Abstract: Objective To construct the male and female rat model of fluorosis and to explore the gender difference in fluorosis. Methods A total of 48 clean?grade SD rats with the body weight of about 150 g (male∶ female = 1∶ 1) were equally divided into the control group and fluorosis model group. Rats in the fluorosis model group were fed with fluorine-containing (100 mg/ kg) feedstuff. The general condition, changes in body weight and dental fluorosis of the rats were observed every three days. A batch of female and male rats were sacrificed by femoral artery bleeding on the 70th and 110th day of experiment, respectively, when all rats showed dental fluorosis. The levels of urinary fluoride and bone fluoride of the rats were measured by a fluoride ion-selective electrode. Results All the male and female rats in the control group did not show dental fluorosis during the entire experiment. The female and male rats in the fluorosis group showed dental fluorosis visible to naked eye began approximately on the 60th and 80th day, respectively,indicating that the appearance of dental fluorosis of the male rats was about 20 days later than the female rats. After 30 days or so, the male and female rats went into a rapid growth period, and there were significant differences between the body weights of the male and female rats (P < 0.01). The body weight of the male and female rats in the fluorosis group was higher than that of the control group on the 110th day. With the progression of fluorosis, the levels of urinary fluoride and bone fluoride of the rats were gradually increased, and finally significantly higher than those of the control group (P < 0.01). There was a positive correlation between the levels of urinary and bone fluoride and the time of fluorosis. The levels of urinary and bone fluoride of the male rats were significantly higher than those of the female rats (P < 0.01), indicating that they are affected by gender. Conclusions The body weight of the rat model of fluorosis, the starting time when dental fluorosis occurs and the levels of urinary and bone fluorine are all different between male and female rats.

Abstract: Objective To compare different regimens of intraperitoneal injection of cyclophosphamide (CTX) to establish a rabbit model of premature ovarian failure (POF), and provide a useful experimental tool for further research of premature ovarian failure. Methods A total of twenty-one 5 -6 months old rabbits were randomly divided into 4 groups. The group A (normal control group) included 3 rabbits without any treatment. The group B (the first model group) included 6 rabbits, received a single intraperitoneal injection of 50 mg/ kg cyclophosphamide. Six rabbits in the group C (the second model group) were injected with 50 mg/ kg cyclophosphamide once daily for 2 days. The group D (the third model group, also n =6) was injected with 50 mg/ kg cyclophosphamide on the first day and then followed by 8 mg/ (kg·d) injection q. d. in the 14 consecutive days. Body weight and ovary weight of the rabbits in each group were measured, and the changes of body weight and the ovary index were analyzed. Morphological changes of the ovarian follicles were observed by HE staining and the numbers of normal and abnormal follicles at different developmental stages were counted and analyzed. Cell apoptosis was analyzed by TUNEL staining and changes in the serum levels of estradiol (E2) were detected by ELISA. Results The body weight of rabbits in both groups B and group C was not significantly changed during the experimental period (P > 0.05). Rabbits in the group D showed a slight growth (P < 0.05) and high mortality. The ovary index in group C was significantly lower than that in the group A (P < 0.05). The ratios of abnormal primordial and primary follicles in groups B and C were significantly increased (P < 0.017), and the ratio of abnormal primordial follicles in the group C was increased more significantly (P < 0.017). However, there was no significant difference in the ratios of abnormal primary follicles between groups B and C (P > 0.017). Among the groups A, B and C, there was no significant difference in the ratios of abnormal secondary and antral follicles (P > 0.05). Apoptosis mainly occurred in granulosa cells of the ovarian follicles. The apoptosis rate of groups B and C was significantly higher than that in the group A (P < 0.05), and the apoptosis rate of group C was higher than that in the group B (P < 0.05). In the group B, the serum E2 level reached the peak value on the 7th day, significantly higher than that on the 35th day (P < 0.05), and then the level was decreased gradually. In the group C, the E2 level was continuously decreased and the level on the last day before drug injection was significantly higher than that at the 35th day (P < 0.05). Conclusions Intraperitoneal injection of 50 mg/ kg cyclophosphamide once daily for 2 days is a most suitable method for the establishment of rabbit model of premature ovarian failure (POF).

Abstract: Objective To compare the hepatotoxicity of matrine (MT) and oxymatrine (OMT) and explore the severity and characteristics of their toxicity, and to preliminarily elucidate their toxic mechanisms. Methods Liver cell line LO-2 cells were treated with acetaminophen (APAP), matrine and oxymatrine for 24 h, and the IC₅₀ values, the contents of enzymes in the liver cells, the pathological changes, the contents of malondialdehyde (MDA) and glutathione (GSH) and the cell apoptosis rate were detected. In addition, adult zebrafish were treated with APAP, matrine and oxymatrine for 96 h, and the LC₅₀ values, the pathological morphology of the liver cells, the contents of MDA and GSH and the apoptosis rate were detected. Meanwhile, the expression of oxidative stress-related gene, zgc: 136383, and the apoptosis-related genes, EIF4EBP3 and zgc: 123120, was also detected. Results Matrine and oxymatrine had toxic effects on liver cells in vitro. The IC₅₀ value of matrine was 5.3 mmol/ L, and that of oxymatrine was > 19 mmol/ L. The contents of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the liver cells treated with matrine or oxymatrine were increased, and the cells appeared swollen, with an increase in the MDA level and a decrease in the GSH level. The cell apoptosis rate was also increased (P< 0.05). Furthermore, matrine and oxymatrine had toxic effects on the zebrafish. The LC₅₀ value of matrine was 0.41 mmol/ L, and that of oxymatrine was > 3.8 mmol/ L. The hepatocytes of zebrafish treated with matrine and oxymatrine appeared vacuolization in a mild to moderate degree, with an increase of the MDA content and a decrease of the GSH content. The cell apoptosis rate was increased (P < 0.05 for all). Expression of the oxidative stress-related gene zgc: 136383 (P < 0.05) and the apoptosis-resistant gene EIF4EBP3 (P < 0.05) was down?regulated by matrine, but that of the apoptosis-promoting gene zgc: 123120 was up-regulated (P < 0.05). Conclusions Results of the experiments using liver cells in vitro are consistent with those using the in vivo zebrafish model. Matrine (MT) and oxymatrine (OMT) both have hepatotoxicity, with similar toxic characteristics, and the toxicity of matrine is greater than oxymatrine. The mechanism of their hepatotoxicity is related with oxidative stress and cell apoptosis. Matrine reduces lipid transportation and activates oxidative stress reactions through down-regulation of gene zgc: 136383. In addition, matrine induces apoptosis in the liver cells via up-regulation of the apoptosis-promoting gene zgc: 123120 and down-regulation of the apoptosis-resistant gene EIF4EBP3.

Abstract:Objective To further definite the distribution of caudal arteries and veins of rat by anatomical dissection and to deepen the understanding of their physiological functions, and provide a basis for standardization of animal experimental techniques and design of animal models. Methods Eighteen SPF adult SD rats were used in this study. Several techniques were used in combination to study the anatomy and histology of the rat tail blood vessels: paraformaldehyde perfusion through the abdominal aorta was performed for rapid and thorough fixation, blue and red paints were injected to visualize the tail veins and arteries, respectively, arterial microangiography was performed to illustrate the distribution of tail arteries, and the microscopic structure of arteries and veins was verified by histological examination. Results Three longitudinal superficial arterial and venous systems of rat tail were confirmed and a dorsal arterial and venous chain structure was defined, which deeped our knowledge about the distribution of the deep blood vessels. In addition, the caliber of arteries was not corresponding with that of veins, providing a basis of their physiological functions. A bilayer cage connecting structure of the rat tail vasculature was for the first time defined. Conclusions The rich vascular structure of rat tail is described in details in this study. The existence of basal vascular system of rat tail is clarified. A concept of bilayer framework of the rat tail vasculature is proposed, which lays a good foundation for related researches of their physiological functions, and provides a good basis for avoiding major injuries and compensatory responses of hindlimb ischemia during animal experiments.

Abstract:Objective To compare the effects of different local intervention temperatures of pressure ulcer on endoplasmic reticulum stress (ERS) and apoptosis in rats, and to provide an experimental evidence for clinical prevention and treatment of pressure ulcer. Methods The rat model of pressure ulcer was established by ischemia reperfusion, and a total of 40 SPF adult, male SD rats were divided into 4 groups: the sham group (anesthesia only, without other treatment), model group (ischemia at 22℃ for 1 h and reperfusion at 22℃ as one cycle, repeated for 5 cycles), high-temperature intervention group (ischemia at 22℃ for 1 h and reperfusion at 32℃ as one cycle, repeated for 5 cycles) and low-temperature intervention group (ischemia at 22℃ for 1 h and reperfusion at 12℃ as one cycle, repeated for 5 cycles). At the end of the experiment, muscle tissues at the sites under pressure of the rats were taken on ice. The pathological changes of skeletal muscle tissues were observed by HE staining. The expression levels of ERS-related proteins GRP78, caspase-12 and CHOP were detected by Western blot, and the expression of caspase-12 and CHOP was also observed by immunofluorescence. Moreover, apoptosis in the skeletal muscle cells was examined by TUNEL staining. Results Compared with the model group, skeletal muscle cell damages became more severe and apoptotic cells were increased in the high-temperature intervention group. Besides, the results of the immunofluorescence assay showed an increased positive expression of caspase-12 and CHOP, and the results of Western blot showed that the expression levels of GRP78, caspase-12 and CHOP were all higher than those of the model group (P < 0.05). In contrast, skeletal muscle cell damages were alliviated and apoptotic cells were reduced in the low-temperature intervention group. Meanwhile, the positive expression of caspase-12 and CHOP was decreased, as shown by immunofluorescence, and all the expression levels of GRP78, caspase-12 and CHOP detected by Western blot were lower than the control group (P < 0.05). Conclusions Local low-temperature intervention can alleviate the pressure ulcer damages in rats through inhibition of the ERS-mediated apoptotic pathway. Local high-temperature intervention may exacerbate the pressure ulcer damages in rats by activating the ERS-mediated apoptotic pathway and promoting cell apoptosis. Local low?temperature intervention may be promising in clinical prevention and treatment of pressure ulcer.

Abstract: Objective To investigate the effects of 2,2,6,6-tetramethyl-4-piperidinol (tempol) on NF-κB signaling pathway of myocardial hypertrophy in rats. Methods The rat model of myocardial hypertrophy was established by intraperitoneal injection of isoprenaline (ISO) (5 mg/ kg, twice per day, 2 weeks). A total of 42 male SD rats were randomly divided into 3 groups, including the control group, myocardial hypertrophy model group (ISO + sterile saline) and tempol treatment group (ISO + tempol) [tempol 100 mg/ (kg·d), 8 weeks]. Eight weeks after the corresponding drug intervention, the heart weight index (HWI) and left ventricular weight index (LVWI) were determined. Morphology and fibrosis of the myocardium were observed by HE staining, and the myocardial fibrosis of the rats was observed by Masson staining. The mRNA levels of TNF-α and IL-6 in the rat myocardial tissues were detected by qRT-PCR, and the expression levels of IκBα, p-p65 and p65 were detected by Western blot. Results Compared with the control group, the HWI and LVMI, mRNA levels of TNF-α and IL-6, and expression of p-p65/ p65 in the model group were significantly increased (P < 0.05), while the expression level of IκBα, an NF-κB inhibitory protein was significantly decreased (P <0.05). The pathological examination of the myocardial tissues showed thickening and disordered arrangement of myocardial fibers, and increased cross-sectional area of the myocardial fibers. The pathology by Masson staining showed aggravated myocardial fibrosis and increased collagen fibers in the myocardial interstitium. Compared with the model group, the HWI and LVMI, the mRNA levels of TNF-α and IL-6, and the expression of p-p65/ p65 of the tempol group were significantly decreased (P < 0.05), while the expression level of IκBα was significantly increased (P < 0.05). HE staining showed that the degrees of myocardial disarrangement and cardiomyocyte hypertrophy were decreased. Meanwhile, Masson staining showed that the extent of myocardial fibrosis was reduced, and the interstitial collagen fibers were decreased. Conclusions Tempol can improve the isoprenaline-induced myocardial hypertrophy, which may be closely related with the inhibition of the activity of NF-κB signaling pathway.

Abstract: Objective Sialic acid and its derivatives in mammalian cells mainly include N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc) and deaminoneuraminic acid (KDN), among which Neu5Ac can be catalyzed by cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) for the synthesis of Neu5Gc. In this study, the transcriptional level of CMAH in different tissues of BALB/ c mice were determined by relative fluorescence quantitative PCR, to provide a reference for further analysis of Neu5Gc levels in different tissues. Methods The mRNA sequence of CMAH was searched in the NCBI database and specific primers were designed. The mouse β-actin was selected as an internal control, and the transcriptional levels of CMAH in 9 different organ tissues of BALB/ c mice were detected by relative fluorescence quantitative PCR using SYBR Green dye. Results Among the 9 mouse organs, the transcriptional level of CMAH in the liver tissue was the highest, which was 2.46 times higher of that in the spleen, 3.17 times of the kidney, 5.14 times of the trachea, 11.70 times of the lung, 21.12 times of the myocardium, 31.37 times of the skeletal muscles, 66.90 times of the small intestine and 1056.99 times of the brain tissue, respectively. Conclusions CMAH is transcribed in many organ tissues of mice, and its transcriptional levels vary in a quite wide range.

Abstract: Objective To study the effects of simple portal hypertension on the endotoxin levels in serum and intestinal mucosa of rats. Methods A total of 16 rats were divided into the blank control group (4 rats) and the model groups (3-day group, 7-day group and 10-day group, 4 rats in each group). The rat model of partial portal vein ligation was established in the model groups, and samples of blood and jejunum, ileum and colon of the rats were taken on the 3rd, 7th and 10th days, respectively. Changes in the serum endotoxin levels were detected by ELISA. Histopathological changes of the intestinal tissues were examined by HE staining. Results The rat model of partial portal vein ligation was successfully established in all the model groups. The serum levels of endotoxin on the 3rd, 7th and 10th days in the model groups were not significantly different from that in the normal control group. Damages of different intestinal segments were not serious on the 3rd day after modeling. However, on the 7th day after modeling, there were some sowllen and damaged intestinal villi in the intestinal mucosa of each intestinal segment, and the connection between the epithelial cells and the lamina propria was broken, compared with that at 3 days after modeling. In addition, there were obvious damages in the intestinal mucosa and lamina propria on the 10th day, compared with that at 3 d and 7 d after modeling. Conclusions In the case of normal liver function, portal hypertension can cause intestinal mucosal damages within a short period of time, but the amount of endotoxin produced by intestine does not exceed the processing capacity of the liver and thus does not cause an increase in the serum endotoxin level.

Abstract: Objective To explore the effect of general anesthesia on Wuzhishan miniature pigs induced by a mixture of ketamine, Sumianxin II and midazolam, and maintained by ketamine and propofol in surgery lasting up to 8 hours. Methods A total of 18 Wuzhishan miniature pigs (body weight (20.3 ± 1.9) kg, 14 male and 4 female) were used in this study. The induction of anesthesia was performed with intramuscular injection of ketamine (8 - 10 mg/ kg) Sumianxin II (1.5 mL) and midazolam (10 mg) behind the ear, and the general anesthesia was maintained with a mixture containing 0.9% sodium chloride 8 mL, ketamine 100 mg/2 mL and propofol 200 mg/40 mL, continuously injected through the marginal ear vein through a syringe infusion pump. The time spent for anesthesia induction and the duration time of anesthesia were recorded. Physiological indexes including body temperature, blood pressure, heart rate and respiratory rate, the reflex activities, and the effects of analgesia, sedation and muscular relaxation of the miniature pigs under anesthesia at 0, 0.5, 1, 1. 5, 2, 4, 6, 8 h were observed. Results All the 18 pigs were successfully anaesthetized, but 4 pigs died during surgery due to hypovolemic shock, anesthesia accident, left main coronary thrombosis and reperfusion arrhythmia, respectively. During anesthesia, the analgesia, sedation and muscular relaxation effects on the pigs were obvious. The average time spent for anesthesia induction was (4.8 ± 1.2) min and the duration time of anesthesia was (54.1 ±5.8) min. The eyelid reflex, corneal reflex and anal reflex in the pigs were weak or disappeared during 1 - 8 h after the anesthesia was induced. The body temperature of the pigs was decreased gradually, with a significant difference between 1 h and 0 h (P < 0.05), reaching the lowest point at 4 h, and then maintained stable. The blood pressure was gradually decreased, reaching the lowest level at 2 h (P < 0.05), then somehow increased, and maintained at a stable level until the end of surgery. The respiratory rate fluctuated during the anesthesia, with no significant difference. Conclusions The anesthesia induced by a combination of ketamine, Sumianxin II and midazolam and maintained with a combination of ketamine and propofol is simple to operate, shows effects fast, and has good effects of analgesia, sedation and muscular relaxation, keeping the circulatory system and respiratory system relatively stable throughout the anesthesia. Thus it is suitable for general anesthesia for miniature pigs.

Abstract: Objective To evaluate the method for detection of urinary mercury using a Zeeman atomic absorption mercury analyzer and to provide a reference for selecting a convenient method for mercury detection in experiments and clinical diagnoses. Methods Urinary mercury was detected by Zeeman atomic absorption spectroscopy (ZAAS) and hydride generation atomic absorption spectrometry ( HG-AAS), and the detection limit, accuracy, precision and consistency of the two methods were compared. Results The Data collected by ZAAS and HG-AAS showed a good linear relationship in the range of 0 - 1000 ng/ mL (ZASS, R²= 1.0000) and 0 - 20 ng/ mL (HG-AAS, R² = 0.9990). The detection limits of ZAAS was 0.156 ng/ mL and that of HG-AAS was 1.593 ng/ mL, indicating that ZAAS is more sensitive. The recovery rate of standard addition of ZAAS was between 97.5% and 103.2%, and that of HG?AAS was between 95.6% and 104.5%. After measurement of 10 ng/ mL and 100 ng/ mL mercury standard solutions repeated for 10 times, the relative standard deviation (RSD) of ZAAS was 0.30% and 0.36% respectively, and the RSD of HG-AAS was 2.82% and 1.11%, respectively. The accuracy and precision of both the two method met the standards of GBZ/ T 210.5 - 2008, and the precision of ZAAS was better. A total of 30 urine samples were measured by these two methods . The results were compared with paired-samples t-test and showed a non-significant difference ( P > 0.05), indicating a high consistency of these two method (R² = 0.9961). Conclusions ZAAS is a convenient and accurate method for the detection of urinary mercury, with a relatively low detection limit and better precision.

Abstract:Objective To improve the success rate of cerebrospinal fluid (CSF) collection in rats using a modified suction device with negative pressure. Methods A flow regulator was added to the original apparatus to adjust the intensity of negative pressure and to limit the volume of CSF collected each time. A total of 36 male Sprague?Dawley (SD) rats were randomly divided into 3 groups, and the CSF was collected in 3 ways: drawing from the cerebellomedullary cistern via percutaneous puncture, using a suction device with negative pressure and using a modified device. Kruskal?Wallis test was used to evaluate the differences in result between these three methods. Results The modified suction device with negative pressure effectively reduced bleeding. The quality of CSF collected with it was 75% of 12 rats,significantly higher than that obtained with the original device (33.3%, P < 0.01) or drawn from the cerebellomedullary cistern via percutaneous puncture (0%, P < 0.001). The success rate of qualified sample collection was highly superior to those of previously reported CSF collection methods. Conclusions Our modified suction device for CSF collection is simple and user?friendly, with minimal damage and little bleeding to rats. It can obviously improve the success rate of CSF collection in rats.

Abstract:Objective Grey red?backed voles (Myodes rufocanus) are agile, fierce and hard to catch, thus, it is difficult to judge their gender by external appearance, especially for the juvenile voles. Therefore, it may cause difficulties to their allocation and later breeding in laboratories. The aim of this paper is to establish a rapid, simple and accurate method for gender identification of grey red?backed voles. Methods Fresh hair follicles were taken from 6 adult male voles, 3 adult females and 14 4?week?old juvenile voles, 5 male and 5 female 9?week?old Wistar rats, and 5 male and 3 female 6?week?old BALB/ c mice. The genomic DNA was extracted using Chelex?100 resin and the zinc?finger Y/ X gene (ZFY/ZFY) and the gene of sex?determining region of the Y (SRY) chromosome were amplified by PCR, and a double PCR amplification method was established. Results The ZFY/ZFY gene and SRY gene were simultaneously amplified from the male voles, while only the ZFY/ZFY gene was amplified from the females. The gender of all 23 voles, 10 Wistar rats and 8 BALB/ c mice were correctly identified with this method, and the PCR results were consistent with the phenotypic and autopsy results. Conclusions Using fresh hair follicles as experimental materials for gender identification of grey red?backed voles can alleviate shock and damage to the animals. The established double PCR amplification method is accurate,simple, rapid, and deserves to be used for gender identification of grey red?backed voles.

Abstract:Objective To observe the changes of circadian characteristics and stress?response?related physiological parameters including respiration, blood pressure, electrocardiography and body temperature of conscious rhesus monkeys by implantable telemetry technique. Methods Surgery was performed on 8 rhesus monkeys (half male and half female, 3-5 years old) for implantation of a telemetry transmitter. After 3 weeks of recovery, the physiological parameters of respiration, blood pressure, electrocardiography and body temperature of the conscious rhesus monkeys without binding were automatically recorded by a DSI telemetry system and the data were analyzed by the Ponemah software. Results Some electrocardiographic indexes showed significant differences at daytime and nighttime (P < 0.05 or P < 0.01) including mean heart rate (HR) (155.0-122.4 times/ min), respiratory rate interval (RR?I) (410.8-535.7 ms), T?wave amplitude (T?A) (0.181-0.157 mV), PR interval (PR?I) (80.4-87.4 ms), QT interval (QT?I) (224.8-263.9 ms), and corrected QTcb interval (QTcb) (352.3-366.7 ms). The indexes of blood pressure and respiration at daytime were significantly higher than those at nighttime (P < 0.01), including the mean systolic pressure (SYS) at daytime and nighttime (144.6-131.6 mmHg), diastolic pressure (DIA) (99.8-89.9 mmHg), mean arterial pressure (MAP) (121.5-110.2 mmHg), tidal volume (TV) (64.5-36.6 mL), minute ventilation (MV) (1931.9-920.1 mL/ min), and respiratory rate (RR) (32.3-25.4 times/ min). Cleaning and feeding activities of the laboratory staff at 9:00 a. m. and 2:00 p. m. had a certain effect on the stress?responses in the monkeys. Conclusions The parameters of respiration, blood pressure, electrocardiography and body temperature of the conscious rhesus macaques observed by implanted telemetry system show obvious circadian changes, which can truly reflect the changes of physiological indexes at daytime and nighttime, and avoid the stress in hungry monkeys caused by the feeding and cleaning activities of laboratory staff. This technique can improve the efficiency of drug safety pharmacology studies, reduce the number of animals used and meet the requirements of 3R principles.

Abstract:Objective To explore the feasibility of needle?embedding therapy in the treatment of chronic myocardial ischemia using a miniature pig model established by placement of an Ameroid constrictor at the left anterior descending branch (LAD) of coronary artery in Bama miniature pigs during surgery. Methods The miniature pig model of chronic myocardial ischemia was established by placement of an Ameroid constrictor at the left anterior descending branch of the left coronary artery in Bama miniature pigs. The pig models were randomly divided into the treatment group (the “Neiguan” group) and the control group ( the “ Zusanli ” group ), and were treated with needle?embedding electroacupuncture at the “Neiguan” (PC6) and “Zusanli” (ST36) acupoints, respectively. Myocardial samples were taken at 6 weeks after surgery for light and electron microscopic examinations. Results Gross pathology showed that ischemic area in the myocardium appeared in both experimental groups. The ischemic area in the “Zusanli” group was larger than that of the “Neiguan” group. Histopathology showed that the acupuncture treatment at the “Neiguan” acupoint reduced the ischemic injury in the pig myocardial tissues. Ultrastructural observation of the myocardium showed mitochondrial vacuolization in cardiomyocytes and myocardial fibrosis in both groups. Conclusions Acupuncture therapy at the “Neiguan” acupoint of pericardial channel may exert protective effect on the myocardial ischemia by reducing the ischemia?injury of cardiomyocytes, but can not inhibit the already existed ischemia?induced cardiomyocytic injuries. Our findings suggest that the establishment of miniature pig model of chronic myocardial ischemia by surgically placing an Ameroid constrictor on the left anterior descending branch of left coronary artery and the needle?embedding in acupoints is feasible for the treatment of chronic myocardial ischemia in this pig model.

Abstract:Cytochrome P450 (CYP450) is a superfamily of heme?thiolate proteins, which is involved in the metabolism and activation of various endogenous and exogenous substances, including food, drugs and pollutants. Previous studies of the CYP450 genes mainly focused on their function in drug metabolism. However, in recent years, studies have found that CYP450 are also involved in the development and progression of various diseases, including Parkinson’s disease (PD), cancer, cardiomyopathy and heart failure (HF). By far, the process and related mechanisms of CYP450 in the metabolism of endogenous substances in brain tissues has not been clarified yet. In this paper, we summarized the research progress of CYP450 genes involved in the metabolism of endogenous substances, in order to provide a new idea for the exploration of the functions of CYP450 genes expressed in the brain.

Abstract:The patient?derived orthotopic xenograft (PDOX) model better maintains the genetic characteristics of the primary tumor, and keep stable in histology, transcriptome, polymorphism and copy number variations. It also retains the interaction between the tumor mesenchyma, microvessels and stroma, and the tumor metastatic properties. Therefore, PDOX model can predict disease prognosis more accurately and can be used to screen appropriate individualized treatment strategies, thus, shows perfect prospect in clinical application. However, due to the differences between mouse and human microenvironment, morphological distinctions between orthotopic xenograft tumors and primary tumors still exist, and tumor metastasis can not be ensured by orthotopic xenograft. Thus, in order to construct the individualized PDOX model and to promote its clinical translation, it is necessary to analyze the histomorphology of orthotopic xenografts, to establish database of the transplantation model and share the information of the model. In this review, we will summarize the main features of PDOX models with its advantages and limitations, and looking forward to its application in the future.

Abstract:Tau protein, a kind of microtubule?associated protein, plays an important role in the pathogenesis of Alzheimer’s disease (AD) and other tauopathies, and has drawn more and more attention of scientific researchers.Appropriate animal models of mutated tau protein are important in the studies of the pathogenesis and drug therapy of tauopathies. So far, some transgenic animal models expressing human tau protein have been established, among which the transgenic animal model overexpressing P301L mutated form of tau protein has been widely used because of its obvious pathological changes. In this review, we will review the research progress in the pathological manifestations of the P301L tau transgenic animal model and its applications in pharmacological studies.