[Correlation between elevation of brachial artery pulse pressure increased and coronary heart disease in different genders].

Objective: To explore the relationship between elevation of brachial pulse pressure and coronary heart disease in different genders. Methods: A total of 5 116 inpatients with suspected stable coronary heart disease were consecutively enrolled from December 2011 to June 2017 in the Affiliated Hospital of Chengde Medical College, and divided into coronary heart disease group (n=3 694) and non-coronary heart disease group (n=1 422). The clinical data of all inpatients were collected. A binary logistic regression model of coronary heart disease in different genders were separately established. Results: The morbidity of hypertension, dyslipidemia, type 2 diabetes, ischemic stroke and elevated pulse pressure were all higher in the coronary heart disease group than those in the non-coronary heart disease group (all P<0.05). The area under curve (AUC) of pulse pressure in the male group was 0.540, with an optimal diagnostic threshold of 50 mmHg. The AUC of pulse pressure in the female group was 0.612, with an optimal diagnostic threshold of 60 mmHg. Besides hypertension, type 2 diabetes, increase of low-density lipoprotein cholesterol, ischemic stroke, smoking, and aging, elevated pulse pressure was also an independent risk factor for coronary heart disease in both male and female groups (all P<0.05). Additionally, the risk of elevated pulse pressure for coronary heart disease was higher in female group than that of male group (odds ratio (OR): 1.741 vs 1.284, P<0.05). Conclusion: Elevated pulse pressure may be a new risk factor for coronary heart disease, and its risk for coronary heart disease is higher in women than in men.

The association between sarcopenia and osteoporotic vertebral compression refractures.

Sarcopenia was reported to be significantly associated with osteoporosis. In this study, we reported for the first time that sarcopenia was an independent risk predictor of osteoporotic vertebral compression refractures (OVCRFs). Other risk factors of OVCRFs are low bone mass density T-scores, female sex, and advanced age. INTRODUCTION: The purpose of this study was to investigate the association between osteoporotic vertebral compression refractures (OVCRFs) and sarcopenia, and to identify other risk factors of OVCRFs. METHODS: We evaluated 237 patients with osteoporotic vertebral compression fracture who underwent percutaneous kyphoplasty (PKP) in our hospital from August 2016 to December 2017. To diagnose sarcopenia, a cross-sectional computed tomography (CT) image at the inferior aspect of the third lumbar vertebra (L3) was selected for estimating muscle mass. Grip strength was used to assess muscle strength. Possible risk factors, such as age, sex, body mass index (BMI), bone mineral density (BMD), location of the treated vertebra, anterior-posterior ratio (AP ratio) of the fractured vertebra, cement leakage, and vacuum clefts, were assessed. The multivariable analysis was used to determine the risk factors of OVCRFs. RESULTS: During the follow-up period, OVCRFs occurred in 64 (27.0%) patients. Sarcopenia was present in 48 patients (20.3%), including 21 OVCRFs and 27 non-OVCRFs patients. Sarcopenia was significantly correlated with advanced age, lower BMI, lower BMD, and hypoalbuminemia. Compared with non-sarcopenic patients, sarcopenic patients had higher OVCRFs risk. In univariate analysis, sarcopenia (p = 0.003), female (p = 0.024), advanced age (≥ 75 years; p < 0.001), lower BMD (p < 0.001), lower BMI (p = 0.01), TL junction (vertebral levels at the thoracolumbar junction) (p = 0.01), cardiopulmonary comorbidity (p = 0.042), and hypoalbuminemia (p = 0.003) were associated with OVCRFs. Multivariable analysis revealed that sarcopenia (OR 2.271; 95% CI 1.069-4.824, p = 0.033), lower BMD (OR 1.968; 95% CI 1.350-2.868, p < 0.001), advanced age (≥ 75 years; OR 2.431; 95% CI 1.246-4.744, p = 0.009), and female sex (OR 4.666; 95% CI 1.400-15.552, p = 0.012) were independent risk predictors of OVCRFs. CONCLUSIONS: Sarcopenia is an independent risk predictor of osteoporotic vertebral compression refractures. Other factors affecting OVCRFs are low BMD T-scores, female sex, and advanced age.

[The robot-assisted system YunSRobot for soft endoscopy: a trial of remote manipulation on simulation models].

Objective: To evaluate the feasibility and safety of the robot-assisted system YunSRobot for remote manipulation endoscopy. Methods: When the master of YunSRobot was installed in the gastroenterology office in Chinese PLA General Hospital, the robot slave and upper gastrointestinal simulation model (Takahashi Lm103, Japan) were installed at the same time in the State Key Laboratory of Robotics, Shenyang Institute of Automation. Three physicians were trained to operate the master robotics and performed gastroscopy on the simulation model based on network cloud. Each physician performed 3 procedures of oesophagogastroduodenoscopy (EGD) by YunSRobot using traditional manual endoscopy, on-site operating mode, and remote manipulation mode, respectively. The operating time, lumenal anatomic exposure, man-machine interaction and other parameters were recorded. Results: The number of standard pictures obtained by traditional manual endoscopy group, on-site operating group and remote manipulation group were 39.9±0.3, 39.8±0.4, 39.9±0.3, respectively. The images of all five lesions could be obtained by each operation. The operating time in the duodenum of remote group was longer than that of on-site group, with average time (78.2±16.0)s vs. (68.9±15.8)s (P=0.021) respectively. As to the operating time on other parts or total time, all three groups were comparable. Although there was a mean delay of (572.1±48.5) ms in remote operation group, the operation was still smooth. However, compared with on-site group, the percentage of clear view time in the duodenum was significantly shortened in remote group: [(77.8±8.2)% vs. (83.9±6.4)%, P=0.024]. Statistically significant difference was detected in percentage of clear view time neither in other sites, nor was in the total operating time between two groups. The operating time in each part of remote group was obviously longer than that of manual group as followings, pharyngeal (27.3±4.2) s vs. (9.2±1.3)s (P<0.001), esophageal (29.7±6.4)s vs. (19.3±1.6)s (P=0.004), stomach (56.7±17.0)s vs. (40.3±7.0)s (P=0.003), pylorus (20.2±5.5)s vs. (9.3±1.3)s (P<0.001), duodenum (78.2±16.0)s vs. (29.3±5.6)s (P<0.001). Thus the total operating time was also longer in remote group as (559.0±87.2)s vs. (253.1±16.6)s (P<0.001). The respective time in pharynx, esophagus, stomach, pylorus, duodenum, or the overall time was all longer in remote group than that in manual group. Conclusions: The soft endoscopy robot YunSRobot has satisfactory safety and stability. Remote upper gastrointestinal endoscopy can be completed based on common network and an endoscope simulation model with smooth operation. The inspection time by YunSRobot robot per part and the overall time are longer than those of manual operation on site, still, remote operating time meets the standard of upper gastrointestinal endoscopy.

[A robot-assisted system YunSRobot for soft endoscopy: the first trial of upper gastrointestinal endoscopy on human volunteers].

Objective: To evaluate robot-assisted system YunSRobot to perform oesophagogastroduodenoscopy(EGD) in simulation model and human volunteers. Methods: The YunSRobot was invented for soft endoscopy by our team. In this trial, gastroenterologists operated the double handles of YunSRobot to perform EGD endoscopy with Olympus GIF-H 260 in simulation model Lm103 of Koken Japan and human volunteers. The operating time, lumenal anatomic exposure, man-machine interaction and other parameters were recorded and compared with manual endoscopy. Results: In the endoscopy on model, each of four doctors performed 5 procedures of EGD by YunSRobot and traditional manual endoscopy, respectively. The average time of one procedure was (626.4±120.7) seconds in the robot group and (241.5±24.7) seconds in the manual group, the operating time in robot group was more than that in manual endoscopy group. (t=14.0, P<0.001). However, the robotic manipulation time of the four endoscopists was significantly shortened from the first case to the fifth case with ((783.5±154.8)s, (667.75±85.1)s, (582.0±74.7)s, (555.0±28.9)s, (543.8±29.7)s, F=15.353, P=0.03). In the endoscopy on human, three physicians operated the EGD endoscopy in 21 volunteers, each physician performed seven volunteers by YunSRobot and traditional manual endoscopy respectively. The average time of each procedure in the robot group and the manual endoscopy group was (875.6±179.8) vs (378.8±80.4)s, the operating time in robot group was also more than that in manual endoscopy group (t=10.278, P<0.001). Like the endoscopy on model, the robotic manipulation time by the three operators was significantly reduced from the first case to the seventh cases ((954.7±62.1)s, (936.7±116.9)s, (968.7±227.1)s, (1 008.0±229.4)s, (876.7±110.5)s, (735.0±149.2)s, (649.3±81.0)s, F=3.79, P=0.024). All endoscopic anatomy of EGD were clearly and skillfully observed including esophgus, cardia, fundus, body, gastric angle, antrum, pylorus, first and second parts of duodenum, and papilla in both groups. In all procedures, there were no complications. Conclusions: The soft endoscopy robot YunSRobot is competent to conduct endoscopy of EGD on human. Presently the initial learning time of YunSRobot for EGD is longer than that of experienced manual endoscopy. The learning curve shows that the time of robot manipulation reduces rapidly in the initial procedures. It indicates that YunSRobot system has user-friendly functions and is easy to master.

Clinical efficacy and mechanism of lymphoplasma exchange in the treatment of Guillain-Barre syndrome.

Guillain-Barre syndrome (GBS) is an autoimmune disease of the nervous system and is the most common acute polyneuropathy. Both cellular and humoral immunity are believed to be involved in the pathogenesis of GBS, and various types of activated CD4+ T cells are thought to orchestrate the onset and progression of GBS. Lymphoplasma exchange (LPE) filtering out activated lymphocytes while exchanging plasma has been used for GBS treatment for years. However the treatment is still not yet optimal. In order to assess the efficacy of this treatment, we evaluate the effect of LPE and determine the appropriate frequency of LPE treatments for GBS patients through comparing the neurological deficit scores and the changes in related immunology indicators of GBS patients before and after LPE treatment. Twenty-four patients with GBS who received LPE were evaluated for immunologic indicants before treatment, on the second day, and the fourth day after the treatment. The immunoglobulin complement and CD4+ T lymphocyte subsets were tested by flow cytometry. The patients' Medical Research Council sum scores were increased from 25.7±10.4 up to. 36.7±10.4 (P=0.019) and their Hughes scores decreased from 3.7±0.76 to 3.1±0.73 (P=0.027) at 7 days after LPE. In the peripheral blood from patients received LPE treatment, the levels of immunoglobulin, complement, monocytes and fibrinogen were significantly reduced. The percentages of Th1 and Th17 cells in the CD4+ T lymphocyte subsets were significantly decreased, whereas the Th2 and Treg cells were increased in patients after treatment. The changes in CD4+T lymphocyte subsets were correlated with patient MRC score changes. Our data indicate that LPE is effective in treating GBS patients by directly removing immunoglobulin, complement, monocytes, and fibrinogen as well as regulating lymphocyte subsets in the peripheral blood.

Genome-wide analysis of TCP family in tobacco.

The TCP family is a transcription factor family, members of which are extensively involved in plant growth and development as well as in signal transduction in the response against many physiological and biochemical stimuli. In the present study, 61 TCP genes were identified in tobacco (Nicotiana tabacum) genome. Bioinformatic methods were employed for predicting and analyzing the gene structure, gene expression, phylogenetic analysis, and conserved domains of TCP proteins in tobacco. The 61 NtTCP genes were divided into three diverse groups, based on the division of TCP genes in tomato and Arabidopsis, and the results of the conserved domain and sequence analyses further confirmed the classification of the NtTCP genes. The expression pattern of NtTCP also demonstrated that majority of these genes play important roles in all the tissues, while some special genes exercise their functions only in specific tissues. In brief, the comprehensive and thorough study of the TCP family in other plants provides sufficient resources for studying the structure and functions of TCPs in tobacco.

Molecular characterization and upregulation of cytosolic manganese superoxide dismutase by imidazole derivative KK-42 in Macrobrachium nipponense.

Imidazole derivative KK-42 is a well-known regulator of insect growth. KK-42 pretreatment has been shown to promote the survival of Macrobrachium nipponense infected with Aeromonas hydrophila, possibly via activation of superoxide dismutase (SOD). In this study, the cytMnSOD gene was cloned from the hepatopancreas of M. nipponense using the rapid amplification of cDNA ends technique. The full-length cDNA of cytMnSOD was 1233 bp long, and the open reading frame was 858 bp long, encoding a 286-aa protein with a 60-aa leader sequence. The calculated molecular mass of the translated cytMnSOD protein was 31.33 kDa, with an estimated isoelectric point of 5.62. cytMnSOD contained two N-glycosylation sites, four conserved amino acids responsible for binding manganese, and a manganese SOD domain (DVWEHAYY). Real-time RT-PCR analysis showed that cytMnSOD was expressed in all tissues examined with the highest expression observed in the hepatopancreas. Levels of the cytMnSOD transcript in the hepatopancreas were highest in stage C of the molting cycle. Real-time PCR analysis revealed that cytMnSOD expression increased significantly 3, 6, and 12 h after KK-42 treatment, with simultaneous increases in SOD activity from 6 to 12 h. Our results demonstrate that cytMnSOD expression and SOD activity may be induced by KK-42, which may represent one of the molecular mechanisms through which KK-42 promotes increased survival of prawns infected with A. hydrophila.

Expression of N-cadherin in myocardial tissues during the development of a rat heart.

We investigated the expression and distribution of N-cadherin during the development of a rat heart. Immunohistochemistry (IHC) was performed to detect the expression and distribution of N-cadherin in the myocardial tissues of rats at embryonic day 18 (E18d), postnatal day 5 (P5d), postnatal day 19 (P19d), postnatal day 40 (P40d), and postnatal year 1 (P1y). Reverse transcription polymerase chain reaction was used to determine mRNA expression levels of N-cadherin in the myocardial tissues at E18d, P5d, P19d, P40d, and P1y. The IHC results showed that at E18d N-cadherin was dispersedly distributed both on the cell surface and in the cytoplasm of the myocardial cells, and gradually became concentrated at the end-to-end intercalated discs of the cardiomyocytes from birth through immaturity. In the young, middle-aged, and old rats, N-cadherin was typically distributed at the intercalated discs at the end of the myocardial cells. No significant differences in the mRNA expression levels of N-cadherin were detected in the myocardial tissue of rats at E18d, P5d, P19d, P40d, and P1y. During the development of the rat heart, observable changes in the distribution of N-cadherin occurred in the myocardial tissues, but there were no detectable changes in the expression of N-cadherin, indicating that N-cadherin is indispensable to maintaining the physical structure and function of the heart.

Homology-based analysis of the GRAS gene family in tobacco.

Members of the GRAS gene family are important transcriptional regulators. In this study, 21 GRAS genes were identified from tobacco, and were classified into eight subgroups according to the classification of Arabidopsis thaliana. Here, we provide a preliminary overview of this gene family in tobacco, describing the gene structure, gene expression, protein motif organization, phylogenetic analysis, and comparative analysis in tobacco, Arabidopsis, and rice. Using the sequences of 21 GRAS genes in Arabidopsis to search against the American tobacco genome database, 21 homologous GRAS genes in tobacco were identified. Sequence analysis indicates that these GRAS proteins have five conserved domains, which is consistent with their counterparts in other plants. Phylogenetic analyses divided the GRAS gene family into eight subgroups, each of which has distinct conserved domains and biological functions. Furthermore, the expression pattern of these 21 GRAS genes reveals that most are expressed in all six tissues studied; however, some have tissue specificity. Taken together, this comprehensive analysis will provide a rich resource to assist in the study of GRAS protein functions in tobacco.

[Retrospective study of role of neoadjuvant rectal scores in evaluating the 10-year disease-free survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy followed by surgery].

Objective: To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy. Methods: Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores. Results: Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46-63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44-58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1-2 in 246 patients (50.5%) and 3-4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8-16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7-133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8-16, and >16 were 85.1%, 80.5%, and 66.4%, respectively (P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408-0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559-4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer (P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62-0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49-0.60). The two scores differed significantly in accuracy (Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion: The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.

Genetic variability in copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with Alzheimer's disease in a Chinese population.

Previous experiments demonstrated that transgenic mice carrying both amyloid precursor protein and mutant ATP7B transgenes reduce amyloid plaques and diminish plasma Abeta levels. These experiments showed that a structural change of ATP7B may affect Alzheimer’s disease (AD) susceptibility. In this study three missense SNPs in ATP7B gene (rs1801243, rs1801244, and rs1801249) were chosen to test whether they were associated with AD. We tested this hypothesis using a case control design. The experimental data showed that there was a significant deviation from Hardy-Weinberg equilibrium (HWE) for SNP rs1801249 (c.3419 T greater than C, Val1140Ala) in the case group (p = 0.014) but not in the control group and that there was an association between SNP rs1801249 and AD under a recessive model (p = 0.003). The data also showed that the genotype frequency distribution of the ATP7B c.1366 G greater than C polymorphism (rs1801244, Val456Leu) differed significantly between the AD patients and the normal subjects (p = 0.012). In addition, the frequency of the TGC haplotype of SNPs rs1801243, rs1801244, and rs1801249 was significantly higher in the AD patients compared with the normal subjects (p = 8.49×10-7). These observations suggested that genetic variations in the copper transporter gene ATP7B might contribute to AD pathogenesis in the Taiwanese population.

Ang II receptor expression and effect of Ang II receptor blockade in thyrotoxic rat myocardium.

AIM: To investigate the relationship between expression of the angiotensin II (Ang II) receptors and thyroid hormones in the myocardium of rats with thyrotoxicosis. MATERIALS AND METHODS: Forty-four adult male Sprague-Dawley rats were divided into four groups: control group (saline), losartan group (10 mg/kg), thyrotoxicosis group (0.5 mg/kg L-thyroid hormone sodium) and thyrotoxicosis-plus-losartan group (0.5 mg/kg L-thyroid hormone plus 10 mg/kg losartan) and treated intragastrically daily for four weeks. The heart weight (HW), body weight (BW) and HW/BW ratios were determined. The Ang II protein contents in cardiac homogenates and serum were determined by ELISA. The serum concentrations of levothyroxine (T3), trilodothyronine (T4) and thyroid stimulating hormone (TSH) were measured by radioimmunoassay. The expression of angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) were quantified by real-time PCR and Western blotting. RESULTS: The thyrotoxicosis group had an increased BW/HW and higher cardiac AT1R and AT2R expression compared to controls. AT1R and AT2R expressions significantly reduced in the thyrotoxicosis-plus-losartan group, compared to the thyrotoxicosis group. CONCLUSIONS: Thyroid hormone upregulated cardiac AT1R and AT2R, leading to cardiac remodeling, which was reversed by losartan. Cardiac damage in thyrotoxic rats may be related to upregulation of the Ang II receptors.

A multiline fitting method for measuring ethylene concentration based on WMS-2f/1f.

Coal spontaneous combustion risk assessment is a global technical challenge for the sustainable development of deep mining technology, and C2H4 is a key indicator for early warning of coal spontaneous combustion. Tunable diode laser absorption spectroscopy (TDLAS) has the advantages of high selectivity, high sensitivity, high accuracy and real-time on-line measurement, and it can detect multiple gases simultaneously, so it has significant advantages in the accurate detection of coal spontaneous combustion indicator gases. To address the problem of cross-interference between the near-infrared absorption lines of CH4 and C2H4, which are the indicator gases of spontaneous combustion in coal, a multi-line fitting method was proposed in this study to calibrate the concentration of C2H4. The high-precision Environics2000 automatic standard gas dispenser from the United States, which has a built-in CPU computer control and data control and processing system, was used. Its gas concentration accuracy: ± 1.0%, gas flow accuracy: ± 1.0%, gas repeatability accuracy: ± 1.0%, flow linearity accuracy: ± 0.5%, and inlet operating pressure: minimum 10 psig (0.67 bar) ~ 75 psig (5.04 bar). The measured and simulated WMS-2f/1f signals were multilinearly fitted using a multilinear fitting algorithm and wavelength modulation spectroscopy (WMS), and the measurement of C2H4 concentration was achieved based on the extracted spectral line information. The results show that the maximum relative error of C2H4 concentration measurement is 2.40%, which is 54% lower than that of the conventional 2f peak measurement method, thus demonstrating the effectiveness of the multilinear fitting algorithm in the inversion of C2H4 concentration under the interference of absorption lines. In addition, this study has far-reaching implications for the application of TDLAS technology in the accurate detection of coal spontaneous combustion indicator gases.

The association between gut microbiome and growth in infants with cystic fibrosis.

BACKGROUND: In cystic fibrosis (CF), pathophysiologic changes in the gastrointestinal tract lead to malnutrition and altered gut microbiome. Microbiome alterations have been linked to linear growth, gut inflammation and respiratory manifestations. Elucidating these gut microbiome alterations may provide insight into future nutritional management in CF. METHODS: Infants were followed for 12-months at four sites in the United States (US-CF) and Australia (AUS-CF). 16S rRNA gene sequencing was performed on longitudinal stool samples. Associations between microbial abundance and age, antibiotic prophylaxis, malnutrition, and breast feeding were evaluated using generalized linear mixed models. Taxonomic and predictive functional features were compared between groups. RESULTS: Infants with CF (N = 78) were enrolled as part of a larger study. AUS-CF infants had higher mean weight-for-age z-scores than US-CF infants (p = 0.02). A subset of participants (CF N = 40, non-CF disease controls N = 10) provided stool samples for microbiome analysis. AUS-CF infants had lower stool alpha diversity compared to US-CF infants (p < 0.001). AUS-CF infants had higher relative abundance of stool Proteobacteria compared to US-CF infants which was associated with antibiotic prophylaxis (p < 0.001). Malnutrition (weight-for-age <10th percentile) was associated with depleted Lactococcus (p < 0.001). Antibiotic prophylaxis (p = 0.002) and malnutrition (p = 0.012) were linked with predicted decreased activity of metabolic pathways responsible for short chain fatty acid processing. CONCLUSIONS: In infants with CF, gut microbiome composition and diversity differed between the two continents. Gut microbial diversity was not linked to growth. The relationship between malnutrition and antibiotic prophylaxis with reduced SCFA fermentation could have implications for gut health and function and warrants additional investigation.

Association analysis of dopaminergic gene variants (Comt, Drd4 And Dat1) with Alzheimer s disease.

Defects in dopaminergic transmission play important roles in the disturbance of synaptic plasticity and even in advanced cognitive behavior. However, the relationship between genes involved in the regulation of dopamine levels and predisposition for Alzheimer s disease (AD) remains unclear. The potential association of dopamine-modulating gene polymorphisms with AD was evaluated. We performed a case-control study with 120 patients and 86 healthy controls. Two catechol-O-methyltransferase (COMT) single-nucleotide polymorphisms (SNPs) (rs2020917 and rs4646312), two dopamine D4 receptor (DRD4) SNPs (rs3758653 and rs916455), and four dopamine transporter (DAT1) SNPs (rs2937639, rs6347, rs12516948 and rs11133762) were investigated. The T allele at the DRD4 SNP (rs3758653) was found to be significantly associated with AD. Our results also showed that haplotype frequencies, observed from the analyzed SNPs, were distributed significantly differently in AD patients vs control subjects. Moreover, a strong association was observed between the A allele at rs6347 of DAT1 and moderate stage of dementia. These observations suggest that genetic variations in the dopamine-modulating genes, COMT, DRD4 and DAT1, may contribute to AD pathogenesis in the Taiwanese population.

Effects of CAR structure and culture conditions on memory CAR-T cells.

Adoptive CAR T cell therapy (chimeric antigen receptor T-Cell) has received increasing attention in recent years; however, its efficacy is undesirable and differs from person to person. Understanding how to overcome this obstacle is important to improve therapy. Infusion of poorly differentiated CAR-CD62L+ T cells, such as T memory stem cell populations, leads to enhanced T cell implantation, expansion, and persistence, which ultimately leads to more stable tumour regression. Here, we reviewed emerging findings demonstrating that CAR structure and cell culture conditions can influence CAR T cell differentiation and antitumour efficacy.

LncRNA APPAT regulated miR-328a/Pkp1 signal pathway to participate in breast cancer.

OBJECTIVE: Recent studies indicated long non-coding RNA (lncRNA) is involved in the development of breast cancer, which is the pathological basis of breast cancer. Here, we reported the molecular mechanisms by which lncRNA APPAT regulated in the progression of breast cancer. MATERIALS AND METHODS: QPCR was used to inspect the expression of lncRNA APPAT and miR-328a in breast cancer cell lines. Luciferase reporter assay confirmed the direct target effect of APPAT and miR-328a. Western blot was used to check Pkp1 protein expression in breast cancer cell lines. RESULTS: The expressions of lncRNA APPAT, Pkp1 protein levels and miR-328a were commonly expressed in breast cancer cells. The inhibition of lncRNA APPAT expression repressed cell proliferation, migration and invasion in breast cancer and reverse results were found after lncRNA APPAT overexpressing. Mechanistically, the binding targets of lncRNA APPAT vs. miR-328a and Pkp1 vs. miR-328a were checked in breast cancer. Meanwhile, miR-328a silencing enhanced the proliferation, migration and invasion of breast cancer cells. Moreover, the effect caused by Pkp1 silencing on cell proliferation, migration and invasion was reversed by miR-328a inhibitor in MCF-7 and BT594 cells. Additionally, Pkp1 knockout reversed the effect of cell proliferation, migration and invasion triggered by APPAT elevated. Taken together, these results showed miR-328a as a downstream target of lncRNA APPAT linking lncRNA APPAT to Pkp1. CONCLUSIONS: LncRNA APPAT regulated the proliferation, migration, invasion of breast cancer by regulating miR-328a/Pkp1 signaling pathway, providing a novel possible strategy for the treatment of breast cancer.

MiR-145 targeting BNIP3 reduces apoptosis of chondrocytes in osteoarthritis through Notch signaling pathway.

OBJECTIVE: The purpose of this study was to explore the effect of micro ribonucleic acid (miR)-145 on the apoptosis of chondrocytes in osteoarthritis (OA), and to research the association between its targeting on B-cell lymphoma-2 (Bcl-2)/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) and Notch signaling pathway and chondrocyte apoptosis. MATERIALS AND METHODS: The mouse model of OA was established via surgery, and chondrocytes were isolated and cultured in vitro. Then, the chondrocytes were transfected with miR-145 inhibitor, miR-145 mimics, miR-negative control (NC), BNIP3-siRNA and BNIP3-vector, respectively, with those normally cultured as the control. After that, the expression levels of miR-145 and BNIP3 in cells were detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), the apoptosis rate was detected via flow cytometry, and the apoptosis level was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the target gene sequences were predicted and compared using the software, and the BNIP3 Luciferase reporter vectors containing predicted target sites for miR-145 were constructed. Finally, the protein expressions of BNIP3, Notch1, and P21 were determined through Western blotting. RESULTS: The results of qRT-PCR showed that in OA chondrocytes, the expression of miR-145 was lower than that in normal chondrocytes (p<0.05), while the mRNA and protein expressions of BNIP3 were higher than those in normal chondrocytes (p<0.05). According to flow cytometry, the apoptosis rate was (4.4±0.6)% in normal cartilage tissues and (29.2±2.1)% in OA cartilage tissues. Overexpression of miR-145 significantly reduced chondrocyte apoptosis (p<0.05), while overexpression of BNIP3 markedly increased chondrocyte apoptosis (p<0.05). In addition, the Luciferase reporter system showed that miR-145 mimics evidently inhibited BNIP3 (p<0.05) and suppressed the Notch signaling pathway (p<0.05), while BNIP3 enhanced the expression of Notch signaling pathway (p<0.05). CONCLUSIONS: MiR-145 can reduce OA-induced chondrocyte apoptosis through targeted inhibition on BNIP3 and regulation on Notch signaling pathway.