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ATP-binding cassette subfamily A (ABCA) has received wide recognition because it possesses the capacity to translocate its derivatives, xenobiotics, vitamins, and cholesterol across biological membranes. Some ABCA members have causative relevance to inborn diseases, and a number of studies have explored their functions in cancer progression and metastasis. Here, we explored the interrelation between ABCA genes and lung adenocarcinoma (LUAD). We specified the expression and functions of ABCA members in LUAD using the GEPIA, GEO, Human Protein Atlas, UALCAN, TIMER, and Kaplan-Meier Plotter databases. ABCA5, ABCA6, ABCA8, ABCA9, and ABCA10 were found to be significantly less expressed in LUAD and correlated with TP53 mutation in patients with LUAD. Furthermore, ABCA5, ABCA6, and ABCA8 were relevant to overall survival of patients with LUAD. In conclusion, this study showed that ABCA members may be related to the TP53 mutation of LUAD. Moreover, it may serve as a potential marker for the prognosis of LUAD.

Laryngopharyngeal reflux (LPR) may be associated with the severity of obstructive sleep apnea (OSA). However, it is unknown whether LPR may be associated with arousal.To clarify the effect of LPR on arousal in OSA.This study included 120 OSA patients. The correlations between LPR scores and arousal index (ArI) were analyzed. Finally, to further clarify the effect of LPR on ArI, we analyzed the correlations between respiratory event-related arousal index (BERAI), leg-movement-related arousal index (LMRAI), snore-related arousal index (SRAI), spontaneous arousal index (SAI), and RSI score.Partial correlation analysis showed that the RSI score was positively correlated with ArI (The effect of LPR symptoms on arousal in OSA exists. The more severe the LPR was, the more frequent the arousal in OSA patients was. Thereinto, respiratory event-related arousal and spontaneous arousal were the most obvious.

We combined our generalized energy-based fragmentation (GEBF) approach and machine learning (ML) technique to construct quantum mechanics (QM) quality force fields for proteins. In our scheme, the training sets for a protein are only constructed from its small subsystems, which capture all short-range interactions in the target system. The energy of a given protein is expressed as the summation of atomic contributions from QM calculations of various subsystems, corrected by long-range Coulomb and van der Waals interactions. With the Gaussian approximation potential (GAP) method, our protocol can automatically generate training sets with high efficiency. To facilitate the construction of training sets for proteins, we store all trained subsystem data in a library. If subsystems in the library are detected in a new protein, corresponding datasets can be directly reused as a part of the training set on this new protein. With two polypeptides, 4ZNN and 1XQ8 segment, as examples, the energies and forces predicted by GEBF-GAP are in good agreement with those from conventional QM calculations, and dihedral angle distributions from GEBF-GAP molecular dynamics (MD) simulations can also well reproduce those from ab initio MD simulations. In addition, with the training set generated from GEBF-GAP, we also demonstrate that GEBF-ML force fields constructed by neural network (NN) methods can also show QM quality. Therefore, the present work provides an efficient and systematic way to build QM quality force fields for biological systems.

The aim of the study is to investigate the effect of CT-guided artificial pneumothorax combined with a thoracoscopic and central venous catheter on empyema drainage effect and pulmonary function in children. A total of 82 pediatric patients with empyema admitted to our hospital from January 2020 to December 2021 were retrospectively analyzed. The control group was treated with artificial pneumothorax combined with thoracoscopy. The study group was treated with a CT-guided and central venous catheter. The operation time, intraoperative bleeding, surgical field exposure, WBC, C-reactive protein, and pulmonary function were compared between the two groups. The size of effusion and sonographic staging were compared between the two groups. All children underwent spirometry and a maximal incremental cardiopulmonary exercise test. The operation indicators (operation time, intraoperative blood loss, etc.) and adverse reactions were compared between the two groups. The differences in the operation time, intraoperative blood loss, postoperative hospital stay, postoperative drainage volume, and surgical field exposure between the two groups had a statistical significance ( P < 0.05 ); the differences in the body temperature, total peripheral white blood cell count, C-reactive protein, size of effusion, and sonographic staging between the two groups had no statistical significance ( P > 0.05 ); before operation, the differences in the expression levels of FVC (%), FEV1 (%), FEV1/FVC, and MVV (%) and indicators of cardiopulmonary function including VE/VO2, breathing reserve(%), VD/VT(%), and VO2/work between the two groups had no statistical significance, but at 6 months after operation, FVC (%), FEV1 (%), FEV1/FVC, and MVV (%) in the study group were significantly higher than those in the control group ( P < 0.05 ) and VE/VO2 and VD/VT(%) in the study group were obviously lower than those in the control group ( P < 0.05 ); the incidence rate of chest pain, pulmonary edema, and skin infection in the study group was lower than that in the control group ( P < 0.05 ). CT-guided artificial pneumothorax combined with thoracoscopic and central venous catheter drainage of empyema in children is more thorough, with less bleeding, less trauma, rapid recovery of pulmonary function, and is worthy of clinical promotion.

Clinical relevance: Those with high myopia are more likely to have glaucoma compared to those without myopia and intraocular pressure was a key factor for developing glaucoma. Thus, investigating the distribution of intraocular pressure and associated factors among those with high myopia is of high importance.Background: The aim of this work is to investigate the distribution of intraocular pressure and the correlated risk factors in a highly myopic Chinese population.Methods: A total of 884 Chinese participants with bilateral high myopia (≤ -6.00 D spherical power) were included from the Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study. All participants underwent a comprehensive ocular examination, including ocular biometry, cycloplegic refractometry, and intraocular pressure measurement with Goldmann applanation tonometry. Information on smoking and drinking status was also collected.Results: The mean spherical equivalence of left eyes was -10.02 ± 3.58 D with a mean axial length of 27.48 ± 1.55 mm. The overall mean intraocular pressure was 15.1 ± 2.4 mmHg (95% confidence interval, 15.0 to 15.3 mmHg). The intraocular pressure in the -6.00D to -7.99D spherical equivalence group, -8.00D to -9.99D spherical equivalence group, and ≤ -10.00 D group were 15.3 ± 2.4 mmHg, 15.1 ± 2.5 mmHg, and 15.0 ± 2.4 mmHg, respectively (p = 0.979). In multiple regression models, intraocular pressure in high myopes was not associated with spherical equivalence (p = 0.354) or axial length (p = 0.601), but significantly higher in those who were younger (non-standardised beta, -0.018; p = 0.007), smoked tobacco (non-standardised beta, 1.085; p = 0.001) and had greater central corneal thickness (non-standardised beta, 0.021; p

We investigated the effects on humans, in terms of skin conductance levels (SCLs) and positive and negative affect schedule (PANAS) scores, of plant communities that differed in their vegetation structure (single-layer woodland, tree-shrub-grass composite woodland, tree-grass composite woodland, and single-layer grassland) through two perceptual methods: onsite surveying and photo elicitation. The results showed that (1) the choice of perception method significantly impacted the PANAS scores of the participants but had no influence on the SCL and (2) viewing a single-layer grassland reduced the SCL (representing the physiological stress level) and improved the positive affect score. The recovery effects for the four vegetation communities were ranked in the order of single-layer grassland > tree-shrub-grass composite woodland > single-layer woodland > tree-grass composite woodland. (3) Gender and professional background significantly impacted the plant community perception methods and landscape experience, and negative affect scores were lower for male participants than for female participants. Participants without backgrounds in landscape design exhibited higher positive affect scores under photo elicitation. Based on the conclusions drawn above, the onsite survey is preferable between the two perception methods. It is recommended that in future landscape designs, combinations of plant community types should be reasonably matched through onsite perception. These research results can provide a scientific basis for the future design of landscapes based on perception experience.

Objective: To explore the application of lingual artery ultrasound (US) for midline glossectomy in patients with obstructive sleep apnea (OSA). Methods: Lingual artery US was performed in 57 OSA patients (OSA group) and 20 normal persons (control group). The differences in the depths of the lingual arteries and the distances between the bilateral lingual arteries were compared between two groups. The correlations between apnea-hypopnea index (AHI), AHI after the nasopharyngeal tube insertion (NPT-AHI), Friedman tongue position (FTP) and all the parameters of lingual arteries were analyzed. Results: Both the depths of the lingual arteries and the distances between the bilateral lingual arteries in the OSA group were larger than those in the control group ( P < .01). All the parameters of the lingual arteries in OSA patients were positively correlated with AHI, NPT-AHI and FTP ( P < .05). While controlling for body mass index (BMI), all the parameters of the lingual arteries in OSA patients were still correlated with NPT-AHI positively ( P ≤ .01). Conclusion: Pre-operative US can show the course of the lingual artery clearly for pre-operative planning. The depth and width of the lingual artery in OSA patients were different from controls. NPT-AHI has high sensitivity in predicting all the parameters of the lingual arteries. FTP is closely correlated with the depth of the lingual arteries.

Strategies for selectively imaging and delivering drugs to tumours typically leverage differentially upregulated surface molecules on cancer cells. Here, we show that intravenously injected carbon quantum dots, functionalized with multiple paired α-carboxyl and amino groups that bind to the large neutral amino acid transporter 1 (which is expressed in most tumours), selectively accumulate in human tumour xenografts in mice and in an orthotopic mouse model of human glioma. The functionalized quantum dots, which structurally mimic large amino acids and can be loaded with aromatic drugs through π–π stacking interactions, enabled—in the absence of detectable toxicity—near-infrared fluorescence and photoacoustic imaging of the tumours and a reduction in tumour burden after the targeted delivery of chemotherapeutics to the tumours. The versatility of functionalization and high tumour selectivity of the quantum dots make them broadly suitable for tumour-specific imaging and drug delivery., Intravenously injected functionalized carbon quantum dots that bind to the large neutral amino acid transporter 1 and that structurally mimic large amino acids selectively accumulate in human tumours in mice, facilitating targeted theranostics.

Dynamically monitoring the clonal evolution of lung cancer and performing molecular analyses on tumor cells are challenging but necessary tasks to adjust therapeutic interventions and evaluate treatment efficacy. Circulating tumor cells (CTCs), as a "liquid biopsy", may offer an auxiliary tool to identify phenotypic transformation of solid tumors at primary or metastatic sites and uncover their corresponding molecular variation. Herein, we developed an aptamer-modified PEG-PLGA-nanofiber (PPN) microfluidic system optimized for recognizing rare CTC subtypes in lung cancer patients. This unique purification system can be adopted to monitor the clonal evolution of solid tumors by following the intrinsic immunophenotypes of CTCs, while significantly enhancing capture efficiency for polyclonal-derived tumor cells, further facilitating therapeutic evaluation via dynamic CTC enumeration. Combining with downstream single-cell sequencing, the aptamer-modified-PPN microfluidic system was able to provide early insight into tumor heterogeneity and predict histologic transformation in advance, broadening its clinical applications in lung cancer patients.

Rationale: Cancer stem cells (CSCs) are considered to be essential for tumorigenesis, recurrence, and metastasis and therefore serve as a biomarker for tumor progression in diverse cancers. Recent studies have illustrated that specific miRNAs exhibit novel therapeutic potential by controlling CSC properties. miR-1275 is upregulated in lung adenocarcinoma (LUAD) and enhances its stemness. However, the underlying mechanisms have not been elucidated. Methods: miRNA expression microarray of LUAD and adjacent nontumor tissues was used to identify miRNAs involved in LUAD malignant progression. miR-1275 expression level was determined using quantitative real-time PCR (RT-qPCR) and in situ hybridization (ISH), and its correlation with clinicopathological characteristics was analyzed in LUAD specimens. The upstream regulator of miR-1275 was validated by chromatin immunoprecipitation (ChIP). The biological functions and underlying mechanisms of miR-1275 were investigated both in vitro and in vivo. Results: MiR-1275 was highly upregulated in lung cancer cell lines and LUAD tissues. Overexpression of miR-1275 in lung cancer patients was associated with shorter overall- and recurrence-free-survival. Proto-oncogene HIF-1ɑ was identified as the transcription mediator of miR-1275. Activation of Wnt/β-catenin and Notch signaling by miR-1275 was found to enhance the stemness of LUAD cells, while antagonizing miR-1275 or suppressing Wnt/β-catenin and Notch pathways potently reversed miR-1275-induced pathway co-activation and stemness. Enhanced stemness dramatically promoted tumorigenicity, recurrence, and metastasis. miR-1275 directly targeted multiple antagonists of Wnt/β-catenin and Notch pathways, including DKK3, SFRP1, GSK3β, RUNX3, and NUMB, respectively, which resulted in signaling activation. Conclusions: Our findings identified miR-1275 as a potential oncogene in LUAD that exerts its tumorigenic effect through co-activating Wnt/β-catenin and Notch signaling pathways. Thus, HIF-1ɑ-regulated miR-1275 might be a potential therapeutic target for LUAD.

For bilinguals, language control is needed for selecting the target language during language production. Numerous studies have examined the neural correlates of language control and shown a close relationship between language control and domain-general cognitive control. However, it remains unknown how these brain regions coordinate with each other when bilinguals exert cognitive control over linguistic and nonlinguistic representations. We addressed this gap using an extended unified structural equation modeling (euSEM) approach. Sixty-five Chinese-English bilinguals performed language switching and nonverbal switching tasks during functional magnetic resonance imaging (fMRI) scanning. The results showed that language control was served by a cooperative brain network, including the frontal lobe, the parietal cortex, subcortical areas, and the cerebellum. More importantly, we found that language control recruited more subcortical areas and connections from frontal to subcortical areas compared with domain-general cognitive control, demonstrating a reconfigurable brain network. In addition, the reconfiguration efficiency of the brain network was mainly determined by general cognitive ability but was also mediated by second language (L2) proficiency. These findings provide the first data-driven connectivity model that specifies the brain network for language control in bilinguals and also shed light on the relationship between language control and domain-general cognitive control.

Genetic factors play a crucial role for the pathophysiology of treatment-resistant depression (TRD). It has been established that Catechol-O-methyltransferase (COMT) and cyclic amp-response element-binding protein (CREB) are associated with antidepressant response. The aim of this study was to explore the association between single nucleotide polymorphisms (SNPs) in COMT and CREB1 genes and TRD in a Chinese population. We recruited 181 patients with major depressive disorder (MDD) and 80 healthy controls, including 81 TRD patients. Depressive symptoms were assessed with the Hamilton Depression Rating Scale-17 (HDRS). Genotyping was performed using mass spectrometry. Genetic analyses were conducted by PLINK Software. The distribution of COMT SNP rs4818 allele and genotypes were significantly different between TRD and controls. Statistical differences in allele frequencies were observed between TRD and non-TRD groups, including rs11904814 and rs6740584 in CREB1 gene, rs4680 and rs4818 in COMT gene. There were differences in the distribution of HDRS total scores among different phenotypes of CREB1 rs11904814, CREB1 rs6740584, COMT rs4680 and rs4818. Gene–gene interaction effect of COMT–CREB1 (rs4680 × rs6740584) revealed significant epistasis in TRD. There findings indicate that COMT and CREB1 polymorphisms influence the risk of TRD and affect the severity of depressive symptoms of MDD.

Background Convenient and precise assessment of the severity in coronavirus disease 2019 (COVID-19) contributes to the timely patient treatment and prognosis improvement. We aimed to evaluate the ability of CT-based radiomics nomogram in discriminating the severity of patients with COVID-19 Pneumonia. Methods A total of 150 patients (training cohort n = 105; test cohort n = 45) with COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR) test were enrolled. Two feature selection methods, Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO), were used to extract features from CT images and construct model. A total of 30 radiomic features were finally retained. Rad-score was calculated by summing the selected features weighted by their coefficients. The radiomics nomogram incorporating clinical-radiological features was eventually constructed by multivariate regression analysis. Nomogram, calibration, and decision-curve analysis were all assessed. Results In both cohorts, 40 patients with COVID-19 pneumonia were severe and 110 patients were non-severe. By combining the 30 radiomic features extracted from CT images, the radiomics signature showed high discrimination between severe and non-severe patients in the training set [Area Under the Curve (AUC), 0.857; 95% confidence interval (CI), 0.775–0.918] and the test set (AUC, 0.867; 95% CI, 0.732–949). The final combined model that integrated age, comorbidity, CT scores, number of lesions, ground glass opacity (GGO) with consolidation, and radiomics signature, improved the AUC to 0.952 in the training cohort and 0.98 in the test cohort. The nomogram based on the combined model similarly exhibited excellent discrimination performance in both training and test cohorts. Conclusions The developed model based on a radiomics signature derived from CT images can be a reliable marker for discriminating the severity of COVID-19 pneumonia.

Objective Medical disorders in patients with bipolar disorder (BD) have attracted more and more attention. So far, there is still a lack of studies on this issue utilizing large sample sizes in the Chinese sample. Therefore, we conducted this study to explore the clinical characteristics of BD patients comorbid medical disorders in a relatively large Chinese sample. Methods This was a cross-sectional study including 1,393 BD patients (882 patients with medical disorders and 511 patients without medical disorders). Their demographic and clinical characteristics were obtained by the Hospital Information System and self-designed questionnaires. Results The comorbidity rate of medical disorders in BD was 63.32%. The average number of medical disorders for a BD patient was 2.69. The top five comorbid medical disorders in BD patients were circulatory system diseases (19%), nervous system diseases (18%), endocrine and metabolic diseases (17%), digestive system diseases (16%), and respiratory system diseases (8%). BD patients with comorbid medical disorders had an older average age, lower education level, longer illness course, later onset age, lower ratio of psychotic features, more admission numbers, higher ratio of smoking and drinking alcohol, more number of manic episodes (All P P Conclusions Medical disorders in Chinese BD patients are highly prevalent. The smoking, number of depressive episodes, onset age, illness course, are correlated with BD patients comorbid medical disorders. Clinicians should pay attention to the medical disorders comorbidities in BD patients, and take effective measures to improve treatment outcome and reduce the suffering. The integrative approach should be the imperative in clinical practice.

Previous research has shown that training on inhibitory control (IC) leads to functional neural plastic changes, although this effect on individuals with different levels of IC abilities has yet to be studied. Here, we examined the individual differences in IC abilities of 85 participants, who performed a Simon task while undergoing a functional magnetic resonance imaging (fMRI) scan. Participants in the experimental group followed an 8-day training session on IC between the pre- and the post-test, whereas the control group did not receive any training. The fMRI results reported that, in comparison to the control group, the training session elicited different patterns of neural adaptation between participants with high- and low-IC abilities in the experimental group. While training reduced activation levels in the supplementary motor area (SMA), bilateral thalamus, and left anterior cingulate cortex (ACC) of individuals with low-IC performance prior to the training, the same pattern was not found in participants with high-IC performance. In addition, individual differences in IC abilities before training also positively correlated with activation reduction in these brain regions after training. These results suggest that individual differences in IC abilities modulate the neural plasticity of IC, and IC training specifically enhanced neural efficiency in individuals with low-IC abilities. Our findings provide a novel perspective for investigating the functional neuroplasticity of the IC system by highlighting the interaction between individual variances in IC abilities and short-term training effects.

Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

Objectives: Studies documenting the association between rapid eye movement sleep behavior disorder (RBD) and subtypes of multiple system atrophy (MSA) are rare. In this study, we investigated the presence of clinical RBD in MSA patients and compared the prevalence and severity of RBD in patients with MSA-P and MSA-C subtypes. Methods: We evaluated 54 consecutive patients presenting with MSA and hospitalized in the neurology ward of Beijing Hospital from February 2012 to June 2020. The healthy control (HC) group consisted of 100 healthy individuals who came to our hospital for physical examination. The clinical diagnosis of RBD was based on the minimal diagnostic criteria of International Classification of Sleep Disorders, revised. The severity of clinical RBD was rated on a digital scale from 0 to 3. The patients were divided into 2 subgroups: MSA-P and MSA-C. The MSA and HC groups were compared in terms of frequency of clinical RBD. The MSA-P and MSA-C subgroups were compared with each other for age, sex, onset age, disease duration, and features of clinical RBD. The correlation between severity of clinical RBD and clinical characteristics of MSA was analyzed in the patient groups. Results: The frequency of clinical RBD in MSA and HC groups was 70.4% (38/54) and 5% (5/100), respectively. The difference between 2 groups was significant (χ2 = 74.453, p = 0.000). Among the patients, 57.4% (31/54) had the MSA-P subtype. There were no significant differences between MSA-P and MSA-C subtypes in the prevalence (χ2 = 1.734, p = 0.188) and severity (χ2 = 1.776, p = 0.412) of clinical RBD. The onset of clinical RBD during the premotor period was not different between the subtypes of MSA, either in patients’ number of preceding the onset of motor symptoms (χ2 = 0.581, p = 0.446) or the preceding time (Z = −0.550, p = 0.582). For the MSA-C patients, there was a negative correlation between the score of severity of the RBD scale and RBD preceding motor symptoms (r = −0.482, p = 0.020). Conclusion: In our study, the prevalence of clinical RBD is unrelated to the subtypes of MSA. The onset of clinical RBD during the premotor period was not different between subtypes of MSA. However, we found that the severity of RBD occurring before the motor symptoms was more than that occurring after the motor symptoms in MSA-C patients. Our results showed that MSA-P and MSA-C patients may have a probable indicator for the similar pathologic mechanism of the disease and its sleep problems.

In recent years, some studies have started to explore the impact of individual general executive functions (EFs) on bilingual language control. To our knowledge, few studies have systematically examined various components of EFs on different levels of language control in bilinguals. In two experiments, we investigated the effects of two components of IC on different levels of bilingual language control. The language-switching task was used to tap into language control at different levels. The Simon task was used to measure interference suppression in Experiment 1, and a go/no-go task was used to measure response inhibition in Experiment 2. Experiment 1 found that the smaller the Simon effect was, the larger the asymmetry of switch costs was. Experiment 2 found that the shorter the go response time was, the larger the global slowing effect was. Taken together, these findings suggest that the interference suppression component of domain-general IC facilitates local level language control, while response inhibition impacts global level language control in bilinguals.

To determine the effect of transanal total mesorectal excision (taTME) procedure on the postoperative bowel evacuation function of patients with low rectal cancer. Bowel evacuation function was investigated in 316 patients with rectal cancer after taTME in 18 hospitals in China. Low anterior resection syndrome (LARS) score, Wexner score, and EORTC QLQ-C30 were used for functional evaluation. The association between perioperative risk factors and LARS score was determined by univariate and multivariate analyses. The prevalence rate of no LARS, minor LARS, and major LARS in patients after taTME was 39.9%, 28.2%, and 31.9%, respectively. The two most frequently reported symptoms of LARS after taTME were bowel clustering (72.8%) and fecal urgency (63.3%). Patients with major LARS had significantly higher Wexner score and worse global health status and financial difficulties according to the EORTC QLQ-C30 questionnaire than those without major LARS. Preoperative chemoradiotherapy was an independent risk factor of major LARS occurrence after taTME (OR: 3.503, P = 0.044); existing preoperative constipation (OR: 0.082, P = 0.040) and manual anastomosis (OR: 4.536, P = 0.021) were favorable factors affecting bowel evacuatory function within 12 months after taTME, but for patients whose follow-up time was longer than 12 months, postoperative chemoradiotherapy (OR: 8.790, P = 0.001) and defunctioning stoma (OR: 3.962, P = 0.010) were independent risk factors. The bowel evacuation function after taTME is acceptable. Perioperative chemoradiotherapy, anastomotic method, and preoperative constipation are factors associated with bowel dysfunction after taTME.

Circular RNA RNF13 (circ-RNF13; ID: hsa_circ_0067717) is newly identified to be abnormally upregulated in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients. However, its role and mechanism remain to be further annotated. First of all, real-time quantitative PCR (RT-qPCR) was utilized to examine RNA expression, and circ-RNF13 was upregulated in HBV-infected human HCC tissues and HBV-expressing cells (Huh7-HBV and Hep3B-HBV), accompanied with TGFβ-induced factor homeobox 2 (TGIF2) upregulation and microRNA (miR)-424-5p downregulation. Loss-of-functional experiments were performed using MTS assay, colony formation assay, flow cytometry, enzyme-linked immunosorbent assay, transwell assay, and xenograft tumor model. As a result, blocking circ-RNF13 enhanced the apoptosis rate of Huh7-HBV and Hep3B-HBV cells, but inhibited cell proliferation, colony formation, migration, and invasion in vitro, along with suppressed tumor growth in vivo. Besides, RT-qPCR data showed that HBV DNA copies and levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were diminished by circ-RNF13 knockdown in Huh7-HBV and Hep3B-HBV cells. Mechanistically, circ-RNF13 and TGIF2 could directly interacting with miR-424-5p according to dual-luciferase reporter assay, suggesting that circ-RNF13 and TGIF2 served as competing endogenous RNAs (ceRNAs) for miR-424-5p. Functionally, overexpressing miR-424-5p mimicked and silencing miR-424-5p counteracted the effects of circ-RNF13 depletion in HBV-expressing HCC cells in vitro; TGIF2 restoration partially abrogated the role of miR-424-5p upregulation. In conclusion, circ-RNF13 might sponge miR-424-5p to suppress HBV-associated HCC cells malignant progression and HBV infection by regulating TGIF2, providing a novel insight into the occurrence and treatment of HBV-associated HCC.

Although several cross-sectional studies have shown an association of metabolic syndrome (MetS) with nodular thyroid disease, related prospective studies are scarce. This study investigated the association of MetS with thyroid nodule (TN) incidence in Chinese adults, and explored whether the development of or recovery from MetS is associated with changes in the risk of developing TNs. A total of 4,749 Chinese aged 18–65 years were involved in this 6-year prospective study. The association of MetS with TN prevalence was examined. TN-free individuals at baseline (n = 3,133) were further examined. TN incidence rates in groups with different MetS statuses (MetS-free, MetS-developed, MetS-recovery and MetS-chronic) were analyzed. Of all participants, 18.21 and 31.65% had MetS and TNs, respectively. MetS patients had a higher TN prevalence than the non-MetS group (31.08 vs. 19.81% in males, p < 0.01; 59.52 vs. 39.59% in females, p < 0.01). Sex, age and MetS were independent risk factors for TNs. At a median follow up of 5.94 years, the MetS-chronic group (4.37/100 person-years) had a higher risk of TNs (adjusted incidence rate ratio [IRR] = 1.288 [95% CI 1.014–1.636]) compared with the MetS-free group (2.72/100 person-years) in the whole cohort. In males, the MetS-chronic group (3.76/100 person-years) had a higher risk of TNs (adjusted IRR = 1.367 [95% CI 1.017–1.835]) compared with the MetS-free group (2.31/100 person-years). In females, the risk of TNs was significantly higher in the MetS-chronic (6.44/100 person-years) and MetS-developed (6.31/100 person-years) groups compared with the MetS-free group (3.23/100 person-years).

Bilingual language experience, such as switching between languages, has been shown to shape both cognitive and neural mechanisms of non-linguistic cognitive control. However, the neural adaptations induced by language switching remain unclear. Using fMRI, the current study examined the impact of short-term language switching training on the neural network of domain-general cognitive control for unbalanced Chinese-English bilinguals. Effective connectivity maps were constructed by using the extended unified structural equation models (euSEM) within 10 common brain regions involved in both language control and domain-general cognitive control. Results showed that, the dorsal anterior cingulate cortex/pre-supplementary motor area (dACC/pre-SMA) lost connection from the right thalamus after training, suggesting that less neural connectivity was required to complete the same domain-general cognitive control task. These findings not only provide direct evidence for the modulation of language switching training on the neural interaction of domain-general cognitive control, but also have important implications for revealing the potential neurocognitive adaptation effects of specific bilingual language experiences.

Background Clopidogrel is one of the most commonly used anti-platelet agents in cardiovascular diseases. We analyzed the relationship between the platelet function analyzer (PFA)-200 P2Y (INNOVANCE PFA-200 System, Siemens Healthcare, Germany) results and occurrence of major adverse cardiac events (MACEs) in Korean patients with recent-onset acute coronary syndrome (ACS) taking clopidogrel. Methods Between August 2013 and June 2016, we prospectively enrolled 106 patients with recent-onset ACS who had been treated with clopidogrel. We obtained blood samples and measured closure time (CT) using the PFA-200 P2Y test. Patients were divided into two groups on the basis of a CT cut-off value of 106 seconds. We compared patient characteristics and various MACEs that occurred during the follow-up period. Results The CTs for 78 patients exceeded the cut-off value. At the time of these analyses, 11 patients had been diagnosed with MACEs. In the time-to-event analysis, there was a difference between the two groups (P

To explore the application of three-dimensional (3D) reconstruction technology for midline glossectomy in patients with obstructive sleep apnea (OSA). Fifteen patients with OSA were included in this study. Each of them received computed tomography angiography (CTA) examination of lingual arteries in the resting tongue position and fully extended tongue position respectively. The two-dimensional CTA images were converted to 3D models using 3D reconstruction technology. We simulated the midline glossectomy in different tongue positions with a safe margin of 3 mm. The differences in the distances between bilateral lingual arteries, the depths of the lingual arteries and the surgical resectable volumes of the tongue were compared between different tongue positions in 3D models. The depths of the lingual arteries, the distances between bilateral lingual arteries based on three measuring sections and the surgical resectable volumes of the tongue in the fully extended tongue position were significantly smaller than those in the resting tongue position (P

Objectives Previous studies have shown that Helicobacter pylori infection might make clinical status worse in patients with Parkinson’s disease and Helicobacter pylori eradication might improve clinical status by modifying the pharmacokinetics of L-dopa. Here, we investigate whether Helicobacter pylori eradication could benefit idiopathic parkinsonism and Helicobacter pylori infection will effect which aspect of motor symptom significantly. Patients and methods A cohort study involving idiopathic Parkinson’s disease patients, screened for Helicobacter status by 13 C urea breath test. Clinical status was evaluated by using the Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn-Yahr stage. If patients had motor complications, they were quantified at the “on” time. The Helicobacter pylori positive patients could choose to receive Helicobacter pylori eradication or not by themselves. Group 1 was Helicobacter pylori negative patients. Group 2 was Helicobacter pylori positive patients who didn’t receive eradication treatment. Group 3 was Helicobacter pylori positive patients who received successful eradication treatment. Repeat clinical assessments and 13 C urea breath test was performed at 1 year later. Numerical data were expressed as mean ± standard deviation (SD) Results Ninety-four consecutive patients with Parkinson’s disease were recruited and underwent the initial 13 C urea breath test, but only forty-eight patients successfully completed the total study. In Group 3, the UPDRS-III scores (=Motor Examination Section Scores) were significantly lower 1 year later compared to baseline (18.3 ± 8.38 vs. 25.9 ± 8.37, P = 0.007). The differences were main in UPDRS-23 (=Finger Taps) (1.7 ± 1.16 vs. 2.4 ± 1.51, P = 0.045), UPDRS-25 (Rapid Alternation Movements of Hands) (1.6 ± 1.35 vs. 2.4 ± 1.71, P = 0.031) and UPDRS-26 (=Leg Agility) (1.3 ± 1.25 vs.2.1 ± 0.99, P = 0.011). There was difference among three groups in the UPDRS-26 (P = 0.040) of clinical status change of one year. Conclusion The eradication of Helicobacter might improve the clinical status of idiopathic parkinsonism, especially on bradykinesia.

BACKGROUND The aim of this study was to investigate duplication of the vertebral artery (VA) using three-dimensional time-of-flight (3D TOF) magnetic resonance angiography (MRA) in a large study population to further our understanding of vascular variations. MATERIAL AND METHODS A retrospective analysis of 3D TOF-MRA data in 12 826 cases was performed. The occurrence rate of VA duplication was calculated and accompanied vascular anomalies were recoded. RESULTS Twenty-one VA duplication patients were found, with an occurrence rate of 0.164%; 12 of them had left VA duplication with 2 branches initially arising from the aortic arch and left subclavian artery; 9 of them were right VA duplication with the branches originating from the right subclavian artery. In the 21 cases, 11 had other vascular abnormalities. CONCLUSIONS VA duplication is very rare and often associated with other vascular abnormalities. 3D TOF-MRA can accurately display the duplication variation. Better understanding of the variation is instrumental for disease diagnosis, interventional therapy, and surgical operation.

The success of checkpoint inhibitors in cancer treatment is associated with the infiltration of tissue-resident memory T (Trm) cells. In this study, we found that about 30% of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment of gastric adenocarcinoma were CD69

To investigate the effects of neoadjuvant chemotherapy combined with enteral nutrition on perioperative immunity, inflammation and intestinal flora in gastric cancer patients.A total of 96 gastric cancer patients scheduled to undergo operation were selected and randomly divided into the observation group (n=48) and the control group (n=48). The patients in the control group were treated with neoadjuvant chemotherapy before operation, while those in the observation group received enteral nutrition before operation based on the treatment in the control group. The changes in immune indexes, inflammatory indexes and intestinal flora were compared between the two groups.After treatment, the levels of serum interleukin-2 (IL-2), IL-6, IL-10 and C-reactive protein (CRP) elevated gradually, while the level of serum tumor necrosis factor-alpha (TNF-α) lowered gradually in both groups (p0.05). The indexes of nutritional status in the control group declined gradually after operation, and the levels of nutritional indexes, T cell subsets and immunoglobulins in the observation group were significantly higher than those in the control group (p0.05). In the observation group, after operation, the levels of Bifidobacterium and Lactobacillus rose gradually, but those of Escherichia coli and Enterococcus exhibited progressive decline (p0.05).Neoadjuvant chemotherapy combined with enteral nutrition can markedly relieve the perioperative inflammatory responses, improve the body immunity and maintain the structure of intestinal flora in gastric cancer patients, so it has certain clinical application value.

Background Circulating tumor cells (CTC) shows great prospect to realize precision medicine in cancer patients. Methods We developed the NanoVelcro Chip integrating three functional mechanisms. NanoVelcro CTC capture efficiency was tested in stage III or IV lung adenocarcinoma. Further, ALK-rearrangement status was examined through fluorescent in situ hybridization in CTCs enriched by NanoVelcro. Results NanoVelcro system showed higher CTC-capture efficiency than CellSearch in stage III or IV lung adenocarcinoma. CTC counts obtained by both methods were positively correlated (r = 0.45, p

To determine the incidence of surgical site infection (SSI) after abdominal surgery and to further evaluate the related risk factors of SSI in China.The multicenter cross-sectional study collected clinical data of all adult patients who underwent abdominal surgery from May 1, 2018 to May 31, 2018 in 30 domestic hospitals, including basic information, perioperative parameters, and incisional microbial culture results. The primary outcome was the incidence of SSI within postoperative 30 days. SSI was classified into superficial incision infection, deep incision infection, and organ/gap infection according to the US Centers for Disease Control and Prevention (CDC) criteria. The secondary outcome variables were ICU stay, postoperative hospital stay, total hospital stay, 30-day mortality and treatment costs. Multivariate logistic regression was used to analyze the risk factors of SSI.A total of 1666 patients were enrolled in the study, including 263 cases of East War Zone Hospital of PLA, 140 cases of Affiliated Hospital of Qingdao University, 108 cases of The First Affiliated Hospital of Nanchang University, 87 cases of Central War Zone Hospital of PLA, 77 cases of West China Hospital, 74 cases of Guangdong General Hospital, 71 cases of Chenzhou First People's Hospital, 71 cases of Zigong First People's Hospital, 64 cases of Zhangjiagang First People's Hospital, 56 cases of Nanyang City Central Hospital, 56 cases of Lanzhou General Hospital of Lanzhou Military Command, 56 cases of Shandong Provincial Hospital, 52 cases of Shangqiu First People's Hospital, 52 cases of People's Hospital of Xinjiang Uygur Autonomous Region, 48 cases of The Second Xiangya Hospital of Central South University, 48 cases of Chinese PLA General Hospital, 44 cases of Affiliated Hospital of Xuzhou Medical University, 38 cases of Hunan Province People's Hospital, 36 cases of Dongguan Kanghua Hospital, 30 cases of Shaoxing Central Hospital, 30 cases of Northern Jiangsu People's Hospital, 29 vases of The First Affiliated Hospital of Zhengzhou University, 27 cases of General Hospital of Tianjin Medical University, 22 cases of Zigong Fourth People's Hospital, 21 cases of The Second Hospital of University of South China, 18 cases of Tongji Hospital, 15 cases of Nanchong Central Hospital, 12 cases of The 901th Hospital of PLA, 11 cases of Hunan Cancer Hospital, 10 cases of Lanzhou University Second Hospital. There were 1019 males and 647 females with mean age of (56.5±15.3) years old. SSI occurred in 80 patients (4.8%) after operation, including 39 cases of superficial incision infection, 16 cases of deep incision infection, and 25 cases of organ/interstitial infection. Escherichia coli was the main pathogen of SSI, and the positive rate was 32.5% (26/80). Compared with patients without SSI, those with SSI had significantly higher ICU occupancy rate [38.8%(31/80) vs. 13.9%(220/1586), P0.001], postoperative hospital stay (median 17 days vs. 7 days, P0.001) and total hospital stay (median 22 days vs. 13 days, P0.001), and significantly higher cost of treatment (median 75 000 yuan vs. 44 000 yuan, P0.001). Multivariate analysis showed that male rise(OR=2.110, 95%CI:1.175-3.791, P=0.012), preoperative blood glucose level rise(OR=1.100, 95%CI: 1.012-1.197, P=0.026), operative time (OR=1.006, 95%CI:1.003-1.009, P0.001) and surgical incision grade (clean-contaminated incision:OR=10.207, 95%CI:1.369-76.120, P=0.023; contaminated incision: OR=10.617, 95%CI:1.298-86.865, P=0.028; infection incision: OR=20.173, 95%CI:1.768-230.121, P=0.016) were risk factors for SSI; and laparoscopic surgery (OR=0.348, 95%CI:0.192-0.631, P=0.001) and mechanical bowel preparation(OR=0.441,95%CI:0.221-0.879, P=0.020) were protective factors for SSI.The incidence of postoperative SSI in patients with abdominal surgery in China is 4.8%. SSI can significantly increase the medical burden of patients. Preoperative control of blood glucose and mechanical bowel preparation are important measures to prevent SSI.

To understand the distribution of Parkinson's disease questionnaire-39 (PDQ-39) scores in Parkinson's disease (PD) patients with or without depression, and to analyze the factors that influence the quality of life of PD patients.300 PD patients were enrolled. Patients' general information and the results of assessments including UPDRS, H-Y, HAMD, HAMA, ADL and PDQ-39 were collected. They were divided into depression group and non-depression group according to HAMD score. The relationship between PD-related depression and quality of life and the factors that influence the quality of life of PD patients were analyzed based on PDQ-39 score.111 patients with depression (37.0 %) and 189 patients without depression (63.0 %) were enrolled. The scores of PDQ-39 summary index (PDQ-39 SI) in the depression group were significantly higher than those in the non-depression group in all domains (P0.05). Patients in the depression group had a longer disease duration (6.89 ± 4.70 vs. 5.52 ± 4.12, P0.038), a higher UPDRS-III score (30.1 ± 13.55 vs. 25.2 ± 11.73, P0.001), and a higher H-Y stage level (2.41 ± 0.853 vs. 2.13 ± 0.707, P0.001), compared with patients in the non-depression group. All factors including age, disease duration, UPDRS-III, H-Y stage, HAMD score and HAMA score, may independently affected PDQ-39SI in PD patients, among which HAMD had the greatest effect. HAMD and HAMA were correlated with PDQ-39 in its all eight domains.PD patients with psychological problems such as anxiety and depression may lead to a significant decline in the quality of life of patients in all domains.

Background An association has been reported between CYP2C19 polymorphism and the altered antiplatelet activity of clopidogrel. We investigated this association using the newly introduced platelet function analyzer (PFA)-200 (INNOVANCE PFA-200 System; Siemens Healthcare, Germany) P2Y test. Methods Polymorphisms of CYP2C19*2, *3, *17 and the degree of inhibition of platelet function were determined in 83 patients. Three different platelet function tests were used to evaluate the degree of platelet inhibition and to check the association with genotype. Results The post-procedure PFA-200 values of extensive metabolizers (EM) patients (285.3±38.8) were higher than those of intermediate metabolizers (IM) and poor metabolizers (PM) patients (227.7±98.3 and 133.7±99.2, respectively; P=0.024). Light transmittance aggregometry (LTA) and the VerifyNow system showed that the post-procedure values for EM patients were lower than those of IM and PM patients (LTA: 24.4±15.7, 34.1±17.6, and 42.2±16.9, respectively, P

Two new clerodane diterpenoids (1-2), one new clerodane diterpenoid alkaloid (3), as well as thirteen known compounds were isolated from Croton crassifolius. The structures of new compounds were established by a combination of spectroscopic methods, including HRMS, (1)H NMR, (13)C NMR, (1)H (1)H COSY, HSQC, HMBC, NOESY and X-ray crystallographic analysis. Compound 3 is firstly reported as the clerodane-type diterpenoid alkaloid in natural products. All of the compounds were evaluated for in vitro cytotoxic activities against CT26.WT cell using the MTT method.

Purpose: Examining the role of developmental signaling pathways in “driver gene–negative” lung adenocarcinoma (patients with lung adenocarcinoma negative for EGFR, KRAS, BRAF, HER2, MET, ALK, RET, and ROS1 were identified as “driver gene–negative”) may shed light on the clinical research and treatment for this lung adenocarcinoma subgroup. We aimed to investigate whether developmental signaling pathways activation can stratify the risk of “driver gene–negative” lung adenocarcinoma. Experimental Design: In the discovery phase, we profiled the mRNA expression of each candidate gene using genome-wide microarrays in 52 paired lung adenocarcinoma and adjacent normal tissues. In the training phase, tissue microarrays and LASSO Cox regression analysis were applied to further screen candidate molecules in 189 patients, and we developed a predictive signature. In the validation phase, one internal cohort and two external cohorts were used to validate our novel prognostic signature. Results: Kyoto Encyclopedia of Genes and Genomes pathway analysis based on whole-genome microarrays indicated that the Wnt/β-catenin pathway was activated in “driver gene–negative” lung adenocarcinoma. Furthermore, the Wnt/β-catenin pathway–based gene expression profiles revealed 39 transcripts differentially expressed. Finally, a Wnt/β-catenin pathway–based CSDW signature comprising 4 genes (CTNNB1 or β-catenin, SOX9, DVL3, and Wnt2b) was developed to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter overall survival [HR, 10.42; 6.46–16.79; P < 0.001) than patients with low-risk scores. Conclusions: The CSDW signature is a reliable prognostic tool and may represent genes that are potential drug targets for “driver gene–negative” lung adenocarcinoma.

Artificial intelligence (AI)-based methods have emerged as powerful tools to transform medical care. Although machine learning classifiers (MLCs) have already demonstrated strong performance in image-based diagnoses, analysis of diverse and massive electronic health record (EHR) data remains challenging. Here, we show that MLCs can query EHRs in a manner similar to the hypothetico-deductive reasoning used by physicians and unearth associations that previous statistical methods have not found. Our model applies an automated natural language processing system using deep learning techniques to extract clinically relevant information from EHRs. In total, 101.6 million data points from 1,362,559 pediatric patient visits presenting to a major referral center were analyzed to train and validate the framework. Our model demonstrates high diagnostic accuracy across multiple organ systems and is comparable to experienced pediatricians in diagnosing common childhood diseases. Our study provides a proof of concept for implementing an AI-based system as a means to aid physicians in tackling large amounts of data, augmenting diagnostic evaluations, and to provide clinical decision support in cases of diagnostic uncertainty or complexity. Although this impact may be most evident in areas where healthcare providers are in relative shortage, the benefits of such an AI system are likely to be universal.

OBJECTIVE This study evaluated the diagnostic value of measuring the levels of procalcitonin (PCT) and C-reactive protein (CRP) to differentiate children co-infected with H1N1 influenza and bacteria from children infected with H1N1 influenza alone. METHODS Consecutive patients (children aged

Background To investigate, using Magnetic Resonance Imaging (MRI) and voxel-based morphometry (VBM), morphometric changes of cerebellum in Parkinson's disease with different motor and affective subtypes. Methods Fifty-four patients with idiopathic Parkinson's disease (PD) were classified into tremor-predominant-PD (PDT) (n = 37) and akinetic/rigidity-predominant-PD (PDAR) (n = 17). Moreover, PD groups were divided into four affective subtypes, including depressive but not anxious PD (dPD, n = 5), anxious but not depressive PD (aPD, n = 8), comorbid depressive and anxious PD (coPD, n = 8), and PD patients without depressive or anxious symptoms (nPD, n = 33). They were additionally compared at a group level with thirty-nine normal controls (NCs). An analysis of covariance followed by post hoc tests was performed to examine the alterations of cerebellar grey matter volume (GMV) in different groups of PD. Results Compared with NCs, PD showed grey matter (GM) atrophy in the right Crus II, pyramis, culmen, the right lobules IV, and V, and the left lobule VI. PDT, PDAR and NCs did not differ in the volume of the cerebellum. Relative to nPD group, dPD group exhibited GMV reduction in the left Crus I, while aPD group showed GMV reduction in the tonsil and the right lobule VIII. The GM atrophy was also found in the coPD group compared to NCs, including the tonsil, the left lobule VIII, the right lobule VI, the left Crus I, and vermis IV, and V. There was a significant negative correlation between the Hamilton Rating Scale for Depression (HAMD) score and the right lobule IX volume, and a significant negative correlation between the Hamilton Rating Scale for Anxiety (HAMA) score and the right lobule VIII volume. Conclusions These findings suggest that cerebellar changes are involved in PD. It also supports a possible role of the cerebellum in the depressive and anxious symptoms in PD.

Background The strong invasive and metastatic nature of non-small cell lung cancer (NSCLC) leads to poor prognosis. Collagen triple helix repeat containing 1 (CTHRC1) is involved in cell migration, motility and invasion. The object of this study is to investigate the involvement of CTHRC1 in NSCLC invasion and metastasis. Methods A proteomic analysis was performed to identify the different expression proteins between NSCLC and normal tissues. Cell lines stably express CTHRC1, MMP7, MMP9 were established. Invasion and migration were determined by scratch and transwell assays respectively. Clinical correlations of CTHRC1 in a cohort of 230 NSCLC patients were analysed. Results CTHRC1 is overexpressed in NSCLC as measured by proteomic analysis. Additionally, CTHRC1 increases tumour cell migration and invasion in vitro. Furthermore, CTHRC1 expression is significantly correlated with matrix metalloproteinase (MMP)7 and MMP9 expression in sera and tumour tissues from NSCLC. The invasion ability mediated by CTHRC1 were mainly MMP7- and MMP9-dependent. MMP7 or MMP9 depletion significantly eradicated the pro-invasive effects mediated by CTHRC1 on NSCLC cells. Clinically, patients with high CTHRC1 expression had poor survival. Conclusions CTHRC1 serves as a pro-metastatic gene that contributes to NSCLC invasion and metastasis, which are mediated by upregulated MMP7 and MMP9 expression. Targeting CTHRC1 may be beneficial for inhibiting NSCLC metastasis. Electronic supplementary material The online version of this article (10.1186/s12885-018-4317-6) contains supplementary material, which is available to authorized users.

MicroRNAs (miRNAs) possess oncogenic and tumour‑suppressive roles in the carcinogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) by regulating the expression of numerous cancer‑related genes. Thus, the investigation on the expression and roles of miRNAs in PDAC may facilitate the identification of novel and effective targets for the clinical diagnosis and treatment of patients with PDAC. miRNA‑539 (miR‑539) has been studied in multiple types of human cancer. However, its expression and potential biological function in PDAC remain unclear. In the current study, the expression level, clinical significance, roles and underlying molecular mechanism of miR‑539 in PDAC. The present results demonstrated that miR‑539 expression was downregulated in PDAC tissues and cell lines. A low miR‑539 level was associated with TNM stage and lymph node metastasis of patients with PDAC. miR‑539 overexpression induced a significant reduction in the proliferation, colony formation and invasion of PDAC cells. Insulin‑like growth factor 1 receptor (IGF‑1R) was confirmed as a direct target gene of miR‑539 in PDAC. Further analysis indicated that IGF‑1R was overexpressed in PDAC tissues. Notably, the mRNA expression of IGF‑1R was negatively correlated with miR‑539 levels in PDAC tissues. In addition, the recovered IGF‑1R expression also partially counteracted the suppressive roles of miR‑539 overexpression in PDAC cells. Overall, miR‑539 may inhibit the aggressive behaviour of PDAC by directly targeting IGF‑1R and may serve as a novel therapeutic target for patients with this disease.

Acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide, while early diagnosis still represents an upmost priority. While platelet activation is critical for AMI pathogenesis, the role of platelet microRNAs (pmiRNAs) as biomarkers for AMI is unclear. Furthermore, correlations between the levels of pmiRNAs and indices of platelet activity are also unknown. Expression of platelet miR-1, miR-21, miR-126, miR-150 and miR-223 were prospectively assessed in 20 ST-segment elevation myocardial infarction (STEMI) patients, and 40 healthy volunteers. Platelet reactive units (PRU) were assessed with cartridge analyzer, and vasodilator-stimulated phosphoprotein (VASP) was measured by flow cytometry. There were no significant changes in pmiR-1 expression. Expressions of pmiR-21 and pmiR-126 were decreased, while pmiR-150 and pmiR-223 were increased in STEMI patients when compared to controls (all p

The polysomnography after nasopharyngeal tube insertion (NPT-PSG) was used to assess glossopharyngeal airway obstruction in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS), and was compared with that obtained using spiral computed tomography (CT). A total of 125 patients diagnosed with moderate-to-severe OSAHS using PSG were subjected to PSG after NPT insertion, and spiral CT was used for continuous scan of the upper respiratory tract. The NPT-PSG and CT scan results were subjected to correlation analysis. In addition, the two sets of data were used separately to determine whether there was glossopharyngeal airway stenosis or obstruction, and the results were compared. Neither apnea hypopnea index (AHI) nor lowest oxygen saturation (LSaO2) obtained from the first PSG was significantly correlated with the cross-sectional area or the inner diameter of the glossopharyngeal airway. NPT-PSG AHI was significantly correlated with the cross-sectional area and anteroposterior diameter of the glossopharyngeal airway, with correlation coefficients of 0.264 and 0.185, and P values of 0.003 and 0.039, respectively. NPT-PSG AHI was not significantly correlated with the left-right diameter of the airway, and NPT-PSG LSaO2 was not significantly correlated with the cross-sectional area or the inner diameter of the glossopharyngeal airway. With NPT-PSG, 52 patients showed obvious glossopharyngeal airway stenosis while 73 patients did not, and with CT scan 41 patients showed obvious glossopharyngeal airway stenosis while 84 patients did not. The two methods reached the same diagnosis in 86 cases, with a consistency rate of 68.8 %. Spiral CT and NPT-PSG show certain degrees of consistency by assessing the presence of glossopharyngeal airway stenosis or obstruction, and there are also notable differences. Clinical assessment on glossopharyngeal airway obstruction should be based on a combination of multiple methods.

Background/Aims: Golgi phosphoprotein 3 (GOLPH3) is a newly reported oncogene that plays a significant role in regulating cell growth. Recent research has shown that overexpression of GOLPH3 is correlated with patient survival and M classification in breast cancer and other cancers. However, the mechanisms by which GOLPH3 contributes to metastasis in non-small cell lung cancer (NSCLC) have not been previously clarified and are therefore the focus of this work. Methods: Immunohistochemistry (IHC) and western blotting analysis were performed to assess the GOLPH3 protein level, small interfering RNA (siRNA) and transwell assays were conducted to investigate the role of GOLPH3 in migration and invasion, and real-time PCR was performed to estimate the level of GOLPH3 mRNA expression. Results: GOLPH3 was significantly correlated with clinicopathological variables, such as the clinical stage (P=0.012), T classification (P=0.002) and metastasis (M classification) (P=0.008), in NSCLC patients and was negatively correlated with the prognosis. Knockdown of GOLPH3 significantly suppressed the migratory and invasive ability of NSCLC cell lines and downregulated the enzyme activity and protein levels of MMP-2 and MMP-9. Conclusions: The expression level of GOLPH3 is correlated with metastasis and prognosis in NSCLC, and GOLPH3 mediates metastasis by regulating the protein levels of MMP-2 and MMP-9 in vitro.

Purpose: The purpose of this study was to identify measles virus in Shanghai in 2012 and study the genotype trend of measles virus epidemic strains during 2000–2012. Methods: Nose and throat swab specimens were collected from 34 suspected measles cases in Shanghai. Measles virus was isolated using Vero-SLAM cells (African green monkey kidney cells/lymphoid signal activating factor-transfected African green monkey kidney cells). The 450 bp of C terminus of the N gene and the entire hemagglutinin gene sequence was amplified using RT-PCR. Phylogenetic analysis was performed by comparing the seven measles strains in Shanghai with the reference strains for H1a, H1b and D8 genotypes, as well as the Chinese measles virus vaccine strain. Results: Seven measles viruses strains were isolated from the 34 throat swap specimens. Six strains were genotype H1a, which is the predominant strain in China and one strain was genotype D8, which is the first imported strain since 2000. All these seven strains maintained most of the glycosylation sites except subtype H1a, which lost one glycosylation site. Conclusion: Since 2000, measles virus strains in Shanghai are consistent with measles virus from other provinces in China with H1a being the predominant genotype. This study is also the first report of genotype D8 strain in Shanghai. All strains maintained their glycosylation sites except H1a that lost one glycosylation site. These strains could still be neutralized by the Chinese measles vaccine. We suggest that Shanghai Center for Disease Control laboratories should strengthen their approaches to monitor measles cases to prevent further spread of imported strains. Keywords: D8 genotype, Importation, Measles virus, Molecular epidemiology

The goals of this study were to explore the reasons after failed uvulopalatopharyngoplasty (UPPP) in some patients with obstructive sleep apnea–hypopnea syndrome (OSAHS), and to observe the efficacy of the second surgery. Twenty-three OSAHS patients with failed UPPP were included in the study. Routine physical exams, electronic endoscopy, computed tomography scan and polysomnography after nasopharyngeal tube insertion were performed to assess the site of upper airway obstruction, and corresponding appropriate surgical treatment was carried out based on the diagnosis. Comprehensive evaluation of the 23 patients revealed that the sites of obstruction after failed UPPP were as follows: 7 cases predominantly in the oropharyngeal area, 2 cases in the nasal, nasopharyngeal and oropharyngeal area, 5 cases predominantly in the glossopharyngeal area and 9 cases in the oropharyngeal and glossopharyngeal areas. Correspondingly, 7 cases underwent improved UPPP alone, 2 cases underwent adenoidectomy or nasal expansion and improved UPPP, 5 cases underwent glossopharyngeal surgery alone and 9 cases underwent improved UPPP and glossopharyngeal surgery. Follow-up for more than 12 months showed that there were four cured cases, 12 cases with marked improvement, and 7 cases with treatment failure. The success rate was 69.6 %. After undergoing UPPP, OSAHS patients may still have oropharyngeal airway obstruction. By performing a detailed preoperative assessment on the patient’s airway condition and clarifying the site of obstruction, performing the second surgical treatment can still achieve a relatively satisfactory treatment outcome.

Yu Sun,1,* Yangshan Chen,1,* Shuhua Li,1,* Yiyan Lei,2 Di Xu,3 Neng Jiang,1 Yang Zhang,4 Jessica Cao,5 Zunfu Ke1,* 1Department of Pathology, 2Department of Thoracic Surgery, TheFirst Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Thoracic Surgery, The Central Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China; 4Biomedical Engineering, The University of Texas atEl Paso, El Paso, TX, USA; 5Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada *These authors contributed equally tothis work Abstract: Lung adenocarcinoma (LADC) is among the most malignant cancers that frequently develops micrometastases even in early stages of the disease. Circulating tumor cell (CTC) number, matrix metalloproteinase (MMP) 7, and MMP9 show great prospects as predictive biomarkers in many tumors. However, the interactions between these biomarkers and the molecular basis of their roles in the metastasis and prognosis of LADC remain unclear. The present study revealed that an elevated CTC count and overexpression of MMP7 and MMP9 correlate with metastasis and clinical progression in LADC patients (n=143). Furthermore, MMP7 and MMP9 upregulation facilitates LADC cell migration in vitro and enhances serum CTC levels in a xenograft mouse model. More importantly, receiver operating characteristic (ROC) curves and Kaplan–Meier analysis confirmed more accurate prediction of metastasis and overall survival (OS) with a combination panel of CTC, MMP7, and MMP9. Taken together, our data show, for the first time, the involvement of MMP7 and MMP9 in the release of CTCs into the peripheral blood, and our data reveal that CTC count and expression of MMP7 and MMP9 can be used together as an effective clinical prediction panel for LADC metastasis and prognosis. Keywords: lung adenocarcinoma, circulating tumor cell, MMP7/MMP9, metastasis, prognosis&nbsp

// Zunfu Ke 1, * , Weiling He 2, * , Yuanhui Lai 3, * , Xuefeng Guo 4 , Sharon Chen 5 , Shuhua Li 1 , Yuefeng Wang 1 , Liantang Wang 1 1 Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 2 Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 3 Vascular and Thyroid Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 4 Department of Gastrointestinal Surgery, the Sixth Affliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 5 Department of Molecular and Medical Pharmacology, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA USA * These authors contributed equally to this work. Correspondence to: Dr. Zunfu ke, e-mail: kezunfu@mail.sysu.edu.cn Dr. Liantang Wang, e-mail: wanglt@mail.sysu.edu.cn Keywords: CTHRC1 non-small cell lung cancer β-catenin metastasis prognosis Received: August 04, 2014 Accepted: August 28, 2014 Published: September 24, 2014 ABSTRACT Collagen triple helix repeat-containing 1 (CTHRC1), a novel oncogene, was identified to be aberrantly overexpressed in several malignant tumors. However, the expression profile of CTHRC1 and its clinical significance in non-small cell lung cancer (NSCLC) remain unknown. In this study, we showed that CTHRC1 was evidently overexpressed in human NSCLC tissues and NSCLC cell lines at the protein and mRNA level. Ectopic up-regulation of CTHRC1 in cancer cells resulted in elevated invasive and proliferative abilities, which were attenuated by the specific CTHRC1 siRNA. The biological effect of CTHRC1 on metastasis and proliferation was mediated by the activation of the Wnt/β-catenin pathway. Furthermore, CTHRC1 immunoreactivity was evidently overexpressed in paraffin-embedded NSCLC tissues (212/292, 72.60%) in comparison to corresponding adjacent non-cancerous tissues (6/66, 9.09%) ( p

The major goal of traditional platelet function tests has been to screen and diagnose patients who present with bleeding problems. However, as the central role of platelets implicated in the etiology of arterial thrombotic diseases such as myocardial infarction and stroke became widely known, platelet function tests are now being promoted to monitor the efficacy of antiplatelet drugs and also to potentially identify patients at increased risk of thrombosis. Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, are mediators of inflammation, and have immunomodulatory activity. As new potential biomarkers and technologies arrive at the horizon, platelet functions testing appears to take on a new aspect. This review article discusses currently available clinical application of platelet function tests, placing emphasis on essential characteristics.

The objective of the study was to evaluate a surgical method to treat patients with obstructive sleep apnea hypopnea syndrome (OSAHS) caused by suspected glossoptosis. Seventy-eight patients with OSAHS caused by suspected glossoptosis were non-randomly divided into two groups. The 45 patients in the first group received uvulopalatopharyngoplasty (UPPP) and tongue-base suspension (Repose). The 33 patients in the second group received UPPP alone. Follow-up was conducted over 6 months, and polysomnography was used to determine the effects of treatment. Follow-up results revealed that the apnea-hypopnea index (AHI) and ESS scores of the patients from both groups were substantially decreased compared to the corresponding values before surgery. The lowest oxygen saturation (LaSo2) of both groups was improved, compared to the level before surgery. The degree of improvement in patients treated with UPPP + Repose was significantly greater than that seen in patients treated with UPPP alone. In the UPPP + Repose group, 17 patients were cured, 23 showed marked improvement, and 5 did not improve. In the UPPP alone group, 1 patient was cured, 16 showed marked improvement, and 16 did not improve. The marked improvement rates of the two groups were 88.9 and 51.5 %, respectively, a significant difference. Patients who show glossopharyngeal obstruction during sleep, and have normal glossopharyngeal airway morphology when awake, should be suspected to have glossoptosis. Repose surgery is an effective operation for the patients with OSAHS suspected glossoptosis.

The lingua/pharynx (L/P) ratio has high sensitivity and specificity in predicting the severity of retroglossal obstruction in patients with obstructive sleep apnea hypopnea syndrome (OSAHS).To evaluate the diagnostic value of the L/P ratio in predicting the severity of retroglossal obstruction in patients with OSAHS.Airway computed tomography (CT) was performed in 115 patients with OSAHS. The retroglossal cross-sectional area (RCSA) was measured at the axial level of the hypopharynx, immediately superior to the tip of the epiglottis. Moreover, nine lines, which were lined up in the order of n = 1, 2, 3, …, 9, were drawn from the genial tubercle (point G) to nine points (point P n ) proximally on the posterior pharyngeal wall and hard palate in the sagittal plane. Meanwhile, the nine lines intersected the lingual surface at point Ln, respectively. The L/P ratios of the lingual segment (G to L n distance) to the pharyngeal segment (G to P n distance) were measured. We analyzed the correlations between nine L/P values (L/P n ) and RCSA.Both simple linear correlation analysis and multiple linear regression analysis showed that L/P6 and L/P9 had significant negative correlations with RCSA.

Conclusions: Modified Friedman stage can be used to predict glossopharyngeal obstruction better than before in patients with obstructive sleep apnea (OSA).Objective: To evaluate the diagnostic value of modified Friedman stage in predicting glossopharyngeal obstruction in patients with OSA.Methods: Eighty-five OSA patients with Friedman stage III were divided into IIIa group and IIIb group based on an imaginary line drawn in the horizontal and middle position of the soft palate. Polysomnography (PSG) was performed after nasopharyngeal tube (NPT) insertion (NPT-PSG) to diagnose glossopharyngeal obstruction. Apnea-hypopnea index (AHI) determined by NPT-PSG (NPT-AHI) and glossopharyngeal obstruction result determined by NPT-PSG (NPT-PSG result) were compared between the two groups.Results: There were significant differences in NPT-AHI (p