Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective Three different doses of diethylnitrosamine(DEN)were used to establish a rat primary liver cancer(PLC)model to establish an efficient,stable,and economical animal model of PLC.Methods Forty-five male SD rats were randomly divided into four groups:normal group,DEN 50 mg/kg dose group(low dose group),70 mg/kg dose group(medium dose group),and 200 mg/kg dose group(high dose group).There were 6 animals in the normal group and 13 animals in each of the other groups.The normal control group received no treatment.The model group and low dose groups were injected intraperitoneally twice a week during weeks 1～4 and once a week during weeks 5～12;the medium dose group was injected intraperitoneally once a week for 16 consecutive weeks;and the high dose group was administered only once in the first week.The rats in each group were then followed for 16 weeks.The establishment of the model and optimal evaluation were verified by survival rate,pathological tests,biochemical tests,liver and spleen index calculation,immunohistochemistry,enzyme-linked immunosorbent assay(ELISA),and other assays.Results The survival rate was 100％in the normal group,46.15％in the low dose group,69.23％in the medium dose group,and 84.61％in the high dose group.The liver tissues of the rats in the normal group showed no abnormality to the naked eye;the liver of the rats in the low dose group became darker in color,rougher in surface,with a small number of cancerous nodules and slightly hard texture;the liver of the rats in the medium dose group was rough in surface,with several small cancerous nodules and scattered massive occupying nodules and hard texture;The liver of rats in the high dose group became lighter in color,slightly rougher in surface,with no obvious cancerous nodules;HE staining showed that the liver tissues of rats in the low and medium dose groups were structurally disorganized,with large cellular heterogeneity and tumor cells.HE staining showed that the liver tissues of rats in the low and medium dose groups were structurally disorganized,with large cellular heterogeneity and tumor cell formation,while the structure of the liver lobules of the high dose group was unclear,with different degrees of edema,degeneration and necrosis of liver cells,and no obvious tumor cell formation was seen.Compared with the normal group,serum liver function alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)were elevated in the low,medium,and high dose groups;ALT and AST were significantly elevated in the low dose group(P<0.05),the difference was statistically significant,ALT,AST and TBIL were significantly elevated in the medium dose group(P<0.05),the difference was statistically significant,and the difference was statistically significant,although liver function in the high dose group was elevated,he increase was not significant,the difference was not statistically significant(P>0.05);compared with the normal group,the international normalized ratio(INR)of coagulation function was significantly higher in the low dose group,with a statistically significant difference(P<0.05),and the activated partial thromboplastin time(APTT),prothrombin time(PT),and alpha-fetoprotein(AFP)levels were increased(P<0.05),and the difference was not statistically significant;serum APTT,PT,INR,and AFP levels were significantly increased in the medium dose group(P<0.05),and the difference was statistically significant;serum PT and AFP levels were increased in the high dose group(P<0.05),the difference was statistically significant,and plasma APTT levels were slightly increased(P>0.05),the difference was not statistically significant;liver and spleen indexes were increased in the medium dose group(P<0.05),the spleen index increased in the low dose group(P<0.05),and the liver index increased in the high dose group(P<0.05),the difference was statistically significant;the optical density value of liver tissue AFP increased significantly in the low,medium and high dose groups(P<0.05),the difference was statistically significant.Conclusions Both the low and medium dose groups could successfully induce the PLC rat model,but the pathological changes and biochemical findings of the medium dose group were more consistent with the pathogenesis of human liver tissue from liver injury to hepatic fibrosis to cirrhosis to hepatocellular carcinoma,and the number of administrations of the drug is less,and the survival rate of the rats is higher so that a more cost-effective and superior PLC model can be established.

Objective To explore the molecular mechanism of histone acetyltransferase(p300)mediated peroxisome proliferator activated receptor-γ(PPAR-γ)influencing diabetes retinopathy through lipid peroxidation.Methods Diabetes models were established in 65 SD rats by intraperitoneal injection of streptozotocin,and the remaining 10 SD rats were simultaneously intraperitoneally injected with an equal amount of sterile physiological saline and recorded as the normal group.The successfully modeled rats were randomly divided into six groups:p300 upregulated group,p300 downregulated group,PPAR-γ upregulated group,PPAR-γ downregulated group,empty control group,and model group.Except for the normal group and the model group(which were simultaneously injected with an equal amount of sterile physiological saline through vitreous injection),each group was injected with pcDNA-p300,si-p300,pcDNA PPAR-γ,si-PPAR-γ,and pcDNA adenovirus solution through vitreous injection.Five rats were selected from each group,and Evans blue method was used to detect the degree of damage to the left eye blood retinal barrier.The fully automated biochemical analyzer detects lipids in each group,including triglycer-ides(TG),cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),as well as peroxidation reaction indicators such as superoxide dismutase(SOD)activity,malondialde-hyde(MDA)content,and reactive oxygen species(ROS)levels.Five rats from each group were selected to take retinal tissue from their right eyes for hematoxylin eosin(HE)staining to observe pathological changes.After the remaining rats in each group were euthanized by decapitation,real time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expressions of p300,PPAR-γ,protein kinase C β(PKC β),and adaptor protein p66Shc(P66Shc)messenger RNA(mRNA)in the left eye retinal tissues,and Western blot was used to detect the expression of the aforementioned proteins and the phosphorylation level of P66Shc in the retinal tissues of the right eye.Results Compared with the normal group,the Evans blue concentrations,albumin penetrations,serum TG,TC,LDL-C,MDA contents,and ROS levels increased in all other groups,while HDL-C,SOD activity,p300,PPAR-γ,PKC β,P66Shc expressions,and P66Shc phosphorylation levels decreased(P<0.05).Compared with the model group,the p300 downregulated group showed a decrease in p300 expression(P<0.05),the Evans blue concentration,albumin permeability,serum TG,TC,LDL-C,MDA contents,and ROS levels were all increased in the p300 downregulated group and PPAR-γ downregulated group,while HDL-C and SOD activity,PPAR-γ,PKC β,P66Shc expression,and P66Shc phosphorylation levels were all decreased(P<0.05).The p300 upregulated group showed an increase in p300 expression(P<0.05),and the Evans blue concentration,albumin permeability,serum TG,TC,LDL-C,MDA contents,and ROS levels all decreased in the p300 upregu-lated group and PPAR-γ upregulated group,while HDL-C and SOD activity,PPAR-γ,PKC β,P66Shc expres-sions,and P66Shc phosphorylation levels all increased(P<0.05).There were no statistically significant differ-ences in blood retinal barrier damage,lipid and peroxidation indicators,PPAR-γ,PKC β,P66Shc expression,and P66Shc phosphorylation between the p300 downregulated group and PPAR-γ downregulated group,p300 upregulated group and PPAR-γ upregulated group,unloaded control group and model group(P>0.05).Normal group rats showed no pathological changes in retinal tissues,while significant pathological changes were observed in the model group and empty control group.Severe pathological changes were observed in the p300 downregulated group and PPAR-γ downregulated group,while slight pathological changes were observed in the p300 upregulated group and PPAR-γ upregulated group.Conclusion Up-regulation of p300 can positively mediate PPAR-γ to con-trol lipid peroxidation and alleviate diabetes retinopathy,while down-regulation of p300 can promote diabetes reti-nopathy by inhibiting PPAR-γ to activate lipid peroxidation.

Owing to their high genetic and physiological similarities to humans,non-human primates(NHPs)have become pivotal animal models in life sciences research and biomedical development.NHP laboratory animals are not only an ideal platform for exploring the mechanisms of neurological diseases and infectious diseases,but they are also widely used in preclinical safety evaluations of macromolecular drugs,which are considered the"gold standard".Nevertheless,this biological similarity increases the risk of zoonotic disease transmission to personnel working with NHP laboratory animals,their tissues,and body fluids.In light of recent domestic and international outbreaks of zoonotic diseases as well as the implementation of the Biosafety Law,this study examines the occupational risk factors encountered by personnel working with NHPs.This includes biological,chemical,and physical factors.This paper also covers common zoonoses,classification of the corresponding pathogens,transmission routes,risk severity levels,and protocols for post-exposure management.A multidimensional prevention and control framework is proposed,which includes the following components.(1)Risk Assessment and Emergency Response:Regularly identify hazards through an Occupational Health and Safety Committee(OHSC)and develop post-exposure emergency protocols.(2)Optimization of Management Systems:Improve facility design,optimize the allocation of personal protective equipment,and enhance health surveillance and vaccination programs.(3)Technical Training and Standardized Operations:Provide specialized training in NHP laboratory animal ethology and biosafety practices.Additionally,implement intelligent monitoring technologies to reduce the occurrence of aggressive incidents.This paper outlines measures designed to enhance health and safety awareness among personnel working with NHP laboratory animals.It emphasizes the need for strengthened guidance on the use of personal protective equipment(PPE)and the standardization of professional operational practices.The goal is to safeguard personnel health and safety,reduce occupational exposure rates,and effectively prevent occupational diseases related to laboratory animals.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Owing to their high genetic and physiological similarities to humans,non-human primates(NHPs)have become pivotal animal models in life sciences research and biomedical development.NHP laboratory animals are not only an ideal platform for exploring the mechanisms of neurological diseases and infectious diseases,but they are also widely used in preclinical safety evaluations of macromolecular drugs,which are considered the"gold standard".Nevertheless,this biological similarity increases the risk of zoonotic disease transmission to personnel working with NHP laboratory animals,their tissues,and body fluids.In light of recent domestic and international outbreaks of zoonotic diseases as well as the implementation of the Biosafety Law,this study examines the occupational risk factors encountered by personnel working with NHPs.This includes biological,chemical,and physical factors.This paper also covers common zoonoses,classification of the corresponding pathogens,transmission routes,risk severity levels,and protocols for post-exposure management.A multidimensional prevention and control framework is proposed,which includes the following components.(1)Risk Assessment and Emergency Response:Regularly identify hazards through an Occupational Health and Safety Committee(OHSC)and develop post-exposure emergency protocols.(2)Optimization of Management Systems:Improve facility design,optimize the allocation of personal protective equipment,and enhance health surveillance and vaccination programs.(3)Technical Training and Standardized Operations:Provide specialized training in NHP laboratory animal ethology and biosafety practices.Additionally,implement intelligent monitoring technologies to reduce the occurrence of aggressive incidents.This paper outlines measures designed to enhance health and safety awareness among personnel working with NHP laboratory animals.It emphasizes the need for strengthened guidance on the use of personal protective equipment(PPE)and the standardization of professional operational practices.The goal is to safeguard personnel health and safety,reduce occupational exposure rates,and effectively prevent occupational diseases related to laboratory animals.

Objective Three different doses of diethylnitrosamine(DEN)were used to establish a rat primary liver cancer(PLC)model to establish an efficient,stable,and economical animal model of PLC.Methods Forty-five male SD rats were randomly divided into four groups:normal group,DEN 50 mg/kg dose group(low dose group),70 mg/kg dose group(medium dose group),and 200 mg/kg dose group(high dose group).There were 6 animals in the normal group and 13 animals in each of the other groups.The normal control group received no treatment.The model group and low dose groups were injected intraperitoneally twice a week during weeks 1～4 and once a week during weeks 5～12;the medium dose group was injected intraperitoneally once a week for 16 consecutive weeks;and the high dose group was administered only once in the first week.The rats in each group were then followed for 16 weeks.The establishment of the model and optimal evaluation were verified by survival rate,pathological tests,biochemical tests,liver and spleen index calculation,immunohistochemistry,enzyme-linked immunosorbent assay(ELISA),and other assays.Results The survival rate was 100％in the normal group,46.15％in the low dose group,69.23％in the medium dose group,and 84.61％in the high dose group.The liver tissues of the rats in the normal group showed no abnormality to the naked eye;the liver of the rats in the low dose group became darker in color,rougher in surface,with a small number of cancerous nodules and slightly hard texture;the liver of the rats in the medium dose group was rough in surface,with several small cancerous nodules and scattered massive occupying nodules and hard texture;The liver of rats in the high dose group became lighter in color,slightly rougher in surface,with no obvious cancerous nodules;HE staining showed that the liver tissues of rats in the low and medium dose groups were structurally disorganized,with large cellular heterogeneity and tumor cells.HE staining showed that the liver tissues of rats in the low and medium dose groups were structurally disorganized,with large cellular heterogeneity and tumor cell formation,while the structure of the liver lobules of the high dose group was unclear,with different degrees of edema,degeneration and necrosis of liver cells,and no obvious tumor cell formation was seen.Compared with the normal group,serum liver function alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)were elevated in the low,medium,and high dose groups;ALT and AST were significantly elevated in the low dose group(P<0.05),the difference was statistically significant,ALT,AST and TBIL were significantly elevated in the medium dose group(P<0.05),the difference was statistically significant,and the difference was statistically significant,although liver function in the high dose group was elevated,he increase was not significant,the difference was not statistically significant(P>0.05);compared with the normal group,the international normalized ratio(INR)of coagulation function was significantly higher in the low dose group,with a statistically significant difference(P<0.05),and the activated partial thromboplastin time(APTT),prothrombin time(PT),and alpha-fetoprotein(AFP)levels were increased(P<0.05),and the difference was not statistically significant;serum APTT,PT,INR,and AFP levels were significantly increased in the medium dose group(P<0.05),and the difference was statistically significant;serum PT and AFP levels were increased in the high dose group(P<0.05),the difference was statistically significant,and plasma APTT levels were slightly increased(P>0.05),the difference was not statistically significant;liver and spleen indexes were increased in the medium dose group(P<0.05),the spleen index increased in the low dose group(P<0.05),and the liver index increased in the high dose group(P<0.05),the difference was statistically significant;the optical density value of liver tissue AFP increased significantly in the low,medium and high dose groups(P<0.05),the difference was statistically significant.Conclusions Both the low and medium dose groups could successfully induce the PLC rat model,but the pathological changes and biochemical findings of the medium dose group were more consistent with the pathogenesis of human liver tissue from liver injury to hepatic fibrosis to cirrhosis to hepatocellular carcinoma,and the number of administrations of the drug is less,and the survival rate of the rats is higher so that a more cost-effective and superior PLC model can be established.

Objective To explore the molecular mechanism of histone acetyltransferase(p300)mediated peroxisome proliferator activated receptor-γ(PPAR-γ)influencing diabetes retinopathy through lipid peroxidation.Methods Diabetes models were established in 65 SD rats by intraperitoneal injection of streptozotocin,and the remaining 10 SD rats were simultaneously intraperitoneally injected with an equal amount of sterile physiological saline and recorded as the normal group.The successfully modeled rats were randomly divided into six groups:p300 upregulated group,p300 downregulated group,PPAR-γ upregulated group,PPAR-γ downregulated group,empty control group,and model group.Except for the normal group and the model group(which were simultaneously injected with an equal amount of sterile physiological saline through vitreous injection),each group was injected with pcDNA-p300,si-p300,pcDNA PPAR-γ,si-PPAR-γ,and pcDNA adenovirus solution through vitreous injection.Five rats were selected from each group,and Evans blue method was used to detect the degree of damage to the left eye blood retinal barrier.The fully automated biochemical analyzer detects lipids in each group,including triglycer-ides(TG),cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),as well as peroxidation reaction indicators such as superoxide dismutase(SOD)activity,malondialde-hyde(MDA)content,and reactive oxygen species(ROS)levels.Five rats from each group were selected to take retinal tissue from their right eyes for hematoxylin eosin(HE)staining to observe pathological changes.After the remaining rats in each group were euthanized by decapitation,real time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expressions of p300,PPAR-γ,protein kinase C β(PKC β),and adaptor protein p66Shc(P66Shc)messenger RNA(mRNA)in the left eye retinal tissues,and Western blot was used to detect the expression of the aforementioned proteins and the phosphorylation level of P66Shc in the retinal tissues of the right eye.Results Compared with the normal group,the Evans blue concentrations,albumin penetrations,serum TG,TC,LDL-C,MDA contents,and ROS levels increased in all other groups,while HDL-C,SOD activity,p300,PPAR-γ,PKC β,P66Shc expressions,and P66Shc phosphorylation levels decreased(P<0.05).Compared with the model group,the p300 downregulated group showed a decrease in p300 expression(P<0.05),the Evans blue concentration,albumin permeability,serum TG,TC,LDL-C,MDA contents,and ROS levels were all increased in the p300 downregulated group and PPAR-γ downregulated group,while HDL-C and SOD activity,PPAR-γ,PKC β,P66Shc expression,and P66Shc phosphorylation levels were all decreased(P<0.05).The p300 upregulated group showed an increase in p300 expression(P<0.05),and the Evans blue concentration,albumin permeability,serum TG,TC,LDL-C,MDA contents,and ROS levels all decreased in the p300 upregu-lated group and PPAR-γ upregulated group,while HDL-C and SOD activity,PPAR-γ,PKC β,P66Shc expres-sions,and P66Shc phosphorylation levels all increased(P<0.05).There were no statistically significant differ-ences in blood retinal barrier damage,lipid and peroxidation indicators,PPAR-γ,PKC β,P66Shc expression,and P66Shc phosphorylation between the p300 downregulated group and PPAR-γ downregulated group,p300 upregulated group and PPAR-γ upregulated group,unloaded control group and model group(P>0.05).Normal group rats showed no pathological changes in retinal tissues,while significant pathological changes were observed in the model group and empty control group.Severe pathological changes were observed in the p300 downregulated group and PPAR-γ downregulated group,while slight pathological changes were observed in the p300 upregulated group and PPAR-γ upregulated group.Conclusion Up-regulation of p300 can positively mediate PPAR-γ to con-trol lipid peroxidation and alleviate diabetes retinopathy,while down-regulation of p300 can promote diabetes reti-nopathy by inhibiting PPAR-γ to activate lipid peroxidation.

Porcine circovirus type 2(PCV2)mainly damages the immune cells of pigs,causing lym-phocyte depletion and immune suppression.Interleukin(IL)-15 regulates immune functions wide-ly,and plays an important regulatory role in the survival,proliferation,differentiation and immune function of a variety of immune cells such as natural killer(NK),CD8+T cells and NKT cells.In this study,in order to determine the effect of PCV2 on IL-15 expression,4-week-old piglets(n=4)were infected with PCV2 and the negative control group(n=4)was set up.On day 7 post-infec-tion,the inguinal lymph nodes of the infected and control groups were collected,and porcine cyto-kine antibody microarray(QAP-CYT-1)was employed to quantify the expression of cytokines in the tissues,screen for differential cytokines,and GO and KEGG enrichment analysis for IL-15 were conducted.Real-time quantitative fluorescent PCR(qPCR)and ELISA were used to verify the level of IL-15 mRNA and protein,and those in porcine peripheral blood mononuclear cells(PBMC)and serum were simultaneously detected.Compared with the negative control group,the expression lev-el of IL-15 was significantly reduced in the infected group(P＜0.05);IL-15 was mainly involved in cytokine-cytokine receptor interactions,immune responses,cellular activation,and the regulation of JAK-STAT and TNF signaling pathways.The levels of IL-15 mRNA and protein in inguinal lymph nodes in the infected group were significantly lower than those in the control group(P＜0.05),which was consistent with the detection results of QAP-CYT-1.However,there was no significant difference in IL-15 mRNA and protein levels in PBMC and serum.These results indicate that PCV2 can inhibit IL-15 in the inguinal lymph node microenvironment of piglets.This study can provide important information for further revealing the immunosuppressive mechanism of PCV2.