China's Space Animal Experiments Obtained Achievements

Entering into the 1990s, Chinese scientists have made mice, drosophila and silkworm eggs experiments in space with satellites and achieved remarkable results. These animals were put in space environment units with the ability of adjusting pressure, temperature and moisture control, air conditioning and purifying as well as foods and water supply. After 8-days’ flight, all performance parameters were normal and met the design requirements. The two mice kept alive for 5 days and 10 hours

Biocompatibility of vascular stents manufactured using metal injection molding in animal experiments

This study aimed to evaluate the feasibility and safety of a novel stent manufactured by metal injection molding(MIM)in clinical practice through animal experiments.Vessel stents were prepared using powder injection molding technology to considerably improve material utilization.The influence of MIM carbon impurity variation on the mechanical properties and corrosion resistance of 316L stainless steel was studied.In vitro cytotoxicity and animal transplantation tests were also carried out to evaluate the safety of MIM stents.The results showed that the performance of 316L stainless steel was very sensitive to the carbon content.Carbon fluctuations should be precisely controlled during MIM.All MIM stents were successfully implanted into the aortas of the dogs,and the MIM 316L stents had no significant cytotoxicity.The novel intravascular stent manufactured using MIM can maintain a stable form and structure with fast endothelialization of the luminal surface of the stent and ensure long-term patency in an animal model.The novel intravascular stent manufactured using MIM demonstrates favorable structural,physical,and chemical stability,as well as biocompatibility,offering promising application in clinical practice.

Finding biomarkers of experience in animals

At a time when there is a growing public interest in animal welfare,it is critical to have objective means to assess the way that an animal experiences a situation.Objectivity is critical to ensure appropriate animal welfare outcomes.Existing behavioural,physiological,and neurobiological indicators that are used to assess animal welfare can verify the absence of extremely negative outcomes.But welfare is more than an absence of negative outcomes and an appropriate indicator should reflect the full spectrum of experience of an animal,from negative to positive.In this review,we draw from the knowledge of human biomedical science to propose a list of candidate biological markers(biomarkers)that should reflect the experiential state of non-human animals.The proposed biomarkers can be classified on their main function as endocrine,oxidative stress,non-coding molecular,and thermobiological markers.We also discuss practical challenges that must be addressed before any of these biomarkers can become useful to assess the experience of an animal in real-life.

Biosafety and data quality considerations for animal experiments with highly infectious agents at ABSL-3 facilities

Animal models are crucial for the study of severe infectious diseases,which is essential for determining their pathogenesis and the development of vaccines and drugs.Animal experiments involving risk grade 3 agents such as SARS CoV,HIV,M.tb,H7N9,and Brucella must be conducted in an Animal Biosafety Level 3(ABSL-3)facility.Because of the in vivo work,the biosafety risk in ABSL-3 facilities is higher than that in BSL-3 facilities.Undoubtedly,management practices must be strengthened to ensure biosafety in the ABSL-3 facility.Meanwhile,we cannot ignore the reliable scientific results obtained from animal experiments conducted in ABSL-3 laboratories.It is of great practical significance to study the overall biosafety concepts that can increase the scientific data quality.Based on the management of animal experiments in the ABSL-3 Laboratory of Wuhan University,combined with relevant international and domestic literature,we indicate the main safety issues and factors affecting animal experiment results at ABSL-3 facilities.Based on these issues,management practices regarding animal experiments in ABSL-3 facilities are proposed,which take into account both biosafety and scientifically sound data.

Role of CD36 in central nervous system diseases

CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and microglia.CD36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord injury.CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or functions.Here,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule compounds.Moreover,we predicted the structures of binding sites between CD36 and antagonists.These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.

Research advances in experiments on correlation between schizophrenia and myelin sheath abnormality

Schizophrenia,as a common mental disease,seriously threatens the physical and mental health of human beings.It is characterized by many mental and behavioral disorders,such as uncoordinated thinking and emotional mode which separated from the actual living environment.Patients with schizophrenia are prone to relapse and deterioration due to their long course of disease,resulting in the loss of labor force.It has been proved that the occurrence and development of schizophrenia is closely related to the abnormal development of oligodendrocytes,which have the function of myelin formation and the dysfunction of myelin sheath itself.For a comprehensive understanding of myelin abnormal effects on the pathogenesis of schizophrenia,this paper is to review the literature,then summarize and discuss the animal experimental literature related to the abnormal myelin sheath in schizophrenia from the perspectives of behavioristics,neuroimaging,protein expression and stereology,in order to further clarify the influence of the abnormal myelin sheath on the pathogenesis of schizophrenia and provide ideas for the diagnosis of schizophrenia and the research and development of new drugs.

Experimental Studies on the Irradiation of Facial Bones in Animals:A Review

Introduction: Radiotherapy is often used to treat head and neck malignancies, with inevitable effects on the surrounding healthy tissues. We have reviewed the literature concerning the experimental irradiation of facial bones in animals. Materials and Methods: A PubMed search was performed to retrieve animal experiments on the irradiation of facial bones that were published between January 1992 and January 2012. The search terms were “irradiation facial bone” and “irradiation osteoradionecrosis”. Results: Thirty-six publications were included. The irradiation sources were Cobalt60, orthovoltage, 4 - 6 megavolt photons, and brachytherapy. The total dose varied between 8 - 60 Gy in single or multiple fractions. The literature presents a broad range of animal studies that differ in terms of the in vivo model, irradiation, observation period, and evaluation of results. Discussion: The different animal models used leave many questions unanswered. A detailed and standardized description of the methodology and results would facilitate the comparability of future studies.

Animal experimental studies using small intestine endoscope

AIM To assess the feasibility and safety of a novel enteroscope,negative-pressure suction endoscope in examining the small intestine of a porcine model.METHODS In vitro experiments in small intestinal loops from 20pigs and in vivo experiments in 20 living pigs were conducted.RESULTS In in vitro experiments,a negative pressure of>0.06MPa was necessary for optimal visualization of the intestine,and this pressure did not cause gross or histological damage to the mucosa.For satisfactory examination of the small intestine in vivo,higher negative pressure(>1.00 MPa)was required.Despite this higher pressure,the small intestine did not show any gross or microscopic damage in the suctioned areas.The average time of examination in the living animals was 60±7.67 min.The animals did not experience any apparent ill effects from the procedure.CONCLUSION Small intestine endoscope was safely performed within a reasonable time period and enabled complete visualization of the intestine in most cases.

Preparation of Filling Porous Osteoconduction Materials and Its Animal Experiment Study

Titanium rods were processed into implant samples with cavity and groove in which was filled with HAP/β-TCP porous osteoconduction composite materials in order to increase the mechanical stability of the implant in vivo.The phase compositions of the composite was characterized by X-ray diffraction （XRD） and scanning electron microscopy（SEM）.Histological evaluation showed that the biogradable composite could enhanced the ability of new bone formation.The composite can conduct new bone tissue growing into the cavities gradually after implanted into animal,and then achieve mechanical fixation.The filling biogradable compound exhibited excellent biocompatibility,which combined with the new bone tissues tightly without inflammation and loosing.

Study on prescription medication mode and mechanism of traditional Chinese medicine in the treatment of noncritical COVID-19 based on data mining

Background:As of 2023,coronavirus disease 2019(COVID-19)is still spreading globally.Therefore,we aim to integrate non-critical COVID-19 high-frequency and high-targeting Chinese medicines to provide a reference for clinical prescriptions to improve COVID-19-related symptoms.Materials and methods:The information on non-critical COVID-19 high-frequency Chinese medicines in the diagnosis and treatment of COVID-19 was obtained by the TCM inheritance support platform.Using network pharmacology and molecular docking technology,high-targeting Chinese medicines with good docking activity with COVID-19 receptors angiotensin-converting enzyme-II(ACE2),3CLpro and tyrosine-protein kinase receptor UFO(AXL)were obtained.A new prescription for non-critical COVID-19 was established by integrating high-frequency and high-targeting Chinese medicines.Rats with acute lung injury induced by lipopolysaccharide were used as the experimental model.The histopathological changes in the lungs of rats in each group were observed by hematoxylin-eosin staining.The lung coefficient of rats was measured.The levels of IL-6,TNF-α,and IL-1βin serum were detected by enzyme-linked immunosorbent assay.The mRNA and protein levels of ACE2 and AXL in lung tissue were detected by real-time quantitative polymerase chain reaction and western blot.Results:Through data mining,it was found that there were 39 high-frequency traditional Chinese medicines for non-critical COVID-19 in the diagnosis and treatment guidelines.According to network pharmacology and molecular docking,30 highly targeted traditional Chinese drugs for COVID-19 were found.The new prescriptions for non-critical COVID-19 were comprehensively obtained,including Glycyrrhizae Radix,Ephedra Herba,Amygdalus Communis Vas,Gypsum Fibrosum,Descurainiae Semen,Atractylodes Lancea,Scutellariae Radix,Amomum Tsao-Ko Crevostet,Forsythiae Fructus,Pogostemon cablin,Magnolia Officinalis.Compared with the LPS-induced lung injury model group,the medium dose of the new prescription group had significantly alleviated pathological changes in lung tissue,decreased lung coefficient,decreased contents of IL-6,TNF-αand IL-1β,and increased mRNA and protein expression of ACE2 and AXL(P<0.05).Conclusion:Based on data mining,network pharmacology and molecular docking technology,the new prescription for non-critical COVID-19 established by this method has an anti-inflammatory effect on rats with acute lung injury induced by lipopolysaccharide and can provide a reference for clinicians to alleviate the symptoms related to non-critical COVID-19.

Sensory innervation around immediately vs. delayed loaded implants: a pilot study

Although neurophysiological and psychophysical proof of osseoperception is accumulating, histomorphometric evidence for the neural mechanisms of functional compensation following immediate and delayed implant loading is still lacking. For this randomized split-mouth study, six mongrel dogs randomly received one of four treatment protocols at 36 implant-recipient sites over 16 weeks （third maxillary incisor, third and fourth mandibular premolar）： immediate implant placement and immediate loading （liP＋ IL）; delayed implant placement and delayed loading （DIP＋DL）; delayed implant placement and immediate loading （DIP＋IL）; and natural extraction socket healing （control）. Histomorphometry was performed in the peri-implant bone and soft tissues within 300 pm around the implants. Immunocytochemistry and transmission electron microscopy were used to confirm the presence of neural structures and to reveal their ultrastructural characteristics, respectively. Myelinated nerve fibres densely populated the peri-implant crestal gingival and apical regions, although they were also identified in the woven bone and in the osteons near the implant threads. Compared with the control group in the mandible, the group that received IIP＋IL showed a higher innervation （in N.mm^-2, 5.94±1.12 vs. 3.15±0.63, P〈0.001） and smaller fibre diameter （in pm, 1.37±0.05 vs. 1.64±0.13, P=0.016）, smaller axon diameter （in pm, 0.89±0.05 vs. 1.24±0,10, P=0.009） and g-ratio （0.64±0.04 vs. 0.76±0.05, P〈0.001） in the middle region around the implants. Compared with DIP＋IL in the mandible, IIP＋IL had a higher nerve density （in N.mm^-2, 13.23±2.54 vs. 9.64±1.86, P=0.027）, greater fibre diameter （in pm, 1.32±0.02 vs. 1.20±0.04, P=0.021）, greater axon diameter （in μm, 0.92±0.01 vs. 0.89±0.03, P=-0.035） and lower g-ratio （0.69±0.01 vs. 0.74±0.01, P=-0.033） in the apical region around the implants. It may be assumed that the treatment protocol with liP＋ IL is the preferred method to allow optimized peri-implant re-innervation, but further functional measurements are still required.

关于种植体受持续水平力作用发生移动的实验研究

目的:通过对已完成骨结合的种植体施加水平方向的力,观察种植体在水平力作用下发生移动的情况,并对这种情况下种植体的骨结合情况进行组织病理学观察。材料和方法:6只健康成年杂种犬,恒牙列完全萌出,随机分为A、B两组,每组三只。拔除两组验动物的第一,二前磨牙。拔牙创愈合三个月后,单侧下颌分别植入两枚羟基磷灰石涂层柱状种植体种植体愈合三个月后,在种植体上安装修复基台,并安装加力装置,A,B组分别施加大小为1000g和1500g的持续水平力,第3,6,12周时,测量种植体基台之间的距离。加力12周后处死动物,取标本,固定,包埋制作硬组织磨片,观察种植体-骨界面的骨结合情况。实验结果:A,B组种植体受1000g和1500g的水平力后距离发生了明显变化。X线检查种植体周围没有明显的骨吸收。组织病理学研究显示,加力后的种植体与周围骨组织骨结合情况良好。结论:已经完成骨结合的种植体能够在持续水平力的作用下能够发生倾斜移动,并且能够保持与周围骨组织的骨结合。

Phenotypic and Genetic Characteristics of a Bordetella hinzii Isolated from a Rex Rabbit

A Bordetella hinzii strain, isolated from the lung of a dead breast-feeding infant rex rabbit with a respiratory infection, was used as study object to investigate its phenotypic and genetic characteristics. The strain could grow on MacConkey agar and was gram-negative, oxidase-positive, catalase-positive, short rodshaped, and it can produce alkali from malonate. Its 6S rRNA sequence was partially identical with B. hinzii （AF177667）. Animal experiments revealed nasal mucous hyperemia, tracheal congestion and bronchopneumonia in 28-day old rex rabbits. To sum up, this Bordetella hinzii isolate was deemed as a novel causative agent of respiratory disease in rex rabbit.

Quantitative Assessment of Protective Effects of Antioxidant Agents against Drug-Induced Nephrotoxicity Using Dynamic Contrast-Enhanced Computed Tomography

Purpose: The purpose of this study was to develop a method for quantifying the extent of renal dysfunction due to drug-induced nephrotoxicity using dynamic contrast-enhanced computed tomography (DCE-CT) and to investigate the protective effects of various antioxidant agents against cis-dichlorodiammineplatinum (cisplatin)-induced nephrotoxicity in rats using this method. Materials and Methods: The DCE-CT studies were performed in 8-week-old male Sprague-Dawley rats. The CT scanning started 4 s before a bolus intravenous injection of iodinated contrast agent (CA) (150 mgI/kg) from the tail vein using an automatic injector and lasted 90 s at 1-s intervals. The contrast clearance per unit renal volume (K1) was estimated from the DCE-CT data using the Patlak model. The renal volume (V) was calculated by manually delineating the kidney on the CT image. The contrast clearance of the entire kid-ney (K) was obtained by . First, to investigate the effect of CA itself, the DCE-CT studies were performed without injecting cisplatin 2, 4, and 7 days after the first DCE-CT study on day 0. Second, to investigate the effect of injected dose of cisplatin, the DCE-CT study was performed after the intraperitoneal (i.p.) injection of cisplatin (1.8 mg/kg) and was repeated every other day for one week. Finally, to investigate the protective effects of antioxidant agents [L-arginine (300 mg/kg), N-acetylcysteine (500 or 1000 mg/kg), methimazole (40 mg/kg), captopril (60 mg/kg), and taurine (750 mg/kg)], the DCE-CT studies were performed on days 0, 2, 4, and 7 after the i.p. injection of cisplatin (3.6 mg/kg). For comparison, the DCE-CT data were also acquired without injecting the antioxidant agents (CDDP group). Results: When cisplatin was not injected, there were no significant changes in the K value as compared to that on day 0 within the studied period. The K valuesignificantly (p < 0.05) decreased with increasing dose of cisplatin. Although some differences were observed in the extent of change in the K value normalized by that on day 0, depending on the antioxidant agents and their injected dose and schedule, the normalized K values on day 7 in the groups injected with the antioxidant agents were significantly higher than those in the CDDP group, suggesting that the antioxidant agents studied here had protective effects against cisplatin-induced nephrotoxicity in varying degrees. Conclusion: Our method appears useful for quantitatively evaluating the protective effects of antioxidant agents against cisplatin-induced nephrotoxicity and for investigating the optimal injected dose and schedule of the agents, because it allows repeated measurements of split renal function in a single animal.

MR DIFFUSION WEIGHTED IMAGING FOR EVALUATION OF RADIOTHERAPEUTIC EFFECTS ON RABBIT VX2 TUMOR MODEL

Objective To investigate the feasibility of magnetic resonance （MR） diffusion weighted imaging （DWI） for evaluation of radiotherapeutic effects on rabbit VX2 tumor model. Methods Sixteen New Zealand white rabbits received a subcutaneous implantation of VX2 tumor cell suspension 0.5 mL （4× 10^7 ceUs/mL） in their right thighs to set up tumor model. And 2 weeks later they were randomly divided into therapy group （Group T, n = 10） and control group （Group C, n = 6）. Group T received radiotherapy at a single dose of 10 Gy. MR imaging （MRI） scan including short TI inversion recovery echo-planar imaging DWI, T1-weighted imaging （T1WI） and T2-weighted imaging （T2WI） sequences were performed 1 day prior to as well as 1 day, 2 days, 3 days and 7 days after radiotherapy. Group C received only MRI scan at the same time points without any treatment. MRI appearance on T2WI, TlWI, and DWI images was compared and tumor volume was calculated. Apparent diffusion coefficient （ADC） values of the tumor were evaluated in all cases. HE staining was used for pathological study. Results Necrosis （n = 8） and hemorrhage （n = 2） were seen gradually on T2WI and T1WI images of Group T after time point of day 2 after irradiation. In Group C, no obvious necrosis was found until day 7. There was no significant difference in tumor volume between the two groups before radiotherapy. After radiotherapy, tumors in Group T showed a gradual growth but not as obvious as Group C. There was a significant difference in tumor volume between the two groups from day 2 on （P 〈 0.05）. ADC value changed dramatically fight from the 1st day after radiotherapy in Group T [（0.99 ± 0.15） ×10^-3 mm^2/s for 1 day before radiotherapy, （1.23 ± 0.08） ×10^-3 , （1.45 ± 0.07） ×10^-3 , （1.63 ± 0.06） ×10^-3 , and （2.02 ± 0.18） ×10^-3 mm^2 for day 1, 2, 3, and 7]; and ADC value had no significant changes after radiotherapy in Group C except day 7 [（1.07±0.08） ×10^-3 mm^2 for 1 day before radiotherapy, （1.03 ± 0.04）×10^-3 , （1.05 ± 0.02）×10^-3 , （1.05 ± 0.05） ×10^-3 , and （0.95 ± 0.07） ×10^-3 mm^2 for day 1, 2, 3, and 7]. There was significant difference in ADC value between the two groups for each time point after radiotherapy （P 〈 0.01）. Pathological study showed that the number of viable tumor cells in Group T decreased 1 day after radiotherapy, and the inflammatory cell infiltration was marked and almost all viable tumor cells disappeared by day 7 after radiotherapy. Conclusions DWI is a new promising technique for monitoring radiotherapy outcomes. ADC value may give a prior clue on physiological changes of radiotherapy before routine MRI could tell.

Structural shift of gut microbiota during chemopreventive effects of epigallocatechin gallate on colorectal carcinogenesis in mice

AIM To investigate the effect of epigallocatechin gallate(EGCG) on structural changes of gut microbiota in colorectal carcinogenesis.METHODS An azoxymethane(AOM)/dextran sodium sulfate(DSS)-induced colitis mouse model was established. Fortytwo female FVB/N mice were randomly divided into the following three groups: group 1(10 mice, negative control) was treated with vehicle, group 2(16 mice, positive control) was treated with AOM plus vehicle, and group 3(16 mice, EG) was treated with AOM plus EGCG. For aberrant crypt foci(ACF) evaluation, the colons were rapidly took out after sacrifice, rinsed with saline, opened longitudinally, laid flat on a polystyrene board, and fixed with 10% buffered formaldehyde solution before being stained with 0.2% methylene blue in saline. For tumor evaluation, the colon was macroscopically inspected and photographed, then the total number of tumors was enumerated and tumor size measured. For histological examination, the fixed tissues were paraffin-embedded and sectioned at 5 mm thickness. Microbial genomic DNA was extracted from fecal and intestinal content samples using a commercial kit. The V4 hypervariable regions of 16 S r RNA were PCR-amplified with the barcoded fusion primers. Using the best hit classification option, the sequences from each sample were aligned to the RDP 16 S r RNA training set to classify the taxonomic abundance in QIIME. Statistical analyses were then performed.RESULTS Treatment of mice with 1% EGCG caused a significant decrease in the mean number of ACF per mouse, when compared with the model mice treated with AOM/DSS(5.38 ± 4.24 vs 13.13 ± 3.02, P < 0.01). Compared with the positive control group, 1% EGCG treatment dependently decreased tumor load per mouse by 85%(33.96 ± 6.10 vs 2.96 ± 2.86, respectively, P < 0.01). All revealed that EGCG could inhibit colon carcinogenesis by decreasing the number of precancerous lesions as well as solid tumors, with reduced tumor load and delayed histological progression of CRC. During the cancerization, the diversity of gut microbiota increased, potential carcinogenic bacteria such as Bacteroides were enriched, and the abundance of butyrate-producing bacteria(Clostridiaceae, Ruminococcus, etc.) decreased continuously. In contrast, the structure of gut microbiota was relatively stable during the intervention of EGCG on colon carcinogenesis. Enrichment of probiotics(Bifidobacterium, Lactobacillu, etc.) might be a potential mechanism for EGCG's effects on tumor suppression. Via bioinformatics analysis, principal coordinate analysis and cluster analysis of the tumor formation process, we found that the diversity of gut microbiota increased in the tumor model group while that in the EGCG interfered group(EG) remained relatively stable.CONCLUSION Gut microbiota imbalance might be a potential mechanism for the prevention of malignant transformation by EGCG, which is significant for diagnosis, treatment, prognosis evaluation, and prevention of colorectal cancer.

Is it necessary to use the entire root as a donor when transferring contralateral C7 nerve to repair median nerve？

If a partial contralateral C7 nerve is transferred to a recipient injured nerve, results are not satisfactory. However, if an entire contralateral C7 nerve is used to repair two nerves, both recipient nerves show good recovery. These findings seem contradictory, as the above two methods use the same donor nerve, only the cutting method of the contralateral C7 nerve is different. To verify whether this can actually result in different repair effects, we divided rats with right total brachial plexus injury into three groups. In the entire root group, the entire contralateral C7 root was transected and transferred to the median nerve of the affected limb. In the posterior division group, only the posterior division of the contralateral C7 root was transected and transferred to the median nerve. In the entire root ＋ posterior division group, the entire contralateral C7 root was transected but only the posterior division was transferred to the median nerve. After neurectomy,the median nerve was repaired on the affected side in the three groups. At 8, 12, and 16 weeks postoperatively, electrophysiological examination showed that maximum amplitude, latency, muscle tetanic contraction force, and muscle fiber cross-sectional area of the flexor digitorum superficialis muscle were significantly better in the entire root and entire root ＋ posterior division groups than in the posterior division group. No significant difference was found between the entire root and entire root ＋ posterior division groups. Counts of myelinated axons in the median nerve were greater in the entire root group than in the entire root ＋ posterior division group, which were greater than the posterior division group. We conclude that for the same recipient nerve, harvesting of the entire contralateral C7 root achieved significantly better recovery than partial harvesting, even if only part of the entire root was used for transfer. This result indicates that the entire root should be used as a donor when transferring contralateral C7 nerve.

Effect of Fujian tablet on the expression of Nogo-A mRNA in the cervical spinal cord of middle cerebral artery occlusion model rats

Inhibiting the expression of Nogo-A in cervical spinal cord by use of interaction of antigen and antibody can help the remodeling of corticospinal projection of focal cerebral ischemia model rats to facilitate neurological recovery, which provides a new possible mechanism for drugs to promote neurological recovery. However, the effects of drugs on the expression of Nogo-A in cervical spinal cord are still unclear. OBJECTIVE： To observe the effect of Fujian tablet on the expression of Nogo-A mRNA in cervical spinal cords of middle cerebral artery occlusion （MCAO） rats, and to investigate the possible regulatory effect of Fujian tablet on the regenerated microenvironment of spinal conduction bundle. DESIGN： A randomized and controlled trial taking Wistar rats as experimental animals. SETTING： Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine. MATERIALS： This experiment was carried out in the laboratory of Shandong Academy of Medical Science between June 2005 and July 2006. A total of 40 healthy male Wistar rats, aged 12 weeks, weighing 250 - 300 g, were provided by the Experimental Animal Center of Shandong University. Fujian tablets （main components： Heshouwu, Yinyanghuo, etc） were provided by office of Pharmaceutics of Shandong University of traditional Chinese medicine. Nogo-A detection kit was provided by Wuhan Boster Biotechnology Co.,Ltd., and batch number was 040309009. This experiment was approved by Local Animal Ethics Committee. METHODS： Forty male rats were randomly divided into 4 groups, with 10 in each： normal group, sham-operation group, model group and administration group. Rats in the administration group and model group were subjected to MCAO. Rats in the sham-operation group underwent the same craniotomy, and their middle cerebral arteries （MCA） were not occluded. Rats in the normal group were untouched. Rats in administration group were intragastrically administrated with the solution of Fujian tablet at a dose of 9 g/kg and others were given equal dosage of normal saline two days later. The treatments were done once a day and the course totaled 2 weeks. MAIN OUTCOME MEASURES： The expression of Nogo-A mRNA in slices of cervical spinal cords. RESULTS： Forty rats were involved in the final analysis. The expression of Nogo-A mRNA in the cervical spinal cord of rats in the administration group and model group was significantly decreased as compared with that in the normal group （P 〈 0.01 and P 〈 0.05, respectively）. The expression of Nogo-A mRNA in the administration group was also significantly weaker than that in the model group （P 〈 0.05 ） . CONCLUSION： Fujian tablet can inhibit the expression of Nogo-A mRNA in cervical spinal cords of MCAO rats, which facilitates regeneration and remodeling of cervical spinal cords.

Stem cell therapy for Alzheimer's disease

Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment.It is caused by synaptic failure and excessive accumulation of misfolded proteins.To date,almost all advanced clinical trials on specific AD-related pathways have failed mostly due to a large number of neurons lost in the brain of patients with AD.Also,currently available drug candidates intervene too late.Stem cells have improved characteristics of self-renewal,proliferation,differentiation,and recombination with the advent of stem cell technology and the transformation of these cells into different types of central nervous system neurons and glial cells.Stem cell treatment has been successful in AD animal models.Recent preclinical studies on stem cell therapy for AD have proved to be promising.Cell replacement therapies,such as human embryonic stem cells or induced pluripotent stem cell–derived neural cells,have the potential to treat patients with AD,and human clinical trials are ongoing in this regard.However,many steps still need to be taken before stem cell therapy becomes a clinically feasible treatment for human AD and related diseases.This paper reviews the pathophysiology of AD and the application prospects of related stem cells based on cell type.

Neural stem cell therapy for brain disease

Brain diseases, including brain tumors, neurodegenerative disorders, cerebrovasculardiseases, and traumatic brain injuries, are among the major disordersinfluencing human health, currently with no effective therapy. Due to the lowregeneration capacity of neurons, insufficient secretion of neurotrophic factors,and the aggravation of ischemia and hypoxia after nerve injury, irreversible lossof functional neurons and nerve tissue damage occurs. This damage is difficult torepair and regenerate the central nervous system after injury. Neural stem cells(NSCs) are pluripotent stem cells that only exist in the central nervous system.They have good self-renewal potential and ability to differentiate into neurons,astrocytes, and oligodendrocytes and improve the cellular microenvironment.NSC transplantation approaches have been made for various neurodegenerativedisorders based on their regenerative potential. This review summarizes anddiscusses the characteristics of NSCs, and the advantages and effects of NSCs inthe treatment of brain diseases and limitations of NSC transplantation that need tobe addressed for the treatment of brain diseases in the future.