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.

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.

Objective To explore the protection of early autophagy activation on podocyte injury induced by aldosterone.Methods In vitro cultured mouse podocyte clones (MPC5) were treated with aldosterone for 6,12,24,48 h respectively.Apoptosis of podocytes was detected by Annexin V combined with flow cytometry.After 24 h treatment with aldosterone,the existence of apoptotic body and autophagosome was observed by electron microscopy.The protein expressions of LC3,caspase-3 and nephrin were examined by Western blotting.The mRNA expression of Beclin-l was detected by real-time PCR.Results The induction of apoptosis and autophagy by aldosterone in podocytes was in timedependent mannner.After 24 h treatment with aldosterone,the apoptosis was increased by 26.5％ (P ＜ 0.05)and the expression of nephrin was decreased by 28.0％ (P ＜ 0.05) compared to control group.Aldosterone remarkably induced the expression of Beclin-1 at 6 h and promoted the transformation of LC3-Ⅰ to LC3-Ⅱat 12 h (P ＜ 0.05).Compared to simple aldosterone treatment,the apoptosis rate of podocyte was increased by 39.0％ (P ＜ 0.05) and the expression of nephrin was declined by 19.5％ (P ＜ 0.05) after 3-methyladenine (3-MA) pre-treatment.Conclusions Aldosterone can induce autophagy and apoptosis in podocytes.Autophagy occurs earlier (12 h) than apoptosis (24 h).The occurrence of autophagy can inhibit the apoptosis,so the autophagy pathway may be a new research topic of glomerular disease treatment.

Objective To detect the α1-antitrypsin (AAT) concentration in urine samples of children with primary nephrotic syndrome (PNS) before initiation of glucocorticoid treatment,in order to verify whether it could predict the response to glucocorticoid-based therapy.Methods Forty-three children diagnosed as PNS initially were chosen as subjects,namely steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) depending on reaction to glucocorticoid therapy four weeks later,and 15 healthy children serving as normal control.The mid stream of the first morning urine samples were collected from children before taking glucocorticoid.ELISA kit was used to quantify the urinary AAT concentration which was revised by urine creatinine further.The data of urine AAT/Cr were expressed as median with interquartile range.Data analysis was performed using the SPSS 17.0.Results AAT was absent in urine samples of normal healthy children,and there were no statistic differences of the AAT concentrations in urine between children with SSNS and SRNS [(30.4+4.5) mg/L vs (31.8+4.6) mg/L,t=-1.0,P=0.33].The level of urine AAT/Cr in children with SRNS was higher than that in children with SSNS [0.049(0.028-0.073) vs 0.028(0.022-0.036),Z=2.4,P=0.02].Among the laboratory parameters of the two subgroups before taking glucocortiod,the levels of platelet,blood white cell count,serum globulin,urine white cell count,urine red cell count,urine IgG and urine α1-microglobulin were significantly different (P＜0.05).Three parameters that included urine AAT/Cr (OR=6.81 × 1028,P=0.O05),serum globulin (OR=1.69,P=0.01) and urine α1-microglobulin (OR=1.05,P=0.009) further entered the logistic regression model to predict the SRNS independently.The ROC curve based on the level of the urine AAT/Cr was constructed,and the area under the curve (AUC) was 0.72.When the cutoff value of urine AAT/Cr was 0.035,the sensitivity and specificity of the urine AAT/Cr prediction were 68％ and 75％ respectively (Youden' s index 0.43).The AUC that based on the logistic regression model which included urine AAT/Cr,serum globulin and urine α1-mieroglobulin was improved to 0.94,and the sensitivity and specificity of the model prediction were 95％ and 83％ respectively (Youden' s index 0.78).There was no significant difference of the urine AAT/Cr level among the different pathological types of the children undergoing renal biopsy.Conclusions There are no statistic differences of the AAT concentrations in urine between children with SSNS and SRNS.The level of urine AAT/Cr is significantly higher in the SRNS than that in the SSNS which can be as a candidate biomarker to predict the response to glucocorticoid-based therapy.It has a better prediction efficacy based on the model which includes urine AAT/Cr,serum globulin and urine α1-microglobulin.

Objective:To study the antibacterial properties and in vivo and vitro biocompatibility of Cu-Fe-Zn alloy microfilament dressings, and to evaluate their wound healing promoting effect through clinical application.Methods:We evaluated the comprehensive antibacterial performance of dressings in vitro using plate counting method; After co culturing the extract of Cu-Fe-Zn alloy microfilament dressings with epidermal cells (HaCaT) and fibroblasts (NIH-3T3), their in-vitro biocompatibility was determined through the cell counting kit-8 (CCK-8) test; Further, Cu-Fe-Zn alloy microfilament dressing was applied to the wound surface of diabetes mice to test the biocompatibility of the material in vivo; Through a prospective randomized controlled trial, 50 burn and trauma patients admitted to the Burn and Plastic Surgery Department of the Third Xiangya Hospital of Central South University were selected and divided into an observation group of 25 patients and a control group of 25 patients. The observation group was treated with Cu-Fe-Zn alloy microfilament dressing, and the control group was treated with silver nanoparticle antibacterial dressing. The wound healing time and wound treatment effect of the two groups were compared.Results:The Cu 2+ release concentration of Cu-Fe-Zn alloy microfilament dressings detected by inductively coupled plasma-mass spectrometry (ICP-MS) was 1.3 μ g/ml, which had the effect of promoting the proliferation of HaCaT and NIH-3T3 cells (all P<0.05). The antibacterial rate of Cu-Fe-Zn alloy microfilament dressing against pseudomonas aeruginosa, escherichia coli and staphylococcus aureus reached 100%. The wound healing rate [(87.39±1.83)%] of diabetes mice treated with Cu-Fe-Zn alloy microfilament dressing was significantly higher than that of the control group [(58.66±3.54)%, P<0.05]. The inflammatory response of the wound tissue was relatively mild and the wound margin matrix was intact. The wound healing time of 25 patients treated with Cu-Fe-Zn alloy microfilament dressing [(23.52±10.02)d] was shorter than that of the control group [(40.84±21.22)d] ( t=17.159, P<0.001), and the overall treatment response rate of patients (96%) was significantly higher than that of the control group patients (64%) (χ 2=8.472, P=0.015). Conclusions:Cu-Fe-Zn alloy microfilament dressings have good antibacterial properties and biocompatibility, and have significant therapeutic effects on promoting wound healing. They not only effectively promote wound healing but also exert anti infection effects, and are expected to be a new type of wound repair dressing.

Objective:To determine the prognostic values of clinical and laboratory features at the time of presentation on renal survival of patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody(ANCA)-associated glomerulonephritis (MPO-ANCA-GN).Methods:A total of 172 patients with MPO-ANCA-GN and hospitalized at the First Affiliated Hospital of Nanjing Medical University from January 2005 to December 2018 were enrolled. The baseline clinical characteristics and renal biopsy pathological data were analyzed, and the renal prognosis was followed up. The clinical and pathological characteristics of different renal prognosis in all patients and 112 patients who underwent renal biopsy were analyzed, and the related factors affecting renal survival were further discussed.Results:Among these 172 patients, 81 were males and 91 were females. The median serum creatinine at diagnosis was 343.7(174.2, 606.6) μmol/L and the median estimated glomerular filtration rate (eGFR) was 15.81(7.61, 38.04) ml·min -1·(1.73 m 2) -1. In total, 76 patients (44.2%) received initial renal replacement therapy (RRT). During a median follow-up duration of 20(3, 60) months, 73 patients (42.4%) progressed to end-stage renal disease (ESRD) and required dialysis, including 6 (8.2%) patients who entered RRT during follow-up and 67 (91.8%) patients who received RRT at the beginning. Among the 112 patients who underwent renal biopsy, the proportion of patients who progressed to ESRD in the sclerotic group was the highest (15/25, 60.0%). The baseline serum creatinine level ( P<0.001), urine red blood cell count ( P=0.012) and the proportion of glomerular sclerosis ( P=0.002) in the non-dialysis dependent group were significantly lower than those in the dialysis dependent group, while the levels of eGFR ( P<0.001), serum albumin ( P=0.002) and hemoglobin ( P<0.001) were higher than those of the dialysis-dependent group. Kaplan-Meier survival analysis showed that the renal survival rate of the focal group was the highest ( χ2=19.488, P<0.001, log-rank test), while the renal survival rate of the sclerotic group was significantly lower than that of the crescentic group ( χ2=5.655, P=0.017); higher levels of serum creatinine (>320 μmol/L, χ2=77.229, P<0.001) and urine red blood cell count (>300 cells/μl, χ2=8.511, P=0.004), lower levels of rheumatoid factor (<20 IU/ml, χ2=8.610, P=0.003), serum albumin (<30 g/L, χ2=11.060, P=0.001) and hemoglobin (<90 g/L, χ2=21.921, P<0.001) were associated with lower renal survival rate; in terms of treatment, the renal survival rate of the glucocorticoids plus mycophenolate mofetil group was significantly higher than that of the glucocorticoids plus cyclophosphamide ( χ2=5.056, P=0.025) or the glucocorticoids alone group ( χ2=16.459, P<0.001). Multivariate Cox regression showed that baseline serum creatinine >320 μmol/L ( HR=8.803, 95% CI 3.087-25.106, P<0.001) and serum albumin <30 g/L ( HR=2.566, 95% CI 1.246-5.281, P=0.011) were the related factors affecting renal survival. Conclusion:Serum creatinine and albumin levels of MPO-ANCA-GN patients at diagnosis may be the related factors that affect the patient's renal prognosis.

Objective: Currently, parathyroid hormone (PTH) is mainly measured by the second generation intact PTH (iPTH) assay which detects both full-length (1-84)PTH and (7-84)PTH fragments. The third generation whole PTH (wPTH) assay however has turned out to be specific for (1-84) PTH. The aim of this study is to investigate the features of plasma iPTH, (1-84)PTH, (7-84)PTH levels in patients with stage 5 chronic kidney disease (CKD), and evaluate the effects of parathyroidectomy (PTX) on above markers in severe secondary hyperparathyroidism (SHPT) patients. Methods: A cross-sectional study including 90 controls and 233 stage 5 CKD patients, and a prospective follow-up study in 31 severe SHPT patients were conducted. Plasma iPTH and (1-84)PTH levels were measured by the second and third generation assay, respectively. Circulating (7-84)PTH level was calculated by subtracting the (1-84)PTH value from the iPTH value. Results: Plasma levels of iPTH, (1-84)PTH, (7-84)PTH were higher (P<0.01), and (1-84)PTH/iPTH was lower (P<0.01) in stage 5 CKD patients than in controls. For severe SHPT patients with PTX (n=74), plasma iPTH, (1-84)PTH and (7-84)PTH concentrations were significantly increased compared to non-PTX group (n=159) (P<0.01), and the increase of (7-84)PTH level was more striking than (1-84)PTH. Meanwhile, the value of (1-84)PTH/iPTH was decreased (P<0.01). Plasma iPTH level was strongly correlated with (1-84)PTH level (r=0.980, P<0.01) in stage 5 CKD patients. Also, both iPTH and (1-84)PTH levels were positively correlated with serum alkaline phosphatase, dialysis vintage and serum phosphorus (P<0.01). After PTX (median interval of follow-up: 7.1 months), plasma iPTH, (1-84)PTH, (7-84)PTH concentrations were decreased (by 92.9%, 89.7%, 95.8%, P<0.01, respectively) greatly and (1-84)PTH/iPTH was increased (P<0.01). Conclusions In stage 5 CKD patients, plasma iPTH, (1-84)PTH, (7-84)PTH levels are greatly increased while (1-84)PTH/iPTH is decreased, and PTX can significantly improve abnormality of above markers in severe SHPT patients. The second generation PTH assay overestimates the severity of SHPT, and the accurate measurement of (1-84)PTH by the third assays is more conducive to diagnosis and treatment of CKD and SHPT patients.

The cytochrome P450 (CYP) family is the most important drug-metabolizing enzyme in human body and is responsible for the metabolism of endogenous and exogenous compounds. As the main site of the expression of the CYP family, the liver is the metabolic center of drugs, and in recent years, the role of the CYP family in the liver has attracted wide attention from the scholars in China and globally. This article reviews the distribution differences of the CYP family from the aspects of anatomy, genetics, and genomics, changes in the expression of the CYP family in the pathological processes such as non-alcoholic fatty liver disease, alcoholic liver disease, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma, and the effect of CYP family-mediated enzyme activity on the treatment effect of pharmacotherapy for metabolic-associated liver diseases, in order to provide important enlightenment for identifying key drug intervention targets in diseases and enhancing clinical efficacy and safety.