Endovascular interventional therapy is currently the main treatment for acute ischemic stroke，but some patients still have not achieved neurological function independence. Analysis of the predictive value of various factors for postoperative neurological function changes can provide more reference for selecting appropriate patient groups and treatment plans.

Objective To enhance the cyclic peptide compound's membrane permeability,structural stability,and neuroprotective activity,based on the amino acid sequence of peptides of Tat-GluA2-3Y,by designing and synthesizing a serial of cyclic peptides through strategies including polypeptide cyclization,replacement of the cell-penetrating peptide,substitution with D-amino acids,and incorporation of mini polyethylene glycol fragments.Methods The target peptides were synthesized based on standard Fmoc solid-phase method,followed by analysis and purification via reverse phase high-performance liguid chromatography(RP-HPLC).The cytoprotective activity of the peptides was evaluated by using the HT-22 cell model.The transmembrane transport efficiency of the peptides was determined based on the Caco-2 monolayer intestinal epithelial cell model.Plasmatic plasma and metabolic stability of the peptides were measured by in vitro co-incubation experiments with rat plasma and human liver microsomes.Finally,the in vivo neuroprotective activity of the peptides was validated by using a mouse middle cerebral artery occlusion model.Results Seven cyclic peptides were successfully designed and synthesized by using the standard Fmoc solid-phase method,with purities exceeding 90%as confirmed by RP-HPLC.Cytoprotective activity assay demonstrated that both Tat-GluA2-3Y and CMT-C3Y exhibited activity at concentrations above 125 nmol/L,with CMT-C3Y showing superior activity as compared to Tat-GluA2-3Y.The results of the transmembrane assay demonstrated that,compared to Tat-GluA2-3Y,CMT-C3Y exhibited significant transmembrane capabilities at all tested concentrations(P<0.001).CMT-C3Y was classified as a highly permeable compound,whereas Tat-GluA2-3Y was categorized as a moderately permeable compound.Plasma stability studies indicated that over 50%of Tat-GluA2-3Y was metabolized after 4 h of co-incubation with rat plasma.After 8 h of coincubation with CMT-C3Y,the remaining amount was 88.1%,and no obvious degradation phenomenon occurred.In human liver microsomal stability tests,the half-life of Tat-GluA2-3Y was 26.1 min,as compared to 103.8 min for CMT-C3Y,highlighting the enhanced stability of CMT-C3Y.Tat-GluA2-3Y and CMT-C3Y were classified as a fast-metabolizing drug and a moderate-metabolizing drug,respectively.Animal experiments further demonstrated that at a dose of 8 mg/kg the neuroprotective activity of CMT-C3Y was significantly superior to that of Tat-GluA2-3Y(P<0.001).Conclusion The designed bicyclic peptide CMT-C3Y demonstrates significantly higher cell-penetrating efficiency and superior plasma stability as compared to Tat-GluA2-3Y,along with enhanced neuroprotective activity at both cellular and animal levels.

Objective:To investigate the value of T 1ρ mapping in the assessment of myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). Methods:Forty HCM patients and 16 healthy volunteers who underwent CMR examination between December 2021 and May 2022 were prospectively enrolled. T 1ρ mapping, pre-and post-contrast T 1 mapping, and gadolinium contrast-enhanced delayed enhancement (LGE) imaging were performed in HCM patients, while T 1ρ mapping and T 1 mapping were performed in volunteers. HCM patients were further divided into LGE-positive (LGE+) and LGE-negative (LGE-) groups based on the presence or absence of LGE. The T 1ρ and pre-contrast T 1 values of the left ventricular myocardium of HCM patients and volunteers were measured, and the extracellular volume fraction (ECV) of the left ventricular myocardium of HCM patients was measured using pre-and post-contrast T 1 mapping. One-way ANOVA was used to compare the T 1ρ and pre-contrast T 1 values among the LGE+, LGE-, and volunteer groups, and pairwise comparisons were further corrected using the Bonferroni method. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of pre-contrast T 1 and T 1ρ values in distinguishing LGE+ and LGE- patients from volunteers. The chi-square test or Fisher′s exact probability test was used for categorical variable comparisons. Pearson correlation coefficient was used to evaluate the correlation between T 1ρ and pre-contrast T 1, and ECV. Results:There were no significant differences in age, gender, and body surface area among the LGE+, LGE-, and healthy control groups ( P>0.05). Compared to the HC group, both the T 1ρ value ( t=5.74, P<0.001) and the pre-contrast T 1 value ( t=3.99, P<0.001) increased in LGE positive group, as well as in the LGE negative group (T 1ρ: t=4.19, P<0.001; T 1: t=2.06, P<0.044). ROC analysis showed that the area under the curve (AUC) of T 1ρ and pre-contrast T 1 in distinguishing LGE+patients from healthy controls were 0.93 (sensitivity 84.0%, specificity 93.8%) and 0.87 (sensitivity 84.0%, specificity 87.5%), respectively. The AUC of T 1ρ and pre-contrast T 1 in distinguishing LGE-patients from healthy controls were 0.84 (sensitivity 86.7%, specificity 68.8%) and 0.68 (sensitivity 60%, specificity 68.8%), respectively. The correlation analysis showed that the T 1ρ value of the left ventricular myocardium was positively correlated with the pre-contrast T 1 value ( r=0.31, P=0.02) and ECV value ( r=0.38, P=0.02). Conclusion:Without the use of contrast agents, T 1ρ mapping shows good performance for myocardial replacement fibrosis and diffuse fibrosis in HCM patients.

Background; Immunological dysfunction plays a key role in the pathogenesis of inflammatory bowel disease (I B D). Notopterol is the main ingredient of the traditional Chinese herb medicine Notopterygium ineisum Ting ex H. T. Chang and has anti-inflammatory effect. Aims; To explore the effect of notopterol on dextran sulfate sodium (DSS)-induced colitis in mice. Methods; C57BL/6 mice were randomly divided into normal group, negative control group, model group and notopterol group. Mice in model group and notopterol group were treated with 2% DSS to induce colitis. Mice in negative control group and notopterol group were injected intraperitoneally with notopterol 40 mg/kg, and mice in normal group and model group were injected intraperitoneally with 0. 9% NaCl solution. Mice were sacrificed 10 days later, and disease activity index (DAI) score, colon length and histopathologieal score were determined. The levels of TNF-α, IL-1β, IL-6, IL-17A were assessed by ELISA. The mRNA expressions of IL-17A, RORγt were detected by quantitative PCR. Results; Compared with the normal group, DAI score, histopathologieal score, levels of TNF-α, IL-1β, IL-6, IL-17A, mRNA expressions of IL-17A and RORγt in model group were significantly increased (P < 0. 0 1), and colon length were significantly shortened (P < 0. 0 1). Compared with the model group, notopterol significantly reduced DAI score and histopathologieal score (P<0.01), downregulated levels of TNF-α, IL-1β, IL-6, IL-17A (P<0.01), inhibited the mRNA expressions of IL-17A, ROR-γt (P < 0. 0 1), and greatly recovered colon length (P < 0. 0 1). Conclusions; Notopterol has protective effects on DSS-induced colitis in mice. The mechanism may be related to reducing the secretion of pro-inflammatory cytokines and inhibiting the function and differentiation of Thl7 cells.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

Objective:To investigate the relationship between enlarged perivascular space (EPVS) and retinal vessel abnormalities in transient ischemic attack (TIA) and mild stroke patients.Methods:TIA and mild cerebral infarction (National Institutes of Health Stroke Scale score≤3) patients were enrolled from March to August 2019 in Changzhou Second People′s Hospital. Magnetic resonance imaging and retinal fundus photography were performed in all patients. Retinal arteriovenous diameter was semi-automatically measured, and retinal arteriosclerosis grades, vascular curvature, hemorrhages, microangioma, hard exudation, soft exudation, arteriovenous nicking and venous beads were assessed. Patients were divided into two groups according to the existence of EPVS: EPVS group and non-EPVS group. The baseline data of the two groups were compared and further multivariate Logistic regression was carried out. After normal transformation of the number of EPVS, the correlation between the grades of EPVS and converted EPVS was analyzed. The relationship between the number of converted EPVS and the grades and retinal fundus vascular lesions was further analyzed.Results:A total of 123 patients were included, including 99 patients with cerebral infarction, 24 patients with TIA; 52 patients without EPVS and 71 patients with EPVS. The EPVS group was more than the non-EPVS group in age ((68.61±12.71) years and (63.37±13.53) years, t=-2.198, P=0.030), history of hypertension (52 (73.2%) and 25 (48.1%), χ 2=8.118, P=0.004), hemangioma (17 (23.9%) and 5 (9.6%), χ 2=4.196, P=0.041), arteriovenous nicking (50 (70.4%) and 8 (15.4%), χ 2=36.488, P<0.05) and arteriosclerosis grades (1 (1, 2) and 0 (0, 1), Z=-7.454, P<0.05), and less than the non-EPVS group in central retinal artery equivalent (CRAE; (106.31±15.02) mm and (113.89±11.86) mm, t=3.014, P=0.003) and arteriole-to-venule ratio (AVR; 0.54±0.07 and 0.59±0.05, t=4.553, P<0.05). Multivariate Logistic regression analysis showed arteriosclerosis grades ( OR=7.781, 95 %CI 2.876-21.055, P<0.05) and hypertension ( OR=3.203, 95 %CI 1.049-9.777, P=0.041) were related factors for EPVS. Adjusting for age, sex, hypertension and diabetes, the normally transformed EPVS was found positively correlated with arteriovenous nicking ( B=0.556, 95 %CI 0.203-0.910, P=0.003) and arteriosclerosis grade ( B=0.417, 95 %CI 0.259-0.576, P<0.05), and negatively correlated with AVR ( B=-4.213, 95 %CI-6.712--1.714, P=0.001). The grades of EPVS were positively correlated with arteriosclerosis ( r=0.764, P<0.05), and negatively correlated with CRAE ( r=-0.287, P<0.05) and AVR ( r=-0.422, P<0.05). Conclusions:Hypertension and retinal arteriosclerosis are related factors of EPVS in mild stroke and TIA patients. EPVS is correlated with retinal vessel abnormalities. The more serious of EPVS is, the more serious of retinal arteriosclerosis is, the higher ratio of arteriovenous nicking is, the smaller of CRAE and AVR are.

Objective: Remuzzi scoring system is utilized for assessing the degree of renal tissue damage in donors with hypertensive cerebral hemorrhage and donors with brain trauma after cardiac death. To explore the prognosis of hypertensive cerebral hemorrhage donor kidney in renal transplant recipients. Methods: The kidney donated by DCD between January 1, 2016 to June 1, 2018 were retrospectively reviewed. Pathological biopsy was performed before transplantation and hematoxylin-eosin (HE) staining after sectioning. The degree of renal tissue lesions was evaluated by Remuzzi scoring system. According to the source of donor kidney, they were divided into two groups of donors with heart failure due to hypertensive cerebral hemorrhage (HCH) and those with brain trauma (BT). Both groups of donor kidneys were preserved by low-temperature machine perfusion. The immunosuppressive regimen was identical in both groups. The prognosis of two groups was compared by serum creatinine (Scr) at Month 1/6/12 post-operation and cumulative graft survival rate over a follow-up period of 12-36 months. Results: The renal Remuzzi score of HCH donors was significantly higher than that of BT donors. The maximal creatinine clearance rate was significantly lower than that of BT donors [(86.8±27.8) vs (115.4±23.2) ml/min, P<0.05]. At 1/6/12 months post-transplantation, serum creatinine levels were (76.1±18.5), (72.4±16.2) and (71.4±16.8) μmol/L in BT group and (160.3±33.4), (154.3±32.6) and (146.4±29.1) μmol/L in HCH group. The SCr in BT group at 1/6/12 months was lower than that in HCH group (P<0.05). Kaplan-meier analysis showed no significant inter-group difference in graft survival between two groups over a follow-up period of 12 to 36 months (Log-Rank test, P=0.485). Conclusions No significant difference exists in short-term survival rate of kidneys from HCH and BT donors. The recipients of HCH donor's kidney have higher serum creatinine levels than those of BT donors. Selective use of kidney transplants in patients with cardiac death caused by HCH may greatly reduce the waste of donor kidney and improve the quality-of-life of patients with end-stage renal disease.

Objective To analyze the factors and prognosis of graft recovery after donation after citizens death (DCD) donor renal transplantation.Methods A retrospective analysis of 67 cases of DCD renal transplantation from August 2012 to September 2015 in our hospital was carried out.According to the stability of renal function after operation,the patients were divided into group A (51cases) with stable renal function,and 16 cases in group B (delayed graft function after operation).The clinical data of two groups including age,gender,cause of death,warm ischemia time,type of dialysis,and application of norepinephrine before operation were collected and analyzed.The related factors of graft function recovery were analyzed.Logistic regression analysis was used to analyze the risk factors of graft functional recovery after operation.The 3-month,6-month,1-year and 18-month survival rate after operation in the two groups was compared.Results The causes of death,the time of ischemia,the type of dialysis before operation,the application of norepinephrine before operation,infants and young donors were related factors of graft function recovery (P ＜ 0.05).Logistic regression analysis showed that cerebral hemorrhage death donor,the long thermal ischemia time,the preoperative hemodialysis and the application of norepinephrine before operation were the risk factors of delayed graft function recovery (P＜0.05).The 3-month,6-month,1-year and 18-month survival rate after operation in group A was higher than that in group B,with the difference being statistically significant (P＜0.05).Conclusion Cerebral hemorrhage death donor,the long thermal ischemia time,the preoperative hemodialysis and the application of norepinephrine before operation were the independent risk factors of delayed graft function recovery.And the prognosis of patients with delayed graft function was poor.Clinical risk should be eliminated or reduced in clinical practice,which can effectively prevent the delayed graft function and further improve the prognosis of the patients.

Objective To explore the role of hydrogen sulfide (H 2S ) in acute liver injury induced by crush-ing hind lim bs of rats. Methods The rats w ere random ly divided into the follow ing groups:control, crush-ing, H 2S donor sodium hydrosulfide (NaHS) + crushing, H 2S inhibitor propargylglycine (PAG ) + crush-ing group. The acute liver injury m odel w as established by crushing the hind lim bs of rats w ith standard w eight. R ats w ere sacrificed at 30 m in and 120 m in after the crush. The activities of serum aspartate am inotransferase (AST) and alanine am inotransferase (ALT) w ere m easured by colorim etric m ethod, and the content of H 2S in plasm a and the contents of m alondialdehyde (MDA), protein carbonyl, glutathione (GSH) in the liver and the activity of H 2S generating enzym e (cystathionine γ-lyase, CSE) w ere deter-m ined by chem ical m ethod. The expression of CSEm R N Ain liver w as detected by R T-PCR . Results For crush injury group, the levels of ASTand ALTin serum , MDAand protein carbonyl in liver in-creased. The levels of GSH, CSE, CSEm R N Ain liver and H 2S in serum decreased. The adm inistration of NaHS before lim bs crush could attenuate the changes of liver injury, but the pre-treatm ent w ith PAG could exacerbate the changes. Conclusion The decrease of H 2S production could involve in m ediating the acute liver injury induced by traum atic stress in rats.