Ketamine induces insomnia-like symptom of zebrafish at environmentally relevant concentrations by mediating GABAergic synapse.

Although the stimulative effects on the normal behaviors of fish posed by ketamine (KET) were well-studied, the adverse effects on the behavioral functions induced by KET at nighttime were unknown. Here, we used zebrafish larvae as a model exposed to KET (10, 50, 100, and 250 ng/L) at environmental levels for 21 days. The behavioral functions at nighttime, morphological changes during exposure stage, and alterations on the associated genes transcriptional levels of fish were determined. The difficultly initiating sleep was found in the fish exposed to KET, while the sleep duration of the animals was at the normal levels in exposure groups. The significant suppressions of the developmentally relevant genes, including bmp2, bmp4, and pth2ra were consistent with the developmental abnormalities of fish found in exposure groups. Moreover, the expression of γ-aminobutyric acid (GABA) receptor increased and melatonin (MTN) receptor decreased while the levels of GABA and MTN remained unchanged after exposure, by gene expression analysis and molecular docking. In addition, the transcriptional expression of apoptotic genes, including tp53, aifm1, and casp6, was significantly upregulated by KET. After a 7-day recovery, the insomnia-like behaviors (shorter sleep duration) were observed in zebrafish from the 250 ng/L-KET group. Accordingly, the adverse outcome pathway framework of KET was constructed by prognostic assessment of zebrafish larvae. This study suggested that the adverse outcomes of KET on the sleep health of organisms at environmentally relevant concentrations should be concerned.

A one-year follow-up study on dynamic changes of leukocyte subsets and virus-specific antibodies of patients with COVID-19 in Sichuan, China.

Background: SARS-CoV-2 infection causes immune response and produces protective antibodies, and these changes may persist after patients discharged from hospital. Methods: This study conducted a one-year follow-up study on patients with COVID-19 to observe the dynamic changes of circulating leukocyte subsets and virus-specific antibodies. Results: A total of 66 patients with COVID-19 and 213 healthy patients with inactivated SARS-CoV-2 vaccination were included. The virus-specific total antibody, IgG and IgM antibody of patients after one year of recovery were higher than those of healthy vaccinated participants (94.13 vs 4.65, 2.67 vs 0.44, 0.09 vs 0.06, respectively) (P < 0.001). Neutrophil count (OR = 1.73, 95% CI: 1.10-2.70, P = 0.016) and neutrophil-to-lymphocyte ratio (OR = 1.59, 95% CI: 1.05-2.41, P = 0.030) at discharge were the influencing factors for the positivity of virus-specific IgG antibody in patients after one year of recovery. The counts of CD4+ and CD8+ T, B and NK cells increased with the time of recovery, and remained basically stable from 9 to 12 months after discharge. After 12 months, the positivity of IgG antibody was 85.3% and IgM was 11.8%, while the virus-specific antibody changed dynamically in patients within one year after discharge. Conclusions: The SARS-CoV-2 specific antibody of recovered patients showed dynamic fluctuation after discharge, while the leukocyte subsets gradually increased and basically stabilized after 9 months.

The Relationship between Lymphocyte Subsets and the Prognosis and Genomic Features of Lung Cancer: A Retrospective Study.

Background: It has been shown that the prognosis of malignant tumors was closely related to the composition and function of immune system, which was associated with genomic features. However, the prognostic value of peripheral T lymphocyte subsets and its relationship with genomic features in lung cancer has not been analyzed extensively. Therefore, this study was intended to evaluate the relationship between lymphocyte subsets and the prognosis and genomic features of lung cancer. Methods: 598 lung cancer patients with complete data were included in this study between 2011 and 2018. Kaplan-Meier method and Pearson analyses were conducted to study the prognostic value of CD3+, CD4+, CD8+ T lymphocytes and the rate of CD4/CD8. Results: Patients with EGFR mutation has lower mean percentage of CD8+ lymphocytes than patients with EGFR wild-type (24.71 versus 26.62, respectively, P=0.041). Patients with high CD3 had better OS than those with low (27 versus 14 months, P=0.002). Patients with higher CD4 and CD4/CD8 rate had longer OS than with lower (27 versus 12 months, P=0.002; 25 versus 9 months, P=0.008, respectively). Patients with high CD8 had poor PFS than low group (6 versus 11 months, P=0.009). There was a negative correlation between CD3+ and CD4+ cells and OS in smoking stage Ⅱ female lung cancer patients (PCC = 0.626, P<0.05; PCC = 0.534, P<0.05, respectively). In stage Ⅰ male lung cancer patients, CD8+T cell is negatively correlated with OS and PFS (PCC = 0.295, P<0.05; PCC = 0.280, P<0.05, respectively) Conclusions: Lung cancer patients with EGFR mutation had lower percentage of CD8+ lymphocytes. Lymphocyte subsets might be potential prognostic biomarkers of lung cancer, but they are affected by gender and tumor stage.

Assessment on the lung injury of mice posed by airborne PM2.5 collected from developing area in China and associated molecular mechanisms by integrated analysis of mRNA-seq and miRNA-seq.

Some epidemiological evidences showed exposure of airborne fine particulate matter (PM2.5) was associated with lung dysfunction. However, the adverse effects of PM2.5 from mid-scale city of China on the respiratory system were unknown. Correspondingly, the mechanisms, especially the epigenetic mechanism regulated by miRNAs, involved in PM2.5-induced lung injury has not been fully understood. In this study, male Balb/C mice were exposed to PM2.5 collected from mid-scale city (Baoji), China for 8 weeks (mean concentration 298.52 ± 25.86 µg/m3 at exposure chamber) using a whole-body exposure system. The carbon component was the main ingredient (45.80%) of PM2.5 followed by ions (43.19%). Meanwhile, the sum concentrations of polycyclic aromatic hydrocarbons (PAHs) and n-alkanes (C18-C33) were 570.48 and 2029.13 ng/m3 in the exposure chamber, respectively. Obvious lung injury including pulmonary inflammation and fibrosis (p < 0.05 compared with the control) were found from PM2.5 exposure group determined by micro-CT and histopathological assays, respectively, suggesting the health risk posed by PM2.5 from mid-scale city of China should be concerned. The integrated analysis between mRNA-seq and miRNA-seq revealed the differentially expression genes in lung tissues were enriched in immune pathways including B cell receptor signaling (p = 0.078) and cell adhesion molecules (CAMs) (p = 0.0068). The expression profiles of the genes and corresponding mRNAs involved into the immune pathways determined by RT-qPCR analysis were consistent with them conducted by transcriptome. Moreover, the expression levels of the proteins (i.e., CD19, CD81, PIK3CD, and CD22) involved into B cell receptor signaling pathway from exposure group were 1.71- to 6.948- folds compared with the control, validating the results of the genes expression profiles. Further, canonical correlation analysis (CCA) and multiple correlation analysis between the target genes and components of PM2.5 documented the organic compounds (i.e., Benzo(a)pyrene (p = 0.012) and octadecane (p = 0.05)) and inorganic elements (i.e., Cl-, Ti, Al, and Zn) was the key environmental factors. Cd19, Pik3cd, and Cd8b1 might be the key genes for lung dysfunction induced by PM2.5 illuminated using interactive analysis (p < 0.05). This work for the first time showed the adverse effects of PM2.5 in mid-scale city in China on respiratory system should be concerned, and the associated epigenetic mechanism regulated by miRNA were revealed. These results may provide new insight into the development of future assessment on the air pollution associated respiratory disease.

Diagnostic efficacy of long non-coding RNA in lung cancer: a systematic review and meta-analysis.

The detection of long non-coding RNA (lncRNA) is a novel method for lung cancer diagnosis. However, the diagnostic efficacy of lncRNA in different studies is inconsistent. Therefore, we conducted this meta-analysis to elucidate the diagnostic efficacy of lncRNA in identification of lung cancer including small cell lung cancer. The online PubMed, Medline, EMBASE, CNKI and Wanfang literature databases were searched to identify all related articles about the diagnostic efficacy of lncRNA for lung cancer. 28 articles including 3044 patients with lung cancer and 2598 controls were enrolled in our meta-analysis. lncRNA sustained a high diagnostic efficacy, pooled sensitivity of 0.82 (95% CI 0.79 to 0.84), specificity of 0.82 (95% CI 0.78 to 0.84) and area under the curve (AUC) of 0.88 (95% CI 0.85 to 0.91) in identification of patients with lung cancer from controls. Furthermore, the diagnostic efficacy of paralleled lncRNA was better than single lncRNA (sensitivity: 0.86 vs 0.80; specificity: 0.88 vs 0.78; AUC: 0.93 vs 0.86). MALAT1 had a better diagnostic efficacy than GAS5 (AUC: 0.90 vs 0.81; sensitivity: 0.83 vs 0.70; specificity: 0.83 vs 0.78). lncRNA in tissues was observed to achieve lower diagnostic efficacy than that in plasma or serum (AUC: 0.87 vs 0.90 vs 0.90) when stratified by sample types. In summary, our meta-analysis suggests that lncRNA might be a promising biomarker(s) for identifying lung cancer and the combination of lncRNA or with other biomarkers had a better diagnostic efficacy.

A multi-omics investigation of the lung injury induced by PM2.5 at environmental levels via the lung-gut axis.

Long-term exposure to fine particulate matter (PM2.5) posed injury for gastrointestinal and respiratory systems, ascribing with the lung-gut axis. However, the cross-talk mechanisms remain unclear. Here, we attempted to establish the response networks of lung-gut axis in mice exposed to PM2.5 at environmental levels. Male Balb/c mice were exposed to PM2.5 (dose of 0.1, 0.5, and 1.0 mg/kg) collected from Chengdu, China for 10 weeks, through intratracheally instillation, and examined the effect of PM2.5 on lung functions of mice. The changes of lung and gut microbiota and metabolic profiles of mice in different groups were determined. Furthermore, the results of multi-omics were conjointly analyzed to elucidate the primary microbes and the associated metabolites in lung and gut responsible for PM2.5 exposure. Accordingly, the cross-talk network and key pathways between lung-gut axis were established. The results indicated that exposed to PM2.5 0.1 mg/kg induced obvious inflammations in mice lung, while emphysema was observed at 1.0 mg/kg. The levels of metabolites guanosine, hypoxanthine, and hepoxilin B3 increased in the lung might contribute to lung inflammations in exposure groups. For microbiotas in lung, PM2.5 exposure significantly declined the proportions of Halomonas and Lactobacillus. Meanwhile, the metabolites in gut including L-tryptophan, serotonin, and spermidine were up-regulated in exposure groups, which were linked to the decreasing of Oscillospira and Helicobacter in gut. Via lung-gut axis, the activations of pathways including Tryptophan metabolism, ABC transporters, Serotonergic synapse, and Linoleic acid metabolism contributed to the cross-talk between lung and gut tissues of mice mediated by PM2.5. In summary, the microbes including Lactobacillus, Oscillospira, and Parabacteroides, and metabolites including hepoxilin B3, guanosine, hypoxanthine, L-tryptophan, and spermidine were the main drivers. In this lung-gut axis study, we elucidated some pro- and pre-biotics in lung and gut microenvironments contributed to the adverse effects on lung functions induced by PM2.5 exposure.

Chromosome-level genome and multi-omics analyses provide insights into the geo-herbalism properties of Alpinia oxyphylla.

Introduction: Alpinia oxyphylla Miquel (A. oxyphylla), one of the "Four Famous South Medicines" in China, is an essential understory cash crop that is planted widely in the Hainan, Guangdong, Guangxi, and Fujian provinces. Particularly, A. oxyphylla from Hainan province is highly valued as the best national product for geo-herbalism and is an important indicator of traditional Chinese medicine efficacy. However, the molecular mechanism underlying the formation of its quality remains unspecified. Methods: To this end, we employed a multi-omics approach to investigate the authentic quality formation of A. oxyphylla. Results: In this study, we present a high-quality chromosome-level genome assembly of A. oxyphylla, with contig N50 of 76.96 Mb and a size of approximately 2.08Gb. A total of 38,178 genes were annotated, and the long terminal repeats were found to have a high frequency of 61.70%. Phylogenetic analysis demonstrated a recent whole-genome duplication event (WGD), which occurred before A. oxyphylla's divergence from W. villosa (~14 Mya) and is shared by other species from the Zingiberaceae family (Ks, ~0.3; 4DTv, ~0.125). Further, 17 regions from four provinces were comprehensively assessed for their metabolite content, and the quality of these four regions varied significantly. Finally, genomic, metabolic, and transcriptomic analyses undertaken on these regions revealed that the content of nootkatone in Hainan was significantly different from that in other provinces. Discussion: Overall, our findings provide novel insights into germplasm conservation, geo-herbalism evaluation, and functional genomic research for the medicinal plant A. oxyphylla.

Isoflurane enhances both fast and slow synaptic inhibition in the hippocampus at amnestic concentrations.

BACKGROUND: Inhibition mediated by γ-aminobutyric acid type A (GABA A) receptors has long been considered an important target for a variety of general anesthetics. In the hippocampus, two types of phasic GABA A receptor-mediated inhibition coexist: GABA A,fast, which is expressed primarily at peri-somatic sites, and GABAA,slow, which is expressed primarily in the dendrites. Their spatial segregation suggests distinct functions: GABA A,slow may control plasticity of dendritic synapses, whereas GABA A,fast controls action potential initiation at the soma. We examined modulation of GABA A,fast and GABA A,slow inhibition by isoflurane at amnesic concentrations, and compared it with modulation by behaviorally equivalent doses of the GABA A receptor-selective drug etomidate. METHODS: Whole cell recordings were obtained from pyramidal cells in organotypic hippocampal cultures prepared from C57BL/6 × 129/SvJ F1 hybrid mice. GABA A receptor-mediated currents were isolated using glutamate receptor antagonists. GABAA,slow currents were evoked by electrical stimulation in the stratum lacunosum-moleculare. Miniature GABA A,fast currents were recorded in the presence of tetrodotoxin. RESULTS: 100 µM isoflurane (approximately EC50,amnesia) slowed fast- and slow-inhibitory postsynaptic current decay by approximately 25%. Higher concentrations, up to 400 µM, produced proportionally greater effects without altering current amplitudes. The effects on GABA A,slow were approximately one-half those produced by equi-amnesic concentrations of etomidate. CONCLUSIONS: Isoflurane enhances both types of phasic GABA A receptor-mediated inhibition to similar degrees at amnesic concentrations. This pattern differs from etomidate, which at low concentrations selectively enhances slow inhibition. These effects of isoflurane are sufficiently large that they may contribute substantially to its suppression of hippocampal learning and memory.

Ketamine induction of physiological functions alterations in Caenorhabditis elegans by chronic and multigenerational exposure and corresponding aquatic environmental risk assessment.

Although ketamine (KET) has been widely detected in aquatic environments, the ecotoxicity data in aquatic invertebrates and associated risk remained unclear. This study aimed to investigate the adverse effects on benthos (Caenorhabditis elegans (C.elegans)) posed by KET from chronic (10 days) and multigenerational (four generations) exposure. Such exposure induced dose-dependent alterations on apoptosis, reactive oxygen species (ROS) induction, locomotion activity, feeding rate, chemotaxis, and brood size of nematodes, showing a cumulative damage through generations. KET posed vulva deformations and worm bags of C. elegans with a dosed-dependent increase. As a consequence, the fecundity and viability of worms would be impaired, which could eventually impact aquatic ecosystem equilibrium. Meanwhile, the bioactivation/detoxification process of xenobiotics and longevity regulating pathway induced by KET might be responsible for the physiological function disorders. Accordingly, the risk quotients (RQ) of KET in surface water in China were calculated using the 90% indicator protection concentration (C0.1) derived from multiple toxicity indicators cumulative analyses. The results would be more objective considering numerous biomarkers changes of one species in comparison with traditional method using no observed effect concentrations (NOEC) of teratogenesis. The risk in surface water in southern China was up to high level (RQ > 1), suggesting long-term monitoring was imperative.

PM2.5 induced weight loss of mice through altering the intestinal microenvironment: Mucus barrier, gut microbiota, and metabolic profiling.

The experimental evidences linking PM2.5 exposure to weight status disorder and the associated mechanisms were lacked. Here, we demonstrated exposure of 198.52 µg/m3 PM2.5 (Baoji city, China) for 40 days induced body weight loss of male Balb/C mice, and then increased after 14-day recovery. Correspondingly, gut microbiota dysbiosis, ileum metabolism alterations, and histopathological changes of liver and ileum elucidated the underlying mechanism. The richness and function modules of flora in feces significantly reduced after exposure, and the ratios of Bacteroidetes/Firmicutes reduced from 1.58 to 0.79. At genus level, Lactobacillus and Clostridium increased markedly, while Bacteroides and Parabacteroides decreased at day 40. After recovery, Oscillospira became the dominant genus. Additionally, the key metabolites in the ileum mediated by PM2.5 identified by metabolomics included arachidonic acid, prostaglandin H2, prostaglandin F2α, 5(S)-HPETE, AMP, and deoxyadenosine. Accordingly, conjoint analysis between the gut micorbiota and metabolic profiling revealed suppression of Arachidonic acid metabolism, linoleic acid metabolism, and PPAR signaling pathway and stimulation of ABC transporters might contribute to the liver injury, ileum inflammation, and then weight loss of mice. Our findings suggested PM2.5 affected weight status of mice by meditating intestinal microenvironment, and provided new insight for further diagnosis of the air pollution dependent disease.

Chinese expert consensus on prevention and intervention for the elderly with malnutrition (2022).

Malnutrition is a state of altered body composition and body cell mass due to inadequate intake or utilization of energy or nutrients, leading to physical and mental dysfunction and impaired clinical outcomes. As one of the most common geriatric syndromes, malnutrition in the elderly is a significant risk factor for poor clinical outcomes, causing a massive burden on medical resources and society. The risk factors for malnutrition in the elderly are diverse and include demographics, chronic diseases, and psychosocial factors. Presently, recommendations for the prevention and intervention of malnutrition in the elderly are not clear or consistent in China. This consensus is based on the latest global evidence and multiregional clinical experience in China, which aims to standardize the prevention and intervention of malnutrition in the elderly in China and improve the efficacy of clinical practice and the prognosis of elderly patients.

Assessment on chronic and transgenerational toxicity of methamphetamine to Caenorhabditis elegans and associated aquatic risk through toxicity indicator sensitivity distribution (TISD) analysis.

Evidence about the adverse effects of methamphetamine (METH) on invertebrates is scarce. Hence, C. elegans, a representative invertebrate model, was exposed to METH at environmental levels to estimate chronic and transgenerational toxicity. The results of chronic exposure were integrated into an underlying toxicity framework of METH in invertebrates (e.g., benthos) at environmentally relevant concentrations. The induction of cellular oxidative damage-induced apoptosis and fluctuation of ecologically important traits (i.e., feeding and locomotion) might be attributed by the activation of the longevity regulating pathway regulated by DAF-16/FOXO, and detoxification by CYP family enzymes. The adverse effects to the organism level included impaired viability and decreased fecundity. The results from transgenerational exposure elucidated the cumulative METH-induced damage in invertebrates. Finally, a new risk assessment method named toxicity indicator sensitivity distribution (TISD) analysis was proposed by combining multiple toxicity indicator test data (ECx) to derive the hazardous concentration for 10% indicators (C10) of one species. The risk quotient (RQ) values calculated by measured environmental concentrations and C10 in southern China, southeastern Australia, and the western US crossed the alarm line (RQ = 5), suggesting a need for long-term monitoring.

Impacts of Frailty on Prognosis in Lung Cancer Patients: A Systematic Review and Meta-Analysis.

Background: Frailty is a common geriatric syndrome and is described as a limited ability to compensate and recover from stressors. Lung cancer is largely diagnosed in old age, when frailty is common and might have predictive value on prognosis. Therefore, we performed a systematic review to evaluate the prognostic role of frailty in lung cancer. Methods: The online PubMed, Web of Science, CNKI and Wanfang literature databases were searched to identify all related articles that reported the predictive value of frailty for mortality and therapeutic toxicity. Review Manager 5.3 was used to analyze results by standard meta-analysis methodology. Results: Seven studies were included in this review, and only six studies with 2,359 patients were enrolled in meta-analysis. Patients in two studies received chemotherapy, two studies radiotherapy, two studies surgery, one study not reported. Compared to non-frail patients, frail patients had a higher risk of overall mortality [Hazard Ratio (HR) = 1.57, 95% confidence interval (CI), 1.32-1.87], and therapeutic toxicity [Odds Ratio (OR) = 2.60, 95% CI, 0.82-8.24]. Prefrail patients also showed higher overall mortality and therapeutic toxicity than non-frail patients (HR = 1.20, 95% CI, 1.05-1.38; OR = 1.72, 95% CI, 1.18-2.51, respectively). Conclusions: Frailty is a powerful predictor of overall mortality and therapeutic toxicity in lung cancer patients.

Follow-Up Study of the Cardiopulmonary and Psychological Outcomes of COVID-19 Survivors Six Months After Discharge in Sichuan, China.

PURPOSE: Some studies have shown that patients with coronavirus disease 2019 (COVID-19) still have sequelae after discharge. However, little is known about the long-term physical and psychological sequelae of patients, especially factors that influenced the prognosis. PATIENTS AND METHODS: Patients with COVID-19 were followed up for 6 months. The psychological status of patients was evaluated by DASS-21 questionnaire, while physical functions were determined using medical history, laboratory examination, thoracic computed tomography (CT), and echocardiography. RESULTS: Fifty patients infected with COVID-19 were enrolled, and 11 (22%) patients still showed symptoms related to COVID-19. The mean contents (cells/ul) of CD3+ cells, CD4+ and CD8+ T, B lymphocytes and NK cells of the survivors elevated significantly after 6-month discharge (P < 0.001). The frequency of ground-glass opacities and consolidations decreased from 90% to 42% (P < 0.001), and 54% to 20%, (P = 0.001), respectively, while the changes of reticulation and bronchiectasis were insignificant (P > 0.05). The frequency of left ventricular diastolic dysfunction decreased from 40% to 15% (P = 0.002). Depression was observed in 5 (12.5%) participants, stress in 3 (7.5%), anxiety in 6 (15%), and among them 1 (2.5%) showed extremely severe anxiety. Covariation analysis elucidated age might be a risk factor (OR: 1.09, 95% CI: 1.01-1.18, P = 0.038), while NK cell was a good prognostic factor for pulmonary recovery. The comorbidities were significantly positive correlated with persist pulmonary damage (r = 0.33, P = 0.020). Compared with patients with antiviral therapy, patients without antiviral therapy had higher anxiety score (3 vs 0, P = 0.033). CONCLUSION: After 6-month discharge, the persisting cardiopulmonary damage was observed in recovery patients, and psychological implications should not be ignored. Age, comorbidities, NK cell and antiviral therapy might be associated with the prognosis of COVID-19.

Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing.

Lung adenocarcinomas (LUAD) arise from precancerous lesions such as atypical adenomatous hyperplasia, which progress into adenocarcinoma in situ and minimally invasive adenocarcinoma, then finally into invasive adenocarcinoma. The cellular heterogeneity and molecular events underlying this stepwise progression remain unclear. In this study, we perform single-cell RNA sequencing of 268,471 cells collected from 25 patients in four histologic stages of LUAD and compare them to normal cell types. We detect a group of cells closely resembling alveolar type 2 cells (AT2) that emerged during atypical adenomatous hyperplasia and whose transcriptional profile began to diverge from that of AT2 cells as LUAD progressed, taking on feature characteristic of stem-like cells. We identify genes related to energy metabolism and ribosome synthesis that are upregulated in early stages of LUAD and may promote progression. MDK and TIMP1 could be potential biomarkers for understanding LUAD pathogenesis. Our work shed light on the underlying transcriptional signatures of distinct histologic stages of LUAD progression and our findings may facilitate early diagnosis.

Amnestic concentrations of etomidate modulate GABAA,slow synaptic inhibition in hippocampus.

BACKGROUND: Gamma-aminobutyric acid type A (GABA(A)) receptor-mediated inhibition in the central nervous system exists in two forms: phasic (inhibitory postsynaptic currents, IPSCs) and tonic (nonsynaptic). Phasic inhibition is further subdivided into fast (GABA(A,fast)) and slow (GABA(A,slow)) IPSCs. By virtue of its dendritic location and kinetics, GABA(A,slow) has been proposed to control synaptic plasticity and memory. Etomidate is a nonbarbiturate, intravenous anesthetic that selectively modulates GABA(A) receptors and produces amnesia at low doses in vivo. This study tested whether correspondingly low concentrations of etomidate in vitro alter GABA(A,fast) and GABA(A,slow) phasic inhibition. METHODS: Electrophysiological recordings were obtained from hippocampal slices prepared from postnatal day 3-8 mice and maintained in organotypic culture for 10-14 days. Etomidate was applied at concentrations corresponding to one-half to four times the half maximal effective concentration that impairs hippocampus-dependent learning and memory--i.e., 0.125-1.0 microm. RESULTS: Etomidate 0.25 microm (the half maximal effective concentration) doubled the time constant of decay of GABA(A,slow) IPSCs, but it had no detectable effect on GABA(A,fast) IPSCs. Higher concentrations of etomidate had stronger effects on both types of phasic inhibition: 0.5 and 1 microm etomidate prolonged the time constant of decay by 310% and 410% for GABA(A,slow) and by 25% and 78% for GABA(A,fast). Concentrations of etomidate up to 1 microm had no significant effects on the amplitudes of either GABA(A,fast) or GABA(A,slow) IPSCs. CONCLUSIONS: At concentrations that impair hippocampus-dependent memory, etomidate modulates GABA(A,slow) more strongly than GABA(A,fast) IPSCs. Effects of etomidate on GABA(A,slow) IPSCs may contribute to etomidate-induced amnesia.

Round versus Anatomical Implants in Primary Cosmetic Breast Augmentation: A Meta-Analysis and Systematic Review.

BACKGROUND: Choosing implant shape (round or anatomical) is one of the most essential yet controversial decisions in cosmetic breast augmentation. Many surgeons choose implant shape based on personal experience or expert opinion. This is the first systematic review and meta-analysis comparing the aesthetic effect between anatomical and round implants in primary cosmetic breast augmentation. METHODS: The authors searched the PubMed, MEDLINE, Embase, ScienceDirect, Web of Knowledge, Scopus, and Cochrane Central Register of Controlled Trials databases for studies that compared anatomical and round implants in primary cosmetic breast augmentation. Primary outcomes were postoperative aesthetic effect and correct identification rate of implant shape. Random effects models were used to obtain pooled standardized mean difference and 95 percent confidence intervals. RESULTS: One randomized comparative and four observational comparative studies met the inclusion criteria. No aesthetic superiority was found in the anatomical implant group with regard to overall appearance (standardized mean difference, 0.06; 95 percent CI, -0.40 to 0.53), naturalness (standardized mean difference, 0.18; 95 percent CI, -1.51 to 1.15), projection, upper pole contour, and lower pole contour. Pooled correct identification rate of implant shape by plastic surgeons was 52 percent (95 percent CI, 0.46 to 0.58). CONCLUSIONS: Generally, anatomical implants do not seem to have an aesthetic superiority compared to round implants. Plastic surgeons seemed to be unable to accurately differentiate the two implant shapes in vivo. Further studies should focus on identifying the specific indications for the use of anatomical implants.

The Open Chromatin Landscape of Non-Small Cell Lung Carcinoma.

Non-small cell lung carcinoma (NSCLC) is a major cancer type whose epigenetic alteration remains unclear. We analyzed open chromatin data with matched whole-genome sequencing and RNA-seq data of 50 primary NSCLC cases. We observed high interpatient heterogeneity of open chromatin profiles and the degree of heterogeneity correlated to several clinical parameters. Lung adenocarcinoma and lung squamous cell carcinoma (LUSC) exhibited distinct open chromatin patterns. Beyond this, we uncovered that the broadest open chromatin peaks indicated key NSCLC genes and led to less stable expression. Furthermore, we found that the open chromatin peaks were gained or lost together with somatic copy number alterations and affected the expression of important NSCLC genes. In addition, we identified 21 joint-quantitative trait loci (joint-QTL) that correlated to both assay for transposase accessible chromatin sequencing peak intensity and gene expression levels. Finally, we identified 87 regulatory risk loci associated with lung cancer-related phenotypes by intersecting the QTLs with genome-wide association study significant loci. In summary, this compendium of multiomics data provides valuable insights and a resource to understand the landscape of open chromatin features and regulatory networks in NSCLC. SIGNIFICANCE: This study utilizes state of the art genomic methods to differentiate lung cancer subtypes.See related commentary by Bowcock, p. 4808.

Do Breast Implants Influence Breastfeeding? A Meta-Analysis of Comparative Studies.

BACKGROUND: Aesthetic breast implant augmentation surgery is the most popular plastic surgery worldwide. Many women choose to receive breast implants during their reproductive ages, although the long-term effects are still controversial. Research aim: We conducted a meta-analysis to assess the influence of aesthetic breast augmentation on breastfeeding. We also compared the exclusive breastfeeding rates of periareolar versus inframammary incision. METHODS: A systematic search for comparative studies about breast implants and breastfeeding was performed in PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect, Scopus, and Web of Science through May 2018. Meta-analysis was conducted with a random-effects model (or fixed effects, if heterogeneity was absent). RESULTS: Four cohorts and one cross-sectional study were included. There was a significant reduction in the exclusive breastfeeding rate for women with breast implants compared with women without implants, pooled relative risk = 0.63, 95% confidence interval [0.46, 0.86], as well as the breastfeeding rate, pooled relative risk = 0.88, 95% confidence interval [0.81, 0.95]. There was no evidence that periareolar incision was associated with a reduction in the exclusive breastfeeding rate, pooled relative risk = 0.84, 95% confidence interval [0.45, 1.58]. CONCLUSION: Participants with breast implants are less likely to establish breastfeeding, especially exclusive breastfeeding. Periareolar incision does not appear to reduce the exclusive breastfeeding rate.

Changes of Subfoveal Choroidal Thickness after Cataract Surgery: A Meta-Analysis.

PURPOSE: To investigate the effect of cataract surgery on subfoveal choroid thickness (SFCT) using enhanced-depth imaging optical coherence tomography (EDI-OCT). MATERIALS AND METHODS: Relevant publications were searched systematically through various databases from inception to March 2018. The unit of choroidal thickness measurements is micrometers. Studies comparing SFCT before and after cataract surgery were retrieved. All qualified articles were analyzed using RevMan 5.3. RESULTS: A total of 13 studies with 802 eyes from 646 patients were identified for inclusion. There was a significant increase of SFCT at 1 week (MD = 6.62, 95% CI: 1.20-12.05, P=0.02, I2 = 0%), 1 month (MD = 8.30, 95% CI: 3.20-13.39, P=0.001, I2 = 0%), and 3 months (MD = 8.28, 95% CI: 1.84-14.73, P=0.01, I2 = 0%) after cataract surgery. In subgroup analysis, SFCT in Asians and patients without nonsteroidal anti-inflammatory drugs (NSAIDs) in postoperative medication was significantly thicker (P < 0.05). No statistically significant increase of SFCT was found in diabetic mellitus (DM) patients for 1 day (P=0.89), 1 week (P=0.59), 1 month (P=0.52), and 3 months (P=0.42) after cataract surgery. CONCLUSIONS: This meta-analysis suggested that SFCT increased since 1 week after the cataract surgery and the increase lasted for at least 3 months. Asians and patients without NSAIDs in postoperative medication were more likely to have a thicker SFCT after cataract surgery, whereas DM patients were less likely to increase in SFCT.