Objective To investigate the effects and mechanism of Yuyin Qianyang Tongluo Formula on cognitive function in Alzheimer's disease mice.Methods Transgenic negative mice were designated as the normal group,while APP/PS1 double transgenic mice were randomly divided into six groups(ni=6 per group):model group,low-dose Yuyin Qianyang Tongluo Formula group,medium-dose group,high-dose group,and positive drug group.The Yuyin Qianyang Tongluo Formula low-,medium-,high-dose groups correspondingly received intragastric administration of 0.75,1.5,and 3 g·kg-1·d-1,respectively.The positive drug group received 2 mg·kg-1·d-1 donepezil hydrochloride tablets,while the model and normal groups received equal volumes of saline.All groups were treated once daily for 8 weeks.Behavioral tests were conducted using the Morris water maze and Y-maze.Hippocampal β-amyloid(Aβ)1-42 level was measured by enzyme-linked immunosorbent assay(ELISA).Hippocampal CA1 and CA3 neurons were observed hematoxylin-eosin(HE)staining,and Nissl bodies were examined Nissl staining.Protein expression levels of Aβ transporter low-density lipoprotein receptor-related protein 1(LRP-1)and endoplasmic reticulum stress marker glucose-regulated protein 78(GRP78)were detected by Western Blot analysis.Results(1)Compared with the normal group,the model group showed significantly prolonged escape latency(P＜0.000 1),reduced platform crossings,decreased movement distance and time around the platform of Morris water maze test(P＜0.05 or P＜0.01),significantly lower spontaneous alternation percentage in Y-maze test(P＜0.05),and significantly elevated hippocampal Aβ1-42 level(P＜0.000 1).Compared with the model group,all Yuyin Qianyang Tongluo Formula dose groups and the positive drug group exhibited significantly shortened escape latency of Morris water maze test(P＜0.000 1).The high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed significantly increased platform crossings,movement distance and time around the platform of Morris water maze test(P＜0.05),significantly higher spontaneous alternation percentage in Y-maze test(P＜0.05).All Yuyin Qianyang Tongluo Formula dose groups and the positive drug group showed significantly reduced hippocampal Aβ1-42 level(P＜0.000 1).(2)Compared with the normal group,the model group exhibited disordered and deformed hippocampal neurons and Nissl bodies.Compared with the model group,all Yuyin Qianyang Tongluo Formula groups and positive drug group showed improved neuronal and Nissl body organization,with the improvement degree positively correlated with dosage.(3)Compared with the normal group,the model group showed decreased LRP1 level and increased GRP78 level,but there were no statistically significant differences(P＞0.05).Compared with the model group,the high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed increased LRP1 level,while all Yuyin Qianyang Tongluo Formula dose groups and positive drug group exhibited decreased GRP78 level,but there were no statistically significant differences(P＞0.05).Conclusion Yuyin Qianyang Tongluo Formula significantly improves cognitive and memory function in model mice in a dose-dependent manner,potentially through reducing Aβ aggregation in the brain via endoplasmic reticulum stress pathway.

Objective:To explore the significance of combined detection of biomarkers in the diagnosis of early stage primary liver cancer.Methods:A retrospective study model was adopted to analyze 60 patients who were hospitalized from January 2018 to September 2019 in General Hospital of Xuzhou Mining Group and were pathologically diagnosed as early stage primary liver cancer (early stage liver cancer group), and 60 patients with liver cirrhosis (liver cirrhosis group), 30 patients with hepatitis (hepatitis group), 30 healthy examiners (healthy control group) who were admitted during the same period were selected. All participants were tested for liver cancer biomarkers such as alpha-fetoprotein (AFP), vitamin K deficiency Ⅱ-inducing protein (PIVKA-Ⅱ), alpha-fetoprotein variant (AFP-L3) and Golgi protein 73 (GP73). The receiver operating characteristic curve (ROC) was used to compare the differences in the diagnosis of early stage primary liver cancer between individual and combined detection of different indicators.Results:The levels of AFP-L3, AFP, PIVKA-Ⅱ and GP73 in the early stage liver cancer group were higher than those in the cirrhosis group, hepatitis group and healthy control group, and the differences were statistically significant (all P < 0.05). PIVKA-Ⅱ had the largest area under the receiver operator characteristic curve (AUC) for diagnosing early stage liver cancer, which was 0.776; AFP-L3 had the highest specificity for diagnosing early stage liver cancer, which was 82.2%; GP73 had the highest sensitivity for diagnosing early stage liver cancer, which was 80.0%. The AUC of the four indicators in the diagnosis of early stage liver cancer was 0.922, which was higher than a single indicator, and the sensitivity reached 91.7%. Conclusions:Liver cancer biomarkers AFP-L3, PIVKA-Ⅱ, AFP and GP73 all have certain diagnostic value in the diagnosis of early stage primary liver cancer. The combined detection has important clinical significances for diagnosis of early stage primary liver cancer and assessment of liver damage.