Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aβ and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aβ, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aβ: β-amyloid, GABA: gamma-aminobutyric acid.

目的 了解黄连解毒汤加减方对阿尔茨海默病(AD)模型小鼠学习记忆功能的影响并探索相关机制.方法 4月龄5×FAD小鼠分别灌胃给予黄连解毒汤加减方、黄连解毒汤原方治疗3个月,采用水迷宫等行为学方法检测小鼠学习记忆功能,采用膜片钳等电生理学方法检测神经元及突触功能,采用免疫印迹、免疫组化及电镜等检测小鼠脑内Aβ沉积及神经血管单元变化情况.结果 与模型组相比,黄连解毒汤加减方治疗能提高5×FAD小鼠的学习记忆功能,改善海马及皮层区突触结构及功能,减少Aβ沉积和星形胶质细胞增殖,上调ZO-1/Occludin等紧密连接蛋白表达,下调IL-1β、TNF-α等炎性因子及RAGE/NF-κB等信号分子表达,改善微血管超微结构;且加减方作用优于原方.结论 黄连解毒汤加减方可能通过抑制5×FAD小鼠脑内Aβ沉积、RAGE/NF-κB通路介导的神经炎症,改善神经血管单元损伤,从而改善AD模型小鼠的学习记忆功能.

Alzheimer’s disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson’s disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg−1·d−1, i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5×FAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5×FAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 μM) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing Aβ generation by inhibiting the β-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by Aβ plaque deposition in the retinas of 5×FAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and Aβ generation in early AD, which is a potential therapeutic intervention for early AD treatment.

Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson’s disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown. We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice. Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.

阿尔茨海默病(AD),即老年性痴呆,是一种起病隐匿、进行性发展的神经系统退行性疾病,尽早诊断与治疗有利于延缓疾病进程.AD的病因及病理机制复杂,其中特异性细胞毒性病理改变及应激/炎症反应、脑微血管病变及代谢失衡、神经微环路兴奋/抑制失衡等因素导致退行性改变进行性发展,尤其值得关注.我们认为上述病理改变在微观层面具有中医"虚痰瘀毒"特征,其中"浊毒损络"可作为AD的核心病机和治疗的关键切入点,且在AD早期就存在"浊毒损络"核心病机.AD疾病进程中,嗅觉、视觉等外周感觉功能异常早于认知功能障碍,上述外周感觉功能异常可作为AD早期病理进程的重要预警指标.我们探索了开心散加味优化方、黄连解毒汤加减方等经典名方及其有效成分早期干预对AD模型认知功能及视觉、嗅觉等功能的影响,并探索了相关机制,希望为中医药治疗早期AD提供现代生物医学依据.

目的:研究芪参益气滴丸对动脉粥样硬化中调节性T细胞的影响.方法:采用6周龄雄性C57BL/6J小鼠和ApoE基因敲除小鼠,分为正常组、模型组、芪参低剂量组、芪参高剂量组,每组6只.除正常组外,其他3组小鼠均给予高脂饲料喂养,药物组还给予高、低剂量的芪参益气滴丸,8周后评价内脏指数、动脉粥样硬化病变、调节性T细胞情况.结果:与模型组比较,芪参高剂量组可显著降低肝指数(P＜0.05),减少动脉粥样硬化斑块面积(P＜0.05,P＜0.01),并增加脾脏调节性T细胞数量(P＜0.01).结论:芪参益气滴丸可能通过增加脾脏调节性T细胞数量抑制动脉粥样硬化形成.

目的 观察复方威灵仙颗粒对高尿酸血症(HUA)患者血尿酸(UA)临床疗效及胰岛素抵抗的影响.方法 HUA患者63例,随机分成复方威灵仙颗粒组31例和别嘌呤醇组32例,在基础治疗的基础上,分别给予复方威灵仙颗粒(1剂/d,2次/d)及别嘌呤醇片(100 mg/次,3次/d),8 w为1个疗程.观察治疗前后血UA及临床疗效、空腹血糖(FPG)、空腹胰岛素(FINS)及胰岛素抵抗指数.结果 复方威灵仙颗粒组与别嘌呤醇组治疗后的血UA均较治疗前有明显下降(P<0.01),治疗总有效率分别为86.7%与90%,2组对血UA的疗效相当,差异无统计学意义(P>0.05),复方威灵仙颗粒组治疗后与治疗前比较FINS及胰岛素抵抗指数明显降低(P<0.01),而别嘌呤醇组治疗后与治疗前比较FINS及胰岛素抵抗指数无明显下降(P>0.05).结论 复方威灵仙颗粒具有降低血UA及改善胰岛素抵抗作用.

Objective: The aim of this study was to explore potential immunoregulatory mechanisms underlying the suppressive effect on atherosclerosis of QiShenYiQi pill (QSYQ). Methods and Results: Male ApoE-/-mice were maintained on a Western-type diet and QSYQ treatment for eight weeks. Determination of atherosclerosis demonstrated that QSYQ attenuated plaque formation and decreased the level of blood low-density lipoproteins-cholesterol. QSYQ treatment did not affect body weight but reduced the ratio of liver weight and body weight. Western blots of liver showed that QSYQ increased the expression of liver X receptor alpha and ATP-binding cassette sub-family G member 5. Western blots of atherosclerotic aorta revealed that QSYQ inhibited the expression of cluster of differentiation 36, promoted the expression of forkhead box P3 and decreased interleukin-17A expression. Western blots of spleen showed that QSYQ decreased the expression of mothers against decapentaplegic homolog 2/3 and forkhead box P3, as well as attenuated the expression of spleen interleukin-6, RAR-related orphan receptor gamma and interleukin-17A. Conclusions: QSYQ exerted an anti-atherosclerosis effect by promoting regulatory T cells in atherosclerotic lesion, inhibiting T helper 17 cells in plaque and spleen and accelerating liver cholesterol excretion.

In the research of Chinese medicine constitution classification,tongue manifestation is the easiest to master and is the easiest to objectify.In present constitution classification,tongue manifestation is most from the clinical examination or summary of ancient and modern literature by researchers.There is a gap between results from a large sample survey of modern constitution and tongue manifestation described in common constitution diagnostic criteria.The authors think that Chinese medicine visceral manifestations,Qi-blood theories,and modem image processing and analysis technology should be combined.The intrinsic association regulation between tongue manifestation characteristics and constitution type should be explored.Regional Chinese medicine constitution tongue manifestation database of different ages should be constructed to provide feasible technical means for realizing differentiating tongue to test constitution.

CD8(+) memory T (Tm) cells are a significant barrier to transplant tolerance induction in alloantigen-primed recipients, and are insensitive to existing clinical immunosuppressants. Here, we studied the inhibition of CD8(+) Tm cells by arsenic trioxide (As2O3) for the first time. Alloantigen-primed CD8(+) Tm cells were transferred to T cell immunodeficient nude mice. The mice were subjected to heart allotransplantation, and treated with As2O3. The transplant survival time was determined, and the inhibitory effects of As2O3 on CD8(+) Tm cell-mediated immune rejection were assessed through serological studies and inspection of the transplanted heart and lymphoid organs. We found that As2O3 treatment prolonged the mean survival time of the graft and reduced the number of CD8(+) Tm cells in the spleen and lymph nodes. The expression of the genes encoding interleukin (IL)-2, and IFN-γ was reduced, while expression of IL-10 and transforming growth factor-β was increased in the transplant. Our findings show that As2O3 treatment inhibits allograft rejection mediated by alloreactive CD8(+) Tm cells in the mouse heart transplantation model.

Metabonomics is a new developing omics after genomics,transcriptomics and proteomics.It can detect small molecular metabolite profiling in the human body fluid to reflect human physiological and pathological state.and TCM syndrome is a pathologic generalization in a stage in the progress of the disease of cause,location,nature and trend of disease.Obviously,it brings a new idea for using metabonomics to study the essence of TCM syndrome.

The low-grade inflammation is a non-specific,chronic,continuous,low-grade inflammation.It often appears on obesity,diabetes mellitus,hyperlipidemia,hypertension,coronary heart disease,cerebral infarction,metabolic syndrome,malignant tumours,polycystic ovary syndrome and so on,and plays a very important role in the pathogenesis,damage characteristics and diagnosis and prognosis of these diseases.Based on TCM theory,its pathogenesis is deficiency in origin and excess in superficiality,deficiency is focused on Qi,and excess is mainly caused by Qi stagnation,phlegm retention,blood stasis and heat-toxin.Qi deficiency and Qi stagnation are important conditions in occurrence of low-grade inflammation,phlegm retention and blood stasis are the pathogenic causes of low-grade inflammation,and heat-toxin is an important factor in development of low-grade inflammation.

<正>五苓散出自张仲景的《伤寒论》,药物组成有泽泻、茯苓、猪苓、白术、桂枝,具有利水渗湿、温通经脉、温阳化气、宁心安神之功,原方主治口渴烦躁、小便不利、水肿等病症。现代临床以五苓散为主方治疗原发性高血压、肾性高血压、代谢性高血压等已取得较好的

目的 探讨超敏C反应蛋白(hs-CRP)的变化与偏头痛发病机制的关系,观察颅痛煎治疗偏头痛疗效及对hs-CRP的影响.方法 选取65例偏头痛患者和30例健康人进行检测hs-CRP,再将65例病人随机分为颅痛煎汤治疗组(简称颅头煎组)32例,给予颅痛煎,一日一剂,水煎分2次服;西比灵对照组(简称西比灵组)33例,给于西比灵5mg,一天1次,谷维素20mg,一天3次.共治疗28天后.观察两组患者的治疗前后疼痛程度、持续时间、发作频度及检测hs-CRP,计算其头痛指数和头痛疗效.结果 偏头痛组hs-CRP含量明显高于正常对照组(P<0.01),治疗后颅痛煎组的hs-CRP水平明显低于西比林组(P<0.05),颅痛煎组的临床基本恢复、总有效率、头痛指数明显好于西比灵组(P<0.01、<0.05).结论 hs-CRP的增高与偏头痛的发生有关,颅痛煎治疗偏头痛疗效明显优于西比灵,可能与颅痛煎降低偏头痛患者的hs-CRP有关.

按照中医理论,由瘀血内阻而产生的的证候即为血瘀证;而血栓前状态则是一种有血栓形成倾向但尚未形成血栓的病理过程,这二者与缺血性中风密切相关。探讨血瘀、血栓前状态与缺血性中风的关系,总结治疗经验。

目的:探讨急性脑梗死中医辨证分型与血浆同型半胱氨酸(Hcy)、血清超敏C反应蛋白(hs-CRP)水平的关系.方法:选取210例急性脑梗死患者及30例健康者,对脑梗死患者按中医辨证分为风痰瘀阻型、阴虚风动型、气虚血瘀型、痰热腑实型、风痰火亢型、风火上扰型、痰湿蒙神型7组,分别测定急性脑梗死患者和健康对照者血浆Hey及血清hs-CRP水平,并进行组间比较.结果:急性脑梗死患者血浆Hey及血清hs-CRP水平显著高于对照组(P＜0.01),且急性脑梗死各中医证型中,风痰瘀阻型血浆Hcy水平较其他6型明显增高(P＜0.05);痰热腑实型、风痰火亢型、风火上扰型的血清hs-CRP水平较风痰瘀阻型、气虚血瘀型、阴虚风动型及痰湿蒙神型显著升高(P＜0.05).结论:血液Hcy、hs-CRP水平的升高是动脉粥样硬化性血栓性脑梗死的重要危险因素,血液Hcy、HsCRP水平可作为急性脑梗死中医辨证分型的客观指标.

炎症反应贯穿动脉粥样硬化(atherosclerosis,AS)发生、发展及易损斑块形成和破裂的全过程。中医毒邪致病理论,即外来之毒与内生之毒相互作用产生的痰毒、瘀毒、热毒在粥样斑块的形成中起重要作用,说明炎症反应贯穿"痰瘀热毒"产生的全过程,痰毒、瘀毒和热毒作为病邪又可诱发机体炎症反应,这样反复循环,可致粥样斑块形成和不断增大。因此,AS发生、发展全过程的炎症反应与中医毒邪致病理论是相吻合的。

Impaired glucose regulation(IGR)were in stage of Prediabetes,belongs to the field of Sweet Taste In Mouth and Food Retention in Chinese Medicine.These patients were High-risk population in Diabetes and Cardiovascular Disease.The majority patients in the stage of IGR were reversible,it should be in early intervention progress,this were fit in the theory of"Preventive Treatment of Disease"in Chinese Medicine.This article focus on analyzing the Chinese medical pathogenesis of Prediabetes.

目前代谢综合征的中医辨证分型主要依据个人经验、文献古籍记载,尚未统一,这样的辨证分型较易出现偏倚,可信度低.提出应该制定代谢综合征的中医证候临床调查表,进行大样本、前瞻性、多中心的中医证候临床流行病学调查,使用现代数理统计方法进行证候分类,探讨证型与发病机制有关临床检测指标的关系,通过"以方测证"方法来反证辨证分型的可靠性,从而建立代谢综合征的中医辨证论治体系.

The pathogenesis of metabolic syndrome in traditional Chinese medicine is mainly phlegm,blood stasis and stagnation,toxin and the mixture of them,while the basis of the pathogenesis of metabolic syndrome in western medicine is low-grade systemic inflammation condition,so the low-grade systemic inflammation condition is formed the material basis of the pathogenesis of metabolic syndrome.