Induced dual-target rebalance simultaneously enhances efficient therapeutical efficacy in tumors.

Multiple gene abnormalities are major drivers of tumorigenesis. NF-κB p65 overactivation and cGAS silencing are important triggers and genetic defects that accelerate tumorigenesis. However, the simultaneous correction of NF-κB p65 and cGAS abnormalities remains to be further explored. Here, we propose a novel Induced Dual-Target Rebalance (IDTR) strategy for simultaneously correcting defects in cGAS and NF-κB p65. By using our IDTR approach, we showed for the first time that oncolytic adenovirus H101 could reactivate silenced cGAS, while silencing GAU1 long noncoding RNA (lncRNA) inhibited NF-κB p65 overactivation, resulting in efficient in vitro and in vivo antitumor efficacy in colorectal tumors. Intriguingly, we further demonstrated that oncolytic adenoviruses reactivated cGAS by promoting H3K4 trimethylation of the cGAS promoter. In addition, silencing GAU1 using antisense oligonucleotides significantly reduced H3K27 acetylation at the NF-κB p65 promoter and inhibited NF-κB p65 transcription. Our study revealed an aberrant therapeutic mechanism underlying two tumor defects, cGAS and NF-κB p65, and provided an alternative IDTR approach based on oncolytic adenovirus and antisense oligonucleotides for efficient therapeutic efficacy in tumors.

18F-FDG PET/CT based model for predicting malignancy in pulmonary nodules: a meta-analysis.

BACKGROUND: Several studies to date have reported on the development of positron emission tomography (PET)/computed tomography (CT)-based models intended to effectively distinguish between benign and malignant pulmonary nodules (PNs). This meta-analysis was designed with the goal of clarifying the utility of these PET/CT-based conventional parameter models as diagnostic tools in the context of the differential diagnosis of PNs. METHODS: Relevant studies published through September 2023 were identified by searching the Web of Science, PubMed, and Wanfang databases, after which Stata v 12.0 was used to conduct pooled analyses of the resultant data. RESULTS: This meta-analysis included a total of 13 retrospective studies that analyzed 1,731 and 693 malignant and benign PNs, respectively. The respective pooled sensitivity, specificity, PLR, and NLR values for the PET/CT-based studies developed in these models were 88% (95%CI: 0.86-0.91), 78% (95%CI: 0.71-0.85), 4.10 (95%CI: 2.98-5.64), and 0.15 (95%CI: 0.12-0.19). Of these endpoints, the pooled analyses of model sensitivity (I2 = 69.25%), specificity (I2 = 78.44%), PLR (I2 = 71.42%), and NLR (I2 = 67.18%) were all subject to significant heterogeneity. The overall area under the curve value (AUC) value for these models was 0.91 (95%CI: 0.88-0.93). When differential diagnosis was instead performed based on PET results only, the corresponding pooled sensitivity, specificity, PLR, and NLR values were 92% (95%CI: 0.85-0.96), 51% (95%CI: 0.37-0.66), 1.89 (95%CI: 1.36-2.62), and 0.16 (95%CI: 0.07-0.35), with all four being subject to significant heterogeneity (I2 = 88.08%, 82.63%, 80.19%, and 86.38%). The AUC for these pooled analyses was 0.82 (95%CI: 0.79-0.85). CONCLUSIONS: These results suggest that PET/CT-based models may offer diagnostic performance superior to that of PET results alone when distinguishing between benign and malignant PNs.

The influence of flow distribution strategy for the quantification of pressure- and wall shear stress-derived parameters in the coronary artery: A CTA-based computational fluid dynamics analysis.

For image-based computational fluid dynamics (CFD) analysis to characterize the local coronary hemodynamic environment, the accuracy depends on the flow rate which is in turn associated with outlet branches' morphology. A good flow distribution strategy is important to mitigate the effect when certain branches cannot be considered. In this study, stenotic coronary arteries from 13 patients were used to analyze the effect of missing branches and different flow distribution strategies. Pressure- and wall shear stress (WSS)-derived parameters around the stenotic region (ROI) were compared, including fractional flow reserve (CT-FFR), instantaneous wave-free ratio (CT-iFR), resting distal to aortic coronary pressure (CT-Pd/Pa), time-averaged WSS, oscillatory shear index (OSI) and relative residence time (RRT). Three flow distribution strategies were the Huo-Kassab model at distal outlets (Type I), flow distribution based on outlet resistances (Type II), and a developed algorithm distributing flow at each bifurcation until the final outlets (Type III). Results showed that Type III strategy for models with truncated branch(es) had a good agreement in both pressure- and WSS-related results (interquatile range less than 0.12% and 4.02%, respectively) with the baseline model around the ROI. The relative difference of pressure- and WSS-related results were correlated with the flow differences in the ROI to the baseline mode. Type III strategy had the best performance in maintaining the flow in intermediate branches. It is recommended for CFD analysis. Removal of branches distal to a stenosis can be undertaken with an improved performance and maintained accuracy, while those proximal to the ROI should be kept.

The assessment of pathological response to neoadjuvant chemotherapy in muscle-invasive bladder cancer patients with DCE-MRI and DWI: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this meta-analysis was to determine the value of dynamic contrast-enhanced-MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in evaluating the pathological response of muscle invasive bladder cancer (MIBC) to neoadjuvant chemotherapy (NAC), and further indirectly compare the diagnostic performance of DCE-MRI and DWI. METHODS: Literatures associated to DCE-MRI and DWI in the evaluation of pathological response of MIBC to NAC were searched from PubMed, Cochrane Library, web of science, and EMBASE databases. The quality assessment of diagnostic accuracy studies 2 tool was used to assess the quality of studies. Pooled sensitivity (SE), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curves (AUC) with their 95% confidence intervals (CIs) were calculated to evaluate the diagnostic performance of DCE-MRI and DWI in predicting the pathological response to NAC in patients with MIBC. RESULTS: There were 11 studies involved, 6 of which only underwent DCE- MRI examination, 4 of which only underwent DWI examination, and 1 of which underwent both DCE- MRI and DWI examination. The pooled SE, SP, PLR, NLR, DOR of DCE-MRI were 0.88 (95% CI: 0.78-0.93), 0.88 (95% CI: 0.67-0.96), 7.4 (95% CI: 2.3-24.2), 0.14 (95% CI: 0.07-0.27), and 53 (95% CI: 10-288), respectively. The pooled SE, SP, PLR, NLR, DOR of DWI were 0.83 (95% CI: 0.75-0.88), 0.88 (95% CI: 0.81-0.93), 7.1 (95% CI: 4.3-11.7), 0.20 (95% CI: 0.14-0.28), and 36 (95% CI:18-73), respectively. The AUCs of SROC curve for DCE-MRI and DWI were 0.93 (95% CI: 0.91-0.95) and 0.92 (95% CI: 0.89-0.94), respectively. There were no significant differences between DWI and DCE-MRI for SE, SP, and AUC. CONCLUSION: This meta-analysis demonstrated high diagnostic performance of both DCE-MRI and DWI in predicting the pathological response to NAC in MIBC. DWI might be a potential substitute for DCE-MRI, with no significant difference in diagnostic performance between the two. However, caution should be taken when applying our results, as our results were based on indirect comparison. ADVANCES IN KNOWLEDGE: No previous studies have comprehensively analysed the value of DCE-MRI and DWI in evaluating the pathological response to NAC in MIBC. According to the current study, both DCE-MRI and DWI yielded high diagnostic performance, with the AUCs of 0.93 and 0.92, respectively. Indirect comparison no significant difference in the diagnostic performanceof DCE-MRI and DWI.

Radiomics nomogram based on optimal VOI of multi-sequence MRI for predicting microvascular invasion in intrahepatic cholangiocarcinoma.

OBJECTIVE: Microvascular invasion (MVI) is a significant adverse prognostic indicator of intrahepatic cholangiocarcinoma (ICC) and affects the selection of individualized treatment regimens. This study sought to establish a radiomics nomogram based on the optimal VOI of multi-sequence MRI for predicting MVI in ICC tumors. METHODS: 160 single ICC lesions with MRI scanning confirmed by postoperative pathology were randomly separated into training and validation cohorts (TC and VC). Multivariate analysis identified independent clinical and imaging MVI predictors. Radiomics features were obtained from images of 6 MRI sequences at 4 different VOIs. The least absolute shrinkage and selection operator algorithm was performed to enable the derivation of robust and effective radiomics features. Then, the best three sequences and the optimal VOI were obtained through comparison. The MVI prediction nomogram combined the independent predictors and optimal radiomics features, and its performance was evaluated via the receiver operating characteristics, calibration, and decision curves. RESULTS: Tumor size and intrahepatic ductal dilatation are independent MVI predictors. Radiomics features extracted from the best three sequences (T1WI-D, T1WI, DWI) with VOI10mm (including tumor and 10 mm peritumoral region) showed the best predictive performance, with AUCTC = 0.987 and AUCVC = 0.859. The MVI prediction nomogram obtained excellent prediction efficacy in both TC (AUC = 0.995, 95%CI 0.987-1.000) and VC (AUC = 0.867, 95%CI 0.798-0.921) and its clinical significance was further confirmed by the decision curves. CONCLUSION: A nomogram combining tumor size, intrahepatic ductal dilatation, and the radiomics model of MRI multi-sequence fusion at VOI10mm may be a predictor of preoperative MVI status in ICC patients.

Clinical and magnetic resonance imaging features predict microvascular invasion in intrahepatic cholangiocarcinoma.

Introduction: Clinical features and magnetic resonance imaging (MRI)-related data are commonly employed in clinical settings and can be used to predict the microvascular invasion (MVI) status of intrahepatic cholangiocarcinoma (ICC) patients. Aim: To generate a clinical and MRI-based model capable of predicting the MVI status of ICC patients. Material and methods: Consecutive ICC patients evaluated from June 2015 to December 2018 were retrospectively enrolled in a training group to establish a predictive clinical MRI model. Consecutive ICC patients evaluated from January 2019 to June 2019 were prospectively enrolled in a validation group to test the reliability of this model. Results: In total, 143 patients were enrolled in the training group, of whom 46 (32.2%) and 96 (67.8%) were MVI-positive and MVI-negative, respectively. Logistics analyses revealed larger tumour size (p = 0.008) and intrahepatic duct dilatation (p = 0.01) to be predictive of MVI positivity, enabling the establishment of the following predictive model: -2.468 + 0.024 × tumour size + 1.094 × intrahepatic duct dilatation. The area under the receiver operating characteristic (ROC) curve (AUC) for this model was 0.738 (p < 0.001). An optimal cut-off value of -1.0184 was selected to maximize sensitivity (71.7%) and specificity (61.9%). When the data from the validation group were incorporated into the predictive model, the AUC value was 0.716 (p = 0.009). Conclusions: Both larger tumour size and intrahepatic duct dilatation were predictive of MVI positivity in patients diagnosed with ICC, and the predictive model developed based on these variables can offer quantitative guidance for assessing the risk of MVI.

Predicting post-resection recurrence by integrating imaging-based surrogates of distinct vascular patterns of hepatocellular carcinoma.

Background & Aims: Distinct vascular patterns, including microvascular invasion (MVI) and vessels encapsulating tumour clusters (VETC), are associated with poor outcomes of hepatocellular carcinoma (HCC). Imaging surrogates of these vascular patterns potentially help to predict post-resection recurrence. Herein, a prognostic model integrating imaging-based surrogates of these distinct vascular patterns was developed to predict postoperative recurrence-free survival (RFS) in patients with HCC. Methods: Clinico-radiological data of 1,285 patients with HCC from China undergoing surgical resection were retrospectively enrolled from seven medical centres between 2014 and 2020. A prognostic model using clinical data and imaging-based surrogates of MVI and VETC patterns was developed (n = 297) and externally validated (n = 373) to predict RFS. The surrogates (i.e. MVI and VETC scores) were individually built from preoperative computed tomography using two independent cohorts (n = 360 and 255). Whether the model's stratification was associated with postoperative recurrence following anatomic resection was also evaluated. Results: The MVI and VETC scores demonstrated effective performance in their respective training and validation cohorts (AUC: 0.851-0.883 for MVI and 0.834-0.844 for VETC). The prognostic model incorporating serum alpha-foetoprotein, tumour multiplicity, MVI score, and VETC score achieved a C-index of 0.748-0.764 for the developing and external validation cohorts and generated three prognostically distinct strata. For patients at model-predicted medium risk, anatomic resection was associated with improved RFS (p <0.05). By contrast, anatomic resection had no impact on RFS in patients at model-predicted low or high risk (both p >0.05). Conclusions: The proposed model integrating imaging-based surrogates of distinct vascular patterns enabled accurate prediction for RFS. It can potentially be used to identify HCC surgical candidates who may benefit from anatomic resection. Impact and implications: MVI and VETC are distinct vascular patterns of HCC associated with aggressive biological behaviour and poor outcomes. Our multicentre study provided a model incorporating imaging-based surrogates of these patterns for preoperatively predicting RFS. The proposed model, which uses imaging detection to estimate the risk of MVI and VETC, offers an opportunity to help shed light on the association between tumour aggressiveness and prognosis and to support the selection of the appropriate type of surgical resection.

In-depth understanding of higher-order genome architecture in orphan cancer.

The human genome is intertwined, folded, condensed, and gradually constitutes the 3D architecture, thereby affecting transcription and widely involving in tumorigenesis. Incidence and mortality rates for orphan cancers increase due to poor early diagnosis and lack of effective medical treatments, which are now getting attention. In-depth understanding in tumorigenesis has fast-tracked over the last decade, however, the further role and mechanism of 3D genome organization in variant orphan tumorigenesis remains to be fully understood. We summarize for the first time that higher-order genome organization can provide novel insights into the occurrence mechanisms of orphan cancers, and discuss probable future research directions for drug development and anti-tumor therapies.

A chemoenzymatic process for preparation of highly purified dehydroepiandrosterone in high space-time yield.

Dehydroepiandrosterone (DHEA) is an important neurosteroid hormone to keep human hormonal balance and reproductive health. However, DHEA was always produced with impurities either by chemical or biological method and required high-cost purification before the medical use. To address this issue, a novel chemoenzymatic process was proposed and implemented to produce DHEA. An acetoxylated derivate of 4-androstene-3,17-dione (4-AD) was generated by chemical reaction and converted into DHEA by an enzyme cascade reaction combining a hydrolysis reaction with a reduction reaction. The hydrolysis reaction was catalyzed by a commercial esterase Z03 while the reduction reaction was catalyzed by E. coli cells co-expressing a 3ß-hydroxysteroid dehydrogenase SfSDR and a glucose dehydrogenase BtGDH. After the condition optimization, DHEA was synthesized at a 100 mL scale under 100 mM of substrate loading and purified as white powder with the highest space-time yield (4.80 g/L/h) and purity (99 %) in the biosynthesis of DHEA. The successful attempt in this study provides a new approach for green synthesis of highly purified DHEA in the pharmaceutical industry.

Inflammation Disrupts the Brain Network of Executive Function after Cardiac Surgery.

OBJECTIVE: To investigate postoperative functional connectivity (FC) alterations across impaired cognitive domains and their causal relationships with systemic inflammation. BACKGROUND: Postoperative cognitive dysfunction commonly occurs after cardiac surgery, and both systemic and neuroinflammation may trigger its development. Whether FC alterations underlying deficits in specific cognitive domains after cardiac surgery are affected by inflammation remains unclear. METHODS: Seventeen patients, who underwent cardiac valve replacement, completed a neuropsychological test battery and brain MRI scan before surgery and on days 7 and 30 after surgery compared to age-matched healthy controls. Blood samples were taken for tumor necrosis factor-a and interleukin-6 measurements. Seed-to-voxel FC of the left dorsolateral prefrontal cortex (DLPFC) was examined. Bivariate correlation and linear regression models were used to determine the relationships among cognitive function, FC alterations, and cytokines. RESULTS: Executive function was significantly impaired after cardiac surgery. At day 7 follow-up, the surgical patients, compared to the controls, demonstrated significantly decreased DLPFC FC with the superior parietal lobe and attenuated negative connectivity in the default mode network, including the angular gyrus and posterior cingulate cortex. The left DLPFC enhanced the connectivity in the right DLPFC and posterior cingulate cortex, all of which were related to the increased tumor necrosis factor-a and decreased executive function up to day 7 after cardiac surgery. CONCLUSIONS: The decreased FC of executive control network and its anticorrelation with the default mode network may contribute to executive function deficits after cardiac surgery. Systemic inflammation may trigger these transient FC changes and executive function impairments.

Comparison of the effectiveness of anchoring needles and coils in localizing multiple nodules in the lung.

BACKGROUND: Recently, a new type of pulmonary nodule positioning needle has been adopted clinically. We aimed to evaluate the efficacy and safety of a new type of localization needles compared with coils for the simultaneous localization of multiple pulmonary nodules guided by computed tomography (CT) prior to video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: From January 2021 to March 2022, 87 pulmonary nodules from 40 patients were localized using the new localization needle. From January 2020 to December 2020, 68 pulmonary nodules in 31 patients were localized using coils. The relative outcomes were compared. RESULTS: The success rate of pulmonary nodule localization in the needle group was 97.7% while that in the coil group was 98.5%. In the needle group, the time needed to locate the first nodule was significantly shorter than in the coil group (10.9 min vs. 17.2 min, P = 0.001). Moreover, the time needed per patient was also significantly shorter for the needle group compared with the coil group (23.7 min vs. 30 min, P = 0.017). The incidence of pneumothorax in the needle group was 25.0% vs. 12.9% in the coil group (P = 0.204). The rate of pulmonary hemorrhage in the needle group was 40.0% vs. 32.3% in the coil group (P = 0.502). The success rate of VATS wedge resection was 100% in both groups. CONCLUSION: Both disposable pulmonary nodule localization needles and coils are safe and effective for CT-guided localization of multiple pulmonary nodules of the same stage prior to VATS. However, the use of needles is time-saving compared with the use of coils. The coil localization may exhibit better safety than needle localization.

Iodine-125 seeds insertion with trans-arterial chemical infusion for advanced lung cancer: a meta-analysis.

Purpose: Local treatments, including iodine-125 (125I) seeds insertion (ISI) and trans-arterial chemical infusion (TAI), were used for advanced non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC) cases. The present meta-analysis investigated the clinical efficacy of combined TAI and ISI for advanced lung cancer (LC). Material and methods: This meta-analysis was performed according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Relevant studies were searched in PubMed, Embase, Cochrane Library, CINK, Wanfang, and VIP (until October 2021) databases, using the following key words: (((((Iodine-125) OR (I125)) OR (125I)) OR (brachytherapy)) AND ((lung cancer) OR (NSCLC))) AND (chemotherapy). Outcomes included complete response rate (CRR), treatment success rate (TSR), disease control rate (DCR), 1-year survival rate, 2-year survival rate, overall survival (OS), and treatment-related toxicity. RevMan v. 5.3 and Stata v. 12.0 were applied for meta-analysis. Results: Eight studies were included in the evaluation. Three hundred and seventy-seven patients underwent combined TAI and ISI treatment (combined group), while 397 patients underwent TAI alone (TAI alone group). The pooled CRR (p = 0.001), TSR (p < 0.00001), DCR (p < 0.00001), 1-year survival rate (p < 0.00001), OS duration (p = 0.0002), and gastrointestinal reaction rate (p = 0.02) were superior in combined group. The pooled 2-year survival rate increased in combined cohort than in TAI alone group (p = 0.08). The pooled myelosuppression rates were comparable between the 2 groups (p = 0.29). Publication bias was not found in any of endpoints. Conclusions: ISI can enhance TAI clinical efficacy in clinical cases of advanced LC, excluding severe adverse events.

An antigen-strengthened dye-modified fully-human-nanobody-based immunoprobe for second near infrared bioimaging of metastatic tumors.

Conventional immunoprobes have absorption capabilities across the visible to near infrared (NIR-I, 650-900 nm) region. Recently, second near infrared (NIR-II, 1000-1700 nm) window have gained much attention due to their deeper penetration depth and improved visualization. Here, we describe the design and synthesis of a fully human nanobody-based fluorescent immunoprobe (ICGM-n501) for NIR-II bioimaging with strengthened fluorescent emission by antigen for the first time. By site-directed conjugation of an FDA-approved dye analogue, indocyanine green decorated with maleimide (ICGM), into a tumor-specific n501, ICGM-n501 provides real-time monitoring of abdominal transportation pathway of antibody-based bioagents with high resolution (0.21 mm), presents better accuracy and lower dosage (0.21 µmol kg-1) in bioimaging of peritoneal metastatic tumors than bioluminescence agent D-luciferin. In this work, ICGM-n501 demonstrates its potential in clinical surgery guidance, provide an expanded category of available NIR-II fluorophores and a template for next-generation immunoassay bioagents.

Construction of efficient enzyme systems for preparing chiral ethyl 3-hydroxy-3-phenylpropionate.

Ethyl 3-hydroxy-3-phenylpropionate (EHPP), (R)-EHPP or (S)-EHPP, is an important chiral intermediate for pharmaceuticals. Its synthesis from ethyl benzoyl acetate (EBA) by alcohol dehydrogenase is regarded as a green method. However, scarcely any alcohol dehydrogenase has been reported competent in asymmetric synthesis of chiral EHPP at high EBA loading. Present study developed two robust and efficient bio-catalysts Mu-S2 and Mu-R4 for preparation of (S)-EHPP and (R)-EHPP respectively by rational design of alcohol dehydrogenase PcSDR from Pedobacter chitinilyticus based on molecular dynamics (MD) simulation analysis. BtGDH, a glucose dehydrogenase from Bacillus toyonensis catalyzing the oxidation of glucose for cofactor regeneration, was co-expressed with the screened mutants to form enzyme systems Mu-S2-BtGDH and Mu-R4-BtGDH. After reaction condition optimization, Mu-S2-BtGDH and Mu-R4-BtGDH were efficient in the synthesis of (S)-EHPP (94% conv. and 99% e.e.) and (R)-EHPP (99% conv. and 98% e.e.) respectively in 100 mL scale under 500 mM of EBA loading in 10 h following a substrate continuous feeding mode. After purifying, the isolated yield for each EHPP enantiomer is > 93%. This work not only provides potential biocatalysts for the industrial production of (R)-EHPP and (S)-EHPP, but also enriches the constructure-function relationship of alcohol dehydrogenases.

A Multi-Parametric Radiomics Nomogram for Preoperative Prediction of Microvascular Invasion Status in Intrahepatic Cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer with increasing incidence in the last decades. Microvascular invasion (MVI) is a poor prognostic factor for patients with ICC, which correlates early recurrence and poor prognosis, and it can affect the selection of personalized therapeutic regime. Purpose: This study aimed to develop and validate a radiomics-based nomogram for predicting MVI in ICC patients preoperatively. Methods: A total of 163 pathologically confirmed ICC patients (training cohort: n = 130; validation cohort: n = 33) with postoperative Ga-DTPA-enhanced MR examination were enrolled, and a time-independent test cohort (n = 24) was collected for external validation. Univariate and multivariate analyses were used to determine the independent predictors of MVI status, which were then incorporated into the MVI prediction nomogram. Least absolute shrinkage and selection operator logistic regression was performed to select optimal features and construct radiomics models. The prediction performances of models were assessed by receiver operating characteristic (ROC) curve analysis. The performance of the MVI prediction nomogram was evaluated by its calibration, discrimination, and clinical utility. Results: Larger tumor size (p = 0.003) and intrahepatic duct dilatation (p = 0.002) are independent predictors of MVI. The final radiomics model shows desirable and stable prediction performance in the training cohort (AUC = 0.950), validation cohort (AUC = 0.883), and test cohort (AUC = 0.812). The MVI prediction nomogram incorporates tumor size, intrahepatic duct dilatation, and the final radiomics model and achieves excellent predictive efficacy in training cohort (AUC = 0.953), validation cohort (AUC = 0.861), and test cohort (AUC = 0.819), fitting well in calibration curves (p > 0.05). Decision curve and clinical impact curve further confirm the clinical usefulness of the nomogram. Conclusion: The nomogram incorporating tumor size, intrahepatic duct dilatation, and the final radiomics model is a potential biomarker for preoperative prediction of the MVI status in ICC patients.

Preoperative computed tomography-guided localization for lung nodules: localization needle versus coil.

PURPOSE: To compare the clinical efficacy of computed tomography (CT)-guided localization needle and coil insertion as approaches to preoperative lung nodule (LN) localization. MATERIAL AND METHODS: Between January 2018 and December 2019, 52 patients awaiting video-assisted thoracoscopic surgery (VATS) resection underwent CT-guided coil insertion to facilitate LN localization. Additionally, 41 patients underwent CT-guided localization needle insertion between January and June 2021. RESULTS: In total, 62 and 54 LNs were localized in 52 and 41 patients in the coil and localization needle groups, respectively, with respective technical localization success rates of 96.8% and 100% (p = .498). The localization needle group exhibited a significantly shorter duration of localization relative to the coil group (p < .001), whereas comparable rates of pneumothorax (p = .918) and hemorrhage (p = .712) were evident in these groups. VATS-guided LN resection procedures achieved 100% technical success rates in both groups, and there were no significant differences between groups with respect to the type of resection (p = .113) or the mean duration of VATS (p = .778). CONCLUSION: Coil- and localization needle-based approaches can be successfully used for LN localization prior to VATS resection, with localization needle insertion being associated with a shorter duration of localization.

I-125 seeds insertion with TACE for advanced HCC: a meta-analysis of randomized controlled trials.

PURPOSE: To assess the effectiveness of I-125 seeds (IS) insertion with transcatheter arterial chemoembolization (TACE) in treating patients with advanced hepatocellular carcinoma (HCC). MATERIAL AND METHODS: An extensive search was conducted for relevant randomized controlled trials (RCTs) from the establishment date of each database to November 2020. RESULTS: A total of nine RCTs were included in this study. Our analysis showed no significant changes in the pooled Δalpha-fetoprotein values (p = .06), incident rates of myelosuppression (p = .46), vomit occurrence (p = .27), and abnormal liver function (p = .42) between the two treatment groups. However, the complete response (p < .00001), total response (p < .00001), and disease control (p < .00001) rates were significantly higher in patients who underwent TACE with IS insertion, as opposed to patients who received TACE alone. Furthermore, patients who underwent TACE with IS insertion experienced markedly longer pooled overall survival (OS) time (p < .0001), with better OS rates at the six-month (p = .0002), one-year (p < .0001), and three-year (p = .0003) follow-ups than patients who received TACE alone. CONCLUSION: TACE with IS insertion can significantly improve clinical response and prolong the survival of advanced HCC patients.

Radioactive Seed Strand Efficacy in Superior Vena Cava Stenting Due to Non-small-cell Lung Cancer Obstruction.

PURPOSE: This study aims to determine the clinical effectiveness of a stent with radioactive seed strand (RSS) inserted in patients with superior vena cava (SVC) obstruction (SVCO) secondary to non-small-cell lung cancer (NSCLC). METHODS: Between January 2013 and December 2019, 63 patients with SVCO related to NSCLC received stent implantation with (n = 30) or without (n = 33) RSS insertion at our center. The clinical efficacy, stent patency duration, and overall survival (OS) were compared between these two groups. RESULTS: Both groups achieved 100% clinical and technical success rates. There were no obstacles associated with the procedure performed for the patients. Two patients in the RSS group and 7 patients in the stent-alone group experienced stent re-stenosis. The rate of re-stenosis between the two groups was not significantly different (P = .099). Patients in the RSS group had significantly longer median patency than those in the stent-alone group (381 vs 309 days, P = .045). All patients died because of the development of tumors during the follow-up. Patients in the RSS group had a significantly longer median OS than those in the stent-alone group (229 vs 178 days, P = .026). During the follow-up, no patient in the RSS group suffered RSS migration or brachytherapy-related complications. CONCLUSION: For patients with SVCO secondary to NSCLC, a stent with RSS insertion is efficacious and safe, and it may improve stent patency and OS.

A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants.

The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19.