The epigenetically active small chemical N-methyl pyrrolidone (NMP) prevents estrogen depletion induced osteoporosis

Currently, there are several treatments for osteoporosis however; they all display some sort of limitation and/or side effects making the need for new treatments imperative. We have previously demonstrated that NMP is a bioactive drug which enhances bone regeneration in vivo and acts as an enhancer of bone morphogenetic protein (BMP) in vitro. NMP also inhibits osteoclast differentiation and attenuates bone resorption.In the present study, we tested NMP as a bromodomain inhibitor and for osteoporosis prevention on ovariectomized (OVX) induced rats while treated systemically with NMP. Female Sprague–Dawley rats were ovariectomized and weekly NMP treatment was administrated 1 week after surgery for 15 weeks. Bone parameters and related serum biomarkers were analyzed. 15 weeks of NMP treatment decreased ovariectomy-induced gained weight in average by 43% and improved bone mineral density (BMD) and bone volume over total volume (BV/TV) in rat femur on average by 25% and 41% respectively. Moreover, mineral apposition rate and bone biomarkers of bone turnover in the treatment group were at similar levels with those of the Sham group.Due to the function of NMP as a low affinity bromodomain inhibitor and its mechanism of action involving osteoblasts/osteoclasts balance and inhibitory effect on inflammatory cytokines, NMP is a promising therapeutic compound for the prevention of osteoporosis.     

Air Pollution modifies the association between successful and pathological aging throughout the frailty condition

The rapid growth in the number of older adults has many implications for public health, including the need to better understand the risks posed by environmental exposures. Aging leads to a decline and deterioration of functional properties at the cellular, tissue and organ level. This loss of functional properties yields to a loss of homeostasis and decreased adaptability to internal and external stress. Frailty is a geriatric syndrome characterized by weakness, weight loss, and low activity that is associated with adverse health outcomes. Frailty manifests as an age-related, biological vulnerability to stressors and decreased physiological reserves. Ambient air pollution exposure affects human health, and elderly people appear to be particularly susceptible to its adverse effects.The aim of this paper is to discuss the role of air pollution in the modulation of several biological mechanisms involved in aging. Evidence is presented on how air pollution can modify the bidirectional association between successful and pathological aging throughout the frailty conditions.     

氨甲喋呤诱导的大鼠持续性肠黏膜损伤模型的建立与评价

摘要: 目的：建立一种大鼠肠黏膜持续损伤模型。方法：SD大鼠腹腔注射氨甲喋呤（MTX）建立肠黏膜炎模型。100只大鼠随机分为空白组(Control Group)、模型组Ⅰ（MTX Group Ⅰ）、模型组Ⅱ (MTX Group Ⅱ)和模型组Ⅲ (MTX Group Ⅲ),其中MTX Group Ⅰ10只大鼠,其余每组各30只。第0天,MTX Group Ⅰ大鼠注射MTX （20 mg/kg）,MTX Group Ⅱ和 MTX Group Ⅲ大鼠注射MTX（10 mg/kg）。第6天,MTX Group Ⅱ大鼠再次注射MTX 10 mg/kg,MTX Group Ⅲ大鼠注射MTX 5 mg/kg。Control Group在第0天和第6天均注射生理盐水。实验期间观察大鼠活动状态,并记录进食量和体重变化。MTX Group Ⅰ在第4天全部处死,其余每组于造模后第4、5、6、10、11、12天各处死5只大鼠,HE染色进行病理学分析,并检测血浆中的D-乳酸、二胺氧化酶(DAO)及小肠组织中的髓过氧化物酶(MPO)、丙二醛(MDA)水平。结果：在第4天时,三个模型组大鼠小肠组织损伤评分(Chiu评分)均明显高于Control Group (p<0.05),血浆中D-乳酸含量、DAO活力及小肠组织中MPO活力、MDA含量也均显著高于Control Group (p<0.05)。在第5天时MTX Group Ⅱ和 MTX Group Ⅲ大鼠小肠黏膜损伤程度开始恢复,Chiu评分、D-乳酸含量、DAO活力、MPO活力和MDA含量逐渐降低,在第6天时与Control Group基本无差异。二次注射后,在第10天,MTX Group Ⅱ和 MTX Group Ⅲ大鼠Chiu评分再次升高,血浆中D-乳酸含量、DAO活力及小肠组织中MPO活力、MDA含量也显著高于Control Group (p<0.05),之后逐渐降低,损伤再次恢复。与MTX Group Ⅱ相比,二次注射后MTX Group Ⅲ损伤程度较轻（p<0.05）。结论：20 mg/kg MTX诱发大鼠肠黏膜炎是一个急性损伤过程,整个病程大约为4至5天,适用于药物治疗评价;两次间歇式10 mg/kg注射MTX可以造成大鼠肠黏膜的持续损伤,该模型更加适合中长期的营养治疗评价。     

Association between the Root Canal Configuration,Endodontic Treatment Technical Errors,and Periapical Hypodensities in Molar Teeth: A Cone-beam Computed Tomographic Study

IntroductionThis study aimed to evaluate the association between the root canal configuration (RCC), endodontic technical errors, and periapical hypodensities in molars using cone-beam computed tomographic (CBCT) images.MethodsTwo hundred twenty-one roots were assessed from 79 patients referred for CBCT examination because of symptomatology in endodontically treated molars. Two oral and maxillofacial radiologists classified the RCC of each dental root according to Vertucci's classification. Root canals were assessed for the presence of technical errors from endodontic treatment. The presence of periapical hypodensity for each dental root and the coronal sealing condition of each tooth were also recorded.ResultsFor RCC type I, the most prevalent technical error was underfilling (17.4%). For types II and VIII, nonfilled canals were found in 54% and 100% of the cases, respectively. For type III, underfilling, nonhomogeneous filling, and nonfilled canals were equally frequent (33.3%), whereas for type IV underfilling and nonfilled canals had a prevalence of 42%. In general, there was a higher prevalence of apical hypodensities among roots with technical errors. It was also observed for type I, with an increase from 41.2%–62.9% when a technical error was present.ConclusionsThe prevalence of different endodontic technical errors varies depending on the RCC for molars. A greater complexity of RCC is related to a higher occurrence of errors and a higher prevalence of periapical hypodensity.     

粤港澳大湾区公共卫生体系建设的现状及思考

粤港澳大湾区（大湾区）同时具有三种不同体制下的公共卫生体系,在我国公共卫生体系建设中具有重要地位。进一步加强大湾区公共卫生体系建设对我国未来公共卫生体系优化和升级具有重要借鉴作用。本文基于中国工程院重大战略研究与咨询项目“我国现代公共卫生体系及能力建设战略研究”,深入分析大湾区公共卫生体系建设的现状和存在的问题,提出要健全和创新大湾区公共卫生风险协同防控、资源协同和共研共享、信息共享和交流、人才培养和队伍建设等机制,全面提升大湾区公共卫生体系的能力,助推健康中国建设。     

Impact of including boys in the national school-based human papillomavirus vaccination programme in Singapore: A modelling-based cost-effectiveness analysis

Globally, gender-neutral Human Papillomavirus (HPV) vaccination programmes are gaining traction. Although cervical cancer remains the most prevalent, other HPV-related cancers are increasingly recognised as important, especially among men who have sex with men. We assessed if including adolescent boys in Singapore’s school-based HPV vaccination programme is cost-effective from the healthcare perspective.We adapted a World Health Organization-supported model, Papillomavirus Rapid Interface for Modelling and Economics, and modelled the cost and quality-adjusted life years (QALY) associated with vaccinating 13-year-olds with the HPV vaccine. Cancer incidence and mortality rates were obtained from local sources and adjusted based on the expected direct and indirect vaccine protection for various population subgroups at an 80 % vaccine coverage.Moving to a gender-neutral vaccination programme with a bivalent or nonavalent vaccine could avert 30 (95 % uncertainty interval [UI]: 20–44) and 34 (95 % UI: 24–49) HPV-related cancers per birth cohort, respectively. At a 3 % discount rate, a gender-neutral vaccination programme is not cost-effective. However, with a 1.5 % discount rate, which puts more value on long-term health gains from vaccination, moving to a gender-neutral vaccination programme with the bivalent vaccine is likely cost-effective, with an incremental cost-effectiveness ratio of SGD$19 007 (95 % UI: 10 164–30 633) per QALY gained.The findings suggest the need to engage experts to examine, in detail, the cost-effectiveness of gender-neutral vaccination programmes in Singapore. Issues of drug licensing, feasibility, gender equity, global vaccine supplies, and the global trend towards disease elimination/eradication should also be considered. This model provides a simplified method for resource-strapped countries to gain a preliminary estimate of the cost-effectiveness of a gender-neutral HPV vaccination programme before investing resources for further research.