拘束冷应激对大鼠肾脏热休克蛋白表达和血清皮质醇含量的动态影响

目的：研究拘束冷应激对大鼠肾脏组织热休克蛋白（heat shock protein 70,HSP70）表达和血清中皮质醇（Cortisol,CORT）含量的动态影响及可能的机制。方法：选取50日龄清洁级大鼠77只,随机分为7组,即0、0.5、1.0、1.5、2.0、2.5和3.0 h。采用拘束冷应激法,应激相应时间后,用免疫组织化学方法观察大鼠肾脏组织HSP70的表达,并检测血清中CORT含量。结果：血清中的CORT浓度在1.5 h呈现最高值,其余各时点变化不明显。光镜下可见HSP70在肾小球毛细血管内皮细胞的胞核及肾小管上皮细胞的胞核和胞浆中均有表达。肾脏中HSP70的表达首先呈增加的趋势,1.5～2.5 h HSP70持续高表达（P〈0.01）,之后下降（P〈0.05）。结论：适当强度的拘束冷应激能诱导肾脏组织中HSP70的合成,并且随着时间的延长而增加,但过度的拘束冷应激则可能降低或阻断肾脏HSP70的表达。     

寒凝血瘀对结肠癌肺转移模型小鼠肺组织VEGF、 MMP-2表达的影响

目的:观察寒凝血瘀状态下Balb/c 小鼠C26 人工血行肺转移组织血管内皮生长因子(VEGF)、基质金属蛋白酶-2(MMP-2)表达.方法:将小鼠随机分为空白对照组、寒凝血瘀组、单纯荷瘤组、复合造模组,分别进行造模,通过免疫组化、Western Blot方法检测肺转移灶中VEGF、MMP-2的表达.结果:复合造模组小鼠基质金属蛋白酶-2(MMP-2)表达高于单纯荷瘤组,差异有统计学意义(P<0.05),复合造模组小鼠血管内皮生长因子(VEGF)表达较单纯荷瘤组小鼠有增高趋势,差异无统计学意义(P>0.05).结论:寒凝血瘀状态可能通过促使结肠癌小鼠肿瘤组织VEGF和MMP-2表达的上调,促使小鼠C26结肠癌血行肺转移,促进疾病进展.     

10℃冷水试验方法在评价振动职业危害中的应用研究

研究１０℃冷水试验方法在评价振动职业危害中的应用。「方法」对白指病人、接振工人及对照工人进行冷水试验检查,用热电偶温度计测量冷试前后手部皮肤温度。「结果」白指病人和对照工人比较,在冷试前后手部皮肤温度和各时间的复温率均明显降低,而接振组和对照组比较,在１５ｍｉｎ、２０ｍｉｎ、３０ｍｉｎ的皮肤温度降低,各时间的复温率均组。各组间恢复到冷试前的人数有显著性差异。「结论」１０℃的冷水试验方法能用于评价振     

厌食儿童维生素A营养状况的研究

本文采用血清维生素A(V_A)水平,暗适应时间、膳食调查3项指标对30例厌食儿童V_A营养状况进行综合评价.结果表明:厌食儿童血清V_A水平明显低于对照组;暗适应时间明显长于对照组;66.7％的患儿膳食VA摄入不足.其中2项指标均异常者20例,占66.7％,3项指标均异常者6例,占20％.提示厌食儿童中有相当比例存在亚临床型V_A缺乏,值得临床医生注意     

冷适应过程中大鼠脑垂体、下丘脑和血浆生物活性肽的变化及其对免疫功能的影响

我们采用RP-HPLC方法研究了SD纯系雄性大鼠冷适应期间脑垂体(P)、下丘脑(HT)和血浆(BP)生物活性肽变化。冷适应期间P、HT和BP肽类(MW≤30000)RP-HPLC图谱均出现一些新的肽洗脱峰。而且,所有这些肽类都能增强淋巴细胞(LC)转化活性。在P和HT肽类刺激下,脾LC[~3H]-TdR参入分别增加725 cpm(P<0.01)和1274 cpm(P<0.001)。将这些肽类进一步经Sep-Pack C_(18)柱纯化后仍分别增加[~3H]-TdR参入cpm值597(P<0.05)和333。这些结果表明了免疫系统(ImS)与神经内分泌系统(NES)双向调节环路的一个方面:NES作用于ImS。     

The acquisition of cold sensitivity during TRPM8 ion channel evolution

To cope with temperature fluctuations, molecular thermosensors in animals play a pivotal role in accurately sensing ambient temperature. Transient receptor potential melastatin 8 (TRPM8) is the most established cold sensor. In order to understand how the evolutionary forces bestowed TRPM8 with cold sensitivity, insights into both emergence of cold sensing during evolution and the thermodynamic basis of cold activation are needed. Here, we show that the trpm8 gene evolved by forming and regulating two domains (MHR1-3 and pore domains), thus determining distinct cold-sensitive properties among vertebrate TRPM8 orthologs. The young trpm8 gene without function can be observed in the closest living relatives of tetrapods (lobe-finned fishes), while the mature MHR1-3 domain with independent cold sensitivity has formed in TRPM8s of amphibians and reptiles to enable channel activation by cold. Furthermore, positive selection in the TRPM8 pore domain that tuned the efficacy of cold activation appeared late among more advanced terrestrial tetrapods. Interestingly, the mature MHR1-3 domain is necessary for the regulatory mechanism of the pore domain in TRPM8 cold activation. Our results reveal the domain-based evolution for TRPM8 functions and suggest that the acquisition of cold sensitivity in TRPM8 facilitated terrestrial adaptation during the water-to-land transition.

Given that temperature influences all biological operations, the evolution of thermosensory adaptation is crucial in shaping the specialized temperature-dependent inhabitation of an organism. At the cellular level, thermosensory neurons in the dorsal root ganglia or trigeminal ganglia innervate the skin and transmit temperature information to the spinal cord and the brain. To bestow such neurons with thermal sensitivity, animals have a toolkit of temperature-sensitive ion channels located on the cell membrane at the molecular level. Accordingly, several members of the transient receptor potential (TRP) superfamily with steep thermosensitivity (referred to as thermoTRP) have attracted the general interest in the field of thermal biology, as they sufficiently cause steep changes in depolarizing currents upon either heating or cooling and thus are considered as the primary molecular sensors of temperature (1–4). Therefore, the evolutionary strategy for directly tuning the thermal activation in thermoTRPs can be employed by animals for their specialized thermosensory adaptation, as seen in vampire bats, pit-bearing snakes, platypus, penguins, squirrels, and camels (5–9).As heat sensation (warmth and extreme heat) provides the precondition of a fundamental and conserved biological survival process, the genes that encode heat sensors are considered ancient in many metazoan organisms. The annotation of trpv1 is consistently available in the genomes of fishes, insects, amphibians, reptiles, birds, and mammals. Despite the species-specific temperature-sensitive ranges, a growing number of studies have reported the functional convergence of these heat-sensitive thermoTRP orthologs at the protein level (10), suggesting the essential role of these channels in heat perception across species. Compared to heat sensors, the cold-sensitive thermoTRP likely evolved late. As the most established cold sensor responsive to low temperatures and cooling compounds, transient receptor potential melastatin 8 (TRPM8) was found in somatosensory neurons, and genetic ablation of trpm8 either in the neurons or mice led to a largely decreased cold sensitivity (4, 11–13). Interestingly, cold activation of amphibian TRPM8 has been tested (14), while sequencing efforts indicated the absence of the trpm8 gene in 12 fish species from 10 different orders (15). Several specific domains that may alter TRPM8 cold activation have been reported, including the pore domain, voltage sensing apparatus, and C terminus (8, 16–19). Notably, although the efficacy of cold activation is largely altered by residue substitutions in the pore domain, the channel mutants are still cold sensitive (8). Therefore, these findings based on domain/residue swapping among cold-sensitive TRPM8 orthologs may not draw an overall picture in functionally important domains responsible for cold sensitivity. How did the trpm8 gene originate? How did TRPM8 integrate and modulate cold sensitivity throughout evolution? The answers to such questions probably lead us to understand the evolution of temperature perception and identify the essential structural elements that shape TRPM8 cold activation.In this study, we show the presence of the young trpm8 gene in lobe-finned fishes, believed to be the ancestors that gave rise to all land vertebrates (20). Such a young type of trpm8 derived from the trpm2 exon shuffling was originated and formed during the expansion of lobe-finned fish genomes. By detecting the positive selection-rich domains, we described the formation of the thermosensitive MHR1-3 domain in amphibian and reptile species that enables TRPM8 to undergo conformational changes at low temperatures. Furthermore, we found that the TRPM8 pore domain of terrestrial vertebrates evolved to tune the efficacy of cold activation, in which a cold-sensitive MHR1-3 domain is indispensable to achieve such a modulatory mechanism. Together, our findings suggest that the trpm8 gene origination and formation of the TRPM8 MHR1-3 domain contributed to the transition of vertebrate life from water to land and that the efficacy of cold activation tuned by the TRPM8 pore domain diversified the setting of temperature-adaptive phenotypes in terrestrial vertebrates.     

张伯礼教授辨治感冒经验

感冒四季皆发,一般症状轻浅,但少数反复发作,缠绵难愈,患者深受其苦。张伯礼教授注重感冒防-治-康全流程辨治,首以病证合参,明确风邪犯肺,可累及鼻咽;再明辨寒热虚实,关注兼夹之证,把握小儿感冒的疾病特点和治疗策略;注重病程变化,久病不忘气血并调,内外兼治,强调先安未受邪之地;重视防治养生,综合调节,知冷暖,劳逸结合。     

冷适应过程中小鼠非特异性细胞免疫功能的变化

本文观察了冷适应过程中非特异性细胞免疫功能的变化。对小鼠腹腔巨噬细胞吞噬活性和脾细胞自然杀伤活性进行了检测。结果表明冷暴露第1周,两项指标均降低,第3天自然杀伤活性达最低水平(P<0.01),第7天吞噬活性达最低水平(P<0.05),2周以后恢复且略高于正常水平。吞噬活性与自然杀伤活性 相关性统计有意义(P<0.05)。     

5种感冒药的药物经济学及用药风险分析

运用药物经济学的方法对杭州市场上常用的5种感冒药的成本、效果及用药风险进行了分析,结果显示：E组（快克）成本最低,成本效果比最小;B组（白加黑）用药风险最小。     

Can Radiotherapy Empower the Host Immune System to Counterattack Neoplastic Cells? A Systematic Review on Tumor Microenvironment Radiomodulation

Despite the rising evidence in favor of immunotherapy (IT), the treatment of oncological patients affected by so-called “cold tumors” still represents an open issue. Cold tumors are characterized by an immunosuppressive (so-called cold) tumor microenvironment (TME), which favors host immune system suppression, cancer immune-escape, and a worse response to IT. However, the TME is not a static element, but dynamically mutates and can be changed. Radiotherapy (RT) can modulate a cold microenvironment, rendering it better at tumor killing by priming the quiescent host immune system, with a consequent increase in immunotherapy response. The combination of TME radiomodulation and IT could therefore be a strategy for those patients affected by cold tumors, with limited or no response to IT. Thus, this review aims to provide an easy, rapid, and practical overview of how RT could convert the cold TME and why cold tumor radiomodulation could represent an interesting strategy in combination with IT.