Abstract: Objective To establish a cough variant asthma (CVA) guinea pig model induced by cigarette smoke exposure and OVA sensitization. Methods Twenty-four specific pathogen-free guinea pigs were randomLy assigned to three experimental groups: control (n= 8), OVA (n= 8), and CS ( cigarette smoke) +OVA ( n= 8). Guinea pigs in the OVA group were sensitized with ovalbumin (OVA)and those in the CS+OVA group were sensitized with ovalbumin and exposed to cigarette smoke. At the end of experiment, airway resistance (RI) challenged by four doses of methacholine (0. 2 mL, 0. 4 mL, 0. 6 mL, 0. 8 mg / mL) and lung compliance (Cydn) were measured to determine airway hyper-responsiveness (AHR), and cough latency and the frequency of coughing challenged by capsaicin within 10 minutes were analyzed to evaluate symptoms. Hematoxylin and eosin staining and the Ashcroft score were used to observe the state of lung injury. Results Compared with the control group, RI, Ashcroft score, and the frequency of coughing in OVA and OVA+CS groups were increased significantly, and Cydn and cough latency were decreased significantly. Compared with the OVA group, the OVA+CS group had better performance in terms of cough symptoms and RI, which was more similar to the characteristics of cough variant asthma. This may be closely related to appropriate reduction of the OVA dose. Conclusions The CS+OVA guinea pig model is more consistent with the clinical features of cough variant asthma and can be used as an animal model of cough variant asthma.

Abstract: Objective To establish a rat model of external jugular vein catheter-related thrombosis ( CRT), observe the formation of CRT in rats, detect the levels of tissue factor (TF), thrombomodulin (TM), and von Willebrand factor ( vWF) in the serum of rats, and study their relationship with CRT formation. Methods A total of 120 male Sprague-Dawley rats were randomly divided into blank control ( n= 40), sham operation ( n= 40), and model ( n= 40) groups. Eight rats were randomly selected at 1, 4, 7, 10, and 14 days and pathological sections were used to observe the thrombosis in the rats and serum TF, TM, and vWF levels were measured by enzyme linked immunosorbent assay. Results There was no thrombosis in blank control or sham operation groups. There were 34 CRTs in the model group, and the CRT incidence rate was 85%. The TM level in the model group with CRT rats was significantly higher than that without CRT rats (P<0. 01). The TM level in the model group without CRT rats was significantly higher than that in the sham operation group (P<0. 01). TM and vWF levels in rats without CRT were significantly higher than those in the blank control group (P<0. 01). At each time point after surgery, TF and TM levels of the model group were significantly higher than those of blank control and sham operation groups (P<0. 01). At 4, 7, 10, and 14 days after the operation, the vWF level of the model group was significantly higher than that in blank control and sham operation groups (P<0. 01). Over a prolonged observation time in the model group, TF, TM, and vWF levels increased gradually, and the levels of TF and vWF increased sharply from 1 to 4 days after operation, which peaked at 10 days after the operation and then decreased rapidly. TM levels increased the most at 4-7 days after the operation, which peaked at 7 days after the operation and then began to decrease. Conclusions The formation of rat CRT is closely related to abnormal levels of TF, TM, and vWF in serum.

Abstract: Objective To evaluate the advantages and disadvantages of three surgical models of extrahepatic cholestasis in rats using serological, imaging, and pathological examinations. Methods Fifteen female Sprague Dawley rats were randomly divided into traditional, modified, and electrocoagulation groups. The surgical models were bile duct ligation (n= 5) (BDL), modified hepatic duct ligation (HDL) ( n= 5), and choledochal electrocoagulation (CE) ( n= 5), respectively. Preoperative and postoperative computerized tomography (CT) scans were performed to compare changes in liver density and bile duct diameter. Blood samples were collected 7 d after surgery, and aspartate aminotransferase(AST), alanine aminotransferase ( ALT), total bilirubin ( TBIL), and direct bilirubin ( DBIL) were measured using enzyme-linked immunosorbent assay. All rats were sacrificed using excessive anesthesia after blood collection, part of the liver was collected and fixed with 4% formalin solution, and pathological changes observed using paraffin section hematoxylin and eosin staining. Results Different degrees of liver injury and cholestasis were observed 7 d after surgery in all three groups. AST, TBIL, and DBIL were higher in the BDL group than in the CE group (P<0. 05). AST, ALT, TBIL, and DBIL were higher in the BDL group than in the HDL group (P<0. 05). There was no significant difference in ALT between the BDL group and CE group (P>0. 05), and no significant difference in AST, ALT, TBIL, and DBIL between the HDL group and CE group (P>0. 05). Pathology showed that biliary hyperplasia and biliary wall thickening were most serious in the BDL group, least serious in the HDL group, and moderate in the CE group. CT showed that the extrahepatic bile duct diameter was larger in the BDL group than in the HDL and CE groups (P<0. 05), but there was no significant difference between the HDL and CE groups (P> 0. 05). Liver CT value decreased after surgery in the BDL group (P< 0. 05), and showed no significant difference after surgery between the HDL and CE groups (P>0. 05). Conclusions Both the CE and HDL models effectively prolonged the course of cholestasis in rats, and better simulated human extrahepatic cholestasis diseases, suggesting their utility for dynamic observation of the course of cholestasis.

Abstract: Objective To investigate the effect of exosomes derived from osteosarcoma stem cells (OSCs) on the proliferation and differentiation of T cells and to explore its mechanism. Methods OSCs were obtained using serum-free suspension culture and identified using stem cell marker logistics separation technology. The exosomes (OSCs-exo) secreted by OSCs were extracted using an exosome extraction kit and identified using transmission electron microscopy ( TEM), particle size analysis, and Western blot. Coculture of OSCs-exo with peripheral blood mononuclear cells, carboxyfluorescein succinimidyl ester (CFSE) staining, and flow cytometry were used to detect the effect on T-cell proliferation. Western blot was used to detect the phosphorylation of extracellular signal-regulated kinase ( ERK) protein in the ERK signaling pathway. Immunomagnetic beads were used to separate CD4⁺ T cells and coculture them with OSCs-exo in the differentiation medium induced by different CD4⁺ T cell subsets. Western blot was used to detect the expression of phosphorylated STAT1, STAT3, and STAT5 proteins in the STAT signaling pathway. Results OSCs CD133⁺MG-63 was successfully isolated. The result of TEM, particle size analysis, and Western blot showed that OSCs-exo is a round or oval vesicle with a diameter of 30-100 nm. The CFSE staining, flow cytometry, and Western blot result showed that OSCs-exo inhibits the proliferation of CD3⁺ , CD4⁺ , and CD8⁺ T cells by inhibiting the phosphorylation of ERK protein, and inhibits the differentiation of CD4⁺ T cells to Th1, Th17, TH₂, and Treg cells by inhibiting the expression of phosphorylated STAT1 and STAT3 protein. Conclusions Exosomes derived from OSCs can inhibit the proliferation of T cells by downregulating the phosphorylation of ERK protein and reducing the expression of phosphorylated STAT1 and STAT3 protein to induce CD4⁺ T cells to differentiate into TH₂ and Treg cells. They can also inhibit the differentiation of CD4⁺ T cells into Th1 and Th17 cells to downregulate cellular immune function and promote tumor progress.

Abstract: Objective To study the role of transcription factor Yin-Yang 1 (YY1) upregulating the expression of programmed death ligand 1 (PD-L1) in promoting immune escape of gallbladder cancer. Methods Immunohistochemistry was used to detect the expression level of YY1 protein in gallbladder cancer, adjacent, and normal gallbladder tissues. The levels of YY1 were measured by Real-time quantitative PCR (qRT-PCR) in normal human gallbladder epithelial cell line HGBEC and human gallbladder cancer cell lines GBC-SD, SGC-996, and IH-GB1. YY1 siRNA-1675 was transfected into GBC-SD cells. The experiment included BC, YY1 siRNA NC, and YY1 siRNA-1675 groups. The levels of PD-L1, CD69, and CD25 and the apoptosis rate of human T lymphocytes were measured by flow cytometry. The levels of interleukin (IL)- 2, IL-4, IL-10, and interferon-gamma (IFN-γ) in supernatants were determined by enzyme-linked immunosorbent assay. The PROMO website was used to predict the potential target genes of YY1, which were verified by dual luciferase reporter assays. Results Compared with normal tissues, the expression rate of YY1 in paracancerous and gallbladder cancer tissues was increased significantly (P < 0. 05). Compared with adjacent tissues, the expression rate of YY1 protein in gallbladder cancer tissues was increased significantly (P < 0. 05). Compared with HGBEC cells, YY1 levels in IH-GB1, SGC-996, and GBC-SD cells were significantly higher (P < 0. 05), and the level of YY1 in GBC-SD cells was the highest. Therefore, GBC-SD cells were used in subsequent experiments. Compared with BC and YY1 siRNA-NC groups, the levels of IL-2, IL- 4, IL-10, IFN-γ, CD69, and CD25 in the YY1 siRNA-1675 group were significantly higher (P < 0. 05), while the levels of YY1 and PD-L1 and the apoptosis rate of human T lymphocytes were decreased significantly (P < 0. 05). The PROMO website predicted that PD-L1 was a target gene of YY1, and dual luciferase reporter assays confirmed that PD-L1 was a target gene of YY1. Conclusions Downregulating the level of YY1 inhibits the expression of PD-L1, which may inhibit the immune escape of gallbladder cancer.

Abstract: Objective To explore the regulatory effect and mechanism of calycosin on oxidative stress injury of SY5Y cells induced by H₂O₂ . Methods MTT assays were used to assess the effect of calycosin on the activity of SY5Y cells to screen for the appropriate drug concentration; The experiment included a PBS control group, H₂O₂(250 μmol / L) model group, and H₂O₂(250 μmol / L) + calycosin (0. 035 μmol / mL) intervention group. Kits were used to detect MDA content and SOD activity. Immunofluorescence staining was used to detect nuclear transfer of Nrf2 and expression of HO-1. Western blotting detected the levels of total Nrf2, nuclear Nrf2, NQO1, and HO-1 proteins. Results Compared with the PBS control group, the activity of SY5Y cells in the H₂O₂ group was reduced and calycosin improved H₂O₂ -induced cell damage, reduced the level of MDA, and increased the activity of SOD. Calycosin also activated Nrf2 and promote its translocation into the nucleus, which significantly upregulated the levels of total Nrf2, nuclear Nrf2, NQO1, and HO-1 after H₂O₂ injury. Conclusions Calycosin inhibited H₂O₂ -induced oxidative stress injury in SY5Y cells by activating Nrf2 / HO-1 signaling.

Abstract: Objective To investigate the role of LncRNA HULC in hepatoma cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) via the miR-372 / CXCR4 axis. Methods The online bioinformatics TargetScan database was used to predict target genes. Cell transfection was used to establish gene overexpression and silencing cell models. qRT-PCR and Western blot were used to detect gene and protein expression, respectively. CCK-8 assays were used to assess cell viability. Cell colony formation assays were used to analyze cell proliferation. Annexin V-FITC/ PI was used to analyze apoptosis. Immunohistochemical staining was used to detect expression of proteins. Results In liver cancer tissues and cells, HULC and CXCR4 expression was upregulated, and miR-372 expression was downregulated. TargetScan database analysis and dual luciferase assays revealed a relationship between miR-372 and HULC or CXCR4. CCK-8 assays showed that HULC and CXCR4 increased cell viability, and miR-372 inhibited cell viability. Colony formation assays showed that HULC and CXCR4 promoted cell proliferation, and miR-372 inhibited cell proliferation. Flow cytometry showed that HULC and CXCR4 inhibited apoptosis, and miR-372 promoted apoptosis. Western blot analysis showed that HULC and CXCR4 inhibited the expression of E-cadherin and promoted the expression of Vimentin, while miR-372 promoted the expression of E-cadherin and inhibited the expression of Vimentin. Conclusions HULC inhibits the expression of miR- 372, thereby promoting CXCR4 expression, proliferation, and EMT progression of hepatoma cells, while inhibiting apoptosis .

Abstract: Objective To explore the application of intraluminal shunt in the establishment of heterotopic heart transplantation model in rats. Methods Forty male SD rats were divided into traditional and improved groups, each with 20 rats. Rats were anesthetized by an intraperitoneal injection of 2% pentobarbital sodium. The donor rats were intubated through their mouth and mechanical ventilation was provided after thoracotomy. A 20G needle inserted through the right common carotid artery was used to inject about 10 mL of 4℃ HTK solution to induce cardiac arrest. After obtaining the donor heart, it was placed in 4℃ HTK solution for preservation. In the traditional group, the classic abdominal heterotopic heart transplantation was still established. The following method were used in the improved group. In the improved group, the inferior vena cava and abdominal aorta were clamped. The shunt was inserted into the vessel and fixed at both ends. The donor’s main pulmonary artery and ascending aorta were anastomosed with the recipient’s inferior vena cava and abdominal aorta. The inferior vena cava and abdominal aorta were occluded again. After removing the shunt, the suture was tightened and knotted. After confirmation of no bleeding, the clamps were opened. Results In the improved group, 10 rats were operated successfully. The donor heart survived for more than 72 hours. There was no ischemia, paraplegia or anastomotic bleeding in improved group. In the traditional group, nine rats were operated successfully with one dying of anastomotic bleeding. The improved group was better than the traditional group in terms of lower lamb muscle histopathological manifestations, total ischemic time, CKM and LDH content. Conclusions In abdominal heterotopic heart transplantation of rats, the use of the intraluminal shunt shortened the time of vascular occlusion, reduce the difficulty of vascular anastomosis, and increased the success rate of the operation.

Abstract: Objective To explore the role of miR-199a in LPS-induced rat primary cardiomyocytes. Methods The primary rat cardiomyocytes were divided into control group (NC), LPS group, LPS+miR-199a mimic group and LPS+ miR-199a inhibitor group. CCK8 assays were used to explore the effect of miR-199a on cell viability of rat primary cardiomyocytes. ELISAs were used to detect the release of inflammatory factors such as TNF-α and IL-1β by HRNA-199a induced by LPS in rat primary cardiomyocytes. Expression of apoptotic proteins in rat primary cardiomyocyte induced by LPS by miR-199a was detected by flow cytometry. Western blot was used to study the expression of miR-199a mimic- or inhibitor-treated cells, and the expression of p-p65, p65, and p-iκBα, iκBα and apoptotic proteins in rat primary cardiomyocytes induced by LPS. Results Compared with the control group, LPS inhibited the viability of primary rat cardiomyocytes ( P < 0. 01 ). However, after LPS induction and simulant treatments, the viability of primary rat cardiomyocytes was more severely inhibited ( P < 0. 05). Therefore, miR-199a may aggravate cardiomyocyte damage in myocarditis. Compared with the mimics, inhibition of miR-199a reduced LPS-induced rat primary cardiomyocyte viability (P<0. 01). Compared with the NC group, LPS induced the release of TNF-α and IL-1β (P<0. 05). Compared with the LPS group, miR-199a mimic aggravated the release of TNF-α (P<0. 01) and IL-1β (P<0. 05). However, after treatment with miR-199a inhibitors, the release of TNF-α ( P< 0. 01) and IL-1β ( P< 0. 05) was decreased. Flow cytometry and Western blot showed that 50nmol / L miR-199a mimetics aggravate dapoptosis of primary rat cardiomyocytes induced by LPS (P<0. 05). This may be related to the further upregulation of caspase3 and bax expression through miR-199a mimetics and downregulation of bcl2 expression ( LPS) induced the activation of the NF-κB pathway in primary rat cardiomyocytes, which was specifically manifested by upregulation of p-iκBα and p-p65 expression. However, compared with the LPS group, p-p65 and p-iκBα were more upregulated after treatment with the mimics. After blocking miR-199a, expression of p- p65 and p-iκBα was downregulated compared with the mimic group. These findings indicate that treatment with mimics aggravate activation of the NF-κB signaling pathway in LPS-induced myocarditis in vivo. Further use of NF-κB pathway inhibitors showed that miR-199a mimics did not exacerbate the inhibitory effect of LPS on primary rat cardiomyocytes, which further suggested that miR-199a exacerbates cardiomyocyte damage through the NF-κB pathway. Conclusions miR- 199a aggravates damage of myocardial cells in myocarditis, which is mainly mediatedthrough the NF-κB signaling pathway.

Abstract: Objective We analyzed the mechanism of action of glabrous greenbrier rhizome in the treatment of fever based on network pharmacology. Methods We screened for the active components and targets of Poria cocos using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform( TCMSP, https: / / tcmspw. com/ tcmsp.php), with Oral bioavailability(OB) and Drug-likeness(DL) as indicators. We used the UniProt database to convert discovered entries to respective gene symbols, and then GeneCards to obtain disease-related information that intersects with glabrous greenbrier rhizome target genes. We then constructed a protein interaction network using the STRING (Search Tool for the Retrieval of Interacting Genes/ Proteins) Web resource and R software for Gene Ontology ( GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis. AutoDock Vina software was used for molecular docking modeling simulations. Results Twelve active ingredients of Poria cocos, corresponding to 145 gene symbols were discovered in our analyses. Of these, five are core components of glabrous greenbrier rhizome and another five are fever core targets. glabrous greenbrier rhizome may affect regulation of the body’ s response to external stimuli and resistance to EGFR inhibitors.Molecular docking simulations show a strong affinity for the core components and core targets. Conclusions Naringenin, β-sitosterol, quercetin, diosgenin, and stigmasterol are the primary core components of glabrous greenbrier rhizome treatment, and the main targets are IL-6, EGFR, CASP3, MYC, and VEGFA.

Abstract: Objective To explore the inhibitory effect of various concentrations of low molecular weight heparin on the formation of catheter-related thrombosis ( CRT). Methods Forty rabbits were divided into group A ( control group), group B (low concentration low molecular weight heparin group), group C (medium concentration low molecular weight heparin group), and group D (high concentration low molecular weight heparin group) in accordance with a random number table. After successfully establishing the PICC catheterized rabbit model, a 0. 9% sodium chloride solution, or 50 μ/ (mL·d), 100 μ/ (mL·d), or 200 μ/ (mL·d) low molecular weight heparin sodium solutions were applied. The solution was injected subcutaneously into the abdomen of the rabbits once a day for 7 consecutive days. The auricular vein,anterior vena cava, and PICC catheters of the rabbits were removed for HE staining, and the incidence of CRT and coagulation functions in different parts were observed and compared under a light microscope. Results The incidence of CRT in group A was 100% and there was no thrombosis in group D. The difference in the incidence of thrombus between group A and the other three groups was statistically significant ( P < 0. 01). The incidences of rabbit auricular vein thrombosis in groups A-C were significantly different from that of group D (P<0. 01). The incidences of PICC catheter thrombosis in groups A and B were significantly different from that in groups C and D (P<0. 01). One week after PICC insertion, blood PT, APTT, TT, FIB, and D-D dimer levels were significantly different among the groups (P< 0. 01). Conclusions Different concentrations of low molecular weight heparin have a preventive effect on the formation of CRT. A high concentration low molecular weight heparin 200 μ/ (mL·d) effectively prevents the formation of CRT and reduces its incidence, which has important clinical significance.

Abstract: Objective To investigate the effect of scalp acupuncture combined with repeated transcranial magnetic stimulation (rTMS) on neurological function in stroke rats and its effect on the protein kinase A (PKA) / cyclophosphine response element binding ( CREB) protein signaling pathway. Methods Fifty rats were randomly divided into a sham operation group, model group, scalp group, rTMS group, and combined group (10 rats per group). Nylon thread was not inserted in the sham operation group. The other groups were used to prepare a model of focal stroke rats using sutures. Nine rats in the model group, eight in the scalp group, eight in the rTMS group, and nine in the combined group were successfully modeled. Rats in the model group and sham operation group did not receive the intervention. The scalp group received scalp acupuncture, the rTMS group received rTMS, and the combined group received scalp acupuncture + rTMS. After the last intervention, neurological deficit score and Morris water maze test performance were assessed. After triphenyl tetrazolium chloride (TTC) and hematoxylin and eosin (HE) staining, the pathological cortical changes in and around the infarct of brain tissues were observed. The expressions of PKA, CREB protein, and phosphorylated CREB ( p-CREB) protein were measured. Results Compared with the sham operation group, the model group, scalp group, rTMS group, and combined group had higher neurological injury scores, longer escape latency, and shorter target quadrant stay duration (P< 0. 05). Compared with the model group, the scalp group, rTMS group, and combination group showed lower neurological injury scores, shorter escape latency, and longer target quadrant stay duration (P<0. 05). Compared with the scalp group and the rTMS group, the combined group showed decreased neurological injury score, shortened escape latency, and prolonged target quadrant stay duration (P<0. 05). TTC staining identified white infarcts in the cerebral cortex of the ischemic side of the model group and mild erosion. The infarct area of the cerebral cortex of the ischemic side of the scalp acupuncture group, rTMS group, and combination group reduced and the appearance of the brain tissue improved; the improvement effect was most obvious in the combination group. The brain tissue structure of the model group was loose and showed liquefying necrosis in the cribriform network, with a large number of neurons disappearing and a large number of microglia infiltrating. The brain tissue structure of the scalp acupuncture group and rTMS group showed less damage than that of the model group, with some remaining normal neurons. However, some cytoplasm showed vacuolation and edema. The brain tissue structure and neuron morphology of the combined group tended to be positive. Compared with the sham operation group, the model group, scalp acupuncture group, rTMS group, and combination group showed decreased relative expressions of PKA and p-CREB protein (P<0. 05). Compared with the model group, the scalp acupuncture group, rTMS group, and combination group showed increased relative expressions of PKA and p-CREB protein ( P < 0. 05 ); the expression was higher in the combined group than in the scalp acupuncture group and rTMS group (P<0. 05). Conclusions Scalp acupuncture combined with rTMS can effectively improve neurological function in stroke rats. Its mechanism may play a regulatory role by activating the PKA/ CREB signaling pathway.

Abstract: Objective To observe the protective effect of Kangxianzengzhi granules on hippocampal neurons of juvenile epileptic rats and explore its regulating effect on Toll-like receptor 4 (TLR4) / high mobility positive group box 1 (HMGB1) / phosphorylated nuclear factor inhibitory protein α (p-IκB-α) signaling pathways. Methods Epilepsy models were established. In the positive group, 5. 9 mg / kg topiramate was dissolved in 2 mL/ 100 g normal saline, and in the low-, medium-, and high-concentration groups, 1. 28, 2. 56, and 5. 12 g / kg Kangxianzengzhi granules were infused into the stomach, respectively. Model and normal groups had normal saline infused into the stomach once a day for 4 weeks. The changes in behavior and learning / memory abilities before and after the interventions were evaluated by the Racine grading standard and Morris water maze. Hematoxylin-eosin staining was used to observe pathological changes of the hippocampus. Expression of TLR4 and HMGB1 mRNAs in the hippocampus as detected by Real-time quantitative reverse transcription polymerase chain reaction, and relative expression of TLR4, HMGB1, IκB-α, and P-IκB-α was detected by Western blot. Results After the interventions, the behavioral Racine grade and learning / memory ability indexes of the positive group and three concentration groups were improved significantly compared with those before treatments. After interventions, pathological changes of hippocampal neurons in the model group were serious, which were improved in the positive group and three concentration groups. Damage of hippocampal neurons in the positive group and three concentration groups was alleviated. The relative expression of TLR4 and HMGB1 mRNAs and proteins and the level of P-IκB-α in the model group were significantly higher than those in the normal group ( P < 0. 01 ), and those in the positive group and three concentration groups were significantly lower than those in the model group (P < 0. 01). There was no significant difference between the two groups ( P > 0. 05), and the effect of Kangxianzengzhi granules was dependent on concentration. Conclusions Kangxianzengzhi granules improve the behavioral and learning / memory abilities of young epileptic rats and the degeneration and necrosis of hippocampal neurons. The effects of high concentration drugs is better than those of topiramate. These effects are presumed to be achieved by regulating TLR4 / HMGB1 / p-IκB-α.

Abstract: Objective The study aim was to explore the effect of feeding microenvironment on laboratory animals. Macroenvironment and microenvironment parameters were compared under the dynamic operation of a specific pathogen free laboratory animal room. Methods An isothermal body surface heat transfer model and a tray moisture and ammonia model were established in rabbits, and the laboratory animal room environment under static and dynamic operation were compared and analyzed using computational fluid dynamic simulation. Results The dynamic environment of the laboratory animal room under dynamic operation was not obvious, but the air flow of the microenvironment changed, resulting in heat dissipation, moisture dissipation, and exclusion of pollutants. Some microenvironment parameters may exceed the standard. Conclusions Changes in environmental factors under static and dynamic operation were observed. Enhanced control of the breeding microenvironment status could ensure the welfare and quality of laboratory animals.

Abstract: Objective To evaluate the effect of the individual ventilated cage (IVC) changing standard operating procedure ( SOP) for viral pathogen transmission in laboratory mice. Methods Six-week-old male BALB/ c mice were infected with mouse hepatitis virus (MHV, A59 strain). The infection status of these infected mice and sentinel mice in close cages on the same shelf, in cages on a different shelf but in the same IVC system, and outside the IVC system but in the same facility were monitored. Serological conversion of MHV antibodies was detected using immunofluorescent antibody reaction and enzyme-linked immunosorbent assay. MHV in mouse feces was detected using reverse transcription polymerase chain reaction. Results MHV nuclear acid was detected 6 d after infection in the artificial infected mice, and serological conversion was detected 3 weeks postinfection. At 5 weeks postinfection, there was no positive detection in sentinel mice. Conclusions The IVC-changing SOP is useful for pathogen transmission management in laboratory mice.

Abstract:Preeclampsia (PE) is a disease of pregnancy and one of the leading causes of maternal and perinatal morbidity and mortality. Its etiology is unclear, and termination of pregnancy is known to be an effective treatment. However, there is an increasing focus on pregnancy safety. The establishment of an optimal PE animal model would provide a good foundation for the study of PE etiology and pathogenesis. This would help to prevent or delay disease progression, reduce maternal and fetal mortality, and improve pregnancy safety. Because of economy of use, easy access, strong survival ability, and short gestation period, rats and mice are widely used in animal experiments on clinical diseases. Referring to domestic and foreign literature, rat and mouse models of PE are summarized according to pathogenesis or generating method , including decreased uterine blood flow, overactivation of inflammatory immunity, vascular endothelial cell injury, blood hypercoagulability, and genetic modification. The construction method and phenotypes of rat and mouse models of PE are briefly reviewed.

Abstract:Long non-coding RNAs (lncRNA) are a novel class of RNA molecules that are extensively involved in tumor development and progression. The testis developmental related gene 1 (TDRG1) lncRNA is aberrantly expressed in a variety of cancers, influences tumor proliferation, invasion, and metastasis by different mechanisms, and is closely correlated with patient prognosis. In this paper, we will review the biological effects of TDRG1 on tumors and the underlying molecular mechanisms.

Abstract:Parkinson’ s disease ( PD) is the second most common central nervous system degenerative disease worldwide. One pathological feature is a-synuclein accumulation in the substantia nigra, and an early sign is mitochondrial dysfunction. The PD-related proteins PINK1, Parkin, DJ-1, and a-synuclein are involved in the process of mitochondrial autophagy and quality control. The mutation of PD-related proteins leads to abnormal autophagy and mitochondrial function. A failure of selective clearance of damaged mitochondria and mitochondrial dysfunction may eventually lead to dopaminergic neuron death. Therefore, the loss of control of PD-related proteins is closely related to PD occurrence. This article reviews the associations between mitochondrial autophagy, dysfunction, and Parkinson’s disease.

Abstract:Bone metastasis is a common complication of lung cancer, and patient survival rate increases its risk. Animal models of bone metastasis are useful to investigate lung cancer bone metastasis. An explanation of the pathophysiology of lung cancer bone metastasis is important for medical research in lung cancer. In this paper we review domestic and foreign reports on the research status of animal models of lung cancer bone metastasis and discuss lung cancer cell lines, experimental animal strains, model building method , and evaluation method in detail. It is hoped that this paper will be an important reference for the study of lung cancer.

Abstract:Stem cells self-renew, undergo multidirectional differentiation, and have great therapeutic potential for diabetes, brain injury, and acute myocardial infarction as examples. There are many types of stem cell products and many variations among batches. Therefore, quality control is particularly important for stem cell products before clinical use. Stem cells are immunogenic as living exogenous cells, and immunodeficient and humanized mice play an important role in stem cell quality control. Here, we review stem cell immunogenicities, summarize the commonly used immunodeficient and humanized mice, and outline the model applications of stem cell quality control to provide for a reference for stem cell quality control.

Abstract:Achalasia of the cardia is a movement disorder characterized by the absence of normal peristalsis of the esophagus and abnormal relaxation of the lower esophageal sphincter. In recent years, the incidence of this disease has increased yearly, and its pathogenesis and treatment have become a research focus. Studying the pathogenesis of AC is beneficial for the treatment and prognosis of this disease. Its main pathogeneses include inheritance, nerves, immunity, viral infection, and psychology or multifactorial interactions. This article discusses the pathogenesis of achalasia cardia.