Objective To investigate effects of metabotropic glutamate receptor subtype 5 (mGluR5) antagonist MTEP on the nociceptive behavior and the expression of glial fibrillary acidic protein (GFAP) in spinal cord associated with bone cancer pain. Methods C3H/HeNCrlVr 60 male mice were randomly divided into 5 groups: ( 1 ) normal control group: the mice were given food and water ad libitum; ( 2 ) MTEP + Tumor group: the mice were treated by intrathecal gdministration ( once daily on the days 14 ～20 after inoculation of tumor cells)with MTEP (150 nmol); (3) physiological saline + Tumor group:the tumor mice were treated with the same volume of physiological saline; (4) MTEP + Sham group: the sham mice were treated with the same dose of MTEP;(5) physiological saline + Sham group: the sham mice were treated with the same volume of physiological saline.the mice pain behaviors were assessed with the paw withdrawal thermal latency (PWTL) at the corresponding time points, then the mice were killed and the samples of spinal cord were used to real-time PCR and western blot detection of GFAP mRNA and protein expression. Results The basic values of PWTL had no significant differences among all groups (P＜0.05). At day 14 after operation,no significant difference was found in the PWTL value between normal control group and the sham operation group. But in tumor group, the PWTL value was significantly lower than in the normal control group (P＜ 0.05 ). At day 21 after operation,the PWTL and the level of GFAP expression in the spinal cord had no significant differences among normal control group, MTEP + Sham group and physiological saline + Sham group (P ＞ 0.05 ); the PWTL ( (6. 18 ± 1.29 ) s) in physiological saline + Tumor group was significantly lower than in normal control group ( ( 15.91 ± 1.65 )s), physiological saline + Sham group ( ( 16.57 ± 1.86) s) and MTEP + Sham group ( ( 17.05 ± 2.43 ) s) (P ＜ 0.05 ), but the level of GFAP expression was higher than in the above three groups. In MTEP +Tumor group ,the PWTL (9.39 ± 1.94s) was higher than in physiological saline + Tumor group, and the level of GFAP expression was lower than in physiological saline +Tumor group (P ＜ 0.05 ). Conclusion Inhibiting spinal activation of astrocytes may be one of the MTEP anticancer pain mechanisms.

Objective To observe the change of capillary pericapillary cells in rats with myocardial infarction and the influence of supplementing qi and activating blood circulation herbs, and explore its mechanism of improving myocardial perfusion. Methods The rat model was established by ligaturing the left anterior descending coronary artery. On the base of ECG evaluation, successfully modeled rats were randomly divided into the model group, group treated with supplementing qi and activating blood circulation Chinese medicine (activating blood and supplementing qi group), group treated with Perindopril (Perindopril group), group treated with Tongxinluo Capsules (Tongxinluo group). The sham-operation group was taken as the control. There were totally 5 groups. The model group and the sham-operation group were treated with normal saline. The changes of myocardial capillary density (MCD) and number of pericapillary cells on the 7th, 28th day after medicinal administration were observed. Results On the 7th and 28th day, the MCD decreased significantly and the number of capillary pericapillary cells increased significantly in the model group compared with the sham-operation group (P<0.01). The MCD increased significantly in the activating blood and supplementing qi group, Perindopril group and Tongxinluo group compared with the model group (P<0.01). The number of pericapillary cells decreased significantly in the activating blood and supplementing qi group, Perindopril group and Tongxinluo group compared with the model group (P<0.01). Conclusion The supplementing qi and activating blood circulation herbs can improve regional myocardial blood supply by decreasing the number of pericytes and promoting regeneration of capillary.

Objective:ATP-binding cassette transporter A1 (ABCA1) is an integral membrane protein that plays a key role in cellular lipid metabolism,preventing the accumulation of lipids that contribute to the initiation and progression of atherosclerosis.Tiaozhi Tongmai Granules are a Chinese herbal compound that is capable of treating atherosclerosis.This study was de-signed to explore the potential pharmacological mechanism by which Tiaozhi Tongmai Gran-ules protect against atherosclerosis.Methods:Forty-nine male New Zealand rabbits were randomly divided into seven groups:normal control group,normal diet;model groups 1 and 2:balloon injury and high-fat diet for 6 or 12 weeks;statin groups 1 and 2:balloon injury and high-fat diet plus atorvastatin for 6 or 12 weeks;and Chinese herb groups 1 and 2:balloon injury and high-fat diet plus Tiaozhi Tongmai Granules for 6 or12 weeks.The granules were administered at a dose of 1.14 g/kg/d,with atorvastatin(1.14 mg/kg/d) serving as positive control.Serum lipid profiles and liver function indices were measured.Atherogenesis was viewed after H&rE staining and quantified by thickened intimal area percentage and maximal intimal thickness percentage.The ABCA1 protein expression in athero-sclerotic plaque macrophages of the common carotid arteries (CCA),thoracic aortae (TA),and liver tissues were observed by immunohistochemical staining and evaluated using mean optical density (OD) value in macrophages and ABCA1-positive hepatocyte number.Results:Compared with model group 1 at week 6,Chinese herb group 1 and statin group 1 dis-played significant reductions in total cholesterol (TC) (P =0.027,0.012) and low-density lipopro-tein cholesterol (LDL-C) (P =0.039,0.028) levels,as well as marked increases in ABCA1-positive hepatocyte numbers (Pall ＜0.001),and only statin group 1 displayed a markedly reduced maximal intimal thickness percentage in the CCA (P =0.018).Compared with model group 2 at week 12,Chinese herb group 2 and statin group 2 all presented significant reductions in TC (P =0.011,0.003),LDL-C (P =0.017,0.010) and thickened intimal area percentage in the CCA (P =0.001,0.022),as well as prominent increases in the ABCA1OD value of both the CCA (P =0.001,0.039) and TA (P =0.001,0.025) and positive hepatocyte number (P all ＜0.001).Chinese herb group 2 had a markedly reduced maximal intimal thickness percentage compared with model group 2 (P =0.006) and a higher positive hepatocytes number than statin group 2 (P =0.001).Conclusions:Tiaozhi Tongmai Granules appear to have an anti-atherogenic effect that is most likely mediated by simultaneously upregulating the protein expression of ABCA1 in rabbit athero-sclerotic plaque macrophages and in the liver.

Carcinoma, Squamous Cell ; diagnosis ; Carcinoma, Verrucous ; diagnosis ; Epidermis ; pathology ; Humans

Background::Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, there are limited reports on the relationship between serum uric acid levels and biological treatment efficacy. The purposes of this study were to compare the differences in serum uric acid levels between patients with psoriasis and healthy controls and analyze the risk of hyperuricemia.Methods::A total of 196 patients with psoriasis and 191 age- and sex-matched healthy controls were enrolled in this retrospective cohort study. One hundred and twenty-seven patients with severe psoriasis were treated with biologics. Sixty-eight patients received adalimumab, and 59 patients received secukinumab. Serum uric acid levels were measured at baseline, week 24, and week 48 of treatment.Results::Patients with psoriasis had higher serum uric acid levels than healthy controls (6.4 ± 1.7 mg/dL vs. 5.7 ± 1.5 mg/dL, P < 0.001). Hyperuricemia was found in 33.7% (66/196) of patients with psoriasis, which was significantly higher than that in healthy controls (13.1% [25/191], P < 0.001). Serum uric acid levels and hyperuricemia were not related to the severity of psoriasis ( P > 0.05). No significant changes in serum uric acid levels and hyperuricemia were observed following adalimumab treatment ( P > 0.05). The serum uric acid level in patients treated with secukinumab was 6.7 ± 1.6 mg/dL at week 24, which was not statistically different from that at baseline (6.6 ± 1.4 mg/dL, P = 0.885). Serum uric acid levels were significantly decreased at week 48 (6.3 ± 1.5 mg/dL vs. 6.6 ± 1.4 mg/dL, P = 0.007) in patients treated with secukinumab. Secukinumab had no significant effect on hyperuricemia either ( P > 0.05). Conclusions::The serum uric acid levels and prevalence of hyperuricemia in patients with psoriasis were significantly higher than those in healthy controls. Secukinumab treatment for 48 weeks successfully decreased serum uric acid levels in patients with psoriasis, whereas adalimumab had no significant effect on serum uric acid levels.

Objective To investigate the reduce of experimental autoirnmune encephalomyelitis(EAE) susceptivity after lipopolysaccharide (LPS) exposure in neonatal rats and its relation with inhibition of macrophage immune function.Methods Litter male neonatal rats were divided into blank control group (n=1 1),phosphate buffer (PBS) group (n=12) and LPS group (n=12);rats in the LPS group were performed intraperitoneal injection of 50 μL LPS on postpartum day 3 and 5.Rats in the PBS group and LPS group were established EAE models by immune induce of spinal cord homogenate of guinea pig with complete Freund's adjuvant at 12 weeks old,while rats in the blank control group were given immune induce of complete Freund's adjuvant.Since the day of induce,the behavioral scale scores of all the rats were assessed.On the 20th d,all rats were sacrificed and paraffin sections were cut and stained with HE to detect inflammatory cell infiltration.The number of infiltrating macrophages and the expressions of CD86,CD80,MHC-Ⅱ were determined by flow cytometry.The transcriptional levels of C-C chemokine receptor type 2 (CCR2),interleukin (IL)-1β and tumor necrosis factor (TNF)-α in macrophages were determined by real-time fluorogenic quantitative PCR.Results As compared with the PBS group,LPS group had significantly lower EAE incidence (11/12 vs.5/12) and higher EAE latency ([10.50±0.71] d vs.[12.17± 1.17] d),and statistically decreased cumulative clinic scores and peak clinic scores (20.00±9.13 vs.5.58±7.12;2.58±1.08 vs.1.03±0.83,P＜0.05).The inflammation in the spinal cord of the PBS group was severer than that in the LPS group (2.83±0.75 vs.1.17±1.17,P＜0.05).The number of infiltrating macrophages of the PBS group was significantly larger than that in the LPS group ([202.70 ±81.89] × 103 cells vs.[92.58 ±42.65] × 103 cells,P＜0.05).The expressions of CD80 and MHC-Ⅱ,and mRNA levels of CCR2,IL-1β and TNF-α in the PBS group were significantly higher than those in the LPS group (P＜0.05).Conclusion Neonatal LPS exposure reduces the severity of EAE,which may relate to impaired macrophage immune function.

Objective To investigate the effect of omeprazole on plasma concentration, efficacy and adverse reactions of capecitabine in patients with colon cancer. Methods Seventy?two patients with colon cancer treated with capecitabine were analysed retrospective. The patients treated with capecitabine combined with omeprazole were identified as experimental group and the capecitabine treatment alone as control group. The differences of blood concentration and the side effects of capecitabine between these two groups were compared. Results The plasma concentration of 5?Fluorouracilum in experimental group was ( 126.25 ± 50.59) μg／ml, without significant difference of (123.09±56.70) μg／ml in control group (P＝0.121). The incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and hand?foot syndrome in experimental group were 13.8%, 0%, 0% and 19.4%, respectively. In control group, the incidence ofⅢto Ⅳdegree bone marrow suppression, nausea, vomiting, diarrhea and the hand?foot syndrome were 11.1%, 0%, 0% and 19.4%, respectively, without significant difference of experimental group ( P＞0.05). The incidence of acid reflux and heartburn in the control group was 72.2%, significantly higher than 44.4% of the experimental group ( P＜0.05). The objective response rate ( ORR) and progression?free survival time (PFS) in these two groups were 30.6% and 33.3%, and 8.0 month and 8.5 month, respectively, without significant difference (P＞0.05). Conclusion The intravenous omeprazole attenuates reflux and heartburn of colon cancer patients treated with capecitabine, without affecting its plasma concentration and side effects and has no impact on the PFS of these patients.

Objective To investigate the myocardial expressions of protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathway and effective mechanism of Yiqi Huoxue Fang depending on model of myocardial ischemia.Methods The model of acute myocardial infarction (AMI) was established through ligation of left coronary anterior descending branch in SD rats, and randomly divided into model group, perindopril group, Qishen Yiqi Gutta Pills group, Yiqi Huoxue Fang group and sham-operation group, and all groups were given orally corresponding medications respectively 2 d after operation.The observation time points were set on the 7th d and 28th d.The changes of heart function and structure were detected by using ultrasonic testing, changes of myocardial pathomorphology were observed after HE staining, and expressions of Akt, mTOR, p-Akt and p-mTOR in infarction marginal zone were detected by using Western blot test, real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry technique in all groups.Results The level of left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) decreased significantly in model group compared with sham-operation group on the 7th d and 28th d (P<0.01).The level of left ventricular end-systolic volume (LVESV) increased significantly on the 7th d (P<0.01), and levels of LVESV and left ventricular end-diastolic volume (LVEDV) increased significantly (P<0.01) on the 28th d in model group.The levels of LVEF and LVFS increased and levels of LVEDV and LVESV decreased significantly in all medicated groups compared with model group (P<0.01).The thinner ventricular wall, less cardiomyocytes, disorder myocardial cells arrangement and inflammatory cell infiltration were observed in infarction marginal zone in model group, and disorder myocardial cells arrangement and less cardiomyocytes were observed in all medicated groups.The ratio of p-Akt/Akt and p-mTOR/mTOR increased (P<0.05), expressions of Akt m-RNA and mTOR m-RNA increased significantly (P<0.01), and levels of p-Akt and p-mTOR positive cell rates increased significantly (P<0.01) in model group.The ratio of p-Akt/Akt and p-mTOR/mTOR increased (P<0.05), expressions of Akt m-RNA and mTOR m-RNA increased (P<0.05 or P<0.01), and levels of p-Akt and p-mTOR positive cell rates increased significantly (P<0.05) in all medicated groups.Conclusion Yiqi Huoxue Fang can improve heart function and protect myocardial cells through activating cardiac self-protective mechanism-Akt/mTOR signaling pathway in rats with myocardial infarction.

Objective To investigate the effect of omeprazole on plasma concentration, efficacy and adverse reactions of capecitabine in patients with colon cancer. Methods Seventy?two patients with colon cancer treated with capecitabine were analysed retrospective. The patients treated with capecitabine combined with omeprazole were identified as experimental group and the capecitabine treatment alone as control group. The differences of blood concentration and the side effects of capecitabine between these two groups were compared. Results The plasma concentration of 5?Fluorouracilum in experimental group was ( 126.25 ± 50.59) μg／ml, without significant difference of (123.09±56.70) μg／ml in control group (P＝0.121). The incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and hand?foot syndrome in experimental group were 13.8%, 0%, 0% and 19.4%, respectively. In control group, the incidence ofⅢto Ⅳdegree bone marrow suppression, nausea, vomiting, diarrhea and the hand?foot syndrome were 11.1%, 0%, 0% and 19.4%, respectively, without significant difference of experimental group ( P＞0.05). The incidence of acid reflux and heartburn in the control group was 72.2%, significantly higher than 44.4% of the experimental group ( P＜0.05). The objective response rate ( ORR) and progression?free survival time (PFS) in these two groups were 30.6% and 33.3%, and 8.0 month and 8.5 month, respectively, without significant difference (P＞0.05). Conclusion The intravenous omeprazole attenuates reflux and heartburn of colon cancer patients treated with capecitabine, without affecting its plasma concentration and side effects and has no impact on the PFS of these patients.

Objective:To verify the value of whole genomic copy number variation (WGCNV) detection and scoring system in the diagnosis and prognosis of lung adenocarcinoma.Methods:Seventy-six lung adenocarcinoma specimens including ninety-one tumor samples and twenty adjacent non-tumor lung tissue samples were collected using Laser capture microdissection (LCM). Whole genomic amplification (WGA) was used to enrich DNA and construct a sequencing library for next generation sequencing (NGS). Changes of larger than 5Mb CNV in this study were analyzed and scored. The nuclear grading and score of tumor cells in the surgery and pleural effusion cytology of lung adenocarcinoma specimens were evaluated separately. For each case, we evaluated (1) nuclear size, (2) mitotic counts, (3) nuclear atypia, (4) atypical mitoses. The data of disease-free survive (DFS) and overall survive (OS) were collected for assessing the prognostic value of WGCNV score. Meanwhile, receiver operating characteristic (ROC) and area under curve (AUC) were used to define a cut-off value and evaluate the diagnostic significance in lung adenocarcinoma.Results:The WGCNV scores of twenty adjacent non-tumor lung tissue samples were treated as normal control and all of WGCNV scores of tumor samples range from 0 to 9.95, the median score was 2.7. The WGCNV scores were divided into three groups: low score group <1.74, medium score grade 1.74~4.23, high score grade >4.23. The WGCNV score was positively associated with the nuclear grade scoring ( r=0.780 90, P<0.001). The result for evaluation of prognostic value of the WGCNV scores showed that comparing with low WGCNV score group, Hazard Ratio (HR) of medium score group was 4.11 (95% CI=0.72~23.57) and high score group was 2.07 (95% CI=0.30~14.12). These results suggested that the risks of the medium and high WGCNV score group elevated. According to the analysis results of ROC curve, when the cut off value was 0.01, the sensitivity and specificity for lung adenocarcinoma diagnosis were 97.8% and 95.0% respectively, the positive predictive value (PPV) and negative predictive value (NPV) were 99.0% and 90.1%, respectively, the AUC was 0.981. In the differentiation of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) group and invasive adenocarcinoma group, when the cut off value was 1.8, the sensitivity and specificity between the two groups were 78.1% and 94.4%, and the PPV and NPV were 98.0% and 52.0%, respectively, the AUC was 0.896. Conclusion:This study verifies that WGCNV scoring system has a potential diagnostic and prognostic value in lung adenocarcinoma.