The effectiveness of transplanted bone marrow mesenchymal stem cells (MSCs) for cardiac repair has been limited; thus, strategies for optimizing stem-cell-based myocardial therapy are needed.The present study was designed to test our central hypothesis that hypoxia-preconditioned MSCs (HP-MSCs) are more effective than MSCs cultured under ambient oxygen levels for the treatment of myocardial injury in a large-scale (N=49), long-term (9 months), nonhuman primate (Cynomolgous monkeys) investigation.MSCs were engineered to express green fluorescent protein, cultured under ambient oxygen or 0.5% oxygen (HP-MSCs) for 24 hours and then tested in the infarcted hearts of Cynomolgus monkeys (1×10(7) cells per heart). Hypoxia preconditioning increased the expression of several prosurvival/proangiogenic factors in cultured MSCs, and measurements of infarct size and left-ventricular function at day 90 after myocardial infarction were significantly more improved in monkeys treated with HP-MSCs than in monkeys treated with the control vehicle; functional improvements in normal cultured bone marrow mesenchymal stem cells-treated monkeys were not significant. HP-MSCs transplantation was also associated with increases in cardiomyocyte proliferation, vascular density, myocardial glucose uptake, and engraftment of the transplanted cells and with declines in endogenous cell apoptosis, but did not increase the occurrence of arrhythmogenic complications.Hypoxia preconditioning improved the effectiveness of MSCs transplantation for the treatment of myocardial infarction in nonhuman primates without increasing the occurrence of arrhythmogenic complications, which suggests that future clinical trials of HP-MSCs transplantation are warranted.
Abstract Background : Breast cancer is a leading cause of cancer in females, and is the second leading cancer-related cause of death in this group. Early diagnosis is essential to breast cancer to be effectively treated, and ultrasound, mammography, and magnetic resonance imaging (MRI) represent three key technologies that are utilized for the diagnosis of breast lesions. Breast-specific gamma imaging (BSGI) is an approach to molecular breast imaging that allows for high-resolution radio-imaging that is not adversely impacted by breast tissue density. This study was therefore designed to assess the relative diagnostic efficacy of BSGI, MRI, mammography, and ultrasound in different molecular subtypes of breast cancer among Chinese women. Methods : Diagnostic findings from 390 patients that had undergone diagnosis and treatment in our breast surgery department were retrospectively reviewed. Patients had been diagnosed via BSGI, mammography, ultrasound, and MRI. The diagnostic efficacy of these different imaging modalities and their associated biological characteristics were compared in the present study. Results: A total of 229 of these 390 patients (58.7%) were diagnosed with malignant breast cancer, with the remaining 161 (41.3%) cases having been found to be benign. BSGI, MRI, mammography, and ultrasound yielded respective sensitivity values of 91.7%, 92.5%, 77.3%, and 82.1%, while the respective specificity values for these imaging modalities were 80.7%, 69.7%, 74.5%, and 70.8%. For lesions > 1 cm, BSGI offered a sensitivity of 92.5%. For mammographic breast density A, B, C, and D, BSGI offered a sensitivity of 93.3%, 94.0%, 91.5%, and 89.3%, respectively. BSGI also yielded a significantly higher lesion-to-normal lesion ratio (LNR) for malignant lesions relative to benign lesions (2.76±1.32 vs 1.46±0.49). Conclusions : These findings confirm that BSGI is highly sensitive and is superior to mammography in the detection and diagnosis of ductal carcinomas in situ (DCIS). Such diagnostic efficacy can be further improved by using BSGI as an auxiliary modality to mammography and ultrasound, potentially improving the reliability of breast lesion diagnosis, thereby ensuring that patients receive rapid and effective treatment without the risk of misdiagnosis or unnecessary surgical treatment.
Although China has made remarkable achievements in ecological governance, it is imperative to acknowledge the persisting challenges. Firstly, the ecological monitoring and early warning system exhibit noteworthy imperfections, and access to information is delayed. Secondly, data integration and analysis are slow, and management decision-making lacks timeliness and accuracy. Thirdly, the ecological governance model implemented by the government's central authority is not energetic, and cross-sectoral cooperation is insufficient. China's efforts to improve the effectiveness of ecological governance are hindered by these obstacles. As one of the most important technological developments in the digital age, research indicates that artificial intelligence can expand the coverage of ecological monitoring, increase the speed of information acquisition and processing in ecological governance, improve the timeliness and scientificity of ecological decision-making, and strengthen multi-party cooperation to promote innovation in ecological governance models. Applying artificial intelligence to China's ecological governance will definitely improve its effectiveness and promote sustainable development goals.
Background: The present retrospective study was designed to evaluate the relative diagnostic utility of breast-specific gamma imaging (BSGI) and breast magnetic resonance imaging (MRI) as means of evaluating female breast cancer patients in China. Methods: A total of 229 malignant breast cancer patients underwent ultrasound, mammography, BSGI, and MRI between January 2015 and December 2018 for initial tumor staging. Of these patients, 73 were subsequently treated via definitive breast surgery following neoadjuvant chemotherapy (NAC), of whom 17 exhibited a complete pathologic response (pCR) to NAC. Results: BSGI and MRI were associated with 76.8% (43/56) and 83.9% (47/56) sensitivity (BSGI vs. MRI, p = 0.341) values, respectively, as a means of detecting residual tumors following NAC, while both these approaches exhibited comparable specificity in this diagnostic context. The specificity of BSGI for detecting residual tumors following NAC was 70.6% (12/17), and that of MRI was 58.8% (10/17) (BSGI vs. MRI, p = 0.473). Conclusion: These results demonstrate that BSGI is a useful auxiliary approach to evaluating pCR to NAC treatment.
Pre-clinical studies have shown that hypoxia preconditioning can enhance stem cell therapeutic potential for myocardial repair. We sought to investigate the safety and feasibility of intracoronary administration of hypoxia-preconditioned bone marrow mononuclear cells (HP-BMCs) for acute ST segment elevation myocardial infarction (STEMI).We randomized 22 patients with acute STEMI to receive intracoronary administration of normoxia bone marrow mononuclear cells (N-BMCs) (n=11) or HP-BMCs (n=11) following successful reperfusion. Another 14 patients receiving standard therapy were recruited as control (n=14).There were no differences in the occurrence of major adverse cardiovascular events at 30 days and 1 year among three groups. There were significant improvement in the change of left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) in HP-BMC group both at 6 and 12 months compared with N-BMCs or control group (P<0.05). No differences were observed in the change of left ventricular ejection fraction (LVEF), or wall motion score index (WMSI) among three groups. Nevertheless, WMSI was improved in HP-BMCs and N-BMC group (P<0.05, within group), but not in control. The ratio of myocardial perfusion defect determined by SPECT was significantly decreased in HP-BMCs and N-BMC groups at 6months compared with baseline (P<0.05, within group), but no significant differences were observed among three groups.Our results provide the first-in-man evidence that intracoronary administration of HP-BMCs following acute MI appears to be safe and feasible. These results provide the basis for future prospective randomized clinical trials in a larger patient cohort.NCT01234181 (http://clinicaltrials.gov/ct2/show/NCT01234181?term=NCT01234181&rank=1).
1736 Objectives: One of the key factors of glucose catabolism in the cell is thought to be the level of hexokinase expression. This study was to investigate the relationship between HK-II expression and 18F-fluoro-2-deoxy-D-glucose (FDG) uptake in human untreated head and neck carcinoma. Methods: Pre-operatively FDG positron emission tomography (PET) was performed 60 min after FDG injection in all the 36 patients. The tumor FDG uptake was evaluated by using maximum standardized uptake value (SUV). Tumor sections were stained immunohistochemically for HK-II. Results: All the tumor sections stained positive for HK-II. Thirty-four (94%) tumors in HK-II showed immunostained positive area >50%. HK-II findings revealed twenty-one (58%) tumors with strong intensity, twelve (33%) with moderate intensity and four with weak intensity (10%). There was no statistically significant correlation between SUV and the expression of HK-II (p = 0.50). Conclusions: In conclusion, head and neck carcinoma showed increased FDG accumulation and overexpression of HK-II. No significant relationship was found between high FDG uptake and overexpression of HK-II in this patient population, and thus other properties need to be evaluated in order to elucidate key factors responsible for FDG activity in head and neck carcinoma.
Background: Experiments in rodents have shown that hypoxic preconditioning (HP) can increase the therapeutic effectiveness of transplanted bone-marrow mesenchymal stem cells (MSCs) for myocardial infarction (MI). Here, we investigated whether the benefits associated with HP-MSC transplantation are also observed in non-human primates with MI. Methods: Allogeneic MSCs engineered to express GFP via lentiviral transfection were cultured in 21% oxygen (N-MSCs) or in 0.5% oxygen (HP-MSCs) for 24 hours. MI was surgically induced in Cynomolgus monkeys by ligating the left anterior-descending coronary artery distal to the first diagonal branch. 30 minutes later, 28 monkeys were each treated with 10 million MSCs intramyocardially injection. (N-MSCs: 13 monkeys; HP-MSCs: 15 monkeys). 11 additional monkeys treated with saline were served as control. LVEF and infarct sizes (IS) were measured echocardiographically, and the change in each parameter (ΔLVEF, ΔIS) was calculated by subtracting measurements taken 3 days post MI from measurements taken 28 days post MI. Incidents of ventricular arrhythmia were continuously detected via telemetry. Vascularity, arteriole density, proliferation, and endogenous progenitor-cell activation were evaluated via immunofluorescent assessments of CD31, SMA, Ki67, and c-kit expression, respectively; Engraftment was evaluated via RT-PCR measurements of GFP expression. Apoptosis was assessed with TUNEL staining, and the expression of pro-survival and/or pro-angiogenic genes was evaluated via immunoblot. Results: HP increased the expression of several pro-survival/pro-angiogenic factors (Ang 1, EPO, HGF, PDGF-BB) in cultured MSCs, and treatment with HP-MSCs, but not with N-MSCs was associated with significant improvements in ΔLVEF, ΔIS, vascularity, proliferation, and apoptosis. Vascularity and proliferation were also greater in HP-MSC animals than in N-MSC animals, and HP improved measurements of cell engraftment at Day 3, but not at Day 28. The incidence of arrhythmia (PVCs or NSVT) in all three experimental groups was similar. Conclusions: HP improved the effectiveness of MSC transplantation for the treatment of MI in non-human primates without increasing the occurrence of arrhythmogenic complications.
Abstract This research expounds on a novel reflective chirped grating, characterized by its differentiated functionality under various polarization modes. Under perpendicular incidence, this intricately grating produces a quintuple-channel diffraction output of the 0th, ±1st, and ±2nd orders in transverse electric (TE) polarization and a triple-channel diffraction output of the 0th and ±1st orders in transverse magnetic (TM) polarization. Both polarization modes exhibit excellent overall diffraction efficiency and uniformity. At an incident wavelength of 1550 nm, the diffraction efficiencies for the 0th, ±1st, and ±2nd orders under TE polarization are 20.16%, 19.27%, and 20.25%, respectively. Simultaneously, under TM polarization, the efficiencies for the 0th and ±1st orders are 31.79% and 31.57%, respectively. Grating parameters were meticulously derived using the finite element method (FEM) and subsequently corroborated through rigorous coupled-wave analysis (RCWA) to ensure superior grating accuracy. The study also exhaustively analyzes the manufacturing tolerances and robustness of the grating, affirming its practical applicability and effectiveness in practical applications. The dual-function grating splitter proposed in this paper enables the implementation of multiple functionalities within simple setups, suitable for applications requiring varied beam splitting. As photonic systems and fiber technology evolve, the potential applications of dual-function reflective splitters in these fields are increasingly highlighted.
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