Retraction Note: BNIP1 inhibits cell proliferation, migration and invasion, and promotes apoptosis by mTOR in cervical cancer cells.

The article "BNIP1 inhibits cell proliferation, migration and invasion, and promotes apoptosis by mTOR in cervical cancer cells", by F.-H. Li, L. Xiang, L. Ran, S. Zhou, Z. Huang, M. Chen, W.-F. Yu, published in Eur Rev Med Pharmacol Sci 2019; 23 (4): 1397-1407-DOI: 10.26355/eurrev_201902_17096-PMID: 30840260 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer regarding a possible overlap in Figure 2A, the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The journal investigation revealed a duplication in Figure 2A between BNIP1 panels, migration and invasion, respectively and in Control and invasion panels. Consequently, the Editor in Chief mistrusts the results presented and has decided to withdraw the article. The authors have been informed about the journal's investigation but remained unresponsive. https://www.europeanreview.org/article/17096 This article has been retracted. The Publisher apologizes for any inconvenience this may cause.

[Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase].

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

[Establishment of hysteroscopic scoring system of chronic endometritis and correlative analysis with pregnancy outcomes of in vitro fertilization-embryo transfer in infertile patients].

Objective: To establish a hysteroscopic chronic endometritis (hCE) scoring system for patients with chronic endometritis, and observe the correlation of hCE score with in vitro fertilization-embryo transfer (IVF-ET) pregnancy outcomes in infertile women. Methods: The study retrospectively investigated the correlation of morphologic features and hCE score with pregnancy outcomes during IVF-ET in infertile women with CE (n=429) at Yantai Yuhuangding Hospital between January 2017 and September 2018. The clinical pregnancy rate and live birth rate with different score levels (1-3,4-7 and 8-14) after IVF-ET treatment were analyzed. Multivariate regression analysis was performed to adjust for confounding factors. The correlation and regression between hCE score and pregnancy outcomes was analyzed by curve fitting. Results: The age of 429 patients [M(Q1, Q3)] was 31 (29, 35) years. There were 50.6% (217 cases), 35.4% (152 cases), and 14.0% (60 cases) of patients with hCE score of 1-3, 4-7, and 8-14, respectively. The pregnancy rates of the three groups were 60.8% (132 cases), 44.7% (68 cases) and 16.7% (10 cases), P<0.001; The live birth rates were 51.2% (111 cases), 36.8% (56 cases) and 13.3% (8 cases), respectively (P<0.001). Compared with patients with hCE of 1-3, pregnancy rates in those with hCE of 4-7 and 8-14 were lower, and the OR values were 0.521 (0.342-0.793) and 0.129 (0.062-0.268). The live birth rates in patients with hCE of 4-7 and 8-14 were lower than that in patients with hCE of 1-3, and the OR values were 0.570 (0.372-0.873) and 0.162 (0.073-0.360), all P<0.05. Quadratic curve fitting results showed that clinical pregnancy rate and live birth rate decreased with the increase of hCE score. Conclusions: With the increase of hCE score, the clinical pregnancy rate and live birth rate of patients gradually decrease. hCE 4 is an important cut-off threshold significantly affecting the pregnancy outcome.

Combined training prescriptions for improving cardiorespiratory fitness, physical fitness, body composition, and cardiometabolic risk factors in older adults: Systematic review and meta-analysis of controlled trials.

Background: Improved physical fitness is important for preventing COVID-19-related mortality. So, combined training can effectively increase peak oxygen consumption, physical fitness, body composition, blood pressure, and the healthrelated characteristics of adults; however, its impact in the elderly remains unclear. Methods: This systematic review and meta-analysis aimed to evaluate the effects of combined training on older adults. Four electronic databases (PubMed, Scopus, Medline, and Web of Science) were searched (until April 2021) for randomized trials comparing the effect of combined training on cardiorespiratory fitness, physical fitness, body composition, blood pressure, and cardiometabolic risk factors in older adults. Results: Combined training significantly improved peak oxygen consumption compared to no exercise (WMD = 3.10, 95% CI: 2.83 to 3.37). Combined resistance and aerobic training induced favorable changes in physical fitness (timed up-and-go = -1.06, 30-s chair stand = 3.85, sit and reach = 4.43, 6-minute walking test = 39.22, arm curl = 4.60, grip strength = 3.65, 10-m walk = -0.47, maximum walking speed = 0.15, one-leg balance = 2.71), body composition (fat mass = -2.91, body fat% = -2.31, body mass index = -0.87, waist circumference = -2.91), blood pressure (systolic blood pressure = -8.11, diastolic blood pressure = -4.55), and cardiometabolic risk factors (glucose = -0.53, HOMA-IR = -0.14, high-density lipoprotein = 2.32, total cholesterol = -5.32) in older individuals. Finally, the optimal exercise prescription was ≥ 30 min/session × 50-80% VO2peak, ≥ 3 times/week for ≥ 12 weeks and resistance intensity 70-75% one-repetition maximum, 8-12 repetitions × 3 sets. Conclusions: Combined training improved VO2peak and some cardiometabolic risk factors in older populations. The dose-effect relationship varied between different parameters. Exercise prescriptions must be formulated considering individual needs during exercise.

Contexte: L'amélioration de la condition physique est importante pour prévenir la mortalité liée au COVID-19. Ainsi, l'entraînement combiné peut augmenter efficacement la consommation maximale d'oxygène, la forme physique, la composition corporelle, la tension artérielle et les caractéristiques liées à la santé des adultes; cependant, son impact chez les personnes âgées reste incertain. Méthodes: Cette revue systématique et cette méta-analyse visaient à évaluer les effets de l'entraînement combiné chez les personnes âgées. Quatre bases de données électroniques (PubMed, Scopus, Medline et Web of Science) ont été consultées (jusqu'en avril 2021) pour trouver des essais randomisés comparant l'effet d'un entraînement combiné sur l'aptitude cardiorespiratoire, la forme physique, la composition corporelle, la tension artérielle et les facteurs de risque cardiométabolique chez les personnes âgées. Résultats: Au total, 37 publications ont été incluses dans cette étude. L'entraînement combiné a considérablement amélioré la consommation maximale d'oxygène par rapport à l'absence d'exercice (DMP = 3,10, IC95 % : 2,83 à 3,37). La combinaison résistance + entraînement aérobie a entraîné des changements favorables dans la forme physique (démarrage chronométré = −1,06, position assise pendant 30 s = 3,85, position assise et lever = 4,43, test de marche de 6 minutes = 39,22, flexion des bras = 4,60, adhérence force = 3,65, marche de 10 m = −0,47, vitesse de marche maximale = 0,15, équilibre sur une jambe = 2,71), composition corporelle (masse grasse = −2,91, pourcentage de graisse corporelle = −2,31, indice de masse corporelle = −0,87, taille circonférence = −2,91), tension artérielle (pression artérielle systolique = −8,11, pression artérielle diastolique = −4,55) et facteurs de risque cardiométabolique (glucose = −0,53, HOMA-IR = −0,14, lipoprotéines de haute densité = 2,32, cholestérol total = −5,32) chez les personnes âgées. Enfin, la prescription d'exercice optimale était ≥ 30 min/séance × 50­80 % VO2pic, ≥ 3 fois/semaine pendant ≥ 12 semaines et résistance à une intensité de 70­75 % une répétition maximale, 8­12 répétitions × 3 séries. Conclusions: L'entraînement combiné a amélioré la VO2pic et certains facteurs de risque cardiométabolique chez les populations âgées. La relation dose-effet variait entre les différents paramètres. Les prescriptions d'exercice doivent être formulées en tenant compte des besoins individuels pendant l'exercice.

[Effect of neuregulin-1 on cardiac glucose metabolism in rats with experimental myocardial infarction].

Objective: To investigate the effect of neuregulin-1(NRG-1) on cardiac glucose metabolism in Sprague Dawley (SD) rats with experimental myocardial infarction (MI). Methods: Adult male SD rats were randomly divided into three groups: the sham-operated group, MI group, and MI+NRG1 group. The rat MI model was established via ligation of the left anterior descending coronary artery. Two weeks after operation, echocardiography was performed, MI rats with left ventricular ejection fraction (LVEF) between 0.3-0.5 were selected and randomly assigned to MI group and MI+NRG-1 group. Rats in MI+NRG-1 group were treated with recombinant human NRG-1ß (100 µg/kg) via tail vein at 2 weeks after operation (twice per week for 6 weeks); while rats in sham-operated group and MI group received equal volume of physiological saline. By the end of administration, echocardiography and small animal positron emission tomography (PET) were performed to detect cardiac function and myocardial glucose uptake. Myocardial morphology and collagen volume fraction, cardiomyocyte apoptosis and reactive oxygen species (ROS) production were evaluated by histopathologic analysis. Myocardial pyruvate dehydrogenase (PDH) and citrate synthase (CS) activity, as well as ATP production were detected by commercial kits. The mRNA and protein expression levels of NRG-1, p-ErbB4, and key factors involved in glucose metabolism (including Glut-4, HK2, PDK4, PDH, CS) were detected by quantitative real-time PCR (qRT-PCR) and Western blot assay, respectively. Results: With the MI model successfully established, the left ventricular ejection fraction(LVEF) and left ventricular shortening fraction(LVFS) were significantly lower in MI group and MI+NRG-1 group than that in sham group (both P<0.01), while there was no significant difference between MI group and MI+NRG-1 group(all P>0.05). After 6 weeks of NRG-1ß intervention, the LVEF and LVFS were significantly higher in MI+NRG-1 group than in MI group (both P<0.01). By the end of experiment, PET imaging showed that the mean standardized uptake value (SUVmean) were lower in MI+NRG-1 group than in the sham group (4.06±0.28 vs. 5.18±0.37, P<0.01), while significantly higher than that in MI group (4.06±0.28 vs.2.86±0.49, P<0.01). Histopathological analysis showed that compared with MI group, rats in MI+NRG-1 group exhibited significantly decreased left ventricle collagen volume fraction ((7.83±1.24) % vs. (18.31±3.58) %, P<0.01), cardiomyocyte apoptosis((37.98±4.26)% vs. (67.04±5.38)%, P<0.01), and DHE fluorescence intensity(0.057 28±0.007 06 vs. 0.076 94±0.008 46, P<0.01), indicating that NRG-1ß could reduce ROS production. PDH activity, CS activity, and ATP production were significantly higher in MI+NRG-1 group than in MI group (all P<0.05). qRT-PCR demonstrated an upregulated Glut-4, HK2 and CS, but downregulated PDK4 mRNA expression in MI+NRG-1 group compared with MI group (all P<0.01). Western blot assay showed significantly higher protein expression of NRG-1, p-ErbB4, Glut-4, HK2, PDH, CS in MI+NRG-1 group than in MI group (all P<0.01). Conclusion: NRG-1 could improve glucose uptake and utilization in myocardium by activating phosphorylation of myocardial ErbB4 receptor in MI rats, thus providing a therapeutic option for improving energy metabolism after MI.

[Efficacy and safety of Kangbingdu granules in the treatment of influenza: a randomized, double-blind, double-dummy, positive-drug parallel control multicenter clinical trial].

Objective: To observe the efficacy and safety of Kangbingdu granules (KBD) in the treatment of influenza. Methods: A multicenter, randomized, double-blind, double-dummy, and positive-drug parallel control trial was conducted in 27 Grade ⅢA hospitals in China and the subjects were randomly assigned to the KBD test group or the oseltamivir phosphate capsule control group at a ratio of 1∶1. 200 subjects were planned to be enrolled in each group. The experimental group was given KBD (18g each time, 3 times a day) and oseltamivir phosphate simulator orally, while the control group was given oseltamivir phosphate capsule (75 mg each time, twice a day) and KBD simulator orally for 5 days. The primary efficacy indicators included the remission time of major clinical symptoms and the time of complete defervescence. The secondary efficacy indicators included dosage of acetaminophen, the change of traditional Chinese medicine (TCM) syndrome score and the remission time of other important clinical symptoms. The efficacy of KBD in the test group and Oseltamivir phosphate control group were compared. Adverse events or adverse reactions were observed at the same time to evaluate the safety of KBD Granules. Results: A total of 393 subjects from 27 Grade ⅢA hospitals in China were enrolled. The experimental group included 195 subjects and 191 subjects (97.95%) completed the trial, While the control group included 198 subjects and 195 subjects (98.48%) completed the trial. There was no significant difference in the shedding rate and rejection rate between the two groups (P>0.05). In the Full Analysis Set (FAS), the mean age of the experimental group was (34.9±14.4) years old, with 83 males (42.78%). The mean age of the control group was (33.3±13.5) years old, with 78 males (39.59%). There were no statistically significant differences between the two groups in demographic data, physical examination, viral pathogen detection, total score of TCM syndromes and scores of each symptom at baseline (P>0.05). In the FAS, the remission time M (Q1, Q3) of major clinical symptoms was 3.0 (3.0, 4.0) days in the experimental group and 3.0 (3.0, 4.0) days in the control group, and the difference was not statistically significant (P>0.05). The time M (Q1, Q3) of complete defervescence was 34.0 (20.3, 49.0) hours in the experimental group and 36.5 (19.6, 48.8) hours in the control group, and the difference was not statistically significant (P>0.05). KBD granules had the same effect as Oseltamivir phosphate capsule (P>0.05) in terms of acetaminophen dosage, TCM syndrome effect and disappearance rate of most important clinical symptoms. Meanwhile, the disappearance rate of dizziness and chest distress on day 3 in the KBD granules group was better than that of oseltamivir phosphate capsule (P<0.05). Conclusion: KBD granules have the same efficacy as Oseltamivir Phosphate capsule in the treatment of influenza and the drug safety is good.

microRNA-23B inhibits non-small cell lung cancer proliferation, invasion and migration via downregulation of RUNX2 and inhibition of Wnt/Β-catenin signaling pathway.

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. MicroRNAs (miRNAs/miRs) have been reported to play significant roles in the progression of human tumors, however, the expression and biological role of miR-23b in NSCLC remains elusive. Underexpression of miR-23b was detected in NSCLC tissues in comparison with the matched para-carcinoma tissues. The clinical value of miR-23b was analyzed, and the findings showed that miR-23b expression was negatively correlated with poor overall survival and malignant clinicopathologic characteristics of NSCLC patients. Furthermore, functional assays demonstrated that overexpression of miR-23b inhibited NSCLC cell viability, invasion and migration. Luciferase reporter assay and qRT-PCR revealed that RUNX2 was a functional target of miR-23b. The elevated expression of RUNX2 was positively correlated with overall survival of NSCLC patients. Additionally, Western blot analysis indicated that EMT and Wnt/ß-catenin pathways were blocked by the upregulation of miR-23b. Taken together, these data demonstrated that dysregulation of miR-23b/RUNX2 signal may be a novel therapeutic target for the treatment of NSCLC.

MiR-20a promotes lung tumorigenesis by targeting RUNX3 via TGF-ß signaling pathway.

MiR-20a shows a significant role in the development of various human tumors. However, its specific biological function in non-small-cell lung cancer (NSCLC) is still not clear. qRT-PCR was applied for detecting miR-20a expression. The analysis of cell growth and apoptosis were performed by MTT, xenograft models, Western blot assays. Dual luciferase reporter, Western blotting and qRT-PCR were carried out to verify the potential target of miR-20a. In NSCLC tissues and cells, miR-20a was highly expressed and RUNX3 was lowly expressed. Moreover, up-regulation of miR-20a expression promoted NSCLC cell proliferation, invasion and migration, while low-expression of miR-20a showed the converse case on cell proliferation, invasion and migration. RUNX3 was verified as the direct target of miR-20a and it could overturn its biological function in NSCLC cells. Moreover, miR-20a negatively regulated RUNX3 expression. Mechanistically, increasing miR-20a expression inhibited RUNX3 expression and then activated the TGF-ß signaling pathway. Taken together, our results demonstrated that re-expression of miR-20a promoted lung tumorigenesis by down-regulation of RUNX3 and facilitating the activation of TGF-ß signaling pathway.

[Comparison of radiological and clinicopathological features of craniofacial fibro-osseous lesions].

Objective: To investigate the clinicopathological and radiological features of benign fibro-osseous lesion (BFOL). Methods: Sixty-five cases of craniofacial BFOL, eight cases of peripheral ossifying fibroma (POF) and one case of low-grade central osteosarcoma diagnosed at Sichuan Provincial People's Hospital between January 2010 and March 2019 were collected. The clinicopathologic features, hematoxylin-eosin and immunohistochemical (IHC) staining and radiographic features were analyzed. MDM2 gene amplification was detected by FISH in difficult borderline cases. Results: This cohort of BFOLs included 50 cases of fibrous dysplasia (FD), 12 cases of ossifying fibroma (OF), and three cases of juvenile psammomatoid ossifying fibroma (JPOF). The average ages of patients with FD,OF and JPOF were 31.7, 39.2 and 26.0 years respectively. The male to female ratio was 1.0∶1.8.The average age of POF was 47.0 years, with male to female ratio of 1∶7. Patient of low-grade central osteosarcoma was a 48-year-old man. Twenty-seven cases of FD were located in the jaw, and 23 cases were in other craniofacial bones. Nine cases of OF were located in the jaw, and three cases were in the nasal cavity. Two cases of JPOF were in the nasal sinus, and one was in the jaw. All POF were located in the gingiva, and low-grade central osteosarcoma was located in the mandible. The imaging features of FD were luffa-like or ground-glass like signal shadows with poorly defined borders with expansion. OF had clear borders or sclerosing margins. Both JOF and low-grade central osteosarcoma were expansile intraosseously and with focally invasive nodular masses with ground-glass like signal shadows; and POF showed soft tissue mass with bone formation. Histological features of BFOLs showed mixed fibrous and irregular osteoid lesions. FD had no clear relationship with the host bone and no osteoblasts surrounded the bone trabeculae. Osteoblasts rimming was found in OF, and the boundaries of the host bone were clear. JPOF and low-grade central osteosarcoma infiltrated the host bone focally, and the latter showed mild cellular atypia. MDM2 amplification was detected in low-grade central osteosarcoma. Conclusions: BFOLs are a group of fibro-osseous lesions with similar morphology in the head and neck and face, but their clinical features and prognosis are different; and their imaging and histological characteristics are also slightly different. Attentions should be given to the combination of clinical, imaging and pathologic features of BFOLs, especially the differential diagnosis between BFOLs and low-grade central osteosarcoma. Molecular detection could be used to assist the diagnosis in difficult cases.

PCAT1 promotes the proliferative and migratory potentials of ovarian cancer via targeting NEK2.

OBJECTIVE: The aim of this study was to clarify the potential role of PCAT1 in the occurrence and development of ovarian cancer (OC). PATIENTS AND METHODS: Expression levels of PCAT1 and NEK2 in OC tissues and cell lines were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Correlation between PCAT1 expression with tumor stage and prognosis of OC patients was analyzed. Knockdown or over-expression of PCAT1 and NEK2 were achieved by siRNA or lentivirus transfection, respectively. Subsequently, cell viability, apoptosis, cell cycle progression and migration were determined by cell counting kit-8 (CCK-8), flow cytometry and transwell assay, respectively. Furthermore, the protein levels of relative genes in Wnt pathway were detected by Western blot. RESULTS: PCAT1 was highly expressed in OC tissues and cell lines, especially in tumor tissues with stage III-IV compared with stage I-II. The prognosis of OC patients with higher expression of PCAT1 was significantly worse than those with lower expression. In vitro experiments confirmed that PCAT1 knockdown obviously inhibited proliferative and migratory potentials, whereas induced apoptosis of OC cells. No significant changes were observed in cell cycle progression of OC cells after knockdown or overexpression of PCAT1. Meanwhile, overexpression of PCAT1 remarkably upregulated the expression level of NEK2, which was the target gene of PCAT1. Interestingly, NEK2 knockdown could obviously suppress cell migration. Furthermore, Western blot results elucidated that PCAT1 knockdown could inhibit the protein levels of relative genes in Wnt pathway in OC cells. CONCLUSIONS: PCAT1 was highly expressed in OC tissues than adjacent normal tissues. PCAT1 overexpression significantly promoted proliferative and migratory potentials, whereas inhibited apoptosis of OC cells through upregulating NEK2 expression via Wnt pathway.

Differential protein analysis of Heracleum moellendorffii Hance seeds during stratification.

Heracleum moellendorffii Hance is a medicinal vegetable species, and the seed dormancy of this species has caused many agricultural problems. One stratification technique involves alternating layers of seeds and substrate to allow post-ripening of dormant seeds under appropriate environmental conditions and to release dormancy. Non-stratified seeds (NS), cotyledon-stage-embryo seeds (CS) and germinated seeds (GS) represent key stages of H. moellendorffii seeds during stratification. To better understand the breaking of dormancy caused by stratification, tandem mass tag (TMT) mass spectrometry (MS)/MS was used to detect proteins among NS, CS and GS. A total of 876 proteins were identified, which were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The results showed that carbohydrate metabolic processes, responses to stress and ribosome biogenesis were the main biological processes. The changes in protein accumulation were validated by qRT-PCR. The results showed that starch, sucrose, pyruvate and fatty acid metabolism played significant roles and that the contents of stored substances were gradually degraded during stratification. This study provides a theoretical basis in terms of proteomics for exploring the post-ripening and germination of H. moellendorffii seeds.

[Clinical efficacy of catheter-directed thrombolysis combined with endovascular interventions for acute lower limb ischemia].

Objective: To explore the risk factors and treatment of acute lower limb ischemia with catheter-directed thrombolysis combined with endovascular interventions. Methods: Totally 191 patients (191 lower limbs) with acute lower limb ischemia in department of vascular surgery of the First Affiliated Hospital of Chongqing Medical University from June 2012 to June 2017 who underwent catheter-directed thrombolysis combined with endovascular interventions were collected. According to imaging findings and clinical characteristics, the patients were divided into acute arterial embolism group (n=36) and acute arterial thrombosis group (n=155). The treatment effect, long-term follow-up and the risk factors closely related to primary patency were analyzed. Results: Among the 191 patients, the immediate success rate of surgery was 100%, the amputation rate within 30 days was 8.4% (16/191), and the mortality rate within 30 days was 2.6% (5/191). The mean follow-up was 31.0 (1.0-60.0) months. The 1-year overall survival rate was 92.1% and the 5-year was 79.5%. The primary patency rate was 74.3% within 1 year and 61.5% within 5 years. Primary vascular patency rate within 1 year and 5 years was mainly affected by occlusion segment (OR=3.5, 2.9, P<0.05), outflow tract (OR=3.2, 2.8, P<0.05) and ischemia degree (OR=3.4, 3.6, P<0.05). Conclusion: Catheter-directed thrombolysis combined with endovascular interventions for acute lower limb ischemia is a safe and effective method. Risk factors for primary patency at 1 and 5 years are occlusion segment, outflow tract and ischemia degree.

Correlation between endometrial receptivity with expressions of IL-1 and VEGF in rats with polycystic ovary syndrome.

OBJECTIVE: To investigate the correlation between endometrial receptivity with expressions of interleukin-1 (IL-1) and vascular endothelial growth factor (VEGF) in rats with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: A total of 24 female Sprague-Dawley (SD) 21 days old were randomly divided into control group (n=12) and PCOS group (n=12). Rats in the control group were normally raised, and PCOS model was established in rats of the PCOS group. All the rats were sacrificed when they grew to 80 days old. Immunohistochemistry was applied to detect the expressions of IL-1 and VEGF. Western blotting was performed to measure the relative expressions of IL-1 and VEGF proteins. Quantitative Polymerase Chain Reaction (qPCR) was utilized to determine the relative messenger ribonucleic acid (mRNA) expressions of IL-1 and VEGF. Data related to endometrial receptivity were detected. RESULTS: The expression levels of IL-1 and VEGF in the PCOS group declined markedly compared with those in the control group, and the differences were statistically significant (p<0.05). PCOS group had notably lower protein expressions of IL-1 and VEGF than the control group, with statistically significant differences (p<0.05). The mRNA expressions of IL-1 and VEGF in PCOS group were significantly lower than those in the control group, displaying statistically significant differences (p<0.05). Compared with that in the control group, the endometrial receptivity of rats in the PCOS group was reduced evidently, and the difference was statistically significant (p<0.05). Both IL-1 and VEGF had positive correlations with the endometrial receptivity. CONCLUSIONS: Both IL-1 and VEGF are positively correlated with the endometrial receptivity in the case of PCOS, which can serve as therapeutic targets for PCOS and improve endometrial receptivity in the future.

Characterization and identification of ferulic acid esterase-producing Lactobacillus species isolated from Elymus nutans silage and their application in ensiled alfalfa.

AIMS: Ferulic acid esterase (FAE)-producing Lactobacillus species isolated from ensiled Elymus nutans growing on the Qinghai-Tibetan plateau were characterized, and effects of their application to the alfalfa ensiling process and the evidence to synergic effect between cellulase and FAE were investigated. METHODS AND RESULTS: The results of 16S rRNA gene sequence and species-specific polymerase chain reaction amplification showed that two screened strains with high FAE activity were Lactobacillus plantarum A1 (LP) and L. brevis A3 (LBr). The optimum temperature and pH for the LP and LBr was 37°C and 6·4 respectively. The FAE exhibited a good stability at temperatures between 25 and 50°C and at pH values of 5·0-7·0. The two strains and a commercial cellulase (CE) were applied as additives to alfalfa silage. After 60 days of ensiling, the lactic acid in the control and CE groups were significantly lower than those of the other treatment groups. The neutral detergent fibre and acid detergent fibre contents in the LP group were significantly lower than those observed in the other groups. At the same time, the combination of CE and FAE-producing lactic acid bacteria synergistically improved the fermentation quality of the silage. CONCLUSIONS: The addition of the FAE-producing strain of L. plantarum A1 to alfalfa silage improved its fermentation quality, and reduced the fibre content of the silage. SIGNIFICANCE AND IMPACT OF THE STUDY: The screened homo-fermentative and FAE-producing strain of L. plantarum A1 could be a candidate strain in improving fermentation quality and fibre digestibility of ensiled forages.

BNIP1 inhibits cell proliferation, migration and invasion, and promotes apoptosis by mTOR in cervical cancer cells.

OBJECTIVE: BNIP1, a member of the BH3-only protein family, plays essential roles in a variety of biological processes. However, the mechanism and function of BNIP1 are still unknown in cervical cancer. We aim to explore the roles of BNIP1 on cervical cancer cell proliferation, apoptosis, migration, and invasion abilities by mTOR signaling pathway. PATIENTS AND METHODS: qRT-PCR and Western blot assays were performed to assess BNIP, mTOR, and p70S6K1 expressions. CCK-8, transwell and flow cytometry assays were used to measure the representative proliferation, migration, invasion, and apoptosis abilities. RESULTS: Our findings indicated that BNIP1 is down-expressed in cervical cancer tissues and cells, and was negatively associated with lymphatic metastasis. Overexpression of BNIP1 suppressed proliferation, migration and invasion, and promoted apoptosis of cervical cancer cells. Silence of BNIP1 by siRNAs accelerated proliferation, migration and invasion, and inhibited apoptosis of cervical cancer cells. In addition, we found that BNIP1 significantly inhibited mTOR, p70S6K1, and p-p70S6K1 expressions; BNIP1 affected the proliferation, apoptosis, migration, and invasion abilities of cervical cancer cells by regulating mTOR expression. CONCLUSIONS: BNIP1 can be considered a marker for cervical carcinoma therapy.

Characteristics of Pediococcus pentosaceus Q6 isolated from Elymus nutans growing on the Tibetan Plateau and its application for silage preparation at low temperature.

AIMS: Characteristics of a strain Pediococcus pentosaceus Q6 isolated from Elymus nutans growing on the Tibetan plateau and its effects on E. nutans silage fermentation stored at low temperature were investigated. METHODS AND RESULTS: Sugar fermentation pattern and growth profiles of the strain Q6 and its reference strain APP were characterized. The strain Q6 and APP were inoculated to E. nutans at ensiling respectively; and ensiled at different temperatures (10, 15 and 25°C) for 30, 60 and 90 days. The results indicated that Q6 could grow at pH 3·0 and at 4°C. In contrast to APP, Q6 could ferment mannitol, saccharose, sorbitol and rhamnose. Lower pH in Q6-treated silages fermented for 60 days at 10 and 15°C was found compared with the control and APP-treated groups. For the silages that were stored at 10 or 15°C, the greatest lactic acid content were detected in Q6-inoculated silages ensiled for 30 and 60 days respectively. There were no differences in pH and lactic acid content between Q6- and APP-treated silages ensiled at 10 and 15°C for 90 days respectively. CONCLUSIONS: Inoculation of the strain P. pentosaceus Q6 could improve fermentation quality of ensiled E. nutans at the early stage of ensiling stored at low temperature (10 or 15°C). SIGNIFICANCE AND IMPACT OF THE STUDY: The selection of P. pentosaceus inoculants for improving silage quality at low temperature, which provides a candidate strain to make high-quality silage in regions with frigid climate.

Dietary butylated hydroxytoluene improves lipid metabolism, antioxidant and anti-apoptotic response of largemouth bass (Micropterus salmoides).

A 10-week growth trail was conducted to investigate the efficacy and tolerance of dietary butylated hydroxytoluene (BHT) by evaluating inflammation, apoptosis and hepatic disease related to oxidative stress in largemouth bass (Micropterus salmoides). Four experimental diets were prepared with BHT supplement levels of 0 (B0), 150 (B150), 300 (B300) and 1500 (B1500) mg/kg, in which B150 was at the maximum recommended level established by European Union Regulation, and the B300 and B1500 levels were 2 and 10-fold of B150, respectively. Each diet was fed to 6 replicates with 30 largemouth bass (initial body weight, IBW = 6.20 ± 0.01 g) in each tank. The BHT inclusion level did not affect the specific growth rate, but fish in the B150 group showed the lowest feed conversion rate (P < 0.05). BHT inclusion significantly decreased the levels of plasma TC, TG, LDL, ALT and AKP, and increased the (HDL-C)/TC ratio (P < 0.05). Plasma MDA was significantly decreased in the B150 group and GSH-Px was extremely enhanced in each BHT inclusion group (P < 0.05). Hepatic T-AOC was significantly enhanced and O2- was significantly decreased in each BHT inclusion group compared to the B0 group (P < 0.05), as well as hepatic MDA was significantly decreased in B1500 group (P < 0.05). Dietary BHT inclusion down-regulated the hepatic mRNA levels of inflammation, apoptosis and fibrosis related genes, including TNFα, TGF-ß1, α-SMA, IL8, IL11ß and caspase-9. Moreover, BHT could improve hepatic lipid metabolism via up-regulating the mRNA levels of APOA1, CYP7A1, CYP8B1, and down-regulating the mRNA levels of PPAR-γ and APOB. Histological examination of the liver morphology with H&E and Sirius Red staining showed that BHT inclusion decreased necrotic degenerative changes and collagen deposition in largemouth bass. An immunofluorescence examination revealed significantly decreased cleaved caspase-3 signals in the BHT groups. In conclusion, the results demonstrated that ROS induces hepatic cell apoptosis and fibrosis via the intrinsic pathway of apoptosis by activating caspase-9 in the mitochondria and then initiates apoptosis by activating caspase-3. Consuming 2.32-23.80 mg/kg·bw/d (150-1500 mg/kg in diet) of BHT effectively improved the plasma and hepatic lipid metabolism, antioxidant response as well as reduced ROS production, protecting hepatic cells from injury. It is implied that even a 10-fold increase of the maximum level of BHT (150 mg/kg) is safe for the largemouth bass.

Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice.

Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.

Design of ultrafast laser-driven microactuator based on photoacoustic mechanism.

In this work, an ultrafast laser-driven microactuator based on the photoacoustic mechanism was proposed with large amplitude and high response frequency. The microactuator was fabricated by LIGA technology. The displacement of the microactuator could be up to 11 µm at resonance state when the repeat frequency was around 14 kHz using a nanosecond pulse laser. Theoretical model was set up and the calculated results agree reasonably well with the experimental data. The microactuator based on the photoacoustic mechanism provides a more efficient actuation method.