High performance liquid chromatography-time-off-flight mass spectrometer (HPLC-TOFMS) technology coupled with partial least squares discriminant analysis (PLS-DA) processed by SIMCA-P software was applied to investigate serum endogenous metabolites alternations of valsartan in spontaneous hypertension rats (SHR). And MetPA platform was used to connect identified potential biomarkers in corresponding metabolic pathways to find possible therapeutic mechanism of valsartan. Valsartan significantly declined the blood pressure of SHRs (P < 0.05) at fourth week. The metabolic profiling significantly changed and four metabolites involved in G protein-coupled pathway were identified. Metabolomics is able to detect holistic and microcosmic alternations in organism, so as to elucidate therapeutic mechanism of drugs.
Animals ; Biomarkers ; blood ; Blood Pressure ; Chromatography, High Pressure Liquid ; Discriminant Analysis ; Least-Squares Analysis ; Mass Spectrometry ; Metabolome ; Metabolomics ; Rats ; Rats, Inbred SHR ; Valsartan ; pharmacology

Objective: To explore the research method suitable for the component compatibility and optimization design of Chinese materia medica (CMM) by taking the blood pressure-lowering effect of the effective components in Ramulus Uncariae cum Uncie total alkaloids (RUCUTA) and Semen Raphani total alkaloids (SRTA) as the research objects. Methods: According to the procedure of "orthogonal design-evaluation on drug effect-partial least-squares regression (PLSR)", using contractive pressure as index, the ratio of RUCUTA and SRTA was optimized by orthogonal design method. The data were analyzed by range analysis, variance analysis, multiple regression analysis, and PLSR analysis. Results: According to the result of the data analysis and considering the economic costs, the optimal ratio of the two components was 25 μg/g RUCUTA and 30 μg/g SRTA. Conclusion: The compatibility of RUCUTA and SRTA could effectively reduce blood pressure. The orthogonal design method combined with PLSR could eliminate the interaction among the various factors and be suitable for the component compatibility in CMM and optimization design.

OBJECTIVETo explore effective approaches of treating elderly patients with distal tibiofibular fractures.

METHODSFrom August 2008 to October 2012,175 elderly patients with distal tibiofibular fractures were treated with locking compression plate (LCP) through anterior tibial. There were 112 males and 63 females with an average of 71.3 (ranged 60 to 83) years old. Of them,89 cases were treated by anterior tibial tension reduced incision with LCP,including 62 males and 27 females with a mean age of (71.8 +/- 6.4) years old. Eighty-six patients were treated by distal tibial incision with LCP,including 58 males and 28 females with a mean age of (70.3 +/- 6.7) years old. Swelling time, operation time, intraoperative blood loss, hospital stay, healing time, complications and AOFAS scores were compared between two groups after operation.

RESULTSSwelling time in anterior tension reduced incision with LCP and distal tibial incision with LCP was (5.6 +/- 1.3) and (9.7 +/- 2.1) days, healing time was (4.2 +/- 1.4) and (5.4 +/- 1.9) months,and complications were found 3 in tension reduced incision and 10 in distak tibial incision respectively;and all data shown statistically significant differences between two groups (P < 0.05). At 12 months after operation,AOFAS score was 89.0 +/- 9.7, 87.9 +/- 9.4; and there was no statistically significant difference between two groups (P > 0.05).

CONCLUSIONTension reduced incision through anterior tibial combined with locking compression plate fixation in treating elderly patients with distal tibiofibular fractures can provide good clinical effects with quick fracture healing and low complications.

Adult ; Aged ; Aged, 80 and over ; Bone Plates ; Female ; Fibula ; injuries ; surgery ; Fracture Fixation, Internal ; instrumentation ; methods ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; Tibia ; injuries ; surgery ; Tibial Fractures ; surgery ; Treatment Outcome

In recent years, non-viral gene vectors have attracted great attention for efficient gene delivery due to the advantages, including low toxicity, low immunogenicity and simple preparation. Polyethylenimine (PEI) is one of the typical non-viral gene carriers that have been widely utilized for gene delivery owing to its superior capabilities in gene compression and buffering capacity. This article discusses the processes of gene delivery and the barriers of PEI-based carrier during the gene delivery, such as low biocompatibility, cytotoxicity, lack of specific targeting and insufficient gene release, etc. Therefore, we summarize the multiple approaches for the modifications of PEI in terms of improved biocompatibility, degradability, specific targeting and buffering capacity. Furthermore, we also review on the recent impressive progresses of smart stimuli-responsive PEI carriers, including endogenous stimuli (pH, reactive oxygen species, glutathione, biomolecular, etc), exogenous stimuli (light, temperature, magnetic field, etc) and dual-responsive strategies, which might provide guidance for the development of more efficient and safer non-viral gene vectors.

Complex genetic variation has been known to occur during the transmission of human enterovirus (HEV), and the HEV virulence and pathogenicity enhanced by genetic recombination also pose a serious threat to human health. In recent years, the interest in recombination mechanism of genetic plasticity has been renewed with the emergence of pathogenic recombinant circulating vaccine-derived polioviruses, which were implicated in poliomyelitis outbreaks in several regions of the world with insufficient vaccination coverage. This paper reviews recent research progress in HEV genome, including evolutionary characteristics, recombination types, and in vitro recombinant construction.
Animals ; Biomedical Research ; trends ; Enterovirus ; classification ; genetics ; Enterovirus Infections ; virology ; Humans ; Recombination, Genetic ; Viral Proteins ; genetics

Adult ; Chronic Disease ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Occupational Diseases ; Radiation Injuries

Objective To confirm the predictive value of diaphragm thickening fraction (DTF) on successful weaning by bedside ultrasound in patients with myasthenia gravis crisis. Methods A prospective study was conducted. The patients with myasthenia gravis crisis undergoing mechanical ventilation admitted to Department of Critical Care Medicine of the Affiliated Hospital of Qingdao University from March 2015 to February 2017 were enrolled. All patients underwent a low level pressure support mode of spontaneous breathing test (SBT), and rapid shallow breathing index (RSBI) was recorded. The indicators of right diaphragm thickness at the end of inspiration (DTei) and expiration (DTee) were determined by bedside ultrasound at 5 minutes and 60 minutes of SBT, and DTF was calculated, the changes in above parameters were observed during SBT. The patients were divided into successful weaning group and failure weaning group, and the differences in above indexes were compared between the two groups. Receiver operating characteristic curve (ROC) was used to evaluate the predictive value of DTF and RSBI at 60 minutes of SBT on successful weaning. Results A total of 37 patients were enrolled in the study. Ultrasonic measurement data of 63 person-times at 5 minutes of SBT and 50 at 60 minutes of SBT were obtained. There were no statistical differences in RSBI, DTei, DTee, and DTF at 5 minutes of SBT between successful weaning group (n = 33) and failure weaning group (n = 30). At 60 minutes of SBT, compared with successful weaning group (n = 33), the patients in failure weaning group (n = 17) had a higher RSBI (times·min-1·L-1: 80.41±29.08 vs. 63.94±23.84, t = 2.146, P = 0.037), and lower DTee, DTei and DTF [DTee (mm): 22.00±6.25 vs. 25.45±4.99, t = 2.127, P = 0.039; DTei (mm): 27.94±6.19 vs. 38.48±6.15,t = 5.731, P = 0.000; DTF: (24.46±14.11)% vs. (62.04±30.21)%, t = 4.845, P = 0.000]. There were no statistical differences in RSBI, DTei, DTee, and DTF between 5 minutes and 60 minutes of SBT in 33 person-time successful weaning (all P > 0.05). In 17 person who had 60 minutes of SBT but failed weaning, the RSBI at 60 minutes of SBT was significantly higher than that at 5 minutes (times·min-1·L-1: 80.41±29.08 vs. 57.29±22.46, t = 2.400, P = 0.029), and DTei and DTF were significantly decreased [DTei (mm): 27.94±6.19 vs. 35.35±6.84, t = 3.024, P = 0.000; DTF:(24.46±14.11)% vs. (61.89±23.97)%, t = 5.810, P = 0.000], but the change of DTee during SBT showed no statistical significance. ROC curve analysis showed that the area under ROC curve (AUC) of DTF at 60 minutes of SBT for predicting successful weaning was 0.898; when DTF ≥ 27.9% as the cut-off point, the sensitivity was 93.9%, specificity was 70.6%. The AUC of RSBI for predicting successful weaning was 0.669; when RSBI ≥ 86.50 times·min-1·L-1 as the cut-off point, the sensitivity was 81.8%, specificity was 52.9%. Conclusion DTF at 60 minutes of SBT is the effective index of successful weaning prediction in mechanical ventilation patients with myasthenia gravis crisis.

OBJECTIVETo explore the clinical effects of Dynesys system for the treatment of multiple segment lumbar degenerative disease.

METHODSA total of 28 patients with lumbar degenerative disc disease treated with Dynesys system from December 2008 to May 2011 were retrospectively reviewed. There were 16 males and 12 females, aged from 27 to 75 years old with an average of 49.1 years. Thirteen patients with multiple segmental lumbar intervertebral disc protrusion, including L3-L5 in 7 cases, L2-L4 in 1 case and L4-S1 in 5 cases. Fifteen patients with multiple segmental lumbar spinal stenosis, including L3-L5 in 10 cases, L4-L5 in 4 cases and L2-S1 in 1 case. The symptoms of lumbago and (or) intermittent claudication in all patients were treated with conservative treatments for more than 6 months and these methods did not work. Visual analogue scale (VAS) was used to analyze the lumbar and leg pain, imaging data were used to measure the intervertebral space height and intervertebral motion of fixed segment and upper adjacent segment, Oswestry Disability Index (ODI) was used to evaluate the clinical effect.

RESULTSAll operations were successful and the patients were followed up from 38 to 65 months with an average 50.6 months. At final follow-up, ODI and VAS of the low back pain and leg pain were (25.10±6.52)%, (1.25±0.70) points and (1.29±0.89) points, respectively and were decreased compared with preoperative (P<0.05). Postoperative intervertebral space heights were increased and intervertebral motions were decreased in fixed segment compared with preoperative (P<0.05). There were no significant differences in intervertebral space heights and intervertebral motions of upper adjacent segment between preoperative and postoperative (P>0.05).

CONCLUSIONDynesys system may obtain long-term clinical curative effect in treating multiple lumbar degenerative disease. It can partially preserve the intervertebral motions of the fixed segments, have little effect on adjacent segments. The long-term clinical effect of Dynesys still need longer time follow-up observation.

Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc Degeneration ; pathology ; surgery ; Joint Instability ; Lumbar Vertebrae ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Visual Analog Scale

The skin ulceration syndrome of sea cucumber is a kind of desease induced by bacterium.In order to investigate the bacterium of infected sea cucumber and detect the N-acyl-homoserine lactones(AHLs) se-cretion of the bacterium,7 bacterial strains were isolated from the infected sea cucumber.These strains were identified by physiological-biochemical characteristics and 16S rDNA sequence.Results show that strain C6 belongs to Tenacibaculum,strain 4 belongs to Shewanella putrefaciens group,strain TB belongs to Vibrio,strain BP2,BP3,BP4 and BP6 belong to Pseudoalteromonas,respectively.AHLs were detected with strain Agrobacterium tumefaciens KYC55.Among these bacterial strains,strain C6,4,TB,BP3 and BP4 can se-cret AHLs,while strain BP2 and BP6 can’t.And the AHLs activity differs,from the highest to the lowest are 4,TB,BP4,BP3 and C6.

OBJECTIVETo study the changes of urine metabolites in hypertension patients of ascendant hyperactivity of Gan yang syndrome (AHGYS), and to explore its essence in hypertension patients.

METHODSTen typical hypertension patients of AHGYS were recruited as the patient group, and the other twelve healthy volunteers were recruited as the normal group. The metabolite profiling in the urine were collected using by high performance liquid chromatography coupled with time of flight mass spectrometry (HPLC-TOFMS). The principal component analysis (PCA) and partial least-square discriminant analysis (PLS-DA) were analyzed using SIMCA-P Software. The differential metabolites in the urine were found out and identified. The possible relevant metabolic pathways were explained.

RESULTSThe data from the analysis by PCA in the urine samples of the patient group and the normal group showed, two sets of data could be obviously classified in the score plot. Compared with the normal group, significant changes happened to the body metabolism in the patient group. The metabolites relevant to hypertension patients of AHGYS were determined using the PLS-DA. Fifteen compounds of the structure and metabolic pathways had been confirmed through inquiring KEGG Database, mainly including amino acids, free fatty acids, sphingosine, and so on.

CONCLUSIONSThe hypertension patients of AHGYS were studied using HPLC-TOFMS combined with pattern recognition, thus finding out small molecular metabolic markers from the microscopic field, which was advantageous in probing the biological nature of Chinese medicine syndromes.

Adult ; Aged ; Case-Control Studies ; Chromatography, High Pressure Liquid ; methods ; Discriminant Analysis ; Female ; Humans ; Hypertension ; diagnosis ; urine ; Least-Squares Analysis ; Male ; Mass Spectrometry ; methods ; Medicine, Chinese Traditional ; methods ; Metabolome ; Middle Aged ; Principal Component Analysis