目的:建立利培酮(RIS)血药浓度测定方法,探讨RIS治疗精神分裂症病人的血药浓度与甲状腺功能指标的相关性。方法:血浆样品经乙腈沉淀后,以氯米帕明为内标,采用超高效液相色谱-串联质谱(UPLC-MS/MS)法测定,色谱柱为BEH C 18,流动相为乙腈-...目的:建立利培酮(RIS)血药浓度测定方法,探讨RIS治疗精神分裂症病人的血药浓度与甲状腺功能指标的相关性。方法:血浆样品经乙腈沉淀后,以氯米帕明为内标,采用超高效液相色谱-串联质谱(UPLC-MS/MS)法测定,色谱柱为BEH C 18,流动相为乙腈-水(含5 mmol/L乙酸铵溶液和0.01%氨水),梯度洗脱,流速为0.5 mL/min,柱温为40℃,进样量为2μL,采用多反应监测模式扫描,对UPLC-MS/MS进行方法学考察,将其用于测定116例临床精神分裂症病人血浆中RIS浓度,收集相关病例的住院信息,并探讨RIS血药浓度与甲状腺功能指标的相关性。结果:RIS、9-羟基利培酮(9-OHRIS)在0.4~120.0 ng/mL范围内线性关系良好;日内、日间准确度、提取回收率、基质效应及稳定性均符合要求。病人体内平均稳态血药质量浓度为(49.76±18.07)ng/mL;治疗各时间点病人的稳态血药浓度差异无统计学意义(P>0.05),甲状腺功能指标除促甲状腺激素外(P>0.05),其他4个指标治疗后随着时间的推移呈波动上升趋势(P<0.01);病人的血药浓度与甲状腺功能指标无相关性(P>0.05),但女性病人的RIS血药浓度与四碘甲状腺原氨酸、游离三碘甲状腺素、游离甲状腺素均呈正相关(r=0.480、0.524、0.454,P<0.05)。结论:该方法准确简便、快速灵敏、重现性好,可用于测定精神分裂症病人体内RIS的血药浓度。女性病人体内较高的血药浓度可能会影响甲状腺功能指标,进而影响病人甲状腺功能,需要引起临床的注意。展开更多
目的观察阿立哌唑治疗老年痴呆伴精神障碍(behavioral and psychological symptoms of dementia,BPSD)的疗效和对体重、糖脂代谢的影响,探究阿立哌唑血药浓度与BPSD临床疗效的相关性。方法入组30例BPSD患者给予阿立哌唑抗精神病治疗6周...目的观察阿立哌唑治疗老年痴呆伴精神障碍(behavioral and psychological symptoms of dementia,BPSD)的疗效和对体重、糖脂代谢的影响,探究阿立哌唑血药浓度与BPSD临床疗效的相关性。方法入组30例BPSD患者给予阿立哌唑抗精神病治疗6周,分别于治疗前及第2、4、6周末进行阿尔茨海默病病理行为量表(BEHAVE-AD)、治疗副反应量表(TESS)评定并测定BMI指数、空腹血糖、胆固醇、甘油三酯、高密度脂蛋白,同时应用高效液相色谱法测定阿立哌唑的血药浓度。结果患者经阿立哌唑治疗6周后BEHAVE-AD评分显著下降(P<0.01);治疗前后患者BMI指数、空腹血糖、胆固醇、甘油三酯及高密度脂蛋白均无显著性差异;治疗第4周末及第6周末阿立哌唑血药浓度与BEHAVE-AD减分率呈显著正相关,有效组血药浓度显著高于无效组。结论阿立哌唑治疗老年痴呆伴精神障碍的疗效确切,且对患者体重及糖脂代谢影响较小,适用于伴有心脑血管疾病的老年痴呆伴精神障碍患者;阿立哌唑治疗老年痴呆伴精神障碍的血药浓度与临床疗效存在相关性,提示用血药浓度指导治疗更客观,也有利于调整药物剂量,能够为临床合理用药提供依据。展开更多
Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture(EA) in experimental models of Alzheimer’s disease(AD) in vivo. Methods: Senescenceaccelerated mouse prone 8(SA...Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture(EA) in experimental models of Alzheimer’s disease(AD) in vivo. Methods: Senescenceaccelerated mouse prone 8(SAMP8) mice were used as AD models and received EA at Yingxiang(LI 20, bilateral) and Yintang(GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin(2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier(BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid-β(Aβ), and ionized calcium-binding adapter molecule 1(IBa-1) in mouse hippocampus(CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction(qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining.Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining. Results: Fibrin was time-dependently deposited in the hippocampus of SAMP8mice and this was inhibited by EA treatment(P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice(P<0.01), which was reversed by fibrin injection(P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability(P<0.05 or P<0.01).Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8mice, which was reversed by fibrin injection(P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1(HMGB1)/toll-like receptor 4(TLR4) and receptor for advanced glycation end products(RAGE)/nicotinamide adenine dinucleotide phosphate(NADPH) signaling pathways(P<0.01). Conclusion: EA may potentially improve cognitive impairment in AD via inhibition of fibrin/Aβdeposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.展开更多
文摘目的运用复杂网络技术,分析针刺治疗胃脘痛的选穴规律。方法检索中国期刊全文数据库(CNKI)、万方数据知识服务平台(Wanfang Data)、中文科技期刊数据库(VIP)、中国生物医学文献服务系统(SinoMed)、PubMed、Embase、Cochrane Library和Web of Science建库至2022年11月30日收录的针刺治疗胃脘痛的临床研究文献,严格按照筛选标准对文献进行筛选,并提取针刺处方。利用Excel2021建立针刺治疗胃脘痛处方数据库,并统计腧穴频次、归经、特定穴及中医证型;运用Gephi0.9.6完成复杂网络建模,并进行拓扑结构分析、核心腧穴分析及社团分析。结果共纳入105篇文献,包含175首针刺处方,涉及83个腧穴,腧穴总频次为1058次。高频腧穴前5位分别为足三里、中脘、内关、胃俞、脾俞,高频组穴前3位为足三里-中脘、足三里-内关、中脘-内关,通过k-core层次分析法筛选出足三里、中脘、内关、胃俞、脾俞、公孙、太冲、天枢、气海及梁丘等24个核心腧穴,采用社团分析法得到4类证-穴社团。结论针刺治疗胃脘痛选穴以特定穴为主,尤以五输穴居多,多运用上下配穴法和俞募配穴法,临证注重辨证论治,可为临床针刺治疗胃脘痛提供参考。
文摘目的观察阿立哌唑治疗老年痴呆伴精神障碍(behavioral and psychological symptoms of dementia,BPSD)的疗效和对体重、糖脂代谢的影响,探究阿立哌唑血药浓度与BPSD临床疗效的相关性。方法入组30例BPSD患者给予阿立哌唑抗精神病治疗6周,分别于治疗前及第2、4、6周末进行阿尔茨海默病病理行为量表(BEHAVE-AD)、治疗副反应量表(TESS)评定并测定BMI指数、空腹血糖、胆固醇、甘油三酯、高密度脂蛋白,同时应用高效液相色谱法测定阿立哌唑的血药浓度。结果患者经阿立哌唑治疗6周后BEHAVE-AD评分显著下降(P<0.01);治疗前后患者BMI指数、空腹血糖、胆固醇、甘油三酯及高密度脂蛋白均无显著性差异;治疗第4周末及第6周末阿立哌唑血药浓度与BEHAVE-AD减分率呈显著正相关,有效组血药浓度显著高于无效组。结论阿立哌唑治疗老年痴呆伴精神障碍的疗效确切,且对患者体重及糖脂代谢影响较小,适用于伴有心脑血管疾病的老年痴呆伴精神障碍患者;阿立哌唑治疗老年痴呆伴精神障碍的血药浓度与临床疗效存在相关性,提示用血药浓度指导治疗更客观,也有利于调整药物剂量,能够为临床合理用药提供依据。
基金Supported by the National Natural Science Foundation of China (No.82074552)Shaanxi Science and Technology Department Project (No.2018JM7041)Shaanxi Province TCM "Double Chain Integration" Young and Middle-Aged Scientific Research Innovation Team Construction Project (No.2022-SLRH-LJ-012)。
文摘Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture(EA) in experimental models of Alzheimer’s disease(AD) in vivo. Methods: Senescenceaccelerated mouse prone 8(SAMP8) mice were used as AD models and received EA at Yingxiang(LI 20, bilateral) and Yintang(GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin(2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier(BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid-β(Aβ), and ionized calcium-binding adapter molecule 1(IBa-1) in mouse hippocampus(CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction(qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining.Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining. Results: Fibrin was time-dependently deposited in the hippocampus of SAMP8mice and this was inhibited by EA treatment(P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice(P<0.01), which was reversed by fibrin injection(P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability(P<0.05 or P<0.01).Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8mice, which was reversed by fibrin injection(P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1(HMGB1)/toll-like receptor 4(TLR4) and receptor for advanced glycation end products(RAGE)/nicotinamide adenine dinucleotide phosphate(NADPH) signaling pathways(P<0.01). Conclusion: EA may potentially improve cognitive impairment in AD via inhibition of fibrin/Aβdeposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.
