Rare tandem repeat expansions associate with genes involved in synaptic and neuronal signaling functions in schizophrenia.

Tandem repeat expansions (TREs) are associated with over 60 monogenic disorders and have recently been implicated in complex disorders such as cancer and autism spectrum disorder. The role of TREs in schizophrenia is now emerging. In this study, we have performed a genome-wide investigation of TREs in schizophrenia. Using genome sequence data from 1154 Swedish schizophrenia cases and 934 ancestry-matched population controls, we have detected genome-wide rare (<0.1% population frequency) TREs that have motifs with a length of 2-20 base pairs. We find that the proportion of individuals carrying rare TREs is significantly higher in the schizophrenia group. There is a significantly higher burden of rare TREs in schizophrenia cases than in controls in genic regions, particularly in postsynaptic genes, in genes overlapping brain expression quantitative trait loci, and in brain-expressed genes that are differentially expressed between schizophrenia cases and controls. We demonstrate that TRE-associated genes are more constrained and primarily impact synaptic and neuronal signaling functions. These results have been replicated in an independent Canadian sample that consisted of 252 schizophrenia cases of European ancestry and 222 ancestry-matched controls. Our results support the involvement of rare TREs in schizophrenia etiology.

Effectiveness of peer-delivered sleep health education and social support in increasing OSA evaluation among at-risk blacks.

To assess the effectiveness of culturally and linguistically tailored, peer-delivered obstructive sleep apnea education and of social support to increase adherence to physician-recommended obstructive sleep apnea evaluation among blacks. In a two-arm randomised controlled trial, we ascertained the effectiveness of peer-delivered obstructive sleep apnea education in increasing obstructive sleep apnea evaluation among 319 blacks at risk of obstructive sleep apnea (intervention = 159 and control = 160); their average age was 47 ± 12.9 years, and 41% were male. Obstructive sleep apnea risk was assessed with the Apnea Risk Evaluation System questionnaire, administered in community venues. Participants in the intervention arm received tailored obstructive sleep apnea education during a 6 month period; those in the control arm received standard sleep and healthy lifestyle information. Analysis focussed on the effectiveness of peer-delivered obstructive sleep apnea education on adherence to obstructive sleep apnea evaluation, but also considered the role of psychosocial factors. The results showed no significant differences in baseline demographic and clinical measures when contrasting participants in the study arms. The adherence rates for home-based obstructive sleep apnea evaluation in the intervention and control arms were 45.9% and 45.6%, respectively. Overall, participants in both study arms (adherers) who underwent obstructive sleep apnea evaluations were likely to experience a greater level of social support (8.2 ± 2.4 vs. 7.3 ± 2.4; p = 0.06). Moreover, adherers showed greater psychosocial scores (i.e., Dysfunctional Beliefs and Attitudes about Sleep scale, Apnea Beliefs Scale (ABS) (and Apnea Knowledge) compared with non-adherers (6.0 ± 1.8 vs. 4.9 ± 2.2; p = 0.02; 77.0 ± 7.1 vs. 73.2 ± 7.4; p = 0.04, and 6.4 ± 3.1 vs. 7.6 ± 2.4; p = 0.06, respectively). The results of the present randomised controlled trial favoured a potential role of peer-based social support and psychosocial factors, associated with obstructive sleep apnea adherence behaviour.

Prediction of Fuhrman grade of renal clear cell carcinoma by multimodal MRI radiomics: a retrospective study.

AIM: To explore the value of multimodal magnetic resonance imaging (MRI) radiomics combined with traditional radiologist-defined semantic characteristics and conventional (cMRI) and functional MRI (fMRI) texture features in predicting Fuhrman grade of clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: The data of 89 patients with histopathologically proven ccRCC (low-grade, 54; high-grade, 35) were collected. Texture features were extracted from cMRI (T1- and T2-weighted imaging) and fMRI (Dixon-MRI; blood-oxygen-level dependent [BOLD]-MRI; and susceptibility-weighted imaging [SWI]) images, and the traditional characteristics (TC) were evaluated. Logistic regression analysis was performed to develop models based on TC, cMRI, and fMRI texture features for grading. Receiver operating characteristic (ROC) curve analysis and leave-group-out cross-validation (LGOCV) were performed to test the reliability of combined models. RESULTS: Two T2-weighted imaging-based, two Dixon_W-based, one Dixon_F-based, one BOLD-based, and three SWI-based texture features, and three TC were extracted for feature selection. TC, cMRI, fMRI, cMRI+fMRI, cMRI+TC, fMRI+TC, and cMRI+fMRI+TC models were constructed. The AUC of the cMRI+fMRI+TC model for differentiating high- from low-grade ccRCC was 0.74, with 81.42% accuracy, 75.93% sensitivity, and 91.43% specificity. The fMRI+TC model exhibited a performance similar to that of the cMRI+fMRI+TC model (p>0.05). The areas under the curve (AUCs) of the fMRI+TC and cMRI+fMRI+TC models were significantly higher than those of the other five models (all p<0.05). For the cMRI+fMRI+TC model, the mean accuracy was 85.40% after 100 LGOCV for the test sets. CONCLUSION: Multimodal MRI radiomics combined with TC, cMRI, and fMRI texture features may be a reliable quantitative approach for differentiating high-grade ccRCC from low-grade ccRCC.

The impact of educational attainment, intelligence and intellectual disability on schizophrenia: a Swedish population-based register and genetic study.

Schizophrenia (SCZ) is highly heterogenous and no subtypes characterizing treatment response or longitudinal course well. Cognitive impairment is a core clinical feature of SCZ and a determinant of poorer outcome. Genetic overlap between SCZ and cognitive traits is complex, with limited studies of comprehensive epidemiological and genomic evidence. To examine the relation between SCZ and three cognitive traits, educational attainment (EDU), premorbid cognitive ability, and intellectual disability (ID), we used two Swedish samples: a national cohort (14,230 SCZ cases and 3,816,264 controls) and a subsample with comprehensive genetic data (4992 cases and 6009 controls). Population-based analyses confirmed worse cognition as a risk factor for SCZ, and the pedigree and SNP-based genetic correlations were comparable. In the genotyped cases, those with high EDU and premorbid cognitive ability tended to have higher polygenetic risk scores (PRS) of EDU and intelligence and fewer rare exonic variants. Finally, by applying an empirical clustering method, we dissected SCZ cases into four replicable subgroups characterized by EDU and ID. In particular, the subgroup with higher EDU in the national cohort had fewer adverse outcomes including long hospitalization and death. In the genotyped subsample, this subgroup had higher PRS of EDU and no excess of rare genetic burdens than controls. In conclusion, we found extensive evidence of a robust relation between cognitive traits and SCZ, underscoring the importance of cognition in dissecting the heterogeneity of SCZ.

[The comparison of modified ESUR score and Mehralivand grade based on biparametric MRI for assessing extracapsulare extension in prostate cancer].

Objective: To compare the value of the modified European Society of Urogenital Radiology (ESUR) score and Mehralivand grade based on biparametric MRI (bpMRI) in the assessment of extracapsular extension (ECE) in patients with prostate cancer (PCa). Methods: Data of 235 patients with postoperative pathology confirmed PCa, who underwent preoperative 3.0 T bpMRI examinations between March 2019 and March 2022 in the First Affiliated Hospital of Soochow University were retrospectively evaluated, including 107 ECE positive and 128 ECE negative cases, aged [M (Q1, Q3)] [71 (66, 75)] years. Reader 1 and 2 assessed the ECE using the modified ESUR score and Mehralivand grade, and the receiver operating characteristic curve and Delong test were used to evaluate the performance of the two scoring methods. Then, the statistically significant variables were included in multivariate binary logistics regression analysis to obtain the risk factors, which were combined with the scores of reader 1 to establish combined models. The assessment ability of the two combined models and the two scoring methods were compared subsequently. Results: The AUC of Mehralivand grade in reader 1 were higher than that of the modified ESUR score in reader 1 and 2 [0.746 (95%CI: 0.685-0.800) vs 0.696 (95%CI: 0.633-0.754) and 0.691 (95%CI: 0.627-0.749), both P<0.05]. The AUC of Mehralivand grade in reader 2 was higher than that of the modified ESUR score in reader 1 and 2 [0.753 (95%CI: 0.693-0.807) vs 0.696 (95%CI: 0.633-0.754) and 0.691 (95%CI: 0.627-0.749), both P<0.05]. The AUC of the combined model 1 based on the modified ESUR score and the combined model 2 based on Mehralivand grade were higher than that in the separate modified ESUR score [0.826 (95%CI: 0.773-0.879) and 0.841 (95%CI: 0.790-0.892) vs 0.696 (95%CI: 0.633-0.754), both P<0.001], and also higher than that in the separate Mehralivand grade [0.826 (95%CI: 0.773-0.879) and 0.841 (95%CI: 0.790-0.892) vs 0.746 (95%CI: 0.685-0.800), both P<0.05]. Conclusion: Based on bpMRI, the Mehralivand grade showed better diagnostic performance for assessing ECE preoperatively in patients with PCa than the modified ESUR score. The combination model of scoring methods and clinical variables can further enhance the diagnostic certainty in the assessment of ECE.

[Cortical thickness and cognitive impairment in patients with amyotrophic lateral sclerosis].

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with high morbidity and mortality. There are about 5%-15% of ALS patients combining with frontotemporal lobe degeneration (FTLD) at the same time and 50% of patients combing with cognitive function changes. The analysis of cortical thickness based on MRI is an important imaging method to evaluate brain structure. The aim of the study was to explore the changes of brain structure in ALS patients by cortical thickness analysis, and to explore the correlation between the brain structure and cognitive function. METHODS: In the study, 18 ALS patients treated in Department of Neurology, Peking University Third Hospital and 18 normal controls (age, gender and education level matched) were included. 3D magnetization prepared rapid gradient echo imaging (MPRAGE) sequence MRI was performed and the cortical thickness was analyzed. At the same time, all the ALS patients took neuropsychology assessments, including: mini-mental state examination (MMSE), verbal fluency test (VFT), Stroop color word test (SCWT), prospective memory (PM), emotional picture perception and recognition, and faux pas story test. RESULTS: After cognitive assessment, two ALS patients had cognitive impairment. One was in accordance with ALS-frontotemporal dementia (FTD) diagnosis and the other one was in accordance with ALS cognitive impairment (ALSci) diagnosis. In all the 18 ALS patients and 18 normal controls, the cortical thickness of the left medial orbitofrontal lobe and the medial temporal lobe were significantly reduced (P < 0.05) in ALS group by the vertex-wise comparison. Cortical thickness of the left entorhinal cortex, the left inferior temporal gyrus, the left medial orbitofrontal lobe and the left insular lobe was significantly reduced (P < 0.05) by the region-wise comparison. However, when only concluded the 16 ALS non-cognitive impairment patients, there was no significant difference between the two groups (P>0.05). There were correlations between the scores of prospective memory, emotional picture perception and recognition, faux pas story test and the cortical thickness of their corresponding regions (P < 0.05). CONCLUSION: The cortical thickness of ALS patients are correlated with neuropsychological scores which may reflect the changes of cortical structure corresponding to the cognitive assessment, and may provide help for the early diagnosis of cognitive changes in ALS patients.

[Endoscopic diagnosis and treatment of early colorectal cancer and precancerous lesions: current status and future prospects].

Early detection of colorectal cancer and precursor lesions under colonoscopy, and timely and optimal treatment remain the crucial means for reducing colorectal cancer-related deaths. In this article, we focused on the hot spots in recent years, reviewed the progress of endoscopic diagnosis and treatment of serrated lesions and inflammatory bowel disease (IBD)-related dysplasia, the application of endocytoscopy and the management of early colorectal cancer/precancerous lesions, and provided new prospects for future studies.

[The characteristics of gut microbiota in type 2 diabetes mellitus patients with hypertriglyceridemia].

Objective: To investigate the characteristics of gut microbiota in type 2 diabetes mellitus (T2DM) patients with hypertriglyceridemia (HTG). Methods: Eighty-one patients first diagnosed with T2DM were enrolled in the Third Xiangya Hospital of Central South University from January 2018 to December 2020, including 58 patients [46 males and 12 females, aged (43±13) years] with HTG [HTG group, triglyceride (TG)≥1.7 mmol/L]. There were 23 cases without HTG (NTG group), including 20 males and 3 females, aged (46±13) years. According to the severity of HTG, the patients of HTG group were divided into severe HTG group (STG group, TG ≥5.6 mmol/L) and mild HTG group (MTG group, 1.7 mmol/L≤TG<5.6 mmol/L). Thirty healthy controls were matched accordingly, including 21 males and 9 females, aged (45±6) years. Clinical laboratory indicators and feces of the subjects were collected and 16S rRNA sequencing was performed to compare the differences in intestinal flora among the groups. Results: The Shannon and Simpson indexes in HTG group were lower than those in NTG group and healthy control group (5.02±0.91 vs 5.45±0.55 and 5.60±0.63, P=0.003; 0.90±0.06 vs 0.93±0.04, 0.94±0.04, P=0.002). Compared with healthy control group and NTG group, the abundance of intestinal P_Proteobacteria, g_Escherichia_Shigella, s_Escherichia_Coli and g_Clostridium_sensu_stricto_1 increased in HTG group, while the abundance of p_Firmicutes, g_Faecalibacterium and Faecalibacterium_prausnitzii decreased. The abundance of g_Clostridium_sensu_stricto_1 in the STG group was higher than that of NTG and MTG groups, while the abundance of g_Faecalibacterium decreased. Spearman correlation analysis suggested that g_Clostridium_sensu_stricto_1 was positively correlated with glycosylated hemoglobin (r=0.22, P=0.044), fasting blood glucose (r=0.36, P=0.001), TG (r=0.27, P=0.015) and total cholesterol (r=0.44, P<0.001). Logistic regression analysis indicated that g_Faecalibacterium was a protective factor for T2DM with HTG(OR=0.90, 95%CI:0.83-0.97, P=0.006). Conclusions: The intestinal flora of T2DM patients with HTG was dysregulated, which was manifested as decreased diversity, increased abundance of P_Proteobacteria and decreased abundance of p_Firmicutes. g_Faecalibacterium is a protective factor for T2DM with HTG.

[Review of risk evaluation scores for benign end stage liver diseases recipients].

Liver transplant is an unreplaceable method for benign end-stage liver disease. The risk evaluation for the waiting list recipients and for post-transplant survival could provide practical indication for organ allocation. In recent years, there are two major kinds of evaluation scores. The first kind of evaluation scores is based on model for end-stage liver disease(MELD) score,including SOFT/P-SOFT score,UCLA-FRS score and BAR score. The other evaluation system is based on the concept of acute-on-chronic liver failure,including CLIF-C-ACLF score,TAM score,AARC-ACLF score and COSSH-ACLF score. The scores based on ACLF have been shown superior power in predicting waiting list survival and post-transplant prognosis than MELD. This article reviews the two kinds of evaluation scores,aiming for the better allocation policy and the better prognosis of benign end-stage liver disease.

[Review of risk evaluation scores for benign end stage liver diseases recipients].

Liver transplant is an unreplaceable method for benign end-stage liver disease. The risk evaluation for the waiting list recipients and for post-transplant survival could provide practical indication for organ allocation. In recent years, there are two major kinds of evaluation scores. The first kind of evaluation scores is based on model for end-stage liver disease(MELD) score,including SOFT/P-SOFT score,UCLA-FRS score and BAR score. The other evaluation system is based on the concept of acute-on-chronic liver failure,including CLIF-C-ACLF score,TAM score,AARC-ACLF score and COSSH-ACLF score. The scores based on ACLF have been shown superior power in predicting waiting list survival and post-transplant prognosis than MELD. This article reviews the two kinds of evaluation scores,aiming for the better allocation policy and the better prognosis of benign end-stage liver disease.

Wolbachia affects reproduction in the spider mite Tetranychus truncatus (Acari: Tetranychidae) by regulating chorion protein S38-like and Rop.

Wolbachia-induced reproductive regulation in hosts has been used to control pest populations, but little is known about the molecular mechanism underlying Wolbachia regulation of host genes. Here, reproductive regulation by Wolbachia in the spider mite Tetranychus truncatus was studied at the molecular level. Infection with Wolbachia resulted in decreasing oviposition and cytoplasmic incompatibility in T. truncatus. Further RNA-seq revealed genes regulated by Wolbachia in T. truncatus. Real-time quantitative polymerase chain reaction (qPCR) showed that genes, including chorion protein S38-like and Rop were down-regulated by Wolbachia. RNA interference (RNAi) of chorion protein S38-like and Rop in Wolbachia-uninfected T. truncatus decreased oviposition, which was consistent with Wolbachia-induced oviposition decrease. Interestingly, suppressing Rop in Wolbachia-infected T. truncatus led to increased Wolbachia titres in eggs; however, this did not occur after RNAi of chorion protein S38-like. This is the first study to show that chorion protein S38-like and Rop facilitate Wolbachia-mediated changes in T. truncatus fertility. In addition, RNAi of Rop turned the body colour of Wolbachia-uninfected T. truncatus black, which indicates that the role of Rop is not limited to the reproductive regulation of T. truncatus.

Association test using Copy Number Profile Curves (CONCUR) enhances power in rare copy number variant analysis.

Copy number variants (CNVs) are the gain or loss of DNA segments in the genome that can vary in dosage and length. CNVs comprise a large proportion of variation in human genomes and impact health conditions. To detect rare CNV associations, kernel-based methods have been shown to be a powerful tool due to their flexibility in modeling the aggregate CNV effects, their ability to capture effects from different CNV features, and their accommodation of effect heterogeneity. To perform a kernel association test, a CNV locus needs to be defined so that locus-specific effects can be retained during aggregation. However, CNV loci are arbitrarily defined and different locus definitions can lead to different performance depending on the underlying effect patterns. In this work, we develop a new kernel-based test called CONCUR (i.e., copy number profile curve-based association test) that is free from a definition of locus and evaluates CNV-phenotype associations by comparing individuals' copy number profiles across the genomic regions. CONCUR is built on the proposed concepts of "copy number profile curves" to describe the CNV profile of an individual, and the "common area under the curve (cAUC) kernel" to model the multi-feature CNV effects. The proposed method captures the effects of CNV dosage and length, accounts for the numerical nature of copy numbers, and accommodates between- and within-locus etiological heterogeneity without the need to define artificial CNV loci as required in current kernel methods. In a variety of simulation settings, CONCUR shows comparable or improved power over existing approaches. Real data analyses suggest that CONCUR is well powered to detect CNV effects in the Swedish Schizophrenia Study and the Taiwan Biobank.

[Consensus and controversy on accurate diagnosis and treatment of resectable gastric cancer].

Gastric cancer is a common malignant tumor of digestive tract in China. Precise, minimally invasive and standardized surgical operation is an important part of comprehensive treatment for gastric cancer. In recent years, indications for minimally invasive surgery have been expanding, research on precision surgery has been deepening, and the standardized surgical quality evaluation and control system has been improving. Accurate diagnosis and staging, multi-disciplinary comprehensive diagnosis and treatment model, enhanced recovery after surgery and whole-process management of nutrition support and other aspects have been comprehensively developed. A number of Chinese expert consensus has been issued, which is conducive to the rapid and good recovery of patients, achieving the double benefits of improving the quality of life and prolongation of survival. However, the precise treatment of complex conditions is still full of controversy. This consensus is formulated to facilitate the standardization of the diagnosis and treatment of gastric cancer.

[Preliminary application of the Asia-Pacific colorectal screening score combined with the quantitative fecal occult blood in colorectal neoplasia screening].

To evaluate the efficacy of the Asia-Pacific colorectal screening (APCS) score combined with the quantitative fecal immunochemical test in colorectal neoplasia screening. Subjects who appointment to receive colonoscopy were recruited from August 2017 to May 2019 in the digestive endoscopy center. Before the colonoscopy, all subjects were scored by the Asia Pacific colorectal cancer screening scoring system and measured by quantitative fecal immunochemical test (QFIT). The detection rates of colorectal neoplasia were compared to evaluate the efficacy of the combined assay in colorectal neoplasia screening between APCS score and QFIT. A total of 1 420 subjects were enrolled in this study, APCS score medium-risk (MR) and high-risk (HR) groups were 847 (59.7%) and 573 (40.4%) and 26 cases (1.8%) of colorectal cancer, 196 cases (13.8%) of advanced adenoma, and 395 cases (27.8%) of non-advanced adenoma were detected. With the combination of APCS score and QFIT, participants were classified into 4 groups high-risk with positive QFIT result group G1, high-risk with negative QFIT result group G2, medium-risk with positive QFIT group G3, medium-risk negative QFIT group G4. The prevalence of colorectal neoplasia was 64.3%, 16.4%, 55.0%, and 9.8%, respectively. The prevalence of advanced neoplasia in high-risk with QFIT results was significantly higher than that in other 3 groups. HR and positive QFIT were the indicators for further colonoscopy, and MR with FIT negative group could postpone colonoscopy and conduct annual QFIT follow-up. The combination of APCS score and QFIT for colorectal neoplasia screening can reduce unnecessary colonoscopy, improve colonoscopy compliance and screening efficiency, and has important clinical significance and promotion value in colorectal tumor screening.

PATCHING RETINAL BREAKS WITH HEALAFLOW IN 27-GAUGE VITRECTOMY FOR THE TREATMENT OF RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To report the surgical outcomes of primary rhegmatogenous retinal detachment (RRD) repaired by 27-gauge pars plana vitrectomy combined with Healaflow patch and air tamponade. METHODS: In an initial vitro experiment, we observed and compared the dissolution and displacement of the dispersion spots of 0.05-mL Healaflow and sodium hyaluronate. We then performed a prospective, interventional cohort study on 38 eyes in 37 consecutive patients with primary rhegmatogenous retinal detachment. All eyes underwent pars plana vitrectomy combined with Healaflow patch and air tamponade; the postoperative period did not involve prone positioning. The primary and final anatomical attachment rate, best-corrected visual acuity, and intraoperative and postoperative complications were evaluated. RESULTS: In the in vitro experiment, the viscoelastic Healaflow remained adherent with no change in the size of the area; however, the control dissolved completely in the balance solution. The patient study included 16 women (43.2%) and 21 men (56.8%) (mean age, 59.5 ± 9.5 years; mean follow-up period, 8.9 ± 3.8 months). A single break was present in 21 (55.3%) and 2 to 5 breaks in 17 cases (44.8%). The macula was involved in 25 (65.8%) and attached in 13 cases (34.2%) intraoperatively. Initial reattachment was achieved in 37 (97.4%) and final reattachment in 38 cases (100%). In one case (2.6%), the macula redetached because of failure of the chorioretinal scar to develop around the treated break. Mean preoperative and postoperative best-corrected visual acuities were 1.02 ± 0.82 logarithm of the minimum angle of resolution (median Snellen acuity: 20/125, range: 20/20,000-20/20) and 0.23 ± 0.17 logarithm of the minimum angle of resolution (median Snellen acuity: 20/32, range: 20/100-20/20), respectively (P < 0.001). Intraocular pressure was elevated transiently in 28 eyes (73.7%). There were no other intraoperative complications or postoperative scleral incision leakage. CONCLUSION: A 27-gauge pars plana vitrectomy combined with Healaflow patch, and air tamponade results in a high reattachment rate in the treatment of rhegmatogenous retinal detachment. Thus, patients can benefit from early visual recovery and less complications.

[The optimal thresholds of the quantitative fecal immunochemical test for opportunistic screening of colorectal neoplasia].

Objective: To investigate the significance of quantitative fecal immunochemical test (FIT) for opportunistic screening of colorectal neoplasia, and to propose the most optimal thresholds to improve the screening level of early colorectal neoplasia. Methods: The opportunistic screening participants were recruited from the Department of Gastroenterology & GI Endoscopy Center of the Seventh Medical Center of PLA General Hospital, and stool sample was collected before colonoscopy and the quantitative FIT was analyzed by OC-MICRO analysator for each patient. We assessed test performance in detecting colorectal neoplasia (advanced adenoma and CRC)with different thresholds on sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: A total of 1 448 objects were enrolled in this study, including 714 male (49.3%)and 734 female (50.7%).All participants were classified according to the result of colonoscopy and pathology, and 242 cases of colorectal neoplasia were found, containing 157 advanced adnoma and 85 colorectal cancer. The FIT threshold increased from 50 µg/L to 200 µg/L, while the positivity rate dropped from 11.5% to 8.6% and the sensitivity in detecting colorectal neoplasia dropped from 47.9% to 38.8%. However, the specificity increased from 96.8% to 98.2% and the positive predictive value increased from 82.3% to 87.0%.The miss rate of colorectal cancer increased from 11.8% (n=10) to 17.6% (n=15) along with the increase in FIT thresholds, but the miss rate of 100 µg/L and 150 µg/L was the same as 12.9% (n=11). Conclusions: Quantitative FIT,which is simple and fast,with the threshold of 100 µg/L for opportunistic screening, has a high sensitivity and specificity for the diagnosis of colorectal neoplasia,and is an important index in screening and diagnosis of colorectal neoplasia.

Systematic review and meta-analysis of elective and urgent late open conversion after failed endovascular aneurysm repair.

BACKGROUND: In this study, we systematically reviewed late open conversions after failed endovascular aneurysm repair (EVAR), assessed the methodologic quality of the included studies, and performed a meta-analysis on the 30-day mortality rates for urgent and elective late conversions. METHODS: Electronic databases were systematically searched for studies published up to June 2018 that focused on late open conversion of failed EVAR (ie, >30 days after the initial EVAR), reported the primary outcome of 30-day mortality rate, and distinguished the 30-day mortality rate between urgent and elective late conversions. Two independent reviewers assessed the methodologic quality of the included studies with the Methodological Index for Non-Randomized Studies. Data on baseline demographics, indication for conversion, surgical approach, and early and late mortality rates were recorded. Reported data correspond to the average or range of the means reported in the individual studies. A random-effects model was used to pool 30-day mortality rates for urgent and elective late conversion. RESULTS: There were 27 retrospective studies with a total of 791 patients available for analysis, with 617 elective and 174 urgent late conversions. The methodologic quality was mostly poor (median, 6; interquartile range, 5-7). The mean time from primary EVAR to conversion was 35.1 months (95% confidence interval [CI], 30.4-39.8 months). The most commonly explanted endografts were Excluder (W. L. Gore & Associates, Flagstaff, Ariz) in 16.2%, Talent (Medtronic, Minneapolis, Minn) in 14.5%, and AneuRx (Medtronic) in 13.7%. Nineteen other types of endografts were used in 43.3%; the type of endograft was not reported in 12.3%. A transperitoneal approach was used in a mean 74.0% of conversions (95% CI, 70.9%-77.0%), and complete endograft explantation was performed in 478 (60.4%) patients (95% CI, 57.0%-63.8%). The complication rate was 36.7% (95% CI, 27.0%-46.4%). Temporary or permanent hemodialysis after conversion was required in 3.9% of patients (95% CI, 2.6%-5.2%). The pooled estimate for the 30-day mortality rate was 2.8% (95% CI, 1.5%-4.0%; P = .726) for elective late conversions and 28.1% (95% CI, 18.9%-37.3%; P < .001) for urgent late conversions. CONCLUSIONS: Type I endoleak and rupture are the most common indications for, respectively, elective and urgent conversions. A 10 times higher 30-day mortality rate was observed for patients treated with late open conversion in an urgent vs elective setting. The 30-day mortality rate of elective late open conversions is almost comparable to that of primary elective open abdominal aortic aneurysm repair procedures. For the interpretation of the outcomes of the review, however, the methodologic quality of the available literature should be considered.

Micro124-mediated AHR expression regulates the inflammatory response of chronic rhinosinusitis (CRS) with nasal polyps.

MicroRNAs represent a component of the innate immune responses that can restrain inflammatory signaling, miR124 is an important member of inflammation-associated miRNAs, and abnormal miR124 expression is observed in many inflammatory diseases and immune disorders. However, the role and signaling pathways of miR124 in chronic rhinosinusitis with nasal polyps (CRSwNPs) have not been studied in detail. The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is highly conserved in evolution and plays important roles in the inflammatory response process. In our study, we describe the role of miR124 in the inflammatory response of CRS with nasal polyps. We found that the expression of miR124 was decreased in nasal polyps, and negatively correlated with the expression of AHR. MiR124 can inhibit AHR expression by directly target 3' untranslated region (3'-UTR) of AHR. To further investigate the relationship between miR124, AHR and CRS inflammatory response, we transfect HNEpC cells with miR124 mimic, miR124 inhibitors or siRNA of AHR, then all the results showed that miR124 could regulates cellular inflammatory response through negatively regulating AHR expression. This study demonstrated that the regulation of AHR expression by miR124 is critical to the development of inflammatory response in CRSwNPs.

Evolutionary divergence of mitochondrial genomes in two Tetranychus species distributed across different climates.

There is increasing evidence that mitochondrial genomes (mitogenomes) can be under selection, whereas the selective regimes shaping mitogenome evolution remain largely unclear. To test for mitogenome evolution in relation to the climate adaptation, we explored mtDNA variation in two spider mite (Tetranychus) species that distribute across different climates. We sequenced 26 complete mitogenomes of Tetranychus truncates, which occurs in both warm and cold regions, and nine complete mitogenomes of Tetranychus pueraricola, which is restricted to warm regions. Patterns of evolution in the two species' mitogenomes were compared through a series of dN /dS methods and physicochemical profiles of amino acid replacements. We found that: (1) the mitogenomes of both species were under widespread purifying selection; (2) elevated directional adaptive selection was observed in the T. truncatus mitogenome, perhaps linked to the cold climates adaptation of T. truncatus; and (3) the strength of selection varied across genes, and diversifying positive selection detected on ND4 and ATP6 pointed to their crucial roles during adaptation to different climatic conditions. This study gained insight into the mitogenome evolution in relation to the climate adaptation.

Genome-wide association study of positive emotion identifies a genetic variant and a role for microRNAs.

Positive affect denotes a state of pleasurable engagement with the environment eliciting positive emotion such as contentment, enthusiasm or happiness. Positive affect is associated with favorable psychological, physical and economic outcomes in many longitudinal studies. With a heritability of ⩽64%, positive affect is substantially influenced by genetic factors; however, our understanding of genetic pathways underlying individual differences in positive affect is still limited. Here, through a genome-wide association study of positive affect in African-American participants, we identify a single-nucleotide polymorphism, rs322931, significantly associated with positive affect at P<5 × 10-8, and replicate this association in another cohort. Furthermore, we show that the minor allele of rs322931 predicts expression of microRNAs miR-181a and miR-181b in human brain and blood, greater nucleus accumbens reactivity to positive emotional stimuli and enhanced fear inhibition. Prior studies have suggested that miR-181a is part of the reward neurocircuitry. Taken together, we identify a novel genetic variant for further elucidation of genetic underpinning of positive affect that mediates positive emotionality potentially via the nucleus accumbens and miR-181.