Association of age at menarche with valvular heart disease: An analysis based on electronic health record (CREAT2109)

BackgroundThe association between age at menarche and coronary heart disease has been reported, but the association between age at menarche and valvular heart disease (VHD) has not been described. We aimed to examine the association between age at menarche and VHD.MethodsBy collecting data from four medical centers of the Affiliated Hospital of Qingdao University (QUAH) from January 1, 2016, to December 31, 2020, we sampled 105,707 inpatients. The main outcome of this study was newly diagnosed VHD, which was diagnosed based on ICD-10 coding, and the exposure factor was age at menarche, which was accessed through the electronic health records. We used logistic regression model to investigate the association between age at menarche and VHD.ResultsIn this sample (mean age 55.31 ± 13.63 years), the mean age at menarche was 15. Compared with women with age at menarche 14–15 years, the odds ratio of VHD in women with age at menarche ≤13, 16–17, and ≥18 years was 0.68 (95% CI 0.57–0.81), 1.22 (95% CI 1.08–1.38), and 1.31 (95% CI 1.13–1.52), respectively (P for all < 0.001). By restricting cubic splines, we found that later menarche was associated with increased odds of VHD (P < 0.001). Furthermore, in subgroup analysis of different etiologies, the similar trend persisted for non-rheumatic VHD.ConclusionsIn this large inpatient sample, later menarche was associated with higher risk of VHD

Boundary mode lubrication of articular cartilage with a biomimetic diblock copolymer

We report the design of a diblock copolymer with architecture and function inspired by the lubricating glycoprotein lubricin. This diblock copolymer, synthesized by sequential reversible addition–fragmentation chain-transfer polymerization, consists of a cationic cartilage-binding domain and a brush-lubricating domain. It reduces the coefficient of friction of articular cartilage under boundary mode conditions (0.088 ± 0.039) to a level equivalent to that provided by lubricin (0.093 ± 0.011). Additionally, both the EC50 (0.404 mg/mL) and cartilage-binding time constant (7.19 min) of the polymer are comparable to purified human and recombinant lubricin. Like lubricin, the tribological properties of this polymer are dependent on molecular architecture. When the same monomer composition was evaluated either as an AB diblock copolymer or as a random copolymer, the diblock effectively lubricated cartilage under boundary mode conditions whereas the random copolymer did not. Additionally, the individual polymer blocks did not lubricate independently, and lubrication could be competitively inhibited with an excess of binding domain. This diblock copolymer is an example of a synthetic polymer with lubrication properties equal to lubricin under boundary mode conditions, suggesting its potential utility as a therapy for joint pathologies like osteoarthritis

DESIGN, SYNTHESIS, AND EVALUATION OF LUBRICIN MIMETIC POLYMERS AND THEIR LUBRICATION OF CARTILAGE AND BONE

The body naturally creates biomacromolecules to lubricant joints and provide incredibly low friction under tremendous load for decades. One of the biolubricants, lubricin, demonstrates boundary mode lubrication and chondroprotective abilities that arise from its composition and structure. As a promising therapeutic approach for the treatment of joint diseases such as osteoarthrosis (OA), the challenge to produce lubricin recombinantly restricts its clinical application, which inspires the design of synthetic molecules that mimic lubricin’s structure. In this dissertation, a class of lubricin mimetic diblock copolymers, consisting of a cationic cartilage binding block and a brush lubrication block, are synthesized and their tribological properties are evaluated in comparison to lubricin (Chapter 2). Like lubricin, the tribological properties of these polymers are dependent on the molecular architecture. The roles of structure are explored to characterize how changing the molecular architecture affects the lubrication on cartilage surfaces and the results are summarized as a set of design principles of synthetic lubricants (Chapter 3). Additionally, this class of polymers demonstrates their ability to bind to and lubricate bone surfaces, which is absent in natural lubricin, thus extending its potential application as a therapeutic approach for OA treatment (Chapter 4)

I. Prodrugs based on the sulfamate linkage II. Seleninic acids as biomimetic enzyme inhibitors

The most important two features of a successful drug are the biochemical effects of active pharmaceutical ingredients and the efficacy of their delivery methods. Synthetic organic chemistry plays crucial roles in virtually both of these aspects for the design and the development of new drugs. Herein, in the first half part of the dissertation, a novel synthesis strategy of sulfamate esters is developed, which has been successfully applied into the synthesis of several tripartate pro-drugs with the purpose of improving the delivery efficiency of ethinyl estradiol. Their pharmaceutical effects are evaluated by both in vitro and in vivo studies as described. In the second half part, novel synthesis of several biomimetic enzyme inhibitors, including selenoxide, diselenide, seleninic acid, and various other organoselenium compounds is reported. Evaluation of these biomimetics will be elucidated in the future.M.S.Includes bibliographical referencesIncludes vitaby Zhexun Su

Biohybrid -Se-S- Coupling Reactions of an Amino Acid Derived Seleninate

We describe the synthesis of the N-(2-seleninatoethyl) amide of N-Boc-phenylalanine, serving here as a peptide model, and its reductive coupling reactions under mild conditions with unprotected thiouridine and glutathione. Selenosulfide products such as these comprise reversibly conjugated bio-components, and can potentially find uses as probes of biological function, such as enzyme inhibitors, delivery systems, or structural mimics

Datasheet1_Association of age at menarche with valvular heart disease: An analysis based on electronic health record (CREAT2109).docx

BackgroundThe association between age at menarche and coronary heart disease has been reported, but the association between age at menarche and valvular heart disease (VHD) has not been described. We aimed to examine the association between age at menarche and VHD.MethodsBy collecting data from four medical centers of the Affiliated Hospital of Qingdao University (QUAH) from January 1, 2016, to December 31, 2020, we sampled 105,707 inpatients. The main outcome of this study was newly diagnosed VHD, which was diagnosed based on ICD-10 coding, and the exposure factor was age at menarche, which was accessed through the electronic health records. We used logistic regression model to investigate the association between age at menarche and VHD.ResultsIn this sample (mean age 55.31 ± 13.63 years), the mean age at menarche was 15. Compared with women with age at menarche 14–15 years, the odds ratio of VHD in women with age at menarche ≤13, 16–17, and ≥18 years was 0.68 (95% CI 0.57–0.81), 1.22 (95% CI 1.08–1.38), and 1.31 (95% CI 1.13–1.52), respectively (P for all ConclusionsIn this large inpatient sample, later menarche was associated with higher risk of VHD.</p