Effects of Berbamine on PAF Production in Human Neutrophils and on Platelet Aggregation

本实验研究了双苄基异喹啉类生物碱小檗胺（Ｂｅｒｂａｍｉｎｅ）对人中性粒细胞血小板激活因子（ＰＡＦ）的产生及ＰＡＦ引起的兔血小板聚集的影响，并与钙通道阻断剂维拉帕米进行比较。结果表明，小檗胺（５０μｍｏｌ／Ｌ，１００μｍｏｌ／Ｌ）和维拉帕米（１０μｍｏｌ／Ｌ，１００μｍｏｌ／Ｌ）预处理的人粒细胞，用Ａ－２３１８７攻击后，ＰＡＦ的产生明显降低。小檗胺和维拉帕米也能抑制ＰＡＦ（７０ｐｍｏｌ／Ｌ）引起的血小板聚集，其抑制作用呈剂量依赖性。本实验结果提示，小檗胺和维拉帕米对ＰＡＦ生成及血小板聚集的抑制作用可能与阻断钙离子内流有关。

Berbamine induces apoptosis in human hepatoma cell line SMMC7721 by loss in mitochondrial transmembrane potential and caspase activation

Objective:To investigate the effect of berbamine on human hepatoma cell line SMMC7721.Methods:The effects of 24 h and 48 h incubation with different concentrations(0～64 μg/ml) of the berbamine on SMMC7721 cells were evaluated using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide(MTT) assay.Hoechst 33258 staining was conducted to distinguish the apoptotic cell,and the appearance of sub-G1 stage was determined by PI(propidium iodide) staining,the percentage of apoptotic cell was determined by flow cytometry following annexin V/PI staining.Flow cytometry was performed to analyze the cell cycle distribution and the mitochondrial membrane potential(?ψm);the expression of activated caspase3 and caspase9 was analyzed by Western-blot.Results:The proliferation of SMMC7721 was decreased after treatment with berbamine in a dose-and time-dependent manner.Berbamine could induce apoptosis in SMMC7721 cells and could cause cell cycle arrest in G0/G1 phase,to induce loss of mitochondrial membrane potential(?ψm) and activate caspase3 and caspase9.Berbamine-induced apoptosis could be blocked by the broad caspase inhibitor z-VAD-fmk.Conclusion:Berbamine exerts antiproliferative effects on human hepatocellular carcinoma SMMC7721 cells.The anticancer activity of berbamine could be attributed partly to its inhibition of cell proliferation and induction of apoptosis in cancer cells through loss in mitochondrial transmembrane potential and caspase acti-vation.

Identification of berbamine dihydrochloride from barberry as an anti-adipogenic agent by high-content imaging assay

Objective:Lipid droplet(LD)deposition in adipose tissue is a critical factor leading to metabolic dysfunction.Various herbal medicines in traditional Chinese medicine(TCM)are used to treat hyperlipidemia,type 2 diabetes,obesity,and other diseases.The objective of this study was to identify potential anti-adipogenic agents from TCM herbal compounds.Methods:One hundred and twenty compounds were evaluated in terms of their effect on adipocyte differentiation through image-based high content screening.Anti-adipogenic effects of identified hits were further confirmed at various concentrations.In addition,drug-induced liver injury assay was performed with HepG2 cells to test the hepatotoxicity of hit compounds.Results:Berbamine(BBM),a chemical isolated from barberry,and a derivative of BBM,berbamine dihydrochloride(BBMD),reduced LDs formation by more than 50%.Dose-dependent effects were observed and the IC50 values of the two hits,BBM and BBMD,were determined as 1.88 mM and 0.95 mM,respectively.Moreover,BBM induced mild HepG2 cell injury,while its dihydrochloridedBBMD did not exhibit hepatotoxicity within 40 mM.Conclusion:This study demonstrates that BBMD may be a potential therapeutic candidate for disorders associated with elevated LDs accumulation.

Roles of berbamine in the normal and ischemia/reperfusion hearts

Myocardial infarction resulting from coronary atherosclerosis is the leading cause of death in modern soci- ety. Reperfusion is an essential treatment to salvage ischemia myocardium from necrosis, while it also leads to addi- tional damage. Therefore, exploring effective medicines to protect the heart from post-ischemic injury is one of the major objectives of cardiovascular research. Berbamine is a nature compound of bisbenzylisochinoline alkaloids from Barberry. We found that it displays positive inotropic and lusitropic effects at lower concentrations by increasing myofilament Ca2＋ sensitivity via a PKCe-dependent signaling pathway. Moreover, berbamine preconditioning con- fers cardioprotection against ischemia/reperfusion （I/R） injury by attenuating the Ca2＋ overloading and preventing the calpain activation through the activating of PI3K-Akt-GSK3β pathway and subsequently opening of the mitoKATP channel. Furthermore, we demonstrate that berbamine postconditioning conferred the cardioprotective effect against I/R injury by the regulation of autophagy. These findings reveal new roles and mechanisms of berbamine in the heart and cardioprotection against I/R injury.

液氧液甲烷同温共底贮存瞬态热力特性仿真研究

针对大面积冷屏保护下的液氧/液甲烷同温共底贮箱,建立了耦合真空多层绝热与主动制冷系统的瞬态传热模型,研究了液氧/液甲烷共底自增压与零蒸发贮存过程中贮箱外部绝热结构与内部气液相的热力参数变化规律,讨论了共底夹层采用不具有绝热能力的材料对液氧/液甲烷共底零蒸发贮存特性的影响。研究结果表明,在适当的冷量输入条件下,大面积冷屏方案可以实现外界漏热的有效阻挡;采用铝合金共底夹层有利于稳定液氧和液甲烷的共底贮存状态,使液氧/液甲烷在20 h内快速达到热平衡;在零蒸发贮存周期内,液氧/液甲烷共底贮存温度波动小于0.2 K,压力波动小于2.46 kPa且具有抗热扰动的能力。

基于共轭梯度法的晶闸管电热耦合模型快速求解方法研究

为解决传统求解技术在处理效率和计算成本上的局限问题,针对晶闸管电热应力耦合交互模型,提出一种基于共轭梯度法的高效解析方法。通过优化迭代过程和收敛条件来显著提升求解效率和精度。新的参数选择策略被引入以自动调整算法迭代步长,加快收敛速度,减少计算资源消耗。相比传统求解方法,所提优化方法在求解时间上平均减少10%,求解精度提高8%。这一进展证明自适应共轭梯度法在电热应力耦合模型快速求解中的有效性,可为电力电子设备热管理提供高效、可靠的计算工具。所提方法在多种测试条件下均表现出显著的提升效率和良好的精确度,为晶闸管电热耦合模型的高效求解提供了创新方案,同时对电力电子领域的相关研究具有重要的实践意义。

白葡奈氏菌片联合布地奈德雾化吸入治疗小儿急性肺炎的临床疗效

目的 探究白葡奈氏菌片联合布地奈德雾化治疗小儿急性肺炎(AP)的临床疗效。方法 选取2021年2月至2023年2月界首市人民医院收治的92例AP患儿,采用随机数字表法将其分为观察组与对照组,每组各46例,对照组在常规治疗的基础上给予安慰剂治疗,观察组在常规治疗的基础上口服白葡奈氏菌片。治疗5 d后评估两组患儿疗效,酶联免疫法检测血清炎症因子水平,流式细胞法检测免疫功能水平,脉冲震荡肺功能仪检测患儿呼吸力学指标,并观察治疗方案的安全性。结果 与对照组相比,观察组总有效率(78.26%vs. 95.65%)升高(P<0.05);观察组治疗后肿瘤坏死因子-α(TNF-α)水平低于对照组[(16.02±2.54) ng/L vs.(18.47±2.39) ng/L],白细胞介素-10(IL-10)水平也低于对照组[(105.68±12.59) ng/L vs.(146.92±17.33) ng/L],干扰素-γ(IFN-γ)水平高于对照组[(189.76±24.59) ng/L vs.(161.40±20.76) ng/L](P<0.05);两组患儿治疗后CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)水平均升高,观察组各免疫指标优于对照组(P<0.05);两组患儿治疗后5 Hz时气道阻力(R5)、共振频率(Fres)均降低,总顺应性(Ct)升高(P<0.05);观察组各项呼吸力学指标优于对照组(P<0.05);观察组退热时间、咳嗽消失时间、肺啰音消失时间及住院时间均短于对照组(P<0.05);两组患儿治疗期间均未见明显的不良反应。结论 白葡奈氏菌片联合雾化治疗能够提高AP患儿的疗效,减轻机体炎症反应,提高患儿呼吸功能及免疫功能,加速改善临床症状,且安全性较高。

壮医莲花针拔罐逐瘀疗法治疗风痰瘀阻型缺血性中风恢复期的临床效果

目的 探讨壮医莲花针拔罐逐瘀疗法治疗风痰瘀阻型缺血性中风恢复期的临床效果。方法 选取2023年1月至10月广西国际壮医医院风痰瘀阻型缺血性中风恢复期的72例患者,按照随机数字表法将其分为治疗组与对照组,每组36例。对照组采用基础治疗,治疗组在对照组基础上,增加壮医莲花针叩刺、刺拔、吸附。两组均治疗28 d。比较两组的临床效果和治疗前、治疗14 d后、治疗28 d后的中医证候积分、日常生活活动(ADL)量表评分、生活质量评分、美国国立卫生研究院卒中量表(NIHSS)评分。结果 治疗组临床疗效优于对照组(P<0.05)。整体分析发现:中医症候评分组间比较、时间点比较及交互作用差异均有统计学意义(P<0.05)。NIHSS、ADL、生活质量评分组间比较、时间点比较差异均有统计学意义(P<0.05)。组内比较:治疗14、28 d后两组中医症候、NIHSS评分均低于治疗前,治疗28 d后两组中医症候、NIHSS评分均低于治疗14 d后;治疗14、28 d后两组ADL、生活质量评分均高于治疗前,治疗28 d后两组ADL、生活质量评分均高于治疗14 d后(P<0.05)。组间比较:治疗14、28 d后治疗组中医症候、NIHSS评分低于同期对照组,ADL、生活质量评分均高于同期对照组(P<0.05)。结论 壮医莲花针拔罐逐瘀疗法是治疗风痰瘀阻型缺血性中风恢复期患者的一种有效方法,可改善神经功能缺损、提高日常生活活动能力。

CXC chemokines and chemokine receptors in gastric cancer: From basic findings towards therapeutic targeting

Gastric cancer is the fourth most common cancer,and the second-highest cause of cancer-related deaths worldwide.Despite extensive research to identify novel diagnostic and therapeutic agents,patients with advanced gastric cancer suffer from a poor quality of life and poor prognosis,and treatment is dependent mainly on conventional cytotoxic chemotherapy.To improve the quality of life and survival of gastric cancer patients,a better understanding of the underlying molecular pathologies,and their application towards the development of novel targeted therapies,is urgently needed.Chemokines are a group of small proteins associated with cytoskeletal rearrangements,the directional migration of several cell types during development and physiology,and the host immune response via interactions with G-protein coupled receptors.There is also growing evidence to suggest that chemokines not only play a role in the immune system,but are also involved in the development and progression of tumors.In gastric cancer,CXC chemokines and chemokine receptors regulate the trafficking of cells in and out of the tumor microenvironment.CXC chemokines and their receptors can also directly influence tumorigenesis by modulating tumor transformation,survival,growth,invasion and metastasis,as well as indirectly by regulating angiogenesis,and tumor-leukocyte interactions.In this review,we will focus on the roles of CXC chemokines and their receptors in the development,progression,and metastasis of gastric tumors,and discuss their therapeutic potential for gastric cancer.

Simultaneous modulated accelerated radiation therapy for esophageal cancer:A feasibility study

AIM:To establish the feasibility of simultaneous modulated accelerated radiation therapy(SMART) in esophageal cancer(EC).METHODS:Computed tomography(CT)datasets of 10patients with upper or middle thoracic squamous cell EC undergoing chemoradiotherapy were used to generate SMART,conventionally-fractionated three-dimensional conformal radiotherapy(3DCRT)and intensity-modulated radiation therapy(cf-IMRT)plans,respectively.The gross target volume(GTV)of the esophagus,positive regional lymph nodes(LN),and suspected lymph nodes(LN±)were contoured for each patient.The clinical target volume(CTV)was delineated with 2-cm longitudinal and 0.5-to 1.0-cm radial margins with respect to the GTV and with 0.5-cm uniform margins for LN and LN(±).For the SMART plans,there were two planning target volumes(PTVs):PTV66=(GTV+LN)+0.5 cm and PTV54=CTV+0.5 cm.For the 3DCRT and cfIMRT plans,there was only a single PTV:PTV60=CTV+0.5 cm.The prescribed dose for the SMART plans was 66 Gy/30 F to PTV66 and 54 Gy/30 F to PTV54.The dose prescription to the PTV60 for both the 3DCRT and cf-IMRT plans was set to 60 Gy/30 F.All the plans were generated on the Eclipse 10.0 treatment planning system.Fulfillment of the dose criteria for the PTVs received the highest priority,followed by the spinal cord,heart,and lungs.The dose-volume histograms were compared.RESULTS:Clinically acceptable plans were achieved for all the SMART,cf-IMRT,and 3DCRT plans.Compared with the 3DCRT plans,the SMART plans increased the dose delivered to the primary tumor(66Gy vs 60 Gy),with improved sparing of normal tissues in all patients.The Dmax of the spinal cord,V20 of the lungs,and Dmean and V50 of the heart for the SMART and 3DCRT plans were as follows:38.5±2.0 vs 44.7±0.8(P=0.002),17.1±4.0 vs 25.8±5.0(P=0.000),14.4±7.5 vs 21.4±11.1(P=0.000),and 4.9±3.4vs 12.9±7.6(P=0.000),respectively.In contrast to the cf-IMRT plans,the SMART plans permitted a simultaneous dose escalation(6 Gy)to the primary tumor while demonstrating a significant trend of a lower irradiation dose to all organs at risk except the spinal cord,for which no significant difference was found.CONCLUSION:SMART offers the potential for a 6Gy simultaneous escalation in the irradiation dose delivered to the primary tumor of EC and improves the sparing of normal tissues.

Effects of oral tacrolimus as a rapid induction therapy in ulcerative colitis

AIM:To determine the efficacy and safety of rapid induction therapy with oral tacrolimus without a meal in steroid-refractory ulcerative colitis(UC)patients.METHODS:This was a prospective,multicenter,observational study.Between May 2010 and August 2012,49 steroid-refractory UC patients(55 flare-ups)were consecutively enrolled.All patients were treated with oral tacrolimus without a meal at an initial dose of 0.1mg/kg per day.The dose was adjusted to maintain trough whole-blood levels of 10-15 ng/m L for the first 2 wk.Induction of remission at 2 and 4 wk after tacrolimus treatment initiation was evaluated using Lichtiger’s clinical activity index(CAI).RESULTS:The mean CAI was 12.6±3.6 at onset.Within the first 7 d,93.5%of patients maintained high trough levels(10-15 ng/m L).The CAI significantly decreased beginning 2 d after treatment initiation.At 2wk,73.1%of patients experienced clinical responses.After tacrolimus initiation,31.4%and 75.6%of patients achieved clinical remission at 2 and 4 wk,respectively.Treatment was well tolerated.CONCLUSION:Rapid induction therapy with oral tacrolimus shortened the time to achievement of appropriate trough levels and demonstrated a high remission rate 28 d after treatment initiation.Rapid induction therapy with oral tacrolimus appears to be a useful therapy for the treatment of refractory UC.

Hybrid vs sequential therapy for eradication of Helicobacter pylori in Taiwan: a prospective randomized trial

AIM: To evaluate the efficacy of sequential vs hybrid therapy in patients with Helicobacter pylori(H. pylori) infection.METHODS: From March 2013 to May 2014,one hundred and seventy-five H. pylori infected patients who had not been treated for H. pylori before wererandomized to receive either sequential therapy(rabeprazole 20 mg and amoxicillin 1 g twice daily for 5 d,followed by rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg twice daily for 5 d) or hybrid therapy(rabeprazole 20 mg and amoxicillin 1 g for 7 d,followed by rabeprazole 20 mg,amoxicillin 1 g,clarithromycin 500 mg and metronidazole 500 mg twice daily for 7 d). H. pylori status was confirmed by positive results of both rapid urease test and histology examination or a positive result of culture. Eradication efficacy was assessed by follow-up endoscopy with rapid urease test and histological examination 8 wk after the end of anti-H. pylori therapy,or 13C-urea breath test at least 4 wk after completion of treatment. The primary outcome was H. pylori eradication by intension-to-treat(ITT) and per-protocol(PP) analyses.RESULTS: One hundred and sixty-seven patients(83 patients in the sequential group and 84 patients in the hybrid group) completed the study. The compliance rates were 97.6% and 97.7% for the two groups,respectively. The eradication rate was 78.2% for the sequential group and 92% for the hybrid group by ITT analysis(P = 0.01). The eradication rate was 81.9% for the sequential group and 96.4% for the hybrid group by PP analysis(P = 0.01). Univariate analysis for the clinical and bacterial factors did not identify any risk factors associated with treatment failure. Severe adverse events were observed in 2.3% of patients in the sequential group and 2.4% of those in the hybrid group.CONCLUSION: Due to a grade A(> 95%) success rate for H. pylori eradication by PP analysis,similar compliance and adverse events,hybrid therapy seems to be an appropriate eradication regimen in Taiwan.

Thermal Fatigue Behaviour of Co-Based Alloy Coating Obtained by Laser Surface Melt-Casting on High Temperature Alloy

A thermal fatigue behaviour of Co-based alloy coating obtained by laser surface meltcasting on the high temperature alloy GH33 was studied.The results show that after each time of thermal cycling,the final residual stress was formed in the melt-casting layer which is attributed to the thermal stress and structural stress.Through the first 50 times of thermal cycling,the morphology of coating still inherits the laser casting one,but the dendrites get bigger;After the second 50 times of thermal cycling,corrosion pits emerge from coating,and mostly in the places where coating and substrate meet.The fatigue damage type of coating belongs to stress corrosion.

Frequency and prognostic role of mucosal healing in patients with Crohn's disease and ulcerative colitis after one-year of biological therapy

AIM:To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease(CD)and ulcerative colitis(UC).METHODS:The data from 41 patients with CD and 22 patients with UC were assessed.Twenty-four CD patients received infliximab,and 17 received adalimumab.The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn’s disease in CD and with the Mayo endoscopic subscore in UC.RESULTS:Mucosal healing was achieved in 23 CD and7 UC patients.Biological therapy had to be restarted in78%of patients achieving complete mucosal healing with CD and in 100%of patients with UC.Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC.CONCLUSION:Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped.

SYNTHESIS AND THERMAL STABILITY OF NANOCOMPOSITE nc-TiN/a-TiB_2 THIN FILMS

Several nc-TiN/a-TiB2 thin films comprised of nanocrystalline (nc-) TiN and amor phous (a-) TiB2 phases were deposited on Si(100) at room temperature by reactive unbalanced dc magnetron sputtering, followed by vacuum annealed at 400, 600, 80 0 and 1000℃ for 1h, respectively. Effects of B content on microstructure, mecha nical behaviors and thermal microstructure stability have been investigated by X -ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and nanoindentation measurements. The results indicated that B addition greatly affected both microstructure and mechanical behavior of nc-Ti N/a-TiB2 thin films. With increasing B content the grain size decreased. A maxim um hardness value of about 33GPa was obtained at B content of about 19at.%. The improved mechanical properties of nc-TiN/a-TiB2 films with the addition of B int o TiN were attributed to their densified microstructure with development of fine grain size. Only addition of sufficient B could restrain grain growth during an nealing. High B content resulted in high microstructure stability. The crystalli zation of amorphous matrix occurred at about 800℃, forming TiB or TiB2 crystall ite, depending on B content. Before that no change in bonding configuration was found.

THERMAL DECOMPOSITION BEHAVIOR OF AMMONIUM THIO TUNGSTATE in H_2

The ther m al deco m position mechanism of a m m oniu m thiotungstate of the size of 63 ～75 μmin H2 has been investigated by D T A and X R D methods . The ther m al deco m position activationenergies and the orders of a m m oniu m thiotu ngstate were calculated by means of Kissinger , Freem an Carroll and Coast Redfern m ethods . It w as also obtained that therm al deco m posi tion is cond ucted according to four reaction equations :( N H4) 2 W S4· H2 O(s) ( N H4) 2 W S4(s) + H2 O(g) W S2(s) + 2 N H3(g) + H2(g) + 2 S(s) + H2 O(g) W S2(s) + 2 N H3(g) + 2 H2 S(g) + H2 O(g) W S2(s) + W(s) + 2 N H3(g) + 2 H2 S(g) + H2 O(g) .

Nanoscale mass sensing based on vibration of single-layered graphene sheet in thermal environments

Based on vibration analysis, single-layered graphene sheet （SLGS） with multiple attached nanoparticles is developed as nanoscale mass sensor in thermal environments. Graphene sensors are assumed to be in simplysupported configuration. Based on the nonlocal plate the- ory which incorporates size effects into the classical theory, closed-form expressions lot the frequencies and relative fre- quency shills of SLGS-based mass sensor are derived using the Galerkin method. The suggested model is justified by a good agreement between the results given by the present model and available data in literature. The effects of tem- perature difference, nonlocal parameter, the location of the nanoparticle and the number of nanoparticles on the relative frequency shift of the mass sensor are also elucidated. The obtained results show that the sensitivity of the SLGS- based mass sensor increases with increasing temperature difference.

On stability of elastic domain during isothermal solid-solid phase transformationin a tube configuration

Under isothermal quasi-static stretching the phase transition of a superelastic NiTi tube involves the formation （during loading） and vanishing （in unloading） of a high strain （martensite） domain. The two events are accompanied by a rapid stress drop/rise due to the formation/vanishing of do- main fronts. From a thermodynamic point of view, both are instability phenomena that occur once the system reaches its critical state. This paper investigates the stability of a shrink- ing cylindrical domain in a tube configuration during unload- ing. The energetics and thermodynamic driving force of the cylindrical domain are quantified by using an elastic inclu- sion model. It is demonstrated that the two domain fronts ex- hibit strong interaction when they come close to each other, which brings a peak in the total energy and a sign change in the thermodynamic driving force. It is proved that such domain front interaction plays an important role in control- ling the stability of the domain and in the occurrence of stress jumps during domain vanishing. It is also shown that the pro- cess is governed by two nondimensional length scales （the normalized tube length and normalized wall-thickness） and that the length scale dependence of the critical domain length and stress jump for the domain vanishing can be quantified by the elastic inclusion model.

Thermo-mechanical Properties of In-situ Formed Al_2O_3-SiC-SiAION Composites

Al2 O3 - SiC - SiAION composite specimens have been prepared using fused alumina, ultra fine α-Al2O3, Si and Al powders as starting materials and liquid phenol formaldehyde resin as binder and firing at 1 500 ℃ for 3 h in carbon embedded condition. Thermo-mechanical properties of Al2 O3 - SiC - SiAlON composites have been studied. The results show ： （ 1 ） Al2 O3 - SiC - SiAION composites can be prepared and sintered at 1 500 ℃ under carbon embedded condition. When Si/Al ratio is 8/0 and 7/1, the prepared composite is Al2O3 - SiC - O＇ -SiAlON; when Si/Al ratio is 5/3 and 3/5, the pre- pared composite is Al2 O3 - SiC - β-SiAION. （ 2 ） The composites possess high temperature strength properties. Hot modulus of rupture at 1 400 ℃ is 10 - 30 MPa. They are in elastic range up to 1 000 ℃, after which plastic deformation is observed; even at 1 400 ℃, amount of deformation is relatively low. （3） The com- posites possess good thermal shock resistance, their resid- ual strength ratio （AT = 1 100 ℃ ） is 65% - 80%. （4） The marked improvement in thermo-mechanical properties of Al2O3 - SiC - SiAlON composites may be at- tributed to the in-situ formation of SiC, SiAlON and AIN, the fibrous SiC, columnar SiAlON and tabular-like AlN fill in the corundum skeleton structure creating strengthening and toughening effects.