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.

Objective:To analyze the clinicopathological characteristics and prognostic factors of patients with Castleman disease (CD).Methods:A retrospective case-series study was conducted. A total of 85 patients newly diagnosed with CD in the First Affiliated Hospital of Air Force Medical University between July 2007 and August 2024 were collected. Their clinical characteristics and prognostic factors were analyzed.Results:Among the 85 patients, 45 had unicentric Castleman disease (UCD) and 40 had multicentric Castleman disease (MCD). In the UCD group, females were more commonly affected (64.4%, 29/45), with a median age of onset of 39 years. The primary lesions were mainly located in the retroperitoneum, neck, abdomen, and axilla; and the hyaline vascular subtype was the predominant pathological type (69.4%, 25/36). In the MCD group, males were more frequently affected (62.5%, 25/40), with a median age of onset of 50 years; and the plasmacytic subtype was the main pathological type (68.2%, 15/22). Compared with UCD patients, MCD patients presented more systemic symptoms and signs [85.0% (34/40) vs. 13.3% (6/45), χ2 = 43.66, P < 0.001], splenomegaly [42.5% (17/40) vs. 2.2% (1/45), χ2 = 20.58, P < 0.001], hepatomegaly [25.0% (10/40) vs. 0 (0/45), χ2 = 10.46, P = 0.001], edema or effusion in serous cavity [67.5% (27/40) vs. 8.9%(4/45), χ2 = 31.40, P < 0.001], hematological system involvement [32.5% (13/40) vs. 0 (0/44), χ2 = 16.92, P < 0.001], and renal involvement [22.5% (9/40) vs. 2.3%(1/44), χ2 = 6.36, P = 0.012]. Laboratory findings showed that the levels of hemoglobin and albumin in MCD patients were lower than those in UCD patients, while white blood cell count in MCD patients was higher than that in UCD patients. Additionally, MCD patients exhibited elevated levels of C-reactive protein, interleukin-6, vascular endothelial growth factor, erythrocyte sedimentation rate, and ferritin compared to UCD patients (all P < 0.05). Among UCD patients, 40 cases underwent simple surgical resection, with no deaths during follow-up and the 5-year overall survival (OS) rate of 100.0%; among MCD patients, 34 cases received chemotherapy, 4 received siltuximab, 3 died during follow-up with a 5-year OS rate of 87.5%; and there was no statistically significant difference in OS between the MCD and UCD groups ( χ2 = 3.67, P = 0.055). Among MCD patients, the OS of those with renal involvement (9 cases) was worse than that of those without renal involvement (31 cases) ( χ2 = 8.39, P = 0.004). Conclusions:CD is a highly heterogeneous disorder. Surgical resection is the primary treatment for UCD, with a favorable prognosis. Chemotherapy is the main treatment for MCD, with a relatively poor prognosis.

Objective:To investigate the effect of circulating plasma cell(CPC)on the prognosis of multiple myeloma(MM),and to es-tablish and validate a modified CPC-RISS staging system based on CPC and RISS.Methods:A retrospective analysis was performed for the clinical data of 639 treatment-na?ve patients with MM who were treated in Department of Hematology,Xijing Hospital,from January 2006 to June 2023.Peripheral blood smear was used to calculate the percentage of CPC in patients,and the impact of CPC and other related factors on the prognosis of MM patients was analyzed.A CPC-RISS staging system was established based on RISS stage and the percentage of CPC,and the differences in survival and prognosis were analyzed between patients with different stages.Results:Compared with the patients without CPC,detectable CPC was significantly associated with various high-risk factors for MM,and the MM patients with CPC had a lower complete remission rate and shorter overall survival time and progression-free survival time.The modified CPC-RISS staging system was used to classify the patients with MM into four stages,and there were significant differences in median survival time and progression-free survival time between the patients with different stages of MM.Conclusion:The MM pa-tients with the presence of CPC exhibit more aggressive features,worse response to treatment,and a reduction in long-term survival rate.The modified CPC-RISS staging system can effectively predict the prognosis of treatment-na?ve MM patients.

Objective To investigate the role of exosomal microRNA(miRNA)miR-210-3p in chemoresistance and stem cell property formation in cervical cancer,and to elucidate its underlying mechanism through targeting of F-box protein 31(FBXO31).Methods Exosomes were isolated from cisplatin-sensitive HeLa cells and cisplatin-resistant HeLa/DDP cells via ultracentrifugation,and their uptake by HeLa/DDP cells was verified using the PKH26 red fluorescent labeling method.HeLa cells were transfected with NC inhibitor,miR-210-3p inhibitor alone,or in combination with si-NC and si-FBXO31.After 24 hours of transfection,exosomes were extracted and co-cultured with HeLa/DDP cells for 48 hours.Consequently,HeLa/DDP cells were divided into five groups:the Ctrl group(PBS blank control),the NC inhibitor group,the miR-210-3p inhibitor group,the miR-210-3p inhibitor+si-NC group and the miR-210-3p inhibitor+si-FBXO31 group.RT-qPCR was used to measure miR-210-3p and FBXO31 expression levels.The half-maximal inhibitory concentration(IC50)of cisplatin was determined using the MTT assay.Stem cell properties were assessed via tumor sphere formation assays.Western blot analysis was performed to detect the protein expression of FBXO31 and stem cell markers(e.g.,SOX2,OCT4,NANOG).The targeting relationship between miR-210-3p and FBXO31 was validated using dual-luciferase reporter assays.The effect of exosomal miR-210-3p on the metastasis of cervical cancer in vivo was evaluated by nude mice xenograft tumor.Resuts Compared with human normal cervical epithelial cells(HCeEpiC),miR-210-3p expression was significantly upregulated in cervical cancer cell lines(HeLa,HT3,C33A,and CaSki),while FBXO31 expression was significantly downregulated(P<0.05).HeLa/DDP cells(cisplatin-resistant)exhibited significantly higher miR-210-3p expression levels and IC50 values for cisplatin compared with parental HeLa cells(P<0.05),and HeLa exosomes were efficiently taken up by HeLa/DDP cells.Compared with the NC inhibitor groupThe miR-210-3p inhibitor group showed significantly reduced expression levels of miR-210-3p,OCT4,SOX2,and NANOG,as well as a significantly lower IC50(P<0.05),while FBXO31 expression was significantly increased(P<0.05).Compared with the miR-210-3p inhibitor+si-NC group,the miR-210-3p inhibitor+si-FBXO31 group exhibited significantly decreased FBXO31 expression(P<0.05)and increased IC50,Oct-4,SOX2,and NANOG expression(P<0.05).Compared with the control group and the empty vector group,the tumor weight and volume were significantly lower in the miR-210-3p than in the control and empty vector groups(P<0.05).Conclusion Exosomal miR-210-3p promotes chemoresistance to DDP and enhances stem cell-like properties in CC cells by directly targeting and inhibiting FBXO31.

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 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 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 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.