Epitranscriptic regulation of HRAS by N6-methyladenosine drives tumor progression.

Overexpression of Ras, in addition to the oncogenic mutations, occurs in various human cancers. However, the mechanisms for epitranscriptic regulation of RAS in tumorigenesis remain unclear. Here, we report that the widespread N6-methyladenosine (m6A) modification of HRAS, but not KRAS and NRAS, is higher in cancer tissues compared with the adjacent tissues, which results in the increased expression of H-Ras protein, thus promoting cancer cell proliferation and metastasis. Mechanistically, three m6A modification sites of HRAS 3' UTR, which is regulated by FTO and bound by YTHDF1, but not YTHDF2 nor YTHDF3, promote its protein expression by the enhanced translational elongation. In addition, targeting HRAS m6A modification decreases cancer proliferation and metastasis. Clinically, up-regulated H-Ras expression correlates with down-regulated FTO and up-regulated YTHDF1 expression in various cancers. Collectively, our study reveals a linking between specific m6A modification sites of HRAS and tumor progression, which provides a new strategy to target oncogenic Ras signaling.

LCDR regulates the integrity of lysosomal membrane by hnRNP K-stabilized LAPTM5 transcript and promotes cell survival.

Lysosome plays important roles in cellular homeostasis, and its dysregulation contributes to tumor growth and survival. However, the understanding of regulation and the underlying mechanism of lysosome in cancer survival is incomplete. Here, we reveal a role for a histone acetylation-regulated long noncoding RNA termed lysosome cell death regulator (LCDR) in lung cancer cell survival, in which its knockdown promotes apoptosis. Mechanistically, LCDR binds to heterogenous nuclear ribonucleoprotein K (hnRNP K) to regulate the stability of the lysosomal-associated protein transmembrane 5 (LAPTM5) transcript that maintains the integrity of the lysosomal membrane. Knockdown of LCDR, hnRNP K, or LAPTM5 promotes lysosomal membrane permeabilization and lysosomal cell death, thus consequently resulting in apoptosis. LAPTM5 overexpression or cathepsin B inhibitor partially restores the effects of this axis on lysosomal cell death in vitro and in vivo. Similarly, targeting LCDR significantly decreased tumor growth of patient-derived xenografts of lung adenocarcinoma (LUAD) and had significant cell death using nanoparticles (NPs)-mediated systematic short interfering RNA delivery. Moreover, LCDR/hnRNP K/LAPTM5 are up-regulated in LUAD tissues, and coexpression of this axis shows the increased diagnostic value for LUAD. Collectively, we identified a long noncoding RNA that regulates lysosome function at the posttranscriptional level. These findings shed light on LCDR/hnRNP K/LAPTM5 as potential therapeutic targets, and targeting lysosome is a promising strategy in cancer treatment.

Hierarchical Hollow Carbon Particles with Encapsulation of Carbon Nanotubes for High Performance Supercapacitors.

A novel and sustainable carbon-based material, referred to as hollow porous carbon particles encapsulating multi-wall carbon nanotubes (MWCNTs) (CNTs@HPC), is synthesized for use in supercapacitors. The synthesis process involves utilizing LTA zeolite as a rigid template and dopamine hydrochloride (DA) as the carbon source, along with catalytic decomposition of methane (CDM) to simultaneously produce MWCNTs and COx -free H2 . The findings reveal a distinctive hierarchical porous structure, comprising macropores, mesopores, and micropores, resulting in a total specific surface area (SSA) of 913 m2  g-1 . The optimal CNTs@HPC demonstrates a specific capacitance of 306 F g-1 at a current density of 1 A g-1 . Moreover, this material demonstrates an electric double-layer capacitor (EDLC) that surpasses conventional capabilities by exhibiting additional pseudocapacitance characteristics. These properties are attributed to redox reactions facilitated by the increased charge density resulting from the attraction of ions to nickel oxides, which is made possible by the material's enhanced hydrophilicity. The heightened hydrophilicity can be attributed to the presence of residual silicon-aluminum elements in CNTs@HPC, a direct outcome of the unique synthesis approach involving nickel phyllosilicate in CDM. As a result of this synthesis strategy, the material possesses excellent conductivity, enabling rapid transportation of electrolyte ions and delivering outstanding capacitive performance.

Construction of scalable multi-channel DNA nanoplatform for the combined detection of ctDNA biomarkers of ovarian cancer.

Single-level biomarker detection has the limitation of insufficient accuracy in cancer diagnosis. Therefore, the strategy of developing highly sensitive, multi-channel biosensors for high-throughput ctDNA determination is critical to improve the accuracy of early diagnosis of clinical tumors. Herein, in order to achieve efficient detection of up to ten targets for early diagnosis of ovarian cancer, a DNA-nanoswitch-based multi-channel (DNA-NSMC) biosensor was built based on the multi-module catalytic hairpin assembly-mediated signal amplification (CHA) and toehold-mediated DNA strand displacement (TDSD) reaction. Only two different fluorescence signals were used as outputs, combined with modular segmentation strategy of DNA-nanoswitch-based reaction platform; the multi-channel detection of up to ten targets was successfully achieved for the first time. The experimental results suggest that the proposed biosensor is a promising tool for simultaneously detecting multiple biomarkers for the early diagnosis of ovarian cancer, offering new strategies for the early screening, diagnosis, and treatment not only for ovarian cancer but also for other cancers.

Hydrogel-Coated Microelectrode Resists Protein Passivation of In Vivo Amperometric Sensors.

Passivation of electrodes caused by nonspecific adsorption of protein can dramatically reduce sensing sensitivity and accuracy, which is a great challenge for in vivo neurochemical monitoring. However, most antipassivation strategies are not suitable to carbon fiber microelectrodes (CFMEs) for in vivo measurement, and these methods also do not work on electrochemical biosensors that fix biometric elements. In this study, we demonstrate that chitosan hydrogel-coated microelectrodes can avoid the current passivation caused by protein adsorption on the surface of carbon fiber because the chitosan hydrogel prepared by local pH gradient caused by hydrogen evolution reaction has three-dimensional networks containing large amounts of water. The highly hydrophilic three-dimensional structure of hydrogel not only forms a biocompatible interface to confine enzymes but also keeps the fast mass transfer of analytes, such as dopamine, ascorbic acid, and glucose. The consistency of the precalibration and postcalibration of the prepared sensor enables in vivo amperometric detection of both electroactive species based on their redox property and electroinactive species based on the enzyme. This study provides a simple and versatile strategy to constitute an amperometric sensor interface to resist passivation of protein adsorption in a complex biological environment such as the brain.

Hypoxia inhibits HUNK kinase activity to induce epithelial-mesenchymal transition.

Hypoxia is a common hallmark of cancer and plays a crucial role in promoting epithelial-mesenchymal transition (EMT). Hormonally Upregulated Neu-associated Kinase (HUNK) regulates EMT through its kinase activity. However, whether hypoxia is involved in HUNK-mediated EMT is incompletely understood. This study unveils an association between HUNK kinase activity and hypoxia in colorectal cancer (CRC). Importantly, hypoxia does not alter the expression levels of HUNK, but directly affects the phosphorylation levels of downstream proteins with indication of HUNK activity. Functionally, the upregulation of migration, invasion, and expression of EMT markers in CRC cells under hypoxic conditions can be attributed, in part, to the downregulation of HUNK-mediated phosphorylation of downstream proteins. These findings highlight the intricate relationship between HUNK, hypoxia and the molecular mechanisms of cancer EMT. Understanding these mechanisms may provide valuable insights into therapeutic targets for inhibiting cancer metastasis.

A combined bioinformatics and experimental approach identifies RMI2 as a Wnt/ß-catenin signaling target gene related to hepatocellular carcinoma.

BACKGROUND: The Wnt/ß-catenin signaling pathway plays an important role in embryogenesis and tumorigenesis. In human cancer, abnormal activity of Wnt/ß-catenin signaling pathway induces overexpressed of downstream genes, and initiate oncogene. There are several target genes known to be key players in tumorigenesis, such as c-myc, cyclin D1, MMPs or survivin. Therefore, identifying the target genes of Wnt/ß-catenin signaling pathway is important to understanding Wnt/ß-catenin-mediated carcinogenesis. In this study, we developed a combined bioinformatics and experimental approach to find potential target genes. METHODS: Luciferase reporter assay was used to analyze the promoter activity of RMI2. WST1 cell proliferation assays and transwell assays were performed to determine the proliferation and migration capacities of RMI2 overexpressing or knockdown stable hepatic cells. Finally, xenograft experiments were performed to measure the tumor formation capacity in vivo. RESULTS: The results showed that RMI2 mRNA was upregulated after LiCl treatment and Wnt3a-conditioned medium in a culture of SK-hep-1 cell lines. A chromatin immunoprecipitation (ChIP) assay showed that the ß-catenin/T cell-specific factor (TCF) complex binds to the putative TCF binding site of the RMI2 promoter. We then found a TCF binding site at - 333/- 326 of the RMI2 promoter, which is crucial for ß-catenin responsiveness in liver cell lines. RMI2 was overexpressed in hepatoma tissue and cell lines, and it promoted the migration and invasion of HCC cells. Moreover, RMI2 upregulated the expression of epithelial-mesenchymal transition (EMT) markers and the Wnt3a/ß-catenin-related genes, but silencing RMI2 had the opposite effects. Notably, the expression of RMI2 was positively correlated with the clinical data of HCC patients who had significantly shorter overall survival (OS) and disease-free survival (DFS) (Both: P < 0.05). In addition, a total of 373 HCC patients' data from the Caner Genome Atlas project (TCGA) were used to validate our findings. CONCLUSIONS: Taking all these findings together, we determined that RMI2 was a new target gene of the Wnt/ß-catenin signaling pathway. We also found that RMI2 promotes EMT markers, HCC cell invasion, and metastasis, which indicated that RMI2 is a potential target for preventing or at least mitigating the progression of HCC.

Cleaner outdoor air diminishes the overall risk of intracerebral hemorrhage but brings differential benefits to subpopulations: a time-stratified case-crossover study.

BACKGROUND: Short-term air pollution exposure and intracerebral hemorrhage (ICH) risk are related. However, the impact of the pollutant levels decline on this relationship, which attributes to clean air policy implementation and the COVID-19 pandemic lockdown, is unclear. In the present research, we explored the influence of different pollutant levels on ICH risk during eight years in a southwestern China megacity. METHODS: Our research used a time-stratified case-crossover design. We retrospectively analyzed ICH patients in a teaching hospital from January 1, 2014, to December 31, 2021, and divided 1571 eligible cases into two groups (1st group: 2014-2017; 2nd group: 2018-2021). We observed the trend of every pollutant in the entire study period and compared the pollution levels in each group, using air pollutants data (PM2.5, PM10, SO2, NO2, CO, and O3) documented by the local government. We further established a single pollutant model via conditional logistic regression to analyze the association between short-term air pollutants exposure and ICH risk. We also discussed the association of pollution levels and ICH risk in subpopulations according to individual factors and monthly mean temperature. RESULTS: We found that five air pollutants (PM2.5, PM10, SO2, NO2, CO) exhibited a continuous downward trend for the whole duration, and the daily concentration of all six pollutants decreased significantly in 2018-2021 compared with 2014-2017. Overall, the elevation of daily PM2.5, SO2, and CO was associated with increased ICH risk in the first group and was not positively associated with risk escalation in the second group. For patients in subgroups, the changes in the influence of lower pollutant levels on ICH risk were diverse. In the second group, for instance, PM2.5 and PM10 were associated with lower ICH risk in non-hypertension, smoking, and alcohol-drinking participants; however, SO2 had associations with increased ICH risk for smokers, and O3 had associations with raised risk in men, non-drinking, warm month population. CONCLUSIONS: Our study suggests that decreased pollution levels diminish the adverse effects of short-term air pollutants exposure and ICH risk in general. Nevertheless, the influence of lower air pollutants on ICH risk in subgroups is heterogeneous, indicating unequal benefits among subpopulations.

Construction and validation of infection risk model for patients with external ventricular drainage: a multicenter retrospective study.

PURPOSE: External ventricular drainage (EVD) is a life-saving neurosurgical procedure, of which the most concerning complication is EVD-related infection (ERI). We aimed to construct and validate an ERI risk model and establish a monographic chart. METHODS: We retrospectively analyzed the adult EVD patients in four medical centers and split the data into a training and a validation set. We selected features via single-factor logistic regression and trained the ERI risk model using multi-factor logistic regression. We further evaluated the model discrimination, calibration, and clinical usefulness, with internal and external validation to assess the reproducibility and generalizability. We finally visualized the model as a nomogram and created an online calculator (dynamic nomogram). RESULTS: Our research enrolled 439 EVD patients and found 75 cases (17.1%) had ERI. Diabetes, drainage duration, site leakage, and other infections were independent risk factors that we used to fit the ERI risk model. The area under the receiver operating characteristic curve (AUC) and the Brier score of the model were 0.758 and 0.118, and these indicators' values were similar when internally validated. In external validation, the model discrimination had a moderate decline, of which the AUC was 0.720. However, the Brier score was 0.114, suggesting no degradation in overall performance. Spiegelhalter's Z-test indicated that the model had adequate calibration when validated internally or externally (P = 0.464 vs. P = 0.612). The model was transformed into a nomogram with an online calculator built, which is available through the website: https://wang-cdutcm.shinyapps.io/DynNomapp/ . CONCLUSIONS: The present study developed an infection risk model for EVD patients, which is freely accessible and may serve as a simple decision tool in the clinic.

An Electrochemical Nanosensor for Monitoring the Dynamics of Intracellular H2 O2 Upon NADH Treatment.

Reactive oxygen species (ROS)-based therapeutic strategies play an important role in cancer treatment. However, in situ, real-time and quantitative analysis of intracellular ROS in cancer treatment for drug screening is still a challenge. Herein we report one selective hydrogen peroxide (H2 O2 ) electrochemical nanosensor, which is prepared by electrodeposition of Prussian blue (PB) and polyethylenedioxythiophene (PEDOT) onto carbon fiber nanoelectrode. With the nanosensor, we find that the level of intracellular H2 O2 increases with NADH treatment and that increase is dose-dependent to the concentration of NADH. High-dose of NADH (above 10 mM) can induce cell death and intratumoral injection of NADH is validated for inhibiting tumor growth in mice. This study highlights the potential of electrochemical nanosensor for tracking and understanding the role of H2 O2 in screening new anticancer drug.

Ag2S/Ag Nanoparticle Microelectrodes for In Vivo Potentiometric Measurement of Hydrogen Sulfide Dynamics in the Rat Brain.

Hydrogen sulfide (H2S) plays a pivotal role in gas signal transduction, neuroprotection, and regulation of physiological and pathological processes. However, in vivo tracking the dynamic of hydrogen sulfide in the complex brain environment still faces huge challenges. This study demonstrates a new potentiometric method to monitor in vivo the dynamics of hydrogen sulfide in the rat brain using silver nanoparticles (AgNPs)-modified carbon fiber microelectrodes (AgNPs/CFE) pretreated with Na2S (i.e., Ag2S/AgNPs/CFE), which acts as a solid-contact and ion-selective microelectrode. The Ag2S/AgNPs/CFE exhibits good potential response toward hydrogen sulfide in the range of 2.5-160 µM, with a detection limit of 0.8 µM. Because of the presence of Ag2S, the Ag2S/AgNPs/CFE shows good selectivity to hydrogen sulfide, avoiding the interference from coexistent electroactive neurochemicals and the analogies, such as ascorbic acid and cysteine in the central nervous system. This good selectivity combined with the reversibility, protein antifouling, and biocompatibility of the microelectrode enables the Ag2S/AgNPs/CFE to detect hydrogen sulfide in the rat brain during local microinfusion of Na2S and the change in pH. Our study provides a reliable method to track hydrogen sulfide selectively in vivo, which will help to explore the function of hydrogen sulfide in neurophysiology and pathology.

Establishment of a Nomogram for Predicting Lumbar Drainage-Related Meningitis: A Simple Tool to Estimate the Infection Risk.

BACKGROUND: Lumbar drainage (LD) is one of the common treatment techniques in neurosurgery. There is a risk of secondary meningitis when using this modality. We aim to predict the probability of the complication by designing a nomogram. METHODS: A retrospective study was conducted in a teaching hospital. Data were collected and LD-related meningitis (LDRM) was identified, mainly based on clinical manifestations and cerebrospinal fluid analysis. Univariate analysis was used to screen the risk factors, and binary logistic analysis was performed to build the prediction model, which was furtherly transferred into a nomogram. The prediction performance was evaluated by receiver operating characteristic (ROC) curve, Hosmer-Lemeshow test, and nomogram calibration plot. Internal validation was processed by using ordinary bootstrapping. RESULTS: A total of 273 patients who match the research criteria were enrolled, in which 37 cases (13.6%) were confirmed to have LDRM. Univariate analysis showed the risk factors included diabetes (p = 0.003), admission on surgical intensive care unit (p = 0.012), duration time (p < 0.001), site leakage (p < 0.001), and craniotomy (p < 0.001). In multivariate analysis, four of the variables were identified as independent risk factors to establish a prediction model, and a graphical nomogram was designed. The area under the ROC curve was 0.837, and the p value in the Hosmer-Lemeshow test was 0.610, with a mean absolute error in the calibration plot calculated as 0.022. The indices in the testing set were in good accordance with the original set when internal validation was performed. CONCLUSIONS: This is the first study to transform the prediction model of LDRM into a nomogram, which can be considered as a tool for clinicians to assess infection risk.

[Negative HBsAg and HBsAb in Women of Child-bearing Age in Mianyang].

OBJECTIVES: To investigate the distribution of women with negative HBsAg and HBsAb at child-bearing age in Mianyang. METHODS: A total of 62 551 women aged 15-49 yr. were selected randomly using a multistage sampling strategy in Mianyang to participate in a questionnaire survey. Blood samples were collected during the survey. HBsAg and HBsAb were detected by enzyme-linked immunosorbent assay (ELISA). Those who were both HBsAg and HBsAb negative were deemed as susceptible to future infection of HBV. RESULTS: Data from 62 035 participants were valid for analysis: 28 460 (45.88%) were both HBsAg and HBsAb negative. Those aged 15-20 yr. had the lowest negative rate. Higher HBsAg and HBsAb negative rates were found in Han (lowest in Tibetan), rural residents, widowed/divorced (lowest in married), peasants (lowest in medical workers), those with a family history of Hepatitis B and without vaccination ( P<0.005). CONCLUSIONS: A high proportion of women at child-bearing age in Mianyang was found to be HBsAg and HBsAb negative. They should be monitored and vaccinated as a priority population in the prevention of mother-to-children infection of hepatitis B.

Trends, correlates, and disease patterns of antidepressant use among elderly persons in Taiwan.

PURPOSE: The population-based National Health Insurance database was used to investigate the trends, correlates, and disease patterns for elderly people in Taiwan who use antidepressants. METHODS: The National Health Research Institute provided a database of 1000,000 random subjects for study. We created a sample of subjects who were older than 65 years from 1997 to 2005. Trends, prevalence, and associated factors of antidepressant use were detected. We also examined the proportion of antidepressant use for psychiatric and medical disorders. RESULTS: The one-year prevalence of antidepressant use in elderly persons increased from 5.8 % in 1997 to 9.8 % in 2005. The one-year prevalence rates of tricyclic antidepressant (TCA), selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), serotonin modulator, and other antidepressant use in 2005 were 5.3, 2.6, 0.4, 2.9, and 0.6 %, respectively. Overall antidepressant use was higher for those in the 75- to 84-year-old age group, females, and those with higher Charlson Comorbidity Index scores. Among subjects using TCAs, 77.6 % users did not have a psychiatric diagnosis. Psychiatric disorders were commonly found in most SSRI and SNRI users (85.1 and 90.1 %, respectively). Subjects using SSRIs and SNRIs had higher proportions of psychiatric disorders such as neurotic depression, major depression, senile and presenile organic psychotic conditions, and anxiety. CONCLUSION: The prevalence of antidepressant use among elderly persons increased greatly from 1997 to 2005. SSRIs, SNRIs, and other antidepressants were used mostly by subjects with psychiatric disorders, whereas TCAs were used mostly by subjects with nonpsychiatric disorders.

WSSV early protein WSSV004 enhances viral replication by suppressing LDH activity.

White spot syndrome virus (WSSV) is known to upregulate glycolysis to supply biomolecules and energy for the virus's replication. At the viral genome replication stage, lactate dehydrogenase (LDH), a glycolytic enzyme, shows increased activity without any increase in expression. In the present study, yeast 2-hybrid screening was used to identify WSSV proteins that interacted with LvLDH isoform 1 and 2, and these included the WSSV early protein WSSV004. The interaction between WSSV004 and LvLDH1/2 was confirmed by co-immunoprecipitation. Immunofluorescence showed that WSSV004 co-localized with LvLDH1/2 in the cytoplasm. dsRNA silencing experiments showed that WSSV004 was crucial for WSSV replication. However, although WSSV004 silencing led to the suppression of total LvLDH gene expression during the viral late stage, there was nevertheless a significant increase in LvLDH activity at this time. We also used affinity purification-mass spectrometry to identify cellular proteins that interact with WSSV004, and found a total of 108 host proteins and 3 WSSV proteins with which it potentially interacts. Bioinformatics analysis revealed that WSSV004 and its interacting proteins might be responsible for various biological pathways during infection, including vesicular transport machinery and RNA-related functions. Collectively, our study suggests that WSSV004 serves as a multifunctional modulator to facilitate WSSV replication.

N6-methyladenosine enhances the expression of TGF-ß-SMAD signaling family to inhibit cell growth and promote cell metastasis.

TGF-ß-SMAD signaling pathway plays an important role in the progression of various cancers. However, posttranscriptional regulation such as N6-methyladenosine (m6A) of TGF-ß-SMAD signaling axis remains incompletely understood. Here, we reveal that insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) is low expression as well as associated with poor prognosis in clear cell renal cell carcinoma (ccRCC) patients and inhibits proliferation as well as promotes metastasis of ccRCC cells. Mechanistically, IGF2BP2 systematically regulates TGF-ß-SMAD signaling family, including TGF-ß1/2, TGF-ßR1/2 and SMAD2/3/4, through mediating their mRNA stability in an m6A-dependent manner. Furthermore, the functional effects of IGF2BP2 on ccRCC cells is mediated by TGF-ß-SMAD signaling downstream effector SMAD4, which is identified three m6A sites in 5'UTR and CDS. Our study establishes IGF2BP2-TGF-ß-SMAD axis as a new regulatory effector in ccRCC, providing new insights for developing novel therapeutic strategies.

DRAIC mediates hnRNPA2B1 stability and m6A-modified IGF1R instability to inhibit tumor progression.

Type 1 insulin-like growth factor receptor (IGF1R) plays an important role in cancer, however, posttranscriptional regulation such as N6-methyladenosine (m6A) of IGF1R remains unclear. Here, we reveal a role for a lncRNA Downregulated RNA in Cancer (DRAIC) suppress tumor growth and metastasis in clear cell Renal Carcinoma (ccRCC). Mechanistically, DRAIC physically interacts with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and enhances its protein stability by blocking E3 ligase F-box protein 11 (FBXO11)-mediated ubiquitination and proteasome-dependent degradation. Subsequently, hnRNPA2B1 destabilizes m6A modified-IGF1R, leading to inhibition of ccRCC progression. Moreover, four m6A modification sites are identified to be responsible for the mRNA degradation of IGF1R. Collectively, our findings reveal that DRAIC/hnRNPA2B1 axis regulates IGF1R mRNA stability in an m6A-dependent manner and highlights an important mechanism of IGF1R fate. These findings shed light on DRAIC/hnRNPA2B1/FBXO11/IGF1R axis as potential therapeutic targets in ccRCC and build a link of molecular fate between m6A-modified RNA and ubiquitin-modified protein.

Trends, correlates, and disease patterns of antipsychotic use among children and adolescents in Taiwan.

PURPOSE: We used Taiwan's population-based National Health Insurance database to investigate the trends, correlates, and disease patterns of antipsychotic use among children and adolescents. METHODS: The National Health Research Institutes provided a database of 1,000,000 random subjects for study. We chose subjects who were aged 18 years or younger during 1997-2005. In this sample, subjects who were given at least one antipsychotic prescription, including first-generation antipsychotics (FGAs) or second-generation antipsychotics (SGAs), were identified. Trends, prevalence, and associated factors of antipsychotic use were determined. The proportion of antipsychotic use for psychiatric and medical disorders was also analyzed. RESULTS: The 1-year prevalence of SGA use increased from 0.00 % in 1997 to 0.09 % in 2005, whereas the 1-year prevalence of FGA use ranged from 2.24 to 3.43 % during this same period, with no significant change. Age and male gender were associated with higher SGA use. Among SGA users, the greatest proportion suffered from psychiatric disorders, including tics, hyperkinetic syndrome of childhood, schizophrenia, affective disorders, and autism. Among FGA users, a larger proportion was for medical conditions, including diseases of the digestive and respiratory systems. CONCLUSION: The prevalence of pediatric SGA use increased greatly from 1997 to 2005. Among pediatric subjects using antipsychotics, SGAs were mostly used for psychiatric disorders, whereas FGAs were mostly prescribed for medical conditions. Future research will focus on indication, dosage, frequency, duration, adverse effects, and off-label use of antipsychotics in the pediatric population.

[Isolation and preliminary identification of stem-like cells in pituitary adenoma].

OBJECTIVE: To isolate and identify the pituitary adenoma stem-like cells from pituitary adenoma tissue. METHODS: Total RNA was prepared with 42 cases of pituitary adenoma tissue samples frozen in liquid nitrogen, the expression of Nestin was detected by RT-PCR. Tumor spheres were cultured in serum-free conditions and the immunefluorescence were used to detect the expression of stem cell markers such as Nestin, Sox2. RESULTS: The positive rate of Nestin mRNA expression was 88.1% (37/42). The cultured tumor spheres were found positive for Nestin, Sox2 by immunefluorescence detection. CONCLUSION: Stem cell markers are expressed in the pituitary adenoma tissue and the pituitary adenoma stem-like cells can be cultured in serum-free condition.

[Effects of bromocriptine on the treatment of prolactinomas in male patients and its influences on their sexual function].

OBJECTIVE: To explore the effect of bromocriptine in the treatment of male patients with prolactinoma and its impacts on their sexual function. METHODS: The clinical data of 29 male patients with prolactinomas treated with Bromocriptine were analysed, International Index of Erectile Function-5 (IIEF-5) was used to assess the sexual function of married patients before and after the treatment of Bromocriptine. RESULTS: The main clinical symptoms of male patients with prolactinomas were sexual dysfunction, headache and hypopsia, which were released significantly at 6 months after Bromocriptine therapy, with the decrease of serum prolactin (PRL) level (P < 0.05) and the improvement of basal testosterone (T) level (P < 0.05). The total normalization rate of PRL was 82.8%, and total effective rate of Bromocriptine therapy was 100%. According to the assessment of IIEF-5, all the male patients had their sexual function improved in various degree. CONCLUSION: Bromocriptine can improve the clinical symptoms of male patients with prolactinoma and their sexual function.