Tough Adhesive Hydrogel for Intraoral Adhesion and Drug Delivery.

Oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS) are common chronic inflammatory conditions, manifesting as painful oral lesions that negatively affect patients' quality of life. Current treatment approaches are mainly palliative and often ineffective due to inadequate contact time of the therapeutic agent with the lesions. Here, we developed the Dental Tough Adhesive (DenTAl), a bioinspired adhesive patch with robust mechanical properties, capable of strong adhesion against diverse wet and dynamically moving intraoral tissues, and extended drug delivery of clobetasol-17-propionate, a first-line drug for treating OLP and RAS. DenTAl was found to have superior physical and adhesive properties compared to existing oral technologies, with ~2 to 100× adhesion to porcine keratinized gingiva and ~3 to 15× stretchability. Clobetasol-17-propionate incorporated into the DenTAl was released in a tunable sustained manner for at least 3 wk and demonstrated immunomodulatory capabilities in vitro, evidenced by reductions in several cytokines, including TNF-α, IL-6, IL-10, MCP-5, MIP-2, and TIMP-1. Our findings suggest that DenTAl may be a promising device for intraoral delivery of small-molecule drugs applicable to the management of painful oral lesions associated with chronic inflammatory conditions.

Molecular simulation of linear octacosane via a CG10 coarse grain scheme.

Following our previous work on the united-atom simulation on octacosane (C28H58) (Dai et al., Phys. Chem. Chem. Phys., 2021, 23, 21262-21271), we developed a coarse grain scheme (CG10), which is able to reproduce the pivotal phase characteristics of octacosane with highly improved computational efficiency. The CG10 octacosane chain was composed of 10 consecutive beads, maintaining the fundamental zigzag chain morphology. When the potential functions were set up and the coefficients were parameterized, our CG10 models yielded solid phase diagrams and transitions during an annealing process. We also detected the melting point by various means: direct observation, bond order, density tracking, and an enthalpy plot. Furthermore, our CG10 successfully reproduced the liquid density with only 2% underestimation, indicating its applicability across the solid and liquid phases. Therefore, with the ability to reproduce critical structure and property characteristics, our CG10 scheme provides an effective means of numerically modelling octacosane with highly improved computational efficiency.

Molecular dynamics simulation of octacosane for phase diagrams and properties via the united-atom scheme.

We used the united-atom scheme to build three types of crystalline structures for octacosane (C28H58) and carried out molecular dynamics simulations to investigate their phase properties. By gradually heating the three polymorphs, we managed to reproduce the sequence of experimentally reported crystalline phases and rotator phases. By studying the system density, molecule morphology, chain tilt angle and cell anisotropy, we hypothesized three mechanisms behind the observed system deformations and phase transformations during the annealing process. Furthermore, our model successfully predicted the melting temperature and heat of fusion. We also reproduced the characteristics of the rotator phases and the liquid phase, validating the transferability of the united-atom scheme among the different condensed phases of octacosane. Our methodology represents an effective and efficient means of numerical study for octacosane and may be used for other members of the n-alkane family.

[Prevalence and risk factors of dyslipidemia in a rural population of Henan Province, China].

Objective: The purpose of this study was to investigate the prevalence and risk factors of dyslipidemia in a rural population of Henan Province, China. Methods: A total of 20 194 participants aged ≥18 years were selected randomly by cluster sampling from two townships(towns)in Henan Province from July to August 2007 and July to August 2008. Investigations included questionnaires, anthropometric measurements, fasting plasma glucose, and lipid profile examination at baseline. A total of 16 155 participants were followed up from July to August 2013 and July to October 2014. Overall, 13 869 participants were included in the study, after excluding 2 286 participants with incomplete dyslipidemia follow-up data. Distributions of the characteristics of dyslipidemia were determined, and prevalence was standardized by age according to data of the 2010 Sixth National Population Census. Risk factors for dyslipidemia were analyzed using a logistic regression model after adjusting for sex, age, education level, marital status, and income status. Results: The prevalence of dyslipidemia was 53.72%(7 450/13 869)for residents aged ≥22 years living in rural areas of Henan Province(59.32%(3 069/5 174)for men and 50.39%(4 381/8 695)for women). The adjusted prevalence of dyslipidemia was 50.50%(59.27% for men and 45.53% for women). The prevalence of hypercholesterolemia, hypertriglyceridemia, low HDL-C, and high LDL-C was 4.34%(602/13 868), 20.42%(2 826/13 837), 42.75%(5 927/13 865), and 3.14%(420/13 375), respectively, and the adjusted prevalence was 2.44%, 18.84%, 41.42%, and 1.86%, respectively. Logistic regression analyses showed that alcohol consumption(OR=1.27, 95% CI: 1.05-1.53), family history of hyperlipidemia(OR=1.29, 95% CI: 1.17-1.43), overweight(OR=1.40, 95% CI: 1.22-1.61), obesity(OR= 1.65, 95% CI: 1.39- 1.96), abnormal waist circumference(OR=1.22, 95% CI: 1.04- 1.43), and abnormal waist-height ratio(OR=1.21, 95% CI: 1.01-1.45)were significant independent risk factors, and high levels of physical activity(OR=0.85, 95% CI: 0.77- 0.95)and underweight(OR=0.52, 95% CI: 0.36- 0.75)were protective factors for dyslipidemia after adjusting for sex, age, education level, marital status, and income status. Conclusion: The prevalence of dyslipidemia was very high for this rural population. Alcohol consumption, family history of hyperlipidemia, overweight, obesity, abnormal waist circumference, and abnormal waist-height ratio were significant independent risk factors for dyslipidemia.

[Body mass index, waist circumference and waist-to-height ratio associated with the incidence of type 2 diabetes mellitus: a cohort study].

OBJECTIVE: To investigate the association between body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and the incidence risk of type 2 diabetes mellitus (T2DM). METHODS: In total, 20 194 participants ≥18 years old were selected randomly by cluster sampling from two township (town) of the county in Henan province from July to August of 2007 and July to August of 2008 and the investigation included questionnaires, anthropometric measurements, fasting plasma glucose, and lipid profile examination were performed at baseline; 17 236 participants were enrolled in this cohort study. 14 720 (85.4%) were followed up from July to August 2013 and July to October 2014. Finally, 11 643 participants (4 301 males and 7 342 females) were included in this study. Incidence density and Cox proportional hazards regression models were used to evaluate the risk of T2DM associated with baseline BMI, WC, WHtR, and their dynamic changes. RESULTS: After average of 6.01 years following up for 11 643 participants, 613 developed T2DM and the incidence density was 0.89 per 100 person-years. After adjusted for baseline sex, age, smoking, drinking, family history of diabetes, as well as the difference of fasting plasma-glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP) between baseline and follow-up, Cox Proportional-Hazards regression analysis indicated that T2DM risk of baseline BMI overweight group, BMI obesity group, abnormal WC group and abnormal WHtR group were significantly higher than that of the corresponding baseline normal groups , and the incidence risk of T2DM reached the highest for those whose baseline BMI, WC and WHtR were all abnormal, the corresponding HR (95%CI) were 2.05 (1.62-2.59), 3.01 (2.33-3.90), 2.34 (1.89-2.90), 2.88 (2.21-3.74), 3.32 (2.50-4.40), respectively. Whether baseline BMI/WC was normal or not, T2DM risk increased if baseline WHtR was abnormal, and the HR (95%CI) of baseline normal BMI/abnormal WHtR group, baseline abnormal BMI/abnormal WHtR group, baseline normal WC/abnormal WHtR group, baseline abnormal WC/abnormal WHtR group were 1.88 (1.29-2.74), 3.08 (2.34-4.05), 2.15(1.53-3.00), 3.22 (2.45-4.23), respectively. The analysis for dynamic changes of BMI, WC, and WHtR indicated that in baseline normal WC or WHtR group, T2DM risk increased when baseline normal WC or WHtR developed abnormal at follow-up, and the corresponding HR (95%CI) were 1.79 (1.26-2.55), 2.12(1.32-3.39), respectively. In baseline abnormal WC or WHtR group, T2DM risk decresed when baseline abnormal WC or WHtR reversed to normal at follow-up, and the corresponding HR (95%CI) were 2.16 (1.42-3.29), 2.62 (1.63-4.20), respectively. CONCLUSION: BMI, WC, and WHtR were associated with increased T2DM risk. The more abnormal aggregation of BMI, WC, and WHtR presents, the higher T2DM risk was. T2DM risk could be decreased when abnormal WC or WHtR reversed to normal.

Mechanisms of leukocyte trafficking into the CNS.

HIV-1 encephalitis occurs in up to one-third of HIV-1-infected individuals. The mechanisms through which this pathology develops are thought to involve viral passage across the blood-brain barrier (BBB), as well as entry of HIV-infected and/or uninfected inflammatory cells into the central nervous system (CNS). Viral proteins and cytokines may also contribute to the pathogenesis of encephalitis. We show that the chemokines SDF-1 and MCP-1 induce transmigration of uninfected human lymphocytes and monocytes across our model of the BBB, a co-culture of human fetal astrocytes and endothelial cells. We also demonstrate that the HIV-1 protein Tat induces adhesion molecule expression and chemokine production by human fetal astrocytes and microglia, which could further contribute to leukocyte entry into the CNS. Finally, our data indicate that inflammatory cytokines modulate the expression of CXCR4, a co-receptor for HIV-1, on human fetal astrocytes, suggesting that these cytokines may potentially modulate the infectability of astrocytes by HIV-1. These findings support the hypothesis that there may be several different mechanisms that contribute to the development and progression of HIV-1 encephalitis.

Limiting systemic plasminogenolysis reduces the bleeding potential for tissue-type plasminogen activators but not for streptokinase.

Clinical experience suggests that thrombolytic-induced bleeding is associated with systemic activation of the thrombolytic system. Using fibrin specific variants of tissue-type plasminogen activator (t-PA) and making use of the apparent fibrin specificity of streptokinase (SK) in the rabbit we tested the hypothesis that minimizing systemic plasmin production and fibrinogenolysis will decrease hemorrhages in models of peripheral bleeding and embolic stroke. t-PA consumed 51% of the available fibrinogen; caused cerebral bleeds and increased peripheral bleeding time. Fibrin-specific variants of t-PA depleted less than 20% of the fibrinogen and did not cause peripheral or cerebral bleeding. However, an equipotent dose of SK converted only 12% of the available fibrinogen but increased bleeding time and caused hemorrhagic conversion in 75% of embolic stroke model animals treated. The data suggest that bleeding associated with tissue-type plasminogen activators is linked to systemic plasmin generation and subsequent fibrinogenolysis. This hypothesis does not explain the mechanism(s) of SK-induced bleeding.

A comparison of results of type I and type II radical operations for carcinoma of the gastric cardia.

During 1954-1981, 527 patients with cancer of the gastric cardia underwent resection. Of these, 146 underwent type I radical operation (transthoracic resection) with eight (5.5%) operative deaths; 344 underwent type II radical operation (abdominothoracic resection) with 42(12.2%) operative deaths; and 37 with Stage IV lesions underwent extended operation or palliative operation with 4(10.8%) operative deaths. Of 440 cases of Stage I-III cases that survived the operation, the 5-year survival rate was 18.5%, and the 10-year survival rate was 10.7%. For stage I cancer, the end results of type I and type II radical operations were similar. In Stage II, whether the lymph nodes were positive or negative, the end result of the type II operation was better, but without statistical significance. In Stage III cancer without lymph node metastases, the end result of the type II operation was better, but without statistical significance; in those with lymph node metastases, the type II operation was definitely better than the type I operation (P less than 0.05).