[Correlation between gene polymorphisms of killer cell immunoglobulin-like receptors and their ligands and Graves' disease].

Objective: To explore the relationship between gene polymorphism of killer cell immunoglobulin-like receptor (KIR) and its ligand-specific human leukocyte antigen C (HLA-C) and Graves' disease (GD). Methods: Case-control study. A total of 118 unrelated GD patients (GD group) admitted to Shandong Provincial Hospital from January 2011 to December 2017 and 108 age-and sex-matched healthy controls (healthy control group) were included. The KIR genotype and its ligand HLA-C allele were detected by polymerase chain reaction sequence-specific primers (PCR-SSP). The distribution of KIR/HLA-C gene combination in GD patients and control population was analyzed to explore its association with the occurrence of GD. Results: In GD group, there were 29 males and 89 females, aged (38±14) years. In the healthy control group, there were 28 males and 80 females, aged (37±13) years. Compared with the healthy control group, the occurrence frequency of HLA-Cw01 was higher in GD group[36.4%(43/118) vs 18.5%(20/108), P=0.003], and the occurrence frequency of HLA-Cw03 and HLA-Cw06 was lower in GD group[11.9%(14/118) vs 39.8%(43/108), P<0.001; 9.3%(11/118) vs 18.5%(20/108), P=0.045]. The frequency of KIR2DL1/HLA-C2 gene combination in GD group was lower than that in control group [17.8%(21/118) vs 34.3%(37/108), P=0.005]. Logistic regression analysis showed that KIR2DL1/HLA-C2 gene combination was a protective factor for GD occurrence (OR=0.308, 95%CI: 0.126-0.752, P=0.010). Conclusions: The polymorphism of KIR/HLA-C gene is related to GD. The low expression of KIR2DL1/HLA-C2 in GD patients may be a protective factor for GD.

Impact of pre-transplant dialysis modality on kidney transplant outcomes: a systematic review and meta-analysis.

OBJECTIVE: For end-stage renal disease (ESRD), patients receiving kidney transplantation, peritoneal dialysis (PD) and hemodialysis (HD) are both appropriate modes of pre-transplant dialysis. The aim of this review is to assess the impact of pre-transplant PD compared to HD on kidney transplant outcomes in ESRD patients. MATERIALS AND METHODS: A comprehensive search in digital databases, like PubMed, SCOPUS and EMBASE and a manual search were conducted to identify cohort studies comparing the kidney transplant outcomes of both pre-transplant dialysis modalities. The data were subjected to both qualitative and quantitative analysis. A meta-analysis was carried out to calculate the effect estimate for patient survival, graft survival and delayed graft function, death-censored graft survival, acute rejection-free graft survival, graft vessel thrombosis, urological complications, surgical complications, any infections, and onset of diabetes after transplantation. The qualities of the included studies were judged by the New-castle Ottawa scale. RESULTS: The overall patient survival is shown to be better with patients who underwent pre-transplant PD compared to HD with OR 1.34 95% CI [1.11, 1.61], p = 0.002. Delayed graft function was found to be highly associated with HD compared to PD with OR 0.60 [0.52, 0.70], p<0.0001 with moderate heterogeneity (i2 = 48%). However, no difference was observed in terms of graft survival, complications, infections, and new onset of diabetes mellitus compared to patients undergoing pre-transplant HD. CONCLUSIONS: Within the limitations of the review, it can be concluded that ESRD patients undergoing pre-transplant PD were found to have better patient survival and lower incidence of delayed graft function.

[Patient factors influencing preoperative expectations of patients undergoing total knee arthroplasty].

OBJECTIVE: To investigate the expectations of patients for total knee arthroplasty (TKA), and to analyze its influencing factors. METHODS: Experimental design: Single center, retrospective, multiple regression analysis. The data including the age, height, and weight of 108 patients undergoing unilateral TKA due to end-stage osteoarthritis were obtained. The patients' preoperative Hospital for Special Surgery (HSS) knee arthroplasty expectation score, the Western Ontario and McMaster Universities (WOMAC) score, Knee Society score (KSS), the MOS 36-item short-from health survey (SF-36) score, and visual analogue scale (VAS) were evaluated, and the 30-second chair-stand test (30-CST), 40-meter fast-paced walk test (40-FPWT), 12-level stair-climb test (12-SCT), 3-meter timed up-and-go test (TUG), 6-minute walk test (6-MWT), and recorded daily steps for 7 consecutive days were performed. The SPSS 22.0 software was used for statistical analysis. The observed values of various data were described. Pearson correlation analysis was used to evaluate the correlation between various parameters, and the multi-factor linear regression analysis was used to investigate the influencing factors of the patients preoperative expectation scores. RESULTS: The average expectation score of this group of patients was 58.98±5.44. In the Pearson correlation analysis, the patient's preoperative expectation had a weak correlation to the result of the patient's 12-SCT, TUG, 6-MWT, KSS function score, and SF-36 mental component score (correlation coefficient 0.1-0.3). The patient's preoperative expectation had a moderate correlation to the patient's daily average steps, 30-CST, 40-FPWT, KSS, WOMAC and its pain, stiffness, function scores, SF-36 physical functioning, role-physical, bodily pain, vitality, and physical component score (correlation coefficient 0.3-0.6). In the multivariate linear regression analysis, only the results of 30-CST and the role-physical, bodily pain and vitality in the SF-36 scale were related to the patient's expectation score (P < 0.05). CONCLUSION: The estimated expectation score of patients before TKA is not high. Patients with more severe preoperative pain, worse physical function, and lower overall health are more eager to improve after surgery. Thus surgeons must communicate fully with patients with unrealistic expectations before surgery in order to obtain more satisfactory results postoperatively.

Lipopolysaccharide-stimulated bone marrow mesenchymal stem cells-derived exosomes inhibit H2O2-induced cardiomyocyte inflammation and oxidative stress via regulating miR-181a-5p/ATF2 axis.

OBJECTIVE: Myocardial infarction (MI) is a cardiovascular disease that seriously endangers human health. Exosomes secreted by stem cells have big potential for the treatment of many diseases. The purpose of this study was to study the therapeutic effects of exosomes derived from lipopolysaccharide (LPS)-stimulated bone marrow mesenchymal stem cells (BMSCs) on MI. PATIENTS AND METHODS: The surface markers of BMSCs were detected by Western blot. After BMSCs were stimulated with LPS for 2 days, the exosomes secreted by BMSCs were extracted and observed by transmission electron microscopy (TEM), and their specific surface markers were detected by Western blot. H9c2 cells were co-cultured with exosomes for 24 hours, and then, treated with H2O2 for 4 hours. Next, H9c2 cells were transfected with miRNA-181a-5p mimic (MIM) or negative control (NC). Inflammation and oxidative stress of H9c2 cells were detected by Western blot, cell staining, reactive oxygen species (ROS) quantification, and SOD activity assay. At last, miR-181a-5p expression in BMSCs, exosomes, and H9c2 cells was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). RESULTS: The results revealed that the expression of miR-181a-5p was increased in LPS-stimulated BMSCs (L-BMSC) and in their secreted exosomes. Besides, the expressions of TNF-α and IL-1ß were decreased, while those of SOD1 and SOD2 were increased in H9c2 cells co-cultured with exosomes secreted by LPS-stimulated BMSCs (L-EXO) and transfected with MIM. Moreover, the fluorescence intensity of IL-1ß immunofluorescence was decreased in H9c2 cells co-cultured with L-EXO or transfected with MIM. The level of ROS was also decreased in H9c2 cells co-cultured with L-EXO or transfected with MIM. Furthermore, miR-181a-5p was found to target ATF2 through target gene prediction databases and Western blot and Dual-Luciferase reporter assays. CONCLUSIONS: LPS stimulation can increase the expression of miR-181a-5p in BMSCs, and miR-181a-5p inhibits myocardial inflammation and oxidative stress by targeting ATF2.

[Effect of education and tailored exercise therapy on knee osteoarthritis patients].

Objective: To evaluate the effect of patient education and tailored exercise in the knee osteoarthritis (OA) patients. Methods: One hundred and eighty-five patients with knee OA were enrolled in this ongoing prospective cohort study at Arthritis Clinic and Research Center, Peking University People's Hospital since May, 2016.The treatment consisted of two one-hour sessions of patient education and six weeks of supervised, in-group, tailored exercise.The contents of the patient education were evidence-based and its overall focus was to increase the knowledge of the participants regarding OA and how to treat it.The exercise program was a neuromuscular exercise based on biomechanical and neuromuscular principles that aimed at restoring a neutral functional alignment of the lower extremities by improving sensorimotor control and obtaining compensatory functional stability.The outcomes were evaluated at baseline, 3 and 6 months, which included pain on the visual analogue scale (VAS, 0-100), quality of life on the Euro-quality of life-5 Dimensional (EQ-5D) VAS form, Knee Injury and Osteoarthritis Outcome Score (KOOS), 30-second chair stand test, 40-meter walk test and use of analgesics.The participants were also asked to rate their opinion of this program on a five-point scale (very satisfactory, satisfactory, neither satisfactory nor dissatisfactory, dissatisfactory, very dissatisfactory). One way analysis of variance was applied to compare the outcomes at baseline and 3 and 6 months follow-up. Results: One hundred and forty-two participants completed the 6-month follow-up.There were significant improvements in pain VAS, EQ-5D-VAS, 30-second chair stand test and 40-meter walk test at the follow-up at 3 and 6 months when compared with those at baseline (F=22.9, 8.4, 3.4, 4.1, 3.8, all P<0.05). The rate of analgesics use in the past two week at baseline was 43.2%, and it decreased to 18.9% at 6-month follow-up (P<0.001). Most participants (71.1%, 101 out of 142) rated the program as 'Very Satisfactory' and the rest (28.9%, 41 out of 142) rated the program as 'Satisfactory'. Conclusion: This program comprising the group patient education and tailored exercise therapy is effective in relieving pain, improving the function and quality of life in patients with knee OA.

[Evaluation of physical function for the end-stage osteoarthritis patient waiting for the total knee replacement].

OBJECTIVE: To collect comprehensive data of the physical function of the end-stage osteoarthritis (OA) patients, and compare it with patients with mild OA. To evaluate the correlations among pain, self-reported questionnaire, performance based physical function and actual daily life activity level. METHODS: In this prospective study, the comprehensive physical function parameters of 87 end stage OA patients waiting for total knee replacement, and that of 60 patients with mild OA [Kellgren-Lawrence (K-L) grade 0-2] were collected. The comprehensive physical function parameters including: age, height, body weight, 30 s chair stand test (30-CST), 40 m fast-paced walk test (40-FPWT), 12 steps stair climb test (12-SCT), timed up & go test (TUG), 6 minutes walk test (6-MWT), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee society score (KSS), visual analogue scale (VAS) pain scale, and everyday steps counts for continuous 7 days. The data were analyzed with the soft ware SPSS 22.0. The descriptive report of all the parameters was made. Because the Kolmogorv-Smirnov test results for all the parameters were negative for normal distribution, nonparative Mann-Whitney test was used to analysis the differences between the two groups, as well as the Spearman test for the correlations. RESULTS: All the parameters of the mild OA group were better than those of the end stage group, and the differences were significant (P<0.05). In the mild OA group, there were no correlations or weak correlations between all the physical function test and questionnaire, however, in the end stage group, the correlations were weak, moderate, or strong. CONCLUSION: The usage of lots of different physical parameters from Chinese OA patients were reported in this study. The results showed that there are no good correlations among performance based physical function test, actual daily activity level, self reported questionnaires, and the pain scales. More comprehensive evaluation for the OA patients needs to be made, in order to make better decision for arthroplasty.

Large piezoelectric response of BiFeO3/BaTiO3 polycrystalline films induced by the low-symmetry phase.

BaTiO3, BiFeO3 and BiFeO3/BaTiO3 polycrystalline films were prepared by the radio frequency magnetron sputtering on the Pt/Ti/SiO2/Si substrate. The phase structure, converse piezoelectric coefficient and domain structure of BaTiO3, BiFeO3 and BiFeO3/BaTiO3 thin films are characterized by XRD and PFM, respectively. The converse piezoelectric coefficient d33 of BiFeO3/BaTiO3 thin films is 119.5 pm V(-1), which is comparable to that of lead-based piezoelectric films. The large piezoelectric response of BiFeO3/BaTiO3 thin films is ascribed to the low-symmetry T-like phase BiFeO3, because the spontaneous polarization vector of T-like phase (with monoclinic symmetry) BiFeO3 can rotate easily under external field. In addition, the reduced leakage current and major domains with upward polarization are also attributed to the large piezoelectricity.

Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner.

To identify more therapeutic targets and clarify the detailed mechanisms of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) on breast cancer cells both in vitro and in vivo. PA-MSHA was administered to epidermal growth factor receptor (EGFR)-positive human breast cancer cell lines MDA-MB-231HM and MDA-MB-468 in vitro and to mice bearing tumor xenografts. The mannose cocultured test was used to detect the effect of mannose on PA-MSHA-induced cell proliferation, cell cycle arrest, apoptosis, and EGFR pathway signaling. We found that cells stimulated with PA-MSHA exhibited a downregulation of EGFR signaling. The addition of mannose partially inhibited the PA-MSHA-stimulated cell anti-proliferative effect, cell apoptosis, cell cycle arrest, activation of apoptosis-associated caspases, and even downregulation of the EGFR signaling pathway. In vivo, PA-MSHA treatment significantly suppressed mammary tumorigenesis in xenografts in mice and decreased lung metastasis in MDA-MB-231HM cell-transplanted mice. Tumor sample analyses confirmed inhibition of the EGFR pathway in the PA-MSHA-treated mice. In conclusion, this study showed that the involvement of the mannose-mediated EGFR pathway has a critical function in the preclinical rationale for the development of PA-MSHA for the treatment of human breast cancer. It also suggests the potentially beneficial use of PA-MSHA in adjuvant therapy for breast tumors with EGFR overexpression.

Disparate distribution of activating and inhibitory killer cell immunoglobulin-like receptor genes in patients with systemic lupus erythematosus.

The genes of killer cell immunoglobulin-like receptors (KIRs), which are involved in the activation of T cells and natural killer cells, are highly variable. In recent years, the role of KIRs in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of the polymorphism of KIR genes with the susceptibility to systemic lupus erythematosus (SLE). The polymorphism of KIR genes of 93 patients with SLE together with 123 healthy donors as the control group was determined by polymerase chain reaction with sequence-specific primers. Twenty-seven novel gene combinations were found. Genotypic frequencies of KIR2DL2 (p < 0.001) and KIR2DS1 (p < 0.001) were much higher in patients with SLE than in control subjects. Individuals with two and more than two activating KIR genes were found more frequently in patients than in control subjects (80.7% versus 66.7%, p = 0.022). The results suggest that a genetic disturbance between activating and inhibitory KIR genes may be one of the key factors underlying the pathogenesis of SLE.

Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential.

In addition to the role in regulating leukocyte trafficking, chemokines recently have been shown to be involved in cancer growth and metastasis. Chemokine network in tumor neovascularity may be regulated by decoy receptors. Duffy antigen receptor for chemokines (DARC) is a specific decoy receptor binding with the angiogenic CC and CXC chemokines. To investigate the effects of DARC on the tumorigenesis and the metastasis potential of human breast cancer cells, human DARC cDNA was reintroduced into the MDA-MB-231 and MDA-MB-435HM cells which have a high capability of spontaneous pulmonary metastasis. We demonstrated that DARC overexpression induced inhibition of tumorigenesis and/or metastasis through interfering with the tumor angiogenesis in vivo. This inhibition is associated with decreasing CCL2 protein levels, and MVD and MMP-9 expression in xenograft tumors. In human breast cancer samples, we also demonstrated that low expression of the DARC protein is significantly associated with estrogen receptor (ER) status, MVD, lymph node metastasis, distant metastasis and poor survival. Our results suggest for the first time that DARC is a negative regulator of growth in breast cancer, mainly by sequestration of angiogenic chemokines and subsequent inhibition of tumor neovascularity.

Direct observation of molecular images of lanthanide phthalocyanines: III. Structural defects.

The crystal imperfections in thin films of lanthanide phthalocyanines (LnPc2H, Ln = Nd, Tb, Er, Tm, Yb, and Lu) grown expitaxially on KCl have been observed by molecular imaging. Grain and twin boundaries, stacking faults, point defects, vacancies, mosaic structures, and sometimes even some amorphous islands exist in the well-crystallized specimens. Combined with the results reported earlier, the packing characteristics of planar LnPc2H molecules can be well understood.