m6A modification of lncRNA PHKA1-AS1 enhances Actinin Alpha 4 stability and promotes non-small cell lung cancer metastasis.

Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non-small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1-AS1) in the progression of NSCLC were explored. The increased level of N6-methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1-AS1. Subsequently, high-expressed PHKA1-AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1-AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1-AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1-AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.

Altered functional connectivity of the nucleus tractus solitarii in patients with chronic cough after lung surgery: an rs-fMRI study.

BACKGROUND: To explore the altered functional connectivity (FC) of the nucleus tractus solitarii (NTS) in patients with chronic cough after lung surgery using resting-state functional magnetic resonance imaging (rs-fMRI), and the association between abnormal FC and clinical scale scores. METHODS: A total of 22 patients with chronic cough after lung surgery and 22 healthy controls were included. Visual analog scale (VAS), Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC), and Hamilton anxiety rating scale (HAMA) scores were assessed, and rs-fMRI data were collected. The FC analysis was performed using the NTS as the seed point, and FC values with all voxels in the whole brain were calculated. A two-sample t-test was used to compare FC differences between the two groups. The FC values of brain regions with differences were extracted and correlated with clinical scale scores. RESULTS: In comparison to healthy controls, FC values in the NTS and anterior cingulate cortex(ACC) were reduced in patients with chronic cough after lung surgery (GRF correction, p-voxel < 0.005, p-cluster < 0.05) which were positively correlated with LCQ-MC scores (r = 0.534, p = 0.011), but with VAS (r = -0.500, p = 0.018), HAMA (r = -0.713, p < 0.001) scores were negatively correlated. CONCLUSIONS: Reduced FC of the NTS with ACC may be associated with cough hypersensitivity and may contribute to anxiety in patients with chronic cough after lung surgery.

Mechanism of electroacupuncture at acupoints of the lung meridian through PKA/PKC regulation of TRPV1 in chronic cough after lung surgery in guinea pigs.

Background: Acupuncture has achieved good results in the treatment of cough, asthma, chronic obstructive pulmonary disease (COPD) and other lung diseases, but the mechanism associated with acupuncture in the treatment of chronic cough induced by lung surgery is unknown. We investigated whether acupuncture therapy could improve the symptoms of chronic cough after lung surgery through cyclic-AMp dependent protein kinase A (PKA)/cyclic-AMp dependent protein kinase C (PKC) regulation of the transient receptor potential vanilloid-1 (TRPV1) signaling pathway. Methods: The guinea pigs were divided into 5 groups: the Sham operation Group (Sham), the Model Group (Model), the Electroacupuncture + Model Group (EA + M), the H89 + Model Group (H89 + M) and the Go6983 + Model Group (Go6983 + M). The effect of treatment was determined by measuring cough symptoms (number of coughs/cough incubation period) as the outcome criterion. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and blood were determined by enzyme-linked immunosorbent assays (ELISA). Lung tissue was stained with hematoxylin and eosin (H&E). The expression of p-PKA, p-PKC and p-TRPV1 proteins was measured by Western blotting. The mRNA levels of TRPV1, Substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin-1R (NK1R) were measured by real-time polymerase chain reaction (RT-PCR). Results: Acupuncture significantly reduced the cough frequency and prolonged the cough latency of chronic cough in guinea pigs after lung surgery. In addition, acupuncture reduced the damage to lung tissue. The levels of inflammatory cytokines decreased in all treatment groups, the expression levels of p-PKA, p-PKC and p-TRPV1 were significantly inhibited and the mRNA levels of TRPV1, SP, CGRP and NK1R decreased significantly after acupuncture treatment. Conclusions: Acupuncture therapy ameliorated chronic cough in guinea pigs after lung surgery by regulating the TRPV1 signaling pathway via PKA/PKC. Our results showed that acupuncture may be an effective treatment of chronic cough after lung surgery, and also clarified the potential mechanism, which provides a theoretical basis for the clinical treatment of patients with chronic cough after lung surgery.

Comparison of automated 4D-MSPECT and visual analysis for evaluating myocardial perfusion in coronary artery disease.

The aim of this study was to assess the reproducibility and diagnostic performance for coronary artery disease (CAD) of an automated software package, 4D-MSPECT, and compare the results with a visual approach. We enrolled 60 patients without previously known CAD, who underwent dual-isotope rest Tl-201/stress Tc-99m sestamibi myocardial perfusion imaging and subsequent coronary angiography within 3 months. The automated summed stress score (A-SSS), summed rest score (A-SRS) and summed difference score (A-SDS) were obtained using a 17-segment five-point scale model with 4D-MSPECT. For intraobserver and interobserver variability assessment, automated scoring was done by a nuclear medicine physician twice and by a nuclear medicine technologist. The visual summed stress score (V-SSS), summed rest score (V-SRS), and summed difference score (V-SDS) were obtained by consensus of two nuclear medicine physicians. The intraobserver and interobserver agreements of automated segmental scores were excellent. The intraobserver and interobserver summed scores also correlated well. Agreements between visual and automated segmental scores were moderate (weighted kappa of 0.55 and 0.50 for stress and rest images, respectively). Correlations between automated and visual summed scores were high, with correlation coefficients of 0.89, 0.85 and 0.82 for SSS, SRS and SDS, respectively (all p < 0.001). The receiver operating characteristic area under the curve for diagnosis of CAD by V-SSS, V-SDS, A-SSS and A-SDS were 0.78 +/- 0.06, 0.87 +/- 0.05, 0.84 +/- 0.05 and 0.90 +/- 0.04, respectively. A-SDS had better diagnostic performance than A-SSS and V-SSS (p = 0.043 and p = 0.032, respectively), whereas there was no statistically significant difference between A-SDS and V-SDS (p = 0.56). Using V-SDS > or = 2 as a diagnostic threshold, the sensitivity, specificity, and accuracy for CAD were 83.7%, 76.5% and 81.7%, respectively. Using A-SDS > or = 3 as a diagnostic threshold, the sensitivity, specificity, and accuracy for CAD were 79.1%, 82.4% and 80.0%, respectively. In conclusion, the reproducibility of automated semiquantitative analysis with 4D-MSPECT was excellent. The diagnostic performance of automated semiquantitative analysis with 4D-MSPECT was comparable with the visual approach.

Novel Compliance Index derived from digital volume pulse associated with risk factors and exercise capacity in patients undergoing treadmill exercise tests.

OBJECTIVE: Although large-artery stiffness is a well-known independent factor for cardiovascular risk, the importance of small-artery stiffness is not well elucidated. We have developed a novel Compliance Index as a marker of small-artery stiffness. This study aimed to determine the clinical significance of this index by evaluating 140 patients without left ventricular dysfunction referred for treadmill exercise tests. METHODS: Immediately after a 10-min rest period before the test, the pulse wave velocity and Compliance Index were measured. The patients were then given a symptom-limited treadmill test using Bruce's protocol. Our dual-channel photoplethysmography system automatically measured the area under the curve of each digital volume pulse, which represented the volume change in the finger with each heart beat. The Compliance Index was calculated by dividing the area under the curve of finger digital volume pulse by pulse pressure. RESULTS: The Compliance Index was significantly correlated with pulse wave velocity (r=-0.254, P=0.002), systolic blood pressure (r=-0.606, P<0.001), and diastolic blood pressure (r=-0.323, P<0.001). It was lower in males (3.3+/-1.4 versus 4.8+/-2.4 units, P<0.001), in hypertensive patients (3.2+/-1.5 versus 4.4+/-2.2 units, P<0.001), and in smokers (3.0+/-1.5 versus 4.1+/-2.1 units, P=0.006). CONCLUSIONS: The Compliance Index was lower in patients with risk factors and was associated with poor exercise capacity. This index may be clinically useful for evaluating arterial stiffness.

Increased expression of microRNA-150 is associated with poor prognosis in non-small cell lung cancer.

OBJECTIVES: The aim was to evaluate the clinical significance and prognostic value of tissue miR-150 expression in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Quantitative real-time PCR was used to analyze the expression of miR-150. Overall survival (OS) was estimated using the Kaplan-Meier method, and the differences in survival were compared using the log-rank test. A Cox proportional hazards model was used for multivariate analysis. RESULTS: Mean miR-150 levels were significantly higher in NSCLC tissues compared with matched non-cancerous tissues (4.07 ± 2.33 vs. 1.00 ± 0.46, P < 0.0001). The level of miR-150 in NSCLC was strongly correlated with lymph node metastasis (P = 0.04), distant metastasis (P = 0.01) and clinical TNM stage (P = 0.02). Kaplan-Meier analysis showed that the cumulative 5-year OS rate was 40.8% in the high expression group, and 69.2% in the low expression group. The log-rank test showed that the OS rate of patients with high miR-150 expression was significantly poorer than that of the remaining cases (P = 0.007). CONCLUSION: Our data indicated that overexpression of miR-150 in NSCLC tissues has prognostic value.

Application of Aidi injection (艾迪注射液) in the bronchial artery infused neo-adjuvant chemotherapy for stage III A non-small cell lung cancer before surgical operation.

OBJECTIVE: To study the effect of Aidi Injection (艾迪注射液,ADI) applied in the bronchial artery, applied in the bronchial artery infused (BAI) neo-adjuvant chemotherapy for stage III A non-small cell lung cancer (NSCLC) before surgical operation. METHODS: The 60 patients with NSCLC stage III A underwent two courses BAI chemotherapy before tumor incision were assigned to two groups, the treatment and the control groups, using a random number table, 30 in each group. ADI (100 mL) was given to the patients in the treatment group by adding into 500 mL of 5% glucose injection for intravenous dripping once daily, starting from 3 days before each course of chemotherapy, and it lasted for 14 successive days, so a total of 28 days of administration was completed. The therapeutic effectiveness and the adverse reaction that occurred were observed, and the levels of T-lymphocyte subsets, natural killer cell activity, and interleukin-2 in peripheral blood were measured before and after the treatment. RESULTS: The effective rate in the treatment group was higher than that in the control group (70.0% vs. 56.7%, P<0.05). Moreover, as compared with the control group, the adverse reaction that occurred in the treatment group was less and mild, especially in terms of bone marrow suppression and liver function damage (P<0.05). Cellular immune function was suppressed in NSCLC patients, but after treatment, it ameliorated significantly in the treatment group, showing significant difference as compared with that in the control group (P<0.05). CONCLUSION: ADI was an ideal auxiliary drug for the patients in stage III A NSCLC received BAI neo-chemotherapy before surgical operation; it could enhance the effectiveness of chemotherapy, ameliorate the adverse reaction and elevate patients' cellular immune function; therefore, it is worthy for spreading in clinical practice.

[Effect of osmotic pressure on nitrification].

The effect of osmotic pressure on nitrification was investigated in the internal-loop air-lift nitrifying reactor. When influent ammonia concentration is kept at 420mg x L(-1) and influent osmotic pressure is increased from 4.3 to 18.8 x 10(5) Pa, the ammonia conversion of the nitrifying bioreactor is maintained between 93% and 100%. After influent osmotic pressure is further increased to 19.2 x 10(5)Pa, the ammonia conversion goes down to 69.2%. The influence of osmotic pressure on nitrification takes place without any alarm and the critical osmotic pressure is between 18.8 x 10(5) and 19.2 x 10(5) Pa. During osmotic stress, the nitrifying bacterial populations in the activated sludge become simplified, the cell size becomes smaller, the inner membrane becomes less and some unknown inclusion particles are formed. The cell structure is restored as soon as the osmotic pressure is removed. Addition of potassium is able to relieve the effect of osmotic pressure on nitrification. The nitrifying activity of the activated sludge is stimulated by the osmotic stress, and the specific ammonia conversion is increased from 0.083 kg x kg(-1) x d(-1) to 0.509 kg x kg(-1) x d(-1) and 2.569 kg x kg(-1) x d(-1), respectively.

Roles of DegP in prevention of protein misfolding in the periplasm upon overexpression of penicillin acylase in Escherichia coli.

Enhancement of the production of soluble recombinant penicillin acylase in Escherichia coli via coexpression of a periplasmic protease/chaperone, DegP, was demonstrated. Coexpression of DegP resulted in a shift of in vivo penicillin acylase (PAC) synthesis flux from the nonproductive pathway to the productive one when pac was overexpressed. The number of inclusion bodies, which consist primarily of protein aggregates of PAC precursors in the periplasm, was highly reduced, and the specific PAC activity was highly increased. DegP was a heat shock protein induced in response to pac overexpression, suggesting that the protein could possibly suppress the physiological toxicity caused by pac overexpression. Coexpression of DegP(S210A), a DegP mutant without protease activity but retaining chaperone activity, could not suppress the physiological toxicity, suggesting that DegP protease activity was primarily responsible for the suppression, possibly by degradation of abnormal proteins when pac was overexpressed. However, a shortage of periplasmic protease activity was not the only reason for the deterioration in culture performance upon pac overexpression because coexpression of a DegP-homologous periplasmic protease, DegQ or DegS, could not suppress the physiological toxicity. The chaperone activity of DegP is proposed to be another possible factor contributing to the suppression.