Benzydamine hydrochloride ameliorates ethanol-induced inflammation in RAW 264.7 macrophages by stabilizing redox homeostasis

Objective:To evaluate the protective effect of benzydamine hydrochloride against ethanol-induced oxidative stress and inflammation in RAW 264.7 macrophages.Methods:RAW 264.7 macrophages were treated with ethanol(100 mM)and benzydamine hydrochloride(7.5μM).The imflammatory status was confirmed by measuring pro-(TNF-αand IL-6)and anti-inflammatory(IL-10)cytokines through ELISA and RT-PCR assays.Reactive oxygen species generation and mitochondrial membrane potential were investigated to study the protective role of benzydamine hydrochloride against ethanol-induced oxidative stress.Apoptosis detection was also investigated using flow cytometry and acridine orange/ethidium bromide staining.Results:Benzydamine hydrochloride significantly decreased the secretion of TNF-αand IL-6,as well as the generation of reactive oxygen species inside the cells,thereby stabilizing the mitochondrial membrane potential and reducing DNA fragmentation.The ethanol-induced cellular necrosis was also reversed by the administration of benzydamine hydrochloride.Conclusions:Benzydamine hydrochloride ameliorates ethanol-induced cell apoptosis and inflammation in RAW macrophages.

Carbon-doped CuFe_(2)O_(4) with C-O-M channels for enhanced Fenton-like degradation of tetracycline hydrochloride: From construction to mechanism

Carbon-doped copper ferrite(C–CuFe_(2)O_(4))was synthesized by a simple two-step hydrothermal method,which showed enhanced tetracycline hydrochloride(TCH)removal efficiency as compared to the pure CuFe_(2)O_(4) in Fenton-like reaction.A removal efficiency of 94%was achieved with 0.2 g L^(-1) catalyst and 20 mmol L^(-1) H_(2)O_(2) within 90 min.We demonstrated that 5%C–CuFe_(2)O_(4) catalyst in the presence of H_(2)O_(2) was significantly efficient for TCH degradation under the near-neutral pH(5–9)without buffer.Multiple techniques,including SEM,TEM,XRD,FTIR,Raman,XPS M€ossbauer and so on,were conducted to investigate the structures,morphologies and electronic properties of as-prepared samples.The introduction of carbon can effectively accelerate electron transfer by cooperating with Cu and Fe to activate H_(2)O_(2) to generate·OH and·O_(2)^(-).Particularly,theoretical calculations display that the p,p,d orbital hybridization of C,O,Cu and Fe can form C–O–Cu and C–O–Fe bonds,and the electrons on carbon can transfer to metal Cu and Fe along the C–O–Fe and C–O–Cu channels,thus forming electron-rich reactive centers around Fe and Cu.This work provides lightful reference for the modification of spinel ferrites in Fenton-like application.

Clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride on mild-to-moderate depression

BACKGROUND Depression is a common,chronic,and recurrent mood disorder that has become a worldwide health hazard.Fluoxetine hydrochloride,a common treatment method,can inhibit 5-hydroxytryptamine(5-HT)recycling in the presynaptic membrane;however,the efficacy of a single drug is inadequate.At present,mildto-moderate depression can be treated with acupuncture of ghost caves,but the clinical curative effect of combined therapy with fluoxetine hydrochloride has not been sufficiently reported.AIM To evaluate the clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride in the treatment of mild-to-moderate depression.METHODS This retrospective study included 160 patients with mild-to-moderate depression who were admitted to Shanghai Hospital of Integrated Traditional Chinese and Western Medicine,Affiliated to Shanghai University of Traditional Chinese Medicine,between January 2022 and June 2023.Patients were separated into a single-agent group(fluoxetine hydrochloride treatment,n=80)and a coalition group(fluoxetine hydrochloride treatment combined with acupuncture at ghost points,n=80).Pre-treatment symptoms were recorded,and the clinical curative effect and adverse reactions[Asberg Antidepressant Side Effects Scale(SERS)]were assessed.Depression before and after treatment[Hamilton Depression Scale(HAMD)-24],neurotransmitter levels[5-HT,norepinephrine(NE),dopamine(DA)],oxidative stress indicators[superoxide dismutase(SOD),malondialdehyde(MDA)],and sleep quality[Pittsburgh Sleep Quality Index(PSQI)]were compared.RESULTS The total efficacy rate was 97.50%in the coalition group and 86.25%in the single-agent group(P<0.05).After 2,4,6,and 8 wk of treatment,the HAMD,self-rating depression scale,and SERS scores of the coalition and single-agent groups decreased compared with pre-treatment,and the decrease was more significant in the coalition group(P<0.05).After 8 wk of treatment,the levels of NE,DA,5-HT,and SOD in the coalition and single-agent groups increased,while the levels of MDA decreased;the increases and decrease in the coalition group were more significant(P<0.05).The PSQI scores of the coalition and single-agent groups decreased,and the decrease was more significant in the coalition group(P<0.05).CONCLUSION Acupuncture at ghost points combined with paroxetine tablets can safely improve depressive symptoms and sleep disorders,regulate neurotransmitter levels,and reduce stress responses in patients with mild-to-moderate depression.

Design and optimization of purification process of sinomenine hydrochloride

Sinomenine hydrochloride is generally produced from Caulis Sinomenii. At present, the purification process in industrial production suffers from large amount of solid waste, high solvent toxicity, and low sinomenine hydrochloride yield. In this study, a new purification process for sinomenine hydrochloride was proposed by using the extract obtained from acid extraction of Caulis Sinomenii as the starting material.The process included the following steps: alkalization, extraction, water washing, acid–water stripping,drying, and crystallization. 1-Heptanol was used as the extractant. The distribution coefficients of sinomenine and sinomenine hydrochloride in 1-heptanol–water system were 27.4 and 0.0167, respectively.The dissociation constants of sinomenine hydrochloride were 8.27 and 11.24, respectively. Process parameters of the new purification process were optimized with experimental design. The extractant1-heptanol and sinomenine hydrochloride in the crystallization mother solution can be recycled in the new process. The purity of the obtained sinomenine hydrochloride crystals exceeded 85%, and the yield was about 70%. Compared with current industrial processes, safer extractant, less solid waste, and higher sinomenine hydrochloride yield can be achieved using the new purification process of sinomenine hydrochloride provided in this study.

Physico-chemical parameters for the assembly of moxifloxacin hydrochloride and cetyltrimethylammonium chloride mixture in aqueous and alcoholic media

The aggregation behavior of the mixture of cetyltrimethylammonium chloride(CTAC), a cationic surfactant, and moxifloxacin hydrochloride(MFH), a fourth-generation fluoroquinolone antibiotic drug, has been studied using the conductivity technique in aqueous and alcoholic(EtOH, 1-PrOH, and 2-BuOH)media. The study was performed at several temperatures between 298.15 and 323.15 K at 5 K intervals.The assembly has been characterized by evaluating the micellar parameters, such as the critical micelle concentration(CMC) and the counter ion binding(β), of the CTAC + MFH mixture. The values of the CMC for the assembly of the CTAC + MFH mixture were reliant on the composition of alcohols in the mixed solvents and the temperature. The CMC values of the CTAC + MFH mixture increased with increasing temperature;that is, assembly was delayed by increased temperature. The micellization of the CTAC + MFH mixed system was delayed in alcoholic media. The observed-ΔG0mvalues for the association of the CTAC + MFH mixed system demonstrated a spontaneous aggregation process under all study conditions.Based on the-ΔH^(0)_(m) and +ΔS^(0)_(m) values, the association of the CTAC + MFH mixture is exothermic and the interaction forces acting between the CTAC and MFH species are hydrophobic, ion–dipole, and electrostatic interactions. The transfer properties and enthalpy–entropy compensation were also assessed and described comprehensively.

Volumetric and ultrasonic properties of thiamine hydrochloride drug in aqueous solutions of choline-based deep eutectic solvents at different temperatures

Important efforts have been made over the past years to improve the drug acts,which leads to the discovery of novel drug preparations and delivery systems.The optimal design of such processes requires a molecular-level understanding of the interactions between drug molecules and biological membranes.The thermodynamic investigation provides deep and complete knowledge of interactions and the choice of appropriate and suitable production compounds in pharmaceutical fields.Particularly,the analysis of drugs+co-solvents in aqueous media is the central issue in many types of research because they exert their impact by interacting with biological membranes.This work is aimed to measure the density and speed of sound for the thiamine hydrochloride in water+deep eutectic solvents(DESs)mixtures(choline chloride/urea,choline chloride/ethylene glycol and choline chloride/glycerol)at temperature range(293.15-308.15)K.By correlation of the evaluated parameters in some standard relations,the partial molar parameters i.e.apparent molar volumes,Vφ,m,and apparent molar isentropic compression,κ_(s,φ,m),are calculated.In addition,apparent molar isobaric expansion,E^(0)_(φ,m),and Hepler’s constant are computed from the density and speed of sound data.For fitting the experimental Vφ,m andκ_(s,φ,m)the Redlich-Meyer equation was employed that the important quantities;standard partial molar volume,V^(0)_(m),and partial molar isentropic compression,κφ,m0,were obtained.The thermodynamic analysis of the studied system also plays a crucial role in the pharmaceutical industry.

The dose regimen formulation of doxycycline hydrochloride and florfenicol injection based on ex vivo pharmacokinetic-pharmacodynamic modeling against the Actinobacillus pleuropneumoniae in pigs

Doxycycline hydrochloride and florfenicol combination(DoxHcl&FF)is an effective treatment for respiratory diseases.In the study,our objective Was to evaluate the activity of DoxHcl&FF against Actinobacillus pleuropneumoniae(APP)in porcine pulmonary epithelial lining fluid(PELF)and the optimal dosage scheme to avoid the development of resistance.The DoxHcl&FF Was administered intramuscularly(IM)at 20mg/kg,and the PELF was collected at differ-ent time points.The minimum inhibitory concentration(MIC)and time-mortality curves were also included in the study.Based on the sigmoid Emax equation and dose equations,the study integrated the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data to obtain the area under concentration time curve(AUCo-24h)MIC values in PELF and achieve bacteriostatic activity,bactericidal activity and the virtual eradication of bacteria.The study showed that the combination of DoxHcl and FF caused no significant changes in PK parameters.The peak concentration(Cmax)of FF in healthy and diseased pigs was 8.87±0.08 and 8.67±0.07μg/mL,the_AUCo-24h were.172.75±2.52 and 18022±3.13 h-μg/mL,the Cmax of DoxHcl was 7.91±0.09 and 7.99±0.05μg/mL,and the AUCo-24h was 129.96±3.70 h-μg/mL and 169.82±4.38 h-μg/mL.DoxHcl&FF showed strong concentra-tion-dependent tendencies.The bacteriostatic,bactericidal,and elimination activity were calculated as 5.61,18.83 and 32.68 h,and the doses were 1.37(bacteriostatic),4.59(bactericidal)and 7.99(elimination)mg/kg.These findings indicated that the calculated recommended dose could assist in achieving more precise administration,increasing the effectiveness of DoxHcl&FF treatment for APP infections.

Application of sintilimab combined with anlotinib hydrochloride in the clinical treatment of microsatellite stable colorectal cancer

BACKGROUND Microsatellite stable(MSS)colorectal cancer(CRC)is a common type of tumor with limited treatment options.Sintilimab and anlotinib hydrochloride are two extensively studied anticancer drugs.AIM To probe the clinical value of combining sintilimab with anlotinib hydrochloride in MSS CRC treatment.METHODS During the period spanning from April 2019 to April 2022,Zhejiang Provincial People’s Hospital accommodated a cohort of 92 patients diagnosed with MSS CRC who were classified into two distinct groups in our study,the observation group and the control group.The control group was administered anlotinib hy-drochloride as their designated therapy,whereas the observation group received the additional treatment of sintilimab in conjunction with the therapy assigned to the control group.The administration of treatment occurred in cycles consisting of a duration of 3 wk,and the evaluation of effectiveness took place subsequent to the completion of two consecutive cycles of treatment within both groups.A comparative analysis between the two groups was conducted to assess the short-term efficacy and ascertain the incidence of adverse events transpiring throughout the duration of the treatment period.Changes in the levels of carcinoembryonic Life Questionnaire-Core 30 were compared between the two groups prior to and subsequent to therapy.Finally,a 1-year follow-up was conducted for both groups of patients,and the survival status was recorded and analyzed.RESULTS The short-term effectiveness displayed by the observation group surpassed that exhibited by the control group,with a statistically significant discrepancy(76.09%vs 50.00%),reaching a significance level denoted as P<0.05.Following the administration of treatment,the observation group manifested a considerable reduction in numerous serum indicators,which were found to be lower than the corresponding pretreatment levels within the same group as well as the post-treatment levels observed in the control group(P<0.05).Post-treatment,the T lymphocyte subset levels within the observation group demonstrated a remarkable amelioration,surpassing the corresponding pre-treatment levels observed within the same group as well as the post-treatment levels observed in the control group(P<0.05).Subsequent to the therapeutic intervention,the observation group showcased a notable amelioration in the scores associated with multiple dimensions of life quality.These scores outperformed the pretreatment scores within the same group as well as the post-treatment scores observed in the control group(P<0.05).The safety levels of drug use in the two group were comparable(19.57%vs 13.04%),and no distinct difference was observed upon comparison(P>0.05).After the completion of treatment,both groups of patients underwent a 1-year follow-up outside the hospital.Throughout this period,1 patient within the observation group and 2 patients within the control group became untraceable and were lost to follow-up.During the follow-up period of the observation group,12 patients died,resulting in a survival rate of 73.33%(33/45),while in the control group,21 patients died,resulting in a survival rate of 52.27%(23/44).The implementation of Kaplan-Meier survival analysis revealed a conspicuous contrast in survival rates exhibited by the two groups(log-rank=4.710,P=0.030).CONCLUSION The combination of sintilimab and anlotinib hydrochloride demonstrated favorable efficacy in the treatment of MSS CRC patients,leading to improvements in patient immunity and prognosis.Additionally,it exerted inhibitory effects on the expression of carcinoembryonic antigen,CA199,and CA125.

Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers

Aims:To determine the safety and efficacy of microwave ablation(MWA)and transarterial chemoembolization(TACE)with doxorubicin hydrochloride liposome(DHL)in patients with primary liver cancer(PLC)and metastatic liver cancer(MLC).Materials and methods:The medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed.Treatment-related adverse events(AEs)were recorded.Local tumor response was evaluated according to the modified RECIST criteria.Local tumor progression-free survival(LTPFS)and overall survival(OS)were calculated using the Kaplan-Meier method.Results:Altogether,96 patients with liver cancer were included(PLC,n=45;MLC,n=51).Forty(41.7%)patients experienced AEs during treatment,and eight(8.3%)patients developed grade 3 AEs.Compared to before treatment,the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment.The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC.The median OS was not reached in patients with PLC or MLC.The 1-month and 3-month disease control rates reached more than 80%in both groups.Conclusion:MWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer.

Research Progress on Pharmacological Effects of Lycorine Hydrochloride

Lycoris radiata,a Chinese herbal medicine,is a plant of Amaryllidaceae family,which has the antidotal,expectorant,diuretic,emetic and insecticidal effects.Lycorine hydrochloride is an alkaloid extracted from the bulb of L.radiata.Studies have shown that lycorine hydrochloride has many pharmacological effects(anti-fungal,anti-viral and anti-tumor).In this paper,the related research on pharmacological effects and mechanism of lycorine hydrochloride is systematically summarized in order to provide a theoretical basis for further research and application of lycorine hydrochloride.

Pharmacological Effects and Molecular Mechanism of Synephrine Hydrochloride

Synephrine hydrochloride,an alkaloid compound extracted from immature bitter orange,has many pharmacological effects such as anticancer effect,antioxidant effect and antidepression effect.In this paper,the pharmacological effects and mechanism of synephrine hydrochloride were reviewed in order to provide a theoretical basis for the development and application of synephrine hydrochloride.

Nonclinical Study of the Active Components of Doxorubicin Hydrochloride Liposome Injection in Vivo

Objectives: A non-clinical study was performed to establish a LC-MS/MS method to determine the in vivo active components of doxorubicin hydrochloride liposome injection in the plasma of Sprague-Dawley rats. Methods: Ten male SD rats were administered tail vein with a single dose of 10 mg/kg, and the concentrations of doxorubicin hydrochloride in plasma, heart, liver, spleen, lung, and kidney were determined by liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated. Results: The final concentration of doxorubicin hydrochloride ranged from 500 ng/mL to 250,000 ng/mL, and the lower limit of quantification was 500 ng/mL;the main pharmacokinetic parameters: T1/2 was (19.282 ± 10.305) h, Cmax was (118514.828 ± 26155.134) ng/mL, AUC0-24 and AUC0-∞ were (1216659.205 ± 192706.268) ng/mL⋅h and (2082244.523 ± 860139.487) ng/mL⋅h, MRT0-24 and MRT0-∞ were (9.237 ± 0.423) h and (26.52 ± 14.015) h, respectively, and clearance (CL) was (0.005 ± 0.002) mL/h⋅ng. Conclusions: The method is simple, rapid, and sensitive, which can be used for the determination of doxorubicin hydrochloride concentration in the plasma of SD rats and pharmacokinetic non-clinical studies.

Fluoxetine Hydrochloride的NMR数据解析

由美国Lilly公司开发的第二代抗抑郁症药物盐酸氟西汀(Fluoxetine hydrochloride),属于选择性5-羟色胺再摄取抑制剂(SSRI),除了用于治疗各类抑郁症,包括轻性或重性抑郁症,尤宜用于老年性抑郁症之外,对于强迫症、惊恐发作、贪食症、经前期焦虑等亦有很好疗效.Fluoxetine hydrochloride是一种双环化合物,与传统的三环类、杂环类或单胺氧化酶抑制剂抗抑郁药相比,具有疗效好、不良反应轻而少,安全性高、耐受性好等特点,目前已作为一线的抗抑郁药得到广泛应用.本文对Fluoxetine hydrochloride进行了1H NMR和13C NMR检测,并通过DEPT和1H-1HCOSY、HMBC、HSQC等2D NMR技术对其1H NMR和13C NMR数据进行了较为详细的解析和比文献[1]更为全面的NMR归属,为以后的分析鉴定提供更完善的依据.

治疗睡眠障碍新药——盐酸达利雷生(daridorexant hydrochloride)

治疗睡眠障碍新药盐酸达利雷生片(daridorexant hydrochloride tablets,简称达利雷生)于20世纪90年代末由强生制药(J.&J.)有限公司并购的瑞士Actelion生物制药公司开始研发,2017年6月Actelion生物制药公司将新药发现和药物的早期临床开发资产从强生制药有限公司剥离,注入新成立的瑞士Idorsia生物制药公司;2019年12月,Idorsia生物制药公司与日本持田制药公司签订独家协议,将共同开发、营销和供应达利雷生片。达利雷生是双重食欲素受体拮抗药,通过阻断食欲素受体与促觉醒神经肽食欲素的结合,抑制过度活跃的不眠状态。临床试验受试者包含多种形式睡眠障碍,如入睡困难、早醒、睡眠维持困难、睡眠质量下降、睡眠结构紊乱等。结果表明,达利雷生治疗组患者进入持续性睡眠所需时间(LPS)和入睡后觉醒(WASO)的变化均优于安慰药组。达利雷生能显著改善患者入睡和睡眠维持的客观指标,以及患者报告的总睡眠时间(sTST);并能减少患者次日嗜睡情况。2020年8月,Idorsia生物制药公司与美国跨国合同研究组织(Syneos Health)在美国的商业化签订营销协议Actelion生物制药公司与日本持田制药公司于2021年8月联合向美国食品药品管理局(FDA)提出新药上市申请。FDA于2022年1月7日批准其上市,商品名为QUVIVIQ^(■)。该文对治疗睡眠障碍新药达利雷生片的非临床和临床药理毒理学、临床研究、不良反应、适应证、剂量与用法、用药注意事项及知识产权状态和国内外研究进展等进行介绍。

治疗儿童和青少年注意力缺陷多动症--盐酸维洛沙嗪(viloxazine hydrochloride)缓释胶囊

盐酸维洛沙嗪(viloxazine hydrochloride)是去甲肾上腺素再摄取抑制药,作为治疗儿童和青少年注意力缺陷多动障碍(ADHD)的非兴奋药,由美国专门从事中枢神经系统疾病治疗药物的Supernus制药公司自主研发。20世纪60—70年代,Supernus制药公司将盐酸维洛沙嗪研制成速释胶囊,用于治疗抑郁症,在英国和欧洲其他几个国家上市销售,因治疗服药剂量大,疗效难于与同类药物相似,撤出市场。Supernus制药公司转为开发新的缓释胶囊剂,主攻治疗儿童和青少年ADHD,经多批次Ⅲ期临床试验,取得良好疗效,均达到治疗终点,且有广泛的安全性。Supernus制药公司原订计划于2010年1月向美国FDA提交盐酸维洛沙嗪缓释胶囊用于治疗6~17岁儿童和青少年ADHD适应证新药上市申请(NDA),因该公司内部药物分析部门搬迁新址,分析数据未能满足NDA申请要求,收到FDA完整回函(CRL)。经协商,研发公司于2021年2月2日重新补充全部申报资料。美国食品药品管理局(FDA)于2021年4月2日正式批准盐酸维洛沙嗪缓释胶囊上市,商品名为Qelbree。这是近十年来FDA批准的首个针对ADHD的新型非刺激性疗法。而盐酸维洛沙嗪缓释胶囊在ADHD成人中进行的Ⅲ期临床试验研究也于2020年12月取得积极结果,按计划Supernus公司将于2021年下半年递交针对成人ADHD的补充NDA。该文对盐酸维洛沙嗪缓释胶囊的非临床和临床药理毒理学、临床研究、不良反应、适应证、剂量与用法、用药注意事项及知识产权状态和国内外研究进展等进行介绍。

Electrodeposition of aluminium and aluminium-copper alloys from a room temperature ionic liquid electrolyte containing aluminium chloride and triethylamine hydrochloride

The electrodeposition of A1 and A1-Cu binary alloys on to gold substrates from a room temperature ionic liquid electrolyte containing A1C13-EtaNHC1 was studied. The electrochemical behavior of the electrolyte and the mechanism of deposition were investigated through cyclic voltammetry （CV）, and the properties of deposits obtained were assessed by scanning electron microscopy with energy dispersive X-ray spectroscopy （SEM-EDS） and X-ray diffraction （XRD）. A1 of 70μm in thickness and an A1-Cu alloy of 30μm in thickness with 8at% copper were deposited from the electrolyte. SEM images of the deposits indicate that the A1 deposit was smooth and uniform, whereas the Al-Cu deposit was nodular. The average crystalline size, as determined by XRD patterns, was found to be （30±5） and （29±5） nm, respectively, for A1 and A1-Cu alloys. Potentiodynamic polarization （Tafel plots） and electrochemical impedance spectroscopic （EIS） measurements showed that Al-Cu alloys are more corrosion resistant than Al.

Neuroprotective effect of penehyclidine hydrochloride on focal cerebral ischemia-reperfusion injury

Penehyclidine hydrochloride can promote microcirculation and reduce vascular permeability. However, the role of penehyclidine hydrochlodde in cerebral ischemia-reperfusion injury remains unclear. In this study, in vivo middle cerebral artery occlusion models were established in experimental rats, and penehyclidine hydrochloride pretreatment was given via intravenous injection prior to model establishment. Tetrazolium chloride, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and immunohistochemical staining showed that, penehyclidine hydrochloride pretreatment markedly attenuated neuronal histopathological changes in the cortex, hippocampus and striatum, reduced infarction size, increased the expression level of BcI-2, decreased the expression level of caspase-3, and inhibited neuronal apoptosis in rats with cerebral ischemia-reperfusion injury. Xanthine oxidase and thiobarbituric acid chromogenic results showed that penehyclidine hydrochloride upregulated the activity of superoxide dismutase and downregulated the concentration of malondialdehyde in the ischemic cerebral cortex and hippocampus, as well as reduced the concentration of extracellular excitatory amino acids in rats with cerebral ischemia-reperfusion injury. In addition, penehyclidine hydrochloride inhibited the expression level of the NR1 subunit in hippocampal nerve cells in vitro following oxygen-glucose deprivation, as detected by PCR. Experimental findings indicate that penehyclidine hydrochloride attenuates neuronal apoptosis and oxidative stress injury after focal cerebral ischemia-reperfusion, thus exerting a neuroprotective effect.

Fasudil hydrochloride differentiates bone marrow mesenchymal stem cells into neurons via notch signaling

BACKGROUND： Notch signaling regulates bone marrow mesenchymal stem cell （MSC） proliferation, differentiation, and apoptosis, Notch signaling and Rho kinase signaling exhibit a crosstalk phenomenon with JAK/STAT, and both participate in the neuronal dendritic spine development. Inhibition of RhoA/Rho kinase signaling may regulate MSC differentiation into neuronal-like cells. OBJECTIVE： To investigate the effect of Notch1 signaling on the differentiation of rat MSCs into neurons induced by fasudil hydrochloride （C14H17N3O2S-HCI）, a Rho kinase inhibitor, through a siRNA approach. DESIGN, TIME AND SETTING： An in vitro cytological experiment was performed in the Cell Laboratory of Henan Academy of Medical and Pharmaceutical Sciences between December 2007 and May 2009. MATERIALS： MSCs were obtained from Wistar rat femoral bone, fasudil hydrochloride was provided by -Tianjin Chase Sun Pharmaceutical Co., Ltd. Rn-notchl-siRNa, negative control siRNA （Cy3 label） and Rn-MAPK1 control siRNA were provided by QIAGEN, Coloqne, German. METHODS： The cultured MSCs were divided into non-transfected, transfected group （transfected with Rn-Notchl-siRNA）, positive control （transfected with Rn-MAPK-1 control siRNA）, and negative control （transfected with negative control siRNA） groups. Fasudil hydrochloride was applied to induce MSCs to differentiate into neurons. MAIN OUTCOME MEASURES： The fluorescence expression by the transfected MSCs was observed under an inverted fluorescence microscope; the expression of Notch1 mRNA, Hesl mRNA, and MAPK1 mRNA in MSCs was detected by reverse transcription polymerase chain reaction; the expression of Notch1 protein, nestin, neurofilament M, and glial fibrillary acidic protein was detected by immunocytochemistry. The viability of MSCs was detected by tetrazolium bromide assay. RESULTS： MSC fluorescence increased following a 72-hour siRNA transfection, with transfection efficiencies of up to （0.91 ± 0.04）; the Notch1 mRNA and Hesl mRNA expressed by transfected MSCs was significantly decreased （P 〈 0.05） compared with non-transfected cells. Fasudil hydrochloride induced MSCs to differentiate into neurons with greater efficiency in the transfected group （P 〈 0.05）. CONCLUSION： Fasudil hydrochloride induces rat MSCs to differentiate into neurons; inhibition of Notch1 signaling and Hesl expression may jointly promote the differentiation of MSCs into neurons.

Quantitative Determination of Benoxinate Hydrochloride by Three Wavelength Spectrophotometry

hree wavelength spectrophotometry was used to determine the content ofbenoxinate hydrochloride.Using this method could effectively eliminate the devia-tion of background absorption caused by the change of concentration and the errorof quantitative anaiysis caused by asymmetric peaks, and at the same time the lean-ing degree of base line was corrected.This method was simple, the recovery was98. 62% 101. 86% and the coefficient of variation was 0. 551%.

Penehyclidine Hydrochloride Premedication Is Not Associated with Increased Incidence of Post-Operative Cognitive Dysfunction or Delirium:A Systemic Review and Meta-Analysis

Objective Post-operative cognitive dysfunction(POCD)and post-operative delirium(POD)are two common post-operative cerebral complications.The current meta-analysis was to systematically review the effects of penehyclidine hydrochloride(PHC)on POCD and POD in surgical patients.Methods Electronic databases were searched to identify all randomized controlled trials comparing PHC with atropine/scopolamine/placebo on POCD and POD in surgical patients.Primary outcomes of interest included the incidences of POCD and POD;the secondary outcomes of interest included peri-operative minimental state examination(MMSE)scores.Two authors independently extracted peri-operative data,including patients'baseline characteristics,surgical variables,and outcome data.For dichotomous data(POCD and POD occurrence),treatment effects were calculated as odds ratio(OR)and 95%confidential interval(Cl).Each outcome was tested for heterogeneity,and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity.For continuous variables(MMSE scores),treatment effects were calculated as weighted mean difference(WMD)and 95%CI.Statistical significance was defined as P<0.05.Results Our search yielded 33 studies including 4017 patients.Meta-analysis showed that,the incidence of POCD in PHC group was comparable to that in saline group(OR=0.97;95%Ck 0.S8-1.64;P=0.92),scopolamine group(OR=0.78;95%CI:0.48-1.27;P=0.32)and atropine group(0R=1.20;95%Ch 0.86-1.67;P=0.29).The incidence of POD in PHC group was comparable to that in saline group(OR=1.53;95%CI:0.81-2.90;P=0.19)and scopolamine group(OR=0.53;95%CI:0.06-4.56;P=0.56),but higher than that in atropine group(OR=4.49;95%CI:1.34-15.01;P=0.01).Conclusions PHC premedication was not associated with increased incidences of POCD or POD as compared to either scopolamine or placebo.