Anemia is a risk factor for rapid eGFR decline in type 2 diabetes.

Objective: To investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes. Methods: This was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis. Results: The prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine ß2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline. Conclusion: Anemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.

Construction of bioengineered corneal stromal implants using an allogeneic cornea-derived matrix.

The bioengineering of corneal scaffolds that mimic native human cornea has attracted interest owing to the scarcity of donor corneas for the transplantation-based treatment of corneal blindness. However, an optimally engineered corneal tissue for clinical use has yet to emerge. Herein, human corneal tissues discarded during allogeneic corneal transplantation surgery were used to construct allogeneic cornea-derived matrix (ACM) scaffolds with favorable optical properties and structural strength. During scaffold fabrication, collagen and glycosaminoglycan levels were well preserved, while DNA decreased significantly. Scanning electron microscopy revealed the presence of fiber-like structures on the scaffold surface and specific structures featuring multiple interlaced lamellae in cross-sections. Moreover, corneal epithelial cells grown on the ACM formed a continuous multi-stratified epithelium with a strong expression of the corneal epithelial differentiation marker CK3/12, gap junction marker Connexin43, and stem-cell-specific marker p63α, while corneal stromal cells expressed the keratocyte-specific marker KERA and the adhesion marker integrin ß1. When the ACM was implanted into rabbit corneal stromal pockets, the rabbit cornea remained transparent throughout the follow-up period. These results indicate that the construction of corneal stromal implants from discarded human corneal tissues may pave the way for the generation of high-quality corneal tissue for transplantation.

Descemet membrane endothelial keratoplasty for corneal decompensation caused by a phakic anterior chamber intraocular lens implantation.

PURPOSE: To describe the clinical outcomes of Descemet membrane endothelial keratoplasty combined with phacoemulsification/posterior chamber intraocular lens implantation (triple procedure) for treatment of corneal decompensation induced by a phakic anterior chamber intraocular lens (AC IOL) implantation. METHODS: Ten patients (10 eyes) with corneal decompensation due to phakic AC IOL implantation that had undergone the triple procedure were included in this study. Among the 10 eyes, 5 eyes underwent explantation of AC IOL prior to the transplantation, and then underwent the triple procedure. The remaining 5 eyes with a phakic AC IOL in situ underwent the triple procedure with concurrent explantation of AC IOL. Corrected distance visual acuity (CDVA), subjective refraction, endothelial cell density (ECD), and complications were documented. RESULTS: The triple procedure was performed across all eyes without any adverse events. The average CDVA improved from 1.32 ± 0.24 preoperatively to 0.15 ± 0.05 logarithm of the minimum angle of resolution (logMAR), which represents an improvement in Snellen equivalent from 20/400 (0.05) preoperatively to 20/28 (0.71) at 12 months after surgery. At 12 months, all eyes reached a CDVA of 20/32 (0.63) or better, and 50% of eyes reached a CDVA of 20/25 (0.8) or better. The mean donor ECD±SD was 2868.7 ± 67.9 cells/mm2, which decreased to 1724.1 ± 84.6 cells/mm2 at 12 months, representing 39.9% of endothelial cell loss. Patients did not experience any severe adverse events. CONCLUSION: The triple procedure is a safe and effective option for corneal decompensation induced by a phakic AC IOL implantation, helping achieve a satisfactory visual rehabilitation with few complications.

The association between secondhand smoke and childhood asthma: A systematic review and meta-analysis.

BACKGROUND: Secondhand smoke (SHS) exposure can trigger asthma exacerbations in children. Different studies have linked increased asthma symptoms and even deaths in children with SHS, but the risk has not been quantified uniformly across studies. We aimed to investigate the role of SHS exposure as a risk factor of asthma among children. METHODS: We performed a systematic review in PubMed, Scopus, and Google Scholar from June 1975 to 10 March 2020. We included cohort, case-control, and cross-sectional studies reporting odds ratio (OR) or relative risk estimates and confidence intervals of all types of SHS exposure and childhood asthma. RESULTS: Of the 26 970 studies identified, we included 93 eligible studies (42 cross-sectional, 41 cohort, and 10 case-control) in the meta-analysis. There were significantly positive associations between SHS exposure and doctor-diagnosed asthma (OR = 1.24; 95% confidence interval (CI) = 1.20-1.28), wheezing (OR = 1.27; 95% CI = 1.23-1.32) and asthma-like syndrome (OR = 1.34; 95% CI = 1.34-1.64). The funnel plots of all three outcomes skewed to the right, indicating that the studies generally favor a positive association of the disease with tobacco exposure. Subgroup analysis demonstrated that younger children tended to suffer more from developing doctor-diagnosed asthma, but older children (adolescents) suffered more from wheezing. There was no evidence of significant publication or small study bias using Egger's and Begg's tests. CONCLUSION: The results show a positive association between prenatal and postnatal secondhand smoking exposure and the occurrence of childhood asthma, asthma-like syndrome, and wheezing. These results lend support to continued efforts to reduce childhood exposure to secondhand smoke.

AICAR prolongs corneal allograft survival via the AMPK-mTOR signaling pathway in mice.

Immune rejection is a critical complication that results in the graft failure after corneal transplantation. Thus, there remains a need for new therapies for allograft rejection. AICAR (aminoimidazole-4-carboxamide ribonucleoside) is an, as adenosine monophosphate-activated protein kinase (AMPK) activator and a purine nucleoside with a wide range of metabolic effects, including activation of AMPK. More recently, it was reported that it is possible to inhibiting organs rejection and prolong the graft survival time in various models of organ transplantation. In this study, we systematically evaluated the efficacy of AICAR as a treatment modality for inhibiting allograft rejection in a mouse model of corneal transplantation. We found that AICAR significantly suppressed the opacity, edema, and vascularization of the graft, resulting in prolonged corneal allograft survival. AICAR treatment also significantly decreased central corneal thickness. Moreover, the AICAR-treated group showed decreased expression of IB4 and VEGF as compared to the control group. In addition, the mRNA expression of T helper 1 cytokines (IL-2, INF-γ, and TNF-α) was suppressed, and the expression of T helper 2 cytokines (IL-4, IL-5, and IL-13) was elevated by AICAR. Furthermore, the western blotting results revealed that AICAR stimulated AMPK activation and inhibited angiogenesis and inflammation possibly by subsequently suppressing mTOR phosphorylation. By contrast, the AMPK inhibitor Compound C (also called dorsomorphin) had the opposite effect. Our results showed that Compound C blocked AMPK-mTOR signaling and promoted the angiogenesis and inflammation, thus compromising the graft survival. These results suggest that AICAR may be a potential option for inhibiting the corneal graft rejection and for prolonging the graft survival.

The ROCK inhibitor, thiazovivin, inhibits human corneal endothelial­to­mesenchymal transition/epithelial­to­mesenchymal transition and increases ionic transporter expression.

Corneal diseases exhibit a high prevalence and are prone to cause blindness; furthermore, maintaining the morphology and ionic transporter expression in corneal endothelial cells (CECs) is crucial for treatment of these diseases. This study aimed to investigate the effects of the novel Rho associated coiled-coil containing protein kinase (ROCK) inhibitor, thiazovivin (2,4­disubstituted thiazole, TZV), on human corneal endothelial­to­mesenchymal transition/epithelial­to­mesenchymal transition (EndMT/EMT), cell morphology, junction proteins and ionic transporter expression in human CECs (HCECs) in vitro and then to clarify the mechanisms of action of TZV. In the present study, primary HCECs were cultured in vitro and passaged. The expression levels of adhesion proteins (E­cadherin and N­cadherin), the EndMT/EMT marker, α smooth muscle  actin (α­SMA), the tight junction protein, Zonula occludens-1 (ZO­1), and the ionic transporter, Na+/K+­ATPase, were detected by immunofluorescence. The proliferative ability of the HCECs was determined by CCK-8 assay. The mRNA expression of the EndMT/EMT­inducing gene, Snail, was examined by RT­PCR. The protein expression levels of ROCK1/2 were evaluated by western blot analysis. The HCECs were cultured with TZV at various concentrations (2, 4, or 6 µM) for different periods of time (24 or 48 h). We found that the the cell states of the HCECs co­cultured with 4 µM TZV for 48 h reached the optimum, and corneal EndMT/EMT was inhibited, as evidenced by the significantly upregulated expression of ZO­1 and E­cadherin, and the markedly downregulated expression of N­cadherin and α­SMA. Furthermore, the cells exhibited a normal, tightly connected hexagonal or pentagonal morphology. Additionally, the protein expression of ROCK1/2 and the mRNA expression of Snail were significantly decreased. However, there was no significant difference between the TZV­treated and the control groups as regards HCEC proliferative ability. These findings suggested that the ROCK inhibitor, TZV (4 µM), was effective in improving the morphology, cell junctions and ionic transporter expression of HCECs by inhibiting EndMT/EMT, but had no effect on HCEC proliferation.