Aims. To evaluate the efficacy of rosiglitazone (TZD) and electroacupuncture (EA) combined therapy as a treatment for type 2 diabetes mellitus (T2DM) patients by randomized single-blind placebo ...controlled clinical trial. Methods. A total of 31 newly diagnostic T2DM patients, who fulfilled the study's eligibility criteria, were recruited. The individuals were randomly assigned into two groups, the control group (TZD, N=15) and the experimental group (TZD + EA, N=16). Changes in their plasma free fatty acid (FFA), glucose, and insulin levels, together with their homeostasis model assessment (HOMA) indices, were statistically compared before and after treatment. Hypoglycemic activity (%) was also compared between these two groups. Results. There was no significant difference in hypoglycemic activity between the TZD and TZD + EA group. The effectiveness of the combined therapy seems to derive from an improvement in insulin resistance and a significant lowering of the secreted insulin rather than the effect of TZD alone on T2DM. The combined treatment had no significant adverse effects. A lower plasma FFA concentration is likely to be the mechanism that causes this effect. Conclusion. This combined therapy seems to suppress endogenous insulin secretion by improving insulin resistance via a mechanism involving a reduction in plasma FFA. This trial is registered with ClinicalTrials.gov NCT01577095.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Abstract Background The association between blood lead levels and mortality in patients on maintenance hemodialysis remains unclear. Methods A cross-sectional and 18-month prospective study included ...927 patients on maintenance hemodialysis. Baseline variables and blood lead levels were measured before hemodialysis and categorized as 3 equal groups: high (>12.64 μg/dL), middle (8.51-12.64 μg/dL), and low (<8.51 μg/dL). Mortality and cause of death were recoded for longitudinal analyses. Results At baseline, after related variables were adjusted, logarithmic transformation of blood lead level was negatively related to log ferritin and positively related to the vintage of hemodialysis and the percentage of urban area patients. By the end of the follow-up, 59 patients had died. Kaplan–Meier survival analysis showed that the high blood lead level group had greater mortality than the low blood lead level group (log-rank test, P < .001). After adjustment for potential variables, Cox multivariate analysis demonstrated that by using the low blood lead level as the reference, high blood lead levels were associated with increased hazard ratios (HRs) for all-cause (HR 4.70; 95% confidence interval CI, 1.92-11.49; P =. 003), cardiovascular-cause (HR 9.71; 95% CI, 2.11-23.26; P =. 005), and infection-cause (HR 5.35; 95% CI, 1.38-20.83; P =. 046) 18-month mortality in patients on maintenance hemodialysis. Moreover, there was a significant trend ( P = .032) of HRs for all-cause mortality among the 3 study groups. Conclusion High blood lead level is associated with increased HRs for all-cause, cardiovascular-cause, and infection-cause 18-month mortality in patients on maintenance hemodialysis.
Telomere dynamics are linked to aging hallmarks, and age-associated telomere loss fuels the development of epithelial cancers. In Apc-mutant mice, the onset of DNA damage associated with telomere ...dysfunction has been shown to accelerate adenoma initiation via unknown mechanisms. Here, we observed that Apc-mutant mice engineered to experience telomere dysfunction show accelerated adenoma formation resulting from augmented cell competition and clonal expansion. Mechanistically, telomere dysfunction induces the repression of EZH2, resulting in the derepression of Wnt antagonists, which causes the differentiation of adjacent stem cells and a relative growth advantage to Apc-deficient telomere dysfunctional cells. Correspondingly, in this mouse model, GSK3β inhibition countered the actions of Wnt antagonists on intestinal stem cells, resulting in impaired adenoma formation of telomere dysfunctional Apc-mutant cells. Thus, telomere dysfunction contributes to cancer initiation through altered stem cell dynamics, identifying an interception strategy for human APC-mutant cancers with shortened telomeres.
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•Telomere dysfunction augments intestinal tumor initiation•DNA damage represses EZH2, upregulating Wnt antagonist expression•Elevated Wnt antagonists impair adjacent normal stem cell growth•Boosting Wnt signaling in normal stem cells reduces clonal expansion
LaBella et al. address a long-standing question as to how telomere dysfunction accelerates intestinal tumor initiation and demonstrate the interrelationship of telomere dysfunction, EZH2, and Wnt signaling in early tumorigenesis. These mechanistic insights define an interception strategy to quell the tumor-initiating potential of APC-mutant cells with shortened telomeres.
This research was designed to investigate the effects of low pressure radio-frequency (RF) oxygen plasma treatment (OPT) on the surface of commercially pure titanium (CP-Ti) and Ti6Al4V. Surface ...topography, elemental composition, water contact angle, cell viability, and cell morphology were surveyed to evaluate the biocompatibility of titanium samples with different lengths of OP treating time.
CP-Ti and Ti6Al4V discs were both classified into 4 groups: untreated, treated with OP generated by using oxygen (99.98%) for 5, 10, and 30 min, respectively. After OPT on CP-Ti and Ti6Al4V samples, scanning probe microscopy, X-ray photoelectron spectrometry (XPS), and contact angle tests were conducted to determine the surface topography, elemental composition and hydrophilicity, respectively. The change of surface morphology was further studied using sputtered titanium on silicon wafers. 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay and F-actin immunofluorescence stain were performed to investigate the viability and spreading behavior of cultivated MG-63 cells on the samples.
The surface roughness was most prominent after 5 min OPT in both CP-Ti and Ti6Al4V, and the surface morphology of sputtered Ti sharpened after the 5 min treatment. From the XPS results, the intensity of Ti(°), Ti(2+), and Ti(3+) of the samples' surface decreased indicating the oxidation of titanium after OPT. The water contact angles of both CP-Ti and Ti6Al4V were increased after 5 min OPT. The results of MTT assay demonstrated MG-63 cells proliferated best on the 5 min OP treated titanium sample. The F-actin immunofluorescence stain revealed the cultivated cell number of 5 min treated CP-Ti/Ti6Al4V was greater than other groups and most of the cultivated cells were spindle-shaped.
Low pressure RF oxygen plasma modified both the composition and the morphology of titanium samples' surface. The CP-Ti/Ti6Al4V treated with 5 min OPT displayed the roughest surface, sharpest surface profile and best biocompatibility.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BackgroundBackground: Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically; however, incidences of abscopal ...tumor remission are extremely rare. We sought to unravel the post-irradiation immune escape mechanisms in CRC.MethodsMethodsFlow cytometry, gene knockdown, RNA and T cell receptor sequencing, and multiple murine syngeneic CRC models were used to interrogate mechanisms of CRC immune evasion following radiotherapy. Comparison of immunohistochemistry staining between pretreatment biopsy and post-irradiation surgical specimens was performed in rectal patients who underwent neoadjuvant radiotherapy with 5 Gy for 5 fractions.ResultsResultsWe find that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells (APCs) to phagocytose them thereby preventing TAA cross-presentation. This post-irradiation CD47 and PD-L1 upregulation can be observed in CRC cells treated with either photon or proton radiotherapy and across a wide variety of human solid tumor cells. Concordantly, rectal cancer patients who responded poorly (tumor regression grade 4–5, n = 10) to neoadjuvant radiotherapy exhibited significantly elevated post-irradiation CD47 levels (P = 0.005). In murine CRC models, the combination of radiotherapy, αSIRPα, and αPD-1 (RSP) profoundly enhances TAA uptake, activation of innate immune sensors, and TAA cross-priming across various antigen-presenting myeloid populations in the irradiated tumor microenvironment and facilitates TAA-presenting APC migration to secondary lymphoid organs. Furthermore, we observed robust production of TAA-specific CD8 T cells, functional activation of effector T cells, and increased tumor-infiltrating T cell clonality and clonal diversity in mice treated with RSP. Importantly, radiotherapy coupled with phagocytosis checkpoint blockade significantly improves complete response rates in both irradiated and abscopal tumors and prolongs survival in three distinct murine CRC models, including a cecal orthotopic model. In addition, αSIRPα exerts superior tumoricidal efficacy than αCD47 in combination with RT and αPD-1. We find RSP efficacy to be STING dependent as knockout animals lose most benefit of phagocytosis checkpoint blockade.ConclusionATR-mediated CD47 and PD-L1 upregulation restrains radiation-induced immune priming in CRC. Blockade of the phagocytosis checkpoints SIRPα and PD-1 during radiotherapy promotes vigorous anti-CRC immune priming leading to systemic tumor regression.AcknowledgementsThis study is supported in part by NIH grant P30 CA16672, the MD Anderson Andrew Sabin Family Fellowship, and Chang Gung Memorial Hospital grant CMRPG3K1751. RCH was supported by the CPRIT Research Training Grant (RP170067) and Ralph B. Arlinghaus Ph.D. Scholarship. The authors are grateful to the members of the Advanced Cytometry & Sorting Facility at South Campus, Tissue Bank of Chang Gung Memorial Hospital at Linkou, and MHC Tetramer Core Facility at Baylor College of Medicine for their invaluable help.Ethics ApprovalThis study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, Taiwan; approval number: 202001191B0C601.
A low-power content-addressable memory (CAM) using a differential match line (ML) sense amplifier is proposed in this work. The proposed self-disabled sensing technique can choke the charge current ...fed into the ML right after the matching comparison is generated. Instead of using typical nor/ nand-type CAM cells with the single-ended ML, the proposed novel nand CAM cell with the differential ML design can boost the speed of comparison without sacrificing power consumption. In addition, the 9-T CAM cell with disabled read-out circuit provides the complete write, read, and comparison functions to refresh the data and verify its correctness before searching. The CAM with the proposed technique is implemented on silicon to justify the performance by using a standard 0.13-¿m complementary metal-oxide-semiconductor process. The energy consumption of the searching process is 1.872 fJ/bit/search.
One-Time-Implantable Spinal Cord Stimulation System Prototype Hsu, Chia-Hao; Tseng, Shao-Bin; Hsieh, Yi-Jie ...
IEEE transactions on biomedical circuits and systems,
2011-Oct., 2011-Oct, 2011-10-00, 20111001, Volume:
5, Issue:
5
Journal Article
Peer reviewed
A prototype of a one-time-implantable spinal cord stimulation (SCS) system using wireless power and data-transmission techniques is presented in this paper. The power of the implant is induced by ...wireless coil coupling, and duplex amplitude-shift keying-load-shift keying wireless communication is used so that digital packets can be transmitted by the same inductive link. The proposed novel ASK demodulator attains high demodulation performance and small area without using any resistors and capacitors. The proposed SCS system utilizes many power saving schemes to reduce power dissipation (e.g., dual supply voltages on-chip, high-voltage impulse generation using small current, etc.). Meanwhile, the excess energy induced by the coils is stored in a rechargeable battery to extend the implant's operation time so that the number of battery replacement surgeries will be reduced significantly. The system-on-chip (SOC) is physically implemented on silicon and integrated in the implant as the system controller. The fabricated SOC area is 1410 × 1710 μm 2 . Compared with existing commercial products, the proposed SCS system attains better flexibility and longer operation time.
In autologous tissue breast reconstruction, recipient vessels are important for artery perfusion and venous drainage to ensure free flap survival. There are insufficient clinical outcomes to select ...efficient recipient vessels in bi-pedicled deep inferior epigastric perforator (DIEP) flap reconstruction.
We presented a retrospective observational series of 108 patients regarding the diameter, anastomosis time, and re-anastomosis rate in internal mammary (IM), circumflex scapular (CS), thoracodorsal (TD), thoracoacromial (TA), lateral thoracic (LT), and internal mammary perforator (IMP) vessels of bi-pedicled DIEP flaps for breast reconstruction after mastectomy. The outcomes were the vessel re-anastomosis rate, flap failure rate, vessel anastomosis time, and complications. Data were gleaned from the chi-square test, Fisher’s test, and analysis of variance using Scheffe’s test as a post hoc analysis. The level of significance was p < 0.05.
There were no significant differences in the diameters of the artery, first vein, and second vein across the recipient vessels (p > 0.05). However, the anastomosis time was longer in IM and TA than in CS, TD, and LT (p < 0.001). Also, there were no significant differences for re-anastomosis, flap necrosis, and fat necrosis among different recipient vessels (p > 0.05).
Because of the altered mastectomy incisions, this study provides complete anatomical vascular properties and suggests that altering recipient vessel selection for bi-pedicled DIEP flaps can shorten anastomosis time and better conceal scars.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The excellent electron transport properties of a ZnO interfacial layer in conventional perovskite solar cells (PSCs) lead to high power conversion efficiency (PCE). The perovskite layers are ...generally affected by decomposition via the interfacial layers of ZnO. In this work, we address the decomposition issue by modifying the ZnO surface with a uniformly assembled thin layer of poly-vinylpyrrolidone (PVP) or p-aminobenzoic acid (PABA), creating an interfacial modification layer. The PVP or PABA-modified ZnO surface provides better wettability and adhesion during the deposition of the perovskite active layer structure above it, making the perovskite morphology more uniform and pinhole-free. PSCs with PVP and PABA-modified ZnO substrates achieve PCE values of 14.12% and 14.07%, respectively. The modified ZnO surface also has high thermal stability (60 min at 90 °C).
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•To increase PSCs device stability, we deposited a buffer layer between ZnO and the perovskite active layer.•PVP- or PABA-modified ZnO can reduce the decomposition of a device.•The buffer layer effectively isolates ZnO and perovskite layers, leading to high device stability and performance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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