升降散临床应用研究进展

升降散为中医升降气机、开郁透热的著名方剂。临床上,该方或其加味方,或与西医药联合使用,用于包括呼吸、消化、循环、泌尿、神经、内分泌、皮肤等在内的多科及多种疾病的治疗,均取得一定疗效。现基于循证的角度,对近10年来关于升降散临床运用方面的研究进行系统梳理和评析,为该方的临床疗效评价及合理运用提供参考。     

乳酸菌阴道胶囊联合达克宁栓治疗妊娠期外阴阴道假丝酵母菌病的疗效对照研究

目的：探讨乳酸菌阴道胶囊联合达克宁栓治疗妊娠期外阴阴道假丝酵母菌病的疗效.方法：选择68例妊娠期外阴阴道假丝酵母菌病患者,随机分为联合组和对照组.两组患者均予以达克宁栓放入阴道置于阴道后穹隆处,每晚1枚,连用3d.联合组加用乳酸菌阴道胶囊放入阴道置于阴道后穹隆处,早上2枚,连用5d.对照组除不使用乳酸菌阴道胶囊外余治疗均同联合组.观察两组患者治疗结束后1周的临床疗效,并随访治疗后3个月的复发率.结果：联合组患者治疗后的临床总有效率明显高于对照组（χ2=6.93,P〈0.01）.对照组与联合组治疗后3个月内分别复发13例和4例.联合组患者治疗后3个月内复发率明显低于对照组（χ2=6.35,P〈0.05）.结论：乳酸菌阴道胶囊联合达克宁栓治疗妊娠期外阴阴道假丝酵母菌病较确切,能明显降低复发率,具有治疗和预防外阴阴道假丝酵母菌病复发的作用.     

基于生信学数据挖掘和实验验证阿魏酸介导间充质干细胞外泌体调控炎症miRNA表达情况

目的 基于生信分析筛选出人脐血间充质干细胞来源的外泌体(human umbilical cord blood mesenchymal stem cells-derived exosomes,hUCBMSC-Exos)中可用于调控炎症过程的微小RNA (microRNA,miRNA)。在此基础上,研究阿魏酸(ferulic acid,FA)对hUCBMSC-Exos中与炎症调控相关miRNA的影响。方法 从现有数据库中分别筛选hUCBMSC-Exos中的miRNAs和与调控炎症相关的miRNAs,取2组miRNAs的交集,从而获得hUCBMSC-Exos中与调控炎症相关的候选miRNA分子组。取足月健康新生儿脐带血,将分离所得的单个核细胞置于DMEM/F12培养基培养至P4代细胞,进行成骨、成软骨和成脂诱导分化鉴定。实验分为2个部分来验证FA对hUCBMSC-Exos及hUCBMSCs分泌相关炎症因子的作用：①将鉴定成功的hUCBMSC-Exos随机分为实验组及对照组,实验组用2 mg·L^-1 FA干预,对照组用等体积PBS液处理,培养24 h。采用超速离心法结合超滤法提取hUCBMSC-Exos,通过透射电子显微镜观察其形态,蛋白印迹法鉴定其特征表面标志物CD9、CD63和TSG101,采用BCA法测定hUCBMSC-Exos浓度,RT-qPCR法检测各组外泌体中炎症调控相关候选miRNAs的表达。②另将鉴定成功的人hUCBMSCs按随机数字表法随机分为实验组、模型组和对照组,实验组与模型组用含30 mmo1·L^-1的葡萄糖DMEM/F12培养基培养120 h,建立高糖诱导损伤hUCBMSCs细胞模型后,实验组用2 mg·L^-1 FA干预,模型组和对照组用等容量的PBS液处理。每组均培养24 h后用ELISA试剂盒检测3组上清液中炎性因子含量。结果 通过对GEO测序数据分析和对文献的筛选最终获得7个在hUCBMSC-Exos中可能高表达且与炎症调控相关的miRNAs：miR-125b、miR-126、miR-145、miR-146a、miR-21、miR-221、miR-31-5p。成功培养、分离和鉴定得到hUCBMSCs,并进一步收集到hUCBMSC-Exos,培养24 h后,实验组hUCBMSC-Exos的浓度为(1.179±0.03)μg·mL^-1,明显高于对照组(0.881±0.03)μg·mL^-1(P<0.01)。与对照组相比,实验组中部分炎症调控相关miRNA变化显著,miR-126-3p和miR-146a-5p显著上升,miR-145及miR-31-5p显著下降,差异有统计学意义(P<0.05)。与模型组相比,在2 mg·L^-1 FA干预下,实验组中hUCBMSCs分泌IL-1β、MCP-1水平明显降低,分泌IL-10、M-CSF明显水平升高,差异具有统计学意义(P<0.05),2组间IL-6分泌差异无统计学意义。与对照组相比,模型组hUCBMSCs分泌IL-1β、IL-6、MCP-1水平明显增高,差异具有统计学意义(P<0.05),2组间IL-10、M-CSF分泌差异无统计学意义。结论 FA可能通过介导hUCBMSC-Exos中调控炎症的miRNA (miR-126-3p、miR-146a-5p、miR-145及miR-31-5p)分泌,进一步调控hUCBMSCs分泌相关炎症因子从而调控机体炎症反应,本研究进一步从外泌体水平证实FA具有调控炎症的潜能。为进一步研究FA通过hUCBMSC-Exos调控机体炎症反应奠定坚实基础。     

移动增强现实技术在神经解剖教学中的应用效果研究

目的　探索将移动增强现实（mobile augmented reality,mAR）技术应用到神经解剖学教学中,观察其对学生学习成绩及认知负荷的影响。方法　通过收集并设计各种神经解剖学的多媒体教学资源（图形、动画和视频）,运用AR基于标记的图像识别技术,将多媒体资源放置在传统书页中的标记处,使书籍具有交互性;并且通过移动设备将各种多媒体资源与传统印刷书结合在一起。40名学生被分配至试验组或对照组,试验组采取mAR多媒体资源教学,对照组采取传统方式教学。6学时课程完成后,全部学生进行统一测试,使用学业成绩测验和PAAS（platform-as-a-service）认知负荷量表进行数据收集和分析。采用SPSS 18.0进行方差（MANOVA和ANOVA）分析。结果　单向MANOVA检验用于确定通过mAR学习对学习成绩和认知负荷的影响,结果表明试验组和对照组之间差异有统计学意义（P<0.05）。单变量ANOVA检验发现通过mAR学习神经解剖的试验组学生在测试成绩上比对照组学生更高。此外,与对照组学生相比,试验组学生的认知负荷明显降低了,差异有统计学意义（P<0.05）。结论　通过教学实践发现,使用mAR学习神经解剖学有助于学生在减轻认知负荷的情况下提高学习成绩。     

Janus nanocarriers for magnetically targeted and hyperthermia-enhanced curcumin therapy of liver cancer

Curcumin is regarded as a promising chemotherapeutic agent due to its anti-cancer activity and excellent biosafety. Nevertheless, the poor bioavailability and insufficient therapeutic efficacy have limited its further application in the clinic. Hence, we designed Janus magnetic mesoporous silica nanoparticles (Janus M-MSNs) for magnetically targeted and hyperthermia-enhanced curcumin treatment of liver cancer. In this study, curcumin was loaded into the silica components of Janus M-MSNs via surface-decorated pH-sensitive groups. Janus M-MSNs-Cur exhibited superior superparamagnetic properties, high curcumin loading ability and a tumor microenvironment-responsive curcumin release fashion. Additionally, an external magnetic field promoted the anti-tumor effectiveness of Janus M-MSNs-Cur through increasing the cellular internalization of Janus M-MSNs-Cur. More importantly, magnetic hyperthermia therapy supplemented the chemotherapeutic effect through a synergistic effect. Our outcomes demonstrated that Janus M-MSNs-Cur possessed a high therapeutic efficiency and excellent biosafety both in vitro and in vivo, indicating that Janus M-MSNs-Cur might be a promising therapeutic agent for liver cancer treatment.

Curcumin is regarded as a promising chemotherapeutic agent due to its anti-cancer activity and excellent biosafety.     

Double-ratiometric fluorescence imaging of H2Se and O2˙− under hypoxia for exploring Na2SeO3-induced HepG2 cells' apoptosis

Sodium selenite (Na₂SeO₃), as an anti-tumor drug for inducing tumor cells'' apoptosis, has been widely studied under normoxic conditions and has been shown to exhibit oxidative stress process-induced apoptosis. However, since the real tumor environment is hypoxic, the actual mechanism is still unclear. Hence, considering the main metabolite of Na₂SeO₃ in the metabolic process to be hydrogen selenide (H₂Se) and also that it can be converted to superoxide anion (O₂˙⁻) instantaneously in the presence of oxygen, a dual-ratiometric fluorescence imaging system for simultaneous monitoring of the changes of H₂Se and O₂˙⁻ induced by Na₂SeO₃-guided tumor cell apoptosis under hypoxic conditions was constructed. Two molecular probes NIR-H₂Se and dihydroethidium were used to detect H₂Se and O₂˙⁻, respectively, whereas Rhodamine 110 was used as the reference fluorophore. Notably, H₂Se levels significantly increased under hypoxic conditions, but there was no change in the level of O₂˙⁻, which is inconsistent with the results of the previous researches. Therefore, we hypothesize that the mechanism of Na₂SeO₃-induced apoptosis for tumor cells is caused by reductive stress; also, this method can be applied for the future study of other anti-cancer selenium compounds.

Sodium selenite (Na₂SeO₃), as an anti-tumor drug for inducing tumor cells'' apoptosis, has been widely studied under normoxic conditions and has been shown to exhibit oxidative stress process-induced apoptosis.     

Fibroblast-derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa

Patients with the genetic skin blistering disease recessive dystrophic epidermolysis bullosa (RDEB) develop aggressive cutaneous squamous cell carcinoma (cSCC). Metastasis leading to mortality is greater in RDEB than in other patient groups with cSCC. Here we investigate the dermal component in RDEB using mRNA expression profiling to compare cultured fibroblasts isolated from individuals without cSCC and directly from tumor matrix in RDEB and non-RDEB samples. Although gene expression of RDEB normal skin fibroblasts resembled that of cancer-associated fibroblasts, RDEB cancer-associated fibroblasts exhibited a distinct and divergent gene expression profile, with a large proportion of the differentially expressed genes involved in matrix and cell adhesion. RDEB cancer-associated fibroblasts conferred increased adhesion and invasion to tumor and nontumor keratinocytes. Reduction of COL7A1, the defective gene in RDEB, in normal dermal fibroblasts led to increased type XII collagen, thrombospondin-1, and Wnt-5A, while reexpression of wild type COL7A1 in RDEB fibroblasts decreased type XII collagen, thrombospondin-1, and Wnt-5A expression, reduced tumor cell invasion in organotypic culture, and restricted tumor growth in vivo. Overall, our findings show that matrix composition in patients with RDEB is a permissive environment for tumor development, and type VII collagen directly regulates the composition of matrix proteins secreted by dermal and cancer-associated fibroblasts.     

Tiagabine is neuroprotective in the N171-82Q and R6/2 mouse models of Huntington's disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by chorea, incoordination, and shortened life-span, and by huntingtin inclusions and neurodegeneration. We previously screened the 1040 FDA-approved compounds from the NINDS compound library and found that a compound, nipecotic acid, significantly reduced mutant huntingtin aggregations and blocked cell toxicity in an inducible cell model of HD. Because nipecotic acid does not cross the blood–brain barrier (BBB), we studied its analogue, tiagabine, which is able to cross the BBB, in both N171-82Q and R6/2 transgenic mouse models of HD. Tiagabine was administered intraperitoneally at 2 and 5 mg/kg daily in HD mice. We found that tiagabine extended survival, improved motor performance, and attenuated brain atrophy and neurodegeneration in N171-82Q HD mice. These beneficial effects were further confirmed in R6/2 HD mice. The levels of tiagabine at effective doses in mouse serum are comparable to the levels in human patients treated with tiagabine. These results suggest that tiagabine may have beneficial effects in the treatment of HD. Because tiagabine is an FDA-approved drug, it may be a promising candidate for future clinical trials for the treatment of HD.     

辨证治疗颈椎病术后50例疗效观察

[目的]探讨颈椎病术后运用中药治疗的效果。[方法]对50例颈椎病术后患者运用中药对症治疗。[结果]50例颈椎病术后的患者均获得随访,其中治愈10例,好转34例,未愈6例,总有效率为88.0%。[结论]采用中药治疗颈椎病术后的患者,有比较好的临床疗效。