Abstract:Objective To investigate whether RIP3 (receptor-interacting protein 3) is involved in the inductionof influenza antigen specific CD8⁺ T cell responses in C57BL/6 mice upon H1N1 influenza virus infection. Methods RIP3knockout (RIP3^{-/ -} ) and wild type (WT) C57BL/6 mice were infected by influenza virus H1N1 PR8 with the dose of 0. 7×10³ TCID₅₀(50% tissue culture infective dose). Splenocytes were isolated from the infected mice which were sacrificed at 8days post infection (d.p.i), and fluorescence-activated cell sorting (FACS) were used for the comparison of quantities andfunctions of influenza viral antigen specific CD8⁺ T cells between the RIP3^{-/ -} group and WT group. Surface staining ofinfluenza viral MHC I tetramer was performed to quantify the antigen specific CD8⁺ T cells. Intracellular cytokine staining(ICS) was carried out to dissect the production levels of effector cytokines, such as IFN-γ, TNF-α and IL-2. Granzyme B,which is related to the cytotoxic effect of the antigen specific CD8⁺ T cells, was also assayed by ICS. Results On average,the percentages of influenza viral antigen specific CD8⁺ T cells in the WT group of mice were about 2. 71 fold comparingwith that in the RIP3^{-/ -} group of mice. Furthermore, the production levels of IFN-γ, TNF-α and IL-2 by the antigen specificCD8⁺ T cells in the WT group of mice were significantly higher than those levels in the counterpart group of RIP3^{-/ -} mice( P < 0. 01); and in regards to granzyme B, the same trend was showed when comparing the expression levels between thosetwo group mice, i.e., WT group was higher than the RIP3^{-/ -} group ( P < 0. 01). Conclusions The data of the presentstudy reported that the deficiency of RIP3 molecule in C57BL/6 mice will decrease the quantity and functionality of theinfluenza viral antigen specific CD8⁺ T cells at 8 d.p.i. upon influenza virus H1N1 PR8 infection, which indicates that RIP3 is indispensable for the induction of influenza viral antigen specific CD8⁺ T cells at effector stage.

Abstract:Objective In 2017,a large number of poultry deaths occurred in several poultry markets, and H7N9avian influenza virus was isolated from the dead chickens. This study will track the tendency of the pathogenicity of H7N9virus and analyze the possible pathogenic mechanism. Methods The pathogenicity of the A/ Guangdong/ Th005/2017(Th005) and A/ Anhui/1/2013(Anhui) viruses were compared with the intravenous pathogenicity index (IntravenousPathogenic Index, IVPI) test in chickens. The body temperatures, body weights, and clinical symptoms of the chickens inthe infection groups were continuously measured post-infection. Meanwhile, pharyngeal swabs and cloacal swabs werecollected for viral titer determinations. Results Compared with the Anhui strain, the pathogenicity of Th005 wassignificantly increased in chickens. The IVPI score of Th005 reached 3 in avian. Th005 infected chickens caused asignificant decrease in body weight, body temperature increased above 42℃, and all died. However, the Anhui straincaused no obvious symptoms in chickens. The virulence of Anhui strain was further increased after circulated in chickens.Conclusions Th005 exhibits a high pathogenicity to poultry which may impair poultry industry and increase the existenceof viruses in the environment. Surveillance for the H7N9 influenza viruses, such as Th005, which had risen the virulence,should be stepped up.

Abstract:Objective To compare the pathogenicity of two subtypes of influenza A virus A/ Shanghai/37T/2009(H1N1) (pdm09) and A/ PuertoRico/8/34 (H1N1) (PR8) and the immunogenicity of those two subtypes of influenza Avirus to induce antigen specific CD8⁺ T cells in C57BL/6 mice. Methods ①The wild type C57BL/6 mice were infectedwith 50% tissue infection dose (TCID₅₀) of PR8 and pdm09 respectively. The situations of the infected mice were observeddaily (14 days), and the death rate was recorded. The mice were sacrificed at 1 and 3 days (days post infection, d.p.i),the lungs were collected to weigh and the lung indexes were calculated, and the left lobes of lung were fixed by 4%paraformaldehyde and stained with H&E to observe the pathological changes of the lung after infection. The viral load inlung tissue was detected by real-time fluorescence quantitative PCR (qRT-PCR). ② The mice were intranasally infectedwith 0. 25 times lethal dose (lethal dose 50%, LD50) of PR8 and pdm09, respectively. The infected mice were weighedevery day and monitored continuously for 14 days. The splenocytes were isolated on the 8 d.p.i. The percentages of influenzaviral antigen specific CD8⁺ T cells, the expression levels of IFN-γ, TNF-α, IL-2, granzyme B and immunosuppressivecheckpoint molecules PD-1, LAG-3, Tim-3 and CTLA-4 were detected by fluorescence-activated cell sorting (FACS).Results ①After the same TCID₅₀ influenza virus infections, the mice in both groups were morbid. All the mice in thePR8 group died on the 5th day after infection, and the mortality rate in the PR8 group was significantly higher than thatin the pdm09 group on the 1st and 3rd day ( P <0. 01), and the lung index and viral load on the 1st and 3rd day in thePR8 group were significantly higher than those in the pdm09 group. The result of H&E staining showed that thepathological injury of lung tissue was mild and the inflammatory infiltration was less in the pdm09 group. ② After thesame LD₅₀ influenza virus infection, the weight-loss and pathological changes in the lung tissues in the PR8 group weresignificantly more serious than in the pdm09 group. The result of flow cytometry showed that the proportion of virusspecificCD8⁺ T cells in the PR8 group was higher than that in the pdm09 group, but the productions of IFN-γ, TNF-αand IL-2 by activated CD8⁺ T cells in the PR8 group were significantly lower than that in pdm09 group. Further detectionof exhaustion makers on the activated CD8⁺ T cells revealed that the cells of the PR8 group express moreimmunosuppressive molecules PD-1 and LAG-3 than those cells of the pdm09 group. Conclusions Influenza A virusPR8 can cause more serious damage in mice compared with pdm09, which may be due to the functional exhaustion ofactivated antigen specific CD8⁺ T cells, resultsing in lower protective immunity against influenza viral infection and more severe pathological injury than pdm09 infection.

Abstract:Objective The aim of this study was to establish an influenza A virus-induced inflammation model inmice to analyze the pathogenicity of influenza A virus. Methods Forty-four 5-week old SPF healthy female BALB/ c micewere used in this study. A/ swine/ Jiangsu/ C1/08 (H9N2) (H9C1), A/ swine/ Shandong/731/2009 (SD731) and A/Puerto Rico/8/34 ( H1N1) ( PR8) influenza viruses were administered by intranasal instillation to BALB/ c mice,inoculated in a dose of 50 μL 1 × 10⁶ TCID₅₀, respectively, 11 mice in each group. The changes of body weight, clinicalsigns and death of the mice were observed every 24 hours from 1 to 14 dpi (days post inoculation). Blood and lung sampleswere taken for virus titer and inflammation detection. Results Compared with the PBS control group, SD731 and PR8virus infected mice showed a strong inflammation, and the mortality rate of SD731 virus infected BALB/ c mice was 80%and that of the PR8 virus infection was 100%. H9C1 virus infection caused a mild inflammatory response compared toSD731 and PR8 virus infection, and no significant weight loss and no death from 1 to 14 dpi. Conclusions In this study,the successfully established mouse model of influenza A virus-infected inflammation provides a strategy for the study of thepathogenesis of influenza virus, and a useful working basis for research of the pathogenesis, drug development, and vaccine evaluation of this disease.

Abstract:Objective Evaluating motion and perception behavior to investigate the functional changes of brainregions in non-human primates is an important strategy to develop clinical transformation study for major diseases in brainscience research. Methods In this study, 7- to 9-year-old male cynomolgus monkeys were used to establish a Parkinson’smodel induced by right internal carotid artery injection of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and anischemic stroke model induced by left middle cerebral artery occlusion. The testing apparatus for hill and valley staircasetasks were used to evaluate the effect of unilateral brain injury on contralateral perception and motion function. Results Ina 10-day evaluation for hill and valley staircase tasks, full scores were marked for the left and right hands of normalmonkeys. After injection of MPTP into the right internal carotid artery, three experimental monkeys showed damageddopaminergic neurons in the right substantia nigra by PET-CT image analysis. In hill and valley staircase tasks, the lefthand motor function of two experimental monkeys was significantly injured, and the spatial recognition ability was normal.One experimental monkey not only had left hand motor ability damage but also showed abnormal spatial recognition ability orright hand motor ability. After left middle cerebral artery occlusion by electrocoagulation, typical ischemic infarctionappeared in the right brain in the experimental monkey in MRI analysis. In hill and valley staircase tasks, the right handmotor function of the experimental monkey was impaired, but the spatial recognition ability was normal. Conclusions Thehill and valley staircase tasks can be effectively applied to evaluate motion and perception behavior in a unilateral brain injury non-human primate animal model.

Abstract:Objective The mouse FcγR2b, FcγR3, and FcγR4 gene clusters of about 90 kb in length wereknocked out by CRISPR/ Cas9 genome editing technique to lay the foundation for constructing an FcγR gene humanizedmouse. Methods Single guide RNAs (sgRNAs) were designed using online software to target exons of FcγR2b andFcγR3. Five candidate sgRNAs with lower off-target effects were selected for each target site. The cleavage activity ofsgRNAs was tested in vitro by the CRISPR/ Cas9 activity assay kit. The sgRNA with high cleavage activity was selected forin vitro transcription and microinjected with Cas9 mRNA into zygotes. Results A genetic modified mouse with 89,711 bpknockout fragment was confirmed by PCR detection and sequencing. The 5′ end of the FcγR2b gene, the 3′ end of theFcγR3 gene and FcγR4 gene were knocked out at the same time. Moreover, 8 sites with the highest probability of off-targetwere predicted by software, and all 8 off-target sites of the founder mouse genome were sequenced and confirmed. No smallfragment insertion or deletion was found in any predicted off-target sites. Conclusions We established a large fragmentknockout technique using CRISPR/ Cas9 genome editing technique, which may provide a new method to establish humanized mouse models by combining with BAC transgenic strategies.

Abstract:Objective To observe the early neuroprotective effect of shenzhiling oral liquid on AD mice, andto observe the effect of shenzhiling oral liquid on the ultrastructure of myelin sheath and synapse in CA1 area ofhippocampus and the changes of special staining of myelin sheath. Methods The App / Ps1 transgenic mouse model isformed by PrP-hAppk595N / M596L single transgenic dementia model mice and PrP-hPs1dE9 single transgenicdementia model mice, which is a common disease model to study Alzheimer’ s disease. The 3-month-old App / Ps1double-transgenic mice were randomly divided into the following groups (n = 9 per group): model group, donepezilgroup [0. 92 mg/ (kg·d)], shenzheling high-dose group [50 g/ (kg·d)], shenzheling medium-dose group [25 g /(kg·d)], and shenzheling low-dose group [12. 5 g/ (kg·d)]. C57BL/6J mice of the same age and background wereused as the control group. After 3 months of continuous intragastric administration, the hippocampal CA1 tissue ofmice was obtained for electron microscopic analysis, and the ultrastructural changes of myelin sheath and synapses inthis area were observed. The myelin sheath was stained and analyzed by luxol fast blue staining of nerve myelins.Results The number of synapses in the hippocampal CA1 area was decreased in the model group compared withcontrols ( P < 0. 01); the structure of neurons showed degenerative changes, the morphology of oligodendrocytesshowed pre-apoptotic state, and the structure of myelin sheath layer collapsed. The number of synapses in thehippocampal CA1 area of mice in each drug intervention group was increased compared with the model group ( P <0. 01); the morphological structure of neurons and oligodendrocytes was relatively complete, the morphologicalstructure of neurons and oligodendrocytes was intact, the chromatin was uniform, and the myelin lamellar structure wasimproved. Luxol fast blue staining revealed that myelin fibers in the model group were significantly decreased and thestaining was lighter than that in the control group. The myelin fibers in the intervention groups were increased andstaining was deepened to different degrees. Conclusions Shenzheling oral liquid may play an early neuroprotectiverole in Alzheimer’s disease by increasing the number of synapses in the hippocampal CA1 area of App / Ps1 transgenic mice and improving the structure and morphology of myelin sheath, oligodendrocytes and neurons.

Abstract:Objective We examined the virological, biochemical and pathological features of two compositemouse models of hepatitis B fibrosis. Methods Mice were transfected with rAAV8-1. 3HBV adeno-associated virus andC57BL/6 N-Tg(1. 28HBV) / Vst type hepatitis B virus transgenic mice, combined with CCl₄ to induce hepatitis B liverfibrosis in mice. The mice were divided into the following groups: wild-type control group ( WT), rAAV8-1. 3HBVtransfection control group (rAAV), CCl₄ control group (CCl₄ ), rAAV8-1. 3HBV transfection with CCl₄ model group(rAAV+CCl₄), C57BL/6 N-Tg (1. 28HBV) / Vst hepatitis B virus transgenic control group (Tg), and HBV transgenic complex CCl₄ model group (Tg+CCl₄ ).After 12 weeks,the levels of HBsAg and HBeAg were measured by ELISA. TheHBV-DNA load was detected by PCR. The expression of HBsAg and HBcAg in the liver tissue was observed byimmunohistochemical staining. Serum ALT, AST and AKP were determined by a biochemical kit, and hydroxyproline(Hyp) content was detected by hydrochloric acid hydrolysis method. HE staining and Sirius red staining were used toobserve the pathological changes. Results ELISA result showed positive serum HBsAg and HBeAg,meanwhile the PCRexamined the HBV-DNA load was higher than 1. 0×10⁴ IU/ mL in all the groups except for the WT and CCl₄ group. TheHBsAg and HBeAg content in the Tg+CCl₄ group was higher than in the rAAV+CCl₄ group. The levels of HBV-DNA in therAAV and rAAV+CCl₄ groups were higher than those in the Tg and Tg+CCl₄ groups. Immunohistochemistry showed positiveHBsAg and HBcAg in the liver tissues in all groups except the WT group and CCl₄ group. The expression of HBsAg wasdecreased but HBcAg was significantly increased in the rAAV+group compared with the Tg group. No significant differencewas detected in HBsAg between the Tg+CCl₄ group and rAAV+CCl₄ group, but the HBcAg positive expression wasobviously increased in the latter group. The levels of ALT, AST and liver Hyp were significantly increased in the CCl₄group, Tg+CCl₄ group and rAAV+CCl₄ group. The Hyp content in the Tg+CCl₄ group was higher than in the rAAV+CCl₄group. The biopsy showed that there were significantly increased inflammation reaction and collagen deposition in the CCl₄group, Tg+CCl₄ group and rAAV+CCl₄ group. The Tg+CCl₄ group collagen deposition was higher than in the rAAV+CCl₄group. Conclusions The two composite mouse models conform to the hepatits B liver fibrosis model and the differences areconcentrated in virological indicators and pathological changes. The rAAV + CCl₄ group has an advantage in HBV-DNA load, and the Tg + CCl₄ group was more obvious in fibrosis progress.

Abstract:Objective To investigate the changes of inflammatory factors interleukin-2 (IL-2) and interleukin 4(IL-4) in the pathogenesis of mouse mastitis. Methods Twelve lactating female BALB/ C mice were randomly divided intothe control group (group A), high concentration group (group B), medium concentration group (group C) and lowconcentration group (group D). Group A was injected with normal saline. Groups B, C and D were injected with differentconcentrations of Staphylococcus aureus, 1. 2×10⁵ CFU/ mL, 1. 2×10⁴ CFU/ mL and 6. 0×10³ CFU/ mL, respectively. Thepathological changes were observed using H&E staining. The expression of IL-2 and IL-4 mRNA and protein in the mousemammary glands were detected by qRT-PCR, immunohistochemistry and western blot. Results The pathologicalexamination showed that the pathological changes of breast tissue were gradually aggravated with the increase of theconcentration of S. aureus. Immunohistochemistry, qRT-PCR and western blot assays showed that the expression levels ofIL-2 in the groups B, C and D were significantly higher than that in the group A ( P < 0. 05) However, as the concentrationof infectious bacteria increased, the expression level of IL-2 gradually decreased. Compared with the group A, the groupsB, C and D showed significantly increased expression levels of IL-4 ( P < 0. 05), but the expression level increasedgradually with the increase of concentration of infectious bacteria. Conclusions The inflammatory factors IL-2 and IL-4 areinvolved in the development of mastitis caused by S. aureus, which lays a foundation for the pathologic mechanism of S.aureus mastitis and provide a theoretical scientific basis for studying the immune mechanism of breast.

Abstract:Objective To explore the effect of L -arginine on pupation time, eclosion time, eclosion rate andmale/ female ratio in Drosophila melanogaster. Methods Two groups of fruit flies were included in this study, the controlgroup received corn meal agar medium (basic medium) and the experimental group received 1% L -arginine added in thebasal medium. Seven pairs of fruit flies were placed in each tube, female: male=1∶1, 12 replicates in each group, and theparent flies were removed after 72 h. The time of pupation, the time of feathering, the number of feathering, and thenumber of males and females in each group were counted. Results After the addition of 1% L -arginine in the basicmedium, the numbers of pupation and feathering, and the feathering rate of the white eye (w¹¹¹⁸ ), residual wing (CyO)and wild type Drosophila melanogaster were increased by 313. 64% and 303. 53% ( P < 0. 01), 157. 09% and 182. 76% ( P < 0. 01), and 233. 33% and 239. 03% ( P < 0. 01), respectively. In the group with addition of 1% L -arginine, thepupation time of the both white eye and wild type flies was 2 days earlier than the control group. Conclusions Addition of1% L -arginine in the basic medium, used under the conditions of this experiment, can increase the fertility of laboratory fruit flies and can be applied to the expansion of laboratory fruit flies.

Abstract:Objective To establish a mouse model of intestinal allergy by epicutaneous sensitization (ES).Methods After comparing the degree of intestinal allergy induced by ES (on the ear or back skin) or intraperitonealinjection, the method of ES (on ear skin) with higher sensitivity and easier operation was selected. Calcipotriol ointmentwas used for induction of the inflammation of mice ear skin. At the same time, mice were epicutaneously sensitized withovalbumin (OVA) for two weeks. The established model was evaluated according to the below symptoms, includingintestinal allergic symptoms, jejunal capillary permeability, plasma tIgE and mMCP-1 levels, and jejunal histopathologicalchanges after OVA challenge (i.g.). Results In contrast to intraperitoneal injection, the ES induced higher production ofplasma tIgE and mMCP-1. Moreover, the mice in the model group showed obvious intestinal allergy symptoms, such asrapid scratching, arching back and diarrhea, hypothermia (the rectal temperature was decreased about 1. 2℃), increasedjejunal capillary permeability (about 2 times), and robustly increased plasma tIgE and mMCP-1 levels. Histologicalchanges were also observed, such as the damage of jejunum mucosa, infiltration of inflammatory cells and the increase ofmast cells (about 5 times). Conclusions The established mouse model not only has typical pathological characteristics offood allergy, but also represents the sensitization pathway of skin exposure to allergens. It may also provide a new research tool for further mechanism research and the prevention/ treatment of food allergy.

Abstract:Objective To diagnose the spontaneous diabetic cynomolgus monkey and examine their bonemicrostructure, and establish an animal model of spontaneous diabetic osteoporosis. Methods Four spontaneous diabeticcynomolgus monkeys (13 to 20 years old) were included. Animals of similar ages were used as a control group. Fastingblood glucose and glucose tolerance were measured using a fast blood glucose meter. TC, LDL-C, HDL-C, TG, Crea, andBUN were measured to make the diagnosis of spontaneous diabetic cynomolgus monkeys. Micro-CT was used to measure thebone structure of distal femur and upper tibia. Results In the spontaneous diabetic group, the fasting blood glucose washigher than 8. 0 mmol/ L, and the blood glucose was higher than 10. 0 mmol/ L at 120 min of the glucose tolerance test. TGand LDL-C of the spontaneous diabetic cynomolgus monkeys were significantly higher than the control group, while HDL-Cand Crea were significantly lower than the control group ( P < 0. 05). There was no significant difference between TC andBUN, which could be diagnosed as spontaneously spontaneous diabetic cynomolgus monkeys. Micro-CT results showed thatthe distal femur and upper tibia of the spontaneous diabetic cynomolgus monkeys were damaged indicating osteoporosis.Moreover, the trabecular area, trabecular volume and bone mineral content of cancellous bone in the distal femur and uppertibia of the spontaneous diabetic cynomolgus monkeys were significantly lower than the control group. There were nosignificant differences in the cortical bone of the distal femur and upper tibia between the two groups. Conclusions The spontaneous diabetic cynomolgus monkeys have similar clinical characteristics with human patients, and may be used as an excellent animal model in studies of diabetic osteoporosis.

Abstract:Objective To observe the effect of a Chinese traditional medicine prescription, Shenren Huoxue(SRHX) granules, on the TGF-β1/ Smad signaling pathway in rats with CCl₄-induced liver fibrosis and to explore theunderlying mechanism. Methods Fifty male SD rats were randomly divided into five groups: control group, model group,low-dose SRHX, middle-dose SRHX and high-dose SRHX groups. The control group was given saline 1 mL/ kg; the modelgroup and SRHX granules groups were given 40% carbon tetrachloride (CCl₄ ) 0. 2 mL/100 g by intraperitoneal injectiontwice a week for 8 weeks. From the fourth week, the SRHX groups were given low-dose (1. 575 g/ (kg?bw) / d), middledose(3. 15 g/ (kg?bw) / d) and high-dose (6. 3 g/ (kg?bw) / d) SRHX by gastric gavage for 4 weeks and euthanized atweek 8. HE staining and Masson staining were used to detect the degree of liver fibrosis in rats. Immunohistochemistry wasused to detect the expression of collagen I, collagen III and TGF-β1. Real-time PCR and western blot were used to detectthe expression of TGF-β1, Smad3 and Smad7 in rat liver tissues. Results Compared with the control group, the liver ofthe model group showed destruction of liver lobular structure, inflammatory cell infiltration, significantly increased fibersand pseudolobule formation ( P < 0. 05). Compared with the model group, the degree of liver fibrosis was significantlyimproved and the high-dose of SRHX granules was the most effective ( P < 0. 05). The expressions of collagen I, collagenIII, TGF-β1 and Smad3 in the model group were significantly higher than those in the control group ( P < 0. 05), while theexpression of Smad7 was significantly lower than the control group ( P < 0. 05). Compared with the model group, theexpressions of collagen I, collagen III, TGF-β1 and Smad3 in all SRHX groups were decreased while the expression ofSmad7 was increased. The high-dose of SRHX granules was better effective ( P < 0. 05). Conclusions SRHX granules canimprove the pathological changes of liver tissue in SD rats with hepatic fibrosis and alleviate the degree of liver fibrosis andliver inflammation in hepatic fibrosis in rats. The mechanism may be related to SRHX granules decreasing the synthesis of collagen I and collagen III by decreasing the expression of TGF-β1 and Smad3 and upregulating the expression of Smad7.

Abstract:Objective To investigate the effects of selenium-enriched rice bran on the growth performance andantioxidant function in weaned rabbits. Methods Sixty 35-day-old weaned rabbits were randomly divided into three groups(n =20, 1∶1 male ∶female) and were fed with feed added ordinary rice bran, ordinary rice bran plus selenium-enrichedyeast or selenium-enriched rice bran for 30 days. Feed consumption was recorded daily and the rabbits were weighed at 0 d,5 d, 10 d, 15 d, 20 d, 25 d and 30 d, respectively. After 30 days, serum was collected and the content of blood glucose,uric acid, total protein, albumin, globulin, and albumin/ globulin ratio were measured by the IDEXX Catalyst Dx Analyzer.The activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) and the content ofmalondialdehyde (MDA) were detected by assay kits. The liver, spleen and kidney were weighed, organ index wascalculated, and the selenium content in the kidney was determined. Results There were no significant differences in dailyweight gain, feed conversion ratio, organ index, kidney selenium content and the blood biochemical indexes among thethree groups ( P >0. 05). However, the activity of GSH-Px and SOD in the selenium-enriched rice bran group and theactivity of GSH-Px and CAT in the organic selenium group were significantly higher than that in the ordinary rice bran group( P <0. 05). The MDA content in these two groups was significantly lower than that of the ordinary rice bran group ( P <0. 05). In addition, the antioxidant capacity was comparable between the selenium-enriched rice bran group and organicselenium group. Conclusions Selenium in selenium-enriched rice bran plays a positive role in promoting growth andresisting oxidation in weaned rabbits, which is similar to the selenium in yeast. These findings indicate selenium-enriched rice bran can be used as a selenium source of feed for weaned rabbits.

Abstract:Objective The aim of this study was to investigate the effect of lysyloxidase inhibitor betaaminopropionitrile(BAPN) on the aortic wall in rats, to analyze the gross and pathological changes of arterial and othertissues of rats treated with BAPN at different concentrations, and to compare with the characteristics of human dissected aneurysm. Methods Eighteen SPF SD rats (4-5-week old) were divided into three groups: SD-0. 2 (Group A), SD-0. 4(Group B), and SD-0. 6 (Group C). The groups A, B and C were given 0. 2%, 0. 4%, and 0. 6% BAPN solution,respectively, as drinking water for seven weeks. Forty SPF C57BL/6 mice (3-week old) were randomly divided into four groups: C57-0. 2 (Group D), C57-0. 4 (Group E), C57-0. 6 (Group F) and the control group and given 0. 2%, 0. 4%,or 0. 6% BAPN or distilled water as drinking water, respectively, for seven weeks. All experimental animals were free to drink water. The daily water intake was recorded and the weight was measured once a week. Rats that died during theexperiment or survived after the experiment were dissected. The aortas were dissected and visually examined. The aorta was divided into four parts: ascending aorta, descending aorta, abdominal aorta above the renal artery and abdominal aorta under the renal artery. The aortic tissues were cut into 4 μm sections and stained with hematoxylin and eosin for pathological examination. The vascular diameter, and area of the tunica media were measured by image analysis. The pathological changes of aorta and dissecting aneurysm of 10 patients were also observed and compared with the rat aorta with dissecting aneurysms. Results BAPN significantly affected the water intake and weight gain of rats or mice. BAPN caused thickening of the tunica media in the aorta of rats or mice, and reduction and disordered arrangement of elastic protein. Their pathological changes were similar to the pathological changes of human aneurysms. Conclusions The incidence of dissecting aneurysm in C57BL/6 mice was much higher than that of SD rats, indicating that mice may be an ideal animal model for further study. In SD rats, the rate of pathological changes in other systems, such as intestinal rupture and scoliosis, was higher than that in the dissection aneurysm. Further exploration for SD rats as an animal model of aortic dissecting aneurysm is needed.

Abstract:Objective To study the neuroprotective effect of berberine on cerebral ischemia-reperfusion injury in rats based on the B cell lymphoma/ lewkmia-2 (Bcl-2) / Beclin-1 complex. Methods A total of 108 SPF grade SD ratswere randomly divided into the follow groups: sham group, model group (I/ R), berberine low, medium and high dosegroup ( BBR-L, BBR-M, BBR-H), and nimodipine pretreatment group ( NMDP group). The rats were scored forneurological function after modeling and the area of cerebral infarction was observed by TTC staining. HE staining was used to observe the his topathological changes of rat brain, and the expressions of Bcl-2, caspase-3 and Bax in brain tissues were detected by RT-PCR, while western blot was used to detect the expressions of Bcl-2, caspase-3, Bax and Beclin-1 incerebral cortex. Results The neurological function scores in the I/ R group at 6 h, 24 h and 48 h was significantly higher than that in the sham group, with the highest score at 24 h. Compared with the model group, the scores of neurologicalimpairment in the BBR group and NMDP group were significantly reduced at 24 h and 48 h ( P <0. 05). The percentage ofinfarct area and the percentage of cell necrosis in the I/ R group were increased significantly compared with the sham group( P <0. 05), while BBR group and NMDP group decreased significantly compared with the I/ R group ( P <0. 05). Bcl-2,caspase-3, Bax mRNA and protein levels in the I/ R group were significantly increased compared with the sham group. The levels of Bcl-2 mRNA and protein in the BBR group and NMDP group were increased significantly compared with the I/ Rgroup, while the levels of caspase-3, Bax mRNA and protein decreased significantly. The Bcl-2/ Bax ratio in the I/ R groupdecreased significantly compared with the sham group. The Bcl-2/ Bax ratio of each treatment group was increase dsignificantly compared with the I/ R group and was increased in a dose-dependent manner. Beclin-1 protein level and Bcl-2/Beclin-1 ratio were increased in the I/ R group compared with the sham group ( P <0. 05). The levels of Beclin-1 protein inthe BBR group and NMDP group were increased significantly compared with the I/ R group ( P <0. 05), the ratio of Bcl-2/Beclin-1 was decreased, and there was no significant difference in Bcl-2/ Beclin-1 between the BBR-M group, BBR-Hgroup and NMDP group. Conclusions Berberine has a neuroprotective effect on cerebral ischemia-reperfusion injury in rats. Berberine regulates the levels of autophagy protein and apoptotic protein, so that autophagy can reach an appropriate level and play a neuroprotective role.

Abstract:Spinal cord injury is currently a major focus of research, and the study of spinal cord ischemicreperfusion injury (SCII) has been a major challenge worldwide. Many animal models are currently used to study SCII, but there is still a lack of the most simple, effective and most similar model to human SCII. An animal model of SCII plays avital role in the study of etiology and pathological mechaism of SCII related diseases, as well as in the guidance of clinical medication and the research and development of new drugs. This paper reviews the animal species, methods and applications used in SCII modeling in the relevant literature and describes the establishment of a simple, effective and highly similar model to human SCII.

Abstract:The patient-derived gastric cancer xenograft (PDGCX) model well maintains the heterogeneity of the primary tumor. Further establishment of an individualized metastasis model that simulates clinical features is of great significance for gastric cancer research. In this review, we focus on the establishment methods, influencing factors and evaluation indexes of the PDGCX metastasis model and summarize the method of screening gastric cancer metastasis-related genes. We further analyze the application of the PDGCX model in the identification of therapeutic targets and screening of potential markers for metastasis of gastric cancer.

Abstract:This study reviewed the effects and physiological response mechanisms of high +Gz exposure on thecardiovascular, respiratory, central nervous and endocrine systems and other tissues and organs, and to discuss if these results and theoretical mechanisms could be adapted to human body. The results showed that high +Gz has a significantimpact on the blood circulation in the whole body and various organs, resulting in ultrastructural alterations of thecardiovascular system, lung tissue, endocrine glands and brain tissue, etc. With the application of radioimmunoassay andbiochemical method, mechanical finite element model, gene chip and other technologies, better understanding of the physiological stress response and pathogenic mechanism under high +Gz load will be achieved.

Abstract:The animal model of interstitial cystitis is critical for the study of interstitial cystitis/ bladder painsyndrome (IC/ BPS). However,many problems still exist in the establishment of the animal model. There is no goldstandard for the pathological diagnosis of IC/ BPS, and most animal models show one or several phenotypes of IC/ BPS. Inthis paper, the establishment method and applications of rat models, the most commonly used IC/ BPS rodents models, are summarized.

Abstract:Contrast-induced nephropathy is defined as the sudden deterioration in renal function following the exposure to contrast media. The morbidity and mortality of contrast-induced nephropathy are on the rise, which has become a serious threat to public health. The pathogenic mechanisms of contrast-induced nephropathy have not well elucidated yet.Animal experiments are important in the etiology, pathogenesis as well as the prevention and treatment of the contrastinduced nephropathy. Therefore, the successful development of animal models is the first step of our relevant research. In this paper, we will discuss the progress of generating contrast-induced nephropathy animal models.