Prognostic significance of a pathological response in metastatic lymph nodes of patients with gastric cancer who underwent neoadjuvant chemotherapy followed by surgery.

PURPOSE: To grade the pathological response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC) and investigate its prognostic significance. METHODS: This retrospective study included 196 patients who underwent NAC, followed by radical gastrectomy for LAGC between January 2010 and October 2019. Pathological responses were evaluated based on the proportion of residual tumor cells within the tumor area in the primary tumor (PT) and LNs and included the following categories: 1a (0%), 1b (< 10%), 2 (10-50%), and 3 (> 50%). RESULTS: Among 166 patients with clinically node-positive disease, 38/27/39/62 were classified as having LN regression grade (LRG) 1a/1b/2/3, respectively. Compared to LN non-responders (LRG 2 or 3), LN responders (LRG 1a or 1b) had significantly higher 5-year overall survival (72.5% vs. 19.0%, P < 0.001) and recurrence-free survival rates (67.8% vs. 22.2%, P < 0.001), irrespective of PT response. Furthermore, a multivariate analysis revealed that the LN response was an independent risk factor for the overall survival (hazard ratio [HR] 0.417, 95% confidence interval [CI] 0.181-0.962, P = 0.040) and recurrence-free survival (HR 0.490, 95% CI 0.242-0.991, P = 0.047), but not the PT response (P > 0.05). CONCLUSIONS: The pathological LN response may be a reliable prognostic prediction tool in patients with LAGC who received NAC.

Prevention of the return of extinguished fear by disrupting the interaction of neuronal nitric oxide synthase with its carboxy-terminal PDZ ligand.

Exposure therapy based on the extinction of fear memory is first-line treatment for post-traumatic stress disorder (PTSD). However, fear extinction is relatively easy to learn but difficult to remember, extinguished fear often relapses under a number of circumstances. Here, we report that extinction learning-induced association of neuronal nitric oxide synthase (nNOS) with its carboxy-terminal PDZ ligand (CAPON) in the infralimbic (IL) subregion of medial prefrontal cortex negatively regulates extinction memory and dissociating nNOS-CAPON can prevent the return of extinguished fear in mice. Extinction training significantly increases nNOS-CAPON association in the IL. Disruptors of nNOS-CAPON increase extracellular signal-regulated kinase (ERK) phosphorylation and facilitate the retention of extinction memory in an ERK2-dependent manner. More importantly, dissociating nNOS-CAPON after extinction training enhances long-term potentiation and excitatory synaptic transmission, increases spine density in the IL, and prevents spontaneous recovery, renewal and reinstatement of remote fear of mice. Moreover, nNOS-CAPON disruptors do not affect other types of learning. Thus, nNOS-CAPON can serve as a new target for treating PTSD.

Dorsal Hippocampus to Infralimbic Cortex Circuit is Essential for the Recall of Extinction Memory.

Posttraumatic stress disorder subjects usually show impaired recall of extinction memory, leading to extinguished fear relapses. However, little is known about the neural mechanisms underlying the impaired recall of extinction memory. We show here that the activity of dorsal hippocampus (dHPC) to infralimbic (IL) cortex circuit is essential for the recall of fear extinction memory in male mice. There were functional neural projections from the dHPC to IL. Using optogenetic manipulations, we observed that silencing the activity of dHPC-IL circuit inhibited recall of extinction memory while stimulating the activity of dHPC-IL circuit facilitated recall of extinction memory. "Impairment of extinction consolidation caused by" conditional deletion of extracellular signal-regulated kinase 2 (ERK2) in the IL prevented the dHPC-IL circuit-mediated recall of extinction memory. Moreover, silencing the dHPC-IL circuit abolished the effect of intra-IL microinjection of ERK enhancer on the recall of extinction memory. Together, we identify a dHPC to IL circuit that mediates the recall of extinction memory, and our data suggest that the dysfunction of dHPC-IL circuit and/or impaired extinction consolidation may contribute to extinguished fear relapses.

[Analysis of the principles of Tibetan medicine processing].

Tibetan medicine processing ensures the safety of clinical application of Tibetan medicine. It is of great significance to analyze the principles of Tibetan medicine processing in the development, inheritance, and innovation of Tibetan medicine. However, due to the late start of modern Tibetan medicine research and the disciplinary division, the current research on Tibetan medicine processing focuses on the exploration and collation of traditional techniques and the analysis of the processing mechanism of Tibetan medicine through chemical and pharmacological research, but its principles and traditional theories have been rarely reported. In view of this, after analyzing the concept, essence, theories, purposes, and functions of Tibetan medicine processing through the integration of Tibetan medicine, Tibetan pharmacology, and clinical research of Tibetan medicine, this study proposed that the essence of Tibetan medicine processing was to change the "five sources" composition of medicinal materials through physical, chemical, and biological means, or the comprehensive means, and the theoretical principle of Tibetan medicine processing was to change or transform the positive and adverse effects or the obvious and recessive effects by altering the "five sources" composition of the drug to maximize the positive effect and minimize the adverse effect and the damage to the body, thereby achieving the purposes of toxicity reduction, efficacy enhancement, and drug property harmonization represented by sharpening, softening, nourishing, and reasonable compatibility. This study is expected to provide references for the construction of the theoretical system of Tibetan medicine processing, the inheritance of processing techniques, and innovative research.

Application of Restriction Site-Associated DNA Sequencing (RAD-Seq) for Copy Number Variation and Triploidy Detection in Human.

At present, low-pass whole-genome sequencing (WGS) is frequently used in clinical research and in the screening of copy number variations (CNVs). However, there are still some challenges in the detection of triploids. Restriction site-associated DNA sequencing (RAD-Seq) technology is a reduced-representation genome sequencing technology developed based on next-generation sequencing. Here, we verified whether RAD-Seq could be employed to detect CNVs and triploids. In this study, genomic DNA of 11 samples was extracted employing a routine method and used to build libraries. Five cell lines of known karyotypes and 6 triploid abortion tissue samples were included for RAD-Seq testing. The triploid samples were confirmed by STR analysis and also tested by low-pass WGS. The accuracy and efficiency of detecting CNVs and triploids by RAD-Seq were then assessed, compared with low-pass WGS. In our results, RAD-Seq detected 11 out of 11 (100%) chromosomal abnormalities, including 4 deletions and 1 aneuploidy in the purchased cell lines and all triploid samples. By contrast, these triploids were missed by low-pass WGS. Furthermore, RAD-Seq showed a higher resolution and more accurate allele frequency in the detection of triploids than low-pass WGS. Our study shows that, compared with low-pass WGS, RAD-Seq has relatively higher accuracy in CNV detection at a similar cost and is capable of identifying triploids. Therefore, the application of this technique in medical genetics has a significant potential value.

Atomic transport properties of liquid iron at conditions of planetary cores.

Atomic transport properties of liquid iron are important for understanding the core dynamics and magnetic field generation of terrestrial planets. Depending on the sizes of planets and their thermal histories, planetary cores may be subject to quite different pressures (P) and temperatures (T). However, previous studies on the topic mainly focus on the P-T range associated with the Earth's outer core; a systematic study covering conditions from small planets to massive exoplanets is lacking. Here, we calculate the self-diffusion coefficient D and viscosity η of liquid iron via ab initio molecular dynamics from 7.0 to 25 g/cm3 and 1800 to 25 000 K. We find that D and η are intimately related and can be fitted together using a generalized free volume model. The resulting expressions are simpler than those from previous studies where D and η were treated separately. Moreover, the new expressions are in accordance with the quasi-universal atomic excess entropy (Sex) scaling law for strongly coupled liquids, with normalized diffusivity D⋆ = 0.621 exp(0.842Sex) and viscosity η⋆ = 0.171 exp(-0.843Sex). We determine D and η along two thermal profiles of great geophysical importance: the iron melting curve and the isentropic line anchored at the ambient melting point. The variations of D and η along these thermal profiles can be explained by the atomic excess entropy scaling law, demonstrating the dynamic invariance of the system under uniform time and space rescaling. Accordingly, scale invariance may serve as an underlying mechanism to unify planetary dynamos of different sizes.

Uncoupling nNOS-PSD-95 in mPFC inhibits morphine priming-induced reinstatement after extinction training.

Extremely high relapse rate is the dramatic challenge of drug abuse at present. Environmental cues play an important role in relapse of drug abuse. However, the specific mechanism underlying relapse remains unclear. Using morphine conditioned place preference (CPP) model, we show that association of neuronal nitric oxide synthase (nNOS) with postsynaptic density-95 (PSD-95) plays a significant role in morphine priming-induced reinstatement. The nNOS-PSD-95 coupling and c-Fos expression in the medial prefrontal cortex (mPFC) was significantly increased after extinction of morphine CPP. Dissociation of nNOS-PSD-95 in the mPFC by ZL006 inhibited the reinstatement of morphine CPP induced by a priming dose of morphine. Significantly reduced phosphorylation of cAMP-response element binding protein (CREB) in the mPFC was observed in the mice exposed to morphine after the extinction training. Uncoupling nNOS-PSD-95 reversed the morphine-induced CREB dysfunction. Moreover, effects of ZL006 on the reinstatement of morphine CPP and CREB activation depended on nNOS-PSD-95 target. Together, our findings suggest that nNOS-PSD-95 in the mPFC contributes to reinstatement of morphine CPP, possibly through CREB dysfunction, offering a potential target to prevent relapse of drug abuse.

Prevalence, involved domains, and predictor of cognitive dysfunction in systemic lupus erythematosus.

BACKGROUND: Cognitive Dysfunction (CD) can occur in Systemic Lupus Erythematosus (SLE) before the occurrence of Neuropsychiatric Lupus Erythematosus (NPSLE). Given the reversibility and fluctuation of SLE-related CD, the research for possible predictors is of great significance for early detection and intervention. OBJECTIVE: We sought to determine the prevalence, involved domains, and possible predictors of CD in SLE patients. METHODS: We conducted a retrospective cross-sectional study at Nanfang Hospital from 2018 to 2019. A total of 78 SLE patients were recruited. The Montreal Cognitive Assessment (MoCA) scale was used to screen cognitive function. Demographic, clinical, and laboratory characteristics were collected. The serum anti-methyl-d-aspartate receptor (anti-NMDAR) antibody and S100ß were measured by enzyme-linked immunosorbent assay (ELISA). Multivariate logistic regression analysis and ROC curve were used to assess the predictor of SLE-related CD. RESULTS: Of 78 recruited patients,53 (67.9%) had CD. It mainly involved delayed recall, abstract generalization, verbal repetition, and fluency. The disease activity index (SLEDAI) was not associated with SLE-related CD (p > 0.05). Multivariate logistic regression showed that an increase in each year of education there was a decrease in the likelihood of CD (OR 0.261, CI 0.080-0.857, p = 0.027) whereas with each unit increase in serum anti-NMDAR antibody there was an increased likelihood of SLE-related CD (OR 1.568, CI 1.073-2.292, p = 0.020). CONCLUSION: The prevalence of SLE-related CD was 67.9% in our study and SLE-related CD was not associated with disease activity. Serum anti-NMDAR antibody can be used as a predictor for SLE-related CD.

Evolutionary game dynamics of the Wright-Fisher process with different selection intensities.

Evolutionary game dynamics in finite populations can be described by a frequency-dependent, stochastic Wright-Fisher process. The fitness of individuals in a population is not only linked to environmental conditions but also tightly coupled to the types and frequencies of competitors, leading to different types of individuals with different selection intensities. We studied a 2 × 2 symmetric game in a finite population and established a dynamic model of the Wright-Fisher process by introducing different selection intensities for different strategies. Thus, we provided another effective way to study the evolutionary dynamics of a finite population and obtained the analytical expressions of fixation probabilities under weak selection. The fixation probability of a strategy is not only related to a game matrix but also to different selection intensities. The conditions required for natural selection to favor one strategy and for that strategy to be an evolutionary stable strategy (ESSN) are specified in our model. We compared our results with those of a Moran dynamic process with different selection intensities to explore these two processes better. In the two processes, the conditions conducive to the strategy's taking fixation are the same. By simulation analysis, the dynamic relationships between the fixation probabilities and selection intensities were intuitively observed in the prisoner's dilemma, coordination, and coexistence games. The fixation probability of the cooperative strategy in the prisoner's dilemma decreases with the increase of its own selection intensity. In the coexistence and coordination games, the fixation probability of the cooperative strategy increases with its own selection intensity. For the three types of games, the fixation probability of the cooperative strategy decreases with the increase of the selection intensity of the defection strategy.

[Alleles dropout patterns of Y-short tandem repeats in infertile males with Y chromosome microdeletions].

Y chromosomal short tandem repeat (Y-STR) typing is the most commonly used genetic technique in forensic studies. However, there may be a limit to the application of Y-STR in forensic science as Y-STR loci are subject to loss or variation caused by the higher chromosomal structures' spontaneous mutation rate. Located in the long arm of the Y chromosome, azoospermia factor (AZF) have been shown to participate in spermatogenesis and its deletion could cause infertility. However, little is known about the Y-STR dropout pattern in individuals with Y chromosome microdeletions. In this study, 85 infertile males with Y chromosome interstitial deletion were identified and special Y-STR allele dropout patterns were analyzed by employing a Y-STR Commercial Kit and a Y chromosome Deletion Kit. Results demonstrate that AZF a region deletion are related to DYS439-DYS389I-DYS389II alleles dropout, while AZF b region or c region deletions correlate to DYS448 allele dropout. Null DYS385-DYS392-DYS448 alleles were observed in AZF b+c+d region deletion individuals. While null DYS390-Y-GATA-H4-DYS385-DYS392-DYS448 alleles were observed in AZF a+b+c+d large region deletion individuals. Our data suggest that Y chromosome microdeletions may indicate specific Y-STR locus dropout patterns.

RISK FACTORS FOR NONREMISSION AND PROGRESSION-FREE SURVIVAL AFTER I-131 THERAPY IN PATIENTS WITH LUNG METASTASIS FROM DIFFERENTIATED THYROID CANCER: A SINGLE-INSTITUTE, RETROSPECTIVE ANALYSIS IN SOUTHERN CHINA.

OBJECTIVE: Prognostic factors related to progression-free survival (PFS) have not received much attention in the literature regarding iodine-131 ((131)I) therapy for patients with differentiated thyroid cancer and lung metastases. We sought to explore the factors associated with PFS and nonremission in a group of patients with differentiated thyroid cancer and pulmonary metastases at initial diagnosis and to investigate the impact of (131)I therapy on pulmonary function and peripheral blood counts in the same cohort of patients. METHODS: The medical records of 1,050 patients with differentiated thyroid cancer treated at the Zhujiang Hospital of Southern Medical University from January 2006 to January 2015 were retrospectively reviewed. Among them, 107 patients fulfilled the inclusion criteria. RESULTS: Multivariate Cox regression analysis indicated that age ≥45 years and (131)I nonavidity were independent risk factors for disease progression. Multivariate logistic regression analysis revealed that pulmonary nodule size ≥1 cm and (131)I nonavidity were the strongest risk factors predicting nonremission. Varying cumulative (131)I dosage had no association with posttreatment pulmonary function or peripheral blood cell counts. CONCLUSION: Similar to earlier studies, our results confirm that (131)I nonavidity was associated with an increased risk of disease progression and greater odds of nonremission. In addition, patients with differentiated thyroid cancer and lung metastases with pulmonary nodules ≥1 cm had a reduced likelihood of achieving remission. Furthermore, special attention is needed when monitoring patients over 45 years at a higher risk of disease progression. ABBREVIATIONS: CI = confidence interval DTC = differentiated thyroid cancer (18)F-FDG = fluoro-18 fluorodeoxyglucose FEF = forced expiratory flow FTC = follicular thyroid cancer FVC = forced vital capacity GR = granulocytes Hb = hemoglobin HR = hazard ratio (131)I = iodine-131 LN = lymph node OR = odds ratio OS = overall survival PET/CT = positive positron emission tomography/computed tomography PFS = progression-free survival PT = partial thyroidectomy PTC = papillary thyroid cancer RAI = radioactive iodine RBC = red blood cell Tg = thyroglobulin TgAb = thyroglobulin antibody TSH = thyroid-stimulating hormone TT = total thyroidectomy WBC = white blood cells WBS = whole body scan.

Evaluation of meropenem regimens suppressing emergence of resistance in Acinetobacter baumannii with human simulated exposure in an in vitro intravenous-infusion hollow-fiber infection model.

The emergence of resistance to carbapenems in Pseudomonas aeruginosa can be suppressed by optimizing the administration of meropenem. However, whether the same is true for Acinetobacter baumannii is not fully understood. We assessed the bactericidal activity of meropenem and its potency to suppress the emergence of resistance in A. baumannii with human simulated exposure in an in vitro intravenous-infusion hollow-fiber infection model (HFIM). Two clinical strains of carbapenem-susceptible multidrug-resistant A. baumannii (CS-MDRAB), CSRA24 and CSRA91, were used, and their MICs and mutant prevention concentrations (MPCs) were determined. Six meropenem dosage regimens (0.5, 1.0, or 2.0 g given every 8 h [q8h] with a 0.5-h or 3-h infusion for seven consecutive days) were simulated and then evaluated in the HFIM. Both the total population and resistant subpopulations of the two strains were quantified. Drug concentrations were measured by high-performance liquid chromatography. All dosage regimens, except for the lowest dosage (0.5 g for both the 0.5-h and 3-h infusions), showed 3-log CFU/ml bacterial killing. Dosage regimens of 2.0 g with 0.5-h and 3-h infusions exhibited an obvious bactericidal effect and suppressed resistance. Selective amplification of subpopulations with reduced susceptibility to meropenem was suppressed with a percentage of the dosage interval in which meropenem concentrations exceeded the MPC (T>MPC) of ≥20% or with a ratio of T>MPC to the percentage of the dosage interval in which drug concentrations are within the mutant selection window of ≥0.25. Our in vitro data support the use of a high dosage of meropenem (2.0 g q8h) for the treatment of severe infection caused by CS-MDRAB.

Exploring the diagnostic value of CLR and CPR in differentiating Kawasaki disease from other infectious diseases based on clinical predictive modeling.

Background: Kawasaki disease (KD) is an important cause of acquired heart disease in children and adolescents worldwide. KD and infectious diseases can be easily confused when the clinical presentation is inadequate or atypical, leading to misdiagnosis or underdiagnosis of KD. In turn, misdiagnosis or underdiagnosis of KD can lead to delayed use of intravenous immunoglobulin (IVIG), increasing the risk of drug resistance and coronary artery lesions (CAL). Objectives: The purpose of this study was to develop a predictive model for identifying KD and infectious diseases in children in the hope of helping pediatricians develop timely and accurate treatment plans. Methods: The data Patients diagnosed with KD from January 2018 to July 2022 in Shenzhen Longgang District Maternity & Child Healthcare Hospital, and children diagnosed with infectious diseases in the same period will be included in this study as controls. We collected demographic information, clinical presentation, and laboratory data on KD before receiving IVIG treatment. All statistical analyses were performed using R-4.2.1 (https://www.rproject.org/). Logistic regression and Least Absolute Shrinkage with Selection Operator (LASSO) regression analyses were used to build predictive models. Calibration curves and C-index were used to validate the accuracy of the prediction models. Results: A total of 1,377 children were enrolled in this study, 187 patients with KD were included in the KD group and 1,190 children with infectious diseases were included in the infected group. We identified 15 variables as independent risk factors for KD by LASSO analysis. Then by logistic regression we identified 7 variables for the construction of nomogram including white blood cell (WBC), Monocyte (MO), erythrocyte sedimentation rate (ESR), alanine transaminase (ALT), albumin (ALB), C-reactive protein to procalcitonin ratio (CPR) and C-reactive protein to lymphocyte ratio (CLR). The calibration curve and C-index of 0.969 (95% confidence interval: 0.960-0.978) validated the model accuracy. Conclusion: Our predictive model can be used to discriminate KD from infectious diseases. Using this predictive model, it may be possible to provide an early determination of the use of IVIG and the application of antibiotics as soon as possible.

Discovery, Synthesis, and Activity Evaluation of Novel Five-Membered Sulfur-Containing Heterocyclic Nucleosides as Potential Anticancer Agents In Vitro and In Vivo.

A series of novel five-membered sulfur-containing heterocyclic nucleoside derivatives were designed, synthesized, and evaluated for their anticancer activities in vitro and in vivo. The structure-activity relationship studies revealed that some of them showed obvious antitumor activities in several cancer cell lines. Among them, compound 22o exhibited remarkable antiproliferative activity against HeLa cells and was more potent than cisplatin (IC50 = 2.80 vs 7.99 µM). Furthermore, mechanism studies indicated that 22o inhibited cell metastasis, induced cell apoptosis, decreased mitochondrial membrane potential, and activated autophagy through the PI3K-Akt-mTOR signaling pathway. Moreover, drug affinity responsive target stability and the cellular thermal shift assay revealed that 22o targeted RPS6 and inhibited its phosphorylation. Importantly, 22o inhibited the growth of the HeLa xenograft mouse model with a low systemic toxicity. These results indicated that 22o may serve as potent anticancer agents that merit further attention in future anticancer drug discovery.

[Clinical value of MLPA in the prenatal gene diagnosis of Duchenne muscular dystrophy].

OBJECTIVE: To investigate the clinical value of multiplex ligation-dependent probe amplification (MLPA) in the prenatal gene diagnosis of high risk pregnant women from Duchenne muscular dystrophy (DMD) families. METHODS: The 155 high risk pregnant women from DMD families were recruited from 2005 to 2012 in 4 hospitals in Guangzhou, such as Southern Hospital of Southern Medical University and the Third Affiliated Hospital of Guangzhou Medical University. Among all the samples, 7 were chorionic villus samples taken from early-stage pregnancy and 148 were amniotic fluid samples from mid-stage pregnancy. After the maternal contamination was eliminated, the fetal DMD gene screening was carried out by using MLPA. The mutation rates in DMD exons were calculated in all the 155 families. RESULTS: (1) Among the 155 fetuses of the DMD high risk pregnant women, there were 72 male fetuses and 83 female fetuses. In the male fetuses, there were 27 sufferers (38%). In the female fetuses, there were 28 carriers (34%). And there were 100 normal fetuses. (2) Among the 27 DMD sufferers, 22 cases were DMD exon homozygous deletions (14.2%, 22/155) and 5 cases were DMD exon duplications (3.2%, 5/155). Among the 28 carriers, 25 cases were gene heterozygous deletions (16.1%, 25/155) and 3 cases were gene heterozygous duplications (1.9%, 3/155). In the 155 families, the DMD mutations mainly occurred in exons 45-52, and the exon 49 had the highest mutation rates of 22 times. (3) Among the 7 cases of prenatal gene diagnosis using chorionic villus samples, 2 fetuses had the identical DMD genotypes with their mothers and probands. One was a DMD sufferer and the other was a carrier. Termination or continuation of pregnancy was suggested based on the genotype of the fetus. CONCLUSIONS: MLPA provides an accurate method in the prenatal diagnosis of DMD. It could be used to distinguish DMD gene homozygous deletions from heterozygous deletions and duplications. Therefore, it is valuable for DMD prenatal diagnosis in high-risk women. Chorionic villus sampling can be applied to the early prenatal diagnosis for DMD disease.

Changes in neurotransmitter levels, brain structural characteristics, and their correlation with PANSS scores in patients with first-episode schizophrenia.

BACKGROUND: In patients with schizophrenia, the brain structure and neurotransmitter levels change, which may be related to the occurrence and progression of this disease. AIM: To explore the relationships between changes in neurotransmitters, brain structural characteristics, and the scores of the Positive and Negative Symptom Scale (PANSS) in patients with first-episode schizophrenia. METHODS: The case group comprised 97 patients with schizophrenia, who were evaluated using the Canadian Neurological Scale and confirmed by laboratory tests at Ningbo Mental Hospital from January 2020 to July 2022. The control group comprised 100 healthy participants. For all participants, brain structural characteristics were explored by measuring brain dopamine (DA), glutamic acid (Glu), and gamma-aminobutyric acid (GABA) levels, with magnetic resonance imaging. The case group was divided into negative and positive symptom subgroups using PANSS scores for hierarchical analysis. Linear correlation analysis was used to analyze the correlations between neurotransmitters, brain structural characteristics, and PANSS scores. RESULTS: Patients in the case group had higher levels of DA and lower levels of Glu and GABA, greater vertical and horizontal distances between the corpus callosum and the inferior part of the fornix and larger ventricle area than patients in the control group (P < 0.05). Patients with positive schizophrenia symptoms had significantly higher levels of DA, Glu, and GABA than those with negative symptoms (P < 0.05). In patients with positive schizophrenia symptoms, PANSS score was significantly positively correlated with DA, vertical and horizontal distances between the corpus callosum and the infrafornix, and ventricular area, and was significantly negatively correlated with Glu and GABA (P < 0.05). In patients with negative schizophrenia symptoms, PANSS score was significantly positively correlated with DA, vertical distance between the corpus callosum and the infrafornix, horizontal distance between the corpus callosum and the infrafornix, and ventricular area, and was significantly negatively correlated with Glu and GABA (P < 0.05). CONCLUSION: In patients with first-episode schizophrenia, DA levels increased, Glu and GABA levels decreased, the thickness of the corpus callosum increased, and these variables were correlated with PANSS scores.

Nos1+ and Nos1- excitatory neurons in the BLA regulate anxiety- and depression-related behaviors oppositely.

BACKGROUND: The basolateral amygdala (BLA) neurons are primarily glutamatergic and have been associated with emotion regulation. However, little is known about the roles of BLA neurons expressing neuronal nitric oxide synthase (nNOS, Nos1) in the regulation of emotional behaviors. METHODS: Using Nos1-cre mice and chemogenetic and optogenetic manipulations, we specifically silenced or activated Nos1+ or Nos1- neurons in the BLA, or silenced their projections to the anterdorsal bed nucleus of the stria terminalis (adBNST) and ventral hippocampus (vHPC). We measured anxiety behaviors in elevated plus maze (EPM) and open-field test (OFT), and measured depression behaviors in forced swimming test (FST) and tail suspension test (TST). RESULTS: BLA Nos1+ neurons were predominantly glutamatergic, and glutamatergic but not GABAergic Nos1+ neurons were involved in controlling anxiety- and depression-related behaviors. Interestingly, by selectively manipulating the activities of BLA Nos1+ and Nos1- excitatory neurons, we found that they had opposing effects on anxiety- and depression-related behaviors. BLA Nos1+ excitatory neurons projected to the adBNST, this BLA-adBNST circuit controlled the expression of anxiety- and depression-related behaviors, while BLA Nos1- excitatory neurons projected to vHPC, this BLA-vHPC circuit contributed to the expression of anxiety- and depression-related behaviors. Moreover, excitatory vHPC-adBNST circuit antagonized the role of BLA-adBNST circuit in regulating anxiety- and depression-related behaviors. CONCLUSIONS: BLA Nos1+ and Nos1- excitatory neuron subpopulations exert different effects on anxiety- and depression-related behaviors through distinct projection circuits, providing a new insight of BLA excitatory neurons in emotional regulation. LIMITATIONS: We did not perform retrograde labeling from adBNST and vHPC regions.

Sex Differences in Association Between Gut Microbiome and Essential Hypertension Based on Ambulatory Blood Pressure Monitoring.

BACKGROUND: Sex differences in the pathogenesis of hypertension exist. While gut microbiota (GM) has been associated with hypertension, it is unclear whether there are sex-linked differences in the association between GM and hypertension. METHODS: We conducted a cross-sectional study to investigate the sex differences in associations between GM characterized by shotgun sequencing, GM-derived short-chain fatty acids, and 24-hour ambulatory blood pressure in 241 Hong Kong Chinese (113 men and 128 women; mean age, 54±6 years). RESULTS: The hypertensive group was associated with GM alterations; however, significant differences in ß-diversity and GM composition in hypertensive versus normotensive groups were only observed in women and not in men under various statistical models adjusting for the following covariates: age, sex, body mass index, sodium intake estimated by spot urine analysis, blood glucose, triglycerides, low- and high-density lipoprotein cholesterol, smoking, menopause, and fatty liver status. Specifically, Ruminococcus gnavus, Clostridium bolteae, and Bacteroides ovatus were significantly more abundant in the hypertensive women, whereas Dorea formicigenerans was more abundant in the normotensive women. No bacterial species were found to be significantly associated with hypertension in men. Furthermore, total plasma short-chain fatty acids and propionic acid were independent predictors of systolic and diastolic blood pressure in women but not men. CONCLUSIONS: GM dysregulation was strongly associated with 24-hour ambulatory blood pressure in women but not men, which may be mediated through propionic acid. Our work suggests that sex differences may be an important consideration while assessing the role of GM in the development and treatment of hypertension.

[A study on indicator system for early-warning on hemorrhagic fever with renal syndrome epidemic].

OBJECTIVE: To establish an early-warning indicator system on outbreak of hemorrhagic fever with renal syndrome by Delphi method seeking expert advices. METHODS: Firstly, the literature review and the experts meeting method were used to formulate the initiator frame work and indicators. A two-round consultation was used to filter indicators, discuss the boundary of indicators and determine the weighting coefficient among 25 experts from 14 provinces, municipalities and autonomous regions. The relative weightiless of indicators was determined by the weight coefficients method. RESULTS: The experts' average length of service in prevention and control of hemorrhagic fever with renal syndrome was (23.80 ± 11.70) years. The positivity coefficients of the two-round experts were 100% and 72%. Kendall's coefficients of the two-round consultation were 0.50 (χ(2)(R) = 148.95, P < 0.01) and 0.54 (χ(2)(R) = 212.63, P < 0.01) and opinions among experts became consistent and the consultation had achieved the need of forecast. Four first-class indicators (host animals, risk population, social environment and case-related indicators) and 14 second-class indicators were filtered to develop the indicators system. The weight coefficients of the first-class indicators were 0.28, 0.23, 0.23 and 0.26. CONCLUSION: The early-warning index system of hemorrhagic fever with renal syndrome has been established and it could provide a reference for the forest and warning of HFRS outbreak.

Coping Ability and Promotion Countermeasures of Medical and Health Institutions Reputation Crisis: A Case Study in Hubei Province.

At present, the doctor-patient relationships in Chinese medical and health institutions (MHI) are increasingly tense, and the reputation crisis challenges are being faced by MHI more frequently. However, the reputation crisis management level of the MHI is directly related to the future development and construction of the MHI and is an important management link that cannot be ignored. Therefore, how to quantify the impact of the relevant crisis on hospitals has become a major problem. First of all, this paper uses the situational crisis communication theory (SCCT) to combine the characteristics of hospital reputation crisis with the theory and classification of MHI reputation crisis from three perspectives: victim crisis, accidental crisis, and preventable crisis. Second, a more comprehensive analysis of MHI reputation crisis management model is conducted in the research cases, based on the relevant data of Union Hospital, Tongji Medical College Huazhong University of Science and Technology (UH), Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology (TJ), Zhongnan Hospital of Wuhan University (ZN), Renmin Hospital of Wuhan University (RM), and Maternal and Child Hospital of Hubei Province (MC). Third, we divide MHI reputation positioning into four types, namely robust, growth, fragile, and sensitive, and innovate SCCT to build a new MHI crisis classification type. Finally, this paper provides appropriate crisis management strategies for sample MHI based on the above examples and theories. Furthermore, we realize the lifecycle management of MHI reputation by identifying, evaluating and responding to reputation issues. This study provides a theoretical reference for the MHI reputation crisis management level and the adjustment of future management strategies.