Reliability and validity of the Tibetan medicine constitution scale: a cross-sectional study of the general population in Beijing,China

Background:The constitutional theory is an important aspect of Tibetan medicine,however a quantitative measurement tool for constitution identification still does not exist.The objective of this study is to evaluate the reliability and validity of a Tibetan medicine constitution scale(TMCS)that consists of three sub-scales and 31 items.Methods:From June to July 2019,622 people from the general population in Beijing,China,aged 18 to 60 were investigated.We employed Cronbach’s alpha(α),split-half reliability,and test-retest reliability to determine the reliability of the scale.The content validity and contract validity of the TMCS were evaluated using factor analysis and correlation analysis based on Tibetan medicine theory.The items were screened according to the reliability test results.Results:After the items were screened,22 items remained in the scale.The Cronbach’s alpha value for the internal consistency reliability of the TMCS was 0.754(95%confidence interval(CI):0.700–0.761).The correlation coefficient for the two-week test-retest of the total score was 0.726(95%CI:0.571–0.834).The split-half coefficient was 0.689(95%CI:0.640–0.734).The scale can be explained by eight potential factors,including morphological structure,physiological function,personality,adaptability,etc.The body mass index was negatively correlated with the score of the sub-rlung scale(r=−0.376),slightly positively correlated with the sub-mkhris pa scale(r=0.099),and positively correlated with the sub-bad kan scale(r=0.362).Conclusion:The TMCS is a reliable and valid instrument that can be used to assess the body constitution of the general population in Beijing,China.Future studies are needed to explore the differences in biological characteristics among the constitutional types and the association between constitution and disease.     

Cool Mist Irrigation Improves Heat Dissipation during Surgical Bone Drilling

Objective High-speed drilling generates heat in small cavities and may pose a risk for neurovascular tissues. We hypothesize that a continuous pressurized cold mist could be an alternative approach for better cooling during drilling of bone to access cranial lesions. This study aims to examine this idea experimentally. Design Ex-vivo drilling tests with controlled speed, feed, and depth were performed on cortical bone samples. Thermocouples were embedded underneath the drilling path to compare the temperature rises under mist cooling (at 3°C, < 300 mL/h) and flood irrigation (at 22°C, > 800 mL/h). Results A significant difference exists between these two systems (p value < 0.05). The measured temperature was ∼ 4°C lower for mist cooling than for flood irrigation, even with less than a third of the flow rate. Conclusion Experimental data indicate the capability of mist cooling to reduce heat generation while simultaneously enabling flow reduction and targeted cooling. An improved field of view in an extremely narrow access corridor may be achieved with this technology.     

Comparison of the isomerization mechanisms of human melanopsin and invertebrate and vertebrate rhodopsins

Comparative modeling and ab initio multiconfigurational quantum chemistry are combined to investigate the reactivity of the human nonvisual photoreceptor melanopsin. It is found that both the thermal and photochemical isomerization of the melanopsin 11-cis retinal chromophore occur via a space-saving mechanism involving the unidirectional, counterclockwise twisting of the =C11H-C12H= moiety with respect to its Lys340-linked frame as proposed by Warshel for visual pigments [Warshel A (1976) Nature 260(5553):679–683]. A comparison with the mechanisms documented for vertebrate (bovine) and invertebrate (squid) visual photoreceptors shows that such a mechanism is not affected by the diversity of the three chromophore cavities. Despite such invariance, trajectory computations indicate that although all receptors display less than 100 fs excited state dynamics, human melanopsin decays from the excited state ∼40 fs earlier than bovine rhodopsin. Some diversity is also found in the energy barriers controlling thermal isomerization. Human melanopsin features the highest computed barrier which appears to be ∼2.5 kcal mol⁻¹ higher than that of bovine rhodopsin. When assuming the validity of both the reaction speed/quantum yield correlation discussed by Warshel, Mathies and coworkers [Weiss RM, Warshel A (1979) J Am Chem Soc 101:6131–6133; Schoenlein RW, Peteanu LA, Mathies RA, Shank CV (1991) Science 254(5030):412–415] and of a relationship between thermal isomerization rate and thermal activation of the photocycle, melanopsin turns out to be a highly sensitive pigment consistent with the low number of melanopsin-containing cells found in the retina and with the extraretina location of melanopsin in nonmammalian vertebrates.For a long time it was assumed that the human retina contains only two types of photoreceptor cells: the rods and cones responsible for dim-light and daylight vision, respectively. However, recent studies have revealed the existence of a small number of intrinsically photosensitive retinal ganglion cells (ipRGCs) that regulate nonvisual photoresponses (1). ipRGCs express an atypical opsin-like protein named melanopsin (2, 3) which plays a role in the regulation of unconscious visual reflexes and in the synchronization of endogenous physiological responses to the dawn/dusk cycle (circadian rhythms) (4, 5).Melanopsins are unique among vertebrate photoreceptors because their amino acid sequence shares greater similarity to invertebrate than vertebrate rhodopsin (i.e., the photoreceptor of rods) (6, 7). Like rhodopsins, melanopsins feature an up–down bundle architecture of seven transmembrane α-helices incorporating the 11-cis isomer of retinal as a covalently bound protonated Schiff base (PSB11 in Fig. 1A). Light-induced (i.e., photochemical) isomerization of PSB11 to its all-trans isomer (PSBAT) triggers an opsin conformational change that, ultimately, activates the receptor and signaling cascade (8, 9). However, similar to invertebrate and in contrast to vertebrate rhodopsins, melanopsins are bistable (10). Indeed, although vertebrate rhodopsins need a retinoid cycle (11) to regenerate PSB11, melanopsins have an intrinsic light-driven chromophore regeneration function via PSBAT back-isomerization. Furthermore, past studies have shown that melanopsins use an invertebrate-like signal transduction cascade (12).Open in a separate windowFig. 1.PSB11 chromophore reactivity. (A) Chromophore structure and isomerization to PSBAT. (B) Schematic representation of the photochemical (full arrows) and thermal (dashed arrows) isomerization paths. The CI is located energetically above the TS, features a different geometrical structure, and drives a far-from-equilibrium process. ΔE_S1-S0, τ_cis→trans, and Ea^T (in red) are the fundamental quantities computed in the present work.Melanopsins are held responsible for photoentrainment, using the changes of irradiance and spectral composition to adjust the circadian rhythm (13). The different studies carried out so far on melanopsin light sensitivity do not lead to consistent results. Although Do et al. (14) argue that ipRGCs work at extremely low irradiation intensities showing a single-photon response larger than rods, Ferrer et al. (15) conclude that the melanopsin has a reduced sensitivity relative to visual pigments. On the other hand, these photoreceptors would be expected to display high light sensitivity (14). In the vertebrate retina their density is 10⁴ times lower than that of rhodopsins. Moreover, the receptor is not confined in a dedicated cellular domain such as the outer segment of rods and cones, resulting in a ipRGCs photon capture more than 10⁶-fold lower than that of rods and cones per unit of retina illumination. A high sensitivity of melanopsins would also be consistent with their presence in extraretina locations such as in pineal complex, deep brain, and derma of nonmammalian vertebrates (e.g., amphibian) (16–18). The amount of light that can penetrate into such regions is limited and enriched in the red component due to light scattering by the surrounding tissues (14).The molecular-level understanding of the primary light response of melanopsin is a prerequisite for the comprehension of more complex properties such as its activation and sensitivity. Despite numerous studies carried out since its discovery (16), there is presently little information on the molecular mechanism of melanopsin activation. The common PSB11 chromophore of melanopsins and rhodopsins does not guarantee that the same mechanism operates in both photoreceptors. This not only concerns light-induced activation but also thermal activation: a process whose rate limits the photoreceptor light sensitivity and that is currently associated with thermal, rather than photochemical, PSB11 isomerization (19–24).The mechanism of light-induced PSB11 isomerization in vertebrate rhodopsins has been extensively investigated. Spectroscopic studies have shown that in bovine rhodopsin (Rh) the isomerization occurs on a subpicosecond timescale (25–27). Moreover, the observation of ground state (S₀) vibrational coherence (28) is consistent with a direct transfer of the excited state (S₁) population to the photoproduct (Fig. 1B) passing through a conical intersection (CI). Such a path has been located along the S₁ potential energy surface by constructing a multiconfigurational quantum chemistry (MCQC) based computer model of the photoreceptor (29–31) and spectroscopically supported by probing in the infrared (31). More recently (32), the same computer model has been used to map the Rh thermal isomerization path (Fig. 1B) providing information on the transition states controlling the reaction.Here we present a computational study focusing on the mechanism of photochemical and thermal isomerization of human melanopsin (hMeOp). This would require the construction of a computer model of hMeOp starting from the receptor crystal structure. However, the lack of hMeOp crystallographic data does not allow the use of the protocol previously applied in Rh studies. The significant sequence similarity between squid rhodopsin (sqRh), whose crystal structure is available (PDB code: 2Z73) (33), and hMeOp (40%, SI Appendix, Fig. S1) provides the fundamentals for constructing a structural model of hMeOp at a significant atomic resolution. Building on a study by Batista and coworkers (34) on murine melanopsin, we combine comparative modeling of hMeOp with MCQC to construct a quantum mechanics/molecular mechanics (QM/MM) computer model capable of simulating the photochemical and thermal isomerization reactions of hMeOp. The results are then compared with those found using Rh and sqRh models constructed using the same protocol. Such a comparison is expected to provide information on the differences in spectral and functional properties of these evolutionary distant pigments. As we will show below, the models indicate that hMeOp has a faster photochemical isomerization dynamics and a higher thermal isomerization barrier than both Rh and sqRh.     

Volcano-induced regime shifts in millennial tree-ring chronologies from northeastern North America

Dated records of ice-cap growth from Arctic Canada recently suggested that a succession of strong volcanic eruptions forced an abrupt onset of the Little Ice Age between A.D. 1275 and 1300 [Miller GH, et al. (2012) Geophys Res Lett 39(2):L02708, 10.1029/2011GL050168]. Although this idea is supported by simulation experiments with general circulation models, additional support from field data are limited. In particular, the Northern Hemisphere network of temperature-sensitive millennial tree-ring chronologies, which principally comprises Eurasian sites, suggests that the strongest eruptions only caused cooling episodes lasting less than about 10 y. Here we present a new network of millennial tree-ring chronologies from the taiga of northeastern North America, which fills a wide gap in the network of the Northern Hemisphere''s chronologies suitable for temperature reconstructions and supports the hypothesis that volcanoes triggered both the onset and the coldest episode of the Little Ice Age. Following the well-expressed Medieval Climate Anomaly (approximately A.D. 910–1257), which comprised the warmest decades of the last millennium, our tree-ring-based temperature reconstruction displays an abrupt regime shift toward lower average summer temperatures precisely coinciding with a series of 13th century eruptions centered around the 1257 Samalas event and closely preceding ice-cap expansion in Arctic Canada. Furthermore, the successive 1809 (unknown volcano) and 1815 (Tambora) eruptions triggered a subsequent shift to the coldest 40-y period of the last 1100 y. These results confirm that series of large eruptions may cause region-specific regime shifts in the climate system and that the climate of northeastern North America is especially sensitive to volcanic forcing.Tree-ring chronologies are the type of proxy record most used to develop climate reconstructions covering the last millennium (1). These chronologies have been integrated into large-scale networks, often with additional proxies, to document the amplitude, duration, and forcing mechanisms of the Medieval Climate Anomaly, the Little Ice Age, and the recent warming trend. However, the spatial coverage of long tree-ring records must be improved to allow a better understanding of regional variations in past climate (1, 2). For example, in eastern North America, millennial climate reconstructions have been constructed from tree species and sites sensitive to drought and precipitation (3), whereas temperatures were inferred solely from low-resolution proxies, such as pollen data (4, 5). Furthermore, only tree-ring-based climate reconstructions shorter than a millennium or using chronologies poorly replicated before A.D. 1500 have been published for the entire North American boreal forest (6, 7), whereas several millennial, highly replicated, temperature-sensitive tree-ring records have been developed across the Eurasian boreal zone. This lack of data is an important issue that causes the poor representation of North America in long-term, large-scale temperature reconstructions (1, 4).The feasibility of reconstructing volcanic forcing from tree-ring data has been debated, especially in regards to large and successive eruptions. Two of the largest eruptions of the last millennium, the A.D. 1257 Samalas and A.D. 1815 Tambora events, were both closely followed and preceded by additional large eruptions in 1227, 1275, 1284, 1809, and 1835 (8−11). Whereas general circulation model experiments suggest that the impacts of large and successive eruptions might have influenced climate systems for periods ranging from 20 y to several decades, or even centuries (12–16), Northern Hemisphere tree-ring-based temperature reconstructions only display negative temperature anomalies lasting between 2 and 10 y (17–20). Region-specific responses of the climate system to volcanic forcing may in part explain this discrepancy (17). For example, large and successive eruptions may have had stronger impacts on summer temperatures in northeastern North America (hereafter NENA) than elsewhere. An extensive Northern Hemisphere network of tree-ring density chronologies supports this idea, showing that the coldest 1816 temperature anomalies occurred over the Quebec-Labrador Peninsula (21), where they may have persisted for several decades (7). The idea is also supported by the abrupt acceleration of ice-cap growth in the Eastern Canadian Arctic during A.D. 1275–1300, at the onset of the Little Ice Age, as a consequence of a series of eruptions (22). However, the lack of millennial, well-replicated, and temperature-sensitive tree-ring chronologies in the NENA sector precludes the examination of the volcano−temperature relationship in a long-term context with an annual resolution.In this study, we have built a network of six highly replicated millennial tree-ring chronologies from large stocks of black spruce [Picea mariana (Mill.) B.S.P.] subfossil trees preserved in lakes of the NENA taiga from which we developed a millennial reconstruction (A.D. 910–2011) of regional July−August temperatures. For this purpose, we selected homogeneous sites with infrequent and well-documented ecological disturbances (23), and sampled homogeneous subfossil and living samples to maximize the robustness of our reconstruction. We then used a Bayesian mixture of probability distributions with dependence (also referred to as hidden Markov models or Markov switching models; see refs. 24 and 25) to detect possible regime shifts in summer temperatures triggered by series of large eruptions and to provide new insights concerning the climate history of NENA during the last 1,100 y.     

内外兼治法对血瘀气滞型腰痛病腰腿痛症状改善的影响

目的:观察外治法、外治法+口服药物治疗气滞血瘀型腰腿痛的远期疗效。方法:选取北京中医医院顺义医院2015年1月至2016年4月共74例符合:血瘀气滞证型的腰痛病且诊断腰椎间盘突出症住院的患者,随机分成治疗、对照组各自37例。对照组外治(磁振热理疗仪)、观察组内外兼治(身痛逐瘀汤口服、磁振热理疗仪外用)。分别计算治疗前及治疗后3个月患者的腰腿VAS评分。结果:3个月后腰腿痛VAS评分观察组治疗后VAS评分(3.17±1.02)分、对照组治疗后为(4.28±1.21)分,优良率及总有效率,观察组优于对照组(P0.05)。结论:应用内外兼治法治疗血瘀气滞型腰痛病具有较好的远期临床疗效。     

基于数据挖掘技术的含诃子藏药组方规律分析

该研究基于中医传承辅助平台(TCMISS),分析《中国医学百科全书——藏医学》、《藏医成方制剂现代研究与临床应用》、《常用藏成药诠释》等中含诃子藏药组方规律。应用该平台V2.5软件,将含诃子的方剂构建数据库,利用软件关联规则apriori算法、改进的互信息法等数据挖掘方法,分析含诃子藏药中的常用药物、药物组合频次、关联规则与核心药物组合等。对502首含诃子藏药分析后,总结出诃子常用药物组合14个,其所用药物多具有清热解毒、活血止痛、温中理气之功;主治疾病640种,其中使用频率较高(频率≥12)的有22种疾病。选择高频疾病"赤巴病"、"陈旧热症"、"食物中毒"对比分析得出诃子治疗不同疾病的核心药物组合。通过TCMISS对含诃子藏药进行统计分析,总结了诃子的临床组方规律和常用药物组合特点,为其临床应用和新药研发提供参考与新思路。     

基于藏医白脉理论的中风病诊疗规律探析

藏医将人体的经脉分为黑脉和白脉。藏医认为因季节环境、饮食不当、瘟毒热邪侵入脉道,或外伤等损害白脉,导致三因素中的隆和血液紊乱而诱发白脉病。白脉病是藏医白脉系统遭受致病因素的影响后所致的一系列疾病的总称,临床上很多疾病归属于“白脉病”。中风病是藏医白脉病的一种,临症时需根据疾病的寒热属性、发病时间、病位及其三因素（赤巴、隆、培根）归属情况,据理选药、对治疾病,是藏医辨治白脉病的基本规律,临床时应按照藏医的诊疗规律、综合诊查病因、把握疾病证候变化规律来施治用药。     

Manipulating the Properties of Poly(1,4‐Cyclohexylenedimethylene Terephthalate) (PCT) Just by Tuning Steric Configuration of 1.4‐Cyclohexanedimethanol (CHDM)

The properties of poly(1,4‐cyclohexylenedimethylene terephthalate) (PCT) are manipulated only by tuning the steric configuration of 1,4‐cyclohexanedimethanol (CHDM). The chemical structures and compositions of PCTs are confirmed by nuclear magnetic resonance (¹H NMR and ¹³C NMR) before their thermal and mechanical properties are investigated by differential scanning calorimeter, thermogravimetric analyzer, and dynamic mechanical analysis. Results show that the ratio of cis‐ to trans‐CHDM in PCTs has significant influences on their properties. The melting temperature of PCTs is varied from 251 to 313 °C, and the glass transition temperature is increased from 73 to 92 °C when the content of trans‐CHDM in PCTs is increased from 10% to 96%. In addition, the crystallizability of PCT is also increased with the content of trans‐CHDM. However, its thermal stability is decreased seriously when the melting temperature of PCT is higher than 280 °C. It is concluded that when the content of trans‐CHDM is lower than 50% (PCT‐10, PCT‐28, and PCT‐46), the balance of melting temperature, glass transition temperature, and thermal stability for PCT can be achieved. Just by varying the cis/trans ratio of CHDM, rather than the addition of other components, the properties of PCT can be manipulated.