1.Association between sarcopenia and post-stroke cognitive impairment in elderly patients with first-time acute minor ischemic stroke
Zhang CHEN ; Hui LIU ; Yanggang LIN ; Fan FAN ; Qingsong WANG
Chinese Journal of Geriatrics 2021;40(4):444-449
Objective:To investigate the correlation between sarcopenia and post-stroke cognitive impairment(PSCI)in elderly patients with first-time acute minor ischemic stroke.Methods:This was a prospective study.Elderly patients over 60 years of age with first-time acute minor ischemic stroke admitted to the Department of Neurology of the General Hospital of Western Theater Command from October 2018 to June 2019 were continuously enrolled.Patients received the SARC-F score assessment within 24h after admission and were divided into two groups according to their SARC-F scores: the non-sarcopenia group(SARC-F score<4)and the sarcopenia group(SARC-F score≥4). Cognitive function was assessed by using the Mini-Mental State Examination(MMSE)within 24 h of admission and at 3-month follow-up.Results:A total of 211 patients were enrolled in this study, including 31 patients(31/211, 14.69%)in the sarcopenia group and 180 patients(180/211, 85.31%)in the non-sarcopenia group.The incidence of PSCI was higher in the sarcopenia group than in the non-sarcopenia group(83.87% or 26/31 vs.55.56% or 100/180, χ2=8.814, P=0.003). The total MMSE score, orientation, immediate memory, attention, calculation and language functions were lower in the sarcopenia group compared with non-sarcopenia group( P<0.05). Logistic regression analysis showed that sarcopenia was an independent risk factor for PSCI( OR=3.478, 95% CI: 1.039-11.642, P=0.043)in the elderly with first-time acute minor ischemic stroke. Conclusions:Sarcopenia is an independent risk factor for PSCI in elderly patients with first-time acute minor ischemic stroke.Sarcopenia assessment in the acute phase of stroke might help doctors to assess the risk of PSCI and reduce the incidence of PSCI in stroke patients.
2.Effects of chronic cerebral hypoperfusion on cognitive function and intestinal mucosal barrier in rats
Yanggang LIN ; Dan WANG ; Zhang CHEN ; Hui LIU ; Qingsong WANG
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(2):97-103
Objective:To explore the correlation between cognitive impairment and intestinal mucosal barrier injury in rats after chronic cerebral hypoperfusion(CCH), and to quantitatively analyze the changes in cognitive behavior of experimental rats caused by chronic cerebral hypoperfusion, as well as the expression changes of the intestinal mucosal barrier claudin-1 and osteopontin.Methods:Thirty male SD rats were randomly divided into CCH group ( n=15) and sham operation (SHAM) control group ( n=15). The CCH model was established by permanent ligation of bilateral common carotid arteries.Rats in the SHAM group only separated the common carotid artery without ligation.Four weeks later, open field experiment, object discrimination experiment, and Morris water maze experiment were used to detect the emotional arousal ability, the ability to explore new things, and the ability of spatial learning and memory in rats.HE staining and immunofluorescence experiments were conducted to detect the damage of rat ileum tissue.Western blot was used to detect OPN expression, and ELISA was used to detect serum OPN.SPSS 23.0 and GraphPad 8.0 statistical softwares were used to process the data, and the t-test and repeated measures one-way analysis of variance were used for data analysis. Results:In the open field test, compared with the SHAM group ((28.70±10.70)times, (1 030.45±81.51)cm), the number of standing and total exercise distance of rats in the CCH group ((16.70±7.13)times, (736.64±136.71)cm) were decreased( t=1.59, 4.16, both P<0.05). In the object discrimination experiment, the discrimination index of rats in the CCH group (0.44±0.26) was lower than that of the SHAM group (0.91±0.07, t=-7.76, P<0.05). Morris water maze positioning navigation experiment showed that the group main effect and time main effect were both significant( F=383.36, 153.87, P<0.05). Simple effect analysis showed that, compared with the SHAM group, the escape latency and total swimming distance of rats in CCH group increased( P<0.05). Space exploration experiment showed that, compared with SHAM group ((7.20±1.81)times, (9.96±2.95)s), the number of crossings of rats in CCH group ((3.00±0.82)times) decreased, and the incubation period ((29.70±6.28)s) was prolonged( t=4.65, 7.04, both P<0.05). The intestinal mucosal pathology score of SHAM group ((1.98±0.34)points) was lower than that of the CCH group ((4.52±0.27)points), and the difference was significant( t=18.53, P<0.01). Immunofluorescence experiment showed that, compared with SHAM group (125 028.58±33 077.39), the cumulative optical density of claudin-1 between the intestinal epithelial cells of the CCH group(47 154.50±7 507.29) decreased( t=16.10, P<0.01). Western blot experiment showed that, compared with the SHAM group (0.38±0.11), the expression of OPN in the intestines of the CCH group (1.20±0.95) increased( P<0.05). ELISA experiment showed that, compared with the SHAM group ((3.42±0.66)μg/L), the serum OPN content of the CCH group ((14.92±1.45)μg/L) significantly increased( P<0.05). The degree of cognitive impairment was negatively correlated with intestinal mucosal epithelial claudin-1 expression and serum OPN content( P<0.01). Intestinal mucosal epithelial claudin-1 expression was negatively correlated with serum OPN content ( r=-0.952, P<0.01). Conclusion:CCH may cause obvious cognitive impairment in rats and the destruction of the intestinal mucosal barrier.Serum OPN may be a potential serological marker of CCH-induced cognitive impairment and intestinal mucosal barrier destruction in rats.
3.Association of complement C3 with urine protein level and proteinuria remission status in patients with primary membranous nephropathy
Si CHEN ; Ying PAN ; Yifei LU ; Li QIAN ; Qing LI ; Yili XU ; Suyan DUAN ; Lin WU ; Bo ZHANG ; Changying XING ; Huijuan MAO ; Yanggang YUAN
Chinese Journal of Nephrology 2024;40(9):705-715
Objective:To investigate the correlation between complement C3 and urine protein level and proteinuria remission status in patients with primary membranous nephropathy (PMN), and better guide individualized clinical treatment.Methods:It was a single-center retrospective study. The clinical data of PMN patients who underwent renal biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2017 to June 2022 were collected. Patients with 24 h urinary protein ≥ 3.5 g were followed up after receiving standard treatment, and the last outpatient or inpatient review was used as the end point of follow-up. 24 h urine protein was collected to evaluate the remission status of proteinuria. Kaplan-Meier method was used to analyze the correlation between serum and renal complements and proteinuria remission. Cox regression analysis method was used to analyze the correlation between serum C3 level and renal tissue C3 deposition and proteinuria remission.Results:This study included 507 PMN patients with 312 (61.54%) males, aged 54 (43, 64) years old. Compared with 24 h urinary protein < 3.5 g group, proportion of males ( χ2=22.479, P<0.001), age ( Z=-2.521, P=0.012), systolic blood pressure ( Z=-4.148, P<0.001), diastolic blood pressure ( Z=-4.084, P<0.001), serum anti-phospholipase A2 receptor (PLA2R) antibody titer ( Z=-7.019, P<0.001), total cholesterol ( Z=-8.796, P<0.001), triglyceride ( Z=-6.158, P<0.001), low density lipoprotein cholesterol ( Z=-8.716, P<0.001), serum creatinine ( Z=-7.368, P<0.001), serum C3 ( Z=-3.663, P<0.001), serum C4 ( Z=-6.560, P<0.001), proportion of glucocorticoid use ( χ2=116.417, P<0.001) and proportion of immunosuppressant use ( χ2=53.839, P<0.001) were all higher, while serum albumin ( Z=12.518, P<0.001), estimated glomerular filtration rate ( Z=6.345, P<0.001) and serum IgG ( Z=7.321, P<0.001) were all lower in 24 h urinary protein ≥3.5 g group. There were 268 patients included in the follow-up cohort with baseline 24 h urinary protein of 7.15 (5.14, 10.24) g, serum anti-PLA2R antibody titer of 61.44 (14.35, 193.24) RU/ml, serum C3 of 1.005 (0.864, 1.150) g/L, and serum C4 of 0.260 (0.214, 0.317) g/L. Kaplan-Meier survival curve showed that the incomplete remission rate of proteinuria in serum C3 > 1.005 g/L group was lower than that in serum C3 ≤ 1.005 g/L group (log-rank χ2=4.757, P=0.029). There was no significant difference in the incomplete remission rate of proteinuria between serum C4 ≤ 0.260 g/L group and serum C4 > 0.260 g/L group (log-rank χ2=3.543, P=0.060). Renal C1q (log-rank χ2=0.167, P=0.683) and C4 (log-rank χ2=1.927, P=0.165) deposition had no significant effects on proteinuria remission in PMN patients. The incomplete remission rate of proteinuria in patients with renal C3 deposition was higher than that in patients without renal C3 deposition (log-rank χ2=7.018, P=0.008). Univariate Cox regression analysis showed that serum C3 level and C3 deposition in renal tissues were influencing factors of incomplete remission of proteinuria (both P<0.05), while adjusting for gender, age, mean arterial pressure, serum anti-PLA2R antibody, serum albumin and 24 h urinary protein, serum C3 ≤ 1.005 g/L ( HR=1.374, 95% CI 1.021-1.849, P=0.036), C3 deposition in renal tissues ( HR=1.949, 95% CI 1.098-3.460, P=0.023), and serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues ( HR=1.472, 95% CI 1.093-1.983, P=0.011) were independent influencing factors of incomplete remission of proteinuria. Conclusions:The serum C3 level and C3 deposition in renal tissues are closely related to urinary protein level and proteinuria remission status in PMN patients. The patients with higher urinary protein have higher serum C3. For patients with massive proteinuria, serum C3 ≤ 1.005 g/L, C3 deposition in renal tissues, serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues are independent risk factors of incomplete remission of proteinuria.