Porcine parvovirus(PPV)is a causative agent of porcine parvovirus infection(PPI),which significantly impacts the pig industry due to its association with reproductive dysfunction.The condition is characterized by stillbirth,mummified fetuses,fetal weakness,and abortion in pregnant sows.The pathogenic mechanism remains incompletely understood,with no effective therapeutic drugs available currently.Despite extensive research on the host's response to PPV in-fection and identification of various signaling pathway transduction mechanisms,a comprehensive understanding is still lacking.This review aims to summarize the current knowledge regarding al-terations in related signaling pathways following PPV infection,provide novel insights into the pathogenesis of PPV and facilitate the drug development.

This study aims to investigate the effects of Japanese encephalitis virus(JEV)on TLRs signaling pathway and its regulation of the secretion of inflammatory factors during the infection of testicular interstitial cells,In this study,the mRNA levels of TLR3,TLR7,TLR8,TRIF and MyD88 genes were detected by qPCR after 1 MOI dose of JEV was inoculated into testicular stro-mal cells at different time periods.Western blot assay was used to detect the expression levels of TLR3,TLR7,TRIF and MyD88 protein at 6 h after JEV infection,and ELISA was used to detect the expression levels of IL-1β,IL-6 and TNF-α at different time periods(6,12 and 24 h).The re-sults showed as follows:After 6 h of JEV infection,the mRNA levels of TLR3,TLR7,TRIF and MyD88 genes were significantly up-regulated(P＜0.05),and the mRNA levels of TLR8 genes were down-regulated(P＜0.05).Western blot results showed that the protein expressions of TLR3,TLR7,TRIF and MyD88 were significantly up-regulated when JEV infected testicular stromal cells for 6 h(P＜0.05),which was consistent with the corresponding mRNA transcription levels.There was no significant change in TLR8 protein expression.ELISA results showed that 6 h after JEV infection of testicular stromal cells,IL-6 was significantly increased(P＜0.01),and the expressions of IL-1β and TNF-α were not changed.TLR3,TLR7,TLR8,TRIF and MyD88 were si-lenced by siRNA,and the silenced cells were inoculated with JEV for 6 h,and IL-6 expression lev-els were detected by ELISA.The results showed that silenced TLR3,TLR7,TLR8,TRIF and MyD88 could significantly reduce the increase of IL-6 secretion induced by JEV infection(P＜0.05).These results indicated that JEV could induce the expression of inflammatory factor IL-6 by activating TLR3,TLR7 and TLR8 signaling pathway after infection of testicular stromal cells.This study provides a reference for further elucidating the mechanism of reproductive disorders caused by JEV infection.

Porcine circovirus type 2(PCV2)is the main pathogen causing porcine circovirus related diseases.PCV2 infection in pigs may lead to porcine dermatitis and nephrotic syndrome(PDNS)and weaned piglets multiple system failure syndrome(PMWS),etc.At present,the pathogenic mechanism is not fully understood.PCV2 is a single strand of negative link DNA,which can cause immune suppression in the body and lead to increased secondary susceptibility,which has a syner-gistic effect with various pig diseases and brings major economic losses to the pig industry.Al-though there are commercial vaccines,the prevention of vaccines has certain limitations and there is no effective drug treatment so far,an outbreak will threaten people's life and health and public safety,resulting in significant economic losses.In order to understand the latest progress of PCV2 escape mechanism and prevention and control,this paper summarizes the inhibition of interferon production,regulation of apoptosis,regulation of autophagy,regulation of pyroptosis and inflam-matory response,evasion of adaptive immune response,and prevention and control of PCV2,in or-der to provide new theoretical ideas for the research and prevention and control of PCV2.

Objective: To evaluate the relationship between p38 mitogen-activated protein kinase (p38MAPK) and G protein-coupled receptor kinase 2 (GRK2) in the development of persistent postoperative pain in rats. Methods: Pathogen-free healthy male Sprague-Dawley rats, weighing 200-250 g, aged 2 months, were used in this study.Sixty rats in which intrathecal catheters were successfully implanted were divided into 6 groups (n=10 each) using a random number table method: sham operation group (group S), sham operation plus dimethyl sulfoxide (DMSO) group (group D), sham operation plus GRK2 degradation inhibitor MDL28170 group (group M), persistent postoperative pain group (group PPP), persistent postoperative pain plus DMSO group (group PPP+ D) and persistent postoperative pain plus MDL28170 group (group PPP+ M). Persistent postoperative pain was evoked by skin/muscle incision and retraction (SMIR). Immediately after operation and at 1, 2 and 3 days after operation, normal saline 20 μl was intrathecally injected once a day in S and PPP groups, 5% DMSO 10 μl was intrathecally injected once a day in D and PPP+ D groups, and MDL28170 10 μl (50 μg) was intrathecally injected once a day in M and PPP+ M groups.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before operation and 3, 7, 14 and 21 days after operation (T_1-4). Four rats in each group were selected after behavioral testing at T₃ and sacrificed, and the L_4-6 segments of the spinal cord were removed for determination of the expression of phosphorylated p38MAPK (p-p38MAPK) by Western blot. Results: There was no significant difference in MWT at each time point or expression of p-p38MAPK among group S, group D and group M (P>0.05). Compared with group S, the MWT was significantly decreased, and the expression of p-p38MAPK was up-regulated in PPP, PPP+ D and PPP+ M groups (P<0.05). Compared with group PPP, the MWT was significantly increased, and the expression of p-p38MAPK was down-regulated in group PPP+ M (P<0.05), and no significant change was found in the MWT or expression of p-p38MAPK in group PPP+ D (P>0.05). Conclusion Down-regulated expression of spinal GRK2 can promote the activation of p38MAPK in the spinal cord and is involved in the development of persistent postoperative pain in rats.

Objective To investigate the change of spinal G protein-coupled receptor kinase 2 (GRK2) expression in persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR) in rats.Methods 40 male Sprague Dawley (SD) rats were divided into 2 groups (n =20) using a random number table:sham operation group and skin/muscle incision and retraction group (SMIR group).A rat model of peristent postoperativepain evoked by SMIR was made according to the method described by Flatters.Pain behavior was assessed by paw mechanical withdrawal threshold (MWT) to yon Frey filament stimulationintensity at 1 d before operation (T0) and 3 d (T1),7 d (T2),14 d (T3) and 21 d (T4) after operation.4 rats in each group were sacrificed at T0-4,the L4-L6 segments of the spinal cord were obtained for determination of GRK2 expression in the spinal cord by Western blot.Results Compared with T0,the MWT was significantly decreased and the expression of spinal GRK2 was down-regulated at T1-T4 in SMIR group (P ＜ 0.05).Compared with sham operation group,the MWT and the expression of spinal GRK2 was decreased at T1-T4 in SMIR group (P ＜ 0.05).Conclusions The down-regulation of expression of spinal GRK2 may be involved in the development and maintenance of persistent postoperative pain in rats evoked by SMIR.

Objective To evaluate the role of p38 mitogen-activated protein kinase (p38MAPK) in the spinal cord in the development of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR) and the relationship with Toll-like receptor 4 (TLR4).Methods One hundred and twenty male SpragueDawley rats,weighing 200-250 g,aged 2 months,in which intrathecal catheters were successfully implanted,were randomly divided into 5 groups (n =24 each) using a random number table:sham operation group (group S),SMIR group,SMIR + dimethyl sulfoxide (DMSO) group (group DMSO),SMIR + p38MAPK inhibitor SB203580 group (group SB203580) and SMIR + TLR4 small interference RNA (siRNA) group (group TLR4siRNA).The rats were anesthetized with intraperitoneal chloral hydrate 400 mg/kg.The skin and superficial muscle of the medial thigh were incised and a small pair of retractors inserted.This tissue was retracted for 1 h causing potential stretch of the saphenous nerve.2％ DMSO 10 μl and SB203580 5 μg were injected intrathecally at 30 min before operation and 1-12 days after operation in DMSO and SB203580 groups,respectively.TLR4siRNA 2 μg was administered intrathecally at 1 day before operation and 1-12 days after operation once a day in group TLR4siRNA.Mechanical paw withdrawal threshold to von Frey filament stimulation (MWT) was measured at 1 day before operation and 1,3,7,12 and 22 days after operation.Four rats in each group were sacrificed after measurement of MWT at each time point,and the L4-6 segments of the spinal cord were obtained for detection of the expression of phosphorylated p38MAPK (p-p38MAPK) by Western blot analysis.Results Compared with group S,MWT was significantly decreased after operation,and the expression of p-p38MAPK was up-regulated after operation in SMIR and DMSO groups.Compared with group SMIR,MWT was significantly increased after operation,and the expression of p-p38MAPK was down-regulated after operation in SB203580 and TLR4siRNA groups,and no significant changes in MWT and p-p38MAPK expression were found at each time point in group DMSO.Conclusion TLR4-triggered activation of p38MAPK in spinal cord is involved in the development of SMIR-evoked persistent postoperative pain in rats.

Objective To investigate the effect of angiotensin converting enzyme (ACE) genetic polymorphism on the cardiovascular response to endotracheal intubation in patients with hypertension.Methods The patients with primary hypertension,ASA Ⅱ or Ⅲ,aged 54-64 yr,weighing 50-70 kg,scheduled for elective operation under general anesthesia,were enrolled in this study.Polymerase chain reaction-restriction fragment length polymorphism was used to detect the polymorphism of ACE gene.The patients were assigned into 3 groups according to their genotypes:homozygote DD group (group DD),heterozygote ID group (group ID),and homozygote Ⅱ group (group Ⅱ).Systolic blood pressure (SBP),diastolic blood pressure (DBP) and heart rate (HR) were recorded before and after induction of anesthesia,and at 0,1.5 and 5.0 min after intubation (T0-4).The rate-pressure product (RPP) was calculated.The cardiovascular events were recorded.Results In groups DD,ID and Ⅱ,40,39 and 40 cases were included in the analysis respectively.Compared with group ID,there was no significant difference in SBP,DBP,HR and RPP at T0-4 in group DD (P ＞ 0.05).Compared with groups DD and ID,SBP,DBP,HR and RPP were significantly deceased at T2,3,and SBP,HR and RPP were significantly deceased at T4 in group Ⅱ (P ＜ 0.05).The incidences of the myocardial ischemia during intubation and cardiovascular response to intubation were significantly lower in group C than in groups DD and ID (P ＜ 0.05).Conclusion ACE genetic polymorphism exerts an effect on the cardiovascular response to endotracheal intubation in patients with hypertension,and homozygote DD and heterozygote ID have the most influence.

Objective To investigate the role of Toll-like receptor4 (TLR4) activation in spinal cord in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction(SMIR).Methods Ninetysix male SD rats weighing 200-250 g were randomly divided into 4 groups(n =24 each):group sham operation; group SMIR; group SMIR + IT scramble siRNA and group SMIR + IT TLR4siRNA.The rat model of persistent postoperative pain evoked by SMIR was established according to the method described by Flatters.The TLR4 siRNA were administered intrathecally for 7 days starting from 1 day beforc surgcry.Pain behavior was assessed by paw mechanical withdraw threshold (MWT) to Electronic von Frey Anesthesiometer stimulation at 1 day before and 1,3,7,12,and 22 days after operation.Four animals were sacrificed at each time point in each group for detection of the expression of TLR4 protein in the spinal cord by Western blot analysis.Results Compared to group sham group,MWT was significantly descreased at 3,7,12,and 22 days after operation,while the expression of TLR4 protein in the spinal cord were significantly increased at 3,7,12 days after operation in group SMIR and group SMIR + IT scramble siRNA ; IT TLR4siRNA significantly attenuated the hyperalgesia induced by SMIR and descreased the expression of TLR4 protein at 3,7,12 days after operation in group SMIR + IT TLR4siRNA.Conclusion TLR4 activation in spinal cord plays an important role in the development of SMIR-evoked persistent postoperative pain in rats.

Objective To investigate the role of microglial activation in spinal cord in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR) .Methods Seventy-two male SD rats weighing 200-250 g in which intrathecal (IT) catheter was successfully inserted were randomly divided into 3 groups ( n = 24 each) : group sham operation; group SMIR and group SMIR + FT minocycline (a specific microglia inhibitor) . The rat model of persistent postoperative pain evoked by SMIR was established according to the method described by Flatters. Pain behavior was assessed by paw mechanical withdrawal threshold ( MWT) to von Frey filament stimulation at 1 day before (T0,baseline) and 3, 7, 12, 22 and 32 days after operation (T1-5,) . Four animals were sacrificed at each time point in each group for detection of the expression of Iba-1 (a specific marker of microglia) in the spinal dorsal horn by immunofluorescence and the microglia was counted. Results MWT was significantly decreasedat T1-4, while the expression of Iba-1 and microglia counts in the spinal dorsal horn were significantly increased at T1, 2 by SMIR in group Ⅱ. IT minocycline significantly attenuated the hyperalgesia induced by SMIR at T1-4 and decreased Iba-1 expression and microglia counts at T1,2 in group Ⅲ. Conclusion Microglial activation in the spinal cord plays an important role in the development and maintenance of SMIR-evoked persistent postoperative pain in rats.

Objective To investigate the role of gamma-aminobutyric acid transporter-1 (GAT-1) in the spinal cord in a rat model of bone cancer pain.Methods Eighty female SD rats weighing 150-180 g were randomly divided into 5 groups (n =16 each): sham operation group(group Ⅰ ),bone cancer pain group(group Ⅲ ),sham operation+ NO-711 group(group Ⅲ ),Ⅳ group BCP + NO-711 group(group Ⅳ ) and BCP + vehicle group (group Ⅴ ).Bone cancer pain was induced by inoculating Walker-256 mammary gland carcinoma cells into medullary cavity of tibia.NO-711 (20 μg,10 μl) was administered intrathecally once a day for 3 consecutive days from the 14th day after operation.Mechanical withdrawl threshold (MWT) of mechanical stimulus was determined the day before operation and at days 3,5,7,10,14 and 16 after operation.The animals were sacrificed on the 16th day after operation,and then the spinal cords were removed for determination of the expression of GAT-1 and double immunostaining of GAT-1 and glial fibrillary acidic protein (GFAP,astrocyte marker).Results MWT were significantly decreased in groups Ⅱ,Ⅳ and Ⅴ as compared with groups.Ⅰ and Ⅲ.The expression of GAT-1 significantly up-regulated in groups Ⅱ,Ⅴ as compared with groups Ⅰ and Ⅲ.NO-711 significantly increased MWT,while decreased the expression of GAT-1 in group Ⅳ compared with groups Ⅱ and Ⅴ.The expression of GAT-1 up-regulation appeared colocalizes with in astrocytes activation in spinal dorsal horn.Conclusion The up-regulation of expression of GAT-1 in spinal cord is involued in the development and maintenance of bone cancer pain,which may be related to the astrocytes activation.