Abstract: Fifteen novel ligustrazine-tetrahydroisoquinoline derivatives were designed and synthesized according to the association principle of pharmaceutical chemistry. The structures were identified by IR, NMR and ESI-MS. The inhibitory activities of platelet aggregation induced by ADP and AA have been measured by Bron method. Preliminary pharmacological results showed that compounds 7g, 7h and 7n had potent inhibitory activity against platelet aggregation induced by AA, and the compound 7o showed significant inhibitory activity against platelet aggregation induced by ADP.

Objective To explore the relationship between coagulation/anticoagulation imbalance and oxidative stress in the patients with chronic obstructive pulmonary disease during acute exacerbation (AECOPD)before and after treatment.Methods Plasma tissue factor(TF)and tissue factor pathway inhibitor(TFPl)activity was detected by chromogenic assay in 28 AECOPD patients before and after treatment as well as in 30 healthy controls.The total antioxidative capacity(TAC),malondialdehyde (MDA)and gtutathione peroxidase(GSH-PX)in plasma were measured in both groups.Results The levels of plasma TF and TFPI,and their ratio(TF/TFPI)in AECOPD patients before treatment were significantly higher than those after treatment(all P<0.0 1),the latter were still higher than those in the healthy persons(all P<0.01).The levels of the TAC and GSH-PX in plasma in AECOPD patients before treatment were significantly lower than those after treatment(all P<0.01),the latter were still lower than those in the healthy persons(all P<0.01).The plasma MDA in AECOPD patients before treatment was significantly higher than that after treatment(P<0.0 1),which was still higher than that in the healthy persons(P<0.05).There were negative correlations between TF/TFPI ratio and TAC(r=-0.518.P<0.01),GSH-PX(r=-0.454,P<0.05),PaO2(r=-0.511,P<0.01)respectively and a positive correlation between TF/TFPI ratio and the percentage of neutrophils(r=0.379,P<0.05)in AECOPD patients before treatment.There still were negative correlations between TF/TFPI ratio and TAC (r=-0.420,P<0.05),FEV1% to predicted(r=-0.480,P<0.05)respectively,and a positive correlation between TF/TFPI ratio and MDA(r=0.45 1,P<0.05)in AECOPD patients after treatment.Conclusions There existed coagulation/anticoagulation imbalance and oxidation/antioxidation imbalance before and after treatment in AECOPD patients and their relationship was explored.

Objective To explore the characteristics of cesarean scars pregnancy(CSP)and discuss differ-ent therapeutic methods and clinical outcomes. Methods Clinical data of 96 cases of CSP were collected from Sep-tember 2013 to October 2016 and patients′ clinical features,intra-operative findings,β-HCG,vaginal bleeding duration,hospital stay and cost and effects of different treatments were recorded and analyzed. Results The types of CSP were the determinant of lesion resection ,followed by the tumor size and blood β-HCG levels. The cases of uterine lesion resection and general uterine curettage with UAE had less blood loss than those without UAE. The cases of uterine lesion resection had short hospital stay and those with general uterine curettage had longer vaginal bleeding duration. Conclusion TVCD and MRI have important values in the diagnosis of CSP. During the treatment of CSP,personalized treatment planning,early diagnosis and treatment exert influence on reducing complications.

Objective:To explore the clinical value of stereotactic wire-localized biopsy(SWLB)in digital mammography in the detection of microcalcification of the breast.Methods:A total of 45 patients with nonpalpable breast lesions which were positive for microcalcification by mammography but could not be detected clinically underwent SWLB.Their mammography fndings were analyzed in detail with pathology.Results:Among the 45 cases,13 cases(28.9%)had malignant lesions including ductal carcinoma in situ in 3 cases (20.1%),ductal carcinoma in situ with microinvasion in 4 cases(30.8%),invasive ductal carcinoma in 5 cases (38.5%)and intraductal papillary carcinoma in 1 case(7.7%).Thirty-two cases(71.1%)had benign lesions,2 cases(6.3%)of which were severe atypical hyperplasia.Conclusion:SWLB can accurately guide the surgical excision of nonpalpable breast microcalcification lesions and diagnose microcalcifications exactly,which is helpful for increasing the detection rate of eady-stage breast cancer.

Objective:To study the infiltration mode of local immune cells in prostate cancer and to explore the role of immune cells in the development of prostate cancer.Methods:Gene expression profile chip dataset of normal prostate and prostate cancer tissues were downloaded from Gene Expression Omnibus (GEO) database. The proportion of 22 immune cells in the two groups was calculated by using R and SPSS software; the differences in the proportion of immune cells between the two groups were compared. The correlation coefficients among immune cells in prostate cancer tissues were calculated.Results:The dataset GSE62872 was downloaded, and a total of 424 samples were obtained, including 160 normal prostate tissues and 264 prostate cancer tissues. There were 20 228 mRNA detected in each sample. Deconvolution algorithm was used to obtain the proportion data of 22 kinds of immune cells after data correction. The samples were screened with P < 0.01, and 63 normal prostate tissues and 57 prostate cancer tissues were obtained. The immune cells with higher expression included CD8 + T cells [(23.48±6.16)%], plasma cells [(18.46±5.74)%], monocytes [(12.15±3.82)%] and activated NK cells [(11.11±2.97)%]. The immune cells with higher constituent ratio correlation coefficient included CD8 + T cells and unactivated memory CD4 + T cells ( r = -0.609, P < 0.01), M 0 macrophages and M 2 macrophages ( r = -0.596, P < 0.01). Compared with normal tissues, the infiltration degree of M 1 macrophages and unactivated dendritic cell was increased, and the difference was statistically significant ( Z = -2.783, P = 0.005; Z = -2.129, P = 0.033). Conclusions:The infiltrated immune cells in the tumor microenvironment of prostate cancer are mainly CD8 + T cells, plasma cells, monocytes and activated NK cells. With the effect of the tumor microenvironment, M 0 macrophages mainly differentiate into M 2 macrophages cells, which may be involved in the occurrence and development of prostate cancer, providing new clues to find potential immunotherapy targets.

OBJECTIVE To predict the amount of colorants used in the preparation of placebo of Chinese medicine by construc-ting particle swarm optimization-back propagation neural network PSO-BPNN compound granules,and to provide a new idea for the simulation of placebo color of Chinese medicine compound granules.METHODS The BP neural network was used to establish the model of sample color parameters L,a?,b?and pigment mass fraction.The global search ability of particle swarm optimization algo-rithm was used to optimize the weight and bias of BP neural network to prevent the local minimum value of the model.The linear reduc-tion weight coefficient method and the introduction of mutation operator were used to improve the global optimization ability of particle swarm optimization algorithm.The color comprehensive evaluation index(ΔE)was used as the objective evaluation standard to verify the test results.RESULTS The training results show that the fitting accuracy of the improved PSO-BP neural network was up to 98.31%.The prediction results show that the prediction error of the improved PSO-BP neural network was the smallest,and the mean absolute percentage error(MAPE),root mean square error(RMSE)and mean color difference(ΔE)were 0.411 5,2.164 6 and 2.56,respectively.The verification samples of three kinds of particles were prepared for verification.The ΔE of the verification sample and the model drug were 1.73,2.63 and 4.11,respectively.The color difference between the two groups and the model drug was small by visual evaluation.CONCLUSION The BP neural network based on the improved particle swarm optimization algorithm can simulate the prediction of the amount of colorants used in the preparation of Chinese medicine compound granules,and can be used as a recommended optimization model for placebo color matching research.

Objective:To analyze the influencing factors of short-term efficacy of 125I seed implantation for recurrent cervical metastatic lymph nodes of esophageal squamous cell carcinoma after external beam radiation therapy (RESCC). Methods:From January 2013 to March 2019, 47 patients (42 males, 5 females; age: 47-77 years) with RESCC who underwent CT guided 125I seed implantation in Hebei General Hospital were retrospectively analyzed. Patients were divided into effective group (complete remission (CR)+ partial remission (PR)) and ineffective group (stable disease (SD)+ progressive disease (PD)) according to response evaluation criteria in solid tumors (RECIST) at 3 months after implantation. Multivariate logistic regression was used to analyze the independent influencing factors of short-term efficacy. Cut-off values were determined by ROC curve. Results:Of 47 patients, 26 were effective (3 were CR and 23 were PR) and 21 were ineffective (7 were SD, 14 were PD). Multivariate regression analysis showed that tumor diameter, immediate postoperative dose delivered to 90% gross tumor volume ( D90), recurrence interval time were independent influencing factors of short-term efficacy (odds ratio ( OR; 95% CI): 4.240(1.220-14.737), 0.999(0.999-1.000), 0.989(0.979-1.000), Wald values: 5.163, 5.043, 3.956, all P<0.05). ROC curve showed that the AUC of tumor diameter, D90 and recurrence interval time were 0.782, 0.786 and 0.838 respectively, with cut-off values of 4.85 cm, 115.78 Gy and 297.5 d respectively. Conclusions:The short-term efficacy of 125I seed implantation for RESCC is mainly related to the tumor diameter, immediate postoperative D90 and recurrence interval time. Patients with tumor diameter <4.85 cm, immediate postoperative D90>115.78 Gy and recurrence interval time >297.5 d have better efficacy.

Purpose: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). Materials and Methods: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. Results: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. Conclusions RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

Objective: To analyze the factors influencing the short-term efficacy of CT-guided ¹²⁵I seeds implantation in the treatment of recurrent and metastatic tumors in head and neck. Methods: A total of 73 patients (61 males, 12 females; age: (59.1±11.5) years) with head and neck tumors recurrence and metastasis treated by ¹²⁵I seeds implantation in Hebei General Hospital from January 2015 to April 2019 were retrospectively enrolled. The implanted seeds activity was 11.1-29.6 MBq, and the prescription dose was 80.0-145.0 Gy. CT examination was conducted 3 months after ¹²⁵I seeds implantation. According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, short-term efficacy was classified as effective (complete remission (CR), partial remission (PR)) and ineffective (stable disease (SD), progressive disease (PD)). Univariate analysis of factors affecting short-term effect (gender, age, history of radiation therapy, Karnofsky performance status (KPS) scores, pathological type, the longest diameter of tumor, implantation patterns, seeds activity, immediate postoperative dose delivered to 90% gross tumor volume (D₉₀), and with adjuvant chemotherapy post-surgery or not) were conducted. Variables with P<0.2 were enrolled in logistic multivariate regression analysis. In addition, artificial neural network (ANN) was constructed with all influencing factors as independent variables and short-term efficacy as dependent variables. Finally, receiver operating characteristic (ROC) curve analysis was performed for the common influencing factors in logistic regression analysis and ANN analysis. Results: There were 34 with effective results and 39 with ineffective results. Logistic regression analysis indicated that the longest diameter of tumor, immediate postoperative D₉₀, with adjuvant chemotherapy post-surgery or not had significant impacts on the short-term efficacy (Wald values: 6.950, 4.804, 4.790, all P<0.05); According to results of ANN analysis, the top 5 in order of importance for short-term efficacy prediction were immediate postoperative D₉₀, the longest diameter of tumor, age, seeds activity and gender. ROC curve analysis indicated that the longest diameter of tumor and immediate postoperative D₉₀ were the best predictors for short-term efficacy, with the threshold of 5.25 cm and 110.05 Gy respectively, and the area under the curve (AUC) was 0.843 and 0.847 respectively (both P<0.001). Conclusions The short-term efficacy of ¹²⁵I seeds implantation in the recurrence and metastasis of head and neck tumors is mainly related to the longest diameter of tumor and immediate postoperative D₉₀. Patients with the longest diameter of tumor <5.25 cm and with D₉₀>110.05 Gy can achieve better efficacy.