Machine-learning-based models to predict cardiovascular risk using oculomics and clinic variables in KNHANES.

BACKGROUND: Recent researches have found a strong correlation between the triglyceride-glucose (TyG) index or the atherogenic index of plasma (AIP) and cardiovascular disease (CVD) risk. However, there is a lack of research on non-invasive and rapid prediction of cardiovascular risk. We aimed to develop and validate a machine-learning model for predicting cardiovascular risk based on variables encompassing clinical questionnaires and oculomics. METHODS: We collected data from the Korean National Health and Nutrition Examination Survey (KNHANES). The training dataset (80% from the year 2008 to 2011 KNHANES) was used for machine learning model development, with internal validation using the remaining 20%. An external validation dataset from the year 2012 assessed the model's predictive capacity for TyG-index or AIP in new cases. We included 32122 participants in the final dataset. Machine learning models used 25 algorithms were trained on oculomics measurements and clinical questionnaires to predict the range of TyG-index and AIP. The area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score were used to evaluate the performance of our machine learning models. RESULTS: Based on large-scale cohort studies, we determined TyG-index cut-off points at 8.0, 8.75 (upper one-third values), 8.93 (upper one-fourth values), and AIP cut-offs at 0.318, 0.34. Values surpassing these thresholds indicated elevated cardiovascular risk. The best-performing algorithm revealed TyG-index cut-offs at 8.0, 8.75, and 8.93 with internal validation AUCs of 0.812, 0.873, and 0.911, respectively. External validation AUCs were 0.809, 0.863, and 0.901. For AIP at 0.34, internal and external validation achieved similar AUCs of 0.849 and 0.842. Slightly lower performance was seen for the 0.318 cut-off, with AUCs of 0.844 and 0.836. Significant gender-based variations were noted for TyG-index at 8 (male AUC=0.832, female AUC=0.790) and 8.75 (male AUC=0.874, female AUC=0.862) and AIP at 0.318 (male AUC=0.853, female AUC=0.825) and 0.34 (male AUC=0.858, female AUC=0.831). Gender similarity in AUC (male AUC=0.907 versus female AUC=0.906) was observed only when the TyG-index cut-off point equals 8.93. CONCLUSION: We have established a simple and effective non-invasive machine learning model that has good clinical value for predicting cardiovascular risk in the general population.

Renal Artery Coil Embolization as an Endovascular Approach for Establishing a Rabbit Model of Chronic Kidney Disease.

PURPOSE: To investigate the safety and feasibility of renal artery coil embolization for establishing chronic kidney disease (CKD) in rabbits. MATERIALS AND METHODS: Ten male adult New Zealand rabbits underwent renal artery coil embolization. Initially, the main renal artery on 1 side was completely embolized, followed by embolization of approximately two-thirds of the primary branches of the contralateral renal artery 1 week later. Four rabbits were randomly chosen for sacrifice at 4 weeks after embolization, whereas the remaining 6 were sacrificed at 8 weeks after embolization. The assessment encompassed the animals' general condition, angiography, biochemical parameters, inflammatory markers, and histopathological examination of the kidneys and hearts. RESULTS: Four weeks after embolization, serum creatinine level showed a substantial increase (2.4 mg/dL [SD ± 0.6]; P = .009 vs baseline), with a subsequent 4.12-fold elevation at 8 weeks after embolization (4.9 mg/dL [SD ± 1.4]; P < .001 vs baseline). Additionally, considerable increases in serum blood urea nitrogen, calcium, and potassium ions were observed at 8 weeks after embolization (58.3 mg/dL [SD ± 19.0]; P < .001 vs baseline; 23.1 mg/dL [SD ± 4.4]; P < .001 vs baseline; and 6.3 mEq/L [SD ± 0.7]; P < .001 vs baseline, respectively). The completely embolized kidney exhibited notable atrophy, severe fibrosis, and cortical calcification, whereas the contralateral partially embolized kidney displayed compensatory hypertrophy, along with glomerulosclerosis, tubular dilation, tubular casts, and interstitial fibrosis. CONCLUSIONS: Renal artery coil embolization proved to be effective and safe for establishing a CKD model in rabbits.

The effect of traditional Chinese medicine soaking method on the healing of diabetic foot ulcers: A meta-analysis.

Foot infections, sores or deep tissue damage from diabetes can be a serious psychological and physical injury. This paper aims at making meta-analyses on the therapeutic effects of traditional Chinese medicine (TCM) on diabetic foot ulcers. The Chinese National Knowledge Infrastructure, VIP Database, Wanfang Database and so on, has conducted a randomized controlled trial to evaluate the clinical effect of TCM soaking method for diabetes patients with diabetes. Literature has been determined to be included by computer search and by hand rough checks. The search period was from the creation of the database to October 2023. Review Manager 5.3 was used to analyse the meta data and evaluate it systematically. Altogether, 479 research was conducted in China's data base and 20 of them were eventually collected for the final statistical analysis. In all, 1361 patients were enrolled in the trials. The results indicated that TCM immersion in diabetic foot resulted in significantly improved obvious wound healing (OR, 3.2; 95% CI, 2.5, 4.09, p < 0.0001); results showed that TCM immersion therapy significantly increased the efficiency of effective wound healing (OR, 4.55; 95% CI, 3.25, 6.37, p < 0.001). Statistical significance was found. Using Egger's approach to detect publishing bias suggests that there is no risk of publishing bias in terms of marked wound healing and effective healing. Traditional Chinese drug immersion can increase obviously the recovery ratio and the effective recovery ratio of diabetic foot.

[Mechanism of n-butanol fraction of Wenxia Formula combining with gefitinib in treating non-small cell lung cancer based on network pharmacology and in vitro experiment].

This study combined network pharmacology, molecular docking, and in vitro experiments to explore the potential mechanism of the active components of the n-butanol fraction of Wenxia Formula(NWXF) combined with gefitinib(GEF) in treating non-small cell lung cancer(NSCLC). Ultra-performance liquid chromatography-quadrupole Orbitrap mass spectrometry(UPLC-Q-Orbitrap MS) was employed to detect the main chemical components of NWXF. The active components of NWXF were retrieved from SwissADME, and the candidate targets of these active components were retrieved from SwissTargetPrediction. Online Mendelian Inheritance in Man(OMIM) and GeneCards were searched for the targets of NSCLC. Cytoscape 3.9.0 and STRING were employed to build the protein-protein interaction(PPI) network with the common targets shared by NWXF and NSCLC. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment were performed in DAVID to predict the potential mechanisms. Finally, molecular docking between the main active ingredients and key targets was conducted in SYBYL-X 2.0. The methyl thiazolyl tetrazolium(MTT) assay was employed to evaluate the inhibitory effects of NWXF and/or GEF on the proliferation of human non-small cell lung cancer cells(A549 and PC-9). Additionally, the impact of NWXF on human embryonic lung fibroblast cells(MRC-5) was assessed. The effectiveness of the drug combination was evaluated based on the Q value. The terminal-deoxynucleoitidyl transferase mediated nick-end labeling(TUNEL) assay was employed to examine the apoptosis of A549 and PC-9 cells treated with NWXF and/or GEF. Quantitative real-time PCR(qRT-PCR) was employed to measure the mRNA levels of epidermal growth factor receptor(EGFR), c-Jun N-terminal kinase(JNK), and Bcl2-associated X protein(Bax) in the A549 and PC-9 cells treated with NWXF and/or GEF. Western blot was employed to determine the protein levels of EGFR, p-EGFR, JNK, p-JNK, and Bax in the A549 and PC-9 cells treated with NWXF and/or GEF. A total of 77 active components, 488 potential targets, and 49 key targets involved in the treatment of NSCLC with NWXF were predicted. The results of GO annotation showed that NWXF may treat NSCLC by regulating the biological processes such as cell proliferation, apoptosis, and protein phosphorylation. KEGG enrichment revealed that the key targets of NWXF in treating NSCLC were enriched in the mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT), hypoxia-inducible factor-1(HIF-1), and microRNA-related signaling pathways. Molecular docking results showed that 91.9% of the docking scores were greater than 5, indicating the strong binding capability between main active components and key targets. The cell experiments demonstrated that NWXF combined with GEF synergistically inhibited the proliferation, promoted the apoptosis, decreased p-EGFR/EGFR and p-JNK/JNK values, down-regulated the mRNA levels of EGFR and JNK, and up-regulated the mRNA and protein levels of Bax in A549 and PC-9 cells. In conclusion, NWXF combined with GEF can regulate the EGFR/JNK pathway to promote the apoptosis of NSCLC cells, thus treating NSCLC.

CA-UNet Segmentation Makes a Good Ischemic Stroke Risk Prediction.

Stroke is still the World's second major factor of death, as well as the third major factor of death and disability. Ischemic stroke is a type of stroke, in which early detection and treatment are the keys to preventing ischemic strokes. However, due to the limitation of privacy protection and labeling difficulties, there are only a few studies on the intelligent automatic diagnosis of stroke or ischemic stroke, and the results are unsatisfactory. Therefore, we collect some data and propose a 3D carotid Computed Tomography Angiography (CTA) image segmentation model called CA-UNet for fully automated extraction of carotid arteries. We explore the number of down-sampling times applicable to carotid segmentation and design a multi-scale loss function to resolve the loss of detailed features during the process of down-sampling. Moreover, based on CA-Unet, we propose an ischemic stroke risk prediction model to predict the risk in patients using their 3D CTA images, electronic medical records, and medical history. We have validated the efficacy of our segmentation model and prediction model through comparison tests. Our method can provide reliable diagnoses and results that benefit patients and medical professionals.

Optimal Parameter Configuration of a Microfluidic Chip for High-Throughput, Label-Free Circulating Tumor Cell Separation and Enrichment Based on Inertial Focusing.

To simply, quickly, and efficiently separate circulating tumor cells from blood has always been an enormous challenge. Leveraging the principle of inertial focusing, we here designed a simply structured microfluidic chip that maintained excellent CTC separation efficiency with high robustness and low velocity sensitivity across a broad velocity range. The parameter configuration of the chip was systematically examined, especially the most influential parameters such as the arc radius and arc angle. With optimal parameters, the designed chip achieved an outstanding particle separation efficiency of 99.8% and, more importantly, enabled the efficient separation and enrichment of CTCs in blood samples. This design can be readily integrated with other functional modules for further sample processing, serving as a promising tool for cancer diagnosis and therapeutics.

Pipeline embolization devices for the treatment of nonsaccular aneurysms in pediatric patients.

Objective: Pediatric nonsaccular aneurysms are rare but challenging lesions; pipeline embolization devices (PEDs) are their potential treatment option. In this study, we aimed to evaluate the safety and efficacy of PEDs for treatment of these aneurysms. Methods: We retrospectively selected pediatric patients with nonsaccular aneurysms treated using PEDs between June 2015 and July 2021 from our prospectively maintained database. For each patient, demographics, aneurysm characteristics, procedure details, and clinical and angiographic follow-up data were collected and summarized. Results: This study included 16 pediatric patients with 16 nonsaccular aneurysms treated with PEDs. A median clinical follow-up time of 1,376 days was achieved in 93.75% of the patients. The complication rate of the included patients was 25%, with two patients developing mass effect, one patient undergoing major ischemic stroke, and one patient experiencing stent foreshortening after the procedure. The complete occlusion rate of aneurysms without any neurologic sequelae was 93.33%, with a median angiographic follow-up period of 246 days. The mortality rate was 6.25%. Conclusions: The use of PEDs to treat pediatric nonsaccular aneurysms is feasible, with a high rate of complete occlusion of the aneurysm and favorable follow-up outcomes.

A Comparative Study of the Etiology of Intracranial Vertebral Artery Dissection and Carotid Artery Dissection.

BACKGROUND: Both extrinsic (trauma or violent movement) and intrinsic (structural abnormality, atherosclerosis, or hemodynamic instability) factors may result in arterial dissection. The role of these factors in the origin or progression of dissection remains unclear. This study aimed to characterize the clinical features, radiologic features, and outcomes of intracranial vertebral artery dissection compared with carotid artery dissection and to determine the major causative factors. METHODS: Consecutive patients with craniocervical dissection (n=127) were retrospectively analyzed. Patients with intracranial vertebral artery dissection (n=77) and those with carotid artery dissection (n=35) were compared with respect to patient age, sex, cerebrovascular risk factors, laboratory indices, and radiologic features. RESULTS: Intracranial vertebral artery dissection was the most common craniocervical arterial dissection in our cohort (n=77, 60.6%). Body mass index in the intracranial vertebral artery dissection group was significantly greater than that in carotid artery dissection group. Clinical manifestations of intracranial vertebral artery dissection included ischemic stroke (37.7%), dizziness or vertigo (39.0%), and headache or neck pain (44.2%). Two patients had a definite history of trauma. The frontal and lateral tortuosity ratios of the vertebral basilar artery were significantly greater while the vertex angle was smaller in the intracranial vertebral artery dissection group compared with carotid artery dissection group. A positive correlation between the tortuosity ratios and subarachnoid hemorrhage and a significant inverse correlation between the tortuosity ratios and lipid parameters (high-density lipoprotein; apolipoprotein A1) were identified. CONCLUSIONS: Intrinsic causes may play a more important role in the development of intracranial vertebral artery dissection than carotid artery dissection.

Fast, Reusable, Cell Uniformly Distributed Membrane Filtration Device for Separation of Circulating Tumor Cells.

Isolation of circulating tumor cells (CTCs) is of great significance for the diagnosis, prognosis, and treatment of metastatic cancer. Among CTC capture methods independent of antibodies, membrane filtration-based methods have the advantages of simplicity, rapidity, and high throughput but usually have problems such as clogging, high pressure drop, and impaired cell viability. In this study, we designed and tested a reusable device that used horizontal rotor and fluid-assisted separation to capture CTCs by centrifugal membrane filtration, achieving simple, fast, highly efficient, and viable cell capture on traditional centrifuge. The average capture efficiency was 95.8% for different types of cancer cells with >90% survival, and the removal of white blood cells can reach 99.72% under four times cleaning of the membrane after filtration. A further clinic demo was performed using the device to detect residual leukemic cells in patients; the results showed a 10-fold enrichment of the leukemic cells in peripheral blood samples. Taken together, the simple, robust, and efficient CTC capture device may have the potential for clinic routine detection and analysis of circulating tumor cells.

Pipeline for the treatment of distal cerebral circulation aneurysms: A multicenter study focusing on periprocedural Complications.

BACKGROUND AND AIM: Distal cerebral circulation aneurysms (DCCAs) remain treatment challenges for neurointervention. The off-label use of the pipeline embolization device (PED) for these aneurysms remains controversial. This study aimed to evaluate the safety and efficacy of PED for DCCAs in a multicenter cohort of patients. METHODS: Between March 2016 and June 2021, we retrospectively analyzed the neurointerventional data on the clinical and radiological records of all patients undergoing PED treatment of DCCAs at three medical centers. RESULTS: A total of 53 consecutive patients with 53 DCCAs were treated with PED. The mean aneurysm size was 12.3 ± 5.7 mm. In total, 75.4% (40/53) were fusiform and 24.5% (13/53) were saccular. Of these, 17.0% (9/53) were recurrent aneurysms that were previously treated with endovascular or microsurgical approaches. The technical success rate was 100%, among which 81.1% (43/53) procedures were completed with a single PED, and the rest (10/53, 18.8%) required telescoping with two devices. Angiographic follow-up data were available for 51 patients, with a median follow-up time of 12 months. At the latest follow-up, 46/51 (90.2%) aneurysms showed complete obliteration, and 4/51 (7.8%) showed reduced filling. Periprocedural complications such as hemorrhage were observed in two patients with MCA aneurysms (3.8%, 2/53), and ischemic events occurred in six patients (11.3%, 6/53). The overall mortality and morbidity rates were 7% (4/53). CONCLUSIONS: PED is a viable option for treating DCCAs, especially for recurrent aneurysms. Coverage of bifurcation branches and perforator may increase the risk of complications.

Modified minimally invasive technique for decompression and reduction of thoracolumbar burst fracture with neurological symptoms: Technical Note.

PURPOSE: There are few reports about minimally invasive decompression and fixation for patients with thoracolumbar fracture and neurological symptoms. The previously reported method requires complete laminectomy, and removal of the medial part of the pedicle to expose the spinal canal for reduction. Thus, some approach-related damage to the bony structure and soft tissue still occurs. This study was performed to describe a modified minimally invasive tube technique for decompression and reduction of thoracolumbar fracture with neurological symptoms. This modified technique preserves most of the posterior structures of the spine as well as the muscle. METHODS: Percutaneous pedicle screws were placed on the vertebrae superior and inferior to the fracture and at the fracture segment on the side with less severe symptoms. After retraction, the tube for decompression was placed on the facet joint where the decompression was needed. Under microscopic vision, part of the lamina and ligamentum flavum were removed to expose the spinal canal, and an L-shaped probe was used to reduce the bone fragment. RESULTS: The modified method was successfully used in eight patients. Complete decompression was achieved and the bone fragment was safely reduced through the tube under microscopy in all cases. Fluoroscopy confirmed that the positioning of the percutaneous pedicle screw was good and the bone fragment was reduced. The neurological status was improved in all patients at last follow up. CONCLUSION: The modified method of minimally invasive decompression and fusion is effective in treating thoracolumbar fractures with neurological symptoms and preserves most of the ligaments and bone structure.

Simultaneous Stenting for Symptomatic Tandem Extracranial and Intracranial Posterior Circulation Stenoses: Long-Term Outcomes and Procedural Experience.

Few studies have reported on simultaneous endovascular stenting for tandem posterior circulation (PC) stenoses and its long-term outcomes. Thus, our aim was to investigate the safety and efficacy of simultaneous stenting in patients with symptomatic tandem extra- and intracranial PC stenoses. From September 2014 to June 2018, 16 such patients with symptomatic stenoses who underwent simultaneous stent placement were analyzed. The primary outcome was occurrence of any stroke, TIA, or death within 30 days after the procedure. The secondary outcomes were technical success, clinical success, and the occurrence of in-stent restenosis ≥50% during follow-up. Technical success was defined as stent coverage of all tandem lesions and residual stenosis <30%. Clinical success was determined based on any occurrence of neurological events or death within 3 months after the procedure. All stents (19 intracranial and 14 extracranial) were placed with a technical success rate of 100%. One patient experienced a pontine ischemic stroke 2 days after the procedure and had recovered well at discharge. One patient experienced a minor complication of groin hematoma. The clinical success rate was 93.75% (15/16). During a median follow-up of 36.0 ± 11.0 months, two patients developed ISR ≥50% at the 1-year follow-up. None of the patients experienced stroke, TIA, or death after discharge during follow-up. Simultaneous stenting for symptomatic tandem extra- and intracranial PC stenoses is safe and feasible. Its impact on long-term stroke prevention is promising, and further study of a larger patient population is needed.

Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy.

Cancer stem cell (CSC) is thought to be the major cause of radio-resistance and relapse post radiotherapy (RT). Recently ultra-high dose rate "FLASH-RT" evokes great interest for its decreasing normal tissue damages while maintaining tumor responses compared with conventional dose rate RT. However, the killing effect and mechanism of FLASH irradiation (FLASH-IR) on CSC and normal cancer cell are still unclear. Presently the radiation induced death profile of CSC and normal cancer cell were studied. Cells were irradiated with FLASH-IR (∼109 Gy/s) at the dose of 6-9 Gy via laser-accelerated nanosecond particles. Then the ratio of apoptosis, pyroptosis and necrosis were determined. The results showed that FLASH-IR can induce apoptosis, pyroptosis and necrosis in both CSC and normal cancer cell with different ratios. And CSC was more resistant to radiation than normal cancer cell under FLASH-IR. Further experiments tracing lysosome and autophagy showed that CSCs had higher levels of lysosome and autophagy. Taken together, our results suggested that the radio-resistance of CSC may associate with the increase of lysosome-mediated autophagy, and the decrease of apoptosis, necrosis and pyroptosis. To our limited knowledge, this is the first report shedding light on the killing effects and death pathways of CSC and normal cancer cell under FLASH-IR. By clarifying the death pathways of CSC and normal cancer cell under FLASH-IR, it may help us improve the understanding of the radio-resistance of CSC and thus help to optimize the future clinical FLASH treatment plan.

Ultra-High Dose Rate FLASH Irradiation Induced Radio-Resistance of Normal Fibroblast Cells Can Be Enhanced by Hypoxia and Mitochondrial Dysfunction Resulting From Loss of Cytochrome C.

Ultra-high dose rate FLASH irradiation (FLASH-IR) has got extensive attention since it may provide better protection on normal tissues while maintain tumor killing effect compared with conventional dose rate irradiation. The FLASH-IR induced protection effect on normal tissues is exhibited as radio-resistance of the irradiated normal cells, and is suggested to be related to oxygen depletion. However, the detailed cell death profile and pathways are still unclear. Presently normal mouse embryonic fibroblast cells were FLASH irradiated (∼109 Gy/s) at the dose of ∼10-40 Gy in hypoxic and normoxic condition, with ultra-fast laser-generated particles. The early apoptosis, late apoptosis and necrosis of cells were detected and analyzed at 6, 12, and 24 h post FLASH-IR. The results showed that FLASH-IR induced significant early apoptosis, late apoptosis and necrosis in normal fibroblast cells, and the apoptosis level increased with time, in either hypoxic or normoxic conditions. In addition, the proportion of early apoptosis, late apoptosis and necrosis were significantly lower in hypoxia than that of normoxia, indicating that radio-resistance of normal fibroblast cells under FLASH-IR can be enhanced by hypoxia. To further investigate the apoptosis related profile and potential pathways, mitochondria dysfunction cells resulting from loss of cytochrome c (cyt c-/-) were also irradiated. The results showed that compared with irradiated normal cells (cyt c+/+), the late apoptosis and necrosis but not early apoptosis proportions of irradiated cyt c-/- cells were significant decreased in both hypoxia and normoxia, indicating mitochondrial dysfunction increased radio-resistance of FLASH irradiated cells. Taken together, to our limited knowledge, this is the first report shedding light on the death profile and pathway of normal and cyt c-/- cells under FLASH-IR in hypoxic and normoxic circumstances, which might help us improve the understanding of the FLASH-IR induced protection effect in normal cells, and thus might potentially help to optimize the future clinical FLASH treatment.

Modified minimally invasive-transforaminal lumbar interbody fusion under microscopic view to achieve bilateral decompression and fusion through a single approach to treat developmental lumbar spinal stenosis.

PURPOSE: To describe a modified minimally invasive spine (MIS) procedure to treat lumbar developmental spinal stenosis (DSS) to achieve complete decompression and fusion. The method preserves the muscles, ligaments, and most of the bony structures. DSS is not considered a good indication for MIS procedures and few reports discuss alternative treatments. Because MIS has the advantages of low blood loss, rapid recovery, and short hospital stay, it would be ideal for DSS. METHODS: After confirming the screw positions, we placed a tube retractor in the facet joint on the decompressed side. The inferior facet joint and part of the superior joint of the lower segment were removed, the spinal canal was carefully exposed under a microscopic view, and fusion was performed through Kambin's triangle. Next, the operation table was rotated to the contralateral side and angled to approximately 15-20 degrees. We then tilted the tube retractor in the facet joint toward the operation side by 15-20 degrees, which provided access to the contralateral canal for decompression. The ligament flavum was carefully removed and the dural sac was gently retracted to expose the lateral recess on the other side. We then examined the nerve root on the contralateral side to ensure there was no compression. RESULTS: Eight patients with lumbar DSS were treated using this method. Patients' neurological symptoms improved greatly without complications and patients were able to walk the day after surgery. The inner plate of the contralateral lamina and muscle as well as most of the ligaments that contribute to stability were preserved. CONCLUSION: This modified MIS decompression procedure successfully treated DSS by providing spinal canal decompression and preserving most of the stabilizing structures.

Electrochemical Detection and Point-of-Care Testing for Circulating Tumor Cells: Current Techniques and Future Potentials.

Circulating tumor cells (CTCs) are tumor cells that escaped from the primary tumor or the metastasis into the blood and they play a major role in the initiation of metastasis and tumor recurrence. Thus, it is widely accepted that CTC is the main target of liquid biopsy. In the past few decades, the separation of CTC based on the electrochemical method has attracted widespread attention due to its convenience, rapidness, low cost, high sensitivity, and no need for complex instruments and equipment. At present, CTC detection is not widely used in the clinic due to various reasons. Point-of-care CTC detection provides us with a possibility, which is sensitive, fast, cheap, and easy to operate. More importantly, the testing instrument is small and portable, and the testing does not require specialized laboratories and specialized clinical examiners. In this review, we summarized the latest developments in the electrochemical-based CTC detection and point-of-care CTC detection, and discussed the challenges and possible trends.

A novel microfluidic device integrating focus-separation speed reduction design and trap arrays for high-throughput capture of circulating tumor cells.

Isolation and analysis of circulating tumor cells (CTCs) from peripheral blood provides a potential way to detect and characterize cancer. Existing technologies to separate or capture CTCs from whole blood still have issues with sample throughput, separation efficiency or stable efficiency at different flow rates. Here, we proposed a new concept to capture rare CTCs from blood by integrating a triangular prism array-based capture apparatus with streamline-based focus-separation speed reduction design. The focus-separation design could focus and maintain CTCs, while removing a considerable proportion of liquid (98.9%) containing other blood cells to the outlet, therefore, a high CTC capture efficiency could be achieved in the trap arrays with a high initial flow rate. It is worth mentioning that the new design works well over a wide range of flow rates, so it does not require the stability of the flow rate. The results showed that this novel integrated chip can achieve a sample throughput from 5 to 40 mL h-1 with a stable and high CTC capture efficiency (up to 94.8%) and high purity (up to 4 log white blood cells/WBC depletion). The clinical experiment showed that CTCs including CTC clusters were detected in 11/11 (100.0%) patients (mean = 31 CTCs mL-1, median = 25 CTCs mL-1). In summary, our chip enriches and captures CTCs based on physical properties, and it is simple, cheap, fast, and efficient and has low requirements on flow rate, which is very suitable for large-scale application of CTC testing in clinics.

Construction and Preclinical Evaluation of a 124/131I-Labeled Radiotracer for the Detection of Mesothelin-Overexpressing Cancer.

Mesothelin is a molecular biomarker of many types of solid cancers, which may represent a highly promising new target in the development of cancer-targeted diagnostic agents. A human anti-mesothelin antibody with a low molecular weight, ET210sc, was applied; this antibody has potent affinity and can penetrate tissue quickly and stably without causing immunoreactions. We developed a new 124/131I-labeled radiotracer of ET210sc. The 124/131I-labeled ET210sc radiotracer showed excellent radiochemical quality (with over 99% radiolabeling yield, 0.07 GBq/µmol specific activity) and remarkable stability in phosphate-buffered saline (>95% at 3 days). The radiotracer retained its potent affinity (dissociation constant, Kd = 0.101 nM). The radiotracer specifically bound to mesothelin-positive cells in vitro. Interestingly, the radiotracer exhibited significant positive-to-negative tumor uptake ratios (1.5:1) 3 days postinjection. The estimated absorbed doses of each organ (e.g., 0.704 mGy/MBq for the rectum; 0.341 mGy/MBq for the spleen) met the medical safety standards for further clinical applications. Our findings provide an initial proof of concept for the potential use of 124/131I-labeled ET210sc radiotracers to detect mesothelin-overexpressing cancer. 124I-ET210sc is proposed to be an ideal imaging agent for further clinical applications.

Association of extracellular matrix microarchitecture and three-dimensional collective invasion of cancer cells.

As much as 90% of cancer associated mortality follows metastasis of a primary tumor. Circulating tumor cells (CTCs) and CTC clusters are important for metastasis. Compared to CTCs, CTC clusters formed by collective invasion exhibit a 23-50 fold increase in metastatic potential, but the factors that influence collective invasion are largely unknown. Using well defined three-dimensional matrices and different extracellular matrix (ECM) concentrations, we found that cancer cells were more prone to collective invasion at low ECM concentration. Moreover, despite variation of biological factors, changes in ECM microarchitecture, especially the pore size of the matrix, was correlated with the probability of collective invasion, which indicates that the physical microarchitecture of ECM plays an important role in collective invasion of cancer cells.