改性壳聚糖基导电复合材料神经导管的体内降解及组织相容性观察

目的探讨改性壳聚糖基导电复合材料神经导管的体内降解及组织相容性，以期为组织工程神经构建提供新的支架材料。方法采用微乳液聚合法合成纳米聚吡咯（polypyrrole，PPy），与壳聚糖共混后注入定制的成管模型，冷冻干燥及脱酸后，制成改性纳米 PPy/壳聚糖复合材料导管（记作 CP 导管）；再经不同程度乙酰化（乙酰化反应时间分别为 30、60、90 min）改性，制备不同乙酰度的 CP 导管（记作 CAP1、CAP2、CAP3 导管）。各导管予红外光谱、扫描电镜进行表征，使用四探针电导仪测定电导率。取 30 只雌性 SD 大鼠，于背部左、右侧各制备 4 个皮下筋膜隧道，分别植入上述导管。术后 2、4、6、8、10、12 周取材，大体观察导管形态及完整性、扫描电镜观察导管微观结构、测量导管降解率，以观察导管体内降解性能；行 HE 染色及抗巨噬细胞免疫荧光染色，观察导管体内组织相容性。结果经表征证实乙酰化改性后的各导管 1 562 cm^–1左右的酰胺Ⅱ谱带增强，表示壳聚糖乙酰化改性成功。各导管均具备导电性能，组间电导率差异无统计学意义（P>0.05）。扫描电镜观察示各导管表面相对光滑、结构致密，无明显差异。导管植入体内后，随时间延长均出现一定程度塌陷，其中 CAP3 导管尤为明显；亦出现不同程度质量丢失，且乙酰化度越高，质量变化越大（P<0.05）。扫描电镜观察示植入 12 周后材料出现较多孔隙，且随着乙酰化度增加，孔隙呈增大趋势。组织学观察显示术后早期各导管均有较多巨噬细胞、淋巴细胞浸润，随着植入时间延长，淋巴细胞有所减少、成纤维细胞增多、胶原纤维增生明显。 结论不同乙酰度的改性壳聚糖基导电复合材料神经导管均有较好的体内生物相容性、可导电、可降解，且降解性与乙酰度相关，有望为组织工程神经构建提供一种新的支架材料。     

Renal impairment and its impact on clinical outcomes in patients who are critically ill with COVID-19: a multicentre observational study

Renal impairment is common in patients who are critically ill with coronavirus disease-19 (COVID-19). We examined the association between acute and chronic kidney disease with clinical outcomes in 372 patients with coronavirus disease-19 admitted to four regional intensive care units between 10 March 2020 and 31 July 2020. A total of 216 (58%) patients presented with COVID-19 and renal impairment. Acute kidney injury and/or chronic kidney disease was associated with greater in-hospital mortality compared with patients with preserved renal function (107/216 patients (50%) (95%CI 44–57) vs. 32/156 (21%) (95%CI 15–28), respectively; p < 0.001, relative risk 2.4 (95%CI 1.7–3.4)). Mortality was greatest in patients with renal transplants (6/7 patients (86%) (95%CI 47–100)). Mortality rates increased in patients with worsening renal injury according to the Kidney Disease: Improving Global Outcomes classification: stage 0 mortality 33/157 patients (21%) (95%CI 15–28) vs. stages 1–3 mortality 91/186 patients (49%) (95%CI 42–56); p < 0.001, relative risk 2.3 (95%CI 1.7–3.3). Survivors were less likely to require renal replacement therapy compared with non-survivors (57/233 patients (24%) vs. 64/139 patients (46%), respectively; p < 0.001, relative risk 1.9 (95%CI 1.4–2.5)). One-fifth of survivors who required renal replacement therapy acutely in intensive care continued to require renal support following discharge. Our data demonstrate that renal impairment in patients admitted to intensive care with COVID-19 is common and is associated with a high mortality and requirement for on-going renal support after discharge from critical care. Our findings have important implications for future pandemic planning in this patient cohort.