藏药独一味药理作用及临床应用新进展

简要综述了独一味及其制剂的药理作用和临床应用研究的最新进展,并对其今后的研究方向提出了建议。认为独一味有良好地利用价值和开发潜力,对其研究开发的前景广阔;对其药效的物质基础及作用机理的研究有待深入,尤其应重点关注其疗效确切的镇痛活性。     

Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure

Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neu^hi), but low levels of CD8⁺ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neu^hi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.     

Comparison of six anthropometric measures in discriminating diabetes: A cross‐sectional study from the National Health and Nutrition Examination Survey

BackgroundTraditional anthropometric measures, including body mass index (BMI), are insufficient for evaluating the risk of diabetes. This study aimed to evaluate the performance of new anthropometric measures and a combination of anthropometric measures for identifying diabetes.MethodsA total of 46 979 participants in the National Health and Nutrition Examination Survey program were included in this study. Anthropometric measures, including weight, BMI, waist circumference (WC), waist‐to‐height ratio (WtHR), conicity index (CI), and A Body Shape Index (ABSI), were calculated. Logistic regression analysis and restricted cubic splines were used to evaluate the association between the anthropometric indices and diabetes. The receiver operating characteristic (ROC) curve analysis was performed to compare the discrimination of different anthropometric measures.ResultsAll anthropometric measures were positively and independently associated with the risk of diabetes. After adjusting for covariates, the per SD increment in WC, WtHR, and CI increased the risk of diabetes by 81%, 83%, and 81%, respectively. In the ROC analysis, CI showed superior discriminative ability for diabetes (area under the curve 0.714), and its optimum cutoff value was 1.31. Results of the combined use of BMI and other anthropometric measures showed that among participants with BMI <30 kg/m², an elevated level of another metric increased the risk of having diabetes (P < .001). Similarly, at low levels of weight, CI, and ABSI, an elevated BMI increased diabetes risk (P < .001).ConclusionsWtHR and CI had the best ability to identify diabetes when applied to the US noninstitutionalized population. Anthropometric measures containing WC information could improve the discrimination ability.     

低辐射剂量CT扫描技术在脑动脉3D打印中的应用研究

目的：探讨低辐射剂量CT扫描数据在脑动脉3D打印的可行性研究。方法：将临床拟行脑动脉3D打印的40例患者随机分为2组,每组20例。A组（常规剂量CT扫描方案）：120 kVp,350 mA和滤波反投影（FBP）算法;B组（低剂量CT扫描方案）：80 kVp,自动管电流调制技术（ATCM）和自适应统计迭代重建（ASiR）算法;2组对比剂浓度均为350 mgI/mL。采用两独立样本t检验（非正态分布采用Mann-Whitney U检验）来比较2组的临床资料、辐射剂量、CT DICOM数据客观评价指标及2组方案完成3D打印产物质量的主观评分。结果：A、B 2组患者的临床资料差异均无统计学意义（P＞0.05）。2组的CT辐射剂量差异具有显著统计学意义（P＜0.05）,B组辐射剂量[（1.30 ± 0.47） mSv]较A组[（4.15 ± 0.62） mSv]减少约68.7%。2组脑动脉3D打印结果主观评分差异无统计学意义（P＞0.05）。2组CT DICOM数据客观评价指标：A组的背景噪声（BN）明显高于B组（P=0.000）,而A组的信噪比（SNR）及对比噪声比（CNR）均低于B组（P=0.000）。结论：采用80 kVp、ATCM技术及ASIR算法的数据行脑动脉3D打印,在保证3D打印质量的同时,可以有效减低辐射剂量。     

角膜曲率计与角膜地形图仪测量角膜屈光度的对比研究

目的：对使用角膜曲率计与角膜地形图仪测量角膜屈光度的结果进行对比研究,提出两种仪器各自在白内障术前测算人工晶状体度数中提供K值的精确性。方法;在无眼表疾病的38例（76只眼）分别使用美国生产的角膜地形图仪和日本生产的角膜曲率计测量角膜屈光度,然后进行统计学处理。结果：角膜曲率计和角膜地形图仪检查结果略有差异,但经统计学处理无显著意义（P＞0．05）。结论：角膜地形图仪系统测量角膜屈光度更为准确、全面,尤其对角膜过陡、过平、有斑翳、云翳者的检测结果更有参考价值。     

Association of Gut Microbiota Enterotypes with Blood Trace Elements in Women with Infertility

Infertility is defined as failure to achieve pregnancy within 12 months of unprotected intercourse in women. Trace elements, a kind of micronutrient that is very important to female reproductive function, are affected by intestinal absorption, which is regulated by gut microbiota. Enterotype is the classification of an intestinal microbiome based on its characteristics. Whether or not Prevotella-enterotype and Bacteroides-enterotype are associated with blood trace elements among infertile women remains unclear. The study aimed to explore the relationship between five main whole blood trace elements and these two enterotypes in women with infertility. This retrospective cross-sectional study recruited 651 Chinese women. Whole blood copper, zinc, calcium, magnesium, and iron levels were measured. Quantitative real-time PCR was performed on all fecal samples. Patients were categorized according to whole blood trace elements (low levels group, <5th percentile; normal levels group, 5th‒95th percentile; high levels group, >95th percentile). There were no significant differences in trace elements between the two enterotypes within the control population, while in infertile participants, copper (P = 0.033), zinc (P < 0.001), magnesium (P < 0.001), and iron (P < 0.001) in Prevotella-enterotype was significantly lower than in Bacteroides-enterotype. The Chi-square test showed that only the iron group had a significant difference in the two enterotypes (P = 0.001). Among infertile patients, Prevotella-enterotype (Log(P/B) > −0.27) predicted the low levels of whole blood iron in the obesity population (AUC = 0.894; P = 0.042). For the high levels of iron, Bacteroides-enterotype (Log(P/B) <−2.76) had a predictive power in the lean/normal group (AUC = 0.648; P = 0.041) and Log(P/B) <−3.99 in the overweight group (AUC = 0.863; P = 0.013). We can infer that these two enterotypes may have an effect on the iron metabolism in patients with infertility, highlighting the importance of further research into the interaction between enterotypes and trace elements in reproductive function.     

高分子聚合物微流控细胞芯片的改性研究

目的 探讨2种不同硅烷化试剂对高分子聚合物材料PDMS芯片的改性效果和改性后芯片在细胞捕获/筛选的初步应用.方法 接触角实验考察不同硅烷化试剂处理的PDMS样本亲水性,筛选硅烷化试剂及其浓度,以芯片上的非特异性细胞捕获实验验证筛选结果,并连接抗体构建功能化芯片,进行细胞捕获实验的初步研究.结果 2种硅烷化试剂均对...     

Cryo-EM structure of DNA-bound Smc5/6 reveals DNA clamping enabled by multi-subunit conformational changes

Structural maintenance of chromosomes (SMC) complexes are essential for chromatin organization and functions throughout the cell cycle. The cohesin and condensin SMCs fold and tether DNA, while Smc5/6 directly promotes DNA replication and repair. The functions of SMCs rely on their abilities to engage DNA, but how Smc5/6 binds and translocates on DNA remains largely unknown. Here, we present a 3.8 Å cryogenic electron microscopy (cryo-EM) structure of DNA-bound Saccharomyces cerevisiae Smc5/6 complex containing five of its core subunits, including Smc5, Smc6, and the Nse1-3-4 subcomplex. Intricate interactions among these subunits support the formation of a clamp that encircles the DNA double helix. The positively charged inner surface of the clamp contacts DNA in a nonsequence-specific manner involving numerous DNA binding residues from four subunits. The DNA duplex is held up by Smc5 and 6 head regions and positioned between their coiled-coil arm regions, reflecting an engaged-head and open-arm configuration. The Nse3 subunit secures the DNA from above, while the hook-shaped Nse4 kleisin forms a scaffold connecting DNA and all other subunits. The Smc5/6 DNA clamp shares similarities with DNA-clamps formed by other SMCs but also exhibits differences that reflect its unique functions. Mapping cross-linking mass spectrometry data derived from DNA-free Smc5/6 to the DNA-bound Smc5/6 structure identifies multi-subunit conformational changes that enable DNA capture. Finally, mutational data from cells reveal distinct DNA binding contributions from each subunit to Smc5/6 chromatin association and cell fitness. In summary, our integrative study illuminates how a unique SMC complex engages DNA in supporting genome regulation.

Structural maintenance of chromosomes (SMC) complexes are essential genome regulators in both prokaryotes and eukaryotes. In eukaryotes, the cohesin and condensin SMC complexes organize DNA, while the Smc5/6 complex (referred to as Smc5/6) directly regulates DNA replication and repair (1). At the structural level, SMC complexes share similarities while possessing unique attributes (1). Each complex contains a pair of SMC subunits and a set of non-SMC subunits. The SMC subunits define the tripartite filamentous architecture of the complex: their approximal 50-nm long coiled coil arm region connects their dimerized hinge and adenosine triphosphatase (ATPase) head regions (1). A non-SMC kleisin subunit uses its N- and C-terminal domains to link the head of one SMC to the head-proximal arm region (neck) of another SMC, forming a trimeric SMC-kleisin structure. In cohesin and condensin, two large U-shaped HEAT (Huntington, elongation factor 3, PR65/A, TOR) repeat HAWK (HEAT proteins associated with kleisins) subunits attach to the middle region of the kleisin. By contrast, the Smc5/6 kleisin (Nse4) binds to smaller WH (winged helix)-containing KITE (kleisin interacting tandem WH elements) subunits (Nse1 and Nse3) (2).SMC-mediated functions depend on interactions with DNA. Recent cryogenic electron microscopy (cryo-EM) structures of DNA-bound cohesin and condensin revealed that their HAWK subunits and the SMC head-neck regions form a clamp to enclose a single DNA double helix (3–7). DNA clamping can be critical for cohesin and condensin to extrude DNA loops for chromatin folding (5, 7–9). DNA loop extrusion additionally requires arm bending at a region called the elbow, which is found in both cohesin and condensin (5, 7–9). By contrast, a lack of arm bending in Smc5/6 was suggested by negative stain EM and cross-linking mass spectrometry (CLMS) data (10–14). Since Smc5/6 does not contain HAWK proteins nor shows arm-bending, it has remained unclear how Smc5/6 engages DNA to accomplish its multiple functions.Here we address the molecular mechanisms by which this unique SMC complex binds DNA using an integrative approach, coupling a cryo-EM-based structural characterization with CLMS analyses and functional investigation. Our atomic structure of a DNA-bound Saccharomyces cerevisiae Smc5/6 complex reveals that the head-neck Smc5-6 regions and the Nse1-3-4 subcomplex together form a clamp entrapping the DNA helix. The structure further reveals protein subunit folds and association, as well as how the subunits collaborate to entrap DNA. Comparison of CLMS analyses of DNA-free Smc5/6 with the structure of the DNA-bound Smc5/6 unveils large scale, multi-subunit conformational changes that enable Smc5/6 to encircle DNA. Finally, our mutational data suggest distinct contributions from each of the DNA binding regions to Smc5/6 chromatin association and cellular fitness. Comparison of our findings with those of other SMCs reveals that diverse SMC complexes use a similar DNA clamping strategy despite structural differences, and that Smc5/6 possesses unique features distinct from cohesin, condensin, and prokaryotic SMCs. Our work lays the foundation for an in-depth understanding of how Smc5/6 fulfills unique roles in genome protection.     

新型冠状病毒肺炎后潜水员适潜性评估

新型冠状病毒肺炎（COVID?19）自2019年底爆发以来,对人类生命健康造成了极其严重的危害。作为一种呼吸系统疾病,COVID?19对全身几乎所有器官都会产生影响,其中最主要的受累器官为肺和心脏。随着COVID?19 “康复”患者数量不断增加,越来越多的证据表明,因COVID?19而住院治疗得到“康复”的患者中有相当大比例的人群存在着后遗症,主要表现为呼吸系统和心血管系统的症状。对于潜水员,COVID-19后运动耐受、心肺功能的恢复对于其适潜性具有重要的影响。一些组织和机构对于潜水员COVID-19后的适潜性评估,发布了指南。本文对COVID-19后呼吸和心血管后遗症以及相关的适潜性评估方案进行简要介绍,并基于已有的相关要求和我国实际,初步提出我国潜水员COVID-19后的适潜性评估要求。