Silencing circ_0000644 inhibits papillary thyroid cancer cell malignancy by combining with miR-671-5p to release the inhibition on ANXA2.

BACKGROUND: Papillary thyroid cancer (PTC) is life-threatening due to its malignant progression. Considerable evidence demonstrates that circular RNA (circRNA) regulates PTC development. This study aims to explore the mechanism of circ_0000644 modulating PTC malignant progression. METHODS: The RNA levels of circ_0000644, microRNA-671-5p (miR-671-5p) and annexin A2 (ANXA2) were detected by quantitative real-time polymerase chain reaction. Western blot was performed to check protein expression. Cell proliferation and cell apoptosis were investigated by 5-ethynyl-29-deoxyuridine and flow cytometry. Angiogenic capacity, migration and invasion were analyzed by tube formation assay and transwell assay. The interaction between miR-671-5p and circ_0000644 or ANXA2 was identified by dual-luciferase reporter assay. Xenograft mouse model assay was performed to analyze the effect of circ_0000644 on tumor formation in vivo. RESULTS: Circ_0000644 and ANXA2 expression was significantly upregulated, while miR-671-5p was downregulated in PTC tissues and cells when compared with control groups. Circ_0000644 knockdown inhibited PTC cell proliferation, tube formation, migration, and invasion, but induced apoptosis in vitro. Moreover, circ_0000644 knockdown led to delayed tumorigenesis in vivo. In addition, circ_0000644 acted as a miR-671-5p sponge and mediated PTC cell tumor properties through miR-671-5p. ANXA2 was identified as a target gene of miR-671-5p, and its overexpression relieved miR-671-5p-induced effects in PTC cells. Furthermore, circ_0000644 depletion inhibited ANXA2 production by combining with miR-671-5p. CONCLUSION: Circ_0000644 depletion repressed PTC cell tumor properties through the miR-671-5p/ANXA2 axis.

Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial.

Importance: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy of RIC for acute moderate ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021. Interventions: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). Main Outcomes and Measures: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group. Conclusions and Relevance: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03740971.

[Comparison of MR Perfusion Weighted Imaging and CT Perfusion Imaging in Assessing Hemodynamics of Patients with Moyamoya Disease].

OBJECTIVE: To determine consistencies between MR perfusion weighted imaging (PW-MRI) and CT perfusion imaging (CTP) in assessing hemodynamics of patients with moyamoya disease (MMD). METHODS: Images of PWI and CTP scan [including the map of cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and mean transmit time (MTT)] of 24 MMD patients diagnosed by digital subtraction angiography(DSA) or time of flight-MR angiography (TOF-MRA) were obtained in the week before vascular reconstruction operations. Relative perfusion parameters (rCBF, rCBV, rMTT, rTTP) at the operative side within the middle cerebral artery territory and cerebellar hemisphere were compared with those of 17 patients without hypoperfusion and cerebrovascular disease using independent sample t test. Paired t test and Pearson correlation analyses were performed between the results of PWI-MRI and CTP. RESULTS: Different parameters were found in the MMD patients compared with the controls (P<0.05). The parameter results of PWI-MRI differed from those of CTP, but they were strongly correlated. CONCLUSION: Both PWI-MRI and CTP can detect the area and degree of hypoperfusion of MMD patients.

The Impact of Cysteine-Rich Intestinal Protein 1 (CRIP1) on Thyroid Carcinoma.

BACKGROUND/AIMS: CRIP1 (cysteine-rich intestinal protein 1) has been found in several tumor types; however, its prognostic impact and role in cellular processes, particularly in thyroid carcinoma, are still unclear. METHODS: To elucidate the prognostic impact of CRIP1, we analyzed tissues from 58 primary invasive thyroid carcinomas using immunohistochemistry. Western blotting was performed to investigate CRIP1 protein expression in the thyrocyte cell line Nthy-ori 3-1 and four different thyroid carcinoma cell lines, K1, TPC-1, TT, and SW579. Endogenous expression of CRIP1 was suppressed using a siRNA (si-CRIP1). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to investigate cell viability. Flow cytometric analysis was used to detect cell cycle progression and cell apoptosis. The effects of silencing CRIP1 on cell migration and invasion were detected using the transwell assay. RESULTS: The immunohistochemistry results showed that CRIP1 was overexpressed in thyroid carcinoma. CRIP1 expression was associated with tumor size, TNM stage, and lymphatic metastasis, but not with age, gender, and tumor location. In addition, the expression of CRIP1 in K1, TPC-1, TT, and SW529 cells was higher than that in the Nthy-ori 3-1 cells. The highest expression was observed in the SW579 and TT cells. Furthermore, silencing CRIP1 inhibited the proliferation, migration, and invasion of thyroid carcinoma cell lines SW579 and TT. We also found that silencing CRIP1 induced G1 arrest and apoptosis of thyroid carcinoma cell lines SW579 and TT. CONCLUSION: In conclusion, CRIP1 acts as an oncogene in the cell proliferation, migration, and invasion processes of thyroid carcinoma. CRIP1 may serve well as an independent prognostic marker with significant predictive power for use in thyroid carcinoma therapy.

Isolation and functional analysis of the pathogenicity-related gene VdPR3 from Verticillium dahliae on cotton.

The fungal plant pathogen Verticillium dahliae is the causal agent of vascular wilt, a disease that can seriously diminish cotton fiber yield. The pathogenicity mechanism and the identity of the genes that interact with cotton during the infection process still remain unclear. In this study, we investigated the low-pathogenic, non-microsclerotium-producing mutant vdpr3 obtained in a previous study from the screening of a T-DNA insertional library of the highly virulent isolate Vd080; the pathogenicity-related gene (VdPR3) in wild-type strain Vd080 was cloned. Knockout mutants (ΔVdPR3) showed lower mycelium growth and obvious reduction in sporulation ability without microsclerotium formation. An evaluation of carbon utilization in mutants and wild-type isolate Vd080 demonstrated that mutants-lacking VdPR3 exhibited decreased cellulase and amylase activities, which was restored in the complementary mutants (ΔVdPR3-C) to levels similar to those of Vd080. ΔVdPR3 postponed infectious events in cotton and showed a significant reduction in pathogenicity. Reintroduction of a functional VdPR3 copy into ΔVdPR3-C restored the ability to infect cotton plants. These results suggest that VdPR3 is a multifunctional gene involved in growth development, extracellular enzyme activity, and virulence of V. dahliae on cotton.

The Extracellular Calcium-Sensing Receptor (CASR) Regulates Gonadotropins-Induced Meiotic Maturation of Porcine Oocytes.

Gonadotropins and epidermal growth factor (EGF) play crucial roles in promoting oocyte maturation. The regulatory network downstream of these key factors is not well understood. The present study was designed to investigate the role of the calcium-sensing receptor (CASR) in porcine oocyte in vitro maturation. CASR expression was up-regulated in oocytes matured in gonadotropin-containing medium. Cortical distribution of CASR was enhanced with gonadotropins but not EGF. Supplementation of a CASR agonist (NPS R-568) in the gonadotropin (FSH and/or LH)-containing maturation medium significantly enhanced oocyte nuclear maturation. Addition of NPS2390, a CASR antagonist, compromised oocyte nuclear maturation. Furthermore, increased cortical distribution and decreased expression of CASR was observed after the NPS R-568 treatment. Oocytes treated with NPS R-568 had higher concentration of CYCLIN B1, decreased reactive oxygen species, and increased glutathione levels, indicative of advanced cytoplasmic maturation. In contrast, NPS2390 treatment compromised oocyte cytoplasmic maturation. A higher blastocyst formation rate after parthenogenetic activation was observed when oocytes were matured in the presence of the CASR agonist, NPS R-568. MAPK3/1 phosphorylation was increased during in vitro maturation and after NPS R-568 treatment, and decreased following CASR antagonist supplementation. Taken together, our data showed that the CASR is a gonadotropin-regulated factor that promotes porcine oocyte maturation in a MAPK-dependent manner.

[Effects of transgenic cotton expressing chitinase and glucanase genes on the diversity of soil bacterial community].

The transgenic cotton expressing chitinase and glucanase genes was studied using nontransgenic cotton as a control. Specifically, the effects of exogenous genes on bacterial community diversity in rhizospheres of cotton at stages of seedling, budding, boll forming and boll opening were evaluated through comparing the number of cultivable bacteria and analyzing 16S rRNA gene clone libraries. The results showed that the number of cultivable bacteria was not affected by exogenous genes but the cotton growth period, and the number peaked at the stage of boll forming with vigorous metabolism. The 16S rRNA gene clone library prepared from soil bacteria in rhizospheres of transgenic and nontransgenic cotton at different stages contained 2400 clones which covered 283 genera. Among them, Acidobacterium was the most dominant group which contained 642 clones, followed by unclassified bacterium and Flavisolibacter. Compared with nontransgenic cotton, the rhizosphere bacterial diversity of transgenic cotton exhibited lower level at the same growth stage, however, their common bacterial communities increased with growth and development. Our results suggest that chitinase and glucanase genes decrease the rhizosphere bacterial diversity at distinct degrees, however, the difference of bacterial diversity between transgenic and nontransgenic cotton reduces gradually with the extension of cultivation period.

[Treatment of Radical Resected NSCLC by Chinese Medicine Combined with Adjuvant Chemother- apy: a Clinical Study].

OBJECTIVE: To evaluate the efficacy of Chinese medicine (CM) combined adjuvant chemotherapy in postponing relapse and metastasis of radical resected Ib-IIIa stage non-small cell lung cancer (NSCLC) patients, and to explore its effect in improving their quality of life (QOL) and clinical symptoms. METHODS: We designed a cohort study of 336 radical resected Ib-IIIa NSCLC patients by analyzing disease free survival (DFS) using Log-rank test. They were randomly assigned to the control group (155 cases, treated by adjuvant chemotherapy group) and the test group (181 cases, treated by adjuvant chemotherapy combined CM). By using controlled method, 60 radical resected NSCLC patients undergoing NP/NC program in 2012 (vinorelbine 25 mg/m2, combined with cisplatin 75 mg/m2 on day 1 and day 8/on day 1 or on day 1, 2, and 3; or carboplatin AUC = 5 on day 1) were assigned to the control group (29 cases) and the test group (31 cases). QOL scores (using EORTC QLQ-LC43 questionnaire) and TCM symptoms scores were compared between the two groups before chemotherapy, peri-chemotherapy (one day before the 2nd course of chemotherapy) , and after chemotherapy (20 days after ending the 4th course of chemotherapy). RESULTS: (1) The median DFS was longer in the test group than in the control group, but with no statistical difference between the two groups (42.73 months vs 35.57 months , P = 0.179). In the subgroup analysis, there was statistical difference in IIIa stage DFS. The median IIIa stage DFS of was longer in the test group than in the control group with statistical difference (27.87 months vs 19. 93 months, P = 0.047). (2) In the control study, repeated measured data indicated there was significant difference in physical functions between the two groups (P < 0.05). Total scores for health states decreased more in the test group than in the control group, but with no statistical difference (P > 0.05). Scores for constipation and CM syndrome scores were higher in the test group than in the control group (P < 0.05). CONCLUSIONS: CM had advantages in postponing DFS of radical resected NSCLC patients, especially in IIIa stage. CM could improve their QOL and clinical symptoms during adjuvant chemotherapy.

Effects of lipoic acid on immune function, the antioxidant defense system, and inflammation-related genes expression of broiler chickens fed aflatoxin contaminated diets.

This study was designed to evaluate the effect of low level of Aflatoxin B1 (AFB1) on oxidative stress, immune reaction and inflammation response and the possible ameliorating effects of dietary alpha-lipoic acid (α-LA) in broilers. Birds were randomly allocated into three groups and assigned to receive different diets: basal diet, diet containing 74 µg/kg AFB1, and 300 mg/kg α-LA supplementation in diet containing 74 µg/kg AFB1 for three weeks. The results showed that the serum levels of malondialdehyde, tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) in the AFB1-treated group were significantly increased than the control group. In addition, the increased expressions of interleukin 6 (IL6), TNFα and IFNγ were observed in birds exposed to the AFB1-contaminated diet. These degenerative changes were inhibited by α-LA-supplement. The activities of total superoxide dismutase and glutathione peroxidase, the levels of humoral immunity, and the expressions of nuclear factor-κB p65 and heme oxygenase-1, however, were not affected by AFB1. The results suggest that α-LA alleviates AFB1 induced oxidative stress and immune changes and modulates the inflammatory response at least partly through changes in the expression of proinflammatory cytokines of spleen such as IL6 and TNFα in broiler chickens.

Tenecteplase Plus Butyphthalide for Stroke Within 4.5-6 Hours of Onset (EXIT-BT): a Phase 2 Study.

To date, the benefit of intravenous thrombolysis is confined to within 4.5 h of onset for acute ischemic stroke (AIS) without advanced neuroimaging selection. The current trial aimed to investigate the safety and efficacy of intravenous tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6 h of onset. In this randomized, multicenter trial, eligible AIS patients were randomly assigned to receive intravenous TNK (0.25 mg/kg) plus NBP or NBP within 4.5 to 6 h of onset. The primary endpoint was symptomatic intracranial hemorrhage (sICH). Secondary endpoints included excellent functional outcome defined as a modified Rankin Scale score of 0 to 1 at 90 days. 100 patients diagnosed by non-contrast CT (NCCT) were enrolled, including 50 in TNK group and 50 in control group. sICH occurred in 2.0% (1/50) in TNK group and 0.0% (0/49) in control group with no difference (unadjusted P = 0.998). The proportion of excellent functional outcome was 77.6% (38/49) in TNK group and 69.4% (34/49) in control group with non-significance (absolute difference 8.2%, P = 0.36). A significant decrease in NIHSS score at 24 h (P = 0.004) and more early neurological improvement (20.4% vs 4.1%; P = 0.026) was observed in TNK vs control group, but there was no difference in other secondary outcomes. This phase 2 study suggests that intravenous TNK with adjuvant NBP seems safe, feasible and may improve early neurological function in AIS patients within 4.5 to 6 h of symptom onset selected using NCCT.Clinical Trials Registration: This trial was registered with ClinicalTrials.gov (NCT05189509).

[Analysis of mortality and years of life lost of malignant tumors among inhabitants in rural area of Feicheng city from 2000 to 2010].

OBJECTIVE: To analyze the mortality trends and disease burden of malignant tumors in rural area of Feicheng city from 2000 to 2010, and to provide basic information for the prevention and treatment of malignant tumors in this area. METHODS: The data of cancer mortality from 2000 to 2010 from Feicheng Cancer Registry database were checked. Mortality rate, standardized mortality rate, potential years of life Iost (PYLL), standardized potential years of life lost (SPYLL), average years of life lost (AYLL) and other indexes were calculated and analyzed. The trend of the standardized rates transformed by the natural logarithm over time was assessed by Prais-Winsten regression method in which the errors was assumed to follow a first-order autoregressive process. STATA 12.0 was used to analyze the data. RESULTS: In average, the crude mortality rate was 199.67 per 100 000 (264.69 per 100 000 in males and 137.24 per 100 000 in females), and the standardized mortality rate was 157.00 per 100 000 (200.49 per 100 000 in males and 101.31 per 100 000 in females). There were no significant changes in the trends of all standardized rates. For males, the mortality rates of lung and colorectal cancers increased significantly, and for females, the rates of lung and breast cancers had increased trend while the rate of esophageal cancer showed a downward trend. There were no statistically significant changes in other main malignant tumors. During 2000 to 2010, the PYLL of malignant tumors in Feicheng was 183 685.0 person-years, and PYLL rate was 23.3 per 1000. The SPYLL was 153 091.0 person-years, SPYLL rate was 19.4 per 1000, and AYLL was 14.8 years. CONCLUSIONS: There are no obvious changes in the trends of standardized mortality rates in rural area of Feicheng over the past 11 years. For males, the mortality of lung cancer and colorectal cancer is increasing, and for females, the rates of lung and breast cancers have an increasing trend while the rate of esophageal cancer shows a decreasing trend. The prevention and control of digestive malignant tumors, lung cancer and breast cancer are getting seriously important and should be the focal point in this issue.

Prognostic Value of Metabolic Syndrome in Patients With Non-ST Elevated Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Objective: We aim to investigate the prognostic effects of metabolic syndrome (MS) on patients with non-ST elevated myocardial infarction (NSTEMI) after percutaneous coronary intervention (PCI). Methods: Patients with NSTEMI undergoing PCI were consecutively collected. According to the presence or absence of MS, they were divided into two groups and followed up for 1 year. The endpoint was major adverse cardiovascular events (MACE), including all-cause death, unstable angina hospitalization, heart failure (HF) hospitalization, non-fatal recurrent myocardial infarction (MI), and target lesion revascularization. Also, six subgroups were made according to gender, age, left ventricular ejection fraction (LVEF), Global Registry of Acute Coronary Events (GRACE) score, hypersensitive troponin (hsTNT), and several diseased vessels. Cox proportional hazard model was adopted to analyze the effect of MS on MACE in all the patients and different subgroups. Results: A total of 1,295 patients were included in the current analysis and 660 (50.97%) of them had MS. About 88 patients were lost to follow-up, and the overall average follow-up was 315 days. MS was an independent risk factor for MACE (HR 1.714, CI 1.265-2.322, p = 0.001), all-cause death, heart failure (HF) hospitalization, and non-fatal recurrent MI. In the MS component, BMI ≥28 kg/m2 was positively associated with MACE. Subgroup analysis indicated the prognostic value of MS was more striking for patients with the following: age of >60, LVEF of ≤40%, GRACE of >140, multivessel disease, or hsTNT of >0.1 ng/ml. Conclusions: The MS was a robust adverse prognostic factor in patients diagnosed with NSTEMI, especially among those of older age and at higher ischemic risk. A BMI of ≥28 kg/m2 independently predicted the occurrence of MACE. Prognosis may be improved by controlling abdominal obesity.

Dietary lipoic acid influences antioxidant capability and oxidative status of broilers.

The effects of lipoic acid (LA) on the antioxidant status of broilers were investigated. Birds (1 day old) were randomly assigned to four groups and fed corn-soybean diets supplemented with 0, 100, 200, 300 mg/kg LA, respectively. The feeding program included a starter diet from 1 to 21 days of age and a grower diet from 22 to 42 days of age. Serum, liver and muscle samples were collected at 42 days of age. For antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in serum, liver and breast muscle significantly increased in chickens fed with LA. The concentration of malondiadehyde (MDA), an indicator of lipid peroxidation, was significantly lower in serum, liver and leg muscle in birds that received LA than in the control group. Treatments with LA significantly increased glutathione (GSH) content in liver and increased α-tocopherol content in leg muscle as compared to the control. These results indicate that dietary supplementation with 300 mg/kg LA may enhance antioxidant capability and depress oxidative stress in broilers.

[Antagonistic Effect and Mechanism of Nano Titanium Dioxide and Cadmium on the Growth of Scenedesmus obliquus].

The release of manufactured nanomaterials (MNMs) into the environment has raised concerns about combined toxicological risks, as MNMs could significantly alter the environmental behavior and fate of co-existing contaminants. Numerous studies have been published on the combined toxicity of MNMs and co-existing contaminants, but the potential mechanisms controlling the combined toxicity, especially the biological response mechanism, remain unclear. This study investigated the combined toxicity of nano-titanium dioxide (nTiO2), a typical MNM, and the heavy metal cadmium (Cd2+), using Scenedesmus obliquus as the test organism. The molecular mechanism was examined under different concentrations, using an equivalent dose (toxic ratio 1 ∶1) on S. obliquus. The results showed that the 72h-EC50 of nTiO2 and Cd2+ at the equivalent dose was significantly higher than that of single exposure, indicating an antagonistic effect. Further transcriptomics analysis revealed that the photosynthesis, chlorophyll metabolism, and starch and sucrose metabolism pathways involved in the energy metabolism of S. obliquus were significantly up-regulated in the presence of nTiO2. The arginine and proline metabolic pathways related to the anti-stress effect of algae cells also showed positive stimulation. The results of this study provide an important reference and a research basis for in-depth understanding of the environmental effects of MNMs and co-existing contaminants.

Evaluation of sleep disorder in orthopedic trauma patients: a retrospective analysis of 1129 cases.

BACKGROUND: In the trauma center wards, it is not unusual for patients to have sleep disorders, especially patients with an acute injury. Meanwhile, there is substantial evidence that sleep disorder is a predictor of depression and is an important feature of posttraumatic stress disorder. METHODS: All orthopedic trauma patients confined in a trauma ward in West China Hospital of Sichuan University between April 2018 and July 2019 were included in this retrospective study. Patients with mental impairment or craniocerebral injuries were excluded from the study. Basic demographic data and the Injury Severity Score (ISS) classification based on medical records were collected. The Pittsburgh sleep quality index (PSQI) was used to evaluate sleep quality, the visual analog scale (VAS) was used to evaluate physical pain, and the Barthel Index (BI) was used to evaluate activities of daily living (ADL). Univariate linear regression analysis and multivariate linear regression analysis were used to identify independently related factors. RESULTS: The average PSQI score was 6.3 (± 4.0). A total of 581 (51.4%) patients had a PSQI score > 5, indicating the presence of sleep disorders. The PSQI score was > 10 in 174 (15.4%) patients. Univariate statistical analysis showed that age, sex, education, ADL, and ISS classification were associated with increased PSQI scores. Marital status and pain were not associated with increased PSQI scores. When we used multivariate analysis to control for confounding variables, sex, ADL, and ISS classification remained independently associated with PSQI (P = 0.002, < 0.000, and 0.002, respectively). CONCLUSIONS: In our study, sleep disorders were common (51.4% with PSQI > 5) and serious (15.4% with PSQI > 10) in patients with traumatic orthopedic injury. The following factors were closely associated with sleep disorders: sex, ADL, and ISS classification. Moreover, age and educational attainment have an independent impact on sleep quality. Unexpectedly, the VAS score for pain was not independently associated with the seriousness of sleep quality, which may be related to preemptive and multimodal analgesia. Further studies are required to clarify this ambiguity.

Dietary supplementation with acidifiers improves the growth performance, meat quality and intestinal health of broiler chickens.

This experiment was conducted to study the effects of dietary supplementation with acidifiers on the growth performance, meat quality, and intestinal health of broiler chickens. A total of 648 male Arbor Acres broiler chickens at 1 d old were randomly divided into 6 groups, and each group consisted of 6 replicates with 18 broilers per replicate. The dietary treatments were as follows: negative control (NC, the basal diet), NC + antibiotic (enramycin, 8 mg/kg, positive control [PC]), NC + phosphoric acid (PA, 0.1, 0.2, and 0.3 g/kg), and NC + lactic acid (LA, 0.3 g/kg). The feeding trial lasted for 42 d. The results showed that the feed-to-gain ratio of the NC + acidifier groups was lower than that of the NC and PC groups from 1 to 42 d (P < 0.05). Compared with the values in the NC group, the pH of breast muscle was significantly higher in the NC + PA (0.2 g/kg) and LA (0.3 g/kg) groups (P < 0.05), and the cooking loss was lower in the breast muscle of the NC + PA (0.1 g/kg) and LA (0.3 g/kg) groups (P < 0.05). In addition, the shear force of the breast muscle and thigh muscle and the pH value in the crop, gizzard and duodenum of the antibiotic and acidifier groups were significantly decreased (P < 0.05). Moreover, the trypsin, chymotrypsin, and lipase activities of the duodenum in the NC + PA (0.2 and 0.3 g/kg) groups, as well as the villus height-to-crypt depth (VH:CD) ratio of the duodenum in the NC + PA (0.1 g/kg) group was significantly greater (P < 0.05) compared with those in the NC group. Meanwhile, the number of total aerobic bacteria, Escherichia coli and Salmonella in the cecum of the NC + PA (0.1 g/kg) and LA (0.3 g/kg) groups were decreased (P < 0.05). Collectively, diet supplementation with acidifiers could improve the growth performance, meat quality, and intestinal health of broilers, in which the effects of PA (0.1 g/kg and 0.2 g/kg) are better than the other supplementations.

Human urinary kallidinogenase in acute ischemic stroke: A single-arm, multicenter, phase IV study (RESK study).

AIMS: Human urinary kallidinogenase (HUK) has shown favorable efficacies in acute ischemic stroke (AIS) treatment. We sought confirmation of the safety and efficacy of HUK for AIS in a large population. METHODS: RESK study enrolled patients with AIS of anterior circulation to receive HUK infusion. The primary endpoint was the incidence of treatment-emergent adverse events (AEs). Secondary endpoints assessed neurological and functional improvements and stroke recurrent rate. RESULTS: Of 1206 eligible patients, 1202 patients received at least one dose of HUK infusion and 983 (81.5%) completed the study. The incidence of treatment-emergent AEs and serious AEs were 55.99% and 2.41%, respectively. Pre-specified AEs of special interest occurred in 21.71% of patients, but the majority were mild and unrelated to therapy. Hypertension, age, treatment time, and drug combination were identified to be associated with drug-related blood pressure reduction. Neurological and functional evaluations revealed favorable outcomes from baseline to post-treatment assessment. The cumulative recurrence rate of stroke was 2.50% during the 90-day assessment. CONCLUSION: HUK had an acceptable safety and tolerability profile in AIS patients. Besides, HUK demonstrated the neurological and functional improvements in AIS, further confirming its clinical efficacy in a real-world large population.

[Analysis of prognostic risk factors in the patients with acute exacerbation of chronic cor pulmonale and obstructive sleep apnea-hypopnea syndrome in high altitude area].

OBJECTIVE: To assess the prognostic risk factors in the patients with acute exacerbation of chronic cor pulmonale (AEHACCP) and obstructive sleep apnea-hypopnea syndrome (OSAHS) in high altitude area. METHODS: The relations between neck circumference (Nc), body mass index (BMI), arterial blood gases, polysomnography (PSG) parameters and prognosis from 66 patients with AEHACCP and OSAHS (31 survivors, 35 non-survivors) were studied by one variable analysis and multivariable Logistic regression analysis. RESULTS: The results of one variable analysis showed that in patients with AEHACCP and OSAHS, Nc> or =45 cm, BMI > or =28 kg/m(2) , arterial oxygen partial pressure (PaO(2))< or =40 mm Hg (1 mm Hg= 0.133 kPa), mean pulmonary arterial pressure (mPAP)> or =45 mm Hg, apnea-hypopnea index (AHI)> or = 40 times/h, sleep mean arterial oxygen saturation (MSaO(2))< or =0.70, percentage of the duration of SaO(2)<0.70 during sleep(T(70) )> or =50% and difference between basic and minimum SaO(2) during sleep(Delta SaO(2))> or = 0.20 were closely correlated with prognosis. The Logistic regression models showed that Nc> or =45 cm [odds ratio (OR)=6.781, 95% confidence interval (95%CI)=1.153-17.502, P=0.007], BMI> or =28 kg/m(2) (OR=7.562, 95%CI=1.012-23.457, P=0.004), mPAP> or =45 mm Hg (OR=6.991, 95%CI=1.353-20.155, P=0.003), AHI> or =40 times/h (OR=7.258, 95%CI=1.526-18.022, P=0.006), MSaO(2)< or =0.70 (OR=6.488, 95%CI=1.562-26.878, P=0.008), T(70) > or =50% (OR=5.593, 95%CI=1.265-21.589, P=0.008) and Delta SaO(2)> or =0.20 (OR=6.551, 95%CI=1.495-18.920, P=0.007) were independent significant risk factors in prognosis of patients with AEHACCP and OSAHS. CONCLUSION: The patients with AEHACCP and OSAHS, Nc> or =45 cm, BMI> or =28 kg/m(2), mPAP> or =45 mm Hg, AHI> or = 40 times/h, MSaO(2)< or =0.70, T(70) > or =50% and Delta SaO(2)> or =0.20 are risk factors leading to a rise in mortality. It is important to use these parameters to guide clinical therapy, and to judge the prognosis so as to reduce the mortality of patients with AEHACCP and OSAHS by monitoring the above risk factors in clinical practice.

[Delimitation of urban development boundary based on ecological sensitivity evaluation and CA-Markov simulation in plain city:A case of Nanchang, Jiangxi, China]. / 基于生态敏感性评价和CA-Markov模拟的平原型城市开发边界划定­­ä»¥å—昌市为例.

The rational delimitation of urban development boundary plays an important role in guiding the orderly growth of urban space and ensure proper environment health of urban space. In this study, we evaluated the ecological sensitivity of Nanchang City from four aspects (soil erosion, habitat, geological disaster and water resource) and simulated urban expansion in 2020 based on CA-Markov and land use data in 2000, 2010 and 2015. Spatial decision-making analysis of the two aspects was carried out in combination to the future development of the study area. We proposed a new method of delimitating urban development boundary integrating environmental protection and urban development through the dynamic coordination of both aspects. The results showed that ecological sensitivity of Nanchang City was moderate. The scale of urban construction land based on CA Markov simulation was 1239.67 km2, which slightly exceeded the planned construction land target (1201.65 km2). When the dynamic adjustment was done by superimposing the ecological sensitivity evaluation results with the expansion simulation results, the adjusted construction land scale of Nanchang City was 1193.15 km2, which met the planned requirement. Consideration of the coordination of protection and development could not only protect the ecological space, but also help to guide the orderly growth of urban space and ensure the healthy development of urban space, and thus was an important way to achieve a win-win situation between rational urban development and ecological protection.

Up-regulation of VANGL1 by IGF2BPs and miR-29b-3p attenuates the detrimental effect of irradiation on lung adenocarcinoma.

Accumulating evidence suggests that radiation treatment causes an adaptive response of lung adenocarcinoma (LUAD), which in turn attenuates the lethal effect of the irradiation. Previous microarray assays manifested the change of gene expression profile after irradiation. Bioinformatics analysis of the significantly changed genes revealed that VANGL1 may notably influence the effect of radiation on LUAD. To determine the role of VANGL1, this study knocked down or overexpressed VANGL1 in LUAD. M6A level of VANGL1 mRNA was determined by M6A-IP-qPCR assay. Irradiation caused the up-regulation of VANGL1 with the increase of VANGL1 m6A level. Depletion of m6A readers, IGF2BP2/3, undermined VANGL1 mRNA stability and expression upon irradiation. miR-29b-3p expression was decreased by irradiation, however VANGL1 is a target of miR-29b-3p which was identified by Luciferase report assay. The reduction of miR-29b-3p inhibited the degradation of VANGL1 mRNA. Knockdown of VANGL1 enhanced the detrimental effect of irradiation on LUAD, as indicated by more severe DNA damage and increased percentage of apoptotic cells. Immunocoprecipitation revealed the interaction between VANGL1 with BRAF. VANGL1 increased BRAF probably through suppressing the protein degradation, which led to the increase of BRAF downstream effectors, TP53BP1 and RAD51. These effectors are involved in DNA repair after the damage. In summary, irradiation caused the up-regulation of VANGL1, which, in turn, mitigated the detrimental effect of irradiation on LUAD by protecting DNA from damage probably through activating BRAF/TP53BP1/RAD51 cascades. Increased m6A level of VANGL1 and reduced miR-29b-3p took the responsibility of VANGL1 overexpression upon irradiation.