Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells / 中国结合医学杂志

OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

A Conformational Restriction Strategy for the Control of CRISPR/Cas Gene Editing with Photoactivatable Guide RNAs.

The CRISPR/Cas system is one of the most powerful tools for gene editing. However, approaches for precise control of genome editing and regulatory events are still desirable. Here, we report the spatiotemporal and efficient control of CRISPR/Cas9- and Cas12a-mediated editing with conformationally restricted guide RNAs (gRNAs). This approach relied on only two or three pre-installed photo-labile substituents followed by an intramolecular cyclization, representing a robust synthetic method in comparison to the heavily modified linear gRNAs that often require extensive screening and time-consuming optimization. This tactic could direct the precise cleavage of the genes encoding green fluorescent protein (GFP) and the vascular endothelial growth factor A (VEGFA) protein within a predefined cutting region without notable editing leakage in live cells. We also achieved light-mediated myostatin (MSTN) gene editing in embryos, wherein a new bow-knot-type gRNA was constructed with excellent OFF/ON switch efficiency. Overall, our work provides a significant new strategy in CRISPR/Cas editing with modified circular gRNAs to precisely manipulate where and when genes are edited.

Bioinformatics analysis of ferroptosis in spinal cord injury.

Ferroptosis plays a key role in aggravating the progression of spinal cord injury (SCI), but the specific mechanism remains unknown. In this study, we constructed a rat model of T10 SCI using a modified Allen method. We identified 48, 44, and 27 ferroptosis genes that were differentially expressed at 1, 3, and 7 days after SCI induction. Compared with the sham group and other SCI subgroups, the subgroup at 1 day after SCI showed increased expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 and the oxidative stress marker malondialdehyde in the injured spinal cord while glutathione in the injured spinal cord was lower. These findings with our bioinformatics results suggested that 1 day after SCI was the important period of ferroptosis progression. Bioinformatics analysis identified the following top ten hub ferroptosis genes in the subgroup at 1 day after SCI: STAT3, JUN, TLR4, ATF3, HMOX1, MAPK1, MAPK9, PTGS2, VEGFA, and RELA. Real-time polymerase chain reaction on rat spinal cord tissue confirmed that STAT3, JUN, TLR4, ATF3, HMOX1, PTGS2, and RELA mRNA levels were up-regulated and VEGFA, MAPK1 and MAPK9 mRNA levels were down-regulated. Ten potential compounds were predicted using the DSigDB database as potential drugs or molecules targeting ferroptosis to repair SCI. We also constructed a ferroptosis-related mRNA-miRNA-lncRNA network in SCI that included 66 lncRNAs, 10 miRNAs, and 12 genes. Our results help further the understanding of the mechanism underlying ferroptosis in SCI.

Application value of biofluid-based biomarkers for the diagnosis and treatment of spinal cord injury.

Recent studies in patients with spinal cord injuries (SCIs) have confirmed the diagnostic potential of biofluid-based biomarkers, as a topic of increasing interest in relation to SCI diagnosis and treatment. This paper reviews the research progress and application prospects of recently identified SCI-related biomarkers. Many structural proteins, such as glial fibrillary acidic protein, S100-ß, ubiquitin carboxy-terminal hydrolase-L1, neurofilament light, and tau protein were correlated with the diagnosis, American Spinal Injury Association Impairment Scale, and prognosis of SCI to different degrees. Inflammatory factors, including interleukin-6, interleukin-8, and tumor necrosis factor α, are also good biomarkers for the diagnosis of acute and chronic SCI, while non-coding RNAs (microRNAs and long non-coding RNAs) also show diagnostic potential for SCI. Trace elements (Mg, Se, Cu, Zn) have been shown to be related to motor recovery and can predict motor function after SCI, while humoral markers can reflect the pathophysiological changes after SCI. These factors have the advantages of low cost, convenient sampling, and ease of dynamic tracking, but are also associated with disadvantages, including diverse influencing factors and complex level changes. Although various proteins have been verified as potential biomarkers for SCI, more convincing evidence from large clinical and prospective studies is thus required to identify the most valuable diagnostic and prognostic biomarkers for SCI.

Effects of 5-Aza-2′-deoxycytidine on proliferation of human breast cancer cell line Hs578T and methylation of PRDM10 gene / 天津医药

Objective To investigate effects of 5-Aza-2′-deoxycytidine (5-Aza-CdR) on proliferation of human breast cancer cell line Hs578T,and the methylation status of PRDM10 gene in vitro in this cell line.Methods The human breast cancer cell line Hs578T was cultured with 1,3 and 5 μmol/L DNA methylation inhibitor 5-Aza-CdR respectively, and untreated cells were used as control.Cell proliferation was detected by MTT assay.Methylation-Specific PCR(MSP)was used to detect the methylation status of PRDM10 gene. The mRNA and protein expression levels of PRDM10 gene were detected by RT-PCR and Western blot assay. Results MTT results showed that the higher the concentration of 5-Aza-CdR,and the longer the treatment time,the more significant inhibitory effect on the proliferation of Hs578T cells.Compared with the control group(0 μmol/L),the proliferation of Hs578T was significantly inhibited after the treatment for 72 h in the 1 μmol/L group, and for 48 h in the 3 μmol/L and 5 μmol/L groups (P<0.05). MSP results showed that the higher the concentration of 5-Aza-CdR,the more significant demethylation of PRDM10.Results of RT-PCR and Western blot showed that the higher the concentration of 5-Aza-CdR, the higher the expression levels of mRNA and protein in PRDM10 (P<0.05).Conclusion 5-Aza-CdR could inhibit the cell proliferation of Hs578T,which might be related to the demethylation of PRDM10 gene in the cells.

Acute coronary syndrome in women below 50 years of age: risk factors and clinical and angiographic features / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the risk factors and angiographic features of acute coronary syndrome (ACS) in women below 50 years of age.</p><p><b>METHODS</b>A total of 131 women with ACS aged 50 years or younger were enrolled in this study as the case group, with another 425 women aged below 50 years with normal coronary angiographic findings as the control group. The risk factors and clinical and coronary angiographic features of ACS were analyzed.</p><p><b>RESULTS</b>Compared with the control group, significantly higher frequencies of dyslipidemia, hypertension (especially diastolic hypertension), diabetes, or a positive family history for coronary artery disease (CAD) were found in ACS group (P<0.05) . The proportion of post-menopausal women and the menopausal ages were similar between the two groups (P>0.05), but the mean diastolic pressure was significantly higher in ACS group than in the control group (P<0.05). Among the menopausal women, the conventional risk factors for ACS were similar between the two groups with the exception of family history CAD, which was more frequent in ACS group. Serum total cholesterol and triglyceride levels were significantly higher in ACS group than in the control group (P<0.05), but the levels of high- and low-density lipoprotein cholesterol levels were comparable between them. Positive findings of urine protein were more frequent in ACS group. In ACS group, 54.2% of the patients had a single diseased artery, 29.6% had more than one diseased artery, and 16.0% had slightly diseased or even normal coronary arteries; the lesion was found most commonly in the left anterior descending artery.</p><p><b>CONCLUSION</b>In women with ACS below 50 years of age, the risk factors of ACS included the conventional risk factors of CAD and a positive finding of urine protein. Menopause is not associated with an increased incidence of ACS. A substantial portion of these ACS patients can have slightly diseased and even normal coronary arteries.</p>

The pump flow test of a percutaneous left ventricular assist device / 医用生物力学

Objective To design a percutaneous left heart assist device (blood pump) which can be used in critical cardiovascular diseases. Methods According to the aerofoil theory, a percutaneous left ventricular assist device was designed. The flow produced by blood pumps with 3 different design parameters (rotation angle of the blade, distance of the outlet from the blade, length of the outlet ) was measured so as to choose the optimal design of the blood pump. Results The flow was measured with a simple flow measurement device. When the blood pump was designed to adopt a single blade with the rotation angle of 720°, or the distance between the outlet and the blade was 0 mm, or the length of the outlet was 4 mm, the flow of the blood pump was the maximum. Conclusions To choose the design parameters that produce the maximum flow can contribute to manufacture a percutaneous left ventricular assist device with the function of pumping in vitro, which will provide a theoretical and data support for the eventual development of the percutaneous left ventricular assist device in clinic.

A new technique for bilateral angiography in a single radial access / 中华心血管病杂志

<p><b>OBJECTIVE</b>To develop a new technique of bilateral angiography in a single radial access (BASiRalA) which can reduce a puncture site.</p><p><b>METHODS</b>From March 2011 to February 2012, 13 cases of coronary heart disease patients with chronic total occlusion (CTO) were treated (6 CTOs in right coronary artery and 7 in left anterior descending artery). All patients underwent percutaneous coronary intervention (PCI) via the right radial artery access and 6 F guiding catheters were delivered to the diseased artery. Once the wires crossed the CTO lesions and were uncertain if the wires were in true lumen or not, BASiRalA was performed. The Finecross microcatheters were advanced out of the 6 F guiding catheter, then withdraw 6F guiding catheter to the opening of diseased artery, the soft wires were manipulated into the middle portion of opposite coronary artery. After that, the microcatheters were advanced to this segment or the branches relative to the collateral vessels connected with CTOs. After pulling out the wires, microcatheter injections can be performed for contralateral angiography. BASiRalA related complications were observed after the procedure.</p><p><b>RESULTS</b>BASiRalA technique was applied to 13 CTOs and 10 procedures succeeded (76.92%). BASiRalA failed in 3 cases and the wires and microcatheters could not be advanced to the opposite coronary arteries within 20 minutes. Alternatively, contralateral angiography via femoral arteries was performed in these 3 patients. The average time of BASiRalA technique was 7 (5 - 13) minutes and the shortest time of wires crossing to the opposite coronary artery was 5 seconds. There was no procedure induced complication during procedure or post procedure.</p><p><b>CONCLUSION</b>BASiRalA technique is feasible in treating CTO patients by PCI.</p>

Electrophysiologic characteristics of the Crista terminalis and implications on atrial tachycardia in rabbits.

The objective of this study was to evaluate the electrophysiologic characteristics of Crista terminalis (CT) and their implication in the pathogenesis of atrial tachycardia in rabbits. For this purpose, 27 New Zealand rabbits were used. Using standard glass microelectrode technique, cellular action potentials (APs) of CT and pectinate muscle (PM) were recorded in normal Tyrode's perfusion and Tyrode's perfusion with 4 µM isoproterenol. Longitudinal conduction velocity (V(L)) and transverse conduction velocity (V(T)) of CT were measured. As our data show, CT tissue had a trend of spontaneous phase IV depolarization. Conduction anisotropy (V(L)/V(T)) of CT was 4.53 ± 0.91. The duration of the AP of CT was longer than that of PM cells. APD(20) and APD(90) for CT were 28.1 ± 3.5 and 145.3 ± 7.1 ms; and for PM cells were 21.8 ± 4.1 and 125.3 ± 6.3 ms, respectively (all P values < 0.01). The early and delayed action depolarizations were recorded after isoproterenol perfusion. A fast paroxysmal irregular rhythm was recorded which could be arrested by 0.1 mmol/l Isoptin. It was, therefore, concluded that the latent autorhythmicity, trigger activity, and conduction properties of CT might provide the electrophysiologic basis for the occurrence and sustenance of atrial arrhythmia.

Retrograde percutaneous recanalization of chronic total occlusion of the coronary arteries via epicardial coronary collateral artery in 5 patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>to explore the feasibility of percutaneous recanalization by retrograde approach via epicardial collaterals.</p><p><b>METHODS</b>retrograde percutaneous coronary intervention (PCI) via epicardial collaterals was performed in 5 patients with previously failed antegrade PCI from April 2009 to November 2009. 7 F guiding catheters were engaged in donor artery. Hydrophilic wires and microcatheters were crossed to the distal ends of chronic total occlusion (CTO) lesions via epicardial collaterals. Four retrograde wires were exchanged into stiffer wires and further crossed the CTO, eventually went into the 6 F antegrade guiding catheters and were jailed by a 2.5 mm balloon. After dilatations of retrograde balloons, the lesions were crossed by antegrade wires, and finalized by conventional PCI method. One case was recanalized with retrograde wire trapping technique and another case was recanalized by reverse CART technique.</p><p><b>RESULTS</b>the epicardial collaterals were reached from left anterior descending branch (LAD) to distal right coronary artery (RCA) via apex in 3 patients, from left circumflex branch via left atrium branch to posterior descending artery and RCA in 1 patient and from obtuse marginal artery to diagonal artery and LAD in 1 patient. CTO was successfully recanalized and stents were implanted in 4 patients and failed in 1 patient despite successful wire positioning to the distal end of CTO. There was no procedure-induced cardiovascular event in all cases.</p><p><b>CONCLUSIONS</b>epicardial collaterals may not be used as a routine route in retrograde approach PCI due to the potential risk of myocardial rupture and pericardial tamponade. In some cases with unavailable or unsuitable septal collaterals, epicardial collaterals may be used as an alternative route for CTO recanalization.</p>

Effect of CS(2) occupational exposure on personality and intelligence / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of CS(2) occupational exposure on thumbprint and intelligence.</p><p><b>METHODS</b>According to the monitoring results of CS(2) concentration, which were got at various workplace in chymic fiber factory, the workers were divided into three groups including the low-concentration group (TWA < 5 mg/m(3)), the high-concentration group (TWA >or= 5 mg/m(3)) and the control group. The method of cluster sampling was used respectively. 139, 129 and 327 people were taken at random from three groups and they were given thumbprint and intelligence examinations through following three methods, including MMPI, SCL-90 and SPM.</p><p><b>RESULTS</b>MMPI test showed that Hy, Pa, Pt, Sc positive rates in the low-concentration group were 7.19%, 2.16%, 26.62% and 10.07%, Hs, D, Hy, Pa, Pt, Sc, Ma, Si positive rates in the high-concentration group were 32.56%, 8.53%, 9.30%, 24.81%, 2.33%, 42.64%, 15.50%, 5.43% and 6.20%. There was a significant difference with the control group (Hs, D, Hy, Pd, Pa, Pt, Sc, Ma, Si was 14.07%, 2.14%, 2.14%, 14.07%, 0.00%, 17.74%, 3.67%, 1.22%, 1.22% respectively). The differences of Hs, Pt positive rates between high-concentration and low-concentration group were significantly. SCL-90 showed that the total positive rate in the low concentration and the high concentration groups was 15.8% and 20.2%. The positive rate of the basic factors were significantly different among the low-concentration group, the high concentration group and the control group while there was no significant difference in the positive rate between the high concentration and low concentration group. SPM test found that the positive rates of the intelligence in the low concentration group and the high concentration group were 35.1% and 35.7% respectively and the control group (15.1%) was significantly different from low-concentration and high concentration group. Moreover, there was no obvious difference between high-concentration and the low-concentration group. The intelligence damage was associated with the length of CS(2) occupational exposure and the correlation coefficient had statistical significance.</p><p><b>CONCLUSION</b>The low-concentration CS(2) occupational exposure could affect personality and intelligence, and the degree of this influence is associated with the length of CS(2) occupational exposure.</p>

Study of medical instrument sterilization based on plasma / 中国医疗器械杂志

In this paper, the generation of the plasma, its principle and its application in the sterilization of medical instruments are described. The relation between discharge voltage and air pressure, frequency, electrode distance is analysed and discussed in glow discharge so as to get a new formula of discharge voltage in the whole frequency range and a design has been made to produce a plasma RF power. The result of the study has a great significance to the application of plasma sterilization of medical instruments.

Electrophysiology of cardiocytes in ligament of Marshall of canine / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate electrophysiology of cardiocytes in ligament of Marshall.</p><p><b>METHODS</b>The single cardiocytes obtained from ligament of Marshall were direct observed under inverted microscope. The cardiocyte action potential and current density of I(Na), I(Ca), L, I(to), I(K) and I(K1) were researched by whole-cell patch-clamp techniques.</p><p><b>RESULTS</b>There were two different cardiomyocytes in ligament of Marshall, one was rod shape, the other was short-rectangle shape. The short-rectangle myocyte was short and thick; the rod myocyte was long and thin. The short-rectangle myocyte was more than rod myocyte. The length/width rate of short-rectangle myocyte was less than that of rod myocyte (2.99 +/- 0.95 vs 12.05 +/- 2.41, P < 0.01). The action potential of ligament myocytes was similar to fast responsive cells. The action potential amplitude (APA) and duration (APD) of short-rectangle cells were less than those in rod cells. APA (mV), APD(50) (ms) and APD(90) (ms) were respectively 80.02 +/- 3.68 vs 91.72 +/- 7.56, 69.62 +/- 6.33 vs 83.14 +/- 3.66 and 107.55 +/- 4.25 vs 144.00 +/- 5.15, P < 0.05. The ion current density of I(Na), I(Ca), L, I(to), I(K1) was different between the two kind cells.</p><p><b>CONCLUSIONS</b>There are two different cardiocytes in ligament of Marshall. The action potential and ion current density of I(Na), I(Ca), L, I(to), I(K1) are different between the two kind cardiocytes.</p>