单克隆抗体博来霉素A6偶联物对白血病细胞特异性结合与内化

抗CCT2单克隆抗体博来霉素A6偶联物可吸附胶体金颗粒(McAb-A6-Au)。电镜观察表明,在4℃,1h,表面有McAb-A6-Au颗粒的CEM细胞最高达78%;在37℃,4h,内化McAb-A6-Au颗粒的CEM细胞高达72%。而抗原性无关的U937细胞仅为14%。并且McAb-A6-Au颗粒能直接穿过细胞膜、核膜进入细胞浆和细胞核。37℃,1h已有10～18%的CEM细胞核内有McAb-A 6-Au颗粒。实验结果提示了单抗与博来霉素A6的偶联物与选择性地结合靶细胞,而且进入细胞速度快、穿透力强,有可能成为治疗白血病药物。     

脉络舒通丸对下肢深静脉血栓疗效观察及对炎性反应因子的影响

目的:探讨脉络舒通丸对深静脉血栓的疗效及对炎性反应因子的影响。方法:选取2017年8月至2019年3月解放军联勤保障部队第960医院收治的下肢深静脉血栓患者76例作为研究对象,按照随机数字表法分为对照组和观察组,每组38例。对照组患者采用绝对的卧床休息,患肢抬高于床面约30 cm,与床面呈约30°,嘱托严禁进行按压和热敷,保持绝对制动,仅配合服用肠溶阿司匹林及空白安慰剂等基础治疗措施不采用其他任何消肿、镇痛药物。观察组患者在对照组治疗的基础上,给予口服脉络舒通丸治疗,口服每次1瓶,3次/d,7 d为1个疗程。每个疗程结束测量患者患肢周径、疼痛感、色素沉着评分和血液中C-反应蛋白(CPR)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)和纤维蛋白原(FBI)4个炎性反应因子水平,患者所有指标连续2个疗程稳定后视为稳定疗效。结果:2组患者在疗程结束后总治愈率有明显差别,观察组总治愈率为78.94%,优于对照组的总治愈率52.26%,平均治愈时间分别为(18.6±3.2) d、(30.8±5.4) d差异有统计学意义(P 0.05)。观察组患者的临床指标和C-反应蛋白CPR、白细胞介素IL-1β、IL-6和纤维蛋白原FBI 4种炎性反应因子水平均优于对照组差异有统计学意义(P 0.05)。观察组不良反应发生率与对照组比较,差异无统计学意义(P0.05)。结论:脉络舒通丸治疗深静脉血栓的疗效显著,可明显降低血液中炎性反应因子水平并具有很高的安全性。     

推拿手法结合中药内服治疗老年颈性眩晕55例

颈性眩晕是指颈椎及其有关软组织发生器质性或功能性变化所引起的眩晕,又称Barre-Lieon综合征,是老年眩晕患者最常见的原因。近年来,笔者采用推拿手法结合中药内服治疗该病55例,疗效满意。     

妊娠期糖代谢异常孕妇血脂水平与围产结局的关系

目的 分析妊娠期糖代谢异常孕妇血脂水平与围产结局的关系。方法选 择确诊为妊娠期糖代谢异常的孕妇358例,包括妊娠合并糖尿病（DM）28例（DM组）,妊娠期糖尿病（GDM）178例（GDM组）,妊娠期糖耐量受损（GIGT）152例（GIGT组）,用Beckman—CX9型全自动生化分析仪测定血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL—C）及低密度脂蛋白胆固醇（LDL—C）,详细记录各组孕妇确诊时血脂水平及孕妇年龄、孕周、检测时间、治疗方法、并发症等。结果 （1）GIGT组与GDM组TG分别为（2．7±0．7）mmoL／L和（2．9±0．7）mmoL／L,TC分别为（6．2±1．1）mmol／L和（6．7±1．9）mmol／L,HDL—C分别为（1．78±0．22）mmol／L和（1．64±0．31）mmol／L,LDL-C分别为（3．8±0．9）mmol／L和（3．7±0．8）mmol／L,两两比较,差异均无统计学意义（P〉0．05）;DM组TG和LDL—C分别为（3．6±0．9）mmol／L和（4．8±0．6）mmol／L,均高于GIGT组和GDM组,而HDL-C[（1．24±0．19）mmol／L]低于GIGT组和GDM组,差异均有统计学意义（P〈0．05）。（2）DM组、GDM组、GIGT组,子痫前期发生率分别为35．7％（10／28）、16．8％（30／178）和14．5％（22／152）;早产发生率分别为39．3％（11／28）、16．8％（30／178）和19．7％（30／152）,分别比较,差异均有统计学意义（P均〈0．05）;羊水过多、胎膜早破发生率3组比较,差异无统计学意义（P〉0．05）;胎儿窘迫发生率GDM组低于GIGT和DM组,分别为9．8％（15／152）、20．2％（36／178）和21．4％（6／28）;GDM组和GIGT组巨大儿发生率高于DM组,分别为11．2％（20／178）、14．5％（22／152）和3．5％（1／28）,分别比较,差异均有统计学意义（P〈0．05）。结论 妊娠期糖代谢异常孕妇血脂水平是监测围产结局的有效指标之一,有效降低血脂水平能降低子痫前期和早产的发生率。     

起搏器囊袋破溃12例临床分析

目的探讨起搏器囊袋破溃的常见原因及合理的处理方法。方法通过回顾性分析我院心血管内科2007年1月至2011年3月的12例起搏器囊袋破溃的基本资料,比较不同处理措施的临床疗效。结果①12例患者平均年龄75.3岁,男性7例,女性5例,其中11例合并高血压、心衰及糖尿病。3例为早发型、9例为迟发型囊袋破溃。②随访(31.6±6.8)个月。8例在对侧安置新的起搏系统,2例取出原起搏器,2例原电极与原起搏器被深埋在患侧胸大肌深面。所有患者新的起搏系统工作良好。③所有患者原电极未拔除。6例残余电极前浅埋皮下者,半数残余电极刺破皮肤。4例残余电极和2例原电极深埋者,均达到完全痊愈。结论起搏器囊袋破溃原因复杂,加强局部清创、深埋残余电极等可获得较好的疗效。     

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.     

A stable and reliable animal model for hepatocellular carcinoma with portal vein tumor thrombus

<正>To the Editor:Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide [1,2].Portal vein tumor thrombus (PVTT) has been demonstrated to be a poor prognostic indicator for HCC [3-5].However,effective treatment for the condition is still limited.Understanding the insight into the molecular mechanisms behind PVTT development may help to establish a new therapeutic strategy.Animal models which mimic the development of PVTT in humans are necessary to figure out the molecula...     

活血化瘀法在慢性肝病治疗中的应用体会

慢性肝病顽固难愈,包括慢性乙型肝炎、肝纤维化及肝硬化等疾病,往往出现"久病必瘀"的病理机转,所以治疗慢性肝病常在辨证论治的基础上配合活血化瘀法。活血化瘀同时与清热解毒、疏肝理气、健脾益气、补肾益气、软坚散结等法相配伍应用,在慢性肝病的治疗中取得一定疗效。     

Association of body mass index with risk of prediabetes in Chinese adults: A population‐based cohort study

Aims/IntroductionOverweight and obesity in adults are strongly associated with an increased risk of prediabetes, and this study set out to gain a better understanding of the optimal body mass index (BMI) range for assessing the risk of prediabetes in the Chinese population.Materials and MethodsThe cohort study included 100,309 Chinese adults who underwent health screening. Participants were divided into six groups based on the cut‐off point for BMI recommended by the World Health Organization (underweight: <18.5 kg/m², normal‐weight: 18.5–24.9 kg/m², pre‐obese: 25.0–29.9 kg/m², obese class I: 30.0–34.9 kg/m², obese class II: 35.0–39.9 kg/m², and obese class III ≥40 kg/m²). The association of BMI with prediabetes and the shape of the correlation were modeled using multivariate Cox regression and restricted cubic spline regression, respectively.ResultsIn the multivariate Cox regression model, with normal weight as the control group, underweight people had a lower risk of developing prediabetes, whereas obese and pre‐obese people had a higher risk of prediabetes. Additionally, in the restricted cubic spline model, we found that the association of BMI with prediabetes follows a positive dose–response relationship, but does not conform to the pattern of obesity paradox. Among the general population in China, a BMI of 23.03 kg/m² might be a potential intervention threshold for prediabetes.ConclusionsThe national cohort study found that the association of BMI with prediabetes follows a positive dose–response relationship, rather than a pattern of obesity paradox. For Chinese people with normal weight, more attention should be paid to glucose metabolism when BMI exceeds 23.03 kg/m².