Residual status and source analysis of phthalate esters in Ulungur Lake, China.

Ulungur Lake is the largest lake in northern Xinjiang and undertakes important aquatic tasks. It is the No. 1 fishing ground in northern Xinjiang, and the problem of persistent organic pollution in the water has received much attention. However, there are few studies on phthalate esters (PAEs) in the water of Ulungur Lake. Understanding the pollution levels, distribution characteristics and sources of PAEs is of great significance for the protection and prevention of water. Fifteen sampling sites are established in Ulungur Lake to collect water samples during flood and dry periods, then seventeen PAEs are extracted from the water samples and purified by liquid-liquid extraction-solid-phase purification. Gas chromatography-mass spectrometry is used to detect the pollution levels and distribution characteristics of the 17 PAEs and analyse their sources. Results show that the concentrations of PAEs in the dry and flood periods are 0.451-9.97 µg/L and 0.0490-6.38 µg/L, respectively. The concentration of ∑PAEs with time is characterised by the dry period > the flood period. The change in flow is the main reason for the diverse concentration distributions of PAEs in different periods. The concentration of ΣPAEs in the dry period is much lower on the side near the lake entrance of the Ulungur River and Irtysh River. In the dry period, PAEs mainly come from chemical production and the use of cosmetics and personal care products; in the flood period, they mainly come from chemical production. River input and atmospheric sedimentation are the main sources of PAEs in the lake.

KCNQ1OT1 affects the progression of diabetic retinopathy by regulating miR-1470 and epidermal growth factor receptor.

Long noncoding RNAs have been reported to play important roles in the pathogenesis of diabetic retinopathy (DR), which has been considered as the most common disease leading to vision loss. However, it is still unclear whether KCNQ1 overlapping transcript 1 (KCNQ1OT1) could affect DR. In this study, regarding quantitative reverse transcription polymerase chain reaction assay, KCNQ1OT1 level was upregulated while microRNA-1470 (miR-1470) was decreased in DR patients and human retinal endothelial cells. High KCNQ1OT1 expression was correlated with DR stage and low visual function. Using miR-1470 mimic or knockdown of KCNQ1OT1 could lead to the similar phenomenon; phospho-AKT, Bax, B-cell lymphoma 2, and cleaved poly-ADP ribose polymerase (PARP) were regulated, while vascularization was inhibited and apoptosis was promoted. Regarding bioinformatics analysis and in vitro dual luciferase reporter assay, there should be a negative correlation between KCNQ1OT1 and miR-1470. Additionally, mRNA of epidermal growth factor receptor (EGFR) was proved as the target of miR-1470 and EGFR targeting by miR-1470 initiated KCNQ1OT1 deficiency-induced apoptosis and promoted proliferation. KCNQ1OT1 and miR-1470 were proved to be the promoter and repressor of EGFR, respectively. The results suggested that KCNQ1OT1 could sponge miR-1470 and further regulate EGFR in DR.

Transthyretin Exerts Pro-Apoptotic Effects in Human Retinal Microvascular Endothelial Cells Through a GRP78-Dependent Pathway in Diabetic Retinopathy.

BACKGROUND/AIMS: Diabetic retinopathy (DR) is one of the main causes of blindness in the world. Our previous study showed that transthyretin (TTR) regulates key genes in the Tie2 pathway and inhibits the development of neovascularization in DR, but the mechanism is still unclear. Here, we investigated how TTR affects the progression of neovascularization in DR. METHODS: Natural and simulated DR media (hyperglycemia and hypoxia) were used to culture human retinal microvascular endothelial cells (hRECs). Flow cytometry was employed to investigate the effect of TTR on apoptosis of hRECs. Fluorescent labeling and immunofluorescence staining were used to determine the TTR distribution in hRECs. The membrane proteins of hRECs were extracted and applied to a sepharose-TTR column, and the captured proteins were identified by Mass Spectrometric analysis. Gene knock-down and western blotting assays were used to study the key signal pathway of the most abundant identified protein. RESULTS: TTR induced apoptosis of hRECs in an environment that simulated hypoxia. Immunofluorescent staining showed that TTR could enter the nuclei of hRECs. A total of 30 unique TTR-captured proteins were identified by Mass Spectrometry, and glucose-regulated protein 78 (GRP78) was one of the most abundant. Western blotting and gene knock-down indicated that TTR might upregulate GRP78 and facilitate apoptosis through the eIF2α/CHOP pathway. CONCLUSIONS: In the DR environment (hyperglycemia and hypoxia), TTR was shown to repress neovascularization by promoting apoptosis of hRECs through a GRP78-dependent pathway.

[Association between brain-derived neurotrophic factor and severity of asthma in children].

OBJECTIVE: To investigate the association between the serum level of brain-derived neurotrophic factor (BDNF) and the severity of asthma in children. METHODS: A total of 60 children with acute exacerbation of asthma were enrolled and divided according to the severity of the disease into mild group (n=18), moderate group (n=25), and severe group (n=17). Sixty healthy children were enrolled as controls. ELISA was used to measure the serum BDNF level in each group and the association between serum BDNF level and the severity of asthma was analyzed. RESULTS: The asthmatic children at the acute exacerbation and remission stages had significantly higher serum BDNF levels than healthy controls (P<0.05). The serum BDNF level was significantly reduced in the remission stage compared with that in the acute exacerbation stage in asthmatic children (P<0.05). The children with varying degrees of severity at the acute exacerbation stage had different serum BDNF levels: the severe group had the highest serum BDNF level and the mild group had the lowest level (P<0.05). CONCLUSIONS: BDNF may play an important role in the pathogenesis of childhood asthma and is related to the severity of the disease.

Does continuous positive airway pressure reduce aldosterone levels in patients with obstructive sleep apnea?

PURPOSE: Aldosterone is associated with the development of obstructive sleep apnea (OSA) and cardiovascular diseases. Continuous positive airway pressure (CPAP) is an effective treatment for OSA, but the impact of CPAP therapy on aldosterone levels in patients with OSA remains unclear. To address this issue, a meta-analysis was conducted to evaluate the effects of CPAP therapy on serum aldosterone levels in OSA. METHODS: Two reviewers independently searched PubMed, Cochrane library, Embase, and Web of Science before March 2015. Information on characteristics of subjects, study design, and pre- and post-CPAP treatment of serum aldosterone was extracted for analysis. Standardized mean difference (SMD) was calculated to estimate the treatment effects of CPAP therapy. RESULTS: A total of 5 studies involving 329 patients were pooled into this meta-analysis, including 3 observational studies and 2 randomized controlled studies. Results indicated significantly decreased aldosterone levels after CPAP therapy (SMD = -0.236, 95 % confidence interval (CI) = -0.45 to -0.02, z = 2.12, p = 0.034). CONCLUSIONS: This meta-analysis suggested that CPAP therapy was associated with a decrease in serum aldosterone in patients with OSA. Further large-scale, well-designed interventional investigations are needed to clarify this issue.

[Effect of obesity on treatment outcome of asthma predictive index-positive infants and young children with wheezing].

OBJECTIVE: To study the effect of obesity on the treatment outcome of asthma predictive index (API)-positive infants and young children with wheezing. METHODS: A total of 208 API-positive infants and young children with wheezing were enrolled. According to the Kaup index, the patients were divided into an obese group (n=93) and a non-obese group (n=115). The patients were given multimodality therapy in an acute episode of wheezing and aerosol inhalation of inhaled corticosteroid (ICS) budesonide suspension in the remission stage. The dose of ICS was adjusted according to clinical control. The patients were treated for 6 months, and were followed up at 2 weeks after treatment and once per month afterwards. RESULTS: At 2 weeks and 1 month after treatment, the obese group had significantly lower remission rates of clinical symptoms than the non-obese group (35.5%/75.3% vs 53.0%/87.8%; P<0.05). Compared with the non-obese group, the obese group had significantly higher incidence rates of wheezing at 3 and 6 months after treatment and a significantly higher proportion of patients who visited the emergency service or were hospitalized due to wheezing within 6 months (P<0.05). CONCLUSIONS: Obesity can inhibit the response to ICS treatment in API-positive infants and young children with wheezing.

[Clinical characteristics of different ages of children with acute exacerbation of bronchial asthma].

OBJECTIVE: To investigate the clinical characteristics of different ages of children with acute exacerbation of bronchial asthma. METHODS: The clinical data of 118 children with an acute exacerbation of bronchial asthma between June 2012 and June 2015 were retrospectively analyzed. These patients were classified into infant group (<3 years old), preschool group (3-6 years old), and school-age group (6-14 years old) to compare their clinical characteristics. RESULTS: The infant group had the highest rate of pneumonia, the highest rate of hospital use of antibacterial agents, the highest hospital costs, and the longest length of hospital stay, followed by the preschool group and the school-age group (P<0.05). For the maintenance treatment of asthma, the rate of use of inhaled corticosteroids was highest in the school-age group (70%), followed by the preschool group (50% )and the infant group (38%) (P<0.05). CONCLUSIONS: The clinical characteristics vary between different ages of children with acute exacerbation of bronchial asthma: the children less than 3 years old have a higher rate of pneumonia, a higher rate of use of antibacterial agents, higher hospital costs, a longer length of hospital stay, and a lower rate of standard treatment.

Hysteresis-Free and Bias-Stable Organic Transistors Fabricated by Dip-Coating with a Vertical-Phase-Separation Structure.

The morphology of organic films plays a pivotal role in determining the performance of transistor devices. While the dip-coating technique is capable of producing highly oriented organic films, it often encounters challenges such as limited coverage and the presence of defects in gaps between strips, adversely affecting device performance. In this study, we address these challenges by increasing solution viscosity through the incorporation of a substantial proportion of dielectric polymers, thereby enhancing the participation of additional molecules during the film formation process when pulled up. This method produces continuous and oriented organic films with a notable absence of gaps, significantly improving the carrier mobility of transistor devices by more than twofold. Importantly, the fabricated devices exhibit remarkable reliability, showing no hysteresis even after 200 cycles of measurement. Furthermore, the current and threshold voltages of the devices demonstrate exceptional stability, maintaining steady after 10,000 s of bias measurement. This approach provides a solution for the cost-effective and large-scale production of organic transistors, contributing significantly to the advancement of organic electronics.

Case report: Treatment-resistant depression with acute psychosis in an adolescent girl with Cushing's syndrome.

Cushing's syndrome (CS) is a rare disease with multiple somatic signs and a high prevalence of co-occurring depression. However, the characteristics of depression secondary to CS and the differences from major depression have not been described in detail. In this case, we report a 17-year-old girl with treatment-resistant depression with a series of atypical features and acute psychotic episodes, which is a rare condition secondary to CS. This case showed a more detailed profile of depression secondary to CS and highlighted the differences with major depression in clinical features, and it will improve insight into the differential diagnosis especially when the symptoms are not typical.

Content level and risk assessment of phthalate esters in surface water of Bosten Lake, China.

Bosten Lake is the main fishing and grazing area in Xinjiang. The pollution of phthalate esters (PAEs) in water has attracted much attention, but limited research has been conducted on PAEs in Bosten Lake. The distribution of PAEs in fifteen sampling sites of surface water in the dry and flood seasons were investigated to explore the content level of PAEs in Bosten Lake, and the risk was evaluated. Seventeen PAEs were detected by GC-MS after liquid-liquid and solid-phase purification. Results showed that the content of ∑PAEs in the water during dry and flood seasons is ND-26.226 µg/L and ND-7.179 µg/L. The content of PAEs in the water of Bosten Lake is at a medium level. DBP and DIBP are the main PAEs. The content of PAEs is related to the physicochemical properties of water, and the physicochemical properties of water in dry season have a more serious impact on PAEs. PAEs in water mainly come from domestic pollution and chemical production. The results of health risk assessment indicate that PAEs in water do not pose a carcinogenic risk or a non carcinogenic risk to human, which can meet the conditions of Bosten Lake as a fishing ground and livestock base, but the pollution of PAEs cannot be ignored.

[Influence of mutations in epidermal growth factor receptor gene on growth, metastasis and survival rate of non-small cell lung carcinoma].

OBJECTIVE: To evaluate the influence of mutations in epidermal growth factor receptor (EGFR) gene on the prognosis of non-small cell lung cancer (NSCLC). METHODS: A total of 107 NSCLC patients undergoing tumor resection from December 2005 to August 2009 at our hospital were recruited. Mutations of exons 18 - 21 of EGFR gene in patients were detected by polymerase chain reaction (PCR) amplification and gene sequencing. The influence of mutations in EGFR gene on the growth, metastasis and survival rate of NSCLC was evaluated. RESULTS: EGFR mutations were detected in 30 (28.0%) of 107 patients. The mutation distribution was as follows: exon 18 (n = 1), exon 19 (n = 8), exon 21 (n = 20), and exons 18 and 19 multiple (triple mutations, n = 1). NSCLC with EGFR mutations had a higher growth velocity than that without EGFR mutations [M(Q(1-3)): 0.42 (0.17 - 1.04) mm/d vs 0.21 (0.19 - 1.00) mm/d, P < 0.05]. EGFR mutations had no significant impaction on neither the lymph node metastasis of NSCLC (P > 0.05) nor on the tumor metastasis to other organs (P > 0.05). The mean survival time of patients with and without EGFR mutations were (18.2 ± 8.9) and (25.5 ± 7.8) months respectively. The 1, 2 and 3-year survival rate were 62.2% vs 72.2%, 47.7% vs 57.3% and 46.9% vs 56.3% respectively between patients with and without EGFR mutations. Log-rank test didn't show a significant difference among them (χ(2) = 0.59, P > 0.05). CONCLUSIONS: The EGFR mutations promote the growth of NSCLC. But it may not be a factor of predicting prognosis.

An Acute Manic Episode During 2019-nCoV Quarantine.

BACKGROUND: The 2019-nCov pandemic is currently a stressor for the general public worldwide. In China, people who have a history of contact with infected or suspected individuals need to quarantine for at least 2 weeks. Many people experienced anxiety, panic and depression in the quarantine period. However, acute manic episode triggered by stressful events is not common and was neglected. CASE PRESENTATION: A 32-year-old woman with direct contact history with her infected colleagues showed elevated mood and increased activity when she was identified negative of nuclear acid amplification test, after experiencing extreme stress in quarantine. She was diagnosed with acute manic episode finally. The social zeitgeber and reward hypersensitivity theoretical models have attempted to use psychobiological perspectives to determine why life stress can trigger a mood episode, including (hypo)mania. Besides, the temporal correlation between her somatic symptoms and psychological stimuli indicated a possibility of functional disturbance under acute stress. CONCLUSION: Quarantine is a major stressful event disrupting social zeitgebers for people who have had contact with infected individuals, especially for vulnerable individuals with a hypersensitive reward system. Stress could act as a trigger in the onset of manic episode, so psychological support should be more targeted at the vulnerable individuals in the initial phase of emergent crisis.

Indoor phthalate concentrations in residences in Shihezi, China: implications for preschool children's exposure and risk assessment.

Despite the risks associated with phthalate exposure, there are few studies emphasizing preschool children's exposure to phthalates in residences in Northwest China. In this study, seven phthalates from indoor dust samples were measured in 50 residences in Shihezi, China. Preschool children's exposure doses via non-dietary intake were calculated by Monte Carlo simulation. Risk assessment was conducted by comparing the simulated exposure dose with benchmarks for reproductive toxicity and cancer specified in Proposition 65 of California. The detection frequencies for all selected phthalates were more than 75%, with the exception of benzyl butyl phthalate (BBP) and di-n-octyl phthalate (DNOP). Bis(2-ethylhexyl) phthalate (DEHP) was the most principal compound in the dust samples (median = 455 µg/g and 462 µg/g in the bedroom and living room, respectively). The simulation displayed that the median DBP daily intake was 1.5-1.9 µg/day/kg for preschool children in Shihezi, which was considered a high level compared with similar studies around the world. The risk assessment indicated that almost all preschool children face potential reproductive risk due to dibutyl phthalate (DBP) exposure, with medians of hazard index (HI) from 9.6 to 12.4 for all age groups. Therefore, from a children's health perspective, attention should be paid to reducing indoor phthalate pollution and exposure in this area.

A novel transthyretin/STAT4/miR-223-3p/FBXW7 signaling pathway affects neovascularization in diabetic retinopathy.

MicroRNAs (miRNAs) are small RNAs without protein-coding functions that negatively regulate target genes and play important roles in physiological and pathological processes. The aim of this work was to reveal a novel miRNA/gene pathway in diabetic retinopathy (DR). A microarray was used to screen miRNAs in samples from nondiabetic controls and patients with DR, and miR-223-3p was screened as a potential candidate. Quantitative real-time PCR (qRT-PCR) revealed that the level of miR-223-3p was frequently overexpressed in DR samples and human retinal endothelial cells (hRECs) in hyperglycemia, but it was decreased in hyperglycemia after the addition of transthyretin (TTR). In addition, according to cell proliferation, tube formation, and wound healing assays, the downregulation of miR-223-3p suppressed cell migration and proliferation, whereas miR-223-3p upregulation showed the opposite effects. Furthermore, luciferase assays identified F-box and WD repeat domain-containing 7 (FBXW7) as a target mRNA of miR-223-3p. High glucose conditions facilitated the recruitment of signal transducer and activator of transcription 4 (STAT4) and promoted the transcription of miR-223-3p. In hRECs, in a hyperglycemic environment, TTR inhibited STAT4 expression, downregulated the level of miR-223-3p, and finally promoted FBXW7 expression. This study found a novel mechanism whereby TTR might affect neovascularization through a newly identified STAT4/miR-223-3p/FBXW7 cascade in DR.

Maternal Deprivation Influences Pup Ultrasonic Vocalizations of C57BL/6J Mice.

Maternal deprivation (MD) is frequently used as an early life stress model in rodents to investigate behavioral and neurological responses under stressful conditions. However, the effect of MD on the early postnatal development of rodents, which is when multiple neural systems become established, is rarely investigated due to methodological limitations. Ultrasonic vocalizations (USVs) are one of the few responses produced by neonatal rodents that can be quantitatively analyzed, and the quantification of USVs is regarded as a novel approach to investigate possible alterations in the neurobehavioral and emotional development of infant rodents under stress. To investigate the effect of MD on pup mice, we subjected C57BL/6J mice to MD and recorded the USVs of pups on postnatal days 1, 3, 7, 8, and 14. To determine whether the effect of MD on USVs was acute or cumulative, pre- and post-separation USV groups were included; sex differences in pup USV emission were also investigated. Our results suggest that (i) USV activity was high on postnatal days 3-8; (ii) the MD effect on USVs was acute, and a cumulative effect was not found; (iii) the MD mice vocalized more and longer than the controls at a lower frequency, and the effect was closely related to age; and (iv) female pups were more susceptible than males to the effect of MD on USV number and duration between postnatal days 3-8.

[Clinical application of portable spirometry in asthma].

OBJECTIVE: To investigate the clinical applications of portable spirometry in asthma. METHODS: Twenty patients with asthma were recruited from Peking Union Medical College Hospital. Flow-volume loop, simultaneous asthma symptoms, and mood were monitored three times a day for consecutive 14 days. RESULTS: In patients with a normal daytime spirometry, marked decline of forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) were observed at night and/or in the early morning. A within subject correlation analysis between FEV1, PEF, and asthma symptoms showed that the correlation between symptoms and airway obstruction was found only in seven out of twenty patients (35%). Four patients (20%) reported many symptoms with nearly normal portable spirometry. Accordingly, their symptoms were not correlated with FEV1 and PEF. This group of patients was defined as over-perceivers. On the contrary, another two patients (10%) did not report any symptoms while obvious airways obstruction was recorded by a portable spirometry. These patients were defined as under-perceivers. CONCLUSIONS: Dynamic monitoring of flow-volume loop with a portable spirometry is more accurate than routine lung function test in assessment of asthma severity. In addition, combined with simultaneous monitoring of symptoms, it would be of particularly helpful in identifying two specific types of asthma patients, e.g. over-perceivers and under-perceivers.

Family Perception and 6-Month Symptomatic and Functioning Outcomes in Young Adolescents at Clinical High Risk for Psychosis in a General Population in China.

BACKGROUND AND AIMS: Given the difficulty of treating schizophrenia and other forms of psychosis, researchers have shifted focus to early detection and intervention of individuals at clinical high risk (CHR) for psychosis. Previous studies have shown that elements in family functioning could predict symptom outcome in CHR individuals. However, associations between self reported family functioning and symptom or functioning outcome of CHR individuals was rarely reported. Our study aimed to investigate the characteristics and the role of family functioning in the development of CHR individuals among young adolescents. METHODS: A sample of 32 CHR individuals was recruited from 2800 university students. The characteristics of family perception were evaluated by both Family Assessment Device (FAD) and Family cohesion and adaptability evaluation Scale II (FACES II). 6 month follow up data was available with 25 of the recruited CHR individuals. Baseline socio-demographic characteristics and family functioning were compared between CHR and control group. We also measured the associations between different dimensions of perceived family functioning and both severity of prodromal symptoms and global functioning at baseline and 6-month follow up. RESULTS: CHR individuals showed more maladaptive family functioning compared to control in nearly all of the dimensions of FAD and FACES II except for Affective Involvement. Better Problem Solving and Affective Responsiveness predicted less severe positive and negative symptoms respectively. Family cohesion and adaptability were not only correlated with the baseline severity of general symptoms, but also positively associated with the general and disorganized symptom outcome. CONCLUSIONS: This study contributed preliminary evidence towards the associations between family perception and symptom outcome of CHR individuals. It also provided evidence for the importance of family interventions on CHR individuals.

[Medically unexplained dyspnea in children: a review of 34 cases].

OBJECTIVE: Medically unexplained dyspnea is common in adult and accounts for 14% patients complaining of dyspnea. Its occurrence in children is seldom recognized. In the present paper, 34 children with medically unexplained dyspnea (age 10 to 18 years) seen in Peking Union Medical College Hospital from 1996 to 2002 are reported. METHODS: The diagnosis of medically unexplained dyspnea was clinical: it was based on the presence of dyspnea and other complaints which cannot be explained by an organic disease. The patients answered Nijmegen questionnaire and state and trait anxiety (STAI), and performed hyperventilation provocation test. Twenty sessions of breathing therapy were applied and 13 out of 34 children were followed up after the therapy. RESULTS: Among the children, 75% started to have symptoms at the age of 13 to 16 years, though the age of first episode could be as early as 8 years. In most of the cases, the course was chronic clinically. In addition to marked dyspnea, their clinical profile included symptoms of hyperventilation i.e. blurred vision, dizziness, tingling, stiff fingers or arm. The symptoms of anxiety were less frequent in children and accordingly the level of anxiety evaluated by means of STAI was lower in children compared to adult patients. The precipitating psychological factors appeared to be related to middle school competition. Pressure from exams, reprimand from stern and unsympathetic teachers coupled with high parental expectation could be emotionally damaging to psychologically susceptible children. Thirteen patients were followed up after 2-3 months of breathing therapy with emphasis on abdominal breathing and slowing down of expiration. After therapy, the sum score of the Nijmegen Questionnaire was markedly decreased. Dyspnea and symptoms of hyperventilation were improved. The level of anxiety was minimally modified. CONCLUSION: The cases illustrated the need for careful diagnostic evaluation and treatment because of the high rate of chronicity of the disorder.