High affinity binding of an enkephalin analog in the cerebral ganglion of the insectLeucophaea maderae (Blattaria)

Specific high affinity binding sites for a synthetic enkephalin analog, DALA (D-Ala2-Met-enkephalinamide) were demonstrated in the cerebral ganglia of adults and nymphs of the insect Leucophaea. In both sexes binding was monophasic and saturable with respect to the concentration of the radioligand used. The same amount of brain tissue from adult females had 30% more binding sites for DALA than that from adult males. By contrast, no sex-related difference in binding-site density per mg protein was observed in the brains from immature (nymphal) specimens. The results strongly suggest the presence, in this invertebrate, of opiate receptors that appear to be confined to certain areas of the nervous tissue.     

Reproductive and hormonal factors and risk of lung cancer in women: a prospective cohort study

Several lines of evidence suggest that endocrine factors may play a role in the development of lung cancer, but the evidence is limited and inconsistent. We investigated the association of reproductive and hormonal factors with risk of lung cancer in the National Breast Screening Study, which included 89,835 Canadian women aged 40-59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases provided data on cancer incidence and deaths from all causes, respectively, with follow-up ending between 1998 and 2000. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between hormonal factors and lung cancer. During a mean of 16.4 years of follow-up, we observed 750 incident lung cancer cases. After adjustment for covariates, parous women were not at increased risk of lung cancer (HR = 1.18, 95% CI 0.94-1.47) relative to nulliparous women; however, there was a modest increase in risk with increasing parity, reaching a HR of 1.42, 95% CI 1.06-1.88 in women who had 5 or more live births (p for trend 0.02). Among parous women, age at first live birth was inversely associated with risk. Women who had their first live birth at age 30 or older were at reduced risk relative to women who had their first live birth below age 23 (HR 0.68, 95% CI 0.50-0.93, p for trend 0.004). These associations did not differ by age at enrollment (40-49 vs. 50-59 years old), but were somewhat strengthened when attention was restricted to never smokers. Ever use of exogenous hormones showed little association with lung cancer risk; however, long-term users of hormone replacement therapy were at slightly increased risk. Our results add to the limited existing evidence that certain reproductive and hormonal factors may be associated with lung cancer risk in women.     

Instrumental variables estimation and inference in the presence of many exogenous regressors

Summary We consider a standard instrumental variables model contaminated by the presence of a large number of exogenous regressors. In an asymptotic framework where this number is proportional to the sample size, we study the impact of their ratio on the validity of existing estimators and tests. When the instruments are few, the inference using the conventional 2SLS estimator and associated t and J statistics, as well as the Anderson–Rubin and Kleibergen tests, is still valid. When the instruments are many, the LIML estimator remains consistent, but the presence of many exogenous regressors changes its asymptotic variance. Moreover, the conventional bias correction of the 2SLS estimator is no longer appropriate. We provide asymptotically correct versions of bias correction for the 2SLS estimator, derive its asymptotically correct variance estimator, extend the Hansen–Hausman–Newey LIML variance estimator to the case of many exogenous regressors, and propose asymptotically valid modifications of the J overidentification tests based on the LIML and bias‐corrected 2SLS estimators.     

Tolerability and Safety of a Novel Ketogenic Ester,Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults

Nutritional ketosis is a state of mildly elevated blood ketone concentrations resulting from dietary changes (e.g., fasting or reduced carbohydrate intake) or exogenous ketone consumption. In this study, we determined the tolerability and safety of a novel exogenous ketone diester, bis-hexanoyl-(R)-1,3-butanediol (BH-BD), in a 28-day, randomized, double-blind, placebo-controlled, parallel trial ({"type":"clinical-trial","attrs":{"text":"NCT04707989","term_id":"NCT04707989"}}NCT04707989). Healthy adults (n = 59, mean (SD), age: 42.8 (13.4) y, body mass index: 27.8 (3.9) kg/m²) were randomized to consume a beverage containing 12.5 g (Days 0–7) and 25 g (Days 7–28) of BH-BD or a taste-matched placebo daily with breakfast. Tolerability, stimulation, and sedation were assessed daily by standardized questionnaires, and blood and urine samples were collected at Days 0, 7, 14, and 28 for safety assessment. There were no differences in at-home composite systemic and gastrointestinal tolerability scores between BH-BD and placebo at any time in the study, or in acute tolerability measured 1-h post-consumption in-clinic. Weekly at-home composite tolerability scores did not change when BH-BD servings were doubled. At-home scores for stimulation and sedation did not differ between groups. BH-BD significantly increased blood ketone concentrations 1-h post-consumption. No clinically meaningful changes in safety measures including vital signs and clinical laboratory measurements were detected within or between groups. These results support the overall tolerability and safety of consumption of up to 25 g/day BH-BD.     

Paradoxical Roles of IL-4 in Tumor Immunity

Interleukin (IL)-4 is a crucial cytokine in tumor immunology. In the initial murine experiments, IL-4 exhibited potent anti-tumor ability. Tumors genetically modified to produce IL-4 were rejected, while parental tumors grew progressively. Mice rejected IL-4-producing tumors got long-lasting anti-tumor immunity. The comparative study showed that IL-4 induced the most effective immune response among several cytokines in both prophylactic and therapeutic models. All of these indicate IL-4 has strong potential as a tumor therapy agent. However, contrary evidence indeed exists, and is becoming more and more abundant which shows IL-4 is a tumor-promoting molecule. IL-4 amounts are usually elevated in human cancer patients. IL-4 knockout mice are more resistant to tumor challenge than IL-4 competent mice. Furthermore, tumor cells of various histological origins often express increased levels of IL-4 receptor in comparison to their normal counterparts. By carefully examining presently available data, we found the effects of IL-4 in tumor immunity are closely related to its sources, expressing time and dose, as well as the molecular and cellular environments. In this mini-review, we concentrate on illustrating the paradoxical roles and underlying mechanisms of IL-4 in tumor immunity and try to understand how one molecule has opposite effects.     

Kinetics of repair of sublethal radiation injuries in early hematopoietic precursors

All-Union Hematologic Scientific Center, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. I. Vorob'ev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 1, pp. 74–76, January, 1991.     

从《伤寒论》发病观看六经辨证的特色

内外结合、整体联系是《伤寒论》发病观的主要特点,六经辨证本源于阴阳辨证,最接近于中医的“本”。     

试论《伤寒论》方证权变

运用"权不离经"、"行经必假之以权"的权变哲学观念解析《伤寒论》方证辨证体系。以实际事例与后世《方剂学》、《内科学》相关内容相比较,阐述《伤寒论》方证变法,认为这是《伤寒论》历经千余年仍具有学习和研究价值的重要原因。     

腺相关病毒载体对心肌细胞感染和外源基因表达的作用

目的:为进一步研究肌质网钙ATP酶转基因在心力衰竭中的质粒价值,并观察腺相关病毒对心肌细胞感染的动态过程和对外源基因的表达能力。方法:构建含肌质网钙ATP酶的腺相关病毒载体(recombinantade-no-associatedvirus-sarcoplasmicreticulumcalciumATPase2a,rAAV-SERCA2a),利用激光共聚焦显微镜观察了活体异硫氰酸荧光素标记的腺相关病毒(fluoresceinisothiocyanate-rAAV,FITC-rAAV)进入心肌细胞的过程,利用流式细胞仪检测含绿色荧光蛋白的腺相关病毒rAAV-GFP感染心肌细胞后绿色荧光蛋白表达细胞的百分率。结果:构建、生产的重组病毒rAAV-SERCA2a的滴度为7×1014v·g/L,并可以有效介导肌质网钙ATP酶基因转录;FITC-rAAV感染心肌细胞后,大约15min可见病毒吸附在细胞膜上,30min时可大部分进入细胞内;未加丁酸钠组腺相关病毒介导的绿色荧光蛋白表达效率最高达33.3%,加用丁酸钠组该数据为48.7%。结论:成功构建了含肌质网钙ATP酶的腺相关病毒载体,该病毒可有效介导目的基因的表达。在体外腺相关病毒能有效感染心肌细胞,感染后的心肌细胞能有效表达外源基因。     

外源性因素影响髁突生长改建的研究进展

髁突是下颌骨的一个重要生长区,以软骨内成骨的方式参与下颌骨的生长。髁突软骨属于继发性软骨,既受遗传因素的影响,又受应力、药物等局部因素的影响。为了促进下颌骨的生长,各种外源性局部因素被用于改变髁突软骨的生物学环境,以刺激髁突的软骨内成骨过程。本文就外源性因素影响髁突生长改建的研究作一综述,以期为下颌骨发育不足患者的治疗提供一定的参考。