There are difficulties in the treatment of Alzheimer's disease (AD) in medical community. Since the surgery of cervical deep lymphatic vessel/lymphatic node-vein anastomosis (LVA/LnVA) has made clinical improvement in patients with AD, it offers a surgical option to treat AD. Especially improvements in cognitive impairment. However the mechanism in treatment of AD is not yet made clear. This article preliminarily explores the mechanism in improvement of some symptoms in patients with AD through cervical deep LVA/LnVA on the basis of morphological characteristics of the cribriform plate-cervical lymphatic pathway.

There are difficulties in the treatment of Alzheimer's disease (AD) in medical community. Since the surgery of cervical deep lymphatic vessel/lymphatic node-vein anastomosis (LVA/LnVA) has made clinical improvement in patients with AD, it offers a surgical option to treat AD. Especially improvements in cognitive impairment. However the mechanism in treatment of AD is not yet made clear. This article preliminarily explores the mechanism in improvement of some symptoms in patients with AD through cervical deep LVA/LnVA on the basis of morphological characteristics of the cribriform plate-cervical lymphatic pathway.

Objective To investigate the effect of Gouteng Jiangya Jieyu Perscription(Uncariae Ramulus cum Uncis,Gastrodiae Rhizoma,Pheretima,Puerariae Lobatae Radix,etc.)modulating the TLR4/NF-кB signaling pathway on the polarization of hippocampal microglia in rats with hypertension complicated with depression(HD)Methods Forty primary hypertensive rats were randomly divided into five groups:the model group,the positive drug group,and the high-,medium-,and low-dose groups of Gouteng Jiangya Jieyu Perscription,with 8 rats in each group;and another 8 SD rats were taken as the control group.The HD model was replicated using 42 days of continuous chronic unpredictable mild stress(CUMS)combined with solitary rearing.The modeling was accompanied by the administration of drugs,including 29.61,14.81,and 7.40 g·kg-1 of Gouteng Jiangya Jieyu Perscription in the high-,medium-,and low-dose groups of Chinese herbal medicine,respectively,and 0.45 mg·kg-1 of Levamlodipine Besylate+1.8 mg·kg-1 of Fluoxetine in the positive group;the volume of the gavage was 10 mL·kg-1,once a day,for 42 consecutive days.The systolic blood pressure of rat tail artery was measured by non-invasive sphygmomanometer before drug administration and in the morning of the last day of each week;the behavioural test of Sucrose Preference Test(SPT)was carried out once in the second week and once in the last week after the start of the modelling;the water maze experiment was carried out after the end of the modelling;the levels of serum inflammatory factor tumor necrosis factor-α(TNF-α),interleukin(IL)1β and IL-10 were determined by ELISA;the pathological changes of rat hippocampal tissue neurons were observed by HE staining and Nissl stain were used to observe the neuronal pathological changes in rat hippocampal tissue;immunofluorescence double staining was used to detect the expressions of microglia M1(CD16)and M2(CD206)types in the hippocampal region;and Western Blot was used to detect the protein expressions of TLR4 and NF-кB p65 in the hippocampal tissue.Results Compared with the control group,the systolic blood pressure in the tail artery of rats in the model group from week 1 to week 6 were all significantly increased(P＜0.01);sucrose preference rate was significantly decreased(P＜0.01);evasion latency was significantly prolonged(P＜0.05,P＜0.01),the number of times of traversing the plateau and the percentage of time spent in the target quadrant were significantly decreased(P＜0.01);the contents of serum TNF-α and IL-1β were significantly increased(P＜0.01),IL-10 content was significantly decreased(P＜0.01);cytosolic nuclei were deeply stained,cytoplasmic solidification and apoptosis were obvious;the fluorescence intensity ratio of CD206/CD16 in hippocampal microglial cells were significantly decreased(P＜0.05);the protein expressions of TLR4 and NF-кB p65 in hippocampal tissues were significantly up-regulated(P＜0.01).Compared with the model group,the systolic blood pressure in the tail artery of rats in the first to sixth weeks of the drug administration group were all significantly reduced(P＜0.01);the sucrose preference rates were all significantly increased(P＜0.05);the contents of serum TNF-α and IL-1β were significantly decreased(P＜0.01),and the content of IL-10 was significantly increased(P＜0.01);the Nissl substances are abundant and apoptosis is significantly reduced,and apoptosis were significantly reduced.The escape latency of rats in the positive drug group and the high-dose group of Gouteng Jiangya Jieyu Perscription was significantly shortened(P＜0.05,P＜0.01),and the number of times of crossing the plateau and the percentage of time spent in the target quadrant were significantly increased(P＜0.05);the ratio of fluorescence intensity of hippocampal microglial cells,CD206/CD16 was significantly increased(P＜0.05,P＜0.01);and the hippocampal tissues,protein expressions of TLR4 and NF-κB p65 were significantly down-regulated(P＜0.05,P＜0.01).Conclusion Gouteng Jiangya Jieyu Perscription may regulate the polarisation state of hippocampal microglial cells,modulate the secretion of inflammatory factors,and attenuate the damage of hippocampal neurons in HD rats by inhibiting the TLR4/NF-кB pathway.

Objective:To evaluate the clinicopathologic characteristics and prognosis of primary squamous cell carcinoma of the thyroid (PSCCT).Methods:We reported 16 cases who were operated on and histologically diagnosed with primary squamous cell carcinoma of the thyroid from Jan 2012 to Dec 2016.Results:Among the 16 patients with PSCCT,there were 10 females (62%) and 6 males (38%),mean age was (58.13±11.21) years old. Univariate analysis showed that gender ( χ2=4.367, P=0.037), tumor size ( χ2=5.630, P=0.018) and radical surgery ( χ2=11.123, P=0.001) were important predictive factors for overall survival.COX regressing analysis showed radical surgery was independent prognostic factors ( P=0.034). Conclusions:PSCCT is a rare thyroid cancer with an aggressive nature and poor prognosis. Radical surgery was associated with a fair outcome.

Objective:To evaluate the clinicopathologic characteristics and prognosis of primary squamous cell carcinoma of the thyroid (PSCCT).Methods:We reported 16 cases who were operated on and histologically diagnosed with primary squamous cell carcinoma of the thyroid from Jan 2012 to Dec 2016.Results:Among the 16 patients with PSCCT,there were 10 females (62%) and 6 males (38%),mean age was (58.13±11.21) years old. Univariate analysis showed that gender ( χ2=4.367, P=0.037), tumor size ( χ2=5.630, P=0.018) and radical surgery ( χ2=11.123, P=0.001) were important predictive factors for overall survival.COX regressing analysis showed radical surgery was independent prognostic factors ( P=0.034). Conclusions:PSCCT is a rare thyroid cancer with an aggressive nature and poor prognosis. Radical surgery was associated with a fair outcome.

Objective:To study the protective effect and possible mechanism of psoralen corylifolia on non-alcoholic steatohepatitis (NASH) induced by high-fat diet in mice.Methods:The newly weaned female mice in the offspring of C57BL/6J mice fed with normal diet were selected as the control group (gavage of distilled water); the newly weaned female mice in the offspring of C57BL/6J mice fed with high-fat diet were randomly divided into model group (gavage distilled water), low-dose group[psoralen corylifolia 1.125 mg/(g·d)], high-dose group [psoralen corylifolia 2.25 mg/(g·d)] and vitamin E group [vitamin E 0.01 mg/(g·d)]. Six mice in each group were fed continuously for 8 weeks. Automatic biochemical analyzer was used to detect serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), total cholesterol (TC) level in mice; The liver tissue pathological changes were observed by hematoxylin-eosin (HE) and Sirius-red (SR) staining; The level of reactive oxygen species (ROS) in liver tissue was detected by dihydroethidium (DHE) fluorescence probe; the activity of NADPH oxidase was detected by kit; The protein expressions of nuclear factor-κB (NF-κB), phosphatidylinositol 3 kinase (PI3K p85), protein kinase B (Akt), P47 phox and protein kinase C-α (PKC-α) were detected by Western blot.Western blot. Results:The levels of serum ALT, AST, TG, TC and homeostasis model assessment of insulin resistance (HOMA-IR) index in the model group were higher than those in the control group (all P<0.01). After treatment, the levels of serum ALT, AST, TG, TC and HOMA-IR in low-dose group, high- dose group and vitamin E group were lower than those in model group (all P<0.05). HE and SR staining showed that hepatocytes in the model group were swollen, and there were lipid droplets of different sizes, vacuoles and obvious fibrosis. After treatment, hepatocyte steatosis and fibrosis decreased and the contents of ROS and NADPH oxidase in liver decreased(all P<0.05); Western blot showed that the p-p65/p65, p-Akt/Akt, p-PKC-α/PKC-α, PI3K, p85 and P47 phox protein expression in the model group were higher than those in the control group (all P<0.01). After treatment, the protein expression levels of p-p65/p65, p-Akt/Akt, p-PKC-α/PKC-α, PI3K, p85 and P47 phox decreased (all P<0.01). Among the above indexes, the protective effect of high-dose group on liver NASH was better than those of vitamin E group and low-dose group (all P<0.05). Conclusions:Psoralen corylifolia can improve the liver function of NASH model mice, which may be related to the inhibition of oxidative stress, inflammatory reaction and liver fibrosis, which provides a new idea for the prevention and treatment of children with NASH.

Objective:To investigate clinicobiological characteristics and treatment principles of diffuse calcified variant of papillary thyroid carcinoma.Methods:Twenty one patients with diffuse calcified thyroid glands admitted to the Department of Head and Neck Surgery of Tianjin Medical University Cancer Hospital from Jan 2011 to Dec 2015 were enrolled in the study group. One humdred and five patients with papillary thyroid carcinoma (PTC) confirmed by postoperative pathology (non-diffuse calcified thyroid nodules) during the corresponding period were included into the control group. The clinicobiological characteristics of different cases were analyzed by collecting the following information: gender, age, ultrasonic features, thyroid function, pathological type, lymph node metastasis, BRAF V600E mutation and follow-up.Results:No significant difference was found between the study group and the control group in gender, age or the number of patients complicated with Hashimoto′s thyroiditis; while there were significant differences in bilateral involvement of central lymph node metastasis, lateral neck lymph node metastasis and positive rate of BRAF V600E mutant protein expression in postoperative specimens ( P<0.01). As found by postoperative follow-up, there was no significant difference in the rate of neck lymph node recurrence between the two groups. Conclusions:Diffuse calcified variant of papillary thyroid carcinoma is a new subtype of PTC with unique clinicobiological characteristics, and more active clinical treatment programme should be adopted for the diffuse calcified thyroid carcinoma.

Objective: To establish an accurate and selective UPLC-MS/MS) method for the determination of afatinib in rat plas-ma. Methods: Protein precipitating by acetonitrile was used to prepare the samples. A CORTECS BEH C18column ( 50 mm × 2. 1 mm, 1. 6 μm) was used to separate the analytes at 40℃. The mobile phase consisted of acetonitrile and water (0. 1% formic acid) with the flow rate of 0. 4 ml·min-1. The analytes were quantified by multiple reaction monitoring ( MRM) mode with positive electrospray ionization, while the target fragment ions were m/z 486. 19→112. 1 for afatinib and m/z 557. 3→112. 15 for neratinib (IS). Results: The calibration curve obtained good linearity for afatinib within the range of 1–200 ng·ml-1(r=0. 998 1), and the LLOQ in rat plasma was 1. 0 ng/ml. The intra-and inter-day precisions were both≤9. 51% . The recovery of afatinib from plasma was above 77. 1% . After intragastric administration and intravenous administration of afatinib in rats, the t1/2was 7. 19 h and 2. 69 h, Cmax was 97. 78 ng·ml-1and 123. 37 ng·ml-1,and AUC(0-∞)was 1 505. 4 ng·ml-1·h and 405. 55 ng·ml-1·h, respectively. Con-clusion: The validated method can be applied in the pharmacokinetic study of afatinib at the intragastric and intravenous dosage of 10 and 2 mg·kg-1, respectively.

Objective To explore the executive function in patients with mild traumatic brain injury (mTBI). Methods The evaluation of executive function was conducted in 63 mTBI patients in 1 week, 1, 3 and 6 month after injury and 60 health controls. The executive function was evaluated using Trail Making Test (TMTA), Hopkins Verbal Learning Test-revised (HVLT-R), Brief Visuospatial Memory Test-revised (BVMT-R), Stroop Color Word Tes and Con-tinuous Performance Test (CPT). Results There were significant differences between mTBI patients and controls in TM-TA, HVLT-R, BVMT-R, Stroop Color Word Test and CPT a week following TBI (P<0.05). There were a significant in-crease in scores of TMTA and a significant decrease in HVLT-R, BVMT-R, stroop and CPT-IP at 1, 3 and 6 month compared with 1 week following TBI (P<0.05). There were a significant decrease in TMTA and a significant increase in BVMT-R and stroop 1 month compared with 1 week following TBI (P<0.05). There were a significant increase in stroop, BVMT-R and CPT-IP at 3 month compared with 1 month following TBI (P<0.05). There was a significant increase in stroop and CPT-IP at 6 month compared with 3 month following TBI (P<0.05). Conclusions Patients with mTBI have executive function impairment. The recovery times of different executive function are different in patients with mTBI.

Objective To research the effect ofparecoxib on hippocampal nerve cell apoptosis and expressions of B cell lymphoma/lewkmia-2 (Bcl-2),Bcl-2 associated X protein (Bax) and caspase-3 of epilepsy rats.Methods Thirty SD male rats were randomly divided into three groups (n=10):control group,parecoxib treatment group and epilepsy group.The rats in the parecoxib treatment group and epilepsy group were injected with 4 mg/kg of parecoxib and same volume of saline,respectively,and 3 d after that,they both were injected intraperitoneally with 3 mmol/kg of lithium chloride,and then,20 h after that,they were injected intraperitoneally with 30 mg/kg ofhydrochloride pilocarpine; while rats in the control group were only injected intraperitoneally with the same volume of saline.The behavior changes of rats in the three groups were observed.After 7 d,terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) was used to evaluate the neuronal apoptosis and Western blotting was employed to evaluate the expressions of Bcl-2,Bax and caspase-3 in the hippocarnpus of all groups.Results All epilepsy rats were very irritable; spontaneous seizures (SRS) times of precoxib treatment group were significantly reduced as compared with those of epilepsy group (P＜0.05).As compared with those in the control group,the Bcl-2,Bax and caspase-3 expressions and Bcl-2/Bax ratio in the epilepsy group were increased with statistically significant differences (P＜0.05); As compared with those in the epilepsy group,the Bcl-2,Bax and caspase-3 expressions and Bcl-2/Bax ratio in the precoxib treatment group were decreased with statistically significant differences (P＜0.05).As compared with that in the control group,the number of TUNEL positive cells in hippocampus of rats in the precoxib treatment group and epilepsy group were significantly increased (P＜0.05); as compared with that in the epilepsy group,the number of TUNEL positive cells in the hippocampus of precoxib treatment group was statistically reduced (P＜0.05).Conclusion Parecoxib can reduce the apoptosis of hippocampus neurons through inhibiting the protein expressions of Bax and caspase-3 to affect the Bcl-2 protein expression,whose mechanism may be related to the pathways of Bcl-2/Bax and Caspase-3 proteins.