lncRNA DLG1-AS1 promotes cervical cancer cell gemcitabine resistance by regulating miR-16-5p/HDGF.

AIM: To investigate the long non-coding RNA DLG1 Antisense RNA 1 (lncRNA DLG1-AS1) mechanism in cervical cancer cells with gemcitabine (GEM) resistance. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect DLG1-AS1, miR-16-5p, and hepatoma-derived growth factor (HDGF) expression in cervical cancer cells. The effects of DLG1-AS1 knockdown on cell viability, proliferation, and apoptosis were investigated in GEM-resistant cervical cancer cells. The binding of DLG1-AS1 with miR-16-5p and of miR-16-5p with HDGF was confirmed through dual-luciferase reporter assays. HDGF expression was detected through Western blotting. A xenograft model was established using stably transfected GEM-resistant cervical cancer cells to detect the role of DLG1-AS1 in tumorigenesis in vivo. RESULTS: DLG1-AS1 expression was significantly elevated in HeLa/GEM and SiHa/GEM cells. DLG1-AS1 silencing significantly reduced the viability and proliferation of GEM-resistant cervical cancer cells. DLG1-AS1 also promoted GEM sensitivity in cervical cancer cells by inhibiting miR-16-5p. Moreover, the tumor volume in nude mice in the DLG1-AS1 knockdown group decreased after GEM treatment. In addition, DLG1-AS1 targeted miR-16-5p, and miR-16-5p targeted HDGF. The miR-16-5p inhibitor reversed the DLG1-AS1 knockdown effect in GEM-resistant cervical cancer cells. CONCLUSION: Knockdown of DLG1-AS1 promoted GEM sensitivity in cervical cancer cells by regulating miR-16-5p/HDGF.

[Complex network analysis of law on Chinese herbal drugs intervention on radiation induced lung injury].

To mainly analyze the prescription rules of Chinese herbal drugs for radiation induced lung injury, optimize the prescriptions, and provide a reference for the clinical treatment of radiation induced lung injury. The major Chinese databases CNKI, CBM and Wanfang data were searched to obtain the literature on Chinese herbal drugs for radiation induced lung injury. BICOMS 2 software was used to extract and collect all Chinese herbal drugs information and generate the co-occurrence matrix; NetDraw and Gcluto software were then used to make network map and visualization matrix for analysis. A total of 552 articles (19 types and 304 Chinese herbal drugs) were included. Ophiopogon japonicus had the highest frequency (229 times), followed by Astragalus membranaceus(181 times), Glycyrrhiza uralensis (166 times), and Scutellaria baicalensis (150 times). After the classification of efficacy, deficiency-supplementing medicinal (69 kinds of Chinese herbs), heat-clearing medicine (51 kinds of Chinese herbs) and phlegm cough medicine (42 kinds of Chinese herbs) accounted for 53.29% of all the Chinese herbs, acting in the main position. After the prescription analysis for the top 25 herbal prescriptions, six main structures of common prescriptions were found for the treatment of radiation induced lung injury. There are many kinds of Chinese herbal drugs for the treatment of radiation induced lung injury in clinical application. In the future, researchers can mainly focus on Ophiopogon japonicus etc. as the main drugs, combine with other high-frequency Chinese herbal drugs found in this study, or directly refer to the main structures of commonly used prescriptions found in this analysis.

Spleen atrophy related immune system changes attributed to infection of Angiostrongylus cantonensis in mouse model.

The spleen is one of the most important peripheral immune organs, which is frequently affected in infectious diseases. Infectious diseases can induce splenic alterations including splenic atrophy and functional alteration, while splenic atrophy may in turn interferes with recovery of infectious diseases. Angiostrongyliasis is an infectious disease by Angiostrongylus cantonensis (A. cantonensis), which invade non-permissive hosts, such as humans and mice, to cause severe damage to the central nervous system (CNS) and acute inflammatory response. A. cantonensis infection-induced CNS injury has been confirmed to be due to profound immunopathology derived from peripheral immune components. However, the mechanism of immunopathology remains largely unknown. Here, we found that A. cantonensis invaded non-permissive hosts such as mice in the brain, but not in the other peripheral organs. However, this infection induced severe spleen atrophy. We further recognized that this atrophy is associated with a decrease of total splenocyte number and disruption of splenic structure due to reduced proliferation and increased apoptotosis. These also resulted in deterioration of T cell profile in the periphery with a low CD4/CD8 ratio and B/T cell ratio, and increased ratio of CD4+CD25+Foxp3+ Treg, CD8+CD28- T, and CD38+T lymphocyte of spleen. Albendazole treatment can alleviate spleen atrophy and set T cell immune reconstitution in some extend. Our data showed that A. cantonensis infection can cause splenic atrophy. These results are suggested to put more emphasis to improve the function of immune system. Meanwhile, infection and treatment model will be useful to evaluate new therapeutic approaches which can prevent or reverse immunosuppression and infectious complications.

In vivo suppression of microRNA-24 prevents the transition toward decompensated hypertrophy in aortic-constricted mice.

RATIONALE: During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca(2+) channels in the cell membrane/T-tubules and ryanodine receptors in the sarcoplasmic reticulum becomes defective, partially because of the decreased expression of a T-tubule-sarcoplasmic reticulum anchoring protein, junctophilin-2. MicroRNA (miR)-24, a junctophilin-2 suppressing miR, is upregulated in hypertrophied and failing cardiomyocytes. OBJECTIVE: To test whether miR-24 suppression can protect the structural and functional integrity of L-type Ca(2+) channel-ryanodine receptor signaling in hypertrophied cardiomyocytes. METHODS AND RESULTS: In vivo silencing of miR-24 by a specific antagomir in an aorta-constricted mouse model effectively prevented the degradation of heart contraction, but not ventricular hypertrophy. Electrophysiology and confocal imaging studies showed that antagomir treatment prevented the decreases in L-type Ca(2+) channel-ryanodine receptor signaling fidelity/efficiency and whole-cell Ca(2+) transients. Further studies showed that antagomir treatment stabilized junctophilin-2 expression and protected the ultrastructure of T-tubule-sarcoplasmic reticulum junctions from disruption. CONCLUSIONS: MiR-24 suppression prevented the transition from compensated hypertrophy to decompensated hypertrophy, providing a potential strategy for early treatment against heart failure.

[Growth Differentiation Factor 15 Inhibits Elevated Expression of Matrix Metalloproteinase 1 Induced by Pooled Serum in Patients with Coroanry Artery Ectasia].

OBJECTIVE: To observe the effects of coroanry artery ectasia (CAE) patients' pooled serum on the main proteinases and extracellular matrix (ECM) synthesis and explore whether the growth differentiation factor 15(GDF 15) can regulate the characteristic changes induced by CAE patients' pooled serum. METHODS: Serum samples were collected from 32 CAE patients, 30 patients with coronary heart disease (CHD), and 31 subjects with normal coronary arteries (CON) and then mixed in the same volumes by groups. Then human umbilical vein smooth muscle cells were cultured with the media containing 25% pooled serum. After having been disposed, proteinase system and ECM synthesis system were detected in the cell and culture media samples. GDF15 or GDF15 antibodies was added into the 25% pooled serum in each group to observe if GDF 15 could impact the characteristic changes induced by CAE patients' pooled serum. RESULTS: The expression of matrix metalloproteinases (MMP) 1 mRNA in CAE group was significantly higher than CON group (P=0.002) and CHD group (P=0.000), the secretory MMP1 protein and total MMPs activity in culture media were also upregulated in CAE group (both P<0.01). After adding GDF 15 into the culture media (GDF15+CAE group), the MMP1 mRNA ,secretory MMP1 protein, and total MMPs activity were significantly lower than CAE group (all P<0.01), while in the GDF15 antibody+CAE group, the MMP1 mRNA and total MMPs activities were significantly higher than in GDF15+CAE group (both P<0.01), but the secretory MMP1 protein was not different from GDF 15+CAE group (P>0.05). CONCLUSION: The vascular smooth muscle cells may participate in the CAE process mainly by regulating MMPs system but not the elastase 2 or ECM synthesis system, and GDF15 may be an compensatory factor to prohibit the over-destruction of coronary ECM induced by MMPs.

Spatial second-order interference of pseudothermal light in a Hong-Ou-Mandel interferometer.

The spatial second-order interference of two independent pseudothermal light beams in a Hong-Ou-Mandel interferometer is studied experimentally and theoretically. The similar cosine modulation in the second-order coherence function as the one with entangled-photon pairs in a Hong-Ou-Mandel interferometer is observed. Two-photon interference based on Feynman's path integral theory is employed to interpret the results. The experimental results and theoretical simulations agree with each other very well.

Defects and asymmetries in the visual pathway of non-human primates with natural strabismus and amblyopia.

Strabismus and amblyopia are common ophthalmologic developmental diseases caused by abnormal visual experiences. However, the underlying pathogenesis and visual defects are still not fully understood. Most studies have used experimental interference to establish disease-associated animal models, while ignoring the natural pathophysiological mechanisms. This study was designed to investigate whether natural strabismus and amblyopia are associated with abnormal neurological defects. We screened one natural strabismic monkey ( Macaca fascicularis) and one natural amblyopic monkey from hundreds of monkeys, and retrospectively analyzed one human strabismus case. Neuroimaging, behavioral, neurophysiological, neurostructural, and genovariation features were systematically evaluated using magnetic resonance imaging (MRI), behavioral tasks, flash visual evoked potentials (FVEP), electroretinogram (ERG), optical coherence tomography (OCT), and whole-genome sequencing (WGS), respectively. Results showed that the strabismic patient and natural strabismic and amblyopic monkeys exhibited similar abnormal asymmetries in brain structure, i.e., ipsilateral impaired right hemisphere. Visual behavior, visual function, retinal structure, and fundus of the monkeys were impaired. Aberrant asymmetry in binocular visual function and structure between the strabismic and amblyopic monkeys was closely related, with greater impairment of the left visual pathway. Several similar known mutant genes for strabismus and amblyopia were also identified. In conclusion, natural strabismus and amblyopia are accompanied by abnormal asymmetries of the visual system, especially visual neurophysiological and neurostructural defects. Our results suggest that future therapeutic and mechanistic studies should consider defects and asymmetries throughout the entire visual system.

Liver Stiffness Measurement can Predict Liver Inflammation in Chronic Hepatitis B Patients with Normal Alanine Transaminase.

Background and Aims: To determine whether liver stiffness measurement (LSM) indicates liver inflammation in chronic hepatitis B (CHB) with different upper limits of normal (ULNs) for alanine aminotransferase (ALT). Methods: We grouped 439 CHB patients using different ULNs for ALT: cohort I, ≤40 U/L (439 subjects); cohort II, ≤35/25 U/L (males/females; 330 subjects); and cohort III, ≤30/19 U/L (males/females; 231 subjects). Furthermore, 84 and 96 CHB patients with normal ALT (≤40 U/L) formed the external and prospective validation groups, respectively. We evaluated the correlation between LSM and biopsy-confirmed liver inflammation, and determined diagnostic accuracy using area under the curve (AUC). A noninvasive LSM-based model was developed using multivariate logistic regression. Results: Fibrosis-adjusted LSM values significantly increased with increasing inflammation. The AUCs of LSM in cohorts I, II, and III were 0.799, 0.796, and 0.814, respectively, for significant inflammation (A≥2) and 0.779, 0.767, and 0.770, respectively, for severe inflammation (A=3). Cutoff LSM values in all cohorts for A≥2 and A=3 were 6.3 and 7.5 kPa, respectively. Internal, external, and prospective validations showed high diagnostic accuracy of LSM for A≥2 and A=3, and no significant differences in AUCs among the four groups. LSM and globulin independently predicted A≥2. The AUC of an LSM-globulin model for A≥2 exceeded those of globulin, ALT, and AST, but was similar to that of LSM. Conclusions: LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.

Antithrombotic treatment strategy for patients with coronary artery ectasia and acute myocardial infarction: A case report.

BACKGROUND: There is no consensus on the antithrombotic treatment strategy for patients with coronary artery ectasia (CAE). CASE SUMMARY: This case reports the dynamic observation of a patient for 48 mo after a diagnosis of CAE with acute myocardial infarction (AMI). The first antithrombotic agents used were aspirin (100 mg/d) and clopidogrel (75 mg/d). During the sixth month of observation, a second AMI occurred involving the same culprit vessel; therefore, antithrombotic agents were changed to aspirin (100 mg/d) and ticagrelor (90 mg twice per day). Twelve months after the second AMI, an attempt to reduce the dosage ticagrelor failed; therefore the original dose was continued. The CAE was relatively stable during the following 4 years. CONCLUSION: This case indicates that a combination of aspirin and ticagrelor may be more effective for CAE patients with AMI than aspirin and clopidogrel.

Thalamic neurons in the pigeon compute distance-to-collision of an approaching surface.

The thalamofugal and tectofugal pathways in birds are two parallel visual pathways to the telencephalon and might be comparable to the geniculocortical and colliculo-pulvinar-cortical pathways in mammals, respectively. It is known that some tectal neurons in the tectofugal pathway can signal the time-to-collision of an approaching object. Here we show by single cell recording in the pigeon that a population of visual neurons in the nucleus opticus principalis thalami (nOPT) in the thalamofugal pathway is able to detect the distance-to-collision of a large surface approaching towards the animal. These neurons began response firing when the surface reached a threshold distance to the viewing eye and thereafter their firing rates increased exponentially until collision occurred at distance = zero. The response onset distance is nearly constant for a wide range of stimulus velocities and is equal to the product of velocity of approaching stimulus and response onset time of a nOPT cell. Furthermore, onset distance of looming responses in nOPT cells is close to that causing cardioacceleration in the pigeon viewing the approaching surface. It appears that nOPT and tectal neurons are dichotomized functionally to a large extent for detecting imminent dangers, and the pigeon's ability to compute the distance-to-collision of an approaching surface may benefit avoiding large obstacles during flight.

Cardiac Hypertrophy is Positively Regulated by MicroRNA­24 in Rats

Background: MicroRNA-24 (miR-24) plays an important role in heart failure by reducing the efficiency of myocardial excitation-contraction coupling. Prolonged cardiac hypertrophy may lead to heart failure, but little is known about the role of miR-24 in cardiac hypertrophy. This study aimed to preliminarily investigate the function of miR-24 and its mechanisms in cardiac hypertrophy. Methods: Twelve Sprague-Dawley rats with a body weight of 50 ± 5 g were recruited and randomly divided into two groups: a transverse aortic constriction (TAC) group and a sham surgery group. Hypertrophy index was measured and calculated by echocardiography and hematoxylin and eosin staining. TargetScans algorithm-based prediction was used to search for the targets of miR-24, which was subsequently confirmed by a real-time polymerase chain reaction and luciferase assay. Immunofluorescence labeling was used to measure the cell surface area, and 3H-leucine incorporation was used to detect the synthesis of total protein in neonatal rat cardiac myocytes (NRCMs) with the overexpression of miR-24. In addition, flow cytometry was performed to observe the alteration in the cell cycle. Statistical analysis was carried out with GraphPad Prism v5.0 and SPSS 19.0. A two-sided P < 0.05 was considered as the threshold for significance. Results: The expression of miR-24 was abnormally increased in TAC rat cardiac tissue (t = -2.938, P < 0.05). TargetScans algorithm-based prediction demonstrated that CDKN1B (p27, Kip1), a cell cycle regulator, was a putative target of miR-24, and was confirmed by luciferase assay. The expression of p27 was decreased in TAC rat cardiac tissue (t = 2.896, P < 0.05). The overexpression of miR-24 in NRCMs led to the decreased expression of p27 (t = 4.400, P < 0.01), and decreased G0/G1 arrest in cell cycle and cardiomyocyte hypertrophy. Conclusion: MiR-24 promotes cardiac hypertrophy partly by affecting the cell cycle through down-regulation of p27 expression.

Sonographic features of papillary thyroid microcarcinoma predicting high-volume central neck lymph node metastasis.

OBJECTIVE: To study the correlations between the sonographic features of papillary thyroid microcarcinoma (PTMC) and the presence of high-volume lymph node metastasis. METHOD: Medical records of 2363 PTMC patients were reviewed form October 2013 to December 2015. All the patients with lymph node metastasis identified by histopathology were included. Preoperative sonographic features, such as multifocality, tumour size, echogenicity, calcification, vascularity of papillary microcarcinoma, and capsule invasion, were recorded. Univariate and multivariate analyses were performed to investigate the relationships between sonographic features and high-volume lymph node metastasis (number of metastatic lymph nodes >5). RESULTS: In total, 152 patients had high-volume central lymph node metastasis (6.4%, 152/2363). Multiple logistic regression analysis showed that the preoperative ultrasonic features of microcalcifications (OR = 3.33, p = 0.022), larger tumour size (>7 mm) (OR = 2.802, p < 0.001), and capsule invasion (OR = 2.141, p = 0.006) were independent risk factors for high-volume lymph node metastasis in the central compartment of PTMC. CONCLUSION: The sonographic features of primary papillary microcarcinoma of the thyroid are correlated with high-volume central lymph node metastasis.

Laparoscopic versus open liver resection for colorectal liver metastases: A systematic review and meta-analysis of studies with propensity score-based analysis.

BACKGROUND: This meta-analysis collected studies with propensity score matching analysis (PSM) and focused on comparing the short-term and oncological outcomes of patients with colorectal liver metastases (CRLM) who underwent laparoscopic liver resection (LLR) versus open liver resection (OLR), to provide relatively high-level evidence of the additional value of LLR in treating patients with CRLM in comparison with OLR. METHODS: A systematic literature search was performed using the PubMed, Embase and Cochrane Library databases. Bibliographic citation management software (EndNote X7) was used for literature management. Quality assessment was performed based on a modified version of the Newcastle-Ottawa Scale. The data were analyzed using Review Manager (Version 5.1), and sensitivity analysis was performed by omitting one study in each step. Dichotomous data were calculated by odds ratio (OR) and continuous data were calculated by weighed mean difference (WMD) with 95% confidence intervals (CI). RESULTS: Overall, 10 studies enrolling 2259 patients with CRLM were included in the present meta-analysis. The pooled analysis suggested that LLR was associated with significantly less overall morbidity (OR, 0.57; 95% CI 0.40 to 0.80; I2 = 57%; P < 0.001), reduced blood loss (WMD, -124.68; 95% CI, -177.35 to -72.01; I2 = 83%; P < 0.00001), less transfusion requirement (OR, 0.46; 95% CI 0.35 to 0.62; I2 = 0%; P < 0.00001), shorter length of hospital stay (WMD, -2.13; 95% CI, -2.68 to -1.58; I2 = 0%; P < 0.00001), but longer operative time (WMD, 39.48; 95% CI, 23.68 to 55.27; I2 = 66%; P = 0.04). However, no significant differences were observed in mortality (OR, 0.50; 95% CI 0.21 to 1.2; I2 = 0%; P = 0.12). For oncological outcomes, no significant differences were observed in negative surgical margins (R0 resection), tumor recurrence, 3-year disease-free survival, 5-year disease-free survival, 5-year overall survival between the approaches. Nevertheless, LLR tended to provide higher 3-overall survival rate (OR, 1.37; 95% CI 1.11 to 1.69; I2 = 0%; P = 0.003). The pooled OR for overall morbidity in each subgroup analysis was consistent with the overall pooled OR. Additionally, the pooled OR for overall morbidity varied from (0.63; 95% CI 0.45to 0.88; I2 = 49%; P = 0.007) to (0.51; 95% CI 0.37 to 0.69; I2 = 39%; P < 0.0001) in sensitivity analysis. CONCLUSION: LLR is a beneficial alternative to OLR in select patients, and provides more favorable short-term outcomes such as less overall morbidity, shorter length of hospital stay, less blood loss, lower blood transfusion rate. Simultaneously, LLR does not compromise oncological outcomes including surgical margins R0, tumor recurrence, disease-free survival, 5-overall survival, as well as even yielding better 3-overall survival. Considering unavoidable bias from non-randomized trials, high-quality RCTs are badly needed to determine whether LLR can become standard practice for treating patients with CRLM.

[Effect of electroacupuncture on proprioception in cynomolgus monkeys after unilateral anterior cruciate ligament injury].

OBJECTIVE: To study the effect of electroacupuncture on proprioception in cynomolgus monkeys after unilateral anterior cruciate ligament (ACL) injury. METHODS: Twenty-seven cynomolgus monkeys were randomized equally into 3 groups, namely unilateral ACL injury with electroacupuncture group, unilateral ACL injury model group and blank control group. One week after modeling, the monkeys in electroacupuncture group were treated daily for 12 weeks with electroacupuncture at the acupoints Wei Yang, Yin Gu, Xi Yangguan and Qu Quan. At 4, 8, and 12 weeks during the treatment, the changes in the somatosensory evoked potentials (SEPs) and motor nerve conduction velocity (MCV) of the nerves of the ACL were examined with neural electrophysiological method; the changes in the morphology and the total and variable number of the proprioceptors in the ACL were observed with gold chloride staining. RESULTS; In the mokeys in the model group, the incubation period of the SEPs and MCV on the injured side of the knee were significantly extended and the amplitudes were decreased with the passage of time (P<0.05). Intervention with electroacupuncture significantly reduced the incubation period and increased the amplitudes of the SEPs and MCV (P<0.05). The total number of the proprioceptors in the ACL was significantly decreased and the variable number of the proprioceptors in ACL was increased with time in the monkeys in the model group (P<0.05); electroacupuncture intervention obviously slowed the reduction rate of total number of the proprioceptors (P<0.05) but without affecting the variable number of the proprioceptors (P>0.05). CoONCLUSION: ACL injury causes attenuation of the proprioception on the injury side, and electroacupuncture intervention can produce a positive effect on the proprioception in cynomolgus monkeys.

Soluble antigens from the neurotropic pathogen Angiostrongylus cantonensis directly induce thymus atrophy in a mouse model.

The nematode Angiostrongylus cantonensis (A.C.) is a neurotropic pathogen; stage-III larva invade the human (non-permissive host) central nervous system (CNS) to cause eosinophilic meningitis or meningoencephalitis accompanied by immunosuppression. In an A.C.-infectedmouse (another non-permissive host) model, CNS damage-associated T cell immune deficiency and severe inflammation were proposed to result from activation of the hypothalamic-pituitary-adrenal (HPA) axis. However, glucocorticoids are anti-inflammatory agents. Additionally, while defects in thymic stromal/epithelial cells (TECs) are the major reason for thymic atrophy, TECs do not express the glucocorticoid receptor. Therefore, activation of the HPA axis cannot fully explain the thymic atrophy and inflammation. Using an A.C.-infected mouse model, we found that A.C.-infected mice developed severe thymic atrophy with dramatic impairments in thymocytes and TECs, particularly cortical TECs, which harbor CD4+CD8+ double-positive thymocytes. The impairments resulted from soluble antigens (sAgs) from A.C. in the thymuses of infected mice, as intrathymic injection of these sAgs into live mice and the addition of these sAgs to thymic cell culture resulted in thymic atrophy and cellular apoptosis, respectively. Therefore, in addition to an indirect effect on thymocytes through the HPA axis, our study reveals a novel mechanism by which A.C. infection in non-permissive hosts directly induces defects in both thymocytes and TECs via soluble antigens.

Response characteristics of the pigeon's pretectal neurons to illusory contours and motion.

Misinterpretations of visual information received by the retina are called visual illusions, which are known to occur in higher brain areas. However, whether they would be also processed in lower brain structures remains unknown, and how to explain the neuronal mechanisms underlying the motion after-effect is intensely debated. We show by extracellular recording that all motion-sensitive neurons in the pigeon's pretectum respond similarly to real and illusory contours, and their preferred directions are identical for both contours in unidirectional cells, whereas these directions are changed by 90 deg for real versus illusory contours in bidirectional cells. On the other hand, some pretectal neurons produce inhibitory (excitatory) after-responses to cessation of prolonged motion in the preferred (null) directions, whose time course is similar to that of the motion after-effect reported by humans. Because excitatory and inhibitory receptive fields of a pretectal cell overlap in visual space and possess opposite directionalities, after-responses to cessation of prolonged motion in one direction may create illusory motion in the opposite direction. It appears that illusory contours and motion could be detected at the earliest stage of central information processing and processed in bottom-up streams, and that the motion after-effect may result from functional interactions of excitatory and inhibitory receptive fields with opposite directionalities.