Development of an earthworm-based soft robot for colon sampling.

Colorectal cancer as a major disease that poses a serious threat to human health continues to rise in incidence. And the timely colon examinations are crucial for the prevention, diagnosis, and treatment of this disease. Clinically, gastroscopy is used as a universal means of examination, prevention and diagnosis of this disease, but this detection method is not patient-friendly and can easily cause damage to the intestinal mucosa. Soft robots as an emerging technology offer a promising approach to examining, diagnosing, and treating intestinal diseases due to their high flexibility and patient-friendly interaction. However, existing research on intestinal soft robots mainly focuses on controlled movement and observation within the colon or colon-like environments, lacking additional functionalities such as sample collection from the intestine. Here, we designed and developed an earthworm-like soft robot specifically for colon sampling. It consists of a robot body with an earthworm-like structure for movement in the narrow and soft pipe-environments, and a sampling part with a flexible arm structure resembling an elephant trunk for bidirectional bending sampling. This soft robot is capable of flexible movement and sample collection within an colon-like environment. By successfully demonstrating the feasibility of utilizing soft robots for colon sampling, this work introduces a novel method for non-destructive inspection and sampling in the colon. It represents a significant advancement in the field of medical robotics, offering a potential solution for more efficient and accurate examination and diagnosis of intestinal diseases, specifically for colorectal cancer.

An AFM-Based Model-Fitting-Free Viscoelasticity Characterization Method for Accurate Grading of Primary Prostate Tumor.

Viscoelasticity is a crucial property of cells, which plays an important role in label-free cell characterization. This paper reports a model-fitting-free viscoelasticity calculation method, correcting the effects of frequency, surface adhesion and liquid resistance on AFM force-distance (FD) curves. As demonstrated by quantifying the viscosity and elastic modulus of PC-3 cells, this method shows high self-consistency and little dependence on experimental parameters such as loading frequency, and loading mode (Force-volume vs. PeakForce Tapping). The rapid calculating speed of less than 1ms per curve without the need for a model fitting process is another advantage. Furthermore, this method was utilized to characterize the viscoelastic properties of primary clinical prostate cells from 38 patients. The results demonstrate that the reported characterization method a comparable performance with the Gleason Score system in grading prostate cancer cells, This method achieves a high average accuracy of 97.6% in distinguishing low-risk prostate tumors (BPH and GS6) from higher-risk (GS7-GS10) prostate tumors and a high average accuracy of 93.3% in distinguishing BPH from prostate cancer.

Design, Synthesis, and Activity Evaluation of Novel Acyclic Nucleosides as Potential Anticancer Agents In Vitro and In Vivo.

In the present work, 103 novel acyclic nucleosides were designed, synthesized, and evaluated for their anticancer activities in vitro and in vivo. The structure-activity relationship (SAR) studies revealed that most target compounds inhibited the growth of colon cancer cells in vitro, of which 3-(6-chloro-9H-purin-9-yl)dodecan-1-ol (9b) exhibited the most potent effect against the HCT-116 and SW480 cells with IC50 values of 0.89 and 1.15 µM, respectively. Furthermore, all of the (R)-configured acyclic nucleoside derivatives displayed more potent anticancer activity compared to their (S)-counterparts. Mechanistic studies revealed that compound 9b triggered apoptosis in the cancer cell lines via depolarization of the mitochondrial membrane and effectively inhibited colony formation. Importantly, compound 9b inhibited the growth of the SW480 xenograft in a mouse model with low systemic toxicity. These results indicated that acyclic nucleoside compounds are viable as potent and effective anticancer agents, and compound 9b may serve as a promising lead compound that merits further attention in future anticancer drug discovery.

IL-6-targeted ultrasmall superparamagnetic iron oxide nanoparticles for optimized MRI detection of atherosclerotic vulnerable plaques in rabbits.

Vulnerable plaques of atherosclerosis (AS) are the main culprit lesion for the serious risk of acute cardiovascular disease (CVD). Therefore, developing new non-invasive methods to detect vulnerable plaques and to evaluate their stability effectively is of great value in the early diagnosis of CVD. IL-6 plays a vital role in the development and rupture of AS. In this study, IL-6-targeted superparamagnetic iron oxide nanoparticles (Anti-IL-6-USPIO) are synthesized by a chemical condensation reaction. An AS model was established by damaging rabbit abdominal aortic intima with Foley's tube in combination with a high cholesterol diet. The results confirm that Anti-IL-6-USPIO have excellent IL-6-targeting ability and usefulness in detecting vulnerable plaques in vitro and in vivo, which may provide a novel, non-invasive strategy for evaluating acute cardiovascular risk or exploiting anti-atherosclerotic drugs.

Association Between Serum LDL-C and ApoB and SYNTAX Score in Patients With Stable Coronary Artery Disease.

The aim of this study was to examine the relationship between low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) B levels and the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) score (SS) in patients with stable angina pectoris. We enrolled 594 patients who were suspected to have coronary heart disease (CHD) and who underwent coronary angiography. Patients were divided into 4 groups based on the SS: normal (SS = 0, n = 154), low SS (SS ≤ 22, n = 210), intermediate SS (22 < SS < 32, n = 122), and high SS (SS ≥ 33, n = 63). Positive correlations between lipoprotein (a), LDL-C, ApoB, total cholesterol, and SS were significant ( r = 0.132, 0.632, 0.599, and 0.313, respectively; P < .01), whereas high-density lipoprotein cholesterol (HDL-C), ApoA1, and ApoA1/ApoB levels showed a significant negative correlation ( r = -0.29, -0.344, and -0.561, respectively; P < .01). Multivariate linear regression analysis revealed that LDL-C, ApoB, ApoA1/ApoB, fibrinogen (Fg), and HDL-C levels had an effect on SS (standardized regression coefficients were 0.41, 0.29, -0.12, 0.08, and -0.09, respectively; P < .05). In conclusion, LDL-C, ApoB, ApoA1/ApoB, Fg, and HDL-C levels affected the SS and were predictors of CHD complexity.

Mask-free fabrication of a versatile microwell chip for multidimensional cellular analysis and drug screening.

Cells are frequently studied because they are basic structural, functional, and biological units of living organisms. Extracting features from cellular behaviors can facilitate decision making in medical diagnoses and represents an important aspect in the development of biomedical engineering. Previous studies have just focused on either the individual cell or cell clusters separately, which leads to a great lack of information. Microwell technologies could address the challenges of in vitro cellular studies, from individual cell studies to 3D functional assays, by providing more information from smaller sample volumes and enabling the incorporation of low-cost high-throughput assays in the drug discovery process. To this end, the present study describes an easy-to-use method for fabricating a versatile microwell chip that utilizes a digital micro-mirror device printing system, and the chip can be employed in multidimensional cellular analysis, ranging from the single cell to the 3D spheroid level. The microwell manufacturing process, using a digital mask in place of a conventional physical mask, is based on shadowed light and is full of flexibility. Three different dimensions (single cell (1D), cell monolayer (2D) and cell spheroid (3D)) of one cell type can be formed using a microwell array and the analyses of biological characteristics are achieved separately. Single cells and cell clusters can be controlled via customized geometries of microfabricated selectively adhesive poly(ethylene glycol) diacrylate (PEGDA) wells. The effects of shape on cellular growth and hybrid tissue layers were investigated by peeling off the microwells. Furthermore, 3D multicellular spheroids were successfully established in a controllable and high-throughput format. Preclinical drug screening was investigated and distinct differences were observed in the tolerance response to drug testing between the 2D and 3D conditions. The study results further demonstrate that the high-density microwell chip is an easy-to-use multidimensional cellular analysis and rapid drug screening technique, and it could be easily adapted for a wide range of biological research applications.

Facile modulation of cell adhesion to a poly(ethylene glycol) diacrylate film with incorporation of polystyrene nano-spheres.

Poly(ethylene glycol) diacrylate (PEGDA) is a common hydrogel that has been actively investigated for various tissue engineering applications owing to its biocompatibility and excellent mechanical properties. However, the native PEGDA films are known for their bio-inertness which can hinder cell adhesion, thereby limiting their applications in tissue engineering and biomedicine. Recently, nano composite technology has become a particularly hot topic, and has led to the development of new methods for delivering desired properties to nanomaterials. In this study, we added polystyrene nano-spheres (PS) into a PEGDA solution to synthesize a nano-composite film and evaluated its characteristics. The experimental results showed that addition of the nanospheres to the PEGDA film not only resulted in modification of the mechanical properties and surface morphology but further improved the adhesion of cells on the film. The tensile modulus showed clear dependence on the addition of PS, which enhanced the mechanical properties of the PEGDA-PS film. We attribute the high stiffness of the hybrid hydrogel to the formation of additional cross-links between polymeric chains and the nano-sphere surface in the network. The effect of PS on cell adhesion and proliferation was evaluated in L929 mouse fibroblast cells that were seeded on the surface of various PEGDA-PS films. Cells density increased with a larger PS concentration, and the cells displayed a spreading morphology on the hybrid films, which promoted cell proliferation. Impressively, cellular stiffness could also be modulated simply by tuning the concentration of nano-spheres. Our results indicate that the addition of PS can effectively tailor the physical and biological properties of PEGDA as well as the mechanical properties of cells, with benefits for biomedical and biotechnological applications.

Regulation of breast cancer cell behaviours by the physical microenvironment constructed via projection microstereolithography.

A considerable number of studies have examined how intrinsic factors regulate breast cancer cell behaviours; however, physical microenvironmental cues may also modulate cellular morphology, proliferation, and migration and mechanical properties. In the present study, the surrounding microenvironment of breast cancer cells was constructed using projection microstereolithography, enabling the investigation of the external environment's effects on breast cancer cell behaviours. A poly(ethylene) glycol diacrylate (PEGDA) solution was polymerized by programmable ultraviolet exposure to create arbitrary shapes with high biocompatibility, efficiency, flexibility and repeatability, and the resistance to cell attachment enabled the PEGDA coated film to hinder cell adhesion, allowing cells to grow in specific patterns. Furthermore, breast cancer cell morphology and mechanical properties were modified by altering the microenvironment. Proliferation was higher in breast cancer as compared to normal cells, consistent with the primary characteristic of malignant tumors. Moreover, breast cancer cells migrated more rapidly when grown in a narrow channel as compared to a wider channel. These findings enhance our understanding of the role of the microenvironment in breast cancer cell behaviours and can provide a basis for developing effective anticancer therapies.

Selective pattern of cancer cell accumulation and growth using UV modulating printing of hydrogels.

Fabrication of extracellular microenvironment for cancer cell growth in vitro is an indispensable technique to precisely control the cell spatial arrangement and proliferation for cell-behavior research. Current micropatterning methods usually require relatively complicated operations, which makes it difficult to investigate the effects of different cell growth patterns. This manuscript proposes a DMD-based projection technique to quickly pattern a poly(ethylene) glycol diacrylate (PEGDA)-based hydrogel on a common glass substrate. Using this method, we can effectively control the growth patterns of cells. Compared with these traditional methods which employ digital dynamic mask, polymerization of PEGDA solution can be used to create arbitrary shaped microstructures with high efficiency, flexibility and repeatability. The duration of UV exposure is less than 10 s through controlling the projected illumination pattern. The ability of patterned PEGDA-coated film to hinder cell adhesion makes it possible to control area over which cells attach. In our experiments, we take advantage of the blank area to pattern cells, which allows cells to grow in various pre-designed shapes and sizes. And the patterning cells have a high viability after culturing for several days. Interestingly, we found that the restricted space could stiffen and strengthen the cells. These results indicate that cells and extracellular microenvironment can influence each other.

Blood lipid profiles and factors associated with dyslipidemia assessed by a point-of-care testing device in an outpatient setting: A large-scale cross-sectional study in Southern China.

OBJECTIVE: To promote the concept of POCT and to investigate dyslipidemia in Guangzhou, China, we performed a study examining blood lipids assessed by POCT and reported factors associated with dyslipidemia. DESIGN AND METHODS: This multicenter, cross-sectional study enrolled outpatients from 9 Guangzhou hospitals from May through September 2013. After informed consent was obtained, the following information was collected: age; gender; the presence of diabetes mellitus, obesity, and hypertension as well as current use of cigarettes or alcohol. Patients were asked to fast for 8h before the blood examination performed on a POCT device, the CardioChek PA. RESULTS: Of 4012 patients enrolled (1544 males, 2468 females; mean age 60.35±9.41 years), 1993 (49.7%) patients had dyslipidemia, but only 101 (5.1%) took statins. The multivariate tests of associations between demographic variables, comorbidities, and the risk of having dyslipidemia found that the significant predictors of dyslipidemia were male gender, age ≥60 years, being a current smoker or alcohol drinker, and hypertension. CONCLUSION: Most dyslipidemia patients in Guangzhou remain untreated. POCT in China is feasible, and its widespread use might improve dyslipidemia awareness, treatment and control.

[Ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance angiography combined with inflammatory factors for detecting atherosclerotic plaques in rabbits].

OBJECTIVE: To investigate the feasibility of Ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance angiography (USPIO-MRA) combined with interleukin-6 (IL-6) and IL-10 detection for detecting atherosclerotic plaques in rabbits. METHODS: Twenty-four normal male rabbits were randomly assigned (n=8) into group A with atherosclerosis induced by damaging the aortic tunica intima with Foley's tube in combination with a high fat diet, group B with a high fat diet, and group C without any intervention. At week 12, plain and USPIO-MRA was performed in all the 24 rabbits and the results were compared with pathological examinations; blood samples were collected from the ear vein to examine blood lipids and levels of IL-6 and IL-10. RESULTS: The rabbits in groups A and B showed significantly different IL-6 levels (167 ± 21.3 vs 116 ± 14.3 pg/ml, P<0.05) but comparable blood lipids and IL-10 levels (P>0.05). The levels of IL-6, IL-10, TC, TG, and LDL, but not HDL, differed significantly between groups A and C and between groups B and C (P<0.01). Continuous MRA scan showed significantly different signal-to-noise ratios (SNR) between the 3 groups. CONCLUSION: USPIO-MRA combined with IL-6 and IL-10 detection is feasible in detecting atherosclerotic plaques in rabbits.

[Effect of percutaneous intervention on adrenomedullin and tumor necrosis factor in the coronary circulation].

OBJECTIVE: To evaluate the effect of percutaneous intervention (PCI) on coronary circulation levels of adrenomedullin (ADM) and tumor necrosis factor alpha (TNF-alpha) in patients with coronary heart disease (CHD). METHODS: Thirty-three CHD patients underwent percutaneous transluminal coronary angioplasty (PTCA) and stenting (altogether 48 stents were implanted). Blood samples were collected from the coronary sinus and femoral artery at the time points of immediately before and after angioplasty, immediately after PTCA or stenting, 10 min after procedures, respectively. RESULTS: The ADM and TNF-alpha levels in the coronary sinus varied little after coronary angiography, but were elevated markedly following PTCA from the basal levels of 36.3+/-1.3 pg/ml to 28.9+/-1.9 pg/ml (P<0.01) and from 11.10+/-0.46 ng/ml to 8.84+/-0.37 ng/ml (P<0.01), respectively. Further increases of ADM and TNF-alpha levels were detected immediately after stent deployment. ADM recovered to basal levels 10 min after completion of the procedures, while TNF-alpha underwent further increase. Before the procedure, ADM and TNF-alpha levels were higher in the coronary sinus than in the femoral artery (28.9+/-1.9 pg/ml vs 22.6+/-0.8 pg/ml, P<0.01; 8.84+/-0.37 ng/ml vs 7. 56+/-0.23 ng/ml, P<0.01, respectively), and their levels in the femoral artery did not undergo significant changes in response to the operations. CONCLUSION: The coronary circulation levels of ADM and TNF-alpha increase after PTCA and stenting but not after coronary angiography in CHD patients, which might be attributed to injuries by the procedures as well as the mechanical stimulation by the stent.

[Relation of the ST-segment elevation pattern in acute phase of anterior wall acute myocardial infarction to short-term prognosis].

OBJECTIVE: To observe the relation of ST-segment elevation pattern of electrocardiogram (ECG) recorded in acute phase of anterior wall acute myocardial infarction (AMI) to short-term prognosis. METHODS: Sixty-two patients with first anterior wall AMI were divided into 3 groups according to ST-segment elevation pattern in lead V3 of a 12-lead ECG at admission. Patients in group A (n=18) were characterized by concave type of ST-segment elevation, group B (n=27) by straight type and group C (n=17) by convex type. The peak value of serum creatine phosphate kinase (CPK) and left ventricular ejection fraction (LVEF) were measured. The incidence of serious complications (including malignant arrhythmia, left ventricular dysfunction and cardiogenic shock) and mortality within the initial 4 weeks of hospitalization were recorded. RESULTS: The median value of peak CPK of the 3 groups was 2 014.4, 4 486.8 and 5 826.9 IU/L respectively, and the peak value of CPK in group A was much lower than that in groups B and C ( D<0.05 and P<0.01, respectively). LVEF measured by echocardiogram within 14 d after myocardial infarction were 61.2%, 48.6% and 38.7% respectively, showing significant difference between groups A and B and between groups B and C (P<0.05) as well as between group A and C (P<0.01). The incidences of serious complications and mortality within 4 weeks after AMI in group A were much lower than those in groups B and C (P<0.05), but there was no significant difference between groups B and C ( D>0.05). CONCLUSION: The shape of ST-segment elevation in lead V3 of a 12-lead ECG in acute phase of anterior wall AMI may reflect the severity of myocardial ischemic injury, and convex type of ST-segment elevation in lead V3 in acute phase often indicate poor short-term prognosis.