Objective To compare the proteome difference between multiple myeloma cell line U266 cells treated and untreated with PS-341, to investigate the potential drug targets, and to provide theoretical evidence for clinical therapy of multiple myeloma. Methods Two-dimensional gel electrophoresis (2-DE) was performed to separate proteins from treated and untreated U266 cells with proteasome inhibitor PS-341. ImageMaster 2D Platinum software was used to analyze 2-DE image, and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to identify the differentially expressed proteins. The expression levels of differential protein BAG-2 in the 2 groups of U266 cells lines were detected by Western blot. Results The 2-DE reference pattern of treated and untreated U266 cells with PS-341 was established. A total of 31 differential proteins were identified by MALDI-TOF-MS, 27 of which were down-regulated after PS-341 treatment. The differential expression level of BAG-2 in the 2 groups of U266 cells was confirmed by Western blot. Conclusion Some down-regulated proteins may be the potential drug targets of proteasome inhibitor PS-341.

Objective To investigate the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) and the factors influencing the related changes in cognitive ability.Methods Seventy-five subjects with mild cognitive impairment (the MCI group),32 with Alzheimer's disease (the AD group) and 17 others with normal cognition (the NC group) were recruited.The Montreal Cognitive Assessment (MOCA) and the Mini-mental State Examination (MMSE) were used to assess their cognitive ability.At the same time,relevant clinical information such as their general condition and past history of disease were recorded.The subjects were followed up for 20 months on average to evaluate their annual rates of progression (APRs),and logistic regression was used to highlight any influencing factors.Results By the end of the follow-up,9 of the 75 MCI subjects had progressed to AD,with an APR of 5.25％.Thirteen cases had recovered normal cognitive functioning (97.6 per 1,000 person-years).Also,2 cases in the NC group (11.76％) developed MCI (69.1 per 1,000 person-years),but none of them had yet progressed to AD.Both hyperlipidemia and a body mass index (BMI) lower than 24 kg/m2 significantly predicted the deterioration of cognitive functioning.Heart disease was significantly correlated with cognitive improvement,and selfmanagement of cognitive function was also a significant protective factor.Conclusions Patients with MCI are at greater risk of developing AD than normal persons.Prevention and early treatment of hyperlipidemia as well as maintaining a normal BMI may delay the deterioration of cognitive functioning.Self-management of cognitive function can improve cognition.

Objective To investigate the possibility of immune tole rance induced by bone marrow-derived mesenchymal stem cells in allogeneic organ transplantation. Methods Allogeneic bone marrow-derived mesenchymal stem cells and syngeneic bone marrow cells were cotransplanted to lethally irradiated female C57BL/6 recipient mice. FACS was used to analyze the chimerism 150 days later. Mixed lymphocyte reaction and ConA induced proliferation test were performed to evaluate proliferative activity of mice spleen cells in cell-transplanted group. Skin transplantation test was done to observe immune response of cell-transplanted group mice against organ graft from donor mice. Results About 5 97% donor T cells were detected in splenocytes of cell-transplanted group mice. MLR showed that mean SI of cell-transplanted group mice was 1.79, and that of untreated group mice was 7 28. ConA induced proliferation test showed that mean SI of cell-transplanted group mice was 31 92; and that of untreated group mice was 34 99. Mean survival time of donor-derived skin graft in cell-transplanted group mice was more than 90 days; and that in untreated group mice was 8 days. Conclusion Our results showed for the first time that induction of stable mixed hematopoietic chimerism after allogeneic bone marrow derived mesenchymal stem cells transplantation lead to stable donor-specific tolerance in allogeneic host and skin graft survival from donor mice.

OBJECTIVETo identify ubiquitinated proteins from complex human multiple myeloma (MM) U266 cells, a malignant disorder of differentiated human B cells.

METHODSEmploying a globally proteomic strategy combining of immunoprecipitation, LC-MS/MS and SCX-LC-MS analysis to identified ubiquitination sites, which were identified by detecting signature peptides containing a GG-tag (114.1 Da) and an LRGG-tag (383.2 Da).

RESULTSIn total, 52 ubiquitinated proteins containing 73 ubiquitination sites of which 14 and 59 sites contained LRGG-tag and GG-tag were identified, respectively.

CONCLUSIONClassification analysis by of the proteins identified in the study based on the PANTHER showed that they were associated with multiple functional groups. This suggested the involvement of many endogenous proteins in the ubiquitination in MM.

Cell Line, Tumor ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; physiology ; Humans ; Multiple Myeloma ; metabolism ; Neoplasm Proteins ; genetics ; metabolism ; Proteomics ; methods ; Ubiquitination

Objective:To classify the symptom characteristics of young and middle-aged peritoneal dialysis patients and to explore the differences of demographic functional status and social function of patients with different symptom categories.Methods:A total of 179 peritoneal dialysis patients from 3 peritoneal dialysis centers in Shanghai were investigated from December 2019 to August 2020 by General Information Questionnaire, Peritoneal Dialysis Symptom Distress Scale. Latent class analysis was used to classify young and middle-aged peritoneal dialysis patients according to symptom characteristics. Multiple Logistic regression was used to explore the differences of demographic and disease characteristics of different categories of patients.Results:Peritoneal dialysis patients could be divided into three potential categories according to symptom characteristics ( P<0.05). According to the conditional probability of each category, they were named "low symptom group" (111 cases,62.0%), "high psychological-moderate physical symptom group" (22 cases, 12.3%), "high symptom group" (46 cases,25.7%). There were differences in working status ( OR=0.029, P<0.01), education level ( OR=152.799, P<0.01), duration ( OR=81.307, P<0.05), diabetic nephropathy ( OR=80.619, P<0.01) and CCI score ( OR=91.188, P<0.01) distribution among different potential categories of young and middle-aged peritoneal dialysis patients. Conclusions:There are three types of potential symptoms in young and middle-aged patients undergoing peritoneal dialysis. In clinical practice, medical staff should focus on the psychological status of young and middle-aged patients with low educational background and early stage of dialysis, and encourage them to return to work; at the same time, they should regularly evaluate the symptom burden of patients with diabetic nephropathy and high complication index peritoneal dialysis patients, in order to provide targeted intervention measures to prevent the progression of the disease.

OBJECTIVESTo assess the feasibility and efficacy of eliciting leukemia-specific T-cell responses in syngeneic mice in vitro and in vivo using dendritic cells (DCs) pulsed with total RNA from leukemia cells.

METHODSDCs generated from bone marrow culture in vitro in the presence of combined cytokines were pulsed with cellular total RNA isolated from cultured L615 cells by cationic lipid 1,2-dioleoyloxy-3-(trimethylammonium) propane (DOTAP). T-cell responses were evaluated by in vitro proliferation, and cytotoxicity assay. And in vivo immune protection and prognosis of mice with leukemia were studied.

RESULTSDCs pulsed with total RNA isolated from cultured L615 cells (DCs/RNA) were remarkably effective in stimulating L615-specific T-cell response in vitro, but did not cross-react with other leukemia cells from syngeneic mice. Vaccination of naive mice with viable DCs/RNA vaccine was able to partly protect from challenge with a lethal dose of live L615 cells, leading to low leukemia incidence and overall survival prolongation. Statistically significant survival was also observed in a low lethal dose of L615-bearing mice that received treatment using viable DCs/RNA vaccine alone, suggesting that systemic administration of IL-2 could enhance the anti-tumor efficacy of leukemia RNA/DCs vaccine.

CONCLUSIONSThese data support the use of DCs/RNA vaccine as a feasible and effective route to elicit leukemia immunity against unidentified leukemia-associated antigens for treatment of leukemia-bearing animals.

Animals ; Cancer Vaccines ; Dendritic Cells ; immunology ; Leukemia, Experimental ; immunology ; Mice ; RNA, Neoplasm ; immunology ; isolation & purification ; T-Lymphocytes ; immunology ; Tumor Cells, Cultured

Objective:This study aimed to explore the synergistic effect and underlying mechanism of azacitidine (AZA) in combination with homoharringtonine (HHT) in acute myeloid leukemia (AML) .Methods:The synergistic effects of AZA and HHT were examined by cell proliferation, apoptosis, and colony formation assays. The synergistic effects were calculated using the combination index (CI) , and the underlying mechanisms were explored using RNA sequencing, pathway inhibitors, and gene knockdown approaches.Results:Compared with the single-drug controls, AZA and HHT combination significantly induced cell proliferation arrest and showed a synergistic effect with CI < 0.9 in AML cells. In the combination group versus the single-drug controls, colony formation was significantly decreased, whereas apoptosis was significantly increased in U937 ( P<0.001) and MV4-11 ( P<0.001) cells. AZA and HHT combination activated the integrated stress response (ISR) signaling pathway and induced DDIT3-PUMA-dependent apoptosis in cells. Furthermore, it remarkably downregulated the expression of c-MYC. The combination also activated c-MYC/DDIT3/PUMA-mediated ISR signaling to induce synergy on apoptosis. The synergy of AZA+HHT on apoptosis was induced by activating c-MYC/DDIT3/PUMA-mediated ISR signaling. Conclusion:The combination of AZA and HHT exerts synergistic anti-AML effects by inhibiting cellular proliferation and promoting apoptosis through activation of the ISR signaling pathway via the c-MYC/DDIT3/PUMA axis.

Objective:To conduct the visual analysis of emergency palliative care based on the Web of Science database.Methods:The literature on emergency palliative care collected from 2012 to 2022 was systematically searched in the Web of Science core collection. CiteSpace software was used for visual analysis.Results:A total of 630 articles were included, and the number of publications was on the rise. The country with the highest number of publications was the United States, with 8 out of the top 10 institutions in terms of publication volume coming from the United States. The author with the highest number of publications was Grudzen. The top 10 journals in terms of citation frequency were mostly specialized journals on palliative care and first aid. The results of keyword analysis showed that a total of 15 clustering labels and 20 emergent words were output, reflecting the changes of key research objects, main research types and areas of concern.Conclusions:At present, nursing research in this field is in the development stage in China. We can draw on the practical experience of foreign countries to further explore the emergency palliative care model and service system based on China's national conditions.

The timely use of screening tools to assess the palliative care needs of emergency patients can provide decision-making basis for patient referral and help patients receive palliative care in a timely manner.This paper reviews the palliative care needs screening tools for emergency patients at home and abroad,describes their development methods,scoring criteria and application status,compares and analyzes their characteristics and shortcomings.It aims to provide references for the localized development and application of palliative care needs screening tools in emergency patients.