Efficacy and safety of polyethylene glycol loxenatide in treating mild-to-moderate diabetic kidney disease in type 2 diabetes patients: a randomized, open-label, clinical trial.

Objective: This study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management. Methods: This study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks. Results: Overall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of -29.3% (95% confidence interval [CI]: -34.8, -23.7), compared to that of -31.8% in the dapagliflozin group (95% CI: -34.8, -23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups (p = 0.336). The HbA1c levels decreased by -1.30% (95% CI: -1.43, -1.18) in the PEG-Loxe group and by -1.29% (95% CI: -1.42, -1.17) in the dapagliflozin group (p = 0.905). The TG levels decreased by -0.56 mmol/L (95% CI: -0.71, -0.42) in the PEG-Loxe group and -0.33 mmol/L (95% CI: -0.48, -0.19) in the dapagliflozin group (p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p > 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group. Conclusions: PEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2300070919.

Real-World Clinical Effectiveness of Glucagon-Like Peptide-1 Receptor Agonist on Mild-to-Moderate Diabetic Kidney Disease in Patients with Type 2 Diabetes: A Retrospective, Single-Arm Clinical Trial.

Background: Cardiovascular outcome trials indicate renal benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs); however, real-world efficacy and safety studies in Diabetic kidney disease (DKD) are scarce. Methods: This retrospective, single-arm real-world trial involved adults with DKD treated with GLP-1RA for at least 6 months. The primary endpoint was hemoglobin A1c (HbA1c) levels after 6 months. Results: This study included a total of 364 patients with DKD, 153 (42.0%) of whom were female. The median disease duration was 8.0 years, and the mean values of age, HbA1c level, body mass index, and the urinary albumin-to-creatinine ratio (UACR) were 52.1 years, 8.6%, 27.8 kg/m2, and 88.0 mg/g, respectively. Additionally, 73.6% and 26.4% of patients had mild and moderate DKD, respectively. Following 6 months of GLP-1RA treatment, the mean HbA1c level and UACR declined by 1.77% and 40.3%, respectively (both p < 0.001). Compared to their baseline values, patients exhibited significant improvements in 24-h urinary protein, estimated glomerular filtration rate (eGFR), fasting blood glucose, body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (all p < 0.001). Patients with a disease duration of <10 years had more pronounced changes in the HbA1c level, UACR, and eGFR (all p < 0.001) than those with a disease duration of ≥10 years. Changes in SBP and DBP were more pronounced in patients also taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEis/ARBs) than in those not taking ACEis/ARBs, whereas the changes in UACR and eGFR did not significantly differ. Conclusion: Six-month GLP-1RA treatment improves glucose, blood pressure, lipids, and body weight in patients with mild-to-moderate DKD while slowing down kidney disease progression. It independently reduces proteinuria beyond ACEi/ARB impact, with early use yielding faster outcomes, supporting evidence-based practice.

Prevalence of blindness and low vision: a study in the rural Heilongjiang Province of China.

BACKGROUND: The prevalence of blind individuals in the north of China is unknown. The study aimed to investigate the prevalence and causes of blindness and low vision in rural areas in Heilongjiang province of China in 2008-2009. DESIGN: Cross-sectional study. PARTICIPANTS OR SAMPLES: A cluster random sampling method was used to recruit participants of all ages in rural areas of Heilongjiang. METHODS: Trained professionals performed interviews and clinical examinations to measure visual acuity. The relationships between blindness or low vision and age, gender and education level were analysed. MAIN OUTCOME MEASURES: The main outcome measure was prevalence rates of bilateral blindness and bilateral low vision. RESULTS: Of the 11 787 subjects, 10 384 (88.1%) were surveyed. The overall age-adjusted prevalence rates were 0.7% (95% confidence interval: 0.5-0.8%) for bilateral blindness and 1.7% (95% confidence interval: 1.4-1.9%) for bilateral low vision. The prevalence rates of blindness and low vision were higher in the elderly and uneducated population (P < 0.05). The main causes for blindness and low vision were cataracts (44.1 and 46.0%, respectively) and refractive errors (17.7 and 42.5%, respectively). CONCLUSION: Blindness and low vision are highly prevalent among people with cataracts and refractive errors. Eye care planning must focus on treating the avoidable and curable forms of blindness.

2',3'-Cyclic GMP-AMP Dinucleotides for STING-Mediated Immune Modulation: Principles, Immunotherapeutic Potential, and Synthesis.

The cGAS-STING pathway discovered ten years ago is an important component of the innate immune system. Activation of cGAS-STING triggers downstream signalling, such as TBK1-IRF3, NF-κB and autophagy, which in turn leads to antipathogen responses, durable antitumour immunity or autoimmune diseases. 2',3'-Cyclic GMP-AMP dinucleotides (2',3'-cGAMP), the key second messengers produced by cGAS, play a pivotal role in cGAS-STING signalling by binding and activating STING. Thus, 2',3'-cGAMP has immunotherapeutic potential, which in turn has stimulated research on the design and synthesis of 2',3'-cGAMP analogues for clinical applications over the past ten years. This review presents the discovery, metabolism, and function of 2',3'-cGAMP in the cGAS-STING innate immune signalling axis. The enzymatic and chemical syntheses of 2',3'-cGAMP analogues as STING-targeting therapeutics are also summarized.

RhBMP-2-Loaded PLGA/Titanium Nanotube Delivery System Synergistically Enhances Osseointegration.

Although Ti-based implants have been widely used, osseointegration failure can also be found between implants and the surrounding bone tissue, especially in aged patients or in patients with certain systemic diseases. Therefore, in this research, we establish a sustained rhBMP-2 delivery system on a titanium implant surface, an anodic oxidation TiO2 nanotube layer combined with the PLGA film, to enhance osseointegration. This designed system was characterized as follows: surface topography characterization by SEM and AFM; rhBMP-2 release; and the ability to influence MC3T3 cell adhesion, proliferation, and osteogenic differentiation in vitro. Additionally, we evaluated the ability of this system to generate new bone around implants in rabbit tibias by the histological assay and removal torque test. SEM and AFM showed that PLGA membranes were formed on the surfaces of TiO2 nanotube arrays using 1, 3, and 10% PLGA solutions. The 3% PLGA group showed a perfect sustained release of rhBMP-2, lasting for 28 days. Meanwhile, the 3% PLGA group showed improved cell proliferation and osteogenic mRNA expression levels. In the in vivo experiments, the 3% PLGA group had the ability to promote osteogenesis in experimental animals. The anodized TiO2 nanotube coated with a certain thickness of the PLGA layer was an ideal and suitable rhBMP-2 carrier. This modified surface enhances osseointegration and could be useful in clinical dental implant treatment.

Mitotic arrest deficient protein MAD2B is overexpressed in human glioma, with depletion enhancing sensitivity to ionizing radiation.

Mitotic arrest deficient protein MAD2B, an enzyme involved in translesion DNA synthesis, has been implicated in several cancers. However, its role in human glioma has not been defined. In the present study, we investigated the expression levels of MAD2B in human gliomas and normal brain tissues, and determined whether depletion of MAD2B enhanced the sensitivity of glioma cells to ionizing radiation. Using reverse transcription-polymerase chain reaction and immunohistochemical analysis, MAD2B was found to be overexpressed in glioma specimens compared with normal brain tissue. Silencing of MAD2B markedly reduced clonogenic survival of glioma cells and significantly enhanced apoptosis in response to ionizing radiation. This effect was associated with caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, disruption of MAD2B potentiated radiation-induced genomic damage, as evidenced by increased phosphorylation of gamma histone H2AX (γ-H2AX). Our findings reveal that expression of MAD2B is deregulated in glioma, and targeting MAD2B may be a potential strategy for improving the efficacy of radiotherapy.