Transcranial direct current stimulation improves tardive dyskinesia in long-term hospitalized patients with chronic schizophrenia.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of transcranial direct current stimulation (tDCS) in chronic schizophrenia patients with tardive dyskinesia (TD) who were long-term hospitalized. METHODS: Sixty-four inpatients who met the DSM-IV diagnostic criteria for schizophrenia and TD were randomly assigned to either the active (N=35) or sham (N=29) group. Treatment was given 15 times, with each session lasting for 30 min, and an intensity of 2 mA. The anode was placed on the left dorsolateral prefrontal cortex and the cathode on the right supraorbital region. Primary outcome was measured by the changes in Abnormal Involuntary Movements Scale (AIMS) score. Secondary outcomes were measured using the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). Adverse effects of tDCS were assessed with an experimenter-administered open-ended questionnaire throughout the experiment. RESULTS: Of the 64 patients, 52 (81.25%) completed the study. Compared to the sham group, patients in the active group exhibited a significant reduction in both the total AIMS score and the facial-oral subscore (P<0.05). An improvement of at least 30% in total AIMS scores was observed in the active group (14 patients, 50%) compared to the sham group (2 patients, 8.3%) after treatment (P<0.01). There were no between-group differences in the PANSS and SANS total scores. However, there was a significant difference between the two groups in the occurrence of the reported adverse effect of tingling sensation (P<0.05). CONCLUSIONS: TDCS may be an effective and safe treatment for improving the facial-oral motor symptoms of TD in chronically hospitalized patients with schizophrenia. SIGNIFICANCE: This study provides a novel perspective for the clinical treatment of patients with TD.

Sex-differential association of suicide attempts with thyroid dysfunction in first-episode and drug-naïve young major depressive disorder patients with comorbid anxiety.

This study aimed to explore sex differences in the relationship between thyroid function indicators and suicide attempts in first-episode and drug-naïve young major depressive disorder (MDD) patients with comorbid anxiety (MDA). A total of 917 MDD patients (aged 18-35 years) were recruited. The Hamilton depression rating scale (HAMD-17), Hamilton anxiety rating scale (HAMA), positive and negative syndrome scale (PANSS) positive subscale and clinical global impression of severity scale (CGI-S) were used. 467 patients were classified as MDA. The prevalence of suicide attempts was 31.3% in MDA patients, which was significantly higher than that (7.3%) in MDD patients without anxiety. Compared with MDA patients without suicide attempts, MDA patients with suicide attempts were older, had a later age of onset, higher HAMD-17, HAMA, and PANSS positive symptom subscale scores, as well as higher TSH, TgAb and TPOAb levels. For male patients, TSH and TPOAb levels were independently associated with suicide attempts. For female patients, HAMA, PANSS positive symptom scores, CGI-S score and TPOAb levels were independently associated with suicide attempts. Our results suggest that the indicators of thyroid function which can predict suicide attempts in male and female MDA patients have sex differences.

Prevalence of and relevant factors for depression and anxiety symptoms among pregnant women on the eastern seaboard of China in the post-COVID-19 era: a cross-sectional study.

BACKGROUND: Antenatal depression and anxiety symptoms may have negative consequences for both mothers and offspring, and upward trends in the prevalence of these symptoms were especially apparent during the COVID-19 epidemic. The purpose of this study was to evaluate the prevalence of and relevant factors influencing depressive and anxiety symptoms in Chinese pregnant women in the post-COVID-19 era. METHODS: We conducted an online survey of 1,963 pregnant women in Jiangsu Province, using a cross-sectional design, and collected their general demographic data. The nine-item Patient Health Questionnaire 9 (PHQ-9) was used to evaluate depression symptoms, and the seven-item Generalized Anxiety Disorder 7 (GAD-7) was used to measure anxiety symptoms. RESULTS: The prevalence of reported antenatal depressive symptoms, anxiety symptoms, and depression combined with anxiety symptoms was 25.2%, 27.9%, and 18.6%, respectively. Of the respondents, the prevalence of moderate to severe depression, and anxiety was 7.9% and 7.7%, respectively. Binary logistic regression analysis demonstrated that age, low level of education, rural area, unemployment, pregnancy complications, poor marital relationship, and fair household income were positively association with both depressive and anxiety symptoms (all P < 0.05). The proportion of women reporting anxiety symptoms in the third trimester was 1.91-fold higher than in first trimester. Parity was a relevant factor for depression and anxiety symptoms (all P < 0.05). CONCLUSIONS: In the post-COVID-19 era, the prevalence of depression and anxiety symptoms in pregnant women was higher than expected, and it is vital to establish hospital, community, and family psychological health screening systems based on relevant factors and enhance early preventive measures.

Clinical correlates of autoimmune thyroiditis and non-autoimmune hypothyroidism in treatment-naïve patients with major depressive disorders.

BACKGROUND: Thyroid autoimmunity is a potentially critical factor that is often neglected in the association between subclinical hypothyroidism (SCH) and depressive disorders. This study aimed to investigate the clinical correlates of autoimmune thyroiditis (AIT) and non-autoimmune hypothyroidism (NAIH) in treatment-naïve patients with major depressive disorder (MDD). METHOD: Using a cross-sectional design, we recruited a total of 1718 outpatients with treatment-naïve MDD. Demographic and relevant clinical information including duration of MDD, severity of depression and anxiety, psychotic symptoms, suicide attempts, thyroid function parameters, etc. were collected. According to thyroid function parameters, patients were classified as AIT, NAIH, latent Hashimoto's thyroiditis (LH) and euthyroidism (ET). RESULTS: Patients with SCH (including AIT and NAIH) had older age at onset, and were more likely to have psychotic symptoms compared to those with ET. Multiple linear regression analysis showed that SCH was associated with duration of MDD and HAMD scores. Logistic regression analysis showed that the odds of having more severe anxiety and metabolic syndrome were greater among patients with SCH compared to those with ET. The odds of having suicide attempts were greater among patients with AIT than among those with ET. LIMITATION: Because of the cross-sectional design of this study, we were unable to sort out causality between MDD and SCH. CONCLUSION: Our findings suggested that AIT and NAIH were associated with duration of MDD, HAMD scores, severity of anxiety, and metabolic syndrome. However, only AIT in SCH was associated with suicide attempts.

Significant Contribution of Interleukin-18 Genotypes to Childhood Acute Lymphocytic Leukemia Risk in Taiwanese.

BACKGROUND/AIM: Evidence has shown that interleukin-18 (IL-18) has both antitumor and pro-tumor effects in various types of leukemia. The current study aimed at investigating the contribution of IL-18 polymorphisms to the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: IL-18 promoter -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 266 childhood ALL cases and 266 controls were determined by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The distributions of genotypic and allelic frequencies of IL-18 rs1946519, rs1946518 or rs187238, were not significantly different between childhood ALL cases and controls (all p>0.05). However, in the stratification analysis among the cases, IL-18 rs187238 GC and CC genotypes were associated with increased childhood ALL risk and shorter survival (OR=4.19 and 2.93, 95%CI=2.04-8.64 and 1.19-7.23, p=0.0001 and 0.0250, respectively). No association was found with rs1946519 and rs1946518 (all p>0.05). CONCLUSION: IL-18 rs187238 GC and CC genotypes can serve as predictors for childhood ALL prognosis among Taiwanese. Validation in larger and various populations can greatly extend the feasibility of this novel predictor.

Delayed improvements in visual memory task performance among chronic schizophrenia patients after high-frequency repetitive transcranial magnetic stimulation.

BACKGROUND: Cognitive impairments are core characteristics of schizophrenia, but are largely resistant to current treatments. Several recent studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dor-solateral prefrontal cortex (DLPFC) can reduce negative symptoms and improve certain cognitive deficits in schizophrenia patients. However, results are inconsistent across studies. AIM: To examine if high-frequency rTMS of the DLPFC can improve visual memory deficits in patients with schizophrenia. METHODS: Forty-seven chronic schizophrenia patients with severe negative symptoms on stable treatment regimens were randomly assigned to receive active rTMS to the DLPFC (n = 25) or sham stimulation (n = 22) on weekdays for four consecutive weeks. Patients performed the pattern recognition memory (PRM) task from the Cambridge Neuropsychological Test Automated Battery at baseline, at the end of rTMS treatment (week 4), and 4 wk after rTMS treatment (week 8). Clinical symptoms were also measured at these same time points using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS). RESULTS: There were no significant differences in PRM performance metrics, SANS total score, SANS subscores, PANSS total score, and PANSS subscores between active and sham rTMS groups at the end of the 4-wk treatment period, but PRM performance metrics (percent correct and number correct) and changes in these metrics from baseline were significantly greater in the active rTMS group at week 8 compared to the sham group (all P < 0.05). Active rTMS treatment also significantly reduced SANS score at week 8 compared to sham treatment. Moreover, the improvement in visual memory was correlated with the reduction in negative symptoms at week 8. In contrast, there were no between-group differences in PANSS total score and subscale scores at either week 4 or week 8 (all P > 0.05). CONCLUSION: High-frequency transcranial magnetic stimulation improves visual memory and reduces negative symptoms in schizophrenia, but these effects are delayed, potentially due to the requirement for extensive neuroplastic changes within DLPFC networks.

Suicide attempt rate and the risk factors in young, first-episode and drug-naïve Chinese Han patients with major depressive disorder.

BACKGROUND: In recent years, the rates of suicide among young people have been increasing, and major depressive disorder (MDD) is regarded to be its main cause. Many factors such as thyroid dysfunction and metabolic abnormalities are thought to mediate this process, but the conclusions are inconsistent. This study investigated the rate of suicide attempts and associated risk factors among young, first-episode and drug-naïve Chinese Han patients with MDD. METHODS: A total of 917 patients with MDD (aged 18 ~ 35 years) were recruited. Demographic and clinical data were collected and thyroid function, fasting blood glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), positive symptom subscale of Positive and Negative Syndrome Scale (PANSS) and clinical global impression of severity scale (CGI-S) were adopted to assess depression, anxiety, psychotic symptoms and disease severity respectively. RESULTS: The rate of suicide attempts was 19.5% in young MDD patients. There were significant differences in age (p = 0.003), education level (p = 0.001), age of onset (p = 0.004) and disease duration (p = 0.001) between patients with and without suicide attempts. Compared with patients without suicide attempts, patients with suicide attempts had significantly higher scores on the HAMD-17, HAMA, PANSS positive symptom subscale and CGI-S (all p < 0.001). Patients with suicide attempts had significantly higher levels of TSH (p < 0.001), TgAb (p = 0.004), TPOAb (p < 0.001), TG (p = 0.016), TC (p < 0.001), LDL (p < 0.001), and fasting glucose (p < 0.001), but significantly lower levels of HDL (p < 0.001). Logistic regression analysis showed that marital status (OR = 0.515, 95%CI: 0.280-0.950, p = 0.515), disease duration (OR = 1.100, 95%CI: 1.013-1.194, p = 0.024), HAMA score (OR = 1.313, 95%CI: 1.205-1.430, p < 0.001), CGI-S score (OR = 1.875, 95%CI: 1.339-2.624, p < 0.001), levels of FT3(OR = 0.717, 95%CI: 0.536-0.959, p = 0.025), TPOAb (OR = 1.004, 95%CI: 1.002-1.006, p < 0.001), TC (OR = 1.330, 95%CI: 1.011-1.750, p = 0.042) and LDL (OR = 0.736, 95%CI: 0.558-0.971, p = 0.030) were all independently associated with suicide attempts in young MDD patients. CONCLUSIONS: In China, the rate of suicide attempts in young patients with MDD is quite high and thyroid dysfunction and metabolic abnormalities may be implicated in its pathogenesis.

The Mediating Role of Coping Style in the Relationship Between Sleep Quality and Burnout: A Cross-Sectional Study Among Psychiatric Nurses.

Background: Although sleep quality is clearly associated with job burnout as shown in the existing research, the mechanism underpinning such relationship remains undefined. This work, thus, aimed to assess the current situation of sleep quality and burnout in Chinese psychiatric nurses, and to analyze the relationships between sleep quality, burnout and coping style, in order to provide possible targets to enhance mental health and wellbeing among psychiatric nurses. Method: This cross-sectional study was carried out in seven rehabilitation centers located in four different regions of China. The Pittsburgh Sleep Quality Index, the Epworth Sleeping Scale, the Maslach Burnout Inventory General Survey, and the Coping Style Questionnaire were distributed to 853 nurses in various mental hospitals, with a total of 664 participants being recruited in the final research. Results: The results of this current study showed a high prevalence of sleep disorders and burnout in Chinese psychiatric nurses. Moreover, emotional exhaustion (r = 0.456), cynicism (r = 0.323) and negative coping style (r = 0.191) in nurses were all positively correlated with total Pittsburgh Sleep Quality Index (PSQI) score, while professional efficacy (r = -0.079) and positive coping style (r = -0.140) were negatively correlated with total PSQI score. More interestingly, of all negative coping strategies, we found that self-blame had the most significant effect (ß = 0.156). Conclusions: The above results showed that coping style mediates the association of poor sleep quality with job burnout in Chinese psychiatric nurses. This study claimed that there is an urgent need to development the coping skills to sustain a healthy work life for nurses.

Phylogenomic Analysis Reconstructed the Order Matoniales from Paleopolyploidy Veil.

Phylogenetic conflicts limit our understanding of the evolution of terrestrial life under multiple whole genome duplication events, and the phylogeny of early terrestrial plants remains full of controversy. Although much incongruence has been solved with so-called robust topology based on single or lower copy genes, the evolutionary mechanisms behind phylogenetic conflicts such as polyploidization remain poorly understood. Here, through decreasing the effects of polyploidization and increasing the samples of species, which represent all four orders and eight families that comprise early leptosporangiate ferns, we have reconstructed a robust phylogenetic tree and network with 1125 1-to-1 orthologs based on both coalescent and concatenation methods. Our data consistently suggest that Matoniales, as a monophyletic lineage including Matoniaceae and Dipteridaceae, should be redefined as an ordinal rank. Furthermore, we have identified and located at least 11 whole-genome duplication events within the evolutionary history of four leptosporangiates lineages, and associated polyploidization with higher speciation rates and mass extinction events. We hypothesize that paleopolyploidization may have enabled leptosporangiate ferns to survive during mass extinction events at the end Permian period and then flourish throughout the Mesozoic era, which is supported by extensive fossil records. Our results highlight how ancient polyploidy can result in rapid species radiation, thus causing phylogenetic conflicts yet allowing plants to survive and thrive during mass extinction events.

Association Between Depressive Symptoms and Serum Brain-Derived Neurotrophic Factor Levels in Patients With First-Episode and Drug-Naïve Schizophrenia.

Previous studies have revealed that brain-derived neurotrophic factor (BDNF) levels are inversely associated with the severity of depressive symptoms. In addition, serum BDNF levels tend to increase with improvement in depressive symptoms. There is also evidence that BDNF has a possible role in the pathophysiology of schizophrenia. Therefore, the purpose of this study was to determine whether BDNF levels correlated with depressive symptoms in patients with first-episode and drug-naïve (FEDN) schizophrenia. In this study, 90 patients with FEDN schizophrenia and 60 healthy controls were recruited. The Positive and Negative Syndrome Scale (PANSS) and the 17-item Hamilton Depression Scale (HAMD-17) were used to gage psychopathological and depressive symptoms, respectively. All participants had their BDNF levels measured using a sandwich enzyme-linked immunosorbent test. Serum BDNF levels were lower in patients with FEDN schizophrenia compared with healthy controls. Moreover, patients with depressive symptoms exhibited a higher PANSS total score and a higher general psychopathology score than those without depressive symptoms (p < 0.05). For patients with depressive symptoms, serum BDNF levels were higher than in those without depressive symptoms (p < 0.05). An association between BDNF levels and the positive subscore was also observed (p < 0.01). However, there was no significant association between BDNF levels and HAMD scores (p > 0.05). In conclusion, BDNF levels were shown to be higher in the serum of patients with FEDN schizophrenia with depressive symptoms than in those without. Additionally, low levels of serum BDNF may contribute to the positive symptoms of FEDN schizophrenia but not to depressive symptoms.

Contribution of Cyclin-dependent Kinase Inhibitor 1B Genotypes to Childhood Leukemia Risk.

BACKGROUND/AIM: Although genetic differences in cell-cycle control genes have been associated with cancer risk, to our knowledge, no report has specifically examined the role of gene variants in childhood acute lymphoblastic leukemia (ALL). Cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as p27/KIP1) is a cell-cycle regulating gene. This study aimed at investigating the association between CDKN1B genotypes and childhood ALL risk. MATERIALS AND METHODS: In 266 childhood ALL cases and 266 healthy controls, the CDKN1B rs34330 and 2066827 polymorphisms were genotyped, and the association of CDKN1B genotypes with childhood ALL risk were analyzed. RESULTS: The genotypes of CDKN1B rs34330 and 2066827 were similarly distributed between the control and case groups (p for trend=0.8718 and 0.4030, respectively). The allelic frequency also exhibited no statistical difference (p=1.0000 and 0.6666, respectively). There was no significant interaction between CDKN1B genotypes and age or sex. CONCLUSION: CDKN1B genotypes were not found to be minor contributors to childhood ALL susceptibility in Taiwan.

Diversity, phylogeny, and adaptation of bryophytes: insights from genomic and transcriptomic data.

Bryophytes including mosses, liverworts, and hornworts are among the earliest land plants, and occupy a crucial phylogenetic position to aid in the understanding of plant terrestrialization. Despite their small size and simple structure, bryophytes are the second largest group of extant land plants. They live ubiquitously in various habitats and are highly diversified, with adaptive strategies to modern ecosystems on Earth. More and more genomes and transcriptomes have been assembled to address fundamental questions in plant biology. Here, we review recent advances in bryophytes associated with diversity, phylogeny, and ecological adaptation. Phylogenomic studies have provided increasing supports for the monophyly of bryophytes, with hornworts sister to the Setaphyta clade including liverworts and mosses. Further comparative genomic analyses revealed that multiple whole-genome duplications might have contributed to the species richness and morphological diversity in mosses. We highlight that the biological changes through gene gain or neofunctionalization that primarily evolved in bryophytes have facilitated the adaptation to early land environments; among the strategies to adapt to modern ecosystems in bryophytes, desiccation tolerance is the most remarkable. More genomic information for bryophytes would shed light on key mechanisms for the ecological success of these 'dwarfs' in the plant kingdom.

Sleep status of psychiatric nurses: A survey from China.

AIM: Our study aimed to evaluate the sleep status of psychiatric nurses in Chinese population and analyse the influencing factors. DESIGN: Cross-sectional, correlation design with logistic regression analysis. METHODS: We investigated 1,044 psychiatric nurses from seven psychiatric hospitals in China. Pittsburgh Sleep Quality Index and Maslach Burnout Inventory General Survey were used as main measures. RESULTS: The average Pittsburgh Sleep Quality Index score of 1,044 psychiatric nurses was 7.00 ± 3.59, and 38.63% of nurses had a total Pittsburgh Sleep Quality Index score >7. Our study found that middle-night shift nurses had poor sleep quality and sleep disorders are positively correlated with emotional exhaustion and cynical disregard for job burnout. Middle-night shift nurses showed 1.586 times more likely to suffer from sleep disorders than those non-middle-night shift. The higher the score of emotional exhaustion, the greater the risk of sleep disorders.

Novel Contribution of Long Non-coding RNA MEG3 Genotype to Prediction of Childhood Leukemia Risk.

BACKGROUND/AIM: Acute lymphoblastic leukemia (ALL) is frequent among children. Few studies have researched the relationship between maternally expressed gene 3 (MEG3) and cancer risk. We hypothesized long non-coding RNA MEG3 polymorphisms might influence the risk of childhood ALL. MATERIALS AND METHODS: In a total of 266 patients with childhood ALL and 266 healthy controls, genotypes of MEG3 rs7158663, rs3087918, rs11160608 and rs4081134 single nucleotide polymorphisms were investigated for their associations with childhood ALL. RESULTS: MEG3 rs7158663 AG and AA genotypes were significantly associated with ALL [odds ratio=1.61 (95% confidence interval=1.12-2.31) and 2.21 (1.16-4.22), respectively]. The A allele also exhibited a statistical association with higher risk of ALL (p=0.0015). There was no positive association as for rs3087918, rs11160608 or rs4081134. Interestingly, a significant interaction between MEG3 rs7158663 and age (≥3.5 years) and gender (male) was found. CONCLUSION: MEG3 rs7158663 AG/AA genotypes were associated with higher susceptibility to childhood ALL. These novel findings should be validated in larger populations and different ethnicities.

Prevalence of and risk factors for depressive and anxiety symptoms in a large sample of Chinese adolescents in the post-COVID-19 era.

BACKGROUND: Depressive and anxiety symptoms are widespread among adolescents today, creating a large social problem. However, few previous studies have addressed depression and anxiety among adolescents in Chinese cohorts. The aim of this study was to evaluate the prevalence of and risk factors for depressive and anxiety symptoms among Chinese middle school adolescent students in the post-COVID-19 era. METHODS: A total of 22,380 middle school students from Jiangsu Province were surveyed online, and their general demographic data were collected. The Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms, and the seven-item Generalized Anxiety Disorder (GAD-7) scale was used to measure anxiety symptoms. RESULTS: Of these participants (aged 12-17 years), 25.6% had depressive symptoms, 26.9% had anxiety symptoms, and 20.6% had a combination of depression and anxiety symptoms. The prevalence of depressive symptoms was higher in female adolescents (27.6%) than in male adolescents (23.7%; χ2 = 45.479, P = 0.000), and the proportion with anxiety symptoms was higher among female adolescents (28.6%) than among male adolescents (25.4%; χ2 = 29.390, P = 0.000). Furthermore, binary logistic regression analysis showed that gender, region, and parental relationship were significantly associated with depressive symptoms among adolescents, while age, gender, region, and parental relationship were significantly associated with anxiety symptoms. CONCLUSIONS: Our findings demonstrated that the prevalence of reported depressive and anxiety symptoms in Chinese adolescents are high. Female gender, urban region, and poor parental relationship may be risk factors for depressive and anxiety symptoms. Furthermore, policy makers, schools, and families need to pay more attention to the psychological health of adolescents, develop response plans and take early intervention measures to reduce the prevalence of adolescent depression and anxiety.

Significant Association of CCND1 Genotypes With Susceptibility to Childhood Acute Lymphoblastic Leukemia.

BACKGROUND/AIM: This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653. RESULTS: There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls. CONCLUSION: CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.

Significant Associations of lncRNA H19 Genotypes with Susceptibility to Childhood Leukemia in Taiwan.

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08-2.14, p = 0.0429) and 1.94 (95%CI, 1.15-3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13-1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.

MiR-196a-2 Genotypes Determine the Susceptibility and Early Onset of Childhood Acute Lymphoblastic Leukemia.

BACKGROUND/AIM: The roles of microRNAs (miRNAs) in tumorigenesis have attracted a lot of attention. The current study aimed at examining the association of the miR-196a-2 rs11614913 genotypes with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: This case-control investigation recruited 266 patients with childhood ALL and 266 healthy controls, and the miR-196a-2 rs11614913 genotypes of each participant were examined via the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The frequency of miR-196a-2 C allele in controls was 0.440 compared with 0.423 in ALL patients. In addition, there was no significant association between CT or CC genotypes with susceptibility to childhood ALL (OR=0.89 and 0.89, 95%CI=0.60-1.30 and 0.54-1.45, p=0.5427 and 0.6302). Furthermore, the frequencies of miR-196a-2 polymorphisms were not associated with age, gender and clinical outcomes in ALL cases. CONCLUSION: The miR-19a-2 genotypes are not associated with susceptibility to childhood ALL in Taiwan.

Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus.

Depression may be associated with reduced monoamine neurotransmission, particularly serotonin and norepinephrine (NE). Reuptake of NE by the norepinephrine transporter (NET) is the primary mechanism by which many of the antidepressants are high-affinity substrates for NET. This study aimed to examine the effect of lentivirus-mediated shRNA targeting NET in locus coeruleus (LC) on depression-like behaviors of rats. We randomly assigned 60 male Wistar rats to 6 experimental groups: (1) Control group: without chronic unpredictable mild stress (CUMS) and without NET-shRNA treatment; (2) shRNA group: without CUMS + NET-shRNA; (3) CUMS group: 3-week CUMS without NET-shRNA; (4) CUMS + nonsense shRNA group; (5) CUMS + amygdala (Amy)-shRNA group; (6) CUMS+ locus coeruleus (LC)-shRNA group. First, recombinant lentiviral vector expressing shRNA (ShRNA-629, ShRNA-330, ShRNA-1222, ShRNA-1146 or ShRNA- negative control) against NET were produced, and their efficiency in knocking down of NET in PC12 cells were assessed by Q-PCR and western blot analysis. Second, shRNA was injected into the rat LC bilaterally to investigate whether it could prevent the depressive-like behavior induced by 3-week CUMS. Third, we tested the depressive-like behavior of the rats in the forced swimming test, the open field test, the sucrose preference test, as well as the body weight gain at the end of the seventh week. Finally, the protein expressions of NET was measured by western blot and the NE levels were measured by high performance liquid chromatography. Q-PCR and western blot showed that the ShRNA-1146 had the best interference efficiency targeting on NET in PC12 cells (p < 0.01). Compared to the depression model group, the immobility time in the forced swimming test was significantly reduced (p < 0.01), but the sucrose preference and the total scores in the open field test were significantly increased (all p < 0.01) in the group treated with shRNA in LC. Furthermore, compared with the depression model group, NET levels were significantly decreased (p < 0.01), but NE levels were significantly increased in the group treated with shRNA in LC (p < 0.05). Our findings suggest that Lentivirus-mediated shRNA targeting NET in LC downregulated NET both in vitro and in vivo, resulting in a significant decrease in depressive-like behavior of rats.