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1.
Acta Pharmaceutica Sinica B ; (6): 781-794, 2024.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1011269

RESUMO

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-808777

RESUMO

Objective@#To investigate the dynamic change of paraquant-induced kidney injury in rats and the protective effect of edaravone.@*Methods@#Eighty SD rats were randomly divided into 4 groups: the normal control group, paraquat poisoning group, edaravone treatment group and edaravone control group. The normal control group of 8 rats were given 1 ml of 0.9% sodium chloride through the abdominal cavity, and the same amount of fluid into the abdominal cavity after 30 minutes. The paraquat poisoning group of 24 rats were given 1 ml of paraquat solution (20 mg/kg) through the abdominal cavity to build poisoning models, and the same amount of 0.9% sodium chloride was injected into the abdominal cavity after 30 minutes. The edaravone treatment group of 24 rats were given edaravone (5 mg/kg) through the abdominal cavity after 30 minutes when the poisoning models were set up. The edaravone control group of 24 rats were given 1 ml of 0.9% sodium chloride through the abdominal cavity, and edaravone (5 mg/kg) was injected into the abdominal cavity after 30 minutes. In addition to the normal control group, the other groups processed 1 times a day to mantain 7 d. On 1, 3, 7, 21 d several rats in each group were excuted and the kidney tissue and serum samples were collected, then each pathological changes of the kidney were observed with light microscopy. Serum creatinine, KIM-1, NGAL were measured by ELISA, the expression of HSP70 protein in kidney were observed with immunohistochemical staining.@*Results@#The pathological examination reveald that the damage of kidney tissue in the paraquat group was the most serious on 3 d, and the damage was consistently alleviated in edaravone treatment group at the same time, renal fibrosisn was unseen in each group until 21 d. Compared with normal control group, there was no statistically significant in edaravone control group (P>0.05) . The KIM-1 in blood and kidney in paraquat poisoning group were markedly increased in 1 d (P<0.05) . The NGAL in blood and creatinine were markedly increased in d7 (P<0.05) . The NGAL in kidney increased over time, but had no statistically difference with the control group (P>0.05) .Compared with paraquat poisoning group, the serum creatinine, KIM-1 in blood and kidney, the KIM-1 in kidney had decreased significantly in edaravone treatment group (P<0.05) . The NGAL in kidney has no statistically significant compared with the poisoning group (P>0.05) . HSP70 expression of kidney tissue in edaravone treatment group had significantly increased in d3 compared with the paraquat poisoning group (P<0.05) .@*Conclusion@#Edaravone can prompt a significant rise of HSP70 in kidney tissue, reduce KIM-1 and NGAL levels, and play a protective role in kidney injury of acute paraquat poisoning.

3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-539534

RESUMO

Objective To summarize the experience of early management in elderly patients with serious burning in order to raise cure rate. Methods Elderly patients (63 cases) with serious burning (burned area exceeding 30% or Ⅲ? area exceeding 10% ) admitted from 1990 to 2002 were retrospectively studied. Patients were divided into two groups according to the admission date, before and after January 1, 1996 since new management was extensively applied after 1996. These measures consisted of rapid and adequate fluid resuscitation, early enteral feeding and autograft after eschar excision. Results The incidence of sepsis and MODS was 38.7% and 19.4% respectively after 1996. It was evidently lower than the group before 1996(65.6% vs 43.8%, P

4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-517104

RESUMO

AIM:To study the diagnosis of hyperchloremic triple acid-base disorders (hyperchloremic TABD) and its mechanisms and to find out the cause of hyperchloremic TABD of the burn patients. METHODS:① 154 concomitant arterial blood gas and electrolyte panel of 113 burn patients were diagnosed by clinical approach. ② The plasma aldosterone concentrations of burn patients were tested by radioimmunoassay. RESULTS:9 cases of the 113 burn patients were hyperchloremic TABD. Their plasma aldosterone's values were significantly higher than that of the natural ( P

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