[Mechanism of action and exogenous supplementation of vitamin D in Crohn's disease]. / ç»´ç”Ÿç´ Dåœ¨å ‹ç½—æ©ç— ä¸­çš„ä½œç”¨æœºåˆ¶åŠå¤–æºæ€§è¡¥å 作用.

Vitamin D can not only regulate calcium and phosphorus metabolism, but also exert an immunoregulatory effect. Vitamin D deficiency is common in patients with Crohn's disease (CD). Studies have shown that vitamin D is associated with CD and other autoimmune diseases and can improve the condition of patients with CD and promote their recovery by regulating intestinal immunity, repairing the intestinal mucosal barrier, inhibiting intestinal fibrosis, enhancing the response to infliximab, and regulating intestinal microbiota. Exogenous vitamin D supplementation can induce disease remission while increasing the serum level of vitamin D. However, only a few randomized, double-blind, and placebo-controlled trials have investigated the therapeutic effect of vitamin D in CD, and the optimal form of vitamin D supplementation, the specific dosage of vitamin D supplementation, and the optimal serum maintenance concentration of vitamin D remain to be clarified. This article mainly discusses the mechanism of action of vitamin D in CD and the beneficial effect of exogenous vitamin D supplementation on CD.

[Nutritional status and its influencing factors in children with newly diagnosed inflammatory bowel disease]. / ç‚Žç—‡æ€§è‚ ç— åˆè¯Šæ‚£å„¿è¥å »çŠ¶å†µåŠå½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the nutritional status and its influencing factors in children with newly diagnosed inflammatory bowel disease (IBD). METHODS: A retrospective analysis was conducted on the clinical data of children who were diagnosed with IBD for the first time in Hunan Children's Hospital from January 2015 to December 2021. Diagnostic delay was defined as the time from the symptom onset to IBD diagnosis being in the upper quartile (P76-P100) of all IBD children in the study. Multivariate logistic regression analysis was used to explore the risk factors for emaciation and growth retardation. RESULTS: A total of 125 children with newly diagnosed IBD were included, with Crohn's disease being the main type (91.2%). The rates of emaciation and growth retardation were 42.4% (53 cases) and 7.2% (9 cases), respectively, and the rate of anemia was 77.6% (97 cases). Diagnostic delay was noted in 31 children (24.8%), with the time from the symptom onset to IBD diagnosis of 366 to 7 211 days. Multivariate logistic regression analysis showed that diagnostic delay was a risk factor for emaciation and growth retardation (OR=2.73 and OR=4.42, respectively; P<0.05) and that age was positively associated with emaciation (OR=1.30, P<0.05). CONCLUSIONS: Children with newly diagnosed IBD have poor nutritional status, and the rates of anemia, emaciation, and growth retardation are high. Diagnostic delay is associated with malnutrition in children with IBD.

The effects of N-addition on litter mixture effects depend on decomposition time: A case from mixed-litter decomposition in the Gurbantunggut Desert.

Changes in nitrogen (N) deposition and litter mixtures have been shown to influence ecosystem processes such as litter decomposition. However, the interactive effects of litter mixing and N-deposition on decomposition process in desert regions remain poorly identified. We assessed the simultaneous effects of both N addition and litter mixture on mass loss in a litterbag decomposition experiment using six native plants in single-species samples with diverse quality and 14-species combinations in the Gurbantunggut Desert under two N addition treatments (control and N addition). The N addition had no significant effect on decomposition rate of single-species litter (expect Haloxylon ammodendron), whereas litter mass loss and decomposition rate differed significantly among species, with variations positively correlated with initial phosphorus concentration and negatively correlated with initial lignin concentration. After 18 months, the average mass loss across litter mixtures did not overall differ from those predicted from single species either in control or N addition treatments, that is, mixing of different species had no non-additive effects on decomposition. The N addition, however, did modify the direction of mixture effects and interacted with incubation time. Added N transformed synergistic effects of litter mixtures to antagonistic effects on mass loss after 1 month of decomposition, while transforming neutral effects of litter mixture to synergistic effects after 6 months of decomposition. Our results demonstrated that initial chemical properties played an important role in litter decomposition, while no effects of litter mixture on decomposition process in this desert region. The N addition altered the litter mixture effects on mass loss with incubation time, implying that increased N deposition in the future may have profound effects on carbon turnover to a greater extent than previously thought in desert ecosystems.

Spatial-temporal distribution and pedestrian exposure assessment of size-fractionated particles on crosswalk of urban intersection.

Vehicles tend to produce more pollutants especially particles at an urban intersection than other segments. Meanwhile, pedestrians at an intersection are inevitably exposed to high particle level and suffered from the health problem. Especially, some particles can deposit in different thoracic areas of the respiratory system and cause serious health problems. Hence, in this paper, the particles from 0.3 to 10 µm in 16 channels were measured to compare the spatio-temporal characteristics of them on the crosswalk and the roadside. Based on the roadside of fixed measurements, submicron particles (< 1 µm) are discovered to have a high relation with traffic signal and exhibit a bimodal distribution pattern in the green phase. On the crosswalk of mobile measurements, submicron particles present decreasing trend along the crosswalk while crossing. Additionally, mobile measurements were conducted across six time intervals that correspond to different pedestrian's journey when passing the crosswalk. The results showed that all size particles in the first three journeys present high concentrations than that in other journeys. Furthermore, pedestrian exposure to all 16 channel particles was assessed. The total and regional deposition fractions of these particles in different sizes and age groups are determined. What ought to be paid attention to is that these real-world measurement results contribute to advancing the understanding of pedestrian exposure to size-fractionated particles on crosswalk and assisting the pedestrian to make better informed choice so as to limit particle exposure in these pollution hotspots.

Quantifying traffic-related carbon emissions on elevated roads through on-road measurements.

Vehicles generally move smoothly and with high speeds on elevated roads, thereby producing specific traffic-related carbon emissions in contrast to ground roads. Hence, a portable emission measurement system was adopted to determine traffic-related carbon emissions. The on-road measurement results revealed that the instantaneous emissions of CO2 and CO from elevated vehicles were 17.8% and 21.9% higher than those from ground vehicles, respectively. Based on it, the vehicle specific power was confirmed to exhibit a positive exponential relationship with instantaneous CO2 and CO emissions. In addition to carbon emissions, carbon concentrations on roads were simultaneously measured. The average CO2 and CO emissions on elevated roads in urban areas were 1.2% and 6.9% higher than those on ground roads, individually. Finally, a numerical simulation was performed, and the results verified that elevated roads could deteriorate the air quality on ground roads but improve the air quality above them. What ought to be paid attention to is that the elevated roads present varied traffic behaviour and cause particular carbon emissions, indicating that comprehensive consideration and further balance among the traffic-related carbon emissions are necessary when building elevated roads to alleviate the traffic congestion in urban areas.

High-Risk Breast Lesions Diagnosed by Ultrasound-Guided Vacuum-Assisted Excision.

PURPOSE: The aim of this study was to analyze the role of ultrasound-guided vacuum-assisted excision (US-guided VAE) in the treatment of high-risk breast lesions and to evaluate the clinical and US features of the patients associated with recurrence or development of malignancy. MATERIALS AND METHODS: Between April 2010 and September 2021, 73 lesions of 73 patients underwent US-guided VAE and were diagnosed with high-risk breast lesions. The incidence of recurrence or development of malignancy for high-risk breast lesions was evaluated at follow-up period. The clinical and US features of the patients were analyzed to identify the factors affecting the recurrence or development of malignancy rate. RESULTS: Only benign phyllodes tumors on US-guided VAE showed recurrences, while other high-risk breast lesions that were atypical ductal hyperplasia (ADH), lobular neoplasia (atypical lobular hyperplasia/lobular carcinoma in situ), radial scar, and flat epithelial atypia did not show recurrences or malignant transformation. The recurrence rate of the benign phyllodes tumor was 20.8% (5/24) in a mean follow-up period of 34.3 months. The recurrence rate of benign phyllodes tumor with distance from nipple of less than 1 cm was significantly higher than that of lesions with distance from nipple of more than 1 cm (75% vs. 10%, p < 0.05). CONCLUSIONS: Benign phyllodes tumors without concurrent breast cancer could be safely followed up instead of surgical excision after US-guided VAE when the lesions were classified as BI-RADS 3 or 4A by US.

Gefitinib improves severe bronchorrhea and prolongs the survival of a patient with lung invasive mucinous adenocarcinoma: A case report.

BACKGROUND: Lung invasive mucinous adenocarcinoma (LIMA), formerly referred to as mucinous bronchioloalveolar carcinoma, is a rare disease that usually presents as bilateral lung infiltration, is unsuitable for surgery and radiotherapy, and shows poor response to conventional chemotherapy. CASE SUMMARY: We report a 56-year-old Chinese man with a history of smoking and epidermal growth factor receptor mutation-positivity who was initially misdiagnosed as severe pneumonia, but was ultimately diagnosed as a case of invasive mucinous adenocarcinoma of the lung by computed tomography -guided percutaneous lung biopsy. Bronchorrhea and dyspnea were improved within 24 h after initiation of gefitinib therapy and the radiographic signs of bilateral lung consolidation showed visible improvement within 30 d. After more than 11 months of treatment, there is no evidence of recurrence or severe adverse events. CONCLUSION: Although the precise mechanism of the antitumor effects of gefitinib are not clear, our experience indicates an important role of the drug in LIMA and provides a reference for the diagnosis and treatment of this disease.

Ultrasound-Guided Vacuum-Assisted Excision to Treat Intraductal Papilloma.

BACKGROUND: To evaluate the value of ultrasound-guided vacuum-assisted excision (US-guided VAE) in the treatment of intraductal papillomas, including intraductal papillomas with atypical ductal hyperplasia (ADH), and to evaluate the lesion characteristic features affecting the local recurrence rate. MATERIALS AND METHODS: Between August 2011 and December 2020, 91 lesions of 91 patients underwent US-guided VAE and were diagnosed with intraductal papilloma with or without ADH. The recurrence rate of intraductal papilloma was evaluated on follow-up US. The lesion characteristic features were analyzed to identify the factors affecting the local recurrence rate. RESULTS: The local recurrence rate of intraductal papillomas removed by US-guided VAE was 7.7% (7/91), with the follow-up duration 12-92 months (37.4 ± 23.9 months). Of the 91 patients, five cases diagnosed as intraductal papilloma with ADH did not recur, with the follow-up time 12-47 months (26.4 ± 14.4 months). There were no malignant transformation in all 91 cases during the follow-up period. All 7 patients recurred 7-58 months (22.8 ± 19.2 months) after US-guided VAE. There were no significant differences between the non-recurrence and recurrence groups in terms of age, side, distance from nipple, lesion size, BI-RADS category, with ADH, or history of excision (p > 0.05). CONCLUSIONS: US-guided VAE is an effective method for the treatment of intraductal papilloma, including intraductal papilloma with ADH. It avoids invasive surgical excision, but regular follow-up is recommended to prevent recurrence or new onset due to multifocality. Any suspicious lesions during the follow-up should be actively treated.

Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans.

Candida albicans remains the most common species causing invasive candidiasis. In this study, we present the population structure of 551 global C. albicans strains. Of these, the antifungal susceptibilities of 370 strains were tested. Specifically, 66.6% of the azole-nonsusceptible (NS)/non-wild-type (NWT) strains that were tested belonged to Clade 1. A phylogenetic analysis, a principal components analysis, the population structure, and a loss of heterozygosity events revealed two nested subclades in Clade 1, namely, Clade 1-R and Clade 1-R-α, that exhibited higher azole-NS/NWT rates (75.0% and 100%, respectively). In contrast, 6.4% (21/326) of the non-Clade 1-R isolates were NS/NWT to at least 1 of 4 azoles. Notably, all of the Clade 1-R-α isolates were pan-azole-NS/NWT that carried unique A114S and Y257H double substitutions in Erg11p and had the overexpression of ABC-type efflux pumps introduced by the substitution A736V in transcript factor Tac1p. It is worth noting that the Clade 1-R and Clade 1-R-α isolates were from different cities that are distributed over a large geographic span. Our study demonstrated the presence of specific phylogenetic subclades that are associated with antifungal resistance among C. albicans Clade 1, which calls for public attention on the monitoring of the future spread of these clones. IMPORTANCE Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat. Here, our study suggested that antifungal resistance in C. albicans could also be associated with phylogenetic lineages. Specifically, it was revealed that more than half of the azole-resistant C. albicans strains belonged to the same clade. Furthermore, two nested subclades of the clade exhibited extremely high azole-resistance. It is worth noting that the isolates of two subclades were from different cities that are distributed over a large geographic span in China. This indicates that the azole-resistant C. albicans subclades may develop into serious public health concerns.

[Advances and Application of Genomics in Chronic Obstructive Pulmonary Disease].

Chronic obstructive pulmonary disease (COPD) is a common and frequently-occurring disease in the department of respiratory medicine,the pathogenesis of which involves both environmental factors and genetic factors.In recent years,with the application of new methods such as genome-wide association study,researchers have discovered a large number of gene mutations associated with lung function and COPD,providing a new perspective on the pathogenesis of COPD and potential therapeutic targets.This article reviews the research achievements and application progress of genomics in COPD.

[Clinical features of intestinal polyps and risk factors for secondary intussusception in children: an analysis of 2 669 cases]. / 2 669ä¾‹å„¿ç«¥è‚ æ¯è‚‰çš„ä¸´åºŠç‰¹å¾åŠç»§å‘è‚ å¥—å çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To study the clinical features of intestinal polyps and the risk factors for secondary intussusception in children. METHODS: A retrospective analysis was performed for the medical data of 2 669 children with intestinal polyps. According to the presence or absence of secondary intussusception, they were divided into two groups: intussusception (n=346) and non-intussusception (n=2 323). Related medical data were compared between the two groups. The multivariate logistic regression analysis was used to identify the risk factors for secondary intussusception. RESULTS: Among the children with intestinal polyps, 62.42% were preschool children, and the male/female ratio was 2.08∶1; 92.66% had hematochezia as disease onset, and 94.34% had left colonic polyps and rectal polyps. There were 346 cases of secondary intussusception, with an incidence rate of 12.96% (346/2 669). Large polyps (OR=1.644, P<0.001), multiple polyps (≥2) (OR=6.034, P<0.001), and lobulated polyps (OR=93.801, P<0.001) were the risk factors for secondary intussusception. CONCLUSIONS: Intestinal polyps in children often occur in preschool age, mostly in boys, and most of the children have hematochezia as disease onset, with the predilection sites of the left colon and the rectum. Larger polyps, multiple polyps, and lobulated polyps may increase the risk of secondary intussusception, and endoscopic intervention is needed as early as possible to improve prognosis.

Measuring the impact of an exogenous factor: An exponential smoothing model of the response of shipping to COVID-19.

Following the outbreak of the COVID-19 pandemic, various lockdown strategies restrained global economic growth bringing a significant decline in maritime transportation. However, the previous studies have not adequately recognized the specific impacts of COVID-19 on maritime transportation. In this study, a series of analyses of the Baltic Dry Index (BDI), the China Coastal Bulk Freight Index (CCBFI) and of container throughputs with and without the impact of COVID-19 were carried out to assess changing trends in dry bulk and container transportation. The results show that global dry bulk transportation was largely affected by lockdown policies in the second month during COVID-19, and BDI presented a year-on-year decrease of approximately 35.5% from 2019 to 2020. The CCBFI showed an upward trend in the second month during COVID-19, one month ahead of the BDI. The container throughputs at Shanghai Port, the Ports of Hong Kong, the Ports of Singapore and the Ports of Los Angeles from 2019 to 2020 presented the largest year-on-year drops of approximately 19.6%, 7.1%, 10.6% and 30.9%, respectively. In addition, the authors developed exponential smoothing models of BDI, CCBFI, and container transportation, and calculated the percentage prediction error between the observed and predicted values to examine the impact of exogenous effects on the shipping industry due to the outbreak of COVID-19. The results are consistent with the conclusions obtained from the comparison of BDI, CCBFI, and container transportation during the same period in 2020 and 2019. Finally, on the basis of the findings, smart shipping and special support policies are proposed to reduce the negative impacts of COVID-19.

MK2206 attenuates atherosclerosis by inhibiting lipid accumulation, cell migration, proliferation, and inflammation.

Cardiovascular disease is a common comorbidity in patients with cancer, and the main leading cause of noncancer-related deaths in cancer survivors. Considering that current antitumor drugs usually induce cardiovascular injury, the quest for developing new antitumor drugs, especially those with cardiovascular protection, is crucial for improving cancer prognosis. MK2206 is a phase II clinical anticancer drug and the role of this drug in cardiovascular disease is still unclear. Here, we revealed that MK2206 significantly reduced vascular inflammation, atherosclerotic lesions, and inhibited proliferation of vascular smooth muscle cell in ApoE-/- mice in vivo. We demonstrated that MK2206 reduced lipid accumulation by promoting cholesterol efflux but did not affect lipid uptake and decreased inflammatory response by modulating inflammation-related mRNA stability in macrophages. In addition, we revealed that MK2206 suppressed migration, proliferation, and inflammation in vascular smooth muscle cells. Moreover, MK2206 inhibited proliferation and inflammation of endothelial cells. The present results suggest that MK2206, as a promising drug in clinical antitumor therapy, exhibits anti-inflammatory and antiatherosclerotic potential. This report provides a novel strategy for the prevention of cardiovascular comorbidities in cancer survivors.

[Clostridium difficile infection and its susceptibility factors in children with inflammatory bowel disease].

OBJECTIVE: To investigate the incidence rates of Clostridium difficile colonization and Clostridium difficile infection (CDI) in children with inflammatory bowel disease (IBD) and the susceptibility factors for CDI in children with IBD. METHODS: A total of 62 children diagnosed with IBD were enrolled as the IBD group. Forty-two children who attended the hospital due to persistent or chronic diarrhea and were excluded from IBD were enrolled as the non-IBD group. The incidence rate of CDI was compared between the two groups. According to the presence or absence of CDI, the IBD group was subdivided into two groups:IBD+CDI (n=12) and non-CDI IBD (n=50), and the clinical data were collected from the two groups to analyze the susceptibility factors for CDI. RESULTS: The IBD group had a significantly higher incidence rate of CDI[19% (12/62) vs 2% (1/42); P < 0.05] than the non-IBD group (P < 0.05). Compared with the non-CDI IBD group, the IBD+CDI group had a significantly longer disease course (P < 0.05), and a significantly higher proportion of children with fever, diarrhea, or abdominal pain (P < 0.05). The IBD+CDI group had significantly higher activity indices of pediatric Crohn's disease, C-reactive protein levels and erythrocyte sedimentation rate than the non-CDI IBD group (P < 0.05). The univariate analysis showed that compared with the non-CDI IBD group, the IBD+CDI group had a significantly higher proportion of children with moderate-to-severe disease, use of glucocorticoids, or treatment with broad-spectrum antibiotics for more than 14 days before diagnosis (P < 0.05). CONCLUSIONS: The children with IBD have a higher incidence of CDI than those without IBD. Severe disease conditions and use of broad-spectrum antibiotics or glucocorticoids may be associated with an increased incidence of CDI in children with IBD.

[Effects of exogenous nitrogen addition on litter decomposition and nutrient release in a temperate desert]. / å¤–æºæ°®æ·»åŠ å¯¹æ¸©å¸¦è’æ¼ åœ°è¡¨å‡‹è½ç‰©åˆ†è§£åŠå »åˆ†é‡Šæ”¾çš„å½±å“.

A litterbag decomposition experiment was carried out in southern Gurbantunggut Desert, with four nitrogen treatments: N0(0 g N·m-2·a-1), N5(5 g N·m-2·a-1), N10(10 g N·m-2·a-1) and N20(20 g N·m-2·a-1). The aims were to examine the effects of exogenous nitrogen addition on decomposition rate and nutrient release of Tamarix ramosissima, Salicornia europaea and their mixture. Results showed that decomposition rates were significantly different among litter types. After 345 days, the decomposition rates of T. ramosissima, S. europaea and their mixture under different treatments were 0.64-0.70, 0.84-0.99 and 0.71-0.81 kg·kg-1·a-1, respectively. Both mono- and mixed-litters exhibited nutrient release during decomposition process, with the release rates being 60.6%-67.4%, 56.7%-62.6%, 57.4%-62.3%, 46.8%-63.0% for N, and 51.9%-77.9%, 59.9%-74.7%, 53.0%-79.9%, 52.3%-76.4% for P, respectively for the N0, N5, N10 and N20 treatments. Nitrogen addition did not affect litter decomposition rate. The dynamics of N and P during decomposition of different litter types showed different responses to nitrogen addition. Nitrogen addition inhibited N and P releases of S. europaea litter and P release of the mixed litter, but did not affect the nutrient release of T. ramosissima. The results suggested that nitrogen input would not promote litter decomposition in temperate desert ecosystems, but might retard the nutrient returning to soil system.

Characterizing the variation of particles in varied sizes from a container truck in a port area.

The transportation of container trucks in urban areas not only frequently causes traffic jams but also produces severe air pollution. With regard to this consideration, measurements of particle concentrations and traffic volume on different polluted days were carried out to discover the varied characteristics of particles from container truck transportation in the port area. Based on the original data, descriptive statistics were performed firstly to reveal the statistical characteristics of particle number concentrations (PNC). The Kolmogorov-Smirnov test as well as the Anderson-Darling test was adopted to identify the "best-fit" distributions on PNC data while the corresponding maximum likelihood estimation was conducted to estimate the parameters of the identified distribution. Additionally, the Pearson correlation analysis and principal component analysis were performed respectively to reveal the relationships between traffic volume and PNC. The results showed that on a hazy day, PNC levels in the morning were generally higher than those in the afternoon, while on a non-hazy day, the results were opposite. Particles in all sizes on a non-hazy day and larger than 0.5 µm on a hazy day were verified to fit the lognormal distribution. In contrast to the particles below 2 µm, the particles above 2 µm exhibited higher correlations with the traffic flow of a container truck in the morning on a hazy day. These results indicate the importance of reducing air pollution from a container truck and provide policymakers with a foundation for possible measures in a port city.

Characteristics and prognostic significance of genetic mutations in acute myeloid leukemia based on a targeted next-generation sequencing technique.

To explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next-generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction chemotherapy were associated with a lower number of mutations. NPM1 mutation was closely related to DNMT3A and FLT3-internal tandem duplication (FLT3-ITD) mutations, but mutually exclusive with ASXL1 mutation and CEBPAdouble mutation . In univariate analysis, ASXL1 or TET2 mutation predicted shorter overall survival (OS) or relapse-free survival (RFS), DNMT3A, FLT3-ITD, or RUNX1 mutation predicted a higher likelihood of remission-induction failure, whereas NRAS mutation or CEBPAdouble mutation predicted longer OS. Concurrent DNMT3A, FLT3-ITD, and NPM1 mutations predicted shorter OS. Hypomethylation agents could improve the OS in patients with DNA methylation-related mutations. According to multivariate analysis, TET2 mutation was recognized as an independent prognostic factors for RFS. In summary, our study provided a detailed pattern of gene mutations and their prognostic relevance in Chinese AML patients based on targeted next-generation sequencing screening.

Eu(III)-coordination polymer: inhibitory activity on cervical cancer via inducing ROS mediated apoptosis.

Under the hydrothermal reaction condition, we prepared a new 3D Eu(III)-based coordination polymer (CP) [Eu(H2-DHBDC)0.5(DHBDC)0.5 (H2O)2] n ·H2O (1, H4-DHBDC = 2,5-dihydroxy-1,4-terephthalic acid). Furthermore, we assessed the inhibitory influence on cervical cancer cells of this compound. First, for testing the anti-viability of the compound against cervical cancer cells, the cell counting kit-8 (CCK-8) assay was carried out. Then, reactive oxygen species (ROS) detection kit was used to determine the ROS accumulation in the cervical cancer cells. Finally, after the Annexin V-FITC/PI apoptosis assay was finished, it was used for apoptotic cervical cancer cells after treated with compound. From the results of the software of pose scoring and molecular docking, we can see that the compound may bind to p91 by the functional side-chain of the ligand, which provided potential regulatory mechanisms for the compound.

MicroRNA-153 impairs hippocampal synaptic vesicle trafficking via downregulation of synapsin I in rats following chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) promotes the development of Alzheimer's pathology. However, whether and how CCH impairs the synaptic vesicle trafficking is still unclear. In the present study, we found that the hippocampal glutamatergic vesicle trafficking was impaired as indicated by a significant shortened delayed response enhancement (DRE) phase in CA3-CA1 circuit and decreased synapsin I in CCH rats suffering from bilateral common carotid artery occlusion (2VO). Further study showed an upregulated miR-153 in the hippocampus of 2VO rats. In vitro, overexpression of miR-153 downregulated synapsin I by binding the 3'UTRs of SYN1 mRNAs, which was prevented by its antisense AMO-153 and miRNA-masking antisense oligodeoxynucleotides (SYN1-ODN). In vivo, the upregulation of miR-153 elicited similar reduced DRE phase and synapsin I deficiency as CCH. Furthermore, miR-153 knockdown rescued the downregulated synapsin I and shortened DRE phase in 2VO rats. Our results demonstrate that CCH impairs hippocampal glutamatergic vesicle trafficking by upregulating miR-153, which suppresses the expression of synapsin I at the post-transcriptional level. These results will provide important references for drug research and treatment of vascular dementia.