Astrocytes modulate brain phosphate homeostasis via polarized distribution of phosphate uptake transporter PiT2 and exporter XPR1.

Aberrant inorganic phosphate (Pi) homeostasis causes brain calcification and aggravates neurodegeneration, but the underlying mechanism remains unclear. Here, we found that primary familial brain calcification (PFBC)-associated Pi transporter genes Pit2 and Xpr1 were highly expressed in astrocytes, with importer PiT2 distributed over the entire astrocyte processes and exporter XPR1 localized to astrocyte end-feet on blood vessels. This polarized PiT2 and XPR1 distribution endowed astrocyte with Pi transport capacity competent for brain Pi homeostasis, which was disrupted in mice with astrocyte-specific knockout (KO) of either Pit2 or Xpr1. Moreover, we found that Pi uptake by PiT2, and its facilitation by PFBC-associated galactosidase MYORG, were required for the high Pi transport capacity of astrocytes. Finally, brain calcification was suppressed by astrocyte-specific PiT2 re-expression in Pit2-KO mice. Thus, astrocyte-mediated Pi transport is pivotal for brain Pi homeostasis, and elevating astrocytic Pi transporter function represents a potential therapeutic strategy for reducing brain calcification.

Attentional bias modification and attention control training in PTSD: a systematic review and meta-analysis.

Background: Cognitive models of post-traumatic stress disorder (PTSD) highlighted the effect of maladaptive cognitive processing in the development and maintenance of PTSD. PTSD is related to attentional bias (AB) toward threatening stimuli and greater attentional bias variability (ABV). Attentional bias modification (ABM) and attention control training (ACT) have demonstrated the effect of improving PTSD, but the results of randomized controlled trials (RCTs) are controversial. Objectives: The current study aimed to evaluate the extent of evidence supporting the efficacy of ABM in the treatment of PTSD. Design: Systematic review and meta-analysis. Methods: We searched PUBMED, PsycINFO, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials for articles published between 1980 and 2022. RCTs of ABM for adult participants with PTSD symptoms were identified. The primary outcome was changes in PTSD severity, and the second outcome was changes in AB and ABV. Trial quality was assessed using the Cochrane Risk of Bias Tool. Publication bias was assessed using the Doi plot and Luis Furuya-Kanamori (LFK) index. Results: Eight RCTs comparing the effect of ABM to ACT were included in the review, and six studies were meta-analyzed. Meta-analysis favored ACT in improving PTSD symptoms and ABV, and the effect size was large. ABM and ACT demonstrated similar effects in improving AB. Conclusion: ACT should not only be seen as a control training condition but also has therapeutic values. However, since the current meta-analysis only included a limited number of studies, further research was still needed to examine the clinical value of ACT in PTSD treatment.

Attentional bias modification and attention control training in PTSD We summarized and analyzed studies on attentional bias modification (ABM) and attention control training (ACT) in PTSD. Our findings indicated that ACT was a more effective treatment condition. This study highlights the therapeutic value of ACT.

Proteomic alterations associated with the formation of monocyte extracellular trap induced by Candida albicans hyphae.

Background: The interaction between the host and Candida albicans is dynamic and intricate. We performed proteomic analysis to explore monocyte-C. albicans hyphae interaction. Materials & methods: Primary human monocytes were stimulated by heat-killed C. albicans hyphae and their proteins were profiled by tandem liquid chromatography with mass spectrometry (LC-MS/MS). Results: Based on the protein database of different species for analysis, we found that stimulation of monocytes by hyphae was accompanied by upregulation of histones and activation of extracellular traps (ETs) formation pathway. Meanwhile, monocyte ETs (MoETs) were evoked by synthesis or alteration of C. albicans cell wall proteins expression during the morphological switch to hyphal. Conclusion: MoETs formation is linked to cell wall proteins of C. albicans hyphae.

A machine learning model for identifying systemic lupus erythematosus through laboratory information system and electronic medical record.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Its diagnosis poses significant challenges especially at early stages and in atypical cases. The aim of this study was to develop a machine learning model based on common laboratory tests that can aid SLE diagnosis. METHODS: A standard protocol was developed to collect data of SLE and control immune diseases. A 10-fold cross-validation was performed in the modeling dataset (n=862), and an external dataset (n=198) was used for model validation. Machine learning algorithms were applied to construct a diagnostic model. Performance was evaluated based on area under the curve (AUC) values, F1-score, negative predictive value, positive predictive value, accuracy, sensitivity, and specificity. RESULTS: The optimal model was based on a random forest algorithm with 10 clinical features. Thrombin time, prothrombin activity, and uric acid contributed most to the diagnostic model. The SLE diagnostic model showed sufficient predictive accuracy, with AUC values of 0.8286 in the validation dataset. CONCLUSIONS: Our diagnostic model based on 10 common laboratory tests identified the patients with SLE with high accuracy. An online version of the model can potentially be applied in clinical settings for the differential diagnosis of SLE.

Efficacy of Constraint-Induced Movement Therapy Versus Bimanual Intensive Training on Motor and Psychosocial Outcomes in Children With Unilateral Cerebral Palsy: A Randomized Trial.

IMPORTANCE: Emerging research has demonstrated that constraint-induced movement therapy (CIMT) and bimanual intensive training (BIT) show promising effectiveness for children with unilateral cerebral palsy (UCP). Considering that neurorehabilitative programs have always been designed with long training periods, psychosocial outcomes have received scarce attention and thus have not been investigated sufficiently. OBJECTIVE: To compare the efficacy of CIMT and BIT with 36-hr interventional dosages for both motor and psychosocial outcomes. DESIGN: Randomized trial. SETTING: Community. PARTICIPANTS: Forty-eight children with UCP, ages 6 to 12 yr. INTERVENTION: Both CIMT and BIT delivered via individual intervention for 2.25 hr/day, twice a week, for 8 wk. OUTCOMES AND MEASURES: The Melbourne Assessment 2, Pediatric Motor Activity Log-Revised, Bruininks-Oseretsky Test of Motor Proficiency, ABILHAND-Kids measure, and Parenting Stress Index-Short Form were administrated at pretreatment, midterm, posttreatment, and 6 mo after intervention. An engagement questionnaire for investigating the child's engagement in the intervention was used to collect the perspectives of the children and the parents weekly. RESULTS: Children with UCP who received either CIMT or BIT achieved similar motor improvements. The only difference was that CIMT yielded larger improvements in frequency and quality of use of the more affected hand at the 6-mo follow-up. Similar child engagement and parental stress levels were found in the two groups. CONCLUSIONS AND RELEVANCE: This study comprehensively compared the efficacy of motor and psychosocial outcomes for 36-hr dosages of CIMT and BIT. The promising findings support the clinical efficacy and feasibility of the proposed protocols. What This Article Adds: The core therapeutic principle of CIMT (i.e., remind the child to use the more affected hand) may be more easily duplicated by parents. Parents may have overestimated their child's engagement and given relatively higher scores; therefore, occupational therapists should also consider the opinions of the children themselves.

The impact of insomnia on anxiety and depression: a longitudinal study of non-clinical young Chinese adult males.

Insomnia, anxiety, and depression commonly co-occured and were closely related. Most of the prior studies were cross-sectional, with a poor ability to infer causality. Longitudinal study was needed to classify the relationships. The present study conducted a longitudinal study of non-clinical young Chinese males to investigate whether insomnia predicted the likelihood of future anxiety and depression, and vice versa. Convenient sampling method was applied, and 288 participants was recruited from Shanghai in October 2017 with Athens Insomnia Scale (AIS), Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). 120 of them were re-tested in June 2018. The drop-out rate was 58.33%. Correlation analyses and cross-lagged analysis showed that AIS global score was significantly positively related with scores of depression and anxiety at baseline and follow-up. Insomnia was a predictive factor of anxiety, but it can't predict depression. In sum, insomnia may be an important cause of anxiety, while no predictive relationship was found between insomnia and depression.

Type I Interferon Orchestrates Demand-Adapted Monopoiesis during Influenza A Virus Infection via STAT1-Mediated Upregulation of Macrophage Colony-Stimulating Factor Receptor Expression.

Whether and how a local virus infection affects the hematopoietic system in the bone marrow is largely unknown, unlike with systemic infection. In this study, we showed that influenza A virus (IAV) infection leads to demand-adapted monopoiesis in the bone marrow. The beta interferon (IFN-ß) promoter stimulator 1 (IPS-1)-type I IFN-IFN-α receptor 1 (IFNAR1) axis-mediated signaling was found to induce the emergency expansion of the granulocyte-monocyte progenitor (GMP) population and upregulate the expression of the macrophage colony-stimulating factor receptor (M-CSFR) on bipotent GMPs and monocyte progenitors via the signal transducer and activator of transcription 1 (STAT1), leading to a scaled-back proportion of granulocyte progenitors. To further address the influence of demand-adapted monopoiesis on IAV-induced secondary bacterial infection, IAV-infected wild-type (WT) and Stat1-/- mice were challenged with Streptococcus pneumoniae. Compared with WT mice, Stat1-/- mice did not demonstrate demand-adapted monopoiesis, had more infiltrating granulocytes, and were able to effectively eliminate the bacterial infection. IMPORTANCE Our findings show that influenza A virus infection induces type I interferon (IFN)-mediated emergency hematopoiesis to expand the GMP population in the bone marrow. The type I IFN-STAT1 axis was identified as being involved in mediating the viral-infection-driven demand-adapted monopoiesis by upregulating M-CSFR expression in the GMP population. As secondary bacterial infections often manifest during a viral infection and can lead to severe or even fatal clinical complications, we further assessed the impact of the observed monopoiesis on bacterial clearance. Our results suggest that the resulting decrease in the proportion of granulocytes may play a role in diminishing the IAV-infected host's ability to effectively clear secondary bacterial infection. Our findings not only provide a more complete picture of the modulatory functions of type I IFN but also highlight the need for a more comprehensive understanding of potential changes in hematopoiesis during local infections to better inform clinical interventions.

Management of Restenosis after Stenting in Left Main Coronary Artery Disease.

Background: The optimal alternative treatment strategy to coronary artery bypass graft surgery (CABG) for in-stent restenosis (ISR) in left main (LM) coronary artery disease remains uncertain. Methods: We retrospectively screened all intervention reports from an intervention database and extracted those mentioning an LM stent. We then manually confirmed reports involving LM ISR and divided them into two groups, those in which the patient received a new drug-eluting stent (new-DES) strategy, and those in which the patient received a drug-coated balloon (DCB) only. A composite endpoint of major adverse cardiovascular events (MACEs) and each individual endpoint were compared. We also performed a brief analysis of similar designed studies. Results: Between the new-DES (n = 40) and DCB-only (n = 22) groups, during median respective follow-up times of 581.5 and 642.5 days, no significant statistical differences were detected in MACEs (50.0% vs. 50.0%, p = 0.974), cardiovascular death (27.5% vs. 13.6%, p = 0.214), nonfatal myocardial infarction (30.0% vs. 31.8%, p = 0.835), or target lesion revascularization (35.0% vs. 45.5%, p = 0.542). We analyzed four similar studies and found comparable MACE findings (odds ratio: 0.85, 95% CI: 0.44-1.67). Conclusions: Our findings support both DCB angioplasty and repeat DES implantation for LMISR lesions in patients who were clinically judged to be unsuitable for CABG; the treatments achieved comparable clinical results in terms of MACEs in the medium term.

Association of leukocyte mitochondrial DNA copy number with longitudinal C-reactive protein levels and survival in older adults: a cohort study.

BACKGROUND: Systemic chronic inflammation occurs with age. The association of the leukocyte mitochondrial DNA copy number, a measure of mitochondrial function in aging, with the temporal profile of serum high-sensitivity C-reactive protein and mortality risk remains uncertain. The objectives of this study were to examine the association of the leukocyte mitochondrial DNA copy number with longitudinal high-sensitivity C-reactive protein levels and the association of the longitudinal high-sensitivity C-reactive protein levels with mortality risk. METHODS: This prospective cohort study included 3928 adults aged ≥ 55 years without systemic inflammation in the baseline examination of the Healthy Aging Longitudinal Study in Taiwan, which started in 2009. Each participant received leukocyte mitochondrial DNA copy number measurement using a fluorescence-based quantitative polymerase chain reaction at baseline, serum high-sensitivity C-reactive protein measurements at baseline and the follow-up examination five years later, and the ascertainment of all-cause death (until November 30, 2021). The relationships among the leukocyte mitochondrial DNA copy number, longitudinal serum high-sensitivity C-reactive protein levels, and time to all-cause mortality were examined using the joint longitudinal and survival modeling analysis. RESULTS: Of the 3928 participants (mean age: 69 years; 2060 [52%] were women), 837 (21%) died during follow-up. In the adjusted analysis, one standard deviation lower natural log-transformed baseline leukocyte mitochondrial DNA copy number was associated with an increase of 0.05 (95% confidence interval [CI], 0.02 to 0.08) standard deviation in serum high-sensitivity C-reactive protein in subsequent years. An increase of 1 standard deviation in instantaneous high-sensitivity C-reactive protein levels was associated with a hazard ratio (HR) for all-cause mortality of 1.22 (95% CI, 1.14 to 1.30). Similar results were obtained after further adjusting for baseline high-sensitivity C-reactive protein levels (HR [95% CI], 1.27 [1.16 to 1.38]) and after excluding those with serum high-sensitivity C-reactive protein above 10 mg/L (HR [95% CI], 1.21[1.11 to 1.31]) or 3 mg/L (HR [95% CI], 1.19 [1.06 to 1.31]) during follow-up. CONCLUSIONS: A lower leukocyte mitochondrial DNA copy number was associated with persistently higher high-sensitivity C-reactive protein levels. Moreover, these higher time-varying high-sensitivity C-reactive protein levels were instantaneously associated with a higher risk of death.

Suppression of SREBP-1 Expression by Simvastatin Decreases Visfatin-Induced Chemoresistance to Sunitinib in Human Renal Carcinoma 786-O Cells.

The resistance of renal cell carcinoma (RCC) to sunitinib impedes the success of chemotherapy in cancer treatment. Although several sunitinib resistance mechanisms have been proposed, little is known concerning the impact of obesity and adipokines in RCC cells. The upregulation of sterol-regulatory element-binding protein-1 (SREBP-1) has been reported to modulate the progression of tumor cells. The present study investigated the effect of visfatin on sunitinib-induced cytotoxicity in RCC cells through SREBP-1 expression. We found that visfatin-induced Akt and p70S6K activation increased SREBP-1 expression in 786-O cells. The visfatin-induced SREBP-1 mRNA and protein levels were attenuated through the inactivation of Akt and p70S6K by pharmacological inhibitors. In addition, the SREBP-1 knockdown using siRNA enhanced the cytotoxic effects of sunitinib. Our results also revealed the roles of simvastatin in attenuating the effects of visfatin on 786-O cells by inhibiting the production of reactive oxygen species. In particular, simvastatin co-treatment increased the cell cytotoxicity of sunitinib in visfatin-treated 786-O cells, which were associated with down-regulation of SREBP-1 expression. Our results suggest an important role of SREBP-1 in visfatin-induced drug resistance of RCC cells to sunitinib. The cytotoxic mechanism of simvastatin on RCC cells may provide a new strategy to improve therapeutic outcomes for the RCC treatment.

Loss of function of CMPK2 causes mitochondria deficiency and brain calcification.

Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification.

Differential Urinary Microbiota Composition Between Women With and Without Recurrent Urinary Tract Infection.

Background: Recurrent urinary tract infection (RUTI) is common and burdensome in women. Due to the low concentration or slow-growing of uropathogens in RUTI, standard urine cultures (SUCs) are often negative. Next-generation sequencing (NGS) of bacterial 16S rRNA gene is more sensitive and could be used to reveal the differential microbiota between patients with RUTI and asymptomatic controls. Methods: Women (aged ≥ 18 years) with clinically diagnosed RUTI with negative SUC and age-matched women asymptomatic controls with normal urinalysis were enrolled. Their midstream voided urine specimens were collected and processed for NGS (Illumina MiSeq) targeting the bacterial 16S rRNA gene V3-V4 region. The dataset was clustered into operational taxonomic units (OTUs) using QIIME. Taxonomic analysis, alpha diversity, beta diversity, multivariate statistical analysis, and linear discriminant analysis effect size (LEfSe) for differential analysis were performed and compared between patients with RUTI and asymptomatic controls. Results: A total of 90 patients with RUTI and 62 asymptomatic controls were enrolled in this study. Among them, 74.4% (67/90) and 71.0% (44/62) were successfully amplified and sequenced their bacterial 16S rRNA gene. In the alpha diversity analysis, the chao1 index and observed species index were significantly lower in the RUTI group than in the control group (P = 0.015 and 0.028, respectively). In the beta diversity analysis, there was a significant difference between the 2 groups [Analysis of similarities (ANOSIM), R = 0.209, P = 0.001]. The relative abundance of 36 bacterial taxa was significantly higher, and another 24 kinds of bacteria were significantly lower in the RUTI group compared with the control group [LEfSe analysis, P < 0.05, linear discriminative analysis (LDA) score > 3], suggesting that Ralstonia, Prevotella, Dialister, and Corynebacterium may play an important role in RUTI. Conclusion: The urinary microbiota of women with clinically diagnosed RUTI were significantly different from age-matched asymptomatic controls.

Income and social support related with mental health during COVID-19 outbreak in China.

ABSTRACT: To investigate psychological response of Chinese public during the regular prevention and control of Corona Virus Disease 2019 (COVID-19), and explore the relationship among income loss, social support and mental health.Five hundred twenty-six participants were randomly selected by snowball sampling method. Chinese version of Perceived Psychological Stress Scale, Perceived Social Support Scale, self-rating anxiety scale, and the PTSD Checklist for DSM-5 were used to measure the levels of psychological stress, social support, anxiety, and post-traumatic stress disorder (PTSD) symptoms. Demographic variables, income loss and income satisfaction during the outbreak period were also collected.The prevalence rate of anxiety, PTSD symptoms and stress problems were 19.8%, 23.8%, and 24.7% respectively. Multiple Regression Analysis illustrated that social support associated with stress, anxiety and PTSD after controlling demographic variables; for non-student samples, stress, anxiety, and PTSD were corelated with change in income and social support.During the regular prevention and control of COVID-19, social support might help reducing stress, anxiety, and PTSD symptoms. In addition to social support, change of income level was also an important factor for mental health. This study suggested the importance of maintaining a steady income after acute outbreak of COVID-19.

Microbial Distribution and Antibiotic Susceptibility of Bloodstream Infections in Different Intensive Care Units.

Background: Bloodstream infection (BSI) is an increasing public health concern worldwide, representing a serious infection with significant morbidity and mortality, especially in children and the elderly. The predominant microbial distribution and antibiotic susceptibility were investigated among BSIs in the different intensive care units (ICUs)-pediatric ICU (PICU), surgical ICU (SICU), cardiac ICU (CICU), respiratory ICU (RICU), and geriatric ICU (GICU)-in order to achieve more efficient and appropriate therapies for patients in various ICUs. Methods: In this retrospective cross-sectional study, the blood specimens were collected from five different ICUs of Peking University First Hospital and comprehensive ICU of Miyun Teaching Hospital (Miyun ICU) before antimicrobial treatment from 2017 to 2020. Microorganism cultures of the blood samples were conducted, and positive cultures were tested for type of pathogens and drug susceptibility. Results: The prevalence of BSIs was the highest in the Miyun ICU (10.85%), followed by the RICU (9.48%) and the PICU (8.36%). The total prevalence of Gram-positive bacterial strains (especially Staphylococcus spp. and Enterococcus spp.) in the PICU (44.55%), SICU (57.58%), CICU (55.00%), GICU (49.06%), and Miyun ICU (57.58%) was higher than that of Gram-negative bacteria. The major bacterial strain was Acinetobacter baumannii in the PICU (21.82%); Klebsiella pneumoniae in the SICU (12.88%), CICU (30.00%), and RICU (30.39%); Escherichia coli in the GICU (20.75%); and Staphylococcus epidermidis (18.18%) in the Miyun ICU. Staphylococcus hominis of BSIs remained highly susceptible (>70%) to gentamicin, linezolid, daptomycin, teicoplanin, vancomycin, tigecycline, and rifampicin in all the ICUs. Its antibiotic sensitivity to levofloxacin was moderate in the PICU and CICU, but mild (<30%) in the SICU, RICU, and GICU. K. pneumoniae was highly susceptible to doxycycline, minocycline, and tigecycline in all the ICUs except the RICU, and its antibiotic sensitivity to imipenem, meropenem, amikacin, ciprofloxacin, and levofloxacin was high/moderate in the PICU, CICU, GICU, and Miyun ICU, but mild in the SICU and RICU. Conclusion: The current study demonstrated the distribution of prevalent microorganisms, and their antimicrobial susceptibility exhibited a high divergence among BSIs in different ICUs from a tertiary hospital and an outer suburban hospital in Beijing. Therefore, different antibiotic therapies for various wards and distinct age groups (especially between pediatric and elderly patients) should be considered to control the emergence and spread of highly antibiotic-resistant infections.

Efficacy of the Chinese version interpretation bias modification training in an unselected sample: A randomized trial.

Training individuals to interpret ambiguous information in positive ways might be an effective method of reducing social anxiety. However, little research had been carried out in Chinese samples, and the effect of interpretation training on other processes such as attentional bias also remained unclear. This study examined the effect of interpretation bias modification program (IMP) on interpretation bias, social anxiety and attentional bias, and the possible mediation effects. 51 healthy adults were randomly assigned to either a 5-session IMP training that guided them to endorse benign interpretation in ambiguous scenarios or an interpretation control condition (ICC). Self-reported measures of social anxiety symptoms, attentional bias and interpretation bias were evaluated before and after training. Results showed that compared to control group, IMP group generated more positive interpretations and less negative interpretations after training (F(1,49) = 7.65, p<0.01, ηp2 = 0.14; F(1,49) = 14.60, p<0.01, ηp2 = 0.23respectively). IMP yielded greater interpretation bias reduction (F(1,49) = 12.84, p<0.01, ηp2 = 0.21) and social anxiety reduction (F(1,49) = 21.39, p<0.01, ηp2 = 0.30) than ICC, but change in attentional bias was not significant between IMP and the control group. Change in interpretation bias did not show a significant mediation effect in the relationship between training condition and social anxiety reduction. This study provided preliminary evidence for the efficacy of the Chinese version of IMP training. Possible methodological issues and interpretations underlying the findings were discussed. This study was registered in Chinese Clinical Trial Registry (www.chitr.org.cn), a WHO approved registry. The title of registration trial was "A Study on the efficiency of cognitive bias and attentional bias training on fear and phobia" and the registration number was ChiCTR2100045670.

Accelerated Corneal Endothelial Cell Loss after Phacoemulsification in Patients with Mildly Low Endothelial Cell Density.

By evaluating preoperative endothelial cell density (ECD), ECD loss after phacoemulsification can be predicted. In this retrospective cross-sectional study, we compared outcomes of phacoemulsification with different levels of preoperative ECD. Three-hundred-and-fifty-three patients aged between 18 and 90 years received phacoemulsification at Chang Gung Memorial Hospital. Age (p = 0.003), preoperative logMAR (p = 0.048), cataract grade (p = 0.005), preoperative ECD (p < 0.001), operation time (p = 0.043), phacoemulsification time (p = 0.001), and phacoemulsification energy (p < 0.001) were significantly associated with postoperative ECD change (%). Patients were divided into three groups according to preoperative ECD levels. Level of ECD, coefficient of variation (CV), cell hexagonality (HEX), central corneal thickness (CCT), visual acuity, underlying diseases, and complications were analyzed. With regard to groups, 29, 71, and 252 patients were respectively allocated into the markedly low (group A; ECD below 1000 cells/mm2), mildly low (group B; ECD between 1000 to 2000 cells/mm2), and normal (group C; ECD above 2000 cells/mm2) ECD level groups. The highest CV (40.8 ± 13.9%; p < 0.001) and lowest HEX (58.4 ± 14.6%; p < 0.001) were found in group A. Significant ECD loss was found in group B (28.9 ± 9.2%) as compared to group A (19.9 ± 5.4%) and C (15.0 ± 12.0%) (p < 0.001). No significant differences were found with regard to changes in CV (p = 0.941), HEX (p = 0.937), CCT (p = 0.346), and logMAR (p = 0.557) among the three groups. In conclusion, preoperative ECD level could be a novel predictive value for postoperative cell loss, which was the most prominent in mildly low ECD level group. Less phacoemulsification energy, earlier surgical intervention, or novel topical medications could be suggested for patients with an ECD range from 1000 to 2000 cells/mm2.

Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer.

BACKGROUND: The recent discovery of miRNAs and lncRNAs in urine exosomes has emerged as promising diagnostic biomarkers for bladder cancer (BCa). However, mRNAs as the direct products of transcription has not been well evaluated in exosomes as biomarkers for BCa diagnosis. The purpose of this study was to identify tumor progression-related mRNAs and lncRNAs in urine exosomes that could be used for detection of BCa. METHODS: RNA-sequencing was performed to identify tumor progression-related biomarkers in three matched superficial tumor and deep infiltrating tumor regions of muscle-invasive bladder cancer (MIBC) specimens, differently expressed mRNAs and lncRNAs were validated in TCGA dataset (n = 391) in the discovery stage. Then candidate RNAs were chosen for evaluation in urine exosomes of a training cohort (10 BCa and 10 healthy controls) and a validation cohort (80 BCa and 80 healthy controls) using RT-qPCR. The diagnostic potential of the candidates were evaluated by receiver operating characteristic (ROC) curves. RESULTS: RNA sequencing revealed 8 mRNAs and 32 lncRNAs that were significantly upregulated in deep infiltrating tumor region. After validation in TCGA database, 10 markedly dysregulated RNAs were selected for further investigation in urine exosomes, of which five (mRNAs: KLHDC7B, CASP14, and PRSS1; lncRNAs: MIR205HG and GAS5) were verified to be significantly dysregulated. The combination of the five RNAs had the highest AUC to disguising the BCa (0.924, 95% CI, 0.875-0.974) or early stage BCa patients (0.910, 95% CI, 0.850 to 0.971) from HCs. The expression levels of these five RNAs were correlated with tumor stage, grade, and hematuria degrees. CONCLUSIONS: These findings highlight the potential of urine exosomal mRNAs and lncRNAs profiling in the early diagnosis and provide new insights into the molecular mechanisms involved in BCa.