Supplementary Material for: Long Non-coding RNA RP11-252C15.1 is a Potential Biomarker of Prognosis and Hallmark for Leukemogenesis in Children with B-cell Precursor Acute Lymphoblastic Leukemia

Introduction: Improved understanding of the prognostic biomarkers associated with childhood acute lymphoblastic leukemia (ALL) is needed for accurate risk group stratification. This study aimed to identify potential long-non coding RNA (lncRNA) markers and evaluate their prognostic value in children with ALL. Methods: We selected 50 children with newly diagnosed ALL and 20 age-matched patients with idiopathic immune thrombocytopenia (controls). RNA sequencing was performed to identify differentially expressed lncRNAs between the ALL and control groups. Correlation analysis was performed to determine the relationships between candidate lncRNAs, clinical features, and the risk of leukemogenesis. Results: A total of 1,019 differentially expressed lncRNAs were identified between the ALL and control groups. Reverse-transcriptase (RT-qPCR) revealed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 were significantly upregulated in patients with ALL. Furthermore correlation analysis showed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 represent potential predictors of leukemogenesis; however, only lncRNA RP11-252C15.1 was associated with clinical features and outcome in children with B-cell precursor ALL (BCP-ALL). In vitro experiments confirmed that lncRNA RP11-252C15.1 was significantly overexpressed in BCP-ALL cell lines and promoted proliferation, and repressed apoptosis in MHH-CALL-3 cells. Conclusion: LncRNA RP11-252C15.1 is a potential oncogene in BCP-ALL pathogenesis and a prognostic biomarker in children with BCP-ALL

Supplementary Material for: A Modified Nerve-Sparing Panhysterectomy for Benign Uterine Diseases: Techniques and Evaluation of Postoperative Pelvic Dysfunctions

<b><i>Objective:</i></b> To describe a modified nerve-sparing panhysterectomy and to investigate the feasibility and impact of this nerve-sparing technique in improving postoperative pelvic visceral dysfunctions of benign uterine disease patients. <b><i>Methods:</i></b> From January 2008 to January 2010, a total of 300 patients diagnosed with benign uterine diseases at the Second Affiliated Hospital of Nantong University were enrolled. Of those, 150 randomly selected patients underwent modified panhysterectomy (research group), while the other 150 patients underwent conventional panhysterectomy (control group). The surgery-related parameters, including operation time, intraoperative blood loss, length of hospital stay, postoperative indwelling catheter time, and first voiding and defecation time were compared between the two groups. The extent of nerve damage in both groups was examined using the nerve-specific marker S-100 via immunohistochemistry. Besides, postoperative assessments of bladder and bowel functions were conducted within 1 year after the operation. <b><i>Results:</i></b> The surgery-related parameters in the two groups showed no significant difference (p > 0.05). Immunohistochemistry results showed significantly reduced damage of the nerves in the research group. We also found a better bladder and bowel function in the research group (p < 0.05) and in younger patients (p < 0.05) compared with that in the control group. Recovery trends of the bladder and bowel function were found in both groups (χ² = 7.512, p = 0.006 in the research group; χ² = 7.299, p = 0.007 in the control group). <b><i>Conclusion:</i></b> Modified panhysterectomy for benign uterine diseases seems feasible and safe, with the main advantage of improving postoperative urocystic and rectal dysfunctions through the preservation of the pelvic autonomic nerves

Erratum: The Functional IgE-Blocking Factor Induced by Allergen-Specific Immunotherapy Correlates with IgG4 Antibodies and a Decrease of Symptoms in House Dust Mite-Allergic Children

<b><i>Background:</i></b> At present, there are no validated biomarkers reflecting or predicting the clinical efficacy of allergen-specific immunotherapy (AIT) . We aimed to investigate the correlations between clinical and immunological responses of patients undergoing house dust mite (HDM) AIT. <b><i>Methods:</i></b> Sixty-nine children diagnosed with HDM allergic rhinitis and/or asthma received standardized <i>Dermatophagoides</i><i>pteronyssinus</i> (Dp) subcutaneous AIT for 12 months. Twenty HDM-allergic children served as an open control group. Clinical symptom and medication scores were recorded and Dp-specific IgE, IgG4 and IgE-blocking factor were measured before AIT and after 4 and 12 months of AIT. <b><i>Results:</i></b> Symptom scores decreased after 4 months and continued to decrease during 12 months of AIT. No differences in medication scores were observed between AIT and the control group during the study period. Levels of Dp IgG4 increased after 4 months and correlated to symptom scores at 12 months (r = -0.296, p = 0.013) of AIT. The Dp IgE-blocking factor increased after 4 months of AIT, and correlated with symptom scores at 4 months (r = -0.307, p = 0.010) and 12 months (r = -0.288, p = 0.016) of AIT. A strong correlation between Dp IgE-blocking factor and Dp IgG4 during AIT (4 months: r = 0.680; 12 months: r = 0.636, both p < 0.0001) was observed. Patients with IgE-blocking factor ≥0.2 after 4 months of AIT showed lower symptom scores at 12 months of AIT (p = 0.0093). <b><i>Conclusions:</i></b> Subcutaneous HDM AIT results in a decrease of allergic symptoms among HDM-allergic children. IgE-blocking activity increased after 4 months of AIT and correlated with clinical symptoms. A high IgE-blocking factor at an early stage of AIT is associated with fewer symptoms at a later stage of AIT

Supplementary Material for: Adolescence predatory risk alters social behaviors and cognitive ability and central oxytocin and vasopressin expression in adult Brandt’s voles

Introduction: Stress during adolescence causes long-term behavioral changes in adulthood. We previously found that adolescent exposure to predatory risk augments adolescent social contact and adult parental behavior in Brandt’s voles (Lasiopodomys brandtii). Methods: Here we determined whether this experience alters sexual behavior, pair-bond formation, and recognition ability, as well as basal HPA axis activity, central oxytocin (OT), and arginine-vasopressin (AVP) expression in adulthood. Results: In the social interaction test, repeated cat odor (CO) exposure enhanced the frequency of lordosis by female voles toward an unfamiliar opposite-sex conspecific. CO voles preferred to engage with their partners after 48 h cohabitation whereas the control groups did not, which may reflect stable pair bonds in the CO treatment group. Furthermore, adolescent exposure to CO inhibited novel object and place recognition ability, while it influenced social recognition only among adult males. No effect of adolescent CO exposure was observed for basal HPA axis activity, showing a habituation effect. Finally, we found that CO exposure increased OT and decreased AVP expression in the hypothalamus, including the paraventricular nucleus and anterior hypothalamus. The levels of OT in the medial amygdala were lower, and AVP in the lateral septum was higher in CO voles compared with the control. Discussion/Conclusion: These findings demonstrate that adolescent exposure to predator risk promotes adult reproductive behavior of Brandt’s voles. Deficits in recognition ability may necessitate alterations in reproductive strategies to enhance inclusive fitness. OT and AVP systems may play a modulatory role in the alteration of social behaviors elicited by adolescent predatory risk

Supplementary Material for: Epstein-Barr Virus miR-BART6-3p Inhibits the RIG-I Pathway

Recognition of viral pathogen-associated molecular patterns by pattern recognition receptors (PRRs) is the first step in the initiation of a host innate immune response. As a PRR, RIG-I detects either viral RNA or replication transcripts. Avoiding RIG-I recognition is a strategy employed by viruses for immune evasion. Epstein-Barr virus (EBV) infects the majority of the human population worldwide. During the latent infection period there are only a few EBV proteins expressed, whereas EBV-encoded microRNAs, such as BART microRNAs, are highly expressed. BART microRNAs regulate both EBV and the host's gene expression, modulating virus proliferation and the immune response. Here, through gene expression profiling, we found that EBV miR-BART6-3ps inhibited genes of RIG-I-like receptor signaling and the type I interferon (IFN) response. We demonstrated that miR-BART6-3p rather than other BARTs specifically suppressed RIG-I-like receptor signaling-mediated IFN-β production. RNA-seq was used to analyze the global transcriptome change upon EBV infection and miR-BART6-3p mimics transfection, which revealed that EBV infection-triggered immune response signaling can be repressed by miR-BART6-3p overexpression. Furthermore, miR-BART6-3p inhibited the EBV-triggered IFN-β response and facilitated EBV infection through targeting the 3′UTR of RIG-I mRNA. These findings provide new insights into the mechanism underlying the strategies employed by EBV to evade immune surveillance

Supplementary Material for: Psychotic Symptoms and Attitudes toward Medication Mediate the Effect of Insight on Personal-Social Functions in Patients with Schizophrenia: One-Year Randomized Controlled Trial and Follow-Up

<b><i>Aims:</i></b> This study aimed to investigate the mediating pathway of 3 factors (psychotic symptoms, attitude toward medication, and cognitive processing speed) on the effect of insight on personal-social functioning in patients with schizophrenia. <b><i>Methods:</i></b> Chinese inpatients with schizophrenia (<i>n</i> = 168; mean age 18 ± 50 years) diagnosed according to the DSM-IV were randomly assigned to treatment with antipsychotic medication alone or combined treatment. Positive and Negative Syndrome Scale (PANSS), Drug Attitude Inventory (DAI), Assessment of Insight (SAI), and Social-Personal Performance Scale (PSPS) scores were evaluated at baseline and at 3, 6, and 12 months. Cognitive function was assessed at baseline. Multiple mediation analyses were conducted with baseline data, end point data, and changes-in-scale scores between baseline and the end point, respectively. <b><i>Results:</i></b> At baseline and at 12 months, only psychotic symptoms mediated the effect of insight on personal-social functioning. For changes-in-scale scores over the 12-month follow-up, in patients receiving treatment with medication alone, the effect of improved insight on improved personal-social function was mediated by psychotic symptoms only; in patients receiving a combined treatment, the effect of improved insight on improved personal-social functioning was mediated by both psychotic symptoms and attitudes toward medication, independently. <b><i>Conclusions:</i></b><i></i> The link between insight and personal-social functions is mainly mediated by psychotic symptoms. Psychosocial intervention improves the predicting effect of insight on personal-social function by improving both the attitude toward medication and psychotic symptoms independently