Therapeutic efficacy of novel memantine nitrate MN-08 in animal models of Alzheimer's disease and vascular dementia / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer's disease(AD)and vascular dementia(VD)are the primary causes of dementia in elderly individuals,and therapeutic options for both conditions are limited.Overactivation of N-methyl-D-aspartate(NMDA)receptors,decreased cerebral blood flow,and subsequent pathological events,play signifi-cant roles in the progression of AD and VD.METHODS In this study,we investigated the therapeutic effects and underlying mechanisms of MN-08,a novel memantine nitrate,in mouse models of AD and rats with VD.RESULTS MN-08 was found to inhibit Aβ accumulation,prevent neuronal and dendritic spine loss,and attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice(following a 6-month preventative course)and in 8-month-old triple-transgenic(3×Tg-AD)mice(following a 4-month therapeutic course),as well as in rat models of VD with preventive and therapeutic treatments.In vitro,MN-08 was shown to bind to and antagonize NMDA receptors,inhibit calcium influx,and reverse dysregula-tions of the ERK and PI3K/Akt/GSK3β pathway,subse-quently preventing glutamate-induced neuronal loss.Additionally,MN-08 exhibited favorable pharmacokinet-ics,blood-brain barrier penetration,and safety profiles in rats and beagle dogs.CONCLUSION These findings suggest that the novel memantine nitrate MN-08 may be a useful therapeutic agent for AD and VD.

TBN improves motor function and prolongs survival in SOD1G93A and TDP-43M337V mouse model of ALS / 中国药理学与毒理学杂志

OBJECTIVE Amyotrophic lateral sclerosis(ALS)is a fetal neurodegenerative disease characterized by the progressive loss of upper and lower motor neu-rons,leading to skeletal muscle atrophy,weakness,and paralysis.Oxidative stress plays a crucial role in ALS pathogenesis,including the familial forms of the disease arising from mutations in the gene coding for superox-ide dismutase(SOD1).Additionally,the abnormal accu-mulation of TAR DNA-binding protein of 43 ku(TDP-43)is a pathological feature present in almost all patients,even though the pathogenesis of ALS is unclear.Current-ly,there is no drug that can cure ALS/FTLD.Tetramethyl-pyrazine nitrone(TBN)is a derivative of tetramethylapyr-azine,derived from traditional Chinese medicine Ligusti-cum chuanxiong,which has been extensively proven to have therapeutic effects on various models of neurode-generative diseases.METHODS We investigated the therapeutic effect of TBN in the SOD1G93A and TDP-43M337V ALS mouse models.In the SOD1G93A trans-genic mouse model,TBN was administered to mice via intraperitoneal or intragastric injection after the onset of motor deficits.We injected the TDP-43M337V virus into the striatum of mice unilaterally and bilaterally,and then administered TBN 30 mg·kg-1 intragastrically to observe changes in behavior and survival rate of mice.RESULTS TBN slowed the progression of motor neuron disease,as evidenced by improved motor performance,reduced spi-nal motor neuron loss and associated glial response,and decreased skeletal muscle fiber denervation and fibrosis.TBN treatment activated mitochondrial antioxidant activity through the PGC-1α/Nrf2/HO-1 pathway and decreased the expression of human SOD1.In the mice with unilateral injection of TDP-43M337V into the striatum,TBN improved motor deficits and cognitive impairment in the early stages of disease progression.In mice with bilateral injection of TDP-43M337V into the striatum,TBN not only improved motor function but also prolonged survival.Moreover,we demonstrate that its therapeutic effect may be through activation of the Akt/mTOR/GSK-3β and AMPK/PGC-1α/Nrf2 signaling pathways.CONCLUSION TBN shows promise as an agent for the treatment of ALS/FTLD.TBN is currently undergoing clinical investigation for several indications,including a Phase Ⅱ trial for ALS.

Qualitative systematic review of the safety and feasibility of early mobilization in critically ill patients with femoral catheters / 中国胸心血管外科临床杂志

@#Objective    To investigate the safety and feasibility of early mobilization in critically ill patients with femoral catheters, and to provide reference for guiding clinical rehabilitation training. Methods    The literature on the safety and feasibility of early mobilization in critically ill patients with femoral catheters included in PubMed, EMbase, OVID, Springer-link, Wiley Online Library, and Web of Science up to June 2021 was searched, and relevant data were extracted for analysis. Results    Seventy-two papers were initially screened, and 12 papers that met the criteria were finally included, covering 1 056 patients, and 489 patients had femoral catheters. Patients underwent 6 495 sessions of physical therapy, and a total of 62 patients had adverse events, including 14 (2.86%, 14/489) patients with catheter-related adverse events. Conclusion    Although early mobilization in critically ill patients with femoral catheters may lead to adverse catheter-related events, the incidence is low. Therefore, the associated risks and benefits should be weighed in clinical practice, and femoral catheter is not recommended as a contraindication for early mobilization in critically ill patients.

Effects of multi-disciplinary collaborative nursing on patients with transcatheter aortic valve implantation / 中国胸心血管外科临床杂志

@#Objective     To analyze the clinical intervention effect of multi-disciplinary team (MDT) nursing mode on patients after transcatheter aortic valve implantation (TAVI). Methods     A total of 89 patients who were admitted to our hospital and underwent TAVI surgery from April to December 2021 were selected, including 64 males and 25 females, with an average age of 64.7±11.8 years. The subjects were divided into a MDT intervention group (n=42) and a control group (n=47) according to different postoperative nursing intervention methods. Clinical effectivenesses were compared between the two groups. Results     The left ventricular ejection fraction in the two groups significantly increased on the 7th day after the operation, and the increase in the MDT intervention group was more obvious, with no statistical  difference between the two groups (P=0.14). On the 7th day after surgery, forced vital capacity/predicated value and forced expiratory volume in one second/predicated value significantly decreased, and decreased more significantly in the control group than those in the MDT intervention group with statistical differences (P=0.01). The ICU stay time (P=0.01), hospital stay time (P<0.01) and total postoperative pulmonary complications rate (P=0.03) in the MDT intervention group were significantly shorter or lower than those in the control group The evaluation results of the anxiety and depression status of the patients before and after nursing intervention showed that the scores of anxiety and depression in the two groups were significantly lower than before, and the scores of each scale in the MDT intervention group were lower. The score of quality of life of the two groups significantly improved at the end of 6 months after surgery, and in the MDT intervention group it was significantly higher than that in the control group (P=0.02). Conclusion     MDT intervention mode can promote the rapid recovery of patients after TAVI, effectively reduce the risk of postoperative pulmonary complications, and improve the postoperative quality of life.

Research progress on preoperative inspiratory muscle training for prevention of postoperative pulmonary complications in adult cardiac surgery / 中国胸心血管外科临床杂志

@#In the past two decades, adult cardiac surgery has developed by leaps and bounds in both anesthetic techniques and surgical methods, whereas the incidence of postoperative pulmonary complications (PPCs) has not changed. Until now PPCs are still the most common complications after cardiac surgery, resulting in poor prognosis, significantly prolonged hospital stays and increased medical costs. With the promotion of the concept of enhanced recovery after surgery (ERAS), pre-rehabilitation has been becoming a basic therapy to prevent postoperative complications. Among them, preoperative inspiratory muscle training as a very potential intervention method has been widely and deeply studied. However, there is still no consensus about the definition and diagnostic criteria of PPCs around the world; and there is significant heterogeneity in preoperative inspiratory muscle training in the prevention of pulmonary complications after cardiac surgery in adults, which impedes its clinical application. This paper reviewed the definition, mechanism, and evaluation tools of PPCs, as well as the role, implementation plan and challenges of preoperative inspiratory muscle training in the prevention of PPCs in patients undergoing cardiac surgery, to provide reference for clinical application.

Application of a 3D printed trabecular block cage in treatment of patients with basilar invagination and atlantoaxial dislocation / 中华创伤骨科杂志

Objective:To explore the short-term outcomes of a 3D printed trabecular block cage to assist posterior internal fixation for the treatment of patients with basilar invagination and atlantoaxial dislocation.Methods:Between June 2017 and February 2019, 12 patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial distraction and posterior internal fixation at Department of Orthopedics, The First Affiliated Hospital to Zhengzhou University. They were 5 males and 7 females, aged from 34 to 62 years (average, 45.6 years). 3D printed cages were inserted intraoperatively between the joints of the atlantoaxial lateral mass. The atlanto-dental interval interval (ADI), cervico-medullary angle (CMA) and distance from tip of the odontoid process to Chamberlain's line (DOCL) and the Japanese Orthopedic Association (JOA) scale were compared between preoperation and 12 months postoperation to observe the fusion of the joints of the atlantoaxial lateral mass.Results:Operation went on uneventfully in all the 12 patients. Operation time averaged 116.5 min (from 85 to 190 min), fluoroscopy frequency 9.4 times (from 6 to 21 times), and intraoperative bleeding 82.3 mL (from 50 to 210 mL). No such postoperative complications occurred as cerebrospinal leak, cerebral infarction, or breakage, displacement or loosening of implants. All patients were followed up for 18 to 42 months (mean, 26.3 months). Their preoperative JOA, ADI, CMA and DOCL [8.33±0.98, (8.66±1.64) mm, 119.63°±4.15° and (9.66±2.15) mm] were significantly improved to 14.17±1.03, (2.63±0.59) mm, 153.76°±7.88° and (2.07±0.69) mm ( P<0.05) at 12 months postoperation. Bony fusion was achieved in all the operative segments. Conclusion:In the treatment of patients with basilar invagination and atlantoaxial dislocation, a 3D-printed trabecular block cage can be used to assist posterior internal fixation to achieve satisfactory reduction and maintain the height of joint space, leading to satisfactory short-term outcomes.

Memantine Improves Cognitive Function and Alters Hippocampal and Cortical Proteome in Triple Transgenic Mouse Model of Alzheimer's Disease

Memantine is a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist clinically approved for moderate-to-severe Alzheimer's disease (AD) to improve cognitive functions. There is no report about the proteomic alterations induced by memantine in AD mouse model yet. In this study, we investigated the protein profiles in the hippocampus and the cerebral cortex of AD-related transgenic mouse model (3×Tg-AD) treated with memantine. Mice (8-month) were treated with memantine (5 mg/kg/bid) for 4 months followed by behavioral and molecular evaluation. Using step-down passive avoidance (SDA) test, novel object recognition (NOR) test and Morris water maze (MWM) test, it was observed that memantine significantly improved learning and memory retention in 3xTg-AD mice. By using quantitative proteomic analysis, 3301 and 3140 proteins in the hippocampus and the cerebral cortex respectively were identified to be associated with AD abnormalities. In the hippocampus, memantine significantly altered the expression levels of 233 proteins, among which PCNT, ATAXIN2, TNIK, and NOL3 were up-regulated, and FLNA, MARK 2 and BRAF were down-regulated. In the cerebral cortex, memantine significantly altered the expression levels of 342 proteins, among which PCNT, PMPCB, CRK, and MBP were up-regulated, and DNM2, BRAF, TAGLN 2 and FRY1 were down-regulated. Further analysis with bioinformatics showed that memantine modulated biological pathways associated with cytoskeleton and ErbB signaling in the hippocampus, and modulated biological pathways associated with axon guidance, ribosome, cytoskeleton, calcium and MAPK signaling in the cerebral cortex. Our data indicate that memantine induces higher levels of proteomic alterations in the cerebral cortex than in the hippocampus, suggesting memantine affects various brain regions in different manners. Our study provides a novel view on the complexity of protein responses induced by memantine in the brain of AD.

Effect of Rosuvastatin on fasting plasma glucose after coronary stent implantation in elderly patients / 中华老年医学杂志

Objective@#To investigate the effect of Rosuvastatin on fasting plasma glucose after coronary stent implantation in elderly patients with non-diabetes mellitus.@*Methods@#A total of 216 non-diabetic elderly patients undergoing coronary stent implantation in our hospital from November 2015 to April 2018 were enrolled, with a follow-up in the cardiovascular department after discharge from the Hospital.The demographic data, follow-up time, and laboratory results at hospital admission and the last outpatient visit were collected retrospectively.@*Results@#At the end of follow-up, Fasting plasma glucose(FPG)was increased in 191 patients with normal baseline FPG level as compared with the baseline level(t=-3.783, P=0.000). The incidence of new-onset diabetes was higher in the pre-diabetes group than in the normal blood glucose group(24.0% vs.2.6%, χ2=16.72, P=0.000).@*Conclusions@#Rosuvastatin increases fasting blood glucose levels in elderly non-diabetic patients after coronary stent implantation.Pre-diabetes may increase the risk for rosuvastatin-associated new-onset diabetes.

Effect of Rosuvastatin on fasting plasma glucose after coronary stent implantation in elderly patients / 中华老年医学杂志

Objective To investigate the effect of Rosuvastatin on fasting plasma glucose after coronary stent implantation in elderly patients with non-diabetes mellitus.Methods A total of 216 nondiabetic elderly patients undergoing coronary stent implantation in our hospital from November 2015 to April 2018 were enrolled,with a follow-up in the cardiovascular department after discharge from the Hospital.The demographic data,follow-up time,and laboratory results at hospital admission and the last outpatient visit were collected retrospectively.Results At the end of follow-up,Fasting plasma glucose(FPG)was increased in 191 patients with normal baseline FPG level as compared with the baseline level(t =-3.783,P =0.000).The incidence of new-onset diabetes was higher in the pre-diabetes group than in the normal blood glucose group(24.0％ vs.2.6％,x2 =16.72,P =0.000).Conclusions Rosuvastatin increases fasting blood glucose levels in elderly non-diabetic patients after coronary stent implantation.Pre-diabetes may increase the risk for rosuvastatin-associated new-onset diabetes.

Postoperative delirium prediction model for elderly patients undergoing orthopedic surgery / 中华创伤骨科杂志

Objective To establish a preliminary model which can effectively predict the risk for postoperative delirium (POD) in elderly orthopedic patients and verify its effectiveness.Methods This prospective study involved 2 cohorts.For an analysis cohort,the assessment data of 148 elderly orthopedic patients were collected who had been treated at Department of Orthopaedics,the First Affiliated Hospital of Zhengzhou University from June to October 2017.The relevant risk factors for POD (gender,age,BMI,schooling ＜ 9 years,history of smoking and alcohol drinking,concomitant diseases and perioperative factors) were screened after comparing POD and non-POD patients.All the risk factors were analyzed and a predictive model was established after valuation of independent risk factors.A predictive cohort of 66 patients was included according to the same inclusion and exclusion criteria as the analysis cohort out of the patients who had been treated at our hospital from November to December 2017.The 2 cohorts were scored by the predictive model to verify the validity of the model.Results A total of 18 risk factors were identified in this study.In the analysis cohort,age (P =0.006),schooling ＜ 9 years (P =0.043),cerebrovascular disease or mental illness (P =0.004),preoperative albumin (P =0.038) and intraoperative infusion of allogeneic blood (P =0.019) were risk factors for POD.Of them,age (P =0.037),schooling ＜ 9 years (P =0.003) and intraoperative infusion of allogeneic blood (P =0.042) were independent ones.In the predictive model,age ＞ 75 years was assigned 3 points,schooling ＜ 9 years 2 points and intraoperative infusion of allogeneic blood 5 points.The validity of the ROC curve was verified for the predictive model.According to the ROC curve,the analysis cohort had AUC =0.66 and the predictive cohort AUC =0.75,indicating a certain predictive value of the model.Conclusion Our predictive model can be used to effectively screen out those with a high risk for postoperative delirium from elderly orthopedic patients.

Secondary posterior internal fixation after transoral anterior atlantoaxial release under 3D operative microscopy for irreducible atlantoaxial dislocation / 中华创伤骨科杂志

Objective To explore the clinical efficacy of secondary posterior internal fixation after transoral anterior atlantoaxial release under 3D operative microscopy for treatment of irreducible atlantoaxial dislocation.Methods From January 2014 to May 2016,12 patients with irreducible atlantoaxial dislocation were treated with secondary posterior internal fixation after transoral anterior atlantoaxial release under 3D operative microscopy in our hospital.They were 7 males and 5 females,with an average age of 37.1 years (from 25 to 54 years).The efficacy was analyzed in terms of their visual analogue scale (VAS),Japanese Orthopaedic Association (JOA) scoring,improvement rate of neurological function,American Spinal Injury Association (ASIA) grading,atlas-dens interval (ADI),space available for the cord (SAC) and cervicomedullary angle (CMA) before and one year after operation.Results The patients were followed up for more than one year.All the atlantoaxial joints obtained anatomic reduction.Their preoperative values of VAS (5.73 ± 1.36 points),JOA score (9.03 ± 2.12 points),ADI (8.34 ± 1.12 mm),SAC (9.53 ± 0.69 mm) and CMA (121.23°±4.32°) were significantly improved one year after operation (1.21 ±0.63 points,14.32±2.51 points,2.83 ± 0.36 mm,14.23 ± 1.22 mm and 153.53° ± 9.25°, respectively) (P ＜0.05).The improvement rate of neurological function increased gradually with the postoperative time,reaching 94.14％ ±5.11％ one year after operation.The postoperative ASIA grading was significantly improved too one year after operation (P ＜ 0.05).Conclusion Secondary posterior internal fixation after transoral anterior atlantoaxial release under 3D operative microscopy may lead to fine clinical efficacy one year after operation for patients with irreducible atlantoaxial dislocation.

Traditional Chinese medicine combined with radiotherapy for treatment of middle and advanced esophageal neoplasms: an analysis of prognostic factors / 肿瘤研究与临床

Objective To explore the prognostic factors of middle and advanced esophageal neoplasms treated by traditional Chinese medicine combined with radiotherapy.Methods A total of 462 esophageal neoplasms patients treated by traditional Chinese medicine combined with radiotherapy from March 2009 to March 2012 in Civil Administration Hospital of Hebei Province were retrospectively analyzed.The overall median survival time and the survival rate of 1,3 and 5 years were calculated by using life table.Log-rank test was used for single-factor analysis and Cox model was used for multiple-factor analysis.Results The median survival time of 462 esophageal neoplasm patients was 24.2 months (12.9-36.6 months).The survival rate of 1,3 and 5 years was 80.3 ％,30.6 ％ and 10.5 ％ respectively.Single-factor analysis showed that the age (x2 =89.773,P =0.000),tumor diameter (x2 =102.373,P =0.000),clinical staging (x2 =128.903,P =0.000),concomitant with other diseases (x2 =65.366,P =0.000) and the short term effect (x2 =64.948,P =0.000) were associated with prognosis of middle and advanced esophageal neoplasms treated by traditional Chinese medicine combined with radiotherapy.Multiple-factor analysis showed that the age (RR =1.625,95 ％ CI 1.251-2.111,P=0.000),clinical staging (RR =2.437,95 ％ CI 1.874-3.168,P=0.000),concomitant with other diseases (RR =1.1.628,95 ％ CI 1.278-2.076,P =0.000) and the short term effect(RR =1.865,95 ％ CI 1.594-2.182,P =0.000) were the independent prognosis factors for middle and advanced esophageal neoplasms treated by traditional Chinese medicine combined with radiotherapy.Conclusion Elderly patients,esophageal neoplasms in stage Ⅲ,concomitant with other diseases and poor short-term effect could influence the prognosis of the patients with middle and advanced esophageal neoplasms treated by traditional Chinese medicine combined with radiotherapy.

Effect of Danshensu derivative on angiogenesis in zebrafish / 中国药理学通报

Aim Toinvestigatethepro-angiogenic effects of Danshensu derivative ADTM and explore its underlying possible signaling pathway using zebrafish embryosasinvivomodels.Methods Theangiogenesis activities of ADTM were determined in experimental models of normal and VEGFR tyrosine kinase inhibitorⅡ(VRI )-induced vascular defective zebrafish embry-os.Embryos were treated with various concentrations (50,100,200 μmol · L-1 ) of ADTM for indicated time.The diameter and the numbers of endothelial cells of zebrafish SIVs were evaluated,respectively.In VRI model,the number of intact and defective ISVs in each zebrafish embryo was counted.The total RNA of zebrafish embryos was extracted and transcriptional profiling was analyzed by deep sequencing.Quantita-tive real-time PCR(qPCR)was performed to 4 genes selected from transcriptional profiling to validate the data collected from transcriptome analysis.Results ADTMsignificantlyincreasedsubintestinalvessels (SIVs)diameter in a concentration-dependent manner in normal zebrafish as well as restored VRI-induced blood vessels defect in VRI-exposed zebrafish. The transcriptome data analysis demonstrated that 19 signif-icantly changed genes were mapped to insulin signaling pathway.The qPCR data are in good agreement with those obtained by deep sequencing and support the consistency between the two methods for determining relative expression levels in the zebrafish model.Con-clusion Inzebrafishmodel,ADTMexhibitsthe effects of angiogenesis and blood vessel restoration. The underlying mechanism may be involved in the acti-vation of insulin signaling pathway.

Effects of new drug T-006 on improving learning and memory abilities in scopolamine-induced dementia Kunming mice / 中国药理学通报

Aim ToexploretheeffectsofnewdrugT-006 on improving learning and memory abilities in scopolamine-induced dementia mice and its possible mechanism.Methods 72maleKunmingmicewere randomly divided into six groups:normal control group,model group,donepezil treatment group,T -006 treatment group with different doses(1,3 and 10 mg·kg-1 ).All mice were treated by intragastric ad-ministration for 14 consecutive days. Learning and memory abilities were tested by a five-day Morris water maze trial from the 1 1 th day.the first 4 days of the five-day Morris water maze,the navigation test was performed,the last day of Morris water maze is the spatial probe test.During the navigation test, mice were intraperitoneally given 2 mg · kg-1 scopolamine 20 minutes before entering the water,while normal control group mice administrated with sterile saline in-stead.Mice were not given T-006 nor scopolamine in spatial probe test.After Morris water maze,all mice were sacrificed for hippocampus and cortex.The activi-ties of AchE and SOD and the levels of GSH and MDA in hippocampus and cortex were measured after tissue harvesting.Results Comparedwithmodelgroup,T-006 could obviously improve learning and memory abil-ities in scopolamine-induced mice, significantly in-crease the levels of SOD and GSH and decrease the levelsofMDAandAchE.Conclusion T-006can significantly improve cognitive abilities in scopolamine-induced dementia mice,and its relevant mechanism may be closely related to its antioxidative effect and the ability to decrease AchE level.

Value of CT findings in predicting the need for surgery in patients with small bowel obstruction / 实用放射学杂志

Objective To investigate the value of CT findings in predicting the need for surgery in patients with small bowel obstruction (SBO).Methods Seventy patients with SBO were classified into non-operation and surgery groups according to the clinical treatment.The CT findings were retrospectively compared between the two groups,and the predictive value for surgery of useful CT findings was analyzed.Results Thirty three of 70 patients were cured with non-operative treatment and other 37 with surgery.The incidences of complete collapse of transitional zone,mesenteric edema,ascites,engorgement of mesenteric veins,decreased enhancement of bowel wall,decreased enhancement of mesenteric arteries and veins in surgery group were statistically higher than those in non-operation group,with odds ratios for surgery of 10.56,5.13,4.72,5.45,5.77,3.02 and 6.59,respectively.The diameter of dilated bowel,bowel wall thickness,and the incidence of target sign,intestinal pneumatosis,displacement,convergence and tortuosity of mesenteric vasculatures were not statistically different between the two groups.Conclusion Multiple CT findings of SBO are useful to predict the need for surgery,and may provide important information for clinical management of SBO.

Effects and mechanisms of chloro-oxime derivatives on spatial learning and memory dysfunction in two dementia animal models / 中国药理学通报

Aim To explore the effects and mecha-nisms of choro-oxime derivatives on spatial learning and memory impairment in Kunming mice and SD rats induced by scopolamine and Aβ1-42 , respectively. Methods 40 Kunming mice were randomly divided into 5 groups: control group, model group, donepezil treatment group, arimoclomol treatment group and TCO-2 treatment group. There were 8 mice in each group. Mice of control group were established by intra-peritoneal injection of saline, and mice of other groups were injected with scopolamine and caused memory im-pairment. Both control group and model group were treated with solvent by intraperitoneal administration;donepezil treatment group received donepezil by intra-gastric administration; arimoclomol treatment group and TCO-2 treatment group were given the correspond-ing drugs by abdominal injection, respectively. The solvent and drugs were given at the same time every morning for 8 days. Spatial learning and memory abili-ty were tested by Morris water maze from the fifth day of the drugs administration. 40 SD rats were divided into 5 groups the same as the dementia model men-tioned above. Mice of control group were established by intracerebroventricular injection of saline, and mice of other groups were injected with insoluble Aβ1-42 to be induced of memory impairment. Solvent and drugs were also delivered as mentioned above. Morris water maze was carried out from the fifth day of the drug de-livery. After that, acetyl cholinesterase activity of hip-pocampus was tested with acetyl cholinesterase reagent kit; the content of Aβ1-42 in hippocampus was meas-ured by ELISA assay kit;the expression of phosphoryl-ated tau proteins was detected by Western Blot. Re-sults In both two dementia models, choro-oxime de-rivatives could improve the spatial learning and memory ability, shorten the escape latency and increase the times of crossing the former platform. Choro-oxime de-rivatives could also inhibit the acetyl cholinesterase ac-tivity in animal brain, decrease the concentration of Aβ1-42 and the expression of phosphorylated tau pro-teins in the dementia rats’ hippocampus. Conclusions Spatial learning and memory deficits induced by sco-polamine and Aβ1-42 could be reversed by choro-oxime derivatives. It may be concerned with enhancement of the cholinergic system functions and reduction of the levels of Aβ1-42 and phosphorylated tau proteins in the brain.

Efficacy of pedicle screw technique in treatment of os odontoideum combined with atlantoaxial dislocation / 中华创伤杂志

ObjectiveTo evaluate the efficacy and radiological variation of pedicle screw technique in the treatment of os odontoideum combined with atlantoaxial dislocation.MethodsFifteen patients with os odontoideum combined with atlantoaxial dislocation were treated with occipitocervical fusion or atlantoaxial fixation.Two patients with irreducible atlantoaxial dislocation were treated surgically with transoral anterior atlantoaxial release and one treated with posterior arch removal plus occipitocervical fusion.Two patients with atlas deformity and one infant were treated with occipitocervical fusion.The rest patients were treated with posterior reduction and pedicle screw internal fixation.Clinical manifestations and imaging changes were followed up to evaluate the clinical efficacy.ResultsAll patients were followed-up for average 26 months (range,7-47 months).Neurological recovery was significantly improved in 13 patients and took a turn for the better in two.The average JOA scores was increased from average preoperative 8.27 to postoperative 15. According to Hirabayashi,the average improvement rate was77％,including 10 patients with excellent outcomes and five with good outcomes,with excellence rate of100％.The cervical-medullary angle was increased from average preoperative 130.3° to postoperative151.7°.Postoperative X-rays and CT showed good atlantoaxial alignment and solid bony fusion in all pa-tients,with no shedding or breakage of the fixators.ConclusionOccipitocervical fusion or adantoaxial fixation through pedicle screw technique is an effective method for treatment of os odontoideum combined with irreducible atlantoaxial dislocation.

Synthesis and preliminary evaluation of anti-HIV agent AZT prodrug / 药学学报

In this research, phosphate and thiophosphate prodrugs 3a, 3b of anti-HIV agent AZT were synthesized, and their anti-HIV activities and cytotoxicities were investigated in vitro. Results showed that the prodrugs 3a and 3b with an IC50 value of 11.0 and 4.0 micromol x L(-1), respectively, were less toxic than AZT (1.0 micromol x L(-1)). Although the EC50 values of both 3a (0.04 micromol x (L(-1) and 3b (0.16 micromol x L(-1)) were lower than that of AZT (0.01 micromol x L(-1)), the therapeutic index (IC50/EC50) of prodrug 3a (275) was much higher than that of both AZT (100) and prodrug 3b (25). This indicated that the prodrug 3a merited further investigation as an anti-HIV agent.

Prediction of absorption of 10-hydroxycamptothecin in small intestines of rats with its partition coefficients in phases of liposomes and water / 中国中药杂志

This paper explore the possibility of using the partition of 10-hydroxycamptothecin in the phases of liposome and water to predict the absorption of the drug in small intestine of rats. In order to certify this theory, the in vivo absorption model have been used to study the absorption of 10-hydroxycamptothecin in the small intestine of rats while altering the pH of the medium. The correlation has been explored between the partition of drug in the phases of liposome and water and the absorption of drug in the small intestines of rats. And it was found that the partition of 10-hydroxycamptothecin in the phases of liposome and water and the absorption of the drug in small intestines of rats altered with the changes of pH, and there existed a good relative coefficient between them. All of these indicated that partition of 10-hydroxycamptothecin in phases of liposome and water can be used to predict its absorption in small intestines of rats.