Long-term mortality burden trends attributed to black carbon and PM2·5 from wildfire emissions across the continental USA from 2000 to 2020: a deep learning modelling study.

BACKGROUND: Long-term improvements in air quality and public health in the continental USA were disrupted over the past decade by increased fire emissions that potentially offset the decrease in anthropogenic emissions. This study aims to estimate trends in black carbon and PM2·5 concentrations and their attributable mortality burden across the USA. METHODS: In this study, we derived daily concentrations of PM2·5 and its highly toxic black carbon component at a 1-km resolution in the USA from 2000 to 2020 via deep learning that integrated big data from satellites, models, and surface observations. We estimated the annual PM2·5-attributable and black carbon-attributable mortality burden at each 1-km2 grid using concentration-response functions collected from a national cohort study and a meta-analysis study, respectively. We investigated the spatiotemporal linear-regressed trends in PM2·5 and black carbon pollution and their associated premature deaths from 2000 to 2020, and the impact of wildfires on air quality and public health. FINDINGS: Our results showed that PM2·5 and black carbon estimates are reliable, with sample-based cross-validated coefficients of determination of 0·82 and 0·80, respectively, for daily estimates (0·97 and 0·95 for monthly estimates). Both PM2·5 and black carbon in the USA showed significantly decreasing trends overall during 2000 to 2020 (22% decrease for PM2·5 and 11% decrease for black carbon), leading to a reduction of around 4200 premature deaths per year (95% CI 2960-5050). However, since 2010, the decreasing trends of fine particles and premature deaths have reversed to increase in the western USA (55% increase in PM2·5, 86% increase in black carbon, and increase of 670 premature deaths [460-810]), while remaining mostly unchanged in the eastern USA. The western USA showed large interannual fluctuations that were attributable to the increasing incidence of wildfires. Furthermore, the black carbon-to-PM2·5 mass ratio increased annually by 2·4% across the USA, mainly due to increasing wildfire emissions in the western USA and more rapid reductions of other components in the eastern USA, suggesting a potential increase in the relative toxicity of PM2·5. 100% of populated areas in the USA have experienced at least one day of PM2·5 pollution exceeding the daily air quality guideline level of 15 µg/m3 during 2000-2020, with 99% experiencing at least 7 days and 85% experiencing at least 30 days. The recent widespread wildfires have greatly increased the daily exposure risks in the western USA, and have also impacted the midwestern USA due to the long-range transport of smoke. INTERPRETATION: Wildfires have become increasingly intensive and frequent in the western USA, resulting in a significant increase in smoke-related emissions in populated areas. This increase is likely to have contributed to a decline in air quality and an increase in attributable mortality. Reducing fire risk via effective policies besides mitigation of climate warming, such as wildfire prevention and management, forest restoration, and new revenue generation, could substantially improve air quality and public health in the coming decades. FUNDING: National Aeronautics and Space Administration (NASA) Applied Science programme, NASA MODIS maintenance programme, NASA MAIA satellite mission programme, NASA GMAO core fund, National Oceanic and Atmospheric Administration (NOAA) GEO-XO project, NOAA Atmospheric Chemistry, Carbon Cycle, and Climate (AC4) programme, and NOAA Educational Partnership Program with Minority Serving Institutions.

Evaluating the diagnostic accuracy of a ctDNA methylation classifier for incidental lung nodules: protocol for a prospective, observational, and multicenter clinical trial of 10,560 cases.

BACKGROUND: Lung nodules are a diagnostic challenge. Current clinical management of lung nodule patients is inefficient and therefore causes patient misclassification, which increases healthcare expenses. However, a precise and robust lung nodule classifier to minimize discomfort for patients and healthcare costs is still lacking. The aim of the present protocol is to evaluate the effectiveness of using a liquid biopsy classifier to diagnose nodules compared to physician estimates and whether the classifier can reduce the number of unnecessary biopsies in benign cases. METHODS: A prospective cohort of 10,560 patients enrolled at 23 clinical centers in China with non-calcified pulmonary nodules, ranging from 0.5 to 3 cm in diameter, indicated by LDCT or CT will be included. After signed consent forms, the participants' pulmonary nodules will be assessed using three evaluation tools: (I) physician cancer probability estimates (II) validated lung nodule risk models, including Mayo Clinic and Veteran's Affairs models (III) ctDNA methylation classifier previously established. Each patient will undergo LDCT/CT follow-ups for 2 to 3 years and their information and one blood sample will be collected at baseline, 3, 6, 12, 24 and 36 months. The primary study outcomes will be the diagnostic accuracy of the methylation classifier in the cohort. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) will be used to compare the diagnostic value of each testing tool in differentiating benign and malignant pulmonary nodules. DISCUSSION: We are conducting an observational study to explore the accuracy of using a ctDNA methylation classifier for incidental lung nodules diagnosis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03651986.

[Clinical application of vertebral arch-transverse pathway in pedicle screw implantation].

OBJECTIVE: To investigate the safety and effectiveness of pedicle screw implantation via vertebral arch-transverse pathway in clinical application by a prospective randomized controlled trial. METHODS: Twenty-four patients who were admitted between May 2015 and June 2017 and met the selection criteria for thoracic pedicle screw fixation were included in the study. According to the random number table method, they were divided into the trial group (screw implantation via vertebral arch-transverse pathway) and the control group (traditional screw implantation technology), with 12 patients in each group. There was no significant difference between the two groups in age, gender, cause of injury, injured segment, and the interval between injury and operation (P>0.05). The time of screw implantation was recorded and compared between the two groups. The acceptable rate of screw implantation and the penetration rate of pedicle wall were calculated after operation. RESULTS: The time of screw implantation of trial group was (5.08±1.74) minutes, which was significantly shorter than that of control group [(5.92±1.66) minutes], and the difference was significant (t=4.258, P=0.023). Patients in both groups were followed up 1-2 years, with an average of 1.5 years. During the follow-up, no failure of internal fixation occurred. At 1 week after operation, the screw implantation in trial group was rated as gradeⅠin 54 screws, gradeⅡ in 3 screws, and grade Ⅲ in 2 screws, with the acceptable rate of 93.61%. The screw implantation in control group was rated as gradeⅠin 40 screws, grade Ⅱin 10 screws, grade Ⅲ in 8 screws, and grade Ⅳ in 1 screw, with the acceptable rate of 84.75%. There was significant difference in the acceptable rate of screw implantation between the two groups (χ2=3.875, P=0.037). The penetration rate of pedicle wall in trial group was 8.47% (5/59), which was significantly lower than that in the control group [32.20% (19/59); χ2=4.125, P=0.021]. CONCLUSION: Compared with the traditional technique, the pedicle screw implantation via vertebral arch-transverse pathway can obtain a good position of the screw canal with higher accuracy and simpler operation.

[Effects of N-acetylcysteine on apoptosis induced by myocardial ischemia reperfusion injury in rats' heart transplantation].

OBJECTIVE: To investigate the effect of N-acetylcysteine (NAC) on the apoptosis during myocardial ischemia reperfusion injury in rats' heart transplantation, and to explore the possible role of NAC in myocardial apoptosis. METHODS: Sixty healthy male Lewis rats (weighing, 200-220 g) were randomly divided into 3 groups, 20 rats each group (10 donors and 10 recipients). In control group, 1 mL normal saline was infused via inferior vena cava at 30 minutes before donor harvesting; in donor preconditioning group, NAC (300 mg/kg) was infused via inferior vena cava at 30 minutes before donor harvesting, but no treatment in recipients; and in recipient preconditioning group, NAC (300 mg/kg) was infused via inferior vena cava at 30 minutes before recipient transplantation, but no treatment in donors. Heart transplantation was established in each group. Blood was drawn at 6 and 24 hours after reperfusion for analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) as markers of graft injury; myocardial tissue was harvested to determine the superoxide dismutase (SOD) and lipid hydroperoxide (LPO) activity at 24 hours after reperfusion and to observe the histology and ultrastructural changes. Graft active Caspase-3 protein expression was measured by immunohistochemistry staining, and apoptosis index (AI) was calculated by TUNEL. RESULTS: The heart transplantation operation was successfully completed in all groups, and the rats survived to the end of the experiment. The serum levels of AST, ALT, and LDH in donor and recipient preconditioning groups were significantly lower than those in control group at 6 hours after reperfusion (P < 0.05); the levels of AST and ALT in donor preconditioning group and the levels of AST and LDH in recipient preconditioning group were significantly lower than those in control group at 24 hours (P < 0.05); and no significant difference was found between donor and recipient perconditioning groups (P > 0.05). The levels of AST, ALT, and LDH at 24 hours were significantly lower than those at 6 hours in each group (P < 0.05) except the level of ALT in recipient preconditioning group (P > 0.05). SOD activity and SOD/LPO in donor and recipient preconditioning groups were significantly higher than those in control group (P < 0.05), but no significant difference between donor and recipient preconditioning groups (P > 0.05); there was no significant difference in LPO activity among 3 groups (P > 0.05). Histological staining and transmission electron microscope showed that myocardial injury in recipient preconditioning group was obviously lighter than that in donor preconditioning group and control group. Active Caspase-3 in recipient pretreatment group was significantly higher than that in donor preconditioning group and control group (P < 0.05). AI of donor and recipient preconditioning groups was significantly lower than that of control group (P < 0.05), but no significant difference was found between donor and recipient preconditioning groups (P > 0.05). CONCLUSION: NAC can relieve ischemia reperfusion injury in rats' heart transplantation by improving myocardial SOD content, and reducing active Caspase-3 activity and AI, which has a protective effect on myocardial cell of donor heart.

Effects of a preconditioning oral nutritional supplement on pig livers after warm ischemia.

Background. Several approaches have been proposed to pharmacologically ameliorate hepatic ischemia/reperfusion injury (IRI). This study was designed to evaluate the effects of a preconditioning oral nutritional supplement (pONS) containing glutamine, antioxidants, and green tea extract on hepatic warm IRI in pigs. Methods. pONS (70 g per serving, Fresenius Kabi, Germany) was dissolved in 250 mL tap water and given to pigs 24, 12, and 2 hrs before warm ischemia of the liver. A fourth dose was given 3 hrs after reperfusion. Controls were given the same amount of cellulose with the same volume of water. Two hours after the third dose of pONS, both the portal vein and the hepatic artery were clamped for 40 min. 0.5, 3, 6, and 8 hrs after reperfusion, heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), portal venous flow (PVF), hepatic arterial flow (HAF), bile flow, and transaminases were measured. Liver tissue was taken 8 hrs after reperfusion for histology and immunohistochemistry. Results. HR, MAP, CVP, HAF, and PVF were comparable between the two groups. pONS significantly increased bile flow 8 hrs after reperfusion. ALT and AST were significantly lower after pONS. Histology showed significantly more severe necrosis and neutrophil infiltration in controls. pONS significantly decreased the index of immunohistochemical expression for TNF-α, MPO, and cleaved caspase-3 (P < 0.001). Conclusion. Administration of pONS before and after tissue damage protects the liver from warm IRI via mechanisms including decreasing oxidative stress, lipid peroxidation, apoptosis, and necrosis.

Distribution and differentiation of marrow stem cells transplanted by different ways in ischemic myocardium and other organs in rabbits.

In our study, BrdU-labeled marrow stem cells (MSCs) were directly (group 1), by the coronary artery (group 2), or by the ear vein (group 3) transplanted into myocardium to observe their distribution and differentiation in acute myocardial infarction (AMI) rabbit models. BrdU-positive cells, and BrdU and α-sarcomeric actin double positive cells were visible in the infarcted zones and its peripheral region. Cell processes between BrdU-positive cells and between BrdU-positive cells and host cardiomyocytes linked together. Transverse striation and sarcomere were seen. In above zones, new blood capillaries composed of Brdu-positive endothelial cells were present. Density of new blood capillaries was greater in group 1-3 than in control group (p < 0.05) and was the greatest in group 2. Hear function in group 1-3 was improved and was the best in group 2 (p < 0.05). In group 2 and 3, BrdU-positive cells were found in the lungs, liver, and kidneys. In group 3, BrdU-positive cells were greater in the lungs than in the liver and kidneys. We can see that MSCs transplanted by the three ways all can induce the regeneration of cardiomyocytes and blood capillaries. The order from good to poor effectiveness is group 2, group 1, and group 3.

Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantation.

Free radicals are involved in pathophysiology of ischemia/reperfusion injury (IRI). Melatonin is a potent scavenger of reactive oxygen and nitrogen species. Thus, this study was designed to elucidate its effects in a model of rat kidney transplantation. Twenty Lewis rats were randomly divided into 2 groups (n = 10 animals each). Melatonin (50 mg/kg BW) dissolved in 5 mL milk was given to one group via gavage 2 hr before left donor nephrectomy. Controls were given the same volume of milk only. Kidney grafts were then transplanted into bilaterally nephrectomized syngeneic recipients after 24 hr of cold storage in Histidine-Tryptophan-Ketoglutarate solution. Both graft function and injury were assessed after transplantation through serum levels of blood urea nitrogen (BUN), creatinine, transaminases, and lactate dehydrogenase (LDH). Biopsies were taken to evaluate tubular damage, the enzymatic activity of superoxide dismutase (SOD) and lipid hydroperoxide (LPO), and the expression of NF-kBp65, inducible nitric oxide synthase (iNOS), caspase-3 as indices of oxidative stress, necrosis, and apoptosis, respectively. Melatonin improved survival (P < 0.01) while decreasing BUN, creatinine, transaminases, and LDH values up to 39-71% (P < 0.05). Melatonin significantly reduced the histological index for tubular damage, induced tissue enzymatic activity of SOD while reducing LPO. At the same time, melatonin down-regulated the expression of NF-kBp65, iNOS, and caspase-3. In conclusion, donor preconditioning with melatonin protected kidney donor grafts from IRI-induced renal dysfunction and tubular injury most likely through its anti-oxidative, anti-apoptotic and NF-kB inhibitory capacity.

[Relationship and clinical significance of KiSS-1, nuclear factor kappa B (NF-kappaB), p50, and matrix metalloproteinase 9 expression in breast cancer].

OBJECTIVE: To study the expression of KiSS-1, nuclear factor kappa B (NF-kappaB) p50 and matrix metalloproteinase 9 (MMP-9) in breast cancer tissue and the relationship with clinicpathological factors. METHODS: Immunohistochemical staining for KiSS-1, NF-KappaBp50, and MMP-9 protein was performed in 152 cases of human breast tissue [92 cases of BC, 30 cases of epithelial hyperplasia, and 30 cases of peritumoral breast tissue (PMT)] and 54 cases of axillary lymph node metastases. In-situ hybridization for KiSS-1 mRNA was done in 50 cases of breast cancer, and 20 cases of PMT. RESULTS: (1) The expression of KiSS-1 gene was significantly higher in well-differentiated breast cancer than in PMT, and this expression progressively decreased with decreasing degree of tumor differentiation, increasing pathological grade, TNM stage and the presence of lymph node metastases. The expression of KiSS-1 gene in lymph node metastasis was markedly lower than the corresponding primary tumor. There was correlation between the expression of KiSS-1 mRNA and KiSS-1 protein in breast cancer group. (2) The expression of NF-kappaKBp50 and MMP-9 increased progressively with decreasing degree of tumor differentiation, increasing TNM stage, large tumor size ( >2 cm) and the presence of lymph node metastases. CONCLUSIONS: The expression of KiSS-1 protein showed negative correlation with that of NF-kappaBp50 and MMP-9 respectively. MMP-9 protein expression was positively correlated with NF-kappap50 protein expression. These suggest that the genes of KiSS-1, NF-kappaBp50 and MMP-9 could be involved in the progression and metastasis of breast cancer.

[Experimental study on umbilical vascular compliance and expression of antigen after removing endothelial cell].

OBJECTIVE: To evaluate which is better method zymogen or low temperature frozen in removing vascular endothelial cell so as to lay a foundation for creating a kind of brace which is not to be rejected and the same as own blood vessel. METHODS: Fresh and not damaged umbilical blood vessel was collected from natural labour women, human umbilical blood vessel was remove carefully from normal foetus, then was put into disinfectant at 37 C for 24 hours. They were divided into 3 groups:normal group (NG), zymogen group (ZG) and low temperature frozen group (LG). ZG: 0.1% collagen II enzyme was added in umbilical blood vessel and closed the both sides and the vascular endothelial cell was removed in 37 C water. LG:Umbilical blood vessel was put into liquid nitrogen for 24 hours after frozened step by step, and then it was put into 37 C water for 30-60s and the vascular endothelial cells were washed away by normal saline. NG:Umbilical blood vessel was kept into 4 C Kerb's liquid. The bacteria were cultured in each group. The samples were stained by HE, elastic fiber and collagen fiber were observed by light and scanning electron microscope. The difference of compliance was compared. Human leukocyte antigen ABC (HLA-ABC) and HLA-DR were observed by immunohistochemical method and the expression of antigen of umbilical blood vessel was analysed. Results In LG, umbilical vascular endothelial cells were removed completely; artery showed vertical smooth muscle and vein showed elastic membrane. In ZG, umbilical vascular endothelial cells were removed completely after 20 minutes; artery showed vertical smooth muscle cells and vein showed lower endothelial layer. The vascular compliance in LG was higher than that in NG, and the latter was also higher than that in ZG, but showing no significant differences (P > 0.05). The compliance of umbilical vein was 2-3 times as much as that of umbilical artery. The expression of HLA-ABC and HLA-DR in LG and ZG were lower than that in NG, showing significant differences (P < 0.01). CONCLUSION: Low temperature frozen method and zymogen method (0.1% collagen II enzyme for 20 min) can remove vascular endothelial cells of human umbilical blood vessel completely. Low temperature frozen method was better than zymogen method.