Genomic and functional evaluation of exopolysaccharide produced by Liquorilactobacillus mali t6-52: technological implications.

BACKGROUND: This study explores the biosynthesis, characteristics, and functional properties of exopolysaccharide produced by the strain Liquorilactobacillus mali T6-52. The strain demonstrated significant EPS production with a non-ropy phenotype. RESULTS: The genomic analysis unveiled genes associated with EPS biosynthesis, shedding light on the mechanism behind EPS production. These genes suggest a robust EPS production mechanism, providing insights into the strain's adaptability and ecological niche. Chemical composition analysis identified the EPS as a homopolysaccharide primarily composed of glucose, confirming its dextran nature. Furthermore, it demonstrated notable functional properties, including antioxidant activity, fat absorption capacity, and emulsifying activity. Moreover, the EPS displayed promising cryoprotective activities, showing notable performance comparable to standard cryoprotective agents. The EPS concentration also demonstrated significant freeze-drying protective effects, presenting it as a potential alternative cryoprotectant for bacterial storage. CONCLUSIONS: The functional properties of L. mali T6-52 EPS reveal promising opportunities across various industrial domains. The strain's safety profile, antioxidant prowess, and exceptional cryoprotective and freeze-drying characteristics position it as an asset in food processing and pharmaceuticals.

Reconstructing 3D digital model without distortion for poorly conductive porous rock by nanoprobe-assisted FIB-SEM tomography.

Oil and natural gas prospecting requires precise pore characterisation of insulating rock samples, which involves severe charging problems in the state-of-art FIB-SEM tomography, such as overexposure, drift and distortion. For weak cemented samples with very poor conductivity, the conventional ways such as decreasing accelerating voltage or current as well as coating a thin layer of carbon or gold fail to eliminate all the detrimental effect, leading to image distortion in the form of lateral shift and longitudinal stretching. A new nanoprobe-assisted method is explored in FIB-SEM tomography to address this problem and improve image quality. To be specific, a metallic nanoprobe is induced and attached on the sample surface to create an express path for the export of excess electrons near the region of interest, which effectively removes distortion and drift when imaging. Two adjacent areas were characterised and reconstructed into 3D digital models by FIB-SEM tomography with nanoprobe-assisted method applied to one region only. The lateral shift creates zigzag feature for distorted region and the longitudinal stretching of undistorted object can reach 14%. Average pore size of distorted region is larger than that of the undistorted region, however considering the longitudinal stretching, the average pore size of distorted region can be corrected to the same level as the undistorted region. The systematic error caused by distortion for poorly conductive porous rock is hazardous for digital rock physics analysis. Therefore, the nanoprobe-assisted FIB-SEM tomography should be regarded as a one of the optional and feasible procedures in case decreasing accelerating voltage or current as well as coating a thin layer of conductive material does not work.

Image distortion caused by charging problems influence quantitative analysis and simulation, which is more serious in FIB-SEM tomography. This study is used to correct image distortion and reconstruct 3D digital model for poorly conductive samples such as porous rock by nanoprobe-assisted method applied in FIB-SEM tomography. A metallic nanoprobe is induced and attached on the sample surface to removes distortion and drift when imaging. By comparing two adjacent areas with nanoprobe-assisted method applied for one region only, the degree of distortion and pore size distributions are analysed and computed. We observe and analyse lateral shift creates zigzag feature for distorted region and the longitudinal stretching of undistorted object. The average pore size of distorted region is higher than undistorted region, which can be corrected considering the longitudinal stretching. Such systematic error caused by distortion for poorly conductive porous rock is hazardous for not only digital rock physics analysis but also research of unconductive materials. Therefore, the nanoprobe-assisted FIB-SEM tomography should be regarded as a one of the optional and feasible procedures in case decreasing accelerating voltage or current as well as coating a thin layer of conductive material does not work.

One-dimensional hollow FePt nanochains: applications in hydrolysis of NaBH4 and structural stability under Ga+ ion irradiation.

Pt-based one-dimensional hollow nanostructures are promising catalysts in fuel cells with excellent activity. Herein, one-dimensional hollow FePt nanochains were shown to be efficient nanocatalysts in the hydrolysis of NaBH4. The characterization of composition, structure and morphology identifies an ultrathin shell (∼3 nm) with uniformly distributed Fe30Pt70 constituents. The H2 generation rate of hollow Fe30Pt70 nanochains achieves 16.9 l/(min · g) at room temperature, while the activation energy is as low as 17.6 kJ mol-1 based on the fitting over the whole reaction time span. After the catalysis of NaBH4 hydrolysis, the morphology and composition of hollow FePt nanochains remain unchanged. Furthermore, the structural stability of hollow FePt nanochains under Ga+ ion irradiation is clarified. Theoretical simulation indicates that the stopping range of such a Fe30Pt70 shell is 7.7 keV, which offers a prediction that structure evolves diversely under Ga+ ions below and above such energy. The Ga+ ion irradiation experiments show a consistent trend with the simulation, where Ga+ ions with kinetic energy of 30 keV make the hollow architecture subside and sputter away, while Ga+ ions with kinetic energy of 5 keV only etch the top and lead to an eggshell structure.

Safety assessment of sorafenib in Chinese patients with unresectable hepatocellular carcinoma: subgroup analysis of the GIDEON study.

BACKGROUND: This study aimed to investigate the safety of sorafenib for the treatment of unresectable hepatocellular carcinoma in Chinese patients. METHODS: A subgroup of 345 Chinese patients from the international database of the Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study was included in this analysis. Safety assessment measures were adverse events (AEs) and serious adverse events (SAEs) graded using the National Cancer Institute Common Terminology Criteria version 3.0. RESULTS: Of 331 evaluable patients, 98% started sorafenib at 800 mg/day. The median treatment duration was 22 weeks (range, 0.1-116 weeks), and median overall survival (OS) was 322 days (10.7 months). Approximately 50% of patients had at least one adverse event, and 6% had grade 3-4 adverse events. Drug-related adverse events were experienced by 29% of patients, and 3.6% had grade 3-4 drug-related adverse events. Overall, 23% of patients (n = 77) experienced serious adverse events, among which only 1 event was drug-related (0.3%). No differences in overall adverse events, serious adverse events, and deaths were observed between Child-Pugh A and Child-Pugh B patients. The most frequent drug-related adverse events were dermatological/skin (24%), hand-foot skin reaction (20%), gastrointestinal (11%), and diarrhea (11%). The majority of adverse events occurred within 30 days of beginning sorafenib. CONCLUSION: Sorafenib has satisfactory efficacy and safety in Chinese Child-Pugh A and B patients with unresectable HCC using the recommended dosage of 800 mg/day, and the safety of sorafenib is not affected by liver function. Prophylaxis for gastrointestinal adverse events may help to decrease dose interruptions or discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov ; Identifier: NCT00812175. Date of registration: December 19, 2008.

Efficacy and safety of raltitrexed-based transarterial chemoembolization for colorectal cancer liver metastases.

The liver is the most common site of colorectal cancer metastases. The present study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) with raltitrexed and oxaliplatin for colorectal liver metastases in a prospective, multicenter, single-arm trial conducted in 12 hospitals from different areas in China. A total of 90 patients with colorectal liver metastases were enrolled and treated by TACE with raltitrexed 4 mg and oxaliplatin 100 mg, followed by embolotherapy with 50 mg oxaliplatin and 5-20 ml lipiodol, administered every 28 days for four cycles. Patients were followed up every 3 months after the treatment and up to 12 months. The primary endpoint was time to progression. For the full analysis set (FAS), the median time to progression and overall survival were 9.1 and 17.8 months, respectively. The disease control rate in FAS was 71 (78.9%). Grade 3 or 4 adverse events were reported for 24 (26.7%) out of all 90 patients. Grade 3 thrombocytopenia, transglutaminase abnormality, and decreased neutrophil were observed in eight (8.9%), six (6.7%), and five (5.6%) patients, respectively. No unexpected adverse events or toxic deaths were observed. TACE with raltitrexed plus oxaliplatin is feasible, clinically beneficial, and well tolerated with low-grade toxicity for colorectal cancer patients with liver metastases.

Patterns of sorafenib and TACE treatment of unresectable hepatocellular carcinoma in a Chinese population: subgroup analysis of the GIDEON study.

To analyze safety and efficacy of patterns of sorafenib and TACE therapy under real-life clinical practice conditions. A total of 338 Chinese patients with unresectable hepatocellular carcinoma (HCC) from the international database of the GIDEON non-interventional trial were included in this analysis. Endpoints were overall survival (OS), progression-free survival (PFS), time to progression (TTP) and safety. Two major patterns in the use of sorafenib observed in current Chinese clinical practice were: sorafenib administration subsequent to transarterial chemoembolization (TACE) treatment (n = 226, 66.9%) and sorafenib administration concomitant to TACE (n = 80, 35.4%). Patients receiving TACE prior to sorafenib had worse liver function (43.8% BCLC stage Cat diagnosis and 62.1% BCLC stage C at study entry) than those receiving TACE concomitant to sorefenib (35.0% BCLC stage C at diagnosis and 51.3% BCLC stage three at study entry). For patients undergoing prior TACE and concomitant TACE treatment, median OS time was 354 days vs. 608 days, PFS time was 168 days vs. 201 days, and TTP was 214 days vs. 205 days; and the percentage of patients who experienced drug-related adverse effects after sorafenib therapy in these two groups were 33.3 and 50.0%, respectively. Sorafenib treatment is usually administered in cases of tumor progression or poor liver function status after TACE treatment in China. Under such conditions, patients still gained a relatively satisfactory survival outcome. In addition, the present study suggests that concomitant sorafenib and TACE treatments may lead to a better prognosis, although differences in baseline characteristics may have contributed in part to the better outcomes.

The role of hepatic resection in the treatment of hepatocellular cancer.

UNLABELLED: Current guidelines recommend surgical resection as the primary treatment for a single hepatocellular cancer (HCC) with Child's A cirrhosis, normal serum bilirubin, and no clinically significant portal hypertension. We determined how frequently guidelines were followed and whether straying from them impacted survival. BRIDGE is a multiregional cohort study including HCC patients diagnosed between January 1, 2005 and June 30, 2011. A total of 8,656 patients from 20 sites were classified into four groups: (A) 718 ideal resection candidates who were resected; (B) 144 ideal resection candidates who were not resected; (C) 1,624 nonideal resection candidates who were resected; and (D) 6,170 nonideal resection candidates who were not resected. Median follow-up was 27 months. Log-rank and Cox's regression analyses were conducted to determine differences between groups and variables associated with survival. Multivariate analysis of all ideal candidates for resection (A+B) revealed a higher risk of mortality with treatments other than resection. For all resected patients (A+C), portal hypertension and bilirubin >1 mg/dL were not associated with mortality. For all patients who were not ideal candidates for resection (C+D), resection was associated with better survival, compared to embolization and "other" treatments, but was inferior to ablation and transplantation. CONCLUSIONS: The majority of patients undergoing resection would not be considered ideal candidates based on current guidelines. Not resecting ideal candidates was associated with higher mortality. The study suggests that selection criteria for resection may be modestly expanded without compromising outcomes, and that some nonideal candidates may still potentially benefit from resection over other treatment modalities.

The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: final results of the START trial.

This phase II, investigator-initiated, prospective single-arm multinational study (ClinicalTrials.gov registration NCT00990860) evaluated sorafenib in combination with doxorubicin-based transarterial chemoembolization (TACE) in patients with intermediate-stage, unresectable hepatocellular carcinoma (HCC). Patients with histologically or clinically diagnosed HCC received TACE with interrupted dosing of sorafenib (sorafenib discontinued for 3 days before and 4-7 days after TACE). TACE/sorafenib cycles were repeated every 6-8 weeks. Primary and secondary objectives were, respectively: to evaluate the safety and tolerability of TACE combined with sorafenib, and also their efficacy. The full analysis set comprised 192 patients (mean age 56.1 years). Most were male (87.0%), Eastern Cooperative Oncology Group (ECOG) score 0 (81.8%), Child-Pugh A (91.8%) and Barcelona Clinic Liver Cancer (BCLC) stage B (81.5%); 81.2% had chronic hepatitis B. Combined TACE/sorafenib was well tolerated, with only 8.1% of patients discontinuing owing to adverse events (AEs). The most common grade ≥3 AEs were palmar-plantar erythrodysesthesia syndrome (15.1%) and decreased platelet count (10.9%). Serious AEs (SAEs) occurred in 52 patients during the study; however, only four were considered related to sorafenib. A mean of 2.7 TACE cycles were administered and 52.6% of patients achieved complete response in target lesions; 16.8% achieved partial response, and 5.8% had progression of disease as their best response, evaluated by modified RECIST. Median progression-free survival and time to progression were 384 and 415 days, respectively, and the estimated 3-year overall survival was 86.1%. This study suggests that the combination of TACE and sorafenib is well tolerated and efficacious; the interrupted sorafenib dosing schedule may have contributed to a considerably lower AE profile than observed in other combination trials.

Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial.

UNLABELLED: Transarterial chemoembolization (TACE) is the current standard of treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). Brivanib, a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor signaling, may improve the effectiveness of TACE when given as an adjuvant to TACE. In this multinational, randomized, double-blind, placebo-controlled, phase III study, 870 patients with TACE-eligible HCC were planned to be randomly assigned (1:1) after the first TACE to receive either brivanib 800 mg or placebo orally once-daily. The primary endpoint was overall survival (OS). Secondary endpoints included time to disease progression (TTDP; a composite endpoint based on development of extrahepatic spread or vascular invasion, deterioration of liver function or performance status, or death), time to extrahepatic spread or vascular invasion (TTES/VI), rate of TACE, and safety. Time to radiographic progression (TTP) and objective response rate were exploratory endpoints. The trial was terminated after randomization of 502 patients (brivanib, 249; placebo, 253) when two other phase III studies of brivanib in advanced HCC patients failed to meet OS objectives. At termination, median follow-up was approximately 16 months. Intention-to-treat analysis showed no improvement in OS with brivanib versus placebo (median, 26.4 [95% confidence interval {CI}: 19.1 to not reached] vs. 26.1 months [19.0-30.9]; hazard ratio [HR]: 0.90 [95% CI: 0.66-1.23]; log-rank P=0.5280). Brivanib improved TTES/VI (HR, 0.64 [95% CI: 0.45-0.90]), TTP (0.61 [0.48-0.77]), and rate of TACE (0.72 [0.61-0.86]), but not TTDP (0.94 [0.72-1.22]) versus placebo. Most frequent grade 3-4 adverse events included hyponatremia (brivanib, 18% vs. placebo, 5%) and hypertension (13% vs. 3%). CONCLUSIONS: In this study, brivanib as adjuvant therapy to TACE did not improve OS.

Patterns of FDG uptake in pancreatic non-Hodgkin's lymphoma lesions.

PURPOSE: The aim of this study was to evaluate the pattern of FDG uptake in pancreatic non-Hodgkin's lymphoma (NHL) lesions. METHODS: The study included 9 consecutive patients with newly diagnosed NHL with pancreatic involvement who underwent an F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) scan. The location, size, maximal standardized uptake value (SUVmax), and FDG uptake patterns of the pancreatic lesions were reviewed. RESULTS: Four different patterns of FDG uptake could be distinguished in the affected pancreas corresponding to different types of lymphoma lesions. These included focal FDG uptake by distinct solitary lesions (5 patients), multiple foci of FDG uptake corresponding to separate lymphoma lesions (1 patient), segmental FDG uptake caused by lymphoma infiltration limited to a pancreatic segment (1 patient), and diffuse FDG uptake related to diffuse lymphomatous infiltration of the entire pancreas (2 patients). All types of lesions showed increased metabolic activity with maximal standardized uptake values (SUVmax) ranging from 7.4 to 26.5. On CT images, the segmental and diffuse patterns of FDG uptake correlated to segmental and diffuse pancreatic enlargement accordingly. All lesions showed isodensity or slight hypodensity in relation to pancreatic tissue. The pancreatic head was the most frequent site of involvement (8/9). Mildly dilated pancreatic duct was noted only in 2 patients. CONCLUSIONS: The described patterns of FDG uptake and correlative CT findings may be helpful for a better characterization of NHL involving the pancreas and for differential diagnosis with other lesions, including pancreatic adenocarcinomas.

Fe,Ni-Based Metal-Organic Frameworks Embedded in Nanoporous Nitrogen-Doped Graphene as a Highly Efficient Electrocatalyst for the Oxygen Evolution Reaction.

The quest for economically sustainable electrocatalysts to replace critical materials in anodes for the oxygen evolution reaction (OER) is a key goal in electrochemical conversion technologies, and, in this context, metal-organic frameworks (MOFs) offer great promise as alternative electroactive materials. In this study, a series of nanostructured electrocatalysts was successfully synthesized by growing tailored Ni-Fe-based MOFs on nitrogen-doped graphene, creating composite systems named MIL-NG-n. Their growth was tuned using a molecular modulator, revealing a non-trivial trend of the properties as a function of the modulator quantity. The most active material displayed an excellent OER performance characterized by a potential of 1.47 V (vs. RHE) to reach 10 mA cm-2, a low Tafel slope (42 mV dec-1), and a stability exceeding 18 h in 0.1 M KOH. This outstanding performance was attributed to the synergistic effect between the unique MOF architecture and N-doped graphene, enhancing the amount of active sites and the electron transfer. Compared to a simple mixture of MOFs and N-doped graphene or the deposition of Fe and Ni atoms on the N-doped graphene, these hybrid materials demonstrated a clearly superior OER performance.

Prediction of vascular complications in free flap reconstruction with machine learning.

OBJECTIVE: This study aims to explore the risk factors of vascular complications following free flap reconstruction and to develop a clinical auxiliary assessment tool for predicting vascular complications in patients undergoing free flap reconstruction leveraging machine learning methods. METHODS: We reviewed the medical data of patients who underwent free flap reconstruction at the Affiliated Hospital of Zunyi Medical University retrospectively from January 1, 2019, to December 31, 2021. Statistical analysis was used to screen risk factors. A training data set was generated and augmented using the synthetic minority oversampling technique. Logistic regression, random forest and neural network, models were trained, using this dataset. The performance of these three predictive models was then evaluated and compared using a test set, with four metrics, area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A total of 570 patients who underwent free flap reconstruction were included in this study, 46 of whom developed postoperative vascular complications. Among the models tested, the neural network model exhibited superior performance on the test set, achieving an AUC of 0.828. Multivariate logistic regression analysis identified that preoperative hemoglobin levels, preoperative fibrinogen levels, operation duration, smoking history, the number of anastomoses, and peripheral vascular injury as statistically significant independent risk factors for vascular complications post-free flap reconstruction. The top five predictive factors in the neural network were fibrinogen content, operation duration, donor site, body mass index (BMI), and platelet count. CONCLUSION: Hemoglobin levels, fibrinogen levels, operation duration, smoking history, and anastomotic veins are independent risk factors for vascular complications following free flap reconstruction. These risk factors enhance the ability of machine learning models to predict the occurrence of vascular complications and identify high-risk patients. The neural network model outperformed the logistic regression and random forest models, suggesting its potential to aid clinicians in early identification of high-risk patients thereby mitigating patient suffering and improving prognosis.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Interim analysis of START: Study in Asia of the combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular carcinoma trial.

Transarterial chemoembolization (TACE) represents a first-line noncurative therapy for hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown to be effective and safe monotherapy in patients with advanced HCC and the current study reports the interim results of a prospective Phase II, open label, trial investigating the safety and efficacy of the combination of sorafenib and conventional TACE in patients from the Asia-Pacific region with intermediate HCC. Patients with histologically or clinically diagnosed HCC were treated with conventional TACE followed by sorafenib 4 to 7 days later. TACE was performed by selective transarterial chemotherapy in the vessels feeding the tumor with an emulsion of lipiodol (5-20 ml) and doxorubicin (30-60 mg) followed by embolization with absorbable particles (gel foam). TACE/sorafenib cycles were repeated every 6-8 weeks. Primary objectives were to evaluate the safety and tolerability, in addition to the efficacy of TACE combined with sorafenib for HCC. A total of 147 patients were included in the intention-to-treat analysis and received at least one dose of sorafenib. Gastrointestinal AEs were reported by 62.6% of patients while 57.8% reported skin AEs although most were mild to moderate. The mean number of cycles undertaken was 2.1 and 63.3% of patients achieved either partial response or stable disease. Clinically, the disease control rate was 91.2% while the overall response rate was calculated as 52.4%. Our study shows that concurrent sorafenib and TACE therapy is safe and effective with no unexpected side effects.

Functionalization of gadolinium metallofullerenes for detecting atherosclerotic plaque lesions by cardiovascular magnetic resonance.

BACKGROUND: The hallmark of atherosclerosis is the accumulation of plaque in vessel walls. This process is initiated when monocytic cells differentiate into macrophage foam cells under conditions with high levels of atherogenic lipoproteins. Vulnerable plaque can dislodge, enter the blood stream, and result in acute myocardial infarction and stroke. Imaging techniques such as cardiovascular magnetic resonance (CMR) provides one strategy to identify patients with plaque accumulation. METHODS: We synthesized an atherosclerotic-targeting contrast agent (ATCA) in which gadolinium (Gd)-containing endohedrals were functionalized and formulated into liposomes with CD36 ligands intercalated into the lipid bilayer. In vitro assays were used to assess the specificity of the ATCA for foam cells. The ability of ATCA to detect atherosclerotic plaque lesions in vivo was assessed using CMR. RESULTS: The ATCA was able to detect scavenger receptor (CD36)-expressing foam cells in vitro and were specifically internalized via the CD36 receptor as determined by focused ion beam/scanning electron microscopy (FIB-SEM) and Western blotting analysis of CD36 receptor-specific signaling pathways. The ATCA exhibited time-dependent accumulation in atherosclerotic plaque lesions of ApoE -/- mice as determined using CMR. No ATCA accumulation was observed in vessels of wild type (C57/b6) controls. Non-targeted control compounds, without the plaque-targeting moieties, were not taken up by foam cells in vitro and did not bind plaque in vivo. Importantly, the ATCA injection was well tolerated, did not demonstrate toxicity in vitro or in vivo, and no accumulation was observed in the major organs. CONCLUSIONS: The ATCA is specifically internalized by CD36 receptors on atherosclerotic plaque providing enhanced visualization of lesions under physiological conditions. These ATCA may provide new tools for physicians to non-invasively detect atherosclerotic disease.

Sorafenib in combination with transarterial chemoembolization in Chinese patients with hepatocellular carcinoma: a subgroup interim analysis of the START trial.

AIM: The third interim results of the START trial showed encouraging safety and efficacy profiles, with a median time to progression of 9 months. This subgroup analysis presents results in Chinese patients enrolled in the START trial. MATERIALS & METHODS: Sixty two Chinese patients (median age 52 years) with unresectable hepatocellular carcinoma had transarterial chemoembolization (TACE) performed with an emulsion of Lipiodol(®) (Guerbet, Paris, France) and doxorubicin (30-60 mg) followed by embolization with absorbable particles. Sorafenib (400 mg twice-daily) was administered continuously with dose holidays 4 days prior to and post TACE procedures. TACE was performed every 6-8 weeks and responses were assessed after 4-6 weeks and then every 3 months if no further TACE was indicated. Patients continued receiving sorafenib until disease progression or unacceptable toxicity occurred. RESULTS: Thirty seven patients (59.68%) received no more than two TACE procedures. During sorafenib treatment (median duration 6.4 months; mean daily dose 787.6 mg), 75.8% of patients experienced adverse events, most commonly pyrexia (37.1%), diarrhea (27.4%), skin reactions (22.6%), alopecia (19.4%) and abnormal hepatic function (16.1%). The most common grade 3-4 adverse events were abnormal hepatic function (6.5%) and diarrhea (3.2%). The median time to progression and overall survival were 10.6 and 16.5 months, respectively, and the objective response and stable disease rates were 44.3 and 42.6%, respectively. CONCLUSION: The combination of the TACE and sorafenib proved both safe and effective in the treatment of Chinese patients with unresectable hepatocellular carcinoma.

Iron meteorite evidence for early formation and catastrophic disruption of protoplanets.

In our Solar System, the planets formed by collisional growth from smaller bodies. Planetesimals collided to form Moon-to-Mars-sized protoplanets in the inner Solar System in 0.1-1 Myr, and these collided more energetically to form planets. Insights into the timing and nature of collisions during planetary accretion can be gained from meteorite studies. In particular, iron meteorites offer the best constraints on early stages of planetary accretion because most are remnants of the oldest bodies, which accreted and melted in <1.5 Myr, forming silicate mantles and iron-nickel metallic cores. Cooling rates for various groups of iron meteorites suggest that if the irons cooled isothermally in the cores of differentiated bodies, as conventionally assumed, these bodies were 5-200 km in diameter. This picture is incompatible, however, with the diverse cooling rates observed within certain groups, most notably the IVA group, but the large uncertainties associated with the measurements do not preclude it. Here we report cooling rates for group IVA iron meteorites that range from 100 to 6,000 K Myr(-1), increasing with decreasing bulk Ni. Improvements in the cooling rate model, smaller error bars, and new data from an independent cooling rate indicator show that the conventional interpretation is no longer viable. Our results require that the IVA meteorites cooled in a 300-km-diameter metallic body that lacked an insulating mantle. This body probably formed approximately 4,500 Myr ago in a 'hit-and-run' collision between Moon-to-Mars-sized protoplanets. This demonstrates that protoplanets of approximately 10(3) km size accreted within the first 1.5 Myr, as proposed by theory, and that fragments of these bodies survived as asteroids.

CT-Guided Percutaneous Cryoablation for Lung Metastasis of Colorectal Cancer: A Case Series.

PURPOSE: This study aimed to evaluate the efficacy of computed tomography (CT) guided percutaneous cryoablation (CA) for the management of lung metastases in patients with metastatic colorectal cancer (mCRC). METHODS: Retrospective analysis was performed on 38 mCRC patients with lung metastases, who underwent CT-guided percutaneous CA at our center from May 1, 2020 to November 1, 2021. The technical success rate, 1-year local control (LC) rate, recurrence-free survival (RFS) and treatment-related complications were analyzed. RESULTS: The CA procedure was successfully performed in all patients, with a technical success rate of 100%. The 1-year LC rate was 94.7% (36/38), while 16 patients experienced new distant lung metastases during the follow-up period. The median RFS was 20 months (95% CI: 13.0-27.0). The median RFS of patients with and without extrapulmonary metastasis was 15 and 23 months, respectively. Complications were reported in 18 (47.4%) patients following the CA procedure. Pneumothorax was discovered in 15 (39.5%) patients, and five of these patients (13.2%) required chest tube intubation. Two patients (5.3%) presented with hemoptysis during the CA procedure. One patient developed subcutaneous emphysema as detected in the post-procedure follow-up imaging. All patients tolerated the peri-procedural pain well under local anesthesia, and the mean visual analog scale (VAS) score was 2.8. CONCLUSION: Lung CA is a safe and well-tolerated treatment with a satisfactory local control rate for patients with lung metastases derived from mCRC.

Radioiodine-131-Labeled Theranostic Nanoparticles for Transarterial Radioembolization and Chemoembolization Combination Therapy of VX2 Liver Tumor.

In interventional treatment, materials are administered into the blood supply artery and directly delivered to tumors, offering proper scenarios for nanomedicine potential clinical applications. Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are effective treatment methods for hepatocellular carcinoma (HCC), but postoperative residual tumor may result in intrahepatic recurrence and distant metastasis. The combination therapy of TACE and TARE based on multifunctional nanoparticles (NPs) is expected to overcome the drug resistance in hypoxic tumors and improve the therapeutic effect. Herein, BaGdF5 NPs are synthesized and then coated with polydopamine (PDA), conjugated with the chemotherapeutic drug cis-diamminedichloride platinum (CDDP), radio-labeled with therapeutic radionuclide 131 I, yielding 131 I-BaGdF5 @PDA-CDDP NPs. The in vitro anti-cancer effects of 131 I-BaGdF5 @PDA-CDDP NPs are confirmed using CCK-8 and γ-H2AX assays in Huh7 cells. Mixed with Lipiodol, 131 I-BaGdF5 @PDA-CDDP NPs are injected into the hepatic artery via a microcatheter to realize the TACE and TARE combination therapy in a rabbit VX2 liver tumor model. The results indicate that glucose metabolism is clearly decreased based on 18 F-FDG PET imaging and the apoptosis of tumor cells is increased. Furthermore, 131 I and BaGdF5 NPs can be used for SPECT imaging and CT/MR imaging respectively, facilitating real-time monitoring of the in vivo biodistribution of 131 I-BaGdF5 @PDA-CDDP NPs.

Research trends and areas of focus on cryoablation and oncology: A bibliometric analysis from 2001 to 2020.

BACKGROUND: Cryoablation is an interdisciplinary, widely used treatment approach for several types of solid tumors, making it difficult to obtain a comprehensive picture of its current status and popular research topics. This study aimed to use a bibliometric approach to understand important research themes and trends in cryoablation and oncology. METHODS: Literature studies on cryoablation and oncology from 2001 to 2020 were extracted from the Web of Science. A bibliometric analysis was performed based on the annual publication volume, several journal articles and local citation score, and distribution of keywords and trends in the literature using tools such as COOC version 9.94, VOSviewer version 1.6.17, and the bibliometrix version 3.1.3 R package. RESULTS: This study included 2793 publications. Total yearly publications have plateaued over the last 20 years. Five research themes were presented in the keyword network, including clinical applications of cryoablation in liver, lung, kidney, prostate, and skin cancers and comparison of cryoablation with other energy ablations. After 2012, 2 new research topics emerged: synergy between cryoablation and immunotherapy in tumors and cryoablation of Barrett esophagus. The high cited literatures are dominated by studies related to cryoablation for renal and prostate cancer treatment, but they also reflect the recent increasing interest in immunotherapy and bone metastases. Twenty important journals were identified, with Cryobiology publishing the most articles. CONCLUSION: Bibliometric analysis of studies related to tumor cryoablation can help researchers rapidly comprehend popular topics and determine future trends, guiding future research directions.