Association between speckle tracking echocardiography and pressure-volume loops during cardiogenic shock development.

BACKGROUND: The relationship between speckle tracking assessed global longitudinal strain (GLS) and Doppler-based echocardiography with basic physiological markers of cardiac function derived from pressure-volume loops is poorly elucidated. OBJECTIVE: We aimed to describe the association between LS and Doppler-based echocardiography and direct measurements of central haemodynamic parameters from conductance catheter-based pressure-volume loops in an animal model with increasing left ventricular (LV) dysfunction. METHODS: 12 Danish landrace female pigs (75-80 kg) were used. All instrumentations were performed percutaneously, including the conductance catheter in the LV. Progressive LV dysfunction was induced by embolisation through the left main coronary artery with microspheres every 3 min until a >50% reduction in cardiac output (CO) or mixed venous saturation (SvO2), compared with baseline, or SvO2 <30%. Echocardiography was performed at baseline and 90 s after each injection. RESULTS: With progressive LV dysfunction, mean CO decreased from 5.6±0.9 L/min to 2.1±0.9 L/min, and mean SvO2 deteriorated from 61.1±7.9% to 35.3±6.1%. Mean LS and LV outflow tract velocity time integral (LVOT VTI) declined from -13.8±3.0% to -6.1±2.0% and 16.9±2.6 cm to 7.8±1.8 cm, respectively. LS and LVOT VTI showed the strongest correlation to stroke work in unadjusted linear regression (r2=0.53 and r2=0.49, respectively). LS correlated significantly with stroke volume, end-systolic elastance, systolic blood pressure, ventriculo-arterial coupling and arterial elastance. CONCLUSION: In an animal model of acute progressive LV dysfunction, echocardiographic and conductance catheter-based measurements changed significantly. LS and LVOT VTI displayed the earliest and the largest alterations with increased myocardial damage and both correlated strongest with stroke work.

Animal models of eosinophilic esophagitis, review and perspectives.

Eosinophilic oesophagitis (EoE) is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction. Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response, the exact pathogenesis is complex, and the efficacy of existing treatments is unsatisfactory. Therefore, the study of the pathophysiological process of EOE has received increasing attention. Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents. To maximize the use of existing animal models of EOE, it is important to understand the advantages or limitations of each modeling approach. This paper systematically describes the selection of experimental animals, types of allergens, and methods of sensitization and excitation during the preparation of animal models of EoE. It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

Potential Perturbations of Critical Cancer-regulatory Genes in Triple-Negative Breast Cancer Cells Within the Humanized Microenvironment of Patient-derived Xenograft Models.

PURPOSE: In this study, we aimed to establish humanized patient-derived xenograft (PDX) models for triple-negative breast cancer (TNBC) using cord blood (CB) hematopoietic stem cells (HSCs). Additionally, we attempted to characterize the immune microenvironment of the humanized PDX model to understand the potential implications of altered tumor-immune interactions in the humanized PDX model on the behavior of TNBC cells. METHODS: To establish a humanized mouse model, high-purity CD34+ HSCs from CB were transplanted into immunodeficient NOD scid γ mice. Peripheral and intratumoral immune cell compositions of humanized and non-humanized mice were compared. Additionally, RNA sequencing of the tumor tissues was performed to characterize the gene expression features associated with humanization. RESULTS: After transplanting the CD34+ HSCs, CD45+ human immune cells appeared within five weeks. A humanized mouse model showed viable human immune cells in the peripheral blood, lymphoid organs, and in the tumor microenvironment. Humanized TNBC PDX models showed varying rates of tumor growth compared to that of non-humanized mice. RNA sequencing of the tumor tissue showed significant alterations in tumor tissues from the humanized models. tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) is a shared downregulated gene in tumor tissues from humanized models. Silencing of TNFRSF11B in TNBC cell lines significantly reduced cell proliferation, migration, and invasion in vitro. Additionally, TNFRSF11B silenced cells showed decreased tumorigenicity and metastatic capacity in vivo. CONCLUSION: Humanized PDX models successfully recreated tumor-immune interactions in TNBC. TNFRSF11B, a commonly downregulated gene in humanized PDX models, may play a key role in tumor growth and metastasis. Differential tumor growth rates and gene expression patterns highlighted the complexities of the immune response in the tumor microenvironment of humanized PDX models.

Preclinical study of a novel ingestible bleeding sensor for upper gastrointestinal bleeding.

BACKGROUND/AIMS: Upper gastrointestinal bleeding (UGIB) is a life-threatening condition that necessitates early identification and intervention and is associated with substantial morbidity, mortality, and socioeconomic burden. However, several diagnostic challenges remain regarding risk stratification and the optimal timing of endoscopy. The PillSense System is a noninvasive device developed to detect blood in patients with UGIB in real time. This study aimed to assess the safety and performance characteristics of PillSense using a simulated bleeding model. METHODS: A preclinical study was performed using an in vivo porcine model (14 animals). Fourteen PillSense capsules were endoscopically placed in the stomach and blood was injected into the stomach to simulate bleeding. The safety and sensitivity of blood detection and pill excretion were also investigated. RESULTS: All the sensors successfully detected the presence or absence of blood. The minimum threshold was 9% blood concentration, with additional detection of increasing concentrations of up to 22.5% blood. All the sensors passed naturally through the gastrointestinal tract. CONCLUSION: This study demonstrated the ability of the PillSense System sensor to detect UGIB across a wide range of blood concentrations. This ingestible device detects UGIB in real time and has the potential to be an effective tool to supplement the current standard of care. These favorable results will be further investigated in future clinical studies.

Establishment and application of animal models for portal vein thrombosis / 临床肝胆病杂志

Portal vein thrombosis （PVT） refers to thromboembolism that occurs in the extrahepatic main portal vein and/or intrahepatic portal vein branches. PVT is the result of the combined effect of multiple factors， but its pathogenesis remains unclear. Animal models are an important method for exploring the pathophysiological mechanism of PVT. Based on the different species of animals， this article reviews the existing animal models of PVT in terms of modeling methods， principles， advantages and disadvantages， and application.

Effects of antenatal dexamethasone and postnatal pulmonary surfactant combined with respiratory support on lung fluid clearance in preterm rabbits / 中华围产医学杂志

Objective:To explore the effects of prenatal dexamethasone (DEX), postnatal pulmonary surfactant (PS) and respiratory support on the lung fluid clearance in premature rabbits at gestational age (GA) of 25-28 d (full term: 31 d) and their relationship with dynamic compliance of respiratory system (Cdyn), pulmonary morphology and other parameters.Methods:In our previous publications, premature rabbits were divided into four groups according to the intervention strategy: control group, PS-only group, DEX-only group and DEX+PS group in which data of several parameters including wet-to-dry lung weight ratio (W/D), Cdyn and volume density of alveoli (Vv) were retrieved and the lung tissue sections were scanned to recalculate the ratio of perivascular sheath to vascular sectional area (S/V) and lung injury scores-edema (LIS-E). W/D, LIS-E, S/V and Vv were adjusted for birth weight (BW) (divided by BW, represented as W/D/BW, LIS-E/BW, S/V/BW and Vv/BW) and mean Cdyn (Cdyn-m) was adopted. Based on the grouping of previous studies, the intervention groups in this study were divided as DEX group and non-DEX group, and PS group and non-PS group to analyze the influence of DEX and PS on the above parameters. Two independent samples t-test, one-way analysis of variance, LSD test, Kruskal-Wallis H test, Mann-Whitney U test and Pearson correlation analysis were used for statistical analysis. Results:A total of 196 newborn rabbits receiving mechanical ventilation after birth were included in this study. (1) Effects of DEX: compared with the non-DEX group, the DEX group showed increased W/D/BW (489±69 vs 421±113, t=－2.09), LIS-E/BW (188±57 vs 138±55, t=－2.61) and Vv/BW (20.1±4.9 vs 14.2±4.7, t=－3.60), but decreased S/V (0.33±0.23 vs 0.51±0.25, t=2.23) and S/V/W/D (0.05±0.03 vs 0.07±0.04, t=2.22) at 25 d of gestation; at 26 d of gestation, W/D/BW (472±76 vs 303±44, t=－8.75), LIS-E/BW (189±63 vs 106±36, t=－5.23), Cdyn-m [(0.16±0.07) vs (0.05±0.03) ml/(kg?cmH 2O), 1 cmH 2O=0.098 kPa; t=－7.29] and Vv/BW increased (22.4±5.0 vs 12.2±3.8, t=－7.46), while S/V (0.23±0.19 vs 0.62±0.38, t=4.10), S/V/BW (15.7±12.4 vs 25.7±17.3, t=2.20), S/V/W/D (0.03±0.03 vs 0.08±0.05, t=3.92) and propensity scores decreased [(12.5±1.2) vs (15.1±1.2) scores, t=7.00]; at 27 d of gestation, Cdyn-m increased [(0.23±0.12) vs (0.16±0.07) ml/(kg?cmH 2O), t=－2.43], but S/V (0.32±0.23 vs 0.57±0.39, t=2.57) and S/V/W/D decreased (0.05±0.04 vs 0.09±0.06, t=2.55); at 28 d of gestation, W/D/BW (270±64 vs 162±33, t=－8.09), LIS-E/BW (72±32 vs 35±20, t=－5.17), S/V (0.90±0.60 vs 0.59±0.48, t=－2.81), S/V/BW (34.0±23.6 vs 15.2±12.7, t=－3.77) and Vv/BW increased (16.9±4.3 vs 9.2±2.9, t=－8.04); the differences were all statistically significant (all P<0.05). (2) Effects of PS: compared with the non-PS group, the PS group had decreased LIS-E/BW at 25, 26 and 27 d of gestation, increased Cdyn-m and Vv/BW at 25 and 27 d of gestation and higher propensity scores at 25 d of gestation (all P<0.05). (3) The correlation between gestational age and each index: gestational age was positively correlated with S/V ( r=0.31, P<0.05), but negatively correlated with W/D/BW and LIS-E/BW ( r=－0.73 and－0.63, both P<0.05). Conclusions:The pharmacological action of prenatal DEX on lung fluid clearance is mainly confined to preterm rabbits at the GA of 28 d which is supported by mechanical ventilation. Prenatal treatment with DEX and/or postnatal PS can improve the early respiratory function in preterm rabbits between GA of 25-27 d, but had no substantial impact on lung fluid clearance. The GA-related lung maturation appears to play a crucial role, in comparison with medications, in lung fluid clearance.

Research progress in animal models of oral squamous cell carcinoma and common oral mucosal diseases / 中国基层医药

The pathogeneses of oral squamous cell carcinoma and most oral mucosal diseases are unclear. Therefore, establishing animal models with similar pathogeneses is significant for clinical prevention, diagnosis, and treatment of related diseases. At present, scholars have established animal models for different focuses. This paper aims to introduce the methods for establishing animal models of oral squamous cell carcinoma and common oral mucosal diseases, compare their advantages and disadvantages, and provide evidence for related basic research.

Effects of modified Buzhong Yiqi Decoction on intestinal microflora in a rat model of chronic obstructive pulmonary disease / 中国基层医药

Objective:To investigate the effects of modified Buzhong Yiqi Decoction on intestinal microflora in a rat model of chronic obstructive pulmonary disease. Methods:From April to June 2021, 60 specific pathogen-free Wistar rats were selected for this study. They were randomly divided into blank control, model, traditional Chinese medicine, and western medicine groups with 15 rats per group. Rat models of chronic obstructive pulmonary disease with lung and spleen deficiency were established in all groups except the blank control group. Rat models in the traditional Chinese medicine and western medicine groups were administered modified Buzhong Yiqi Decoction and synbiotics. Rat models in the model and blank control groups were identically administered 0.9% sodium chloride injection. After 7 days, the feces of rats in each group were collected for 16S rRNA sequencing of intestinal flora. Effective sequences were clustered to obtain operational taxonomic units for principal coordinate analysis, species composition analysis, and alpha diversity analysis. The effects of modified Buzhong Yiqi Decoction on the structure, diversity, and abundance changes of intestinal flora were analyzed. Results:The dominant bacteria in the traditional Chinese medicine and western medicine groups were Firmicutes, while the dominant bacteria in the blank control and model groups were Bacteroides. The dominant bacterial groups in each group were mainly Lactobacillus and Bacteroides. Alpha diversity analysis showed that the Shannon index in the community diversity indices of traditional Chinese medicine, western medicine, and blank control groups was (3.65 ± 0.35), (3.65 ± 0.36), and (3.59 ± 0.20), respectively, which were significantly higher than (3.37 ± 0.26) in the model group ( t = 2.49, 2.44, 2.60, all P < 0.05). There was no significant difference in the Shannon index among traditional Chinese medicine, western medicine, and blank control groups (all P > 0.05). The Sobs index of the traditional Chinese medicine, western medicine, and blank control group was (458.67 ± 73.11), (454.80 ± 95.13), and (525.93 ± 101.88), respectively, which were significantly higher than (337.40 ± 37.49) in the model group ( t = 5.72, 4.45, 6.73, all P < 0.05). The Sobs index in the blank control group was higher than that in the western medicine group. There was no significant difference in the Sobs index between blank control and traditional Chinese medicine groups and between western medicine and traditional Chinese medicine groups (both P > 0.05). Principal coordinate analysis revealed that compared with the blank control group, Actinomycetes decreased and Proteobacteria and Desulfurization bacteria increased at the phylum level in the model group, while compared with the blank control group, Bacteroides, Rombutzia,Trichospirillus, and Parabacteroides increased, and Prevotella, Clostridium, Brucella, and Ruminococcus decreased at the genus level. Compared with the western medicine group, Bacillus, Prevotella, Brucella, and Prevotellidae in the traditional Chinese medicine group increased, while Clostridium, Pectinobacter, Christensen, and Trichospirillus decreased in the traditional Chinese medicine group. There was a statistically significant difference in the composition of the bacterial population between groups (all P < 0.05). Conclusion:There is an imbalance in intestinal microecology in a rat model of chronic obstructive pulmonary disease. Modified Buzhong Yiqi Decoction can regulate the intestinal microecology environment, improve the structure of intestinal flora, and increase the diversity and abundance of intestinal flora.

Role of galectin-3 in the early brain injury of mice with subarachnoid hemorrhage is associated with the regulation of microglia polarization / 国际脑血管病杂志

Objective:To investigate the effect of galectin-3 (gal-3) on microglia polarization after subarachnoid hemorrhage (SAH).Methods:C57BL/6 male adult mice were used to induce SAH or sham operation models. Gal-3 siRNA or negative control siRNA was injected into the lateral ventricle 48 h before the model was induced. After 24 h of model preparation, the SAH score, neurological function score, brain water content, and Evans blue exudate were measured. Western blot analysis was used to detect the expressions of M1 phenotypic markers (inducible nitric oxide synthase [iNOS], CD11b, tumor necrosis factor [TNF]-α) and M2 phenotype markers (CD206, YM1/2, arginase-1 [Arg1]).Results:After using Gal-3 siRNA to inhibit Gal-3, the neurological function score significantly increased, while the SAH score, brain water content, and Evans blue exudate significantly decreased ( P<0.001). Western blot analysis showed that the expressions of M1 phenotypic markers (iNOS, CD11b and TNF-α) in microglia were significantly decreased after Gal-3 inhibition, while the expressions of M2 phenotypic markers (CD206, YM1/2 and Arg1) were significantly increased ( P<0.001). Conclusion:Inhibition of Gal-3 expression can alleviate the early brain injury after SAH, and its mechanism may be associated with regulating the polarization of microglia from M1 to M2 phenotype.

Research advances in animal models of cholestatic liver disease / 临床肝胆病杂志

Cholestatic liver diseases (CLD) are a series of diseases due to impaired bile flow and accumulation of bile acid in the liver and/or systemic circulation caused by immune, genetic, and environmental factors. The pathogenesis of CLD remains unclear and CLD is difficult to treat. As a substitute for human diseases, animal models can provide a platform for exploring the etiology and pathogenesis of the disease and finding appropriate therapeutic targets. This article reviews the current research advances in the animal models of CLD.

Replication of Rocio virus in primary cultures of mouse neural cells

ABSTRACT Objective This study verified the replication efficiency of the Rocio virus in a primary culture of mouse neural cells. Methods Mixed primary cultures (neurons/glia) obtained from the brains of newborn isogenic BALB/c mice were inoculated with Rocio virus on the 7 th day of culture, and the development of cytopathogenic effects was monitored. The infection was confirmed via immunocytochemistry (anti-ROCV), while viral replication was quantified in infected primary cultures. The titration method used depended on the infection period. Results Rocio virus efficiently infected primary cultured neural cells, with the highest viral titer causing cytopathic changes was observed at 2 days post infection. The virus-infected primary culture survived for up to 7 days post infection, and viral load quantitation showed viral replication kinetics compatible with the cell death kinetics of cultures. Conclusion The findings of this study suggest that mouse neural cell primary cultures support Rocio virus replication and could be used as an alternative system for studying Flavivirus infection in the central nervous system.

Protocol for a systematic review of the validity of animal models of polydipsia with a basis in schizophrenia aetiology.

Objective: Primary polydipsia most commonly affects those with schizophrenia. The pathophysiology of this occurrence is not established. The aim of this systematic review is to critically assess the internal and external validity of the preclinical animal models available. Search strategy: PubMed and Embase will be searched systematically to identify all relevant animal studies that describe polydipsia induction with a basis in schizophrenia aetiology. The SYRCLE (SYstematic Review Center for Laboratory animal Experimentation) search filters to identify all animal studies in both databases will be used. All studies published up to the date of the search will be considered. Screening and annotation: Two independent reviewers will screen the retrieved studies for eligibility based on (1) title and abstract and (2) full text. Disagreements between researchers will be resolved by discussion and referral back to the predefined eligibility criteria with involvement of a third researcher if required.

Excessive proliferation and apoptosis of parathyroid cells contribute to primary hyperparathyroidism in rabbit model.

To explore the molecular pathogenesis of primary hyperparathyroidism (PHPT), we investigated the proliferation and apoptosis of parathyroid cells in a rabbit model of diet-induced PHPT. A total of 120 adult Chinese rabbits were randomly divided into normal diet (Ca:P, 1:0.7) group (control group) or a high-phosphate diet (Ca:P, 1:7) group (experimental group). The thyroid and parathyroid complexes were harvested for 1-month interval from month 1 to month 6. The expression of proliferation markers, including proliferating cell nuclear antigen (PCNA) and cyclin-D1, and B cell lymphoma-2 (Bcl-2), were evaluated by immunohistochemistry in thyroid and parathyroid tissues. Apoptosis was quantified by DNA-fragment terminal labeling. Our results demonstrated that parathyroid cells in the experimental group started proliferating from the end of the 2nd month, the expression of PCNA, Bcl-2, and cyclin-D1 were significantly higher in the PHPT group than those of the control group (p<0.05). Furthermore, the apoptosis index (AI) was positively correlated with the glandular cell count and expression of PCNA in the 6th month in the PHPT group. Overall, our results suggested that excessive proliferation and apoptosis of parathyroid cells may contribute to the pathogenesis of PHPT through PCNA-related, Bcl-2-related, and cyclin-D1-related pathways.

In pursuit of biomarkers for predicting susceptibility to activity-based anorexia in adolescent female rats.

OBJECTIVE: Identifying risk factors that contribute to the development of anorexia nervosa (AN) is critical for the implementation of early intervention strategies. Anxiety, obsessive-compulsive behavior, and immune dysfunction may be involved in the development of AN; however, their direct influence on susceptibility to the condition remains unclear. Here, we used the activity-based anorexia (ABA) model to examine whether activity, anxiety-like behavior, compulsive behavior, and circulating immune markers predict the subsequent development of pathological weight loss. METHOD: Female Sprague-Dawley rats (n = 44) underwent behavioral testing before exposure to ABA conditions after which they were separated into susceptible and resistant subpopulations. Blood was sampled before behavioral testing and after recovery from ABA to screen for proinflammatory cytokines. RESULTS: Rats that were vulnerable to pathological weight loss differed significantly from resistant rats on all key ABA parameters. While the primary measures of anxiety-like or compulsive behavior were not shown to predict vulnerability to ABA, increased locomotion and anxiety-like behavior were both associated with the extent of weight loss in susceptible but not resistant animals. Moreover, the change in expression of proinflammatory markers IL-4 and IL-6 evoked by ABA was associated with discrete vulnerability factors. Intriguingly, behavior related to risk assessment was shown to predict vulnerability to ABA. DISCUSSION: We did not find undisputable behavioral or immune predictors of susceptibility to pathological weight loss in the ABA rat model. Future research should examine the role of cognition in the development of ABA, dysfunction of which may represent an endophenotype linking anorectic, anxiety-like and compulsive behavior. PUBLIC SIGNIFICANCE: Anorexia nervosa (AN) has among the highest mortality rates of all psychiatric disorders and treatment options remain limited in their efficacy. Understanding what types of risk factors contribute to the development of AN is essential for implementing early intervention strategies. This study describes how some of the most common psychological features of AN could be used to predict susceptibility to pathological weight loss in a well-established animal model.

Lipopolysaccharide preconditioning protects rats against cerebral ischemia reperfusion injury by reducing the damage of blood-brain barrier / 国际脑血管病杂志

Objective:To investigate the protective effect of lipopolysaccharide (LPS) preconditioning on cerebral ischemia reperfusion in rats.Methods:One hundred and twenty adult male SD rats were randomly divided into sham operation group, model group, low-dose LPS group (0.05 mg/kg), medium-dose LPS group (0.15 mg/kg), and high-dose LPS group (0.45 mg/kg). LPS was injected intraperitoneally for preconditioning, once a day for 7 consecutive days. Twenty-four hours after the last injection, the left middle cerebral artery occlusion model was induced by suture-occluded method. The model was reperfused 1.5 h after ischemia. At 24 h after reperfusion, the neurological deficit was evaluated by neurobehavioral score. The volume of cerebral infarction was measured by triphenyltetrazolium chloride staining. The serum levels of proinflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay. The expression of Toll-like receptor 4 (TLR4), matrix metalloproteinase (MMP) -2 and MMP-9 in ischemic brain tissue was detected by Western blot analysis.Results:Compared with the sham operation group, blood-brain barrier permeability was increased in the model group, serum IL-1β, IL-6 and TNF-α were up-regulated, and the expression of TLR4, MMP-2 and MMP-9 proteins in ischemic brain tissue was up-regulated. Compared with the model group, the neurological impairment of each LPS intervention group was significantly reduced, the volume of cerebral infarction was significantly reduced, the permeability of blood-brain barrier was significantly reduced, the serum IL-1β, IL-6 and TNF-α were down-regulated, and the expression of TLR4, MMP-2 and MMP-9 protein in ischemic brain tissue was down-regulated, especially in the medium-dose group and the high-dose group.Conclusions:LPS preconditioning can induce the formation of ischemic tolerance, inhibit the activation of TLR4-MMP-2/MMP-9 signal pathway, reduce the damage and inflammation of blood-brain barrier structure, and thus play a neuroprotective role in rats with cerebral ischemia reperfusion.

Effect of vagus nerve stimulation by electroacupuncture on GFAP and NeuN in hippocampal of juvenile rats with depression induced by chronic unpredictable stress / 中国医师杂志

Objective:To analyze the expression of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) antigen in hippocampus based on the depression model of juvenile rats caused by chronic unpredictable stress (CUS), and to explore the effect of electroacupuncture vagus nerve on CUS depression model.Methods:Six juvenile SD rats were selected as the control group (without any stimulation), and the rest were divided into CUS group, pseudo stimulation group, fluoxetine group and electroacupuncture group by random number method after CUS modeling, with 6 rats in each group. Fluoxetine group was given 10 mg/kg fluoxetine intervention; control group and CUS group were given the same amount of normal saline intervention; In the electroacupuncture group, the distal vagus nerve was stimulated after ligation, while in the pseudo stimulation group, only vagus nerve was isolated without electrical stimulation. After 28 d of intervention, the five groups were subjected to Open-field Test and Sucrose Preference Test. Hippocampal neurons were detected by hematoxylin and eosin (HE) staining, and the expressions of GFAP and NeuN in hippocampal were detected by immunohistochemistry.Results:After CUS modeling and before intervention, the number of vertical and horizontal movements, sucrose consumption and sucrose preference in CUS group, pseudo stimulation group, fluoxetine group and electroacupuncture group were significantly lower than those in the control group (all P<0.01); After the intervention, the above indexes in CUS group and pseudo stimulation group were still lower than those in the control group (all P<0.01), but the above indexes in fluoxetine group and electroacupuncture group were significantly higher than those in CUS group and pseudo stimulation group (all P<0.01). HE staining showed that the arrangement of hippocampal neurons in CUS group and pseudo stimulation group were loose, and there were cell swelling and pyknosis, which was significantly improved in fluoxetine group and electroacupuncture group. Immunohistochemical results showed that compared with the control group, the expression of GFAP increased and NeuN decreased in the hippocampus of CUS group and pseudo stimulation group (all P<0.01); Compared with CUS group and pseudo stimulation group, the expression of GFAP decreased and NeuN increased in fluoxetine group and electroacupuncture group (all P<0.01). Conclusions:Electroacupuncture of vagus nerve can obviously improve the depression symptoms of juvenile rats, which is similar to fluoxetine, and may be related to regulating the expression of GFAP and Neun in hippocampus.

Mechanism of protein S-nitrosylation modification mediated severe acute pancreatitis / 中国医师杂志

Objective:This study aims to explore the pathogenic roles of protein S-nitrosylation modification in the development of severe acute pancreatitis, and provide new insights into the molecular mechanisms driving acute pancreatitis development.Methods:Thirty two Sprague Dawley (SD) rats were randomly divided into sham operation group, mild acute pancreatitis (MAP) group, severe acute pancreatitis (SAP) group and SAP + N-nitro-L-arginine methyl ester (L-NAME) group (treated with nitric oxide synthase inhibitor), 8 rats in each group. All rats were sacrificed to take blood from heart and pancreatic tissues 24 h after model construction. Total protein S-nitrosylation modification level in pancreatic tissues was quantitated by the biotin-switch method, followed by histological evaluation via hematoxylin and eosin (HE) staining. The serum endotoxin, D-lactic acid, diamine oxidase, interleukin-6 and tumor necrosis factor-ɑ(TNF-ɑ), amylase, alanine aminotransferase, urea nitrogen and calcium ions in rat were detected. Pearson correlation analysis was used to analyze the correlation between each index and protein S-nitrosylation.Results:Compared with the sham operation group, the modification level of protein S-nitrosylation in pancreatic tissue of MAP group increased significantly ( P<0.05); Compared with MAP group, the modification level of protein S-nitrosylation in pancreatic tissue of SAP group increased significantly ( P<0.05); Compared with SAP group, the modification level of protein S-nitrosylation in pancreatic tissue of SAP + L-NAME group decreased significantly ( P<0.05). HE staining showed that the degree of pancreatic necrosis and inflammatory cell infiltration in SAP + L-NAME group were significantly weaker than those in SAP group. The concentrations of serum endotoxin, diamine oxidase, D-lactic acid, IL-6 and TNF-ɑ, amylase, alanine aminotransferase, and urea nitrogen in the MAP group were significantly higher than those in the sham operation group (all P<0.05); The above indexes in SAP group were significantly higher than those in MAP group and sham operation group (all P<0.05); The above indexes in SAP + L-NAME group were significantly lower than those in SAP group (all P<0.05). The serum IL-6 and TNF-ɑ levels in rats with acute pancreatitis were positively correlated with protein S-nitrosylation in pancreatic tissue (all P<0.05). Conclusions:Protein S-nitrosylation modification plays essential roles in the development and progression of severe acute pancreatitis.

Exploration of animal model of sepsis caused by lung bacterial infection / 中国医师杂志

Objective:Animal models of sepsis are mainly established by cecal ligation and puncture which causes mixed bacterial infections in the abdominal cavity. However in internal clinic, sepsis is more common to be caused by respiratory bacterial infections. Therefore, it is necessary to establish animal models of sepsis caused by lung Infection.Methods:According to the concentration of Staphylococcus aureus (S. aureus) suspension and Pseudomonas aeruginosa (P. aeruginosa) suspension, Sprague Dawley (SD) rats were equally divided into 10 groups, including S-Cont group, S-0.75 group, S-1.5 group, S-3 group, S-6 group and P-Cont group, P-1 group, P-2 group, P-4 group, P-8 group. Rats in the control group were treated with normal saline nasal drip. Rats in each experimental group were infected by nasal dripping bacterial suspension with 0.75×10 8 CFU/ml, 1.5×10 8 CFU/ml, 3×10 8 CFU/ml, 6×10 8 CFU/ml of S. aureus suspension or 1×10 8 CFU/ml, 2×10 8 CFU/ml, 4×10 8 CFU/ml, 8×10 8CFU/ml P. aeruginosa suspension. Our study detected the body temperature (T), blood pressure (BP), heart rate (HR) of rats in each group before and after infection, as well as blood lactic acid (Lac) and procalcitonin (PCT) level after infection. The lung infections of rats in each group were observed by hematoxylin-eosin (HE) staining. Results:The blood pressure(BP) of S-1.5 group, S-3 group, S-6 group and P-8 group was lower than before infection (all P<0.05). The Lac and PCT of each S. aureus experimental group were higher than that of the S-Cont group (all P<0.01); and they showed an increasing trend with the increase of the bacterial suspension concentration ( P<0.05), except for the S-3 and S-6 group ( P>0.05). The Lac and PCT of each P. aeruginosa experimental group were higher than that of the P-Cont group (all P<0.01); and they showed an increasing trend with the increase of the bacterial suspension concentration (all P<0.05), except for the Lac in the P-4 group and P-8 group ( P>0.05). HE staining showed that different degrees of inflammatory infiltration can be seen in the lungs of the experimental rats in each group. Conclusions:Infection of rats by nasal dripping with 3×10 8 CFU/ml of S. aureus suspension or 4×10 8 CFU/ml of P. aeruginosa suspension could establish relatively stable rat sepsis model induced by lung bacterial infection, of which the former could also establish a relatively stable septic shock model.