Elevated NT-proBNP predicts unfavorable outcomes in patients with acute ischemic stroke after thrombolytic therapy.

OBJECTIVE: Few studies correlated n-terminal pro-brain natriuretic peptide (NT-proBNP) with early neurological deterioration (END) and prognosis of acute ischaemic stroke (AIS) patients with rt-PA intravenous thrombolysis. Therefore this study aimed to investigate the relationship between NT-proBNP and END, and prognosis after intravenous thrombolysis in patients with AIS. METHODS: A total of 325 patients with AIS were enrolled. We performed the natural logarithm transformation on the NT-proBNP [ln(NT-proBNP)]. Univariate and multivariate logistic regression analyses were performed to assess the relationship between ln(NT-proBNP) and END, and prognosis and receiver operating characteristic (ROC) curves were used to show the sensitivity and specificity of NT-proBNP. RESULTS: After thrombolysis, among 325 patients with AIS, 43 patients (13.2%) developed END. In addition, three months follow-up showed a poor prognosis in 98 cases (30.2%) and a good prognosis in 227 cases (69.8%). Multivariate logistic regression analysis showed that ln(NT-proBNP) was an independent risk factor for END (OR = 1.450,95%CI:1.072 ~ 1.963, P = 0.016) and poor prognosis at three months follow-up (OR = 1.767, 95%CI: 1.347 ~ 2.317, P < 0.001) respectively. According to ROC curve analysis, ln(NT-proBNP) (AUC 0.735, 95%CI: 0.674 ~0.796, P < 0.001) had a good predictive value for poor prognosis, with a predictive value of 5.12 and sensitivity and specificity of 79.59% and 60.35% respectively. When combined with NIHSS to predict END(AUC 0.718, 95%CI: 0.631 ~ 0.805, P < 0.001) and poor prognosis(AUC 0.780, 95%CI: 0.724 ~ 0.836, P < 0.001), the predictive value of the model is further improved. CONCLUSION: NT-proBNP is independently associated with END and poor prognosis in patients with AIS following intravenous thrombolysis and has a particular predictive value for END and poor prognosis.

[Multi-center randomized double-blind controlled study on children's anorexia (spleen-stomach disharmony) treated with Child Compound Endothelium Corneum].

Child Compound Endothelium Corneum(CCEC)has the effects in invigorating the spleen and appetizing the appetite, and dissolving the accumulation of food. The recent studies have proved that it could improve gastrointestinal motility, restore physiological gastrointestinal peristalsis, increase gastrointestinal digestive motility, and enhance appetite. This trial aimed to evaluate its clinical efficacy and safety in the treatment of children's anorexia(spleen-stomach disharmony). A total of 240 children with anorexia in line with the inclusion and exclusion criteria were selected and randomly divided into experimental group and control group, with 120 in each group. Patients in the experimental group took CCEC and Erpixing Granules simulant. Patients in the control group took Erpi-xing Granules and CCEC simulant. After 21 days of treatment, there was no statistical difference in the recovery rate of anorexia, reduced food intake, eating time, weight change, traditional Chinese medicine syndrome effect, single symptom effect, and trace element Zn recovery rate between the two groups. Based on the non-inferiority test, the experimental group was not inferior to the control group in efficacy. How-ever, the effect of CCEC in reducing appetite in children with anorexia was better than that of control drugs(P<0.05). There was no statistical difference in the incidence of adverse events and adverse reactions between the two groups during the trial. This experiment confirmed the efficacy and safety of CCEC in the treatment of children's anorexia(spleen-stomach disharmony), with a safety and re-liability in clinical application. In addition, it was a better choice for children with anorexia who were mainly manifested by reduced appetite. Meanwhile, compared with granule, chewable tablets were more convenient to take in clinic. Therefore, the efficacy and safety of CCEC for the treatment of children's anorexia(spleen-stomach disharmony) were not inferior to those of Erpixing Granules, with a safety and reliability in clnic. However, due to the small sample size of this trial, the efficacy results only show a trend. It is suggested to further carry out a large-sample-size clinical study to define the clinical advantages of CCEC.

[Prediction of Cellulose, Hemicellulose, Lignin and Ash Content of Four Miscanthus Bio-Energy Crops Using Near-Infrared Spectroscopy].

Biomass energy is being industrialized rapidly in China in recent years, whereas, research on energy grass is still in primary stage. Only if near-infrared spectroscopy mode was constructed which was used to predict the lignin, cellulose and hemicellulose contents in energy crop, the varieties screening, performance evaluation and on-line control of industrialization would be facilitated. In this study, the prediction model for quality indices (cellulose, hemicellulose, lignin and ash) of four energy grass (Miscanthus) was built using Fourier transform near-infrared (FT-NIR) spectroscopy combined with partial least squares regression (PLSR), and the impacts exerted by particle size on the model were also revealed. The results showed that (1) the root mean error of cross validation (RMSECV) of cellulose, hemicelluloses and lignin contents were 1.35% (R = 0.88), 0.39% (R = 0.91) and 0.35 (R2 = 0.80), respectively in stalk and 0.72% (R = 0.88), 0.85% (R2 = 0.85) and 0.44 (R2 = 0.87), respectively in leaf. The model showed good performance in prediction of corresponding contents in unknown samples, however, no satisfying performance in ash content. (2) Both 2 mm and 0.5 mm grades of particle size can meet accuracy requirements of the model. But considering the time and labor cost, 2 mm grade was suggested for model building.

Gastric mucosal precancerous lesions in Helicobacter pylori-infected pediatric patients in central China: A single-center, retrospective investigation.

BACKGROUND: Helicobacter pylori (H. pylori) infects about 50% of the world population and is the major cause of chronic gastritis, peptic ulcers, and gastric cancer. Chronic H. pylori infection induces gastric mucosal precancerous lesions mostly in adulthood, and it is debatable whether these pathological conditions can occur in childhood and adolescents as well. Since this is a critical issue to determine if intervention should be offered for this population group, we investigated the gastric mucosal precancerous lesions in pediatric patients in an area in central China with a high prevalence of H. pylori and gastric cancer. AIM: To investigate the relationship of H. pylori infection and gastric mucosal precancerous lesions in children and adolescents in central China. METHODS: We screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms, and finally enrolled 1015 pediatric patients with H. pylori infection and endoscopic and histological data. H. pylori infection status was determined by rapid urease test and histopathological examination. Both clinical and pathological data were collected and analyzed retrospectively. Occurrence of gastric mucosal precancerous lesions, inflammatory activity and degree of inflammatory cell infiltration between H. pylori-positive and -negative groups were compared. RESULTS: Among the 1015 eligible children and adolescents, the overall H. pylori infection rate was 84.14% (854/1015). The infection rate increased with age. The incidence of gastric mucosal precancerous lesions in H. pylori-infected children was 4.33% (37/854), which included atrophic gastritis (17 cases), intestinal metaplasia (11 cases) and dysplasia (9 cases). In H. pylori-negative patients, only 1 atrophic gastritis case [0.62%, (1/161)] was found (P < 0.05). Active inflammation in H. pylori-infected patients was significantly higher than that in non-infected patients, and the H. pylori-infected group showed more severe lymphocyte and neutrophil granulocyte infiltration (P < 0.001). In addition, endoscopy revealed that the most common findings in H. pylori-positive patients were antral nodularity, but in H. pylori-negative patients only superficial gastritis was observed. CONCLUSION: In children and adolescents, gastric mucosal precancerous lesions occurred in 4.33% of H. pylori-infected patients in central China. These cases included atrophic gastritis, intestinal metaplasia, and dysplasia. The data revealed an obvious critical issue requiring future investigation and intervention for this population group.

Mesenchymal stem cell treatment for peripheral nerve injury: a narrative review.

Peripheral nerve injuries occur as the result of sudden trauma and lead to reduced quality of life. The peripheral nervous system has an inherent capability to regenerate axons. However, peripheral nerve regeneration following injury is generally slow and incomplete that results in poor functional outcomes such as muscle atrophy. Although conventional surgical procedures for peripheral nerve injuries present many benefits, there are still several limitations including scarring, difficult accessibility to donor nerve, neuroma formation and a need to sacrifice the autologous nerve. For many years, other therapeutic approaches for peripheral nerve injuries have been explored, the most notable being the replacement of Schwann cells, the glial cells responsible for clearing out debris from the site of injury. Introducing cultured Schwann cells to the injured sites showed great benefits in promoting axonal regeneration and functional recovery. However, there are limited sources of Schwann cells for extraction and difficulties in culturing Schwann cells in vitro. Therefore, novel therapeutic avenues that offer maximum benefits for the treatment of peripheral nerve injuries should be investigated. This review focused on strategies using mesenchymal stem cells to promote peripheral nerve regeneration including exosomes of mesenchymal stem cells, nerve engineering using the nerve guidance conduits containing mesenchymal stem cells, and genetically engineered mesenchymal stem cells. We present the current progress of mesenchymal stem cell treatment of peripheral nerve injuries.

[Time-order expression of caspase-3 and iNOS in contused human brain tissue].

OBJECTIVE: To investigate the expression of caspase-3 and iNOS in different intervals and to provide evidence for estimation of injury intervals after brain contusion in human. METHODS: Thirty cases died of serious brain injury were included into the injury groups and 5 cases died of non-brain injury were served as control group. To analyze the changes of caspase-3 and iNOS expression in brain samples at different intervals (2h, 4-8h, 10-14h, 1-2d, 3-5d, 8-11d) by immunohistochemistry and auto-image analysis system. RESULTS: The level of caspase-3 expression started to increase in 2 hours after brain contusion compared to the control group (P<0.05). The level of caspase-3 expression continued to increase in 1-2 days and maintained high level in 3-5 days compared to the control group (P<0.05), then decreased gradually. There was no statistically significant difference between the expression level of iNOS in 2 hours with the control group (P>0.05). But the expression level of iNOS began to increase in 4-8 hours after brain contusion and reached its maximum in 1-2 days, then decreased. Weak expression of iNOS still could be detected in 8-11 days. CONCLUSION: The expression of caspase-3 and iNOS can be used as effective evidence for human brain contusion interval.

Differential effects of overexpression of wild-type and mutant human alpha-synuclein on MPP+-induced neurotoxicity in PC12 cells.

The genetic background and the pathogenesis of familial Parkinson's disease (PD) have not been fully elucidated. Two missense mutations in the alpha-synuclein gene, A30P and A53T, have been linked to familial PD. Increasing evidence suggests the involvement of alpha-synuclein, the dopamine transporter (DAT), and neurotoxins in the pathogenesis of PD, but their relationships to the death of nigral cells remains poorly understood. In the present study, we used the PC12 cell line, a well recognized model of the nigral cell, to investigate the effects of overexpression of wild-type (WT) and mutant human alpha-synuclein on MPP+-induced neurotoxicity. We found that overexpression of mutant alpha-synuclein enhanced the toxicity of MPP+ to PC12 cells and elevated intracellular reactive oxygen species (ROS) levels, whereas overexpression of WT alpha-synuclein protected PC12 cells against MPP+ toxicity and lowered ROS levels. Furthermore, assays of 131I-FP-beta-CIT binding with DAT membrane fractions showed that WT and mutant alpha-synuclein had different effects on the expression of DAT on the cell membrane following exposure to MPP+. WT alpha-synuclein reduced the toxic effect of MPP+ by facilitating DAT internalization, while both A30P and A53T alpha-synuclein aggravated the toxic effect of MPP+ by reducing DAT internalization. These data indicate that alpha-synuclein regulates ROS levels and DAT surface expression in dopaminergic neurons, and thus changes the response of these cells to MPP+.

Necrostatin-1 protection of dopaminergic neurons.

Necroptosis is characterized by programmed necrotic cell death and autophagic activation and might be involved in the death process of dopaminergic neurons in Parkinson's disease. We hypothesized that necrostatin-1 could block necroptosis and give protection to dopaminergic neurons. There is likely to be crosstalk between necroptosis and other cell death pathways, such as apoptosis and autophagy. PC12 cells were pretreated with necroststin-1 1 hour before exposure to 6-hydroxydopamine. We examined cell viability, mitochondrial membrane potential and expression patterns of apoptotic and necroptotic death signaling proteins. The results showed that the autophagy/lysosomal pathway is involved in the 6-hydroxydopamine-induced death process of PC12 cells. Mitochondrial disability induced overactive autophagy, increased cathepsin B expression, and diminished Bcl-2 expression. Necrostatin-1 within a certain concentration range (5-30 µM) elevated the viability of PC12 cells, stabilized mitochondrial membrane potential, inhibited excessive autophagy, reduced the expression of LC3-II and cathepsin B, and increased Bcl-2 expression. These findings suggest that necrostatin-1 exerted a protective effect against injury on dopaminergic neurons. Necrostatin-1 interacts with the apoptosis signaling pathway during this process. This pathway could be a new neuroprotective and therapeutic target in Parkinson's disease.

[Construction of eukaryotic expression vector containing hSNCA gene and its pathogenic mutants and its expression in PC12 cells].

AIM: To construct recombinant eukaryotic expression vectors pEGFP-C3-SNCA containing human wild-type (WT) and pathogenic mutations A30P, A53T alpha-synuclein (SNCA), and to obtain monoclonal PC12 cell lines overexpressing human wild-type and pathogenic mutations A30P, A53T alpha-synuclein by stable transfection. METHODS: Human wild type SNCA gene was cloned by using RT-PCR. By T-A extension cloning, the gene was ligated with T-vector and sequenced. Based on it, the recombinant eukaryotic expression vectors containing wild type SNCA synonymous mutation or its G88C (Ala30Pro) and G209A (Ala53Thr) pathogenic mutation were constructed by site-directed mutagensis using primer variance in mononucleotide. And different recombinant plasmids pEGFP-C3-SNCA were identified with PCR, restriction enzyme digestion and DNA sequencing. PC12 cells were transfected with different recombinant plasmids pEGFP-C3-SNCA by liposome transfection method, screened with G418, and subcloned by limited dilution method to obtain different monoclonal PC12 cell lines stably over-expressing human wild-type, A30P or A53T alpha-synuclein, respectively, and PC12 cells stably transfected with pEGFP-C3 were used as control group. These monoclonal PC12 cell lines were identified with RT-PCR, Western blot and fluorescence microscopy. RESULTS: According to result of PCR, the double digestion and gene sequencing, it was comfirmed that recombinant eukaryotic expression vectors containing wild type SNCA synonymous mutation or its Ala30Pro and Ala53Thr pathogenic mutation had been constructed successfully. By means of RT-PCR, Western blot and fluorescence microscope, it was comfirmed that objective gene sequences in PC12 cells were stably over-expressed. CONCLUSION: The recombinant pEGFP-C3-SNCA vectors containing wild type SNCA synonymous mutation or its Ala30Pro and Ala53Thr pathogenic mutations had been constructed successfully. The transfected monoclonal PC12 cells are obtained in which three SNCA gene isoforms had stable expression.