Objective To study the content of monoamine neurotransmitters and neurotrophic factor in the hippocampus, amygdala and prefrontal cortex in anxious depression rats, and explore the possible pathogenesis.Methods 60 SD rats were randomly divided into normal group, vehicle group, anxiety group, depression group, and anxious depression group, 12 rats in each group.Chronic restraint stress combined with corticosterone injection was used to establish anxiety and depression model, the modeling time was 21 d.After modeling, elevated plus maze test, open field test, and forced swimming test were used to evaluate the anxiety and depression-like behavior, HPLC-ECD was used to detect the content of 5-HT, NE, and DA in the hippocampus, amygdala, and prefrontal cortex of rats.Western-blotting was used to detect the expression of BDNF and NT-3 in rats.Results Rats in anxious depression model group were comparable to the anxiety group in time and frequency entering open arm time, and number of locomotor activity in open field, and it had a significant difference when compared with the control and depression groups (P<0.01 or P<0.05).Immobile time in anxious depression model rats was increased significantly when compared with the control and anxiety groups (P<0.01).Meanwhile, compared with the control group, 5-HT in hippocampus and 5-HT, NE in amygdala or prefrontal cortex were significantly decreased in the depressive rats with anxiety (P<0.01 or P<0.05).Moreover, the content of BDNF and NT-3 was significantly decreased in each brain regions compared with the control group (P<0.01 or P<0.05), and BDNF levels were obviously decreased compared with the anxiety group (P<0.05).Conclusions Rats of anxious depression have significant anxiety and depression-like behaviors.Its mechanism may be associated with the down-regulation of monoamine neurotransmitters and neurotrophic factors BDNF and NT-3 in hippocampus, amygdala, and prefrontal cortex region.

Objective To investigate the regulating effects of Zuogui Jiangtang Jieyu Formula (ZJJF) on Bcl-2, Bax and Caspase-8 in hippocampus neuron damage in diabetes mellitus with depression (DD). Methods Hippocampal neurons from 18 d pregnant rats were primitively cultivated, and then combination of glucose and corticosterone was used to construct DD simulation environment. Cultivated hippocampal neurons were randomly divided into normal group, blank serum group, model group, positive medicine (metformin+fluoxetine) serum group and to-be-tested medicine (ZJJF) serum group. Normal group and model group were given same amount culture medium, while other group were given relevant amont of 10％ medicine serum or blank serum. After modeling intervention for 18 h,Hoechst staining was used to detect the apoptosis of hippocampal neurons. The expression of Bcl-2, Bax and Caspase-8 was detected by high content analysis. Results Compared with the control group, hippocampal neuron dendrites ruptured or decreased, neural network connection decreased, cells showed significant staining, broken, uneven distribution of light spots, the expression of Bcl-2 protein decreased significantly (P<0.05), but Bax and Caspase-8 were increased (P<0.05, P<0.01). Compared with the model group, hippocampal neurons in both positive medicine serum group and ZJJF serum group gradually recovered. Hoechst staining showed that the nuclei were significantly homogenized, local highlights were significantly reduced, Bcl-2 protein expression levels were significantly increased (P<0.05, P<0.01), while Bax and Caspase-8 were obviously down-regulated (P<0.05, P<0.01). Conclusion ZJJF has protective effects on hippocampal neurons in DD of model rats, and its mechanism is related to regulating the expression of Bcl-2, Bax and Caspase-8 in hippocampus neuron.

Objective To compare the biological characteristics of several different anxiety rat models established by different methods of stress at different time points and provide experimental basis for the most appropriate modeling methods .Methods 60 rats were randomly divided into normal , empty bottle stress , chronic emotional stress ( CES ) group, restraint stress for 3h, 6h, and modeling respectively .In the experimental 7 d, 14 d, 21 d, elevated plus maze and fear condition system was used to test anxiety-like behavior in rats , open field test to study anxiety or depression-like behavior , forced swimming test was used to detect depression-like behavior in rats , and using the Elisa test kit to detect the contents of 5-HT, DA in the hippocampus in rats .Results Anxiety-like behavioral test results showed that rats in empty bottle stress, CES, 6 h restraint stress group started to have anxiety-like behavior since 14 d, then anxiety-like behavior was becoming increasingly apparent .Forced swimming test results showed that immobility time in 6 h restraint rats was significantly increased in the first 7 d(P <0.05).Meanwhile, compared with control group, hippocampal 5-HT, DA contents in empty bottle stress and CES rats increased significantly since 14 d.Conclusions Among several stress methods established anxiety model , anxiety-like behavior in 3 h restraint stress was not obvious; 6 h restraint stress exhibited a depression-like behavior in the forced swimming test might be due to prolonged stress .Empty bottle stress and CES can successfully establish the anxiety rat model , and the anxiety behavior of the rats have some differences . Corresponding model methods can be selected according to different experimental purposes .

OBJECTIVE: To detect some proteins associated with the effect of ganoderma lucidium spores (GASP) on promoting the survival and axon regeneration of injured spinal motor neurons in rats. METHODS: The rats were divided into normal control group, untreated group and GASP-treated group, and the rats in the last two groups received ventral root avulsion. GASP preparation was fed to the rats in the GASP-treated group for 14 days. The gray matter tissues of the lumbar spinal were sampled from rats in each group after 14 days following ventral root avulsion, and the extracted proteins from these tissues were detected by using 2-dimensional electrophoresis. Matrix assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) was utilized to identify the differentially expressed proteins among these three groups. RESULTS: There were six kinds of proteins differentially expressed among the three groups, which were collapsin response mediator protein 2 (CRMP-2), F-actin capping protein beta subunit (FCP-beta), isocitrate dehydrogenase [NAD] subunit beta (IDH-beta), ATPase, glutamate oxaloacetate transaminase-1 (GOT1) and M2 pyruvate kinase (M2-PK). The expression levels of CRMP-2, IDH-beta, ATPase and GOT1 were higher in the GASP-treated group than those in the untreated group, while the expression levels of FCP-beta and M2-PK were lower than those in the untreated group. CONCLUSION: GASP maybe promotes the survival and axon regeneration of injured spinal motor neurons in rats by virtue of up- or down-regulating the expression levels of the proteins mentioned above.

Objective To investigate the effects of Zuogui Jiangtang Jieyu Prescription on neurotrophic effects of astrocytes in diabetes mellitus rats with depression. Methods The diabetes mellitus with depression rat models were established by composite method, and then were randomly divided into 5 groups: model group, positive group, Zuogui Jiangtang Jieyu Prescription high-, medium-, low-dose groups, with 12 rats in each group. 12 normal rats were set as control group. Each administration group was given relevenat medicine for gavage for continuous 4 weeks. Open-field test was used to evaluate the depression-like behavior. The expression of GFAP in astrocyte and MAP2 in neuron were tested by immunohistochemistry. The expression of protein and mRNA of BDNF, GDNF, and NGF were tested by Western blot and RT-PCR. Results Compared with the control group, the activities of rats in model group were significantly reduced. The expression of GFAP increased, while the expressions of MAP2, BDNF, GDNF and NGF decreased. Compared with the model group, the depression-like behavior of rats in model group were significantly improved. The expression of GFAP decreased, while the expressions of MAP2, BDNF, GDNF and NGF increased, and GFAP decrseaed significantly. Conclusion The secretion function of astrocyte can be improved by Zuogui Jiangtang Jieyu Prescription. Its anti-depression and neuron-protection function might be correlated with the enhancement of neurotrophic effects of astrocytes.

ObjectiveTo observe the effect ofZuogui Jiangtang Jieyu Formula on the expressions of glutamate, NR2A and NR2B in hippocampus of diabetic rats with depression;To explore the mechanism of protective effect. Methods Diabetes with depression rat models were established and then were randomly divided into the model group, positive medicine group, high-, medium- and low-doseZuogui Jiangtang Jieyu Formula groups. Normal rats acted as normal group, 16 rats per group. After 28 days of administration, Open-field test was used to detect the behavior of the rats;glutamate content of hippocampus was detected by ELISA;the expressions of NR2A and NR2B in rat hippocampus were detected by immunofluorescence.Results Compared with normal group, automatic activity times of rats in model group decreased significantly (P<0.01);both glutamate content (P<0.01) and expressions of NR2A, NR2B (P<0.01) increased significantly. Compared with the model group, automatic activity times of rats in positive medicine group and high-doseZuogui Jiangtang Jieyu Formula group significantly increased (P<0.01);glutamate content dropped (P<0.01);expressions of NR2A and NR2B decreased (P<0.05).ConclusionZuogui Jiangtang Jieyu Formula can improve depressive behavior of diabetic rats with depression, which may be related to the regulation of glutamate content and expressions of NR2A and NR2B in hippocampus.

Objective Based on data mining technology, we discussed the correlation of different gene mutation, fusion or amplification in advanced lung cancer patients. Methods 630 cases in our hospital were collected and the drug database was established by Excel 2016. Frequency analysis and association rules were used for statistical analysis, and statistical analysis was performed on SPSS22.0 and SPSSModerler statistical software.Results There were 26 high frequency genes, such as EGFR-19 mutation, ALK fusion, RET mutation, EGFRL858 R-21 mutation, ALK mutation, and the first 6 cases of T790M mutation. The first 26 were NRAS-G12 D mutation and BRAF-G466 V mutation, MYC-R450 W mutation and CYP2D6 mutation, GATA3 M423 fs mutation and ESR1 mutation, abrupt mutation, mutation and sudden process. The variable classification values are associated with each other. The minimum value of gene association analysis was 50％ and support was 10％. After Apriori module analysis, EGFR-19 mutation and 14 genes were not found (confidence degree 46.667％) , EGFR-19 mutation and T790 M mutation (confidence degree 40％) , EGFR-19 mutation and TP53 mutation (confidence degree 13.333％) , ROS1 fusion and MET amplification (confidence 47.619％) , MET amplification and ROS1 melting (confidence level 50％) , T790 M mutation and EGFR amplification (confidence level 57.895％) , EGFR-19 mutation and EGFR amplification (confidence 42.105％). Cluster analysis BRAF-G466 V and NRAS-G12D, MYC-R450 W and CYP2 D6, GATA3 M423 fs and SRC, PIK3 CA amplification and PIK3CA, Pten and EGFEL861 Q-21, KRAS G12A and blending. Conclusion There are correlations between different genes and mutation, fusion, lack and amplification of lung cancer.

Objective To investigate the influence of Zuogui Jiangtang Jieyu Fang (ZJJF) on hippocampus neuron synaptic plasticity related proteins-CaMKⅡ and SynGap in rats simulated diabetes complicating depression DD.Methods The hippocampus neurons were primitively isolated, purified and cultured in SD rats.The DD model was established by applying intervention of high glucose and cortisone.The cultured hippocampus neurons were randomly divided into normal group, model group, medicated serum of ZJJF (ZJJF group), medicated serum of positive drug (fluoxetine and metform) group (positive drug group) and blank group.The damages of hippocampus neurons were detected by using Nissl's staining in all groups, and expressions of CaMKII and SynGap were detected by using immunofluorescence staining and high-content analysis (HCA) after drug intervervention for 18 d.Results Compared with normal group and blank group, the quantity of Nissl bodies decreased significantly, neural network and dentritic spines ruptured or disappeared, and expressions of CaMKII and SynGap were significantly down-regulated in model group (P<0.01).Compared with model group, the quantity of Nissl bodies, neural network and dentritic spines, and synaptic connection were significantly recovered, and expressions of CaMKII and SynGap were un-regulated in positive drug group and ZJJF group (P<0.01 or P<0.05).Conclusion ZJJF had significant regulative effect on CaMKII and SynGap in simulated condition of diabetes complicating depression, which may be one of important mechanisms of ZJJF antagonizing cellular damage and neural degeneration.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths, patients with non-small cell lung cancer (NSCLC) usually have distant metastases, such as bone metastasis, brain metastasis, and lung metastasis. The purpose of this study was to explore the risk factors for bone metastasis in NSCLC patients. METHODS: A total of 176 cases of NSCLC were selected from May 2009 to May 2011, and patients were divided into two groups, namely the bone metastasis group and non-bone metastasis group. The general clinicopathological data of the two groups and analyzing the independent risk factors of bone metastasis were compared. RESULTS: In the general clinicopathological data of NSCLC patients. The thrombus or not and tumor-node-metastasis (TNM) stage were closely related to the occurrence of bone metastasis, and were statistically significant (all P<0.01). Prothrombin time, activated partial thromboplastin time, Fibrinogen, thrombin time, blood platelet, D-Dimer and alkaline phosphatase have significantly difference between the two groups (all P<0.05). Logistic regression analysis showed that fibrinogen, activated partial thromboplast in time, alkaline phosphatase, T4 phase, N3 phase and d-dimer were independent risk factors for bone metastasis in NSCLC patients. CONCLUSIONS Fibrinogen, alkaline phosphatase, T3, N2 stage and D-Dimer is the independent risk factors of bone metastases in patients with NSCLC.
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Aged ; Bone Neoplasms ; diagnosis ; secondary ; Carcinoma, Non-Small-Cell Lung ; pathology ; therapy ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; pathology ; therapy ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Risk Factors

Objective The aim of this study was to evaluate the efficacy and side effects of sacubitril/valsartan in the treatment of patients with chronic kidney disease(CKD)at stage 5 with resistant hypertension,and to explore the cardiovascular benefits and security of medical in the patients.Methods Patients with CKD5 resistant hypertension diagnosed and treated in the First Affiliated Hospital of Guangxi Medical University from September 2020 to March 2022 were selected and divided into the observation group(treated with routine treatment of kidney disease at end-stage and sacubitril/valsartan)and control group(include droutine treatment of renal disease at end-stage and ACEI or ARB drugs)according to treatment strategy.The patients in both two groups were treated with adequate dialysis treatment and conventional drug treatment of renal disease at end-stage.The patients were followed up for at least 3 months,the clinical efficacy of three months after treated with sacubitril/valsartan was observed,and the efficacy indicators and security indicators and adverse cardiovascular events were observed,the occurrence of adverse effects during the period of drug use were compared with the control group.Results A total of 110 patients were included in this study and there were 55 cases in each group.There were no significant differences in gender,age,age of dialysis,etiology,dialysis mode and blood pressure between the two groups(P>0.05).The Systolic blood pressure(SBP),diastolic blood pressure(DBP),b-type urinary natriuretic peptide precursor(Pro-BNP)and cardiac function grade in the observation group after treatment was significantly decreased compared with before treatment.The left ventricular ejection fraction(LVEF)and the ratio of LVEF<50%in the observation group was significantly reduced after treatment(P<0.05).SBP,DBP and Pro-BNP decreased 3 months after treatment compared with the baseline before treatment,and improved significantly in the first month after treatment(P<0.05).The decrease of DBP and BNP before and after treatment was significantly different between the two groups,and the decrease of DBP and BNP was more significant in the observation group(P<0.05).The difference of LVEF and left ventricular end diastolic diameter(LVEDD)between the two groups before and after treatment was statistically significant,and the improvement was more obvious in the observation group(P<0.05).There were no significant differences in the safety indicators of serum potassium,estimated glomerular filtration rate(eGFR)and liver function between two groups before and after treatment(P>0.05).In terms of adverse reactions,only 1 case in the control group developed hyperkalemia within 3 months of follow-up,and no hypotension or other adverse reactions occurred in the two groups.Conclusions The treatment of patients with CKD stage 5 hypertension with sacubitril/valsartan has obvious cardiovascular benefits.Sacubitril/Valsartan has efficacy in lowering blood pressure,improving cardiac function and reducing volume load,with less adverse events and higher safety than control group.