Objective:To analyze the effects of a novel type of polydopamine (PDA)-coated porous titanium alloy scaffolds loaded with zoledronic acid-gelatin nanoparticles (ZOL-GNPs) for topical sustained drug release on osteoclasts in vitro. Methods:After porous titanium alloy scaffolds were fabricated using electron beam melting technique and ZOL-GNPs with different ZOL concentrations (0, 1, 10, 50, 100, 500 μmol/L) were prepared by desolvation method, PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs were constructed by combining the two. The characteristics of the scaffolds were analyzed. The biomechanics of 3 different scaffolds (bare porous titanium alloy scaffolds, PDA-coated porous titanium alloy scaffolds, and PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs) were investigated. Drug release detection was carried out by high performance liquid chromatography on the 1st, 4th, 7th, 14th, 21st, and 28th days respectively. The osteoclasts were inoculated into the novel scaffolds with different ZOL concentrations. The expression of osteoclast-related genes was detected by real-time quantitative (RT)-polymerase chain reaction (PCR); the expression of osteoclast-related proteins was detected by Western-blot.Results:The PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs were successfully constructed. Electron microscope scanning showed that the GNPs were well spheroidized, smooth in surface, and uniformly dispersed, with a particle size of (243.6±63.4) nm. The ZOL-GNPs were uniformly compounded on the surface and in the pores of the scaffolds, and the spheres were regular in shape with no adhesion. The biomechanical experiments showed that the elastic moduli of the porous titanium alloy scaffolds under 3 different conditions were (1.81±0.12) GPa, (1.80±0.23) GPa and (1.81±0.15) GPa, showing no significant difference ( P> 0.05). The drug release percentage in the porous titanium alloy scaffolds was obviously high on the first day, and increased gradually and slowly in the subsequent 27 days. In the scaffolds with a low concentration ZOL, more osteoclasts adhered and proliferated; in the 50 μmol/L scaffolds, spheroid cells appeared; the spheroid cells increased and even apoptosis occurred with an increase in the ZOL concentration. RT-PCR showed that the expression of Ctsk gene and TRAP gene increased with the increased ZOL concentration, peaked in the 50 μmol/L scaffolds, and then decreased with the increased concentration, showing statistically significant differences ( P < 0.05). Western-blot showed that the expression pattern of Ctsk and TRAP was similar to that of their related genes. Conclusions:The novel PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs demonstrate good mechanical properties and an anti-osteoporosis effect via their topical sustained drug release. The scaffolds with a ZOL concentration of 50 μmol/L may exert the best effect on inhibition of osteoclasts.

OBJECTIVES: This study examined the associations between adverse childhood experiences (ACEs) and diabetes within a social-ecological framework, incorporating personal and environmental unfavorable conditions during childhood from family, school, and community contexts. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (2014 life history survey and 2015 survey), including 9,179 participants aged ≥45 years. ACEs were collected through self-report questionnaires, and participants were categorized based on the number of distinct ACEs experienced (0, 1, 2, 3, or ≥4 ACEs). Diabetes was defined by biomarkers, self-reported diagnosis, and treatment status. Logistic regression was conducted to explore the associations between ACEs and diabetes. Subgroup analyses were conducted by gender, age, and obesity status. RESULTS: Compared with participants without ACEs, those exposed to any ACE (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40), 3 ACEs (OR, 1.32; 95% CI, 1.07 to 1.62) and ≥4 ACEs (OR, 1.29; 95% CI, 1.07 to 1.56) had an increased risk of diabetes. For each additional ACE, the risk of diabetes increased by about 5%. Regarding the source of ACEs, those originating from the family (OR, 1.23; 95% CI, 1.08 to 1.41) were associated with diabetes. In terms of specific ACE types, family members with substance abuse (OR, 1.23; 95% CI, 1.01 to 1.52), emotional abuse (OR, 1.28; 95% CI, 1.12 to 1.46), and poor parental relationship (OR, 1.25; 95% CI, 1.09 to 1.43) were associated with diabetes. CONCLUSIONS ACEs, particularly those originating from the family, were associated with diabetes. Interventions aimed at preventing and mitigating ACEs are essential for the early prevention of diabetes.

OBJECTIVES: This study aimed to investigate the associations of obesity phenotypes with hypertension stages, phenotypes, and transitions among middle-aged and older Chinese. METHODS: Using the 2011-2015 waves of the China Health and Retirement Longitudinal Study, we conducted a cross-sectional analysis included 9,015 subjects and a longitudinal analysis included 4,961 subjects, with 4,872 having full data on the hypertension stage and 4,784 having full data on the hypertension phenotype. Based on body mass index and waist circumstance, subjects were categorized into 4 mutually exclusive obesity phenotypes: normal weight with no central obesity (NWNCO), abnormal weight with no central obesity (AWNCO), normal weight with central obesity (NWCO), and abnormal weight with central obesity (AWCO). Hypertension stages were classified into normotension, pre-hypertension, stage 1 hypertension, and stage 2 hypertension. Hypertension phenotypes were categorized as normotension, pre-hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). The association between obesity phenotypes and hypertension was estimated by logistic regression. A comparison between different sexes was conducted by testing the interaction effect of sex. RESULTS: NWCO was associated with normal→stage 2 (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.11 to 3.42), maintained stage 1 (OR, 1.62; 95% CI, 1.14 to 2.29), and normal→ISH (OR, 1.39; 95% CI, 1.05 to 1.85). AWCO was associated with normal→stage 1 (OR, 1.75; 95% CI, 1.40 to 2.19), maintained stage 1 (OR, 2.77; 95% CI, 2.06 to 3.72), maintained stage 2 (OR, 2.80; 95% CI, 1.50 to 5.25), normal→ISH (OR, 1.56; 95% CI, 1.20 to 2.02), and normal→SDH (OR, 2.54; 95% CI, 1.72 to 3.75). An interaction effect of sex existed in the association between obesity phenotypes and hypertension stages. CONCLUSIONS This study highlights the importance of various obesity phenotypes and sex differences in hypertension progression. Tailored interventions for different obesity phenotypes may be warranted in hypertension management, taking into account sex-specific differences to improve outcomes.

Objective: To evaluate the effect of biofeedback training on bowl function among rectal cancer patients with chemoradiotherapy and temporary enterostomy. Methods: Using randomized controlled trial design, 109 rectal cancer patients were randomly divided into three groups, the first blank control group, the second group pelvic floor muscle exercise group, the third group biofeedback group. High resolution anorectal manometry was used for 6 longitudinal traces in 16 months. Data of bowel function were collected by Memorial Sloan Kettering Cancer Center (MSKCC) Bowel Function Instrument. Results: The main effect of the change of five indicators, anal resting pressure, rectal resting pressure, maximum squeeze pressure, maximum squeeze time and high pressure zone, was time. The other four indicators, rectal volume at first senory, rectal volume at sense of convenience, maximal tolerable rectal volume and rectal compliance, among patients of biofeedback group were (32.71±5.00) ml, (74.26±8.30) ml, (188.40±12.68) ml, (5.69±1.18) ml/kPa and (68.09±6.38). The rectal volume at first senory, rectal volume at sense of convenience, maximal tolerable rectal volume and rectal compliance, among patients of biofeedback group were significant higher than blank control group and pelvic floor muscle exercise group (F=3.589-26.826, P<0.05). Conclusion The biofeedback could significantly improve the sensory indicators of patients with middle and low rectal cancer. High-resolution anorectal manometry could effectively evaluate the effect of biofeedback training in patients with middle and low rectal cancer.

Ubiquitination, one type of the most common post-translational modification, mediates the regulation of protein homeostasis in vivo. Since ubiquitin itself contains multiple lysine residues and one N-terminal free amino group, eight types of ubiquitin chains can be formed. The K27 ubiquitin chain is formed through the ubiquitination of the ubiquitin Lys27 (K27), which adopts a compact conformation. In recent years, biological function of the K27 ubiquitin chain in innate immunity, protein homeostasis and DNA damage has been discovered, but the molecular mechanisms of K27 ubiquitin chain assembly, recognition and hydrolysis are still poorly understood. Here we review the structural features and biological functions of K27 ubiquitin chain, to provide a reference for future studies.