Whole-lesion iodine map histogram analysis in the risk classification of gastrointestinal stromal tumors: comparison with single-slice iodine concentration measurements.

PURPOSE: To evaluate and compare the diagnostic performances of whole-lesion iodine map (IM) histogram analysis and single-slice IM measurement in the risk classification of gastrointestinal stromal tumors (GISTs). METHODS: Thirty-seven patients with GISTs, including 19 with low malignant underlying GISTs (LG-GISTs) and 18 with high malignant underlying GISTs (HG-GISTs), were evaluated with dual-energy computed tomography (DECT). Whole-lesion IM histogram parameters (mean; median; minimum; maximum; standard deviation; variance; 1st, 10th, 25th, 50th, 75th, 90th, and 99th percentile; kurtosis, skewness, and entropy) were computed for each lesion. In other sessions, iodine concentrations (ICs) were derived from the IM by placing regions of interest (ROIs) on the tumor slices and normalizing them to the iodine concentration in the aorta. Both quantitative analyses were performed on the venous phase images. The diagnostic accuracies of the two methods were assessed and compared. RESULTS: The minimum, maximum, 1st, 10th, and 25th percentile of the whole-lesion IM histogram and the IC and normalized IC (NIC) of the single-slice IC measurement significantly differed between LG- and HG-GISTs (p < 0.001 - p = 0.042). The minimum value in the histogram analysis (AUC = 0.844) and the NIC in the single-slice measurement analysis (AUC = 0.886) showed the best diagnostic performances. The NIC of single-slice measurements had a diagnostic performance similar to that of the whole-lesion IM histogram analysis (p = 0.618). CONCLUSIONS: Both whole-lesion IM histogram analysis and single-slice IC measurement can differentiate LG-GISTs and HG-GISTs with similar diagnostic performances.

Deubiquitinase UCHL1 promotes angiogenesis and blood-spinal cord barrier function recovery after spinal cord injury by stabilizing Sox17.

Improving the function of the blood-spinal cord barrier (BSCB) benefits the functional recovery of mice following spinal cord injury (SCI). The death of endothelial cells and disruption of the BSCB at the injury site contribute to secondary damage, and the ubiquitin-proteasome system is involved in regulating protein function. However, little is known about the regulation of deubiquitinated enzymes in endothelial cells and their effect on BSCB function after SCI. We observed that Sox17 is predominantly localized in endothelial cells and is significantly upregulated after SCI and in LPS-treated brain microvascular endothelial cells. In vitro Sox17 knockdown attenuated endothelial cell proliferation, migration, and tube formation, while in vivo Sox17 knockdown inhibited endothelial regeneration and barrier recovery, leading to poor functional recovery after SCI. Conversely, in vivo overexpression of Sox17 promoted angiogenesis and functional recovery after injury. Additionally, immunoprecipitation-mass spectrometry revealed the interaction between the deubiquitinase UCHL1 and Sox17, which stabilized Sox17 and influenced angiogenesis and BSCB repair following injury. By generating UCHL1 conditional knockout mice and conducting rescue experiments, we further validated that the deubiquitinase UCHL1 promotes angiogenesis and restoration of BSCB function after injury by stabilizing Sox17. Collectively, our findings present a novel therapeutic target for treating SCI by revealing a potential mechanism for endothelial cell regeneration and BSCB repair after SCI.

Differential diagnosis of lung cancer and tuberculosis based on 18 F-fluorodeoxyglucose PET/CT multi-time points imaging.

OBJECTIVE: To investigate the value of 18 F-fluorodeoxyglucose(FDG) PET/CT multi-time points imaging (MTPI) on the differential diagnosis between lung cancer (LC) and tuberculosis (TB). METHODS: Sixty-four patients underwent 18 F-FDG PET/CT MTPI. The stdSUVmax, stdSUVavg, retention index, metabolic tumor volume, total lesion glycolysis at four-time points and slope of metabolic curve were measured and calculated, and the sex, age, and uniformity of FDG uptake were recorded. The difference in each index between LC and TB was analyzed, and dynamic metabolic curves (DMCs) of LC and TB were fitted by significance indexes. Artificial neural network (ANN) prediction models were established between squamous cell carcinoma (SCC) and TB, as well as between adenocarcinomas and TB. RESULTS: Differences between SCC and TB, stdSUVmax/avg at four-time points, total lesion glycolysis, stdSUVmax/avg slope (1-2 h,1-3 h and 1-4 h), uniformity of FDG uptake and age were significant. stdSUVavg has the largest area under the 4 h curve; age was only significant between adenocarcinomas and TB. DMCs at 1-4 h fitted by stdSUVavg were more helpful in differentiating LC and TB than stdSUVmax. stdSUVavg(1 h and 4 h), stdSUVavg slope 1-4 h, age, and uniformity of FDG uptake were selected to establish an ANN prediction model between SCC and TB; the area under the curve (AUC) was 100.0%. The same indices were used to establish the prediction model between adenocarcinomas and TB; the AUC was up to 83.5, and after adding stdSUVavg (2 and 4 h) to adenocarcinomas and TB models, the AUC was 87.7%. CONCLUSION: 18 F-FDG PET/CT MTPI fitting DMCs and establishing an ANN prediction model would distinguish SCC from TB relatively accurately and provide certain help in the differentiation between adenocarcinomas and TB.

Dual-responsive antibiotic and baicalein co-delivery nanoparticles with enhanced synergistic antibacterial activity.

Globally, due to the rapid development of bacterial resistance, bacterial infections lead to significant mortality and morbidity which require efficient strategies to eradicate these infections. Herein, we prepared a dual-responsive synergistic drug delivery nanoparticle carrier (NPS@Bai/Cip), which responds to sub-acid bacterial microenvironments and targets phosphatase or phospholipase at infection sites. Nanoparticles surfaces were positively (10.0 mV) charged under acidic conditions, leading to good bacterial adhesion and enhanced drug accumulation. NPS@Bai/Cip showed good antibacterial and anti-biofilm activity against drug-resistant Pseudomonas aeruginosa. NPS@Bai/Cip could inhibit the biofilm formation via affecting the swimming, swarming, and twitching motilities of P. aeruginosa. NPS@Bai/Cip was used to treat drug-resistance P. aeruginosa-induced infection in rats by improving wound healing and reducing inflammatory responses. Thus, NPS@Bai/Cip functioned as an antibacterial and antibiofilm agent with good potential for treating bacteria-induced infections.

Value of dynamic metabolic curves and artificial neural network prediction models based on 18F-FDG PET/CT multiphase imaging in differentiating nonspecific solitary pulmonary lesions: a pilot study.

OBJECTIVE: To investigate the value of dynamic metabolic curves and artificial neural network prediction models based on 18F-FDG PET multiphase imaging in differentiating nonspecific solitary pulmonary lesions. METHODS: This study enrolled 71 patients with solitary pulmonary lesions (48 malignant and 23 benign lesions) who underwent multiphase 18F-fluorodeoxyglucose (18F-FDG)-PET/CT imaging. We recorded information on age, sex and uniformity of FDG uptake, measured standardized uptake value, metabolic tumor volume and total lesion glycolysis at various time points, and calculated individual standardized uptake values, retention index (RI) and slope of metabolic curve. Variables with high diagnostic efficiency were selected to fit dynamic metabolic curves for various lesions and establish different artificial neural network prediction models. RESULTS: There were no significant differences in the retention index, metabolic tumor volume, total lesion glycolysis or sex between benign and malignant lesions; standardized uptake values, the slopes of five metabolic curves, uniformity of FDG uptake, and age showed significant differences. Dynamic metabolic curves for various solitary pulmonary lesions exhibited characteristic findings. Model-1 was established using metabolic parameters with high diagnostic efficacy (area under the curve, 83.3%). Model-2 was constructed as Model-1 + age (area under the curve, 86.7%), whereas Model-3 was established by optimizing Model-2 (area under the curve, 86.0%). CONCLUSIONS: Dynamic metabolic curves showed varying characteristics for different lesions. Referring to these findings in clinical work may facilitate the differential diagnosis of nonspecific solitary pulmonary lesions. Establishing an artificial neural network prediction model would further improve diagnostic efficiency.

Dual-Responsive Curcumin-Loaded Nanoparticles for the Treatment of Cisplatin-Induced Acute Kidney Injury.

Acute kidney injury (AKI) has been a global public health concern leading to high patient morbidity and mortality in the world. Nanotechnology-mediated antioxidative therapy has facilitated the treatment of AKI. Herein, a hierarchical curcumin-loaded nanodrug delivery system (NPS@Cur) was fabricated for antioxidant therapy to ameliorate AKI. The nanoplatform could respond to subacidic and reactive oxygen species (ROS) microenvironments. The subacidic microenvironment led to a smaller size (from 140.9 to 99.36 nm) and positive charge (from -4.9 to 12.6 mV), contributing to the high accumulation of nanoparticles. An excessive ROS microenvironment led to nanoparticle degradation and drug release. In vitro assays showed that NPS@Cur could scavenge excessive ROS and relieve oxidative stress in H2O2-induced HK-2 cells through reduced apoptosis, activated autophagy, and decreased endoplasmic reticulum stress. Results from cisplatin-induced AKI models revealed that NPS@Cur could effectively alleviate mitochondria injury and protect kidneys via antioxidative protection, activated autophagy, decreased endoplasmic reticulum stress, and reduced apoptosis. NPS@Cur showed excellent biocompatibility and low toxicity to primary tissues in mice. These results revealed that NPS@Cur may be a potential therapeutic strategy for efficiently treating cisplatin or other cause-induced AKI.

Microbial mediated arsenate reducing behavior in landfill leachate-saturated zone.

As(V) reduction mediated by microorganisms might be an essential process in resisting As toxicity since As(V) is the major species in the landfill. LSZ has been considered as a trigger of all types of microbial activity inside a landfill site. This research investigated the microbial As(V)-reducing behavior in LSZ. The results revealed that higher As(V)-reduction efficiency in higher As(V) content-stress LSZ scenario. The corresponding microbial diversity also varied with the As(V) content. The microbial community structure was related to arrA and arsC distribution, which encode respiratory As(V) reductase and cytoplasmic As(V) reductase, respectively. The landfill As bio-reduction pathways were modeled, as well as the As functional gene distribution among different As(V) contents at different landfill stages. The C, N, and S metabolic processes generally affected the As(V)-resistance genes distribution. Thiosulfate oxidation, denitrification, and dissimilatory nitrate reduction positively affected arsC, while dissimilatory sulfate reduction and methanogenesis trended to play a negative role. This research provides new insight into As(V) bio-reduction inside a landfill site in terms of functional genes distribution and correlation with nutrient elements metabolic processes.

Inferences of SPECT renal dynamic imaging injection quality based on lung and abdominal aorta imaging features.

OBJECTIVE: To analyze the characteristics of blood flow perfusion images at different injection levels to establish an evaluation standard for renal dynamic imaging injection quality and reduce misdiagnosis. METHODS: Data from 140 single-photon emission computed tomography renal dynamic imaging, collected in our hospital, were retrospectively analyzed. The scans were divided into four groups according to the injection quality: total leakage of the imaging agent (group A), partial leakage (group B), poor bolus injection quality (group C), and good bolus injection quality (group D). The time of appearance and regression of the pulmonary blood perfusion phase, the peak time in the abdominal aorta, and the ratio between peak count and actual drug injection count were analyzed. The renal dynamic imaging was repeated in low-quality examinations, and the comparison between the two exams provided the misdiagnosis rate caused by inadequate injections. RESULTS: The images of the lungs and abdominal aorta in group A were blurred and indistinguishable; thus, these exams were unreliable. Both appearance and fading time of the bilateral lung shadows were significantly different between groups B, C, and D (p = 0.002 and p = 0.003, respectively). The peak time and peak counting ratio in the abdominal aorta were also significantly different between these groups (p = 0.002 and p < 0.001, respectively). The misdiagnosis rates of renal dynamic imaging in groups A, B, and C due to the different injection levels were significantly different at 94.29%, 77.14%, and 18.29%, respectively. CONCLUSIONS: The times of appearance and regression of the lung shadows and the peak time and peak count ratio in the abdominal aorta in the dynamic renal imaging perfusion phase can help assess the imaging agent injection quality and identify the need for a repeated examination. Improving the imaging agent injection quality can effectively reduce the renal function misdiagnosis rate.

Flea index predicts plague epizootics among great gerbils (Rhombomys opimus) in the Junggar Basin China plague focus.

BACKGROUND: The Junggar Basin plague focus was the most recently identified natural plague focus in China. Through extensive field investigations, great gerbils (Rhombomys opimus) have been confirmed as the main host in this focus, and the community structure of their parasitic fleas is associated with the intensity of plague epizootics. The aim of this study is to provide an indicator that can be surveyed to evaluate the risk of plague epizootics. METHODS: Between 2005 and 2016, rodents and fleas were collected in the Junggar Basin plague focus. The parasitic fleas on great gerbils were harvested, and anti-F1 antibody in the serum or heart infusion of great gerbils was detected through indirect hemagglutination assay. Yersinia pestis (Y. pestis) was isolated from the liver and spleen of great gerbils and their parasitic fleas using Luria-Bertani plates. Receiver-operating characteristic (ROC) curve was used to evaluate the predictive value of flea index. RESULTS: Between 2005 and 2016, 98 investigations were performed, and 6778 great gerbils and 68,498 fleas were collected. Twenty-seven rodents were positive for Y. pestis isolation with a positivity rate of 0.4%; 674 rodents were positive for anti-F1 antibody with a positivity rate of 9.9%. Among these 98 investigations, plague epizootics were confirmed in 13 instances by Y. pestis-positive rodents and in 59 instances by anti-F1 antibody-positive rodents. We observed a higher flea index among rodents with confirmed plague epizootic compared to the negative ones (P = 0.001, 0.002), with an AUC value of 0.659 (95% CI: 0.524-0.835, P = 0.038) for Y. pestis-positive rodents and an AUC value of 0.718 (95% CI: 0.687-0.784, P < 0.001) for anti-F1 antibody-positive rodents. CONCLUSIONS: Significantly higher flea index was associated with confirmed plague epizootic cases among great gerbils and could be used to predict plague epizootics in this focus.

Minimal apparent diffusion coefficient in predicting the Ki-67 proliferation index of pancreatic neuroendocrine tumors.

PURPOSE: To investigate the diagnostic performance of the minimal apparent diffusion coefficient (ADCmin) to distinguish between pancreatic neuroendocrine tumors (Pan-NETs) with low and high Ki-67 proliferation index values and to evaluate the relationship between ADCmin and the Ki-67 proliferation index. METHODS: Pre-operative magnetic resonance imaging data and postoperative Ki-67 proliferation index data of 42 patients with primary neuroendocrine tumor of the pancreas from November 2014 to March 2021 were included in this retrospective study. According to the Ki-67 proliferation index value, Pan-NETs were divided into a high-expression group (Ki-67 ≥ 10%, n = 17) and low-expression group (Ki-67 < 10%, n = 25), and mean ADC (ADCmean) and ADCmin values were compared between groups using receiver operating characteristic (ROC) curves to evaluate the performance of ADCmean and ADCmin in judging the expression level of Ki-67 proliferation index. The relationship between ADCmin and the Ki-67 proliferation index was also evaluated. RESULTS: The ADCmin was significantly higher in the low-expression group (Z = - 3.537, p < 0.01). The area under the ROC curve (AUC) for ADCmin was 0.825, which was higher than that for ADCmean (0.781). Using 1.32 × 10-3 mm2/s as the optimal discriminating threshold, the sensitivity, specificity, accuracy, and positive and negative predictive values of the two groups were 80%, 88.2%, 83.3%, 90%, and 75%, respectively. The ADCmin of Pan-NETs showed a significant negative correlation with the Ki-67 proliferation index (rs = - 0.634, p < 0.001). CONCLUSION: The ADCmin is a potential imaging biomarker, which may be helpful for non-invasive preoperative prediction of the Ki-67 proliferation index of Pan-NETs and the subsequent planning of appropriate treatment.

Primary lung invasive adenocarcinoma misdiagnosed as infectious pneumonia in 18F-FDG PET/CT:A case report.

A 64-year-old woman presented to our hospital with cough and a large amount of white foam sputum, F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) showed diffuse ground-glass opacities in both lungs, which was considered as infectious pneumonia. However, after ineffective anti-infection, the primary invasive mucinous adenocarcinoma was finally diagnosed. Pulmonary invasive mucinous adenocarcinoma is rare and special subtype of lung adenocarcinoma, it has a variety of imaging manifestations. When intense tracer uptake, air bronchial sign, honeycomb sign present in diffuse ground-glass opacities in F-FDG PET/CT, lung invasive mucinous adenocarcinoma should be highly suspected.

Diagnostic efficacy of SPECT/CT MPI and CMR in children with myocarditis caused by different infection sources.

This study aimed to analyze the diagnostic efficacy of 99mTc-methoxy isobutyl isonitrile (MIBI) single photon emission tomography (SPECT/CT) myocardial perfusion imaging (MPI) and cardiac magnetic resonance imaging (CMR) in children with myocarditis caused by different infection sources and provide an imaging reference basis for clinical diagnosis and treatment. In total, 232 children diagnosed with myocarditis were retrospectively divided into five groups according to the different infection sources: viral infection (group A), bacterial infection (group B), viral combined with bacterial infection (group C), viral combined with mycoplasma infection (group D), and bacterial combined with mycoplasma infection (group E). A chi-square test and ANOVA were used to analyze the difference between SPECT/CT MPI and CMR in the diagnosis of myocarditis in children according to their categorical infection source group, including the impact of the average daily hospital costs (a=0.05). The positive rates of SPECT/CT in groups A and D were higher than those of CMR, and the positive rates of SPECT/CT in groups C and E were lower than those of CMR, with statistically significant differences (P < 0.05). The SPECT/CT ischemic lesions were located in the anterior wall, or the anterior wall combined with other walls of the left ventricle in 69.5% of patients. SPECT/CT MPI had no effect on the average daily hospitalization cost (P > 0.05); however, the average daily hospitalization cost of CMR-negative patients in group D was higher than that of CMR-positive patients, and it was statistically significant in groups C and E (P < 0.05). In groups A and D, the use of 99mTc-MIBI SPECT/CT MPI was preferred for diagnosing myocarditis. The detection rate of CMR was higher in groups C and E. SPECT/CT MPI findings of ischemic segments were mostly found in the anterior wall. The results of CMR diagnosis affected the average daily hospitalization cost among patients with different infection sources; however, SPECT/CT had no such effect. These findings denote a potential targeted approach to myocarditis diagnosis in pediatric patients based on source of infection.

Lung adenocarcinoma: development of nomograms based on PET/CT images for prediction of epidermal growth factor receptor mutation status and subtypes.

OBJECTIVE: To develop nomograms that combine clinical characteristics, computed tomographic (CT) features and 18F-fluorodeoxyglucose PET (18F-FDG PET) metabolic parameters for individual prediction of epidermal growth factor receptor (EGFR) mutation status and exon 19 deletion mutation and exon 21 point mutation (21 L858R) subtypes in lung adenocarcinoma. METHODS: In total 124 lung adenocarcinoma patients who underwent EGFR mutation testing and whole-body 18F-FDG PET/CT were enrolled. Each patient's clinical characteristics (age, sex, smoking history, etc.), CT features (size, location, margins, etc.) and four metabolic parameters (SUVmax, SUVmean, MTV and TLG) were recorded and analyzed. Logistic regression analyses were performed to screen for significant predictors of EGFR mutation status and subtypes, and these predictors were presented as easy-to-use nomograms. RESULTS: According to the results of multiple regression analysis, three nomograms for individualized prediction of EGFR mutation status and subtypes were constructed. The area under curve values of three nomograms were 0.852 (95% CI, 0.783-0.920), 0.857 (95% CI, 0.778-0.937) and 0.893 (95% CI, 0.819-0.968) of EGFR mutation vs. wild-type, 19 deletion mutation vs. wild-type and 21 L858R vs. wild-type, respectively. Only calcification showed significant differences between the EGFR 19 deletion and 21 L858R mutations. CONCLUSION: EGFR 21 L858R mutation was more likely to be nonsolid texture with air bronchograms and pleural retraction on CT images. And they were more likely to be associated with lower FDG metabolic activity compared with those wild-types. The sex difference was mainly caused by the 19 deletion mutation, and calcification was more frequent in them.

Amphiphilic block versus random copolymer nanoparticles with reactive oxygen species responsiveness as berberine vehicles.

A series of amphiphilic block and random copolymers based on phenylboronic acid pinacol ester were synthesized via reversible addition-fragmentation chain transfer polymerization. The obtained copolymers can self-assemble in aqueous solution into stable block copolymer nanoparticles and random nanoparticles with sizes of 116.1-158.6 and 126.3-187.0 nm, respectively. All nanoparticles showed hydrogen peroxide (H2O2) sensitivity, and the random copolymer nanoparticles presented faster responsiveness to H2O2 than did those derived from block copolymers. Berberine (BBR) can be effectively encapsulated into block and random copolymer nanoparticles with loading capacity of 7.6%-9.1% and 7.3%-8.9%, respectively. The BBR release can be controlled in an H2O2 medium. For the random copolymer nanoparticles, the release rate of BBR was faster and the cumulative release amounts in response to H2O2 were higher over 48 h. The BBR cumulative release amount in the H2O2 medium for the block and random copolymer nanoparticles was 62.2%-70.2% and 68.6%-80.4%, respectively. Moreover, good biocompatibility was observed for the BBR-loaded block and random copolymer nanoparticles. BBR and BBR-loaded nanoparticles can improve Glut4 translocation to the cell membrane and promote glucose transport into cells. BBR-loaded nanoparticles can decrease the blood glucose levels in diabetic rats over 15 days. These results imply that the different chain formulation of block and random copolymers affects the H2O2 responsiveness and that the two kinds of nanoparticles exhibit potential application as novel vehicles for BBR delivery to regulate blood glucose levels.

Co-delivery of antibiotic and baicalein by using different polymeric nanoparticle cargos with enhanced synergistic antibacterial activity.

To evaluate the effect of polymer structures on their unique characteristics and antibacterial activity, this study focused on developing amphiphilic copolymers by using three different molecules through RAFT polymerization. Three amphiphilic copolymers, namely, PBMA-b-(PDMAEMA-r-PPEGMA) (BbDrE), (PBMA-r-PDMAEMA)-b-PPEGMA (BrDbE), and PBMA-r-PDMAEMA-r-PPEGMA (BrDrE), are successfully self-assembled into spherical or oval shaped nanoparticles in aqueous solution and remain stable in PBS, LB, and 10% FBS solutions for at least 3 days. The critical micelle concentrations are 0.012, 0.025, and 0.041 mg/mL for BbDrE, BrDbE, and BrDrE, respectively. The zeta potential values under pH 5.5 and pH 7.4 conditions are 3.18/0.19, 8.57/0.046, and 2.54/-0.69 mV for BbDrE, BrDbE, and BrDrE nanoparticles, respectively. The three copolymers with similar monomer compositions show similar molecular weight and thermostability. Baicalein (BA) and ciprofloxacin (CPX) are encapsulated into the three nanoparticles to obtain BbDrE@BA/CPX, BrDbE@BA/CPX, and BrDrE@BA/CPX nanocomposites, with LC values of 63.9/78.3, 63.9/74.7, and 55.3/64.8, respectively. The two drugs are released from the three drug-loaded nanocomposites with 60%-95% release in pH 5.5 over 24 h and 15%-30% release in pH 7.4. The drug-loaded nanocomposites show synergistic antibacterial activity than the naked drug (2-8 fold reduction for CPX) or single drug-loaded nanocomposites (4-8 fold reduction for CPX) against Pseudomonas aeruginosa and Staphylococcus aureus. The drug-loaded nanocomposites inhibit the formation of bacterial biofilms above their MIC values and eliminate bacterial biofilms observed by fluorescent microscope. Finally, the nanocomposites improve the healing of infection induced by P. aeruginosa and S. aureus on rat dermal wounds. These results indicate that antimicrobial agents with different structures could be an alternative treatment strategy for bacteria-induced infection.

Association between medical resources and the proportion of oldest-old in the Chinese population.

The potential association between medical resources and the proportion of oldest-old (90 years of age and above) in the Chinese population was examined, and we found that the higher proportion of oldest-old was associated with the higher number of beds in hospitals and health centers.

Short-term exposure to air pollution and occurrence of emergency stroke in Chongqing, China.

OBJECTIVE: This study aimed to study the relationship between air pollution and stroke (especially emergency stroke) in different regions and determine which air pollutant is the most significantly associated with stroke. METHODS: The number of patients with emergency stroke, air pollutant data and related meteorological indicators were collected from December 2013 to May 2018 for large comprehensive hospitals in Chongqing. The generalized additive model was used to analyse the relationship between air pollution and emergency stroke. RESULTS: After analysis and adjusting for meteorological indicators and day-of-the-week effects, in the one-pollutant model, every 10 µg/m3 increase in ozone(O3) was associated with a 2.482% (95% CI 1.044%, 3.919%) change in emergency strokes within lag0. For males, every 10 µg/m3 increase of O3 contributed to a 0.77% percent greater change compared with females. For the group younger than 60 years, we observed a 1.14% increase in risk with every 10 µg/m3 increase in O3. The group with pre-existing hypertension had a 0.26% higher risk than the group with no pre-existing hypertension with every 10 µg/m3 increase in O3. In two-pollutant model, when O3 was combined with a 10 µg/m3 increase of NO2, it increased the most significant risk of emergency stroke by 0.22%. CONCLUSION: These findings suggest that short-term exposure to O3 within 0 days is associated with emergency outpatient strokes, and younger people (age < 60 years) males and people with hypertension are more sensitive than older people, females and people without pre-existing hypertension.

Exosomes derived from GIT1-overexpressing bone marrow mesenchymal stem cells promote traumatic spinal cord injury recovery in a rat model.

OBJECTIVE: This study aims to explore the effects of exosomes derived from G protein-coupled receptor kinase 2 interacting protein 1 (GIT1)-overexpressing bone marrow mesenchymal stem cell (GIT1-BMSC-Exos) on the treatment of traumatic spinal cord injury (SCI) in a rat model. METHODS: All the rats underwent a T10 laminectomy. A weight-drop impact was performed using a 10-g rod from a height of 12.5 mm except the sham group. Rats with SCI were distributed into three groups randomly and then treated with tail vein injection of GIT1-BMSCs-Exos, BMSCs-Exos and PBS, respectively. The effects of GIT1-Exos on glutamate (GLU)-induced apoptosis in vitro were also evaluated by TUNEL staining. RESULTS: The results showed that rats treated with GIT1-BMSCs-Exos had better functional behavioral recovery than those treated with PBS or BMSCs-Exos only. The overexpression of GIT1 in BMSCs-Exos not only restrained glial scar formation and neuroinflammation after SCI, but also attenuated apoptosis and promoted axonal regeneration in the injured lesion area. Neuronal cell death induced by GLU was controlled remarkably in vitro as well. CONCLUSION: In conclusion, our study suggested that the application of GIT1-BMSCs-Exos may provide a novel avenue for traumatic SCI treatment.

Salidroside Ameliorates Mitochondria-Dependent Neuronal Apoptosis after Spinal Cord Ischemia-Reperfusion Injury Partially through Inhibiting Oxidative Stress and Promoting Mitophagy.

Ischemia-reperfusion injury is the second most common injury of the spinal cord and has the risk of neurological dysfunction and paralysis, which can seriously affect patient quality of life. Salidroside (Sal) is an active ingredient extracted from Herba Cistanche with a variety of biological attributes such as antioxidant, antiapoptotic, and neuroprotective activities. Moreover, Sal has shown a protective effect in ischemia-reperfusion injury of the liver, heart, and brain, but its effect in ischemia-reperfusion injury of the spinal cord has not been elucidated. Here, we demonstrated for the first time that Sal pretreatment can significantly improve functional recovery in mice after spinal cord ischemia-reperfusion injury and significantly inhibit the apoptosis of neurons both in vivo and in vitro. Neurons have a high metabolic rate, and consequently, mitochondria, as the main energy-supplying suborganelles, become the main injury site of spinal cord ischemia-reperfusion injury. Mitochondrial pathway-dependent neuronal apoptosis is increasingly confirmed by researchers; therefore, Sal's effect on mitochondria naturally attracted our attention. By means of a range of experiments both in vivo and in vitro, we found that Sal can reduce reactive oxygen species production through antioxidant stress to reduce mitochondrial permeability and mitochondrial damage, and it can also enhance the PINK1-Parkin signaling pathway and promote mitophagy to eliminate damaged mitochondria. In conclusion, our results show that Sal is beneficial to the protection of spinal cord neurons after ischemia-reperfusion injury, mainly by reducing apoptosis associated with the mitochondrial-dependent pathway, among which Sal's antioxidant and autophagy-promoting properties play an important role.

Mitochondrial DNA genomes revealed different patterns of high-altitude adaptation in high-altitude Tajiks compared with Tibetans and Sherpas.

High-altitude Tajiks (HA-Tajiks), Tibetans and Sherpas are three groups of high-altitude native people in China. The differences in the mtDNA genome between the three populations and the role of the mtDNA genome in the high-altitude adaptation of HA-Tajiks were seldom investigated. In this study, 80 HA-Tajiks were enrolled, and their whole mtDNA genomes were sequenced. The haplogroup of each subject was determined by comparison to the revised Cambridge Reference Sequence (rCRS). Ten additional populations from East Asia and Central Asia, including Tibetans and Sherpas, were selected as references. The top haplogroup was U, followed by H, T and J. Principle component analysis and genetic distance analysis indicated that HA-Tajiks showed a close relationship with Wakhi Tajiks, Pamiri Tajiks and Sarikoli Tajiks, indicating that they should be considered one nation scattered around the Pamirs. The difference in the mtDNA genome between HA-Tajiks and Sherpas was significantly greater than that between HA-Tajiks and Tibetans. Among the 13 genes related to the OXPHOS pathway encoded by the mtDNA genome, HA-Tajiks showed more significant differences in ND3 and CYTB compared to Tibetans. Compared to Sherpas, HA-Tajiks showed more significant differences in ND1, ND2, COX1, ATP8, ATP6, ND3, ND4L, ND4, ND5 and CYTB. The associated functional changes and underlying molecular mechanisms should be explored by molecular and biochemical investigations in further studies.