Effects of Individualized Gait Rehabilitation Robotics for Gait Training on Hemiplegic Patients: Before-After Study in the Same Person.

Background: Lower-limb exoskeleton robots are being widely used in gait rehabilitation training for patients with stroke. However, most of the current rehabilitation robots are guided by predestined gait trajectories, which are often different from the actual gait trajectories of specific patients. One solution is to train patients using individualized gait trajectories generated from the physical parameters of patients. Hence, we aimed to explore the effect of individual gaits on energy consumption situations during gait rehabilitation training for hemiplegic patients with lower-limb exoskeleton robots. Methods: A total of 9 unilateral-hemiplegic patients were recruited for a 2-day experiment. On the first day of the experiment, the 9 patients were guided by a lower-limb exoskeleton robot, walking on flat ground for 15 min in general gait trajectory, which was gained by clinical gait analysis (CGA) method. On the other day, the same 9 patients wore the identical robot and walked on the same flat ground for 15 min in an individualized gait trajectory. The main physiological parameters including heart rate (HR) and peripheral capillary oxygen saturation (SpO2) were acquired via cardio tachometer and oximeter before and after the walking training. The energy consumption situation was indicated by the variation of the value of HR and SpO2 after walking training compared to before. Results: Between-group comparison showed that the individualized gait trajectory training resulted in an increase in HR levels and a decrease in SpO2 levels compared to the general gait trajectory training. The resulting difference had a statistical significance of p < 0.05. Conclusion: Using individualized gait guidance in rehabilitation walking training can significantly improve energy efficiency for hemiplegic patients with stroke.

Triptolide inhibits angiogenesis in microvascular endothelial cells through regulation of miR-92a.

Atherosclerosis is one common chronic inflammatory disease in which angiogenesis is involved. Here we established an in vitro cell model of angiogenesis made by human dermal microvascular endothelial cells (HMEC-1) and work to investigate the role of triptolide (TPL) in this model. To induce angiogenesis, HMEC-1 cells were cultured in Matrigel-conditioned medium. The ratio of tubes to nucleus was detected. To evaluate angiogenesis, Western blot assay was carried out to detect endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor receptor-2 (VEGFR2) and VEGF. Cell counting kit-8 was utilized to estimate the viability of HMEC-1 cells. microRNA (miR)-92a was analyzed by qRT-PCR. The targeting relationship between integrin subunit alpha 5 (ITGA5) and miR-92a was verified through luciferase activity assay. The effects of ITGA5 on signaling transducers (ERK, PI3K, and AKT) in a phosphorylated form were valued using Western blot method. After stimulated by TPL, LY294002 and PD98059, the alteration in phosphorylation of the signaling transducers was evaluated by Western blot assay. The ratio of tubes to nucleus and angiogenesis related factors were increased with the delaying of culture time. TPL decreased the expression of angiogenesis factors. Furthermore, miR-92a was upregulated by TPL and miR-92a silence upregulated angiogenesis factors. In addition, TPL decreased ITGA5 which was proved as a target of miR-92a. ITGA5 overexpression resulted in the abundance of angiogenesis factors while ITGA5 silence led to the opposite results. Meanwhile, ITGA5 overexpression increased phosphorylation of ERK, PI3K and AKT while ITGA5 silence reversed the trend. TPL (as an anti-angiogenesis agent) suppressed angiogenesis by upregulating miR-92a, and miR-92a-mediated down-regulation of ITGA5 blocked the signaling transduction of ERK and PI3K/AKT pathways.

Administration of losartan improves aortic arterial stiffness and reduces the occurrence of acute coronary syndrome in aged patients with essential hypertension.

BACKGROUNDS AND AIMS: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blocker losartan is potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of losartan in aged patients with essential hypertension are not entirely investigated. METHODS: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension. RESULTS: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared with patients without essential hypertension. Logistic regression analysis indicated that age, hypertension duration, and losartan treatment are risk factors of arterial stiffness. In a perspective study, long-term administration of losartan (50 mg/d) remarkably reduced PWV in aged patients with essential hypertension. In a longitudinal study, PWV is an independent predictor of the occurrence of acute coronary syndrome (ACS) in elderly patients with essential hypertension by using multivariate analysis. Further, the ACS occurrence was reduced by long-term administration of losartan in aged patients with essential hypertension, compared with the old hypertensive patients without taking losartan. CONCLUSION: Losartan treatment is a negative risk factor of arterial stiffness and reduces the risk of ACS in aged patients with essential hypertension.

Erratum: Fluvastatin inhibits cardiomyocyte apoptosis after myocardial infarction through Toll pathway.

[This corrects the article DOI: 10.3892/etm.2018.6297.].

Fluvastatin inhibits cardiomyocyte apoptosis after myocardial infarction through Toll pathway.

The present study intended to investigate the effect of fluvastatin on cardiomyocyte apoptosis after myocardial infarction in rats. Eighty myocardial infarction rat models were established and randomly divided into 4 groups (n=20): experimental group (n=20) was given fluvastatin treatment; sham operation group (n=20) and normal control group (n=20) were given saline. The dose of fluvastatin was 20 mg/(kg·d), and irrigation gavage was given for 1 week. Western blot analysis and reverse transcription-quantitative PCR (RT-qPCR) were used to detect the expression of TLR4 mRNA and protein in cardiomyocytes. TUNEL method was used to detect the apoptosis of cardiomyocytes. After fluvastatin treatment for 1 week, RT-qPCR found that compared with myocardial infarction group, the TLR4 mRNA expression of fluvastatin treatment group and normal control group was significantly increased, and the differences between groups were a statistically significant difference (P<0.05). Western blot analysis showed that compared with the myocardial infarction group, the expression of TLR4 protein in normal control group, sham operation group and fluvastatin treatment group were significantly decreased, and they all were statistically significant (P<0.05). TUNEL method found that compared with the myocardial infarction group, the fluvastatin treatment group could significantly reduce the apoptosis of cardiomyocytes (19.2±3.8%), and the difference was statistically significant (P<0.05). Fluvastatin can inhibit myocardial infarction and decrease cardiomyocyte apoptosis by increasing the expression of TLR4-like receptor.

Effects of remote ischemic preconditioning on contrast induced nephropathy after percutaneous coronary intervention in patients with acute coronary syndrome.

OBJECTIVE: The aim of this study was to explore the clinical effects of remote ischemic preconditioning (RIPC) on contrast-induced nephropathy after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). PATIENTS AND METHODS: The study was a single-center, prospective, randomized, controlled study. A total of 161 patients with ACS and the rate of estimate glomerular filtration (eGFR) 15 to 70 mL/min/1.73 m2 undergoing PCI were randomly assigned to RIPC group (induced by 4 times of 5-minute inflations of a blood pressure cuff to 200 mmHg around the upper arm, followed by 5-min intervals of reperfusion at 1 hour before PCI therapy) or control group (an uninflated cuff around the arm). Successful completion of the PCI eventually included 107 cases of patients, including 50 cases in the RIPC group and 57 cases in the control group. The level of serum creatinine (Scr), CystatinC (CysC), blood neutrophil gelatinase-associated lipocalin (NGAL), eGFR were measured in all patients at 6 AM before the day of PCI, and 4-hour NGAL, 24-hour CysC, 72-hour Scr, and eGFR after PCI in the 2 groups. The incidence of major adverse events in the kidney (including the incidence of CIN, the need for dialysis, or renal replacement therapy after using contrast agent) and the composite endpoint of cardiovascular events were recorded at 6 months after PCI. RESULTS: There were no statistically significant differences in baseline indicators between the 2 groups. Scr, CysC, and blood NGAL levels and the incidence of CIN in patients with RIPC group were significantly lower than those form the control group after PCI (P < .05), but there were no significant differences between the average value of eGFR and occurrence of Major cardiovascular events in the postoperative 6 months (P > .05). CONCLUSIONS: RIPC can reduce PCI-related CIN and protect renal function in patients with ACS. The benefits of these patients by RIPC may be related to the reduction of the NGAL and CysC.

NPR-C gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: a multicenter study.

To find a new locus that confers significant susceptibility to CAD in Chinese Han population, a genome-wide association study in 200 "extreme individuals" from a Shandong cohort and a pathway-based candidate gene study from a Shanghai cohort (293 CAD/293 controls) were simultaneously performed. Amongst them, 13 SNPs associated with CAD were selected to conduct validation and replication studies in additional 3363 CAD patients and 3148 controls. A novel locus rs700926 in natriuretic peptide receptor C (NPR-C) was identified in Shandong and Hubei cohorts. Then rs700926 and other nine tag SNPs were genotyped in four geographically different populations (Shandong, Shaanxi, Hubei and Sichuan cohorts), and 6 SNPs (rs700926, rs1833529, rs2270915, rs17541471, rs3792758 and rs696831) showed stronger association with CAD, regardless of single or combined analysis. We further genotyped rs2270915 and 10 additional tag SNPs in a central China cohort and identified rs12697273 and rs10066436 as the loci associated with CAD. All these positive associations remained significant after adjustment for traditional risk factors of CAD. NPR-C gene SNPs significantly contribute to CAD susceptibility in the Chinese Han population.

Effects of Tongxinluo on myocardial fibrosis in diabetic rats.

BACKGROUND: The aim of this study was to explore the effect of Tongxinluo on myocardial fibrosis in diabetic rats and its possible mechanism of action. METHODS: Diabetic rat models were established and then divided into three groups: control, diabetes, and Tongxinluo groups. Heart function and myocardial interstitial collagen volume fraction were investigated, and the protein and mRNA expression levels of transforming growth factor beta 1 (TGF-ß1), Smad3, and Smad7 were measured. RESULTS: Heart function was clearly abnormal in the diabetes group compared with that in the control group, and the collagen volume fraction and mRNA expression levels of TGF-ß1 and Smad3 were higher. However, the protein and mRNA expression levels of Smad7 were lower. In the Tongxinluo group, it was observed that these indicators were improved. CONCLUSION: Tongxinluo was effective for the prevention and treatment of myocardial fibrosis in diabetic rats. It probably mediates the expressions of TGF-ß1, Smad3, and Smad7 in rat cardiomyocytes to reduce the occurrence of myocardial fibrosis in diabetic rats.

HLA Class I Expressions on Peripheral Blood Mononuclear Cells in Colorectal Cancer Patients.

OBJECTIVE: To investigate the expression change of human leukocyte antigen (HLA) class I on human peripheral blood mononuclear cells (PBMCs) at both mRNA and protein levels, and to evaluate its roles in the development of colorectal cancer (CRC). METHODS: In the present study, 50 patients with CRC, 35 patients with benign colorectal lesion and 42 healthy volunteers were enrolled. Expression levels of HLA class I mRNA and protein were determined using real-time quantitative reverse transcription PCR (RT-PCR) and flow cytometry analysis, respectively. RESULTS: The expression levels of HLA class I mRNA and proteins were not influenced by age and gender. The relative ratios of HLA class I mRNA were 0.99±0.27 in healthy controls, 0.76±0.19 in benign patients, and 0.48±0.21 in CRC patients. Mean fluorescence intensities of HLA class I were 145.58±38.14 in healthy controls, 102.05±35.98 in benign patients and 87.44±34.01 in CRC patients. HLA class I on PBMCs was significantly down-regulated at both mRNA and protein levels in patients with stage III and IV CRC. CRC patients with lymph node metastasis also showed a decreased HLA class I expression at protein level. CONCLUSION: HLA class I expressions on PBMCs are associated with staging of CRC and lymph node metastasis. Monitoring the expression of HLA class I on PBMCs may provide useful information for diagnosis and metastasis judgement of CRC.

Down-regulation of human leukocyte antigens class I on peripheral T lymphocytes and NK cells from subjects in region of high-incidence gastrointestinal tumor.

BACKGROUND: Many types of human tumors can suppress the immune system to enhance their survival. Loss or down-regulation of human leukocyte antigens (HLA) class I on tumors is considered to be a major mechanism of tumor immune escape. Our previous studies found that HLA class I on peripheral-blood mononuclear cells was significantly lower in gastric cancer patients. The present study made an analysis of HLA class I expression on peripheral-blood T lymphocytes and NK cells from subjects of Lijiadian village, a village with high-incidence gastrointestinal tumor. METHODS: A total of 181 villagers from Lijiadian village and 153 normal controls from the Department of Health Examination Center were enrolled in this study. Using a multi-tumor markers detection system, these villagers were divided into two groups: high-risk group (tumor markers positive group) and low-risk group (tumor markers negative group). The percentage of T lymphocytes and NK cells and levels of HLA class I on their surface were determined in these subjects by flow cytometry. RESULTS: Percentages of T lymphocytes and NK cells in peripheral-blood mononuclear cells did not vary with age. The expression level of HLA class I on peripheral T lymphocytes and NK cells was not affected by age or gender, but was significantly down-regulated in Lijiadian villagers (P < 0.05), especially on the surface of NK cells (P < 0.01). Compared with the low-risk group, there was a significant reduction of HLA class I on peripheral T lymphocytes (P < 0.05) and NK cells (P < 0.05) in the high-risk group. CONCLUSIONS: HLA class I on peripheral T lymphocytes and NK cells may be involved in tumorigenesis and development of gastrointestinal tumor, and understanding their changes in expression may provide new insights into the mechanism of tumor immunity.

Modulation of NRF2 and UGT1A expression by epigallocatechin-3-gallate in colon cancer cells and BALB/c mice.

BACKGROUND: Green tea is an important source of flavonoids in human diets and epidemiological data correlate green tea consumption with a reduced cancer risk. Given its complicated properties at effective concentrations, we put epigallocatechin-3-gallate (EGCG) that previously reported on its anti-proliferative activities against several cancer cell lines on our research agenda to further examine the mechanism of its chemopreventive potential. METHODS: RNA interference (RNAi) expression vector pSilencer 3.1-H1 was used to construct recombinant nuclear factor erythroid 2 related factor 2 (Nrf2)-targeting RNAi plasmids. EGCG (5 microg/ml) was added into the culture fluid of cells before and after transfection. RT-PCR and Western blotting were used to detect the expression of uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A in cells. Forty male BALB/c mice were assigned to four groups: a normal unexposed control and three groups treated with varying doses of EGCG. Four weeks later, the mice were sacrificed, and their colon tissues were subjected to mRNA and protein expression of Nrf2 and UGT1A via RT-PCR and Western blotting analysis. RESULTS: EGCG up-regulated the expression of Nrf2 and increased the level of UGT1A in cells. The blockade of Nrf2 activity via RNA intervention largely attenuated the induction of UGT1A expression by EGCG. In mice, the mRNA and protein levels of Nrf2 and UGT1A detected by RT-PCR and Western blotting increased (both P < 0.05 compared with the control). This increase in Nrf2 expression also had a positive correlation with an increased UGT1A expression. CONCLUSIONS: EGCG mediated its effect in part by inducing the NRF2 signaling pathway and increasing UGT1A expression. Both in vitro and in vivo studies demonstrated the role of NRF2 and UGT1A expression in the potential use of EGCG as a possible chemopreventive agent and supported further study of EGCG for cancer treatment.

Anti-tumor effects of polybutylcyanoacrylate nanoparticles of diallyl trisulfide on orthotopic transplantation tumor model of hepatocellular carcinoma in BALB/c nude mice.

BACKGROUND: Hepatocellular carcinoma (HCC) ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies based on the allicin as a potential chemopreventive analog although is in its infancy at the present time, may have a significant role in the future management of HCC. Diallyl trisulfide (DATS) is a natural compound derived from garlic. In this study, we investigated the inhibitory effects of hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide (DATS-PBCA-NP) on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice. METHODS: DATS-PBCA-NP were detected by transmission electron microscope (TEM) and high-performance liquid chromatography (HPLC). The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mice liver. Successful models (n = 29) were divided into 4 groups: normal saline (NS), empty nanoparticles (EN), DATS and DATS-PBCA-NP were intravenously administered to the mice respectively for 2 weeks. In vivo antitumor efficacy was evaluated by the measurement of tumor volume. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay and protein levels of apoptosis and cell proliferation proteins by immunoblotting in tumor tissues were performed to elucidate the possible mechanism. RESULTS: DATS-PBCA-NP possessed smooth and round appearance, dispersed well, and released in vitro in accord with double phase kinetics model. DATS-PBCA-NP changed the tissue/organ distribution of DATS in vivo. The successful rate of tumor implantation was 100%. Intravenous administration of DATS-PBCA-NP significantly retarded the growth of orthotopically transplanted hepatoma in BALB/c nude mice (compared with the other three groups, all P < 0.05) without causing weight loss (P > 0.05). TUNEL staining showed that the tumors from DATS-PBCA-NP treated mice exhibited a markedly higher apoptotic index compared with control tumors. Western blot analysis of tumor tissue revealed that the down-regulated expression of proliferation cell nuclear antigen (PCNA) and Bcl-2 proteins in DATS-PBCA-NP group, and there were no significant differences in the expression of Fas, FasL and Bax proteins among the four groups (P > 0.05). CONCLUSIONS: DATS-PBCA-NP has good prolonged release effect in vivo and hepatic-targeted activity, and significant anti-tumor effect on the orthotopic transplantation HCC model in mice in association with the suppression of proliferation and the induction of apoptosis of tumor cells. These advantages are probably due to their liver targeting characteristics and consequently bring a higher anti-tumor activity.

Pulse wave velocity as a marker of arteriosclerosis and its comorbidities in Chinese patients.

To obtain reliable data on the epidemiology of arteriosclerosis and the comorbidities in patients with hypertension (HP), coronary heart disease (CHD), type 2 diabetes mellitus (T2DM) and stroke, we evaluated the clinical significance of pulse wave velocity (PWV) as an indicator of arteriosclerosis and its comorbidities in Chinese patients. A total of 910 subjects, including 748 Chinese patients with one or more cardiovascular risk factors (80.2% male, mean age 73.69+/-5.03 years) and 162 healthy volunteers (78.4% male, mean age 73.60+/-5.32 years) were recruited into the study. PWV was measured in 910 subjects, and large artery arteriosclerosis was defined as PWV >or=12 m/s. Multivariable logistic regression analyses were performed to identify risk factors associated with arteriosclerosis. The prevalence of large artery arteriosclerosis in the patients overall was 67.4%, and the prevalence was higher in patients with than in those without HP (63.3% vs. 34.0%; odds ratio [OR]: 3.451), T2DM (24.8% vs. 11.1%; OR: 2.854), CHD (56.1% vs. 45.1%; OR: 1.246) and stroke (26.6% vs. 19.2%; OR: 1.236), but the OR values of CHD and stroke did not differ significantly (p>0.05). After multiple logistic regression analysis, female sex, older age, HP and T2DM were risk factors for large artery arteriosclerosis. In conclusion, PWV can be used as a routine measurement to scan arteriosclerosis in patients with HP or T2DM.

[Determination of the aortic pulse wave velocity in 545 healthy subjects].

OBJECTIVE: To understand the aortic pulse wave velocity (PWV) in mid-aged and elderly populations and to study the correlation between gender and PWV and the tendency of PWV on different age groups. METHODS: According to the clinical trial guideline, we selected 545 healthy subjects (age, 31-85 years, 395 men and 150 women), and measured carotid-femoral PWV, using Complior. RESULTS: The average value of PWV in Chinese healthy subjects was 11.62 +/- 2.97 m/s. There was no significant difference in the PWV values between males and females who were older than 40 years, but the values of PWV were lower in females than in males in the 30-39 year-old group. PWV was positively correlated with age. In the present study, the reference values of PWV were established in the different age groups, based on the regression equations between PWV and age. CONCLUSION: Aortic pulse wave velocity seemed to be influenced by age but hardly influenced by gender in healthy subjects, so that the reference value of PWV should be established according to the different age groups. When aorta got stiffer, the value PWV got larger accordingly when age was increasing.

[Clinical study of the distensibility of large arteries in elderly patients with essential hypertension].

OBJECTIVE: To explore the change in the distensibility of large arteries and its influencing factors in elderly patients with essential hypertension. METHODS: Automatic measuring system for pulse wave velocity (PWV) was applied to examine carotid-femoral PWV as an index reflecting distensibility of large arteries. 118 hypertensive patients aged 64 - 83 (mean age 67.12 +/- 10.26) years were included in the study. Of them, 87 were males and 31 were females. RESULTS: PWV of 118 hypertensive patients increased with increasing age (P < 0.001). Multivariate regressive analysis demonstrated that age and systolic blood pressure had the close relationship with PWV (P < 0.001). CONCLUSION: Hypertension of the elderly could cause reduction of distensibility of large arteries. Age and systolic blood pressure had the close relationship with distensibility of large arteries in elderly patients with essential hypertension.