Effects of whole-body vibration training with different frequencies on the balance ability of the older adults: a network meta-analysis.

Purpose: To compare the effects of whole-body vibration training (WBVT) with different frequencies on the balance ability of older adults. Methods: Randomized controlled trials (RCTs) on the WBVT interventions on balance ability in older adults were searched through PubMed, Web of Science, The Cochrane Library, ProQuest, Embase, Opengrey, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal Database (CSTJ) databases from the establishment of the database to August 2022, and all literature that met the PICOS (Participants, Intervention, Comparison, Outcomes, Study design) criteria were enrolled. Two reviewers screened and assessed the methodological quality of the included literature according to the physiotherapy evidence database (PEDro) scale criteria. Statistical analysis was performed using Stata 14.0 software after data extraction. Results: Twenty-five RCTs with a total of 1267 subjects were finally included. The results of the pairwise comparison of the Network Meta-analysis showed that the Timed Up and Go Test (TUGT) values of Low-frequency whole-body vibration training (LF-WBVT) was lower than the placebo and traditional rehabilitation groups, and the difference was statistically significant [WMD = -1.37, 95% CI (-2.53, -0.20)] [WMD = -1.84, 95% CI(-3.17,-0.51)]. The Five-repetition Sit-to-Stand Test (5STS) values of LF-WBVT, Medium-frequency whole-body vibration training (MF-WBVT), and High-frequency whole-body vibration training (HF-WBVT) were lower than the placebo and traditional rehabilitation groups, but none of them were statistically significant. In addition, the TUGT and 5STS values of HF-WBVT had a tendency to be lower than those of LF-WBVT and MF-WBVT, but neither of them was statistically different. The cumulative probability ranking results of both TUGT and 5STS showed that HF-WBVT was the best protocol. Conclusion: Current evidence shows that HF-WBVT may be the best protocol for improving balance in older adults. Due to the study's limitations, the conclusion obtained in this study still needs to be further confirmed by more high-quality studies. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021250405].

Spatial-temporal variations of forest and grassland phenology in the Yellow River Basin during 2000-2018.

The study of vegetation phenology is of great significance for understanding global climate change. The Yellow River basin has a wide spatial range and a complex ecological environment. The phenological characteristics of forest and grassland need further clarification. Based on the MODIS-EVI data from 2000 to 2018, we extracted the phenology of forest and grassland in the Yellow River basin using piecewise logistic and double logistic phenological models with the corresponding curvature change extremum method and derivative method, respectively. The temporal and spatial variations of phenological parameters were analyzed. The start of growing season (SOS) was at 90-165 day of year (DOY), and gradually delayed from southeast to northwest. The increase of 100 m elevation delayed SOS 0.94 d, and the SOS of forest was earlier than that of grassland. The end of growing season (EOS) was at 270-315 DOY, which delayed from west to southeast. For every 100 m increase in altitude, the EOS advanced 0.63 d, with EOS of forest being later than that of grassland. The length of growing season (LOS) was 110-230 d, which shortened gradually from southeast to northwest. The LOS of forest was larger than that of grassland. During the study, SOS showed an advance trend from 2000 to 2018 with a rate of 4.1 d·(10 a)-1, and the proportion of spatial advance area was 73.2%. There was an obvious advance in the central part of the basin. EOS generally showed a significant postponement trend with a rate of 2.3 d·(10 a)-1, and the proportion of spatially delayed area was 63.4%, the phenological advance and delay of forest was less stronger than that of grassland. LOS showed a significant prolongation trend with a rate of 6.4 d·(10 a)-1, and the proportion of spatial extension was 71.8%. The piecewise Logistic and double Logistic phenological models and the corresponding curvature extremum method and derivative method were suitable for the extraction of natural vegetation in the Yellow River Basin. The overall LOS of forest and grassland showed a prolonging trend, which was shortened with the increases of altitude. The LOS of forest was longer than that of grassland in the study area.

Construction and Manipulation of Serial Gradient Dilution Array on a Microfluidic Slipchip for Screening and Characterizing Inhibitors against Human Pancreatic Lipase.

Obesity is one of the foremost public health concerns. Human pancreatic lipase (hPL), a crucial digestive enzyme responsible for the digestion of dietary lipids in humans, has been validated as an important therapeutic target for preventing and treating obesity. The serial dilution technique is commonly used to generate solutions with different concentrations and can be easily modified for drug screening. Conventional serial gradient dilution is often performed with tedious multiple manual pipetting steps, where it is difficult to precisely control fluidic volumes at low microliter levels. Herein, we presented a microfluidic SlipChip that enabled formation and manipulation of serial dilution array in an instrument-free manner. With simple slipping steps, the compound solution could be diluted to seven gradients with the dilution ratio of 1:1 and co-incubated with the enzyme (hPL)-substrate system for screening the anti-hPL potentials. To ensure complete mixing of solution and diluent during continuous dilution, we established a numerical simulation model and conducted an ink mixing experiment to determine the mixing time. Furthermore, we also demonstrated the serial dilution ability of the proposed SlipChip using standard fluorescent dye. As a proof of concept, we tested this microfluidic SlipChip using one marketed anti-obesity drug (Orlistat) and two natural products (1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose (PGG) and sciadopitysin) with anti-hPL potentials. The IC50 values of these agents were calculated as 11.69 nM, 8.22 nM and 0.80 µM, for Orlistat, PGG and sciadopitysin, respectively, which were consistent with the results obtained by conventional biochemical assay.

Temperature sensitivity of leaf flushing in 12 common woody species in eastern China.

Leaf phenology is one of the most reliable indicators of global warming in temperate regions because it is highly sensitive to temperatures. Temperature sensitivity (ST) is defined as the values of changed days of leaf flushing date (LUD) per degree increase in temperatures. Climate warming substantially advanced LUD in the temperate region, but its effect on ST of LUD is still not clear. We used spring phenological records of 12 woody plants in eastern China in the years of 1983-2014 to explore temporal and spatial changes of LUD and ST. Furthermore, we compared the difference of ST and preseason temperatures in two periods (1983-1997 and 2000-2014), and explored the main factors regulating ST. The results showed that the average LUD significantly advanced (-2.7 days per decade). The mean LUD over the period 1983-2014 was in day of the year (DOY) 87 ± 7 across sites and species for the early leaf flushing species (EFS), and mean DOY 102 ± 5 for the late leaf flushing species (LFS). LUD was earlier in low latitude than that in high latitude. ST of Armeniaca vulgaris was the most sensitive to temperature across all sites (-3.66 d °C-1), while Firmiana simplex was the most insensitive (-2.37 d °C-1). LUD of EFS was more sensitive to temperature warming than that of LFS. At the same site, LUD of EFS would advance more obviously than that of LFS under global warming. For all species, ST decreased significantly with shorter preseason length and warmer temperatures at the preseason end. Our results had demonstrated a strong relationship between ST and the preseason length (mean temperature at the preseason end).

Effect of diffuse fraction on gross primary productivity and light use efficiency in a warm-temperate mixed plantation.

Diffuse radiation (I f) is one of important variables determining photosynthetic rate and carbon uptake of forest ecosystems. However, the responses of gross primary productivity (GPP) and light use efficiency (LUE) to diffuse fraction (DF) are still poorly understood. We used a 6-year dataset of carbon flux at a warm-temperate mixed plantation site in North China to explore the impacts of DF on GPP and LUE. During 2011-2017, ecosystem apparent quantum yield (α) and photosynthesis at photosynthetically active radiation (PAR) of 1800 µmol m-2 s-1 (P 1800) on cloudy days were 63% and 17% higher than on clear days, respectively. Under lower vapor pressure deficit (VPD) and air temperature (T a) conditions, canopy photosynthesis was significantly higher on cloudy skies than on clear skies. On half-hourly scale, increased DF enhanced α and P 1800. Daily GPP peaked at a median DF (=0.5), while daily LUE significantly increased with DF (p<0.01). Both GPP and LUE were mainly controlled directly by DF and PAR. DF had an indirect effect on LUE and GPP mainly through PAR. At high DF levels (>0.5), the increase in LUE did not make GPP enhancement. The direct effect of DF on GPP and LUE under lower T a and VPD was more sensitive than under higher T a and VPD. When DF was incorporated into the Michaelis-Menten model, it performed well in the GPP estimation, and the determination coefficient increased by 32.61% and the root mean square error decreased by 25.74%. These findings highlight the importance of incorporating DF into carbon sequestration estimation in North China.

3D geological implicit modeling method of regular voxel splitting based on layered interpolation data.

In view of the problems in traditional geological modeling methods, such as the insufficient utilization of geological survey data, the inaccurate expression of a stratigraphic model, and the large amount of model data, a 3D geological model cannot be smoothly loaded and rendered on the web end. In this paper, a 3D geological implicit modeling method of regular voxel splitting based on hierarchical interpolation data is proposed. This method first uses the boreholes and geological section data from a geological survey for data conversion and fusion, compares the applicability of different interpolation algorithms through cross-validation research, and uses the best fitting algorithm to interpolate and encrypt discrete points in the formation. Then, it constructs the regular voxels, designs five different regular voxel split types, and divides the voxels. In addition, the data structure design of the voxel split model is implemented, and the irregular voxel metadata structure is analyzed and displayed through Three.js. Using this method, based on the survey data of an area in Zhengzhou, the global workflow from data processing to model construction and visualization is demonstrated. The experimental results show that the model can integrate multisource hierarchical interpolation data; express different stratum structures accurately and smoothly, and can realize the rendering, spatial query and analysis of the internal information of a geological body in a browser.

Suppression of phosphodiesterase IV enzyme by roflumilast ameliorates cognitive dysfunction in aged rats after sevoflurane anaesthesia via PKA-CREB and MEK/ERK pathways.

Postoperative cognitive dysfunction (POCD) is a prevalent disorder after anaesthesia in the elderly patients. Roflumilast (RF), a phosphodiesterase 4 (PDE-4) inhibitor, could improve cognition with no side effects. Here, we sought to explore the efficacy of RF in the improvement of cognitive dysfunction caused by sevoflurane (Sev). Sprague-Dawley rats were anaesthetized, and the hippocampal neurons were treated with Sev to develop in vivo and in vitro POCD models, followed by RF administration. The mechanism of the PKA-CREB and MEK/ERK pathways in the pathogenesis of POCD was explored. Sev impaired the cognitive functions of rats, significantly reduced cyclic adenosine monophosphate (cAMP) concentrations and blocked the PKA-CREB and MEK/ERK pathways. Moreover, the Sev-treated rats and neurons exhibited enhanced apoptosis and reactive oxygen species (ROS). After treatment with RF, rats had better learning and memory function, and the activity of neurons in hippocampus and cortex was improved. Loss-of-function assay indicated that PKA-CREB and MEK/ERK signalling impairment reduced cAMP levels and promoted apoptosis and ROS in rat hippocampus and neurons. Generally, RF promotes neuronal activity in rats after Sev treatment by maintaining cAMP levels and sustaining the activation of PKA-CREB and MEK/ERK pathways. This might offer novel sights for POCD therapy.

Influence of Dexmedetomidine on Post-operative Atrial Fibrillation After Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials.

Background: Previous clinical studies and meta-analysis evaluating the influence of dexmedetomidine on postoperative atrial fibrillation showed inconsistent results. We performed an updated meta-analysis to evaluate the influence of dexmedetomidine on incidence of postoperative atrial fibrillation after cardiac surgery. Methods: Randomized controlled trials that evaluated the potential influence of dexmedetomidine on the incidence of atrial fibrillation after cardiac surgery were obtained by search of PubMed, Embase, and Cochrane's Library databases from inception to April 12, 2021. A random-effects model incorporating the potential publication bias was used to pool the results. Influences of patient or study characteristics on the efficacy of dexmedetomidine on atrial fibrillation after cardiac surgery were evaluated by meta-regression and subgroup analyses. Results: Fifteen studies with 2,733 patients were included. Pooled results showed that dexmedetomidine significantly reduced the incidence of atrial fibrillation compared to control (OR: 0.72, 95% CI: 0.55-0.94, p = 0.02) with mild heterogeneity (I 2 = 26%). Subgroup analysis showed that dexmedetomidine significantly reduced the incidence of atrial fibrillation in studies from Asian countries (OR: 0.41, 95% CI: 0.26-0.66, p < 0.001), but not in those from non-Asian countries (OR: 0.89, 95% CI: 0.71-1.10, p = 0.27; p for subgroup difference = 0.004). Meta-regression analysis showed that the mean age and proportion of male patients may modify the influence of dexmedetomidine on POAF (coefficient = 0.028 and 0.021, respectively, both p < 0.05). Subgroup analysis further showed that Dex was associated with reduced risk of atrial fibrillation after cardiac surgery in studies with younger patients (mean age ≤ 61 years, OR = 0.44, 95% CI: 0.28-0.69, p = 0.004) and smaller proportion of males (≤74%, OR = 0.55, 95% CI: 0.36-0.83, p = 0.005), but not in studies with older patients or larger proportion of males (p for subgroup difference = 0.02 and 0.04). Conclusions: Current evidence supports that perioperative administration of dexmedetomidine may reduce the risk of incidental atrial fibrillation after cardiac surgery, particularly in Asians.

Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish.

BACKGROUND: Cardiomyopathy is a kind of cardiovascular diseases, which makes it more difficult for the heart to pump blood to other parts of the body, eventually leading to heart failure. Naoxintong (NXT), as a traditional Chinese Medicine (TCM) preparation, is widely used in the treatment of cardiovascular diseases, including cardiomyopathy, while its underlying mechanism has not been fully elucidated. The purpose of this study is to investigate the therapeutic effect of NXT on cardiomyopathy and its molecular mechanism in zebrafish model. METHODS: The zebrafish cardiomyopathy model was established using terfenadine (TFD) and treated with NXT. The therapeutic effect of NXT on cardiomyopathy was evaluated by measuring the heart rate, the distance between the sinus venosus and bulbus arteriosus (SV-BA), the pericardial area, and the blood flow velocity of zebrafish. Then, the zebrafish hearts were isolated and collected; transcriptome analysis of NXT on cardiomyopathy was investigated. Moreover, the heg1 mutant of zebrafish congenital cardiomyopathy model was used to further validate the therapeutic effect of NXT on cardiomyopathy. Additionally, UPLC analysis combined with the zebrafish model investigation was performed to identify the bioactive components of NXT. RESULTS: In the TFD-induced zebrafish cardiomyopathy model, NXT treatment could significantly restore the cardiovascular malformations caused by cardiac dysfunction. Transcriptome and bioinformatics analyses of the TFD and TFD + NXT treated zebrafish developing hearts revealed that the differentially expressed genes were highly enriched in biological processes such as cardiac muscle contraction and heart development. As a cardiac development protein associated with cardiomyopathy, HEG1 had been identified as one of the important targets of NXT in the treatment of cardiomyopathy. The cardiovascular abnormalities of zebrafish heg1 mutant could be recovered significantly from NXT treatment, including the expanded atrial cavity and blood stagnation. qRT-PCR analysis further showed that NXT could restore cardiomyopathy phenotype in zebrafish through HEG1-CCM signaling. Among the seven components identified in NXT, paeoniflorin (PF) and salvianolic acid B (Sal B) were considered to be the main bioactive ones with myocardial protection. CONCLUSION: NXT presented myocardial protective effect and could restore myocardial injury and cardiac dysfunction in zebrafish; the action mechanism was involved in HEG1-CCM signaling.

Perfusion Imaging: An Advection Diffusion Approach.

Perfusion imaging is of great clinical importance and is used to assess a wide range of diseases including strokes and brain tumors. Commonly used approaches for the quantitative analysis of perfusion images are based on measuring the effect of a contrast agent moving through blood vessels and into tissue. Contrast-agent free approaches, for example, based on intravoxel incoherent motion and arterial spin labeling, also exist, but are so far not routinely used clinically. Existing contrast-agent-dependent methods typically rely on the estimation of the arterial input function (AIF) to approximately model tissue perfusion. These approaches neglect spatial dependencies. Further, as reliably estimating the AIF is non-trivial, different AIF estimates may lead to different perfusion measures. In this work we therefore propose PIANO, an approach that provides additional insights into the perfusion process. PIANO estimates the velocity and diffusion fields of an advection-diffusion model best explaining the contrast dynamics without using an AIF. PIANO accounts for spatial dependencies and neither requires estimating the AIF nor relies on a particular contrast agent bolus shape. Specifically, we propose a convenient parameterization of the estimation problem, a numerical estimation approach, and extensively evaluate PIANO. Simulation experiments show the robustness and effectiveness of PIANO, along with its ability to distinguish between advection and diffusion. We further apply PIANO on a public brain magnetic resonance (MR) perfusion dataset of acute stroke patients, and demonstrate that PIANO can successfully resolve velocity and diffusion field ambiguities and results in sensitive measures for the assessment of stroke, comparing favorably to conventional measures of perfusion.

An Automatic Concrete Crack-Detection Method Fusing Point Clouds and Images Based on Improved Otsu's Algorithm.

Cracks are one of the main distresses that occur on concrete surfaces. Traditional methods for detecting cracks based on two-dimensional (2D) images can be hampered by stains, shadows, and other artifacts, while various three-dimensional (3D) crack-detection techniques, using point clouds, are less affected in this regard but are limited by the measurement accuracy of the 3D laser scanner. In this study, we propose an automatic crack-detection method that fuses 3D point clouds and 2D images based on an improved Otsu algorithm, which consists of the following four major procedures. First, a high-precision registration of a depth image projected from 3D point clouds and 2D images is performed. Second, pixel-level image fusion is performed, which fuses the depth and gray information. Third, a rough crack image is obtained from the fusion image using the improved Otsu method. Finally, the connected domain labeling and morphological methods are used to finely extract the cracks. Experimentally, the proposed method was tested at multiple scales and with various types of concrete crack. The results demonstrate that the proposed method can achieve an average precision of 89.0%, recall of 84.8%, and F1 score of 86.7%, performing significantly better than the single image (average F1 score of 67.6%) and single point cloud (average F1 score of 76.0%) methods. Accordingly, the proposed method has high detection accuracy and universality, indicating its wide potential application as an automatic method for concrete-crack detection.

Naoxintong restores ischemia injury and inhibits thrombosis via COX2-VEGF/ NFκB signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Naoxintong (NXT) is a traditional Chinese medicine preparation that is often used in combination with aspirin in the treatment of cardiovascular diseases (CVD). One of the main symptoms of CVD is hypoxic-ischemia (HI). The purpose of this study is to find out the molecular nodes targeted by NXT and its related molecular pathways in vascular repair. MATERIALS AND METHODS: First, human vein umbilical endothelial cells (EA.hy926) were utilized to set up the Oxygen-Glucose Deprivation-Reoxygenation (OGD/R) model and treated with NXT. Cell proliferation, damage and apoptosis were detected by MTT, LDH, and flow cytometry assays. Second, transcriptional responses of OGD/R cells to NXT treatment were investigated. qRT-PCR, western blotting and inhibitor assays were performed. Third, the anti-thrombotic effect of NXT was evaluated by the zebrafish thrombosis model. Morphological observation, histological staining and qRT-PCR assays were implemented on zebrafish model to further observe in vivo the therapeutic effects of NXT on ischemia and thrombosis. RESULTS: In OGD/R EA.hy926 cells, NXT treatment could reduce ischemic vascular injury, increase cell viability and decrease the proportion of apoptosis. Through RNA-seq analysis, 183 differentially expressed genes (DEGs) were screened with 110 up-regulated genes and 73 down-regulated genes between OGD/R and OGD/R + NXT treated EA.hy926 cells. VEGF and NFκB pathways were enriched. Among these genes, COX2 was identified as one of important targets via which NXT could restore vascular injury. COX2 inhibitor (NS-398), and aspirin, a drug that prevents the development of CVD by targeting COX2, exhibited similar effects to NXT in the treatment of OGD/R EA.hy926 cells. In zebrafish thrombosis model, NXT could attenuate tail venous thrombus and recover the quantity of heart red blood cells. Furthermore, NXT could prevent the formulation of thrombosis and eliminate inflammation in zebrafish by COX2-VEGF/NFκB signaling. CONCLUSION: Our studies implicated that NXT could restore HI injury and inhibit thrombosis through COX2-VEGF/NFκB signaling, which is consistent with the molecular target of aspirin. This finding might explain the principle of NXT combined with aspirin in the treatment of cardiovascular diseases.

Effect of Pretreatment of S-Ketamine On Postoperative Depression for Breast Cancer Patients.

OBJECTIVE: This study aims to investigate the effect of the pretreatment of S-ketamine on postoperative depression (POD) for breast cancer patients with mild/moderate depression. METHODS: The present randomized, double-blinded controlled trial included 303 breast cancer patients with mild/moderate depression from June 2017 to June 2018. All patients were randomly divided into three groups: (1) control group, patients treated with normal saline; (2) racemic ketamine group, patients treated with racemic ketamine; (3) S-ketamine group, patients treated with S-ketamine. Operation time, blood loss and hospital stay and complications were recorded. The Visual Analog Scale (VAS) score was recorded, and the Hamilton Rating Scale for Depression (HAMD-17) scores, serum brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine (5-HT) were measured at three days, one week, one month and three months after surgery. RESULTS: No significant difference was found in operation time, bleeding volume and complication rate. In both groups, the VAS scores at one day and three days after surgery were significantly lower. The HAMD-17 scores were significantly lower, and the serum levels of both BDNF and 5-HT were remarkably higher at three days, one week and one month after surgery. Meanwhile, the HAMD-17 scores were remarkably lower, while the serum levels of BDNF and 5-HT were remarkably higher in the S-ketamine group. The BDNF and 5-HT levels were negatively correlated with the HAMD-17 score. CONCLUSION: S-ketamine is more effective for reducing POD for breast cancer patients.

Use of Various Doses of S-Ketamine in Treatment of Depression and Pain in Cervical Carcinoma Patients with Mild/Moderate Depression After Laparoscopic Total Hysterectomy.

BACKGROUND This study investigated the effects of various doses of S-ketamine on depression and pain management of cervical carcinoma patients with mild/moderate depression. MATERIAL AND METHODS This randomized, double-blind, controlled study included 417 cervical carcinoma patients who received laparoscopic modified radical hysterectomy from April 2015 to July 2018 and who also had mild/moderate depression symptoms based on HAMD-17 scores (8~24). All patients were randomized into 4 groups: 1) the control group, 2) the racemic ketamine group, 3) the high-dose S-ketamine group; and 4) the low-dose S-ketamine group. Pain was assessed using the Visual Analogue Score (VAS), and depression was assessed using theHAMD-17 score. Serum levels of BDNF and 5-HT were measured. RESULTS The 4 groups of patients showed no significant differences in operation time, bleeding volume, hospitalization duration, or complications. The high-dose S-ketamine group showed significantly lower VAS and HAMD-17 scores than all other groups at 1 day and 3 days postoperatively, but no differences were observed in the low-dose S-ketamine group and the racemic ketamine group. The high-dose S-ketamine group showed significantly higher serum BDNF and 5-HT levels at 1 day and 3 days after surgery. However, 1 week after surgery, no difference was observed in any of the treatment groups. CONCLUSIONS At subanesthetic dose, both 0.5 mg/kg and 0.25 mg/kg S-ketamine improved short-term depression and pain for cervical carcinoma patients after surgery, and the effects were better than with the same dose of racemic ketamine.

Cistanches alleviates sevoflurane-induced cognitive dysfunction by regulating PPAR-γ-dependent antioxidant and anti-inflammatory in rats.

This study aimed to investigate the protective effects and underlying mechanisms of cistanche on sevoflurane-induced aged cognitive dysfunction rat model. Aged (24 months) male SD rats were randomly assigned to four groups: control group, sevoflurane group, control + cistanche and sevoflurane + cistanche group. Subsequently, inflammatory cytokine levels were measured by ELISA, and the cognitive dysfunction of rats was evaluated by water maze test, open-field test and the fear conditioning test. Three days following anaesthesia, the rats were killed and hippocampus was harvested for the analysis of relative biomolecules. The oxidative stress level was indicated as nitrite and MDA concentration, along with the SOD and CAT activity. Finally, PPAR-γ antagonist was used to explore the mechanism of cistanche in vivo. The results showed that after inhaling the sevoflurane, 24- but not 3-month-old male SD rats developed obvious cognitive impairments in the behaviour test 3 days after anaesthesia. Intraperitoneal injection of cistanche at the dose of 50 mg/kg for 3 consecutive days before anaesthesia alleviated the sevoflurane-induced elevation of neuroinflammation levels and significantly attenuated the hippocampus-dependent memory impairments in 24-month-old rats. Cistanche also reduced the oxidative stress by decreasing nitrite and MDA while increasing the SOD and CAT activity. Moreover, such treatment also inhibited the activation of microglia. In addition, we demonstrated that PPAR-γ inhibition conversely alleviated cistanche-induced protective effect. Taken together, we demonstrated that cistanche can exert antioxidant, anti-inflammatory, anti-apoptosis and anti-activation of microglia effects on the development of sevoflurane-induced cognitive dysfunction by activating PPAR-γ signalling.

The short interference RNA (siRNA) targeting NMUR2 relieves nociception in a bone cancer pain model of rat through PKC-ERK and PI3K-AKT pathways.

BACKGROUND/AIM: Bone cancer pain (BCP) causes troubles and burdens to patients globally. Increasing evidence proved that neuromedin U receptor 2 (NMUR2) was involved in pains. Our study was performed to investigate the role of NMUR2 on BCP and the underlying mechanism. METHODS: The rats were raised and BCP rat model was established by injection with Walker 256 cells. The RNA and protein expression levels of NMUR2 in rat neurons-dorsal spinal cord cells, RNdsc cells were detected by qRT-PCR and western blot. The administration with NMUR2 was via intrathecal injection with siRNA to silence NMUR2. The tolerance of rat to pain was measured by mechanical allodynia test and presented by paw withdrawal threshold (PWT) value. The effects on protein kinase C (PKC)/extracellular regulated protein kinases (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signal pathways were examined by western blot. RESULTS: The expression of NMUR2 in both mRNA and protein levels was upregulated in BCP rat model. In addition, siRNA injection significantly decreased the expression of NMUR2 on the 3rd, 7th and 14th day. BCP group revealed lower PWT value compared with control while NMUR2 silence increased the PWT value compared with negative control. The phosphorylation of PKC, ERK, PI3K and AKT was increased in BCP model while was decreased by si-NMUR2. PKC/ERK and PI3K/AKT inhibitor administration increased the PWT value compared with BCP group. CONCLUSION: si-NMUR2 alleviates BCP via inactivation of PKC/ERK and PI3K/AKT signal pathways.

Novel frame shift mutation in ERCC6 leads to a severe form of Cockayne syndrome with postnatal growth failure and early death: A case report and brief literature review.

INTRODUCTION: Cockayne syndrome (CS) is a rare multisystemic autosomal recessive disease. The primary manifestations of which are developmental delay, neurological impairment, abnormal skin sensitivity to sunlight and unique facial appearance as sunken eyes, large ears, and thin large nose. The disorders of the nucleotide excision repair system significantly are caused by mutations of Excision repair cross-complementing group 6 (ERCC6) and Excision repair cross-complementing group 8 (ERCC8) genes, and the ERCC6 gene mutations are present in approximately 65% of cases. CASE PRESENTATION: Here we described a girl in a consanguineous Jordanian family with abnormal facial appearance and postnatal growth delay. She was not able to gain weight. Her condition deteriorated progressively and she developed difficulty of swallowing even to water. The patient was diagnosed as CS based on her facial appearance and neurologic dysfunction. The patient was examined at 3 years old, and died at 4 years old. CONCLUSION: Genetic analysis and sequencing revealed homozygosity for a novel frame shift mutation c.2911_2915del5ins9 (p.Lys971TryfsX14) in the ERCC6. The mutation is predicted to delete 5 nucleotides and add 9 nucleotides with a premature termination, resulting in approximately 34% length reduction of the wild-type transcript. The multisystem malformations of CS are clinically heterogeneous. The frame shift mutation of ERCC6 found in this patient is a novel one, which caused postnatal growth failure and early death. Our findings indicate truncated mutation in CS lead to more severe CS phenotype and add to the genotype-phenotype correlations in CS.

Screening and analysis of key active constituents in Guanxinshutong capsule using mass spectrum and integrative network pharmacology.

Guanxinshutong capsule (GXSTC) is an effective and safe traditional Chinese medicine used in the treatment of cardiovascular diseases (CVDs) for many years. However, the targets of this herbal formula and the underlying molecular mechanisms of action involved in the treatment of CVDs are still unclear. In the present study, we used a systems pharmacology approach to identify the active ingredients of GXSTC and their corresponding targets in the calcium signaling pathway with respect to the treatment of CVDs. This method integrated chromatographic techniques, prediction of absorption, distribution, metabolism, and excretion, analysis using Kyoto Encyclopedia of Genes and Genomes, network construction, and pharmacological experiments. 12 active compounds and 33 targets were found to have a role in the treatment of CVDs, and four main active ingredients, including protocatechuic acid, cryptotanshinone, eugenol, and borneol were selected to verify the effect of (GXSTC) on calcium signaling system in cardiomyocyte injury induced by hypoxia and reoxygenation. The results from the present study revealed the active components and targets of GXSTC in the treatment of CVDs, providing a new perspective to enhance the understanding of the role of the calcium signaling pathway in the therapeutic effect of GXSTC.

Phosphodiesterase 4 Inhibitor Roflumilast Protects Rat Hippocampal Neurons from Sevoflurane Induced Injury via Modulation of MEK/ERK Signaling Pathway.

BACKGROUND/AIMS: Sevoflurane, a commonly used volatile anesthetic, recently has been found has neurotoxicity in the central nervous system of neonatal rodents. This study aimed to reveal whether phosphodiesterase 4 (PDE-4) inhibitor roflumilast has protective functions in sevoflurane-induced nerve damage. METHODS: Hippocampal neurons were isolated from juvenile rats, and were exposed to sevoflurane with or without roflumilast treatment. Cell viability and apoptosis were respectively assessed by CCK-8 and flow cytometry. Western blot analysis was performed to detect the protein expressions of apoptosis-related factors, and core factors in MEK/ERK and mTOR signaling pathways. RESULTS: Toxic effects of sevoflurane on hippocampal neurons were observed, as cell viability was reduced, apoptotic cell rate was increased, Bcl-2 was down-regulated, and Bax, cleaved caspase-3 and -9 were up-regulated after 1% sevoflurane exposure for 16 h. Sevoflurane exhibited a temporarily (less than 16 h) inhibitory effect on MEK/ERK pathway, but has no impact on mTOR pathway. Roflumilast promoted the release of cAMP and down-regulated the protein expression of PDE-4. Roflumilast (1 µM) alone has no impact on viability and apoptosis of hippocampal neurons. However, roflumilast increased cell viability and deceased apoptosis in sevoflurane-injured neurons. Besides, roflumilast could recover sevoflurane-induced deactivation of MEK/ERK pathway. CONCLUSION: To conclude, this study demonstrated a neuroprotective role of roflumilast in sevoflurane-induced nerve damage. Roflumilast promoted hippocampal neurons viability, and reduced apoptosis possibly via modulation of MEK/ERK signaling pathway.