Clinical study on dapagliflozin combined with metformin for the treatment of type 2 diabetes mellitus / 中国基层医药

Objective:To investigate the clinical effect of dapagliflozin combined with metformin on type 2 diabetes mellitus (T2DM).Methods:A total of 100 patients with T2DM who received treatment in The Second People's Hospital of Hefei from June 2019 to May 2021 were included in this study. They were randomly divided into a control group ( n = 50) and an experimental group ( n = 50). The control group was treated with metformin, and the experimental group was treated with dagglitazin combined with metformin. All patients were treated for 3 months. Blood glucose index, blood lipid level, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, fasting blood glucose, 2-hour post-prandial blood glucose, and glycosylated hemoglobin in the experimental group were (5.56 ± 0.37) mmol/L, (8.32 ± 0.23) mmol/L, and (6.17 ± 0.26)% respectively, which were significantly lower than (6.96 ± 0.48) mmol/L, (9.58 ± 0.39) mmol/L, and (7.27 ± 0.26)% respectively in the control group ( t = 3.59, 6.92, 5.03, all P < 0.05). The total cholesterol and triglyceride in the experimental group were (3.58 ± 0.53) mmol/L and (1.25±0.26) mmol/L, respectively, which were significantly lower than (4.94 ± 0.58) mmol/L and (1.93 ± 0.18) mmol/L in the control group ( t = 3.16, 4.25, both P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Dapagliflozin combined with metformin can effectively control blood glucose and blood lipid in T2DM patients without increasing adverse reactions.

Epidemiological analysis of animal plague in natural plague focus of Himalayan Marmot in Yumen City of Gansu Province from 2014 to 2021 / 中华地方病学杂志

Objective:To learn about the epidemic law of animal plague in natural plague focus of Himalayan Marmot in Yumen City of Gansu Province, to explore the epidemiological characteristics of plague in the area and to provide scientific basis for formulating prevention and control strategies of the plague. Methods:The animal plague surveillance data of natural plague focus of Himalayan Marmot in Yumen City, Gansu Province from 2014 to 2021 were collected, main host density, rate of infected with fleas, flea index, small rodent species, bacteriology, serology were studied. Excel 2007 software was used to analyze the plague epidemic situation in the focus. Results:From 2014 to 2021, the total average density was 0.06 per hm 2 of the marmots. A total of 19 300 traps were placed, and 209 rats were caught, with an average catch rate of 1.08%. Among them, Dipus sagitta (59.81%, 125/209) and Mongolian Five-toed Jerboa(31.10%, 65/209) were dominant small rodent species. Totally 877 marmots were checked, 184 with flea. The rate of infected with fleas of marmots was 20.98%, with a flea index of 1.00, Callopsylla dolabris (52.69%, 461/875) and Oropsylla silantiewi (47.20%, 413/875) were dominant species in vector. The rate of infected with fleas of burrow was 7.72% (173/2 241), with a flea index of 0.20. A total of 39 strains of Yersinia pestis were isolated from infected animals. Among them, 35 strains from the marmots, and 4 strains from vectors. Totally 913 serum samples were checked from marmots and shepherd dog, the positive serum was 34. Among them, the positive rate of shepherd dog was 13.98% (33/236). Conclusions:The plague epidemic situation in natural plague focus of Himalayan Marmot in Yumen City of Gansu Province is still serious. The monitoring of plague should be strengthened, and the comprehensive measures for prevention and control of the plague should be carried out to prevent a outbreak of the plague in human being.

Research on the scaffolding teaching in the theory teaching of Clinical Microbiology Laboratory Technology / 中华医学教育探索杂志

The scaffolding teaching is a kind of "student-centered" teaching desgin. In this study, the teacher breaks down complex content into simply conceptual framework so as to enable students to define their learning objectives, provide help for students' learning, and guide students to think independently and explore cooperatively to construct their own knowledge system. Clinical Microbiology Laboratory Technology is a specialized course with very complicated theoretical contents, which can break up the whole into parts by scaffolding instruction, combined with the learning strategies of cooperation, exploration and mind mapping. Finally, "installment fixed deposit" is realized by induction and summary. The scaffolding teaching model promotes students' ability of autonomous learning, analytical reasoning and innovation.

Reduning Injection prevents carrageenan-induced inflammation in rats by serum and urine metabolomics analysis / 中草药·英文版

Objective: To elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level. Methods: Rat inflammatory model was established by carrageenan. UPLC-Q-TOF/MS was used to detect and analyze changes of endogenous metabolites in the serum and urine of carrageenan-induced inflammatory rats. Combined with multivariate analysis and databases analysis, inflammatory-related potential biomarkers were screened and identified to analyze possible metabolic pathways. The reliability and biological significance of these biomarkers was verified by metabolic network analysis and correlation analysis with pharmacodynamic indicators. Results: A total of 16 potential biomarkers were screened and identified by multivariate analysis and metabolite databases, among which 13 species could be adjusted by RDN. The metabolism pathway analysis revealed that histidine metabolism, sphingolipid metabolism, and tyrosine metabolism were greatly disturbed. Their biomarkers involved urocanic acid, sphingosine, and norepinephrine, all of which showed a callback trend after RDN treatment. The three biomarkers had a certain correlation with some known inflammatory-related small molecules (histamine, arachidonic acid, Leukotriene B4, and PGE

Clinical observation on moxibustion therapy plus tuina in treating children with recurrent respiratory tract infections due to qi deficiency of spleen and lung / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of moxibustion therapy plus Liu's pediatric massage (tuina) for children with recurrent respiratory tract infections due to qi deficiency of spleen and lung. Methods: A total of 60 children who met the inclusion criteria were divided into an observation group and a control group according to the visiting sequence, with 30 cases in each group. Children in the observation group were treated with moxibustion therapy plus Liu's pediatric massage, and those in the control group were treated with Liu's pediatric massage alone. The incidence of respiratory tract infections and traditional Chinese medicine (TCM) symptoms score were observed and recorded in both groups before and after treatment. And the clinical efficacy was compared between the two groups. Results: The total effective rate of the observation group was 93.3％, and that of the control group was 83.3％. The difference between the two groups was statistically significant (P<0.05). After treatment, the TCM symptoms score and total times of infections in both groups were all statistically different from those before treatment (all P<0.05). The differences in TCM symptoms score and infection frequency before and after treatment in the observation group were statistically different from those in the control group (both P<0.05). Conclusion: Moxibustion therapy plus Liu's pediatric massage has a better effect in improving the clinical symptoms and reducing the frequency of respiratory tract infections for children with recurrent respiratory tract infections due to qi deficiency of spleen and lung than the pediatric massage alone.

Comparable efficacy of 100 mg aspirin twice daily and rivaroxaban for venous thromboembolism prophylaxis following primary total hip arthroplasty: a randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Aspirin has demonstrated safety and efficacy for venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA); however, inconsistent dose regimens have been reported in the literature. This study aimed to evaluate and compare the safety and efficacy of 100 mg aspirin twice daily with rivaroxaban in VTE prophylaxis following THA.@*METHODS@#Patients undergoing elective unilateral primary THA between January 2019 and January 2020 were prospectively enrolled in the study and randomly allocated to receive 5 weeks of VTE prophylaxis with either oral enteric-coated aspirin (100 mg twice daily) or rivaroxaban (10 mg once daily). Medication safety and efficacy were comprehensively evaluated through symptomatic VTE incidence, deep vein thrombosis (DVT) on Doppler ultrasonography, total blood loss (TBL), laboratory bloodwork, Harris hip score (HHS), post-operative recovery, and the incidence of other complications.@*RESULTS@#We included 70 patients in this study; 34 and 36 were allocated to receive aspirin and rivaroxaban prophylaxis, respectively. No cases of symptomatic VTE occurred in this study. The DVT rate on Doppler ultrasonography in the aspirin group was not significantly different from that in the rivaroxaban group (8.8% vs. 8.3%, χ2 = 0.01, P = 0.91), confirming the non-inferiority of aspirin for DVT prophylaxis (χ2 = 2.29, P = 0.01). The calculated TBL in the aspirin group (944.9 mL [658.5-1137.8 mL]) was similar to that in the rivaroxaban group (978.3 mL [747.4-1740.6mL]) (χ2 = 1.55, P = 0.12). However, there were no significant inter-group differences in HHS at post-operative day (POD) 30 (Aspirin: 81.0 [78.8-83.0], Rivaroxaban: 81.0 [79.3-83.0], χ2 = 0.43, P = 0.67) and POD 90 (Aspirin: 90.0 [89.0-92.0], Rivaroxaban: 91.5 [88.3-92.8], χ2 = 0.77, P = 0.44), the incidence of bleeding events (2.9% vs. 8.3%, χ2 = 0.96, P = 0.33), or gastrointestinal complications (2.9% vs. 5.6%, χ2 = 1.13, P = 0.29).@*CONCLUSION@#In terms of safety and efficacy, the prophylactic use of 100 mg aspirin twice daily was not statistically different from that of rivaroxaban in preventing VTE and reducing the risk of blood loss following elective primary THA. This supports the use of aspirin chemoprophylaxis following THA as a less expensive and more widely available option for future THAs.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR18000202894; http://www.chictr.org.cn/showproj.aspx?proj=33284.

Da Vinci robot-assisted pylorus and vagus nerve-preserving partial gastrectomy for gastric cancer / 中华胃肠外科杂志

Objective: To investigate the safety and feasibility of Da Vinci robot-assisted pylorus and vagus nerve-preserving partial gastrectomy for gastric cancer. Methods: In this study, descriptive case series method was used to retrospectively analyze the data of 3 patients with gastric cancer who underwent Da Vinci robot-assisted pylorus and vagus nerve-preserving partial gastrectomy in the First Affiliated Hospital of Dalian Medical University from December 2020 to February 2021. The linear layout was adopted for the setting of trocar, and the co-axial direction was the line connecting the umbilicus and splenic hilum. The inferior pyloric arteries and veins need to be preserved. The center was the bifurcation of the right gastroepiploic vessel and the inferior pyloric vessel. Dissection and exposure were performed from the upper, lower, right and left sides, and ventral and dorsal sides to complete the dissection of the inferior pyloric lymph nodes. The superior border of the pancreas was treated by the right diaphragmatic crus approach, the left retroperitoneal approach and the esophageal approach to determine the distribution of the posterior vagal trunk and its branches, and to determine the anatomical relationship with the left gastric artery. The left gastric artery was cut off while the celiac branch of vagus nerve and cardia branch of left gastric artery were preserved. Lymph node dissection was performed on the lateral side of nerve fibers around the blood vessels. Result: All the 3 patients successfully completed the robotic surgery without conversion to laparoscopy or laparotomy. The operation time was (340.0±26.4) (300-390) minutes, the intraoperative blood loss was (13.3±3.3) (10-20) ml, the number of dissected lymph nodes was 26.7±3.9 (19-32), the length of pylorus canal preserved was (3.3±0.3) (3-4) cm, the distal margin was (2.3±0.3) (2-3) cm, and the proximal margin was (3.0±0.6) (2-4) cm. No postoperative complications occurred in all the 3 patients. The first flatus time was 2-3 days after operation, and the postoperative hospital stay was 6-7 days. The operation cost of the 3 patients was (40±7) (33-53) thousand yuan. Conclusion: Da Vinci robot-assisted pylorus and vagus nerve-preserving partial gastrectomy is safe and feasible.

Effects of Guizhi Fuling Capsules and Its Main Components on Intestinal Flora of Primary Dysmenorrhea Model Rats / 中国药房

OBJECTIVE：To investigate the effects of Guizhi ful ing capsules and its principal components （paeoniflorin， paeonol and amygdalin ）on the intestinal flora of primary dysmenorrhea model rats. METHODS ：Female SD rats were randomly divided into normal group ，model group ，capsule group（Guizhi fuling capsule ，1 000 mg/kg），paeoniflorin group （15.0 mg/kg）， paeonol group （10.3 mg/kg）and amygdalin group （12.1 mg/kg），with 6 rats in each group. Except for normal group ，other groups were given estradiol benzoate subcutaneously on the back of rats and oxytocin intraperitoneally to induce primary dysmenorrhea model. From the 4th day after subcutaneous injection of estradiol benzoate ，normal group was given constant volume of normal saline intragastrically ；model group was given constant volume of 0.5％CMC-Na solution intragastrically ；administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 7 days. The writhing times and the contents of and MDA in uterus tissue of rats were determined ，and then com the contents of short-chain fatty acids （SCFAs）such as acetic acid，propionic acid ，butyric acid in colonic contents were detected by GC method. Using diver sity index as index ， Rep-PCR and Eric-PCR were used to evaluate the d iversity of intestinal flora in feces of rats. RESULTS ：Compared with normal group，the writhing times of rats were increased significantly in model group ；the contents of NO and MDA in uterus were increased significantly ，while the contents of acetic acid ，propionic acid and butyric acid in colonic contents and total content of SCFAs were decreased significantly （P＜0.05 or P＜0.01）；the number of DNA electrophoresis bands of intestinal flora was significantly reduced ，the brightness of most bands was significantly reduced ，and the diversity indexes （by Rep-PCR and Eric-PCR method ，hereinafter）1 h after administration were significantly reduced （P＜0.05 or P＜0.01）. Compared with model group，writhing times of rats were decreased significantly in capsule group ，paeoniflorin group and paeonol group ；the contents of NO in uterus of rats in capsule group and paeoniflorin group as well as the contents of MDA in capsule group ，paeoniflorin group and paeonol group were decreased significantly （P＜0.05 or P＜0.01）；the propionic acid content and total content of SCFAs in colon of rats in capsule group ，the contents of acetic acid ，propionic acid and butyric acid ，total content of SCFAs in paeoniflorin group as well as the contents of propionic acid and butyric acid ，total content of SCFAs in paeonol group were increased significantly；the content of isovaleric acid was decreased significantly in paeoniflorin group （P＜0.05 or P＜0.01）；DNA electrophoresis bands and its brightness of intestinal flora changed to different extents in administration groups ，and the diversity indexes of intestinal flora 1 h after administration were increased significantly in capsule group and paeoniflorin group ，while those indexes were decreased significantly in paeonol group and amygdalin group （P＜0.05 or P＜0.01）. CONCLUSIONS ：Guizhi fuling capsules can significantly reduce writhing times and the contents of NO and MDA in uterus of primary dysmenorrhea model rats. At the same time ，the capsules also can regulate SCFAs content in colonic contents and intestinal flora diversity of rats. The above effects may be related to paeoniflorin and paeonol in the capsules.

Rapid identification of chemical components in compound Nanxing acesodyne plaster by UPLC-Q-TOF-MS/MS / 中国中药杂志

The study aims to qualitatively analyze the chemical composition of compound Nanxing acesodyne plaster by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). The analysis was performed on Agilent Zorbax SB-C_(18)( 4. 6 mm×250 mm,5 μm) column. The mobile phase consisted of methanol and 0. 2% formic acid-water was used as gradient elution. The flow rate was 1 mL·min~(-1) and column temperature was 30 ℃. The Mass spectrometry was acquired in both positive and negative ion modes using ESI. The components were identified by the precise mass-to-charge ratio,secondary fragmentation and other information combined with reference substance and literature data. As a result,58 compounds were identified and predicted,including alkaloids,flavonoids,coumarins,organic acids and lactone compounds,of which 12 compounds were verified by the reference substances. The results provide reference for the quality control of compound Nanxing acesodyne plaster,and lay the foundation for elucidating the active components mechanism.

Clinical observation of warm acupuncture combined with yoga posture method in the treatment of periarthritis with frozen period / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of warm acupuncture combined with yoga posture method in the treatment of periarthritis with frozen period.@*METHODS@#Ninety patients with periarthritis who met the inclusion criteria were randomly divided into a control group 1, a control group 2 and an observation group, 30 cases in each group. Warm acupuncture was applied in the control group 1 (Jianzhen (SI 9), Jianyu (LI 15), Jianliao (TE 14), etc were selected), yoga posture method was applied in the control group 2, warm acupuncture combined with yoga posture method were given in the observation group, the treatment was given once a day, 10 times as a course with 2 days between courses and continuous for 2 courses. After 2 courses of treatment, the shoulder joint pain score and shoulder function grading were used to evaluate the clinical efficacy, and the clinical efficacy was observed.@*RESULTS@#①The pain scores of the three groups were significantly lower after treatment (all 0.05). ②After treatment, the functional classification of shoulder joints were significantly improved in the three groups (all 0.05). ③After 2 courses of treatment, the effective rate of the observation group was 86.7% (26/30), which was better than 70.0% (21/30) in the control group 1 and 76.7% (23/30) in the control group 2 (both <0.05).@*CONCLUSION@#Warm acupuncture combined with yoga posture method can effectively relieve shoulder pain and improve dysfunction. The clinical comprehensive effect is better than simple acupuncture and yoga posture method.

Molecular Mechanism of Sanjie Zhentong Capsule in Treatment of Endometriosis, Adenomyosis, Secondary Dysmenorrhea / 中国实验方剂学杂志

Objective: To analyze the pharmacological basis and molecular mechanism of Sanjie Zhentong capsule in the treatment of endometriosis, adenomyosis, secondary dysmenorrhea. Method: The 6 compounds of Sanjie Zhentong capsule showed stronger interactions with 87 proteins relating to endometriosis, adenomyosis, and secondary dysmenorrhea in molecular docking. Then the drug-target network was selected, and the network features were analyzed. Result: The molecular docking and network characteristics revealed 5 main active molecules and 23 potential targets of Sanjie Zhentong capsule. Conclusion: The main active ingredients of Sanjie Zhentong capsule have a trong inhibition effect on endometrial angiogenesis and blood circulation, uterine smooth muscle contraction, immune inflammatory reaction and estrogen secretion by acting on the targets of inflammation, cell invasion, metastasis, coagulation system, smooth muscle contraction and neurohormone regulation, so as to treat endometriosis, adenomyosis and secondary dysmenorrhea.

Down-regulated PTTG1 expression promotes the senescence of human prostate cancer LNCaP-AI / 中华男科学杂志

Objective@#To investigate the effect of the down-regulated expression of pituitary tumor-transforming gene 1 (PTTG1) on the senescence of human castration-resistant prostate cancer LNCaP-AI cells.@*METHODS@#Human castration-resistant prostate cancer LNCaP-AI cells were induced in vitro and transfected with siRNA targeting PTTG1 (the siRNA-PTTG1 group), the reagent lip3000 only (the mock group) or siRNA negative control vector (the NC group). All the cells were cultured in fetal bovine serum (FBS) or charcoal-stripped bovine serum (CSS) and counted with the cell counting chamber. The senescence characteristics of the transfected LNCaP-AI cells were examined by senescence-associated β-galactosidase (SA-β-Gal) staining, and the expressions of the senescence-related β-galactosidase-1-like proteins (Glb1), the cyclin-dependent kinase inhibitors p-21CIP1 and p-27Kip1, and the chromatin-regulating heterochromatin protein 1γ (HP1γ) were detected by Western blot.@*RESULTS@#The expression of PTTG1 in the human prostate cancer LNCaP-AI cells was significantly reduced in the siRNA-PTTG1 group compared with those in the mock and NC groups (0.21 ± 0.01 vs 0.56 ± 0.02 and 0.61 ± 0.02, P < 0.05). Culture with FBS markedly increased while that with CSS decreased the number of LNCaP-AI cells transfected with siRNA, but both FBS and CSS enhanced the proliferation of the LNCaP-AI cells in the mock and NC groups. SA-β-Gal staining revealed that reducing the expression of PTTG1 induced a remarkably higher positive rate of the LNCaP-AI cells in the siRNA-PTTG1 than in the mock and NC groups (［63.5 ± 2.35］% vs ［11.3 ± 1.24］% and ［12.4 ± 1.15］%, P < 0.05). The siRNA-PTTG1 group, in comparison with the mock and NC groups, showed a significantly down-regulated expression of PTTG1 (0.21 ± 0.01 vs 0.56 ± 0.02 and 0.61 ± 0.02, P < 0.05), but up-regulated expressions of p-21CIP1 (0.32 ± 0.03 vs 0.20 ± 0.02 and 0.21 ± 0.03, P < 0.05), p-27Kip1 (0.38 ± 0.02 vs 0.20 ± 0.03 and 0.22 ± 0.01, P < 0.05), Glb1 (0.24 ± 0.01 vs 0.13 ± 0.01 and 0.15 ± 0.01, P < 0.05), and HP1γ (0.41 ± 0.01 vs 0.26 ± 0.01 and 0.27 ± 0.02, P < 0.05) in the LNCaP-AI cells.@*CONCLUSIONS@#Down-regulated expression of PTTG1 induces senescence of human castration-resistant prostate cancer LNCaP-AI cells.

The predictive value of cardiopulmonary interaction monitoring technology on volume responsiveness in septic shock patients / 中华急诊医学杂志

Objective To assess the predictive value of cardiopulmonary interaction monitoring technology on volume responsiveness in septic shock patients.Methods A cohort of 45 septic shock patients treated with mechanical ventilation at First People's Hospital of Nantong City from January 2016 to June 2017 were prospectively selected.The hemodynamic variables including heart rate (HR),systolic pressure (SBP),mean arterial pressure (MAP),central venous pressure (CVP),cardiac index (CI),stroke volume variability (SVV),and pulse pressure variability (PPV) were monitored.PEEP elevation test,end-expiratory occlusion test and volume expansion were sequential conducted.Volume responsiveness was defined as an increase in CI (△CI) of 15％ or greater after volume expansion,namely the response group (△CI ≥ 15％) and non-response group (△CI＜15％).Receiver operating characteristic (ROC) curve was constructed to indicate the predictive value of cardiopulmonary interaction monitoring technology in septic shock patients.The best cut-off value was assessed by Youden Index,and sensitivity and specificity were calculated respectively.Results There were 24 patients in the response group and 21 patients in the non-response group.There were no significant differences in basic clinical data between the two groups.△fter PEEP elevation test,CVP increased significantly,while SBP and CI decreased significantly in both groups (P＜0.05).The degrees of △SBP and △CI in the response group were much higher than those in the non-response group (P＜0.05).After end-expiratory occlusion test,CVP decreased significantly,while SBP,MAP and CI increased significantly in both groups (P＜0.05).The degrees of △MAP and △CI in the response group were much higher than those in the non-response group (P＜0.05).SVV and PPV in the response group were higher than those in the non-response group (P＜0.05).The area under the ROC curve (AUC) of the △SBP and △CI after PEEP elevation test and △MAP and △CI after end-expiratory occlusion test were 0.737 (95％CI:0.581-0.89;P＜0.05),0.803 (95％CI:0.660-0.946;P＜0.05),0.763 (95％CI:0.617-0.908;P＜0.05),and 0.808 (95％CI:0.673-0.942;P＜0.05),respectively.These AUC values were higher than or similar to traditional indicators,such as SVV and PPV.The best cut-off value of △CI and △SBP after PEEP elevation test was 12％ and 9.5％,yielding a sensitivity and specificity of 70.8％and 95.2％,75％ and 71.4％,respectively.The best cut-off value of △CI and △MAP after end-expiratory occlusion test was 8.5％ and 5.5％,yielding a sensitivity and specificity of 79.2％ and 76.2％,75％ and 76.2％ respectively.Conclusion △SBP and △CI after PEEP elevation test and △MAP and △CI after endexpiratory occlusion test can accurately predict volume responsiveness in septic shock patients.

Expression of G-protein coupled estrogen receptor in the testis of the male mouse with kidney yin or kidney yang deficiency and its impact on the reproductive function of the mouse / 中华男科学杂志

Objective@#To investigate the expression of the G-protein coupled estrogen receptor (GPER) in the testis of the male mouse with kidney yin or kidney yang deficiency and its influence on the reproductive function of the mouse.@*METHODS@#We randomized 30 six-week-old male Kunming mice into three groups of equal number: kidney yang deficiency, kidney yin deficiency, and normal control, and established the models of kidney yang deficiency and kidney yin deficiency by peritoneal injection of hydrocortisone at 50 mg/kg for 5 days and 25 mg/kg for 10 days, respectively. We observed the behavioral changes of the mice using the elevated plus-maze, exhaustive swimming and field experiment, examined the semen quality with the automatic sperm quality analyzer, calculated the average number of the offspring, measured the serum testosterone (T) and estradiol (E2) levels and T/E2 ratio by Roche electrochemiluminescence assay, and determined the localization and expression of GPER in the testis by immunohistochemistry and immunofluorescence staining.@*RESULTS@#Compared with the mice with kidney yin deficiency, those with kidney yang deficiency showed remarkably fewer entries into the open arm and central area (P 0.05); the latter group also exhibited significant decreases in the epididymal sperm count (［7.27 ± 1.30］ vs ［3.05 ± 1.06］ ×108/g, P 0.05), and markedly reduced serum T (［24.96 ± 6.18］ vs ［16.72 ± 5.92］ ng/dl,P <0.05), E2 (［19.81 ± 4.01］ vs ［15.24 ± 1.11］ pg/ml,P <0.05) and T/E2 ratio (1.41 vs 1.25, P <0.05). The expression of GPER was found in the cytoplasm of the Leydig cells, negative in the nuclei and cell membrane, significantly higher in the kidney yang than in the kidney yin deficiency group (P <0.05).@*CONCLUSIONS@#The numbers of sperm and offspring decreased while the percentage of morphologically abnormal sperm increased in both the kidney yang and kidney yin deficiency mice, even more significantly in the former, which might be associated with the up-regulated expression of GPER in the testis of the mouse with kidney yang deficiency and consequently the reduced serum T level and T/E2 ratio.

Effect of compatibility of ginkgolide A, ginkgolide B and ginkgolide K / 中国中药杂志

To investigate the best active compatibility of ginkgolide A, B and K (GA，GB，GK). The effects of GA, GB, GK alone, combinations of each two of them, and combinations of these three components on platelet-activating factor (PAF)-induced platelet aggregation activity and rat cerebral ischemia reperfusion model (tMCAO) were compared in this study. Different compatibilities of GA, GB and GK could significantly reduce the maximum aggregation rate of PAF-induced platelet aggregation, and the effect was most obvious in combination of the three. Different compatibilities of GA, GB and GK could alleviate the neural function, cerebral infarction volume and cerebral edema in the tMCAO model of rats to different degrees, and the effect of combinations of the three was stronger than those of combinations of two and single use. The combination of all of GA, GB and GK had the strongest effect on nerve injury caused by anti-platelet aggregation in tMCAO rats.

New situation and new strategies——research and development and internationalization of new drugs and health products of traditional Chinese medicine / 中国药理学与毒理学杂志

The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.

Network-assisted mechanism investigation of Yaobitong Capsules on lumbar intervertebral discs / 中成药

AIM To explore analgesic mechanism of Yaobitong Capsules (Notoginseng Radix et Rhizoma,Chuanxiong Rhizoma,Corydalis Rhizoma,etc.) on lumbar intervertebral discs.METHODS An array of data mining,molecular docking and network analysis were employed to investigate the active compounds and key target protein.RESULTS Among the forty-six active hits identified by virtual screening,most compounds displayed good oral bioavailability and might confer an optimal CNS exposure.And eleven molecules (coptisine,diligustilide,corypalmine,chuanxiongterpene,etc.) were further confirmed to alleviate lumbar intervertebral discs through their targeting at nineteen proteins (such as p38,CGRP,MMPs,TNFα) to inhibit the inflammatory response and the infiltration of microvasculature,to reduce the nociceptors sensitivity,and to modulate the balance of Collagen and proteoglycans in catabolic and anabolic responses.CONCLUSION Yaobitong Capsules' clear molecular working mechanism and the key active compounds are revealed by this network-assisted investigation highlight the subsequent experiments on targets and active compounds.

Downregulation of PTTG1 expression inhibits the proliferation and invasiveness and promotes the apoptosis of human prostate cancer LNCaP-AI cells / 中华男科学杂志

Objective@#To investigate the effects of down-regulation of PTTG1 expression on the proliferation, invasiveness and apoptosis of androgen-independent human prostate cancer LNCaP-AI cells and their sensitivity to androgen antagonists.@*METHODS@#Human prostate cancer LNCaP-AI cells were transfected with siRNA targeting the PTTG1 gene using the Lipofectamine 2000 transfection reagent. The proliferation, invasiveness and apoptosis of the cells were detected by MTT, Transwell assay and flow cytometry, respectively. The protein expressions of PTTG1, p-Akt, and p-ERK were determined by Western blot and the mRNA expression of PTTG1 measured by agarose gel electrophoresis.@*RESULTS@#The siRNA expression vector markedly down-regulated the expression of PTTG1, which effectively suppressed the proliferation of the LNCaP-AI cells, with the inhibition rates of (19.47 ± 2.12), (24.01 ± 2.13) and (48.02 ± 2.22)% at 24, 48 and 72 hours, respectively, after transfection, with statistically significant differences among the three groups (P <0.05). The number of the cells passing through the polycarbonate film was remarkably decreased at 24, 48 and 72 hours (74.67 ± 9.85, 56.44 ± 8.66 and 37.33 ± 6.14) as compared with the baseline (111.11 ± 13.47) (P <0.01), while the apoptosis rate of the cells was significantly increased at 24, 48 and 72 hours (18.32 ± 0.94), (19.94 ± 1.30) and (21.73 ± 1.88)% in comparison with the baseline (［2.17 ± 0.49］%)， (P <0.05). PTTG1 siRNA combined with androgen antagonist flumatide exhibited even more significant effects in inhibiting the proliferation and promoting the apoptosis of the LNCaP-AI cells than either used alone, and in a flumatide dose-dependent manner. The inhibition and apoptosis rates of the LNCaP-AI cells treated with 50 nmol/L flumatide were (27.13 ± 3.52) and (3.94 ± 0.48)%, and those treated with siRNA + 50 nmol/L flumatide were (67.51 ± 5.13) and (19.93 ± 1.72)%, respectively, both with statistically significant differences between the two groups (P <0.05). The inhibition and apoptosis rates of the cells treated with 100 nmol/L flumatide were (43.72 ± 3.90) and (5.33 ± 0.66)%, and those treated with siRNA + 100 nmol/L flumatide were (73.19 ± 4.78) and (23.43 ± 1.76)%, respectively, both with statistically significant differences between the two groups (P <0.05).@*CONCLUSIONS@#The siRNA expression vector can down-regulate the expression of PTTG1, which can inhibit the proliferation and invasiveness of LNCaP-AI cells, promote their apoptosis, and increase their sensibility to androgen antagonists. Suppressing the expression of PTTG1 may enhance the effect of androgen-deprivation therapy on advanced prostate cancer.

Combination of TMPRSS2 promoter regulation of CD-5-FC gene system and phytochemical drugs effect prostate cancer 22RV1 in vitro / 中华泌尿外科杂志

Objective To explore the effects of TMPRSS2 promoted suicide gene CD-5-FC combined with phytochemicals on the proliferation and apoptosis of prostate cancer (PCa) specific cell-line 22RV1.Methods From March 2016 to October 2016 TMPRSS2-VISA-CD/UPRT'vector was used to deliver pro-drug 5-FC (5-Fluorocytosine) in to PCa specific cell-line 22RV1.Transfection effect was verified by Western-blotting.5-FC,5-FU (5-Fluorouracil) and four phytochemicals epigallocatechin gallate (ECGC),Genistein,Daidzein,and Equol were selected in this study.MTS assay was performed to select dosages,which can kill 10％-40％ of 22RV1 cells,from their pre-set drug concentrations,respectively.According to their select concentrations,either 5-FC plasmid or 5-FU in combination with one of four phytochemicals were added in 22RV1 cells in orders,and then cultured them together.Besides,these four phytochemicals were added in 22RV1 cells individually regarding their selecting concentrations and cultured at the same time.Cell viability was detected by MTS assay on 24hrs,48hrs and 72hrs.Comparing the cell killing rates between the combination groups and each single drug groups on cell-line 22RV1.Results TMPRSS2-VISA-CD/UPRT'plasmid with 5-FC was transfected on PCa specific cell-line 22RV1 successfully.The most obvious transfection occurred on 48hrs.The selected concentration of the pro-drug 5-FC were 83.32 μmol/L and 833.20 μmol/L,5-FU were 76.87 mol/L and 768.70 μmol/L.The concentrations of four phytochemical agents were 2.00 μmol/L,10.00 μmol/L and 20.00 μmol/L.In term of the cell killing numbers,results showed that the combination treatment of 83.32 μmol/L 5-FC/ 76.87μmol/L 5-FU and 10.00 μmol/L/20.00 μmol/L four phytochemicals compared with 10.00 μmol/L/20.00 μmol/L single treatment of four phytochemicals,respectively,there was no significant difference (P ＞0.05),while the combination treatment of 833.20 μmol/L 5-FC/768.70 μ mol/L 5-FU and 2.00 μmol/L/10.00 μmol/L four phytochemicals compared with 2.00 μ mol/L/10.00 μmol/L single treatment of four phytochemicals,respectively,there was a significant difference (P ＜ 0.05).In addition,this study proved that 83.32 μmol/L 5-FC and 76.87 μmol/L 5-FU,833.20 μmol/L 5-FC and 768.70 μmol/L 5-FU reached the same cell killing effect,and there was no statistical difference (P ＞ 0.05).Thus the suicide gene transfection was successful,and its function was the same as the effect of cytotoxic drugs.Conclusions This study has proved that this plasmid with 5-FC suicide gene system can be successfully and efficiently transfected into PCa cells 22RV1.As the pro-drug of 5-FU,5-FC got similar treatment effect with 5-FU,and inhibited cell proliferation.There was no synergistic reaction of enhancing cell apoptosis after combined phytochemical drugs EGCG,Genistein,Daidzen,Equol with suicide gene therapy on 22RV1 cell-line.

Clinical efficacy of surgical treatment for stage Ⅳ gastric cancer after conversion therapy / 中华消化外科杂志

Objective To investigate the clinical efficacy of surgical treatment for stage Ⅳ gastric cancer after conversion therapy.Methods The retrospective cohort study was conducted.The clinicopathological data of 50 stage Ⅳ gastric cancer patients who were admitted to the First Affiliated Hospital of Dalian Medical University between January 2012 and June 2016 were collected.All the 50 patients who were diagnosed with single distal metastasis underwent chemotherapy.After chemotherapy,21 patients with operation indication receiving gastrectomy (R0 or R1 resection) were allocated into the conversion surgery group and 29 without operation indication continuing to chemotherapy were allocated into the chenotherapy group.Patients received S-1 + oxaliplatin or S-1 + docetaxel regimen.Patients underwent open distal or total gastrectomy.Observation indicators:(1) response assessment of chemotherapy (complete remission,partial remission,stable disease and progressive disease),grading of of adverse reactions;(2) intra-and post-operative situations of conversion surgery group:operation procedures,intraoperative situations (operation time,volume of blood loss,number of lymph node dissected and surgical margin) and postoperative situations (complications and duration of hospital stay);(3)comparison of follow-up and survival between the 2 groups;(4) prognostic factors analysis affecting stage Ⅳ gastric cancer patients.Follow-up using outpatient examination,correspondence and telephone interview was performed to detect postoperative survival of patients up to September 2016.Survival time was from operation to the last follow-up or death.Measurement data with normal distribution were represented as x±s.Comparison of count data and univariate analysis were done using the chi-square test.Ordinal data were analyzed by the nonparametric test.The survival rate was calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.Multivariate analysis was done using the COX regression model.Results (1) Response assessment of chemotherapy:of 50 patients,24 received S-1 + oxaliplatin regimen and 26 received S-1 + docetaxel regimen.Twenty-one patients in the conversion surgery group underwent chemotherapy,with negative peritoneal metastasis,N2 and below of lymph node metastasis (No.16 lymph node disappeared or reduced),invasive depth ＜T4b and narrowing or disappeared hepatic metastasis.A median preoperative chemotherapy cycle was 4.2 cycles (range,2.0-9.0 cycles).Chemotherapy reaction of 21 patients:15 had partial remission and 6 had stable disease.Twenty-nine patients without operation indication in the chemotherapy group didn't receive surgery.The median cycle of first-line chemotherapy was 5.5 cycles (range,2.0-10.0 cycles).Chemotherapy reaction of 29 patients:13 had partial remission,11 had stable disease and 5 patient had progressive disease.Chemotherapy adverse reactions of 50 patients:26 had reduced white blood cells (WBCs),including 6 with grade Ⅲ-Ⅳ of adverse reactions;29 had reduced neutrophils,including 12 with grade Ⅲ-Ⅳ of adverse reactions;18 had anemia,including 6 with grade Ⅲ-Ⅳ of adverse reactions;12 had reduced platelets,including 2 with grade Ⅲ-Ⅳ of adverse reactions;27 had apositia,including 5 with grade Ⅲ-Ⅳ of adverse reactions;7 had stomatitis;9 had diarrhea;3 had elevated serum creatinin;4 had hand-foot syndrome;3 had abnormal sensory nerve.There was no chemotherapy-related death.(2) Intra-and post-operative situations of conversion surgery group:of 21 patients in the conversion surgery group,8 underwent radical total gastrectomy + D3 lymph node dissection,6 underwent radical distal gastrectomy + D3 lymph node dissection and 7 underwent radical distal gastrectomy + D2 lymph node dissection (including 4 combined with resection of hepatic metastatic tumors and 1 combined with radiofrequency ablation of hepatic metastatic tumor).Operation time,volume of blood loss,number of lymph node dissected and recovery time of gastrointestinal function of 21 patients were (216±31)minutes,(128±52)mL,31±8 and (3.0± 0.7)days,respectively.There were 17 patients receiving R0 resection and 4 receiving R1 resection (3 with positive gastric margin and 1 with positive hepatic margin).There was no death.Seven of 21 patients with complications were cured by conservative treatment,including 2 with pancreatic fistula,1 with intra-abdominal hemorrhage,1 with intestinal obstruction,1 with pneumonia,1 with intra-abdominal infection and 1 with wound infection.Duration of hospital stay of 21 patients was (13.0±3.0) days.(3) Comparison of follow-up and survival between the 2 groups:50 patients were followed up for 6-46 months,with a median time of 24 months.The 3-year cumulative survival rates in the conversion surgery and chemotherapy groups were respectively 33.3％ and 6.9％,with a statistically significant difference between the 2 groups (x2 =7.678,P＜0.05).Results of further analysis showed that R0 resection of 17 patients and R1 resection of 4 patients in the conversion surgery group were respecgtively (25.3±2.8)months and (8.3±0.9)months,with a statistically significant difference between the 2 groups (X2=16.242,P＜0.05).(4) Prognostic factors analysis affecting stage Ⅳ gastric cancer patients:results of univariate analysis showed that T stage,N stage,response assessment of chemotherapy,surgery after chemotherapy and degree of tumor radical resection were related factors affecting prognosis of stage Ⅳ gastric cancer patients (X2 =5.288,12.645,25.581,8.372,12.001,P＜0.05).Results of multivariate analysis showed that R1 resection after conversion therapy was an independent risk factor affecting prognosis of stage Ⅳ gastric cancer patients (HR=14.021,95％ confidence interval:1.928-10.938,P＜0.05).Conclusion Radical resection after conversion therapy can increase survival rate of stage Ⅳ gastric cancer patients,and R1 resection after conversion therapy is an independent risk factor affecting poor prognosis of stage Ⅳ gastric cancer patients.