pH-Responsive Co-Assembled Peptide Hydrogel to Inhibit Drug-Resistant Bacterial Infection and Promote Wound Healing.

Drug-resistant bacterial infection and biofilm formation are the key inhibitors of wound healing, and new strategies are urgently needed to address these issues. In this study, we designed a pH-responsive co-assembled peptide hydrogel to inhibit Methicillin-resistant Staphylococcus aureus (MRSA) infection and promote wound healing. We synthesized a cationic short peptide (Nap-FFKKK) and a co-assembled hydrogel with curcumin at pH ∼ 7.8. The loaded curcumin was continuously released in a weak acid environment (pH ∼ 5.5). The lysine-rich cationic peptide inhibited biofilm formation in MRSA via electrostatic interaction with the negatively charged bacterial cell surface and, thus, provided a reinforcing antibacterial effect with curcumin. In vitro antibacterial experiments showed that the co-assembled system considerably reduced the minimum inhibitory concentration of curcumin against MRSA by 10-fold and promoted wound healing in a mouse model of MRSA-infected wounds. This study provides a simple and promising strategy to treat drug-resistant bacterial infections in wounds.

Prognosis of concurrent endoscopic dacryocystorhinostomy and nasal septoplasty for chronic dacryocystitis with moderate nasal septum deviation.

CONTEXT: The prognosis of combined septoplasty and endoscopic dacryocystorhinostomy (En-DCR) for moderate nasal septum deviation (NSD) has not yet been fully investigated. PURPOSE: To evaluate whether septoplasty improves the prognosis of En-DCR for moderate NSD. SETTINGS AND DESIGN: A retrospective cohort study in a real-world clinical setting. METHODS: The postoperative FICI DCR ostium grading scores and functional and anatomical information at 1, 2, 3, and 6 months were determined for consecutive patients with chronic dacryocystitis (CD) and moderate NSD who underwent En-DCR. STATISTICAL ANALYSIS USED: Univariate and generalized estimating equation multivariate analyses were used to compare the outcomes of the septoplasty and non-septoplasty groups. RESULTS: En-DCR and septoplasty were concurrently performed for 32 (20.1%, 32/158) cases. The total FICI DCR ostial scores for the septoplasty and non-septoplasty groups were highest at the first (4.97 ± 0.177 vs. 4.97 ± 0.176, P > 0.05) and lowest at the sixth (4.41 ± 1.341 vs. 4.50 ± 1.355, P > 0.05) postoperative months. At the end of follow-up, the two groups showed comparable proportions of patients requiring definitive intervention for the ostium (6.3% vs. 7.1%, P > 0.05), comparabe functional success rates (87.5% vs. 90.5%, P > 0.05) and anatomical success rates (93.8% vs. 92.9%, P > 0.05). Only the non-septoplasty group experienced nasal mucosal adhesions (3.2%, 4/126). CONCLUSIONS: In patients with CD and moderate NSD, nasal septoplasty did not impact En-DCR prognosis, but reduced the complications. Skilled surgeons should reconsider septoplasty in the absence of otolaryngological indications.

Changes in axial length in anisometropic children wearing orthokeratology lenses.

Purpose: There is a particular anisometropia occurring in one eye with myopia, while the other eye has very low myopia, emmetropia, or very low hyperopia. It is unclear how the binocular axial length changes when these children wear unilateral OK lenses only in the more myopic eyes. This study investigates the changes in the axial elongation of both eyes. Methods: This is a 1-year retrospective study. In total, 148 children with myopic anisometropia were included. The more myopic eyes were wearing orthokeratology lenses (treated eyes), whereas the contralateral eyes were not indicated for visual correction (untreated eyes). The untreated eyes were classified into three subgroups based on the spherical equivalent refraction (SER): low myopia (≤ -0.50 D, n = 37), emmetropia (+0.49 to -0.49 D, n = 76), and low hyperopia (≥0.50 D, n = 35). Changes in the axial length (AL) were compared between the untreated and treated eyes and among the three subgroups. Results: The axial elongation was 0.14 ± 0.18 mm and 0.39 ± 0.27 mm in all treated and untreated eyes, respectively (p < 0.001). The interocular AL difference decreased significantly from 1.09 ± 0.45 mm at the baseline to 0.84 ± 0.52 mm at 1 year (p < 0.001). The baseline median (Q1, Q3) SER of the untreated eyes were -0.75 D (-0.56, -0.88 D), 0.00 D (0.00, -0.25 D), and +0.75 D (+1.00, +0.62 D) in low myopia, emmetropia, and low hyperopia subgroups, respectively. The axial elongation was 0.14 ± 0.18 mm, 0.15 ± 0.17 mm, and 0.13 ± 0.21 mm (p = 0.92) in the treated eyes and 0.44 ± 0.25 mm, 0.35 ± 0.24 mm, and 0.41 ± 0.33 mm in the untreated eyes (p = 0.11) after 1 year. Multivariate linear regression analyses only showed significant differences in axial elongation between the emmetropia and low myopia subgroups of untreated eyes (p = 0.04; p > 0.05 between other subgroups). Conclusion: Unilateral orthokeratology lenses effectively reduced axial elongation in the more myopic eyes and reduced interocular AL differences in children with myopic anisometropia. The refractive state of the untreated eyes did not affect the axial elongation of the more myopic eye wearing the orthokeratology lens. In the untreated eyes, AL increased faster in the low myopia subgroup than in the emmetropia subgroup.

Effects of Food and Multiple-dose Administration on the Pharmacokinetic Properties of HR20033, a Sustained-release Formulation of Henagliflozin and Metformin for the Treatment of Diabetes, in Healthy Chinese Volunteers.

Henagliflozin proline and metformin hydrochloride sustained-release tablets (HR20033) are a fixed-dose combination of the novel, highly selective, and effective sodium-glucose cotransporter-2 inhibitor henagliflozin, with a metformin sustained-release layer for the treatment of type 2 diabetes mellitus in conjunction with dietary control and exercise. The aims of this study were to investigate the effect of a high-fat diet on the pharmacokinetics of henagliflozin and metformin after a single administration of HR20033 and the effect of repeated oral administration of HR20033 on their pharmacokinetics in healthy volunteers. The food-effect clinical study involved 18 healthy subjects randomized to receive either HR20033 in the fasted condition followed by HR20033 in the fed condition or the reverse schedule, with the two doses separated by a washout period of at least 7 days. The multiple-dose clinical study was conducted on 10 healthy subjects. In the food-effect study, compared with those in the fasted condition, the area under the blood concentration curve (AUC) and peak concentration (Cmax ) of henagliflozin decreased by 12.64% and 40.89%, respectively, while the AUC of metformin increased by 31.13% and Cmax decreased by 7.09% in the fed state. There was no significant accumulation of HR20033 in the body after multiple oral doses. No serious adverse event was observed in either of the two clinical studies. Food did not have a clinically meaningful effect on the absorption of HR20033.

Microbial spectrum and antibiotic sensitivity in infantile dacryocystitis.

PURPOSE: To identify the characteristics and the spectrum of microbial agents of infantile dacryocystitis and to assess the trends in both antibiotic sensitivities and pathogens over the past 10 years. METHODS: The microbial and medical records of 546 culture-proven patients (546 eyes) of infantile dacryocystitis diagnosed at Henan Eye Hospital between January 2009 and December 2018 were retrospectively reviewed. Patient demographics, microbial analysis, and susceptibility rates to various antibiotics were done. A chi-squared test for trends was applied to evaluate changes in antibiotic susceptibility and microbial spectrum over time. RESULTS: A total of 546 patients with infantile dacryocystitis were documented. The average age was 2.97 ± 4.15 months, and 42.7% were female. The proportion of gram-positive microbes, gram-negative microbes, and fungi was 80.2, 19.4, and 0.4%, respectively. Minocycline was sensitive to gram-positive bacteria (98.0%). Imipenem was sensitive to gram-negative bacteria (89.2%). Increasing susceptibility was observed in two bacterial isolates: Staphylococcus aureus (P = 0.005) and Streptococcus mitis (P = 0.001). Decreasing susceptibility was observed in one bacterial isolate: Staphylococcus epidermidis (P < 0.0001). Increasing microbial susceptibility over time was detected for 12 antibiotics. Decreasing microbial sensitivity was observed for one antibiotic. CONCLUSIONS: The most common cause of infantile dacryocystitis is Staphylococcus epidermidis. Though a significant trend towards increasing microbial sensitivity to some antibiotics was observed, including glycopeptides, cephalosporins, fluoroquinolones, tetracyclines, and lincosamides, a significant trend towards decreasing microbial sensitivity to amikacin was also detected.