Objective: To observe the eff ect and mechanism of chronic high-fat diet on predation behavior in rats. Methods: Ten female SD rats with 4-week-old were randomly divided into a normal control group (NC group,n=5) and a chronic high-fat diet group (HF group,n=5). The rats in the NC group received the regular diet while rats in the HF group were fed with high-fat diet. Fitf een weeks later, the predation behavior of rats was evaluated by open if eld test and food foraging tests. At the end of experiments, the rats were killed and brain tissues were collected for evaluation of c-Fos protein expression in anterior cingulate cortex by immunohistochemical assay. Results: hT e predation behavior of rats in the HF group was signiif cantly impaired in the competitive or non-competitive food foraging test compared with the control rats (P<0.001). hT e c-fos protein expression in anterior cingulate cortex of rats from the HF group was signiif cantly decreased (P<0.001). Conclusion: Long time high-fat diet can aff ect the predation behavior of rats, which is related todysfunction of neuron in anterior cingulate cortex.

Funds management,which has a direct effect on the development of scientific research projects,is an important part of the scientific research management in hospitals.By investigating the present situation of the scientific research funds management in a local hospital in Shanghai,this paper analyzes the problems commonly found in the scientific research funds management.Based on the findings of the analysis,this paper proposes some corresponding recommendations and countermeasures to improve the management.

Objective To investigate the association between the tumour necrosis factor-α-863(TNF-α-863) polymorphism and gout in Han population from the city of Tangshan.Methods We recruited 80 gout patients and 80 healthy individuals into this study.The polymorphisms of TNF-α-863 site were analyzed by polymerase chain reaction-ligase detection reaction(PCR-LDR).The frequencies of different TNF-α-863 genotypes/alleles were analyzed in the gout group and the control subjects.Results No significant differences were observed in the genotype frequencies(x2=2.8807,P=0.0897) and allelic frequencies(x2=4.2646,P=0.1187) of TNF-α-863 site in the comparison between gout and control groups.Conclusion The result of our study suggests that the polymorphism of TNF-α-863 site may not related to gout in Han population in Tangshan.

Objective:To explore the effect of Bushen Huoxue Decoction on ventricular remodeling and myocardial nuclear factor-kappaB (NF-κB) protein in rats with chronic heart failure.Methods:60 male SD rats were randomly divided into sham operation group (15 rats) and experimental group (45 rats). The rats of the experimental group was established CHF model by ligating the left anterior descending coronary artery combined with exhaustive swimming and starvation. Rats with chronic heart failure were randomly divided into model group, Bushen Huoxue group and lisinopril group.The Bushen Huoxue group was perfused with 15.75 g/(kg·d) Bushen Huoxue Decoction, the lisinopril group was perfused with 1.8 mg/(kg·d) of lisinopril suspension, and the sham operation group and model group were perfused with equal volume of distilled water. After 4 weeks of administration, the general mental state of rats was observed. The left ventricular internal systolic diameter (LVIDs) and internal diastolic diameter (LVIDd) were measured by cardiac color Doppler ultrasound, and the left ventricular ejection fraction (LVEF) and short axis shortening fraction (LVFS) were calculated. The expression of NF-κB protein in rat myocardium was detected by Western blot, and the morphology of left ventricular myocytes was observed by hematoxylin eosin staining.Results:Compared with the model group, the myocardial fibers of rats in Bushen Huoxue group and lisinopril group were arranged orderly, with few pyknosis, a small amount of inflammatory cell infiltration. Compared with the model group, the levels of LVIDs [(6.00±0.58)mm vs. (6.99±0.90)mm] and LVIDd [(3.96±0.51)mm vs. (5.14±0.57)mm] significantly decreased, LVEF [(54.48±6.75)% vs. (30.28±4.85)%] and LVFS [(33.86±4.27)% vs. (26.10±4.96)%] significantly increased, as well as the expression of myocardial NF-κB (1.06±0.10 vs. 1.58±0.29) protein significantly decreased ( P<0.05). Conclusion:Bushen Huoxue Decoction can resist ventricular remodeling,improve cardiac function and treat heart failure of CHF rats and the possible mechanism might be it could down-regulate myocardial NF-κB expression.

Objective To investigate the correlation of CD4+ T lymphocyte count and prostaglandin E2 (PGE2) in gingival crevicular fluid(GCF) with periodontal status in HIV-positive patients with periodontitis.Methods Twenty subjects were selected according to inclusion criteria.The plasmatic CD4+ T lymphocytes were counted.All the individuals were divided into three groups,group A (CD4+ T lymphocyte count ＜200 cell/mm3),group B (200 cell/mm3 ≤CD4+ T lymphocyte count≤500 cell/mm3) and group C (CD4+ T lymphocyte count ＞ 500 cell/mm3).Periodontal indexes,including plaque index (PLI),bleeding index(BI),attachment level(AL) and probing depth(PD) were recorded.GCF samples were taken from 120 index teeth by means of sterile paper strips.GCF PGE2 levels were determined by radioimmunoassays.MannWhitney was used to compare the periodontal indexes and PGE2 levels among the three groups.Partial correlations and Spearman correlations were applied to analyze the correlation of CD4+ T lymphocytes count and PGE2 in gingival crevicular fluid with periodontal status.Results BI value,PGE2 concentration and total PGE2 were 3.00 (2.00),90.75 (30.60) μg,/L,447.58 (243.08) pg in group B,which were higher than those in group A[2.00(1.25),79.75(30.50) μg/L and 339.52(200.97) pg respectively] and group C [2.00(1.00),73.38 (14.83) μg/L and 299.18 (108.33) pg respectively] (P ＜ 0.0167).But the differences of PD and AL among the three groups were not significantly different (P ＞ 0.0167).The correlations were observed between CD4+ T lymphocyte count and BI for the subpopulations with CD4+ T lymphocyte count ＜ 200 cells/mm3 (r =0.657,P ＜ 0.05) and between 200-500 cells/mm3 (r =-0.369,P ＜ O.05).PGE2 concentration was negatively correlated with BI,PD and AL(P ＜ 0.05),and total PGE2 was positively correlated with PD and AL (P ＜ 0.05).Conclusions There was an association between the periodontal status and CD4+ T lymphocyte count in HIV + patients.GCF PGE2 level was related to periodontal parameters including BI,PD and AL.

ObjectiveTo compare the effects and differences of Yiqi Liangxue Shengji Formula （益气凉血生肌方） and atorvastatin on the repair of vascular injury in rats from the perspective of metabolomics. MethodsTwenty-four male SD rats were randomly divided into sham-surgery， model， traditional Chinese medicine （TCM）， and ator-vastatin groups， with 6 rats in each group. The rat model was established by balloon-induced abdominal aorta injury. Gavage was started on the day after surgery in all groups of rats. The sham and model groups were given with deio-nized water， TCM group received Yiqi Liangxue Shengji Formula 6 g/（kg·d）， and the atorvastatin group treated with atorvastatin suspension 2 mg/（kg·d） for 4 weeks. HE staining was used to observe the pathological morphology of the injured segment of the abdominal aorta； ELISA detection was used to test serum nitric oxide （NO） and C-reactive protein （CRP） levels； UPLC MS/MS technology was used for widely targeted metabolomics detection in serum， and multivariate statistical analysis was used to screen metabolic markers and pathways of two drugs； finally， compare serum levels of key metabolic markers of the above two medications in rats of each group. ResultsCompared with the sham-surgery group， the neointima significantly thickened， the level of NO decreased significantly and the level of CRP increased in serum of the model group （P＜0.01）； compared with the model group， the degree of arterial intimal hyperplasia in TCM group and atorvastatin group reduced， with an increase in NO levels and a decrease in CRP levels （P＜ 0.05 or P＜0.01）. The results of serum metabolomics showed that TCM group obtained 49 metabolic markers and 6 metabolic pathways， while atorvastatin group obtained 41 metabolic markers and 4 metabolic pathways. The two medications jointly regulated 38 metabolites. Glycerophospholipid metabolism and arginine-related metabolism were common metabolic pathways for both medications. Lysophosphatidylcholine （16∶1/0∶0） ［LPC （16∶1/ 0∶0）］， phosphatidylcholine （15∶0/15∶0） ［PC （15∶0/15∶0）］ were the key metabolites of glycerophospholipid metabolic pathway； ornithine， spermidine were the key metabolites of arginine-related metabolic pathway. The tricarboxylic acid cycle and glutathione metabolism were the unique metabolic pathways of Yiqi Liangxue Shengji Formula. Compared with the sham-surgery group， LPC （16∶1/0∶0）， ornithine， and spermidine levels elevated and PC （15∶0/15∶0） levels decreased in the model group （P＜0.05 or P＜0.01）. Compared with the model group， LPC （16∶1/0∶0）， ornithine， and spermidine levels decreased， and PC （15∶0/15∶0） levels increased in both TCM group and atorvastatin group （P＜0.05 or P＜0.01）. The degree of LPC reduction （16∶1/0∶0） was more significant in atorvastatin group compared with that in the TCM group （P＜0.01）. ConclusionsBoth sham-surgery and atorvastatin could regulate lipid metabolism and arginine-related metabolism， exert the characteristics of lipid-lowering， anti-inflammatory， improve arginine/NO bioavailability， and improve endothelial dysfunction. Atorvastatin showed more advantages in lipid-lowering and anti-inflammatory， while Yiqi Liangxue Shengji Formula has unique characteristics in regulating energy metabolism and improving oxidative stress.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*