At present scopolamine is the most powerful single anti-motion sickness drug, but with prominent unwanted side effects. Many attempts had been made to decrease the unwanted side effects, but no any approach was considered to be successful. Based on our working hypothesis that central cholinolytic activity of anticholinergics may not be parallel completely to their side effects, a series of alicyclic amino alcohol esters were designed, synthesized and evaluated. One of the best compounds, phencynonate HCl, was obtained by transesteration of methyl α-phenyl-α-cyclopentyl-α-hydroxy acetate with N-methyl-3-azabicyclo(3,3,1)nonan-9α-ol. In animal models it was demonstrated that at equivalent anti-motion sickness dose the side effects of phencynonate were milder than those of two other central anticholinergic anti-motion sickness drugs scopolamine HBr and difenidol HCl. In clinical trials the overall effectiveness rates for prevention of seasickness and carsickness of phencynonate (oral 2-4 mg/person) was very significantly higher than that of placebo, and also significantly higher than that of difenidol (oral 25-50 mg/person). In self controlled rotatory chair experiments in hospital laboratory, the preventive effects of phencynonate and difenidol in reducing the changes in electronystagmus and electrogastrogram were statistically significant. In another self controlled rotation experiment, phencynonate (2-4 mg/person) and scopolamine (0.3-0.6 mg/person) showed significant anti-motion sickness effects in reducing the gastric electric cycles of electrogastrogram and the Graybiel scores of acute motion sickness and significant inhibitory effects on visual-vestibular interaction dose-dependently. The anti-motion sickness effects of phencynonate 2 and 4 mg were correspondent with those of scopolamine 0.3 and 0.6 mg, respectively. Student pilots with high susceptibility to airsickness were stimulated by Coriolis acceleration. The course of desensitization and habituation to airsickness training in phencynonate group (3 mg/person) was significantly shorter than that of placebo. There was no rebounding in sensitivity to Coriolis stimulation after discontinuing phencynonate, which was reported in case of scopolamine. The side effects of phencynonate HCl were mild dry mouth (9.7%) and drowsiness (9.97%). The incidence of drowsiness is significantly lower than that of difenidol. The side effect of drowsiness was only appeared in aboard ship and bus experiments, but not in PhaseⅠ trial in hospital or in laboratory rotation tests. The incidence of drowsiness of phencynonate was also lower than that of dramamine in aboard tank experiment. Phencynonate could effectively control the acute attack of vertigo, especially Meniere′s disease and positional vertigo. In animal models of Parkinson′s disease and parkinsonism, phencynonate showed morepotent antagonistic effects than clinical common used trihexyphendyl. In summary, phencynonate is a new central anticholinergic anti-motion sickness drug with higher efficacy and lower central inhibitory side effect than difenidol and scopolamine in prevention of motion sickness. Phencynonate HCl was approved on Dec 25,1993 by State Food and Drug Administration of China as a Class Ⅰ new drug for the prevention and treatment of motion sickness in the market in China.

In the isolated rat's phrenic nerve-diaphragm preparation, 1.5-2.5?10-7M dTC could restore 1.1?10-5'M (2?g/ml) soman-blocked tetany to 40-50% of normal, while ChE remained inhibited. 1.1?10-4M soman could abolish this dTC-restored tetany. The effect of dTC could apparently be inhibited by 1.1?10-(?)M soman given 10 min. before the administration of dTC. In the denervated diaphragm, 1.1?10-(?)M soman could enhance the ACh(5.8?10-(?)M)-induced contraction tension by about 14% owing to its ability of inhibiting ChE. After the inhibition of ChE by pretreatment of soman, the ACh-induced contraction of the denervated diaphragm was decreased by about 30% by 1.1?10-(?)M soman. It is suggested that soman, besides inhibiting ChE, also acts directly on neuro-muscular junctions.

AIM　To study the effects of verapamil on end-plate potentials(EPPs) in isolated non-uniform stretched muscle preparation(INSMP) of rat diaphragms pretreated with neostigmine or 3,4-diaminopyridine(3,4-DAP). METHODS　Using conventional intracellular microelectrode recording technique. RESULTS A sustained depolarization could be induced at the end-plate area pre-incubated with 0.2－5.0 μmol·L-1 neostigmine or 1.0－4.0 mmol·L-1 3,4-DAP. In normal Tyrode solution, verapamil at a concentration of 1, 5, 10 or 20 μmol·L-1 had no significant effect on evoked endplate potentials and miniature endplate potentials. However, the sustained depolarization due to neostigmine or 3,4-DAP could be antagonized by verapamil at 5－20 μmol·L-1 and the duration of the depolarization was shortened in a concentration-dependent manner. CONCLUSIONL-type calcium ion channels can be activated by accumulated acetylcholine in the synaptic cleft and may be involved in producing sustained depolarization, while they play no role in transmitter release under normal physiological conditions.

Objective: In order to reveal the mechanisms of rh-endostatin and its suppression effect on HUVECs at different activating levels. Methods: Three types of HUVEC were prepared. We detected the ex-pression of CD105 and CD62E on the surface of adhering HUVEC, HUVEC of exponential phase of growth, and HUVEC activated with TNF-alpha. The effect of endostatin on these three types of HUVEC was indicated by the variation in the expression of CD105 and CD62E on the cells. The relationship of the changes in cell markers with the time and the concentration of endostatin was analyzed by SPSS 11.5. Results: The expres-sion of CD105 was correlated with time and dose of endostar in all groups. The expression of CD62E was cor-related with the dose of endostar in HUVEC treated with TNF-α for 24h. Conclusion: Endostatin of a certain dose can inhibit the activation of endothelial cells but it cannot induce cell apoptosis.

Objective: To observe the remodeling of diabetic microvessels in diabetic rats. Methods: Diabetic animal models were induced by STZ on SD rats. The rats were treated with nonenzymatic glycosylation inhibitor and blood flow activating and stasis removing traditional Chinese medicine to evaluate the remodeling of diabetic retinal microvessels by trypsin digestion and figure analysis. Results: At 8 weeks, significant alteration of retinal capillary width in diabetic rats were observed( P

Objective:To treat the chronic non-atrophic gastritis patients induced by Helicobacter pylori with Qingweizhitong Weiwan combined with standard triple therapy,and to detect the differential expression of related immflammation genes with PCR array,and to clarify its mechanism.Methods: Ten patients with chronic non-atrophic gastritis complicated with Helicobacter pylori infection were used as treatment group and 10 health people were used as health control group. The patients in treatment group were treated with Qingweizhitong Weiwan combined with standard triple therapy for 14 d. The blood samples of the subjects in treatment group and health control group were collected before and after treatment,and QIAGEN human antibacterial response PCR array was performed to test the total RNA inperipheral blood and to analyze the differential expressions of 84 inflammation-related genes.Results:The differential expressions of 20 inflammation-related genes were found.Compared with health control group,the expression levels of 20 genes in treatment group before treatment were up-regulated (Fold-change>2);after treatment,the expression levels of 20 genes were down-regulated,and 11 of them were similar to the level in health control group (Fold-change< 2).More specifically,part of 20 genes was related to NLRP3 inflammasome.Compared with health control group,the gene expression levels of CASP1,IL1B,NLRP3,and PYCARD in treatment group before treatment were up-regulated (P <0.05).Compared with before treatment,the expression levels of CASP1,IL1B,NLRP3,and PYCARD in treatment group after treatment were down-regulated (P <0.05).Conclusion:The mechanism of Qingweizhitong Weiwan combined with standard triple therapy in the treatment of chronic non-atrophic gastritis patients induced by Helicobacter pylori may be related to inhibiting the expressions of NLRP3 inflammasome-related genes and interfering the antimicrobial innate immune response.

Breast cancer is one of the most common malignant tumors in women, and its incidence has increased year by year, which is one of the most important causes of death among women, especially young women. Studying related cell signal transduction that affects the development and progression of breast cancer can help prevent the occurrence of breast cancer, slow down the cancer progression and improve the prognosis of patients. nitric oxide (NO) is a kind of signaling molecule. Many studies have shown that the production and expression of NO are closely related to breast cancer. NO-related cell signal transduction significantly affects the occurrence and development of breast cancer. However, the understanding of the relationship between NO and breast cancer associated cell signal transduction needs to be further improved. In this paper, the related studies on NO-related cellular signal transduction in breast cancer were reviewed with a view to improving the understanding of the development and progression of breast cancer.

Objective To evaluate the curative effect of transcatheter arterial chemoembolization (TACE)combined with Antike in the treatment of primary liver cancer. Methods The data of 72 patients with primary liver cancer(90 lesions in total)admitted to the First Affiliated Hospital of Hebei North University from August 2016 to December 2017 were retrospectively analyzed. All patients were divided into the observa-tion group(n = 36)and the control group(n = 36)according to the therapeutic schedule. The patients in the control group(40 foci)were treated with TACE only,and the patients in the observation group(50 foci)re-ceived TCAE treatment,oral Antike capsules were taken at the same time with the frequency of three times a day,two capsules each time,and six weeks were planned for one treatment cycle. A total of four cycles were completed. All patients underwent CT enhancement scans one week before TACE treatment and six months after treatment. According to Response Evaluation Criteria in Solid Tumors,complete remission and partial remission were deemed as effectivity. The imaging data of the change of tumor size,postoperative tumor residual,tumor capsule growth and new intrahepatic metastases were analyzed and used to evaluate the curative effect of patients in the two groups. Results After 6 months of treatment,there were 39 effective lesions in the observation group and 23 in the control group. The total effective rate of the observation group was higher than that of the control group(78. 0％ vs. 57. 5％ ),and the difference was statistically significant(χ2 = 4. 357,P = 0. 037). Twenty-three neoplastic capsule lesions were detected in the observation group and 9 in the control group. The detection rate of neoplastic capsule was higher in the observation group than that in the control group(46. 0％vs. 22. 5％ ),and the difference was statistically significant(χ2 = 5. 356,P = 0. 021). There were 27 residual tumors and 5 new intrahepatic metastases in the observation group,30 residual tumors and 13 new intrahepatic metastases in the control group. The residual tumor rate and neohepatic metastasis rate in the observation group were lower than those in the control group(54. 0％ vs. 75. 0％ ;13. 9％ vs. 36. 1％ ),and the differences were statistically significant(χ2 = 4. 220,P = 0. 040;χ2 = 4. 741,P = 0. 029). Conclusion TACE combined with Antike is safe and effective in the treatment of primary liver cancer. It can improve the total clinical effi-ciency,promote the growth of tumor capsule,and reduce the recurrence rate and metastasis rate of tumor. It is worthy of clinical application.

Malignant tumor blood vessels,with phenotypes that are similar to high endothelial venules(HEVs)in secondary lymphoid or-gans(SLO),are known as tumor-associated high endothelial venules(TA-HEVs).The formation mechanism of TA-HEVs is similar to that of HEVs.Moreover,TA-HEVs play an important role in promoting the infiltration of lymphocytes into tumor tissues.With ongoing research,the positive effect of TA-HEVs in the context of radiotherapy,chemotherapy,immunotherapy,and antiangiogenic therapy is being elucidated.The clinical value is gradually becoming prominent,and the mechanisms and pathways involved with TA-HEVs are still under investigation.

A 62-year-old female patient was admitted to the hospital with a mass in the left kidney finding during medical check-up by color doppler imaging 1 day before admission. Unenhanced and contrast enhanced CT of urinary tract showed a mass on the inferior pole of left kidney. The left kidney cancer was diagnosed preoperatively and a left radical nephrectomy was performed laparoscopically. Postoperative diagnosis was thyroid-like follicular carcinoma of the left kidney and suspected derived from thyroid tumors by metastasis. Color doppler and CT examination of thyroid confirmed a mass in the right thyroid. Thyroid fine needle aspiration confirmed follicular carcinoma of the right thyroid, and follicular carcinoma of the right thyroid was diagnosed subsequently. The patient underwent radical resection of thyroid cancer according to the intraoperative frozen-section pathological results, and postoperative pathological diagnosis confirmed follicular carcinoma of the right thyroid and papillary carcinoma of the left thyroid. I 131 radio-iodine therapy and L-thyroxine tablets were administered based on the postoperative diagnosis of thyroid collision tumor. Seven months after surgery, the follow-up CT scan revealed no recurrence or metastases for renal area. Nine months later, no thyroid carcinoma recurrence was observed and no significant abnormality was detected in I 131 image. The composition of collision tumor is complicated and origin is unknown. Thyroid collision tumor with kidney metastasis is extremely rare, and the prognosis is better than primary renal carcinoma. The diagnosis depends on pathological examination.