Search

Child abuse is associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis functioning. However, the unique effects of psychological and physical abuse and protective factors against these effects remain largely unknown. To close these gaps, the present study examined the unique effects of psychological and physical abuse on cortisol stress response and explored the moderating role of psychosocial resources in these associations among a sample of Chinese preadolescent children (N = 150; aged 9-13 years; M

The potential hazards of polycyclic aromatic hydrocarbons (PAHs) on fetus development have raised widespread concerns in recent years, although current epidemiological findings are conflicting. The aim of this case-control study was to investigate the relationship between PAH concentrations in maternal serum and low birth weight (LBW). A questionnaire survey was conducted among 144 (72 pairs) neonates with normal or LBW and their mothers at four different hospitals in Shenzhen, China. Peripheral blood from primiparas and umbilical cord blood from neonates were collected. Concentrations of PAHs were determined by gas chromatography-mass spectrometry. The detection frequencies of PAHs were relatively higher in the peripheral blood samples, while levels of low molecular weight PAHs were greater than high molecular weight PAHs in both peripheral and umbilical cord blood samples. Phenanthrene was frequently detected in blood samples from the case and control groups. Logistic regression analysis showed that acenaphthene in peripheral blood was positively associated with LBW (p 0.05). This study found a relationship between exposure to certain PAHs and LBW, although future studies are needed to confirm these results.

As the main cause of osteoporosis, abnormal activity of osteoclasts could disrupt the balance between bone resorption and formation. Moreover, up-regulation of nuclear factor-kappa ligand (RANKL) expression by chronic inflammation-mediated inflammatory factors might contribute to the differentiation of osteoclast precursor cells. Therefore, an anti-inflammatory agent named yangonin was presented for inhibiting osteoclast and relieving inflammatory osteoporosis through down-regulating inflammatory factors.We established a model of macrophage inflammation and then verified the anti-inflammatory effect of yangonin. The inhibitory effect of yangonin on osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining, Western blotting and quantitative real-time PCR (qRT-PCR). Finally, micro-CT, TRAP and hematoxylin-eosin (HE) staining were used to show the effect of yangonin on inflammatory osteoporosis in vivo.Our results suggested that yangonin was able to reduce the secretion of inflammatory factors, down-regulate osteoclast-related genes such as TRAP, RANKL, cathepsin K (CTSK) and nuclear factor-activated T-cell 1 (NFATc1). Furthermore, it was demonstrated that yangonin could suppress the function of inflammatory cytokines in osteoclast differentiation and reporting, wherein NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways were involved. In an in vivo study, we implied that yangonin has a relieving effect on inflammatory osteoporosis.Our research shows that yangonin down-regulates inflammatory factors and inhibits the bone-breaking effect of inflammation through NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways to achieve the purpose of treating inflammatory osteoporosis.

We aimed to investigate the value of amide proton transfer magnetic resonance imaging (APT-MRI) in the classification of chronic kidney disease (CKD).A total of 30 patients with chronic kidney disease (CKD) and 25 healthy volunteers were enrolled in this study. Patients with chronic kidney disease were divided into two groups according to glomerular filtration rates: mild and moderate-to-severe renal impairment. Differences in cortical and medullary APT values were compared, and the correlation between corticomedullary APT values and glomerular filtration rates was analyzed. Data were statistically analyzed using SPSS 23.0.Based on glomerular filtration rates, 14 patients were assigned to the mild renal impairment group, and 16 were assigned to the moderate-to-severe renal impairment group. Both of the cortical and medullary APT values showed a gradually increasing trend in the control, the mild, and the moderate-to-severe renal impairment groups. Cortical APT values were higher than medullary APT values in all the control and renal impairment groups (P 0.05). APT values of the right renal cortex (r = -0.80, P 0.05) and medulla (r = -0.83, P 0.05) were negatively correlated with the glomerular filtration rate. Results of the receiver operating characteristic (ROC) curve analysis showed that corticomedullary APT values had high diagnostic efficacy in assessing different degrees of renal impairment.The APT values of the cortex and medulla in patients with CKD gradually increased with disease progression. These findings indicated that APT imaging can be used to evaluate renal function and renal injury in patients with CKD.

Background: Only limited data are available on the real-life clinical utilization of aerosolized medications in intensive care unit (ICU) patients. Exploring the utilization of aerosolized medicati...

To explore the clinical characteristics and genetic variant in a neonate with tuberous sclerosis complex (TSC).Clinical data of the neonate was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to next-generation sequencing (NGS).The child was noted to have yellowish hair upon birth. NGS revealed that he has harbored a heterozygous c.3914del (p.P1305Rfs*20) frameshifting variant of the TSC2 gene. The variant has probably caused premature termination of translation, resulting in a truncated protein.Yellowish hair has rarely been described as the first manifestation of TSC. The c.3914del (p.P1305Rfs*20) variant of the TSC2 gene probably underlay the TSC in this patient.

Human periodontal ligament fibroblast (HPDLF) is a major component of the resident cells in the periodontal microenvironment, and plays important roles in periodontitis through multiple mechanisms. Although lipopolysaccharide (LPS) has been shown to cause endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR) in HPDLF, the mechanisms governing HPDLF function in periodontitis are unclear. In this study, we tested the ability of unfolded protein response (UPR) to regulate HPDLF in vitro and examined the underlying mechanisms. We found LPS-pretreated HPDLF induced macrophage polarization toward M1 phenotype. UPR activation reduced the inflammatory cytokine production and downregulated the expression of TLR4 in HPDLF. The phosphorylation of NF-κB p65 and I-κB was also inhibited by UPR activation. Our findings demonstrate that the connection of LPS, UPR, and HPDLF may represent a new concrete theory of innate immunity regulation in periodontal diseases, and suggest that targeting of UPR in HPDLF may be developed as a potent therapy for periodontitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12192-021-01234-0.

Hantaan virus infection may cause severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. The chemokine fractalkine (CX3CL1) acts as a proinflammatory cytokine, and it is elevated in several infectious diseases. However, little is known about the contributions of CX3CL1 to HFRS pathogenesis. Present study detected plasma CX3CL1 levels and expression of the receptor CX3CR1 in HFRS patients and discussed the possible effects of CX3CL1 on pathogenesis of HFRS. Plasma CX3CL1 in acute phase and Critical/Severe groups of HFRS patients were significantly increased compared to that in normal controls (

Hantaan virus (HTNV) infection causes an epidemic of hemorrhagic fever with renal syndrome (HFRS) mainly in Asia. It is well known that T cells mediated anti-viral immune response. Although previous studies showed that double positive T (DP T) cells, a little portion of T lymphocytes, were involved in adaptive immune response during virus infection, their kinetic changes and roles in HTNV infection have not yet been explored. In this study, we characterized DP T cells from HFRS patients based on flow cytometry data combined with scRNA-seq data. We showed that HTNV infection caused the upregulation of DP T cells in the peripheral blood, which were correlated with disease stage. The scRNA-seq data clustered DP T cells, unraveled their gene expression profile, and estimated the ordering of these cells. The production of granzyme B and CD107a from DP T cells and the abundant TCR distribution indicated the anti-viral property of DP T cells. In conclusion, this study identified, for the first time, an accumulation of DP T cells in the peripheral blood of HFRS patients and suggested these DP T cells belonging to CD8

Stress granules (SGs) are non-membranous organelles facilitating stress responses and linking the pathology of age-related diseases. In a genome-wide imaging-based phenomic screen, we identify Pab1 co-localizing proteins under 2-deoxy-D-glucose (2-DG) induced stress in Saccharomyces cerevisiae. We find that deletion of one of the Pab1 co-localizing proteins, Lsm7, leads to a significant decrease in SG formation. Under 2-DG stress, Lsm7 rapidly forms foci that assist in SG formation. The Lsm7 foci form via liquid-liquid phase separation, and the intrinsically disordered region and the hydrophobic clusters within the Lsm7 sequence are the internal driving forces in promoting Lsm7 phase separation. The dynamic Lsm7 phase-separated condensates appear to work as seeding scaffolds, promoting Pab1 demixing and subsequent SG initiation, seemingly mediated by RNA interactions. The SG initiation mechanism, via Lsm7 phase separation, identified in this work provides valuable clues for understanding the mechanisms underlying SG formation and SG-associated human diseases. ispartof: NATURE COMMUNICATIONS vol:13 issue:1 ispartof: location:England status: published

Background: Lung cancer has the highest mortality rate among cancers worldwide, with non-small cell lung cancer (NSCLC) the most common type. Increasing evidence shows that PHB2 is highly expressed in other cancer types; however, the effects of PHB2 in NSCLC are currently poorly understood. Method: PHB2 expression and its clinical relevance in NSCLC tumor tissues were analyzed using a tissue microarray. The biological role of PHB2 in NSCLC was investigated in vitro and in vivo using immunohistochemistry and immunofluorescence staining, gene expression knockdown and overexpression, cell proliferation assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, wound healing assay, Transwell assay, western blot analysis, qRT-PCR, coimmunoprecipitation, and mass spectrometry analysis. Results: Our major finding is that PHB2 facilitates tumorigenesis in NSCLC by interacting with and stabilizing RACK1, which further induces activation of downstream tumor-promoting effectors. PHB2 was found to be overexpressed in NSCLC tumor tissues, and its expression was correlated with clinicopathological features. Furthermore, PHB2 overexpression promoted proliferation, migration, and invasion, whereas PHB2 knockdown enhanced apoptosis in NSCLC cells. The stimulating effect of PHB2 on tumorigenesis was also verified in vivo. In addition, PHB2 interacted with RACK1 and increased its expression through posttranslational modification, which further induced activation of the Akt and FAK pathways. Conclusions: Our results reveal the effects of PHB2 on tumorigenesis and its regulation of RACK1 and RACK1-associated proteins and downstream signaling in NSCLC. We believe that the crosstalk between PHB2 and RACK1 provides us with a great opportunity to design and develop novel therapeutic strategies for NSCLC.

Neuromyelitis optica spectrum disorder (NMOSD) is a central and acute demyelinating disease of the central nervous system with unusual clinical course. The development of novel biomarkers for NMOSD is critical for implementing effective clinical treatment. CD226 is known to be expressed on many types of peripheral lymphoid cells. However, the expression level and function of CD226 on type 1 T regulatory (Tr1) cells during NMOSD is unknown.Eighteen patients with NMOSD and 10 healthy volunteers were enrolled in the test group to probe the difference of CD226 expression on Tr1 cells using flow cytometric analysis.The expression of CD226 on Tr1 cells exhibited significantly increased tendency in NMOSD patients. Additionally, methylprednisolone and rituximab treatment decreased the expression of CD226 on Tr1 cells. Furthermore, the expression of CD226 on Tr1 cells was correlated with disease severity.This study provides a new basic insight into CD226 expression pattern on Tr1 cells, which have great potential to be biomarkers for monitoring the development and treatment of NMOSD.

This study was aimed to investigate the influence of miR-33-5p on the M1/M2 polarization of microglia and the underlying mechanism. Transcriptome sequencing was performed using microglia from miR-33-5p mimic and control groups. In total, 507 differentially expressed genes, including 314 upregulated genes and 193 downregulated genes, were identified. The subnetwork of module A, which was extracted from the protein-protein interaction networks, mainly contained the downregulated genes.

More than 15 million out of 70 million patients worldwide do not respond to available antiepilepticus drugs (AEDs). With the emergence of nanomedicine, nanomaterials are increasingly being used to treat many diseases. Here, we report that tetrahedral framework nucleic acid (tFNA), an assembled nucleic acid nanoparticle, showed an excellent ability to the cross blood-brain barrier (BBB) to inhibit M1 microglial activation and A1 reactive astrogliosis in the hippocampus of mice after status epilepticus. Furthermore, tFNA inhibited the downregulation of glutamine synthetase by alleviating oxidative stress in reactive astrocytes and subsequently reduced glutamate accumulation and glutamate-mediated neuronal hyperexcitability. Meanwhile, tFNA promotes α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization in the postsynaptic membrane by regulating AMPAR endocytosis, which contributed to reduced calcium influx and ultimately reduced hyperexcitability and spontaneous epilepticus spike frequencies. These findings demonstrated tFNA as a potential AED and that nucleic acid material may be a new direction for the treatment of epilepsy.

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone to cortisol in specific peripheral tissues, resulting in the concomitant antagonism of insulin action within these tissues. Dysregulation of 11β-HSD1, particularly in adipose tissues, has been associated with a variety of ailments including metabolic syndrome and type 2 diabetes mellitus. Therefore, inhibition of 11β-HSD1 with a small nonsteroidal molecule is therapeutically desirable. Implementation of a scaffold-hopping approach revealed a 3-point pharmacophore for 11β-HSD1 that was utilized to design a 2-spiroproline derivative as a steroid mimetic scaffold. Reiterative optimization provided valuable insight into the bioactive conformation of our novel scaffold and led to the discovery of several leads, such as compounds 39 and 51. Importantly, deleterious hERG inhibition and pregnane X receptor induction were mitigated by the introduction of a 4-hydroxyl group to the proline ring system.

Background To investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on hospitalizations for neonatal infectious diseases. Methods We analyzed data for neonatal inpatients admitted at a tertiary academic hospital with a principal diagnosis of an infectious disease during January 2015 to December 2020. We compared hospitalizations in 2020 (COVID-19 cohort), corresponding with the impact of COVID-19 pandemic and associated containment measures, and the comparable 2015 to 2019 (pre-COVID-19 cohort). Results 14,468 cases admitted for neonatal infectious diseases were included in our study, with 1201 cases in the COVID-19 cohort and 13,267 cases in the pre-COVID-19 cohort. The leading causes of hospitalizations for neonatal infectious diseases remain being respiratory tract infections (median ratio = 0.461, 95% CI 0.335–0.551), sepsis (median ratio = 0.292, 95% CI 0.263–0.361), gastric intestinal infections (median ratio = 0.095, 95% CI 0.078–0.118) and dermatologic infections (median ratio = 0.058, 95% CI 0.047–0.083). The seasonality of neonatal infectious disease hospitalizations could be obviously observed, with the total number and the overall rate of hospitalizations for neonatal infectious diseases in the first and fourth quarters greater than that of hospitalizations for neonatal infectious diseases in the second and third quarters in each year (1362.67 ± 360.54 vs 1048.67 ± 279.23, P = 0.001; 8176/20020 vs 6292/19369, P Conclusions Despite the outbreak of the COVID-19 pandemic, the leading causes of hospitalizations for neonatal infectious diseases remain unchanged. The seasonality of neonatal infectious disease hospitalizations could be obviously observed. The numbers as well as the overall rates of hospitalizations for neonatal infectious diseases in the COVID-19 cohort dramatically declined with the impact of the COVID-19 pandemic and its mitigation measures.

Objective The current study aimed to examine the stress-buffering effect of children's perceived social support on their hypothalamic-pituitary-adrenocortical axis and autonomic nervous system reactivity to an acute laboratory stressor. Methods A sample of 150 children (aged 9-13 years, mean [standard deviation] age = 10.69 [0.93] years, 74 girls) reported perceived social support, stressful life events, and underwent the Modified Trier Social Stress Test, during which six saliva samples were collected. A two-piece multilevel growth curve model with landmark registration was used to detect trajectory differences in the reactivity and recovery phases of the stress response and account for individual variation in the timing of poststressor peak hormone concentrations. Results The interaction between stressful life events and perceived social support significantly predicted poststressor peak cortisol levels (β = 0.0805, SE = 0.0328, p = .015) and cortisol recovery slope (β = -0.0011, SE = 0.0005, p = .040). Children with more life events and low social support exhibited the lowest poststressor peak cortisol levels and the flattest cortisol recovery slope. In contrast, children high in stressful life events and high in social support displayed cortisol response profiles more similar to those of children with low stressful life events. Conversely, there were no statistically significant two-way interactions of stressful life events and perceived social support on salivary α-amylase parameters (i.e., poststressor peak [p = .38], reactivity slope [p = .81], and recovery slope [p = .32]). Conclusions These results provide preliminary evidence for the buffering effect of children's perceived social support on the association between life stress and hypothalamic-pituitary-adrenocortical axis response profiles.

The study aimed to investigate the relationship between risk factors associated with vaginal microbiota and outcomes of cervical cerclage.A retrospective cohort study of singleton pregnancies with cervical cerclage was conducted. Before cerclage, participants underwent a vaginal microbiota assay, including morphological examination and functional vaginal microecological analysis using a vaginitis multi-test kit. The chi-squared test and logistic and linear regression analyses were performed to evaluate the associations of various risk factors with maternal and neonatal outcomes.Eighty-five participants were included. The mean interval between cerclage and delivery was 69.4 ± 36.7 days, and 12 (14.1%) of newborns died. A higher grade of vaginal cleanliness, a higher pH, a lower abundance of Lactobacillus spp., a higher sialidase-positive percentage, a higher positive percentage of clue cells, a higher lactobacillary grade, a higher Nugent score and a higher rate of microecological dysbiosis were significantly associated with a poor neonatal outcome and shorter cerclage to delivery intervals (P 0.001-0.041). Furthermore, sialidase positivity was associated with the highest risk of cervical cerclage failure (odds ratio [OR] 10.469; 95% confidence interval [CI] 1.096-36.087), followed by the presence of bulging membranes (OR 6.400; 95% CI 0.428-15.641) and vaginal microbiota dysbiosis (OR 6.038; 95% CI 0.173-17.072).An absence of Lactobacillus spp. and some functional factors of vaginal microbiota are potential risk factors that predict subsequent cerclage failure. These findings indicate the potential clinical utility of these factors to predict cervical cerclage failure for managing patient expectations and providing improved postoperative surveillance.

Objectives The aim of this project was to initiate and promote formal and individualized evidence-based education on healthy lifestyle choices during pregnancy for pregnant women. Introduction Evidence suggests that lifestyle choices during pregnancy can have a profound influence on many pregnancy complications and chronic diseases such as preterm birth, diabetes, obesity, fetal growth restriction, breast cancer and hypertensive diseases in both pregnant women and their babies. It is widely accepted that formal, individualized, hospital-directed education about lifestyle choices during pregnancy should commence as early as the first consultation between pregnant women and maternal healthcare workers. Methods The methods of this project were audit and feedback. The approach to data collection used the Joanna Briggs Institute (JBI) Practical Application of Clinical Evidence System and implementation planning utilized the Getting Research into Practice component. A baseline audit of 50 observations of midwife-led education on prenatal lifestyle were conducted and measured against seven best practice audit criteria. Targeted strategies were then implemented to improve compliance to best practice. A follow-up audit was conducted over a 6-month period from June 2019 to November 2019. Results The baseline audit revealed significant deficits between current prenatal education practice and recommended best practice. Zero percent compliance was observed in six out of seven audit criteria, indicating that education provided did not conform to best practice. Total compliance (100%) was observed for one audit criterion at baseline, assessing pregnant women being offered an opportunity to discuss and ask questions regarding the education session or information they had received. Three barriers that prevented midwives from achieving compliance with best practice were identified, and a bundled education strategy was implemented. A follow-up audit indicated 100% compliance of all audit criteria. Conclusion Results demonstrated that formal, individualized, midwife-led prenatal education and provision of relevant evidence-based resources had an immediate positive effect. The project helped to transform care givers' attitudes toward education regarding lifestyle during pregnancy from a passive routine 'must do' task to an active process with focus on healthy lifestyle and engagement of pregnant women. Future strategies such as support from hospital management and social media are planned in conjunction with follow-up clinical audits to ensure sustainability.

Background Primary vulvar melanoma was an aggressive and poorly understood gynecological tumor. Unlike cutaneous melanoma, the incidence of vulvar melanoma was low but the survival was poor. There were no standard staging system and no census on treatment strategies of vulvar melanoma. Therefore, we aimed to conduct and validate a comprehensive prognostic model for predicting overall survival of vulvar melanoma and provide guidance for clinical management. Methods Patients diagnosed with vulvar melanoma between year 2004 and 2015 from Surveillance, Epidemiology, and End Result (SEER) database were randomized to training cohort and validation cohort. Multivariate survival analysis was performed to screen for independent factors of survival. A nomogram was established to predict overall survival of vulvar melanoma. Receiver operating characteristic curve and calibration plot were performed to verify the discrimination and accuracy of the model. The decision curve analysis was performed to verify the clinical applicability of the model. Results Total 737 patients with vulvar melanoma were randomized to the training cohort (n = 517) and the validation cohort (n = 220). Nomogram including age, race, tumor site, depth of tumor invasion, lymph node status, distant metastasis, tumor size, surgery, chemotherapy and radiotherapy was established and validated. The c-indexes for SEER stage, American Joint Committee on Cancer stage and this model were 0.561, 0.635 and 0.826, respectively. The high-risk group scored by this model had worse survival than the low-risk group (P Conclusions Our model was deemed to be a useful tool for predicting overall survival of vulvar melanoma with good discrimination and clinical applicability. We hoped this model would assist gynecologists in clinical decision and management of patients diagnosed with vulvar melanoma.

Several studies have highlighted that facilitators’ attitudes toward interventions are crucial for implementing innovative psychosocial interventions. However, in the emerging implementation science field, little research has examined how organizational and individual factors may influence teachers’ positive attitudes and readiness toward evidence-based interventions. The current study investigated the association between teachers’ quality of work life and their attitudes toward an innovative psychosocial intervention for children affected by parental HIV/AIDS; the study also probed the potential indirect roles of self-efficacy and burnout. A total of 157 teachers with different levels of involvement in the intervention study were recruited from 47 schools to participate in the investigation. Our results revealed that teachers’ quality of work life was positively associated with their attitudes toward the intervention directly and indirectly through enhanced self-efficacy and reduced burnout. The findings highlight the importance of organizational and individual factors in successfully implementing innovative psychosocial interventions for vulnerable children in organizations such as schools. Researchers should work with organizations to provide the necessary quality of work life and sufficient training to semi-professionals in order to boost their self-efficacy, reduce their burnout, and improve their attitudes toward innovative intervention programs to achieve the expected effectiveness of the interventions, particularly in resource-limited regions such as central rural China.

The generation of pancreatic cell types from renewable cell sources holds promise for cell replacement therapies for diabetes. Although most effort has focused on generating pancreatic beta cells, considerable evidence indicates that glucagon secreting alpha cells are critically involved in disease progression and proper glucose control. Here we report on the generation of stem cell-derived human pancreatic alpha (SC-alpha) cells from pluripotent stem cells via a transient pre-alpha cell intermediate. These pre-alpha cells exhibit a transcriptional profile similar to mature alpha cells and although they produce proinsulin protein, they do not secrete significant amounts of processed insulin. Compound screening identified a protein kinase c activator that promotes maturation of pre-alpha cells into SC-alpha cells. The resulting SC-alpha cells do not express insulin, share an ultrastructure similar to cadaveric alpha cells, express and secrete glucagon in response to glucose and some glucagon secretagogues, and elevate blood glucose upon transplantation in mice., Deriving functional pancreatic cell types from human stem cells may have important clinical applications. Building on previous work, here the authors generate stem cell-derived alpha cells via a polyhormonal intermediate, which have a gene expression pattern similar to human islet alpha cells and behave as such when transplanted into mice.

Purpose The purpose of this study was to evaluate the performance of motion-weighted Golden-angle RAdial Sparse Parallel MRI (motion-weighted GRASP) for free-breathing dynamic contrast-enhanced MRI (DCE-MRI) of the lung. Methods Motion-weighted GRASP incorporates a soft-gating motion compensation algorithm into standard GRASP reconstruction, so that motion-corrupted motion k-space (e.g., k-space acquired in inspiratory phases) contributes less to the final reconstructed images. Lung MR data from 20 patients (mean age = 57.9 ± 13.5) with known pulmonary lesions were retrospectively collected for this study. Each subject underwent a free-breathing DCE-MR scan using a fat-statured T1-weighted stack-of-stars golden-angle radial sequence and a post-contrast breath-hold MR scan using a Cartesian volumetric-interpolated imaging sequence (BH-VIBE). Each radial dataset was reconstructed using GRASP without motion compensation and motion-weighted GRASP. All MR images were visually evaluated by two experienced radiologists blinded to reconstruction and acquisition schemes independently. In addition, the influence of motion-weighted reconstruction on dynamic contrast-enhancement patterns was also investigated. Results For image quality assessment, motion-weighted GRASP received significantly higher visual scores than GRASP (P 0.05) between the breath-hold BH-VIBE and motion-weighted GRASP images. For assessment of temporal fidelity, motion-weighted GRASP maintained a good agreement with respect to GRASP. Conclusion Motion-weighted GRASP achieved better reconstruction performance in free-breathing DCE-MRI of the lung compared to standard GRASP, and it may enable improved assessment of pulmonary lesions.

This study is to investigate the association between nickel exposure and serum lipid profiles. We analyzed the population from the National Health and Nutrition Examination Surveys (NHANES) 2017-2018. Urinary nickel exposure was measured using inductively coupled-plasma mass spectrometry. Serum lipid profiles, including triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C), were measured using the standard biochemistry assays. The association between urinary nickel and lipid profiles was examined using multivariable linear regression models and restricted cubic spine plots. There was a significant negative relationship between nickel level and TC (β, - 9.67; 95% CI, - 13.58 to - 5.76), HDL-C (β, - 1.57; 95% CI, - 2.98 to - 0.16), and LDL-C (β, - 5.88; 95% CI, - 11.04 to - 0.71) after adjusting for potential confounding factors. Furthermore, restricted cubic spines showed that only HDL-C was nonlinearly associated with nickel (p for nonlinearity 0.004). However, nickel exposure was not related to the level of triglyceride. The exposure to nickel was linearly associated with serum total cholesterol and LDL-C while nonlinearly associated with HDL-C in general population.

There are mixed opinions on the influence of diabetes on the prognosis of patients receiving percutaneous coronary intervention (PCI). Therefore, in this study, the quantitative flow ratio (QFR), an emerging technology of functional evaluation, was used to explore the impact of diabetes on coronary physiology in patients who underwent PCI.Patients who underwent successful PCI and a 1-year angiographic follow up were retrospectively screened and analyzed by the QFR. Based on the presence or absence of diabetes, 677 enrolled patients (794 vessels) were classified into a diabetes group (211 patients, 261 vessels) and a non-diabetes group (466 patients, 533 vessels). The results of QFR analysis and clinical outcomes were compared between the two groups.The two groups reached a similar level of post-PCI QFR (0.95 ± 0.09 vs 0.96 ± 0.06, P = 0.292). However, at the 1-year follow up, the QFR was lower (0.93 ± 0.11 vs 0.96 ± 0.07, P 0.001), and the degree of QFR decline was more obvious (-0.024 ± 0.090 vs -0.008 ± 0.070, P = 0.023) in the diabetes group. Additionally, diabetes was independently associated with functional restenosis (odds ratio 2.164, 95% confidence interval 1.210-3.870, P = 0.009) and target vessel failure (odds ratio 2.654, 95% confidence interval 1.405-5.012, P = 0.003).As evaluated by the QFR, patients with diabetes received less coronary physiological benefit from PCI, which was consistent with their clinical outcomes.

Endometriosis is a gynecological disease that endometrial cells develop outside the uterus. This event happens when the endometrial glands grow outside the endometrium and uterine muscles, especially in the pelvis. Although endometriosis is widespread, the clinical manifestations of the disease are very different, and it is challenging to adapt to the conventional classification system to divide patients into homogeneous groups. Given the importance of endometriosis, a correct, accurate, and timely diagnosis of this disease can significantly prevent its complications. Using health-related software is one of these ways. Enhanced Endometriosis Archiving Software (ENEAS) is a web-based application based on one of the most widely used open-source database management systems (MySQL), allowing the direct link to other open-source software for data management and storage. In the current study, the effect of ENEAS application was considered in patients with endometriosis, and its influence on IL-8 and MCP-1 gene expression was evaluated. For this purpose, 100 women with endometriosis were divided into two groups of 50 patients. The first group (control group) was examined by a gynecologist and received medication and treatment. In the case group, their demographic and clinical information were entered into ENEAS software. To study the expression of the IL-8 gene and MCP-1 gene, after collecting 5 ml of blood samples in tubes containing anticoagulant, RNA extraction was performed by Total RNA Purification Kit (Cat. 17200, 37500, 17250). Then cDNA synthesis was performed for this purpose, and a Bioneer DNA synthesis kit (South Korea) was used. The results showed that the expression level of the IL-8 gene in the case group was significantly reduced compared to the control group (P = 0.035). MCP-1 gene expression was also decreased compared to the control group, but this decrease was not significant. Therefore, those who used this application for treatment had reduced expression of IL-8 and MCP-1 genes. This event indicates that this application has reduced the amount of inflammation caused by endometriosis with proper analysis.

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone to cortisol in specific peripheral tissues resulting in the concomitant antagonism of insulin action within these tissues. Dysregulation of 11β-HSD1, particularly in adipose tissues, has been associated with metabolic syndrome and type 2 diabetes mellitus. Therefore, inhibition of 11β-HSD1 with a small nonsteroidal molecule is therapeutically desirable. Implementation of a scaffold-hopping approach revealed a three-point pharmacophore for 11β-HSD1 that was utilized to design a steroid mimetic scaffold. Reiterative optimization provided valuable insight into the bioactive conformation of our novel scaffold and led to the discovery of INCB13739. Clinical evaluation of INCB13739 confirmed for the first time that tissue-specific inhibition of 11β-HSD1 in patients with type 2 diabetes mellitus was efficacious in controlling glucose levels and reducing cardiovascular risk factors.

Objective Stage I‐II uterine papillary serous carcinoma (UPSC) has aggressive biological behavior and leads to poor prognosis. However, clinicopathologic risk factors to predict cancer‐specific survival of patients with stage I‐II UPSC were still unclear. This study was undertaken to develop a prediction model of survival in patients with early‐stage UPSC. Methods Using Surveillance, Epidemiology, and End Results (SEER) database, 964 patients were identified with International Federation of Gynecology and Obstetrics (FIGO) stage I‐II UPSC who underwent at least hysterectomy between 2004 and 2015. By considering competing risk events for survival outcomes, we used proportional subdistribution hazards regression to compare cancer‐specific death (CSD) for all patients. Based on the results of univariate and multivariate analysis, the variables were selected to construct a predictive model; and the prediction results of the model were visualized using a nomogram to predict the cancer‐specific survival and the response to adjuvant chemotherapy and radiotherapy of stage I‐II UPSC patients. Results The median age of the cohort was 67 years. One hundred and sixty five patients (17.1%) died of UPSC (CSD), while 8.6% of the patients died from other causes (non‐CSD). On multivariate analysis, age ≥ 67 (HR = 1.45, P = .021), tumor size ≥ 2 cm (HR = 1.81, P = .014) and >10 regional nodes removed (HR = 0.52, P = .002) were significantly associated with cumulative incidence of CSD. In the age ≥67 cohort, FIGO stage IB‐II was a risk factor for CSD (HR = 1.83, P = .036), and >10 lymph nodes removed was a protective factor (HR = 0.50, P = .01). Both adjuvant chemotherapy combined with radiotherapy and adjuvant chemotherapy alone decreased CSD of patients with stage I‐II UPSC older than 67 years (HR = 0.47, P = .022; HR = 0.52, P = .024, respectively). The prediction model had great risk stratification ability as the high‐risk group had higher cumulative incidence of CSD than the low‐risk group (P, Our prediction model of CSD based on proportional subdistribution hazards regression showed good performance in predicting the cancer‐specific survival of early‐stage UPSC patients and contributes to selection of adjuvant therapy for stage I‐II UPSC patients in clinical treatment strategy.

Biofouling is a nuisance in the practical application of biosensor, which seriously influences the reliability and accuracy of the detection. The utilization of antifouling interface material is a promising option for mitigating biofouling. Only highly accumulated antifouling polymeric surface tends to “zero” nonspecific protein adsorption. Herein, superior antifouling coatings based on chondroitin sulfate (CS) were prepared by the NH2-MIL-53 (Al) assisted strategy. This is a novel design to improve antifouling property of material by taking advantage of high specific surface area of three-dimensional MOF to increase the accumulation degree of antifouling functional groups per unit area. And the related chemical technology is simple and easy to operate. As expected, this novel CS-loaded MOF demonstrated an excellent antifouling characteristic in various biological samples, even in 100% goat serum. Only 8.48% changes of differential pulse voltammetry (DPV) were presented. Furthermore, this antifouling interface material is successfully applied for specific detection of tuberculosis (TB) gene in undiluted biofluids. This developed TB biosensor showed the high analytical performance with a wide linear range (1.00×10-16 M to 1.00×10-11 M) and a low detection limit, indicating that it may open new avenues for direct biosensing of disease markers for clinical samples.

Depression is characterized by low moods, anhedonia, and social avoidance. Effective and acceptable treatments are required for depression. Positive effects on mood have been observed in patients with depression after treatment with botulinum toxin A (BoNT/A).A total of 88 patients with depression were randomly assigned to BoNT/A (n = 56) and placebo (saline, n = 22) groups. The primary objective was to determine the change in the 17-item version of the Hamilton Depression Rating Scale (HAMD), 12 weeks after the treatments when compared with the baseline.The BoNT/A and placebo groups did not differ significantly in all the collected baseline characteristics. However, there was a significant improvement in the depressive symptoms of the BoNT/A group compared to those of the placebo group throughout the 12-week follow-up period. This was according to the measurements of HAMD (F (1, 370) = 9.094, P = 0.0027), Self-rating Depression Scale (SDS) (F (1, 370) = 11.26, P0.001), Hamilton Anxiety Scale (HAMA) (F (1, 410) = 8.673, P = 0.0034) and Self-rating Anxiety Scale (SAS) (F (1, 379) = 5.788, P = 0.017). Furthermore, the effectiveness was even higher at the end of the study period.The limitations include the absence of a multicenter study and an inadequate number of cases. Additionally, the mechanism of BoNT/A antidepression was not studied.This study showed that a single treatment with BoNT/A may accomplish a strong and sustained alleviation of depression in patients.

Objective: The study was to investigate the feasibility and accuracy of assessment for living renal donors before transplantation by using 3.0 T non-contrast-enhanced magnetic resonance angiography (NCE-MRA). Methods: 30 renal donors were investigated and underwent computed tomography angiography (CTA) and 3.0 T NCE-MRA before nephrectomy. Two radiologists independently assessed arterial and venous anatomy and potential kidney lesions. The image quality score, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), diameters and lengths of renal arteries and veins were compared between CTA and NCE-MRA. Imaging findings were compared with the surgical results served as reference standard. Agreement was assessed using κ test. The Wilcoxon test and paired sample t test were used for statistically significant differences. Results: The results of image quality score for renal arteries and veins were highly consistent between the two radiologists in NCE-MRA (p < 0.001). There was no significant difference in the scores of renal arterial and venous branches between NCE-MRA and CTA (p > 0.05). The SNR and CNR of renal vessels were higher than CTA (p < 0.001). There were no statistically significant differences in the length of renal vessels measured by the two methods (p > 0.05), and the diameter was smaller than that of CTA (p < 0.05). The detection of normal renal arteries and early branches by both examination techniques was consistent with intraoperative findings. Both methods showed good consistency between the anatomical variation of renal vein and the intraoperative diagnosis (p < 0.001). Conclusion: 3.0 T NCE-MRA can be used for evaluation of main renal arteries and veins with high accuracy for anatomy and variation classification, and can be used for pre-operative vascular evaluation of living donor kidney transplantation. Advances in knowledge: 3.0 T NCE-MRA can be used for evaluation of main renal arteries and veins with high accuracy for anatomy and variation classification, and can be used for pre-operative vascular evaluation of living donor kidney transplantation.

Background The aim of this study was to evaluate the predictive value of the hematological parameters in the identification of human cytomegalovirus (CMV) infection in infants less than 3 months. Methods A single‐center, observational study of infants with CMV infection was conducted retrospectively. Routine blood parameters were analyzed in CMV‐infected infants and controls with no differences of birthweight, sex, gestational age at birth, and date of admission. Furthermore, receiver‐operating curve was used to assess the predictive value of the hematological parameters for CMV infection. Results One hundred ninety cases with CMV infection were studied retrospectively. Compared with the control group, there were significant differences in the white blood cell count, neutrophil count, lymphocyte count, platelet count, hemoglobin, neutrophil‐to‐lymphocyte (NLR), platelet‐to‐lymphocyte (PLR), and lymphocyte‐to‐monocyte (LMR) for the patients with CMV infection (all p 0.28), an elevated PLR (>65.36), or both. NLR‐PLR score for CMV infection prediction yielded higher AUC values than NLR or PLR alone (0.760 vs. 0.689, 0.689; p, NLR‐PLR score for CMV infection prediction yielded higher AUC values than NLR or PLR alone (0.760 vs. 0.689, 0.689; p

Immune evasion and metabolic reprogramming are two fundamental hallmarks of cancer. Interestingly, lactate closely links them together. However, lactate has long been recognized as a metabolic waste product. Lactate and the acidification of the tumor microenvironment (TME) promote key carcinogenesis processes, including angiogenesis, invasion, metastasis, and immune escape. Notably, histone lysine lactylation (Kla) was identified as a novel post-modification (PTM), providing a new perspective on the mechanism by which lactate functions and providing a promising and potential therapy for tumors target. Further studies have confirmed that protein lactylation is essential for lactate to function; it involves important life activities such as glycolysis-related cell functions and macrophage polarization. This review systematically elucidates the role of lactate as an immunosuppressive molecule from the aspects of lactate metabolism and the effects of histone lysine or non-histone lactylation on immune cells; it provides new ideas for further understanding protein lactylation in elucidating lactate regulation of cell metabolism and immune function. We explored the possibility of targeting potential targets in lactate metabolism for cancer treatment. Finally, it is promising to propose a combined strategy inhibiting the glycolytic pathway and immunotherapy.

Children exposed to peer victimization are at increased risk for psychopathology. However, the physiological mechanisms linking peer victimization to child psychopathology and the potential gender differences in these links remain inadequately understood. The present study examined whether cortisol reactivity to acute stress mediated the associations between relational and physical victimization and internalizing and externalizing problems and whether these associations differed between boys and girls. A sample of 150 Chinese children (aged 9-13 years; M

OBJECTIVE Subjective socioeconomic status (SES) is a well-established psychosocial determinant of adolescents' self-report health. However, whether low subjective SES is associated with stress-related physiological risks (e.g., dysregulations in the hypothalamic-pituitary-adrenal axis activity) remains uncertain. This study examined the impact of subjective SES with different reference groups (i.e., perception of family SES relative to other students in the school versus other people in the city) on adolescents' diurnal cortisol profiles. METHODS A sample of 255 adolescents (aged 11-14 years; 53.7% boys) completed a battery of psychological scales, including school-referenced subjective SES and city-referenced subjective SES. Diurnal cortisol was assessed by collecting saliva samples four times a day across two consecutive days. Four cortisol parameters (cortisol at awakening, cortisol awakening response [CAR], cortisol slope, and total cortisol secretion [area under the curve with respect to ground {AUCg}]) were derived. RESULTS Higher levels of school-referenced subjective SES were associated with higher cortisol levels at awakening (β = 0.0483, standard error [SE] = 0.0219, p = .028), steeper cortisol slopes (β = -0.0036, SE = 0.0017, p = .034), and higher cortisol AUCg (b = 0.50, SE = 0.24, p = .036), but not with CAR (p = .77), after adjusting for covariates. In contrast, city-referenced subjective SES was not associated with any of the cortisol parameters (cortisol at awakening [p = .90], CAR [p = .74], cortisol slope [p = .84], and cortisol AUCg [p = .68]). CONCLUSIONS Our findings highlight the importance of the reference group for subjective SES and provide a further understanding of socioeconomic disparities in adolescents' stress physiology.

Cancer research has advanced throughout the years with respect to the personalization of the treatments and to targeting cancer-related molecular signatures on different organs. Still, the adverse events of the treatments such as radiotherapy are of high concern as they may increase the mortality rate due to their severity. With the improved efficiency of cancer treatments, patient survival has been increasing. Consequently, the number of patients with adverse effects from radiotherapy is also expected to increase in the forthcoming years. Therefore, approaches for personalized treatments include the elimination of adverse events and decreasing the toxicity in healthy tissues while increasing the efficiency of cancer cytotoxicity. In this context, this paper aims to discuss the recent advances in the field of thorax irradiation therapy and its related toxicities leading to radiation pneumonitis in cancer patients. Molecular mechanisms involved in the radiation-induced lung injury and approaches used to overcome this lung injury are discussed. The discourse covers approaches such as therapeutic administration of natural products, current and prospective radioprotective drugs, and applications of mesenchymal stem cells for radiation-induced lung injury.

Objective This study aimed to assess the probable relationship between icter in neonates with ABO incompatibility hemolysis and UGT1A1 gene polymorphism. Study Design There were 65 ABO hemolytic disease of the newborn (HDN) neonates of full term in the study group and 82 non-ABO HDN neonates of full term in the compared group. We tested the UGT1A1 gene mutation of neonates of ABO HDN and non-ABO HDN. We compared the incidence of hyperbilirubinemia between neonates with and without UGT1A1 mutations in the ABO HDN and non-ABO HDN, to determine the relationship between icter in neonates with ABO HDN and UGT1A1 gene polymorphism. SPSS 13.0 were used to analyze those two groups' data. Results There was statistically significant difference of the serum bilirubin level between the Gly71Arg homozygous and no mutation group in the ABO HDN patients (p 342 μmol/L, the incidence of hyperbilirubinemia between patients of UGT1A1 and non-UGT1A1 mutations in the ABO HDN group was significantly different (p Conclusion Individuals with Gly71Arg homozygous contributed to their hyperbilirubinemia in ABO HDN patients.

This study aimed to assess the risk of coronavirus disease 2019 in the border areas of southwest China, so as to provide guidance to targeted prevention and control measures in the border areas of different risk levels. We assessed the dependence of the risk of an outbreak in the southwest China from imported cases on key parameters such as the cumulative number of infectious diseases in the border area of southwest China in the past 3 years; the connectivity of the neighboring countries with China's Southwest border, including baseline travel numbers, travel frequencies, the effect of travel restrictions, and the length of borders with neighboring countries; the cumulative number of close contacts of coronavirus disease 2019 patients; (iv) the population density in border areas; the efficacy of control measures in border areas; experts estimated risks in border areas based on experience and then given a score; Spearman correlation and Logistic regression models were used to analyze the associated factors of novel coronavirus. According to the correlation of various factors, we assigned values to each parameter, calculated the risk score of each county, and then divided each county into high, medium, and low risk according to the sick score and took different control measure according to different risk levels. Finally, the total risk level was evaluated according to the Harvard disease risk index model. The number of infectious diseases in the past 3 years, travel numbers, travel frequencies, experts estimated risk score, effect of travel restrictions, and the number of close contacts were associated with the incidence of new coronary pneumonia. It is concluded that bilateral transportation convenience is a risk factor for new coronary pneumonia, (odds ratio = 9.23, 95% confidence interval, 1.99-42.73); the number of observers is a risk factor for new coronary pneumonia (odds ratio = 1.04, 95% confidence interval, 1.00-1.08). We found that in countries with travel numbers, travel frequencies, and experts' estimated risk scores were the influencing factors of novel coronavirus. The effect of travel restrictions and the cumulative number of close contacts of the case are risk factors for novel coronavirus.

Solute carrier 34 A2 (SLC34A2) is a member of SLC34 family that is a group of phosphate transporters. SLC34A2 has been reported to play critical roles in tumorigenesis and progression. However, the researches about the biological roles of SLC34A2 in glioma have not yet been reported. In this study, we analyzed the expression patterns of SLC34A2 in clinical glioma tumor tissues and cell lines. The results demonstrated that SLC34A2 was generally overexpressed in both glioma tissues and cell lines. To further investigate the roles of SLC34A2 in glioma, lentivirus containing specific SLC34A2 short hairpin RNA (sh-SLC34A2) was used to infect glioma cell lines U251 and U87 for the knockdown of SLC34A2. The following studies proved that SLC34A2 knockdown exhibited suppressive effects on cell proliferation and migration/invasion. SLC34A2 knockdown also inhibited epithelial-mesenchymal transition (EMT) phenotype, as evidenced by the increased E-cadherin expression, and the decreased N-cadherin and fibronectin expressions. Besides, knockdown of SLC34A2 enhanced the temozolomide (TMZ) sensitivity of U251 and U87 cells. In vivo tumorigenicity assay demonstrated that SLC34A2 knockdown inhibited tumor growth. Moreover, SLC34A2 knockdown suppressed the activation of epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway in U87 cells. GW2974 (EGFR inhibitor) increased SLC34A2 knockdown-inhibited cell proliferation, migration/invasion, as well as enhanced SLC34A2 knockdown-increased the TMZ sensitivity of glioma cells. These findings suggested that SLC34A2 might be a new potential therapeutic target for the therapy of glioma patients.

The immune system is composed of effectors and regulators. Type 1 regulatory T (Tr1) cells are classified as a distinct subset of T cells, and they secret high levels of IL-10 but lack the expression of the forkhead box P3 (Foxp3). Tr1 cells act as key regulators in the immune network, and play a central role in maintaining immune homeostasis. The regulatory capacity of Tr1 cells depends on many mechanisms, including secretion of suppressive cytokines, cell-cell contacts, cytotoxicity and metabolic regulation. A breakdown of Tr1-cell-mediated tolerance is closely linked with the pathogenesis of various diseases. Based on this observation, Tr1-cell therapy has emerged as a successful treatment option for a number of human diseases. In this review, we describe an overview of Tr1 cell identification, functions and related molecular mechanisms. We also discuss the current protocols to induce/expand Tr1 cells in vitro for clinical application, and summarize the recent progress of Tr1 cells in transplantation.

Parental bonding is a strong determinant of children's health. One of the proposed pathways through which parenting impacts children's health is by altering the functioning of stress response systems. The current study aims to investigate the associations between two types of parental bonding (care and overprotection) and functioning of hypothalamic-pituitary-adrenal (HPA) axis (i.e., diurnal cortisol secretion) in a sample of 255 healthy adolescents (46.3% girls; aged 11-14 years). Participants completed the Parental Bonding Instrument and provided eight cortisol samples across two consecutive days to assess patterns of diurnal cortisol secretion. Multilevel modeling and multiple linear regression were utilized to test the main effects and interactive effects of parental care and overprotection on adolescents' wakeup cortisol, cortisol awakening response, cortisol slope, and total cortisol secretion. Results showed that parental care was associated with higher cortisol levels at awakening, while parental overprotection was associated with lower cortisol levels at awakening. Parental overprotection, but not parental care, was associated with flatter cortisol slopes. No interactive effects between parental care and overprotection on cortisol parameters emerged. The current findings add to the existing literature on parenting behavior and HPA functioning by showing that parental care and overprotection differently regulated daily cortisol parameters implicated in health.

Background Neonatal meningitis is a severe infectious disease of the central nervous system with high morbidity and mortality. Ureaplasma parvum is extremely rare in neonatal central nervous system infection. Case presentation We herein report a case of U. parvum meningitis in a full-term neonate who presented with fever and seizure complicated with subdural hematoma. After hematoma evacuation, the seizure disappeared, though the fever remained. Cerebrospinal fluid (CSF) analysis showed inflammation with CSF pleocytosis (1135–1319 leukocytes/μl, mainly lymphocytes), elevated CSF protein levels (1.36–2.259 g/l) and decreased CSF glucose (0.45–1.21 mmol/l). However, no bacterial or viral pathogens in either CSF or blood were detected by routine culture or serology. Additionally, PCR for enteroviruses and herpes simplex virus was negative. Furthermore, the CSF findings did not improve with empirical antibiotics, and the baby experienced repeated fever. Thus, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the infection. U. parvum was identified by mNGS in CSF samples and confirmed by culture incubation on mycoplasma identification medium. The patient’s condition improved after treatment with erythromycin for approximately 5 weeks. Conclusions Considering the difficulty of etiological diagnosis in neonatal U. parvum meningitis, mNGS might offer a new strategy for diagnosing neurological infections.

To report a case of keratomycosis caused by a very rare pathogen, Myrothecium verrucaria. This is a case report. A 53-year-old man complaint of left eye redness, irritation, intermittent pain after ashes entered his left eye. The patient was examined by slit lamp, anterior segment OCT and in vivo confocal microscopy. The HRT III-RCM image showed massive interlocking white thin lines in the cornea stroma. Corneal scrapings were collected for pathogen culture and PCR test. M. verrucaria was isolated and identified. Hourly topical natamycin (5%) and voriconazole (10 mg/ml) was given as well as intravenous fluconazole (200 mg per day). Treatment was continued with oral itraconazole, 200 mg/day, topical natamycin (5%), 4 times/day, and pranoprofen, 4 times/day. The therapy was tapered off over one and half a month. The cornea lesion healed with scar formation two months later. This is the first case report of M. verrucaria keratomycosis in China. We are the first to show the characteristic of M. verrucaria on cornea with In vivo confocal microscopy. A combination treatment of tropical natamycin, voriconazole and systemic fluconazole was effective in the treatment of M. verrucaria.

Pyrrolizidine alkaloids (PAs) are a class of natural toxins with hepatotoxicity, genotoxicity and carcinogenicity. They are endogenous and adulterated toxic components widely found in food and herbal products. In this study, a sensitive and efficient ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was used to detect the PAs in 386 kinds of Chinese herbal medicines recorded in the Chinese Pharmacopoeia (2020). The estimated daily intake (EDI) of 0.007 μg/kg body weight (bw)/day was adopted as the safety baseline. The margin of exposure (MOE) approach was applied to evaluate the chronic exposure risk for the genotoxic and carcinogenic potential of PAs. Results showed that PAs was detected in 271 out of 386 samples with a content of 0.1–25,567.4 μg/kg, and there were 20 samples with EDI values above the baseline, 0.007 μg/kg bw/day. Beyond that, the MOE values for 10 out of 271 positive samples were below 10,000. Considering the actual situation, Haber’s rule was used to assume two weeks exposure every year during lifetime, and still the MOE values for four out of 271 positive samples were under 10,000, indicating these products may have potential health risk. The developed method was successfully applied to detect the PAs-containing Chinese herbal medicines. This study provides convincing data that can support risk management actions in China and a meaningful reference for the rational and safe use of Chinese herbal medicines.

The predominant cause of elevated total/plasma bilirubin (TB) levels is from an increase in bilirubin production primarily because of ongoing hemolysis. If undiagnosed or untreated, the risk for developing extreme neonatal hyperbilirubinemia and possibly bilirubin-induced neurological dysfunction (BIND) is increased. Since carbon monoxide (CO) and bilirubin are produced in equimolar amounts during the heme catabolic process, measurements of end-tidal CO levels, corrected for ambient CO (ETCOc) can be used as a direct indicator of ongoing hemolysis. A newly developed point-of-care ETCOc device has been shown to be a useful for identifying hemolysis-associated hyperbilirubinemia in newborns. This review summarizes the biology of bilirubin production, the clinical utility of a novel device to identify neonates undergoing hemolysis, and a brief introduction on the use of ETCOc measurements in a cohort of neonates in China.

To detect potential variant in a male neonate affected with congenital nephrogenic diabetes insipidus (CNDI).Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples from the child and his parents. The whole coding regions of the arginine vasopressin V2 receptor (AVPR2) gene were amplified by PCR and subjected to Sanger sequencing.The patient presented recurrent fever and polyuria after birth. Multiple blood gas analyses indicated hypernatremia. Ultrasound showed bilateral hydronephrosis and hydroureter. The patient was partially responsive to hydrochlorothiazide. DNA analysis identified a hemizygous frameshift variant c.890-899delACCCGGAGGC in exon 2 of the AVPR2 gene in the proband. His mother was heterozygous for the same variant.The c.890-899delACCCGGAGGC variant of the AVPR2 gene probably underlies the CNDI in the child. Above discovery has enriched to spectrum of CNDI associated variants.

Tumor mutation burden (TMB) is an essential biomarker to predict immunotherapy response. TMB measurement was mainly evaluated by whole-exome sequencing (WES), which was costly and difficult to be widely applied. In the present study, we aimed to establish and validate a miRNA signature to predict TMB level in endometrial cancer using The Cancer Genome Atlas (TCGA) database. MiRNA expression and somatic mutation profiles of uterine corpus endometrial carcinoma (UCEC) were downloaded from TCGA database. Total 518 patients with UCEC were randomly classified into training set (n=311) and validation set (n=207). Thirty-five differentially expressed miRNAs between high-TMB and low-TMB group were identified in training set. Least absolute shrinkage and selection operator (LASSO) method was performed to select out 26 miRNAs to establish the optimal signature. The accuracy of the miRNA signature for predicting TMB level was 0.833 for training set, 0.749 for validation set and 0.799 for total set. Moreover, the miRNA signature had significant correlation with immune checkpoints related genes (PD-1, PD-L1, CTLA-4) and mismatch repair related genes (BRCA1, BRCA2, MLH1, MSH6) expression. In conclusion, this miRNA signature could predict TMB level in endometrial cancer and might have some merits in providing guidance for immunotherapy in endometrial cancer.

The bacterium Enterococcus faecalis has increasingly attracted global attention as an important opportunistic pathogen due to its ability to form biofilms that are known to increase drug resistance. However, there are still no effective antibiofilm drugs in clinical settings. Here, by drug repurposing, we investigated the antibacterial activity of penfluridol (PF), an oral long‐acting antipsychotic approved by the FDA, against E. faecalis type strain and its clinical isolates. It was found that PF inhibited the growth of E. faecalis planktonic cells with the MIC and MBC of 7.81 µg/ml and 15.63 ~ 62.50 µg/ml, respectively. Moreover, PF could significantly prevent the biofilm formation of E. faecalis at the concentration of 1 × MIC. Furthermore, PF significantly eradicated 24 h pre‐formed biofilms of E. faecalis in a dose‐dependent manner, with a concentration range of 1 × MIC to 8 × MIC. Here, through the checkerboard method with other tested conventional antibiotics, we also determined that gentamycin, penicillin G, and amikacin showed partial synergistic antibacterial effects with PF. Also, PF showed almost no hemolysis on human erythrocytes. In a mouse peritonitis model, a single dose of 20 mg/kg of PF treatment could significantly reduce the bacterial colonization in the liver (~5‐fold reduction) and spleen (~3‐fold reduction). In conclusion, these findings indicated that after structural optimization, PF has the potential as a new antibacterial agent against E. faecalis., Penfluridol shows effective antimicrobial effects against Enterococcus faecalis in vitro and in vivo. The drug prevents biofilm formation and eliminates mature biofilms.

To describe the long-term outcomes of intensive care unit (ICU) survivors of mechanical ventilation, and investigate the views of survivors on ICU rehabilitation clinics.A single-center cross-sectional descriptive study was designed. ICU survivors of mechanical ventilation admitted to the First Affiliated Hospital of Guangzhou Medical University from January to December 2016 were enrolled. Data were collected from August 2017 to March 2018. The general information questionnaire, Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and ICU rehabilitation clinics questionnaire were used to evaluate ICU survivors social-demographic factors, social and economic outcomes, clinical data, quality of life and the views on ICU rehabilitation clinics.A total of 248 ICU survivors of mechanical ventilation were included in the study, 130 (52.4%) of them were followed up successfully. The mean time from ICU discharge to follow-up day was (19.64±3.20) months. The average age of the survivors was (60.09±15.42) years old, and 55.4% of them were over 60 years old. Among 130 ICU survivors, severe pneumonia was the dominant ICU admission diagnosis (23.1%), followed by surgical operations (cardiac surgery 16.9%, other surgical operations 20.8%), lung transplantation (13.1%), and acute exacerbation of chronic obstructive pulmonary disease (AECOPD, 12.3%), etc. The first APACHE II score after ICU admission was 16.88±7.37, the mechanical ventilation time was (12.52±12.34) days, and the length of ICU stay was (16.71±15.11) days. In terms of social and economic outcomes, the proportion of having full-time or part-time jobs decreased from 32.3% (42/130) before ICU admission to 25.4% (33/130) by the date of follow-up, while the unemployed rate increased from 6.9% (9/130) to 18.5% (24/130). Only 45.1% (23/51) of the ICU survivors returned to the post before ICU admission. 36.2% (47/130) of the ICU survivors reported that they needed care from others, and 86.9% (113/130) reported that their treatment experiences in ICU had an impact on their lives. In terms of quality of life, physiological function dimension, which was 34.62±33.15, scored the lowest and suffered the most. The physical pain dimension and mental health dimension suffered the least, and the scores were 90.19±16.98 and 75.28±15.15, respectively. Furthermore, physical component summary (PCS) score was 61.12±17.09, and mental component summary (MCS) score was 65.97±21.85. In terms of the views of ICU rehabilitation clinics, 68.5% (89/130) of the subjects believed that the establishment of ICU rehabilitation clinics was very helpful or helpful.The long-term outcomes of ICU survivors of mechanical ventilation are not optimistic. Their quality of life is lower than that of general people. It is necessary to set up ICU rehabilitation clinics.

Endoplasmic reticulum stress (ER stress) can be induced by virus infection. In this part, we explored whether Hantaan virus (HTNV) infection could induce ER stress in differentiated THP-1 (dTHP-1) cells. It showed that the mRNA and protein levels of ER stress-related 78 kDa glucose-regulated protein (GRP78, HSPA5) and mRNA levels of X box-binding protein 1 (XBP-1), activating transcription factor 6(ATF6) and PKR-like ER kinase (PERK) after HTNV infection, were significantly higher than that in uninfected control group. However, the mRNA levels of C/EBP homologous protein (CHOP), glucose-regulated protein 94 (GRP94, HSPC4), and inositol-requiring enzyme1 (IRE1) were not significantly different between the infected group and the untreated group in 2 h after virus infection. It is unusual in activating GRP78 but not GRP94. Meanwhile, dTHP-1 cells infected with HTNV at 12 h did not show obvious apoptosis. These results indicated that the HTNV infection could induce the unfolded protein response (UPR) in dTHP-1 cells, without directly leading to cell apoptosis during 12 h after virus infection.