Objective To investigate the neuroprotective effect of ligustilide(LIG)-mediated phosphatase and tensin homolog(PTEN)-induced putative kinase 1(PINK1)/Parkin pathway on mitophagy in rats with cerebral ischemia-reperfusion injury.Methods 161 male Sprague Dawley(SD)rats were randomly divided into sham operation(Sham)group,model group,LIG low-dose group,LIG high-dose group,mitophagy inhibitor(Mdivi-1)group,LIG high-dose+Mdivi-1 group,and the positive drug Nimodipine(NMDP)group,each with 23 rats.A modified middle cerebral artery wire thrombus method was used to construct a cerebral ischemia/reperfusion model in rats,and the neurobehavioral scores of rats in each group were compared by Longa's five-point scale;the volume of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TCC)staining,the histopathology and ultrastructure of the hippocampus were examined by hematoxylin-eosin(HE)staining and transmission electron microscope(TEM).And the Na+-K+-Adenosine Triphosphate was measured by enzyme-linked immunosorbent assay(ELISA);double immunofluorescence staining for translocase of the outer membrane of mitochondrion 20(TOMM20)and Microtubule-associated protein 1 light chain 3(LC3)co-localized area percentage.Flow cytometry assay(FCM)to test the level of reactive oxygen(ROS);real-time fluorescence quantitative PCR(qRT-PCR)was used to measure the relative content of mitochondria in hippocampal neurons;and Western blot was performed to test the level of autophagy and the PINK1/Parkin pathway related protein expression.Results Compared with the Sham group,the neurological function score and cerebral infarction volume of the model group were increased,the hippocampal neurons showed pathological damage such as disordered arrangement,nucleolus disappearance and partial shrinkage of the nucleus and plasma,nuclear membrane rupture,swelling,membrane rupture and crista reduction of some mitochondria,a large number of autophagosomes were observed,and the colocalization area percentage of TOMM20 and LC3 was increased.TOMM20 and cytochrome C oxidase subunit IV isoform 1(COX4I1)in hippocampus and selective autophagy adaptor protein 62(p62)protein expression,mitochondrial encoded ATP synthase 6(mt-ATP6)/Ribosomal protein L13(Rpl13)ratio and Na+-K+-ATPase content decreased,while PINK1 and Parkin protein expression,LC3-II/I ratio and ROS relative content increased,and the differences were statistically significant(t=4.602～52.012,all P<0.01).Compared with the model group,the neurological function score,cerebral infarction volume,pathological and ultrastructural damage of hippocampal neurons were significantly improved in the LIG low,high dose and NMDP groups,and the differences were statistically significant(t=4.851～12.525,all P<0.01).The colocalization of TOMM20 and LC3 and the content of Na+-K+-ATPase were increased,while the expression of TOMM20,COX4I1 and p62 proteins and the mt-ATP6/Rpl13 ratio were decreased in the high-dose LIG group.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were increased,and the differences were statistically significant(t=4.087～33.211,all P<0.01).Compared with the LIG high-dose group,the Mdivi-1 and LIG+Mdivi-1 groups had significantly decreased colocalization of TOMM20 and LC3 and Na+-K+-ATPase content,and significantly increased expression of TOMM20,COX4I1 and p62 proteins and mt-ATP6/Rpl13 ratio.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were decreased,and the differences were statistically significant(t=4.008～43.415,all P<0.01).However,the percentage of TOMM20 and LC3 co-localization area,PINK1 and Parkin protein expression,LC3-II/I ratio and Na+-K+-ATPase content in the hippocampus of the LIG+Mdivi-1 group were higher than those of the Mdivi-1 group.The protein expression of COX4I1 and p62,mt-ATP6/Rpl13 ratio and ROS level were lower than those in MDIV-1 group,and the differences were statistically significant(t=3.721～21.513,all P<0.01).Conclusion LIG may activate mitophagy by regulating PINK1/Parkin signaling pathway to protect neurons from cerebral ischemia-reperfusion injury in rats.

Objective To investigate the neuroprotective effect of ligustilide(LIG)-mediated phosphatase and tensin homolog(PTEN)-induced putative kinase 1(PINK1)/Parkin pathway on mitophagy in rats with cerebral ischemia-reperfusion injury.Methods 161 male Sprague Dawley(SD)rats were randomly divided into sham operation(Sham)group,model group,LIG low-dose group,LIG high-dose group,mitophagy inhibitor(Mdivi-1)group,LIG high-dose+Mdivi-1 group,and the positive drug Nimodipine(NMDP)group,each with 23 rats.A modified middle cerebral artery wire thrombus method was used to construct a cerebral ischemia/reperfusion model in rats,and the neurobehavioral scores of rats in each group were compared by Longa's five-point scale;the volume of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TCC)staining,the histopathology and ultrastructure of the hippocampus were examined by hematoxylin-eosin(HE)staining and transmission electron microscope(TEM).And the Na+-K+-Adenosine Triphosphate was measured by enzyme-linked immunosorbent assay(ELISA);double immunofluorescence staining for translocase of the outer membrane of mitochondrion 20(TOMM20)and Microtubule-associated protein 1 light chain 3(LC3)co-localized area percentage.Flow cytometry assay(FCM)to test the level of reactive oxygen(ROS);real-time fluorescence quantitative PCR(qRT-PCR)was used to measure the relative content of mitochondria in hippocampal neurons;and Western blot was performed to test the level of autophagy and the PINK1/Parkin pathway related protein expression.Results Compared with the Sham group,the neurological function score and cerebral infarction volume of the model group were increased,the hippocampal neurons showed pathological damage such as disordered arrangement,nucleolus disappearance and partial shrinkage of the nucleus and plasma,nuclear membrane rupture,swelling,membrane rupture and crista reduction of some mitochondria,a large number of autophagosomes were observed,and the colocalization area percentage of TOMM20 and LC3 was increased.TOMM20 and cytochrome C oxidase subunit IV isoform 1(COX4I1)in hippocampus and selective autophagy adaptor protein 62(p62)protein expression,mitochondrial encoded ATP synthase 6(mt-ATP6)/Ribosomal protein L13(Rpl13)ratio and Na+-K+-ATPase content decreased,while PINK1 and Parkin protein expression,LC3-II/I ratio and ROS relative content increased,and the differences were statistically significant(t=4.602～52.012,all P<0.01).Compared with the model group,the neurological function score,cerebral infarction volume,pathological and ultrastructural damage of hippocampal neurons were significantly improved in the LIG low,high dose and NMDP groups,and the differences were statistically significant(t=4.851～12.525,all P<0.01).The colocalization of TOMM20 and LC3 and the content of Na+-K+-ATPase were increased,while the expression of TOMM20,COX4I1 and p62 proteins and the mt-ATP6/Rpl13 ratio were decreased in the high-dose LIG group.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were increased,and the differences were statistically significant(t=4.087～33.211,all P<0.01).Compared with the LIG high-dose group,the Mdivi-1 and LIG+Mdivi-1 groups had significantly decreased colocalization of TOMM20 and LC3 and Na+-K+-ATPase content,and significantly increased expression of TOMM20,COX4I1 and p62 proteins and mt-ATP6/Rpl13 ratio.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were decreased,and the differences were statistically significant(t=4.008～43.415,all P<0.01).However,the percentage of TOMM20 and LC3 co-localization area,PINK1 and Parkin protein expression,LC3-II/I ratio and Na+-K+-ATPase content in the hippocampus of the LIG+Mdivi-1 group were higher than those of the Mdivi-1 group.The protein expression of COX4I1 and p62,mt-ATP6/Rpl13 ratio and ROS level were lower than those in MDIV-1 group,and the differences were statistically significant(t=3.721～21.513,all P<0.01).Conclusion LIG may activate mitophagy by regulating PINK1/Parkin signaling pathway to protect neurons from cerebral ischemia-reperfusion injury in rats.

Objective:To evaluate the clinical utility of an intelligent endoscope transportation system in the digestive endoscopy center.Methods:A parallel-group controlled trial was conducted at Digestive Endoscopy Center of Qilu Hospital of Shandong University from June 1st to December 31st 2024, comparing robotic intelligent endoscope transport (experimental group) versus manual transport (control group). Performance metrics, including response time, transportation speed, labor efficiency, contamination prevention, closed-loop traceability, and nursing staff satisfaction, were statistically analyzed. Full-time equivalent (FTE) was introduced to quantify the operational efficiency of the experimental group.Results:The study included a total of 60 206 instances of intelligent endoscope transportation and 60 485 instances of manual transportation data. The robotic group demonstrated significantly shorter response times versus manual group for initial dispatch (51.08±14.97 seconds VS 54.44±13.61 seconds, t=35.8, P<0.001) and recovery response time (32.52±11.26 seconds VS 40.20±11.40 seconds, t=103.93, P<0.001). During the 148 days operational period, the success rate was 99.83% (60 104/60 206) and the failure rate was 0.17% (102/60 206) for robotic transports. Primary failure causes were wireless disconnection, pathfinding errors, and mechanical faults, averaging 1.05 malfunctions/month with no adverse events. The success and failure rate was 99.26% (60 043/60 485) and 0.74% (442/60 485) respectively for manual transports. Staff satisfaction was significantly higher for robotic transport in endoscopic transportation (4.65±0.55 scores VS 3.97±0.98 scores, t=96.5, P<0.001) and delivery process (4.71±0.59 scores VS 3.90±1.04 scores, t=210.3, P<0.001). and workload intensity was significantly lower (4.06±0.77 scores VS 4.48±0.63 scores, t=59.9, P=0.025). The system reduced labor requirements by 3.68 FTE, yielding annual savings of ￥657 000. Conclusion:The robotic intelligent endoscope transport system improves work efficiency, reduces nursing labor costs and physical workload, enhances job experience and satisfaction, and enables full-process smart traceability, providing a validated solution for endoscopy center logistics.

Objective:To evaluate the clinical utility of an intelligent endoscope transportation system in the digestive endoscopy center.Methods:A parallel-group controlled trial was conducted at Digestive Endoscopy Center of Qilu Hospital of Shandong University from June 1st to December 31st 2024, comparing robotic intelligent endoscope transport (experimental group) versus manual transport (control group). Performance metrics, including response time, transportation speed, labor efficiency, contamination prevention, closed-loop traceability, and nursing staff satisfaction, were statistically analyzed. Full-time equivalent (FTE) was introduced to quantify the operational efficiency of the experimental group.Results:The study included a total of 60 206 instances of intelligent endoscope transportation and 60 485 instances of manual transportation data. The robotic group demonstrated significantly shorter response times versus manual group for initial dispatch (51.08±14.97 seconds VS 54.44±13.61 seconds, t=35.8, P<0.001) and recovery response time (32.52±11.26 seconds VS 40.20±11.40 seconds, t=103.93, P<0.001). During the 148 days operational period, the success rate was 99.83% (60 104/60 206) and the failure rate was 0.17% (102/60 206) for robotic transports. Primary failure causes were wireless disconnection, pathfinding errors, and mechanical faults, averaging 1.05 malfunctions/month with no adverse events. The success and failure rate was 99.26% (60 043/60 485) and 0.74% (442/60 485) respectively for manual transports. Staff satisfaction was significantly higher for robotic transport in endoscopic transportation (4.65±0.55 scores VS 3.97±0.98 scores, t=96.5, P<0.001) and delivery process (4.71±0.59 scores VS 3.90±1.04 scores, t=210.3, P<0.001). and workload intensity was significantly lower (4.06±0.77 scores VS 4.48±0.63 scores, t=59.9, P=0.025). The system reduced labor requirements by 3.68 FTE, yielding annual savings of ￥657 000. Conclusion:The robotic intelligent endoscope transport system improves work efficiency, reduces nursing labor costs and physical workload, enhances job experience and satisfaction, and enables full-process smart traceability, providing a validated solution for endoscopy center logistics.

Objective:To investigate the effect of single nucleotide variation of osteoprotegerin (OPG) gene on the occurrence of osteoporosis (OP) in patients with gestational diabetes mellitus (GDM) .Methods:From Apr. 2018 to Apr. 2022, 276 pregnant women with GDM who underwent prenatal examination and gave birth in Linyi People’s Hospital were collected for analysis, general data were collected and bone mineral density was tested. According to the bone mineral density test results, they were divided into normal group and OP group. The OPG genotype was tested, and the general information, OPG genotype and allele frequency of the two groups were compared. The differences in bone mineral density among different genotypes of OPG were compared, and the genotypes affecting the risk of OP in GDM patients were analyzed.Results:There was no significant difference in the general data of the two groups of patients (all P>0.05). The allelic distribution of the rs3134069 and rs2073618 loci of the OPG gene in the two groups of patients conformed to the Hardy-Weinberg equilibrium law (all P>0.05). There was a statistically significant difference in the frequency of the AC genotype at rs3134069 between the two groups ( χ2=7.75, P=0.005). Taking patients with the AA genotype as a reference, patients with the AC genotype had a lower risk of developing OP ( OR=0.15, 95% CI: 0.03-0.59). There was a statistically significant difference in the frequency of CC genotype at rs2073618 between the two groups ( χ2=11.30, P=0.001). Taking patients with GG genotype as a reference, patients with CC genotype had a higher risk of developing OP ( OR=7.42, 95% CI: 2.19-27.18). Comparing rs3134069 and rs2073618 loci, there was no significant difference in bone mineral density at each part of the three genotypes (all P>0.05). The multivariate Logistic regression model showed that the AC genotype of rs3134069 ( OR=0.18, 95% CI: 0.03-0.70, P=0.029) was a protective factor for the induction of OP, while GC genotype of rs2073618 ( OR=6.86, 95% CI: 1.57-27.15, P=0.007) were the risk factors for OP in GDM patients. Conclusion:The CC genotype of rs2073618 is significantly positively correlated with the susceptibility to OP in GDM patients.

Objective:To investigate the effects of ursolic acid (UA) on proliferation, migration and iron death of ectopic endometrial stromal cells (EESCs) and its mechanism.Methods:Mouse model of endometriosis was established and the primary EESCs were isolated. The cells were treated with UA at different concentrations (0, 2.5, 5, 10, 20, 40, 50, 80, 100, 200 μmol/L). The cells were divided into Control group (normal culture), 2.5 μmol/L UA group (2.5 μmol/L UA treatment), 5.0 μmol/L UA group (5.0 μmol/L UA treatment), 10.0 μmol/L UA group (10 μmol/L UA treatment), and UA+DUSP19 group (10 μmol/L UA+50 μmol/L JAK2/STAT3 signal pathway activator DUSP19 treatment). Cell survival rate was detected by CCK-8 method. Cell proliferation was detected by plate cloning method. Transwell chamber assay was used to detect cell migration. The levels of Fe 2+ and the contents of malondialdehyde (MDA), reactive oxygen species (ROS) and superoxide dismutase (SOD) were detected by kit. Protein expression levels of Ki67, PCNA, CyclinD1, p-JAK2, p-STAT3, JAK2 and STAT3 were detected by western blot. Results:The number of clones in Control, 2.5 μmol/L UA, 5.0 μmol/L UA and 10.0 μmol/L UA groups were as follows: 152.22±15.47, 121.22±11.54, 92.00±5.54, 66.44±6.88; Ki67 protein expression was 1.08±0.10, 0.73±0.07, 0.61±0.06, 0.45±0.02, respectively; The expression of PCNA protein was 0.85±0.07, 0.64±0.05, 0.41±0.03, 0.31±0.05, respectively; CyclinD1 protein expression levels were 0.98±0.11, 0.65±0.06, 0.51±0.05, 0.42±0.07, respectively. The migration numbers were 92.78±6.27, 62.22±2.20, 50.22±4.59 and 39.11±4.33, respectively; Fe 2+ levels were (1.06±0.07) μmol/g, (1.21±0.11) μmol/g, (1.33±0.08) μmol/g, (1.47±0.09) μmol/g, respectively; MDA content was (0.48±0.06) μmol/g, (0.65±0.07) μmol/g, (0.85±0.08) μmol/g, (1.03±0.11) μmol/g, respectively; ROS contents were (19.85±1.21) %, (24.83±2.79) %, (29.04±1.86) %, (33.87±2.45) %, respectively; SOD content were (36.41±3.56) U/mg, (31.03±2.81) U/mg, (25.63±2.84) U/mg, (19.62±1.67) U/mg, respectively; p-JAK2 protein expression was 0.85±0.10, 0.75±0.06, 0.53±0.05, 0.31±0.03, respectively; p-STAT3 protein expression was 1.08±0.11, 0.79±0.06, 0.63±0.07, 0.42±0.03, respectively. The p-JAK2 protein content in UA group and UA+DUSP19 group was 0.38±0.05 and 0.75±0.08, respectively; p-STAT3 protein expression was 0.46±0.04 and 0.80±0.03, respectively; The cell survival rates were (52.55±2.44) % and (82.18±4.72) %, respectively; Fe 2+ levels were (1.57±0.06) μmol/g and (1.21±0.13) μmol/g, respectively. The differences in the above indicators between the Control group and the 2.5 μmol/L UA group, 5.0 μmol/L UA group and 10.0 μmol/L UA group were statistically significant ( P<0.05). There were statistically significant differences among 2.5 μmol/L UA group, 5.0 μmol/L UA group and 10.0 μmol/L UA group ( P<0.05). There were statistically significant differences in p-JAK2, p-STAT3, cell survival rate and Fe 2+ levels between UA group and UA+DUSP19 group ( P<0.05) . Conclusion:Ursolic acid can inhibit the proliferation and migration of EESCs cells and induce iron death by regulating JAK2/STAT3 signaling pathway, thus playing a protective role in endometriosis.

[摘 要] 目的：体内外实验探讨木鳖子单体化合物对羟基桂皮醛[Momordica cochinchinensis(Lour.)Spreng.p-hydroxycinnamaldehyde，CMSP]对小鼠黑色素瘤移植瘤生长和转移的影响及其作用机制。方法：建立荷瘤小鼠动物模型，并将18只C57BL/6小鼠随机分成3组（每组6只）：对照组（腹腔注射0.1 ml生理盐水）、CMSP治疗组（分别腹腔注射0.1 ml 1、2 mg/ml CMSP），给药的第5天开始，每次给药前用卡尺分别测量和计算小鼠移植瘤的体积，实验结束后称量移植瘤的质量；H-E染色后光镜观察肝组织的病理学变化；免疫组织化学SP法观察移植瘤组织E-cadherin和vimentin蛋白的表达。采用细胞划痕和Transwell实验分别检测CMSP实验组（10、20 µg/ml）黑色素瘤B16细胞24、48 h的迁移能力，qPCR法检测CMSP处理24 h后B16细胞EMT相关mRNA表达，WB法检测CMSP处理B16细胞48 h后β-catenin、p-β-catenin（Ser675）、vimentin和E-cadherin蛋白的表达水平。结果：CMSP治疗组小鼠移植瘤平均体积和肿瘤质量明显降低（均P<0.05）；对照组小鼠肝脏中转移灶的数量明显多于CMSP（1、2 mg/kg）治疗组（均P<0.05），CMSP（2 mg/kg）处理组小鼠的肝组织内未发现明显转移灶。CMSP治疗组（1、2 mg/kg）移植瘤组织中E-cadherin蛋白表达水平明显高于对照组（均P<0.05），而vimentin蛋白表达显著低于对照组（均P<0.01）。体外实验中，CMSP实验组（10、20 μg/ml）B16细胞24、48 h后划痕愈合率较对照组均明显降低（均P<0.05）。20 μg/ml CMSP处理B16细胞24、48 h后穿过Transwell小室的细胞数较对照组则显著下降（均P<0.01）。CMSP（10、20 μg/ml）处理B16细胞后β-catenin mRNA表达水平较对照组明显降低（均P<0.01），E-cadherin mRNA表达水平则明显升高（均P<0.05），而vimentin mRNA表达水平在10 μg/ml处理组与对照组相比差异无统计学意义（P>0.05），20 μg/ml处理组则明显降低（P<0.01）。与对照组相比，CMSP实验组（10、20 μg/ml）处理B16细胞后β-catenin、p-β-catenin和vimentin蛋白表达均显著降低（均P<0.01），而E-cadherin蛋白表达则明显升高（均P<0.01）。结论：CMSP能够抑制小鼠黑色素瘤移植瘤的生长和转移，其作用机制可能与抑制wnt/β-catenin通路的活性相关。

[Abstract] Objective: To observe the effect of allogeneic platelets transfusion on the invasion and metastasis of human lung cancer A549 cells, and to preliminarily explore its mechanism of action. Methods: Eighty-nine patients with advanced lung cancer, who had received platelet transfusion in the Chemotherapy Department of Fourth Hospital of Hebei Medical University between January 2017 and December 2018, were enrolled in this study. The study cells were randomized into Ctrl group (A549 cells co-incubated with culture medium), Before group, and After group (A549 cells co-incubated with plasma Before and After platelet transfusion, respectively). The migration and invasion of A549 cells co-cultured with plasma before and after platelet transfection were detected by Scratch and Transwell experiments. The expression of MMPs, TIMPs and epithelial-mesenchymal transition (EMT) related proteins E-cadherin, N-cadherin and Vimentin, as well as vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR2) were detected by Western blotting (WB) method. Results: The scratch healing ability of A549 cells in After group was significantly higher than that of Ctrl group and Before group [(73.67±2.60)% vs (58.33±2.33)%, (35.33±2.03) %; P<0.01, vs Ctrl group; P<0.05, vs Before group], and there was also a significant difference between Before group and Ctrl group (P<0.05). The results of cell migration experiment showed that the number of transmembrane cells in After group was significantly higher than that in Ctrl group and Before group [(69.67±7.84) vs (18±2.08) and (39.33±2.03), all P<0.01]. The cell invasion experiment showed that the number of transmembrane cells in After group was significantly higher than that in Ctrl group and Before group [(59.34±3.46) vs (18.34±1.56) and (37.58±2.79), all P<0.01]. When A549 cells were co-incubated with plasma before and after platelet transfusion for 48 h, it was found that the expressions of MMP9 and MMP2 were increased (P<0.05), while their inhibitors TIMP1 and TIMP2 were decreased (P<0.01); the expressions of EMT-related proteins N-cadherin and Vimentin were increased (P<0.05), but E-cadherin was decreased (P<0.01); the expressions of angiogenesis related proteins VEGF and VEGFR2 were increased (P<0.05). Conclusion: Alloplatelets transfusion can promote the invasion and metastasis of lung cancer A549 cells, which may be realized by regulation of the expressions of EMT, metallomatrix protease and vascular growth factor-related proteins.

To explore influence of bisoprolol combined benazepril on ECG and left ventricular diastolic function in hypertensive patients with acute heart failure (AHF).Methods :A total of 124 hypertensive patients with AHF were randomly and equally divided into routine treatment group and combined treatment group (received biso‐prolol combined benazepril based on routine treatment ) ,both groups were treated for two months .Therapeutic effect ,ECG indexes ,left ventricular diastolic function indexes ,levels of heart failure and myocardial injury markers etc .before and after treatment were compared between two groups .Results : After two‐month treatment ,total ef‐fective rate of combined treatment group was significantly higher than that of routine treatment group (96. 77% vs. 82. 26%, P＝0.008) ;compared with routine treatment group ,there were significant reductions in QRS wave dura‐tion [ (103. 87 ± 9.70) ms vs.(94.12 ± 8. 93) ms] ,QTc duration [ (432.37 ± 33. 24) msvs .(418.96 ± 29. 64) ms] , plane QRS‐T angle [ (59.75 ± 26. 61)°vs.(48.19 ± 22.30)°] ,mitral annulus late diastolic peak flow velocity (Am) [ (12.84 ± 3.40) cm／svs .(11. 39 ± 3. 11) cm／s] ,plasma levels of N terminal pro brain natriuretic peptide [ (1. 20 ± 0.58) μg／L vs .(0. 75 ± 0.47) μg／L] ,carbohydrate antigen 125 [ (19.10 ± 9.24) U／ml vs.(13.93 ± 7.85) U／ml] ,galectin‐3 [ (4.72 ± 2. 25) μg／L vs .(3.28 ± 1. 65) μg／L] ,cardiac troponin I [ (1.93 ± 0. 97) μg／L vs.(1. 46 ± 0. 85) μg／L] ,and significant rise in mitral early／late diastolic peak flow velocity (E／A) [(1. 18 ± 0.30) vs.(1. 31 ± 0. 28)] and mitral annulus early diastolic peak flow velocity (Em) [ (12.90 ± 3. 76) cm／svs.(14. 49 ± 3.25) cm／s] in combined treatment group , P＜0. 05 or ＜0.01. There was no significant difference in incidence rates of ad‐verse reactions between two groups , P＞0.05 all.Conclusion :Bisoprolol combined benazepril possesses significant therapeutic effect on hypertensive patients with AHF ,and its improving effect on ECG indexes and left ventricular diastolic function is significant .

OBJECTIVE： To study the inhibitory effect of dictamnine on the viability of mice spleen lymphocyte in vitro and explore its potential mechanism. METHODS： The primary spleen lymphocytes of mice were isolated and cultured. The cells were treated with 0 （blank control）， 50， 100， 150 μmol/L dictamnine for 24 h. MTT assay was used to determine the cell viability； Lactic dehydrogenase （LDH） assay was used to determine release rate of LDH. Early apoptosis rate was detected by flow cytometry. Necrosis rate was detected by Hoechst 33342 and PI double staining； Western blot assay was used to detect the protein expressions of Caspase 3 and Cleaved-Caspase 3 in cells. Comet assay was used to detect DNA damage in cells （reflected in the proportion of DNA tail area）. RESULTS： Compared with blank control， 100， 150 μmol/L dictamnine could significantly inhibit the viability of lymphocytes （P＜0.01）. 150 μmol/L dictamnine could significantly increase the release of LDH （P＜0.05）， and release rate reached 79.37％. 50， 100， 150 μmol/L dictamnine could improve the early apoptotic rate of lymphocyte， but there was no statistical significance （P＞0.05）. 150 μmol/L dictamnine could significantly increase the necrosis rate （P＜0.05）， and necrosis rate reached 78.64％. 50， 100， 150 μmol/L dictamnine could increase the protein expression of Caspase 3， but there was no statistical significance （P＞0.05）， while 50， 100 μmol/L dictamnine could improve the protein expression of Cleaved-Caspase 3 significantly （P＜0.05）. DNA damage was induced in a dose-dependent manner by dictamnine， in which 100 and 150 μmol/L dictamnine could significantly increase DNA tail area （P＜0.01）. CONCLUSIONS： Dictamnine can inhibit spleen lymphocyte viability， and the mechanism may be related to inducing spleen lymphocyte necrosis and DNA damage.