hypoxia. The Tween-20 modified BNs (TBNs) demonstrate ∼88.6 % elimination rate against deep-seated tumor cells under hypoxic conditions. In vivo experiments confirm the excellent antitumor efficacy of TBNs, achieving complete tumor elimination within 10 days with no recurrences. Furthermore, due to the high X-ray attenuation of Bi and excellent NIR-Ⅱ absorption, TBNs enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).

The clinical outcomes of patients with vascular invasion after deceased donor liver transplantation.

Background: Vascular invasion is a major risk factor for poor prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC), and this study aimed to evaluate the feasibility and efficacy of deceased donor LT (DDLT) for the treatment of microvascular invasion (MVI) and segmental portal vein tumor thrombus (PVTT). Methods: We retrospectively analyzed 141 patients who received DDLT for HCC combined with vascular invasion from January 2016 to December 2023 at Shulan (Hangzhou) Hospital. To assess the risk of vascular invasion associated with the LT prognosis, we evaluated various clinicopathologic variables. The recurrence-free survival (RFS) and overall survival (OS) based on different types of vascular invasion were also analyzed. Results: A total of 141 patients were enrolled in this study, including patients with MVI (MVI group, n=60), segmental PVTT with segmental branches of the portal vein or above (segmental PVTT group, n=13), and lobar PVTT involving the left and right branches of the portal vein or the main portal vein (lobar PVTT group, n=68). Between the tumor recurrence group and the no recurrence group, there were significant differences in alpha-fetoprotein (AFP) level, tumor total diameter, pretransplant treatment, histological grade, and types of vascular invasion. Subgroup analyses were performed according to the types of vascular invasion, the lobar PVTT group had a significantly higher recurrence rate (lobar vs. MVI: 88.2% vs. 35.0%, lobar vs. segmental: 88.2% vs. 30.8%, both P<0.001), but there was no difference in recurrence rate between the MVI group and the segmental PVTT group (35.0% vs. 30.8%, P>0.99). The 3-year RFS rate and OS rate were as low as 9.1% and 45.9% in the lobar PVTT group, compared with 65.5% and 76.0% in the MVI group, 58.3% and 75.0% in the segmental PVTT group. Multivariate analysis showed that Child-Pugh classification, tumor total diameter, histological grade, and lobar PVTT were the main risk factors affecting RFS, whereas Child-Pugh classification, tumor total diameter, and lobar PVTT were the main risk factors affecting OS. Finally, analysis of the segmental PVTT group revealed that RFS was significantly higher in well and moderately-differentiated patients than in poor-differentiated patients (P=0.01). Conclusions: Lobar PVTT remains a contraindication to LT, whereas segmental PVTT can still be considered for LT after careful screening.

Deep Learning-Based System Combining Chest X-Ray and Computerized Tomography Images for COVID-19 Diagnosis.

Aims/Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for accurate and efficient diagnostic methods. This study aims to improve COVID-19 detection by integrating chest X-ray (CXR) and computerized tomography (CT) images using deep learning techniques, further improving diagnostic accuracy by using a combined imaging approach. Methods: The study used two publicly accessible databases, COVID-19 Questionnaires for Understanding the Exposure (COVID-QU-Ex) and Integrated Clinical and Translational Cancer Foundation (iCTCF), containing CXR and CT images, respectively. The proposed system employed convolutional neural networks (CNNs) for classification, specifically EfficientNet and ResNet architectures. The data underwent preprocessing steps, including image resizing, Gaussian noise addition, and data augmentation. The dataset was divided into training, validation, and test sets. Gradient-weighted Class Activation Mapping (Grad-CAM) was used for model interpretability. Results: The EfficientNet-based models outperformed the ResNet-based models across all metrics. The highest accuracy achieved was 99.44% for CXR images and 99.81% for CT images with EfficientNetB5. The models also demonstrated high precision, recall, and F1 scores. For statistical significance, the p-values were less than 0.05, indicating that the results are significant. Conclusion: Integrating CXR and CT images using deep learning significantly improves the accuracy of COVID-19 diagnosis. The EfficientNet-based models, with their superior feature extraction capabilities, show better performance than ResNet models. Grad-CAM Visualizations provide insights into the model's decision-making process, potentially reducing diagnostic errors and accelerating diagnosis processes. This approach can improve patient care and support healthcare systems in managing the pandemic more effectively.

The first-in-human preclinical evaluation of the new probe [123I]I-PSMA-7 for real-time intraoperative targeted biopsy and SPECT/CT imaging in prostate cancer.

PURPOSE: PSMA/PET has been increasingly used to detect PCa, and PSMA/PET-guided biopsy has shown promising results. However, it cannot be confirmed immediately whether the tissues are the targeted area. In this study, we aimed to develop a novel probe, [123I]I-PSMA-7. First, we hope that [123I]I-PSMA-7 can provide instant confirmation for prostate biopsy. Second, we hope it will help detect PCa. METHODS: We synthesized a high-affinity probe, [123I]I-PSMA-7, and evaluated its properties. We included ten patients with suspected PCa and divided them into two groups. The injection and biopsy were approximately 24 h apart. The activity in biopsy lesions was measured as the cpm by a γ-counter. Moreover, we enrolled 3 patients to evaluate the potential of [123I]I-PSMA-7 for detecting PCa. RESULTS: Animal experiments verified the safety, targeting and effectiveness of [123I]I-PSMA-7, and the tumor-to-muscle ratio was greatest at 24 h, which confirmed the results of this study in humans. After injection of 185MBq [123I]I-PSMA-7, 18/55 cores were positive, and the cpm was significantly greater (4345 ± 3547 vs. 714 ± 547, P < 0.001), with an AUC of 0.97 and a cutoff of 1312 (sens/spec of 94.40%/91.90%). At a lower dose, 10/55 biopsy cores were cancerous, and the cpm was 2446 ± 1622 vs. 153 ± 112 (P < 0.001). The AUC was 1, with a cutoff value of 490 (sens/spec of 100%). When the radiopharmaceuticals were added to 370 MBq, we achieved better SPECT/CT imaging. CONCLUSION: With the aid of [123I]I-PSMA-7 and via cpm-based biopsy, we can reduce the number of biopsies to a minimum operation. [123I]I-PSMA-7 PSMA SPECT/CT can also provide good imaging results. TRIAL REGISTRATION: Chinese Clinical trial registry ChiCTR2300069745, Registered 24 March 2023.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma.

BACKGROUND: The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) as neoadjuvant therapy before liver transplantation (LT) for advanced-stage hepatocellular carcinoma (HCC) and to analyze the prognostic factors. AIM: To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC. METHODS: A total of 99 individuals diagnosed with advanced HCC were studied retrospectively. The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT: DEB-TACE group (n = 45) and control group (n = 54). The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus (PVTT). The DEB-TACE group consisted of two subgroups: Group A (n = 31) without PVTT and group B (n = 14) with PVTT. The control group also had two subgroups: Group C (n = 37) without PVTT and group D (n = 17) with PVTT. Data on patient demographics, disease characteristics, therapy response, and adverse events (AEs) were collected. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS. RESULTS: The DEB-TACE group exhibited an overall response rate of 86.6%. Following therapy, there was a significant decrease in the median alpha-fetoprotein (AFP) level (275.1 ng/mL vs 41.7 ng/mL, P < 0.001). The main AE was post-embolization syndrome. The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group (68.9% vs 38.9%, P = 0.003; 86.7% vs 63.0%, P = 0.008). Within the subgroups, group A had higher 2-year rates of RFS and OS compared to group C (71.0% vs 45.9%, P = 0.038; 83.8% vs 62.2%, P = 0.047). The 2-year RFS rate of group B was markedly superior to that of group D (64.3% vs 23.5%, P = 0.002). Results from multivariate analyses showed that pre-LT DEB-TACE [hazard ratio (HR) = 2.73, 95% confidence interval (CI): 1.44-5.14, P = 0.04], overall target tumor diameter ≤ 7 cm (HR = 1.98, 95%CI: 1.05-3.75, P = 0.035), and AFP level ≤ 400 ng/mL (HR = 2.34; 95%CI: 1.30-4.19, P = 0.009) were significant risk factors for RFS. Additionally, pre-LT DEB-TACE (HR = 3.15, 95%CI: 1.43-6.96, P = 0.004) was identified as a significant risk factor for OS. CONCLUSION: DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Prognostic significance of integrating total metabolic tumor volume and EGFR mutation status in patients with lung adenocarcinoma.

Background: The objective of this study was to investigate the prognostic significance of total metabolic tumor volume (TMTV) derived from baseline 18F-2-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), in conjunction with epidermal growth factor receptor (EGFR) mutation status, among patients with lung adenocarcinoma (LUAD). Methods: We performed a retrospective analysis on 141 patients with LUAD (74 males, 67 females, median age 67 (range 34-86)) who underwent 18F-FDG PET/CT and had their EGFR mutation status determined. Optimal cutoff points for TMTV were determined using time-dependent receiver operating characteristic curve analysis. The survival difference was compared using Cox regression analysis and Kaplan‒Meier curves. Results: The EGFR mutant patients (n = 79, 56.0%) exhibited significantly higher 2-year progression-free survival (PFS) and overall survival (OS) rates compared to those with EGFR wild-type (n = 62, 44.0%), with rates of 74.2% vs 69.2% (P = 0.029) and 86.1% vs 67.7% (P = 0.009), respectively. The optimal cutoff values of TMTV were 36.42 cm3 for PFS and 37.51 cm3 for OS. Patients with high TMTV exhibited significantly inferior 2-year PFS and OS, with rates of 22.4% and 38.1%, respectively, compared to those with low TMTV, who had rates of 85.8% and 95.0% (both P < 0.001). In both the EGFR mutant and wild-type groups, patients exhibiting high TMTV demonstrated significantly inferior 2-year PFS and OS compared to those with low TMTV. In multivariate analysis, EGFR mutation status (hazard ratio, HR, 0.41, 95% confidence interval, CI [0.18-0.94], P = 0.034) and TMTV (HR 8.08, 95% CI [2.34-28.0], P < 0.001) were independent prognostic factors of OS, whereas TMTV was also an independent prognosticator of PFS (HR 2.59, 95% CI [1.30-5.13], P = 0.007). Conclusion: Our study demonstrates that the integration of TMTV on baseline 18F-FDG PET/CT with EGFR mutation status improves the accuracy of prognostic evaluation for patients with LUAD.

Metabolic parameters of pretreatment 2-[18F]fluoro-D-glucose positron emission tomography for prognosis in patients with gallbladder adenocarcinoma: a cohort study.

Background: The incidence of gallbladder adenocarcinoma (GBA) is relatively low, yet it exhibits a high degree of malignancy and a significantly low 5-year survival rate. The aim of this study was to investigate the prognostic value of pretreatment 2-[18F]fluoro-D-glucose positron emission tomography {2-[18F]FDG PET} parameters in predicting outcomes for patients with GBA. Methods: In total, 67 patients with GBA who underwent 2-[18F]FDG PET/computed tomography (CT) before treatment were retrospectively analyzed at Chinese PLA General Hospital from January 2012 to June 2022. All patients were diagnosed by pathology, and their baseline characteristics and clinical data were collected. The metabolic PET parameters of the primary and metastatic lesions were measured, including the maximum and average standardized uptake values (SUVs), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The prognostic significance of metabolic parameters and other clinical variables was assessed using Cox proportional hazards regression models. Differences in progression-free survival (PFS) and overall survival (OS) in relation to metabolic parameters were examined using the Kaplan-Meier method. Results: During a median follow-up period of 14.2 months, 43 patients (64.2%) experienced tumor recurrence or progression, and 38 patients (56.7%) died of cancer. In the univariate Cox regression analysis, liver parenchymal invasion (P=0.001), lymph node metastasis (P=0.007), distant metastases (P=0.049), tumor differentiation (P=0.028), surgery (P=0.014), carcinoembryonic antigen (CEA) level (P=0.030), carbohydrate antigen 19-9 (CA19-9) level (P=0.003), TLG (P=0.005), MTV (P<0.001), sum of the TLGs of the primary and metastatic lesions (total TLG, tTLG) (P=0.001), and sum of the MTVs of the primary and metastatic lesions (total MTV, tMTV) (P<0.001) were significant predictors of PFS. In multivariate analysis, MTV was an independent predictor of PFS [hazard ratio (HR) =2.785; 95% confidence interval (CI): 1.204-6.441; P=0.017]. In the univariate Cox regression analysis, liver parenchymal invasion (P=0.001), lymph node metastasis (P=0.027), distant metastases (P=0.036), tumor differentiation (P=0.047), surgery (P=0.002), neutrophil-to-lymphocyte ratio (NLR) (P=0.011), CEA level (P=0.036), CA19-9 level (P<0.001), TLG (P=0.007), MTV (P<0.001), tTLG (P=0.003), and tMTV (P<0.001) were significant predictors of OS. In the multivariate analysis, higher CA19-9 levels >37 U/mL and a greater tMTV (HR =2.961; 95% CI: 1.092-8.024; P=0.033) were predictive of OS. Conclusions: Our study results suggest that pretreatment 2-[18F]FDG PET parameters can not only assist in the diagnosis of patients with GBA but may also serve as predictive factors for the prognosis of these patients and should thus be applied in their treatment.

Co-exposure with cadmium elevates the toxicity of microplastics: Trojan horse effect from the perspective of intestinal barrier.

Microplastics (MPs) have been shown to adsorb heavy metals and serve as vehicles for their environmental transport. To date, insufficient studies have focused on enterohepatic injury in mice co-exposed to both MPs and cadmium (Cd). Here, we report that Cd adsorption increased the surface roughness and decreased the monodispersity of PS-MPs. Furthermore, exposure to both PS-MPs and Cd resulted in a more severe toxic effect compared to single exposure, with decreased body weight gain, shortened colon length, and increased colonic and hepatic inflammatory response observed. This can be attributed to an elevated accumulation of Cd resulting from increased gut permeability, coupled with the superimposed effects of oxidative stress. In addition, using 16 S sequencing and fecal microbiota transplantation, it was demonstrated that gut microbiota dysbiosis plays an essential role in the synergistic toxicity induced by PS-MPs and Cd in mice. This study showed that combined exposure to MPs and Cd induced more severe intestinal and liver damage in mice compared to individual exposure, and provided a new perspective for a more systematic risk assessment process related to MPs exposure.

Oxygen Vacancy Defect Enhanced NIR-II Photothermal Performance of BiOxCl Nanosheets for Combined Phototherapy of Cancer Guided by Multimodal Imaging.

Narrow photo-absorption range and low carrier utilization are significant barriers that restrict the antitumor efficiency of 2D bismuth oxyhalide (BiOX, X = Cl, Br, I) nanosheets (NSs). Introducing oxygen vacancy (OV) defects can expand the absorption range and improve carrier utilization, which are crucial but also challenging. In this study, a series of BiOxCl NSs with different OV defect concentrations (x = 1, 0.7, 0.5) is developed, which shows full spectrum absorption and strong absorption in the second near-infrared region (NIR-II). Density functional theory calculations are utilized to calculate the crystal structure and density states of BiOxCl, which confirm that part of the carriers is separated by OV enhanced internal electric field to improve carrier utilization. The carriers without redox reaction can be trapped in the OV, leading to great majority of photo-generated carriers promoting the photothermal performance. Triggered by single NIR-II (1064 nm), BiOxCl NSs' bidirectional efficient utilization of carriers achieves synchronously combined phototherapy, leading to enhanced tumor ablation and multimodal diagnostic in vitro and vivo. It is thus believed that this work provides an innovative strategy to design and construct nanoplatforms of indirect band gap semiconductors for clinical phototheranostics.

Association between cigarette smoking history, metabolic phenotypes, and EGFR mutation status in patients with non-small cell lung cancer.

Background: Cigarette smoking exerts a significant impact on metabolic phenotypes and epidermal growth factor receptor (EGFR) mutation status; however, their correlation remains insufficiently established. Therefore, the aim of this study was to investigate the association between cigarette smoking history, metabolic phenotypes, and EGFR mutation status in patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively analyzed 198 consecutive patients with NSCLC who underwent 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) before treatment and were tested for EGFR mutation status between September 2019 and March 2022. Metabolic phenotypes, including the maximum standardized uptake value (SUVmax) of the primary tumors (pSUVmax), metastatic lymph nodes (nSUVmax), and distant metastases (mSUVmax) were assessed. Patients were classified into never-smokers and smokers based on detailed smoking history. The correlations between smoking status, metabolic parameters, and EGFR mutation status were evaluated in patients with NSCLC. Results: We observed EGFR mutations in 73 (60.3%) of 121 never-smokers and 18 (23.4%) of 77 smokers (P<0.001). EGFR-mutant NSCLC had a lower pSUVmax than that of EGFR wild-type (WT; 8.9±4.5 vs. 12.7±6.9, P<0.001). Smokers had a higher pSUVmax than never-smokers (12.5±6.4 vs. 9.9±5.9, P=0.004). With the increase of cumulative smoking dose, the pSUVmax increased significantly (r=0.198, P=0.005). There was no significant difference between nSUVmax and mSUVmax in patients with or without EGFR mutation and smoking history. Cumulative smoking dose, pSUVmax, and their combination predicted EGFR mutation status with areas under the receiver operating characteristic (ROC) curves (AUCs) 0.688, 0.673, and 0.753, respectively. Conclusions: Our findings indicate that cigarette smoking may be one of the triggers for increased pSUVmax and decreased EGFR mutations, further suggesting that EGFR mutations are associated with low pSUVmax, which may guide clinicians in risk stratification and treatment strategy selection for patients with NSCLC.

Nanotechnology-Based Drug Delivery Systems to Control Bacterial-Biofilm-Associated Lung Infections.

Airway mucus dysfunction and impaired immunological defenses are hallmarks of several lung diseases, including asthma, cystic fibrosis, and chronic obstructive pulmonary diseases, and are mostly causative factors in bacterial-biofilm-associated respiratory tract infections. Bacteria residing within the biofilm architecture pose a complex challenge in clinical settings due to their increased tolerance to currently available antibiotics and host immune responses, resulting in chronic infections with high recalcitrance and high rates of morbidity and mortality. To address these unmet clinical needs, potential anti-biofilm therapeutic strategies are being developed to effectively control bacterial biofilm. This review focuses on recent advances in the development and application of nanoparticulate drug delivery systems for the treatment of biofilm-associated respiratory tract infections, especially addressing the respiratory barriers of concern for biofilm accessibility and the various types of nanoparticles used to combat biofilms. Understanding the obstacles facing pulmonary drug delivery to bacterial biofilms and nanoparticle-based approaches to combatting biofilm may encourage researchers to explore promising treatment modalities for bacterial-biofilm-associated chronic lung infections.

Natural course of perianal abscess in infants: a real-world study.

Natural course of perianal abscess (PA) in infancy remains obscure. This study aimed to investigate the natural course of infants with PA after conservative treatment. A retrospective cohort study was conducted in infants with PA who were treated conservatively (due to the parents' refusal of surgery), for more than 2 months between 2014 and 2020 at a single tertiary center. 153 patients (149 boys and 4 girls) were identified. The median follow-up was 5.3 years (range 3-8.2 years). Initially, 119 patients (77.8%) were completely cured by conservative treatment, and 34 (22.2%) failed. Among the 34 patients, 23 continued conservative treatment (20 cure, 3 fistula formation) and 11 underwent surgery. After conservative treatment, the rate of fistula formation, abscess recurrence, and new-onset abscess were 15.0%, 4.6%, and 6.5%, respectively. Overall, 139 patients (90.8%) were cured conservatively without surgery, and 11 (7.2%) underwent surgical management. In addition, 3 (2.0%) patients developed fistula-in-ano (under observation). PA in infants may be a time-limited and self-limited condition. Conservative management should be the first choice of treatment in most cases. Longer periods of conservative treatment may achieve better clinical outcomes in selected cases. There will be a percentage of patients (about 10%) that would require surgical treatment.

Fe3+@PDOPA­b­PSar Nanoparticles for Magnetic Resonance Imaging and Cancer Chemotherapy.

Purpose: Chemotherapy treatments for cancer are always accompanied by a low concentration of drug delivered in the tumor area and severe side effects including systemic toxicity. Improving the concentration, biocompatibility, and biodegradability of regional chemotherapy drugs is a pressing challenge in the field of materials. Methods: N-Phenyloxycarbonyl-amino acids (NPCs) which exhibit significant tolerance to nucleophiles, such as water and hydroxyl-containing compounds, are promising monomers for the synthesis of polypeptides and polypeptoids. Cell line and mouse models were used to comprehensively explore how to enhance the tumor MRI signal and evaluate the therapeutic effect of Fe@POS-DOX nanoparticles. Results: In this study, poly(3,4-dihydroxy-L-phenylalanine)-b-polysarcosine (PDOPA-b-PSar, simplified as POS) was synthesized by the block copolymerization of DOPA-NPC with Sar-NPC. Fe@POS-DOX nanoparticles were prepared in order to utilize the strong chelation of catechol ligands to iron (III) cations and the hydrophobic interaction between DOX and DOPA block to deliver chemotherapeutics to tumor tissue. The Fe@POS-DOX nanoparticles exhibit high longitudinal relaxivity (r 1 = 7.06 mM-1·s-1) and act as T 1-weighted magnetic resonance (MR) imaging contrast agents. Further, the main focus was improving tumor site-specific bioavailability and achieving therapeutic effects through the biocompatibility and biodegradability of Fe@POS-DOX NPs. The Fe@POS-DOX treatment exhibited excellent antitumor effects. Conclusion: Upon intravenous injection, Fe@POS-DOX delivers DOX specifically to the tumor tissues, as revealed by MR, and leads to the inhibition of tumor growth without overt toxicity to normal tissues, thus displaying considerable potential for use in clinical applications.

Identification of EGFR mutation status in male patients with non-small-cell lung cancer: role of 18F-FDG PET/CT and serum tumor markers CYFRA21-1 and SCC-Ag.

BACKGROUND: The high incidence of epidermal growth factor receptor (EGFR) mutations is usually found in female patients with lung adenocarcinoma who have never-smoked. However, reports concerning male patients are scarce. Thus, this study aimed to explore a novel approach based on 18F-fluoro-2-deoxy-2-deoxyglucose (18F-FDG) PET/CT and serum tumor markers (STMs) to determine EGFR mutation status in male patients with non-small-cell lung cancer (NSCLC). METHODS: A total of 121 male patients with NSCLC were analyzed between October 2019 and March 2022. All patients underwent 18F-FDG PET/CT scan before treatment and monitored 8 STMs (cytokeratin 19 fragment [CYFRA21-1], squamous cell carcinoma-related antigen [SCC-Ag], carcinoembryonic antigen [CEA], neuron-specific enolase [NSE], carbohydrate antigen [CA] 50, CA125, CA72-4, and ferritin). A comparison was done between EGFR mutant and wild-type patients in terms of the maximum standardized uptake value of primary tumors (pSUVmax) and 8 STMs. We performed receiver operating characteristic (ROC) curve and multiple logistic regression analyses to determine predictors for EGFR mutation status. RESULTS: EGFR mutations were detected in 39 patients (32.2%). Compared with patients with EGFR wild-type, EGFR-mutant patients had lower concentrations of serum CYRFA21-1 (2.65 vs. 4.01, P = 0.002) and SCC-Ag (0.67 vs. 1.05, P = 0.006). No significant differences of CEA, NSE, CA 50, CA125, CA72-4 and ferritin were found between the two groups. The presence of EGFR mutations was significantly associated with low pSUVmax (< 8.75), low serum SCC-Ag (< 0.79 ng/mL) and CYFRA21-1 (< 2.91 ng/mL) concentrations. The area under ROC curve values were 0.679, 0.655, 0.685 and 0.754, respectively, for low CYFRA21-1, SCC-Ag, pSUVmax and the combination of these three factors. CONCLUSIONS: We demonstrated that low concentrations of CYFRA21-1 and SCC-Ag, as well as low pSUVmax, were associated with EGFR mutations, and that the combination of these factors resulted in a higher differentiation of EGFR mutation status in male patients with NSCLC.

Preoperative prediction of tumor deposits in rectal cancer with clinical-magnetic resonance deep learning-based radiomic models.

Background: This study aimed to establish an effective model for preoperative prediction of tumor deposits (TDs) in patients with rectal cancer (RC). Methods: In 500 patients, radiomic features were extracted from magnetic resonance imaging (MRI) using modalities such as high-resolution T2-weighted (HRT2) imaging and diffusion-weighted imaging (DWI). Machine learning (ML)-based and deep learning (DL)-based radiomic models were developed and integrated with clinical characteristics for TD prediction. The performance of the models was assessed using the area under the curve (AUC) over five-fold cross-validation. Results: A total of 564 radiomic features that quantified the intensity, shape, orientation, and texture of the tumor were extracted for each patient. The HRT2-ML, DWI-ML, Merged-ML, HRT2-DL, DWI-DL, and Merged-DL models demonstrated AUCs of 0.62 ± 0.02, 0.64 ± 0.08, 0.69 ± 0.04, 0.57 ± 0.06, 0.68 ± 0.03, and 0.59 ± 0.04, respectively. The clinical-ML, clinical-HRT2-ML, clinical-DWI-ML, clinical-Merged-ML, clinical-DL, clinical-HRT2-DL, clinical-DWI-DL, and clinical-Merged-DL models demonstrated AUCs of 0.81 ± 0.06, 0.79 ± 0.02, 0.81 ± 0.02, 0.83 ± 0.01, 0.81 ± 0.04, 0.83 ± 0.04, 0.90 ± 0.04, and 0.83 ± 0.05, respectively. The clinical-DWI-DL model achieved the best predictive performance (accuracy 0.84 ± 0.05, sensitivity 0.94 ± 0. 13, specificity 0.79 ± 0.04). Conclusions: A comprehensive model combining MRI radiomic features and clinical characteristics achieved promising performance in TD prediction for RC patients. This approach has the potential to assist clinicians in preoperative stage evaluation and personalized treatment of RC patients.

Metabolic phenotypes, serum tumor markers, and histopathological subtypes in predicting bone metastasis: analysis of 695 patients with lung cancer in China.

Background: Patients with lung cancer who develop bone metastasis (BM) generally have an adverse prognosis. Although several clinical models have been used to predict BM in patients with lung cancer, the results are unsatisfactory. In this retrospective study, we investigated the role of 18F-2-fluoro-2-deoxyglucose (FDG) metabolic activity, serum tumor markers, and histopathological subtypes in predicting BM in patients with lung cancer. Methods: This study included 695 consecutive patients with lung cancer who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) and in whom serum tumor markers were detected prior to treatment. The maximum standardized uptake value of primary tumors (pSUVmax), metastatic lymph nodes (nSUVmax) and distant metastases (mSUVmax), 8 serum tumor markers [carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), squamous cell carcinoma-related antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), carbohydrate antigen (CA) 125, CA50, CA72-4, and ferritin], and histopathological subtypes were compared between patients with and without BM. Receiver operating characteristic (ROC) curve and multiple logistic regression analyses were performed to identify predictors of BM in patients with lung cancer. Results: BM was identified in 133 (19.1%) patients and not in 562 (80.9%). Patients with BM had significantly higher pSUVmax, nSUVmax, and mSUVmax than did those without BM. High concentrations of 6 serum tumor markers (i.e., CEA, ferritin, NSE, CA50, CA125, and CYFRA21-1) were significantly associated with BM. There were significant differences in the proportion of histopathological subtypes between patients with and without BM (χ2=32.35; P<0.001). The area under ROC-derived curve based on metabolic parameters was 0.737 (95% CI: 0.644-0.829) and 0.884 (95% CI: 0.825-0.943) when combined with the 6 serum tumor markers and histopathological subtypes, respectively. Conclusions: High pSUVmax, nSUVmax, and mSUVmax favor the presence of BM in patients with lung cancer, and serum tumor markers and histopathological subtypes are important factors for predicting BM in these patients.

Assessment of Drug Susceptibility for Patient-Derived Tumor Models through Lactate Biosensing and Machine Learning.

A patient-derived tumor model (PDM) is a practical tool to rapidly screen chemotherapeutics for individual patients. The evaluation method of cell viability directly determines the application of PDMs for drug susceptibility testing. As one of the metabolites of "glycosis", the lactate content was used to evaluate cell viability, but these assays were not specific for tumor cells. Based on the "Warburg effect", wherein tumor cells preferentially rely on "aerobic glycolysis" to produce lactate instead of pyruvate in "anaerobic glycolysis" of normal cells, we reported a gold lactate sensor (GLS) to estimate the cell viability of PDMs in drug susceptibility testing. It demonstrated high consistency between the GLS and commercial cell viability assay. Unlike either imaging or cell viability assay, the GLS characterizes the cell viability, enables dynamic monitoring, and distinguishes tumor cells from other cells. Moreover, machine learning (ML) was employed to perform a multi-index assessment for drug susceptibility of PDMs, which proved to be accurate and practical for clinical application. Therefore, the GLS provides an ideal drug susceptibility testing tool for individualized medicine.

Multiparameter diagnostic model based on 18F-FDG PET metabolic parameters and clinical variables can differentiate nonmetastatic gallbladder cancer and cholecystitis.

OBJECTIVE: To evaluate the diagnostic value of a multiparameter model based on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) metabolic parameters and clinical variables in differentiating nonmetastatic gallbladder cancer (GBC) from cholecystitis. PATIENTS AND METHODS: In total, 122 patients (88 GBC nonmetastatic patients and 34 cholecystitis patients) with gallbladder space-occupying lesions who underwent 18F-FDG PET/CT were included. All patients received surgery and pathology, and baseline characteristics and clinical data were also collected. The metabolic parameters of 18F-FDG PET, including SUVmax (maximum standard uptake value), SUVmean (mean standard uptake value), SUVpeak (peak standard uptake value), MTV (metabolic tumour volume), TLG (total lesion glycolysis) and SUVR (tumour-to-normal liver standard uptake value ratio), were evaluated. The differential diagnostic efficacy of each independent parameter and multiparameter combination model was evaluated using the receiver operating characteristic (ROC) curve. The improvement in diagnostic efficacy using a combination of the above multiple parameters was evaluated by integrated discriminatory improvement (IDI), net reclassification improvement (NRI) and bootstrap test. Decision curve analysis (DCA) was used to evaluate clinical efficacy. RESULTS: The ROC curve showed that SUVR had the highest diagnostic ability among the 18F-FDG PET metabolic parameters (area under the curve [AUC] = 0.698; sensitivity = 0.341; specificity = 0.971; positive predictive value [PPV] = 0.968; negative predictive value [NPV] = 0.363). The combined diagnostic model of cholecystolithiasis, fever, CEA > 5 ng/ml and SUVR showed an AUC of 0.899 (sensitivity = 0.909, specificity = 0.735, PPV = 0.899, NPV = 0.758). The diagnostic efficiency of the model was improved significantly compared with SUVR. The clinical efficacy of the model was confirmed by DCA. CONCLUSIONS: The multiparameter diagnostic model composed of 18F-FDG PET metabolic parameters (SUVR) and clinical variables, including patient signs (fever), medical history (cholecystolithiasis) and laboratory examination (CEA > 5 ng/ml), has good diagnostic efficacy in the differential diagnosis of nonmetastatic GBC and cholecystitis.

Integrated manganese (III)-doped nanosystem for optimizing photothermal ablation: Amplifying hyperthermia-induced STING pathway and enhancing antitumor immunity.

Despite the great promise initially demonstrated by photothermal ablation (PTA) therapy, its inability to completely ablate large tumors is problematic, because this has been found to result in residual tumors at ablation margins and bring a relative high rate of subsequent recurrences and metastases. To address this issue, we herein report a smart photothermal nanosystem (PBM) based on FDA-approved Prussian blue (PB) nanoparticles, doped with Mn (III) to suppress the tumor debris left by incomplete ablation. Notably, our study demonstrated that PTA-induced hyperthermia plays a crucial role in initiating the cGAS-STING pathway by generating damaged cytosolic DNA. This PBM nanosystem, which consumes glutathione and continuously releases Mn(II), further amplifies the PTA-induced cGAS-STING pathway in CT26 colon and 4T1 breast tumor models. Moreover, treatment with PBM following PTA boosted the robust immune response in situ and extended to the whole body with a remarkable suppression effect on both local residual and distant tumors. This work, which improves the antitumor efficacy of nonablated areas utilizing hyperthermia-enhanced immune therapy, may therefore provide a promising adjuvant antitumor strategy for the issue of incomplete ablation. STATEMENT OF SIGNIFICANCE: This work discovered, for the first time, that photothermal ablation-induced hyperthermia plays a crucial role in initiating the cGAS-STING pathway. Taking advantage of this finding, we developed a smart photothermal material (PBM) tailored for incomplete tumor ablation. This integrated Mn(III)-doped nanosystem (PBM) demonstrated superior therapeutic benefits due to the thermal ablation process and immune enhancement. As the photothermal ablation-induced cGAS-STING pathway was triggered, the released Mn(III) consumes GSH while continuously transferred to Mn(II), which further amplified STING activation and facilitated a more robust antitumor immunity, thereby remarkably inhibiting both local residual and distant tumors in virtue of the biological changes under thermal ablation.

Study of Drug Resistance in Chemotherapy Induced by Extracellular Vesicles on a Microchip.

Drug resistance in chemotherapy has been greatly challenging for cancer treatment. Research has revealed that extracellular vesicles (EVs) secreted by drug-resistant cells could induce chemoresistance in susceptible cells. However, there are few ways to give direct evidence of it. Herein, we have proposed a microchip-based system to study the drug resistance of a wild-type human lung adenocarcinoma cell line (A549/WT) induced by EVs derived from A549/DDP cells that are resistant to cisplatin (DDP) inherently. EVs derived from A549/DDP were proved to be the crucial factor that enhanced the resistance of A549/WT to DDP through live and dead cell staining, cell viability testing, and immunofluorescence of P-glycoprotein in the off-chip assay. Then, it was further validated that drug resistance of A549/WT cells to DDP significantly increased after being cocultured with A549/DDP cells within 96 h in the on-chip assay. These findings proved that the change of A549/WT drug resistance was caused by intercellular interaction, which was mainly mediated by EVs. In addition, we successfully reversed the EV-induced drug resistance of A549/WT cells by combining DDP and metformin, a hypoglycemic drug with low cytotoxicity when used alone. This microchip system provides a novel tool that has great potential for the investigation of cell interaction, drug resistance, and the tumor microenvironment in fundamental and clinical medicine.