Transmissible gastroenteritis(TGE)is a highly contagious gastrointestinal disease of pigs caused by the transmissible gastroenteritis virus(TGEV).It results in severe diarrhea and high mortality in suckling piglets.As no specific treatment available,vaccination is considered to be one of the most cost-effective measures for preventing and controlling TGE.However,the immune protection provided by vaccines based on traditional TGEV strains is becoming inadequate due to the continuous emergence of strong and new strains of the virus,which poses a serious threat to the pig industry's health and development.Therefore,the development of new vaccines with im-proved efficiency and broad-spectrum coverage is urgently needed.This paper aims to summarize the pathogenic structural characteristics of TGEV,discuss the latest advancements in TGEV vac-cine research and development,and propose future strategies for the development of highly effec-tive TGEV vaccines.The findings of this paper can serve as a valuable reference for effectively pre-venting and controlling TGE in clinical practice.

Aim To investigate the association between cardiovascular health(CVH)score based on life's es-sential 8(LE8)on cognitive function and the mediation role of neutrophil-to-lymphocyte ratio(NLR)between them in ol-der adults,providing basis for the prevention and control of cognitive impairment.Methods The study population was selected from the National Health and Nutrition Examination Survey(NHANES)2011-2014 two cycles of 60 years and a-bove,demographic characteristics,medical history and other variables were collected,the participants'CVH scores were calculated according to LE8 defined by American Heart Association,and cognitive function was assessed using the digit symbol substitution test.The relationship between CVH and cognitive function was explored using a weighted linear re-gression analysis,and the dose-response relationship was analyzed using a restricted cubic spline.Moreover,mediation a-nalysis was used to explore the role of NLR in mediating the relationship between CVH score and cognitive function.Results A total of 2 510 participants were included in this study.After adjusting for relevant factors,cognitive function was positively associated with moderate CVH group score(β=3.36,95％CI:1.43～5.30)and high CVH group score(β=6.01,95％CI:2.89～9.13)compared with the low CVH group score.The LE8 single factor of diet score(β=0.04,95％CI:0.01～0.06),physical activity score(β=0.04,95％CI:0.02～0.05),tobacco exposure score(β=0.05,95％CI:0.02～0.08),blood pressure score(β=0.03,95％CI:0.01～0.05)and blood glucose score(β=0.06,95％CI:0.03～0.09)were positively correlated with cognitive function score.The results of restricted cubic splines showed that the score of CVH was linear positively correlated with the score of cognitive function.The indirect effect of CVH on cognitive function via NLR was 0.002(P＞0.05),and the proportion of mediating effect was 1.29％(P＞0.05),indicating the mediating effect of NLR on the relationship between CVH score and cognitive function was not signif-icant.Conclusions The CVH score based on the LE8 was positively correlated with cognitive function in older adults,underscoring the crucial role of maintaining optimal CVH levels in supporting cognitive health.However,the NLR,as an indicator of inflammation,did not exhibit a significant mediating effect between the CVH score and cognitive function.The relationship between these variables might be influenced by other mechanisms.

Objective To determine the effects of Bushen Huoxue Formula(BHF),a clinically vali-dated traditional Chinese herbal compound,on myelin integrity and cognitive function in mice with chronic cerebral hypoperfusion(CCH).Methods A total of 30 SPF male C57BL/6J mice were randomly divided into sham operation group(n=8)and model group(n=22).Bilateral com-mon carotid artery stenosis was inflicted to establish a mouse model of CCH,while the mice in the sham operation group only received separation of bilateral vagus nerves.In the model group,6 mice died in 2 d after surgery,the left 16 mice were then randomly divided into a model group and a treatment group,with 8 animals in each group.In 2 weeks after surgery,BHF(0.2 ml/d)or pure water was administered via gavage for 60 d to the corresponding groups.Cognitive function was assessed using the Morris water maze(MWM)test.White matter lesions were evaluated by diffu-sion tensor imaging-fractional anisotropy(DTI-FA).Demyelination in the corpus callosum was visualized using Luxol fast blue(LFB)staining,while neuronal damage in the hippocampal CA1 region was analyzed with Nissl staining.Results Compared to the sham group,the model group exhibited significantly prolonged swimming distance and escape latency on day 5 and reduced platform crossings on day 6 in Morris water maze test,decreased DTI-FA value,lower absorbance value of myelin in LFB staining,and fewer Nissl-stained neurons in the hippocampal region(P＜0.05,P＜0.01).In contrast,the treatment group showed significantly shorter swimming distance[188.14(105.19,342.00)cm vs 280.22(168.47,501.37)cm,P＜0.05]and escape latency[10.22(5.77,19.47)s vs 19.39(13.57,31.09)s,P＜0.01]on day 5,increased platform crossings on day 6[3.00(2.00,4.00)times vs 2.00(1.00,3.00)times,P＜0.05],elevated DTI-FA value(0.340±0.014 vs 0.313±0.012,P＜0.01),enhanced absorbance value of myelin[0.353(0.328,0.364)vs 0.305(0.290,0.350),P＜0.05],and greater neuronal counts(9.94±2.22 cells vs 7.11±2.02 cells,P＜0.01)when compared to the model group.Conclusion BHF can alleviate CCH-induced cogni-tive deficits in mice by promoting repair of white matter microstructure and rescue of neuronal loss.

Aim To investigate the association between cardiovascular health(CVH)score based on life's es-sential 8(LE8)on cognitive function and the mediation role of neutrophil-to-lymphocyte ratio(NLR)between them in ol-der adults,providing basis for the prevention and control of cognitive impairment.Methods The study population was selected from the National Health and Nutrition Examination Survey(NHANES)2011-2014 two cycles of 60 years and a-bove,demographic characteristics,medical history and other variables were collected,the participants'CVH scores were calculated according to LE8 defined by American Heart Association,and cognitive function was assessed using the digit symbol substitution test.The relationship between CVH and cognitive function was explored using a weighted linear re-gression analysis,and the dose-response relationship was analyzed using a restricted cubic spline.Moreover,mediation a-nalysis was used to explore the role of NLR in mediating the relationship between CVH score and cognitive function.Results A total of 2 510 participants were included in this study.After adjusting for relevant factors,cognitive function was positively associated with moderate CVH group score(β=3.36,95％CI:1.43～5.30)and high CVH group score(β=6.01,95％CI:2.89～9.13)compared with the low CVH group score.The LE8 single factor of diet score(β=0.04,95％CI:0.01～0.06),physical activity score(β=0.04,95％CI:0.02～0.05),tobacco exposure score(β=0.05,95％CI:0.02～0.08),blood pressure score(β=0.03,95％CI:0.01～0.05)and blood glucose score(β=0.06,95％CI:0.03～0.09)were positively correlated with cognitive function score.The results of restricted cubic splines showed that the score of CVH was linear positively correlated with the score of cognitive function.The indirect effect of CVH on cognitive function via NLR was 0.002(P＞0.05),and the proportion of mediating effect was 1.29％(P＞0.05),indicating the mediating effect of NLR on the relationship between CVH score and cognitive function was not signif-icant.Conclusions The CVH score based on the LE8 was positively correlated with cognitive function in older adults,underscoring the crucial role of maintaining optimal CVH levels in supporting cognitive health.However,the NLR,as an indicator of inflammation,did not exhibit a significant mediating effect between the CVH score and cognitive function.The relationship between these variables might be influenced by other mechanisms.

Transmissible gastroenteritis(TGE)is a highly contagious gastrointestinal disease of pigs caused by the transmissible gastroenteritis virus(TGEV).It results in severe diarrhea and high mortality in suckling piglets.As no specific treatment available,vaccination is considered to be one of the most cost-effective measures for preventing and controlling TGE.However,the immune protection provided by vaccines based on traditional TGEV strains is becoming inadequate due to the continuous emergence of strong and new strains of the virus,which poses a serious threat to the pig industry's health and development.Therefore,the development of new vaccines with im-proved efficiency and broad-spectrum coverage is urgently needed.This paper aims to summarize the pathogenic structural characteristics of TGEV,discuss the latest advancements in TGEV vac-cine research and development,and propose future strategies for the development of highly effec-tive TGEV vaccines.The findings of this paper can serve as a valuable reference for effectively pre-venting and controlling TGE in clinical practice.

Objective To determine the effects of Bushen Huoxue Formula(BHF),a clinically vali-dated traditional Chinese herbal compound,on myelin integrity and cognitive function in mice with chronic cerebral hypoperfusion(CCH).Methods A total of 30 SPF male C57BL/6J mice were randomly divided into sham operation group(n=8)and model group(n=22).Bilateral com-mon carotid artery stenosis was inflicted to establish a mouse model of CCH,while the mice in the sham operation group only received separation of bilateral vagus nerves.In the model group,6 mice died in 2 d after surgery,the left 16 mice were then randomly divided into a model group and a treatment group,with 8 animals in each group.In 2 weeks after surgery,BHF(0.2 ml/d)or pure water was administered via gavage for 60 d to the corresponding groups.Cognitive function was assessed using the Morris water maze(MWM)test.White matter lesions were evaluated by diffu-sion tensor imaging-fractional anisotropy(DTI-FA).Demyelination in the corpus callosum was visualized using Luxol fast blue(LFB)staining,while neuronal damage in the hippocampal CA1 region was analyzed with Nissl staining.Results Compared to the sham group,the model group exhibited significantly prolonged swimming distance and escape latency on day 5 and reduced platform crossings on day 6 in Morris water maze test,decreased DTI-FA value,lower absorbance value of myelin in LFB staining,and fewer Nissl-stained neurons in the hippocampal region(P＜0.05,P＜0.01).In contrast,the treatment group showed significantly shorter swimming distance[188.14(105.19,342.00)cm vs 280.22(168.47,501.37)cm,P＜0.05]and escape latency[10.22(5.77,19.47)s vs 19.39(13.57,31.09)s,P＜0.01]on day 5,increased platform crossings on day 6[3.00(2.00,4.00)times vs 2.00(1.00,3.00)times,P＜0.05],elevated DTI-FA value(0.340±0.014 vs 0.313±0.012,P＜0.01),enhanced absorbance value of myelin[0.353(0.328,0.364)vs 0.305(0.290,0.350),P＜0.05],and greater neuronal counts(9.94±2.22 cells vs 7.11±2.02 cells,P＜0.01)when compared to the model group.Conclusion BHF can alleviate CCH-induced cogni-tive deficits in mice by promoting repair of white matter microstructure and rescue of neuronal loss.

ObjectiveTo investigate the principle and scientific connotation of Euodiae Fructus（EF） processed with Glycyrrhizae Radix et Rhizoma（Gly） by comparing the effects of unprocessed products of EF（UEF） and processed products of EF with the different proportions of Gly（GEFs） at toxic doses on oxidative stress and autophagy in the liver of mice. MethodSeventy mice were randomly divided into 7 groups， namely the control group， the UEF group， the group of the processed products of EF without Gly（PEF） and 4 groups of GEFs（the mass ratios of EF to Gly were 100∶3， 100∶6， 100∶12 and 100∶24， respectively， hereinafter referred to as the processed products of EF with the mass ratios of 100∶3， 100∶6， 100∶12 and 100∶24 of Gly）. The mice were given purified water， the decoction of UEF， PEF and GEFs by gavage at a dose of 30 g·kg^-1. PEF and GEFs were prepared according to the method under EF in the 2020 edition of Chinese Pharmacopoeia. Levels of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were determined by ultraviolet-visible spectrophotometry， hematoxylin-eosin（HE） staining was used to evaluate the pathological changes of liver tissue， the level of reactive oxygen species（ROS） was detected by fluorescence method， the mRNA expression of heme oxygenase-1（HO-1）， quinone oxidoreductase-1（NQO1）， glutathione-S-transferase 1（GSTA1）， Kelch-like epichlorohydrin-associated protein 1（Keap1） and p62 were measured by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， western blot was used to detect the protein expression of phosphorylated mammal target of rapamycin（p-mTOR）， phosphorylated ribosomal p70 S6 protein kinase（p-p70S6K）， p62， microtubule-associated protein 1 light chain 3Ⅰ（LC3Ⅰ） and LC3Ⅱ. ResultCompared with the control group， after 7 d of administration， the increase in body mass of mice in the UEF group began to slow down and the difference gradually increased， and the liver body index significantly increased（P<0.01）， pathomorphological observation showed that the structure of hepatic lobules was disordered， and local hepatic sinuses were narrowed or disappeared， and there were inflammatory infiltration and local bleeding， the levels of ALT and AST in serum and ROS in liver tissue were significantly increased（P<0.01）， and the expressions of Keap1， HO-1， NQO1， GSTA1， p62 mRNA and p-mTOR， p-p70S6K， p62 protein in liver tissue were significantly decreased（P<0.01）， and LC3Ⅱ/LC3Ⅰ was significantly increased（P<0.01）. Compared with the UEF group， the body mass of mice increased， and the liver body index， the levels of ALT and AST in serum， and the level of ROS in liver tissue all decreased in the groups of PEF and GEFs. Among these groups， only the liver lobules in GEF（100∶6） group were intact， and the size of liver sinuses was close to that in the control group. The mRNA expressions of Keap1， HO-1， NQO1， GSTA1 and p62 in liver tissue showed an overall upward trend in the groups of PEF and GEFs. Among these groups， only the ones of the above mRNA in the GEF（100∶6） group had a significant increase（P<0.05， P<0.01）. The protein expressions of p-mTOR， p-p70S6K， p62 and LC3Ⅱ/LC3Ⅰ had a callback in the groups of PEF and GEFs， of which the protein expressions of p-mTOR， p-p70S6K and LC3Ⅱ/LC3Ⅰ in the GEF（100∶6） group and the expression of p62 protein in the GEF（100∶24） group had the largest callback. Except for p-mTOR protein， other protein expressions were statistically significant（P<0.05， P<0.01）. ConclusionThe hepatotoxicity of EF is closely related to its ability to induce oxidative stress， which leads to pathological autophagy and hepatocyte damage. This ability can be reduced by the processing with different proportions of Gly， especially the ratio of 100∶6.

Animals ; Glycyrrhiza/adverse effects* ; Plant Extracts/toxicity* ; Rats ; Rats, Sprague-Dawley ; Sargassum

ObjectiveTo explain the scientific connotation of Morindae Officinalis Radix （MOR） processed by Glycyrrhizae Radix et Rhizoma （Gly） by comparing the effect of raw products of MOR and processed products of MOR with different proportions of Gly （GMOs） on the improvement of renal function and hypothalamic-pituitary-gonadal （HPG） axis， the protein expression of Wnt/β-catenin and transforming growth factor-β₁ （TGF-β₁）/Smad signal pathways in kidney Yang deficiency model rats induced by adenine. MethodGMOs were prepared according to method under MOR in 2020 edition of Chinese Pharmacopoeia. Rat model of kidney Yang deficiency was established by intragastrical administration of adenine， levels of follicle stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂） and testosterone （T） were measured by enzyme-linked immunosorbent assay （ELISA）. Levels of urea nitrogen （BUN） and serum creatinine （SCr） were measured by spectrophotometry， hematoxylin-eosin （HE） staining was used to evaluate the pathological changes of kidney， testis and epididymis. Immunohistochemistry （IHC） was used to analyze the protein expression of E-cadherin， α-smooth muscle actin （α-SMA）， Wnt2b， β-catenin， Smad1 and Smad4. ResultMOR processed with 100∶6 and 100∶12 proportions of Gly （short for GMO/100∶6 and GMO/100∶12） had the most obvious improvement on the body posture of kidney Yang deficiency model rats. GMO/100∶12 had the best effect on reducing the levels of BUN， SCr， FSH， LH and the ratio of E₂/T. GMO/100∶6 and GMO/100∶12 had the best effect on regulating the protein expression of E-cadherin， α-SMA， Wnt2b， β-catenin， Smad1 and Smad4. ConclusionGMO/100∶6 and GMO/100∶12 have the a good effect on the improvement of renal function and HPG axis in kidney Yang deficiency model rats induced by adenine， which is related with the fact that they can regulate Wnt/β-catenin pathway in renal and testicular tissue and TGF-β₁/Smads pathway in testicular tissue.

Objective:To explore the effects of BCR-ABL downstream pathway inhibitors, such as RAF inhibitor SB590885, JAK inhibitor AZD1480, PI3K-mTOR double target inhibitor BEZ235 on chronic myelogenous leukemia (CML) cells, and the effect of BEZ235 on the proliferation, apoptosis of CML cells and the sensitivity of imatinib in vitro.Methods:K562 cells were treated with different concentrations of the drugs. MTS method was applied to detect the proliferation inhibition rate of K562 cells, and 50% inhibitory concentration (IC 50) of all drugs for 48 h was calculated. The cell apoptosis rate was tested by using flow cytometry with Annexin V-FITC/PI double staining. The cell cycle was tested by using flow cytometry with PI staining. K562 cells, imatinib-resistant and T315I-mutant human CML KBM7R cells and imatinib-resistant CML primary cells of patients were treated with different concentrations of the drugs. MTS method was used to test the proliferation inhibition of cells, and IC 50 of all drugs for 48 h was evaluated. KBM7R cells or primary cells of CML patients were treated with 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib or the combination of both, respectively. Flow cytometry with PI staining was used to detect the cell cycle of KBM7R cells. Flow cytometry with Annexin V-FITC/PI double staining was used to detect the cell apoptosis rate in CML primary cells. The expressions of p-AKT, cleaved Caspase-3 and Cyclin D1 proteins were detected by using Western blot. Results:SB590885, AZD1480 and BEZ235 could inhibit the proliferation of K562 cells, and the IC 50 after the treatment of K562 cells for 48 h was (11.49±3.14), (4.83±1.26) and (0.37±0.21) μmol/L, respectively. SB590885, AZD1480 and BEZ235 could promote the apoptosis of K562 cells. The cell apoptosis rates were increased compared with the control group without drug treatment (all P < 0.01). SB590885 and BEZ235 induced G 0/G 1 block (both P < 0.05). AZD1480 induced G 2/M block ( P < 0.05). BEZ235 could inhibit the proliferation of K562 cells, KBM7R cells and CML primary cells, and their IC 50 for 48 h was (0.37±0.21), (0.43±0.27) and (0.49±0.24) μmol/L, respectively. Compared with imatinib alone, the different concentrations of imatinib combined with 0.2 μmol/L BEZ235 could increase the proliferation inhibition of K562 cells, KBM7R cells and CML primary cells, and could reduce the IC 50 of imatinib. After the treatment of imatinib alone and combination with BEZ235 for 48 h, the imatinib IC 50 of K562 cells was (0.14±0.05) and (0.09± 0.04) μmol/L ( t = 1.531, P = 0.249), the imatinib IC 50 of KBM7R cells was (3.93±2.29) and (0.44±0.22) μmol/L ( t = 2.837, P = 0.047), the imatinib IC 50 of the primary cells was (3.12±1.53) and (0.39±0.23) μmol/L ( t = 3.925, P = 0.042). The cell apoptotic rate of the primary cells was (4.9±1.4)%, (13.1±3.2)%, (8.8±2.0)% and (40.6±6.0)%, respectively in the control group without drug treatment, 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib and the combination of 1.0 μmol/L BEZ235 and 1.0 μmol/L imatinib after the treatment of 24 h ( F = 71.031, P < 0.01). Compared with imatinib alone, the expressions of p-AKT and Cyclin D1 proteins were decreased, and the expression of cleaved Caspase-3 protein was increased after the treatment of KBM7R cells for 12 h in the combination group of both BEZ235 and imatinib. Conclusions:BCR-ABL downstream pathway inhibitors can effectively inhibit the proliferation and promote the apoptosis of K562 cells. BEZ235 can inhibit the proliferation and promote the apoptosis of K562 cells, imatinib-resistant and T315I-mutant human KBM7R cells and imatinib-resistant CML primary cells of patients, which has a synergistic effect to imatinib.