茯苓多糖对ApoE-/-AS小鼠肝脏脂质沉积及胆固醇逆向转运相关蛋白表达的影响＊

目的 探讨茯苓多糖对载脂蛋白E基因敲除（ApoE^-/-）动脉粥样硬化（Atherosclerosis，AS）小鼠肝脏脂质沉积及胆固醇逆向转运的影响。方法 采用随机数字表法将30只ApoE^-/-小鼠随机分为模型组、茯苓多糖组、辛伐他汀组，每组10只，10只C57BL/6J小鼠作为正常组。正常组给予基础饲料喂饲，其余小鼠给予高脂饲料喂饲12周。茯苓多糖组以0.2 g/kg/d灌胃，辛伐他汀组以2.275 mg/kg/天灌胃，正常组和模型组给予等体积生理盐水灌胃，共干预4周。全自动生化分析仪检测小鼠血清三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平，苏木素-伊红（HE）染色观察小鼠肝脏病理形态学变化，油红O染色观察小鼠肝脏脂质沉积情况，ELISA检测各组小鼠血清载脂蛋白A1 （ApoA1）、对氧磷酶-1（PON1）含量，Real-time RT-qPCR法及Western Blot法检测肝脏胆固醇酯转运蛋白（CETP）、磷脂转运蛋白（PLTP）、卵磷脂胆固醇酰基转移酶（LCAT）mRNA及蛋白表达。结果 与正常组比较，模型组小鼠血清TG、TC、LDL-C含量均明显上升，HDL-C含量明显下降（P<0.01），肝细胞脂肪变性明显，肝脏脂质沉积明显，小鼠血清ApoA1、PON1含量均明显下降（P<0.01），小鼠肝脏CETP、PLTP mRNA及蛋白表达明显上升，LCAT mRNA及蛋白表达明显下降（P<0.01）。与模型组相比，茯苓多糖组血清TG、TC、LDL-C含量均显著下降（P<0.01），HDL-C含量呈上升趋势（P>0.05），肝细胞脂肪变性、脂质沉积程度均有所减轻，茯苓多糖组ApoA1含量明显上升（P<0.01），PON1含量呈上升趋势（P>0.05），茯苓多糖组CETP、PLTP mRNA及蛋白表达有所下降，LCAT mRNA及蛋白表达有所上升（P<0.05，P<0.01）。结论 茯苓多糖可能通过调控血脂水平与胆固醇逆向转运过程，改善ApoE^-/- AS小鼠肝脏脂质沉积，进而发挥防治AS作用。     

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The anti liver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the anti hepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an anti hepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an anti hepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".     

A case of nodal marginal zone lymphoma with hypersensitivity to mosquito bites as initial symptom

Hypersensitivity to mosquito bites (HMB) refers to skin reactions such as bullae and necrosis, which occurs after being bitten by mosquitoes and can present with multiple systemic reactions such as fever, lymphadenopathy, hepatosplenomegaly simultaneously or subsequently. A 48‐year‐old male patient presented with recurrent erythema, nodules, papules, vesicles and bullae over upper body and bilateral limbs with itching over the sites of mosquito bite for more than 1 year with low‐grade fever and superficial lymph nodes enlargement. The patient's symptoms failed to improve from conventional anti allergic treatment although skin biopsy showed changes of HMB reaction. Subsequently, the lymph node was biopsied and was reported to be nodal marginal zone lymphoma (NMZL), and then the patient was eventually diagnosed with nodal marginal zone lymphoma with HMB. To date only one case of nodal marginal zone lymphoma with HMB has been reported from Korea, and this is the first case to be reported in China.     

补肾活血方通过调节PI3K/Akt/mTOR信号通路改善DOR大鼠卵巢储备功能

目的 观察补肾活血方调节磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/雷帕霉素靶蛋白（mTOR）通路相关因子改善卵巢储备功能下降（DOR）大鼠卵巢储备功能的作用机制。方法 运用Ataya法腹腔注射环磷酰胺复制60只DOR模型大鼠，将其随机分为模型组、戊酸雌二醇组（0.000 9 g·kg^-1），补肾活血方高、中、低剂量组（33，16.5，8.25 g·kg^-1），同时另设正常组，每组12只；各组相应药物治疗，正常组和模型组给予等体积生理盐水，连续灌胃14 d，每天1次。治疗结束后，苏木素-伊红（HE）染色卵巢组织，光镜观察初级卵泡数、成熟卵泡数、总卵泡数的变化；免疫组化检测卵巢组织中血管内皮生长因子（VEGF）的表达，蛋白免疫印迹法（Western blot）检测卵巢组织中PI3K，Akt，mTOR，半胱氨酸天冬氨酸蛋白水解酶-3（Caspase-3）蛋白表达；实时荧光定量聚合酶链式反应（Real-time PCR）法检测卵巢组织中PI3K，Akt，mTOR mRNA表达。结果 与正常组比较，模型组卵巢组织中成熟卵泡数量、总卵泡数量明显减少（P<0.05，P<0.01），卵巢组织中VEGF，Caspase-3表达升高（P<0.05），PI3K，Akt，mTOR蛋白及mRNA表达水平降低（P<0.05，P<0.01）；与模型组比较，补肾活血方中、高剂量组成熟卵泡数量、总卵泡数量均有不同程度上升（P<0.05，P<0.01），VEGF补肾活血方中剂量组升高最为明显（P<0.05），补肾活血方低、中、高剂量组及戊酸雌二醇组Caspase-3下降，补肾活血方中、高剂量组PI3K，Akt，mTOR蛋白及mRNA表达水平均升高（P<0.05，P<0.01），且补肾活血方中剂量组更加接近于正常组。结论 补肾活血方可以有效地改善DOR大鼠卵巢储备功能，促进卵泡数量增加。作用机制可能与补肾活血方通过增加卵巢组织中VEGF的表达有关，进而激活PI3K/Akt/mTOR信号通路，从而调节Caspase-3的含量，最后促进卵泡数量的增加。     

艾烟的作用与安全性评价＊

艾灸作为中医学最古老的疗法之一，作用多样，应用广泛，疗效显著。随着科技的发展，人们对灸法的认识逐渐深入，其中艾烟的相关研究也硕果累累，其安全性广受关注。通过对艾烟作用和安全性评价研究中取得的成果进行归纳分析，以期为艾灸临床安全应用提供指导。     

The natural phytochemical trans‐communic acid inhibits cellular senescence and pigmentation through FoxO3a activation

Ageing is characterized by the accumulation of chronic and irreversible oxidative damage, chronic inflammation and organ dysfunction. To attenuate these ageing‐related changes, various natural phytochemicals are often applied. Trans‐communic acid (TCA), an active component of brown pine leaf extract, has antimicrobial and cancer chemopreventive activity and inhibits ultraviolet B (UVB)‐induced MMP‐1 expression. To determine whether the phytochemical TCA could affect the lifespan of an ageing model, Caenorhabditis elegans prevent ageing‐related phenotypes of the skin. Caenorhabditis elegans (C. elegans) wild‐type N2 and mutant strains were used in this study to explore the lifespan extension effect of TCA and its mechanism. We estimated lipofuscin accumulation and melanin levels, which are closely associated with skin senescence. Moreover, we explored the mechanism of action associated with ageing attenuation. We performed oxidative stress resistance and thermotolerance assays in C. elegans and surface plasmon resonance analysis of TCA binding with the forkhead box‐O3a (FoxO3a) protein. TCA, which is the active component in Korean red pine (Pinus densiflora), attenuated ageing‐related changes in skin cells. TCA lowered lipofuscin accumulation in fibroblasts and decreased melanin levels in melanocytes. These protective effects were mediated by activation of the representative longevity gene FoxO3a, which was induced by direct binding with TCA. Interestingly, TCA extended the lifespan of C. elegans, although it did not affect stress resistance, oxidative stress or thermotolerance. These results strongly suggest that TCA prevents the senescent phenotype of model organisms and exhibits beneficial effects on ageing‐related skin phenotypes through direct FoxO3a activation.