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Hypertension is a significant risk factor of cardiovascular diseases (CVDs) with high prevalence worldwide, the current treatment has multiple adverse effects and requires continuous administration. The glucagon-like peptide-1 receptor (GLP-1R) agonists have shown great potential in treating diabetes mellitus, neurodegenerative diseases, obesity and hypertension. Butyric acid is a potential target in treating hypertension. Yet, the application of GLP-1 analogue and butyric acid in reducing blood pressure and reversing ventricular hypertrophy remains untapped. In this study, we combined the therapeutic capability of GLP-1 and butyric acid by transforming Clostridium butyricum (CB) with recombinant plasmid pMTL007 encoded with hGLP gene to construct the engineered probiotics Clostridium butyricum-pMTL007-GLP-1 (CB-GLP-1). We used spontaneous hypertensive rat (SHR) models to evaluate the positive effect of this strain in treating hypertension. The results revealed that the intragastric administration of CB-GLP-1 had markedly reduced blood pressure and improved cardiac marker ACE2, AT2R, AT1R, ANP, BNP, β-MHC, α-SMA and activating AMPK/mTOR/p70S6K/4EBP1 signalling pathway. The high-throughput sequencing further demonstrated that CB-GLP-1 treatments significantly improved the dysbiosis in the SHR rats via downregulating the relative abundance of Porphyromonadaceae at the family level and upregulating Lactobacillus at the genus level. Hence, we concluded that the CB-GLP-1 greatly improves blood pressure and cardiomegaly by restoring the gut microbiome and reducing ventricular hypertrophy in rat models. This is the first time using engineered CB in treating hypertension, which provides a new idea for the clinical treatment of hypertension.

Background Although COVID-19 pneumonia is spreading internationally, knowledge regarding the factors associated with the illness severity of patients remains limited. We aimed to identify the factors associated with the disease severity of patients with COVID-19 pneumonia induced by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We prospectively enrolled a single-center case series of adult patients with COVID-19 admitted to the Infectious Disease Hospital of Jining, Jining City, Shandong Province, China, from January 24 to March 1, 2020. Demographics, clinical characteristics, and laboratory findings were compared to investigate the risk factors related with the disease severity of COVID-19 pneumonia patients. Results We included a total of 78 patients with COVID-19 pneumonia, of whom 6 had the severe type. As compared to a moderately ill cohort, our analysis showed that shortness of breath, fatigue, neutrophil percentages > 70%, neutrophil counts > 6.3 × 10 9 /L, lymphocyte percentages < 20%, lymphocyte counts < 1.0 × 10 9 /L, platelet < 100 × 10 9 /L, C-reactive protein (CRP) > 10 mg/L, neutrophil to platelet ratio (NPR) > 2.3, neutrophil to lymphocyte ratio (NLR) > 3.9, aspartate aminotransferase (AST) > 40 U/L, albumin < 40 g/L, lactate dehydrogenase (LDH) > 245 U/L, and glucose > 6.1 mmol/L were predictors of disease severity in COVID-19 pneumonia. In the sex-, age-, and comorbid illness-matched case-control study, neutrophil percentages > 70%, neutrophil counts > 6.3 × 10 9 /L, lymphocyte percentages < 20%, NPR > 2.3, NLR > 3.9, albumin < 40 g/L, and LDH > 245 U/L remained associated with the early detection and identification of severe patients. Conclusion We demonstrated that neutrophil percentages > 70%, neutrophil counts > 6.3×10 9 /L, lymphocyte percentages < 20%, NPR > 2.3, NLR > 3.9, albumin < 40 g/L, and LDH > 245 U/L might predict the severity of illness in patients with COVID-19 pneumonia.

Objective Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies in China, and the genetic link of hepatocarcinogenesis remains to be defined. Thus, we explored the role of SET and myeloid translocation protein 8, Nervy, and DEAF1 (MYND) domain containing protein 3 (SMYD3) gene polymorphism on risk and prognosis of HCC. Methods A total of 236 patients with HCC who received treatment in Affiliated Hospital of Jining Medical University for the first time and 230 healthy individuals were enrolled in the study. After DNA extraction for all the subjects, polymerase chain reaction (PCR) was used to amplify and sequence variable numbers of tandem repeat (VNTR) loci of SMYD3 gene. SMYD3 gene was genotyped and its frequency distribution was calculated. Age, education level, income, smoking and drinking history, HCC family history, tumor node metastasis (TNM) staging, maximum tumor diameter, lymph node metastasis (LNM) etc. were investigated. Correlation of SMYD3 gene polymorphism and other risk factors with the occurrence and prognosis of HCC was analyzed. Results The family history of HCC, drinking history, cirrhosis, and HBV or/and HCV infection, SMYD3 VNTR 3/3 were more frequently observed in subjects with HCC. Patients with SMYD3 VNTR 3/3 genotype, drinking-history, family history of HCC, cirrhosis and hepatitis B virus (HBV), TNM staging, maximum tumor diameter, LNM were more vulnerable to HCC. Besides, patients with SMYD3 VNTR 3/3 genotype had lower 2- and 3-year survival rate. The COX regression analysis revealed that drinking history, family history of HCC, SMYD3 VNTR 3/3 genotype, TNM staging, and LNM were all related to the prognosis of HCC. Conclusion This study indicates that drinking history, family history of HCC and SMYD3 VNTR 3/3, TNM staging, maximum tumor diameter, LNM might be risk factors for HCC, and SMYD3 VNTR 3/3 might contribute to a lower 2- and 3-year survival rate of patients with HCC.

Calcific aortic valve disease (CAVD) currently lacks a highly effective in vitro model. The presence of high concentrations of serum inorganic phosphate in patients with end-stage renal disease leads to calcification of vascular and aortic valves. Therefore, we applied inorganic phosphate to induce the osteogenic differentiation of valvular interstitial cells (VICs) and mimic its in vivo pathophysiological effects. Calcification and inflammatory response assays determined that inorganic phosphate-osteogenic induction medium (IP-OIM) was more efficient than classic osteogenic induction medium (OIM) containing organic glycerophosphate. Levels of BMP-2, RhoA, and ROCK-1 were significantly increased in IP-OIM cells. Knockdown efficiency of BMP-2- and RhoA-siRNA in VICs was evaluated, and expression of RhoA and its downstream target ROCK-1 was decreased after BMP-2-siRNA transfection. Moreover, ROCK-1 was significantly downregulated after RhoA knockdown, whereas expression of BMP-2 was unchanged. Interference of BMP-2 had a stronger anti-calcification effect than RhoA, further identifying BMP-2 as an upstream regulator of RhoA/ROCK-1. Stimulation of VICs by IP-OIM led to increased Smad1/5/9 phosphorylation, which peaked at 60 min, while pre-treatment of VICs with the Smad1/5/9 inhibitor Compound C attenuated VICs calcification. These results suggest that IP-OIM induced VICs osteogenic differentiation via Smad1/5/9 signaling. Knockdown of BMP-2 or RhoA also decreased Smad1/5/9 phosphorylation also decreased. We conclude that the RhoA/ROCK-1 axis participates in VICs osteogenic differentiation as a “bypass mediator” of the BMP-2/Smad1/5/9 signaling pathway.

Objective To improve our knowledge of primary benign tracheobronchial tumors and increase the early diagnosis rate. Method The clinical and imaging features of 22 patients with benign tracheobronchial tumors were retrospectively analyzed. The lesions were surgically or pathologically confirmed as schwannomas(n=2),lipomas(n=3),hamartomas(n=3),leiomyomas(n=9),inflammatory myofibroblastoma(n=1),and pleomorphic adenomas(n=2).The early symptoms were concealed and atypical,accompanied by misdiagnoses at different time points.The tumors were located at trachea in 5 patients and at bronchus in 17 patients.All lesions manifested as intraluminal growth with mild to moderate enhancement,without thickening of the tracheobronchial wall.They had smooth margins and wide basements.The lesions were cast-shaped and occluded the lumen in 3 cases;in the remaining 19 cases,the lesions appeared as round or oval nodules. Conclusions Primary benign tracheobronchial tumors are rare.Patients with repeated cough and expectoration that respond poorly to treatment should be screened for benign tracheobronchial tumors.On CT,the benign tracheobronchial tumors are small intraluminal nodules with the smooth surface and wide basement,without thickening of the wall.

XRD, Raman, XPS and FT-IR were used to examine microcrystalline structure changes of Shengli lignite eluted by inorganic acid (HCl, H2SO4 and HCl-HF). By adopting a designed surface adsorption instrument-GC, the samples were oxidized at low temperature through pulse method to investigate their oxygen adsorption under different temperatures. Via low-temperature oxidation, TG/DTG and fixed bed combustion tests, the spontaneous combustion tendency of coal samples were investigated. The results show that the removal of minerals increases the degree of order and graphitization of the coal structure. Compared with raw coal, oxygen absorption of inorganic acid elution samples decreases obviously. With the increase of adsorption temperature, oxygen absorption capacity increases significantly, but decreases with the increasing level of removed minerals, which reduces spontaneous combustion tendency of the treated coal.

MicroRNAs, a group of noncoding regulatory RNAs, are involved in oncogenesis, cell survival, and chemosensitivity. First, microarray-based analysis predicted that far-upstream element-binding protein 2 (FBP2) was upregulated in hepatocellular carcinoma (HCC), which may be regulated by miR-591. In this study, we hypothesize an inhibitory role of miR-591 in HCC via regulating FBP2. Next, reverse transcription quantitative polymerase chain reaction found that FBP2 expressed highly and miR-591 expresses poorly in HCC tissues. Then, the negative correlation between miR-591 and mRNA expression of FBP2 was identified by Pearson’s correlation coefficient, and putative miR-591-binding sites on the 3′-untranslated region of FBP2 was validated using a dual-luciferase reporter gene assay. After the expression of miR-591 and FBP2 was altered in the drug-resistant CD133+/CD44+ cells, a series of in vitro and in vivo experiments demonstrated that either miR-591 overexpression or FBP2 silencing inhibited the abilities of sphere formation and colony formation, drug resistance, as well as tumorigenicity. It was further observed that miR-591 could suppress FBP2 expression by blocking the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin axis. Above results highlighted an inhibitory effect of miR-591 on the development of HCC by reducing the drug resistance of HCC stem cells. It revealed miR-591 as a new target in the treatment of HCC.

A heavy-load positioner with series-parallel mechanism was put forward according to the heavy-load positioner’s task demand. Two rotational DOFs were realized by the spherical 3-DOF mechanism with a restricted embranchment instead of traditional gear-driven mechanism, the other by the serial part. The mechanism has the advantages of large workspace, good flexibility and high stiffness-to-weight ratio. The kinematics, statics and singularity of the positioner mechanism were analyzed. The mathematic model of the positioner mechanism was established. Combining the workspace demand of the positioner, dimension optimization of the mechanism was researched. Finally, the kinematics,statics and the singularity analysis of the positioner mechanism was verified through virtual prototype designed with one group of satisfied dimensions.

Oxygen adsorption and CO2produced of samples at different adsorption temperatures was investigated, Combined with thermal analysis method, the combustion properties of coal samples was determined. The results show that the oxygen adsorption capacity and CO2produced of the samples increase and later decrease with the enhanced of pyrolysis degree. In the process of low-temperature oxidation, coal molecular side chains break, then H2O, CO, CO2and so on are detected in turn; with the enhanced of pyrolysis degree, it reveals that combustion reaction activity decreased and spontaneous combustion tendency weakened.

This study combines the template method and sol-gel method, prepares TiO2 photocatalytic materials with the cotton, leaves and towel gourd as the template, and then makes degradation of phenol in ultraviolet light with the prepared TiO2 photocatalysts. The results show that all the photocatalyst prepared with three kinds of templates have high photocatalytic activity, among which, the catalytic performance of cotton is better, leaves secondly, and towel gourd’s relatively poor. With cotton as templates for the preparation of TiO2 under UV irradiation for 6h, the degradation rate was 80%, leaves as template for the preparation of TiO2 under UV irradiation for 6h, the degradation rate was 63%, and with towel gourd as template for the preparation of TiO2 under UV irradiation for 6h, the degradation rate was 52%.

In order to solve the machining translocation of the nuclear water chamber sealing head, a new Two DOF Heavy Positioner structure is proposed as the auxiliary equipment of processing nuclear water chamber sealing head. The article briefly describes the components of the 2 DOF heavy positioner, analyses the motion of the Turns-over Structure with analytical method and calculates variation of the swinging position of the screw , overturning speed and acceleration with Matlab as a platform，and verifies the correctness and credibility of the results by ADAMS simulation analysis.

Three-dimensional simplified model of auto windshield, mold, hot ring and quench ring was built using UG software in this article. Hot bend-forming numerical simulation process of auto windshield was reserched based on Show-implicit sequence solving algorithm. Finite element dynamic display simulation of press and drop forming and rebound deformation work step were finished. Distortion status, stress and strain distribution in forming process could be real-time displayed. It compared measured value and simulated value in two ways (bending depth and rebound rate) in the three groups product samples randomly selected.The comparison result proved the veracity of numerical simulation result. It had certain actual production guiding significance.

To evaluate the clinical value of magnetic resonance (MR) diffusion-weighted imaging (DWI) for diagnosing radiation-induced liver injury (RILI) and detecting changes in hepatic pathology at different post-irradiation times.Male New Zealand white rabbits received no irradiation (C0, control group; n = 10) or irradiation of 50 Gy/10F once every other day by virtual three dimensional conformal radiotherapy (3D-CRT) for one day (C1; n = 10), three days (C2; n = 10), two weeks (C3; n = 10), one month (C4; n = 10) or two months (C5; n = 10). One member of all groups were sacrificed for DWI examination and pathologic study on post-irradiation day 1, day 3, week 2, month 1 and month 2. The apparent diffusion coefficient (ADC) values were measured using a range of b values (50, 300, 600, 800 and 1000 s/mm2).Hematoxylin-eosin (H-E) staining showed that livers of rabbits in the C3, C4 and C5 groups had the characteristic features of veno-occlusive disease. DWI examination showed that the irradiated livers of rabbits in C2, C3, C4 and C5 groups had significantly lower ADC values than the livers of the non-irradiated rabbits at b values of 300, 600, 800 and 1000 s/mm2 (P less than 0.05). When the b value was 600 s/mm2, the best negative correlation between ADC values and pathological stage was seen for the irradiated livers (Spearman's rank, r = -0.459, P less than 0.01). The threshold ADC value to distinguish the normal group (C0) from an irradiated group (more than or equal toC1) was 1.955 * 10-3 mm2/s at 600 s/mm2 b value. When the b value was 1000 s/mm2, the threshold ADC value to predict an irradiated group with normal H-E staining (C1) from an irradiated group with abnormal H-E staining (more than or equal toC2) was 1.5250 * 10-3 mm2/s; the ADC threshold value was 1.5150 * 10-3 mm2/s to predict groups C0-2 and groups C3-5.DWI has high sensitivity for detecting RILI at three days after irradiation with proper b values. Use of the ADC value is feasible for estimating the evolutionary process of pathological features of RILI damage. DWI may represent an important clinical tool for detection of early pathological changes in RILI.

To evaluate the value of T2 mapping in monitoring the repaired cartilage after matrix-associated autologous chondrocyte implantation/transplantation (MACI/MACT).Four patients (10 plug cartilages) were examined three times by T2 mapping at 1, 3, and 6 months using a 3.0 Tesla MR scan system. Quantitative mean (full-thickness) T2 values were calculated in the transplanted area and control cartilage. Paired t-tests were used to compare the T2 values between transplanted and control cartilage. For analysis of longitudinal T2 values, one-way analyses of variance were performed among 1, 3, and 6 months after MACI.The mean T2 values of the transplanted area at 1, 3, and 6 months after MACI were (82.40±15.23), (71.09±13.06), (53.80±4.86) ms, respectively. There were significant differences between the transplanted and control cartilage at 1 and 3 months (both P0.01) after MACI, but not at 6 months (P=0.196). There were significant differences among T2 values of 1, 3, and 6 months after MACI in transplanted area (P=0.03).T2 mapping provides a useful tool for monitoring the biochemical development of the transplanted cartilage and can be used to evaluate the cartilage repair noninvasively.

To investigate the T2 values and knee thickness in healthy young adults using 3.0 T magnetic resonance imaging(MRI) .Totally 40 volunteers(18-30 years old) with body mass index between 18.5-24.0 kg/m(2) were divided into two groups(22 men and 18 women) according to their gender. Also in addition, each group was divided into two subgroups(right knee and left knee) . The T2 values and the thickness of the areas on the medial condyle of femur, the lateral condyle of femur, the medial tibial plateau, the lateral tibial plateau, and the patella of the knee cartilage were measured.The T2 values and the thickness of the right and left knee cartilages showed no significant differences between men and women (P0.05) . Also, the T2 values in the five parts of the knee cartilage also were not significantly different between men and women (P0.05) . However, the thickness of the 5 parts of the knee cartilage significantly differed between men and women(P0.05) .The thickness of the knee cartilage may different between male and female young adults. The T2 values of the cartilage may be not affected by the gender.

The lung is one of the most important organs that are sensitive to ischemia. We hypothesized that remote postconditioning (RPostC) induced by brief occlusion and reperfusion of the pulmonary artery could attenuate myocardial reperfusion injury.Thirty rabbits were randomized into three groups. Group ischemia-reperfusion (IR) (n = 10) were anesthetized rabbits subjected to 30-minute occlusion of the left anterior descending coronary artery followed by 180-minute reperfusion. Group RPostC (n = 10) had the left pulmonary artery blocked for five minutes followed by a 5-minute reperfusion, and the left anterior descending coronary artery (LAD) occluded for 30 minutes with a 180-minute reperfusion. Group L-N(w)-nitro-L-arginine methylester (L-NAME) + RPostC (n = 10) had the left pulmonary artery blocked for five minutes followed by a 5-minute reperfusion and intravenous infusion of L-NAME (10 mg/kg), and the LAD occluded for 30 minutes with a 180-minute reperfusion. Blood samples were taken for levels of creatine kinase (CK), superoxide dismutase (SOD) and malondialdehyde (MDA) at three different time points. At the end of the experiment, tissue samples of the infarcted region were harvested to calculate the cardiomyocyte apoptosis index (AI) by TUNEL. A piece of left and right lung tissue was harvested to evaluate the damage to the lung.After reperfusion for 180 minutes, the concentration of CK was lower in group RPostC, (4.79 ± 0.27) U/ml, than that in group IR, (6.23 ± 0.55) U/ml (P0.01), and group L-NAME + RPsotC, (5.86 ± 0.42) U/ml (P0.01). The concentration of MDA was lower in group RPostC, (6.06 ± 0.36) nmol/ml, than that in group IR, (11.41 ± 0.91) nmol/ml (P0.01), and group L-NAME + RPostC, (11.06 ± 0.62) nmol/ml (P0.01). The activity of SOD was higher in group RPostC, (242.34 ± 25.02) U/ml, than that in group IR, (148.05 ± 18.24) U/ml (P0.01), and group L-NAME + RPostC, (160.66 ± 9.55) U/ml (P0.01). The apoptosis index was lower in group RPostC, (14.25 ± 5.20)%, than that in group IR, (35.77 ± 10.09)% (P0.01), and group L-NAME + RPostC, (30.37 ± 7.76)% (P0.01). No significant difference caused by pulmonary ischemia was found in the lung tissue among the three groups.RPostC may attenuate myocardial ischemia-reperfusion injury connected to the activity of endothelial nitric oxide synthase. Brief pulmonary ischemia may not be harmful to lungs.

Purpose: Postconditioning, a series of brief ischemia-reperfusion sequences given before an ischemic heart undergoes sustained reperfusion, has been shown to lessen ischemia/reperfusion injury. The current study establishes a rabbit model of myocardial ischemia-reperfusion and studied the effects of pulmonary remote postconditioning in this model. Methods: Serum levels of creatine kinase (CK), superoxide dismutase (SOD), and malondialdehyde (MDA), protein expression of endothelial nitric oxide synthase (eNOS), Rho kinase (ROCK- 2), and protein kinase B (Akt) in myocardial cells and the apoptosis index of myocardial cells were examined. Results: Pulmonary remote postconditioning decreased CK, significantly decreased MDA, and increased SOD. Postconditioning significantly increased eNOS protein expression. Administration of eNOS inhibitor, L-NAME, dramatically suppressed the postconditioning-induced eNOS protein expression and serum SOD level, but significantly increased MDA level. The two longer sessions of postconditioning increased Akt, although this increase was not accompanied by changes in levels of the Akt inhibitor, ROCK-2. Blocking eNOS activity with L-NAME had no visible effect on either Akt or ROCK-2. Conclusion: Our results suggest a role for Akt in remote postconditioning-induced myocardial protection, but do not support an involvement of eNOS in Akt-mediated action.