Individualized model for predicting COVID-19 deterioration in patients with cancer: A multicenter retrospective study.

The 2019 novel coronavirus has spread rapidly around the world. Cancer patients seem to be more susceptible to infection and disease deterioration, but the factors affecting the deterioration remain unclear. We aimed to develop an individualized model for prediction of coronavirus disease (COVID-19) deterioration in cancer patients. The clinical data of 276 cancer patients diagnosed with COVID-19 in 33 designated hospitals of Hubei, China from December 21, 2019 to March 18, 2020, were collected and randomly divided into a training and a validation cohort by a ratio of 2:1. Cox stepwise regression analysis was carried out to select prognostic factors. The prediction model was developed in the training cohort. The predictive accuracy of the model was quantified by C-index and time-dependent area under the receiver operating characteristic curve (t-AUC). Internal validation was assessed by the validation cohort. Risk stratification based on the model was carried out. Decision curve analysis (DCA) were used to evaluate the clinical usefulness of the model. We found age, cancer type, computed tomography baseline image features (ground glass opacity and consolidation), laboratory findings (lymphocyte count, serum levels of C-reactive protein, aspartate aminotransferase, direct bilirubin, urea, and d-dimer) were significantly associated with symptomatic deterioration. The C-index of the model was 0.755 in the training cohort and 0.779 in the validation cohort. The t-AUC values were above 0.7 within 8 weeks both in the training and validation cohorts. Patients were divided into two risk groups based on the nomogram: low-risk (total points ≤ 9.98) and high-risk (total points > 9.98) group. The Kaplan-Meier deterioration-free survival of COVID-19 curves presented significant discrimination between the two risk groups in both training and validation cohorts. The model indicated good clinical applicability by DCA curves. This study presents an individualized nomogram model to individually predict the possibility of symptomatic deterioration of COVID-19 in patients with cancer.

Correlation study on 18F-FDG PET/CT metabolic characteristics of primary lesion with clinical stage in lung cancer.

BACKGROUND: 18F-FDG PET/CT metabolic characteristics provide the crucial biologic and molecular information for tumors. To explore the relationships between 18F-FDG PET/CT derived parameters such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) of primary tumor and clinical stage in different histopathologic subtypes of lung cancer. METHODS: A total of 97 newly diagnosed lung cancer patients (69 males, 28 females; average age 65.1 years) with pathologically proven were retrospectively analyzed, who had undergone 18F-FDG PET/CT scan before treatment from September 2016 to November 2017. SUVmax, MTV and TLG of primary tumor were measured. Clinical stage was mainly determined by 18F-FDG PET/CT, in conjunction with conventional imaging and endoscopic biopsy. Mann-Whitney U test, χ2 test, Spearman correlation test and ROC curve analysis were used for statistical analysis. RESULTS: There were 53 adenocarcinomas (AC), 28 squamous carcinomas (SCC), 13 small cell carcinomas (SCLC), one adenosquamous carcinoma, one mucoepidermoid carcinoma, and one sarcomatoid carcinoma in 97 patients. Both AC and SCLC revealed more cases in stage IV than in stage I-III (P<0.01). There was no significant difference in four stages of SCC (P>0.05). Metabolic parameters of SCC were higher than AC including SUVmax, MTV and TLG (P<0.01). SCLC showed a higher value than AC in TLG (P<0.05). No significant differences were found between AC and SCLC in SUVmax and MTV, also between SCC and SCLC in SUVmax, MTV and TLG (P>0.05). MTV and TLG except SUVmax were positively correlated with stage in AC (P≤0.001). Only MTV showed a positive correlation with stage in SCC (P<0.05). Whereas there were no definitive relationships between metabolic parameters and stage in SCLC (P>0.05). AC with a higher MTV (MTV≥5.965 cm3) indicated a significantly higher rate of distant metastasis than those with a lower MTV (77.5% (31/40) vs. 30.8% (4/13), χ2=9.553, P<0.01), as well as AC with a higher TLG (TLG≥46.922) than those with a lower TLG (88.5% (23/26) vs. 44.4% (12/27), χ2=11.422, P<0.01). CONCLUSIONS: Histopathologic subtypes have a significant influence on the relationships between MTV/TLG not SUVmax of primary foci and stage in lung cancer. Primary MTV/TLG is related to clinical stage closely in AC, and a higher MTV/TLG results in a higher risk of distant metastasis.

The unsynchronized changes of CT image and nucleic acid detection in COVID-19: reports the two cases from Gansu, China.

The novel coronavirus disease (COVID-19) outbreak started in December 2019 in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CT image is used to assess the disease progress, whereas the continued two times of negative results from SARS-CoV-2 nucleic acid detection had been considered as a criterion for ending antiviral treatment. We compared the two COVID-19 cases with similar backgrounds and CT image repeated intervals under treatment. Our report highlighted the unsynchronized expression in the changes of CT image and nucleic acid detection in COVID-19, and lasting positive nucleic acid test result in patients recovered from pneumonia. It may be contributed to recognize the disease and improve prevention.

Genome-wide analysis reveals alcohol dehydrogenase 1C and secreted phosphoprotein 1 for prognostic biomarkers in lung adenocarcinoma.

To seek out novel promising biomarkers for predicting lung adenocarcinoma (LUAD) prognosis, we conducted this study. First, 279 upregulated and 37 downregulated differentially expressed genes were obtained from LUAD and para-carcinoma tissues by the Affymetrix GeneChip Human Transcriptome Array. Then, we randomly classified samples of LUAD data set GSE31210 as training and testing sets in a 1:1 ratio. Alcohol dehydrogenase 1C (ADH1C) and secreted phosphoprotein 1 (SPP1) were finally identified correlating with the LUAD survival through least absolute shrinkage and selection operator penalized Cox proportion hazards regression model, and applied to build a 2-gene signature related to prognosis in training set. Univariate and multivariable survival analyses suggested that overall survival (OS) and relapse-free survival (RFS) in the 2-gene signature low-risk group were better than the high-risk group. Kaplan-Meier curves proved that elevated ADH1C expression and reduced SPP1 expression were related to better OS and RFS. Besides, the SPP1 expressed higher in LUAD than para-carcinoma tissues using quantitative reverse transcription polymerase chain reaction assay. Finally, the association between the two genes and clinicopathological parameters in 80 LUAD were analyzed, it is suggested that SPP1 was relevant to epidermal growth factor receptor mutation. These findings indicated that ADH1C and SPP1 might be novel promising biomarkers for predicting LUAD prognosis.

Elevated Cystatin C Levels Are Associated with Cognitive Impairment and Progression of Parkinson Disease.

OBJECTIVE: We investigated the relationship between serum cystatin C (CysC) levels and cognitive dysfunction and disease progression in patients with Parkinson disease. BACKGROUND: Previous studies have reported altered CysC levels in neurodegenerative disorders, but only a few studies have explored the role of CysC and its relationship to cognitive dysfunction in Parkinson disease. METHODS: We measured serum levels of CysC, creatinine, urea, and uric acid in 142 patients with Parkinson disease and 146 healthy controls. We assessed disease progression using the Hoehn and Yahr scale, and cognitive function using the Montreal Cognitive Assessment (Beijing version). RESULTS: The patients with Parkinson disease had significantly higher CysC levels than the controls (P<0.001). CysC level correlated significantly with age (r=0.494, P<0.001), sex (r=0.150, P=0.011), and serum creatinine level (r=0.377, P<0.001), but not with levels of urea or uric acid (P>0.05). CysC level was a significant independent predictor of Parkinson disease (odds ratio=23.143, 95% confidence interval: 5.485-97.648, P<0.001) in multivariate logistic regression analysis. In the Parkinson disease group, a higher CysC level was associated with a more advanced Hoehn and Yahr stage (r=0.098, P<0.05) and a lower Montreal Cognitive Assessment score (r=-0.381, P=0.003). CONCLUSIONS: Serum CysC levels can predict disease severity and cognitive dysfunction in patients with Parkinson disease. The exact role of CysC remains to be determined.

Parkinson's disease patients with pain suffer from more severe non-motor symptoms.

Non-motor symptoms, including pain, depression, sleep disorder, and olfactory dysfunction, occur frequently in patients with Parkinson's disease (PD), even before the onset of motor symptoms. Although studies have examined the correlation between pain and depression or sleep disorder in PD, few studies have investigated the correlation between pain and a range of other non-motor symptoms of PD. PD patients (n = 142) with or without pain were included in the study. PD severity was evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr (H/Y) staging scale. Pain severity was analyzed with the Visual Analog Scale. The Hamilton Rating Scale for Depression (HRSD; 24 items), Montreal Cognitive Assessment Beijing Version (MoCA), and non-motor questionnaire (NMSQT) measured symptoms of depression, cognitive function, and non-motor symptoms. The incidence of pain was 47.9% in patients with PD, most of whom had moderate pain levels. Patients with pain showed higher HRSD, UPDRS, H/Y, and NMSQT scores and lower MoCA scores compared to those of patients without pain. HRSD and NMSQT scores were closely related with pain (P < 0.001). Non-motor symptoms were more prominent in patients with pain compared to that of controls and PD patients without pain.

Expression and functions of ASIC1 in the zebrafish retina.

It has been demonstrated that acid sensing ionic channels (ASICs) are present in the central and peripheral nervous system of mammals, including the retina. However, it remains unclear whether the zebrafish retina also expresses ASICs. In the present study, the expression and distribution of zasic1 were examined in the retina of zebrafish. Both zasic1 mRNA and protein expressions were detected in the adult zebrafish retina. A wide distribution of ASIC1 in zebrafish retina was confirmed using whole mount in situ hybridization and immunohistochemistry study. Acidosis-induced currents in the isolated retinal ganglion cells (RGCs) were also recorded using whole cell patch clamping. Moreover, blockade of ASICs channel significantly reduced the locomotion of larval zebrafish in response to light exposure. In sum, our data demonstrate the presence of ASIC1 and its possible functional relevance in the retina of zebrafish.

The association of maternal smoking around birth with chronic respiratory diseases in adult offspring: A Mendelian randomization study.

INTRODUCTION: Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. METHODS: Mendelian randomization (MR) study was used to analyze the genome-wide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). RESULTS: After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI: 1.013-1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI: 1.039-5.603; p=0.040), COPD (OR=1.14; 95% CI: 1.013-1.284; p=0.003), and asthma (OR=1.336; 95% CI: 1.161-1.538; p<0.001). Besides, maternal smoking during pregnancy was associated with a greater risk of LUSC (OR=1.229; 95% CI: 0.992-1.523; p=0.059) than the risk of IPF (OR=1.001; 95% CI: 0.999-1.003; p=0.224), LC (OR=1.203; 95% CI: 0.964-1.501; p=0.103), or SCLC (OR=1.11; 95% CI: 0.77-1.601; p=0.577). CONCLUSIONS: In this MR analysis, maternal smoking around birth caused a strong risk factor for the offspring to develop lung problems and CRDs in adulthood. The policy related to smoking cessation for mothers during pregnancy should be encouraged.

Significance of Ribonucleoside-diphosphate Reductase Subunit M2 in Lung Adenocarcinoma.

INTRODUCTION: The Ribonucleoside-diphosphate Reductase subunit M2 (RRM2) is known to be overexpressed in various cancers, though its specific functional implications remain unclear. This aims to elucidate the role of RRM2 in the progression of Lung Adenocarcinoma (LUAD) by exploring its involvement and potential impact. METHODS: RRM2 data were sourced from multiple databases to assess its diagnostic and prognostic significance in LUAD. We evaluated the association between RRM2 expression and immune cell infiltration, analyzed its function, and explored the effects of modulating RRM2 expression on LUAD cell characteristics through laboratory experiments. RESULTS: RRM2 was significantly upregulated in LUAD tissues and cells compared to normal counterparts (p<0.05), with rare genetic alterations noted (approximately 2%). This overexpression clearly distinguished LUAD from normal tissue (area under the curve (AUC): 0.963, 95% confidence intervals (CI): 0.946-0.981). Elevated RRM2 expression was significantly associated with adverse clinicopathological characteristics and poor prognosis in LUAD patients. Furthermore, a positive association was observed between RRM2 expression and immune cell infiltration. Pathway analysis revealed a critical connection between RRM2 and the cell cycle signaling pathway within LUAD. Targeting RRM2 inhibition effectively suppressed LUAD cell proliferation, migration, and invasion while promoting apoptosis. This intervention also modified the expression of several crucial proteins, including the downregulation of CDC25A, CDC25C, RAD1, Bcl-2, and PPM1D and the upregulation of TP53 and Bax (p < 0.05). CONCLUSION: Our findings highlight the potential utility of RRM2 expression as a biomarker for diagnosing and predicting prognosis in LUAD, shedding new light on the role of RRM2 in this malignancy.

Application and interpretation of current autophagy inhibitors and activators.

Autophagy is the major intracellular degradation system, by which cytoplasmic materials are delivered to and degraded in the lysosome. As a quality control mechanism for cytoplasmic proteins and organelles, autophagy plays important roles in a variety of human diseases, including neurodegenerative diseases, cancer, cardiovascular disease, diabetes and infectious and inflammatory diseases. The discovery of ATG genes and the dissection of the signaling pathways involved in regulating autophagy have greatly enriched our knowledge on the occurrence and development of this lysosomal degradation pathway. In addition to its role in degradation, autophagy may also promote a type of programmed cell death that is different from apoptosis, termed type II programmed cell death. Owing to the dual roles of autophagy in cell death and the specificity of diseases, the exact mechanisms of autophagy in various diseases require more investigation. The application of autophagy inhibitors and activators will help us understand the regulation of autophagy in human diseases, and provide insight into the use of autophagy-targeted drugs. In this review, we summarize the latest research on autophagy inhibitors and activators and discuss the possibility of their application in human disease therapy.

Ray-tracing method for creeping waves on arbitrarily shaped nonuniform rational B-splines surfaces.

An accurate creeping ray-tracing algorithm is presented in this paper to determine the tracks of creeping waves (or creeping rays) on arbitrarily shaped free-form parametric surfaces [nonuniform rational B-splines (NURBS) surfaces]. The main challenge in calculating the surface diffracted fields on NURBS surfaces is due to the difficulty in determining the geodesic paths along which the creeping rays propagate. On one single parametric surface patch, the geodesic paths need to be computed by solving the geodesic equations numerically. Furthermore, realistic objects are generally modeled as the union of several connected NURBS patches. Due to the discontinuity of the parameter between the patches, it is more complicated to compute geodesic paths on several connected patches than on one single patch. Thus, a creeping ray-tracing algorithm is presented in this paper to compute the geodesic paths of creeping rays on the complex objects that are modeled as the combination of several NURBS surface patches. In the algorithm, the creeping ray tracing on each surface patch is performed by solving the geodesic equations with a Runge-Kutta method. When the creeping ray propagates from one patch to another, a transition method is developed to handle the transition of the creeping ray tracing across the border between the patches. This creeping ray-tracing algorithm can meet practical requirements because it can be applied to the objects with complex shapes. The algorithm can also extend the applicability of NURBS for electromagnetic and optical applications. The validity and usefulness of the algorithm can be verified from the numerical results.

Alteration of dynein function affects α-synuclein degradation via the autophagosome-lysosome pathway.

Growing evidence suggests that dynein dysfunction may be implicated in the pathogenesis of neurodegeneration. It plays a central role in aggresome formation, the delivery of autophagosome to lysosome for fusion and degradation, which is a pro-survival mechanism essential for the bulk degradation of misfolded proteins and damaged organells. Previous studies reported that dynein dysfuntion was associated with aberrant aggregation of α-synuclein, which is a major component of inclusion bodies in Parkinson's disease (PD). However, it remains unclear what roles dynein plays in α-synuclein degradation. Our study demonstrated a decrease of dynein expression in neurotoxin-induced PD models in vitro and in vivo, accompanied by an increase of α-synuclein protein level. Dynein down-regulation induced by siRNA resulted in a prolonged half-life of α-synuclein and its over-accumulation in A53T overexpressing PC12 cells. Dynein knockdown also prompted the increase of microtubule-associated protein 1 light chain 3 (LC3-II) and sequestosome 1 (SQSTM1, p62) expression, and the accumulation of autophagic vacuoles. Moreover, dynein suppression impaired the autophagosome fusion with lysosome. In summary, our findings indicate that dynein is critical for the clearance of aberrant α-synuclein via autophagosome-lysosome pathway.

[Depression associated with movement disorders].

OBJECTIVE: To explore the incidence of depression in movement disorders and associated factors. METHODS: A total of 121 Parkinson's disease (PD) patients from August 2010 to June 2011 and 62 ET patients from July 2009 to June 2010 were recruited. All of them were outpatients of our hospital. PD patients received the unified Parkinson's disease rating scale (UPDRS) -motor examination and a modified Hoehn and Yahr scale to stage the severity of their disorders while 62 essential tremor (ET) patients were evaluated with tremor rating scale for tremor-motor examination (items 1 - 15 of rating scale). All participants completed Hamilton depression rating scale (24 items) to measure the presence and degree of symptoms of depression. RESULTS: It was found that 56.2% of PD patients and 53.2% of ET patients were depressed (HAMD score of 8 or higher). Among them, the rates of mild depression were 38.9% and 35.5%, moderate depression 15.7% and 17.7% and severe depression 1.7% and 0% in PD and ET patients respectively. No significant differences existed between each group. The factor scores of cognitive impairment were 1.81 ± 1.86 and 1.04 ± 1.07 in PD and ET patients while those of sense of despair were 2.95 ± 1.97 and 4.09 ± 2.08 in each group. The differences had statistical significance in two factor scores of two groups (P < 0.05). No differences in anxiety/somatization, lose weight, day-and-night changes, block and sleep disorders between two groups. For PD patients, the motor score of UPDRS-III was positively correlated with total HAMD score (r = 0.511, P < 0.01). Similarly, for ET patients, tremor rating scale for tremor-motor subscale score and HAMD score were positively correlated (r = 0.828, P < 0.01). CONCLUSION: As two common movement disorders, PD and ET have a high incidence of depression. The severity of depression is similar in two groups. There is no significant intra-group difference in severity and frequency of depression. The most common symptoms are anxiety somatization, anhedonia, working difficulty, slowness and sleep disturbance. The depression and motor symptoms are positively correlated. Like the non-motor symptoms in PD, we should also pay attention to the non-motor symptoms in ET.

[Clinical characteristics in Parkinson's disease patients with cognitive impairment and effects of cognitive impairment on sleep].

OBJECTIVE: To analyze the clinical characteristics, correlation factors and clinical heterogeneities in Parkinson's disease (PD) patients with cognitive impairment and identify whether cognitive impairment could influence the aspect of sleep. METHODS: A total of 130 PD outpatients and inpatients of sleep center at our hospital were eligible for participation. According to Montreal cognitive assessment (MOCA), they were divided into cognitive normal group (MOCA ≥ 26) (n = 51) and cognitive impairment group (MOCA < 26) (n = 79). Their clinical characteristics were mainly evaluated by unified Parkinson's disease rating scale (UPDRS) , Hoehn-Yahr (H-Y) stage, Hamilton depression scale (HAMD-24 item) and Epworth sleepiness scale (ESS). And all of them underwent video-polysomnography (PSG). RESULTS: The proportion of cognitive impairment (MOCA < 26) was 60.76%. Compared to those without cognitive impairment, the PD patients with cognitive impairment had significantly higher score of HAMD (10 ± 7 vs 7 ± 4), increased incidence of hallucinations (40.50% vs 19.60%) and REM behavior disorders (RBD) (63.29% vs 39.21%), significantly higher H-Y stage [2.5(2.0-3.0) vs 2.0 (2.0-2.5)] , United Kingdom Parkinson Disease Society (UPDRS) part III (22 ± 10 vs 19 ± 10) and levodopa-equivalent daily dose (LED) (511 ± 302vs 380 ± 272) (all P < 0.05). However, no significant differences existed in the subscores of MOCA between PD patients with different sides of onset and motor subtypes of onset (all P > 0.05). Non-conditional Logistic regression analysis showed that PD duration, score of HAMD and H-Y stage were the major influencing factors of cognition. On PSG, significantly decreased sleep efficiency (57% ± 21% vs 66% ± 17%), higher percentage of non-REM sleep stage 1 (NREMS1) (37% ± 21% vs 27% ± 13%), lower percentage of NREMS2 (40% ± 17% vs 46% ± 13%) and REM sleep (39% ± 28% vs 54% ± 36%) were found for PD patients with cognitive impairment (all P < 0.05). CONCLUSION: The PD patients with cognitive impairment have more severe disease and partial nonmotor symptoms. And the severity of disease and depression is closely associated with cognitive impairment. Cognitive impairment may also affect sleep to cause decreased sleep efficiency and severe sleep structure disorder.

Overlapping Epstein-Barr virus encephalitis and autoimmune glial fibrillary acidic protein astrocytopathy.

We describe three cases of overlapping Epstein-Barr virus (EBV) Encephalitis and Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy (GFAP-A). The three cases all presented with initial symptoms of fever, headache, coma, and posture tremor of the upper limbs, then followed by limb weakness and dysuria. All of the three cases were on ventilators. Case 1 and 2 improved dramatically after intravenous methylprednisoloneand immunoglobulin treatment. However, case 3 presented dyspneic, and died from gastrointestinal hemorrhage. The GFAP-A triggered by EBV intracranial infection could initially masquerade as EBV encephalitis only, and the detection of GFAP antibody is essential for differentiation.

Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates.

Background: The competing endogenous RNA (ceRNA) network-mediated regulatory mechanisms in small cell lung cancer (SCLC) remain largely unknown. This study aimed to integrate multi-omics profiles, including the transcriptome, regulome, genome and pharmacogenome profiles, to elucidate prioritised ceRNA characteristics, pathways and drug candidates in SCLC. Method: We determined the plasma messenger RNA (mRNA), microRNA (miRNA), long noncoding RNA (lncRNA) and circular RNA (circRNA) expression levels using whole-transcriptome sequencing technology in our SCLC plasma cohort. Significantly expressed plasma mRNAs were then overlapped with the Gene Expression Omnibus (GEO) tissue mRNA data (GSE 40275, SCLC tissue cohort). Next, we applied a multistep multi-omics (transcriptome, regulome, genome and pharmacogenome) integration analysis to first construct the network and then to identify the lncRNA/circRNA-miRNA-mRNA ceRNA characteristics, genomic alterations, pathways and drug candidates in SCLC. Results: The multi-omics integration-based prioritisation of SCLC ceRNA regulatory networks consisted of downregulated mRNAs (CSF3R/GAA), lncRNAs (AC005005.4-201/DLX6-AS1-201/NEAT1-203) and circRNAs (hsa_HLA-B_1/hsa_VEGFC_8) as well as upregulated miRNAs (hsa-miR-4525/hsa-miR-6747-3p). lncRNAs (lncRNA-AC005005.4-201 and NEAT1-203) and circRNAs (circRNA-hsa_HLA-B_1 and hsa_VEGFC_8) may regulate the inhibited effects of hsa-miR-6747-3p for CSF3R expression in SCLC, while lncRNA-DLX6-AS1-201 or circRNA-hsa_HLA-B_1 may neutralise the negative regulation of hsa-miR-4525 for GAA in SCLC. CSF3R and GAA were present in the genomic alteration, and further identified as targets of FavId and Trastuzumab deruxtecan, respectively. In the SCLC-associated pathway analysis, CSF3R was involved in the autophagy pathways, while GAA was involved in the glucose metabolism pathways. Conclusions: We identified potential lncRNA/cirRNA-miRNA-mRNA ceRNA regulatory mechanisms, pathways and promising drug candidates in SCLC, providing novel potential diagnostics and therapeutic targets in SCLC.

[Association of PARK 16 polymorphisms with Parkinson's disease in Han population of Suzhou area].

OBJECTIVE: To investigate whether there is an association of PARK 16 locus with Parkinson's disease (PD) in Han population of Suzhou area. METHODS: Polymerase chain reaction (PCR), sequencing analysis, allele-specific PCR mediated by pfu DNA polymerases and real-time PCR were employed to determine the genotype of each subject. The PARK16 representative SNP rs947211 was analyzed in 160 PD patients and 200 age-matched healthy controls. RESULTS: The results of pfu-mediated allele-specific PCR were 100% concordant with the direct-sequencing analysis. All genotypes were found in this study. A significant distinction occurred in the allelic frequency of rs947211. There was a higher expression of G allele in PD patients versus the controls (60.63% vs 51.00%; χ(2) = 6.662, P = 0.010, OR = 0.676, 95%CI 0.502 - 0.911). There were remarkable differences between G/G genotype and A/G + A/A genotype of two groups (χ(2) = 8.401, P = 0.004, OR = 1.951, 95%CI 1.238 - 3.076). In addition, a significant distinction also existed in different genotypes through H&Y stage (P < 0.05). For example, the stage of G/G was higher than A/A genotype (P = 0.025, 95%CI 0.059 - 0.851) or A/G genotype (P = 0.020, 95%CI 0.058 - 0.654). CONCLUSION: We have established a simple and reliable rs947211 genotyping method mediated by pfu DNA polymerases. The results confirmed the existence of PARK16 in Han population of Suzhou area, rs947211 G/G genotype maybe a risk factor for PD and G/G genotype carriers perhaps obtain higher illness severity.

Osteopontin improves sensitivity to tyrosine kinase inhibitor in lung adenocarcinoma in vitro by promoting epidermal growth factor receptor phosphorylation.

PURPOSE: Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) improve the prognosis of lung adenocarcinoma (LUAD). However, the factors affecting its clinical efficacy remain unclear. This study aimed to determine the correlation between Osteopontin (OPN) and EGFR, and explore the inhibitory effect of first-generation TKI gefitinib on LUAD cells. METHODS: The correlation between OPN and EGFR was determined through bioinformatics technology, and the clinical information as well as samples of related patients were collected to verify the relationship between them. Using three different NSCLC cell lines A549, H1299 and PC9, we studied the effects of OPN expression and EGFR phosphorylation on the first-generation TKI's efficacy in vitro. RESULTS: Our data revealed that OPN staining positively linked to a more advanced clinical stage. Compared with the control group, LUAD cells with elevated OPN levels are more sensitive to the growth inhibitory effect of TKI. Knocking down of OPN decreased the response of cells to gefitinib. Besides, OPN also upregulated the phosphorylation of EGFR, thereby affecting the effect of TKI. CONCLUSION: OPN enhanced the sensitivity of LUAD cells to gefitinib by promoting EGFR phosphorylation. OPN may be a potential target for evaluating TKI efficacy and a potential target for molecular therapy.