Response of microbial community and biological nitrogen removal to the accumulation of nonylphenol in sequencing batch reactor.

The widespread existence of nonylphenol in the environmental rendered from wastewater discharge has become a growing concern for its endocrine disrupting effects on microorganisms. In this study, the performance of nitrifying and denitrifying microbial community in a sequencing batch reactor (SBR) was investigated under different nonylphenol concentrations. The SBR was shown to be less effective in nitrogen removal at higher concentration of nonylphenol. Proteobacteria, Bacteroidetes, and Actinobacteria were characterized by 454 pyrosequencing as the dominant bacteria, nitrogen removal functional bacteria in these three phyla were inhibited by nonylphenol, and Proteobacteria and Actinobacteria were more sensitive to nonylphenol. With the accumulation of nonylphenol, the population of the most abundant denitrifying bacteria (Thauera spp.) and nitrifying bacteria (Nitrosomonas spp.) significantly reduced. Microbial diversity increased due to nonylphenol perturbation, which is indicated by the changes in microbial alpha diversity. Principal component analysis showed high similarity between microbial community in low and high concentration of nonylphenol, and the core genera involved in nitrogen removal had a low correlation with other genera shown in co-occurrence network. Moreover, linear discriminant analysis effect size analysis revealed intergroup differences in microorganisms. The mechanism of accumulated NP on the diversity and metabolism of the microbial community was examined. This paper established a theoretical foundation for the treatment of NP-containing wastewater and provided hints for further research about NP impact on biological nitrogen removal. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-023-04825-9.

Bacterial antibiotic resistance among cancer inpatients in China: 2016-20.

BACKGROUND: The incidence of infections among cancer patients is as high as 23.2-33.2% in China. However, the lack of information and data on the number of antibiotics used by cancer patients is an obstacle to implementing antibiotic management plans. AIM: This study aimed to investigate bacterial infections and antibiotic resistance in Chinese cancer patients to provide a reference for the rational use of antibiotics. DESIGN: This was a 5-year retrospective study on the antibiotic resistance of cancer patients. METHODS: In this 5-year surveillance study, we collected bacterial and antibiotic resistance data from 20 provincial cancer diagnosis and treatment centers and three specialized cancer hospitals in China. We analyzed the resistance of common bacteria to antibiotics, compared to common clinical drug-resistant bacteria, evaluated the evolution of critical drug-resistant bacteria and conducted data analysis. FINDINGS: Between 2016 and 2020, 216 219 bacterial strains were clinically isolated. The resistance trend of Escherichia coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, cefotaxime, piperacillin/tazobactam and imipenem was relatively stable and did not significantly increase over time. The resistance of Pseudomonas aeruginosa strains to all antibiotics tested, including imipenem and meropenem, decreased over time. In contrast, the resistance of Acinetobacter baumannii strains to carbapenems increased from 4.7% to 14.7%. Methicillin-resistant Staphylococcus aureus (MRSA) significantly decreased from 65.2% in 2016 to 48.9% in 2020. CONCLUSIONS: The bacterial prevalence and antibiotic resistance rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, S. aureus and MRSA were significantly lower than the national average.

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer.

BACKGROUND: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. PATIENTS AND METHODS: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. RESULTS: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. CONCLUSION: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.

[Analysis of prognostic factors of pediatric kidney transplantation].

Objective: To evaluate the short-and mid-term efficacy of pediatric kidney transplantation and the risk factors for kidney graft and recipient. Methods: The baseline data and postoperative complications of pediatric donors and recipients of 284 kidney transplants were retrospectively analyzed in the Department of Kidney Transplantation in the First Affiliated Hospital of Zhengzhou University from August 2010 to May 2021 and all subjects were followed up until December 31, 2021. According to the survival status of donors and recipients, they were divided into the graft-loss group and the graft-survival group, and the recipient death group and survival group, respectively. Univariate comparison between groups was performed by Log-rank test, and Cox proportional risk model was used to explore the independent risk factors for the graft and recipient survival. Results: Among the 284 children recipients, 184 cases (64.8%) were male and 100 cases(35.2%) were female, and 19 cases (6.7%) were living relative donor renal transplantation, 19 cases (6.7%) were preemptive transplantation, and 8 cases were secondary transplantation. The age of 284 recipients at the time of transplantation was 13.0 (9.0, 15.0) years, among whom 29 cases aged 0-6 years, 96 cases aged 7-11 years old, and 159 cases aged 12-18 years. The 1, 3, and 5 year survival rates were 92.3%, 88.9% and 84.8% for the kidney grafts, and were 97.1%, 95.6% and 94.4% for the recipients, respectively. Multivariate analysis showed postoperative acute rejection (HR=3.14, 95%CI 1.38-7.15, P=0.006) and perioperative vascular complications (HR=4.73, 95%CI 2.03-11.06, P<0.001) were independent risk factors for the survival of kidney graft. Postoperative infection (HR=14.23, 95%CI 3.45-58.72, P<0.001) was an independent risk factor for the postoperative mortality of recipients. Conclusions: Pediatric kidney transplantation shows a good short-and mid-term prognosis. Postoperative acute rejection and perioperative vascular complications are the risk factors for the survival of kidney graft, and postoperative infection is the risk factor affecting the survival of recipient.

[Benefits and risks of prolonged dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent in patients with stable coronary artery disease and diabetes].

Objective: To compare the efficacy and safety of prolonged dual antiplatelet therapy (DAPT>1 year) in patients with stable coronary artery disease (CAD) and diabetes who were event-free at 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) in a large and contemporary PCI registry. Methods: A total of 1 661 eligible patients were selected from the Fuwai PCI Registry, of which 1 193 received DAPT>1 year and 468 received DAPT ≤1 year. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding, MACCE was defined as a composite of all-cause death, myocardial infarction or stroke. Multivariate Cox regression analysis and inverse probability of treatment weighting (IPTW) Cox regression analysis were performed. Results: After a median follow-up of 2.5 years, patients who received DAPT>1 year were associated with lower risks of MACCE (1.4% vs. 3.2%; hazard ratio (HR) 0.412, 95% confidence interval (CI) 0.205-0.827) compared with DAPT ≤1 year, which was primarily caused by the lower all-cause mortality (0.1% vs. 2.6%; HR 0.031, 95%CI 0.004-0.236). Risks of cardiac death (0.1% vs. 1.5%; HR 0.051, 95%CI 0.006-0.416) and definite/probable ST (0.3% vs. 1.1%; HR 0.218, 95%CI 0.052-0.917) were also lower in patients received DAPT>1 year than those received DAPT ≤ 1 year. No difference was found between the two groups in terms of BARC type 2, 3, or 5 bleeding (5.3% vs. 4.1%; HR 1.088, 95%CI 0.650-1.821). Conclusions: In patients with stable CAD and diabetes who were event-free at 1 year after PCI with DES, prolonged DAPT (>1 year) provides a substantial reduction in ischemic cardiovascular events, including MACCE, all-cause mortality, cardiac mortality, and definite/probable ST, without increasing the clinically relevant bleeding risk compared with ≤ 1-year DAPT. Further well-designed, large-scale randomized trials are needed to verify the beneficial effect of prolonged DAPT in this population.

Current census of oncology critical care medicine in China.

OBJECTIVE: The purposes of this survey were to show the current situation of oncology critical care medicine in China by questionnaire, to understand the resource distribution of oncology critical care medicine and to analyze and evaluate the existing resources and reserve capacity of oncology critical care medicine in China. METHODS: We conducted the survey mainly in the form of an online questionnaire. The Committee of Cancer Critical Care Medicine of the Chinese Anticancer Association (CACA) initiated the survey on 1 November 2017, and 36 member hospitals nationwide participated in the survey. The questionnaire included 10 items: investigator information, hospital information, general information of oncology critical care department, staffing of oncology critical care department, management in oncology critical care department, technical skills in oncology critical care department, patient source in oncology critical care department, equipment configuration in oncology critical care department, special skills in oncology critical care department and summary of the information. RESULTS: The survey results included information from 28 member units, all of which were tertiary hospitals, distributed in 20 provinces and 4 direct-controlled municipalities. The results are as follows. (i) The total ratio of beds in the oncology critical care department to hospital beds was 1.06%, and the average number of beds in the oncology critical care department was 16.36. (ii) The ratio of physicians in the oncology critical care department to beds was ∼0.62:1, and the ratio of nurses to beds was ∼1.98:1. (iii) According to the census of the population and gross domestic product (GDP) of different regions conducted by the State Statistics Bureau in 2017, the ratio of beds in the oncology critical care department for tumor patients to the population was 4.55 beds per 10 million people, and the ratio of beds in the oncology critical care department to GDP was 8.00 beds per RMB 100 billion, on average. (iv) According to the requirements of the guidelines for the development and management of critical care medicine in China, the facilities in departments of oncology critical care medicine meet the requirements, and the technical skills of medical staff are competent. CONCLUSION: The development of oncology critical care in China is becoming better, but there is still a certain gap compared with the intensive care unit standards in China and the average level of the nationwide. The development of oncology critical care medicine is urgent.

Dewetting characteristics of contact lenses coated with wetting agents.

HYPOTHESIS: Although wetting agents have been developed to limit tear film dewetting over contact lenses, systematic analyses correlating wetting agent properties to mechanisms of the tear film destabilization are not readily available. Clarifying destabilization characteristics across key physio-chemical variables will provide a rational basis for identifying optimal wetting agents. EXPERIMENTS: We employ an in-house, in vitro platform to comprehensively evaluate drainage and dewetting dynamics of five wetting agents across seventeen different formulations and two model tear film solutions. We consider the film thickness evolution, film thickness at breakup, dewetted front propagation, and develop correlations to contact angle to compare the samples. FINDINGS: Zwitterionic wetting agents effectively stabilize the tear film by reducing the film thickness at the onset of dewetting, and delaying the propagation of dewetted regions across the lens. Furthermore, tuning wetting agent surface concentrations and utilizing binary mixtures of wetting agents can enhance wetting characteristics. Finally, despite disparities in wetting agent molecular properties, the time to dewet 50% of the lens scales linearly with the product of the receding contact angle and contact angle hysteresis. Hence, we fundamentally establish the importance of minimizing the absolute contact angle and contact angle hysteresis for effective wetting performance.

Longitudinal investigations of anatomical and morphological development of the gastrointestinal tract in goats from colostrum to postweaning.

The digestive tract development in goat kids around weaning is vital to the establishment of digestion and absorption function, growth, and health of adults. The objective was to explore the effects of age and solid feed on the anatomical and morphological development of the gastrointestinal tract of Laiwu Black goat kids. Forty-eight female Laiwu Black goats at 8 ages (1, 7, 14, 28, 42, 56, 70, and 84 d; 6 goats per group) were selected and killed for anatomical and morphological analysis. The goats experienced the following 4 diet phases: maternal colostrum (MC; d 1, d 7), maternal milk (MM; d 14, d 28), maternal milk plus solid diet (MMSD; d 42, d 56) and only solid diet (OSD; d 70, d 84). The body and carcass weights were not significantly changed during MC and MM phases but changed during the MMSD phase. The absolute growth of body and carcass weights were higher in the MMSD phase than in MM phase. In addition, the dressing percentage was the highest in the MMSD phase. The body size indices evolved progressively and increased over time. The percentage of internal and external organs to body weight decreased over time, whereas the percentage to complex stomach percentage increased. The rumen and omasum weight experienced synchronous absolute growth over time, especially in the OSD phase. In contrast, the absolute growth of the reticulum and abomasum was the highest in MMSD and MC phases, respectively. After weaning, the goats showed the highest papillae height, lamina propria, muscle layer thickness, and epithelial thickness. The OSD phase showed the highest colonic mucosa thickness, ileal villus height, and ileal muscle layer thickness. The crypt depth was higher in the MMSD phase than in the MM phase. Moreover, the crypt depth and muscle layer thickness of jejunum increased over time. Furthermore, duodenal crypt depth, muscle layer thickness, and epithelial thickness increased in the OSD phase compared with other stages. In conclusion, the histological investigation supports the improvement of the morphological development of the digestive tract and the growth performance in the solid feed phase. It is recommended to add solid food as early as 4 wk old.

Effect of Polyphenols on Cognitive Function: Evidence from Population-Based Studies and Clinical Trials.

Due to progressive population aging, a new dementia case occurs at every 3 seconds, placing a heavy burden of disease. Identifying potential risk or preventive factors is emphasized owing to a lack of effective treatment for dementia. There has been emerging evidence on the link of certain dietary components, particularly polyphenols, to brain wellness and cognitive outcomes. Findings from animal and in vitro studies appear more consistent and conclusive. However, such an association has not been investigated in depth in human beings. In this review, we examined studies on the effect of dietary polyphenols (including flavonoids, curcumin, and resveratrol) on cognitive function. Intervention in early stages of dementia/Alzheimer's disease might be a target to slow down age-related cognitive decline before disease onset. We summarized 28 epidemiological studies (8 cross-sectional and 20 cohort studies) and 55 trials in this review. Preliminary evidence from epidemiological data provides the necessity for intervention trials, even though the measures of polyphenol intake tend to be less precise. Clinical trials are in favor of the role of some polyphenols in benefiting specific domains of cognition. This review also describes the divergence of results and current limitations of research in this field.

Effects of IL-1ß on hippocampus cell apoptosis and learning ability of vascular dementia rats.

The article "Effects of IL-1ß on hippocampus cell apoptosis and learning ability of vascular dementia rats, by L.-L. Guo, D.-S. Wang, Y.-Y. Xu, K.-G. Cui, published in Eur Rev Med Pharmacol Sci 2018; 22 (18): 6042-6048-DOI: 10.26355/eurrev_201809_15941-PMID: 30280789" has been withdrawn from the authors due to  substantial deficiency in the experimental design. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15941.

[Significance of microRNA 216a, 324-5p and 29a expression in peripheral blood in patients with acute pancreatitis and their correlation with liver injury].

Objective: To investigate the significance of microRNA (miR)-216a, miR-324-5p, miR-29a expression in peripheral blood in patients with acute pancreatitis (AP) and their correlation with liver injury. Methods: It was a case-control study design. To select 130 AP patients admitted from June 2017 to May 2019 in the First People's Hospital of Shangqiu, and the patients were divided into mild AP group (MAP group) and moderately severe AP group (SAP group) according to the disease severity, or 54 patients in the liver injury group (20 were MAP and 34 were SAP) and 76 in the non-liver injury group(all were MAP) according to liver injury. And another 40 healthy volunteers were selected as the healthy group. The expressions of miR-216a, miR-324-5p and miR-29a in peripheral blood of MAP group, SAP group, healthy group and liver injury group, non-liver injury group were compared, and the correlation between the miRNA levels and clinical indexes was analyzed. The predictive value of miRNA levels in peripheral blood for AP complicated with liver injury was analyzed by receiver operating characteristic (ROC) curve. Results: The levels of miR-216a and miR-29a in MAP group and SAP group were higher than those in healthy group, and the level of miR-324-5p was lower than that in healthy group (all P<0.01). The levels of miR-216a and miR-29a in SAP group were higher than those in MAP group, and the level of miR-324-5p was lower than that in healthy group (all P<0.01). Balthazar CT Score, acute physiology and chronic health evaluations (APACHE Ⅱ) score, C-reactive protein level, length of hospital stay were positively correlated with the levels of miR-216a and miR-29a in peripheral blood (all P<0.05), and negatively correlated with the levels of miR-324-5p (P<0.05). The levels of miR-216a and miR-29a in the peripheral blood in the liver injury group were higher than those in the non-liver injury group, and they were higher inSAP patients than those in MAP patients in the liver injury group (all P<0.05). The level of miR-324-5p in the peripheral blood in the liver injury group was lower than that in the non-liver injury group, and it was lower in SAP patients than that in MAP patientsin the liver injury group (all P<0.05). The area under ROC curve of miR-216a, miR-324-5p, and miR-29a in peripheral blood to predicate the AP complicated with liver damage was 0.694, 0.750 and 0.814, respectively. Conclusions: The levels of miR-216a and miR-29a increase in peripheral blood and the level of miR-324-5p decreases in patients with AP, and they are closely related to Balthazar CT score, APACHEⅡ score, C-reactive protein and length of hospital stay. The levels of miR-216a, miR-324-5p, miR-29a has certain predictive value for AP with liver injury, of which miR-29a has the highest predictive value.

JTE-013 supplementation improves erectile dysfunction in rats with streptozotocin-induced type â diabetes through the inhibition of the rho-kinase pathway, fibrosis, and apoptosis.

BACKGROUND: Erectile dysfunction (ED) is a common complication in patients with diabetes mellitus (DM) that severely affects the patients' quality of life. However, the effectiveness of oral phosphodiesterase type 5 inhibitors in these patients is poor. Sphingosine-1-phosphate (S1P) and S1P receptor 2 (S1PR2) are important factors regulating the Rho-kinase pathway, and understanding these factors may provide ideas for new therapeutic strategies for ED. OBJECTIVES: To investigate whether the S1PR2 receptor antagonist JTE-013 could improve DM-induced ED (DMED) in rats and to explore the potential mechanisms. MATERIALS AND METHODS: We used 50 male Sprague Dawley rats (8 weeks old) for this experiment. Type Ⅰ DM was induced in forty-two rats via streptozotocin administration; the rest of the rats served as controls. Eight weeks after DM induction, rats with ED were selected via an apomorphine test. Eight of them were injected intraperitoneally with JTE-013 each day for 4 weeks. The rest were fed under the same conditions for 4 weeks. Erectile function was measured by cavernous nerve electrostimulation. The expression levels of related signaling pathways were evaluated using Western blotting, real-time PCR, and immunohistochemistry. RESULTS: Erectile function was significantly impaired in the DMED group compared with the control group and was partially improved in the DMED + JTE-013 group. The expression of S1PR2 and the activity of the RhoA/ROCK/phospho-myosin phosphatase target subunit 1 (p-MYPT1) pathway proteins were higher in the DMED group than in the other two groups, and JTE-013 treatment significantly reduced the expression/activity of these proteins. Furthermore, the DMED group showed severe corporal fibrosis, a higher apoptotic index and increased activity in the TGF-ß1/LIMK2/Cofilin pathway compared with the control group. JTE-013 supplementation significantly ameliorated these pathological changes. DISCUSSION AND CONCLUSION: JTE-013 supplementation partially improved erectile function in rats with DMED, likely by inhibiting smooth muscle contraction, corporal fibrosis, and apoptosis.

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib.

BACKGROUND: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. PATIENTS AND METHODS: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. RESULTS: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). CONCLUSIONS: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. CLINCALTRIALS.GOV NUMBER: NCT02184195.

[Mechanism of androgen in improving erectile dysfunction in castrated rats by regulating androgen receptor/vascular endothelial growth factor].

Objective: To explore the mechanism of androgen in improving erectile dysfunction in castrated rats. Methods: Forty 8-week-old male Sprague-Dawley (SD) rats were randomly divided into 4 groups:normal control group (Group A); castration group (Group B, in which rats were castrated); intervention groups (group C and D), in which rats were treated with different concentrations of testosterone undecanoate orally every day at 10 mg/kg (low dose) and 20 mg/kg (high dose), respectively after being castrated. Animals in group A and B were given 0.9% NS instead. After 8-week treatment, the level of serum testosterone, intra cavernous pressure (ICP) and mean arterial pressure (MAP) were detected, and the expression of androgen receptor (AR)and vascular endothelial growth factor (VEGF) were detected in the penis by Immunohistochemistry and Western blot. Results: The level of serum testosterone was significantly lower in group B [(1.3±0.6) nmol/L] than in group A [(17.1±1.5) nmol/L] (P<0.05).After testosterone supplementation, serum testosterone levels in group C [(8.7±1.2) nmol/L] and group D [(15.5±1.6) nmol/L] were higher than that in group B (all P<0.05). Max ICP/MAP of group C and D were higher than that in group B (all P<0.05). Immunohistochemistry and Western blot showed that the expression levels of AR and VEGF in group B were significantly lower than those in group A, C and D, and group D > group C (all P<0.05). Conclusion: Androgen replacement therapy with testosterone undecanoate can improve the erectile function of castrated rats by protecting the integrity of endothelial cells through AR/VEGF pathway.

[Association between resting heart rate trajectory pattern and risk of cardiovascular and cerebrovascular diseases].

Objective: To examine whether the long-term resting heart rate (RHR) pattern can predict the risk of cardiovascular and cerebrovascular diseases (CVDs). Methods: This prospective cohort study included 63 040 participants who took part in the health examination in 2006 and one of the health examinations on 2008 or 2010 and were free of myocardial infarction, stroke, arrhythmia, cancer and not treated with ß-recepter blocker. The outcomes were the first occurrence of myocardial infarction and stroke during the follow up ended on December 31, 2015. RHRs were measured in 2006, 2008, and 2010. We used latent mixture modeling SAS Proc procedure to identify RHR trajectories. We identified 4 distinct RHR trajectory patterns based on the data derived from 2006 and on the pattern change during 2006 to 2010 (low-stable, moderate-stable, moderate-increasing, elevated-decreasing). Collected the general clinical data of the patients. Cox regression model was used to determine the association between RHR trajectory patterns and the risk of CVDs during follow up. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling. Results: There were statistical significance among the 4 distinct RHR trajectory patterns on the following variables: age, gender, smoking status, drinking status, physical activity, education status, history of use antihypertensive drugs, history of hypertension,history of diabetes, body mass index, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, and the level of high-sensitivity C-reactive protein (all P<0.01). The moderate-increasing pattern experienced the highest risk of developing stroke and CVDs among all 4 patterns. The cumulative incidence of cerebral infarction, cerebral hemorrhage and CVDs in the order of low-stable trajectory, moderate-stable trajectory and moderate-increasing trajectory. The cumulative incidences of cerebral infarction, cerebral hemorrhage and CVDs in elevated-decreasing trajectory group were significantly lower than those in moderate-increasing trajectory group, but higher than those in moderate-stable trajectory group. Compared to the low-stable pattern, adjusted HR was 1.3 (95%CI 1.0-1.6) for the moderate-increasing pattern after adjustment for potential confounders. Conclusion: Our study finds that individuals with moderate-increasing RHR trajectory pattern are associated with higher risk of cardiovascular and CVDs.

MiR-483 suppresses cell proliferation and promotes cell apoptosis by targeting SOX3 in breast cancer.

OBJECTIVE: To explore the mechanism underlying the effect of microRNA-483 (miR-483) in the progression of breast cancer (BC). PATIENTS AND METHODS: MiR-483 expression was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in both BC cells and tissue samples. The associations between miR-483 expression level and patients' overall survival rate were explored. Furthermore, cell proliferation assay and cell apoptosis assay were conducted, respectively. In addition, Western blot analysis and Luciferase assay were performed to explore the underlying mechanism. RESULTS: The expression level of miR-483 was significantly decreased in tumor samples compared to that in adjacent tissues, which was also associated with patients' overall survival time. Moreover, cell growth was promoted, and cell apoptosis was inhibited after miR-483 was knocked down in vitro. Furthermore, SOX3 acted as a direct target of miR-483, and the expression of SOX3 was negatively correlated with the expression of miR-483 in tumor tissues. CONCLUSIONS: These results suggested that miR-483 could suppress BC cell proliferation and promote BC cell apoptosis via targeting SOX3, which might be a potential therapeutic target in BC.

Effects of dietary protein restriction followed by realimentation on growth performance and liver transcriptome alterations of lamb.

The present study aimed to investigate the compensatory effect of early protein restriction followed by a realimentation on growth performance of lamb and to explore the transcriptomic changes in liver. Thirty-two lambs with an initial birth weight of 2.3 ± 0.20 kg that were weaned on day 15 were randomly divided into two groups. The lambs were fed a basal diet with normal protein level (NPL, protein level in the milk replacer and starter, 25 and 21%, respectively) or low protein level (LPL, protein level in the milk replacer and starter, 19 and 15%, respectively) from 15 to 60 d, after which all lambs consumed the same diet with a normal protein level from 61 to 90 d. Protein restriction led to a significant decrease in average daily gain (ADG), body weight and liver weight (P < 0.05). Transcriptome analysis showed that 302 or 12 differentially expressed genes (DEGs) were identified during the restriction or recovery periods, respectively (P < 0.05). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that DEGs enriched in nutrient metabolism and antioxidant capacity were down-regulated, while vessel development and immunity response-related genes up-regulated. The genes involved in metabolism of tyrosine were still down-regulated in the realimentation phase. Studies in this area indicated the accelerated growth effect of early protein restriction followed by a realimentation on growth performance of lambs and explored the transcriptomics change of liver which can help to develop feeding strategies to optimize the use of feedstuffs and in providing a new perspective for the study of early nutrition and epigenetics in later life.

Effects of IL-1ß on hippocampus cell apoptosis and learning ability of vascular dementia rats.

OBJECTIVE: Vascular dementia (VD) is a type of memory, cognition, and behavior disorder caused by ischemic stroke or hemorrhagic stroke. It is a common pathogenesis of dementia that is only second to Alzheimer's disease. Inflammation plays a key role in VD. Interleukin-1ß (IL-1ß) is a kind of pro-inflammatory cytokine, while its mechanism in VD occurrence and development is still unclear. MATERIALS AND METHODS: The healthy male rats were randomly divided into three groups, including sham group, VD model group (established by bilateral common carotid artery ligation), and IL-1ß group (treated by IL-1ß monoclonal antibody intracerebroventricular injection on based on model group). Rat learning ability was evaluated by Morris water maze assay. IL-1ß expression in brain tissue and peripheral blood was examined by using Real Time-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Hippocampus apoptosis was detected by caspase 3 activity detection kit. B-cell lymphoma-2 (Bcl-2) and p38 mitogen-activated protein kinase (MAPK) protein levels were assessed by Western blot assay. RESULTS: IL-1ß expression was increased, caspase 3 activity was enhanced, Bcl-2 level was declined, and p-P38 phosphorylation was elevated in brain tissue and peripheral blood from VD model group compared to sham group (p<0.05). IL-1ß monoclonal antibody significantly reduced IL-1ß expression, improved learning ability, attenuated caspase 3 activity, increased Bcl-2 level, and declined p-P38 expression in VD rats compared to model group (p<0.05). CONCLUSIONS: IL-1ß can delay VD occurrence and development through the P38-MAPK signaling pathway to regulate cell apoptosis and improve learning ability.

[Problems and suggestions for the application of diagnosis-related groups system in burn surgery].

The diagnostic codes of diagnosis-related groups system used in our country are different from the clinical diagnostic criteria of burns. The author suggests that the diagnostic codes should be improved according to clinical criteria in terms of the total area and depth of burns and inhalation injury, and the diagnosis of burns with related special causes and sites should be added to the clinical criteria.

[The influence of Thymidine Phosphorylase genetic variation on clinical outcomes and safety of colorectal cancer patients received adjuvant chemotherapy after R0 resection].

Objective: To study the association between Thymidine Phosphorylase (TYMP) genetic variation and clinical outcomes and safety of postoperative colorectal cancer (CRC) patients. Methods: A total of 235 patients with colorectal cancer underwent surgical treatment were included in this retrospective analysis. Peripheral blood and the postoperative tissue specimen of the CRC patients were collected for the genotyping of polymorphism and TYMP mRNA expression, respectively. The correlation between polymorphism and clinical outcomes and safety of postoperative CRC patients were analysed. Results: Located in the upstream, 5633C>T was of clinical significance. The prevalence of 5633C>T in TYMP among the CRC patients were as follows: CC genotype 149 cases (63.40%), CT genotype 73 cases (31.06%), TT genotype 13 cases (5.54%), minor allele frequency of 5633C>T is 0.21. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.313). CT genotype and TT genotype patients were merged in the comparison of prognosis. The survival analysis of patients with different genotypes found that the median Overall Survival (OS) of CT/TT genotype and CC genotype were 5.8 and 4.5 year, which was statistically significant (P=0.009). Adjusted in multivariate Cox regression analysis, CT/TT genotype was an independent favorable factor for OS (HR=0.67, P=0.015). Additionally, of the 87 postoperative tissue specimens, the results showed that the expression of TYMP in cancer tissues of the patients with CT or TT genotypes were significantly higher than those of the wild type CC genotype patients (P=0.019). And the safety analysis showed that the incidence of grade 3 hand-foot syndrome among CT/TT genotype patients were higher than that of CC genotype patients (33.72% vs 20.13%, OR=1.68, P=0.021). Conclusion: The polymorphism 5633C>T of TYMP may impact the prognosis of CRC patients received adjuvant chemotherapy by influencing the mRNA expression of TYMP.