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Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants that possess potential toxicity to the human body. The production and utilization of diverse emerging PFAS have resulted in widespread human exposure. Therefore, it is imperative to establish a quantitative methodology encompassing a wide range of PFAS for a comprehensive assessment of human exposure to these compounds. Objective To establish a high-throughput quantitative method for the simultaneous determination of 53 PFAS in human serum based on ultra-high-performance liquid chromatography-Q Exactive high resolution mass spectrometry (UPLC-Q Exactive HRMS). Methods The extraction recoveries of hydrophilic-lipophilic balance (HLB) column, weak anionexchange (WAX) column, and 96-well WAX μElution plate were compared to select the SPE column with the highest recovery. The retention time and peak shape of the target compounds were compared between ACQUITY UPLC BEH C18 column and Accucore aQ column, and the more cost-effective column was chosen. The effects of adding different levels of ammonium formate (0, 2, 5 and 10 mmol·L−1) in mobile phase on peak shape and target response were compared to determine the optimal buffer salt concentration. The optimal spray voltage was obtained by comparing −2 kV and −4 kV. The proposed method was validated from the aspects of selectivity, standard curve, limits of detection, precision, accuracy, and matrix effect. The method was applied to 142 umbilical serum samples. Results The best recovery rate (64%-118%) was achieved by using 96-well WAX μElution plate. The optimal separation and peak shape were obtained by utilizing Accucore aQ column with H2O-methanol (containing 5 mmol·L−1 ammonium formate) as the mobile phase. Less in-source collision and better target response were observed when the spray voltage was set to −2 kV. All target analytes had a good linearity, with R2 > 0.99. The limits of detection ranged from 0.01 to 0.50 μg·L−1, and the recovery ranged from 69% to 127% with the precision less than 26%. A total of 31 PFAS were detected in the 142 actual samples, among which 14 PFAS had a detection frequency over 50%. Perfluorooctanoic acid showed the highest median concentration of 4.16 μg·L−1, followed by 6:2 chlorinated polyfluorinated ether sulfonate and perfluorooctane sulfonates (3.50 μg·L−1 and 1.59 μg·L−1, respectively). Conclusion In this study, we establish a UPLC-Q Excative HRMS method for simutanious determination of 53 PFAS concentrations in serum. This method has the advantages of wide coverage of PFAS, good selectivity, and easy operation, and is suitable for biological detection with a large sample size.
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Objective:To Eveluate the safty and clinical efficacy of combined laparoscopic spleen-preserving distal pancreatectomy and autologous islet transplantation in the treatment of solid pseudopapillary neoplasm.Methods:A 22 years old solid pseudopapillary neoplasm female patient who underwent distal pancreatectomy and an autologous islet transplantation at Tianjin First Central Hospital, clinical date for 6 months follow up was collected and analyzed.Results:The patient was well recovered after surgery, and during the post-operative follow up, the fasting blood glucose was 5.72 mmol/L, HbA1c was 6.1%, remained insulin independent, the liver function was kept well.Conclusions:Combined Laparoscopic spleen-preserving distal pancreatectomy and autologous islet transplantation can effectively prevent diabetes after distal pancreatectomy.
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Background and Objectives@#Adipose tissue-derived mesenchymal stem cells (ASCs) are recognized as an advantaged source for the prevention and treatment of diverse diseases including type 2 diabetes mellitus (T2DM). However, alterations in characteristics of ASCs from the aforementioned T2DM patients are still obscure, which also hinder the rigorous and systematic illumination of progression and pathogenesis. @*Methods@#and Results: In this study, we originally isolated peripancreatic adipose tissue-derived mesenchymal stem cells from both human type 2 diabetic and non-diabetic donors (T2DM-ASCs, ND-ASCs) with the parental consent, respectively. We noticed that T2DM-ASCs exhibited indistinguishable immunophenotype, cell vitality, chondrogenic differentiation and stemness as ND-ASCs. Simultaneously, there’s merely alterations in migration and immunoregulatory capacities in T2DM-ASCs. However, differing from ND-ASCs, T2DM-ASCs exhibited deficiency in adipogenic and osteogenic differentiation, and in particular, the delayed cell cycle and different cytokine expression spectrum. @*Conclusions@#The conservative alterations of T2DM-ASCs in multifaceted characteristics indicated the possibility of autologous application of ASCs for cell-based T2DM treatment in the future.
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Objective To investigate the effect factors of liver enzymes elevation by monitoring the liver function changes before and after intraportal islet transplantation .Methods 16 diabetic patients who received intraportal islet transplantation in our hospital were analyzed .The levels of aspartic aminotransferase (AST ) ,alanine aminotransferase (ALT )and total bilirubin (TBil)were monitored after islet transplantation .Results Among those 16 diabetic patients who received intraportal islet transplantation ,11 patients showed an increased AST and 8 patients showed an increased ALT ,among which a 2 .5-fold increase in AST was observed in 4 patients and over 1 .5-fold elevation of ALT was observed in 3 patients .The level of TBil were in the normal range before and after transplantation in all patients . Transplanted tissue volume of islet was the main factor for significantly increased AST (P< 0 .05) in this study .It is also shown that the change in portal pressure is related to the AST elevation after islet transplantation .Conclusions The amount of transplanted islet tissue volume is related to the liver enzymes elevation after intraportal islet transplantation .Therefore ,the improvement of the purity of islet to reduce the amount of transplanted tissue could be benefit to prevent the liver injury after islet transplantation .Meanwhile ,the purified islets should be injected as slowly as possible to maintain a stable portal pressure .
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Objective@#To investigate the effect factors of liver enzymes elevation by monitoring the liver function changes before and after intraportal islet transplantation.@*Methods@#16 diabetic patients who received intraportal islet transplantation in our hospital were analyzed. The levels of aspartic aminotransferase (AST), alanine aminotransferase (ALT)and total bilirubin (TBil)were monitored after islet transplantation.@*Results@#Among those 16 diabetic patients who received intraportal islet transplantation, 11 patients showed an increased AST and 8 patients showed an increased ALT, among which a 2.5-fold increase in AST was observed in 4 patients and over 1.5-fold elevation of ALT was observed in 3 patients. The level of TBil were in the normal range before and after transplantation in all patients. Transplanted tissue volume of islet was the main factor for significantly increased AST (P<0.05) in this study. It is also shown that the change in portal pressure is related to the AST elevation after islet transplantation.@*Conclusions@#The amount of transplanted islet tissue volume is related to the liver enzymes elevation after intraportal islet transplantation. Therefore, the improvement of the purity of islet to reduce the amount of transplanted tissue could be benefit to prevent the liver injury after islet transplantation. Meanwhile, the purified islets should be injected as slowly as possible to maintain a stable portal pressure.
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The percutaneous transhepatic portal approach is the most commonly used technique for islet transplantation, largely owing to its safety and minimally invasive characteristic. Bleeding complications after islet transplantation are rare. A case of type 1 diabetes mellitus (T1DM) was treated in Tianjin First Center Hospital, who had a massive intra-abdominal hemorrhage after percutaneous transhepatic portal vein catheterization for islet transplantation. Through the review of the overall development of the case, we aim to improve the awareness of the complications of islet transplantation, to reduce the incidence of complications after percutaneous transhepatic portal vein transplantation, and to provide experience.
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Objective To investigate the in vitro effects of bone marrow mesenchymal stem cells (BM MSCs) on the replication of HBV with the participation of lymphocytes and to analyze the possible mechanism.Methods The HBV genomic DNA transfected HepG2.2.15 cell line was used to evaluate the HBV replication.Bone marrow and spleen samples were collected from BN rats for the isolation of BM MSCs and T lymphocyte cells, respectively.Five groups of co-culturing with different cells were designed in this study.The cellular activities of lymphocytes and HepG2.2.15 cells were detected at the time of 24 h, 48 h and 72 h after co-culturing by using MTT method.The levels of HBV DNA and HBV cccDNA were detected by real-time polymerase chain reaction ( PCR) .T cell subsets in co-culture were measured by using fluores-cence labeled antibodies and flow cytometry analysis.ELISA was used to detect the levels of cytokines in the supernatant of cultured cells.Results Compared with HepG2.2.15 cells group, BM MSCs+HepG2.2.15 cells and splenic lymphocytes+HepG2.2.15 cells co-culture groups, the levels of HBV DNA and HBV cccDNA were significantly decreased in splenic lymphocytes+BM MSCs+HepG2.2.15 cells co-culture group after 48 h of culture [ HBV DNA: ( 181.000 ±14.731 ) IU/ml vs ( 6270.000 ±300.450 ) IU/ml, (2564.000±231.058) IU/ml, (2433.300±302.379) IU/ml;HBV cccDNA: (4.330×105 ±0.464×105 ) IU/ml vs (11.100×105±0.375×105) IU/ml, (8.930×105±0.778×105) IU/ml, (9.850×105±0.810× 105) IU/ml;P<0.01].The secretion of IFN-γin the supernatant of co-cultured cells was negatively corre-lated with HBV DNA level, but the levels of IL-10 and IL-22 were positively correlated with HBV DNA.The ratio of CD4+/CD8+cells was increased in splenic lymphocytes+BM MSCs+HepG2.2.15 cells co-culture group.The percentage of CD8+cells showed a positive correlation with HBV DNA.Conclusion BM MSCs could inhibit the expression of HBV DNA to enhance the clearance of HBV strains.It might be possibly due to rebalancing of Tc1/Tc2 cells and regulating the expression of autocrine agents and cytokines.
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The growing demand for new therapeutic strategies in the medical and pharmaceutic fields has resulted in a pressing need for novel druggable targets. Paradoxically, however, the targets of certain drugs that are already widely used in clinical practice have largely not been annotated. Because the pharmacologic effects of a drug can only be appreciated when its interactions with cellular components are clearly delineated, an integrated deconvolution of drug-target interactions for each drug is necessary. The emerging field of chemical proteomics represents a powerful mass spectrometry (MS)-based affinity chromatography approach for identifying proteome-wide small molecule-protein interactions and mapping these interactions to signaling and metabolic pathways. This technique could comprehensively characterize drug targets, profile the toxicity of known drugs, and identify possible off-target activities. With the use of this technique, candidate drug molecules could be optimized, and predictable side effects might consequently be avoided. Herein, we provide a holistic overview of the major chemical proteomic approaches and highlight recent advances in this area as well as its potential applications in drug discovery.