Objective To find out whether NOTCH receptors can serve as direct downstream targets of transforming growth factor β(TGF-β)/Smad4 signaling in endothelial cells.Methods Real-time PCR and Western blotting were performed to verify whether the expression of notch1 and notch4 was regulated by TGF-β pathway.Luciferase reporter assay was employed to investigate how the promoter of notch1 and notch4 was regulated by TGF-β.Then, ChIP assay was used confirm whether the promoter of notch1 and notch4 physically interacted with SMAD protein.Results TGF-β1 and bone morphogenetic protein 4 (BMP4) treatment increased the expression of both notch1 and notch4 at the transcriptional level.In addition, SMAD4 was physically associated with the SMAD binding sites on the notch4 promoter, which was largely enhanced under the treatment of TGF-β1 and BMP4.Importantly, TGF-β1 and BMP4 failed to transactivate notch4 in the absence of endogenous SMAD4 or the SMAD binding regions on the notch4 promoter.Conclusion The expression of NOTCH receptor can be directly up-regulated by SMAD4-mediated TGF-β/BMP signaling in cerebrovascular endothelial cells.

Objective To observe the histopathologic injury of small intestine and intestinal permeability in chronic renal failure (CRF) rats. Methods Twenty male Sprague-Dawley rats were randomly assigned to CRF group (n=10) and control group (n=10). 5/6 nephrectomy was used to establish CRF rats, while sham operation for control. Blood biochemistry was regularly monitored until CRF model was successfully established. The model rats were fed with lactulose (L) and mannitol (M) through intragastric administration. Urine was collected after 6 hours, and the concentration of lactulose and mannitol in urine was measured using high pressure liquid chromatograph with refractive index detector (HPLC-RID), and the ratio of urinary excretion of L/M was calculated to evaluate intestinal permeability. Small intestinal mucosa were stained by hematoxylin-eosin (HE) and observed with light microscope (villus height, thickness of muscle layer and villus count), histological damage score was used to evaluate intestinal injury. Results The L/M ratio of CRF group was higher than that of control group (1.75±0.11 vs 1.20±0.06, P<0.01). The small intestinal mucosal villus height and thickness of muscle layer in CRF group were higher (P<0.01), and the number of villi was lower compared to control group (P<0.01). The score of histopathologic intestine damage of CRF group was higher than that of control group (1.00±0.71 vs 0, P<0.01). Conclusion The intestinal permeability of CRF rats is increased with varying degrees of intestinal damage.

Objective:To explore the mechanisms of regulation of miR-575 on the proliferation and invasion properties of non-small cell lung cancer cell (NSCLC).Methods:Real-time PCR was selected to detect the expression of miR-575 and BLID in differ ent NSCLC cell lines.CCK-8 assay was processed to measure the alternations of A549 cell proliferation at different time points after transfection of miR-575 mimic and miR-575 inhibitor.The invasion ability of A549 cells was evaluated by transwell.The targeting of BLID by miR-575 was predicted by Targetcan software and verified by dual-Luciferase assay.BLID protein expression level was detected by western blot.Results:miR-575 highly expressed in NSCLC cell lines,including A549,SPC-A1,H1299,H1650 (P＜0.001),miR-575 mimic could efficiently elevated the expression ofmiR-575 in A549 cells (P＜0.001),and strengthened the proliferation and invasion ability of NSCLC cells (P＜0.05),while,transfection of miR-575 inhibitor could down-regulate the expression ofmiR-575,and also inhibit the proliferation and invasion ability of NSCLC cells (P＜0.01).Targetscan software predicted that BLID might be the target gene of miR-575,and dual-luciferase assay revealed that miR-575 could obviously decrease the luciferase reaction of wild type BLID 3'UTR (P＜0.01),besides,miR-575 could down-regulate the protein expression ofBLID (P＜0.01).Real-time PCR results showed that NSCLC cell lines had lower level of BLID mRNA expression compared with 16HBE control cells (P＜0.001),and restore of BLID could markedly inhibited cell proliferation and invasion ability (P＜0.05),which could be reversed by miR-575 co-tranfection (P＜0.01).Conclusion:In NSCLC cells,the expression ofmiR-575 could promote cell proliferation and invasion ability by directly regulating downstream target tumor-suppressor gene BLID expression.

Background: The emergence of the severe acute respiratory syndrome coronavirus 2 omicron variant has been triggering the new wave of coronavirus disease 2019 (COVID-19) globally. However, the risk factors and outcomes for radiological abnormalities in the early convalescent stage (1 month after diagnosis) of omicron infected patients are still unknown. Methods: Patients were retrospectively enrolled if they were admitted to the hospital due to COVID-19. The chest computed tomography (CT) images and clinical data obtained at baseline (at the time of the first CT image that showed abnormalities after diagnosis) and 1 month after diagnosis were longitudinally analyzed. Uni-/multi-variable logistic regression tests were performed to explore independent risk factors for radiological abnormalities at baseline and residual pulmonary abnormalities after 1 month. Results: We assessed 316 COVID-19 patients, including 47% with radiological abnormalities at baseline and 23% with residual pulmonary abnormalities at 1-month follow-up. In a multivariate regression analysis, age ≥ 50 years, body mass index ≥ 23.87, days after vaccination ≥ 81 days, lymphocyte count ≤ 1.21 × 10 -9 /L, interleukin-6 (IL-6) ≥ 10.05 pg/mL and IgG ≤ 14.140 S/CO were independent risk factors for CT abnormalities at baseline. The age ≥ 47 years, presence of interlobular septal thickening and IL-6 ≥ 5.85 pg/mL were the independent risk factors for residual pulmonary abnormalities at 1-month follow-up. For residual abnormalities group, the patients with less consolidations and more parenchymal bands at baseline could progress on CT score after 1 month. There were no significant changes in the number of involved lung lobes and total CT score during the early convalescent stage. Conclusion The higher IL-6 level was a common independent risk factor for CT abnormalities at baseline and residual pulmonary abnormalities at 1-month follow-up. There were no obvious radiographic changes during the early convalescent stage in patients with residual pulmonary abnormalities.

Objective:To investigate the clinical characteristics of pediatric methicillin-resistant Staphylococcus aureus (MRSA) infection and the antibiotic sensitivity of the isolates. Methods:The clinical data of children with MRSA infection and antibiotic sensitivity of the isolates from 11 children′s hospitals in Infectious Diseases Surveillance of Paediatrics (ISPED) group of China between January 1, 2018 and December 31, 2018 were collected retrospectively. The children′s general condition, high-risk factors, antimicrobial therapy and prognosis, differences in clinical disease and laboratory test results between different age groups, and differences of antibiotic sensitivity between community-acquired (CA)-MRSA and hospital-acquired (HA)-MRSA were analyzed. The t test and Wilcoxon rank sum test were used for statistical analysis of the quantitative data and Chi-square test were used for comparison of rates. Results:Among the 452 patients, 264 were males and 188 were females, aged from 2 days to 17 years. There were 233 cases (51.5%) in the ≤1 year old group, 79 cases (17.5%) in the>1-3 years old group, 29 cases (6.4%) in the >3-5 years old group, 65 cases (14.4%) in the >5-10 years old group, and 46 cases (10.2%) in the>10 years old group. The main distributions of onset seasons were 55 cases (12.2%) in December, 47 cases (10.4%) in February, 46 cases (10.2%) in November, 45 cases (10.0%) in January, 40 cases (8.8%) in March. There were 335 cases (74.1%) CA-MRSA and 117 (25.9%) cases HA-MRSA. Among all cases, 174 cases (38.5%) had basic diseases or long-term use of hormone and immunosuppressive drugs. During the period of hospitalization, 209 cases (46.2%) received medical interventions. There were 182 patients (40.3%) had used antibiotics (β-lactams, glycopeptides, macrolides, carbapenems, oxazolones, sulfonamides etc) 3 months before admission. The most common clinical disease was pneumonia (203 cases), followed by skin soft-tissue infection (133 cases), sepsis (92 cases), deep tissue abscess (42 cases), osteomyelitis (40 cases), and septic arthritis (26 cases), suppurative meningitis (10 cases). The proportion of pneumonia in the ≤1 year old group was higher than the >1-3 years old group,>3-5 years old group,>5-10 years old group,>10 years old group (57.5% (134/233) vs. 30.4% (24/79), 31.0% (9/29), 38.5% (25/65), 23.9% (11/46), χ 2=17.374, 7.293, 7.410, 17.373, all P<0.01) The proportion of skin and soft tissue infections caused by CA-MRSA infection was higher than HA-MRSA (33.4% (112/335) vs. 17.9% (21/117), χ 2=10.010, P=0.002), and the proportion of pneumonia caused by HA-MRSA infection was higher than CA-MRSA (53.0% (62/117) vs. 42.1% (141/335), χ 2=4.166, P=0.041). The first white blood cell count of the ≤1 year old group was higher than that children > 1 year old ((15±8)×10 9/L vs. (13±7)×10 9/L, t=2.697, P=0.007), while the C-reactive protein of the ≤1 year old group was lower than the 1-3 years old group,>5-10 years old group,>10 years old group (8.00 (0.04-194.00) vs.17.00 (0.50-316.00), 15.20 (0.23-312.00), 21.79(0.13-219.00) mg/L, Z=3.207, 2.044, 2.513, all P<0.05), there were no significant differences in procalcitonin (PCT) between different age groups (all P>0.05). After the treatment, 131 cases were cured, 278 cases were improved, 21 cases were not cured, 12 cases died, and 10 cases were abandoned. The 452 MRSA isolates were all sensitive to vancomycin (100.0%), linezolid (100.0%), 100.0% resistant to penicillin, highly resistant to erythromycin (85.0%, 375/441), clindamycin (67.7%, 294/434), less resistant to sulfonamides (5.9%, 23/391), levofloxacin (4.5%, 19/423), gentamicin (3.2%, 14/438), rifampicin (1.8%, 8/440), minocycline (1.1%, 1/91). The antimicrobial resistance rates were not significantly different between the CA-MRSA and HA-MRSA groups (all P>0.05). Conclusions:The infection of MRSA is mainly found in infants under 3 years old. The prevalent seasons are winter and spring, and MRSA is mainly acquired in the community. The main clinical diseases are pneumonia, skin soft-tissue infection and sepsis. No MRSA isolate is resistant to vancomycin, linezolid. MRSA isolates are generally sensitive to sulfonamides, levofloxacin, gentamicin, rifampicin, minocycline, and were highly resistant to erythromycin and clindamycin. To achieve better prognosis. clinicians should initiate anti-infective treatment for children with MRSA infection according to the clinical characteristics of patients and drug sensitivity of the isolates timely and effectively.