OBJECTIVE: Exploring the formation and aggregation of human islet amyloid polypeptide (hIAPP) (amylin) fibers is significant for promoting the prevention and treatment of type II diabetes mellitus (T2DM). Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect. The present study aimed to investigate the effects of five flavones [naringin (NRG), narirutin (NRR), nobiletin (NOB), sinensetin (SIN), and neohesperidin (NHP)] in pomelo peel on peptide aggregation and explore its possible mechanisms. The cell viability of flavones against peptide aggregation was also evaluated. METHODS: The thioflavin T (ThT) assay and transmission electron microscopy (TEM) were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation. The interaction mechanism was analyzed by endogenous fluorescence, molecular dynamics (MD) simulations, ultraviolet spectroscopy (UV) and isothermal titration calorimetry (ITC) experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and immune assays were performed to characterize the cell viability of flavones against peptide aggregation. RESULTS: The five flavones showed a decrease in fluorescence intensity, fiber number and size under incubation with different molar ratios of hIAPP. The compounds can bind to the aromatic tyrosine (Tyr) residueTyr 37, resulting in the intrinsic fluorescence quenching of the peptides. Five flavones can form hydrogen bonds with hIAPP, which is likely to be based on their phenolic hydroxyl structure. They showed strong binding affinity with peptides. The reaction system of NRG and NRR observed an exothermic reaction, and the others were endothermic reactions. The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects, indicating that there may be π-π stacking interaction. Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers. CONCLUSION A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils, and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious complication following cardiac surgical procedures. The conventional diagnostic methods relying on serum creatinine and urine output changes often exhibit delayed responsiveness. Therefore, there is an urgent need for highly sensitive and specific biomarkers to detect and identify high-risk patients with CSA-AKI at an early stage, allowing for timely intervention and improved clinical outcomes. In this paper, the relevant biomarkers of CSA-AKI were reviewed in order to provide valuable information for the subsequent research on CSA-AKI.

Objective:To explore the characteristics of sleep disorders in patients with Parkinson's disease (PD) and its correlation with homocysteine.Methods:Totally 75 PD patients hospitalized in the department of neurology from January 2017 to June 2021 were selected and divided into sleep disorder group ( n=39) and non-sleep disorder group ( n=36)according to polysomnography, Parkinson's disease sleep scale(PDSS) and Epworth sleepiness scale(ESS). The basic clinical data, hematological examination results, scale evaluation data and polysomnography monitoring data of the above patients were collected during hospitalization to analyze the sleep characteristics of patients with Parkinson's disease and its correlation with homocysteine.SPSS 26.0 statistical analysis software was used for t test, Mann-Whitney U test, Pearson analysis, Spearman analysis and multivariate Logistic analysis. Results:The sleep efficiency (56.82±19.07)%, N2 phase ratio(48.67±17.70)%, N3 phase ratio(9.20%(19.00%)) and the leg movement micro-arousal index(0(1.20)) in the sleep disorder group were lower than those in the non-sleep disorder group (sleep efficiency (82.15±5.55)%, N2 phase ratio(57.02±2.80)%, N3 phase ratio(20.01%(3.93%)), the leg movement micro-arousal index(1.15(1.80)). The differences were statistically significant ( t/ Z=-6.087, -2.905, -3.773, -3.683, all P<0.05). The proportion of AHI (0.90(14.60)), N1 stage (19.50%(15.70%)), and periodic limb index (0(24.80)) in sleep disorder group were higher than those in non-sleep disorder group (AHI (0.60(0.30)), N1 stage (12.15%(3.15%)), and periodic limb index (0(0)). The difference was statistically significant ( Z=2.154, 5.250, 3.559, all P<0.05). The homocysteine (15.80(3.90) μmol/L), NMSS-insomnia correlation score (3.00(5.00)), MDS-UPDRS-Ⅰ(7.00 (10.00)), MDS-UPDRS-Ⅲ (23.00 (16.00)) in the sleep disorder group were higher than those in the non-sleep disorder group (homocysteine (14.10 (4.20)μmol/L), NMSS-insomnia correlation score (0(1.00)), MDS-UPDRS-Ⅰ(3.00 (2.00)), MDS-UPDRS-Ⅲ (17.00 (4.00)), and the differences were statistically significant( Z=2.557, 4.487, 2.952, 2.180, all P<0.05). The NMSS-olfactory correlation scores (2.00(4.00)) and PDSS (99.00 (40.00)) were lower than those in the non-sleep disorder group (NMSS-olfactory correlation scores (4.50 (7.00)) and PDSS (122.00 (28.00)), and the differences were statistically significant ( Z=2.450, 4.126, both P<0.05). Hcy was positively correlated with sleep disorder in PD patients ( r=0.297, P<0.05). Binariate logistic regression analysis showed that elevated homocysteine level might be a risk factor for sleep disorder in PD patients ( β=0.193, OR=1.213, 95% CI=1.029-1.430). Conclusion:Parkinson's disease patients with sleep disorder have the characteristics of sleep structure disorder, often accompanied by more serious motor disorders, and the olfactory function impairment is relatively mild. Elevated homocysteine levels may be a risk factor for sleep disorder in Parkinson's disease.

Objective To investigate the effect of naringenin on the killing rate of natural killer (NK) cells and related mechanism by amplification of human peripheral blood mononuclear cells into NK cells in vitro and co-culture with hepatocellular carcinoma (HCC) CLC5 cells at a ratio of 1∶ 1. Methods A lymphocyte separation medium was used to isolate human peripheral blood mononuclear cells, which were induced with recombinant human interleukin-2 in vitro to culture NK cells. CCK-8 assay was used to measure the proliferation of HCC cells after human HCC cells were treated with naringenin (0, 3.125, 6.25, 12.5, 25, and 50 μmol/L) for 0, 24, and 48 hours, and after human NK cells were treated with different concentrations of naringenin for 24 hours, CCK-8 assay was used to measure the proliferation of NK cells. CellTiter-LumiTM was used to measure the killing rate of NK cells after the NK-HCC cell co-culture system at the ratio of 1∶ 1 was treated with naringenin for 24 hours. Quantitative real-time PCR was used to measure the gene expression of the activating receptor NKG2D in NK cells and NKG2D ligands in HCC cells. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results After being induced and cultured by recombinant human interleukin-2, NK cells were amplified to 82.33%±0.70% of human peripheral blood mononuclear cells. After naringenin treatment for 24 hours, there was no significant difference in the proliferation rate of HCC CLC5 cells between all mass concentration groups (all P > 0.05), and in the 25 and 50 μmol/L mass concentration groups, naringenin significantly promoted the proliferation of NK cells (both P < 0.000 1). After the NK-HCC cell co-culture system at the ratio of 1∶ 1 was treated with naringenin for 24 hours, there was a significant increase in the killing rate of NK cells in the 25 and 50 μmol/L mass concentration groups (both P < 0.000 1). After the co-culture system was treated with naringenin for 24 hours, naringenin had no effect on the expression of NKG2D in NK cells in the 25 and 50 μmol/L mass concentration groups, and it also had no effect on the expression of MICB and ULBP2 in HCC cells (all P > 0.05); it significantly upregulated the expression of the NKG2D ligands such as ULBP1 and ULBP3 in HCC cells (all P < 0.001). Conclusion Naringenin may increase the killing activity of NK cells by upregulating the expression of NKG2D ligands in HCC cells.

Objective:To explore the early surgical outcomes of Thoracoscopic Transmitral Myectomy(TTM) on patients with hypertrophic obstructive cardiomyopathy(HOCM).Methods:Preoperative echocardiography and cardiac magnetic resonance were used to evaluate the patient's hypertrophy extent, mitral valve morphology and function. Myocardial resection was performed via the trans-mitral approach under total thoracoscopy, and the surgical methods and early results were analyzed.Results:From April 2019 to October 2019, a total of 15 cases of TTM were performed by a single surgeon in our ward. Preoperative imaging evaluation revealed that 6 patients(40.0%) had predominantly hypertrophic basal septum while another 9 patients(60.0%) had concomitant midventricular septal hypertrophy. Two(13.3%) patients were interrogated ruptured posterior mitral chord by preoperative echocardiogram. After myocardial resection, the mitral valve was treated as follows: 11 patients(73.3%) underwent anterior leaflet enlargement, and 3(20.0%) were directly reattached to mitral valve annulus, and 1(6.7%) underwent bioprosthetic mitral replacement. There was no case of perioperative death, ventricular septal perforation, residual left ventricular outflow tract obstruction and complete atrioventricular block. Median aortic crossclamp time, cardiopulmonary bypass time, postoperative ventilator use time, ICU stay time, and postoperative hospital stay were 129.0min(116.0, 147.0), 184.0 min(158.0, 227.0), 22.0 h(9.0, 26.0), 3 days(2, 7) and 9 days(7, 14) respectively. No patient lost to follow up, the median follow-up time was 4 months(2, 5). One patient(6.7%) underwent mitral angioplasty three months after surgery due to a tear in the A3 area; the ventricular septal thickness and left ventricular outflow tract pressure decreased significantly(preoperative vs follow-up), and were(19.3±3.3)mm vs. (8.9±4.4) mm( P=0.001), (90.8±23.2)mmHg vs. (8.9±4.4) mmHg(1 mmHg = 0.133kPa)( P<0.001) respectively; no residual SAM was observed during follow-up. Patients with moderate-to severe mitral regurgitation were decreased from 12(80.0%) before surgery to 1(6.7%) during follow up( P<0.001). Conclusion:TTM is a safe and effective procedure for HOCM patients with appropriate surgical indications, providing better exposure to septum from basal to apical area, eliminating left ventricular outflow tract obstruction and SAM-related mitral regurgitation. The anterior mitral valve leaflet should be carefully treated during surgery to reduce the occurrence of residual mitral regurgitation resulted in inappropriate selection of patch size and suturing technique.

Objective To investigate the expression of bone marrow γ-H2AX in the patients with multiple myeloma(MM) and its correlation with the prognosis.Methods The patients with newly diagnosed MM in this hospital were selected as the case group,and the patients with non-hemopoietic system tumor without obvious morphological abnormalities by bone marrow smear and biopsy served as the control group.The immunohistochemistry was adopted to detect the expression level of bone marrow γ-H2AX in the cases group and control group,the image-Pro Plus(IPP) semiquantitative analysis was performed.The expression differences were compared between the two groups,moreover the case group was re-divided into the strong expression group and weak expression group according to γ-H2AX expression level.Then the relation ship between γ-H2AX expression level and the prognosis in the patients with MM.Results The bone marrow γ-H2AX expression level in the case group was significantly higher than that in the control group (P＜0.05);the level of γ-H2AX expression in the strong expression group was significantly stronger than that in the weak expression group (P＜0.05).Conclusion The level of γ-H2AX expression was higher among MM patients,and the over expression of γ-H2AX predicts the shorter survival time.

Objective To investigate the risk factors which can lead to chronic kidney disease (CKD) after radical nephroureterectomy and guide adjuvant chemotherapy for the patients with upper tract urothelial carcinoma (UTUC).Methods 239 patients with UTUC,who were treated at our hospital from October 2010 to February 2015 was analyzed retrospectively.Serum creatinine levels were measured preoperatively and 1 month (range:21days to 35 days) after radical nephroureterectomy.129 males and 110 females patients were enrolled.Ages were from 41 to 94,and mean age was 66 years.All patients underwent radical surgery.The pathological stages included Ta/T1/T2/T3/T4,and grades included G1/G2/G3.We calculated GFR using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in consideration of age,sex,and serum creatinine level.The new-onset CKD after RNU was defined as when the calculated CKD-EPI GFR decreased to less than 60 ml/(min · 1.73 m2).These patients were divided into 2 groups which depended on whether they got CKD after RNU.Cohorts were stratified by gender,age,smoking,BMI,hypertension,diabetes mellitus (DM),tumor location,tumor size,multifocality,pathologic stage,grade,hydronephrosis and preoperative CKD-EPI GFR.The chi-square test was used to examine the relationship among the various cohorts and the CKD after RNU.The Kaplan-Meier method was adopted to identify the relationship between Overall survival (OS).Cancer-specific survival (CSS) and CKD.Univariate and multivariate analyses were performed to study the relationship between clinical factors and CKD after RNU using the Cox proportional hazards regression model and chi-square test.Results In our study,the median follow-up time was 41.3 (range from 2-82) months for 239 patients.Median CKD-EPI GFR for all patients before and after surgery was 71.4 (65.2-108.7) ml/(min · 1.73 m2) and 54.7 (37.6-93.8) ml/(min · 1.73 m2),meanwhile 105 cases became new-onset CKD.There was no significant difference in overall or cancer specific survival between CKD + and CKD-(P =0.137,P =0.190).However age (HR =1.825,95％ CI 1.203-2.768,P =0.017),hydronephrosis (HR =0.243,95 ％ CI 0.106-0.613,P =0.034) and preoperative CKD-EPI GFR (HR =0.237,95 ％ CI 0.109-0.524,P =0.021) were significantly correlative with postoperative new-onset CKD.Conclusion Age,absence of hydronephrosis and preoperative CKD-EPI GFR were independent risk factors predicting new-onset CKD.They can be the predictor of new-onset CKD.

Objective To assess the value of preoperative neutrophil-lymphocyte ratio ( NLR) for predict the prognosis in patients with high grade T1 bladder.Methods From January 2004 to December 2014, the data of 307 patients diagnosed as bladder cancer of Stage 1 and high grade after undergoing TURBT were analyzed, including gender, age, smoking status, tumor number and size, hydronephrosis, intravesical instillations and preoperative blood transfusion of 307 patients diagnosed as bladder cancer of stage 1 and high grade after undergoing TURBT were analyzed retrospectively.All patients were primary urothelial carcinoma.According to preoperative NLR,patients were divided into the low NLR group( NLR≤2.42,n=197) and the high NLR group(NLR >2.42,n =110).Recurrence-free survival (RFS) and progression-free survival ( PFS) were calculated according to the Kaplan-Meier model and compared by the log-rank model.Cox regression models were used for multivariate analyses of the association between NLR and bladder cancer, then the prognostic factors affecting RFS and PFS were evaluated.Result of these 307 patients, the low NLR group accounted for 64.2%(197/307), and the high NLR group accounted for 35. 8%(110/307).The mean follow-up period was 71(range, 1-123)months.The recurrence rate in the low NLR group and the high NLR group recurrence rate were 19.2%( 38/197 ) and 34.5%( 38/110 ) respectively, RFS were 73.0(range, 2-123)months and 67.5(range, 1-122)months respectively.The progression rates were 4.1%(8/197) and 10.9%(12/110) respectively.The recurrence and progression rates in the high NLR group is higher than those in the low NLR group(P<0.01 and P=0.008), and RFS was shorter( P=0.002).Multivariable Cox regression analysis showed that NLR>2.42(P=0.007,HR=1.912)and hydronephrosis (P<0.01, HR =2.485 ) are associated with higher risk of recurrence.Conclusion Elevated preoperative NLR is an independent predictor of RFS and PFS in patients with high grade T1 bladder cancer.

Neuronal guidance factor Netrin-1 has been known to be involved in nervous system development by controlling neuronal migration through both chemoattractive and chemo-repulsive signaling by binding different receptors. Netrin-1 has been shown to play a positively regulatory role during inflammatory process recently. Since the chemorepulsive receptors were found in leukocytes, it is suggest that Netrin-1 played a protective role in tissue through inhibiting leukocyte trafficking and accumulating during inflammatory process in researches. It is demonstrated that Netrin-1 can limit inflammatory response through the involvement of inflammatory cascades, attenuate hypoxia-inducible tissue injury and suppress apoptosis concurrently. It is indicated that Netrin-1 can be a novel target in future through preventing and inhibiting inflammatory diseases in these researches. This review will focus on recent relevant advances and in-depth study to elucidate its mechanism of anti-inflammation.