Aims To study the role of NGF/Trk A sig-naling pathway in Memantine ( MEM) improving APP/PS1 transgenic mice cognitive deficits and to explore its possible mechanisms. Methods Cognitive perform-ance was assessed by Morris water maze( MWM) , pas-sive avoidance test( PAT) and locomotivity test. Aβ1-42 protein levels were determined by immunohistochemis-try. The activities of AChE and ChAT were also exam-ined by ELISA and colorimetry. Western blot was used to detect the expression levels of NGF and its receptor TrkA and the downstream ERK pathway. Results MEM treatment significantly ameliorated the cognitive deficits, dramatically reduced the Aβ1-42 overexpres-sion. MEM increased the activity of choline acetyl-transferase( ChAT) , while decreased that of acetylcho-line esterase( AChE) . Moreover, MEM activiated NGF signaling by increasing the phosphorylation of TrkA fol-lowing the increased phosphorylation of c-Raf, ERK1/2 and downstream effector CREB after MEM treatment. Conclusion MEM treatment may activate the NGF/TrkA signaling in APP/PS1 mice to reduce amyloidosis and cognitive deficits.

Objective To compare the clinical features of pulmonary infections with Mycobacterium intracellulare and Mycobacterium abscessus in the tuberculosis intensive care unit (ICU).Methods Clinical data of 74 patients with non-tuberculous mycobacterial pulmonary infection (NTM) admitted in tuberculosis ICU of Hangzhou Red Cross Hospital from January 2012 to May 2017 were retrospectively analyzed.There were 54 patients infected with Mycobacterial abscesses, 16 patients with Mycobacterial intracellular, 2 patients with Mycobacterium avium and 2 patients with Mycobacterium kansasii.The clinical features, imaging manifestations, treatment and prognosis of patients with Mycobacterial intracellular and Mycobacterial abscesses lung infections were compared.SPSS 21.0 software was used for statistical analysis.Survival curve analysis was performed using GraphPad Prism V 5.01.Results Among 74 patients with NTM lung disease , the infection rate of Mycobacterium abscessus was 72.87%(54/74), and the infection rate of Mycobacterium intracellular was 21.62%( 16/74 ).The age of patients with Mycobacterium intracellularis pulmonary disease was younger and the length of ICU stay was shorter than those of patients with Mycobacterium abscessus (t＝－2.729 and －6.150, P＜0.05 or ＜0.01).There was no significant difference in the gender distribution and APACHE Ⅱ scores between the two groups ( both P＞0.05).The proportion of patients with chronic obstructive pulmonary disease ( COPD) in Mycobacterium intracellularis group was significantly lower and the proportion of patients with bronchiectasis was significantly higher than those in Mycobacterial abscesses group (χ2＝3.902, P＜0.05; χ2＝23.888, P＜0.01).The proportion of patients complicated with stroke sequelae , Parkinson's disease and other central nervous system diseases ( χ2＝14.872, P＜0.01) and diabetes (χ2＝3.902, P＜0.05) in Mycobacterial abscess group was significantly higher, and that of hemoptysis was significantly lower (χ2＝9.717, P＜0.01) than those in Mycobacterium intracellularis group.Respiratory failure (93.75%) and septic shock (6.25%) were the main reasons of ICU admission for patients with Mycobacterium intracellularis lung disease; while respiratory failure (90.74%), heart failure (11.11%) and renal failure (1.85%) were main reasons of ICU admission for patients with Mycobacterial abscesses; there were no significant differences in the causes of ICU admission between the two groups ( all P＞0.05).The proportion of NTM isolated from patients with Mycobacterial intracellular lung disease, prior to mechanical ventilation was significantly higher than that of patients with Mycobacterial abscess ( χ2＝30.366, P ＜0.01 ).In imaging, the proportion of bronchiectasis in Mycobacterium intracellularis lung disease group was significantly higher than that in Mycobacterial abscesses lung disease group (χ2＝23.888, P＜0.01).There was no significant difference in the 28-day mortality rate between the two groups (χ2＝3.244, P＞0.05), while the survival rate in patients with Mycobacterium intracellularis lung disease within 120 days was significantly higher than that in patients with Mycobacterial abscesses lung disease (χ2＝12.780, P＜0.01).Conclusion When critically ill patients are positive for acid-fast staining, the ICU physician should consider the possibility of NTM lung disease.For severe patients with long-term mechanical ventilation , Mycobacterium abscessus infection should be considered first.

Objective To analyze the efficacy and safety of PD-1 inhibitor combined with anlotinib on advanced neuroendocrine carcinoma. Methods We collected the data of patients with advanced neuroendocrine carcinoma who had failed the first-line standard chemotherapy and treated with PD-1 inhibitor combined with anlotinib from the First Affiliated Hospital of Zhengzhou University. Results A total of 45 patients, including 24 males and 21 females, were included. The median age was 57 years old. The primary tumor sites were lung (23 cases, 51.1%), esophagus (8 cases, 17.8%), pancreas (7 cases, 15.6%) and rectum (7 cases, 15.6%). Eighteen cases (40%) had failed the first- and second-line treatments, and 27 cases (60%) had failed the third-line and above treatments. All patients received 2-15 cycles of treatment, 3 cases died due to disease progression, overall objective response rate was 11.1%, disease control rate was 53.5%, median progression-free survival was 5.8 months, and 10-month progression-free survival rate was 25.5%. Adverse events were mainly grade 1-2 myelosuppression and digestive tract reactions. Conclusion PD-1 combined with anlotinib show better efficacy and good tolerance on advanced neuroendocrine carcinoma. It can be used as a choice after the failure of standard first-line treatment of advanced neuroendocrine carcinoma.

Objective To evaluate the effects of enteral immunonutrition on cell immunity level and clinical efficacy in patients with severe tuberculosis. Methods Sixty patients with severe tuberculosis were admitted to the department of tuberculosis intensive care unit of Hangzhou Red Cross Hospital from June 2015 to June 2017, and they were randomly divided into a conventional enteral nutrition group (EN group) and a enteral immunonutrition group (EIN group), each group 30 cases. Based on the patients' gastrointestinal tolerance condition, the EN group was treated with therapies of normal nutrition support, anti-tuberculosis, anti-infection, etc.; the EIN group was treated with enteral immunonutrition (TPF-T), and simultaneously with anti-tuberculosis, anti-infection, etc. therapies according to the disease situation. The target energy maintained at 104.6 kJ·d-1·kg-1and the therapeutic course was 14 days in the two groups. The levels of interleukins (IL-6, IL-10) and interferon-γ (IFN-γ), white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), cell immune indexes (T cell subgroup CD4+, CD8+) were observed before treatment and on day 14 after treatment in the patients of two groups; the changes of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score before treatment and after treatment and 28-day mortality rate were recorded in the two groups. Results After treatment, the levels of WBC, CRP, PCT were obviously lower than those before treatment, while the levels of IL-6, IFN-γ, CD4+in the two groups were significantly higher than those before treatment, and the changes of the EIN group were more significant than those in the EN group [WBC (×109/L): 8.0±3.1 vs. 10.0±2.4, CRP (mg/L): 30.3±9.1 vs. 45.8±6.6, PCT (μg/L): 2.2±1.8 vs. 4.3±2.2, IL-6 (mg/L): 182.53±8.52 vs. 168.42±7.62, IFN-γ (mg/L): 32.52±3.5 vs. 25.41±2.6, CD4+: 0.56±0.06 vs. 0.45±0.08, all P < 0.05]. The level of CD8+after treatment in the two groups was higher than that before treatment (the EN group: 0.28±0.06 vs. 0.27±0.07, the EIN group: 0.27±0.08 vs. 0.26±0.09), the APACHE Ⅱ scores in the two groups were lower than those before treatment (the EN group: 11±6 vs. 18±4, the EIN group: 10±3 vs. 17±6), the 28-day mortality in the EIN group was lower than that in the EN group [13.3% (4/30) vs. 16.7% (5/30)], no statistical significant difference in CD8+, APACHE Ⅱscore, 28-day mortality between the two groups being found (all P > 0.05). Conclusion Enteral immunonutrition can improve the level of cell immunity and decrease the degree of inflammatory response, and increase the clinical curative effect in patients with severe tuberculosis.

Objective:To investigate the clinical feasibility of three-dimensional contrast-enhanced ultrasound (3D-CEUS) in the quantitative assessment of blood perfusion of hepatocellular carcinoma (HCC).Methods:Between January 2020 and August 2021, 36 HCC patients (39 lesions in total) confirmed by pathology and clinical diagnosis without any treatment from Zhongshan Hospital, Fudan University were enrolled and underwent both 2D-CEUS and 3D-CEUS examinations. Each examination last for 150 s and all images were recorded, and then the data were analyzed. A region of interest was manually drawn along the margin of the whole tumor and then the time-intensity curve (TIC) generated. The following perfusion parameters were extracted: peak intensity (PI), peak time (TTP), ascending slope (AS), mean transit time (MTT) and area under the curve (AUC). After calculating the quality of fit (QOF) of the curve, the intraobserver agreement of the 3D-CEUS quantitative parameters obtained by the same doctor between two times were assessed, and the consistency of the 3D-CEUS and 2D-CEUS quantitative parameters was evaluated when QOF>75%. The differences of the quantitative parameters between different groups (divided by depth of 8 cm and necrosis rate of 50%, respectively) in 3D-CEUS were compared.Results:There were 38 lesions (97.4%, 38/39) with QOF>75% in 3D-CEUS. The intraobserver agreement was excellent, the intraclass correlation efficient(ICC) values was 0.85-0.99. The consistency of the time quantitative parameters (TTP and MTT) were high (the ICC values of 0.87 and 0.91), and the correlation of intensity quantitative parameters were substantial, the rs values were 0.71, 0.72 and 0.71. The differences in 3D-CEUS quantitative parameters of the two groups of lesions with different depths were statistically significant (all P<0.05); but there were no significant differences in quantitative parameters between the two groups with different necrosis rate (all P>0.05). Conclusions:Quantitative 3D-CEUS is an useful and creditable tool in evaluating the blood perfusion of HCC, especially when the depth of lesion was less than 8 cm.

Objective:To analyze the serum and urinary amino acid (AA) profiles of urolithiasis patients to explore the potential biomarkers for clinical screening and early diagnosis.Methods:Case-control study. Serum and urine samples were collected from 74 urolithiasis patients (aged 20-82 years, 41 men, 33 female) in the department of urology of the First Affiliated Hospital of Fujian Medical University and 35 healthy controls (HC, aged 22-80 years old, 20 men, 15 female) from the health examination center from February 2015 to October 2017. Serum and urinary AA levels of patients and HC were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS) based metabolomic strategy. The multivariate statistical analysis methods of principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) were employed for modeling. The variable importance projection (VIP) value of OPLS-DA model>1 and P<0.05 of t test were selected to screen the differential amino acid metabolites. The diagnostic capabilities of potential markers were evaluated by receiver operating characteristic (ROC) curve and binary logistic regression analysis. Results:Five AA metabolites including serine, glutamate, aspartic acid, isoleucine and glycine were found, which had statistically significant differences between the patient group and the control group ( P<0.05) and were associated with seven metabolic pathways. Serum serine, glutamate, aspartic acid, isoleucine and urine glycine and aspartic acid were combined into an integrated marker panel whose AUC value was 0.890, the sensitivity was 78.0%, and the specificity was 96.4%. Conclusion:Five amino acids in serum and urine could be used as an integrated biomarker panel for the clinical screening and early diagnosis of urolithiasis, which could provide some experimental basis for molecular urolithiasis research.