Associations of evening-type and insomnia symptoms with depressive symptoms among youths.

BACKGROUND: Evening-type and insomnia symptoms are significantly related to each other and independently associated with depressive symptoms, yet few studies have examined the potential interaction between these two conditions. Therefore, we aimed to examine the associations of evening-type and insomnia symptoms with depressive symptoms among Chinese youths, with a specific focus on the joint effects of the two conditions on depressive symptoms. METHODS: Participants aged between 12 and 25 were invited to participate in an online survey from December 15, 2022, to May 26, 2023. Multivariate logistic regression models and additive interaction models were used to examine the independent and joint effects of chronotypes and insomnia symptoms on depressive symptoms, respectively. RESULTS: Of the 6145 eligible youths, the prevalence of evening-type and insomnia symptoms were 24.9 % and 29.6 %, respectively. Both evening-type (adjusted OR, [AdjOR]: 3.21, 95 % CI: 2.80-3.67) and insomnia symptoms (AdjOR: 10.53, 95 % CI: 9.14-12.12) were associated with an increased risk of depressive symptoms. In addition, the additive interaction models showed that there is an enhanced risk of depression related to interaction between evening-type and insomnia symptoms (relative excess risk due to interaction, [RERI]: 11.66, 95 % CI: 7.21-16.11). CONCLUSIONS: The present study provided additional evidence demonstrating the presence of interaction between evening-type and insomnia symptoms, which can lead to a higher risk of depressive symptoms. Our findings argue the need for addressing both sleep and circadian factors in the management of depressive symptoms in young people.

The dynamic role of platelets in cancer progression and their therapeutic implications.

Systemic antiplatelet treatment represents a promising option to improve the therapeutic outcomes and therapeutic efficacy of chemotherapy and immunotherapy due to the critical contribution of platelets to tumour progression. However, until recently, targeting platelets as a cancer therapeutic has been hampered by the elevated risk of haemorrhagic and thrombocytopenic (low platelet count) complications owing to the lack of specificity for tumour-associated platelets. Recent work has advanced our understanding of the molecular mechanisms responsible for the contribution of platelets to tumour progression and metastasis. This has led to the identification of the biological changes in platelets in the presence of tumours, the complex interactions between platelets and tumour cells during tumour progression, and the effects of platelets on antitumour therapeutic response. In this Review, we present a detailed picture of the dynamic roles of platelets in tumour development and progression as well as their use in diagnosis, prognosis and monitoring response to therapy. We also provide our view on how to overcome challenges faced by the development of precise antiplatelet strategies for safe and efficient clinical cancer therapy.

[Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study]. / æ¹–åŒ—æ©æ–½åœŸå®¶æ—è‹—æ—è‡ªæ²»å·žæ–°ç”Ÿå„¿çª’æ¯å±é™©å› ç´ åˆ†æžåŠåˆ—çº¿å›¾é¢„æµ‹æ¨¡åž‹çš„æž„å»ºï¼šä¸€é¡¹å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS: The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

Nanoparticle-Based Combination Therapy Enhances Fulvestrant Efficacy and Overcomes Tumor Resistance in ER-Positive Breast Cancer.

Nanoparticles (NP) spanning diverse materials and properties have the potential to encapsulate and to protect a wide range of therapeutic cargos to increase bioavailability, to prevent undesired degradation, and to mitigate toxicity. Fulvestrant, a selective estrogen receptor degrader, is commonly used for treating patients with estrogen receptor (ER)-positive breast cancer, but its broad and continual application is limited by poor solubility, invasive muscle administration, and drug resistance. Here, we developed an active targeting motif-modified, intravenously injectable, hydrophilic NP that encapsulates fulvestrant to facilitate its delivery via the bloodstream to tumors, improving bioavailability and systemic tolerability. In addition, the NP was coloaded with abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), to prevent the development of drug resistance associated with long-term fulvestrant treatment. Targeting peptide modifications on the NP surface assisted in the site-specific release of the drugs to ensure specific toxicity in the tumor tissues and to spare normal tissue. The NP formulation (PPFA-cRGD) exhibited efficient tumor cell killing in both in vitro organoid models and in vivo orthotopic ER-positive breast cancer models without apparent adverse effects, as verified in mouse and Bama miniature pig models. This NP-based therapeutic provides an opportunity for continual and extensive clinical application of fulvestrant, thus indicating its promise as a treatment option for patients with ER-positive breast cancer. SIGNIFICANCE: A smart nanomedicine encapsulating fulvestrant to improve its half-life, bioavailability, and tumor-targeting and coloaded with CDK4/6 inhibitor abemaciclib to block resistance is a safe and effective therapy for ER-positive breast cancer.

Effect of birth asphyxia on neonatal blood glucose during the early postnatal life: A multi-center study in Hubei Province, China.

BACKGROUND: Birth asphyxia causes hypoxia or inadequate perfusion to the organs of newborns, leading to metabolism dysfunctions including blood glucose disorders. METHODS: Neonates with and without birth asphyxia were retrospectively recruited from 53 hospitals in Hubei Province from January 1 to December 31, 2018. In summary, 875, 1139, and 180 cases in the control group, the mild asphyxia group, and the severe asphyxia group were recruited, respectively. Neonatal blood glucose values at postnatal 1, 2, 6, and 12 h (time error within 0.5 h was allowed) were gathered from the medical records. RESULTS: The incidence rates of hyperglycemia in the control group, the mild asphyxia group and the severe asphyxia group were 2.97%, 7.90%, and 23.33%, respectively (p < 0.001). Additionally, the incidence rates of hypoglycemia in the three groups above were 3.66%, 4.13%, and 7.78%, respectively (p = 0.042). The blood glucose values of neonates with hypoglycemia in the asphyxia group were lower than in the control group (p = 0.003). Furthermore, the blood glucose values of neonates with hyperglycemia were highest in the severe asphyxia group (p < 0.001). There were 778 and 117 cases with blood glucose records at four predefined time points in the mild and severe asphyxia group, respectively. The incidence of blood glucose disorders in the mild asphyxia group significantly decreased from postnatal 6 h (p＜0.05). However, we found no obvious changes of the incidence of glucose disorders within postnatal 12 h in the severe asphyxia group (p = 0.589). CONCLUSION: Birth asphyxia is likely to cause neonatal blood glucose disorders, both hypoglycemia and hyperglycemia, during the early postnatal life. The neonates with severe asphyxia have higher incidence, worse severity and longer duration of blood glucose disorders than neonates with mild asphyxia.

Bioinformatics analysis identifies ferroptosis­related genes in the regulatory mechanism of myocardial infarction.

Since ferroptosis is considered to be a notable cause of cardiomyocyte death, inhibiting ferroptosis has become a novel strategy in reducing cardiac cell death and improving cardiopathic conditions. Therefore, the aim of the present study was to search for ferroptosis-related hub genes and determine their diagnostic value in myocardial infarction (MI) to aid in the diagnosis and treatment of the disease. A total of 10,286 DEGs were identified, including 6,822 upregulated and 3.464 downregulated genes in patients with MI compared with healthy controls. After overlapping with ferroptosis-related genes, 128 ferroptosis-related DEGs were obtained. WGCNA successfully identified a further eight functional modules, from which the blue module had the strongest correlation with MI. Blue module genes and ferroptosis-related differentially expressed genes were overlapped to obtain 20 ferroptosis-related genes associated with MI. Go and KEGG analysis showed that these genes were mainly enriched in cellular response to chemical stress, trans complex, transferring, phosphorus-containing groups, protein serine/threonine kinase activity, FoxO signaling pathway. Hub genes were obtained from 20 ferroptosis-related genes through the PPI network. The expression of hub genes was found to be down-regulated in the MI group. Finally, the miRNAs-hub genes and TFs-hub genes networks were constructed. The GSE141512 dataset and the use of RT-qPCR assays on patient blood samples were used to confirm these results. The results showed that ATM, PIK3CA, MAPK8, KRAS and SIRT1 may play key roles in the development of MI, and could therefore be novel markers or targets for the diagnosis or treatment of MI.

Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder.

Bipolar disorder (BD) is a complex psychiatric disorder with strong heritability. Identification of new BD risk genes will help determine the mechanism underlying disease pathogenesis. In the present study, we carried out whole genome sequencing for a Chinese BD family with three affected members and three unaffected members, and identified multiple candidate causal variations, including a frameshift mutation in the GOLGB1 gene. Since a GOLGB1 missense mutation was also found in another BD pedigree, we carried out functional studies by downregulating Golgb1 expression in the brain of neonatal mice. Golgb1 deficiency had no effect on anxiety, memory, and social behaviors in young adult mice. However, we found that young adult mice with Golgb1 deficiency exhibited elevated locomotor activity and decreased depressive behaviors in the tail suspension test and the sucrose preference test, but increased depressive behaviors in the forced swim test, resembling the dual character of BD patients with both mania and depression. Moreover, Golgb1 downregulation reduced PSD93 levels and Akt phosphorylation in the brain. Together, our results indicate that GOLGB1 is a strong BD risk gene candidate whose deficiency may result in BD phenotypes possibly through affecting PSD93 and PI3K/Akt signaling.

Reducing Postoperative Recurrence of Early-Stage Hepatocellular Carcinoma by a Wound-Targeted Nanodrug.

New strategies to decrease risk of relapse after surgery are needed for improving 5-year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound-targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti-PD-L1)and an angiogenesis inhibitor (sorafenib)). These nanoparticles consist of highly biocompatible mesoporous silica (MSNP) that is surface-coated with platelet membrane (PM) to achieve surgical site targeting in a self-amplified accumulation manner. Sorafenib is introduced into the MSNP pores while covalently attaching anti-PD-L1 antibody on the PM surface. The resulting nano-formulation, abbreviated as a-PM-S-MSNP, can effectively target the surgical margin when intraperitoneally (IP) administered into an immune competent murine orthotopic HCC model. Multiple administrations of a-PM-S-MSNP generate potent anti-HCC effect and significantly prolong overall mice survival. Immunophenotyping and immunochemistry staining reveal the signatures of favorable anti-HCC immunity and anti-angiogenesis effect at tumor sites. More importantly, microscopic inspection of a-PM-S-MSNP treated mice shows that 2 out 6 are histologically tumor-free, which is in sharp contrast to the control mice where tumor foci can be easily identified. The data suggest that a-PM-S-MSNP can efficiently inhibit post-surgical HCC relapse without obvious side effects and holds considerable promise for clinical translation as a novel nanodrug.

Discovery and development of a novel N-(3-bromophenyl)-{[(phenylcarbamoyl)amino]methyl}-N-hydroxythiophene-2-carboximidamide indoleamine 2,3-dioxygenase inhibitor using knowledge-based drug design.

Indoleamine 2,3-dioxygenase-1 (IDO1) is a potential target for the next generation of cancer immunotherapies. We describe the development of two series of IDO1 inhibitors incorporating a N-hydroxy-thiophene-carboximidamide core generated by knowledge-based drug design. Structural modifications to improve the cellular activity and pharmacokinetic (PK) properties of the compounds synthesized, including extension of the side chain of the N-hydroxythiophene-2-carboximidamide core, resulted in compound 27a, a potent IDO1 inhibitor which demonstrated significant (51%) in vivo target inhibition on IDO1 in a human SK-OV-3 ovarian xenograft tumor mouse model. This strategy is expected to be applicable to the discovery of additional IDO1 inhibitors for the treatment of other diseases susceptible to modulation of IDO1.

Effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia: a multicenter study in Hubei Province, China. / çª’æ¯æ–°ç”Ÿå„¿ç³–ä»£è°¢ç´Šä¹±å¯¹è¿‘æœŸé¢„åŽçš„å½±å“ï¼šä¸€é¡¹æ¹–åŒ—çœå¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, P<0.05) or with severe asphyxia (19.8% vs 8.1%, P<0.05) or hypothermia therapy (4.8% vs 1.5%, P<0.05), as well as a significantly higher incidence rate of disorder of glucose metabolism (18.8% vs 12.5%, P<0.05). Compared with the good prognosis group, the poor prognosis group had a significantly higher incidence rate of disorder of glucose metabolism at 1, 2, and 6 hours after birth (P<0.05). The multivariate logistic regression analysis showed that recurrent hyperglycemia (adjusted odds ratio=2.380, 95% confidence interval: 1.275-4.442, P<0.05) was an independent risk factor for poor prognosis in neonates with asphyxia. CONCLUSIONS: Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.

Knowledge Sharing Among Healthcare Practitioners: Identifying the Psychological and Motivational Facilitating Factors.

There exists a lack of an understanding of how to facilitate knowledge sharing (KS) behaviors in healthcare organizations. This study is among the first to specifically address this issue through synthesizing psychological ownership (PO), self-determination theory, and psychological empowerment (PE) theory. This study developed a research model that described the impact of the psychological and motivational facilitating factors, including autonomous motivation, user PE, and PO on knowledge sharing intention (KSI) and knowledge sharing behavior (KSB). Data collected from 343 healthcare professionals were analyzed using the technique of partial least squares (PLS) to validate the research model. The results indicated that user PE, organization-based PO, and autonomous motivation all had significant direct/indirect positive effects on KSI and KSB as we hypothesized. Surprisingly, knowledge-based PO had a significant positive effect on KSI, which contradicted our original hypothesis. The implications for theory and for practice, limitations, and future research directions are discussed accordingly.

Xanthine Derivatives Reveal an Allosteric Binding Site in Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2).

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) plays an important role in one-carbon metabolism. The MTHFD2 gene is upregulated in various cancers but very low or undetectable in normal proliferating cells, and therefore a potential target for cancer treatment. In this study, we present the structure of MTHFD2 in complex with xanthine derivative 15, which allosterically binds to MTHFD2 and coexists with the substrate analogue. A kinetic study demonstrated the uncompetitive inhibition of MTHFD2 by 15. Allosteric inhibitors often provide good selectivity and, indeed, xanthine derivatives are highly selective for MTHFD2. Moreover, several conformational changes were observed upon the binding of 15, which impeded the binding of the cofactor and phosphate to MTHFD2. To the best of our knowledge, this is the first study to identify allosteric inhibitors targeting the MTHFD family and our results would provide insights on the inhibition mechanism of MTHFD proteins and the development of novel inhibitors.

LPS-Induced Inflammation Affects Midazolam Clearance in Juvenile Mice in an Age-Dependent Manner.

PURPOSE: Inflammation has a significant impact on CYP3A activity. We hypothesized that this effect might be age dependent. Our objective was to conduct a population pharmacokinetic study of midazolam in mice at different developmental stages with varying degrees of inflammation to verify our hypothesis. METHODS: Different doses (2 and 5 mg/kg) of lipopolysaccharide (LPS) were used to induce different degrees of systemic inflammation in Swiss mice (postnatal age 9-42 days, n = 220). The CYP3A substrate midazolam was selected as the pharmacological probe to study CYP3A activity. Postnatal age, current body weight, serum amyloid A protein 1 (SAA1) levels and LPS doses were collected as covariates to perform a population pharmacokinetic analysis using NONMEM 7.2. RESULTS: A population pharmacokinetic model of midazolam in juvenile and adult mice was established. Postnatal age and current body weight were the most significant and positive covariates for clearance and volume of distribution. LPS dosage was the most significant and negative covariate for clearance. LPS dosage can significantly reduce the clearance of midazolam by 21.8% and 38.7% with 2 mg/kg and 5 mg/kg, respectively. Moreover, the magnitude of the reduction was higher in mice with advancing postnatal age. CONCLUSION: Both inflammation and ontogeny have an essential role in CYP3A activity in mice. The effect of LPS-induced systemic inflammation on midazolam clearance in mice is dependent on postnatal age.

Controllable Site-Selective Construction of 2- and 4-Substituted Pyrimido[1,2-b]indazole from 3-Aminoindazoles and Ynals.

A straightforward and novel controllable site-selective construction of 2- and 4-substituted pyrimido[1,2-b]indazole from 3-aminoindazoles and ynals has been developed. The high regioselectivity of this reaction could be easily switched by converting different catalytic systems. In this way, a series of 2- and 4-substituted pyrimido[1,2-b]indazole derivatives were obtained in moderate to good yields. In addition, the photophysical properties of compound 3a prepared by the present method were discussed.

Effects of COVID-19 on career and specialty choices among Chinese medical students.

Coronavirus disease 2019 (COVID-19) pandemic has brought unprecedented challenges to medical education systems and medical students. The aim of this study was to investigate the effects of COVID-19 pandemic on medical career and specialty choices among medical students. An online cross-sectional survey of Chinese medical students was conducted during the COVID-19 pandemic from February to April 2020. The students' willingness to be a doctor before and after the COVID-19 pandemic and changed willingness to specialize in respiratory medicine and infectious diseases were investigated. Multiple linear regression and binary logistic regression was used to explore factors that were associated with changes of willingness. A total of 1,837 medical students, including 1,227 females (66.8%), with a median age of 21.0 years, were recruited. Of the participants, 10.6% and 6.9% showed increased and decreased willingness to be a doctor after the COVID-19 outbreak, respectively. Moreover, 11.7% showed increased willingness and 9.5% showed decreased willingness to major in respiratory medicine and infectious diseases. Students with younger age, lower household income, fewer depressive symptoms, less exposure to negative pandemic information and more satisfaction with their own major after the pandemic were associated with increased willingness to be a doctor. Students who engaged in regular exercise, were males and undergraduate level, were interested in medicine, paid more attention to positive information, were satisfied with their majors, and had increased willingness to be a doctor after the pandemic were more likely to choose to specialize in respiratory medicine and infectious disease. However, the severity of anxiety symptoms was associated with decreased willingness to work in the specialties of respiratory medicine and infectious diseases. Psychological problems and professional satisfaction appear to be independent factors that affect medial career and specialty choices. The impacts of the COVID-19 pandemic on medical students require further research.

Clinical value of energy spectrum curves of dual-energy computer tomography may help to predict pathological grading of gastric adenocarcinoma.

BACKGROUND: To explore the clinical value of energy spectrum curves of dual-energy computer tomography (CT) in quantitative evaluation of different pathological grades of gastric adenocarcinoma. METHODS: A total of 62 patients with 36 poorly, 25 moderately and 1 well differentiated gastric adenocarcinomas confirmed pathologically were collected. Dual-energy CT plain and enhanced scanning were undergone before operation. Dual-Energy software was used to measure the slope of the energy spectrum curves (λ) in arterial and venous phases (VPs) after image reconstruction. Patients were divided into two groups according to the pathological results, including well and moderately differentiated gastric adenocarcinoma group and poorly differentiated gastric adenocarcinoma group. Data of each group were analyzed by independent sample t-test. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficiency of the corresponding parameters. RESULTS: There were significant differences in λ values of 40-50, 40-60, 40-80, 40-90, 40-100, 40-120, 40-130, 40-140 and 40-150 keV energy ranges in VP between the well and moderately differentiated group and poorly differentiated group (P<0.05), but no significant differences in λ values of different energy ranges in arterial phase (AP) between the two groups (P>0.05). And the area under curve in 40-120 keV energy range was the largest in VP. λ40-120keV=2.69 was selected as the diagnostic threshold with the maximum Youden index, the sensitivity and specificity were 61.1% and 76%, respectively. CONCLUSIONS: The energy spectrum curve of dual-energy CT had certain diagnostic value in the quantitative evaluation of pathological grading of gastric adenocarcinoma.

[A clinical epidemiological investigation of neonatal acute respiratory distress syndrome in southwest Hubei, China].

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS: Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.

Psychological impact of the COVID-19 pandemic on healthcare workers: a cross-sectional study in China.

BACKGROUND: Healthcare workers fighting against the coronavirus disease 2019 (COVID-19) pandemic are under tremendous pressure, which puts them at an increased risk of developing psychological problems. AIMS: This study aimed to investigate the prevalence of psychological problems in different healthcare workers (ie, physicians, medical residents, nurses, technicians and public health professionals) during the COVID-19 pandemic in China and explore factors that are associated with the onset of psychological problems in this population during this public health crisis. METHODS: A cross-sectional, web-based survey was conducted in February 2020 among healthcare workers during the COVID-19 pandemic. Psychological problems were assessed using the Generalized Anxiety Disorder Scale, Patient Health Questionnaire and Insomnia Severity Index. Logistic regression analyses were used to explore the factors that were associated with psychological problems. RESULTS: The prevalence of symptoms of anxiety, depression, insomnia and the overall psychological problems in healthcare workers during the COVID-19 pandemic in China was 46.04%, 44.37%, 28.75% and 56.59%, respectively. The prevalence of the overall psychological problems in physicians, medical residents, nurses, technicians and public health professionals was 60.35%, 50.82%, 62.02%, 57.54% and 62.40%, respectively. Compared with healthcare workers who did not participate in front-line work, front-line healthcare workers had a higher risk of anxiety, insomnia and overall psychological problems. In addition, attention to negative or neutral information about the pandemic, receiving negative feedback from families and friends who joined front-line work, and unwillingness to join front-line work if given a free choice were three major factors for these psychological problems. CONCLUSIONS: Psychological problems are pervasive among healthcare workers during the COVID-19 pandemic. Receiving negative information and participating in front-line work appear to be important risk factors for psychological problems. The psychological health of different healthcare workers should be protected during the COVID-19 pandemic with timely interventions and proper information feedback.

Metabolic changes related to the IDH1 mutation in gliomas preserve TCA-cycle activity: An investigation at the protein level.

The discovery of the IDH1 R132H (IDH1 mut) mutation in low-grade glioma and the associated change in function of the IDH1 enzyme has increased the interest in glioma metabolism. In an earlier study, we found that changes in expression of genes involved in the aerobic glycolysis and the TCA cycle are associated with IDH1 mut. Here, we apply proteomics to FFPE samples of diffuse gliomas with or without IDH1 mutations, to map changes in protein levels associated with this mutation. We observed significant changes in the enzyme abundance associated with aerobic glycolysis, glutamate metabolism, and the TCA cycle in IDH1 mut gliomas. Specifically, the enzymes involved in the metabolism of glutamate, lactate, and enzymes involved in the conversion of α-ketoglutarate were increased in IDH1 mut gliomas. In addition, the bicarbonate transporter (SLC4A4) was increased in IDH1 mut gliomas, supporting the idea that a mechanism preventing intracellular acidification is active. We also found that enzymes that convert proline, valine, leucine, and isoleucine into glutamate were increased in IDH1 mut glioma. We conclude that in IDH1 mut glioma metabolism is rewired (increased input of lactate and glutamate) to preserve TCA-cycle activity in IDH1 mut gliomas.