[Application value of neutrophil lymphocyte ratio combined with age in the diagnosis of dual-phenotype hepatocellular carcinoma].

Objective: This study retrospectively analyzed the clinical medical records of patients with dual phenotypic liver cancer (DPHCC) and those (non-DPHCC) in the same period to seek quick and effective biomarkers for differential diagnosis. Methods: A retrospective study was conducted on 164 patients who underwent radical hepatocellular carcinoma resection at Affiliated Hospital of Nantong University from May 2017 to May 2020, including 29 patients with DPHCC, accounting for 17.7% (age: 53.9±10.0). There were 135 non-DPHCC patients, accounting for 82.3% (age, 62.6±9.1). The clinical records of the above patients were collected,including the basic information of the patients, clinical symptoms and signs, history of infection, laboratory test indexes one day before surgery, postoperative pathological report and other relevant data, The follow-up time was 18 months and the data were complete. By analyzing the clinical data of DPHCC patients and non-DPHCC patients in the same period, to find quick and effective differential diagnostic indicators, and to explore the indicators indicating poor prognosis of DPHCC patients. Results: One-way ANOVA showed significant differences in age, AFP[143(4.8-984.8) vs 9.9(2.8-71.3) µg/L], NLR (3.650±1.924 vs 2.220±1.486), neutrophil count, lymphocyte count, vascular infiltration rate, TNM stage, Chinese Hepatocellular carcinoma Staging (CNLC), Child grade, and Japanese General Staging Score (JIS) (P<0.05). Multivariate logistic regression analysis identified age(OR score:0.967,95%CI:0.860-0.957) and NLR(OR score:1.564,95%CI:1.205-2.029) as independent risk factors for DPHCC differential diagnosis. The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficiency of NLR, and the best cut-off value was 2.586. The combination of age at onset improved the efficiency of differential diagnosis. When reaching the maximum diagnostic efficiency, the area under curve(AUC) was 0.836, the sensitivity was 89.66%, and the specificity was 65.93%. Conclusion: NLR combined with the age of disease has certain feasibility in predicting DPHCC and may be an effective index to distinguish DPHCC from non-DPHCC patients.

[Dynamic changes of locus coeruleus damage in Parkinson's disease-like mice induced by paraquat].

Objective: To observe the dynamic changes of brainstem locus coeruleus (LC) damage in Parkinson' s disease (PD) -like mice by paraquat (PQ) . Methods: In October 2019, 36 male C57BL/6 mice were randomly divided into the exposure group and the control group, with 18 mice in each group. The mice in the exposure group were given intraperitoneal injection of 15 mg/kg PQ, and the mice in the control group were given intraperitoneal injection of 0.9% saline, twice a week for 8 weeks. Neurobehavioral changes (pole climbing test, swimming test, open field test, tail hanging test, high plus maze test and water maze test) were observed at 4 weeks, 6 weeks and 8 weeks, respectively, and the changes of motor ability, emotion and cognitive function were evaluated. The brain tissue of mice were taken and stained with Hematoxylin-Eosin (HE) to observe the pathological changes of LC. Nissl staining was used to detect the changes of neuronal Nissl bodies in LC. Immunohistochemistry (IHC) staining was used to detect the expression of neuron nuclear antigen (NeuN) , dopamine (DA) neurons and norepinephrine (NE) neuron markers tyrosine hydroxylase (TH) , α-synuclein (α-syn) in substantia nigra (SN) and LC. The expression levels of NeuN, TH and α-syn in the midbrain and brainstem were detected by Western blotting. TUNEL staining was used to detect neuronal apoptosis in LC. Results: Compared with the 4th week of PQ exposure group, the time of pole climbing and swimming immobility were gradually increased, the ratio of open arm residence time of high plus maze test and the number of times of the platform and the residence time of platform quadrant in water maze test were gradually decreased (P<0.05) in the exposure group with the progress of exposure time. The results of HE and Nissl staining showed that the neurons in LC gradually arranged loosely, the nucleus were deeply stained, the cytoplasm was pyknosis, and the number of Nissl bodies gradually decreased (P<0.05) in the exposure group with the progress of exposure time. IHC results showed that the number of NeuN and TH positive cells in SN and LC of mice were gradually decreased, and the positive expression of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. Western blotting results showed that the expression levels of NeuN and TH in the midbrain and brainstem were gradually decreased, and the expression level of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. TUNEL staining showed that the apoptosis rates of neurons in LC were gradually increased (P<0.05) in the exposure group with the progress of exposure time. Conclusion: PQ induces progressive damage in the LC area of PD-like mice, which may be caused by the abnormal accumulation of pathological α-syn in the LC area.

[Preliminary study on time-dependent changes of intestinal tract and brain-gut axis in mice model of Parkinson's disease induced by paraquat].

Objective: To observe the intestinal time-dependent changes in Parkinson's disease (PD) mouse model constructed by intraperitoneal injection of paraquat (PQ) and to establish the brain-gut axis connection initially. Methods: In October 2019, 48 mice were randomly divided into treated group and control groups: treated 4-week (P-4) group, treated 6-week (P-6) group, treated 8-week (P-8) group, control 4-week (C-4) group, control 6-week (C-6) group, and control 8-week (C-8) group. The treated group was injected with 15 mg/kg PQ solution and the control group was injected with 0.9% saline (0.2 ml/20 g) by intraperitoneal injection twice a week. After the initial state (0 weeks) and the treatment at the end of 4, 6 and 8 weeks, the mood changes and motor functions of mice were assessed by neurobehavioral tests (open field test, pole climbing test, tail suspension test and elevated plus maze test) . And the number of fecal pellets for 1 h and water content were calculated to assess the functional status of the gastrointestinal tract. Western blotting experiments were performed to detect the expression levels of α-synuclein (α-syn) and tyrosine hydroxylase (TH) in the nigrostriatal region of the mouse brain, the tight junction markers zonula occludens-1 (ZO-1) and Occludin, the inflammatory markers of integrin αM subunit (CD11b) , inducible nitric oxide synthase (iNOS) , high mobility group box 1 (HMGB1) , interleukin-1ß (IL-1ß) , and the neuronal markers ßⅢ-tubulin and α-syn protein in the colon.Immunohistochemical staining was performed to detect the expression levels of colonic tight junction proteins ZO-1 and Occludin. Immunofluorescence staining was performed to detect the expression levels of TH in the substantia nigra region of the midbrain, and the co-localization of colonic intestine neuronal marker (ßⅢ-tubulin) and Ser129 α-syn in the colonic. Results: Compared with the initial state (0 weeks) and C-8 group, mice in the P-8 group had significantly higher pole climbing test scores and resting time, and significantly lower total active distance, mean active speed, percentage of open arm entry and 1 h fecal instances (P<0.05) . After poisoning, the 1 h fecal water content of model mice first increased and then decreased, the P-4 and P-6 groups were significantly higher than the simultaneous point control group, and the P-8 groups were significantly lower than the initial state (P<0.05) . Compared with control, P-4 and P-6 groups, the expression levels of ZO-1 and Occludin in the P-8 group were significantly decreased (P<0.05) . Compared with control group, the expression levels of CD11b and IL-1ß in the P-4 group were significantly increased (P<0.05) . Compared with control and P-4 group, the expression levels of CD11b, iNOS, HMGB1 and IL-1ß in the P-6 and P-8 groups were significantly increased (P<0.05) . Compared with the control and P-4 groups, the expression levels of ßⅢ-tubulin in the colon of mice in the P-8 group were significantly decreased, and the expression levels of α-syn and Ser129 α-syn were significantly increased (P<0.05) . The expression level of Ser129 α-syn in the colon of model mice was negatively correlated with the expression level of ßⅢ-tubulin (r(s)=-0.9149, 95%CI: -0.9771--0.7085, P<0.001) . Ser129 α-syn and ßⅢ-tubulin co-localization in the colonic intermuscular plexus region increased gradually with the time of exposure. Compared with the control, P-4 and P-6 groups, the expression level of TH in the nigrostriatal region of the brain was significantly decreased, and the expression levels of α-syn and Ser129 α-syn were significantly increased in the P-8 group (P<0.05) . Correlation analysis showed that the relative expression level of Ser129 α-syn in the nigrostriatal region of the brain was negatively correlated with the expression level of TH in the model mice (r(s)=-0.9716, 95% CI: -0.9925--0.8953, P<0.001) . Conclusion: The PD mouse model is successfully established by PQ, and the intestinal function of the model mice is reduced in a time-dependent manner. And on this basis, it is preliminary determined that the abnormal aggregation of α-syn may be an important substance connecting the brain-gut axis.

[Relative factors analysis of visual field defect in advanced primary glaucoma].

Objective: To explore the relative factors of visual field defect in advanced primary glaucoma. Methods: A retrospective case-control study. The data of patients with primary advanced glaucoma who had the central 5 to 10 degrees of the visual field or the temporal peripheral field and were treated at Eye & ENT Hospital of Fudan University from January 2014 to December 2019 were reviewed. The patients were divded into the central visual field group and the temporal peripheral field group according to the type of visual field defect. Statistical analyses of single-factor (Chi square test or independent sample t test) and multivariate logistic regression were performed to analyze the correlation between the remaining visual field and the risk factors including age, gender, left/right eye, type of glaucoma, baseline glaucoma stage, peak intraocular pressure (IOP), mean IOP, number of operations, family history, high myopia, diabetes, hypertension, hypotension and migraine. Results: A total of 287 patients (287 eyes) were included. There were 101 patients [mean age, (61±15) years; 48 males, 53 females] with the central 5 to 10 degrees of the visual field and 186 patients [mean age, (59±17) years; 107 males, 79 females] with the temporal peripheral field. There was no statistically significant difference between the two groups with respect to age, gender, left/right eye, age of onset, number of operations, family history and history of combined systemic diseases (all P>0.05). Primary open-angle glaucoma, chronic primary angle-closure glaucoma (CPACG) and acute primary angle-closure glaucoma were found in 26, 34 and 41 patients, respectively, in the central visual field group, and in 61, 78 and 47 patients, respectively, in the temporal peripheral field group. The baseline glaucoma was in the moderate stage in 30 and 32 patients, and in the advanced stage in 71 and 154 patients, respectively, in the two groups. The peak IOP was (31.94±4.11) mmHg (1 mmHg=0.133 kPa) and (34.58±6.47) mmHg, and the mean IOP was (22.48±3.99) mmHg and (24.01±4.30) mmHg, respectively, in the two groups. High myopia occurred in 5 and 28 patients, respectively, in the two groups. The differences in the type of glaucoma (χ²=7.24), baseline glaucoma stage (χ²=6.04), peak IOP (t=4.22), mean IOP (t=2.96) and high myopia (χ²=6.57) between the two groups were statistically significant (all P<0.05). In the multivariable model, CPACG (OR=2.021, 95%CI: 1.020 to 4.001), higher peak IOP (OR=1.128, 95%CI: 1.038 to 1.226) and high myopia (OR=5.090, 95%CI: 1.556 to 16.651) increased the risks for the progression to the temporal peripheral field. Conclusion: CPACG, higher peak IOP and concurrent high myopia are all relative factors for the progression to the temporal peripheral field in advanced primary glaucoma.

[Identification of Synthetic Cannabinoid New Psychoactive Substances 4F-MDMB-BUTINACA and MDMB-4en-PINACA].

ABSTRACT: Objective To establish a method that combines a series of techniques including Fourier transform infrared spectrum （FTIR）, gas chromatography-mass spectrometry （GC-MS）, high resolution mass spectrometry and nuclear magnetic resonance spectroscopy （NMR） for identification of unknown substances. Methods The unknown samples （off-white powder and yellow crystal） seized in the actual cases were detected by FTIR, GC-MS （methanol as solvent）, high resolution mass spectrometry （methanol as solvent） and NMR （deuterated methanol as solvent）. Results The mass spectrum characteristic ions m/z of the main components in the samples measured by GC-MS were 219 （base peak）, 363, 307, 304, 275, 145, 131 and 213 （base peak）, 357, 301, 298, 269, 185, 171, 145 and 131, respectively. The accurate mass numbers [M+H]+ measured by high resolution mass spectrometry were 364.203 61 and 358.212 34, respectively. The unknown samples were identified as synthetic cannabinoid new psychoactive substances 4F-MDMB-BUTINACA and MDMB-4en-PINACA after data consultation and database retrieval and comparison, combined with infrared analysis and mass spectrometry data analysis, and their structures were confirmed by 1H-NMR. Conclusion The established multi-technology joint identification method can be used to identify 4F-MDMB-BUTINACA and MDMB-4en-PINACA in unknown samples. This method is fast, convenient, accurate, reliable and practical, and can provide reference for the identification of cases involving such substances in the future.

[Identification of New Psychoactive Tryptamines 4-OH-MET and 4-AcO-DMT Using High Resolution Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy].

ABSTRACT: Objective To detect the uncontrolled new psychoactive tryptamines involved in drug-related cases with high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Methods White and brown powder obtained in actual cases were extracted and analyzed by gas chromatography-quadrupole time-of-flight mass spectrometry （GC-QTOF-MS）, ultra-high performance liquid chromatography-linear ion trap quadrupole-orbitrap mass spectrometry （UPLC-LTQ-Orbitrap MS） and 1H-nuclear magnetic resonance spectroscopy （1H-NMR）. Results After detection by GC-QTOF-MS, the components of white powder showed main characteristic fragment ion peaks at m/z 218.141 0 （molecular ion peak）, 72.080 6 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 219.149 4. The main ions in the secondary mass spectrum under the collision-induced dissociation （CID） mode were m/z 160.076 3 and 72.080 8. After detection by GC-QTOF-MS, the components of brown powder showed main characteristic fragment ion peaks at m/z 246.135 7 （molecular ion peak）, 58.065 1 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 247.145 0. The main ions in the secondary mass spectrum under CID mode were m/z 202.087 1, 160.076 3 and 134.060 5. NIST 17 library retrieval and 1H-NMR confirmed that the white powder and brown powder contained new psychoactive tryptamines 4-OH-MET and 4-AcO-DMT, respectively. Conclusion GC-QTOF-MS, UPLC-LTQ-Orbitrap MS and 1H-NMR can be used together to identify unknown new psychoactive substances.

[Untargeted metabolomic analysis of serum samples from children with mycoplasma pneumonia in a hospital in Beijing].

Objective: This study was aimed to analyze the untargeted metabolomics of serum samples from children with mycoplasma pneumonia in a hospital in Beijing. Methods: A total of 50 children with mycoplasma pneumonia as the case group were recruited from Department of Pediatrics, China-Japan Friendship Hospital in Beijing from January 2019 to February 2020, and meanwhile 50 age-and gender-matched heathy children were selected and formed the control group. 2 ml venous fasting blood samples was collected from all children. Serum metabolites were quantified by using the untargeted ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) technique. Unsupervised principle component analysis and (orthogonal) partial least-squares-discriminant analysis were employed to identify differential metabolites between cases and controls. MBRole software was used for pathway enrichment analysis. Results: There were 27 boys and 23 girls in the case group with an average age of (6.0±3.65) years, and the control group consisted of 28 boys and 22 girls with an average age of (6.62±2.64) years. A total of 392 different metabolites were detected. Compared with the control group, 306 metabolites were decreased and 86 increased in case group. Forty-one differential metabolites with variable important in projection (VIP) values larger than 5 and P values less than 0.05 were teased out, and they mainly concentrated on phospholipid. The levels of 38 metabolites were significantly lower in the case group, yet 4 metabolites were significantly higher than that of the control group. Metabolic enrichment analysis showed that different metabolites were related to the biosynthesis of phenylalanine, tyrosine, tryptophan, unsaturated fatty acid, ammonia acyl tRNA and insulin signaling pathway, as well as the metabolism of ABC transporters. Conclusion: The serum untargeted metabolomics differed remarkably between children with mycoplasma pneumonia and healthy children.

[The mechanism of HDAC6 in paraquat-induced autophagy dysfunction of dopaminergic neurons by mediating aggresome-autophagy-lysosomal pathway].

Objective: To explore the mechanism of HDAC6 mediated aggresome-autophagy-lysosome pathway in paraquat-induced autophagy in dopaminergic neurons. Methods: Human neuroblastoma cell (SH-SY5Y cell) was used as model of dopaminergic neurons in vitro. The cells were treated with terminal concentrations of 0, 25, 50, 100, 200 and 400µmol/L PQ for 24 hours, and the cells were induced by 100 µmol/L PQ for different time (0, 12, 24, 36, 48, 60 and 72 h) . Cell viability was detected by CCK-8 assay. The expression levels of HDAC6, α-syn, Dynein IC1/2, LC3, Beclin1, p62 and Lamp-1 were detected by Western blot. Immunofluorescence double-labeling method was used to observe the expression and localization of HDAC6, α-syn, Dynein IC1/2, LC3, Lamp-1 and γ-tubulin in cells. Results: CCK-8 assay showed PQ induced cell survival rate decrease in a time and dose dependent manner (R=-0.950、-0.960, P<0.05) .Western blot showed that compared with control group, the protein levels of HDAC6, α-syn, p62 in PQ-exposed group were significantly increased (P<0.05) , but there was a significant decrease in expression level of the ratio of autophagy-related protein LC3 Ⅱ/LC3 Ⅰ, Beclin1, Dynein IC1/2, Lamp-1in PQ-exposed group (P<0.05) . The results of immunofluorescence double-labeling showed that compared with the control group, the fluorescence signals of HDAC6 and α-syn in the PQ-exposed group increased, and the protein expression level increased, while the fluorescence signals of Dynein IC1/2, LC3, and Lamp-1 decreased. The protein expression level is reduced. HDAC6 gradually accumulates from the diffuse shape to the nucleus; Under normal circumstances, α-syn, Dynein IC1/2, γ-tubulin, LC3, and Lamp-1 are mainly distributed in the cytoplasm. After PQ is infected, they gather in the nucleus and co-localize with HDAC6 in the area around the nucleus. Conclusion: PQ may induce abnormal aggregation of α-syn by inducing HDAC6-mediated aggresome-autophagy-lysosomal pathway disorder.

[Protective effects of taurine on neurons and microglia in Parkinson's disease-like mouse model induced by paraquat].

Objective: To investigate the protective effect of taurine (Tau) on hippocampus, substantia nigra neurons and microglia in paraquat (PQ) -induced Pakinson's disease-like mice. Methods: In April 2019, the specific pathogen free (SPF) C57BL/6 mice (n=36) were randomly divided into control group (NaCl) , Tau control group (150 mg/kg) , PQ exposure group (10 mg/kg PQ group, 15 mg/kg PQ group) , Tau intervention group (Tau+10 mg/kg PQ group, Tau+15 mg/kg PQ group) , respectively. Tau was used in 1 h before PQ administration for consecutive 6 weeks (twice per week) . General and neurobehavioral tests (Traction test, Open field test, Forced Swimming test, Tail suspension test, High plus maze and Object recognition test) were performed to test motor and cognitive function. After neuroethology detection, mice were euthanized and brains were collected. Nissl staining was used to detect the changes of the number and morphology of Nissl bodies in hippocampus and substantia nigra neurons of mice. Immunohistochemistry (IHC) was used to test the levels of neuron marker neuronal nuclei antigen (NeuN) , substantia nigra dopaminergic neuron marker tyrosine hydroxylase (TH) , α-synuclein (α-syn) , microglia markers ionized calcium bindingadaptor molecule-1 (Iba-1) , inducible nitric oxide synthase (iNOS) and interleukin-1ß (IL-1ß) in mice substantia nigra. The coexpression of Iba-1 and TH double-labeling, α-syn and TH double-labeling in mice substantia nigra were measured by immunofluorescence double staining. Results: General behavioral changes such as slow reaction and reduced action occurred in mice of PQ group. Compared with the control group, the scores of Traction test, and the time ratio of new object recognition in the PQ group decreased (P<0.05) , the fixed time of Swimming test and Tail suspension test increased (P<0.05) , the horizontal crawl number and vertical times of Open field test and the ratio of open arm residence time of High plus maze in the 15 mg/kg PQ group decreased (P<0.05) . Compared with the PQ group, the same dose of Tau+PQ group showed increased scores in Traction test (P<0.05) and decreased fixed time of Swimming test and Tail suspension test (P<0.05) . Compared with the 15 mg/kg PQ group, the horizontal crawl number of Open field test and the time ratio of new object recognition increased in the Tau+15 mg/kg PQ group (P<0.05) . Compared with the control group, the PQ group showed a decrease in the number of Nissl body in the hippocampus and substantia nigra (P<0.05) , a decrease in the number of NeuN and TH positive cells in the substantia nigra (P<0.05) , with a large number of α-syn deposition, Iba-1 activation of microglia cells, and an increase in the expression of inflammatory factors (IL-1ß, iNOS) in the hippocampus and substantia nigra (P<0.05) . Compared with the PQ group, the same dose of Tau+PQ group showed the number of Nissl in the hippocampus and substantia nigra was significantly increased (P<0.05) , the number of NeuN and TH positive cells in the substantia nigra was significantly increased (P<0.05) , the expression levels of α-syn, Iba-1 and inflammatory factors (IL-1ß, iNOS) in the substantia nigra were significantly decreased (P<0.05) . Conclusion: Tau could protect PQ-induced degeneration of substantia nigra dopaminergic neurons and hippocampal neuron loss by inhibiting the activation of microglia cells and release of inflammatory factors, and effectively improve the neurobehavioral and brain histopathological changes of PQ-induced PD-like mice.

Identification of the New Psychoactive Substance Dibutylone.

ABSTRACT: Objective To establish a method to identify unknown samples based on combined use of gas chromatography-mass spectrometry （GC-MS）, high resolution mass spectrometry （HRMS） and nuclear magnetic resonance spectrum （NMR） technique. Methods The unknown samples were dissolved in methanol solution containing internal standard SKF525A and detected by GC-MS and HRMS. The mixed samples were separated and purified by silica gel column chromatography, and then dissolved in methanol-d4 solution for structural analysis of 1H nuclear magnetic resonance spectroscopy （1H NMR）. Results The characteristic fragment ions （m/z） were 86.1 （base peak）, 71.2, 121.1, and 149.0, and the accurate mass number of molecular ion peak was measured by HRMS to be 236.128 89. By combined use of data analysis and database comparison, a new psychoactive substance of the cathinone class, Dibutylone, was detected in the sample, and the sample also contained a small amount of caffeine. The sample was purified, then identified using 1H NMR, and was further confirmed to be Dibutylone. In addition, the GC-MS retention time and characteristic fragment ions of the main components of the sample were consistent with those of Dibutylone reference material. Conclusion The method established in this study can be used for the identification of Dibutylone in mixed samples.

Colonic pressure data processing based on independent component analysis.

The Colonic manometry is an important technique to evaluate human colonic motor functions, which are critical for doctors to understand the pathology of intestinal diseases like slow transit constipation (STC) and colonic inertia (CI). However, in the obtained pressure signals, several patterns of colonic motor activities as well as noises mixed together, which made it difficult to observe the information people really needed. In this article, a new method was proposed to extract patterns of colonic motility from the mixed signals, so that researchers could study them thoroughly. Colonic pressure recordings from 26 volunteers were obtained by the water-perfused manometry catheters. Then independent component analysis (ICA) was introduced, which successfully separated colonic motility patterns and noises into four independent components. And according to the rhythm of contractions examined by ICA, subjects' colonic motility could be divided into three types: regular rhythm (12 subjects), slow rhythm (8 subjects) and disordered (6 subjects), which exactly accorded with their original diagnosis.

Non-invasive method to detect and locate haemorrhagic focus of GI tract.

Traditional diagnostic methods do not work well for gastrointestinal bleeding, and location of the haemorrhagic focus is even more difficult. Here a novel method with a microelectronic system is presented effectively to detect and locate the haemorrhagic focus. The outstanding advantage of this method is that it is non-invasive. The composition and working principles of the system are described in detail. Key to this system is the development of a haemoglobin (Hb) sensor. Through MEMS technology a micro haemoglobin sensor is developed and fabricated. The sensor's response performance, pH dependence and temperature dependence are tested experimentally. Initial tests suggest that the device is sufficiently sensitive to Hb concentration and insensitive to pH and temperature changes in the working range. As a result, the system has potential for development of an advanced instrument for detecting, localizing and treating gastrointestinal bleeding.

An earthworm-like microrobot for colonoscopy.

Miniature robotics for colonoscopy has become a hot research topic with the development of minimally invasive surgery (MIS). In this paper, a novel microrobot for colonoscopy that operates based on a simulation of the squirming motion of the earthworm is described. The robot uses a unique driving unit called a linear electromagnetic driver. The prototype measures 9.5 mm in diameter and 120 mm in length. It is driven by a linear direct current (DC) motor designed and manufactured by the authors. This paper describes the prototype, locomotion principle, and control system in detail. It then describes two models that were built to study the robot's ability to move in the viscoelastic colon environment. A slepe model of motion was developed and some mathematical evaluations of locomotion conditions were conducted. Experiments to test the creeping ability of the prototype on a slope were performed to verify these expressions. From the viscoelastic model relative to acting force between the robot and the colon, a transcendent equation about locomotive efficiency of the critical squirm step was deduced and solved to instruct the design of the robot. Last, in vitro experiments in the fresh colon of a pig were performed. The results show that this kind of microrobot can propel itself freely and reliably in the soft viscoelastic colon. Finally, future areas of research are noted.