Objective To evaluate the effect of intraperitoneal (IP) clonidine on the expression of GAP-43 mRNA in the spinal cord in a rat model of chronic neuropathic pain. Methods Thirty-six male SD rats weighing 180-220 g were randomly assigned to one of 3 groups (n=12 each) : group Ⅰsham operation (S); group Ⅱ chronic constriction injury (CCI) and group Ⅲ tP clonidine + CCI (CL). The animals were anesthetized with IP 10% chloral hydrate 300 mg/kg. The right sciatic nerve was exposed and 4 ligatures were placed in group CCI and CL. Clonidine 1 mg/kg was given IP immediately after surgery in group CL. Paw-withdrawal threshold (PWT) to thermal and von Frey filament stimulation was measured before (T_0, baseline) and at 3, 7 and 14 days after surgery (T_(1-3)). The animals were then killed. The lumbar segment of the spinal cord was removed for determination of the expression of GAP-43 mRNA. Results The PWT to thermal and mechanical stimulation was significantly reduced at 3 days after surgery (T_1) in group CCI and CL as compared with group S, and was significantly higher at T_2 and T_3 in group CL than in group CCI. The GAP-43 mRNA expression in the spinal cord was significantly increased in group CCI and CL as compared with group S and significantly lower in group CL than in group CCI. Conclusion lntraperitoneal clonidine can inhibit hyperalgesia by reducing the expression of GAP-43 mRNA in the spinal cord in a rat model of chronic neuropathic pain.

ObjectiveTo investigate the effect of propofol on endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression in thoracic aorta of hypertensive rats.MethodsHealthy SD rats of both sexes weighing 240-280 g were used in this study.Hypertension was induced by subcutaneous deoxycorticosterone 25 mg/kg twice a week for consecutive 7 weeks.Sixty-four hypertensive rats were randomly divided into four groups (n ＝ 16 each):hypertension group (group H),low,medium and high dose propofol group ( groups P1,P2,P3 ).Groups P1,P2 and P3 received infusion of propofol at a rate of 20,30 and 40 mg* kg- 1 · h- 1 for 3 h respectively,while group H received equal volume normal saline instead of propofol.Mean arterial pressure (MAP) was monitored and recorded before,1 h and 3 h after the start of propofol or normal saline infusion.All animals were sacrificed at 3 h of intravenous administration.Blood samples were collected by taking out the eyeballs for determination of serum NO concentrations by nitrate reductase method.The expression of eNOS mRNA,iNOS mBNA was determined by reverse transcription-polymerase chain reaction.The expression of eNOS and iNOS protein was determined by Western blot.ResultsCompared to group H,MAP was decreased significantly,the serum NO concentrations were increased significantly,the expression of eNOS mRNA and protein in thoracic aorta was up-regulated,and the expression of iNOS mRNA and protein in thoracic aorta was down-regulated in a dose-dependent manner in groups P1,P2 and P3 ( P < 0.05 or 0.01 ).ConclusionPropofol can down-regulate iNOS expression and up-regudate eNOS expression in endothelial cells of thoracic aorta and promote NO release in hypertensive rats,Which is the mechanism of propofol decreasing pressure.

Objective To evaluate the efficacy of ultrasound-guided continuous transverses abdominis plane (TAP) block when used for postoperative analgesia in the patients undergoing total hysterectomy.Methods Forty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 38-64 yr,weighing 50-80 kg,undergoing elective total hysterectomy with general anesthesia,were divided into 2 groups using a random number table:continuous TAP block group (CTAP group,n =21) and patient-controlled intravenous analgesia (PCIA) group (n=19).In group CTAP,bilateral TAP block was performed with 0.2％ ropivacaine 20 ml under ultrasound guidance before operation,and 0.2％ ropivacaine 5 ml/h was infused into bilateral TAPs after extubation.In group PCIA,the patients received PCIA with sufentanil 1 μg/ml after extubation,and the PCIA pump was set up to deliver a 2 ml bolus dose,a 15 min lockout interval and background infusion at a rate of 2 ml/h.Analgesia lasted until 72 h after operation in both groups.When visual analog scale＞4,morphine 5 mg was intramuscularly injected as rescue analgesic.The recovery time of postoperative intestinal function,length of hospital stay,patient's satisfaction with analgesia,requirement for rescue analgesia,TAP block-related adverse reactions and development of postoperative nausea and vomiting were recorded.In group CTAP,blood samples were collected from the peripheral vein immediately after the end of operation and at 2,6,12,24,48 and 72 h after operation for determination of concentrations of ropivacaine in plasma and free ropivacaine in plasma using high-performance liquid chromatography.Results Compared with group PCIA,the requirement for rescue analgesia and incidence of nausea and vomiting were significantly decreased,the recovery time of postoperative intestinal function was shortened,the score for patient's satisfaction with analgesia was increased (P＜0.05),and no significant change was found in the length of hospital stay in group CTAP (P＞0.05).No TAP block-related adverse reactions were found in group CTAP.In group CTAP,the concentration of ropivacaine in plasma began to increase at 2 h after operation and peaked at 48 h after operation,the concentration of free ropivacaine in plasma began to increase at 2 h after operation and peaked at 24 h after operation (P＜0.05).Conclusion Ultrasound-guided continuous TAP block produces good analgesic efficacy when used for the patients undergoing total hysterectomy.

Drug targets discovery is one of the most important elements in new drug development, and a variety of methods have been developed recently from this point of view. This paper proposed a network-based local and global consistency for cardiovascular genes identification. Results were evaluated through the widely used database HPRD and DrugBank. Results showed that our algorithm can give reasonable candidate targets set. The method in this paper could be an impressive solution for targets searching.
Algorithms ; Cardiovascular Diseases ; genetics ; metabolism ; prevention & control ; Databases, Protein ; Drug Delivery Systems ; methods ; Drug Discovery ; methods ; Gene Regulatory Networks ; Humans ; Models, Theoretical ; Pharmaceutical Preparations ; administration & dosage ; metabolism ; Protein Binding ; Protein Interaction Mapping ; methods ; Proteins ; genetics ; metabolism

Network pharmacology, as a new developmental direction of drug discovery, was generating attention of more and more researchers. The key problem in drug discovery was how to identify the new interactions between drugs and target proteins. Prediction of new interaction was made to find potential targets based on the predicting model constructed by the known drug-protein interactions. According to the deficiencies of existing predicting algorithm based bipartite graph, a supervised learning integration method of bipartite graph was proposed in this paper. Firstly, the bipartite graph network was constructed based on the known interactions between drugs and target proteins. Secondly, the evaluation model for association between drugs and target proteins was created. Thirdly, the model was used to predict the new interactions between drugs and target proteins and confirm the new predicted targets. On the testing dataset, our method performed much better than three other predicting methods. The proposed method integrated chemical space, therapeutic space and genomic space, constructed the interaction network of drugs and target proteins, created the evaluation model and predicted the new interactions with good performance.
Algorithms ; Drug Delivery Systems ; methods ; Drug Discovery ; methods ; Genomics ; methods ; Models, Theoretical ; Pharmaceutical Preparations ; administration & dosage ; metabolism ; Protein Binding ; Protein Interaction Mapping ; methods ; Proteins ; genetics ; metabolism

Objective:To investigate the clinical features of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis misdiagnosed as mental disorder, improve the early diagnosis rate and reduce misdiagnosis.Methods:The clinical data of patients with anti-NMDA receptor encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University from 2012 to 2018 were collected. Patients misdiagnosed as mental disorders were screened out. Their psychiatric symptom characteristics, disease course characteristics, imaging and laboratory findings, treatment and prognosis were retrospectively analyzed.Results:A total of 121 cases of anti-NMDA receptor encephalitis were collected, and 43 cases of mental disorders were screened out. Sixteen of the 43 patients (37.2%) had prodromal symptoms, and all the patients had psychiatric behavioral abnormalities (100%), including 32 cases (74.4%) of seizures, 13 cases (30.2%) of decreased level of consciousness, 21 cases (48.8%) of involuntary movements, 15 cases (34.9%) of decreased memory, 8 cases (18.6%) of speech dysfunction, and 8 cases (18.6%) of other neurological symptoms (central hyperventilation, autonomic dysfunction). Memory loss was observed in 15 cases (34.9%), speech dysfunction in 8 cases (18.6%), other neurological symptoms (central hypoventilation, autonomic dysfunction) in 8 cases (18.6%), and various symptoms may appear simultaneously or successively in the same patient. Thirty-eight cases had complete resolution of symptoms or only minor physical impairment, and 5 cases had recurrent admissions with mental abnormalities and seizures. The recurrence rate accounted for 11.6% (5/43).Conclusions:The clinical manifestations of anti-NMDA receptor encephalitis are complex and varied. Most of them have mental behavior abnormalities as the first symptom, which is easily misdiagnosed as mental disorder and delayed treatment will lead to prolonged disease course and poor prognosis.

By combing out the historical development logic of sports and health integration and the current development achievement, the underlying logic of sports and health integration is described systematically in multiple dimensions, and the prominent dilemmas in development are analyzed as follows: lack of residents' health literacy, excessive dependence on medical treatment, low bridging of talent team construction, lack of the guidance of funds centralization, insufficient financial support, imperfect management system and mechanism, and unspecific departmental collaboration.The strategies for solving the problems are as follows: strengthening the integration of sports science and clinical medicine, consolidating the technical integration of sports prescription and clinical standardization process, further improving the business integration of exercise intervention and clinical treatment, and enhancing the industrial integration of sports products and medical treatment.

Objective:To establish a mouse model of gastric cancer by inoculating MKN45 cells into mice with normal immune function utilizing microcarrier technology. Methods:A total of 60 male C57BL/6 mice were randomly divided into three groups, namely, 2D, con-trol, and 3D groups, according to the coculture system of MKN45 and microcarrier. The mouse models of gastric carcinoma were estab-lished by hypodermic injection. The time of tumorigenesis, rate of tumor formation, and pathological features were observed in each group. Results:In the 3D group, the time of tumor formation was short, whereas the rate of tumor formation was high (80%). No de-tectable tumor formations were observed in the 2D and control groups. HE and immunohistochemical staining of the transplantation tumor model showed evident characteristics of human gastric cancer. Conclusion:A human gastric cancer model in normal immune mice was successfully established. The onset and development mechanism of gastric cancer could be more effectively investigated in mice with normal immune function through this model. Moreover, a more valuable and new animal model for the research and devel-opment of anticancer drug was established.

Objective:To investigate therole of serum amylase elevation in the evaluation of diabetic ketoacidosis (DKA) patients and the related factors affecting serum amylase (AMS) levels in patients with diabetic ketoacidosis.Methods:A total of 249 patients with DKA who were admitted to the First Affiliated Hospital of Zhengzhou University from November 2011 to August 2018 were selected for this retrospective study. The patients were divided into the normal group ( n=176) and the elevated group ( n=73) according to the AMS level measured by fasting venous blood samples. The enumeration data such as sex, type of DM, diabetic vascular complications, number of deaths, number of ICU monitoring, and number of acute pancreatitis (AP) after discharge were analyzed by chi-square test or Fisher test, and the measurement data such as age, pH, HbA1c, CO 2CP, Ca 2+, BUN, and Scr were analyzed by independent sample t test to compare the difference between the two groups. Results:The intensive care unit (ICU) monitoring rate was 50.7%, the median length of stay in ICU was 4 days, the median length of hospital stay was 14 days, and the median treatment cost was 28 000 yuan, which were higher in the elevated group than those in the normal group ( P<0.05). There were no significant differences in mortality, AP during hospitalization, and the probability of AP after discharge between the elevated group and the normal group ( P>0.05). The duration of diabetes, the number of previous DKA, the incidence of diabetic vascular complications, HbA1c, pH, BUN, and Scr in the elevated group were all higher than those in the normal group ( P<0.01 or P<0.05). Conclusions:DKA patients with elevated AMS are more likely to be admitted to ICU, and the length of stay in ICU, total length of hospital stay and total cost of treatment are all increased. Where as the overall mortality rate during hospitalization and the likelihood of AP after discharge are not increased.

Objective:To study the protective effects of various doses of Glycyrrhizin on hippocampus of young rats with status epilepticus (SE).Methods:Lithium chloride and pilocarpine were injected intraperitoneally into male Sprague-Dawley (SD) rats (with a postnatal age of 18-21 days), so as to induce SE in rats.The rats were divided into 5 groups according to the random number table method: control group, SE group, SE+ low dose Glycyrrhizin group, SE+ medium dose Glycyrrhizin group and SE+ high dose Glycyrrhizin group.Three different doses of Glycyrrhizin (20 mg/kg, 40 mg/kg and 60 mg/kg) were injected intraperitoneally into the rats.The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in serum of SE rats were determined by enzyme linked immunosorbent assay.Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression levels of TNF- α, IL-1β and IL-6 in hippocampus of SE rats.The expression levels of Bax, Bcl-2 and Caspase-3 in hippocampus were detected by Western blot.The damage of neurons was measured by hematoxylin and eosin (HE) staining and Nissl staining.Neurons apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The mitochondrial changes were observed under transmission electron microscopy.One-way ANOVA followed by Tukey post-hoc test was used for statistical analysis. Results:Compared to the control group, TNF-α[(369.69±58.07) ng/L vs. (75.46±14.64) ng/L], IL-1β[(242.27±25.23) ng/L vs. (45.29±5.90) ng/L] and IL-6[(288.15±24.60) ng/L vs. (46.59±8.80) ng/L] in the serum of SE rats were significantly up-regulated(all P<0.05). Compared to SE group, low, medium and high doses Glycyrrhizin could effectively reduce the levels of TNF-α[(216.67±8.31) ng/L, (158.81±5.03) ng/L and (113.69±12.54) ng/L vs. (369.69±58.07) ng/L], IL-1β[(131.21±5.50) ng/L, (86.60±7.79) ng/L and (65.06±4.39) ng/L vs. (242.27±25.23) ng/L] and IL-6[(150.24±9.48) ng/L, (101.70±5.85) ng/L and (91.60±2.81) ng/L vs. (288.15±24.60) ng/L] released in serum after SE occurred (all P<0.05). The neuronal damage, loss, apoptosis and mitochondrial damage were found in the hippocampus of SE rats.Glycyrrhizin could ameliorate these symptoms.Compared to the control group, Bax levels(0.57±0.01 vs. 0.14±0.01)and Caspase-3 levels(0.54±0.00 vs. 0.11±0.01)in the hippocampus of SE rats were markedly increased, while Bcl-2 levels(0.27±0.01 vs. 0.57±0.02)were decreased(all P<0.05). Compared to the SE group, low, medium and high doses Glycyrrhizin could effectively reduce the levels of Bax(0.51±0.02, 0.45±0.03 and 0.40±0.02 vs. 0.57±0.01)and Caspase-3(0.47±0.02, 0.42±0.02 and 0.37±0.01 vs. 0.54±0.00), and increase the levels of Bcl-2(0.41±0.02, 0.45±0.02 and 0.51±0.01 vs. 0.27±0.01)(all P<0.05). Conclusions:Glycyrrhizin can effectively protect the hippocampus of young rats with SE.