Negative Correlation of Serum Total Bile Acid With Albuminuria in Patients With Type 2 Diabetes Mellitus: A Cross-sectional Study.

Context: The treatment of diabetic nephropathy (DN) is still quite limited. DN remains poorly understood due to the complexity of and differences in its etiology. Therefore, potential biomarkers for diagnosis and targeted treatments are urgently needed. Objective: The study aimed to analyze the associations between circulating total bile acid (TBA) levels and the risk of DN in Chinese patients with type 2 diabetes mellitus (T2DM) and to determine the differences in the TBA levels of males and females, including pre- and postmenopausal women, to find clues for the screening of DN. Design: The research team performed a retrospective study. Setting: The study took place at the Second Affiliated Hospital at the School of Medicine of Zhejiang University in Zhejiang, China. Participants: Participants were 1785 T2DM patients admitted to the hospital between April 2008 and November 2013. Groups: The research team separated participants into three groups: (1) the normoalbuminuria or normal group, with a UACR <30 mg/g·Cr (2) the microalbuminuria (MAU) group, with a UACR of 30-299 mg/g·Cr; and (3) the macroalbuminuria (MAC) group, with a UACR of ≥300 mg/g·Cr. Outcome Measures: Between the three groups, the research team compared: (1) the demographic and clinic characteristics of the normal, MAU, and MAC groups; (2) TBA distribution by age; (3) TBA distribution by gender; and (4) TBA quartiles. The team also examined the associations between TBA and albuminuria, identifying the odds ratios (OR) and relevant 95% confidence intervals (CI) using multiple logistic regression. Results: The study found that: (1) the MAC group's TBA was significantly lower than those of the normal and MAU groups; (2) the TBA of postmenopausal women was significantly higher than that of premenopausal women; (3) the incidence of MAC was obviously increased with TBA levels; (4) the risks for MAU group didn't change significantly with increasing TBA levels; (5) the MAC group's odds ratios (ORs) were 0.61 between Q2 and Q1, 0.44 between Q3 and Q1, and 0.38 between Q4 and Q1; and (6) for men and postmenopausal women, the TBA levels of those in Q3 and Q4 might decrease the risk of MAC, whereas no such correlation existed for MAU. Conclusions: An independent negative association exists between TBA levels and MAC in T2DM. The decrease of circulating TBA might be a prospective clinical factor for determining established DN, especially for males and postmenopausal females.

Glucosamine Use Is Associated with a Higher Risk of Cardiovascular Diseases in Patients with Osteoarthritis: Results from a Large Study in 685,778 Subjects.

Glucosamine is widely used around the world and as a popular dietary supplement and treatment in patients with osteoarthritis in China; however, the real-world cardiovascular risk of glucosamine in long-term use is still unclear. A retrospective, population-based cohort study was performed, based on the Beijing Medical Claim Data for Employees from 1 January 2010 to 31 December 2017. Patients newly diagnosed with osteoarthritis were selected and divided into glucosamine users and non- glucosamine users. The glucosamine users group was further divided into adherent, partially adherent, and non-adherent groups according to the medication adherence. New-onset cardiovascular diseases (CVD) events, coronary heart diseases (CHD), and stroke, were identified during the observational period. COX proportional regression models were used to estimate the risks. Of the 685,778 patients newly diagnosed with osteoarthritis including 240,419 glucosamine users and 445,359 non-users, the mean age was 56.49 (SD: 14.45) years and 59.35% were females. During a median follow-up of 6.13 years, 64,600 new-onset CVD, 26,530 CHD, and 17,832 stroke events occurred. Glucosamine usage was significantly associated with CVD (HR: 1.10; 95% CI: 1.08−1.11) and CHD (HR: 1.12; 95% CI: 1.09−1.15), but not with stroke (HR: 1.03; 95% CI: 0.99−1.06). The highest CVD risk was shown in the adherent group (HR: 1.68; 95% CI: 1.59−1.78), followed by the partially adherent group (HR: 1.26, 95% CI: 1.22−1.30), and the non-adherent group (HR: 1.03; 95% CI: 1.02−1.05), with a significant dose−response relationship (p-trend < 0.001). In this longitudinal study, adherent usage of glucosamine was significantly associated with a higher risk for cardiovascular diseases in patients with osteoarthritis.

Titanium nanosheet as robust and biosafe drug carrier for combined photochemo cancer therapy.

Two-dimensional (2D) Titanium nanosheets (Ti NSs) have shown many excellent properties, such as nontoxicity, satisfactory photothermal conversion efficacy, etc. However, the biomedical applications of Ti NSs have not been intensively investigated. Herein, we synthesized a multifunctional Ti NS drug delivery system modified with polydopamine/polyethylene glycol (Ti@PDA-PEG) and applied simultaneously for photothermal therapy and chemotherapy. Doxorubicin (DOX) was utilized as a model drug. Ti@PDA-PEG NS shows an ultrahigh antitumor drug DOX loading (Ti@PDA-PEG-DOX). The prepared Ti@PDA-PEG-DOX NS as robust drug delivery system demonstrates great stability and excellent multi-response drug-release capabilities, including pH-responsive and near-infrared -responsive behavior and obviously high photothermal efficiency. Both in vitro and in vivo experimental results have shown high biosafety and outstanding antitumor effects. Therefore, this work exhibits the enormous potential of a multifunctional platform in the treatment of tumors and may stimulate interest in the exploration of other new 2D nanomaterials for biomedical applications.

Magnesium isoglycyrrhizinate prevents cadmium-induced activation of JNK and apoptotic hepatocyte death by reversing ROS-inactivated PP2A.

OBJECTIVES: Cadmium (Cd) induces reactive oxygen species (ROS)-mediated hepatocyte apoptosis and consequential liver disorders. This study aimed to investigate the effect of magnesium isoglycyrrhizinate (MgIG) on Cd-induced hepatotoxicity. METHODS: L02 and AML-12 cells were used to study MgIG hepatoprotective effects. Cd-evoked apoptosis, ROS and protein phosphatase 2A (PP2A)/c-Jun N-terminal kinase (JNK) cascade disruption were analysed by cell viability assay, 6-diamidino-2-phenylindole (DAPI) and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, ROS imaging and Western blotting. Pharmacological and genetic approaches were used to explore the mechanisms. KEY FINDINGS: We show that MgIG attenuated Cd-evoked hepatocyte apoptosis by blocking JNK pathway. Pre-treatment with SP600125 or ectopic expression of dominant-negative c-Jun enhanced MgIG's anti-apoptotic effects. Further investigation found that MgIG rescued Cd-inactivated PP2A. Inhibition of PP2A activity by okadaic acid attenuated the MgIG's inhibition of the Cd-stimulated JNK pathway and apoptosis; in contrast, overexpression of PP2A strengthened the MgIG effects. In addition, MgIG blocked Cd-induced ROS generation. Eliminating ROS by N-acetyl-l-cysteine abrogated Cd-induced PP2A-JNK pathway disruption and concurrently reinforced MgIG-conferred protective effects, which could be further slightly strengthened by PP2A overexpression. CONCLUSIONS: Our findings indicate that MgIG is a promising hepatoprotective agent for the prevention of Cd-induced hepatic injury by mitigating ROS-inactivated PP2A, thus preventing JNK activation and hepatocyte apoptosis.

Long-term success of dental implant-supported dentures in postirradiated patients treated for neoplasms of the maxillofacial skeleton: a retrospective study.

OBJECTIVES: The reconstruction of oral function in irradiated patients with craniofacial tumors is a significant challenge. The aim of this study was to detect long-term success of dental implant-supported dentures in postirradiated patients treated for neoplasms of the maxillofacial skeleton. MATERIALS AND METHODS: From 2004 to 2011, 36 irradiated patients underwent oral function reconstruction using implant-supported prostheses. Bone augmentation was completed using vascularized bone grafts in 22 patients. Fourteen patients were treated by hyperbaric oxygen therapy (HBO). A total of 198 dental implants were used in jaw rehabilitation. After loading, implant success rates, biological and prosthetic complications, patient satisfaction, and psychological changes were recorded. RESULTS: Bone augmentation of the jaw was successful and vascularized grafts provided an additional vascular supply in compromised irradiated tissue. Rehabilitation was successful in all of the patients after loading. Thirty-eight dental implants failed, and 35 implants were removed. The success rate of the implants was 93.6 % for 10 years after loading. It was not a significant difference in implant success rate between the HBO group and the other groups. The prosthodontic maintenance results and complication rates showed that patients required intervention 0.19 times per year. All patients were satisfied with the oral restoration results. CONCLUSION: The restoration of oral function in radiotherapy patients with tumor resection using implant-supported prostheses is a viable treatment option. CLINICAL RELEVANCE: Either alone or in combination with HBO, dental implant-supported prostheses can be used an effective therapeutic approach for irradiated patients with oral function reconstruction.

Artesunate exerts an anti-immunosuppressive effect on cervical cancer by inhibiting PGE2 production and Foxp3 expression.

Artesunate (ART), derived from a common traditional Chinese medicine, has beeen used an antimalarial for several years. In this study, the effect and mechanism of ART on anti-human cervical cancer cells was examined. The level of prostaglandin E2 (PGE2 ) and the population of CD4+CD25+Foxp3 regulatory T cells (Treg) in peripheral blood were detected by flow cytometry. In vivo antitumor activity was investigated in mice with cervical cancer by the subcutaneous injection of various concentrations of ART. The concentrations of PGE2 in the supernatants of CaSki cells were measured using an ELISA kit. Cyclooxygenase-2 (COX-2) and Foxp3 expression were determined using quantitative polymerase chain reaction (qPCR) and western blot analysis. The effect of ART on the viability of CaSki and Hela cells was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. It was identified that the level of PGE2 and the population of CD4+CD25+Foxp3 Treg cells in the peripheral blood were significantly higher in cervical cancer patients and mice with cervical cancer. ART was capable of inhibiting orthotopic tumor growth, which correlated with a decrease in the level of PGE2 and the percentage of Treg cells in mice with cervical cancer. Furthermore, ART decreased COX-2 expression and the production of PGE2 in CaSki and Hela cells. Notably, the supernatants of CaSki cells treated with ART lowered the expression of Foxp3 in Jurkat T cells, which was capable of being reversed by exogenous PGE2 . Our data revealed that ART may elicit an anti-tumor effect against cervical cancer by inhibition of PGE2 production in CaSki and Hela cells, which resulted in the decrease of Foxp3 expression in T cells. Therefore, ART may be an effective drug for immunotherapy of cervical cancer.

[Application of pragmatic clinical trials in clinical evaluation of Chinese medicine].

Since the evidence-based medicine (EBM) being evoked widely, to seek out the best evidence is becoming the pivotal step for the development of Chinese medicine (CM), and randomized controlled trial (RCT, at most times, it means explanatory clinical trial--ECT) has been accepted as the general golden standard for the evaluation of clinical intervention. However, it is noted that the traditional RCT (ECT) is unsuitable for the special characteristics of individual treatment in CM. The formation and development of CM theory is found on large amount of clinical experiences, and to evaluate its clinical efficacy and safety is the most primary task. Because the CM intervention measures are complex and individualized, the clinical effectiveness of CM is embodied as a complex system, which impacted greatly by the environment factors. It is deemed that the pragmatic clinical trial (PCT) has the character just fitting for the evaluation. The feasibility of PCT in CM clinical evaluation is discussed in this paper in order to raise a new issue for the evaluation of CM effectiveness.